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Hydrogenation and Hydroamination Reactions Using Boron-Based Frustrated Lewis Pairs
by
Tayseer Mahdi
A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy
Department of Chemistry University of Toronto
copy Copyright by Tayseer Mahdi 2015
ii
Hydrogenation and Hydroamination Reactions Using
Boron-Based Frustrated Lewis Pairs
Tayseer Mahdi
Doctor of Philosophy
Department of Chemistry University of Toronto
2015
Abstract
New main group systems that provide avenues for small molecule activation have been
illustrated using frustrated Lewis pairs (FLPs) ndash combinations of sterically encumbered Lewis
acids and bases which cannot form adducts The research presented herein expands the small
molecule activation and transformation of FLPs using B(C6F5)3
Combination of the aryl amine tBuNHPh and B(C6F5)3 under H2 at room temperature leads to its
heterolytic splitting forming the complex [tBuNH2Ph][HB(C6F5)3] Exposing the salt to elevated
temperatures is found to follow an alternative mechanism resulting in hydrogenation of the N-
bound phenyl ring affording the isolable cyclohexylammonium salt [tBuNH2Cy][HB(C6F5)3]
This finding is extended to include a series of N-phenyl amines in addition to mono- and di-
substituted pyridines quinolines and several other N-heterocycles
The reaction of B(C6F5)3 and H2 with other substrates namely ketones and aldehydes are also
investigated Catalytic hydrogenation of the carbonyl functional group is achieved in an ethereal
solvent to give alcohol products In these cases the borane and ether behave as a FLP to activate
H2 and effect the reduction Similar reductions are also achieved in toluene using B(C6F5)3 in
iii
combination with cyclodextrins or molecular sieves Reductive deoxygenation occurs in the
particular case of aryl ketones
Finally the Lewis acid B(C6F5)3 is found to enable the intermolecular hydroamination of various
terminal alkynes giving iminium alkynylborate complexes of the general formula
[RPhN=C(CH3)R1][R1CequivCB(C6F5)3] The three-component reaction can also be performed
catalytically generating enamine products which are amenable to subsequent hydrogenation
reactions giving their corresponding amines The chemistry is expanded to intramolecular
systems forming N-heterocyclic compounds Furthermore a FLP route to stoichiometric
hydrophosphination of alkynes is developed
iv
Acknowledgments
Graduate school is not a journey taken alone rather it is one travelled with companions I have a
large group of wonderful people to thank for travelling by my side continuously supporting me
and putting a smile on my face
First and foremost I would like to take this opportunity to express my sincere gratitude to my
supervisor Prof Doug Stephan Thank you for your support you were always positive and open
to discussions Aside from developing my knowledge in chemistry you provided me with the
opportunity to build relationships and grow professionally I have also had the honour of having
very helpful committee members over the past few years Profs Bob Morris and Datong Song I
would like to thank you for your guidance and feedback through the seminar series and
committee meetings Prof Andrew Ashley I truly appreciate the time you took to provide me
with feedback for this thesis and attend my examination Thank you to Prof Erker at the
University of Muumlnster for accepting me to do an exchange in his research group
Of course the results in this thesis would not be publishable without the hard work of the staff at
the University of Toronto I would like to thank you all especially Darcy Burns Dmitry
Pichugin Rose Balazs and Matthew Forbes Also I would like to thank Chris Caputo Peter
Mirtchev Conor Prankevicius Alex Pulis and Adam Ruddy for your time in editing this thesis
All of the past and present Stephan group members thank you for the great times and of course
for doing your lab jobs and keeping the lab functional I definitely have to thank you Shanna for
keeping us in check
I want to give a big shout out to all my Athletic Centre gym buddies rock-climbing fellows
Chem Club soccer team champions and amazing Argon crossfitters I cannot express how much I
enjoyed every moment spent doing these outside-the-lab activities
A big I love you to my most amazing siblings Maithem Christina Jacob and Hoda I do not have
enough room here to express how much you guys mean to me but through it all we have stuck
together and this is how we will continue until the end To my future baby niece you have put a
smile on my face even while you are still inside the womb I cannot wait to meet you Finally to
the most supportive and kind-hearted person I have ever met Renan you have been there for me
from the start of this journey until the end Thank you all
v
Table of Contents
Abstract ii
Acknowledgments iv
Table of Contents v
List of Figures xi
List of Schemes xiv
List of Tables xix
List of Symbols and Abbreviations xxi
Chapter 1 Introduction 1
11 Science and Technology 1
111 Boron properties production and uses 2
112 Boron chemistry 3
12 Catalysis 4
13 Frustrated Lewis Pairs 5
131 Early discovery 5
132 Hydrogen activation and mechanism 6
133 Substrate hydrogenation 9
134 Activation of other small molecules 10
1341 Unsaturated hydrocarbons 10
1342 Alkenes 11
1343 Alkynes 11
1344 11-Carboboration 12
1345 CO2 and SO2 13
1346 FLP activation of carbonyl bonds 14
1347 Carbonyl hydrogenation 15
vi
1348 Carbonyl hydrosilylation 16
14 Scope of Thesis 17
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines and N-Heterocyclic Compounds 19
21 Introduction 19
211 Hydrogenation 19
212 Transfer hydrogenation 20
213 Main group catalysts 21
214 Hydrogenation of aromatic and heteroaromatic substrates 22
2141 Transition metal catalysts 22
2142 Metal-free catalysts 23
215 Reactivity of FLPs with H2 23
22 Results and Discussion 24
221 H2 activation by amineborane FLPs 24
222 Aromatic hydrogenation of N-phenyl amines 25
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates 30
223 Mechanistic studies for aromatic hydrogenation reactions 31
2231 Deuterium studies 31
2232 Variable temperature NMR studies 32
2233 Theoretical calculations 33
224 Aromatic hydrogenation of substituted N-bound phenyl rings 35
2241 Fluoro-substituted rings and C-F bond transformations 35
2242 Methoxy-substituted rings and C-O bond transformations 38
22421 Mechanistic studies for C-O and B-O bond cleavage 40
225 Aromatic hydrogenation of N-heterocyclic compounds 45
vii
2251 Hydrogenation of substituted pyridines 45
2252 Hydrogenation of substituted N-heterocycles 49
2253 Proposed mechanism for aromatic hydrogenation 55
2254 Approaches to dehydrogenation 55
23 Conclusions 56
24 Experimental Section 56
241 General considerations 56
242 Synthesis of compounds 57
243 X-Ray Crystallography 79
2431 X-Ray data collection and reduction 79
2432 X-Ray data solution and refinement 79
2433 Selected crystallographic data 81
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation with Frustrated Lewis Pairs 88
31 Introduction 88
311 FLP reactivity with unsaturated C-O bonds 88
32 Results and Discussion 92
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions 92
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents 93
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents 96
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism 97
325 Other hydrogen-bond acceptors for carbonyl hydrogenations 99
326 Other boron-based catalysts for carbonyl hydrogenations 99
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism 100
viii
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system 102
328 Attempted hydrogenation of other carbonyl substrates and epoxides 102
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases 103
3291 Polysaccharides as heterogeneous Lewis bases 104
3292 Molecular sieves as heterogeneous Lewis bases 107
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones 107
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation 110
32101 Verifying the reductive deoxygenation mechanism 111
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins 113
33 Conclusions 113
34 Experimental Section 114
341 General Considerations 114
342 Synthesis of Compounds 116
3421 Procedures for reactions in ethereal solvents 116
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3] 119
3423 Procedures for reactions using heterogeneous Lewis bases 120
3424 Procedures for reductive deoxygenation reactions 121
3425 Spectroscopic data of products in Table 31 121
3426 Spectroscopic data of products in Table 32 125
3427 Spectroscopic data of products in Table 33 125
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a) 127
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b) 128
343 X-Ray Crystallography 130
3431 X-Ray data collection and reduction 130
ix
3432 X-Ray data solution and refinement 130
3433 Selected crystallographic data 131
Chapter 4 Hydroamination and Hydrophosphination Reactions Using Frustrated Lewis Pairs 132
41 Introduction 132
411 Hydroamination 132
412 Reactions of main group FLPs with alkynes 133
4121 12-Addition or deprotonation reactions 133
4122 11-Carboboration reactions 134
4123 Hydroelementation reactions 135
413 Reactions of transition metal FLPs with alkynes 135
42 Results and Discussion 136
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes 136
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes 140
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates 141
4213 Reactivity of the iminium alkynylborate products with nucleophiles 141
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3 142
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes 144
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions 146
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes 147
424 Intramolecular hydroamination reactions using FLPs 148
4241 Stoichiometric hydroamination 148
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines 150
x
425 Reaction of B(C6F5)3 with ethynylphosphines 151
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines 153
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs 154
427 Proposed mechanism for the hydroborationhydrophosphination reactions 156
43 Conclusions 157
44 Experimental Section 157
441 General Considerations 157
442 Synthesis of Compounds 158
4421 Procedures for stoichiometric intermolecular hydroamination reactions 158
4422 Procedures for hydroarylation of phenylacetylene 165
4423 Procedures for catalytic intermolecular hydroamination reactions 167
4424 Procedures for tandem hydroamination and hydrogenation reactions 172
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions 173
4426 Procedures for reactions with ethynylphosphines 177
443 X-Ray Crystallography 179
4431 X-Ray data collection and reduction 179
4432 X-Ray data solution and refinement 180
4433 Platon Squeeze details 180
4434 Selected crystallographic data 181
Chapter 5 Conclusion 185
51 Thesis Summary 185
52 Future Work 186
References 189
xi
List of Figures
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage 8
Figure 12 ndash A highly efficient borenium hydrogenation catalyst 10
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis 21
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates 23
Figure 23 ndash POV-Ray depiction of 24rsquo 26
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+ 27
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($) 27
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right) 28
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right) 31
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-) 33
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol) 34
Figure 210 ndash POV-Ray drawing of 216a 36
xii
Figure 211 ndash POV-Ray drawing of 218 37
Figure 212 ndash POV-Ray drawing of 219 39
Figure 213 ndash POV-Ray drawing of trans-220 40
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c) 42
Figure 215 ndash POV-Ray drawing of 222 43
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right) 46
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring 48
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups 49
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring 49
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c) 50
Figure 221 ndash POV-Ray depiction of the cation for compound 231a 51
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring 52
Figure 223 ndash POV-Ray depiction of the cation for compound 233 52
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right) 53
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine 54
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol () 94
xiii
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol 95
Figure 33 ndash POV-Ray depiction of 31 98
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted 100
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
104
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD) 104
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased 112
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
136
Figure 42 ndash POV-Ray depiction of 47 137
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b) 139
Figure 44 ndash POV-Ray depiction of 410 139
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg 143
Figure 46 ndash POV-Ray depiction of 432 149
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons 152
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b) 153
Figure 49 ndash POV-Ray depictions of 442 155
xiv
List of Schemes
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3 4
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe) 4
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP 6
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c) 7
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K 9
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines 9
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom) 11
Scheme 18 ndash Reaction of FLPs with phenylacetylene 12
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom) 12
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base 13
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I) 14
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs 15
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP 16
xv
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom) 17
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine 20
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b) 24
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom) 25
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23 26
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD 32
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23 32
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts 35
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a 36
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218 37
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219 39
Scheme 211 ndash Synthesis of 220 and 212 40
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b) 41
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3 43
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3 44
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane 45
Scheme 216 ndash Proposed reaction pathway for the formation of 235 54
xvi
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom) 89
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b) 90
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols 90
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom) 91
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH 92
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation 93
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents 97
Scheme 38 ndash Synthesis of 31 98
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond 100
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation 102
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone 108
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b) 110
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones 111
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al) 133
xvii
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c) 134
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes 134
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes 135
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes 135
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
136
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts 140
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3 141
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4] 141
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right) 142
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3 142
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond 144
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes 147
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430 148
xviii
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432 149
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433 150
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH 151
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439 152
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440 154
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH 155
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments 156
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
187
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations 188
xix
List of Tables
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts 29
Table 22 ndash Hydrogenation of substituted pyridines 47
Table 23 ndash Hydrogenation of substituted N-heterocycles 51
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25 81
Table 25 ndash Selected crystallographic data for 216a 218 and 219 82
Table 26 ndash Selected crystallographic data for 220 222 and 224 83
Table 27 ndash Selected crystallographic data for 225 227 and 228 84
Table 28 ndash Selected crystallographic data for 229 230 and 231a 85
Table 29 ndash Selected crystallographic data for 231b 233 and 234a 86
Table 210 ndash Selected crystallographic data for 234b and 235 87
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents 96
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3] 101
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
106
Table 34 ndash Deoxygenation of aryl alkyl ketones 108
Table 35 ndash Deoxygenation of diaryl ketones 109
Table 36 ndash Selected crystallographic data for 31 131
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
138
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3 145
xx
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines 151
Table 44 ndash Selected crystallographic data for 41 47 and 48 181
Table 45 ndash Selected crystallographic data for 49 410 and 413 182
Table 46 ndash Selected crystallographic data for 414 432 and 439 183
Table 47 ndash Selected crystallographic data for 440 and 442 184
xxi
List of Symbols and Abbreviations
9-BBN 9-borabicyclo[331]nonane
α alpha
Aring angstrom 10-10 m
atm atmosphere
β beta
Bpin pinacolborane (4455-tetramethyl-132-dioxaborolane)
br broad
Boc tert-butyloxycarbonyl
Bu butyl
C Celsius
ca circa
calcd calculated
CD cyclodextrin
C6D6 deuterated benzene
C6H5Br bromobenzene
C6D5Br deuterated bromobenzene
CD2Cl2 deuterated dichloromethane
Cy cyclohexyl
δ chemical shift
xxii
deg degrees
d doublet
Da Dalton
DART direct analysis in real time
DEPT Distortionless Enhancement by Polarization Transfer
dd doublet of doublets
de diastereomeric excess
DFT density functional theory
dt doublet of triplets
ee enantiomeric excess
eq equivalent(s)
ESI electrospray ionization
Et ethyl
Et2O diethyl ether
FLP frustrated Lewis pair
γ gamma
ΔG Gibbs free energy
g gram
GC gas chromatography
GOF goodness of fit
xxiii
h hour
HRMS high resolution mass spectroscopy
HMBC heteronuclear multiple bond correlation
HOESY heteronuclear Overhauser effect NMR spectroscopy
HSQC heteronuclear single quantum correlation
Hz Hertz
iPr2O diisopropyl ether
nJxy n-scalar coupling constant between X and Y atoms
K Kelvin
kcal kilocalories
m meta
m multiplet
M molar concentration
Me methyl
Mes mesityl 246-trimethylphenyl
MHz megahertz
μL microliter
μmol micromole
mg milligram
min minute
xxiv
mL milliliter
mmol millimole
MS mass spectroscopy
MS molecular sieves
nPr n-propyl
iPr iso-propyl (CH(CH3)2)
NHC N-heterocyclic carbene
NMR Nuclear Magnetic Resonance
NOE Nuclear Overhauser Effect
o ortho
π pi
p para
POV-Ray Persistence of Vision Raytracer
PGM Platinum Group Metals
Ph phenyl
Ph2O diphenyl ether
ppb parts per billion 10-9
ppm parts per million 10-6
q quartet
quint quintet
xxv
rpm rotations per minute
RT room temperature
σ sigma
s singlet
t triplet
tBu tert-butyl
THF tetrahydrofuran
TMP 2266-tetramethylpiperidine
TMS trimethylsilyl
TMS2O hexamethyldisiloxane
tol toluene
wt weight
1
Chapter 1 Introduction
11 Science and Technology
The advent of the scientific revolution and the scientific method in early modern Europe
dramatically transformed the way scientists viewed the universe as they attempted to explain the
physical world through experimental investigation The long-term effects of the revolution can
be felt today with our dependence upon science to improve the quality of our lives and advance a
globally interconnected world Some scientific discoveries which have paved the way for such
enterprising technologies include the Haber-Bosch process used for the production of ammonia
essential to the synthesis of nitrogen fertilizers1-3 This discovery has dramatically increased food
production globally and allowed for the explosive population growth observed in the past
century Research also intensified to change the world of medicine through discovery of antiviral
agents for treatment of the HIVAIDS pandemic4-5 Ziegler-Natta catalysts have become central
to the polymer industry manufacturing the largest volumes of commodity plastics and
chemicals6-8
While many chemical breakthroughs have had significant benefits on public health their initial
application or even long-term impact on the environment may be detrimental For example
chlorine was used as a weapon during World War I9 while today it plays a vital role in
disinfecting drinking water and sanitation processes10 A more significant example is the
industrial revolution when manufacturing transitioned from manual labour to machines resulting
in unprecedented growth in population and standards of living Our continued reliance on
factories and mass production has led to depletion of natural resources and emission of
greenhouse gases resulting in anthropogenic climate change11-15
Scientists have acknowledged the need to remediate environmental impacts and to find more
environmentally acceptable technologies for the chemical industry To this end chemical
research has focused on implementing the principles of green chemistry16-17 to develop benign
processes which will sustain the growing energy demands of our society18-19 Central to the green
concept is the application of catalysis in chemical transformations in addition to using readily
available non-toxic raw materials in cost effective procedures
2
Rare precious metals such as the Platinum Group Metals (PGM) are extracted by mining of non-
renewable resources normally resulting in negative social and environmental impacts on the
area20 The metals are used in industrial chemical syntheses where they are regularly recovered
and recycled back into production It is essential however to gradually replace these reagents
with more environmentally benign and readily available transition metals in order to reduce
waste processing costs and eliminate the possibility of their release into the environment In this
aspect chemists are actively seeking innovations to advance more green chemical processes21-24
A vast majority of d-block transition metals have energetically accessible valence d-orbitals
allowing for oxidation state changes which are pivotal to substrate activation and accessing
stabilized transition states Additional factors including the steric and electronic tunability of the
ligand framework have led to the development of a broad range of metal catalysts applied in
numerous chemical transformations25-26 Nonetheless a growing number of advancements
involving the use of main group s and p-block elements have also shown reactivities similar to
those of transition metal complexes27-30
Main group elements are relatively abundant on Earth and over the last decade have experienced
a renaissance in chemical transformations Notably frustrated Lewis pair (FLP) systems which
involve the combination of Lewis acids and bases that are sterically and electronically prohibited
from forming a classical adduct have been at the forefront31 The unquenched reactivity of FLPs
has been explored in the activation of numerous small molecules The majority of FLP systems
incorporate boron Lewis acids and phosphorus Lewis bases32 In this thesis the potential to
expand FLP reactivity to nitrogenboron and oxygenboron pairs is explored
111 Boron properties production and uses
Boron (B) is a non-metallic element always found in nature bound to oxygen as orthoboric acid
alkali metal and alkaline earth metal borates33 Prominent sources of boron include the sodium
borate minerals rasorite and kernite found in deposits at the Mojave Desert of California and in
Turkey which is the largest producer of boron minerals33-34 Boron is vastly spread in Nature
however it constitutes only about 3 ppm of the Earthrsquos crust35-36
Industrially the production of pure boron is very difficult as it tends to form refractory materials
containing small amounts of carbon and other elements The method typically used for
3
commercial production of amorphous boron (up to 97 purity) is by reduction of B2O3 with Mg
in a thermite-like reaction Higher purity (gt99) boron is obtained by the reduction of boron
halides with H2 whereas ultra-purity can be achieved by thermal decomposition of boron
halideshydrides or diboranes on tungsten wires followed by zone melting purification37
Regardless of the production method different allotropic forms of boron can be accessed Short
reaction times at temperatures below 900 degC produce amorphous boron longer reaction times
above 1400 degC afford β-rhombohedral and optimal conditions in between the two give α-
rhombohedral36
Amorphous boron consisting of 90 - 92 purity costs approximately $100kg Relatively large
quantities of the material are used as additives in pyrotechnic mixtures Ultrapure (gt9999)
boron costs about $3500kg and is applied in electronics such as a dopant for germanium and
silicon p-type semiconductors Furthermore as the second hardest element inferior only to
diamond there is a growing demand for boron as a light-weight hardenability additive for glass
ceramics and boron filaments used in high-strength materials for the aerospace and steel
industries35-36
112 Boron chemistry
Boron has a valence shell electron configuration of 2s22p1 representing a typical formal
oxidation state of 3+ although due to its high ionization potentials simple B3+ ions do not exist
Boron can form three sp2 hybridized bonds resulting in trigonal planar geometry with a non-
bonding vacant p-orbital orthogonal to the plane susceptible towards electron donation giving
rise to its noted Lewis acidic properties38-40 Scales to quantify Lewis acidity have been designed
by studying the acceptor-donor interactions between Lewis acid and base complexes using NMR
spectroscopy data based on the Gutmann-Beckett41 and Childs42 methods43 IR spectroscopy X-
ray diffraction44 and density functional calculations45
The most common use of Lewis acids are the boron trihalides particularly BF3 and BCl3 in
conjunction with a co-initiator Lewis base such as water initiating cationic polymerization The
unsaturated olefin monomer is protonated generating the [BF3OH]- counterion along with a
carbenium ion which reacts with olefin molecules leading to propagation of the polymer46 With
Lewis acidity comparable to BF3 the Lewis acid B(C6F5)3 was lsquorediscoveredrsquo in the 1990s as an
ideal activator component for Ziegler-Natta olefin polymerization catalysts47 Treatment of a
4
Group 4 dialkyl-metallocene catalyst precursor with one equivalent of B(C6F5)3 results in alkyl
anion abstraction forming the active alkyl-metallocene cation (eg [Cp2ZrMe]+) stabilized by the
weakly coordinating [MeB(C6F5)3]- anion (Scheme 11)48-51
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3
Hydroboration the addition of B-H across multiple bonds of organic substrates such as alkenes
and alkynes provides the most common route to alkyl or alkenyl organoborane reagents
respectively52 The products obtained can be employed as intermediates for further synthetic
derivatization One powerful and general methodology used for the modification of
organoboranes53 is the Suzuki-Miyaura cross-coupling reaction (Scheme 12) These C(sp2)-B
and C(sp3)-B organoboranes readily undergo transmetalation with an electrophilic organo- Cu
Pd Ni or Fe catalyst to give coupled products with new C-C bonds54-55 Other applications of
boron reagents include metal borohydrides as reducing agents transferring hydride nucleophiles
to versatile functional groups56-59 Operating in a similar manner anionic borates consisting of
polarized B-C bonds transfer an organic group to an electrophilic centre38 60
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe)
Of particular relevance to this thesis recent advances in boron chemistry particularly involving
the activation and reactivity of small molecules with FLP systems will be discussed
12 Catalysis
In the early part of the 20th century catalysis developed into a scientific discipline and has
evolved to underlie numerous chemical technologies that benefit human life worldwide61 The
5
function of a catalyst substance added in a sub-stoichiometric amount is to lower the reaction
activation energy and affect selectivity for chemical transformations without being consumed62
Homogeneous catalysts have a long prevalence in industry with applications ranging from bulk
chemicals to complex multi-step processes Among the most prominent examples are the
Monsanto and Cativa processes for the carbonylation of methanol to produce acetic acid and the
oxo process for hydroformylation of olefins to yield aldehydes63 Only touching the tip of the
iceberg other commercial processes include the Wacker process for the oxidation of ethylene
aforementioned Ziegler-Natta olefin polymerization based on immobilized TiCl3 and substrate
hydrogenations using Wilkinsonrsquos Rh and Ru catalysts64-65 Other noteworthy discoveries
essential to the advancement of catalysis include Fischer-Tropsch production of liquid
hydrocarbons asymmetric catalysis olefin metathesis and Pd-catalyzed cross couplings66
The significance of catalysis for the development of chemistry has been recognized by the Nobel
Prize Committee with the earliest accreditation in the field awarded in 1909 to W Ostwald
Shortly thereafter Nobel Prizes were awarded for important contributions by P Sabatier (1912)
F Haber (1918) and C Bosch and F Bergius (1931) Since the turn of the millennium catalysis
has been recognized with four Chemistry Nobel Prizes awarded to 10 laureates66
13 Frustrated Lewis Pairs
131 Early discovery
The acid-base theory proposed by G N Lewis in 1923 is arguably one of the most important
theories in chemistry describing Lewis acid and base species as electron pair acceptors and
electron pair donors respectively67 According to the theory sterically unhindered Lewis acid-
base pairs react to form a Lewis adduct quenching subsequent reactivity This concept is
fundamental in most areas of chemistry involving the interaction of a doubly occupied orbital
(nucleophile) with an empty orbital (electrophile) forming a favourable overlap
Recent advances involving sterically encumbered Lewis pairs preclude such adduct formation
thereby rendering the individual components available for unique reactivity68-70 Astonishingly
in 1942 H C Brown reported that the ldquosteric strainrdquo between the Lewis acid trimethylborane
and the bulky Lewis base 26-lutidine does not result in adduct formation71 These early results
predate the recently popularized concept of frustrated Lewis pairs (FLPs) describing the
6
combination of Lewis acids and bases with sterically and electronically frustrated substituents
which prevent formal adduct formation32 The cooperative behaviour of these frustrated Lewis
centres has been evidenced to activate small molecules72
132 Hydrogen activation and mechanism
The first FLP reactivity was discovered by Stephan et al in 2006 while investigating the
chemistry of phosphonium borate linked zwitterions R2P(H)(C6F4)B(F)(C6F5)2 (R = alkyl or
aryl) generated from nucleophilic aromatic substitution of B(C6F5)3 by bulky secondary
phosphines31 Treatment with Me2SiHCl easily converts the linked zwitterion to the
phosphonium borohydride species containing both protic and hydridic hydrogen atoms In a
remarkable example the linked PHndashBH zwitterion (R = Mes) was found to liberate and rapidly
activate H2 representing the first example of reversible H2 activation using main group
compounds (Scheme 13)
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP
Hydrogen activation by main group compounds is rare the first example was reported in 2005
by the group of Power and co-workers describing the addition of H2 to heavier main group
digermyne compounds RGeequivGeR (R = aryl)30 The seminal finding was followed by the work of
Bertrand using bulky (alkyl)(amino)carbenes displaying both nucleophilic and electrophilic
characteristics to split and add H2 at a single carbon centre28 In a succeeding report by Piers the
antiaromatic Lewis acid perfluoropentaphenylborole was exclusively employed in H2 activation
to yield boracyclopent-3-ene products resulting from H2 addition to the two carbon atoms alpha
to boron73
After the initial breakthrough with FLPs their unique reactivity attracted immediate attention of
the scientific community Erker and co-workers have synthesized intramolecular PB FLPs
derived by the anti-Markovnikov addition of HB(C6F5)2 to vinyl phosphines (Scheme 14 a)74-75
Additionally Rieger and Repo have reported the nitrogen-based intramolecular FLP ansa-
7
aminoborane shown in Scheme 14 (b)76-78 These systems heterolytically split H2 albeit
reversible H2 activation was only demonstrated for the ansa-aminoborane
Hydrogen activation has also been extended to bimolecular systems Combinations of B(C6F5)3
and sterically encumbered tertiary phosphines were found to effect H2 activation (Scheme 14
c)32 In one example the weaker Lewis acid B(p-HC6F4)3 and o-tolyl3P were found to liberate H2
under vacuum79-80
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c)
The initial mechanism proposed for heterolytic splitting of H2 was speculated to be a ldquoside-onrdquo
or ldquoend-onrdquo coordination of H2 to either the boron or phosphorus moiety followed by approach
of the respective FLP partner effecting H-H bond cleavage This mechanism was not found to be
computationally supported despite earlier evidence for the ldquoside-onrdquo mechanism based on BH3-
H2 adducts81-84 While mechanistic details remain debated theoretical investigations by the
groups of Paacutepai85-87 and Grimme88 were performed on the prototype tBu3PB(C6F5)3 FLP Both
groups agree on the formation of an ldquoencounter complexrdquo stabilized by CndashH---F dispersion
interactions between the phosphine methyl groups and C6F5 borane rings As a result the Lewis
pair orient such that the boron is in close proximity to the phosphorus centre The electron
transfer model proposed by Paacutepai89 explains hydrogen activation by synergistic interaction of the
8
Lewis pair inducing polarization on the H2 molecule effecting heterolytic cleavage In this case
donation from the σ orbital of H2 into the empty orbital on the Lewis acid occurs in conjunction
with lone pair donation from the Lewis base to the σ orbital of H2 representing a process
similar to metal-based heterolytic cleavage of H2 (Figure 11 a) In contrast the electric field
model reported by Grimme suggests heterolytic H2 activation is a barrierless process resulting
from the exposure of H2 to a sufficiently strong homogeneous electric field pocket created by the
FLP complex Interpretation of this model does not consider electron donation or the orbitals of
the FLP or H2 (Figure 11 b)
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage
Direct investigation of H2 activation intermediates by standard experimental techniques has been
unquestionably demanding Experimental evidence of an encounter complex has been observed
by 19F1H HOESY NMR studies revealing contacts between all protons of R3P (R = tBu Mes)
and fluorine nuclei of B(C6F5)3 although only a rough orientation of the molecules was
reported90 Examination of a related system has recently been reported by the Piers group In this
case combination of a highly electrophilic boraindene and Et3SiH gave an isolable borane-silane
complex affirming details of adduct formation in FLP hydrosilylation and to a certain extent
extrapolated to the closely related H2 activation reaction (Scheme 15)91
9
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K
133 Substrate hydrogenation
Reversible H2 activation by the initial FLP Mes2P(H)(C6F4)B(H)(C6F5)2 was a landmark
discovery that shed light onto potential important applications of such systems Most significant
of these efforts was demonstrated by employing R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) in the
catalytic reduction of unsaturated substrates specifically bulky imines and N-protected nitriles to
corresponding amines using 5 mol catalyst 5 atm of H2 and temperatures ranging from 80 -
100 degC Concerted investigations in the field revealed that sterically hindered substrates could
also serve as the Lewis base in splitting hydrogen92-93 To this end catalytic amounts of B(C6F5)3
in combination with various bulky aldimines and ketimines were reduced under 5 atm of H2 at
120 degC with isolated yields in the range of 89 - 99 Based on experimental observations the
proposed mechanism suggests H2 is cleaved between the bulky imine and B(C6F5)3 followed by
hydride delivery to the iminium cation (Scheme 16)
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines
10
Following the early reports on metal-free catalytic hydrogenation the reduction of various other
substrates has been demonstrated to include aziridines92 94 enamines93 enones95 silyl enol
ethers96-97 N-heterocycles98 olefins99 and most recently alkynes have been reduced to cis-
alkenes100 Asymmetric hydrogenation by chiral FLPs was first demonstrated in 2008 by
Klankermayer and co-workers to give a chiral amine with 13 ee and later improvements up to
83 were obtained using a camphor derived catalyst101-102 Rieger and Repo saw ee values of
3776 103 while significant improvements up to 89 were achieved by the Du group104
Recently borenium cations have been used as Lewis acids in FLP chemistry with remarkable
catalytic activity for the hydrogenation of imines and enamines at room temperature (Figure
12)105
Figure 12 ndash A highly efficient borenium hydrogenation catalyst
134 Activation of other small molecules
FLP-mediated bond activations have been explored for a multitude of small molecules including
CO2106-107 N2O108-112 SO2113-114 NO115-116 CO107 117-119 NSO120 fluoroalkanes121 ether122
disulfides123 alkenes124-125 and alkynes126-128 FLPs have also been exploited in radical
polymerizations116 and more recently in materials and surface science129 Efforts have also
continued to exploit FLP chemistry in synthetic organic applications130 Beyond here small
molecule transformations that are relevant to the chemistry presented in this thesis will be
discussed
1341 Unsaturated hydrocarbons
Reactivity of unsaturated hydrocarbons has been a field traditionally associated with transition
metal chemistry and has found particular use for organic synthesis131-138 The dramatic evolution
in FLP systems has raised interest in probing the reactivity of main group complexes with
alkenes and alkynes100 139-140 This reactivity is reminiscent of related findings by Wittig and
Benz in 1959 involving the addition of Ph3P and BPh3 to benzyne affording zwitterionic
11
phosphonium-borates141 In the same context Tochtermann showed the addition of the bulky
carbanion [Ph3C]- and Lewis acid BPh3 across the double bond of 13-butadiene rather than
anionic polymerization of the conjugated diene142
1342 Alkenes
The reaction of FLPs with alkenes is particularly intriguing as the individual Lewis components
do not react with the substrate rather the three component combination of R3P B(C6F5)3 and
alkene exhibited intermolecular 12-addition reactions (Scheme 17 top)143-144 Similar activation
results were also observed upon exposure to the ethylene-linked FLP Mes2PCH2CH2B(C6F5)2145-
147 In two remarkable examples the Stephan group provided spectroscopic theoretical148 and
crystallographic149 evidence for Lewis acid-olefin van der Waals complexes forming prior to
FLP additions (Scheme 17 bottom)
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom)
1343 Alkynes
Initial reactivity of FLPs with terminal alkynes featured the facile deprotonation or addition of
phosphineLewis acid (B Al) combinations to afford alkynylborate (aluminate) salts or
zwitterions with selectivity of the reaction correlated to the basicity of the phosphine (Scheme
18)126 128 In a joint report by the Stephan and Erker groups the B(C6F5)3-mediated
intramolecular cyclization of an ortho-ethynylaniline to access a cyclic anilinium borate was
presented150-151 In an analogous fashion Stephan and co-workers showed the cyclization of
alkyne- and alkene-tethered pyridines and quinolines using B(C6F5)3152 The groups of Berke
12
Erker Stephan and Uhl expanded the chemistry by varying the Lewis acid to BPh3 and alanes153
as well as the Lewis base to include phosphines154 polyphosphines155 thioethers amines and
pyridines156 carbenes157 and pyrroles158
Scheme 18 ndash Reaction of FLPs with phenylacetylene
1344 11-Carboboration
Particularly prolific in the research area of FLP reactivity with alkynes the groups of Erker and
Berke separately unravelled the 11-carboboration reaction resulting from the electrophilic
attack of the CequivC triple bond of an alkyne by highly electrophilic boranes RB(C6F5)2 generating
alkenylborane products (Scheme 19)156 159-160
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom)
In the absence of a Lewis base the combination of electrophilic boranes and terminal alkynes are
postulated to generate a vinylidene intermediate stabilized by 12-hydride migration to the
carbocation Subsequently scission of a BndashC bond transfers a substituent from the borane to the
same carbon of the alkyne generating the alkenylborane (Scheme 110 left)159 This simple yet
elegant strategy demonstrates a facile route to borane derivatives with a C(sp2)-B centre that
could be further treated under Suzuki cross-coupling conditions161 In the presence of a Lewis
13
base deprotonation of the vinylidene or nucleophilic addition at the carbocation takes place
(Scheme 110 right)
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base
1345 CO2 and SO2
Following the reactivity of FLPs with olefins successful joint efforts by the Stephan and Erker
groups showed the activation of the greenhouse gas CO2 and acid rain contributor SO2 using the
FLP tBu3PB(C6F5)3 and ethylene-linked PB system Mes2PCH2CH2B(C6F5)2 (Scheme 111 a
and b)113-114 Key differences were observed in the reactivity of the two gases For example the
reversible nature of binding CO2 was not observed with the SO2 bound species Furthermore the
six-membered SO2 adducts derived from linked PB FLPs gave a stereogenic sulphur centre
resulting in a pair of isomers (Scheme 111 b) The Stephan group extended the activation of
CO2 beyond borane Lewis acids To this end 12 combinations of bulky phosphines and AlX3 (X
= halide or C6F5) react with CO2 rapidly leading to the formation of R3P(CO2)(AlX3)2 (Scheme
111 c)
14
Mes2P B(C6F5)2
EO2Mes2P B(C6F5)2
E O
O
R R
gt -20 degC- CO2
tBu3P B(C6F5)3EO2
80 degC- CO2
PB(C6F5)3E
O
O
tBu3
Mes3P 2 AlX3 Mes3PAlX3E
O
O
AlX3
CO2
b)
a)
c)
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I)
In the case of CO2 further chemical transformation of the activated molecule has been
presented107 111 153 162-164 including efforts to reduce CO2 to CH3OH The groups of Ashley and
OrsquoHare presented this reactivity using H2 as the reducing source Stephan et al used ammonia
borane165 and this process has been achieved catalytically by Fontaine using hydroboranes166-168
Additionally Piers reported the catalytic deoxygenative reduction of CO2 to CH4 using silanes169
and Stephan showed the stoichiometric reduction of CO2 to CO using R3PAlX3 FLPs170
1346 FLP activation of carbonyl bonds
Efforts to include oxygen-based substrates in FLP-mediated catalytic transformations have found
limited success due to the high affinity of electrophilic boranes towards oxygen species72 171
Investigations by Erker and co-workers described the irreversible capture of benzaldehyde and
trans-cinnamaldehyde at the C=O functional group by the intramolecular FLP
Mes2PCH2CH2B(C6F5)2 (Scheme 112 top)172-173 Similar alkoxyborate products were obtained
in the reaction of NB FLPs with benzaldehyde (Scheme 112 bottom)174
15
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs
1347 Carbonyl hydrogenation
Metal-free hydrogenation of carbonyl substrates was reported as early as 1961 by Walling and
Bollyky for the homogeneous hydrogenation of ketones catalyzed by alkali metal alkoxides175
About 40 years later Berkessel and co-workers communicated mechanistic studies on the
process which were supported thereafter by computational investigations176 The authors
elucidated mechanistic analogies between base-catalyzed ketone hydrogenation and Ru-
catalyzed transfer hydrogenation by Noyori whereby a Broslashnsted base participates in H2
heterolysis177 Although this is the first example of metal-free reduction of ketone the reactions
are performed at relatively harsh conditions requiring 100 atm of H2 and 200 degC Moreover the
substrate scope was limited to the non-enolizable ketone benzophenone
The reaction of benzaldehyde with the intramolecular H2-activated FLP
R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) was found to proceed in a stoichiometric fashion
reducing the C=O double bond formulating the zwitterion R2P(H)(C6F4)B(C6F5)2OCH2Ph
(Scheme 113) Chemical intuition would perhaps point to proton transfer from the phosphonium
centre this is however prevented by the lower basicity of the oxygen atom contrasting
hydrogenation reactions with nitrogen substrates
16
B(C6F5)2R2P
FF
F F
H
H
O
HPhB(C6F5)2R2P
FF
F F
H O
Ph
R = tBu Mes
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP
Based on the principle for catalytic hydrogenation of imines Repo and co-workers explored
C=O hydrogenations using the aromatic carbonyl substrates benzophenone and benzaldehyde as
Lewis bases along with the Lewis acid B(C6F5)3 Experimental results indicated the reaction to
be challenging generating only sub-stoichiometric amounts of the alcohol products due to rapid
decomposition of the borane178
1348 Carbonyl hydrosilylation
Hydrosilylation is one of the most commonly applied processes within the chemical industry
today New catalytic technologies providing avenues for metal-free SindashH bond activation have
become appealing alternatives to traditional transition metal catalysts179 Impressively in 1996
the Piers group reported 1 - 4 mol of B(C6F5)3 to effect the catalytic hydrosilylation of
aromatic aldehydes ketones and esters at room temperature (Scheme 114 top)180-182 Clever
analysis of the mechanism by Oestreich using a stereochemically pure silane found inversion of
stereochemistry at silicon after hydrosilylation This finding rationalized a concerted SN2 type
displacement at the silicon centre of a (C6F5)3Bδ-middotmiddotmiddotHmiddotmiddotmiddot SiR3δ+ transition state by the substrate
carbonyl oxygen (Scheme 114 bottom)183
17
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom)
14 Scope of Thesis
The objective of this graduate research was to expand the scope of FLP reactions using the Lewis
acid B(C6F5)3 Although previous studies have documented the reactivity of B(C6F5)3 with small
molecules further transformation of the activated species in organic syntheses remains limited
In this work FLP hydrogenation reactions were extended to include the aromatic rings of N-
phenyl amines and N-heterocyclic compounds as described in Chapter 2 Tandem hydrogenation
and transannulation reactions occurred with a para-methoxy substituted aniline affording a 7-
azabicyclo[221]heptane derivative Mechanistic studies of this reactivity provided insight to a
viable approach achieving the catalytic hydrogenation of ketones and aldehydes to form alcohol
products presented in Chapter 3 In addition the reductive deoxygenation of aryl ketones to
aromatic hydrocarbons was investigated Finally Chapter 4 expands FLP catalytic reactions
beyond hydrogenations In this chapter B(C6F5)3 catalyzed hydroamination of terminal alkynes
is investigated with extension to intramolecular systems and stoichiometric hydrophosphination
reactions
All synthetic work and characterizations were performed by the author with the exception of
elemental analyses high resolution mass spectroscopy and X-ray experiments DFT calculations
for the aromatic hydrogenations described in Chapter 2 were performed by Professor Stefan
Grimme at Universitaumlt Bonn Germany Compounds 216 - 218 were initially synthesized by an
undergraduate student Jon Nathaniel del Castillo under the authorrsquos supervision The synthesis
of compounds 439 and 440 were initially performed by the author at the University of Toronto
18
and repeated during a four month research opportunity program in the laboratory of Professor
Gerhard Erker at Universitaumlt Muumlnster Germany Compounds 441 and 442 were prepared at
Universitaumlt Muumlnster and the structure of 442 was obtained and solved by Dr Constantin
Daniliuc All other molecular structures were solved by the author and the authorrsquos supervisor
Professor Douglas Stephan
Portions of each chapter have been published or accepted at the time of writing
Chapter 2 1) Voss T Mahdi T Otten E Froumlhlich R Kehr G Stephan D W Erker G
ldquoFrustrated Lewis Pair Behavior of Intermolecular AmineB(C6F5)3 Pairsrdquo Organometallics
2012 31 2367-2378 2) Mahdi T Heiden Z M Grimme S Stephan D W ldquoMetal-Free
Aromatic Hydrogenation Aniline to Cyclohexylamine Derivativesrdquo J Am Chem Soc 2012
134 4088-4091 3) Mahdi T Castillo J N Stephan D W ldquoMetal-Free Hydrogenation of N-
based Heterocyclesrdquo Organometallics 2013 32 1971-1978 4) Longobardi L E Mahdi T
Stephan D W ldquoB(C6F5)3 Mediated Arene HydrogenationTransannulation of para-
Methoxyanilinesrdquo Dalton Trans 2015 44 7114-7117
Chapter 3 5) Mahdi T Stephan D W ldquoEnabling Catalytic Ketone Hydrogenation by
Frustrated Lewis Pairsrdquo J Am Chem Soc 2014 136 15809-15812 6) Mahdi T Stephan D
W ldquoFacile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive
Deoxygenation of Ketones and Aldehydesrdquo Angew Chem Int Ed 2015 DOI
101002anie201503087
Chapter 4 7) Mahdi T Stephan D W ldquoFrustrated Lewis Pair Catalysed Hydroamination of
Terminal Alkynesrdquo Angew Chem Int Ed 2013 52 12418-12421 8) Mahdi T Stephan D
W ldquoInter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairsrdquo
Chem Eur J 2015 accepted
19
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines
and N-Heterocyclic Compounds
21 Introduction
211 Hydrogenation
Hydrogenation the addition of hydrogen (H2) to unsaturated compounds is one of the simplest
and most attractive chemical processes performed today26 The reaction is employed for the
production of commodity chemicals with widespread application in the petrochemical
pharmaceutical and foods industries One of the largest industrial applications of hydrogenation
is in the Haber-Bosch process63 66 184 This method uses N2 and H2 to produce ammonia which is
essential for the synthesis of nitrogen fertilizers currently sustaining about one-third of the
worldrsquos population Additionally significant is the Fischer-Tropsch process used to generate
liquid hydrocarbons from the chemical reaction of H2 and CO (synthesis gas)185-186
In the early part of the 20th century P Sabatier discovered the catalytic hydrogenation of organic
substrates over finely divided nickel thereby greatly advancing the field of organic chemistry187-
193 Approximately 60 years later Wilkinson uncovered the homogeneous hydrogenation of
olefins using Ru and Rh catalysts a development that was crowned initiator of organometallic
chemistry (Scheme 21 a)194-197 Further developments in metal-based hydrogenations were
made in the 1980s including the Nobel Prize winning work of asymmetric hydrogenations by
Noyori and Knowles (Scheme 21 b)198-207 While precious metal catalysts208-209 are known to
carry out this reactivity (Scheme 21 c) the high cost and low abundance of these metals
necessitates the development of more cost-efficient procedures New technologies providing
avenues for greener transformations have recently been illustrated using first-row transition
metals Fe and Co (Scheme 21 d)136 210-214
20
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine
212 Transfer hydrogenation
A variety of insightful strategies have provided alternative avenues to direct hydrogenation One
such example is transfer hydrogenation the addition of hydrogen to an unsaturated substrate
from a source other than gaseous H2 In the 1920s Meerwein Ponndorf and Verley (MPV)
demonstrated the first example of hydrogen transfer from a sacrificial alcohol to ketone using an
aluminum alkoxide catalyst215-217 Nonetheless interest in using organocatalysts for
hydrogenation reactions increased spectacularly due to novelty of the concept efficiency and
selectivity in organic reactions Particularly recognized are chiral amine catalysts in combination
with Hantzsch ester dihydropyridines which act as mild organic sources of H2218-219 Extensive
research has also focused on new transition metal catalysts for efficient dehydrocoupling of
ammonia borane (H3NBH3) and related amine borane compounds220
Although transfer hydrogenation is a process dominated by precious transition metal catalysts
Earth abundant less toxic Fe-based catalysts have proven remarkably active effecting high
enantioselectivity (Figure 21 a)221 Moreover catalyst-free strategies by Berke and co-workers
have promoted transfer hydrogenation of imines and polarized olefins222 Stephan et al
underscored extension of metal-free catalysis reporting a highly electrophilic phosphonium
cation catalyst for application in dehydrocoupling of protic compounds with silanes and transfer
hydrogenation to olefins (Figure 21 b)223
RhPh3P
Ph3P Cl
PPh3
(a) (b) (c)
(d)
21
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis
213 Main group catalysts
The discovery of sodium borohydride and lithium aluminum hydride in the 1940s introduced
new stoichiometric methods for the hydrogenation of unsaturated functional groups56 59 224 A
variety of these metal hydride reagents possessing a high degree of chemoselectivity have made
the reduction of a broad range of functional groups possible although catalytic procedures are
evidently more desirable In this vein the first non-transition metal catalyst for ketone
hydrogenation employing tBuOK and H2 is regarded as a breakthrough175-176 Early main group
metal catalysts have followed with highlights on a well-defined organocalcium catalyst
developed by Harder225 and the first cationic calcium hydrides by Okuda capable of catalytic
hydrogenation of 11-diphenylethylene226
Renaissance in main group chemistry emerged with the discovery of frustrated Lewis pairs
(FLPs) These relatively common main group reagents have been applied in the hydrogenation of
imines nitriles aziridines enamines silyl enol ethers olefins and alkynes typically using boron
Lewis acids relying on perfluoroaryl substituents227-228 More recently Lewis acidic borenium
ions based on an [NHC-9-BBN]+ framework have also proven ideal for hydrogenation of imine
and enamine substrates105 Du et al described the highly enantioselective hydrogenation of
imines using a chiral borane catalyst derived from the hydroboration of chiral diene
substituents104 Alkyl229 and aryl149 aluminum compounds in addition to metal-activated carbon-
based Lewis acids have been shown to participate in similar reactivity230
(a) (b)
22
214 Hydrogenation of aromatic and heteroaromatic substrates
2141 Transition metal catalysts
Despite advancements in hydrogenation catalysis the reduction of arenes and heteroaromatics to
saturated cyclic hydrocarbons remains challenging and is typically performed in the
heterogeneous phase using transition metal catalysts Such hydrogenations find particular use in
the petrochemical industry to convert alkene and aromatic fossil fuels into liquid hydrocarbons
before application in commodities such as synthetic fuel26 231 The number of complexes capable
of this catalysis is scarce mainly due to the high energy barrier required to disrupt aromaticity
Catalytic hydrogenation of aromatic systems was first demonstrated for phenols anilines and
benzene in the early 1900s by P Sabatier using powdered nickel189-193 Soon after the 14-
reduction of anisole was observed using dissolved alkali metals in liquid ammonia with major
developments emerging to include benzene and naphthalene derivatives232-233 Historically
significant accomplishments include the work of R Adams using finely divided platinum oxide
(Adamrsquos catalyst)234 and M Raney based on digestion of alloys to form finely divided metal
samples (Raney nickel)235 Other highly efficient catalysts include organometallic compounds
particularly Co Ni Ru and Rh deposited on to oxide surfaces236-239
The number of homogeneous systems capable of hydrogenating arene substrates lags well behind
heterogeneous systems The first well-documented homogeneous catalyst is a simple allylcobalt
complex η3-C3H5Co[P(OMe)3]3 reported by Muetterties and co-workers operating at room
temperature (Figure 22 left)240 shadowed by a new generation of TaV and NbV hydride catalysts
featuring bulky ancillary aryloxide ligands by Rothwell (Figure 22 right)241-243 It is noteworthy
that metal complexes of the cobalt group have provided valuable mechanistic information on this
transformation231 Ziegler type catalysts consisting of Ni or Co alkoxides acetylacetonates or
carboxylates with trialkylaluminum activators have also been demonstrated in the large scale
Institut Francais du Petrole (IFP) process231
23
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates
2142 Metal-free catalysts
Non-metal mediated routes such as the facile addition of borohydrides to unsaturated bonds
were developed early on by Brown and co-workers244 To this extent Koumlster has reported the
hydroboration and subsequent hydrogenolysis to convert naphthalenes to tetralins and
anthracenes to coronenes at 170 - 200 degC and 25 - 100 atm of H2245-246 Alternative efforts
demonstrated trialkylborane and tetraalkyldiborane catalysts in hydrogenating olefins and
polycyclic aromatic hydrocarbons including coal tar pitch In another finding homogeneous
iodine and borane catalysts were shown to hydrogenate the aromatic units of high-rank
bituminous coals at temperatures above 250 degC and 150 - 250 atm of H226 In a recent report the
Wang group has demonstrated the hydrogenation of unfunctionalized olefins catalyzed by
HB(C6F5)2247
215 Reactivity of FLPs with H2
The feasibility of FLP systems to activate H2 and hydrogenate unsaturated substrates
particularly heteroaromatic rings has been examined In this respect 26-lutidine and B(C6F5)3
exhibit reversible dissociation of the Lewis acid-base adduct providing a FLP-mode to H2
activation (Scheme 22 a)248-249 Similar acid-base equilibria were observed with N-heterocycles
nonetheless a catalytic amount of B(C6F5)3 and H2 results in reduction of the N-heterocyclic ring
(Scheme 22 b)98 Research by the Sooacutes group extended the scope of such catalytic reductions
using specifically designed Lewis acids250
24
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b)
Following these reports the commercially available Lewis acid B(C6F5)3251-252 was explored in
the hydrogenation of aromatic rings This chapter will describe results in metal-free aromatic
hydrogenation of N-bound phenyl rings of amines imines and aziridines in addition to pyridines
and N-heterocycles While these reductions are stoichiometric they represent rare examples of
homogeneous aromatic reductions that are metal-free and performed under comparatively mild
conditions Moreover the tandem hydrogenation and intramolecular cyclization of a para-
methoxy substituted aniline is presented This reaction provides a unique route to a 7-
azabicyclo[221]heptane derivative
22 Results and Discussion
221 H2 activation by amineborane FLPs
Phosphine-based FLPs have been thoroughly investigated in the activation of small molecules
and particularly revolutionizing is the first demonstration of reversible heterolytic H2 activation
by Mes2P(C6F4)B(C6F5)231 The corresponding chemistry with amineborane FLP systems has
been less explored Combination of the bulky amine tBuNHPh and an equivalent of B(C6F5)3 in
C6D5Br or pentane solutions do not result an apparent interaction by 1H 11B and 19F NMR
spectroscopy indeed supporting the ldquofrustratedrdquo nature of the system Following exposure of this
solution to H2 (4 atm) at 25 degC the gradual precipitation of a white solid was observed and after
12 h the H2 activated species [tBuNH2Ph][HB(C6F5)3] 21 was isolated in 82 yield (Scheme
23 top) The 1H NMR spectrum obtained in C6D5Br showed a broad resonance at 715 ppm
attributable to an NH2 fragment integrating to two protons as well as signals assignable to the
25
phenyl and tBu groups In addition 11B NMR spectroscopy revealed a doublet at -240 ppm (1JB-
H = 78 Hz) and 19F resonances were observed at -1335 -1613 and -1650 ppm These data
along with elemental analysis were consistent with the formulation of 21 Similar treatment of
the diamine 14-C6H4(CH2NHtBu)2 with two equivalents of B(C6F5)3 in toluene and exposure to
H2 (4 atm) resulted in formation of a precipitate at 25 degC Subsequent isolation of the product
afforded quantitative yield of the salt [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 22 (Scheme 23
bottom) The 1H NMR data showed signals at 595 ppm and 339 ppm attributable to the NH2
and BH fragments respectively The 11B and 19F NMR signals were consistent with the presence
of the [HB(C6F5)3]- anion
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom)
222 Aromatic hydrogenation of N-phenyl amines
Repetition of the H2 activation reaction between tBuNHPh and B(C6F5)3 in toluene with heating
at 110 degC for 48 h led to formation of a new product 23 Subsequent workup and
characterization by NMR spectroscopy revealed the presence of the [HB(C6F5)3]- anion The 1H
NMR spectrum displayed a broad resonance at 507 ppm attributed to an NH2 moiety while
aromatic resonances were notably absent Instead multiplets between 272 and 090 ppm along
with a sharp singlet at 091 ppm were observed This data was consistent with the identity of 23
as the cyclohexylamine product [tBuNH2Cy][HB(C6F5)3] (Scheme 24) By 1H NMR
spectroscopy after 48 h at 110 degC the reaction constituted approximately complete conversion
to 23 and was isolated in 84 yield (Table 21 entry 1)
26
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23
Treatment of iPrNHPh with an equivalent of B(C6F5)3 in toluene at 25 degC gave the
crystallographically characterized adduct (iPrNHPh)B(C6F5)3 24rsquo (Figure 23) This compound
exhibited broad resonances in the 1H 11B 13C and 19F NMR spectra at RT indicating a
fluxional adduct Upon cooling the sample to 193 K NMR signals coalesce giving distinct
resonances assignable to the adduct along with 15 inequivalent 19F resonances that are consistent
with a barrier of rotation of the pentafluorophenyl rings
Figure 23 ndash POV-Ray depiction of 24rsquo
Introducing the amine-borane adduct 24rsquo to H2 (4 atm) does not result in any noticeable changes
in the NMR spectra at RT Although thermolysis of the sample up to 70 degC eventually reveals
dissociation of the adduct with concurrent hydrogenation giving products of complete and partial
reduction of the phenyl ring The partially reduced product observed in trace amounts consisted
of olefinic resonances at 577 and 553 ppm and corresponding aliphatic signals at 256 and 222
ppm (Figure 24 insets) Extensive 1H1H COSY and 1H13C HSQC NMR studies confirmed
the compound as the partially hydrogenated 3-cyclohexenyl derivative [3-
(C6H9)NH2iPr][HB(C6F5)3] the cation is depicted in Figure 24
27
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+
Repeating the reaction at 110 degC for 36 h resulted in complete reduction of the aromatic ring
affording the salt [iPrNH2Cy][HB(C6F5)3] 24 in 93 yield (Table 21 entry 1) Monitoring the
reaction in a J-Young tube by 1H NMR spectroscopy at 110 degC showed the gradual growth of the
cyclohexyl methylene resonances with the corresponding consumption of aromatic signals
(Figure 25)
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($)
12 h
9 h
6 h
3 h
15 h
05 h
$
HB HA
28
The hydrogenation protocol was applied to PhCyNH and Ph2NH affording [Cy2NH2][HB(C6F5)3]
25 in yields of 88 and 65 respectively (Table 21 entry 2) Monitoring the reaction of Ph2NH
at 24 h intervals by 1H NMR spectroscopy did not show evidence for formation of PhCyNH
presumably this indicates that complete hydrogenation of both arene rings occurs prior to
addition of the first equivalent of hydrogen to another molecule of Ph2NH In addition to the
NMR spectroscopy data formulation of 24 and 25 were determined via X-ray crystallography
(Figure 26)
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right)
In an analogous fashion further substrates explored in such reductions included iPrNH(2-
MeC6H4) iPrNH(4-RC6H4) (R = Me OMe) iPrNH(3-MeC6H4) and iPrNH(35-Me2C6H3)
affording the arene-reduced products [iPrNH2(2-MeC6H10)][HB(C6F5)3] 26 [iPrNH2(4-
RC6H10)][HB(C6F5)3] (R = Me 27 OMe 28) [iPrNH2(3-MeC6H10)][HB(C6F5)3] 29 and
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] 210 in yields of 77 73 61 82 and 48 respectively (Table
21 entries 3 - 5) In cases where the hydrogenation reactions yield a chiral centre a mixture of
diastereomers was observed
Previously the Stephan group reported the catalytic hydrogenative ring-opening of cis-123-
triphenylaziridine using 5 mol B(C6F5)3 and H2 (4 atm) to give PhNHCHPhCH2Ph in 15 h at
120 degC94 In the following case however employing one equivalent of B(C6F5)3 at 110 ordmC for 96
h resulted in reduction of the N-bound phenyl ring yielding the salt
[CyNH2CHPhCH2Ph][HB(C6F5)3] 211 (Table 21 entry 6) The 1H NMR data were in
agreement with formulation of the cation fragment with notable resonances at 588 and 461
ppm ascribed to the NH2 and methine groups respectively in addition to the phenyl
29
cyclohexyl methylene and BH signals 11B and 19F NMR spectra displayed resonances
characteristic of the [HB(C6F5)3]- anion
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts
30
Reduction of the imine PhN=CMePh to the corresponding amine has also been previously
reported to occur upon exposure of the imine to H2 using 10 mol B(C6F5)392 Under the same
conditions heating the substrate in the presence of one equivalent of B(C6F5)3 for 96 h gave
reduction of the N-bound aromatic ring affording the species [PhCH(Me)NH2Cy][HB(C6F5)3]
212 (Table 21 entry 7) Similarly reduction of 14-C6H4(N=CMe2)2 was observed on heating
for 72 h in the presence of two equivalents of B(C6F5)3 yielding 64 of the product [14-
C6H10(iPrNH2)2][HB(C6F5)3]2 213 (Table 21 entry 8) Aromatic reduction of the bis-arene (14-
C6H4iPrNH)2CH2 with two equivalents of B(C6F5)3 was also achieved affording [(14-
C6H10iPrNH2)2CH2][HB(C6F5)3]2 214 in 76 yield (Table 21 entry 9)
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates
Although this reaction is stoichiometric in B(C6F5)3 hydrogenation of one arene ring takes up
three equivalents of H2 In an attempt to effect reactivity using sub-stoichiometric combinations
of the Lewis acid 5 mol B(C6F5)3 was combined with iPrNHPh pressurized with H2 (4 atm)
and heated at 120 degC After 24 h 1H NMR data yielded complete conversion of the borane to the
[HB(C6F5)3]- anion with only 5 mol conversion of the aniline to the [iPrNH2Cy]+ cation The
remaining 95 of the initial aniline was unaltered Increasing the H2 pressure to 80 atm did not
improve reactivity The inability of the system to turnover could be explained by pKa values of
the conjugate acid for example iPrNHPh has a pKa value of 58 in H2O while the hydrogenated
product has a pKa of about 10 - 11 in H2O (iPr2NH2 pKa 1105 in H2O) thus preventing
reversible activation of H2253-254
Furthermore efforts to hydrogenate the arene ring of iPrNHPh using pre-H2 activated FLPs
[tBu3PH][HB(C6F5)3] [Mes3PH][HB(C6F5)3] and tBu2P(H)(C6F4)B(H)(C6F5)2 did not result in
any observable reactivity by NMR spectroscopy However the stoichiometric combination of the
zwitterion Mes2P(H)(C6F4)B(H)(C6F5)2 evolved H2 at elevated temperatures and ca 10 of
[iPrNH2Cy]+ was observed Similarly 10 mol of the catalyst combination 18-
bis(diphenylphosphino)naphthalene and B(C6F5)3 gave 10 of aromatic reduction as a result of
the borane
Stoichiometric reactions of B(C6F5)3 and the anilines (p-CH3PhO2S)NHPh tBuNH(C6F5) Boc-
NHPh EtNHPh imines 26-(Me2C6H3)N=C(H)Ph PhN=CMe(p-EtOPh) phenols TMSOPh
31
tBuOPh tBuO(p-CF3C6H4) tBuO(p-FC6H4) hydrazine PhNH-NHPh 18-naphthosultam Ph3P
ethers (p-FPh)2O and CF3SPh did not evidence hydrogenation of the arene ring under the
optimized reaction conditions Furthermore the reactivity of iPrNHPh with the boranes BPh3
MesB(C6F5)2 MesB(p-C6F4H)2 PhB(C6F5)2 B(p-C6H4F)3 and B(o-C6H4CF3)3 did not activate
H2 or hydrogenate the aniline arene ring
223 Mechanistic studies for aromatic hydrogenation reactions
2231 Deuterium studies
To gain mechanistic insight into the presented transformation tBuNHPh was combined in a J-
Young tube with an equivalent of B(C6F5)3 in C6H5Br and exposed to D2 (2 atm) at 25 degC After
standing for 12 h multinuclear NMR data certainly indicated heterolytic activation of D2 The 2H
NMR spectrum gave a broad singlet at 658 ppm assigned to a N-D bond and a broad resonance
at 326 ppm attributed to a B-D bond (Figure 27 bottom-left) In addition to the 11B and 19F
NMR spectra these data supported formation of [tBuNHDPh][DB(C6F5)3] 21-d2 After heating
the sample for 3 h at 110 degC the 2H NMR revealed significant diminishing in the B-D resonance
while the N-D resonance was visibly unaltered (Figure 27 top-left) The 1H NMR spectrum of
the corresponding sample evidenced a broad quartet at 325 ppm (1JB-H = 78 Hz) representative
of a B-H bond (Figure 27 top-right) This B-H resonance is absent in the 1H NMR spectrum of
the sample at RT after 24 h (Figure 27 bottom-right)
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right)
Overall the following NMR studies are suggestive of reversible D2 activation in which at
elevated temperatures proton and deuteride from the nitrogen and boron centres of 21-d2
110 degC ND 110 degC BH (3 h) (3h) BD
RT ND BD RT (24 h) (24 h)
32
respectively combine releasing H-D The H-D gas is subsequently reactivated by the free amine-
borane FLP giving rise to [tBuND2Ph][HB(C6F5)3] (Scheme 25)
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD
2232 Variable temperature NMR studies
As supported by the aforementioned deuterium studies the reversible nature of H2 activation by
the aromatic amines and B(C6F5)3 is consistent with observation of species 21 as the initial
product of hydrogenation This is followed by evolution and reactivation of H2 allowing access
to the arene reduced species 23 at elevated temperatures (Scheme 26)
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23
This aspect of reversible H2 acitvation was further verified by variable temperature NMR studies
of the adduct (iPrNHPh)B(C6F5)3 24rsquo under H2 from 45 degC to 115 degC in C6D5Br As temperature
was increased both 11B and 19F NMR spectra displayed resonances pertaining to gradually
dissociating B(C6F5)3 and formation of the [HB(C6F5)3]- anion This is evidenced in Figure 28
by 11B NMR spectroscopy showing liberated B(C6F5)3 at 115 degC (11B δ 53 ppm) and progression
of the resonance at -25 ppm assignable to [HB(C6F5)3]- indicating formation of 24 It is
important to note that the [HB(C6F5)3]- resonance observed at the initiation of the reaction is
attributable to reversible hydride abstraction from the iPr substituent on the aniline
33
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-)
2233 Theoretical calculations
The mechanism of this study is proposed based on quantum chemical calculations performed by
Professor Stefan Grimme at Universitaumlt Bonn Germany Quantum chemical calculations were
performed at the dispersion-corrected meta-double hybrid level (PW6P95 functional) employing
large triple-zeta type basis sets and TPSS-D3 optimized geometries This final theoretical level
denoted as PWP95-D3def2-TZVPPTPSS-D3def-TZVP provides reaction energies with an
estimated accuracy of about 1 - 2 kcalmol Solvation effects of toluene were considered using
the COSMO-RS continuum solvation model255
Theoretical studies indicate a mechanism that supports reactivity to initiate by dissociation of the
weak amine-borane adduct At this stage the FLP could follow two reaction pathways (Figure
29) At moderate temperatures the FLP undergoes splitting of H2 to yield the salt 21 computed
to be 97 kcalmol lower in energy than the amine-borane adduct However the free enthalpy
difference for this species is close to zero hence under equilibrium conditions it can be
considered as a resting state of the reaction This minor difference in free enthalpy is in
agreement with reversible D2 activation results presented earlier using tBuNHPh and B(C6F5)3
45 degC
75 degC
95 degC
65 degC
115 degC
55 degC
85 degC
105 degC
34
An alternative reaction pathway follows at elevated reaction temperatures In this case the
dissociated amine rotates to position the arene para-carbon towards the boron atom creating a
van der Waals complex that is stabilized by significant pi-stacking with a C6F5 group This
complex creates a classical FLP with an electric field to polarize the entrapped H2 and effect
heterolytic splitting at a relatively low energy barrier of 87 kcalmol The free enthalpy for H2
activation relative to the resting state is computed to be 212 kcalmol certainly supporting the
elevated temperatures required to effect this reactivity
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol)
At the transition state the H-H distance is calculated to be about 097 Aring This bond is
significantly elongated compared with PB FLPs where the bond distance ranges between 078
and 080 Aring thus signifying a delayed transition state The corresponding H-H and C-H covalent
Wiberg bond orders are 033 and 041 respectively The B-H bond order is 063 indicating
approximately half-broken and half-formed bonds in the transition state88 256
21
23
35
The resulting intermediate [tBuNHC6H6][HB(C6F5)3] (CH-intermediate) is an ion pair showing
an sp3 hybridized para-carbon and an almost planar tBuNH=C unit in the cation shown in Figure
29 This species has similar energy and free enthalpy to the arene-B(C6F5)3 van der Waals
compound The complexity of subsequent hydrogenation steps to yield 23 has limited further
computations
It is noteworthy that prolonged heating of the more basic amine iPr2NPh with B(C6F5)3 under H2
only yields [iPr2NHPh][HB(C6F5)3] 215 This suggests that the greater basicity of the nitrogen
centre in iPr2NPh (Et2NHPh pKa 66 in H2O) stabilizes 215 thereby inhibiting access to the
amine-borane FLP and subsequent arene reduction (iPrNHPh pKa 58 in H2O)253-254 The overall
proposed reaction mechanism has been summarized in Scheme 27 Observation of the partially
hydrogenated cation [3-(C6H9)NH2iPr]+ illustrated in Figure 24 is presumed to be a result of H2
activation at the ortho-carbon of the arene ring
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts
224 Aromatic hydrogenation of substituted N-bound phenyl rings
2241 Fluoro-substituted rings and C-F bond transformations
Determining functional group tolerance of the demonstrated aromatic hydrogenations reaction
of the fluoro-substituted aniline (2-FPh)NHiPr with B(C6F5)3 under H2 indicated approximately
30 of the salt [(2-FPh)NH2iPr][HB(C6F5)3] after 31 h at RT Heating the sample at 110 degC for
36
24 h afforded a white solid 216a isolated in 59 yield (Scheme 28 a) Multinuclear NMR
spectroscopy revealed approximately 95 of the product consisted of [CyNH2iPr][FB(C6F5)3]
216a Spectral parameters of the cation were in agreement with that of compound 24 The
fluoroborate [FB(C6F5)3]- anionic fragment gave a broad signal at 055 ppm in the 11B NMR
spectrum and four 19F resonances were observed by 19F NMR spectroscopy at -1370 -1612 -
1669 and -1796 ppm The remaining 5 of the reaction mixture consisted of [(2-
FC6H10)NH2iPr][HB(C6F5)3] 216b Single crystals of 216a suitable for X-ray diffraction were
obtained and the structure is shown in Figure 210
Figure 210 ndash POV-Ray drawing of 216a
In a similar fashion heating the reaction of (3-FPh)NHiPr with B(C6F5)3 under H2 after 72 h
afforded the reduced product in 77 yield Approximately 95 of the salt consisted of 216a
and the remainder as [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b (Scheme 28 b) Indeed these
examples illustrate tandem B(C6F5)3 mediated arene hydrogenation and C-F bond activation
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a
37
Analogous reactivity with (4-FPh)NHiPr gave partial hydrogenation of the ring after 72 h
forming the 3-cyclohexenyl derivative [(4-FC6H8)NH2iPr][HB(C6F5)3] 218 in 62 yield
(Scheme 29) In addition to the expected resonances a diagnostic doublet of triplets in the 1H
NMR at 495 ppm and doublet at 1584 ppm (1JC-F = 255 Hz) in the 13C1H NMR spectra
certainly indicate an unsaturated C=C bond with the fluorine atom still intact This was
unambiguously confirmed by X-ray crystallography (Figure 211) It is important to note that
approximately 20 of the isolated product consisted of 216a indicating a much reduced rate of
arene hydrogenation and C-F bond activation in comparison to ortho- or meta-F substituted
anilines In these two cases intial H2 activation is expected to occur through the resonance form
in which the lone pair is at the para carbon (Scheme 27) However in the case of para-F
substituted aniline H2 activation is speculated to preferentially occur through the resonance
structure in which the negative charge is at an ortho carbon This proposal is ascribed to the
electron-withdrawing fluoro substituent which removes electron density from the para position
The partially hydrogenated product 218 is analogous to the cation [3-(C6H9)NH2iPr]+ presented
in Figure 24 in which H2 activation is suggested to initiate at the ortho carbon
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218
Figure 211 ndash POV-Ray drawing of 218
38
In light of recent findings121 a postulated mechanism implies that after reduction of the aromatic
ring B(C6F5)3 activates the C-F bond provoking nucleophilic addition of hydride from a
[HB(C6F5)3]- anion and liberating B(C6F5)3 for further reactivity Interaction of B(C6F5)3 with C-
F bonds were spectroscopically observed in a 11 combination of B(C6F5)3 and CF3-subtituted
anilines In this respect separate combinations of ortho- or para-F3CPhNH(iPr) and B(C6F5)3 in
C6D5Br gave a 19F NMR spectrum showing four broad resonances with a para-meta gap of 86
ppm and a diagnostic broad singlet assignable to a B-F resonance at -1800 ppm The broad
nature of these resonances and absence of a boron resonance in the 11B NMR spectrum do not
indicate formal C-F bond cleavage rather the data supports reversible B(C6F5)3-CF3
interaction121
2242 Methoxy-substituted rings and C-O bond transformations
Reactivity of FLP systems with oxygen-based substituents is noticeably limited due to high
oxophilicity of electrophilic boranes72 171 However recent findings have been reported on
lability of B-O adducts Stephan et al reported that the ethereal oxygen of the borane-oxyborate
(C6F5)2BCH(C6F5)OB(C6F5)3 derived from the reaction of FLPs with syn-gas activates H2 with
the B(C6F5)2 fragment117 Furthermore Et2O effects H2 activation with B(C6F5)3 and was shown
to be an efficient catalyst in the hydrogenation of olefins257 In an effort to further explore the
scope of the presented metal-free aromatic reductions the arene hydrogenation of anilines with
methoxy substituents was attempted
The combined toluene solution of B(C6F5)3 and the para-methoxy substituted imine (p-
CH3OC6H4)N=CCH3Ph was pressurized with H2 (4 atm) and heated at 110 degC for 48 h This
resulted in the formation of a new white crystalline product assigned to
[(C6H10)NHCH(CH3)Ph][HB(C6F5)3] 219 isolated in 30 yield (Scheme 210) Indeed the 1H
NMR spectrum indicated consumption of N-bound aromatic resonances concomitant with the
appearance of two inequivalent doublet of doublets observed at 447 and 374 ppm with the
corresponding 13C1H NMR resonances observed at 652 and 647 ppm respectively These
peaks are assignable to two inequivalent bridgehead CH groups of the resulting bicyclic
ammonium cation The 11B and 19F NMR spectra were in accordance with the presence of
[HB(C6F5)3]- as the anion X-ray diffraction studies further confirmed the bicyclic structure of
the product and the identity of the anion (Figure 212)
39
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219
Figure 212 ndash POV-Ray drawing of 219
In an effort to appreciate the importance of the position of the methoxy substituent on the arene
ring the separate reactions of ortho- and meta-methoxy substituted (CH3OC6H4)NHCH(CH3)Ph
with B(C6F5)3 were attempted under the established hydrogenationtransannulation protocol In
both cases hydrogenation of the N-bound phenyl group was observed although no
transannulation was achieved The amine (o-CH3OC6H4)NHCH(CH3)Ph gave cis and trans
mixtures of [(2-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 220 isolated in 92 yield In contrast
to fluorine abstraction from the ortho carbon position shown in Scheme 28 the methoxy
substituent in this case is not abstracted from the reduced ring due to steric effects preventing
B(C6F5)3 from binding to the substituent However the meta-substituted analogue resulted in C-
O bond cleavage yielding [(C6H11)NH2CH(CH3)Ph][HB(C6F5)3] 212 in 65 isolated yield
(Scheme 211) Ring closure was not obtained for this particular case due to ring strain of the
anticipated product Crystals of 220 suitable for X-ray crystallography were obtained and shown
in Figure 213
40
HB(C6F5)3
NH
OCH3
B(C6F5)3
Ph
+ CH3OH
NH2
OCH3
Ph
NH2Ph
HB(C6F5)3
NHPh
OCH3
220
212
H2
B(C6F5)3
H2
Scheme 211 ndash Synthesis of 220 and 212
Figure 213 ndash POV-Ray drawing of trans-220
In the case of the para-methoxy substituted imine B(C6F5)3 has participated in tandem arene
hydrogenation and transannulation to ultimately afford a 7-azabicyclo[221]heptane derivative a
bicyclic substructure of biological importance258 Unfortunately further expansion of the
substrate scope was not successful giving only the H2 activation product or arene hydrogenation
Such substrate examples include para-methoxyanilines with a methyl substituent at either the
ortho or meta position other para substituents such as HCF2O PhO2S and Br tertiary amine 4-
methoxy-N-phenyl-N-(1-phenylethyl)aniline
22421 Mechanistic studies for C-O and B-O bond cleavage
Studying the mechanism to form the 7-azabicyclo[221]heptane ammonium hydridoborate salt
219 the possibility of an intra- or intermolecular protonation of the methoxy group was initially
41
disproved by heating a toluene sample of the independently synthesized ammonium borate salt
trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] 221a at 110 degC (Scheme 212) No reaction
was evidenced by 1H 11B and 19F NMR spectroscopy However similar treatment of trans-[(4-
CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 221b at 110 degC prompted release of H2 as evidenced
by the 1H NMR signal at 45 ppm eventually giving compound 219 after 12 h at 110 degC
(Scheme 212)
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b)
To verify the liberation of CH3OH in the presented reactions the synthesis of 219 was repeated
starting from the free amine trans-[(4-CH3OC6H10)NHCH(CH3)Ph and B(C6F5)3 under H2
(Figure 214 a) After one week at RT the volatiles were transferred under vacuum from the
reaction vessel into a J-Young tube and the 1H NMR spectrum showed evidence of CH3OH
although a yield was not obtained
42
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c)
This observation implies that ring closing to yield the 7-azabicyclo[221]heptane ammonium
cation does not proceed by intra- or intermolecular protonation of the methoxy group rather
transannulation proceeds via intramolecular nucleophilic attack of the para-carbon by the amine
nitrogen while B(C6F5)3 captures the methoxide fragment To further support this proposed
mechanism the independently synthesized amine trans-(4-CH3OC6H10)NHiPr was treated with
an equivalent of B(C6F5)3 in the absence of H2 (Scheme 213) Interestingly after heating for 2 h
the reaction resulted in quantitative formation of a new product 222 with a sharp 11B resonance
at -242 ppm and 19F resonances at -1354 -1626 and -1668 ppm consistent with the formation
of the borane-methoxide anion [CH3OB(C6F5)3]- The 1H NMR data signified formation of the
diagnostic bridgehead CH protons at 413 ppm The combination of NMR spectroscopy
elemental analysis and X-ray diffraction studies evidenced the formation of compound 222 as
the bicyclic salt [(C6H10)NHiPr][CH3OB(C6F5)3] (Figure 215)
a)
b)
c)
43
Figure 215 ndash POV-Ray drawing of 222
Heating 222 at 110 degC in the absence of H2 eventually results in CH3OH liberation and rapid
degradation of the borane to CH3OB(C6F5)2 and C6F5H In the presence of H2 however 222 is
transformed to 223 with the liberation of CH3OH (Scheme 213) This observation implies that
the ammonium cation of 222 protonates the methoxide bound to boron liberating methanol and
regenerating B(C6F5)3 which undergoes FLP type H2 activation with the bicyclic amine
generating 223 Compound 223 was also prepared from the aniline p-CH3OC6H4NHiPr The
liberated CH3OH was isolated although not quantified and observed by 1H NMR spectroscopy
(Figure 214 b) Interestingly a similar protonation pathway has been previously proposed in a
study by Ashley and OrsquoHare whereby the stoichiometric hydrogenation of CO2 using 2266-
tetramethylpiperidine (TMP) and B(C6F5)3 was reported The authors proposed B-O bond
cleavage of [CH3OB(C6F5)3]- to occur through protonation by the 2266-
tetramethylpiperidinium counter cation259 Additionally most recently Ashley et al proposed
the metal-free carbonyl reduction of aldehydes to possibly proceed through oxonium protonation
of the boron-alkoxide anion [ROB(C6F5)3]-260
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3
44
Despite evidence for the protonation pathway contribution by a second pathway involving the
[CH3OB(C6F5)3]- anion and B(C6F5)3 acting as a FLP to activate H2 cannot be disregarded In
this respect a toluene solution of [NEt4][CH3OB(C6F5)3] and 5 mol B(C6F5)3 were exposed to
H2 (4 atm) at 110 degC After heating for 2 h the 11B and 19F NMR spectra revealed complete
consumption of the [CH3OB(C6F5)3]- anion along with emergence of peaks corresponding to the
H2 activation product [NEt4][HB(C6F5)3] and CH3OH (Scheme 214) This latter mechanism
provides an alternative path to the anion of 223 This type of system draws analogy to H2
activation by the earlier mentioned BO FLP (C6F5)2BCH(C6F5)OB(C6F5)3 suggesting H2
cleavage gives protonated oxygen and borohydride117
Gradual decomposition of the borane catalyst due to CH3OH was also observed as the amine is
not present to displace CH3OH from B(C6F5)3 consequently hindering its decomposition The
pKa of hydroxylic substrates have been shown to be significantly activated by coordination to
B(C6F5)3 generating strong Broslashnsted acids with pKa values comparable with HCl (84 in
acetonitrile)261
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3
Collectively it may be read that compound 219 is formed by initial hydrogenation of the imine
(p-CH3OC6H4)N=CCH3Ph C=N double bond followed by reduction of the arene ring affording
the cyclohexylamine The amine and borane can activate H2 to give the ammonium salt albeit at
elevated temperatures this is reversible allowing the borane to activate the methoxy substituent
and induce transannulation effecting C-O bond cleavage (Scheme 215) Subsequent conversion
of the generated methoxy-borate anion to the hydridoborate anion proceeds under H2 following
the pathways presented in Schemes 213 and 214
45
NH2
R
OCH3
110 oC
NHR
OCH3
NHR
OCH3
(F5C6)3B
+ H2
B(C6F5)3
H2
HB(C6F5)3
- H2HN
R
CH3OB(C6F5)3
+ H2
HB(C6F5)3
HNR
- CH3OH
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane
225 Aromatic hydrogenation of N-heterocyclic compounds
While seeking to extend the scope of aromatic reductions attention was focused on a series of
mono- and di-substituted pyridines quinolines and several other N-heterocycles In this regard
the aromatic hydrogenation of a variety of N-based heterocycles was explored using
stoichiometric combinations of B(C6F5)3 in the presence of H2 (4 atm)
2251 Hydrogenation of substituted pyridines
Detailed studies on the effects of increased steric bulk on pyridine249 and their reactivity with
B(C6F5)3 to activate H2248 at room temperature have been previously reported Stoichiometric
combination of the Lewis base 26-diphenylpyridine and the Lewis acid B(C6F5)3 do not show
evidence of a donor-acceptor interaction by NMR spectroscopy in contrast a reversible adduct is
observed with 26-lutidine Exposure of either combination of 26-diphenylpyridine or 26-
lutidine and B(C6F5)3 under H2 (4 atm) at room temperature activate H2 affording the
corresponding pyridinium hydridoborate salts
Nonetheless heating a mixture of 26-diphenylpyridine and B(C6F5)3 under H2 (4 atm) at 115 degC
for 16 h gives a new product isolated in 92 yield (Table 22 entry 1) The 11B NMR data in
CD2Cl2 displayed a doublet at -246 ppm and three resonances in the 19F NMR spectrum
observed at -1340 -1634 and -1666 ppm confirmed the presence of the [HB(C6F5)3]- anion
The 1H NMR spectrum showed a broad singlet at 590 ppm attributable to the NH2 group
multiplets at 453 and 226 - 189 ppm in addition to signals assignable to the phenyl and BH
46
groups These data were consistent with the formulation of the salt [26-
Ph2C5H8NH2][HB(C6F5)3] 224 Furthermore the 1H NMR data revealed a de of 91 favouring
the meso-diastereomer an assignment that was confirmed via NMR spectroscopy and the
molecular structure shown in Figure 216 (left) In a similar fashion the reaction of 26-lutidine
with B(C6F5)3 under H2 at 115 degC for 60 h afforded the corresponding salt [26-
Me2C5H8NH2][HB(C6F5)3] 225 in 84 yield (Table 22 entry 1) with a de of 80 also
favouring the meso-diastereomer (Figure 216 right) The preferred diastereoselectivity is
consistent with the known ability of B(C6F5)3 to effect epimerization of chiral carbon centres
adjacent to nitrogen by a process previously described to involve hydride abstraction and
redelivery262
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right)
The substrate ethyl 2-picolinate was exposed to the hydrogenation conditions giving a B(C6F5)3
adduct of the reduced substrate (2-(EtOCO)C5H9NH)B(C6F5)3 226 isolated in 74 yield after
36 h (Table 22 entry 2) The 11B NMR spectrum in CD2Cl2 showed a broad singlet at -486 ppm
and 15 inequivalent 19F resonances which were consistent with adduct formation between the
boron and nitrogen centres inhibiting rotation about the bond
47
Table 22 ndash Hydrogenation of substituted pyridines
Multinuclear NMR spectra of 226 displayed the presence of two diastereomers in a 11 ratio
Most distinguishable were the 13C1H resonances at 1674 and 1712 ppm attributable to the
OCO-ester groups and the 1H NMR signals at 418 and 424 ppm arising from the methine
protons Furthermore 1H1H NOESY experiments confirmed the assignment of these peaks to
the respective RSSR and RRSS diastereomers Independent reaction of B(C6F5)3 with the
optically pure piperidine S-2-(EtOCO)C5H9NH at -30 degC in CD2Cl2 afforded the preferential
formation of the SS-diastereomer of 226 However on warming to room temperature over 18 h
racemization at nitrogen eventually afforded a 11 mixture of the SS and SR diastereomers
Even though the pyridine-borane adduct of 2-phenylpyridine has been isolated and characterized
this adduct is reversed at 115 degC Reduction of the substrate using B(C6F5)3 and H2 gave a
mixture of two products isolated in 54 overall yield after 48 h (Table 22 entry 3) A broad 11B
NMR signal at -391 ppm together with a doublet at -240 ppm were consistent with the
48
presence of the adduct (2-PhC5H9NH)B(C6F5)3 227a and the ionic pair [2-
PhC5H9NH2][HB(C6F5)3] 227b in a 41 ratio respectively
The formulation of 227a is further supported by NMR data revealing two distinctively broad
NH singlets in the 1H NMR spectrum at 555 and 581 ppm attributable to a 71 ratio of the
RSSR and RRSS diastereomers The RSSR diastereomer was the more abundant form as
evidenced by NMR and X-ray crystallographic data (Figure 217)
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring
Interestingly the preferential formation of this diastereomer was evidenced by 1H19F HOESY
NMR spectroscopy through intramolecular π-π stacking interactions of the Ph and C6F5 groups
in addition to interactions between the C-H and N-H groups of piperidine and ortho-fluoro
groups of B(C6F5)3 (Figure 218) Identity of compound 227b was confirmed based on
agreement of spectral parameters with the NH2 methine and methylene groups
49
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups
The presence of adduct 227a raised the question about dissociation of the B-N bond and
possible participation of the liberated borane in further pyridine hydrogenation To probe this a
toluene solution of 2-phenylpyridine and 10 mol of 227 was exposed to H2 (4 atm) at 110 degC
After heating for 24 h 1H NMR spectroscopy did not indicate consumption of the pyridine
reagent Similarly repeating the hydrogenation of 2-phenylpyridine with 10 mol B(C6F5)3 did
not result in catalysis
2252 Hydrogenation of substituted N-heterocycles
Attempting to extend the aromatic hydrogenation of N-heterocycles beyond pyridine substrates
attention was focused to 1234-tetrahydroquinoline derivatives which have been reported to
result from the catalytic hydrogenation of N-heterocycles98 In examining the structure of
tetrahydroquinoline the carbocyclic ring fused to the N-heterocycle was observed to be similar
to a secondary aniline (Figure 219) Thus emerging the avenues of previous reports on catalytic
hydrogenation of substituted quinolines and most recent findings on the stoichiometric reduction
of anilines the complete homogeneous hydrogenation of N-heteroaromatic compounds was
explored
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring
50
Exposure of 2-methylquinoline and B(C6F5)3 to H2 (4 atm) at 115 degC for 48 h was found to effect
hydrogenation of not only the N-heterocycle but also the carbocyclic ring to yield [2-
MeC9H15NH2][HB(C6F5)3] 228 in 67 (Table 23 entry 1) In a similar fashion both rings of 2-
phenylquinoline were reduced in the same time frame to give [2-PhC9H15NH2][HB(C6F5)3] 229
in 95 yield (Table 23 entry 1)
The 1H NMR spectra for 228 and 229 exhibited characteristic chemical shifts corresponding to
NH2 methine and methylene groups Both compounds 228 and 229 were produced as mixtures
of diastereomers although in both cases the major isomer was crystallized and found to comprise
of 60 and 73 of the isolated products respectively The molecular structures show both
compounds exhibit SSSRRR stereochemistries in which one of the ring junctions adopts an
equatorial disposition while the other is axially disposed (Figure 220 a and b) Analogous
treatment of 8-methylquinoline with H2 and B(C6F5)3 in toluene for 48 h yielded [8-
MeC9H15NH2][HB(C6F5)3] 230 in 76 (Table 23 entry 1) 1H and 13C1H NMR data suggest
only the presence of the RRRSSS diastereomers (Figure 220 c)
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c)
a) b) c)
51
Table 23 ndash Hydrogenation of substituted N-heterocycles
The corresponding reduction of acridine results in isolation of the fully reduced tricyclic species
in 76 yield (Table 23 entry 2) The isolated product is obtained as a mixture of two isomers
one of which was characterized crystallographically as the salt [C13H22NH2][HB(C6F5)3] 231a
As shown in Figure 221 all ring junctions are equatorially positioned and thus the SRSRRSRS
diastereomers are assigned
Figure 221 ndash POV-Ray depiction of the cation for compound 231a
52
Interestingly a second product was isolated from the pentane work-up crystallographic data
showed it to be the adduct (C13H22NH)B(C6F5)3 231b (Figure 222) In this case however the
stereochemistries of the ring junctions adjacent to nitrogen are inverted affording the RRSSSSRR
diastereomers of the reduced acridine heterocycle Compound 231b was also independently
synthesized in 73 yield from a mixture of isomers of the neutral amine C13H22NH and
B(C6F5)3
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring
Although the substrates 23-dimethyl and 23-diphenylquinoxaline have two Lewis basic
nitrogen centres the reduction reactions required only one equivalent of B(C6F5)3 yielding the
piperazinium derivatives [23-(C4H6Me)2NHNH2][HB(C6F5)3] 232 and [23-
(C4H6Ph)2NHNH2][HB(C6F5)3] 233 in 59 and 55 yield respectively (Table 23 entry 3) In
the case of 232 a single set of diastereomers was observed and the NMR data were consistent
with ring junctions and methyl groups adopting equatorial dispositions In contrast the isolated
product 233 comprised of two diastereomers Crystallographic characterization of one
diastereomer showed the phenyl rings adopt equatorial positions while the ring junctions are
axial and equatorially disposed (Figure 223)
Figure 223 ndash POV-Ray depiction of the cation for compound 233
53
It is noteworthy that while the aromatic ring of the quinoxaline fragment is fully reduced the
phenyl substituents remain intact In a similar situation reduction of 78-benzoquinoline resulted
in the formation of [(C6H4)C7H12NH2][HB(C6F5)3] 234 in 55 yield (Table 23 entry 4) 1H
NMR spectroscopy evidenced a 41 mixture of two diastereomers in which reduction of the
pyridyl and adjacent carbocyclic ring were achieved while aromaticity of the ring remote from
the nitrogen atom was retained X-ray crystallography unambiguously confirmed the dominant
diastereomer 234a to have SRRS stereochemistry while the less abundant diastereomer 234b
showed SSRR stereochemistry (Figure 224)
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right)
Efforts to reduce the related heterocycle 110-phenanthroline in which a pyridyl ring is fused at
the 7 and 8 position of quinoline were undertaken employing one equivalent of B(C6F5)3 After
heating the solution for 14 h at 115 degC under H2 (4 atm) 1H NMR spectroscopy indicated
complete hydrogenation of the N-heterocycle in addition to loss of C6F5H and formation of a
four-coordinate boron centre with a 11B resonance observed at 302 ppm The [HB(C6F5)3]- anion
was not observed and further heating did not reveal hydrogenation of the carbocyclic ring
A second equivalent of B(C6F5)3 was added and the reaction was re-exposed to H2 (4 atm) for a
total of 96 h at 115 degC This resulted in isolation of [(C5H3N)(CH2)2(C5H8NH)B(C6F5)2]
[HB(C6F5)3] 235 in 73 yield (Table 23 entry 5) The 11B NMR spectrum revealed the
presence of two four-coordinate boron centres with resonances at 302 and -254 ppm The
former boron species exhibited six inequivalent fluorine atoms evidenced by 19F NMR
spectroscopy inferring the presence of two inequivalent fluoroarene rings where steric
congestion is inhibiting ring rotation at the B-N and B-C bonds The latter 11B NMR signal
together with the three corresponding 19F resonances arise from the [HB(C6F5)3]- anion X-ray
crystallography confirmed the formulation of 235 as the SRSRSR diastereomer present as 65
of the isolated reaction mixture (Figure 225)
54
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine
In the cationic fragment of compound 235 the boron centre is bound to two perfluoroarene rings
and is chelated by the pyridine and amine nitrogen atoms of partially reduced 110-
phenanthroline The B-N distances in the cation were found for B(1)-N(1)amine to be 1615(3) and
B(1)-N(2)pyridine 1598(3) Aring In this unique case as reduction of the heterocycle proceeds a
single pyridyl ring is initially reduced in which the resulting amine coordinates B(C6F5)3
resulting in loss of C6F5H and chelation of B(C6F5)2 by the pyridyl nitrogen centre affording the
cation (Scheme 216) The second equivalent of the borane remains intact and partakes in partial
hydrogenation of the carbocyclic ring Elimination of C6F5H followed by ring closure is
thermodynamically favoured due to formation of the five-membered borocycle
NN NN
B
B(C6F5)3
(C6F5)3B H
- C6F5H H2
235
(C6F5)2
Scheme 216 ndash Proposed reaction pathway for the formation of 235
Although this arene hydrogenation method is applicable to the presented N-heteroaromatic
substrates the reactivity was not successfully extended to 46-dimethyl-1-phenylpyrimidin-
2(1H)-one 2-methylindoline 3-methylindole 1-methylisoquinoline and carbazole
55
2253 Proposed mechanism for aromatic hydrogenation
The reductions described demonstrate the ability of B(C6F5)3 to mediate the complete aromatic
hydrogenation of a number of N-heterocycles It is clear that the products arise from reduction of
pyridyl andor aniline-type rings and in some cases affording a preferred set of diastereomers as
demonstrated by the ability of B(C6F5)3 to epimerize chiral centers alpha to nitrogen262 Efforts
to monitor several of the mixtures over the course of the reactions failed to provide unambiguous
mechanistic insight By analogy to computational studies presented for aniline hydrogenations
the need for elevated temperatures presumably reflects the fact that hybridizing the para-carbon
of the N-heterocycle is energetically uphill however once this is achieved there is an exothermic
route to the saturated amine Subsequent activation of H2 by the reduced amine and borane
affords the corresponding ammonium salt which is irreversible under the reaction conditions
thus precluding catalytic reduction This could simply be explained by Broslashnsted basicity of the
nitrogen centre An sp2 hybridized nitrogen has the lone pair in a p-orbital therefore it can
participate in resonance making it less basic as opposed to sp3 hybridization which does not have
a p-orbital (pyridine pKa 52 quinoline pKa 492 piperidine pKa 112 all values are in H2O)
While the reactions are nominally stoichiometric multiple turnovers of H2 activation are
achieved For example eight equivalents of H2 are taken up by acridine in the formation of 231
2254 Approaches to dehydrogenation
Although hydrogenation of aromatic substrates is appealing the reversible reaction
dehydrogenation of the products with aim at obtaining a molecular dihydrogen storage device
became a topic of interest Heating compound 231 at 115 degC in a vacuum sealed J-Young tube
did not evolve H2 As an alternative approach the neutral amine C13H22NH was combined with
the electrophilic boranes B(C6F5)3 B(p-C6F4H)3 or (12-C12F9)B(C6F5)2 and heated under
vacuum After 24 h trace amounts of aromatic resonances corresponding to dehydrogenation of
the N-heterocycle and a single carbocyclic ring (five equivalents of H2) was observed by 1H
NMR spectroscopy It is important to note that this process did not liberate H2 rather amine and
B(C6F5)3 abstracted proton and hydride respectively regenerating 231 One can envision this
dehydrogenation process could possibly be applied to transfer hydrogenation of imines similar
to an earlier report by the Stephan group262
56
23 Conclusions
This chapter provides an account on the discovery of N-phenyl amine reductions under H2 using
an equivalent of B(C6F5)3 to yield the corresponding cyclohexylamine derivatives In these
reactions B(C6F5)3 mediates uptake of four equivalents of H2 terminating with a final FLP
activation of H2 affording the cyclohexylammonium salts A possible reaction pathway is
proposed based on experimental evidence and theoretical calculations The substrate scope is
extended to a variety of pyridyl- and aniline-type rings of N-heterocyclic compounds These
reductions represent the first example of homogeneous metal-free hydrogenation of aromatic
rings
Shortly after publishing the presented data on aromatic hydrogenations in two separate reports
the Stephan group communicated the partial reduction of polycyclic aromatic hydrocarbons
using catalysts derived from weakly basic phosphines263 or ethers257 with B(C6F5)3 Additionally
the Du group showed a borane catalyzed route to the stereoselective hydrogenation of
pyridines264
24 Experimental Section
241 General considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane hexane tetrahydrofuran dichloromethane and toluene (Sigma Aldrich) were
dried employing a Grubbs-type column system (Innovative Technology) degassed and stored
over molecular sieves (4 Aring) in the glovebox Bromobenzene (-H5 and -D5) were purchased from
Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring molecular
sieves prior to use Dichloromethane-d2 was purchased from Sigma Aldrich dried over CaH2 and
vacuum distilled onto 4 Aring molecular sieves prior to use Tetrahydrofuran-d8 and toluene-d8 were
purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to use Molecular
sieves (4 Aring) were purchased from Sigma Aldrich and dried at 140 ordmC under vacuum for 24 h
prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at 80 degC under high
vacuum before use Sodium methoxide and tetraethylammonium chloride were purchased from
Sigma Aldrich and dried under vacuum at 140 ordmC for 12 h prior to use
57
All substituted amines anilines quinolines pyridines and other N-heterocycles were purchased
from Sigma Aldrich Alfa Aesar or TCI Potassium tetrakis(pentafluorophenyl)borate and
hydrogen chloride (40 M in 14-dioxane) were purchased from Alfa Aesar The oils were
distilled over CaH2 and solids were sublimed under high vacuum prior to use The following
compounds were independently synthesized following the cited procedure265 unless indicated
otherwise N-tert-butylaniline266 NN-(14-phenylenebis(methylene))bis(tert-butylamine) N-
isopropyl-2-methylaniline N-isopropyl-4-methylaniline N-isopropyl-4-methoxyaniline N-
isopropyl-3-methylaniline N-isopropyl-35-dimethylaniline N-(1-phenylethylidene)aniline
N1N4-di(propan-2-ylidene)benzene-14-diamine 44-methylenebis(N-isopropylaniline) 2-
fluoro-N-isopropylaniline 3-fluoro-N-isopropylaniline 4-fluoro-N-isopropylaniline 4-methoxy-
N-(1-phenylethylidene)aniline 2-methoxy-N-(1-phenylethyl)aniline266 3-methoxy-N-(1-
phenylethyl)aniline266 and alkylation methods267 to prepare trans-(4-
CH3OC6H10)NHCH(CH3)Ph and trans-(4-CH3OC6H10)NHiPr
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Varian 400 MHz spectrometer equipped with an HFX AutoX triple resonance indirect
probe (used for 13C1H 19F experiments) or an Agilent DD2 500 MHz spectrometer Spectra
were referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm
for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) d8-tol (1H = 208 ppm for CH3 13C
= 13748 ppm for ipso carbon) d8-THF (1H = 358 ppm for OCH2 13C = 6721 ppm for OCH2)
or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in ppm and the
absolute values of the coupling constants (J) are in Hz NMR assignments are supported by 2D
and DEPT-135 experiments
Elemental analyses (C H N) were performed in-house employing a Perkin Elmer 2400 Series II
CHNS Analyzer H2 (grade 50) was purchased from Linde and dried through a Nanochem
Weldassure purifier column prior to use High resolution mass spectra (HRMS) were obtained
using an ABSciex QStar Mass Spectrometer with an ESI source MSMS and accurate mass
capabilities
242 Synthesis of compounds
Synthesis of [NEt4][CH3OB(C6F5)3] In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (100 mg 0195 mmol) in CH2Cl2 (10 mL) To the vial
58
Na OCH3 (105 mg 0195 mmol) was added and the reaction was allowed to mix for 3 h at RT
The salt Na CH3OB(C6F5)3 was isolated as a white solid and dried under vacuum (110 mg 0195
mmol gt99) Na CH3OB(C6F5)3 (110 mg 0195 mmol) in CH2Cl2 (10 mL) was subsequently
added to a 4 dram vial containing NEt4 Cl (323 mg 0195 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT for 16 h and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (125 mg
0186 mmol 95)
1H NMR (400 MHz CD2Cl2) δ 322 (q 3JH-H = 73 Hz 8H Et) 311 (s 3H OCH3) 142 (tm 3JH-H = 73 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 3JF-F = 20 Hz 2F o-C6F5)
-1636 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
256 (s BOCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1480 (dm 1JC-F = 240 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1364 (dm 1JC-F = 248 Hz CF) 1246 (br ipso-C6F5) 529 (Et) 519
(OCH3) 710 (Et) Elemental analysis was not successful after numerous attempts
Synthesis of [tBuNH2Ph][HB(C6F5)3] (21) In the glove box a 100 mL Teflon screw cap
Schlenk tube equipped with a stir bar was charged with a yellow solution of B(C6F5)3 (100 mg
0195 mmol) in pentane (7 mL) To the reaction tube N-tert-butylaniline (291 mg 0195 mmol)
was added immediately resulting in a pale orange cloudy solution The reaction tube was
degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2
(4 atm) at -196 ordmC After about 10 min of reaction time at RT white precipitate was observed in
the reaction vessel and the solution became colourless The tube was left to stir at RT for 12 h
The solvent was decanted and the white precipitate was washed with pentane (3 mL) dried under
vacuum and isolated (106 mg 0160 mmol 82)
1H NMR (400 MHz C6D5Br) δ 715 (br s 2H NH2) 712 (t 3JH-H = 73 Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 682 (d 3JH-H = 76 Hz 2H o-Ph) 369 (br q 1JB-H = 78 Hz 1H BH)
102 (s 9H tBu) 19F NMR (377 MHz C6D5Br) δ -1335 (br 2F o-C6F5) -1613 (br 1F p-
C6F5) -1650 (br 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 78 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1494 (dm 1JC-F = 238 Hz CF) 1382 (dm 1JC-F = 244
Hz CF) 1369 (dm 1JC-F = 247 Hz CF) 1309 (p-Ph) 1299 (m-Ph) 1237 (o-Ph) 1244 (ipso-
C6F5) 659 (tBu) 255 (tBu) (ipso-Ph was not observed) Anal calcd () for C28H17BF15N C
5071 H 258 N 211 Found C 5027 H 287 N 219
59
[tBuNHDPh][DB(C6F5)3] (21-d2) This compound was prepared similar to 21 using D2
19F NMR (377 MHz C6H5Br) δ -1332 (m 2F o-C6F5) -1609 (br 1F p-C6F5) -1646 (m 2F
m-C6F5) 11B NMR (128 MHz C6H5Br) δ -238 (s BD)
Synthesis of [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 (22) In a glove box a 100 mL Teflon
screw cap Schlenk tube equipped with a stir bar was charged with a solution of B(C6F5)3 (304
mg 0594 mmol) and NN-(14-phenylenebis(methylene))bis(tert-butylamine) (725 mg 0297
mmol) in toluene (4 mL) The reaction was degassed three times with a freeze-pump-thaw cycle
on the vacuumH2 line The reaction flask was cooled to -196 ordmC and filled with H2 (4 atm)
Immediate precipitation of a white solid was observed at RT The reaction mixture was stirred
overnight at 70 ordmC Pentane (10 mL) was added after which the supernatant was decanted The
residue was washed with pentane (5 mL) and dried in vacuo to give the product as a white
powder (374 mg 0297 mmol gt99)
1H NMR (400 MHz CD2Cl2) δ 727 (s 4H Ph) 595 (br s 4H NH2) 438 (s 4H CH2) 339
(br q 1JB-H = 83 Hz 2H BH) 162 (s 18H tBu) 19F NMR (377 MHz CD2Cl2) δ -1349 (m 3JF-F = 21 Hz 2F o-C6F5) -1635 (t 3JF-F = 21 Hz 1F p-C6F5) -1670 (m 2F m-C6F5) 11B
NMR (128 MHz CD2Cl2) δ -243 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz d8-THF )
δ 1493 (dm 1JC-F = 236 Hz CF) 1461 (quaternary C for C6H4) 1385 (dm 1JC-F = 243 Hz CF)
1374 (dm 1JC-F = 246 Hz CF) 1345 (br ipso-C6F5) 1314 (Ph) 595 (tBu) 461 (CH2) 259
(tBu) Anal calcd () for C51H30B2F30N2 C 4852 H 240 N 222 Found C 4882 H 269 N
252
Compounds 23 ndash 214 were prepared following a common procedure In the glove box a 25 mL
Teflon screw cap Schlenk tube equipped with a stir bar was charged with a yellow solution of
B(C6F5)3 (379 mg 740 μmol) and N-phenyl amine (740 μmol) in toluene (2 mL) The reaction
tube was degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and
filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube was placed in a 110
ordmC oil bath After the appropriate reaction time the toluene was removed under reduced pressure
resulting in crude pale yellow oil The oil was washed with pentane (6 mL) affording the product
as a white powder
60
[tBuNH2Cy][HB(C6F5)3] (23) N-tert-butylaniline (110 mg 740 μmol) reaction time 48 h
product (415 mg 620 μmol 84)
1H NMR (400 MHz C6D5Br) δ 507 (br 2H NH2) 355 (br q 1JB-H = 83 Hz 1H BH) 272 (m
1H N-Cy) 155 (m 2H Cy) 145 (m 2H Cy) 131 (m 1H Cy) 117 (m 3H Cy) 091 (s 9H
tBu) 090 (m 2H Cy) 19F NMR (377 MHz C6D5Br) δ -1327 (m 3JF-F = 21 Hz 2F o-C6F5)
1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1645 (m 2F m-C6F5) 11 B NMR (128 MHz C6D5Br) δ -
240 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 238 Hz
CF) 1382 (dm 1JC-F = 247 Hz CF) 1368 (dm 1JC-F = 247 Hz CF) 1354 (ipso-C6F5) 610
(tBu) 561 (N-Cy) 319 (Cy) 258 (tBu) 244 (Cy) 236 (Cy) Anal calcd () for
C28H23BF15N C 5025 H 346 N 209 Found C 4985 H 357 N 219
Synthesis of PhNHiPrB(C6F5)3 (24rsquo) In a glove box a 20 mL dram vial equipped with a
magnetic stir bar was charged with B(C6F5)3 (176 mg 0344 mmol) and N-isopropylaniline (465
mg 0344 mmol) in toluene (4 mL) All volatiles were removed and the crude oil was washed
with hexane (2 mL) The hexane portion was reduced in volume and placed in a -30 ordmC freezer
Colourless crystals were obtained (122 mg 0192 mmol 55)
1H NMR (400 MHz CD2Cl2 193K) δ 740 - 726 (m 5H Ph) 696 (br 1H NH) 416 (br m
1H iPr) 123 (br 3H iPr) 072 (br 3H iPr) 19F NMR (367 MHz CD2Cl2 193K) δ -1219 (m
1F o-C6F5) -1272 (m 1F o-C6F5) -1279 (m 2F o-C6F5) -1315 (m 1F o-C6F5) -1388 (m
1F o-C6F5) -1543 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F p-C6F5) -1575 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1625 (m 1F m-
C6F5) -1627 (m 1F m-C6F5) -1629 (m 1F m-C6F5) -1636 (m 1F m-C6F5) 11B NMR (128
MHz CD2Cl2 193K) δ -323 (s B-N) 13C1H NMR (101 MHz CD2Cl2 298K) δ 1478 (dm 1JC-F = 246 Hz CF) 1390 (dm 1JC-F = 242 Hz CF) 1365 (dm 1JC-F = 236 Hz CF) 1328
(ipso-Ph) 1301 (o-Ph) 1295 (p-Ph) 1227 (m-Ph) 556 (iPr) 195 (iPr) (ipso-C6F5 was not
observed) Anal calcd () for C27H13BF15N C 5011 H 202 N 216 Found C 4961 H 246
N 209
[iPrNH2Cy][HB(C6F5)3] (24) N-Isopropylaniline (100 mg 740 μmol) reaction time 36 h
product (481 mg 730 μmol 93) Crystals suitable for X-ray diffraction were grown from a
layered dichloromethanepentane solution at -30 ordmC
61
1H NMR (400 MHz C6D5Br) δ 510 (s 2H NH2) 356 (br q 1JB-H = 84 Hz 1H BH) 303 (m 1JH-H = 65 Hz 1H iPr) 276 (m 1H N-Cy) 156 (m 2H Cy) 147 (m 2H Cy) 134 (m 1H
Cy) 099 - 086 (m 5H Cy) 091 (d 1JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1330 (m 3JF-F = 21 Hz 2F o-C6F5) -1609 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-
C6F5) 11 B NMR (128 MHz C6D5Br) δ -239 (d 1JB-H = 84 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1483 (dm 1JC-F = 238 Hz CF) 1384 (dm 1JC-F = 247 Hz CF) 1369 (dm 1JC-F =
248 Hz CF) 1288 (ipso-C6F5) 567 (N-Cy) 498 (iPr) 294 (Cy) 241 (Cy) 240 (Cy) 189
(iPr) Anal calcd () for C27H21BF15N C 4949 H 323 N 214 Found C 4952 H 345 N
219
[Cy2NH2][HB(C6F5)3] (25) Method 1 N-Cyclohexylaniline (130 mg 740 μmol) reaction
time 36 h product (452 mg 650 μmol 88) Method 2 Diphenylamine (125 mg 740 μmol)
reaction time 96 h product (334 mg 480 μmol 65) Crystals suitable for X-ray diffraction
were grown from a concentrated solution in C6D5Br at RT
1H NMR (400 MHz C6D5Br) δ 498 (br s 2H NH2) 317 (br q 1JB-H = 86 Hz 1H BH) 247
(m 2H N-Cy) 122 (m 4H Cy) 111 (m 4H Cy) 099 (m 2H Cy) 070 - 046 (m 10H Cy)
19F NMR (377 MHz C6D5Br) δ -1332 (m 3JF-F = 20 Hz 2F o-C6F5) -1608 (t 3JF-F = 20 Hz
1F p-C6F5) -1648 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 86 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 241 Hz CF) 1380 (dm 1JC-F =
247 Hz CF) 1365 (dm 1JC-F = 248 Hz CF) 1264 (ipso-C6F5) 558 (N-Cy) 293 (Cy) 238
(Cy) 237 (Cy) Anal calcd () for C30H25BF15N C 5182 H 362 N 201 Found C 5217 H
386 N 212
[iPrNH2(2-MeC6H10)][HB(C6F5)3] (26) N-Isopropyl-2-methylaniline (111 mg 740 μmol)
reaction time 36 h product (398 mg 570 μmol 77) NMR data is reported for one isomer
1H NMR (400 MHz C6D5Br) δ 587 (br 2H NH2) 375 (br q 1JB-H = 82 Hz 1H BH) 318 (m
1H N-Cy) 313 (m 3JH-H = 62 Hz 1H iPr) 180 - 118 (m 9H Cy) 113 (d 3JH-H = 64 Hz
6H iPr) 086 (d 3JH-H = 62 Hz 3H Me) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21
Hz 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -237 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) partial δ
1485 (dm 1JC-F = 235 Hz CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF)
1236 (ipso-C6F5) 638 (N-Cy) 593 (iPr) 347 (Cy) 319 (Cy) 304 (CMeH) 291 (Cy) 210
62
(Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C 5021 H
359 N 214
[iPrNH2(4-MeC6H10)][HB(C6F5)3] (27) N-isopropyl-4-methylaniline (111 mg 740 μmol)
reaction time 36 h product (377 mg 540 μmol 73)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 83 Hz 1H BH) 317 (m 3JH-H = 64 Hz 1H iPr) 290 (m 1H N-Cy) 171 (m 2H Cy) 162 (m 2H Cy) 120 (m 3H
Cy) 110 (d 3JH-H = 64 Hz 6H iPr) 086 (d 3JH-H = 66 Hz 3H Me) 077 (m 2H Cy) 19F
NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1613 (t 3JF-F = 21 Hz 1F
p-C6F5) -1652 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -236 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 247
Hz CF) 1367 (dm 1JC-F = 250 Hz CF) 562 (N-Cy) 495 (iPr) 319 (Cy) 304 (CMeH) 291
(Cy) 210 (Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found
C 5014 H 348 N 209
[iPrNH2(4-MeOC6H10)][HB(C6F5)3] (28) N-Isopropyl-4-methoxyaniline (122 mg 740
μmol) reaction time 36 h product (308 mg 450 μmol 61)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 346 (br
4H OMe and CHOMe) 299 (br m 1H N-Cy) 237 (m 1H iPr) 162 (m 2H Cy) 129 (m
2H Cy) 107 (m 4H Cy) 081 (d 3JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1338 (m 3JF-F = 21 Hz 2F o-C6F5) -1623 (t 3JF-F = 21 Hz 1F p-C6F5) -1659 (m 2F m-
C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1484 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 247 Hz CF) 1367 (dm 1JC-F =
247 Hz CF) 1243 (ipso-C6F5) 636 (OMe) 583 (CHOMe) 551 (N-Cy) 497 (iPr) 267 (Cy)
246 (Cy) 183 (iPr) Anal calcd () for C28H23BF15NO C 4908 H 338 N 204 Found C
4945 H 329 N 230
[iPrNH2(3-MeC6H10)][HB(C6F5)3] (29) N-Isopropyl-3-methylaniline (111 mg 740 μmol)
reaction time 36 h product (406 mg 610 μmol 82)
1H NMR (400 MHz C6D5Br) δ 547 (br 2H NH2) 369 (br q 1JB-H = 80 Hz 1H BH) 320 (m
1H iPr) 297 (m 1H N-Cy) 171 (m 3H Cy) 153 (m 1H Cy) 112 (m 1H CMeH) 112 (d
63
3JH-H = 60 Hz 3H iPr) 111 (d 3JH-H = 60 Hz 3H iPr) 104 (m 2H Cy) 086 (d 3JH-H = 66
Hz 3H Me) 078 (m 1H Cy) 068 (m 1H Cy) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1611 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5) 11B
NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ
1488 (dm 1JC-F = 237 Hz CF) 1390 (dm 1JC-F = 250 Hz CF) 1372 (dm 1JC-F = 247 Hz CF)
571 (N-Cy) 503 (iPr) 381 (Cy) 330 (Cy) 315 (CMeH) 293 (Cy) 241 (Cy) 219 (Me)
196 (iPr) 192 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C
5011 H 350 N 216
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] (210) N-Isoporpyl-35-dimethylaniline (121 mg 740
μmol) reaction time 72 h product (243 mg 360 μmol 48) Mixture of isomers was obtained
NMR data for one isomer is reported
1H NMR (400 MHz C6D5Br) δ 555 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 300 -
280 (br m 2H iPr N-Cy) 182 (br m 1H Cy) 149 - 100 (m 5H Cy) 093 (m 6H iPr) 077
- 072 (m 1H Cy) 068 - 062 (m 6H Me) 059 - 048 (m 1H Cy) 19F NMR (377 MHz
C6D5Br) δ -1337 (m 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5)
11B NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 82 Hz BH) 13C1H NMR (100 MHz
C6D5Br) partial δ 1479 (dm 1JC-F = 240 Hz CF) 1378 (dm 1JC-F = 249 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1227 (ipso-C6F5) 560 (N-Cy) 494 (iPr) 410 (Cy) 378 (Cy) 270 (Cy)
212 (Me) 188 (iPr) Anal calcd () for C29H25BF15N C 5097 H 369 N 205 Found C
5087 H 399 N 212
[CyNH2CHPhCH2Ph][HB(C6F5)3] (211) cis-123-Triphenylaziridine (201 mg 740 μmol)
reaction time 96 h product (293 mg 370 μmol 50)
1H NMR (400 MHz CD2Cl2) δ 755 (m 1H p-Ph) 745 (m 4H Ph) 740 (m 3H Ph) 720
(m 2H Ph) 588 (br 2H NH2) 461 (t 3JH-H = 77 Hz 1H PhCH) 369 (br q 1JB-H = 85 Hz
1H BH) 344 (d 2H 3JH-H = 77 Hz PhCH2) 306 (m 1H N-Cy) 203 (m 1H Cy) 168 (m
4H Cy) 137 - 115 (br m 5H Cy) 19F NMR (377 MHz CD2Cl2) δ -1338 (m 3JF-F = 20 Hz
2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1662 (m 2F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -239 (d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F
= 245 Hz CF) 1382 (dm 1JC-F = 248 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1333 (ipso-Ph)
1321 (ipso-Ph) 1310 (p-Ph) 1301 (Ph) 1298 (Ph) 1289 (Ph) 1287 (p-Ph) 1273 (Ph) 1235
64
(ipso-C6F5) 641 (PhCH) 582 (N-Cy) 403 (PhCH2) 306 (Cy) 289 (Cy) 241 (Cy) 238
(Cy) 236 (Cy) Anal calcd () for C38H27BF15N C 5752 H 343 N 177 Found C 5762 H
395 N 187
[PhCH(Me)NH2Cy][HB(C6F5)3] (212) Method 1 N-(1-Phenylethylidene)aniline (144 mg
740 μmol) reaction time 96 h product (303 mg 420 μmol 57) Method 2 B(C6F5) (379 mg
0740 mmol) 3-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol) toluene (5 mL)
product (347 mg 0481 mmol 65)
1H NMR (400 MHz C6D5Br) δ 735 (m 3H o p-Ph) 721 (m 2H m-Ph) 618 (br 1H NH2)
566 (br 1H NH2) 428 (m 1H NH2CHMe) 383 (br q 1JB-H = 83 Hz 1H BH) 288 (m 1H
N-Cy) 190 (m 1H Cy) 166 (m 2H Cy) 157 (m 1H Cy) 154 (d 3JH-H = 69 Hz 3H Me)
146 (m 1H Cy) 126 (m 2H Cy) 098 (m 3H Cy) 19F NMR (377 MHz C6D5Br) δ -1336
(m 2F o-C6F5) -1613 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -234 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 241 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1334
(ipso-Ph) 1296 (o-Ph) 1260 (m-Ph) 574 (NH2CHMe) 573 (N-Cy) 295 (Cy) 288 (Cy)
236 (Cy) 236 (Cy) 188 (Me) (p-Ph was not observed) Anal calcd () for C32H23BF15N C
5358 H 323 N 195 Found C 5374 H 300 N 189
[14-C6H10(iPrNH2)2][HB(C6F5)3]2 (213) N1N4-Di(propan-2-ylidene)benzene-14-diamine (70
mg 0037 mmol) reaction time 36 h product (293 mg 240 μmol 64)
1H NMR (400 MHz d8-THF) δ 784 (br 2H NH2) 376 (br q 1JB-H = 92 Hz 1H BH) 364 (m 3JH-H = 65 Hz 1H iPr) 335 (br m 1H N-Cy) 238 (m 2H Cy) 159 (m 2H Cy) 138 (d 3JH-
H = 65 Hz 6H iPr) 19F NMR (377 MHz d8-THF) δ -1346 (m 3JF-F = 20 Hz 2F o-C6F5) -
1670 (t 3JF-F = 20 Hz 1F p-C6F5) -1697 (m 2F m-C6F5) 11B NMR (128 MHz d8-THF) δ -
254 (d 1JB-H = 92 Hz BH) 13C1H NMR (101 MHz d8-THF) δ 1483 (dm 1JC-F = 237 Hz
CF) 1375 (dm 1JC-F = 242 Hz CF) 1362 (dm 1JC-F = 246 Hz CF) 1259 (ipso-C6F5) 528 (N-
Cy) 486 (iPr) 274 (Cy) 184 (iPr) Anal calcd () for C48H30B2F30N2 C 4701 H 247 N
228 Found C 4686 H 247 N 232
[(14-C6H10(iPrNH2))2CH2][HB(C6F5)3]2 (214) 44-Methylenebis(N-isopropylaniline) (104
mg 370 μmol) reaction time 76 h product (372 mg 280 μmol 76)
65
1H NMR (400 MHz C6D5Br) δ 513 (br 2H NH2) 359 (br q 1JB-H = 81 Hz 1H BH) 301 (m
1H iPr) 276 (m 1H N-Cy) 168 (m 1H Cy) 151 (m 2H Cy) 145 (m 1H CH2) 132 (m
2H Cy) 091 (m 2H Cy) 089 (m 2H Cy) 089 (d 3JH-H = 68 Hz 6H iPr) 19F NMR (377
MHz C6D5Br) δ -1331 (m 3JF-F = 20 Hz 2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -
1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 81 Hz BH) 13C1H
NMR (101 MHz C6D5Br) δ 1486 (dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF)
1385 (dm 1JC-F = 247 Hz CF) 569 (iPr) 500 (N-Cy) 432 (CH2) 296 (Cy) 272 (CH2-Cy)
242 (Cy) 190 (iPr) Anal calcd () for C55H42B2F30N2 C 4995 H 320 N 212 Found C
4973 H 333 N 221
[iPr2NHPh][HB(C6F5)3] (215) In a glove box B(C6F5)3 (379 mg 740 μmol) and NN-
diisopropylaniline (131 mg 740 μmol) were dissolved in C6D5Br (05 mL) and added into a
Teflon capped sealed J-Young tube The J-Young tube was degassed three times through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC and placed
in a 110 ordmC oil bath for 16 h To the C6D5Br solution pentane was added drop wise until the
product precipitated The white solid was isolated (442 mg 640 μmol 87) Crystals suitable
for X-ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H o p-Ph) 693 (m 2H m-Ph) 670 (br 1H NH)
371 (br q 1JB-H = 85 Hz 1H BH) 358 (m 3JH-H = 63 Hz 2H iPr) 093 (d 3JH-H = 63 Hz 6H
iPr) 077 (d 3JH-H = 63 Hz 6H iPr) 19F NMR (377 Hz C6D5Br) δ -1326 (m 3JF-F = 20 Hz
2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -245 ppm (br d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484
(dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1322
(ipso-Ph) 1304 (m-Ph) 1231 (p-Ph) 1211 (o-Ph) 584 (iPr) 188 (iPr) 168 (iPr) Anal calcd
() for C30H21BF15N C 5212 H 306 N 203 Found C 5183 H 329 N 211
Synthesis of 216 - 218 is similar to the general procedure used for compounds 23 - 214 Since
compounds [(2-FC6H10)NH2iPr][HB(C6F5)3] 216b and [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b
were present in trace amounts (5) isolation and characterization proved difficult therefore
spectroscopic data for the two compounds has not been reported
[iPrNH2Cy][FB(C6F5)3] (216a) B(C6F5)3 (379 mg 0740 mmol) 2-fluoro-N-isopropylaniline
(115 mg 0740 mmol) or 3-fluoro-N-isopropylaniline (115 mg 0740 mmol) toluene (5mL)
66
reaction time 72 h product from 2-fluoro-N-isopropylaniline (294 mg 0440 mmol 59)
product from 3-fluoro-N-isopropylaniline (381 mg 0570 mmol 77) Crystals suitable for x-
ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 561 (br 2H NH2) 288 (m 3JH-H = 64 Hz 1H iPr) 262 (br
m 1H N-Cy) 149 (m 2H Cy) 144 (m 2H Cy) 135 (m 1H Cy) 092 - 083 (m 5H Cy)
085 (d 1JH-H = 63 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1370 (m 6F o-C6F5) -1616
(t 3JF-F = 22 Hz 3F p-C6F5) -1669 (m 6F m-C6F5) -1795 (br s 1F BF) 11B NMR (128
MHz CD2Cl2) δ 051 (br s BF) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 239
Hz CF) 1394 (dm 1JC-F = 241 Hz CF) 1373 (dm 1JC-F = 249 Hz CF) 560 (N-Cy) 489
(iPr) 293 (Cy) 245 (Cy) 241 (Cy) 188 (iPr) Anal calcd () for C27H20BF16N C 4817 H
299 N 208 Found C 4804 H 307 N 210
[(4-FC6H8)NH2iPr][HB(C6F5)3] (218) B(C6F5)3 (379 mg 074 mmol) 4-fluoro-N-
isopropylaniline (113 mg 074 mmol) toluene (5 mL) reaction time 72 h product (308 mg
0460 mmol 62) Crystals suitable for X-ray diffraction were obtained from a layered solution
of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 582 (br s 2H NH2) 477 (dm 3JF-H = 14 Hz 1H CH=CF)
355 (br q 1JB-H = 81 Hz 1H BH) 345 (m 1H iPr) 293 (m 1H N-Cy) 192 - 133 (m 6H
CH2 groups of Cy) 081 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -9903
(dm 3JF-H = 14 Hz 1F FC=CH) -1331 (m 3JF-F = 23 Hz 6F o-C6F5) -1606 (t 3JF-F = 21 Hz
3F p-C6F5) -16398 (m 6F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 81 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1584 (d 1JC-F = 255 Hz CF=CH) 1484 (dm 1JC-F =
224 Hz C6F5)1385 (dm 1JC-F = 247 Hz C6F5)1369 (dm 1JC-F = 247 Hz C6F5) 1230 (ipso-
C6F5) 974 (d 2JC-F = 20 Hz CF=CH) 518 (iPr) 504 (N-Cy) 254 (d 2JC-F = 81 Hz CH2CF)
247 (d 3JC-F = 90 Hz CH2CH=CF) 228 (CH2) Anal calcd () for C27H18BF16N C 4831 H
270 N 209 Found C 4793 H 282 N 203
Synthesis of 219 and 220 is similar to the general procedure used for compounds 23 - 214
Synthesis of [C6H10NHCH(CH3)Ph][HB(C6F5)3] (219) Method 1 B(C6F5) (358 mg 0700
mmol) 4-methoxy-N-(1-phenylethylidene)aniline (113 mg 0500 mmol) toluene (4 mL) (107
67
mg 0150 mmol 30) Crystals suitable for X-ray diffraction were obtained from a layered
solution of dichloromethanepentane at -30 degC
Method 2 In the glovebox trans-(4-CH3OC6H10)NHCH(CH3)Ph (81 mg 340 μmol) and
B(C6F5)3 (17 mg 340 μmol) were dissolved in d8-toluene (04 mL) and added into a Teflon
capped J-Young tube The tube was degassed once through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at
110 degC The solvent was removed under vacuum and the residue was washed with pentane (2
mL) The product was dried under vacuum and collected (82 mg 110 μmol 33)
1H NMR (500 MHz CD2Cl2) δ 752 (tm 3JH-H = 77 Hz 1H p-Ph)
746 (tm 3JH-H = 77 Hz 2H m-Ph) 735 (dm 3JH-H = 77 Hz 2H o-
Ph) 555 (br m 1H NH) 447 (dd 3JH-H = 95 Hz 48 Hz 1H H1)
415 (dq 3JH-H = 102 Hz 68 Hz 1H CH(CH3)Ph) 374 (m JH-H = 95
Hz 48 Hz 1H H5) 363 (br q 1JB-H = 83 Hz 1H BH) 229 (m 1H
H3) 223 (m 1H H4) 215 (m 1H H2) 201 (m 1H H3) 196 (m 1H H6) 190 (m 1H H2)
188 (m 1H H4) 177 (d 3JH-H = 68 Hz 3H CH3) 176 (m 1H H6) 19F NMR (377 MHz
CD2Cl2) δ -1304 (m 2F o-C6F5) -1638 (t 1F 3JF-F = 21 Hz p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -249 (d 1JB-H = 83 Hz BH) 13C1H NMR (125 MHz
CD2Cl2) δ 1482 (dm 1JC-F = 236 Hz C6F5) 1378 (dm 1JC-F = 245 Hz C6F5) 1364 (dm 1JC-F
= 249 Hz C6F5) 1346 (ipso-Ph) 1308 (p-Ph) 1301 (m-Ph) 1266 (o-Ph) 1246 (ipso-C6F5)
652 (C5) 647 (C1) 586 (CH(CH3)Ph) 277 (C2) 273 (C6) 254 (C3 C4) 188 (CH3) Anal
calcd () for C32H21BF15N C 5373 H 296 N 196 Found 5384 H 321 N 200
[(o-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (220) Ratio of cis and trans isomers = 11
determined by 1H NMR spectroscopy The trans isomer has been isolated and characterized
B(C6F5) (379 mg 0740 mmol) 2-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol)
toluene (5 mL) product (508 mg 0680 mmol 92) Crystals suitable for X-ray diffraction were
obtained from a layered solution of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H m p-Ph) 691 (m 2H o-
Ph) 655 (br s 2H NH2) 413 (q 3JH-H = 64 Hz 1H CH(Me)Ph) 365
(br q 1JB-H = 92 Hz 1H BH) 313 (ddd 3JH-H = 107 Hz 43 Hz 1H
CHOCH3) 298 (s 3H OCH3) 237 (td 3JH-H = 107 Hz 1H CH2CHNH2) 180 (m 1H DCH2)
68
173 (dm 3JH-H = 136 Hz 1H ACH2) 140 (m 2H DCCH2) 128 (d 3JH-H = 64 Hz 3H
CH(CH3)Ph) 120 (m 1H BCH2) 095 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H BCH2)
066 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H CCH2) 039 (pseudo qd JH-H = 136 Hz 3JH-
H = 31 Hz 1H ACH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -1634 (t 3JF-F =
21 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -246 (d 1JB-H = 92
Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 235 Hz C6F5) 1381 (dm 1JC-F = 246 Hz C6F5) 1367 (dm 1JC-F = 247 Hz C6F5) 1334 (ipso-Ph) 1304 (p-Ph) 1299 (m-
Ph) 1264 (o-Ph) 1239 (ipso-C6F5) 778 (CHOCH3) 611 (CH2CHNH2) 571 (CH(CH3)Ph)
554 (OCH3) 279 (ACH2) 257 (DCH2) 236 (CCH2) 224 (BCH2) 202 (CH3) Anal calcd ()
for C33H25BF15NO C 5303 H 337 N 187 Found 5288 H 357 N 190
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] (221a) Part 1 In a Schlenk
tube trans-(4-CH3OC6H10)NHCH(CH3)Ph (16 mg 680 μmol) was dissolved in pentane (2 mL)
and hydrogen chloride (68 μL 027 mmol 40 M in 14-dioxane) was added drop wise White
precipitate was immediately formed The solvent was decanted and the solid was washed with
pentane (2 mL) and dried in vacuo to yield trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (163 mg
610 μmol 89)
Part 2 In the glovebox a 4 dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph
HCl (61 mg 0026 mmol) in dichloromethane (8 mL) and K B(C6F5)4 (162 mg 260 mmol)
was added at once The reaction was allowed to stir for 16 h at room temperature The mixture
was filtered through Celite and the solvent was removed under vacuum The product was
obtained as a white solid (209 mg 230 μmol 88)
1H NMR (400 MHz C6D5Br) δ 719 (m 2H m-Ph) 690 (m 3H o p-Ph) 510 (br s 2H NH2)
402 (q 3JH-H = 69 Hz 1H CH(CH3)Ph) 310 (s 3H OCH3) 272 (m 2H CyCHOCH3 CyCHN) 174 (m 3H CyCH2) 156 (m 1H CyCH2) 127 (d 3JH-H = 69 Hz 3H CH(CH3)Ph
093 - 084 (m 4H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1318 (m 2F o-C6F5) -1610 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -164 (s
B(C6F5)4)
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (221b) In the glovebox a 4
dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (93 mg 0034 mmol) in
dichloromethane (8 mL) and Na HB(C6F5)3 (185 mg 340 μmol) was added at once The
69
reaction was allowed to stir for 16 h at room temperature The mixture was filtered through
Celite and the solvent was removed under vacuum The product was obtained as a white solid
(193 mg 260 μmol 76) Preparation of Na HB(C6F5)3 is reported in Chapter 3
1H NMR (400 MHz C6D5Br) δ 716 (m 3H Ph) 702 (m 2H Ph) 546 (br 2H NH2) 407 (q 3JH-H = 68 Hz 1H CH(CH3)Ph) 347 (br q 1JB-H = 78 Hz 1H BH) 307 (s 3H OCH3) 283
(tt 3JH-H = 106 Hz 46 Hz 1H CyCHOCH3) 268 (tt 3JH-H = 117 Hz 39 Hz 1H CyCHN) 183
(m 3H CyCH2) 156 (dm 3JH-H = 128 Hz 1H CyCH2) 132 (d 3JH-H = 68 Hz CH(CH3)Ph)
121 (m 2H CyCH2) 084 (m 2H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1334 (m 2F o-
C6F5) -1604 (t 3JF-F = 22 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -238 (d 1JB-H = 78 Hz BH)
Synthesis of [C6H10NH(iPr)][CH3OB(C6F5)3] (222) In the glovebox a Schlenk tube (25 mL)
was charged with trans-(4-CH3OC6H10)NH(iPr) (253 mg 0148 mmol) in toluene (05 mL) and
B(C6F5) (758 mg 0148 mmol) dissolved in toluene (05 mL) was added at once The Schlenk
was sealed and heated at 110 degC for 2 h and the solvent was removed under vacuum The crude
solid was washed with pentane (2 mL) to yield the product as a white solid (991 mg 0145
mmol 98) Crystals suitable for X-ray diffraction were obtained from a layered solution of
dichloromethanepentane at -30 degC
1H NMR (500 MHz CD2Cl2) δ 810 (s 1H NH) 413 (m 2H CH2CH) 315 (m 3JH-H = 66
Hz 1H iPr) 302 (s 3H BOCH3) 222 (dm 1JH-H = 93 Hz 2H ACH2) 205 (dm 1JH-H = 100
Hz 2H BCH2) 181 (dm 1JH-H = 100 Hz 2H BCH2) 172 (dm 1JH-H = 93 Hz 2H ACH2) 136
(d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1351 (br 2F o-C6F5) -1620 (t 3JF-F = 20 Hz 1F p-C6F5) -1664 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -242 (s
BOCH3) 13C1H NMR (125 MHz CD2Cl2) δ 1482 (dm 1JC-F = 241 Hz C6F5) 1388 (dm 1JC-F = 262 Hz C6F5) 1370 (dm 1JC-F = 252 Hz C6F5) 1231 (ipso-C6F5) 634 (CH2CH) 522
(BOCH3) 502 (iPr) 274 (ACH2) 258 (BCH2) 185 (iPr) Anal calcd () for C28H21BF15N05
CH2Cl2 C 4717 H 306 N 193 Found 4674 H 327 N 199 HRMS-DART mz [M] calcd
for C9H18N+ 1401 Found 1401
Synthesis of [C6H10NH(iPr)][HB(C6F5)3] (223) Method 1 In the glovebox trans-(4-
CH3OC6H10)NH(iPr) (250 mg 0150 mmol) and B(C6F5)3 (760 mg 0150 mmol) were
dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The tube was
70
degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4
atm) at -196 ordmC The reaction was complete after 12 h at 110 degC The solvent was removed under
vacuum and the residue was washed with pentane (2 mL) The product was collected as a white
powder (607 mg 930 μmol 62)
Method 2 In the glovebox compound [C6H10NH(iPr)][CH3OB(C6F5)3] (222) (200 mg 290
μmol) was dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The
tube was degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with
H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at 110 degC
1H NMR (400 MHz C6D5Br) δ 510 (br m 1H NH) 367 (br q 1JB-H = 76 Hz 1H BH) 347
(br s 2H CH) 242 (m 1H iPr) 162 (m 2H CH2) 131 (m 2H CH2) 111 (m 2H CH2) 093
(m 2H CH2) 138 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -1338 (m 3JF-F
= 21 Hz 2F o-C6F5) -1622 (t 3JF-F = 21 Hz 1F p-C6F5) -1658 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -239 (d 1JB-H = 76 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483
(dm 1JC-F = 235 Hz CF) 1381 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 248 Hz CF) 1242
(ipso-C6F5) 636 (CHCH2) 500 (iPr) 271 (CH2) 248 (CH2) 186 (iPr) Anal calcd () for
C27H19BF15N C 4964 H 293 N 214 Found C 4924 H 300 N 214
Compounds 224 - 235 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 50 mL Teflon screw cap Schlenk tube equipped with a stir bar was charged
with a solution of B(C6F5)3 (0379 g 0740 mmol) and the respective N-heterocycle in toluene (5
mL) The reaction tube was degassed three times through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube
was placed in a 115 ordmC oil bath for the indicated reaction time The solvent was then removed
under vacuum and the crude product was washed with pentane to yield the product as a white
solid
[26-Ph2C5H8NH2][HB(C6F5)3] (224) 26-Diphenylpyridine (171 mg 0740 mmol) reaction
time 16 h product (511 g 0680 mmol 92) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC Isomer ratio by 1HNMR
spectroscopy meso 91 rac 9
71
meso-[26-Ph2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 734 (tt 3JH-H = 70 Hz
4JH-H = 24 Hz 2H p-Ph) 726 (m 8H o m-Ph) 590 (br 2H NH2) 453 (m 3JH-H = 122 Hz 3JH-H = 24 Hz 2H C(H)Ph) 339 (br q 1JB-H = 90 Hz 1H BH) 226 (br m 3H CH2) 212 (m
2H CH2) 189 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1340 (m 2F o-C6F5) -1634 (t 3JF-F = 20 Hz 1F p-C6F5) -1666 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -246 (d 1JB-H = 90 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1483 (dm 1JC-F = 237 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1367 (dm 1JC-F = 246 Hz CF) 1338 (ipso-Ph) 1313 (p-Ph) 1271
(Ph) 1264 (Ph) 1241 (ipso-C6F5) 657 (C(H)(Ph)) 297 (CH2) 233 (CH2) Anal calcd ()
for C35H21BF15N C 5595 H 282 N 186 Found C 5547 H 303 N 186
[26-Me2C5H8NH2][HB(C6F5)3] (225) 26-Dimethylpyridine (793 mg 0740 mmol) reaction
time 60 h product (390 mg 0621 mmol 84) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC over 48 h Isomer ratio by 1HNMR spectroscopy meso 80 rac 20
meso-[26-Me2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 508 (br 2H NH2) 345
(br q 1JB-H = 83 Hz 1H BH) 268 (m 2H NC(H)Me) 137 (m 4H CH2) 086 (d 3JH-H = 64
Hz 6H CH3) 077 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -
1617 (t 3JF-F = 20 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1485 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF) 1236 (ipso-C6F5) 567
(NCH) 303 (CH2) 220 (CH2) 193 (CH3) Anal calcd () for C25H17BF15N C 4787 H 273
N 223 Found C 4764 H 290 N 222
(2-(EtOCO)C5H9NH)B(C6F5)3 (226) Ethyl 2-picolinate (112 mg 0740 mmol) reaction time
36 h product (366 mg 0547 mmol 74) The isolated product consisted of an equal ratio of
both diastereomers Anal calcd () for C26H15BF15NO2 C 4667 H 226 N 209 Found C
4660 H 247 N 211
RSSR-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2)
δ 590 (m 1H NH) 430 (m 1H CH(H)NH) 418 (br m 1H
CHOCOEt) 393 (dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 373
(dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 320 (dm 2JH-H = 126 Hz 1H CH(H)NH) 217
(m 2H CH2) 204 (dm 2JH-H = 134 Hz 1H CH2) 184 (m 1H CH2) 175 (m 1H CH2) 119
72
(t 3JH-H = 72 Hz 3H Et) 103 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1264 (m 1F o-
C6F5) -1280 (m 1F o-C6F5) -1295 (m 1F o-C6F5) -1297 (m 1F o-C6F5) -1404 (m 1F o-
C6F5) -1433 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F
p-C6F5) -1575 (t 3JF-F = - 21 Hz 1F p-C6F5) -1616 (m 1F m-C6F5) -1621 (m 1F m-C6F5) -
1628 (m 1F m-C6F5) -1631 (m 1F m-C6F5) -1640 (m 1F m-C6F5) -1649 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -486 (s BNH) 13C1H NMR (101 MHz CD2Cl2) δ 1674
(OCO) 636 (Et) 568 (CHOCOEt) 445 (CH(H)NH) 305 (CH2) 208 (CH2) 181 (CH2) 134
(Et)
RRSS-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ
743 (br m 1H NH) 440 (dq 2JH-H = 107 Hz 3JH-H = 71 Hz 1H Et)
438 (dq 2JH-H = 91 Hz 3JH-H = 71 Hz 1H Et) 424 (br m 1H
CHOCOEt) 350 (ddd 2JH-H = 134 Hz 3JH-H = 89 Hz 3JH-H = 49 Hz 1H CH(H)NH) 333
(dm JH-H = 133 Hz 1H CH(H)NH) 218 (m 1H CH2) 208 (m 1H CH2) 185 (m 1H CH2)
154 (m 1H CH2) 151 (m 1H CH2) 135 (t 3JH-H = 71 Hz 3H Et) 124 (m 1H CH2) 19F
NMR (377 MHz CD2Cl2) δ -1276 (m 1F o-C6F5) -1285 (m 2F o-C6F5) -1291 (m 1F o-
C6F5) -1371 (m 1F o-C6F5) -1421 (m 1F o-C6F5) -1549 (t 3JF-F = 21 Hz 1F p-C6F5) -
1572 (t 3JF-F = 21 Hz 1F p-C6F5) -1578 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5)
-1626 (m 1F m-C6F5) -1630 (m 3F m-C6F5) -1633 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -486 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1712 (OCO) 616 (Et) 581
(CHOCOEt) 457 (CH(H)NH) 259 (CH2) 235 (CH2) 171 (CH2) 139 (Et)
(2-PhC5H9NH)B(C6F5)3 (227a) and [2-PhC5H9NH2][HB(C6F5)3] (227b) 2-Phenylpyridine
(115 mg 0740 mmol) reaction time 48 h product (269 mg 0400 mmol 54) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC The isolated product consisted of 227a (RSSR 70) 227a (SSRR 10) 227b (20)
Anal calcd () for C29H15BF15N C 5158 H 254 N 209 Found C 5209 H 258 N 210
RSSR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 727
(m 2H Ph) 714 (m 3H Ph) 555 (br s 1H NH) 415 (ddd 3JH-H = 111
Hz 3JH-H = 94 Hz 36 Hz 1H CHPh) 356 (dm 2JH-H = 132 Hz 1H CH(H)NH) 257 (ddd 2JH-H = 132 Hz 3JH-H = 103 Hz 3JH-H = 31 Hz 1H CH(H)NH) 199 - 135 (m 6H CH2) 19F
NMR (377 MHz C6D5Br) δ -1216 (m 1F o-C6F5) -1236 (m 1F o-C6F5) -1274 (m 1F o-
73
C6F5) -1286 (m 1F o-C6F5) -1312 (m 1F o-C6F5) -1426 (m 1F o-C6F5) -1534 (t 3JF-F =
22 Hz 1F p-C6F5) -1566 (t 3JF-F = 21 Hz 1F p-C6F5) -1567 (t 3JF-F = 21 Hz 1F p-C6F5) -
1615 (m 2F m-C6F5) -1620 (m 3F m-C6F5) -1624 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -391 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1385 (ipso-Ph) 1297 (p-Ph)
1291 (Ph) 1285 (Ph) 646 (CHPh) 521 (NCH2) 355 (CH2) 248 (CH2) 219 (CH2)
SSRR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 710 -
681 (m 5H Ph) 581 (br s 1H NH) 449 (m 1H CHPh) 347 (dm 2JH-H = 125 Hz 1H CH(H)NH) 321 (m 2JH-H = 125 Hz 1H CH(H)NH) 185 (m 2H CH2)
176 (m 2H CH2) 128 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1249 (m 1F o-C6F5)
-1263 (m 1F o-C6F5) -1268 (m 1F o-C6F5) -1287 (m 1F o-C6F5) -1390 (m 1F o-C6F5) -
1431 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1559 (t 3JF-F = 21 Hz 1F p-C6F5)
-1562 (t 3JF-F = 21 Hz 1F p-C6F5) -1598 (m 1F m-C6F5) -1610 (m 1F m-C6F5) -1617 (m
1F m-C6F5) -1620 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1643 (m 1F m-C6F5) 11B NMR
(128 MHz CD2Cl2) δ -39 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1365 (ipso-Ph)1294
(p-Ph) 1283 (Ph) 1256 (Ph) 629 (CHPh) 454 (NCH2) 350 (CH2) 297 (CH2) 260 (CH2)
[2-PhC5H9NH2][HB(C6F5)3] (227b) 1H NMR (400 MHz CD2Cl2) δ 710 - 681 (m 5H Ph)
557 (br s 2H NH2) 355 (dd 3JH-H = 117 Hz 28 Hz 1H CHPh) 330 (br q 1JB-H = 86 Hz
1H BH) 295 (dm JH-H = 124 Hz 1H CH(H)NH2) 244 (pseudo td JH-H = 124 Hz 3JH-H = 30
Hz 1H CH(H)NH2) 186 (m 2H CH2) 165 (m 1H CH2) 157 (m 1H CH2) 141 (m 1H
CH2) 137 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 2F o-C6F5) -1610 (t 3JF-
F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -248 (d 1JB-H
= 86 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1399 (ipso-Ph) 1297 (Ph) 1295 (p-Ph)
1267 (Ph) 625 (CHPh) 471 (NCH2) 327 (CH2) 242 (CH2) 240 (CH2)
[2-MeC9H15NH2][HB(C6F5)3] (228) 2-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (331 mg 500 mmol 67) Crystals suitable for X-ray diffraction were grown from
a layered solution of dichloromethanepentane at -30 ordmC About 60 of the isolated reaction
product consisted of the SSSRRR diastereomer
1H NMR (400 MHz C6D5Br) δ 602 (br 1H NH2) 460 (br 1H NH2) 336 (br q 1JB-H = 83
Hz 1H BH) 315 (dt 3JH-H = 100 Hz 52 Hz 1H NCHCH) 276 (m 1H CHMe) 145 - 096
(m 8H CH2) 110 (m 1H CHCHN) 093 - 067 (m 4H CH2) 081 (d 3JH-H = 64 Hz 3H
74
Me) 19F NMR (377 MHz C6D5Br) δ -1335 (m 2F o-C6F5) -1607 (t 3JF-F = 22 Hz 1F p-
C6F5) -1646 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1384 (dm 1JC-F = 246
Hz CF) 1369 (dm 1JC-F = 249 Hz CF) 1233 (ipso-C6F5) 577 (NCH) 493 (CHMe) 322
(CHCHN) 281 (CH2) 272 (CH2) 255 (CH2) 240 (CH2) 236 (CH2) 211 (CH2) 189 (Me)
Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C 5021 H 331 N 212
[2-PhC9H15NH2][HB(C6F5)3] (229) B(C6F5)3 (289 mg 0564 mmol) 2-phenylquinoline (116
mg 0564 mmol) reaction time 48 h product (391 mg 536 mmol 95) Crystals suitable for
X-ray diffraction were grown from a layered solution of dichloromethanepentane at -30 ordmC
About 73 of the reaction mixture consisted of the reported SSSRRR diastereomer
1H NMR (400 MHz CD2Cl2) δ 733 (tm 3JH-H = 73 Hz 1H p-Ph) 726 (tm 3JH-H = 73 Hz
2H m-Ph) 720 (dm 3JH-H = 73 Hz 2H o-Ph) 646 (br 1H NH2) 501 (br t 1H NH2) 433
(dm 3JH-H = 105 Hz 33 Hz 1H C(H)Ph) 380 (br m 1H CH2C(H)NH2) 320 (br q 1JB-H = 87
Hz 1H BH) 218 - 108 (m 13H CH2C(H)CH2 and CH2) 19F NMR (377 MHz C6D5Br) δ -
1334 (m 2F o-C6F5) -1612 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -242 (d 1JB-H = 87 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1342
(ipso-Ph) 1312 (p-Ph) 1301 (m-Ph) 1269 (o-Ph) 647 (CH2C(H)NH2) 601 (C(H)Ph) 345
(CH2C(H)CH2) 291 (CH2) 285 (CH2) 251 (CH2) 249 (CH2) 248 (CH2) 197 (CH2) Anal
calcd () for C33H23BF15N C 5434 H 318 N 192 Found C 5431 H 331 N 192
[8-MeC9H15NH2][HB(C6F5)3] (230) 8-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (375 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC The reported SSSRRR
diastereomer was only observed
1H NMR (400 MHz C6D5Br) δ 555 (br 1H NH2) 497 (br 1H NH2) 352 (br q 1JB-H = 80
Hz 1H BH) 327 (dm 2JH-H = 121 Hz 1H NH2CH(H)) 263 (dm 3JH-H = 112 Hz coupling to
NH2 is observed in 1H1H-cosy 1H CHN) 252 (qt 2JH-H = 121 Hz 3JH-H = 27 Hz 1H
NH2CH(H)) 141 - 133 (br m 2H CH2) 134 (m 1H CH2CHCH2) 125 - 114 (br m 4H
CH2) 122 (m 1H CHMe) 102 (m 1H CH2) 089 (m 2H CH2) 063 (d 3JH-H = 75 Hz 3H
Me) 058 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1343 (m 2F o-C6F5) -1618 (t 3JF-F
= 21 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -242 (d 1JB-H =
75
80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 249 Hz CF) 1237 (ipso-C6F5) 632 (CHN) 478
(NH2CH(H)) 339 (CH2CHCH2) 337 (CHMe) 271 (CH2) 268 (CH2) 243 (CH2) 231 (CH2)
178 (CH2) 163 (Me) Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C
5026 H 330 N 209
[C13H22NH2][HB(C6F5)3] (231a) Acridine (132 mg 0740 mmol) reaction time 36 h product
(398 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at 25 ordmC The isolated product is a mixture of the SRSRRSRS
and RRSSSSRR isomers in a 11 ratio The SRSRRSRS was separated by crystallization
1H NMR (400 MHz CD2Cl2) δ 626 (br m 1H NH2) 513 (br m 1H NH2) 327 (br q 1JB-H =
86 Hz 1H BH) 285 (dm 3JH-H = 111 Hz 40 Hz 2H CHN) 182 (m 2H NH2CHCH2) 176
(m 2H CyCH2) 175 (m 1H CHCH2CH) 171 (m 2H CyCH2) 167 (m 2H CyCH2) 144 (qt 3JH-H = 111 Hz 3JH-H = 40 Hz 2H CH2CHCH2) 123 (m 2H CyCH2) 122 (m 2H
NH2CHCH2) 118 (m 2H CyCH2) 101 (m 2H CyCH2) 100 (m 1H CHCH2CH) 19F NMR
(377 MHz CD2Cl2) δ -1345 (m 2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -244 (d 1JB-H = 86 Hz BH) 13C1H NMR (101
MHz CD2Cl2) partial δ 639 (CHN) 406 (CH2CHCH2) 371 (CHCH2CH) 318 (CyCH2) 307
(NH2CHCH2) 249 (CyCH2) 248 (CyCH2) Anal calcd () for C31H25BF15N C 5264 H 356
N 198 Found C 5214 H 358 N 196
Synthesis of RRSSSSRR and SRSRRSRS-[(C13H22NH)B(C6F5)3] (231b) Compound 231b
was initially isolated from the pentane wash work-up for the synthesis of 231a Independent
synthesis of 231b was performed and the procedure is described
In a 4 dram vial tetradecahydroacridine (366 mg 0189 mmol) was dissolved in pentane (5
mL) at room temperature To the vial B(C6F5)3 (965 mg 0189 mmol) was added at once and
allowed to mix for 2 minutes The solution was filtered through a bed of Celite to yield a
colourless solution The vial was placed in a -30 ordmC freezer for 3 h and colourless crystals were
collected (973 mg 138 mmol 73) The isolated mixture of compound 231b consisted of a 11
mixture of RRSSSSRR and SRSRRSRS (C13H22NH)B(C6F5)3 only the diagnostic resonances of
RRSSSSRR-(C13H22NH)B(C6F5)3 have been reported
76
RRSSSSRR-[(C13H22NH)B(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 503 (br 1H NH) 353
(dm 3JH-H = 123 Hz 2H NCH) 214 (dm JH-H = 123 Hz 2H NH2CHCH2) 196 - 160 (m
6H CH2) 188 (m 2H CH2CHCH2) 177 (m 4H NH2CHCH2 and CHCH2CH) 149 - 111 (m
6H CH2) 19F NMR (377 MHz CD2Cl2) δ -1270 (m 1F o-C6F5) -1277 (m 1F o-C6F5) -
1281 (m 1F o-C6F5) -1291 (m 2F o-C6F5) -1302 (m 1F o-C6F5) -1558 (t 3JH-H = 21 Hz
1F p-C6F5) -1579 (t 3JH-H = 21 Hz 1F p-C6F5) -1589 (t 3JH-H = 21 Hz 1F p-C6F5) -1624
(m 1F m-C6F5) -1637 (m 3F m-C6F5) -1641 8 (m 1F m-C6F5) -1644 8 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -318 (s BN) 13C1H NMR (101 MHz CD2Cl2) partial δ
630 (NCH) 359 (CHCH2CH) 356 (CH2CHCH2) 299 (NH2CHCH2) Anal calcd () for
C31H23BF15N C 5279 H 329 N 199 Found C 5266 H 328 N 196
[23-(C4H6Me)2NHNH2][HB(C6F5)3] (232) 23-Dimethylquinoxaline (0117 g 0740 mmol)
reaction time 96 h product (402 mg 437 mmol 59) The SRSSRSRR diastereomer was only
observed
1H NMR (400 MHz CD2Cl2) δ 643 (br 1H NH2) 592 (br 1H NH2) 349 (dm 3JH-H = 128
Hz 1H CH2CHN) 334 (br q 1JB-H = 94 Hz 1H BH) 326 (br m 2H NCHMe CH2CHN)
281 (dq 3JH-H = 123 Hz 64 Hz 1H NCHMe) 223 (dm JH-H = 128 Hz 1H CH2) 189 (dm
JH-H = 134 Hz 1H CH2) 179 (dm JH-H = 134 Hz 1H CH2) 162 (dm JH-H = 134 Hz 2H
CH2) 147 (m 1H CH2) 131 (m 1H CH2) 128 (d 3JH-H = 64 Hz 3H Me) 121 (d 3JH-H =
62 Hz 3H Me) 120 (m 1H CH2) (NH was not observed) 19F NMR (377 MHz C6D5Br) δ -
1336 (m 2F o-C6F5) -1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1646 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -241 (d 1JB-H = 94 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481
(dm 1JC-F = 234 Hz C6F5) 1384 (dm 1JC-F = 246 Hz C6F5) 1368 (dm 1JC-F = 247 Hz C6F5)
1232 (ipso-C6F5) 576 (CH2CHN) 563 (NCHMe) 541 (NCHMe) 519 (CH2CHN) 304
(CH2) 242 (CH2) 224 (CH2) 185 (CH2) 178 (Me) 151 (Me) Anal calcd () for
C28H22BF15N C 4929 H 325 N 411 Found C 4909 H 333 N 421
[23-(C4H6Ph)2NHNH2][HB(C6F5)3] (233) 23-Diphenylquinoxaline (0209 g 0740 mmol)
reaction time 96 h product (328 mg 0407 mmol 55) Crystals suitable for X-ray diffraction
were grown from a layered solution of dichloromethanepentane at RT Diastereomers
SRSSRSRR and RRRSSSSR are present in equal ratios The assigned diastereomers were
77
supported by 1H1H NOESY NMR spectroscopy Anal calcd () for C38H26BF15N2 C 5660
H 325 N 347 Found C 5611 H 313 N 321
SRSSRSRR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 763 (m 4H
Ph) 699 - 684 (m 6H Ph) 572 (br 2H NH2) 476 (d 3JH-H = 34 Hz 1H CHPh) 441 (d 3JH-H = 34 Hz 1H CHPh) 407 (br 1H NH) 356 (br q 1JB-H = 82 Hz 1H BH) 314 (td 3JH-H
= 102 Hz 3JH-H = 34 Hz 1H CH2CHN) 260 (m 3JH-H = 102 Hz 34 Hz 1H CH2CHN) 167
(m 1H CH2) 159 (m 1H CH2) 153 (m 1H CH2) 129 (m 1H CH2) 122 (m 2H CH2)
121 (m 1H CH2) 086 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1331 (m 2F o-C6F5)
-1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1362 (ipso-Ph) 1313
(Ph) 1301 (Ph) 1267 (Ph) 637 (CHPh) 619 (CHPh) 597 (CH2CHN) 561 (CH2CHN) 314
(CH2) 282 (CH2) 242 (CH2) 233 (CH2) (ipso-C6F5 was not observed)
RRRSSSSR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (500 MHz CD2Cl2) δ 729 - 708
(m 10H Ph) 657 (br 2H NH2) 451 (dm 3JH-H = 102 Hz 1H CHPh) 429 (dm 3JH-H = 102
Hz 1H CHPh) 386 (dm 3JH-H = 107 Hz 1H CH2CHN) 366 (br 1H NH) 328 (br q 1JB-H =
82 Hz 1H BH) 268 (dm 3JH-H = 107 Hz 1H CH2CHN) 205 (m 1H CH2) 188 (m 2H
CH2) 178 (m 2H CH2) 157 (m 1H CH2) 145 (m 1H CH2) 130 (m 1H CH2) 19F NMR
(377 MHz C6D5Br) δ -1331 (m 2F o-C6F5) -1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 82 Hz BH) 13C1H NMR (125
MHz CD2Cl2) δ 1479 (dm 1JC-F = 235 Hz CF) 1382 (dm 1JC-F = 246 Hz CF) 1366 (dm 1JC-F = 248 Hz CF) 1314 (ipso-Ph) 1304 (Ph) 1301 (ipso-Ph) 1293 (Ph) 1290 (Ph) 1286
(Ph) 1277 (Ph) 1274 (Ph) 1226 (ipso-C6F5) 655 (CHPh) 621 (CHPh) 581 (CH2CHN)
526 (CH2CHN) 308 (CH2) 245 (CH2) 229 (CH2) 188 (CH2)
[(C6H4)C7H12NH2][HB(C6F5)3] (234) 78-Benzoquinoline (133 mg 0740 mmol) reaction
time 48 h product (285 mg 407 mmol 55) Crystals of the SRRS isomer suitable for X-ray
diffraction were grown from a layered solution of bromobenzenepentane at -30 ordmC Crystals of
the SSRR isomer suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC Anal calcd () for C31H19BF15N C 5309 H 273 N 200
Found C 5347 H 291 N 209
78
Isomer ratio by 1HNMR spectroscopy SRRS 80 (pale orange crystals) SSRR 20 (colourless
crystals)
SRRS-[(C6H4)C7H12NH2][HB(C6F5)3] (234a) 1H NMR (400 MHz CD2Cl2) δ 725 (td 3JH-H
= 77 Hz 4JH-H = 14 Hz 1H C6H4) 715 (d 3JH-H = 77 Hz 1H C6H4) 707 (d 3JH-H = 77 Hz
1H C6H4) 700 (t 3JH-H = 77 Hz 1H C6H4) 597 (br 2H NH2) 440 (d 3JH-H = 38 Hz 1H
NCH) 361 (dt JH-H = 131 Hz 3JH-H = 35 Hz 1H NCH(H)) 328 (m 1H NCH(H)) 314 (br q 1JB-H = 80 Hz 1H BH) 294 (dm 2JH-H = 172 Hz 1H C6H4-CH(H)) 285 (dm 2JH-H = 172 Hz
1H C6H4-CH(H)) 239 (m 1H CH2CHCH2) 200 - 188 (br m 6H PiperidineCyCH2) 19F NMR
(377 MHz C6D5Br) δ -1345 (m 2F o-C6F5) -1621 (t 3JF-F = 21 Hz 1F p-C6F5) -1657 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 80 Hz BH) 13C1H NMR (101
MHz CD2Cl2) δ 1483 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1378
(quaternary C for C6H4-CHN) 1368 (dm 1JC-F = 248 CF) 1311 (C6H4) 1307 (C6H4) 1292
(C6H4) 1288 (quaternary C for C6H4-CH2) 1277 (C6H4) 1234 (ipso-C6F5) 605 (NCH) 479
(NCH2) 320 (CH2CHCH2) 286 (C6H4-CH(H)) 274 (PiperidineCH2) 225 (CyCH2) 184
(PiperidineCH2)
SSRR-[(C6H4)C7H12NH2][HB(C6F5)3] (234b) 1H NMR (400 MHz C6D5Br) partial δ 701
(m 1H C6H4) 699 (m 1H C6H4) 685 (m 1H C6H4) 675 (d 3JH-H = 77 Hz 1H C6H4) 350
(d 3JH-H = 104 Hz 1H NCH) 324 (br dm JH-H = 124 Hz 1H NCH(H)) 279 (m 1H
NCH(H)) 254 (m 1H C6H4-CH(H)) 242 (m 1H C6H4-CH(H)) 142 (m 2H CH2) 128 (m
2H CH2) 105 (m 1H CH2CHCH2) 083 (m 2H CH2) (NH2 was not observed) 13C1H
NMR (101 MHz C6D5Br) δ 1370 (quaternary C for C6H4-CHN) 1304 (C6H4) 1291 (C6H4)
1284 (quaternary C for C6H4-CH2) 1264 (C6H4) 1226 (C6H4) 629 (NCH) 474 (NCH2) 378
(CH2CHCH2) 291 (CH2) 288 (C6H4-CH(H)) 276 (CH2) 229 (CH2)
[(C5H3N)(CH2)2(C5H8NH)B(C6F5)2][HB(C6F5)3] (235) B(C6F5)3 (379 mg 0740 mmol) 110-
phenanthroline (667 mg 0370 mmol) reaction time 96 h product (283 mg 0270 mmol 73)
Crystals suitable for X-ray diffraction were grown from a layered solution of
tetrahydrofuranpentane at -30 ordmC Approximately 65 of the reaction mixture consisted of the
SRSRSR diastereomer
1H NMR (400 MHz CD2Cl2) δ 944 (br s 1H NH) 850 (dd JH-H = 47 Hz JH-H = 15 Hz 1H
C5H3N) 744 (dd JH-H = 78 Hz JH-H = 15 Hz 1H C5H3N) 722 (dd JH-H = 78 Hz JH-H = 47
79
Hz 1H C5H3N) 442 (d 3JH-H = 43 Hz 1H NCyCH) 342 (br 1H BH) 322 (dm 2JH-H = 138
Hz 1H NC(H)H) 291 (ddd 2JH-H = 138 Hz 3JH-H = 87 Hz 53 Hz 1H NC(H)H) 276 - 272
(m 2H C6H4-CH(H)) 212 (dm 3JH-H = 121 Hz 38 Hz 1H CH2CHCH2) 196 (m 1H CH2)
188 (m 1H CH2) 173 (m 1H CH2) 132 (dt 2JH-H = 140 Hz 3JH-H = 32 Hz 1H CH2) 091
(qd JH-H = 131 Hz 3JH-H = 38 Hz 1H CH2) 071 (qt JH-H = 137 Hz 3JH-H = 40 Hz 1H CH2)
19F NMR (377 MHz CD2Cl2) δ -1289 (m 2F B(C6F5)2o-C6F5) -1343 (m 6F HB(C6F5)3o-C6F5) -
1348 (m 2F B(C6F5)2o-C6F5) -1491 (t 3JF-F = 20 Hz 1F B(C6F5)2p-C6F5) -1511 (t 3JF-F = 20 Hz
1F B(C6F5)2p-C6F5) -1596 (m 4F B(C6F5)2m-C6F5) -1645 (t 3JF-F = 20 Hz 3F HB(C6F5)3p-C6F5) -
1676 (m 6F HB(C6F5)3m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 391 (s BN) -254 (d 1JB-H =
93 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1484 (quaternary C for C5H3N) 1466
(quaternary C for C5H3N) 1448 (C5H3N) 1354 (C5H3N) 1260 (C5H3N) 581 (CyNCH) 451
(NC(H)H) 296 (CH2C(H)CH2) 241 (CH2) 218 (CH2) 210 (CH2) 206 (CH2) Anal calcd
() for C42H17B2F25N2 C 4822 H 164 N 268 Found C 4783 H 197 N 269
243 X-Ray Crystallography
2431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
2432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
80
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
81
2433 Selected crystallographic data
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25
24 24rsquo 25
Formula C27H21B1F15N1 C27H13B1F15N1 C30H25B1F15N1
Formula wt 65526 64719 69532
Crystal system monoclinic orthorhombic monoclinic
Space group P2(1)c P2(1)2(1)2(1) P2(1)n
a(Aring) 97241(8) 116228(4) 126342(6)
b(Aring) 147348(12) 181284(7) 181939(8)
c(Aring) 188022(15) 236578(9) 128612(6)
α(ordm) 9000 9000 9000
β(ordm) 98826(4) 9000 90269(2)
γ(ordm) 9000 9000 9000
V(Aring3) 26621(4) 49848(3) 29563(2)
Z 4 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1635 1725 1562
Abs coeff μ mm-1 0169 0179 0157
Data collected 18591 28169 50674
Rint 00336 00297 00369
Data used 4685 8773 5207
Variables 401 793 424
R (gt2σ) 00361 00315 00352
wR2 00898 00758 00947
GOF 1007 1021 1024
82
Table 25 ndash Selected crystallographic data for 216a 218 and 219
216a 218 219
Formula C27H20B1F16N1 C27H18B1F16N1 C32H21B1F15N1
Formula wt 67325 67123 71533
Crystal system monoclinic monoclinic orthorhombic
Space group P2(1)c P2(1)n Pbca
a(Aring) 97677(6) 104368(7) 18886(4)
b(Aring) 147079(11) 93382(7) 16050(3)
c(Aring) 190576(14) 273881(18) 19128(4)
α(ordm) 9000 9000 9000
β(ordm) 98934(2) 96910(3) 9000
γ(ordm) 9000 9000 9000
V(Aring3) 27046(3) 26499(3) 5798(2)
Z 4 4 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1653 1683 16388
Abs coeff μ mm-1 0174 0177 0163
Data collected 23565 17203 50412
Rint 00432 00404 00662
Data used 6164 4676 6654
Variables 406 408 442
R (gt2σ) 00522 00496 00687
wR2 01387 01462 01912
GOF 1032 1041 10743
83
Table 26 ndash Selected crystallographic data for 220 222 and 224
220 222 (+05 CH2Cl2) 224 (+05 CH2Cl2)
Formula C33H25B1F15N1O1 C285H22B1Cl1F15N1O1 C355H22B1ClF15N1
Formula wt 74737 72573 79380
Crystal system orthorhombic orthorhombic monoclinic
Space group Pbca Pbca P2(1)n
a(Aring) 173531(15) 17750(5) 109902(9)
b(Aring) 161365(15) 16032(4) 151213(11)
c(Aring) 227522(17) 20783(6) 194765(15)
α(ordm) 9000 9000 90
β(ordm) 9000 96910(3) 92062(3)
γ(ordm) 9000 9000 90
V(Aring3) 63710(9) 5914(3) 32346(4)
Z 8 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 15582 16278 1630
Abs coeff μ mm-1 0154 0250 0235
Data collected 56289 47407 22409
Rint 00406 01159 00306
Data used 7321 5198 5688
Variables 461 440 495
R (gt2σ) 00413 00811 00495
wR2 01112 02505 01363
GOF 10647 10628 0936
84
Table 27 ndash Selected crystallographic data for 225 227 and 228
225 227 (+1 C5H12) 228
Formula C25H17B1F15N1 C63H42B2F30N2 C28H21B1F15N1
Formula wt 62721 141861 66727
Crystal system triclinic monoclinic triclinic
Space group P-1 P2(1)n P-1
a(Aring) 101339(5) 137416(4) 95967(15)
b(Aring) 112923(6) 119983(4) 108364(15)
c(Aring) 118209(6) 191036(7) 14143(2)
α(ordm) 98563(2) 9000 75929(5)
β(ordm) 109751(2) 109317(2) 80009(6)
γ(ordm) 94983(2) 9000 76629(5)
V(Aring3) 124520(11) 297240(17) 13772(4)
Z 2 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1673 1585 1609
Abs coeff μ mm-1 0176 0158 0235
Data collected 18038 22150 16105
Rint 00211 00246 00351
Data used 4357 5230 4743
Variables 379 436 406
R (gt2σ) 00371 00324 00546
wR2 00964 00816 01728
GOF 1044 1014 1028
85
Table 28 ndash Selected crystallographic data for 229 230 and 231a
229 (+05 C6H5Br) 230 231a
Formula C36H255B1Br05F15N1 C28H21B1F15N1 C31H25B1F15N1
Formula wt 80784 66727 70733
Crystal system monoclinic triclinic monoclinic
Space group C2c P-1 P2(1)n
a(Aring) 201550(11) 97752(4) 112914(4)
b(Aring) 133628(11) 120580(4) 183705(7)
c(Aring) 266328(18) 121120(5) 145648(5)
α(ordm) 9000 102296(2) 9000
β(ordm) 111905(6) 100079(2) 90480(2)
γ(ordm) 9000 90901(2) 9000
V(Aring3) 66551(8) 137127(9) 302105(19)
Z 8 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1613 1616 1555
Abs coeff μ mm-1 0749 0165 0155
Data collected 54940 20198 62113
Rint 00530 00245 00383
Data used 7644 4841 7630
Variables 484 406 533
R (gt2σ) 00651 00362 00778
wR2 01802 00971 02335
GOF 1037 1036 1007
86
Table 29 ndash Selected crystallographic data for 231b 233 and 234a
231b (+05 C6H14) 233 234a (+1 CH2Cl2)
Formula C34H30B1F15N1 C38H26B1F15N2 C32H21B1Cl2F15N1
Formula wt 74840 80642 78621
Crystal system triclinic monoclinic monoclinic
Space group P-1 Pn C2c
a(Aring) 107250(6) 99895(4) 181314(6)
b(Aring) 112916(7) 115666(5) 135137(5)
c(Aring) 136756(8) 155410(6) 253612(9)
α(ordm) 70523(2) 9000 9000
β(ordm) 88868(2) 105054(2) 92594(2)
γ(ordm) 86934(2) 9000 9000
V(Aring3) 155914(16) 173405(12) 62077(4)
Z 2 2 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1594 1544 1677
Abs coeff μ mm-1 0155 0147 0327
Data collected 22650 31226 22749
Rint 00233 00381 00512
Data used 5479 8395 7383
Variables 460 517 475
R (gt2σ) 00371 00400 00816
wR2 01066 00893 02554
GOF 0926 1011 1024
87
Table 210 ndash Selected crystallographic data for 234b and 235
234b 235 (+1 C4H8O +1 CH2Cl2)
Formula C31H19B1F15N1 C47H27B2Cl2F25N2O1
Formula wt 70128 120323
Crystal system monoclinic triclinic
Space group P2(1)c P-1
a(Aring) 100455(5) 113115(7)
b(Aring) 118185(5) 117849(8)
c(Aring) 245940(11) 188035(12)
α(ordm) 9000 83850(3)
β(ordm) 96724(2) 88364(3)
γ(ordm) 9000 69766(3)
V(Aring3) 28998(2) 23383(3)
Z 4 2
Temp (K) 150(2) 150(2)
d(calc) gcm-3 1606 1709
Abs coeff μ mm-1 0161 0281
Data collected 20742 36083
Rint 00342 00265
Data used 5101 8235
Variables 433 712
R (gt2σ) 00438 00473
wR2 01153 01198
GOF 1012 1015
88
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation
with Frustrated Lewis Pairs
31 Introduction
The reduction of carbonyl substrates such as aldehydes ketones esters acids and anhydrides to
alcohols is one of the most fundamental and widely used reactions in synthetic chemistry269
Sodium borohydride lithium aluminum hydride and other stoichiometric reducing agents56 224
serve adequately for laboratory scale syntheses however in an industrial setting the process
demands for a more clean environmentally benign and cost-effective procedure More desirable
methods involving H2 gas or transfer hydrogenation have proven practical and circumvent the
work-up operations required for stoichiometric reagents
Heterogeneous catalysts based on PdC and PtC are certainly atom economic however some of
these catalysts are not suitable in cases where mild conditions functional group tolerance and
chemoselectivity are required Therefore substantial research has been directed towards
homogeneous catalysts involving Ir237 Rh239 Ru238 Cu269 and Os238 complexes including metal-
immobilized systems269
Despite the power of these technologies research efforts motivated by cost toxicity and low
abundance have focused on the development of first-row transition metal catalysts based on Fe
and Co210 221 Also on-going interest in the field has been devoted to the discovery of new
asymmetric hydrogenation catalysts131 208-209 263-264136 213-214 270-271 in addition to transfer
hydrogenation via the Meerwein-Ponndorf-Verley reduction procedure216
311 FLP reactivity with unsaturated C-O bonds
In 1961 Walling and Bollyky reported the first metal-free hydrogenation system demonstrating
the reduction of the non-enolizable ketone benzophenone using H2 (100 atm) and tBuOK as the
catalyst at 200 degC175-176 While more recently metal-free reductions have been demonstrated
under more mild conditions using frustrated Lewis pairs (FLPs) These combinations of
sterically encumbered main group Lewis acids and bases have been shown to effect the catalytic
hydrogenation of a variety of unsaturated organic substrates Noticeably absent from these
substrates are ketones and aldehydes This is perhaps surprising given the precedence of catalytic
89
hydrosilylation of ketones established by Piers182 Moreover a number of groups have
demonstrated the ability of FLPs to effect the reduction of CO2 using H2259 silanes169 180 182
boranes111 163 272 or ammonia-borane273 as sources of the reducing equivalents The limited
attention to hydrogenation of ketones and aldehydes has been attributed to the high oxophilicity
of electrophilic boranes72 171 Indeed in an earlier report Erker and co-workers described the
irreversible capture of benzaldehyde and trans-cinnamaldehyde (Scheme 31 top) as well as the
14-addition of conjugated ynones by the intramolecular PB FLP Mes2PCH2CH2B(C6F5)2173 A
number of stoichiometric reductions have also been reported using H2 activated PB FLPs with
an example shown in Scheme 31 (bottom)94 173
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom)
Nonetheless the group of Privalov has computed an energetically viable mechanism for ketone
reduction suggesting a process analogous to imine hydrogenation and carbonyl hydrosilylation
using B(C6F5)3 as the catalyst274 Attempts to realize this prediction experimentally have been
unsuccessful Repo et al described the stoichiometric reaction of aromatic ketones with B(C6F5)3
effecting deoxygenation of the ketone to afford (C6F5)2BOH C6F5H and the corresponding aryl
alkane (Scheme 32 a)178 Furthermore the Stephan group found that similar reduction of alkyl
ketones gave borinic esters via H2 activation hydride delivery and protonation of a C6F5 group
(Scheme 32 b)275
90
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b)
Similar degradation of B(C6F5)3 via B-C bond cleavage affording CH3OB(C6F5)2 and C6F5H was
reported by Ashley and OrsquoHare in their efforts to reduce CO2 in the presence of H2 to CH3OH259
Due to the instability of B(C6F5)3 in these transformations Wang et al approached the catalytic
ketone hydrogenation challenge computationally suggesting that a bifunctional amine-borane
FLP catalyst would be viable276 Interestingly Du et al have taken a detour from direct FLP
hydrogenation of carbonyl groups reporting the catalytic hydrogenation of silyl enol ethers using
a chiral borane to obtain a variety of optically active secondary alcohols after workup (Scheme
33)277
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols
Reaction of main group species with other unsaturated C-O functionalities namely carbon
monoxide is also limited H C Brown established the synthesis of tertiary alcohols by
91
carbonylation of trialkylboranes using carbon monoxide278 although the analogous reactivity by
B-H boranes proved challenging279-282
Recently however Erker et al described the stoichiometric reduction of carbon monoxide by the
reaction of intramolecular PB FLPs and the hydroboration reagent HB(C6F5)2 to yield epoxy-
borate species (Scheme 34 top)118-119 283 Simultaneously the Stephan group exploited the
reaction of a 12 mixture of tBu3P and B(C6F5)3 with syn-gas (CO and H2) to result in sequences
of stoichiometric reactions eventually affording the borane-oxyborate derivative
(C6F5)2BCH(C6F5)OB(C6F5)3 a product of C-O bond cleavage (Scheme 34 bottom)117
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom)
The main group reduction of carbonyl groups has been limited to stoichiometric reactions with
classic hydride reagents In this chapter a remarkably simple approach to the metal-free
hydrogenation of ketones and aldehydes is reported using FLP catalysts derived from B(C6F5)3
and ether The hydrogenation concept was extended towards a heterogeneous avenue using
catalysts derived from the combination of polysaccharides or molecular sieves with B(C6F5)3
Moreover the catalytic reductive deoxygenation of aryl ketones is achieved in the case of
molecular sieves
92
32 Results and Discussion
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions
Heating a toluene solution of 5 mol B(C6F5)3 and 4-heptanone under H2 (60 atm) at 80 degC
yielded complete conversion of B(C6F5)3 to the borinic ester Pr2CHOB(C6F5)2 with concurrent
liberation of C6F5H The remaining 95 of the initial ketone was unaltered This observation
illustrates that borane and ketone act as a FLP to heterolytically cleave H2 affording nominally
[Pr2COH][HB(C6F5)3] At this stage the hydride is presumed to reduce the carbonyl fragment to
generate 4-heptanol which subsequently decomposes B(C6F5)3 to Pr2CHOB(C6F5)2 and C6F5H
It is important to note that the above example of rapid and facile decomposition of B(C6F5)3 to
borinic ester stands in contrast to an observation illustrated in Chapter 2 In this case the CH3OH
generated from ammonium protonation of [CH3OB(C6F5)3]- does not decompose B(C6F5)3 rather
under an atmosphere of H2 the resulting amine and B(C6F5)3 heterolytically split H2 to give the
ammonium [HB(C6F5)3] product (Scheme 35) Thus this observation led to the proposal of two
plausible borane decomposition pathways in ketone hydrogenation reactions
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH
In both pathways the reaction initiates with heterolytic H2 splitting by the ketone and B(C6F5)3
to give the ionic pair [R2COH][HB(C6F5)3] (Scheme 36) At this point the reaction could follow
a pathway in which hydride is transferred from the [HB(C6F5)3]- anion to the activated carbonyl
group generating alcohol and B(C6F5)3 both of which further react to give borinic ester and
C6F5H (Scheme 36 Pathway 1) The second pathway suggests the borane undergoes
protonolysis by the [R2COH]+ cation cleaving a C6F5 group to form HB(C6F5)2 and C6F5H whilst
regenerating the ketone The borane then undergoes hydroboration of the carbonyl group to
afford the borinic ester (Scheme 36 Pathway 2)
93
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation
To test Pathway 1 B(C6F5)3 was added to excess 4-heptanol (10 eq) and heated to 80 degC for 12
h This resulted in no reaction beyond formation of the alcohol-borane adduct
Pr2CHOHmiddotB(C6F5)3 as evidenced by the 11B and 19F NMR spectra (11B δ 197 ppm 19F δ -
1326 -1552 -1628 ppm) On the other hand stoichiometric and 5 mol combinations of
HB(C6F5)2 with 4-heptanone formed the new hydroboration species Pr2CHOB(C6F5)2 after 10
min at RT In addition to the characteristic methine multiplet observed at 405 ppm in the 1H
NMR spectrum 11B NMR spectroscopy gave a broad resonance at 394 ppm with 19F NMR
signals at -1325 -1498 and -1613 ppm representing the three-coordinate boron centre These
experiments provide evidence for Pathway 2 resulting in decomposition of B(C6F5)3 during
ketone hydrogenation
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents
To avoid this degradation pathway an alternative FLP is required This system must be basic
enough to effect H2 activation and stabilize the acidic proton by electrostatic interactions In this
regard the Stephan group previously reported that the ethereal oxygen of the borane-oxyborate
derivative (C6F5)2BCH(C6F5)OB(C6F5)3 is sufficiently Lewis basic to activate H2 with the
coordinating B(C6F5)2 group117 Subsequently the combination of weak Lewis bases such as
Et2O electron deficient triarylphosphines and diaryl amines were shown to be sufficiently basic
for both H2 activation and catalytic reduction of olefins99 257 In the case of Et2O DFT
calculations highlighted that solvation of the protonated ether by a second equivalent of Et2O can
significantly stabilize the proton by hydrogen-bonding interactions
94
To probe the viability of using Et2O in carbonyl reductions a d8-toluene solution of 5 mol
B(C6F5)3 was combined with a 51 ratio of Et2O4-heptanone and heated to 70 degC under H2 (4
atm) Monitoring the J-Young experiment by high temperature 1H NMR spectroscopy showed
gradual hydrogenation of the ketone yielding approximately 50 of 4-heptanol after 12 h The 1H NMR spectrum shows a distinct quintet at 345 ppm diagnostic of the hydrogenated C=O
fragment forming a C-H bond in addition to the multiplets at 128 and 080 ppm (Figure 31)
Increasing the H2 pressure to 60 atm improved the yield of 4-heptanol to 70
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol ()
Alternatively incrementing the ratio of Et2O to 4-heptanone resulted in increased yields in
which case a 81 ratio of Et2O4-heptanone in toluene gave 97 conversion to 4-heptanol after
12 h (Figure 32) The continuous improvement in alcohol yield was a direct result of gradual
preservation of the borane catalyst in the reaction as the Et2O concentration was increased
Employing identical conditions but using Et2O as the solvent resulted in the quantitative
formation of 4-heptanol after 12 h Similarly employing iPr2O as the solvent in analogous
$ $ 12
11
10
9
8
7
6
5
4
3
2
1
95
hydrogenations gave quantitative yields of 4-heptanol The use of Ph2O and TMS2O resulted in
yields of 44 and 42 in the same time frame (Table 31 entry 1)
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol
Using this FLP hydrogenation protocol a range of ketone substrates were treated with 5 mol
B(C6F5)3 in Et2O iPr2O Ph2O or TMS2O and heated for 12 h at 70 degC under H2 (60 atm) The
substrates investigated included several alkyl ketones (Table 31 entries 1 - 9) an aryl ketone
(Table 31 entry 10) benzyl ketones with substituents including F and CF3 groups (Table 31
entry 11 - 15) cyclic ketones including L-menthone and cyclohexanone (Table 31 entries 16
and 17) as well as the aldehyde cyclohexanal (Table 31 entry 18) Evaluating these reductions
by 1H NMR spectroscopy showed yields ranging between 32 - gt99 and isolated yields up to
91 for the reactions carried out in Et2O and iPr2O (Table 31) 1H NMR spectra of the alcohols
displayed characteristic multiplets at about 4 ppm assignable to the distinctive methine protons
with corresponding 13C1H resonances observed at ca 70 ppm as expected
These reactions could also be performed on a larger scale For example 100 g of 4-heptanone
was quantitatively converted to 4-heptanol using 5 mol B(C6F5)3 in Et2O and the alcohol
product was isolated in 87 yield
96
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents
Conversion (Isolated yields)
Entry R R1 Et2O iPr2O Ph2O TMS2O
1 n-C3H7 n-C3H7 gt99 (91) gt99 70 52
2 Me iPr gt99 (76) gt99 44 42
3 Me CH2tBu gt99 gt99 (90) 22 14
4 Me n-C5H11 93 (85) 50 (43) 58 41
5 Me CH2Cl gt99 (85) gt99 91 82
6 Me Cy 77 - - -
7 Et iPr gt99 gt99 (89) - trace
8 Et n-C4H9 gt99 (87) 95 44 38
9 Et CH2iPr 40 47 - -
10 Me Ph 90 69 (52) trace trace
11 Et CH2Ph gt99 (84) 97 trace trace
12 Me n-CH2CH2Ph gt99 (84) 69 58 24
13 Me CH2(o-FC6H4) 97 gt99 (90) trace trace
14 Me CH2(p-FC6H4) gt99 gt99 (90) trace trace
15 Me CH2(m-CF3C6H4) gt99 gt99 (88) 55 trace
16 -(CH2)5- 53 41 - -
17 -(2-iPr-5-Me)C5H8- gt99 (88) 89 47 45
18 Cy H 32 - - -
(-) Reaction was not performed
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents
The mechanism of these reactions is thought to be analogous to that previously described for
imine hydrogenations92 In the present case ether combines with the borane in equilibrium
97
between the classical Lewis acid-base adduct and the corresponding FLP in which the latter
effects the heterolytic cleavage of H2 The resulting protonated ether then associates with ketone
via a hydrogen-bonding interaction284-285 activating the carbonyl fragment for hydride transfer
from the [HB(C6F5)3]- anion Subsequent protonation of the generated alkoxide yields the
product alcohol while liberating etherB(C6F5)3 to further activate H2 (Scheme 37) It has been
experimentally proven that activation of the carbonyl fragment is required prior to hydride
delivery as a 11 combination of 4-heptanone and [NEt4][HB(C6F5)3] do not result in reactivity
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents
The possibility of initial H2 activation by ketoneborane combinations cannot be dismissed
however the proposed mechanism is based on the large excess of ether in comparison to ketone
In support of this proposed mechanism the activation of H2 by ethereal oxygen Lewis bases and
boranes have been described to protonate imines and alkenes en route to the corresponding
hydrogenated products257 286
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism
The proposed H-bonding ether-ketone intermediate was further probed by the stoichiometric
reaction of a toluene solution of Jutzirsquos acid [(Et2O)2H][B(C6F5)4]287 with 1-phenyl-2-butanone
and iPr2O After heating the reaction at 70 degC for 2 h a white crystalline solid 31 was isolated in
87 yield (Scheme 38) The 1H NMR spectrum of 31 showed a broad singlet at 1152 ppm
suggesting a proton involved in hydrogen-bonding Resonances attributable to both 1-phenyl-2-
butanone and iPr2O were unambiguously present although these shifts were deshielded in
98
comparison to the individual components These data in addition to the definite presence of the
[B(C6F5)4]- anion as evidenced by 11B and 19F NMR spectroscopy lead to the assignment of 31
as [(iPr2O)H(O=C(CH2Ph)CH2CH3)][B(C6F5)4]
Scheme 38 ndash Synthesis of 31
The structure of 31 was unambiguously confirmed by single crystal X-ray crystallography
(Figure 33) The molecular structure of this salt shows the proximity of the ketone and ether in
the cation with an O-O separation of 2534(3) Aring Location and complete refinement of the proton
in the cation shows it is associated with the ether oxygen and hydrogen-bonded to the ketone
with O-H distances of 104(2) and 154(2) Aring respectively The resulting angle at H is 1581(3)deg
consistent with that typically seen for hydrogen-bonding interactions288-289 The isolation of 31
provides a direct structural analogue of the proposed intermediate in the ketone hydrogenation
mechanism
The equilibrium position of the generated proton is predicted to favour the ether oxygen atom
where the unshared electron pair is sp3 hybridized making the ether oxygen more basic than the
carbonyl where the unshared pair is sp2 hybridized This is also in agreement with predicted pKa
values of protonated ether and ketone289
Figure 33 ndash POV-Ray depiction of 31
99
325 Other hydrogen-bond acceptors for carbonyl hydrogenations
By analogy to the proposed mechanism with ethereal solvents ketone hydrogenations were
explored with crown ethers in toluene To this end combinations of 5 and 10 mol of 12-crown-
4 18-crown-6 and benzo-12-crown-4 were used with 5 mol B(C6F5)3 and 4-heptanone
However in all cases only trace amounts of 4-heptanol was observed Similar to the results in
ethereal solvents these hydrogenation results could possibly be improved by using an excess of
the crown ether On the other hand inefficient hydrogenation could result due to the multiple
stabilizing hydrogen bonds with the crown (OCH2)n groups
Alternative oxygen containing solvents THF and tetrahydropyran were tested using the
hydrogenation protocol in both cases however catalysis was not observed This result could be
explained by the difference in steric hindrance of the two solvents in comparison to Et2O and
iPr2O Nonetheless performing the hydrogenations in 24-dimethylpentan-3-ol gave the
quantitative reduction of 4-heptanone after 12 h at 70 degC This result led to the proposal that
chiral alcohols could possibly be used as the solvent to induce asymmetric reduction of ketones
Thus testing this theory using enantiomerically pure alcohols (S)-2-octanol (R)-2-octanol (R)-
(+)-1-phenyl-1-butanol (S)-(+)-12-propanediol and (R)-(+)-11rsquo-bi(2-naphthol) the prochiral
ketone substrates in Table 31 entries 2 - 10 were hydrogenated although in all cases the
products were obtained as racemic mixtures
326 Other boron-based catalysts for carbonyl hydrogenations
While exploring other boron-based catalysts in carbonyl reductions borenium cation-based FLP
hydrogenation catalysts105 derived from carbene-stabilized 9-borabicyclo[331]nonane (9-
BBN) were tested in lieu of B(C6F5)3 (Figure 34) However at 70 degC (temperature required for
hydrogenation when using B(C6F5)3) the borenium cation catalysts were found to decompose to
unknown products thereby not resulting in any reactivity
100
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism
Reflecting back on a key result presented in Chapter 2 an alternative mechanism was applied to
successfully achieve B(C6F5)3 catalyzed ketone hydrogenation This finding demonstrates the
participation of the [CH3OB(C6F5)3]- anion and B(C6F5)3 in H2 activation forming CH3OH and
[HB(C6F5)3]- (Scheme 39) thereby signifying the lability of B(C6F5)3-alkoxide bonds
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond
Taking lability of the presented B-O bond into consideration a two component catalyst system
comprising of B(C6F5)3 and [NEt4][HB(C6F5)3] was conceptualized for ketone hydrogenation In
this regard the B(C6F5)3 catalyst is expected to coordinate to the carbonyl group activating it for
hydride delivery from [NEt4][HB(C6F5)3] This will consequently generate B(C6F5)3 and
B(C6F5)3-alkoxide wherein similar to Scheme 39 will react with H2 to form alcohol and
regenerate the catalysts
The proposed catalytic system was examined by combining 5 mol B(C6F5)3 and 5 mol
[NEt4][HB(C6F5)3] with 4-heptanone in toluene and heating at 80 degC under H2 (60 atm) After 12
h 1H NMR data revealed catalyst turnover giving 92 conversion to the product 4-heptanol
(Table 32 entry 1) It is important to note that under similar reaction conditions the
combination of ketone with [NEt4][HB(C6F5)3] does not give any reactivity while B(C6F5)3 alone
is decomposed to the borinic ester
101
Using this hydrogenation protocol dialkyl substituted ketones gave the corresponding alcohols
in 40 - 99 conversions by 1H NMR spectroscopy (Table 32 entries 2 - 6) Conversions were
dramatically reduced for methyl cyclohexyl ketone (Table 32 entry 7) aryl and benzyl
substituted ketones (Table 32 entries 8 - 10) benzylacetone (Table 32 entry 11) in addition to
the cyclic ketones cyclohexanone and 2-cyclohexen-1-one (Table 32 12 and 13) Interestingly
reduction of L-menthone produced the respective alcohol product in 62 by 1H NMR
spectroscopy (Table 32 entry 14)
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3]
Entry R R1 Conversion
1 n-C3H7 n-C3H7 92
2 Me iPr 57
3 Me CH2Cl gt99
4 Me 2-butyl 53
5 Et iPr gt99
6 Et CH2iPr 40
7 Me Cy 18
8 Me Ph 20
9 Ph Ph 20
10 Et CH2Ph 25
11 Me n-CH2CH2Ph 25
12 -(CH2)5- 28
13 -(CH2)3CH=CH- 0
14 -(2-iPr-5-Me)C5H8- 62
All conversions are determined by 1H NMR spectroscopy
102
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system
The mechanism of this reaction is thought to proceed by initial coordination of the Lewis acid
B(C6F5)3 to the carbonyl group assisting hydride transfer from [NEt4][HB(C6F5)3] resulting in
liberation of B(C6F5)3 and generation of [NEt4][RR1C(H)OB(C6F5)3] in which the alkoxide
anion is coordinated to B(C6F5)3 (Scheme 310) This combination of [RR1C(H)OB(C6F5)3]-
anion and B(C6F5)3 act as a FLP to activate H2 and dissociate the alcohol while simultaneously
regenerating B(C6F5)3 and [NEt4][HB(C6F5)3] By 1H NMR spectroscopy the [NEt4]+ cation
does not appear to participate in the reaction
R R1
OH
H
B(C6F5)3
R R1
O
+
B(C6F5)3
R R1
O NEt4
HB(C6F5)3
NEt4
B(C6F5)3
B(C6F5)3
R R1
O
05 H2
05 H2
H+ from H2 activation
H- from H2 activation
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation
In comparison to carbonyl hydrogenations in ethereal solvents the presented Lewis acid-assisted
mechanism has resulted in lower alcohol yields due to steric hindrance of the substrate Lewis
base preventing adequate coordination to the Lewis acid and consequently inefficient activation
of the carbonyl bond Additionally the steric hindrance of the alkoxyborate anion resulting from
hydride delivery slows down the H2 activation step allowing unreacted B(C6F5)3 and ketone to
activate H2 giving the corresponding borinic ester
328 Attempted hydrogenation of other carbonyl substrates and epoxides
Carbonyl reductions employing either the etherB(C6F5)3 FLP catalyst or the two component
catalyst species B(C6F5)3[NEt4][HB(C6F5)3] were unsuccessful for the ketones
diphenylcyclopropenone (ndash)-fenchone 25-hexanedione 6-methyl-35-heptadien-2-one
103
cyclohexane-14-dione 1-acetyl-1-cyclohexene 13-difluoroacetone 2-acetylthiophene 44-
dimethoxybutan-2-one aldehydes 5-methylthiophene-2-carboxaldehyde esters ethyl acetate
ethylchloroformate methylbenzoate ethylpyruvate phenyl acetate carboxylic acids isobutyric
acid pivalic acid 3-phenylpropanoic acid carbonates ethylene carbonate diethyl carbonate
and NN-diethylpropionamide Exposure of diethylmaleate to the hydrogenation conditions only
led to reduction of the C=C double bond
Similar treatment of the epoxides styrene oxide and trans-stilbene oxide were found to undergo
the well-documented Lewis acid catalyzed Meinwald rearrangement forming 2-
phenylacetaldehyde and 22-diphenylacetaldehyde respectively Selectivity of the aldehyde
products is determined by formation of the most stable carbenium intermediate followed by a
hydride shift (2-phenylacetaldehyde) or substituent shift (22-diphenylacetaldehyde)290-291
Moreover an attempt at extending this reduction procedure to the greenhouse gas CO2 was not
successful In this sense a J-Young tube consisting of B(C6F5)3 and 10 eq of Et2O was
pressurized with CO2H2 and heated at temperatures up to 80 degC Multinuclear NMR data only
revealed resonances corresponding to the Et2O-B(C6F5)3 adduct
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases
As presented in Section 322 judicious choice of the FLP catalyst derived from ether and
B(C6F5)3 gives catalytic hydrogenation of carbonyl substrates to their corresponding alcohols
The protonated ether solvent is proposed to hydrogen bond with the ketone substrate stabilizing
the Broslashnsted acidic proton while activating the carbonyl fragment to accept hydride from the
[HB(C6F5)3]- anion (Scheme 37)
Continued interest in ketone and aldehyde hydrogenation reactions led to the investigation of
potential oxygen-rich materials that will mimic ethereal solvents permitting catalytic
hydrogenation in a non-polar solvent To this end FLP hydrogenations were performed in
toluene using the Lewis acid B(C6F5)3 with the addition of heterogeneous Lewis bases including
cyclodextrins (poly)saccharides or molecular sieves (MS) with the formula
Na12[(AlO2)12(SiO2)12] (Figure 35)
104
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
3291 Polysaccharides as heterogeneous Lewis bases
In probing this investigation α-cyclodextrin (α-CD) an oligosaccharide formed of six
glucopyranose units (Figure 35 a) was initially tested in H2 activation In this regard 5 mol
B(C6F5)3 and α-CD were combined in d8-toluene and exposed to HD gas (1 atm) in a J-Young
tube at 60 degC (Figure 36 a) 1H NMR analysis after 1 h revealed signals for H2 resulting from
isotope equilibration thereby signifying the viability of H2 activation between B(C6F5)3 and the
oxygen donors of α-CD (Figure 36 b) Furthermore the 11B and 19F NMR spectra indicated
signals corresponding to unaltered B(C6F5)3 thus suggesting a remarkably simple and
inexpensive H2 activation FLP catalyst It is important to note that B(C6F5)3 or α-CD alone do not
effect HD activation
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD)
To assess the unprecedented FLP system in carbonyl hydrogenation catalysis the ketone 3-
methyl-2-butanone was combined with an equivalent of α-CD and 5 mol B(C6F5)3 in toluene
and heated at 60 degC under H2 (60 atm) After 12 h quantitative reduction to the product 3-
methyl-2-butanol was evidenced by 1H NMR spectroscopy revealing a diagnostic multiplet at
327 ppm corresponding to the product CH group and broad singlet at 182 ppm assignable to the
a) b)
a)
b)
105
OH group (Table 33 entry 1) Repeating the reaction in the absence of H2 does not lead to
reduction of the substrate thus eliminating the possibility of transfer hydrogenation from α-CD
Under similar conditions a series of methyl alkyl (Table 33 entries 2 - 6) and dialkyl ketones
(Table 33 entries 7 - 9) aryl (Table 33 entries 10 - 14) benzyl (Table 33 entries 15 - 19) and
cyclic ketones (Table 33 entries 20 - 22) were hydrogenated in high yields In addition the
catalytic reduction of aldehydes was similarly performed to give the corresponding primary
alcohols (Table 33 entries 23 - 25) The 1H NMR spectra for all products displayed a
characteristic resonance at about 4 ppm diagnostic of CH and CH2 protons for ketone and
aldehyde reductions respectively and the corresponding 13C1H resonances were observed at
ca 70 ppm
The efficient nature of these catalytic reactions imply that B(C6F5)3 and the oxygen atoms of α-
CD act as a FLP to activate H2 initiating hydrogenation catalysis Selective silylation of α-CD at
the 2- and 6-hydroxy positions of the glucose units gave the toluene soluble product hexakis[26-
O-(tert-butyldimethylsilyl)]-α-cyclodextrin292 This derivatization was found to have a marginal
influence on catalysis forming 3-methyl-2-butanol in 70 yield after 12 h at 60 degC Moreover
the hydrogenation protocol was further investigated using the heterogeneous Lewis bases β and
γ-CD oligosaccharides of seven and eight glucopyranose units respectively and the
(poly)saccharides maltitol and dextrin Hydrogenation results are summarized in Table 33
Taking into account that cyclodextrins are used as chiral stationary phases in separation of
enantiomers the prochiral substrates of Table 33 were analyzed by chiral GC However in all
cases the products were found as racemic mixtures
106
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
Entry R R1 α-CD β-CD γ-CD Maltitol Dextrin MS
1 Me iPr gt99 79 77 62 81 gt99
2 Me 2-butyl gt99 74 72 46 75 gt99
3 Me CH2tBu gt99 52 41 40 53 gt99
4 Me CH2Cl gt99 gt99 trace 51 trace 80
5 Me Cy gt99 81 62 31 64 gt99
6 Me n-C5H11 gt99 63 56 36 73 gt99
7 Et iPr gt99 75 75 69 80 gt99
8 Et n-C4H9 95 93 95 58 gt99 93
9 n-C3H7 n-C3H7 gt99 - - - - 92
10a Me Ph 30 13 15 10 27 trace
11 CH2CH2Cl Ph 54 - - - - 50
12 CF3 Ph 20 - - - - 20
13 Me o-CF3C6H4 trace - - - - 25
14 Me p-MeSO2C6H4 60 - - - - 97
15 Me n-CH2CH2Ph gt99 58 90 38 trace gt99
16 Me CH2(o-FC6H4) 75 70 69 66 34 gt99
17 Me CH2(p-FC6H4) gt99 49 31 55 48 gt99
18 Me CH2(m-CF3C6H4) gt99 gt99 62 43 92 gt99
19 Et CH2Ph gt68 20 31 28 46 gt99
20 -(CH2)5- gt99 72 65 68 90 gt99
21b -(CH2)3CH=CH- 67 trace trace trace trace 82
22 -(2-iPr-5-Me)C5H8- gt99 70 60 60 80 gt99
23 Cy H 10 - - - - 44
24 Ph2CH H 47 - - - - 86
25 PhCH(Me) H 20 - - - - 35
a Reported yields are for phenylethanol b Product is cyclohexanol Isolated yields are reported for α-CD and MS
107
3292 Molecular sieves as heterogeneous Lewis bases
The presented (poly)saccharides could be conveniently replaced with the ubiquitous laboratory
drying agent MS293 as HD isotope equilibration experiments evidenced the formation of H2
when exposed to a d8-toluene suspension of MS and B(C6F5)3 It is noteworthy however that
such equilibration was not observed in the absence of B(C6F5)3
Using MS as the heterogeneous Lewis base 5 mol B(C6F5)3 catalyzed the hydrogenation of
ketone and aldehyde substrates reported in Table 33 These reductions could also be performed
on an increased scale with consecutive recycling of the MS For example 100 g of 4-heptanone
in toluene was treated with 5 mol of the catalyst B(C6F5)3 and MS yielding quantitative
conversion to 4-heptanol which was isolated in 95 yield The sieves were washed with solvent
and recombined with borane and ketone in three successive hydrogenations without loss of
activity
Speculation of physisorbed B(C6F5)3 onto MS was probed by reusing filtered sieves that were
washed with toluene without further addition of B(C6F5)3 This gave 30 reduction of 4-
heptanone suggesting that while there is some physisorption it is not sufficient to provide a
significant degree of catalysis
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones
In an effort to reduce the aryl alkyl ketone acetophenone the above protocol using α-CD was
employed for 12 h at 70 degC under H2 (60 atm) 1H NMR data revealed ca 60 consumption of
acetophenone resulting in the formation of two products in almost equal ratios The distinct
quartet at 424 ppm broad singlet at 342 ppm and doublet at 102 ppm were consistent with the
hydrogenated product phenylethanol (Scheme 311) The 1H NMR spectrum of the second
product gave three separate doublet of doublets with olefinic chemical shifts observed at 652
556 and 504 ppm with each signal integrating to one proton Mass spectroscopy confirmed this
species to be styrene derived from reductive deoxygenation (Scheme 311) The reaction was
repeated using MS giving styrene in a significantly improved 92 yield (Table 34 entry 1)
108
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone
To probe this deoxygenation further the ketone 3rsquo-(trifluoromethyl)acetophenone was treated
with 5 mol B(C6F5)3 in toluene and added to a suspension of MS and heated for 12 h at 70 degC
under H2 (60 atm) This resulted in formation of the deoxygenated product 3-
(trifluoromethyl)styrene in 95 yield (Table 34 entry 2) while remainder of the reaction
mixture consisted of the alcohol 3rsquo-(trifluoromethyl)phenyl ethanol Similar treatment of
propiophenone gave trans-β-methylstyrene in 96 yield with trace amounts of the cis isomer
(Table 34 entry 3) In a similar timeframe the deoxygenation of isobutyrophenone was
performed giving 75 of the hydrocarbon 2-methyl-1-phenyl-propene while 10 of the mixture
consisted of the alcohol 1-phenyl-1-propanol (Table 34 entry 4) In this case the comparatively
slower deoxygenation rate is presumably due to increased steric hindrance about the carbonyl
functionality Indeed these effects are more pronounced with 222-trimethylacetophenone as no
reaction was observed Finally the bicyclic ketone 1-tetralone gave 12-dihydronaphthalene in
88 yield (Scheme 312 a)
Table 34 ndash Deoxygenation of aryl alkyl ketones
Entry R R1 R2 Isolated yield
1 H Me CH2 92
2 CF3 Me CH2 95
3 H Et CHCH3 trans 96
cis 4
4 H iPr C(Me)2 75
109
In light of the established tandem hydrogenation and deoxygenation protocol under these
conditions benzophenone is deoxygenated to give diphenylmethane in 81 yield (Table 35
entry 1) Similarly the diaryl ketone derivatives with substituents including CH3O Br tBu and
CH3 groups were reduced affording the corresponding diarylmethane products in yields ranging
from 67 - 99 (Table 35 entries 2 - 5) In the case of p-CF3 substituted benzophenone the
reaction gave 10 of the deoxygenation and 50 of the alcohol products (Table 35 entry 6)
Analogous treatment of 2-methylbenzophenone resulted in only 20 conversion to the aromatic
hydrocarbon (Table 35 entry 7) This example including the result for 2rsquo-
(trifluoromethyl)acetophenone (25 yield) (Table 33 entry 13) certainly infer that increased
steric hindrance about the carbonyl group has a negative impact on reactivity
Finally the tricyclic ketone dibenzosuberone afforded the reduced aryl alkane
dibenzocycloheptene in 73 yield (Scheme 312 b) It is noteworthy that Repo et al have
previously reported B(C6F5)3 mediated reductive deoxygenation of acetophenone in CD2Cl2
however in their case concurrent hydration of the borane affords (C6F5)2BOH and C6F5H178 In
the present system MS preclude this degradation pathway allowing deoxygenation to proceed
catalytically
Table 35 ndash Deoxygenation of diaryl ketones
Entry R R1 Isolated yield
1 H Ph 81
2 CH3O Ph 85
3 Br Ph 67
4 tBu Ph gt99
5 CH3 p-CH3C6H4 75
6 CF3 Ph 10
7 H o-CH3C6H4 20
110
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b)
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation
The mechanism of these ketone and aldehyde reductions is thought to be analogous to the FLP
reductions described earlier in ethereal solvents In the present case the FLP initiating
heterolytic H2 activation is believed to be the Lewis basic oxygen atoms on the surface of the α-
CD or MS and the Lewis acid B(C6F5)3 (Scheme 313) although H2 activation by ketone
B(C6F5)3 cannot be dismissed Proceeding from the former activation method similar to the case
in ethereal solvents the protonated surface hydrogen bonds to the carbonyl fragment polarizing
the bond for hydride transfer from the [HB(C6F5)3]- anion The generated alkoxide anion is then
sufficiently basic to accept proton from the surface thus regenerating the heterogeneous Lewis
base This H2 activation is in agreement with HD equilibration experiments presented for α-CD
and MS
The ease of deoxygenating the ketones Ph2C=O gt PhCH3C=O gave insight to postulate the
reductive deoxygenation mechanism Heterolytic H2 activation occurs between the MS and
B(C6F5)3 although activation between ketoneB(C6F5)3 and alcoholB(C6F5)3 cannot be
dismissed ultimately resulting in protonated alcohol which is hydrogen-bonded to ketone
(Scheme 313) At this stage it appears that C-O bond cleavage with hydride delivery and loss
of H2O affords the aromatic alkene or alkane products Evidence of the alcohol-H-ketone
intermediate proposed in the mechanism is investigated in the following section
111
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones
Experimental results have demonstrated electronic effects directly impact the deoxygenation
mechanism It appears that C-O bond cleavage and loss of H2O is governed by stability of an
alcohol carbocation intermediate Aryl alcohols readily stabilize such an intermediate through
delocalization by the neighbouring π-system while this effect is clearly absent with dialkyl and
primary alcohols Moreover electron withdrawing groups prevent formation of the carbocation
as demonstrated by the reduction results of 222-trifluoroacetophenone and 4-
(methylsulfonyl)acetophenone These compounds exclusively gave the corresponding alcohol
products (Table 33 entries 12 and 14)
32101 Verifying the reductive deoxygenation mechanism
To validate the proposed reductive deoxygenation mechanism treatment of diphenylmethanol
with 5 mol B(C6F5)3 and MS was carried out at 70 degC under H2 (60 atm) (Figure 37)
Surprisingly the reaction only gave 10 mol of diphenylmethane and complete degradation of
B(C6F5)3 Modification of the study to include 5 10 and 50 mol of benzophenone gradually
increased consumption of diphenylmethanol indicating participation of ketone in the
deoxygenation process (Figure 37) Such a mechanism accounts for necessity of a strong
112
Broslashnsted acid to initiate the deoxygenation process by protonating the hydroxyl group
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased
The conversion of carbonyl substrates to hydrocarbons is an important and rather broad area of
research in modern organic chemistry with extensive contribution to the production of fuels
Replacement of an oxo group by two hydrogen atoms is generally carried out through
hydrogenolysis although hydrogenation methods are also well studied Prominent procedures for
this transformation include the Clemmensen reduction294-295 Wolff-Kishner reduction296 and
stoichiometric methods involving LiAlH4-AlCl3 NaBH4-CF3CO2H297 Et3SiH-BF3 or
CF3CO2H298-299 and HI-Phosphorus combinations300-301 in addition to metal-catalyzed
approaches62
From the perspective of FLP systems reductive deoxygenation of carbonyl groups has been
previously achieved using silanes boranes or ammonia borane165 as sacrificial reducing agents
0 mol
5 mol
10 mol
50 mol
Diphenylmethanol (CH) Diphenylmethane (CH2)
113
The Piers group showed the B(C6F5)3 catalyzed deoxygenative hydrosilylation of CO2 to CH4
using TMP B(C6F5)3 and excess Et3SiH169 Such transformations have also been reported using
N-heterocyclic carbenes and hydrosilanes302 The Fontaine group among others111 163 have
shown the hydroboration of CO2 to methanol using FLPs167-168 Significantly more challenging is
H2 as the reducing reagent In a unique example Ashley and OrsquoHare reported the reduction of
CO2 by H2 using a stoichiometric combination of B(C6F5)3 and TMP at 160 degC to give methanol
in 17 - 25 yield259
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins
In the experiments presented 4 Aring pellet MS purchased from Sigma Aldrich were used in
combination with B(C6F5)3 To explore the efficacy of other materials the same hydrogenation
protocol was applied in the reduction of 4-heptanone to give 4-heptanol in the following yields 5
Aring MS pellets (gt99) 4 Aring MS powder (69) 3 Aring MS pellets (68) acidic alumina (30)
silicic acid (15) while no reactivity was observed in the case of silica gel sodium aluminate
neutral and basic alumina
The hydrogenation protocol using 4 Aring MS was also attempted in the reduction of olefins
including 1-hexene cyclohexene 11-diphenylethylene and αp-dimethylstyrene however no
reactivity was observed in either case
33 Conclusions
The following chapter provides an account on the discovery of a metal-free route for the
hydrogenation of ketone and aldehyde substrates to form alcohol products The FLP catalyst is
derived from ether and B(C6F5)3 in which the protonated ether participates in hydrogen-bonding
interactions with the substrate affording an efficient catalyst to mediate the transformations
Moreover B(C6F5)3-assisted ketone hydrogenations using a two component catalyst system
derived from B(C6F5)3 and [NEt4][HB(C6F5)3] has also proven viable
Simultaneous with communicating this finding Ashley et al reported an analogous
hydrogenation catalyst derived from 14-dioxaneB(C6F5)3 that is effective for the hydrogenation
of ketones and aldehydes at 4 atm of H2 and temperatures ranging between 80 and 100 degC260
114
Also an air stable catalyst derived from THFB(C6Cl5)(C6F5)2 was shown to be particularly
effective for the hydrogenation of weakly Lewis basic substrates286
Continuing to explore modifications and applications of this new metal-free carbonyl reduction
protocol catalytic reductions were achieved in toluene using B(C6F5)3 and a heterogeneous
Lewis base including CDs (poly)saccharides or MS This combination of soluble borane and
insoluble materials provided a facile route to alcohol products In the case of aryl ketones and
MS further reactivity of the alcohol resulted in deoxygenation of the carbonyl group affording
either the aromatic alkane or alkene products
34 Experimental Section
341 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane tetrahydrofuran toluene (Sigma Aldrich) were dried employing a Grubbs-type
column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring) in the
glovebox Bromobenzene (-H5 and -D5) were purchased from Sigma Aldrich and dried over
CaH2 for several days and vacuum distilled onto 4 Aring molecular sieves prior to use
Dichloromethane-d2 benzene-d6 and chloroform-d were purchased from Sigma Aldrich
Toluene-d8 was purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to
use Molecular sieves (4 Aring) were purchased from Sigma Aldrich and dried at 120 ordmC under
vacuum for 12 h prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at
80 degC under high vacuum before use
Tetrahydropyran 14-dioxane and hexamethyldisiloxane were purchased from Sigma Aldrich
and distilled over sodiumbenzophenone prior to use Diphenyl ether (ReagentPlusreg ge99) was
purchased from Sigma Aldrich and distilled under high vacuum at 80 degC over anhydrous
calcium chloride prior to use Diethyl ether (anhydrous 99) was purchased from Caledon
Laboratories Ltd and passed through a Grubbs-type column system manufactured by Innovative
Technology and stored over 4 Aring molecular sieves overnight prior to use Diisopropyl ether
(anhydrous 99 contains either BHT or hydroquinone as stabilizer) was purchased from Sigma
Aldrich and used without purification Cyclodextrins (α β and γ) maltitol dextrin from maize
starch and molecular sieves (pellets 32 mm diameter 4 Aring) were purchased from Sigma Aldrich
115
dried under vacuum at 120 degC for 12 h prior to use Deuterium hydride (extent of labeling 96
mol HD 98 atom D) was purchased from Sigma Aldrich Potassium
tetrakis(pentafluorophenyl)borate was purchased from Alfa Aesar Sodium triethylborohydride
(1M in toluene) was purchased from Sigma Aldrich Borenium cation-based FLP catalysts were
prepared by Dr Jeffrey M Farrell and Mr Roy Posaratnanathan following the literature
protocol105
All ketones and alcohols were purchased from Alfa Aesar Sigma Aldrich or TCI The liquids
were stored over 4 Aring molecular sieves and used without purification The solids were placed
under dynamic vacuum overnight prior to use H2 (grade 50) was purchased from Linde and
dried through a Nanochem Weldassure purifier column prior to use For the high pressure Parr
reactor the H2 was dried through a Matheson TRI-GAS purifier (type 452)
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D6 (1H = 716 ppm 13C = 1284 ppm) C6D5Br (1H = 728
ppm for meta proton 13C = 1224 ppm for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384
ppm) d8-tol (1H = 208 ppm for CH3 13C = 13748 ppm for ipso carbon) CDCl3 (1H = 726 ppm 13C = 7716 ppm) or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in
ppm and the absolute values of the coupling constants (J) are in Hz NMR assignments are
supported by additional 2D and DEPT-135 experiments
High Resolution Mass Spectroscopy (HRMS) was obtained using JMS T100-LC AccuTOF
DART with ion source Direct Analysis in Real Time (DART) Ionsense Inc Saugus MA GC-
MS spectra were obtained on an Agilent Technologies 5975C VL MSD with Triple-Axis
Detector and 7890A GC System Column Agilent 19091S-433 (30 m times 250 μm times 025 μm)
Oven 40 degC for first 10 min 10 degCmin to 300 degC for 10 min Injection volume 1 μL The pro-
chiral samples were analyzed using a Perkin Elmer Autosystem CL chromatograph with a chiral
column (CP Chirasil-Dex CB 25 m times 25 mm)
Jutzi acid [(Et2O)2H][B(C6F5)4]287 and silylation of α-CD with tert-butyldimethylsilyl chloride292
were prepared according to literature procedures
116
Solid materials were purchased from commercial sources 5 Aring molecular sieves (pellets 32 mm
Aldrich) 4 Aring molecular sieves (powder Aldrich) 3 Aring molecular sieves (rod 116 inches
Aldrich) aluminum oxide (weakly acidic 150 mesh 58 Aring SA = 155 m2g Aldrich) sodium
metasilicate (18 mesh granular Alfa Aesar) silicic acid (80 mesh powder Aldrich) silica gel
(200-425 mesh 60 Aring high purity grade Silicycle) sodium aluminate (powder Aldrich)
aluminum oxide (basic 150 mesh 58 Aring SA = 155 m2g Aldrich) aluminum oxide (neutral
150 mesh 58 Aring SA = 155 m2g Aldrich)
342 Synthesis of Compounds
3421 Procedures for reactions in ethereal solvents
4-Heptanol-B(C6F5)3 adduct experiment In the glove box an NMR tube was charged with a
d8-toluene (04 mL) solution of B(C6F5)3 (122 mg 240 μmol 100 mol) and 4-heptanol (279
mg 0240 mmol) The NMR tube was sealed with Parafilm and placed in an 80 degC oil bath for
12 h 19F and 11B NMR spectra were obtained No evidence for the formation of C6F5H was
observed
19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1552 (t 3JF-F = 22 Hz 1F p-C6F5) -
1628 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 197 (br s 4-heptanol-B(C6F5)3)
Synthesis of (CH3CH2CH2)2CHOB(C6F5)2from the reaction of 4-heptanone and HB(C6F5)2
In the glove box an NMR tube was charged with a d8-toluene (04 mL) solution of HB(C6F5)2
(834 mg 0240 mmol) and 4-heptanone (274 mg 0240 mmol) A second NMR tube was
charged with a d8-toluene (04 mL) solution of HB(C6F5)2 (83 mg 24 μmol 10 mol) and 4-
heptanone (274 mg 0240 mmol) After 10 min at RT the samples were analyzed by 1H 19F
and 11B NMR spectroscopy
1H NMR (400 MHz d8-tol) δ 405 (tt 3JH-H = 76 38 Hz 1H CH) 168-151 (m 2H CH2)
150 - 134 (m 4H CH2) 133 - 115 (m 2H CH2) 086 (t 3JH-H = 76 Hz 6H CH3) 19F NMR
(377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1498 (t 3JF-F = 20 Hz 1F p-C6F5) -1613 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 394 (br s (CH3CH2CH2)2CHOB(C6F5)2)
High temperature NMR study for the reduction of 4-heptanone using 5 equivalent of Et2O
(J-Young Experiment) In the glove box a 1 dram vial was charged with a d8-toluene (03 mL)
117
solution of B(C6F5)3 (61 mg 12 μmol 50 mol) 4-heptanone (274 mg 0240 mmol) and Et2O
(890 mg 125 μL 120 mmol) The reaction mixture was transferred into an oven-dried Teflon
screw cap J-Young tube The reaction tube was degassed once through a freeze-pump-thaw cycle
on the vacuumH2 line and filled with H2 (4 atm) at -196 degC The reaction was monitored by high
temperature 1H NMR spectroscopy at 70 degC with 15 minute acquisitions (Figure 31)
General procedure for reactions in ethereal solvents (Table 31) The following procedure is
common to the ketone hydrogenation reactions in Et2O iPr2O Ph2O and TMS2O In the glove
box a 2 dram vial equipped with a stir bar was charged with the respective ketone or aldehyde
(048 mmol) and B(C6F5)3 (122 mg 240 μmol 500 mol) To each vial the appropriate ether
(96 mmol 20 eq) was added using a syringe Et2O (10 mL) iPr2O (13 mL) Ph2O (15 mL) and
TMS2O (20 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glove box to be pressurized with hydrogen gas
The hydrogen gas line was thoroughly purged and the reactor was attached to it and purged 10
times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at 70 degC 540 rpm
and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time the reactor was
vented and the vials were exposed to the atmosphere In the case of Et2O and iPr2O the entire
reaction mixture was transferred to a round bottom flask and all the volatiles were collected by
vacuum distillation while cooling the collected distillate with liquid nitrogen The solvent was
then removed by applying a gentle stream of N2 gas The alcohol yields were recorded and the
products were characterized by NMR spectroscopy and GC-MS
General procedure for 100 gram reaction of 4-heptanone in Et2O In the glove box 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol 500 mol) dissolved in Et2O (143 mg 200 mL 0190 mol)
was added to the bottle The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glove box and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 540 rpm After the indicated reaction time the reactor was slowly
vented and all the volatiles were collected by vacuum distillation while cooling the collected
distillate with liquid nitrogen The solvent was removed by applying a gentle stream of N2 gas
118
By 1H NMR spectroscopy the product displayed complete conversion to 4-heptanol and was
isolated in 87 yield
Dependence of Et2O equivalents on the reduction of 4-heptanone (Figure 32) In the glove
box a stock solution consisting of 4-heptanone (192 mg 235 μL 167 mmol) and B(C6F5)3 (427
mg 800 μmol 500 mol) in toluene (35 mL) was prepared in a 2 dram vial The solution was
distributed evenly between seven 2-dram vials (053 mLvial) and each vial was equipped with a
stir bar To each vial the appropriate volume of Et2O was added using a (micro)syringe
Et2O volume 12 μL (005 eq) 25 μL (01 eq) 125 μL (05 eq) 252 μL (10 eq) 504 μL (20
eq) 756 μL (30 eq) 101 μL (40 eq) 126 μL (50 eq) 151 μL (60 eq) 176 μL (70 eq) 202 μL
(80 eq)
The vial was loosely capped and loaded in a Parr pressure reactor sealed carefully and removed
from the glove box to be pressurized with hydrogen gas The hydrogen gas line was thoroughly
purged and the reactor was attached to it and purged 10 times at 15 atm of hydrogen gas The
reactor was then placed in an oil bath set at 70 degC 540 rpm and sealed at 60 atm of hydrogen gas
for 12 h After the indicated reaction time the reactor was vented and the reactions were analyzed
by 1H NMR spectroscopy Percent conversion to 4-heptanol was obtained by integration relative
to the remaining starting material 4-heptanone
Synthesis of [iPr2O-HmiddotmiddotmiddotO=C(CH2Ph)CH2CH3][B(C6F5)4] (31) In the glove box to a 2 dram
vial was added [(Et2O)2H][B(C6F5)4] (130 mg 0157 mmol) 4-phenyl-2-butanone (349 mg
0235 mmol) iPr2O (1284 mg 126 mmol) and toluene (05 mL) The solution was transferred
into a Teflon-sealed Schlenk bomb (25 mL) equipped with a stir bar and heated at 70 degC for 2 h
The solvent was removed under vacuum and pentane (5 mL) was added to result in immediate
precipitation of a white solid that was washed again with pentane (3 mL) and dried under
vacuum (127 g 136 mmol 87) Crystals suitable for X-ray crystallographic studies were
obtained from a layered bromobenzenepentane solution at RT
1H NMR (400 MHz CD2Cl2) δ 1152 (br s 1H iPr2O-HmiddotmiddotmiddotO=C) 741 (m 3H m p-Ph) 718
(m 2H o-Ph) 468 (m 3JH-H = 68 Hz 2H iPr) 403 (s 2H PhCH2) 281 (q 3JH-H = 71 Hz
2H CH2CH3) 146 (d 3JH-H = 68 Hz 12H iPr) 117 (t 3JH-H = 71 Hz 3H CH2CH3) 19F NMR
(377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1617 (t 3JF-F = 22 Hz 1F p-C6F5) -1658 (m
119
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -168 (s B(C6F5)4) 13C1H NMR (125 MHz
CD2Cl2) δ 1480 (dm 1JC-F = 238 Hz CF) 1379 (dm 1JC-F = 243 Hz CF) 1362 (dm 1JC-F =
246 Hz CF5) 1319 (ipso-Ph) 1301 (m-Ph) 1298 (o-Ph) 1288 (p-Ph) 1240 (ipso-C6F5) 828
(iPr) 498 (CH2Ph) 373 (CH2CH3) 197 (iPr) 799 (CH2CH3) (C=O was not observed)
HRMS (DART-TOF+) mass [M]+ calcd for [C16H27O2]+ 25120110 Da Found 25120127 Da
mass [M]- calcd for [C24BF20]- 67897736 Da Found 67897745 Da
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3]
Synthesis of [NEt4][HB(C6F5)3] Part 1 In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (200 mg 0391 mmol) in toluene (10 mL) To the vial
sodium triethylborohydride (1M in toluene) (036 mL 036 mmol) was added drop wise over 15
min The reaction was allowed to mix overnight prior to removing the volatiles under vacuum
The crude mixture was washed with pentane (5 mL) to give the product Na HB(C6F5)3 as a white
solid (187 mg 0348 mmol 89)
Part 2 Na HB(C6F5)3 (187 mg 0348 mmol) was subsequently added to CH2Cl2 (10 mL) and
added to a 4 dram vial containing NEt4 Cl (576 mg 0348 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT overnight and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (206 mg
0320 mmol 92)
1H NMR (400 MHz d8-tol) δ 415 (br q 1JB-H = 91 Hz 1H BH) 211 (q 3JH-H = 74 Hz 8H
Et) 046 (tm 3JH-H = 74 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -13361 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
247 (d 1JB-H = 91 Hz BH)
General procedure for reactions in toluene using B(C6F5)3 and [NEt4][HB(C6F5)3] (Table
32) In the glovebox a 2 dram vial equipped with a stir bar was charged with the respective
ketone (048 mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and [NEt4][HB(C6F5)3] (154
mg 240 μmol 500 mol) in toluene (10 mL) The vial was loosely capped and loaded in a
Parr pressure reactor sealed carefully and removed from the glovebox to be pressurized with
hydrogen gas The hydrogen gas line was thoroughly purged and the reactor was attached to it
and purged 10 times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at
80 degC 540 rpm and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time
120
the reactor was vented and the reactions were analyzed by 1H NMR spectroscopy Percent
conversion to the alcohol product was obtained by integration relative to the remaining starting
material ketone
3423 Procedures for reactions using heterogeneous Lewis bases
General procedure for reactions in toluene using heterogeneous Lewis bases (Table 33) In
the glovebox a 2 dram vial equipped with a stir bar was charged with the respective ketone (048
mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and the respective heterogeneous Lewis base
in toluene (10 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glovebox to be pressurized with hydrogen gas The hydrogen gas
line was thoroughly purged and the reactor was attached to it and purged 10 times at 15 atm of
hydrogen gas The reactor was then placed in an oil bath set at 60 degC 430 rpm and sealed at 60
atm of hydrogen gas for 12 h Products were isolated by appropriate work-up methods The
alcohol yields were recorded and the products were characterized by NMR spectroscopy and
GC-MS
Heterogeneous Lewis bases α-CD (467 mg 0480 mmol) β-CD (467 mg 0410 mmol) γ-CD
(467 mg 0360 mmol) maltitol (168 mg 0480 mmol) dextrin (350 mg) MS (100 mg)
General procedure 100 g scale reduction of 4-heptanone using MS In the glovebox 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol) dissolved in toluene (7 mL ) was added to the bottle in addition
to 302 g of 4 Aring MS The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glovebox and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 430 rpm The reactor was slowly vented and an aliquot was taken in
d8-toluene and complete conversion of 4-heptanone to 4-heptanol was determined by 1H NMR
spectroscopy The reaction mixture was filtered through a frit and washed with dichloromethane
(2 times 10 mL) The collected molecular sieves were extracted with dichloromethane (3 times 10 mL)
and water (20 mL) The organic fraction was dried over magnesium sulfate and combined with
the toluene fraction The two solvents dichloromethane and toluene were removed by fractional
121
distillation 4-Heptanol was then collected under vacuum in a liquid nitrogen cooled Schlenk
flask The product was collected as a colourless liquid (0885 g 762 mmol 87)
3424 Procedures for reductive deoxygenation reactions
General procedure for deoxygenation reactions using molecular sieves (Table 34 and Table
35) This method follows the same procedure for reactions in Table 33 using 4 Aring MS The
reactor was placed in an oil bath set at 70 degC 340 rpm and sealed at 60 atm of hydrogen gas for
12 h Products were isolated by appropriate work-up methods The aromatic hydrocarbon yields
were recorded and the products were characterized by NMR spectroscopy and GC-MS
Verifying the deoxygenation mechanism In the glovebox four separate 2-dram vials were
loaded with diphenylmethanol (442 mg 0240 mmol) and B(C6F5)3 (61 mg 12 μmol 50
mol) To each vial the indicated equivalents of benzophenone were added (21 mg 12 μmol
50 mol 44 mg 24 μmol 10 mol 218 mg 0120 mmol 50 mol) followed by the
addition of d8-toluene (05 mL) and 4 Aring MS (100 mg) The reaction vials were equipped with a
stir bar loosely capped and placed inside a Parr pressure reactor The reactor was sealed
removed from the glovebox and attached to a purged hydrogen gas line The reactor was purged
ten times at 15 atm with hydrogen gas The reactor was then pressurized with 60 atm hydrogen
gas and placed in an oil bath for 12 h at 70 degC and 340 rpm After the indicated reaction time the
reactor was slowly vented and an aliquot was taken in d8-toluene and conversion of the
diphenylmethanol to diphenylmethane was determined by 1H NMR spectroscopy
3425 Spectroscopic data of products in Table 31
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
4-Heptanol (Entry 1) 1H NMR (500 MHz C6D5Br) δ 472 (br s 1H OH) 341 (tt 3JH-H = 70
Hz 46 Hz 1H CH) 124 (m 4H CHCH2) 114 (m 4H CH2CH3) 082 (t 3JH-H = 67 Hz 6H
CH3) 13C1H NMR (125 MHz C6D5Br) δ 721 (CH) 390 (CHCH2) 184 (CH2CH3) 135
(CH3) GC-MS 11928 min mz = 981 [M-H2O] 730 [M-C3H7] 550 [M-C3H9O]
3-Methylbutan-2-ol (Entry 2) 1H NMR (500 MHz C6D5Br) δ 339 (qd 3JH-H = 63 Hz 53
Hz 1H CHOH) 145 (m 1H iPr) 115 (br s 1H OH) 100 (d 3JH-H = 63 Hz 3H CH3) 083
122
(d 3JH-H = 68 Hz 3H iPr) 080 (d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz
C6D5Br) δ 719 (CHOH) 347 (iPr) 200 (CH3) 180 (iPr) 175 (iPr) GC-MS 3150 min mz
= 731 [M-CH3] 551 [M-CH5O]
44-Dimethylpentan-2-ol (Entry 3) 1H NMR (500 MHz C6D5Br) δ 380 (m 1H CH) 368
(br s 1H OH) 127 (dd 2JH-H = 143 Hz 3JH-H = 79 Hz 1H CH2) 116 (dd 2JH-H = 143 Hz 3JH-H = 33 Hz 1H CH2) 105 (d 3JH-H = 62 Hz 3H CH3) 087 (s 9H tBu) 13C1H NMR
(125 MHz C6D5Br) δ 660 (CH) 526 (CH2) 300 (tBu) 299 (tBu) 258 (CH3) GC-MS 6776
min mz = 1011 [M-CH3] 831 [M-CH5O] 701 [M-C2H6O] 571 [M-C3H7O]
Heptan-2-ol (Entry 4) 1H NMR (500 MHz d8-tol) δ 424 (br s 1H OH)
348 (m 3JH-H = 60 Hz 1H H2) 126 (m 2H H6) 123 (m 2H H3 H4)
118 - 114 (m 4H H3 H4 H5) 097 (d 3JH-H = 60 Hz 3H H1) 090 (t 3JH-H = 71 Hz 3H
H7) 13C1H NMR (125 MHz d8-tol) δ 684 (C2) 392 (C3) 319 (C5) 255 (C4) 228 (C1
C6) 139 (C7) GC-MS 12395 min mz = 1011 [M-CH3] 981 [M-H2O] 871 [M-C2H5]
1-Chloropropan-2-ol (Entry 5) 1H NMR (500 MHz C6D5Br) δ 432 (br s 1H OH) 362 (m 3JH-H = 68 Hz 1H CH) 316 (dd 2JH-H = 113 Hz 3JH-H = 35 Hz 1H CH2Cl) 304 (dd 2JH-H =
113 Hz 3JH-H = 68 Hz 1H CH2Cl) 090 (d 3JH-H = 61 Hz 3H CH3) 13C1H NMR (125
MHz C6D5Br) δ 692 (CH) 502 (CH2Cl) 222 (CH3) GC-MS 3383 min mz = 810 [(M+2)-
CH3] 790 [M-CH3]
1-Cyclohexylethan-1-ol (Entry 6) 1H NMR (400 MHz d8-tol) δ 330 (quint 3JH-H = 74 Hz
1H CH) 182 - 147 (m 5H Cy) 131 (br s 1H OH) 125 - 102 (m 4H Cy) 098 (d 3JH-H =
74 Hz 3H CH3) 087 (m 2H Cy) 13C1H NMR (125 MHz d8-tol) δ 721 (CHOH) 452
(CyCH) 287 (Cy) 268 (Cy) 267 (Cy) 205 (CH3) GC-MS 14245 min mz = 1131 [M-CH3]
1101 [M- H2O] 831 [M-C2H5O]
2-Methylpentan-3-ol (Entry 7) 1H NMR (500 MHz C6D5Br) δ 410 (br s 1H OH) 308
(ddd 3JH-H = 88 Hz 52 Hz 38 Hz 1H CHOH) 146 (m 3JH-H = 68 Hz 52 Hz 1H iPr) 133
(dqd 2JH-H = 140 Hz 3JH-H = 75 Hz 39 Hz 1H CH2) 120 (ddq 2JH-H = 140 Hz 3JH-H = 86
Hz 75 Hz 1H CH2) 081 (t 3JH-H = 75 Hz 3H CH3) 077 (d 3JH-H = 68 Hz 3H iPr) 076
(d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz C6D5Br) δ 783 (CHOH) 326 (iPr) 264
123
(CH2) 184 (iPr) 167 (iPr) 994 (CH3) GC-MS 5663 min mz = 841 [M-H2O] 731 [M-
C2H5] 591 [M-C3H7]
Heptan-3-ol (Entry 8) 1H NMR (500 MHz C6D5Br) δ 450 (br s 1H
OH) 335 (tt 3JH-H = 73 Hz 47 Hz 1H H3) 136-130 (m 2H H2) 128-
121 (m 5H H4 H5 H6) 115 (m 1H H5) 084 (t 3JH-H = 57 Hz 3H H7) 083 (t 3JH-H = 57
Hz 3H H1) 13C1H NMR (125 MHz C6D5Br) δ 732 (C3) 362 (C4) 295 (C2) 275 (C5)
226 (C6) 138 (C7) 961 (C1) GC-MS 12171 min mz = 981 [M-H2O] 831 [M-CH5O]
691 [M-C2H7O] 590 [M-C4H9]
5-Methylhexan-3-ol (Entry 9) 1H NMR (400 MHz d8-tol) δ (tt 3JH-H = 87 51 Hz 1H
CHOH) 201 (m 2H CH2CH3) 148 (m 3JH-H = 69 51 Hz 1H iPr) 130 (m 1H CH2iPr)
126 (m 1H CH2iPr) 089 (d 3JH-H = 69 Hz 6H iPr) 085 (t 3JH-H = 72 Hz 3H CH3)
13C1H NMR (101 MHz d8-tol) δ 785 (CHOH) 337 (iPr CH2CH3) 273 (CH2iPr) 188
(iPr) 171 (iPr) 104 (CH3) GC-MS 9458 min mz = 871 [M-Et] 691 [M-C2H7O] 591 [M-
CH2iPr]
1-Phenylethan-1-ol (Entry 10) 1H NMR (400 MHz C6D6) δ 702 (m 5H Ph) 428 (q 3JH-H =
65 Hz 1H CH) 342 (br s 1H OH) 102 (d 3JH-H = 65 Hz 3H CH3) 13C1H NMR (125
MHz CDCl3) δ 1460 (ipso-Ph) 1286 (m-Ph) 1283 (p-Ph) 1254 (o-Ph) 703 (CH) 252
(CH3) GC-MS 17207 min mz = 1221 [M] 1071 [M-CH3] 1040 [M-H2O] 910 [M-CH3O]
770 [M-C2H5O]
1-Phenylbutan-2-ol (Entry 11) 1H NMR (500 MHz CD2Cl2) δ 755 (m 1H OH) 733 (tm 3JH-H = 76 Hz 2H m-Ph) 729 (dm 3JH-H = 76 Hz 2H o-Ph) 725 (tm 3JH-H = 76 Hz 1H p-
Ph) 376 (dq 3JH-H = 81 Hz 42 Hz 1H CH) 286 (dd 2JH-H = 136 Hz 3JH-H = 43 Hz 1H
CH2Ph) 266 (dd 2JH-H = 136 Hz 3JH-H = 81 Hz 1H CH2Ph) 152 (q 3JH-H = 77 Hz 2H
CH2CH3) 102 (t 3JH-H = 77 Hz 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1391 (ipso-
Ph) 1295 (m-Ph) 1284 (o-Ph) 1263 (p-Ph) 739 (CH) 437 (CH2Ph) 303 (CH2CH3) 960
(CH3) GC-MS 20079 min mz = 1321 [M-H2O] 1030 [M-C2H7O] 911 [M-C3H7O]
591[M-C7H7]
4-Phenylbutan-2-ol (Entry 12) 1H NMR (500 MHz C6D5Br) δ 720 (t 3JH-H = 74 Hz 2H m-
Ph) 710 (t 3JH-H = 74 Hz 1H p-Ph) 706 (d 3JH-H = 74 Hz 2H o-Ph) 373 (br s 1H OH)
124
362 (dqd 3JH-H = 74 Hz 62 Hz 50 Hz 1H CH) 255 (m 2H PhCH2) 160 (m 2H CH2CH)
103 (d 3JH-H = 62 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1411 (ipso-Ph) 1281
(m-Ph) 1280 (o-Ph) 1255 (p-Ph) 673 (CH) 403 (PhCH2) 317 (CH2CH) 229 (CH3) GC-
MS 20438 min mz = 1501 [M] 1321 [M-H2O] 1170 [M-CH5O] 1051 [M-C2H5O] 911
[M-C3H7O]
1-(2-Fluorophenyl)propan-2-ol (Entry 13) 1H NMR (500 MHz CD2Cl2) δ
753 (m 1H OH) 733 - 705 (m 4H C6H4F) 406 (m 1H CH) 284 (dd 2JH-
H = 139 Hz 3JH-H = 51 Hz 1H CH2) 276 (dd 2JH-H = 139 Hz 3JH-H = 77
Hz 1H CH2) 124 (d 3JH-H = 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1178 (m
CF) 13C1H NMR (125 MHz CD2Cl2) δ 1611 (d 1JC-F = 240 Hz C1) 1318 (d 3JC-F = 59
Hz C3) 1285 (d 4JC-F = 88 Hz C4) 1257 (d 2JC-F = 16 Hz C2) 1240 (d 3JC-F = 37 Hz C5)
1152 (d 2JC-F = 22 Hz C6) 678 (d 4JC-F = 11 Hz CH) 388 (d 3JC-F = 14 Hz CH2) 229
(CH3) GC-MS 18697 min mz = 1360 [M-H2O] 960 [M-C3H6O]
1-(4-Fluorophenyl)propan-2-ol (Entry 14) 1H NMR (500 MHz CD2Cl2) δ 722 (m 2H o of
C6H4F) 705 (m 2H m of C6H4F) 399 (m 1H CH) 278 (dd 2JH-H = 137 Hz 3JH-H = 48 Hz
1H CH2) 269 (dd 2JH-H = 137 Hz 3JH-H = 78 Hz 1H CH2) 161 (br s 1H OH) 122 (d 3JH-H
= 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1177 (m p-C6H4F) 13C1H NMR (125
MHz CD2Cl2) δ 1616 (d 1JC-F = 243 Hz p of C6H4F) 1348 (d 4JC-F = 46 Hz ipso-C6H4F)
1307 (d 3JC-F = 82 Hz o of C6H4F) 1149 (d 2JC-F = 22 Hz m of C6H4F) 690 (CH) 449
(CH2) 227 (CH3) GC-MS 18697 min mz = 1361 [M-H2O] 960 [M-C3H6O]
1-(3-(Trifluoromethyl)phenyl)propan-2-ol (Entry 15) 1H NMR (500
MHz CD2Cl2) δ 751 (m 2H H1 H5) 744 (m 2H H3 H4) 408 (m 1H
CH) 283 (dd 2JH-H = 136 Hz 3JH-H = 49 Hz 1H CH2) 276 (dd 2JH-H =
136 Hz 3JH-H = 78 Hz 1H CH2) 181 (br s 1H OH) 123 (t 3JH-H = 62
Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -628 (CF3) 13C1H NMR (125 MHz CD2Cl2)
δ 1399 (C2) 1330 (q 4JC-F = 13 Hz C3) 1303 (q 2JC-F = 30 Hz C6) 1288 (C4) 1260 (q 3JC-F = 41 Hz C1) 1242 (q 1JC-F = 277 Hz CF3) 1230 (q 3JC-F = 41 Hz C5) 687 (CH) 447
(CH2) 228 (CH3) GC-MS 19011 min mz = 1861 [M-H2O] 1601 [M-C2H4O] 1171 [M-
CH2F3O]
125
Cyclohexanol (Entry 16) 1H NMR (400 MHz d8-tol) δ 324 (tt 3JH-H = 90 Hz 37 Hz 1H
CH) 177 (m 2H Cy) 168 (m 2H Cy) 142- 130 (m 3H Cy) 126- 115 (m 3H Cy)
13C1H NMR (101 MHz CD2Cl2) δ 706 (CH) 360 (CHCH2) 260 (Cy) 245 (Cy) GC-MS
4029 min mz = 1001 [M] 821 [M-H2O]
2-Isopropyl-5-methylcyclohexan-1-ol (Entry 17) 1H NMR (500 MHz
C6D5Br) δ 390 (q 3JH-H = 29 Hz 1H H1) 346 (br s 1H OH) 168 (ddd 2JH-H = 139 Hz 3JH-H = 36 Hz 24 Hz 1H H2) 164 (m 2H H3 H4) 153
(dm 2JH-H = 132 Hz 1H H5) 143 (dm 3JH-H = 92 Hz 67 Hz 1H H7) 118 (dm 2JH-H = 132
Hz 1H H5) 091 (m 1H H2) 087 (d 3JH-H = 67 Hz 3H H8) 083 (d 3JH-H = 67 Hz 3H
H9) 080 (d 3JH-H = 64 Hz 3H H10) 075 (m 1H H4) 070 (m 1H H6) 13C1H NMR (125
MHz C6D5Br) δ 675 (C1) 473 (C6) 421 (C2) 346 (C4) 288 (C7) 254 (C3) 238 (C5)
221 (C10) 208 (C9) 203 (C8) GC-MS 18912 min mz = 1381 [M-H2O] 1231 [M-CH5O]
951 [M-C3H9O] 811 [M-C4H12O]
Cyclohexylmethanol (Entry 18) 1H NMR (500 MHz CD2Cl2) δ 556 (br s 1H OH) 404 (d 3JH-H = 75 Hz 2H CH2OH) 212-182 (m 1H CyCH2) 180 (m 1H CyCH) 163 - 117 (m 1H CyCH2) 13C1H NMR (125 MHz CD2Cl2) δ 693 (CH2OH) 374 (CyCH) 301 (CyCH2) 262
(CyCH2) 252 (CyCH2) GC-MS 5538 min mz = 1141 [M] 961 [M-H2O] 831 [M-CH3O]
3426 Spectroscopic data of products in Table 32
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
3-Methylpentan-2-ol (Entry 4) 1H NMR (400 MHz CDCl3) δ 376 (m 1H CHOH) 223 (br
s 1H OH) 175 - 142 (m 3H CH(Et) Et) 118 (d 3JH-H = 69 Hz 3H CH3CHOH) 098 (m
6H CH(Et)CH3 Et) 13C1H NMR (125 MHz CD2Cl2) δ 713 (CHOH) 406 (CH(Et)) 223
(Et) 198 (OHCHCH3) 120 (CH(Et)CH3) 111 (Et) GC-MS 10215 min mz = 871 [M-CH3]
561 [M-C2H6O] 450 [C2H5O]
3427 Spectroscopic data of products in Table 33
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
126
222-Trifluoro-1-phenylethan-1-ol (Entry 12) 1H NMR (500 MHz d8-tol) δ 745 (m 2H m-
Ph) 717 (dm 3JH-H = 70 Hz 2H o-Ph) 711 (m 1H p-Ph) 432 (d 3JF-H = 77 Hz 1H CH)
306 (br s 1H OH) 19F NMR (470 MHz d8-tol) δ -783 (d 3JF-H = 77 Hz CF3) 13C1H NMR
(125 MHz d8-tol) δ 1341 (ipso-Ph) 1289 (m-Ph) 1276 (p-Ph) 1272 (q 4JC-F = 12 Hz o-Ph)
1234 (q 1JC-F = 297 Hz CF3) 726 (CH) GC-MS 6130 min mz = 1760 [M] 1701 [M-CF3]
3-Chloro-1-phenylpropan-1-ol (Entry 11) 1H NMR (600 MHz d8-tol) δ 712 (m 3H m p-
Ph) 703 (m 2H o-Ph) 399 (t 3JH-H = 78 Hz 1H CHOH) 312 (t 3JH-H = 67 Hz 2H CH2Cl)
251 (br s 1H OH) 218 (dt 3JH-H = 78 Hz 67 Hz 2H CHCH2CH2) 13C1H NMR (151
MHz d8-tol) δ 1440 (ipso-Ph) 1282 (m-Ph) 1275 (o-Ph) 1260 (p-Ph) 476 (CHOH) 432
(CH2Cl) 387 (CHCH2CH2) GC-MS 11210 min mz = 1701 [M] 1521 [M-H2O] 1070 [M-
C2H4Cl]
1-(2-(Trifluoromethyl)phenyl)ethan-1-ol (Entry 13) 1H NMR (500 MHz
d8-tol) δ 759 (d 3JH-H = 81 Hz 1H H2) 732 (d 3JH-H = 81 Hz 1H H5)
711 (t 3JH-H = 81 Hz 1H H3) 685 (t 3JH-H = 81 Hz 1H H4) 508 (qm 3JH-
H = 67 Hz 1H CHOH) 221 (br s 1H OH) 125 (d 3JH-H = 67 Hz 3H CH3)
19F NMR (470 MHz d8-tol) δ -582 (s CF3) 13C1H NMR (125 MHz d8-tol) δ 1455 (ipso-
C6H4CF3) 1315 (C3) 1314 (C1) 1294 (C4) 1264 (C2) 1244 (C5) 1240 (CF3) 653
(CHOH) 253 (CH3) (JC-F not reported) GC-MS 6453 min mz = 1901 [M] 1750 [M-CH3]
1720 [M-H2O] 1450 [M-C2H5O]
1-(4-(Methylsulfonyl)phenyl)ethan-1-ol (Entry 14) 1H NMR (500 MHz d8-tol) δ 763 (d 3JH-H = 86 Hz 2H o of C6H4SO2CH3) 705 (d 3JH-H = 86 Hz 2H m of C6H4SO2CH3) 437 (m
1H CHOH) 228 (s 3H SO2CH3) 141 (br s 1H OH) 112 (d 3JH-H = 66 Hz 3H CHCH3)
13C1H NMR (125 MHz d8-tol) δ 1522 (p of C6H4SO2CH3) 1402 (ipso-C6H4SO2CH3) 1270
(o of C6H4SO2CH3) 1257 (m of C6H4SO2CH3) 689 (CHOH) 436 (SO2CH3) 252 (CHCH3)
HRMS-DART+ mz [M+NH4]+ calcd for C9H16NO3S 21808509 Found 21808554
22-Diphenylethan-1-ol (Entry 24) 1H NMR (500 MHz d8-tol) δ 704 (m 1H p-Ph) 703 (m
2H m -Ph) 693 (d 3JH-H = 75 Hz 2H o-Ph) 405 (dd 3JH-H = 83 Hz 61 Hz 1H CH) 400
(m 2H CH2) (OH was not observed) 13C1H NMR (125 MHz d8-tol) δ 1418 (ipso-Ph)
1293 (m-Ph) 1287 (o-Ph) 1274 (p-Ph) 763 (CH2) 512 (CH) GC-MS 15178 min mz =
1811 [M-OH] 1671 [M-CH3O]
127
2-Phenylpropan-1-ol (Entry 25) 1H NMR (500 MHz d8-tol) δ 722 (d 3JH-H = 78 Hz 2H o-
Ph) 718 ndash 713 (m 3H m p-Ph) 362 (dd 2JH-H = 100 Hz 3JH-H = 62 Hz 1H CH2) 354 (dd 2JH-H = 100 Hz 3JH-H = 78 Hz 1H CH2) 342 (br s 1H OH) 288 (m 3JH-H = 69 Hz 1H CH)
121 (d 3JH-H = 69 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1459 (ipso-Ph) 1289 (p-
Ph) 1283 (m-Ph) 1274 (o-Ph) 780 (CH2) 435 (CH) 181 (CH3) GC-MS 6462 min mz =
1211 [M-CH3] 1051 [M-CH3O]
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Styrene (Entry 1)1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 77 Hz 2H o-Ph) 708 (t 3JH-
H = 77 Hz 2H m-Ph) 706 (t 3JH-H = 77 Hz 1H p-Ph) 653 (dd 3JH-H = 176 Hz 109 Hz 1H
CH) 556 (dd 3JH-H = 176 Hz 11 Hz 1H CH2) 505 (dd 3JH-H = 109 Hz 11 Hz 1H CH2)
13C1H NMR (125 MHz d8-tol) δ 1379 (CH) 1372 (ipso-Ph) 1286 (o m-Ph) 1284 (p-Ph)
1140 (CH2) GC-MS 4038 min mz = 1041 [M] 911 [C7H7] 781 [C6H6]
1-(Trifluoromethyl)-3-vinylbenzene (Entry 2) 1H NMR (500 MHz d8-
tol) δ 744 (s 1H H1) 718 (d 3JH-H = 77 Hz 1H H5) 706 (d 3JH-H = 77
Hz 1H H3) 686 (t 3JH-H = 75 Hz 1H H4) 631 (dd 3JH-H = 173 Hz 102
Hz 1H CH=CH2) 544 (d 3JH-H = 173 Hz 1H CH=CH2) 504 (d 3JH-H = 102 Hz 1H
CH=CH2) 19F NMR (470 MHz d8-tol) δ -626 (s CF3) 13C1H NMR (125 MHz d8-tol) δ
1379 (ipso-C6H4CF3) 1354 (CH=CH2) 1309 (C2) 1284 (C5) 1245 (CF3) 1237 (C3) 1225
(C1) 1151 (CH=CH2) (JC-F not reported) GC-MS 4290 min mz = 1721 [M] 1531 [M-F]
1451 [M-C2H3] 1031 [M-CF3]
(E)-Prop-1-en-1-ylbenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 73 Hz
2H o-Ph) 712 (t 3JH-H = 73 Hz 2H m-Ph) 702 (t 3JH-H = 73 Hz 1H p-Ph) 626 (dq 3JH-H =
156 Hz 4JH-H = 18 Hz 1H PhCH=CH) 600 (dq 3JH-H = 156 Hz 66 Hz 1H PhCH=CH)
168 (dd 3JH-H = 66 Hz 4JH-H = 18 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1378
(ipso-Ph) 1314 (PhCH=CH) 1283 (m-Ph) 1265 (p-Ph) 1258 (o-Ph) 1248 (PhCH=CH)
1800 (CH3) GC-MS 5888 min mz = 1181 [M] 1171 [M-H] 1031 [M-CH3]
128
(2-Methylprop-1-en-1-yl)benzene (Entry 4) 1H NMR (500 MHz d8-tol) δ 717 (m 4H o m-
Ph) 705 (m 1H p-Ph) 624 (m 4JH-H = 15 Hz 1H CH=C(CH3)2) 180 (d 4JH-H = 15 Hz 3H
CH=C(CH3)2) 175 (d 4JH-H = 15 Hz 3H CH=C(CH3)2) 13C1H NMR (125 MHz d8-tol) δ
1386 (C(CH3)2) 1345 (ipso-Ph) 1287 (o-Ph) 1279 (m-Ph) 1257 (CH=C(CH3)2) 1256 (p-
Ph) 264 (CH3) 188 (CH3) GC-MS 5780 min mz = 1321 [M] 1171 [M-CH3]
12-Dihydronaphthalene (Scheme 312a) 1H NMR (600 MHz CD2Cl2) δ 746 - 731 (m 4H
C6H4) 678 (dm 3JH-H = 96 Hz 1H CH=CHCH2) 632 (m 1H CH=CHCH2) 308 (m 2H
CH2CH2CH) 258 (m 2H CH2CH=CH) 13C1H NMR (125 MHz CD2Cl2) δ 1358
(quaternary C for C6H4) 1344 (quaternary C for C6H4) 1288 (CH=CHCH2) 1280
(CH=CHCH2) 1277 (C6H4) 1271 (C6H4) 1266 (C6H4) 1261 (C6H4) 278 (CHCH2CH2) 236
(CH=CHCH2) GC-MS 7943 min mz = 1301 [M] 1151 [M-CH3] 1021 [M-C2H4]
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Diphenylmethane (Entry 1) 1H NMR (500 MHz d8-tol) δ 708 (t 3JH-H = 75 Hz 2H m-Ph)
701 (t 3JH-H = 75 Hz 1H p-Ph) 700 (d 3JH-H = 75 Hz 2H o-Ph) 372 (s 1H CH2) 13C1H
NMR (125 MHz d8-tol) δ 1413 (ipso-Ph) 1293 (o-Ph) 1286 (m-Ph) 1263 (p-Ph) 422
(CH2) GC-MS 11686 min mz = 1681 [M] 1671 [M-H] 911 [C7H7]
1-Benzyl-4-methoxybenzene (Entry 2) 1H NMR (500 MHz d8-tol) δ 712 (m 2H m-Ph)
711 (m 1H p-Ph) 705 (d 3JH-H = 67 Hz 2H o-Ph) 693 (d 3JH-H = 76 Hz 2H o of
C6H4OCH3) 670 (d 3JH-H = 76 Hz 2H m of C6H4OCH3) 372 (s 2H CH2) 334 (s 3H
OCH3) 13C1H NMR (125 MHz d8-tol) δ 1581 (p of C6H4OCH3) 1416 (ipso-C6H4OCH3)
1328 (ipso-Ph) 1295 (o of C6H4OCH3) 1287 (o-Ph) 1283 (m-Ph) 1278 (p-Ph) 1137 (m of
C6H4OCH3) 542 (OCH3) 410 (CH2) GC-MS 14801 min mz = 1981 [M] 1671 [M-OCH3]
1211 [M-C6H5] 911 [M-C7H7O] 771 [M-C8H9O]
1-Benzyl-4-bromobenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 719 (m 1H p-Ph) 716
(d 3JH-H = 78 Hz 2H m of C6H4Br) 710 (t 3JH-H = 77 Hz 2H m-Ph) 691 (d 3JH-H = 77 Hz
2H o-Ph) 665 (d 3JH-H = 77 Hz 2H o of C6H4Br) 355 (s 2H CH2) 13C1H NMR (125
MHz d8-tol) δ 1407 (ipso-C6H4Br) 1403 (ipso-Ph) 1317 (m of C6H4Br) 1316 (p-Ph) 1308
129
(o of C6H4Br) 1289 (o-Ph) 1285 (m-Ph) 1204 (p-C6H4Br) 414 (CH2) GC-MS 15250 min
mz = 2480 [M+2] 2460 [M] 1671 [M-Br] 911 [M-C6H4Br]
1-Benzyl-4-(tert-butyl)benzene (Entry 4) 1H NMR (500 MHz CD2Cl2) δ 774 (t 3JH-H = 86
Hz 2H m of C6H4tBu) 768 (t 3JH-H = 76 Hz 1H p-Ph) 761 (t 3JH-H = 76 Hz 2H m-Ph)
759 (d 3JH-H = 76 Hz 2H o-Ph) 755 (d 3JH-H = 86 Hz 2H o of C6H4tBu) 435 (s 2H CH2)
178 (s 9H tBu) 13C1H NMR (125 MHz CD2Cl2) δ 1493 (p of C6H4tBu) 1420 (ipso-Ph)
1387 (ipso-C6H4tBu) 1294 (m-Ph o of C6H4tBu) 1286 (p-Ph) 1263 (o-Ph) 1255 (m of
C6H4tBu) 415 (CH2) 347 (tBu) 315 (tBu) GC-MS 15429 min mz = 2242 [M] 2092 [M-
CH3) 911 [C7H7]
Di-p-tolylmethane (Entry 5) 1H NMR (500 MHz d8-tol) δ 699 (d 3JH-H = 78 Hz 2H o of
C6H4CH3) 694 (d 3JH-H = 78 Hz 2H m of C6H4CH3) 375 (s 1H CH2) 215 (s 3H CH3)
13C1H NMR (125 MHz d8-tol) δ 1383 (ipso-C6H4CH3) 1350 (p of C6H4CH3) 1289 (m of
C6H4CH3) 1287 (o of C6H4CH3) 408 (CH2) 206 (CH3) GC-MS 14226 min mz = 1961
[M] 1811 [M-CH3) 1661 [M-2(CH3)] 1051 [M-C7H7] 911 [M- C8H9]
1-Benzyl-4-(trifluoromethyl)benzene (Entry 6) 1H NMR (600 MHz CD2Cl2) δ 800 (d 3JH-H
= 73 Hz 2H o-Ph) 788 (d 3JH-H = 74 Hz 2H m of C6H4CF3) 778 (t 3JH-H = 73 Hz 1H p-
Ph) 767 (t 3JH-H = 73 Hz 2H m-Ph) 751 (d 3JH-H = 74 Hz 2H o of C6H4CF3) 430 (s 2H
CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1458 (ipso-C6H4CF3) 1404 (ipso-Ph) 1296 (p-Ph
o of C6H4CF3) 1285 (m-Ph) 1258 (p of C6H4CF3) 1256 (o-Ph) 1255 (m of C6H4CF3) 1239
(CF3) 415 (CH2) (JC-F not reported) GC-MS 11767 min mz = 2361 [M] 1671 [M-CF3]
1591 [M-C6H5] 911 [C7H7]
1-Benzyl-2-methylbenzene (Entry 7) 1H NMR (600 MHz CD2Cl2) δ
776 (m 2H o-Ph) 767 - 761 (m 3H m p-Ph) 759 - 754 (m 4H
C6H4CH3) 438 (s 2H CH2) 270 (s 3H CH3) 13C1H NMR (151
MHz CD2Cl2) δ 1410 (ipso-Ph) 1393 (ipso-C6H4CH3) 1370 (C-CH3) 1307 (C1) 1303 (m-
Ph) 1292 (o-Ph) 1287 (C4) 1268 (p-Ph) 1263 (C3) 1262 (C2) 395 (CH2) 197 (CH3)
GC-MS 12844 min mz = 1821 [M] 1671 [M-CH3]
130
1011-Dihydro-5H-dibenzo[ad][7]annulene (Scheme 312 b) 1H NMR
(600 MHz CD2Cl2) δ 745 (m 1H H2) 742 (m 1H H4) 740 (m 2H
H3 H5) 438 (s 1H CH2) 342 (s 2H CH2) 13C1H NMR (125 MHz
CD2Cl2) δ 1423 (C6) 1395 (C1) 1298 (C5) 1291 (C2) 1268 (C4) 1263 (C3) GC-MS
15761 min mz = 1941 [M] 1791 [M-CH3] 1651 [M-C2H5]
343 X-Ray Crystallography
3431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
3432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
131
3433 Selected crystallographic data
Table 36 ndash Selected crystallographic data for 31
31 (+05 C6D5Br)
Formula C43H295B1Br05F20O2
Formula wt 100893
Crystal system monoclinic
Space group P2(1)c
a(Aring) 127865(6)
b(Aring) 199241(9)
c(Aring) 170110(7)
α(ordm) 9000
β(ordm) 1067440(10)
γ(ordm) 9000
V(Aring3) 41500(3)
Z 4
Temp (K) 150(2)
d(calc) gcm-3 1607
Abs coeff μ mm-1 0606
Data collected 37469
Rint 00368
Data used 9534
Variables 596
R (gt2σ) 00458
wR2 01145
GOF 1020
132
Chapter 4 Hydroamination and Hydrophosphination Reactions Using
Frustrated Lewis Pairs
41 Introduction
411 Hydroamination
The direct addition of N-H bonds to unsaturated organic compounds provides an atom-economic
route to valuable nitrogen-containing molecules Pursuit of such reactivity is largely motivated
by the ubiquitous nature of substituted amines in the pharmaceutical industry303-306 The
intermolecular hydroamination of alkynes represents an attractive single-step approach to
convert inexpensive and readily available starting materials to synthetic building blocks such as
imines and enamines
Intermolecular hydroamination of alkynes was initially carried out using Hg and Tl salts307-308
however toxicity concerns prompted subsequent development of a wide variety of other catalysts
based on rare-earth metals309 early- and late-transition metals303 310 as well as lanthanides311-312
and actinides313 Based on the pioneering work of Bergman314-316 and Doye317-318 group IV metal
derivatives have become popular catalysts in these reactions More recently the groups of
Richeson319 Odom320-321 Schafer322 Mountford323 and others311 313 321 324 have made significant
contributions to further the development of these catalysts
Nonetheless to date transition metal-free routes remain relatively less explored The Broslashnsted
acid tungstophosphoric acid has been reported by Lingaiah325 to catalyze the hydroamination of
alkynes However in order for this catalyst to operate harsh conditions and electronically
deactivated amines are required An alternative approach using a strong base such as cesium
hydroxide was reported by Knochel although this strategy only tolerated functional groups less
acidic than the amines309 More recently metal-free approaches have been demonstrated in the
work by Beauchemin on the Cope-type inter- and intramolecular hydroaminations326-329
133
412 Reactions of main group FLPs with alkynes
4121 12-Addition or deprotonation reactions
Recent research has been devoted to effect metal-free stoichiometric and catalytic
transformations using frustrated Lewis pairs (FLPs) These main group combinations of bulky
Lewis acids and bases have become the focus of a number of research groups worldwide330-331
Shortly after the discovery of FLP chemistry several reports communicated the organic
manipulation of alkynes analogous to the pioneering hydroboration reactions by H C Brown60
Initial studies showed that FLPs comprised of B(C6F5)3 or Al(C6F5)3(PhMe) and phosphines react
to yield either zwitterionic vinyl phosphonium borate or aluminate salts resulting from a 12-
addition reaction or phosphonium alkynylborates resulting from alkyne deprotonation126 128 The
course of the reaction was found to depend on the basicity of the phosphine donor with less
basic aryl phosphines favouring 12-addition (Scheme 41)
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al)
Berke and co-workers investigated related intermolecular reactions of terminal alkynes and
B(C6F5)3 with 26-lutidine and TMP demonstrating that these systems effect deprotonation of the
alkyne affording ammonium alkynylborates156 Alternatively the groups of Erker and Stephan
reported the intramolecular cyclization of pendant alkyne substituted anilines151 and N-
heterocycles152 via 12-addition reactions using B(C6F5)3 (Scheme 42 a and b) In a similar
fashion ethylene-linked sulphurborane systems were found to add to alkynes with subsequent
elimination of ethylene affording a single-step route to SB alkenyl-FLPs (Scheme 42 c)332
134
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c)
4122 11-Carboboration reactions
The groups of Berke and Erker separately studied the reactivity of Lewis acids with alkynes in
the absence of a Lewis base (Scheme 43) To this extent they identified the 11-carboboration
reaction to generate alkenylboranes156 159-160 Moreover the reaction of propargyl esters with
B(C6F5)3 have been shown to generate boron allylation reagents333
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes
135
4123 Hydroelementation reactions
Catalytic hydroelementation reactions have been reported for alkynes In the presence of 5 - 10
mol B(C6F5)3 internal alkynes have been shown to undergo both hydrostannylation334 (Scheme
44 a) and hydrogermylation335 reactions (Scheme 44 b)
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes
413 Reactions of transition metal FLPs with alkynes
The FLP paradigm has also been studied using transition metal systems in combination with
alkynes Some examples include metalation through the 11-carbozirconation336 and
boroauration337 reactions Additionally the Wass group developed cationic zirconocene
phosphinoaryloxide complexes that selectively deprotonate terminal alkynes (Scheme 45)338 In
a recent paper the Stephan group has shown that Ru-acetylides act as carbon nucleophiles in
combination with Lewis acids to effect trans-addition to alkynes162
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes
Inspired by the reactivity of FLPs with alkynes in this chapter the intermolecular reaction of
amines B(C6F5)3 and a versatile group of terminal alkynes is explored in hydroamination
reactions A catalytic approach to yield enamines and corresponding amines is described In
addition related systems are probed to accomplish stoichiometric and catalytic intramolecular
hydroaminations affording N-heterocycles Finally stoichiometric approaches to
hydrophosphination reactions are discussed
136
42 Results and Discussion
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
With the objective of initiating hydroamination reactivity the three component stoichiometric
reaction of Ph2NH B(C6F5)3 and phenylacetylene was performed in CD2Cl2 The 1H 11B and 19F
NMR spectra revealed consumption of two equivalents of phenylacetylene to afford the salt
[Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] 41 while leaving a portion of the starting materials Ph2NH
and B(C6F5)3 unreacted (Scheme 46) Adjustment of the alkyne stoichiometry to two equivalents
afforded 41 in 90 yield (Table 41 entry 1) This new species results from the sequential
hydroamination and deprotonation reaction of phenylacetylene
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
The 1H NMR spectrum displayed a diagnostic methyl singlet at 289 ppm with the corresponding 13C1H resonance at 283 ppm In addition a downfield 13C1H resonance at 1901 ppm is
attributable to the iminium N=C group The alkynylborate anion [PhCequivCB(C6F5)3]- gave rise to
the 11B NMR signal at -208 ppm and 19F resonances at -1327 -1638 and -1673 ppm The
nature of compound 41 was unambiguously confirmed by X-ray crystallography (Figure 41)
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
137
To probe the generality of this reaction the corresponding reactivity of various substituted
secondary anilines with two equivalents of phenylacetylene were explored In this fashion the
species [RPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (R = iPr 42 Cy 43 PhCH2 44 p-CH3O 45) were
isolated in 88 91 82 and 90 yield respectively (Table 41 entry 1) 1H NMR spectra
showed the iminium cations were formed as a mixture of the E and Z isomers in a 71 ratio for
compounds 42 and 43 41 ratio for 44 and 11 ratio for 45
Analogous reactions of Ph2NH B(C6F5)3 and two equivalents of 1-hexyne revealed two
competitive reaction pathways In addition to the hydroaminationdeprotonation product
[Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] 46 (Table 41 entry 2) the alkenylboranes resulting from
the 11-carboboration of 1-hexyne were also observed by NMR spectroscopy Exposing the same
anilineB(C6F5)3 combination to 9-ethynylphenanthrene produced [Ph2N=C(CH3)C14H9]
[C14H9CequivCB(C6F5)3] 47 in 75 isolated yield (Table 41 entry 3) The molecular structure of
47 was unambiguously characterized by X-ray crystallography (Figure 42)
Figure 42 ndash POV-Ray depiction of 47
138
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
139
In a similar fashion the reaction of two equivalents of ethynylcyclopropane with B(C6F5)3 and
iPrPhNH at room temperature afforded the yellow crystalline solid formulated as
[iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] 48 in 88 yield (Table 41 entry 4) In this case
the 1H NMR spectrum showed the iminium cation is formed as a mixture of the E and Z isomers
in a 17 ratio Furthermore the reaction of iPrPhNHB(C6F5)3 with 2-ethynylthiophene
proceeded cleanly to give the product [iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] 49
obtained as a 71 mixture of EZ isomers and isolated in 78 yield (Table 41 entry 5) Single
crystals suitable for X-ray diffraction were obtained for Z-48 and Z-49 and the structures are
shown in Figure 43 (a) and (b) respectively
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b)
Interestingly addition 14-diethynylbenzene to the stoichiometric combination of Ph2NH
B(C6F5)3 resulted in an instant color change from pale orange to deep red affording the
zwitterionic product [Ph2N=C(CH3)C6H4CequivCB(C6F5)3] 410 in 85 yield (Table 41 entry 6)
The molecular structure of 410 was confirmed by X-ray crystallography (Figure 44)
Figure 44 ndash POV-Ray depiction of 410
(a) (b)
140
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes
The three component reaction is thought to proceed via Lewis acid polarization of the alkyne by
B(C6F5)3 prompting nucleophilic addition of the aniline and generating a zwitterionic
intermediate (Scheme 47) Analogous 12-additions to alkynes have been previously reported for
phosphineborane126 128 thioetherborane339 and pyrroleborane127 FLPs However in the present
study the arylammonium intermediate provides an acidic proton which cleaved the B-C bond
yielding enamine with concurrent release of B(C6F5)3 Subsequent to this hydroamination the
FLP derived from enamine and B(C6F5)3 deprotonate a second equivalent of the alkyne affording
the isolated iminium alkynylborate salts (Scheme 47)
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts
Analogous stoichiometric combination of tert-butylaniline or diisopropylamine and B(C6F5)3
with either one or two equivalents of phenylacetylene resulted exclusively in deprotonation of
the terminal alkyne affording the ammonium alkynylborate salts [tBuPhNH2][PhCequivCB(C6F5)3]
411 and [iPr2NH2][PhCequivCB(C6F5)3] 412 in 99 and 76 yield respectively (Scheme 48) In
these cases the amines are sufficiently bulky to form a FLP with B(C6F5)3 and relatively basic to
preferentially effect deprotonation of the alkyne This reaction pathway has been previously
observed for basic phosphines and B(C6F5)3 with numerous alkynes
141
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates
In separate reactions FLPs comprised of iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 were
combined with the internal alkynes 3-hexyne diphenylacetylene and 1-phenyl-1-propyne At
RT multinuclear NMR data only revealed signals for the FLP and unaltered alkyne Heating
the reactions up to 80 degC did not display signals for hydroamination rather only products of 11-
carboboration were observed
Also interested in extending the unsaturated substrates scope the hydroamination of the olefins
1-hexene cyclohexene styrene αp-dimethylstyrene and 3-(trifluoromethyl)styrene were tested
using the FLPs iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 Thermolysis of the individual samples
up to 100 degC only revealed signals for the starting materials
4213 Reactivity of the iminium alkynylborate products with nucleophiles
An attractive feature of the iminium cation is the unsaturated N=C fragment since it could be
reacted with nucleophiles to give amines and this transformation could potentially be extended to
generate enantioselective variants of the amines Introducing simple fluoride sources such as
[NBu4][Si(Ph)3F2] NBu4F and CsF to compounds 42 and 46 resulted in deprotonation of the
methyl group losing HF and generating the corresponding enamine Nonetheless addition of the
H+ source [(Et2O)2H][B(C6F5)4]287 regenerated the iminium cation (Scheme 49)
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4]
142
Furthermore addition of the organolithium reagents methyl lithium and ethyl lithium at -30 degC
gave a 11 mixture of the alkylation and deprotonation products as evidenced by 1H NMR
spectroscopy while phenyl lithium did not result in any reactivity (Scheme 410 left)
Combinations of stoichiometric hydride sources [tBu3PH][HB(C6F5)3] NaBHEt3 and LiAlH4
only gave saturation of the N=C bond with the lithium reducing agent (Scheme 410 right)
Overall while hydride delivery to the N=C bond was successfully achieved inefficient delivery
of the presented alkyl and aryl nucleophiles shifted focus towards other types of reactivities
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right)
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3
The equimolar reaction of the tertiary amine dibenzylaniline B(C6F5)3 and phenylacetylene was
investigated with the aim of isolating a zwitterionic intermediate analogous to the compound
proposed en route to hydroamination in Scheme 47 In this case however the nucleophilic
centre for this reaction proved to be the para-carbon of the N-bound phenyl ring undergoing
hydroarylation of phenylacetylene to generate the zwitterionic species
(PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 413 in 96 yield (Scheme 411) Single crystal X-ray
diffraction confirmed the structure of 413 and it is shown in Figure 45 (a)
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3
143
Examining the secondary amine N-isopropylanthracen-9-amine in similar reactivity also gave the
hydroarylation of phenylacetylene and this was demonstrated at the C10 position of the
anthracene ring forming iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 414 in 95 yield In this unique
case however a N=C double bond is generated between nitrogen and the anthracene ring as well
as saturation of the C10 centre giving the tetrahedral geometry observed in the solid state
structure of 414 shown in Figure 45 (b) Generally aromatic substitution reactions in the
presence of Lewis acids have been used for the synthesis of numerous aromatic molecules340
Particularly relevant to this thesis the para-carbon of N-bound phenyl rings has been proposed
as the Lewis basic centre to heterolytically split H2 and generate a sp3-hybridized carbon centre
in the arene hydrogenation reactions presented in Chapter 2
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg
Stability of the B-C bond towards acidic conditions was tested In this regard combinations of
413 with the protic salts [(Et2O)2H][B(C6F5)4] or [Ph2NH2][B(C6F5)4] were found to readily
cleave the B-C bond liberating B(C6F5)3 and generating the diphenylethylene-ammonium
derivative as evidenced by the geminal protons at 508 and 504 ppm in the 1H NMR spectrum
(Scheme 412)
(a) (b)
144
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes
With the exception of catalytic hydrogenations the majority of FLPs reported to date react with
small molecules in a stoichiometric fashion Thus seeking to expand the application of FLPs in
catalysis beyond hydrogenations attention was turned to the development of catalytic
hydroamination reactions This motivation was inspired by the hydroaminationdeprotonation
mechanism proposed in Scheme 47 Realizing that deprotonation of alkyne eliminates the
possibility for catalysis the reaction protocol was adjusted in which the alkyne is added slowly
in order to achieve hydroamination and prevent deprotonation by enamine and B(C6F5)3
The slow addition of the terminal alkyne 2-ethynylanisole to a RT solution of Ph2NH and 10
mol of B(C6F5)3 in toluene over 10 h afforded the catalytic hydroamination product 2-
methoxyphenyl substituted enamine Ph2N(2-MeOC6H4)C=CH2 415 in 84 isolated yield (Table
42) The 1H NMR spectrum of 415 displayed two diagnostic singlets at 501 and 490 ppm
characteristic of the inequivalent geminal hydrogen atoms The corresponding carbon centre
gives rise to a 13C1H NMR signal at 108 ppm Further NMR studies of the compound were
consistent with formation of the Markovnikov isomer in which the nitrogen is added to the
substituted carbon of the terminal alkyne
The analogous treatment of Ph2NH with 2-ethynyltoluene in the presence of 10 mol B(C6F5)3
afforded Ph2N(2-MeC6H4)C=CH2 416 in 69 isolated yield while the alkyne 1-
ethynylnaphthalene yielded Ph2N(C10H7)C=CH2 417 in 62 yield (Table 42) The
corresponding reaction of Ph2NH with phenylacetylene and 2-bromo-phenylacetylene afforded
Ph2N(C6H5)C=CH2 418 and Ph2N(2-BrC6H4)C=CH2 419 in yields of 74 and 52 respectively
(Table 42) Similar to 415 the 1H and 13C1H NMR data for these products were in agreement
with the proposed product formulations
145
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3
This hydroamination strategy also proved effective for substituted diphenylamines For example
(p-FC6H4)2NH in combination with 10 mol B(C6F5)3 reacted with halogenated
phenylacetylenes to afford the species (p-FC6H4)2N(2-BrC6H4)C=CH2 420 and (p-FC6H4)2N(2-
146
FC6H4)C=CH2 421 while the corresponding reactivity with 2-thiophenylacetylene gave (p-
FC6H4)2N(2-SC4H3)C=CH2 422 and iPrPhN(2-SC4H3)C=CH2 423 when reacted with iPrNHPh
(Table 42)
The reaction of Ph2NH with 9-ethynylphenanthrene gave Ph2N(C14H9)C=CH2 424 and (p-
FC6H4)2NH was used to prepare (p-FC6H4)2N(C14H9)C=CH2 425 Similarly reactions of the
appropriate combinations of amine and alkyne using 10 mol B(C6F5)3 afforded (p-FC6H4)2N(3-
FC6H4)C=CH2 426 Ph2N(35-F2C6H3)C=CH2 427 and Ph2N(3-CF3C6H4)C=CH2 428 although
in these cases cooling to -30 degC was necessary to maximize yields obtained between 68 - 77
(Table 42) This impact of temperature was most dramatically demonstrated in the case of 426
where performing the reaction at 25 degC gave the product in 19 yield while at -30 degC the yield
was significantly enhanced to 74
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions
The success of these hydroamination reactions strongly depends on the electronic and steric
nature of the amineborane FLP combination thereby preventing 11-carboboration and
deprotonation of the alkyne Interaction of the borane with the terminal alkyne prompts amine
addition to generate a zwitterionic intermediate In the present case the acidic proton of the
anilinium centre migrates to the carbon adjacent to boron cleaving the B-C bond and forming the
enamine product (Scheme 413) The released B(C6F5)3 is then available to participate in further
hydroamination catalysis It is noteworthy that the postulated zwitterion accounts for the
Markovnikov addition of amines to alkynes and thus the nature of the observed enamine
products341
As stated earlier catalytic formation of enamine requires the slow addition of alkyne over 10 h
This is a result of deprotonation of the alkyne by the FLP derived from enamine and borane
consequently generating iminium alkynylborate salts analogous to 42 - 410 The observed
catalytic hydroaminations imply that amine addition to alkyne is faster than enamine
deprotonation of alkyne
147
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes
The catalytic generation of these enamines together with previously established FLP
hydrogenation of enamines93 prompted interest in a one-pot catalytic
hydroaminationhydrogenation protocol
Following the hydroamination procedure described above reaction mixtures generating the two
enamines 421 and 427 were exposed to H2 (4 atm) and heated at 80 degC for 14 h Pleasingly the
B(C6F5)3 catalyst successfully completed hydrogenation of the C=C double bond giving the
amines (p-FC6H4)2N(2-FC6H4)C(H)CH3 429 and Ph2N(35-F2C6H3)C(H)CH3 430 in 77 and
64 overall isolated yields respectively (Scheme 414) Monitoring the hydrogenation portion
of the reactions by 1H NMR spectroscopy revealed in both cases demise of the signals
attributable to the geminal protons of the enamines with simultaneous appearance of a quartet
attributable to the methine proton and a doublet assignable to the methyl group of the respective
amine In an alternative approach to the hydrogenation catalysis subsequent to hydroamination
5 mol of the known hydrogenation catalyst Mes2PH(C6F4)BH(C6F5)294 was added to the
reaction mixture pressurized with H2 (4 atm) and heated to 80 degC In both cases complete
hydrogenation was achieved after 3 h
148
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430
Experimental evidence demonstrated the catalytic hydroaminations are restricted to aryl
acetylenes Examples of other terminal alkynes that were examined include
trimethylsilylacetylene which resulted in 11-carboboration while the acetylene carboxylates
methyl propiolate ethyl propiolate 2-naphthyl propiolate and tert-butyl propiolate did not react
due to formation of a B-O adduct Extending the chemistry to hydrothiolation using thiophenol
was not successful
424 Intramolecular hydroamination reactions using FLPs
4241 Stoichiometric hydroamination
The potential of the above hydroamination reactions to access N-heterocycles was also probed
To this end the alkynyl-substituted aniline C6H5NH(CH2)3CequivCH was prepared and exposed to
an equivalent of B(C6F5)3 in toluene 11B NMR spectroscopy indicated the formation of a B-N
adduct verified by the resonance at -25 ppm although heating the reaction for 2 h at 50 degC
yielded the cyclized zwitterion C6H5N(CH2)3CCH2B(C6F5)3 431 isolated as a white solid in 94
yield (Scheme 415) The 1H NMR spectrum was consistent with consumption of the NH proton
revealing a diagnostic broad quartet at 333 ppm with geminal B-H coupling of 54 Hz indicative
of the B(C6F5)3 bound methylene group In addition a diagnostic sharp singlet at -134 ppm in
149
the 11B NMR spectrum and the N=C iminium 13C1H resonance at 192 ppm were consistent
with the formulation of 431
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432
The analogous 6-membered ring was prepared from the precursor C6H5NH(CH2)4CequivCH and an
equivalent of B(C6F5)3 giving the zwitterion C6H5N(CH2)4CCH2B(C6F5)3 432 in 99 yield The
formulation of 432 was affirmed by NMR spectroscopy in addition to elemental analysis and X-
ray crystallography (Figure 46)
Figure 46 ndash POV-Ray depiction of 432
Similarly substituted isoindoline species are accessible from the reaction of the precursor
C6H5NHCH2(C6H4)CequivCH with B(C6F5)3 in toluene Stoichiometric combination of the two
reagents resulted in a white precipitate believed to be the intramolecular hydroamination product
after 10 min at RT However this compound was sparingly soluble in toluene bromobenzene
and CD2Cl2 not allowing its comprehensive characterization by NMR spectroscopy As such H2
(4 atm) was added to the reaction and heated at 80 degC for 16 h in an effort to synthesize the H2
activated salt which was presumed to be more soluble than the zwitterion The 1H NMR
150
spectrum of this reaction displayed a quartet at 556 ppm and a triplet at 289 ppm with a four-
bond coupling constant of 26 Hz 13C1H NMR data showed a resonance at 182 ppm
attributable to a N=C bond Collectively these data are consistent with the successive
hydroamination and hydrogenation product [2-MeC8H6N(Ph)][HB(C6F5)3] 433 isolated in 54
yield (Scheme 416)
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433
While species 433 is isolated as an insoluble solid from pentane in CD2Cl2 the [HB(C6F5)3]-
anion appears to reversibly deliver hydride to the N=C carbon centre generating isoindoline and
B(C6F5)3 in about 25 This was evidenced by 1H NMR spectroscopy revealing a diagnostic
quartet at 518 ppm two diastereotopic doublets at 472 and 455 ppm and an upfield doublet at
151 ppm data that is collectively assignable to the isoindoline species This was further
supported by 11B and 19F NMR spectroscopy which provided evidence of free B(C6F5)3 Presence
of this equilibrium is consistent with a previous report on reversible hydride abstraction and
redelivery from carbon centres alpha to nitrogen262
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines
This hydroaminationhydrogenation protocol was further adapted for catalytic cyclization
reactions In this fashion the alkynyl substituted aniline C6H5NH(CH2)3CequivCH was treated with
10 mol B(C6F5)3 at 80 degC under H2 (4 atm) for 16 h This gave the desired product 2-methyl-1-
phenyl pyrrolidine 434 in 68 isolated yield (Table 43 entry 1) In a similar fashion the
catalytic hydroaminationhydrogenation of C6H5NH(CH2)4CequivCH gave 2-methyl-1-
phenylpiperidine 435 in 66 yield (Table 43 entry 2) The following protocol was also
applicable to p-fluoro and p-methoxy substituted substrates giving the respective cyclized
products 436 and 437 in 72 and 52 yield respectively (Table 43 entries 3 and 4) Finally
151
similar reactivity with C6H5NHCH2(C6H4)CequivCH gave 1-methyl-2-phenylisoindoline 438 in 70
yield (Scheme 417)
The yields obtained for compounds 436 and 437 strongly reflect the balance of Broslashnsted acidity
required by the amine proton to effect hydroamination In this case the p-fluoro substituent
proved more effective in hydroamination than p-methoxy
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines
Entry R n Isolated yield
1 H 0 68 434
2 H 1 66 435
3 F 1 72 436
4 CH3O 1 52 437
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH
425 Reaction of B(C6F5)3 with ethynylphosphines
The stoichiometric reaction of B(C6F5)3 with the ethynylphosphine tBu2PCequivCH has previously
been shown to give the deprotonation product tBu2P(H)CequivCB(C6F5)3342 Conversely analogous
treatment of Mes2PCequivCH required addition of tBu3P to effect deprotonation of the ethynyl group
due to diminished Lewis basicity of the phosphine Moreover the Erker group reported the
152
reaction of Ph2PCequivCH with B(C6F5)3 to generate a dimeric product formed by a sequential series
of 12-PB additions to the ethynyl unit343
While interested in hydroamination of ethynylphosphines the FLP iPrNHPhB(C6F5)3 was added
to two equivalents of Mes2PCequivCH giving the pale yellow solid 439 in 88 yield (Scheme 418)
The 1H NMR spectrum did not indicate incorporation of aniline into the product rather two
inequivalent vinylic protons with characteristic P-H and H-H coupling were observed at 771 and
574 ppm (Figure 47)
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons
The 31P NMR spectrum revealed two resonances with chemical shifts at -115 and -143 ppm
while the 11B and 19F NMR spectra were in agreement with formation of an alkynylborate
species (11B δ -211 ppm 19F δ -1329 -1616 and -1663 ppm) These data together with
elemental analysis confirm the formulation of the zwitterionic species trans-
Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 439 An X-ray crystallographic study confirmed the
1H
1H31P
153
molecular structure of 439 and it is shown in Figure 48 (a) In the absence of aniline the
reaction leads to the previously reported 11-carboboration product344-345
On another account the same reaction was obtained with 2 equivalents of tBu2PCequivCH and
B(C6F5)3 to give cis and trans isomers of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 440 The cis
isomer was crystallized and characterized by X-ray diffraction studies (Figure 48 b) In this
case the phosphorus centre was basic enough to effect deprotonation thus the reaction proceeded
in the absence of iPrNHPh Monitoring the reaction by 31P NMR spectroscopy the spectrum
indicated the simultaneous presence of tBu2PCequivCH and the deprotonation zwitterion
tBu2P(H)CequivCB(C6F5)3 giving insight to a plausible mechanism en route to the formation of
compounds 439 and 440
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b)
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines
The reaction is proposed to proceed through the mechanism highlighted in Scheme 419 wherein
the mixture of B(C6F5)3 and R2PCequivCH initially effect deprotonation of the ethynyl group
formulating the zwitterion R2P(H)CequivCB(C6F5)3 Under equilibrium conditions a second
equivalent of the ethynylphosphine is protonated consequently prompting nucleophilic addition
of the [R2PCequivCB(C6F5)3]- anion to the terminal carbon followed by proton transfer to generate
the isolated zwitterionic products In the case of Mes2PCequivCH the deprotonation step required a
stronger base therefore iPrNHPh was added to effect reactivity
(a) (b)
154
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs
An earlier report showed the three component reaction of p-tolyl2PH B(C6F5)3 and
phenylacetylene gave the 12-addition phosphonium borate zwitterion p-
tolyl2PH(Ph)C=C(H)B(C6F5)3128 Realizing the acidic hydrogen on the phosphorus atom a
sample of this compound was treated by UV radiation or heated to prompt hydrophosphination
of phenylacetylene in a mechanism analogous to that presented for the hydroamination reaction
In this regard however the zwitterion proved robust and further reactivity was not observed
Similar results were obtained when using Mes2PH or exchanging the borane for the slightly less
Lewis acidic B(p-C6F4H)3
Turning attention towards the borane HB(C6F5)2 the hydrophosphination reaction was attempted
following an alternative approach In this regard Ph2PH was added to a stoichiometric
combination of HB(C6F5)2 and Bpin-substituted 1-hexyne (Scheme 420 a) After 16 h at RT
the acetylenic unit of Bpin was reduced to a C-C single bond as illustrated by a characteristic
multiplet at 353 ppm and a very broad singlet at 148 ppm in the 1H NMR spectrum The
product Bu(H)Ph2PC-C(H)B(C6F5)2Bpin 441 resulting from the sequential hydroboration and
hydrophosphination reactions was isolated in 82 yield NMR spectroscopy data indeed showed
incorporation of all reactants into the isolated product
155
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH
Investigating similar reactivity of 2-methyl-1-buten-3-yne substituted Bpin with HB(C6F5)2 and
Ph2PH a colourless solid was obtained in 73 yield The 1H NMR data unambiguously showed
saturation of the acetylenic fragment however the spectrum consisted of an olefinic proton at
646 ppm in addition to a methylene group at 307 ppm Further spectroscopic data revealed the
product as Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin 442 resulting from nucleophilic addition of
the phosphine at the terminal double bond (Scheme 420) Single crystals suitable for X-Ray
diffraction were obtained and the structure is shown in Figure 49 (b)
Figure 49 ndash POV-Ray depictions of 442
156
427 Proposed mechanism for the hydroborationhydrophosphination reactions
The mechanism of this reaction is envisaged to initiate following the well-documented
hydroboration of the acetylenic group generating the corresponding alkenyl-bisborane species
(Scheme 421)346 At this point the phosphine coordinates to B(C6F5)2 rendering its proton more
Broslashnsted acidic and prompting protonation of the C=C double bond This is followed by
nucleophilic attack of the phosphine at the C2 position of alkynyl-substituted Bpin (441) or C4
position of the enyne-substituted Bpin (442) The 14-addition reaction to conjugated enynes has
been previously investigated using the ethylene-linked PB FLP to give eight membered cyclic
allenes147
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments
Since evidence for the P-B intermediate is not observed by 11B or 31P NMR spectroscopy an
alternative mechanism could be speculated In this case the nucleophilic phosphine could add to
the vinyl bisborane followed by proton transfer However this later mechanism is not highly
supported as the more Lewis basic secondary phosphines tBu2PH and iPr2PH only gave the P-B
adduct with HB(C6F5)2 consistent with retro-hydroboration after coordination of the phosphine
to the vinyl bisborane This adduct remained intact even at elevated temperatures of 80 degC
Similar N-B adducts were observed when the analogous reactivity was explored with the alkyl
and aryl amines iPr2NH iPrNHPh and Ph2NH
157
43 Conclusions
This chapter provides an account on the discovery of consecutive hydroamination and
deprotonation reactions of various terminal alkynes by anilineB(C6F5)3 FLPs to form a series of
iminium alkynylborate complexes The reaction procedure was modified to eliminate the
deprotonation step in order to achieve B(C6F5)3 catalyzed Markovnikov hydroamination of
alkynes yielding enamine products Subsequent to hydroamination catalysis the borane catalyst
was also used for catalytic hydrogenation of the enamine providing a one-pot avenue to the
corresponding amine derivatives Related systems were probed to accomplish the stoichiometric
and catalytic intramolecular hydroamination of alkynyl-substituted anilines generating cyclic
amines While this hydroamination protocol was not extendable to effect hydrophosphination a
new stoichiometric approach using HB(C6F5)2 and Ph2PH was found to result in the sequential
hydroboration and hydrophosphination reactions of an alkynyl- and enynyl-substituted
pinacolborane generating novel PB FLPs
44 Experimental Section
441 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane dichloromethane and toluene (Sigma Aldrich) were dried employing a Grubbs-
type column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring)
in the glovebox Dichloromethane-d2 bromobenzene-d5 and bromobenzene-H5 were purchased
from Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring
molecular sieves prior to use Hexane and ethyl acetate were purchased from Caledon
Laboratories Silica gel was purchased from Silicycle Molecular sieves (4 Aring) were purchased
from Sigma Aldrich and dried at 120 ordmC under vacuum for 24 h prior to use B(C6F5)3 was
purchased from Boulder Scientific and sublimed at 80 degC under high vacuum before use H2
(grade 50) was purchased from Linde and dried through a Nanochem Weldassure purifier
column prior to use
Substituted amines alkynes and phosphines were purchased from Sigma Aldrich Alfa Aesar
Apollo Scientific Strem Chemicals Inc and TCI The oils were distilled over CaH2 and solids
were sublimed under high vacuum prior to use The following reagents were prepared following
158
literature procedures 1-ethynylnaphthalene347 (p-C6H4F)2NH (p-CH3OC6H4)PhNH tBuNHPh
and N-isopropylanthracen-9-amine266 N-(2-ethynylbenzyl)aniline N-(pent-4-ynyl)aniline N-
(hex-5-ynyl)aniline 4-fluoro-N-(hex-5-yn-1-yl)aniline and 4-methoxy-N-(hex-5-yn-1-
yl)aniline348 N-(2-ethynylbenzyl)aniline349 tBu2PCequivCH and Mes2PCequivCH342
CH3(CH2)3CequivCBpin and CH2=C(CH3)CequivCBpin350
Compounds 439 - 442 were prepared by the author during a four month research opportunity in
the group of Professor Gerhard Erker at Universitaumlt Muumlnster Germany Molecular structures and
elemental analyses for 439 and 440 were obtained at the University of Toronto Molecular
structure for 442 was obtained at Universitaumlt Muumlnster and elemental analyses for 441 and 442
were obtained at the University of Toronto
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm for
ipso carbon) and CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) or externally (11B (Et2O)BF3 19F
CFCl3) Chemical Shifts (δ) are reported in ppm and the absolute values of the coupling
constants (J) are in Hz NMR assignments are supported by additional 2D and DEPT-135
experiments
High resolution mass spectra (HRMS) were obtained using an ABSciex QStar Mass
Spectrometer with an ESI source MSMS and accurate mass capabilities Elemental analyses (C
H N) were performed in-house employing a Perkin Elmer 2400 Series II CHNS Analyzer
442 Synthesis of Compounds
4421 Procedures for stoichiometric intermolecular hydroamination reactions
Compounds 41 - 45 were prepared in a similar fashion thus only one preparation is detailed In
the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial phenylacetylene (151
mg 148 mmol) was added drop wise over 1 min In the case where pentane was used as the
solvent the reaction was worked up as follows the solvent was decanted and the product was
washed with pentane (3 times 5 mL) to yield the product as a solid In the case where toluene or
159
dichloromethane was used as the as solvent the reaction was worked up as follows the solvent
was removed under reduced pressure and the crude product was washed with pentane to yield the
product as a solid
Synthesis of [Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] (41) Diphenylamine (0125 g 0740
mmol) pentane (20 mL) reaction time 2 h yellow solid (588 mg 0666 mmol 90) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC
1H NMR (400 MHz CD2Cl2) δ 768 (m 3H H4 H5) 761 (m 1H p-Ph)
745 (m 5H o m p-Ph) 739 (m 4H H3 m-Ph) 728 (dm 3JH-H = 75
Hz 2H H7) 717 (tm 3JH-H = 75 Hz 2H H8) 711 (tm 3JH-H = 75 Hz
1H H9) 710 (dm 3JH-H = 77 Hz 2H o-Ph) 289 (s 3H Me) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F
p-C6F5) -1673 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s
equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1901 (C1) 1352 (p-Ph) 1320 (C5) 1315 (C4)
1312 (p-Ph) 1310 (C7) 1307 (m-Ph) 1298 (Ph) 1293 (Ph) 1277 (C8) 1257 (C9) 1254 (o-
Ph) 1241 (C3) 283 (Me) (C2 C6 ipso-Ph and all carbons for CequivCB(C6F5)3 were not
observed) Elemental analysis was not successful after numerous attempts
Synthesis of E-[iPrPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (42) N-Isopropylaniline (100 mg
0740 mmol) pentane (10 mL) reaction time 1 h pale yellow solid (566 mg 0651 mmol 88)
EZ ratio 71
42 1H NMR (400 MHz CD2Cl2) δ 773 (tm 3JH-H = 77 Hz 1H H5)
772 (m 6H H4 H9 H10) 746 (dm 3JH-H = 77 Hz 2H H3) 728 (dm 3JH-H = 76 Hz 2H H12) 720 (m 2H H8) 716 (t 3JH-H = 76 Hz 2H
H13) 713 (t 3JH-H = 76 Hz 1H H14) 491 (m 3JH-H = 66 Hz 1H H6)
244 (s 3H Me) 126 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1637 (t 3JF-F = 20 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1913
(C1) 1482 (dm 1JC-F = 236 Hz CF) 1381 (dm 1JC-F = 243 Hz CF) 1365 (dm 1JC-F = 245 Hz
CF) 1346 (C2) 1339 (C5) 1319 (C10) 1318 (C7) 1311 (C12) 1310 (C4) 1303 (C9) 1278
(C13) 1274 (C11) 1258 (C14) 1253 (C3 C8) 937 (C15) 619 (C6) 288 (Me) 208 (iPr)
160
(CequivCB(C6F5)3 and ipso-C6F5 were not observed) Anal calcd () for C43H25BF15N C 6066 H
296 N 165 Found 6037 H 317 N 173
Synthesis of E-[CyPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (43) N-Cyclohexylaniline (135 mg
0740 mmol) pentane (10 mL) reaction time 1 h off-white solid (599 mg 0674 mmol 91)
EZ ratio 71
43 1H NMR (400 MHz CD2Cl2) δ 769 (tt 3JH-H = 74 Hz 4JH-H = 24
Hz 1H H5) 762 (m 5H H4 H12 H13) 737 (dm 3JH-H = 74 Hz 2H H3)
720 (dm 3JH-H = 77 Hz 2H H15) 711 (m 4H H11 H16) 703 (tm 3JH-H
= 77 Hz 1H H17) 439 (tt 3JH-H = 119 Hz 3JH-H = 35 Hz 1H H6) 235
(s 3H Me) 184 (dm JH-H = 117 Hz 1H H7) 170 (dm 2JH-H = 145 Hz
2H H8) 145 (dm 2JH-H = 132 Hz 2H H9) 133 (m 1H H7) 104 (pseudo qt JH-H = 138 Hz 3JH-H = 37 Hz 2H H8) 080 (pseudo qt 2JH-H = 132 Hz 3JH-H = 37 Hz 2H H9) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F p-C6F5) -1673 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (101 MHz
CD2Cl2) δ 1916 (C1) 1341 (C5) 1323 (C13) 1315 (C15) 1313 (C4) 1307 (C12) 1282 (C16)
1262 (C17) 1257 (C3) 1254 (C11) 699 (C6) 320 (C7) 291 (Me) 249 (C8) 244 (C9) (C2
C10 C14 and all carbons for CequivCB(C6F5)3 were not observed) Anal calcd () for C46H29BF15N
C 6197 H 328 N 157 Found 6158 H 354 N 153
Synthesis of E-[(PhCH2)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (44) N-Benzylaniline (135 mg
0740 mmol) dichloromethane (10 mL) reaction time 2 h pale yellow solid (544 mg 0607
mmol 82) EZ ratio 41
44 1H NMR (600 MHz CD2Cl2) δ 782 (t 3JH-H = 73 Hz 1H H5) 777
(t 3JH-H = 73 Hz 2H H4) 764 (d 3JH-H = 73 Hz 2H H3) 760 (t 3JH-H =
76 Hz 1H H14) 753 (t 3JH-H = 76 Hz 2H H13) 738 (m 1H H10) 728
(m 4H H9 H16) 716 (t 3JH-H = 73 Hz 2H H17) 710 (t 3JH-H = 73 Hz
1H H18) 699 (d 3JH-H = 76 Hz 2H H12) 679 (d 3JH-H = 76 Hz 2H
H8) 526 (s 2H H6) 259 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
207 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1912 (C1) 1386 (C7) 1342 (C5) 1339
(C2) 1317 (C11 C14) 1311 (C9) 1309 (C13 C15) 1304 (C4 C10) 1296 (C8) 1294 (C16) 1278
B(C6F5)3
N1
2
3
45
7
8
9
10
14
1516
17
18
6
11
12
13
B(C6F5)3
N1
2
3
45
7
8 9
10
11 12
13
14
1617
1815
6
19
161
(C17) 1263 (C3) 1258 (C18) 1241 (C8) 938 (C19) 645 (C6) 286 (Me) (CequivCB(C6F5)3 and all
carbons of B(C6F5)3 were not observed) Anal calcd () for C47H25BF15N C 6276 H 280 N
156 Found 6259 H 296 N 171
Synthesis of [(p-C6H4OMe)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (45) (p-CH3OC6H4)PhNH
(147 mg 0740 mmol) pentane (15 mL) room temperature reaction time 3 h yellow solid (493
mg 0540 mmol 73) Anal calcd () for C47H25BF15NO C 6166 H 275 N 153 Found C
6106 H 262 N 142 EZ ratio 11
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 748 (m 1H H5) 735
(m 2H H3) 730 (m 2H H4) 726 (m 2H H8) 717 (m 2H H15) 707
(tm 3JH-H = 72 Hz 2H H16) 702 (m 1H H17) 696 (m 1H H9) 688
(dm 3JH-H = 87 Hz 2H H11) 670 (dm 3JH-H = 87 Hz 2H H12) 365 (s
3H OMe) 273 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1327 (m
2F o-C6F5) -1637 (t 3JF-F = 21 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (125 MHz CD2Cl2) δ 1884
(C1) 1613 (C13) 1481 (dm 1JC-F = 241 Hz CF) 1421 (C6) 1381 (dm 1JC-F = 244 Hz CF)
1364 1 (dm 1JC-F = 246 Hz CF) 1356 (C10) 1348 (C5) 1325 (C2) 1313 (C7) 1310 (C15)
1305(C8) 1297 (C4) 1292 (C3) 1278 (C16) 1274 (C14) 1269 (C11) 1257 (C17) 1255 (C9)
1155 (C12) 937 (C18) 557 (OMe) 283 (Me)
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 750 (m 1H H5) 735
(m 2H H4) 730 (m 2H H3) 726 (m 2H H8) 717 (m 2H H12) 702 (m
2H H11) 696 (m 1H H9) 378 (s 3H OMe) 279 (s 3H Me) 13C1H
NMR (125 MHz CD2Cl2) δ 1892 (C1) 1620 (C13) 1432 (C6) 1348 (C5)
1345 (C10) 1325 (C2) 1319 (C7) 1310 (C3) 1297 (C4) 1257 (C11) 1255
(C9) 1242 (C8) 1162 (C12) 557 (OMe) 283 (Me) 19F and 11B NMR are the same as above
Compounds 46 - 410 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and either diphenylamine (125 mg 0740 mmol) or N-isopropylaniline
(100 mg 0740 mmol) To the vial the respective alkyne was added over 1 min In the case
where pentane was used as the solvent the reaction was worked up as follows the solvent was
decanted and the product was washed with pentane (3 times 5 mL) to yield the product as a solid In
162
the case where toluene or dichloromethane was used as the as solvent the reaction was worked
up as follows the solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as a solid
Synthesis of [Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] (46) 1-Hexyne (122 mg 148 mmol)
pentane (20 mL) -30 degC to room temperature reaction time 2 h yellow solid (350 mg 414
mmol 56) The reaction also yielded alkenylboranes resulting from 11-carboboration which
were separated from the reaction mixture through the pentane washes during work-up
1H NMR (400 MHz CD2Cl2) δ 768 (m 6H Ph) 738 (m 4H Ph) 282
(m 2H H2) 262 (s 3H Me) 211 (t 3JH-H = 67 Hz 2H H7) 180 (quint
of t 3JH-H = 77 Hz 4JH-H = 28 Hz 2H H3) 141 (m 6H H4 H8 H9) 092
(t 3JH-H = 73 Hz 3H H5) 087 (t 3JH-H = 72 Hz 3H H10) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1643 (t 3JF-F = 21 Hz 1F
p-C6F5) -1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211
(s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1992 (C1) 1482 (dm 1JC-F = 237 Hz CF)
1411 (ipso-Ph) 1407 (ipso-Ph) 1382 (dm 1JC-F = 242 Hz CF) 1363 (dm 1JC-F = 246 Hz
CF) 1319 (Ph) 1315 (Ph) 1314 (Ph) 1236 (Ph) 1234 (Ph) 932 (C6) 389 (C2) 320 (C8)
295 (C3) 248 (Me) 227 (C4) 219 (C9) 199 (C7) 135 (C10) 130 (C5) (CequivCB(C6F5)3 and
ipso-C6F5 were not observed) Anal calcd () for C42H31BF15N C 5966 H 370 N 166
Found 5885 H 366 N 154
Synthesis of [Ph2N=C(CH3)C14H9][C14H9CequivCB(C6F5)3] (47) 9-Ethynylphenanthrene (299
mg 148 mmol) pentane (15 mL) room temperature reaction time 3 h pale yellow solid (602
mg 0555 mmol 75) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 859 (dm 3JH-H = 82 Hz 1H ArH) 853 (dm 3JH-H = 82 Hz
1H ArH) 849 (m 2H ArH) 845 (dm 3JH-H = 82 Hz 1H ArH) 776 (dm 3JH-H = 76 Hz 1H ArH) 773 (tm 3JH-H = 76 Hz 1H ArH) 767 (s 1H borateArH) 765 (tm 3JH-H = 82 Hz 1H ArH) 763 (s 1H amineArH) 760 (m 3JH-H = 82 Hz 1H ArH) 757 (m 3H m p-Ph) 755 (m
2H o-Ph) 753 (dm 3JH-H = 76 Hz 1H ArH) 748 (m 2H ArH) 744 (tm 3JH-H = 76 Hz 1H ArH) 737 (tm 3JH-H = 76 Hz 1H ArH) 732 (m 2H ArH) 703 (tt 3JH-H = 70 Hz 4JH-H = 10
Hz 1H ArH) 696 (tm 3JH-H = 70 Hz 2H m-Ph) 691 (dm 3JH-H = 70 Hz 2H o-Ph) 284
163
(Me) 19F NMR (377 MHz CD2Cl2) δ -1324 (m 2F o-C6F5) -1636 (t 3JF-F = 21 Hz 1F p-
C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -206 (s equivCB) 13C1H NMR
(125 MHz CD2Cl2) δ 1943 (C=N) 1500 (dm 1JC-F = 242 CF) 1444 (ipso-Ph) 1430 (ipso-
Ph) 1400 (dm 1JC-F = 245 CF) 1386 (dm 1JC-F = 250 CF) 1342 (ArC) 1342 (m-Ph) 1337
(p-Ph) 1336 (ArC) 1334 (o-Ph) 1330 (p-Ph) 1326 (ArC) 1325 (ArC) 1321 (ArC) 1320 (m-
Ph) 1319 (ArC) 1317 (ArC) 1315 (ArC) 1313 (ArC) 1310 (ArC) 1307 (ArC) 1306 (ArC)
1303 (ArC) 1301 (ArC) 1298 (ArC) 1297 (ArC) 1286 (ArC) 1284 (ArC) 1284 (ArC) 1280
(ArC) 1272 (ArC) 1261 (o-Ph) 1250 (o-Ph) 1259 (ArC) 1259 (ArC) 1248 (ArC) 1242 (ArC)
1241 (ArC) 937 (CequivCB) 3096 (Me) Anal calcd () for C62H31BF15N C 6859 H 288 N
129 Found C 6812 H 306 N 134
Synthesis of [iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] (48) Cyclopropylacetylene (125 μL
148 mmol) dichloromethane (10 mL) and pentane (5 mL) room temperature reaction time 2 h
pale yellow solid (507 mg 651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 17
48 1H NMR (400 MHz CD2Cl2) δ 765 (m 3H m p-Ph) 717 (m 2H
o-Ph) 483 (m 3JH-H = 66 Hz 1H iPr) 222 (s 3H CH3) 158 (m 1H
H1) 146 (m 4H H2) 131 (d 3JH-H = 66 Hz 6H iPr) 112 (tt 3JH-H = 81
Hz 3JH-H = 51 Hz 1H H4) 057 - 050 (m 4H H5) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1642 (t 3JF-F = 20 Hz 1F p-C6F5) -
1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211(s equivCB)
13C1H NMR (101 MHz CD2Cl2) δ 1937 (N=C) 1486 (dm 1JC-F = 236 Hz CF) 1383 (dm 1JC-F = 243 Hz CF) 1368 (dm 1JC-F = 245 Hz CF) 1356 (ipso-Ph) 1320 (p-Ph) 1313 (m-
Ph) 1266 (o-Ph) 1258 (ipso-C6F5) 958 (C3) 599 (iPr) 218 (C1) 208 (iPr) 161 (CH3) 153
(C2) 84 (C5) 149 (C4) (CequivCB(C6F5)3 was not observed) Anal calcd () for C37H25BF15N C
5702 H 323 N 180 Found 5667 H 330 N 179
Synthesis of E-[iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] (49) 2-Ethynylthiophene (160
mg 148 mmol) dichloromethane (4 mL) and pentane (10 mL) room temperature reaction time
1 h pale pink solid (498 mg 0577 mmol 78) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 71
164
49 1H NMR (400 MHz C6D5Br) δ 738 (d 3JH-H = 45 Hz 1H H3)
733 (t 3JH-H = 72 Hz 1H H10) 731 (d 3JH-H = 45 Hz 1H H5) 726 (t 3JH-H = 72 Hz 2H H9) 693 (d 3JH-H = 38 Hz 1H H12) 674 (d 3JH-H =
53 Hz 1H H14) 667 (t 3JH-H = 45 Hz 1H H4) 664 (dd 3JH-H = 53
Hz 3JH-H = 38 Hz 1H H13) 660 (d 3JH-H = 72 Hz 2H H8) 436 (m 3JH-H = 66 Hz 1H H6) 256 (s 3H Me) 081 (d 3JH-H = 66 Hz 6H
iPr) 19F NMR (377 MHz C6D5Br) δ -1312 (m 2F o-C6F5) -1619 (t 3JF-F = 21 Hz 1F p-
C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -203 (s equivCB) 13C1H NMR
(101 MHz C6D5Br) δ 1724 (C1) 1486 (dm 1JC-F = 240 Hz CF) 1446 (C5) 1438 (C3) 1384
(dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 267 Hz CF) 1346 (C7) 1330 (C2) 1324 (C10)
1312 (C9) 1290 (C12) 1286 (C4) 1272 (C8) 1269 (C13) 1239 (C14) 593 (C6) 214 (Me)
201 (iPr) (C11 C15 ipso-C6F5 and CequivCB(C6F5)3 were not observed) Anal calcd () for
C39H21BF15NS2 C 5425 H 245 N 162 Found 5415 H 259 N 168
Synthesis of (C6F5)3BCequivC(C6H4)C(Me)=NPh2 (410) 14-Diethynylbenzene (934 mg 0740
mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 2 h orange solid
(508 mg 0629 mmol 85) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 760 (m 3H m p-Ph) 735 (m 4H o m-Ph) 729 (m 5H
C6H4 p-Ph) 706 (dm 3JH-H = 77 Hz 2H o-Ph) 277 (s 3H Me) 19F NMR (377 MHz
CD2Cl2) δ -1329 (m 2F o-C6F5) -1630 (t 3JF-F = 20 Hz 1F p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1877
(C=N) 1482 (dm 1JC-F = 236 Hz CF) 1433 (ipso-Ph) 1425 (ipso-Ph) 1383 (dm 1JC-F = 243
Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1364 (quaternary C for C6H4) 1322 (C6H4) 1317 (p-
Ph) 1314 (m-Ph) 1311 (p-Ph) 1308 (m-Ph) 1302 (C6H4) 1282 (quaternary C for C6H4)
1255 (o-Ph) 1244 (o-Ph) 1228 (ipso-C6F5) 937 (CequivCB(C6F5)3) 276 (Me) (CequivCB(C6F5)3
was not observed) Elemental analysis for this compound did not pass after repeated attempts
Synthesis of [tBu(Ph)NH2][PhCequivCB(C6F5)3] (411) tert-Butylaniline (111 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) pentane (10 mL) reaction time 16 h off-white solid
(560 mg 0733 mmol 99)
165
1H NMR (400 MHz CD2Cl2) δ 751 (tm 3JH-H = 77 Hz 1H H4) 741
(tm 3JH-H = 77 Hz 2H H3) 728 (m 2H H7) 727 (m 2H H6) 725 (m
1H H8) 684 (dm 3JH-H = 77 Hz 2H H2) 677 (br s 2H NH2) 113 (s
9H tBu) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5) -1622
(t 3JF-F = 21 Hz 1F p-C6F5) -1661 (m 2F m-C6F5) 11B NMR (128
MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1479 (dm 1JC-F =
236 Hz CF) 1384 (dm 1JC-F = 241 Hz CF) 1366 (dm 1JC-F = 243 Hz CF) 1319 (C7) 1314
(C4) 1310 (C1) 1307 (C3) 1296 (C6) 1283 (C8) 1258 (C5) 1237 (C2) 941 (C9) 654 (tBu)
262 (tBu) Anal calcd () for C36H21BF15N C 5664 H 277 N 183 Found 5608 H 297 N
174
Synthesis of [iPr2NH2][PhCequivCB(C6F5)3] (412) Diisopropylamine (750 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) toluene (10 mL) reaction time 4 h white solid (405
mg 566 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered solution
of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 727 (tm 3JH-H = 76 Hz 2H m-Ph) 721 (dm 3JH-H = 76 Hz
2H o-Ph) 718 (tm 3JH-H = 76 Hz 1H p-Ph) 505 (m 2H NH2) 332 (m 3JH-H = 64 Hz 2H
iPr) 114 (d 3JH-H = 64 Hz 12H iPr) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5)
-1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
208 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1317 (m-Ph) 1292 (o-Ph) 1276
(p-Ph) 511 (iPr) 197 (iPr) Anal calcd () for C32H21BF15N C 5373 H 296 N 196 Found
5318 H 304 N 194
4422 Procedures for hydroarylation of phenylacetylene
Compounds 413 and 414 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of
B(C6F5)3 (0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial
phenylacetylene (756 mg 0740 mol) was added over 1 min The solvent was then removed
under reduced pressure and the crude product was washed with pentane to yield the product as a
solid
166
Synthesis of (PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 (413) NN-Dibenzylaniline (202 mg
0740 mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 1 h yellow
solid (630 mg 0710 mmol 96) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 753 (t 3JH-H = 76 Hz 2H m-Ph) 746 (t 3JH-H = 73 Hz 4H benzylm-Ph) 741 (s 1H =CH) 734 (d 3JH-H = 76 Hz 2H o-Ph) 715 (d 3JH-H = 74 Hz 4H benzylo-Ph) 700 (m 3H p-Ph benzylp-Ph) 691 (d 3JH-H = 86 Hz 2H C6H4) 680 (d 3JH-H = 86
Hz 2H C6H4) 617 (br s 1H NH) 484 (dm JH-H = 126 Hz 2H CH2Ph) 472 (dm JH-H = 126
Hz 2H CH2Ph) 19F NMR (377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1644 (t 3JF-F = 19
Hz 1F p-C6F5) -1680 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -158 (s equivCB)
13C1H NMR (101 MHz CD2Cl2) partial δ 1521 (=CH) 1387 (ipso-Ph) 1317 (m-Ph) 1316
(benzylipso-Ph) 1302 (benzylo-Ph) 1300 (benzylm-Ph) 1292 (o-Ph) 1291 (C6H4) 1271 (benzylp-
Ph) 1206 (C6H4) 1256 (p-Ph) 647 (CH2Ph) Elemental analysis was not successful after
numerous attempts
Synthesis of iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 (414) N-isopropylanthracen-9-amine (170
mg 0740 mmol) dichloromethane (10 mL) room temperature reaction time 5 h bright yellow
solid (597 mg 0704 mmol 95) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 795 (s 1H C=NH) 785 (m 2H m-Ph) 778 (m 2H o-Ph)
773 (d 3JH-H = 83 Hz 1H C14H9) 762 (d 3JH-H = 83 Hz 1H C14H9) 759 (t 3JH-H = 83 Hz
1H C14H9) 758 (m 1H p-Ph) 689 (t 3JH-H = 83 Hz 1H C14H9) 680 (s 1H =CH) 671 (t 3JH-H = 83 Hz 2H C14H9) 603 (d 3JH-H = 83 Hz 2H C14H9) 544 (s 1H CHC(Ph)=CH) 454
(m 1H iPr) 178 (d 3JH-H = 66 Hz 3H iPr) 126 (d 3JH-H = 66 Hz 3H iPr) 19F NMR (377
MHz CD2Cl2) δ -1322 (m 2F o-C6F5) -1645 (t 3JF-F = 20 Hz 1F p-C6F5) -1681 (m 2F m-
C6F5) 11B NMR (128 MHz CD2Cl2) δ -163 (s equivCB) 13C1H NMR (125 MHz CD2Cl2)
partial δ 1707 (C=CH) 1503 (=CH) 1353 (m-Ph) 1308 (o-Ph) 1290 (C14H9) 1284 (p-Ph)
1276 (C14H9) 1274 (C14H9) 1265 (C14H9) 1255 (C14H9) 1224 (C14H9) 599 (CHC(Ph)=CH)
530 (iPr) 233 (iPr) 228 (iPr) Anal calcd () for C43H23BF15N C 6080 H 273 N 165
Found 6059 H 281 N 197
167
4423 Procedures for catalytic intermolecular hydroamination reactions
Compounds 415 - 425 were prepared in a similar fashion thus only one preparation is detailed
In the glovebox a 4 dram vial equipped with a stir bar was charged with diphenylamine (125
mg 740 μmol) (p-C6H4F)2NH (152 mg 740 μmol) or N-isopropylaniline (100 mg 740 μmol)
and B(C6F5)3 (38 mg 74 μmol) in toluene (4 mL) The respective alkyne (740 μmol) was added
at a rate of 10 molh via microsyringe (oils) or by weighing into a vial (solids) Total reaction
time was 10 h after which the reaction was worked up outside of the glovebox The solvent was
removed under vacuum and the crude mixture was dissolved in ethyl acetate (5 mL) and passed
through a short (4 cm) silica column previously treated with Et2NH The crude reaction mixtures
consisted of the starting materials (amine and alkyne) and the product The product was purified
by column chromatography using hexaneethyl acetate (61) as eluent
Compounds 426 - 428 were prepared with slight modifications to the procedure above The
reaction vial was cooled to -30 degC then placed in a pre-cooled -30 degC brass-well before addition
of the alkyne via microsyringe or by weighing into a vial The reaction vial was kept in the brass-
well and warmed up to RT before cooling down the reaction vial again and adding the
subsequent aliquot of alkyne Each addition of alkyne was made in a pre-cooled brass-well The
reactions were worked up similar to the procedure above
(415) Yellow solid (187 mg 620 μmol 84) 1H NMR (400 MHz
CD2Cl2) δ 744 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H5) 721 -713
(m 5H m-C6H5 H3) 712 - 706 (m 4H o-C6H5) 691 (tt 3JH-H = 72 Hz 4JH-H = 11 Hz 2H p-C6H5) 685 (td 3JH-H = 75 Hz 4JH-H = 18 Hz 1H
H4) 679 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H2) 501 (s 1H =CH2) 490 (s 1H =CH2)
376 (s 3H OCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1577 (C6) 1498 (C=CH2) 1481
(ipso-C6H5) 1312 (C5) 1296 (C3) 1290 (m-C6H5) 1283 (C1) 1248 (o-C6H5) 1227 (p-C6H5)
1205 (C4) 1112 (C2) 1077 (=CH2) 558 (OCH3) HRMS-ESI+ mz [M+H]+ calcd for
C21H20NO 30215449 Found 30215453
168
(416) Off-while solid (146 mg 510 μmol 69) 1H NMR (600 MHz
CD2Cl2) δ 750 -743 (m 1H H5) 724 - 716 (tm 3JH-H = 74 Hz 4H m-
C6H5) 715 - 708 (m 6H o-C6H5 H3 H4) 706 -701 (m 1H H2) 700-
692 (tm 3JH-H = 74 Hz 2H p-C6H5) 484 (s 1H =CH2) 470 (s 1H
=CH2) 252 (s 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1526 (C=CH2) 1476 (ipso-
C6H5) 1390 (C1) 1364 (C6) 1309 (C5 C2) 1291 (m-C6H5) 1281 (C4) 1259 (C3) 1255 (o-
C6H5) 1233 (p-C6H5) 1051 (=CH2) 206 (CH3) HRMS-ESI+ mz [M+H]+ calcd for C21H20N
28615957 Found 28615986
(417) Orange solid (147 mg 460 μmol 62) 1H NMR (400 MHz
CD2Cl2) δ 870 (d 3JH-H = 85 Hz 1H H10) 777 (d 3JH-H = 85 Hz 1H
H7) 771 - 768 (m 2H H2 H4) 752 (tm 3JH-H = 85 Hz 1H H9) 743
(tm 3JH-H = 85 Hz 1H H8) 736 (tm 3JH-H = 85 Hz 1H H3) 722 -
709 (m 8H o m-C6H5) 692 (m 2H p-C6H5) 507 (s 1H =CH2)
494 (s 1H =CH2) 13C1H NMR (101 MHz CD2Cl2) δ 1513 (C=CH2) 1478 (ipso-C6H5)
1371 (C1) 1341 (C6) 1319 (C5) 1292 (m-C6H5) 1288 (C7 C2) 1281 (C4) 1266 (C9) 1260
(C8) 1256 (C10) 1254 (C3) 1253 (o-C6H5) 1229 (p-C6H5) 1067 (=CH2) HRMS-ESI+ mz
[M+H]+ calcd for C24H20N 32215957 Found 32216049
(418) Yellow oil (148 mg 550 μmol 74) 1H NMR (500 MHz
CD2Cl2) δ 757 (dm 3JH-H = 73 Hz 2H H2) 728 - 726 (m 3H H3 H4)
720 (tm 3JH-H = 74 Hz 4H m-C6H5) 709 (dm 3JH-H = 74 Hz 4H o-
C6H5) 695 (tm 3JH-H = 74 Hz 2H p-C6H5) 523 (s 1H =CH2) 486 (s
1H =CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1533 (C=CH2) 1482 (ipso-C6H5) 1394 (C1)
1293 (m-C6H5) 1286 (C3) 1285 (C4) 1276 (C2) 1243 (o-C6H5) 1228 (p-C6H5) 1082
(=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H18N 2721433 Found 2721443
(419) Orange solid (134 mg 390 μmol 52)1H NMR (500 MHz
CD2Cl2) δ 753 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H
H2) 744 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H H5)
723 (td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H3) 720 - 715 (m 8H om-
C6H5) 706 (pseudo td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H4) 697 (tt 3JH-H = 70 Hz 4JH-H =
16 Hz 2H p-C6H5) 493 (d 2JH-H = 04 Hz 1H =CH2) 483 (d 2JH-H = 04 Hz 1H =CH2)
169
13C1H NMR (125 MHz CD2Cl2) δ 1513 (C=CH2) 1473 (ipso-C6H5) 1399 (C1) 1337 (C5)
1327 (C2) 1296 (C4) 1291 (m-C6H5) 1275 (C3) 1256 (o-C6H5) 1235 (p-C6H5) 1224 (C6)
1059 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H17BrN 35005444 Found 35005379
(420) Orange solid (191 mg 500 μmol 67) 1H NMR (500 MHz
CD2Cl2) δ 750 (ddm 3JH-H = 78 Hz 4JH-H = 18 Hz 1H H2) 743
(ddm 3JH-H = 78 Hz 4JH-H = 12 Hz 1H H5) 724 (tdm 3JH-H = 78
Hz 4JH-H = 12 Hz 1H H4) 712 (dm 3JH-H = 80 Hz 4H H8) 707
(dm 3JH-H = 78 Hz 1H H3) 690 (tm 3JH-H = 80 Hz 4H H9) 479 (s
1H =CH2) 471 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1202 (tt 3JF-H = 88 Hz 4JF-H
= 52 Hz p-C6H4F) 13C1H NMR (125 MHz CD2Cl2) δ 1593 (d 1JC-F = 242 Hz C10) 1518
(C=CH2) 1433 (d 4JCF = 29 Hz C7) 1395 (C1) 1337 (C5) 1328 (C2) 1298 (C3) 1276 (C4)
1272 (d 3JC-F = 79 Hz C8) 1223 (C6) 1159 (d 2JC-F = 22 Hz C9) 1041 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C20H15BrF2N 38603559 Found 38603477
(421) Yellow oil (188 mg 580 μmol 78) 1H NMR (400 MHz
CD2Cl2) δ 748 (pseudo td 3JH-H = 77 Hz J = 19 Hz 1H H2) 721
(m 1H H4) 707 - 702 (m 5H H3 H8) 697 (m 1H H5) 691 (m
4H H9) 500 (d 5JF-H = 15 Hz 1H =CH2) 488 (s 1H =CH2) 19F
NMR (377 MHz CD2Cl2) δ -1162 (dm 3JF-H = 119 Hz 1F CF of
C6) -1207 (tm 3JF-H = 97 Hz 2F p-C6H4F) 13C1H NMR (101 MHz CD2Cl2) δ 1605 (d 1JC-F = 249 Hz CF of C6) 1591 (d 1JC-F = 244 Hz C10) 1475 (C=CH2) 1438 (d 4JC-F = 28
Hz C7) 1311 (d 3JC-F = 30 Hz C2) 1302 (d 3JC-F = 85 Hz C4) 1271 (d 2JC-F = 116 Hz C1)
1264 (d 3JC-F = 81 Hz C8) 1244 (d 4JC-F = 37 Hz C3) 1162 (d 2JC-F = 22 Hz C5) 1160 (d 2JC-F = 22 Hz C9) 1077 (d 4JC-F = 36 Hz =CH2) HRMS-ESI+ mz [M+H]+ calcd for
C20H15F3N 32611566 Found 32611576
(422) Yellow oil (125 mg 400 μmol 54) 1H NMR (400 MHz
CD2Cl2) δ 718 (dd 3JH-H = 51 4JH-H = 12 Hz 1H H4) 712 (dd 3JH-H
= 36 Hz 4JH-H = 12 Hz 1H H2) 705 - 701 (m 4H H6) 695 - 689
(m 5H H3 H7) 526 (s 1H =CH2) 469 (s 1H =CH2) 19F NMR (377
MHz CD2Cl2) δ -1209 (m 3JF-H = 90 Hz p-C6H4F) 13C1H NMR
(101 MHz CD2Cl2) δ 1589 (d 1JC-F = 241 Hz C8) 1473 (C=CH2) 1442 (d 4JC-F = 26 Hz
170
C5) 1436 (C1) 1276 (C3) 1265 (C2) 1258 (C4) 1257 (d 3JC-F = 80 Hz C6) 1162 (d 2JC-F =
22 Hz C7) 1068 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 31408150 Found
31408200
(423) Yellow oil (104 mg 430 μmol 58) 1H NMR (400 MHz
CD2Cl2) δ 715 (tm 3JH-H = 79 Hz 2H m-C6H5) 712 (dd 3JH-H = 53 Hz 4JH-H = 13 Hz 1H H4) 701 (dd 3JH-H = 35 Hz 4JH-H = 13 Hz 1H H2)
693 (dm 3JH-H = 79 Hz 2H o-C6H5) 685 (m 1H H3) 681 (tm 3JH-H =
79 Hz 1H p-C6H5) 531 (s 1H =CH2) 484 (s 1H =CH2) 426 (m 3JH-H = 66 Hz 1H iPr)
125 (d 3JH-H = 66 Hz 6H iPr) 13C1H NMR (101 MHz CD2Cl2) δ 1466 (ipso-C6H5) 1456
(C1) 1446 (C=CH2) 1296 (m-C6H5) 1274 (C2) 1260 (C3) 1253 (C4) 1208 (o-C6H5) 1206
(p-C6H5) 502 (iPr) 211 (iPr) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 2441154
Found 2441166
(424) Pale yellow solid (206 mg 560 μmol 75) 1H NMR (600
MHz CD2Cl2) δ 881 (dm 3JH-H = 78 Hz 1H H14) 865 (dm 3JH-H =
78 Hz 1H H11) 860 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H10)
797 (s 1H H2) 787 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H7)
766-761 (m 3H H9 H12 H13) 757 (pseudo td 3JH-H = 78 Hz 4JH-H
= 14 Hz 1H H8) 723 (m 4H o-C6H5) 715 (t 3JH-H = 73 Hz 4H m-C6H5) 692 (tt 3JH-H =
73 Hz 4JH-H = 12 Hz 2H p-C6H5) 512 (s 1H =CH2) 503 (s 1H =CH2) 13C1H NMR (125
MHz CD2Cl2) δ 1516 (C=CH2) 1476 (ipso-C6H5) 1357 (C1) 1317 (C3) 1309 (C6) 1307
(C5) 1306 (C4) 1294 (C2) 1292 (m-C6H5) 1291 (C7) 1273 (C9) 1271 (C8 C13) 1268 (C12)
1264 (C14) 1255 (o-C6H5) 1235 (p-C6H5) 1232 (C11) 1228 (C10) 1060 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C28H22N 37217522 Found 37217485
(425) Pale yellow solid (228 mg 560 μmol 75) 1H NMR (400
MHz CD2Cl2) δ 874 (dm 3JH-H = 74 Hz 1H H14) 866 (dm 3JH-H
= 74 Hz 1H H11) 861 (dm 3JH-H = 74 Hz 1H H10) 795 (s 1H
H2) 788 (dm 3JH-H = 74 Hz 1H H7) 767- 762 (m 3H H9 H12
H13) 759 (pseudo td 3JH-H = 74 Hz 4JH-H = 12 Hz 1H H8) 718
(m 4H H16) 686 (m 4H H17) 499 (s 1H =CH2) 495 (s 1H =CH2) 19F NMR (377 MHz
CD2Cl2) δ -1200 (tt 3JF-H = 84 Hz 4JF-H = 42 Hz p-C6H4F) 13C1H NMR (125 MHz
171
CD2Cl2) δ 1592 (d 1JC-F = 240 Hz C18) 1519 (C=CH2) 1437 (d 4JC-F = 26 Hz C15) 1353
(C1) 1316 (C3) 1308 (C6) 1307 (C5) 1306 (C4) 1296 (C2) 1291 (C7) 1274 (C9) 1272 (C8
C12) 1271 (d 3JC-F = 83 Hz C16) 1269 (C13) 1262 (C14) 1233 (C11) 1228 (C10) 1161 (d 2JCF = 219 Hz C17) 1043 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C28H20F2N 40815638
Found 40815576
(426) Yellow oil (178 mg 550 μmol 74) 1H NMR (400 MHz
CD2Cl2) δ 735 (dm 3JH-H = 77 Hz 1H H2) 727- 723 (m 2H H3
H6) 701 (m 4H H8) 697- 691 (m 5H H4 H9) 516 (s 1H =CH2)
478 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1141 (m 1F
CF of C5) -1205 (m 2F p-C6H4F) 13C1H NMR (101 MHz
CD2Cl2) δ 1632 (d 1JC-F = 245 Hz C5) 1592 (d 1JC-F = 244 Hz C10) 1522 (d 4JC-F = 25 Hz
C=CH2) 1442 (d 4JC-F = 28 Hz C7) 1417 (d 3JC-F = 76 Hz C1) 1303 (d 3JC-F = 84 Hz C3)
1261 (d 3JC-F = 81 Hz C8) 1235 (d 4JC-F = 28 Hz C2) 1162 (d 2JC-F = 22 Hz C9) 1154 (d 2JC-F = 21 Hz C4) 1145 (d 2JC-F = 21 Hz C6) 1074 (=CH2) HRMS-ESI+ mz [M+H]+ calcd
for C20H15F3N 32611566 Found 32611485
(427) White solid (154 mg 500 μmol 68) 1H NMR (500 MHz
CD2Cl2) δ 722 (tm 3JH-H = 73 Hz 4H m-C6H5) 710 (m 2H H2) 705
(dm 3JH-H = 73 Hz 4H o-C6H5) 699 (tm 3JH-H = 73 Hz 2H p-C6H5)
670 (tt 3JH-H = 89 Hz 4JH-H = 24 Hz 1H H4) 525 (s 1H =CH2) 490
(s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1107 (t 3JF-H = 81 Hz m-C6H3F2) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (d 1JC-F = 248 Hz C3) 1515 (t 4JC-F = 28 Hz C=CH2)
1477 (ipso-C6H5) 1435 (d 3JC-F = 92 Hz C1) 1295 (m-C6H5) 1244 (o-C6H5) 1234 (p-
C6H5) 1105 (d 2JC-F = 21 Hz C2) 1093 (s =CH2) 1037 (t 2JC-F = 25 Hz C4) HRMS-ESI+
mz [M+H]+ calcd for C20H16F2N 30812508 Found 30812511
(428) Yellow oil (193 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 783 (ddq 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H6)
774 (ddq 3JH-H = 78 Hz 4JH-H = 12 Hz 6JF-H = 06 Hz 1H H2) 749
(dddq 3JH-H = 78 Hz 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H4)
739 (pseudo tq 3JH-H = 78 Hz 5JF-H = 07 Hz 1H H3) 721 (tm 3JH-H = 78 Hz 4H m-C6H5)
707 (dm 3JH-H = 78 Hz 4H o-C6H5) 697 (tm 3JH-H = 78 Hz 2H p-C6H5) 526 (d 1H 2JH-H
172
= 07 Hz =CH2) 493 (d 2JH-H = 07 Hz =CH2) 19F NMR (377 MHz CD2Cl2) δ -630 (s CF3)
13C1H NMR (125 MHz CD2Cl2) δ 1517 (C=CH2) 1474 (ipso-C6H5) 1400 (C1) 1304 (q 5JC-F = 13 Hz C2) 1304 (q 2JC-F = 32 Hz C5) 1290 (m-C6H5) 1287 (C3) 1247 (q 3JC-F = 38
Hz C4) 1242 (o-C6H5) 1241 (q 1JC-F = 271 Hz CF3) 1239 (q 3JC-F = 38 Hz C6) 1228 (p-
C6H5) 1083 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C21H17F3N 34013131 Found
34013065
4424 Procedures for tandem hydroamination and hydrogenation reactions
A general procedure is provided for the preparation of compounds 429 and 430 Following the
10 h catalytic hydroamination reaction in the glovebox the reaction mixture was transferred into
an oven-dried Teflon screw cap glass tube The reaction tube was degassed once through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The tube
was placed in an 80 ordmC oil bath for 14 h The solvent was removed under vacuum and the
mixture was dissolved in ethyl acetate (5 mL) and passed through a short (4 cm) silica column
previously treated with Et2NH The crude reaction mixtures consisted of the starting materials
(amine and alkyne) and the product The product was purified by column chromatography using
hexaneethyl acetate (61) as eluent
Alternative hydrogenation procedure using 5 mol Mes2PH(C6F4)BH(C6F5)2
Mes2PH(C6F4)BH(C6F5)2 (28 mg 37 μmol) was added to the reaction mixture before being
transferred into the glass tube The tube was filled with H2 and placed in an 80 ordmC oil bath The
reaction was stopped after 3 h at 80 ordmC and worked up similar to the procedure above
(429) Yellow oil (186 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 728 - 720 (m 2H H2 H5) 708 - 700 (m 2H H3 H4)
692 (m 4H H9) 680 (m 4H H8) 545 (q 3JH-H = 70 Hz C(CH3)H)
138 (d 3JH-H = 70 Hz C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -
1186 (m 1F F of C6) -1224 (m 2F F of C10) 13C1H NMR (125
MHz CD2Cl2) δ 1610 (d 1JC-F = 247 Hz C6) 1588 (d 1JC-F = 241 Hz C10) 1436 (d 4JC-F =
26 Hz C7) 1310 (d 2JC-F = 131 Hz C1) 1291 (d 2JC-F = 85 Hz C5) 1284 (d 3JC-F = 43 Hz
C2) 1249 (d 3JC-F = 79 Hz C8) 1244 (d 4JC-F = 35 Hz C3) 1159 (d 2JC-F = 22 Hz C9) 1157
173
(d 3JC-F = 22 Hz C4) 517 (C(CH3)H) 197 (C(CH3)H) HRMS-ESI+ mz [M+H]+ calcd for
C20H17F3N 32813131 Found 32813189
(430) Yellow oil (146 mg 470 μmol 64) 1H NMR (500 MHz
CD2Cl2) δ 724 (tm 3JH-H = 78 Hz 4H m-C6H5) 699 (m 4H H2 p-
C6H5) 688 (dm 3JH-H = 78 Hz 4H o-C6H5) 671 (tt 3JF-H = 89 Hz 4JH-H = 24 Hz 1H H4) 524 (d 3JH-H =70 Hz 1H C(CH3)H) 145 (d
3JH-H = 70 Hz 3H C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -1105 (m F of C3) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (dd 1JC-F = 248 Hz 3JC-F = 13 Hz C3) 1496 (t 3JC-F = 79
Hz C1) 1472 (ipso-C6H5) 1297 (m-C6H5) 1235 (o-C6H5) 1212 (p-C6H5) 1100 (dd 2JC-F =
20 Hz 4JC-F = 47 Hz C2) 1202 (t 2JC-F = 27 Hz C4) 579 (C(CH3)H) 203 (C(CH3)H)
HRMS-ESI+ mz [M+H]+ calcd for C20H18F2N 31014073 Found 31014081
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions
Compounds 431 and 432 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 25 mL Schlenk flask equipped with a stir bar was charged with a
toluene (5 mL) solution of B(C6F5)3 (0100 g 0190 mmol) and the respective alkynyl aniline
(0190 mmol) The solution was heated for 2 h at 50 degC and the solvent was subsequently
removed under reduced pressure The crude oil was washed with pentane (2 times 5 mL) to yield the
product as a white solid
Synthesis of C6H5N(CH2)3CCH2B(C6F5)3 (431) N-(Pent-4-ynyl)aniline (300 mg 0190
mmol) product (120 mg 0179 mmol 94)
1H NMR (400 MHz CD2Cl2) δ 746 (m 3H m p-Ph) 691 (dm 3JH-H =
86 Hz 2H o-Ph) 416 (t 3JH-H = 78 Hz 2H H3) 333 (br q 2JB-H = 54
Hz 2H CH2B) 311 (t 3JH-H = 78 Hz 2H H1) 215 (quint 3JH-H = 78 Hz
2H H2) 19F NMR (377 MHz CD2Cl2) δ -1325 (m 2F o-C6F5) -1601 (t 3JF-F = 21 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -134 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 1942 (C=N) 1476 (dm 1JC-F = 241 Hz CF)
1392 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1348 (ipso-Ph) 1324 (p-Ph)
174
1311 (m-Ph) 1231 (o-Ph) 1189 (ipso-C6F5) 651 (C3) 411 (C1) 185 (CH2B C2) Anal
calcd () for C29H13BF15N C 5189 H 195 N 209 Found 5140 H 219 N 191
Synthesis of C6H5N(CH2)4CCH2B(C6F5)3 (432) N-(Hex-5-ynyl)aniline (340 mg 0190
mmol) product (129 mg 0188 mmol 99) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC
1H NMR (600 MHz CD2Cl2) δ 745 (tt 3JH-H = 75 Hz 4JH-H = 22 Hz
1H p-Ph) 740 (tm 3JH-H = 75 Hz 2H m-Ph) 663 (dm 3JH-H = 75 Hz
2H o-Ph) 372 (t 3JH-H = 73 Hz 2H H4) 316 (br q 2JB-H = 63 Hz 2H
CH2B) 275 (t 3JH-H = 73 Hz 2H H1) 197 (m 2H H3) 176 (m 2H
H2) 19F NMR (377 MHz CD2Cl2) δ -1320 (m 2F o-C6F5) -1611 (t 3JF-
F = 20 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -130 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 2005 (C=N) 1481 (dm 1JC-F = 241 Hz CF)
1420 (ipso-Ph) 1384 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1301 (m p-
Ph) 1226 (ipso-C6F5) 1237 (o-Ph) 574 (C4) 380 (CH2B) 326 (C1) 213 (C3) 175 (C2)
Anal calcd () for C30H15BF15N C 5228 H 221 N 204 Found 5206 H 272 N 177
Synthesis of [2-MeC8H6N(Ph)][HB(C6F5)3] (433) In the glovebox a 25 mL Schlenk flask
equipped with a stir bar was charged with a toluene (5 mL) solution of B(C6F5)3 (0100 g 0190
mmol) and N-(2-ethynylbenzyl)aniline (390 mg 0190 mmol) The solution was heated for 16 h
under H2 (4 atm) at 80 degC The solvent was subsequently removed under reduced pressure The
crude oil was washed with pentane (2 times 5 mL) to yield the product as a white solid (740 mg
0103 mmol 54)
1H NMR (600 MHz CD2Cl2) δ 812 (dm 3JH-H = 79 Hz JH-H = 10
Hz 1H H9) 799 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H H8) 786 (dm 3JH-H = 79 Hz 1H H6) 782 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H
H7) 773 - 769 (m 3H H2 and H3) 745 (dm 3JH-H = 76 Hz H1) 556
(q JH-H = 26 Hz 2H H4) 353 (br 1H HB) 289 (t JH-H = 26 Hz Me) 19F NMR (564 MHz
CD2Cl2) δ -1341 (br 2F o-C6F5) -1644 (br 1F p-C6F5) -1674 (br 2F m-C6F5) 11B1H
NMR (192 MHz CD2Cl2) δ -252 (s HB) 13C1H NMR (151 MHz CD2Cl2) 1820 (N=C)
1480 (dm 1JC-F = 247 Hz CF) 1437 (C10) 1373 (C7) 1366 (dm 1JC-F = 241 Hz CF) 1362
(dm 1JC-F = 241 Hz CF) 1347 (ipso-Ph) 1337 (C5) 1322 (C3) 1308 (C2) 1306 (C8) 1266
NB(C6F5)3
4
3
2
1
175
(C9) 1247 (C1) 1234 (C6) 657 (C4) 149 (Me) (ipso-C6F5 was not observed) Anal calcd ()
for C33H15BF15N C 5495 H 210 N 194 Found C 5502 H 212 N 218
Compounds 434 - 438 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 25 mL Schlenk bomb equipped with a stir bar was charged with a toluene (2
mL) solution of B(C6F5)3 (20 mg 40 μmol) and the alkynyl aniline (039 mmol) The solution
was heated for 16 h under H2 (4 atm) at 80 degC The solvent was subsequently removed under
reduced pressure The crude oil was washed with pentane (2 times 5 mL) and purified by column
chromatography using hexaneethyl acetate (61) as eluent
Synthesis of 2-MeC4H7N(Ph) (434) N-(Pent-4-ynyl)aniline (600 mg 0390 mmol) product
(427 mg 0265 mmol 68)
1H NMR (500 MHz CD2Cl2) δ 718 (t 3JH-H = 78 Hz 2H m-Ph) 660 (tt 3JH-H =
78 Hz 4JH-H = 11 H 1H p-Ph) 657 (d 3JH-H = 78 Hz 2H o-Ph) 286 (m 3JH-H =
61 Hz 1H NCHCH3) 282 (ddd 2JH-H = 88 Hz 3JH-H = 78 Hz 35 Hz 1H H3)
254 (pseudo q 3JH-H = 83 Hz 1H H3) 211 - 162 (m 4H H1 and H2) 099 (d 3JH-H
= 61 Hz 3H Me) 13C1H NMR (151 MHz CD2Cl2) δ 1474 (ipso-Ph) 1289 (m-Ph) 1148
(p-Ph) 1116 (o-Ph) 540 (NCHCH3) 478 (C3) 330 (C1) 265 (C2) 197 (Me) HRMS-
DART+ mz [M+H]+ calcd for C11H15N 16212827 Found 16212755
Synthesis of 2-MeC5H9N(Ph) (435) N-(Hex-5-ynyl)aniline (682 mg 0390 mmol) product
(451 mg 0257 mmol 66)
1H NMR (500 MHz CD2Cl2) δ 723 (t 3JH-H = 81 Hz 2H m-Ph) 693 (d 3JH-H =
81 Hz 2H o-Ph) 680 (tt 3JH-H = 81 Hz 4JH-H = 11 H 1H p-Ph) 394 (m 1H
NCHCH3) 323 (dt 2JH-H = 121 Hz 3JH-H = 44 Hz 1H H4) 297 (dm 2JH-H = 121
Hz 1H H4) 190 - 160 (m 6H H1 H2 H3) 100 (d 3JH-H = 672 3H Me) 13C1H
NMR (151 MHz CD2Cl2) δ 1516 (ipso-Ph) 1288 (m-Ph) 1187 (p-Ph) 1173 (o-
Ph) 512 (NCHCH3) 446 (C4) 317 (C1) 261 (C3) 198 (C2) 134 (Me) HRMS- DART+ mz
[M+H]+ calcd for C12H17NO 17614392 Found 17614338
176
Synthesis of 2-MeC5H9N(p-FC6H4) (436) 4-Fluoro-N-(hex-5-yn-1-yl)aniline (745 mg 0390
mmol) product (542 mg 0281 mmol 72)
1H NMR (400 MHz C6D5Br) δ 652 (t JH-H = 88 Hz 2H m-H of C6H4F) 637 (dd 3JH-H = 88 Hz 4JH-F = 48 Hz 2H o-H of C6H4F) 306 (m 1H NCHCH3) 241 (m
1H H4) 135 (m 1H H1) 121 (m 1H H3) 113 (m 2H H23) 102 (m 1H H2)
101 (m 1H H2) 045 (d 3JH-H = 65 Hz 3H CH3) 19F NMR (377 MHz C6D5Br)
δ -1235 (s 1F C6H4F) 13C1H NMR (100 MHz C6D5Br) δ 1582 (q 1JC-F = 297
Hz p-C6H4F) 1479 (ipso-C6H4F) 1202 (d 3JC-F = 77 Hz o-C of C6H4F) 1150 (d 3JC-F = 227 Hz m-C of C6H4F) 518 (NCHCH3) 470 (C4) 321 (C1) 260 (C3) 203 (C2) 146
(CH3) HRMS- ESI + mz [M+H]+ calcd for C12H16NF 1941340 Found 1941337
Synthesis of 2-MeC5H9N(p-CH3OC6H4) (437) N-(Hex-5-yn-1-yl)-4-methoxyaniline (792 mg
0390 mmol) product (416 mg 0203 mmol 52)
1H NMR (500 MHz C6D5Br) δ 712 (d 3JH-H = 85 Hz 2H m-H of C6H4OCH3)
700 (d 3JH-H = 85 Hz 2H o-H of C6H4OCH3) 374 (s 3H OCH3) 349 (m 1H
NCHCH3) 309 (m 1H H4) 302 (m 1H H4) 194 (m 1H H1) 184 (m 1H H3)
178 (m 1H H2) 176 (m 1H H3) 161 (m 1H H1) 158 (m 1H H2) 106 (d 3JH-
H = 65 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1542 (p-C6H4OCH3)
1457 (ipso-C6H4OCH3) 1221 (m-C of C6H4OCH3) 1139 (o-C of C6H4OCH3) 546
(OCH3) 534 (NCHCH3) 496 (C4) 331 (C1) 264 (C3) 214 (C2) 160 (CH3) HRMS-ESI+
mz [M+H]+ calcd for C13H19NO 2061539 Found 2061539
Synthesis of 2-MeC8H7N(Ph) (438) N-(2-Ethynylbenzyl)aniline (808 mg 0390 mmol)
product (571 mg 0273 mmol 70)
1H NMR (400 MHz CD2Cl2) δ 778 (d 3JH-H = 77 Hz 1H C6H4) 745 - 737 (m
5H m-Ph C6H4) 707 (t 3JH-H = 77 Hz 1H p-Ph) 703 (d 3JH-H = 77 Hz 2H o-
Ph) 510 (q 3JH-H = 66 Hz 1H NCH(CH3)) 483 (d 2JH-H = 138 Hz 1H CH2)
463 (d 2JH-H = 138 Hz 1H CH2) 154 (d 3JH-H = 66 Hz 3H CH3) 13C1H NMR
(151 MHz CD2Cl2) δ 1435 (ipso-Ph) 1376 (C1) 1343 (C6) 1297 (m-Ph) 1283
177
(C34) 1245 (C2) 1226 (p-Ph) 1222 (C5) 1161 (o-Ph) 641 (NCH(CH3) 563 (CH2) 182
(CH3) HRMS-DART+ mz [M+H]+ calcd for C15H15N 21012827 Found 21012767
4426 Procedures for reactions with ethynylphosphines
Synthesis of trans-Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 (439) In the glove box a 4 dram
vial equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg
0740 mmol) and iPrNHPh (100 mg 0740 mmol) To the vial Mes2PCequivCH (440 mg 0148
mmol) was added and the reaction was left at RT for 16 h The solvent was removed under
reduced pressure and the crude product was washed with pentane to yield the product as a pale
yellow solid (717 mg 0651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 771 (td JP-H = 286 Hz 3JH-H = 172 Hz 1H =CH) 698 (d 4JPH = 49 Hz 4H Mes) 689 (d 4JPH = 32 Hz 4H Mes) 574 (ddd 2JP-H = 273 Hz 3JH-H =
172 3JP-H = 44 Hz 1H =CH) 235 (s 6H Mes) 229 (s 6H Mes) 223 (s 12H Mes) 218 (s
12H Mes) 19F NMR (377 MHz CD2Cl2) δ -1329(m 2F o-C6F5) -1616 (t 3JF-F = 21 Hz 1F
p-C6F5) -1663 (m 2F m-C6F5) 31P1H NMR (162 MHz CD2Cl2) δ -115 (br s PMes2) -143
(d JP-P = 82 Hz PMes2) 11B NMR (128 MHz CD2Cl2) δ -211 (CB) 13C1H NMR (101
MHz CD2Cl2) partial δ 1540 (d 1JC-P = 31 Hz Mes) 1470 (d 1JC-F = 248 Hz CF) 1437 (d
JC-P = 28 Hz Mes) 1417 (d JC-P = 150 Hz Mes) 1413 (d JC-P = 113 Hz Mes) 1393 (Mes)
1321 (d 3JC-P = 14 Hz Mes) 1303 (d 3JC-P = 56 Hz Mes) 1260 (d JC-P = 11 Hz Mes) 1178
(dd 2JC-P = 99 Hz 3JC-P = 27 Hz =CH) 1120 (dd 2JC-P = 85 Hz 3JC-P = 121 Hz =CH) 219 (d 3JC-P = 68 Hz Mes) 218 (d 3JC-P = 14 Hz Mes) 201 (d 5JC-P = 18 Hz Mes) 198 (Mes)
Anal calcd () for C58H46BF15P2 C 6329 H 421 Found C 6282 H 411
Synthesis of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 (440) In the glove box a 4 dram vial
equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg 0144
mmol) To the vial tBu2PCequivCH (250 mg 0148 mmol) was added and the reaction was left at
RT for 16 h The solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as an off-white solid (580 mg 0570 mmol 77)
Crystals suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC
178
1H NMR (600 MHz CD2Cl2) δ 777 (ddd 2JP-H = 46 Hz 3JH-H =15 Hz 3JP-H = 36 Hz 1H
=CH) 650 (ddd 2JP-H = 28 Hz 3JP-H = 19 Hz 3JH-H =15 Hz 1H =CH) 144 (d 3JP-H = 17 Hz
18H tBu) 101 (d 3JP-H = 11 Hz 18H tBu) 19F NMR (564 MHz CD2Cl2) δ -1322 (m 2F o-
C6F5) -1618 (t 3JF-F = 20 Hz 1F p-C6F5) -1665 (m 2F m-C6F5) 31P1H NMR (242 MHz
CD2Cl2) δ 215 (PtBu2) 251 (PtBu2) 11B NMR (192 MHz CD2Cl2) -212 (CB) 13C1H
NMR (151 MHz CD2Cl2) partial δ 1620 (dd 1JC-P = 42 Hz 2JC-P = 32 Hz =CH) 1210 (dd 1JC-P = 82 Hz 2JC-P = 21 Hz =CH) 371 (d 1JC-P = 48 Hz tBu) 325 (d 1JC-P = 22 Hz tBu) 292
(d 2JC-P = 14 Hz tBu) 266 (tBu) Anal calcd () for C38H38BF15P2 C 5354 H 449 Found C
5314 H 432
Compounds 441 and 442 were prepared following the same procedure In the glove box a
Schlenk tube equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of HB(C6F5)2
(100 mg 0289 mmol) and the appropriate alkynyl-substituted pinacolborane (0289 mmol) was
added at once After 5 minutes Ph2PH (538 mg 0289 mmol) was added to the vial The
reaction was left at RT for 16 h The solvent was then removed under reduced pressure and
pentane (5 mL) was added to the crude oil resulting in precipitate The pentane soluble fraction
was separated from the precipitate concentrated and placed in a -30 degC freezer to give the
product as colourless crystals
Synthesis of Bu(H)Ph2PC-C(H)B(C6F5)2Bpin (441) CH3(CH2)3CequivCBpin (606 mg 0289
mmol) product (175 mg 0237 mmol 82)
1H NMR (600 MHz CD2Cl2) δ 766 (m 2H o-Ph) 757 (tm 3JH-H = 77 Hz 1H p-Ph) 747
(tm 3JH-H = 72 Hz 1H p-Ph) 742 (m 2H m-Ph) 736 (m 2H m-Ph) 733 (m 2H o-Ph) 353
(m 1H CHP) 290 (d 2JH-H = 116 Hz 1H CH2CHP) 278 (d 2JH-H = 116 Hz 1H CH2CHP)
148 (m 1H CHB) 133 (m 2H CH2) 118 (m 2H CH2) 102 (s 6H CH3) 098 (s 6H CH3)
078 (t 3JH-H = 72 Hz 3H CH3) 19F NMR (564 MHz CD2Cl2) δ -1292 (m 2F o-C6F5) -
1328 (m 2F o-C6F5) -1665 (m 2F m-C6F5) -1585 (t 3JF-F = 20 Hz 1F p-C6F5) -1605 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) -1653 (m 2F m-C6F5) 31P1H NMR (242
MHz CD2Cl2) δ 322 (br) 11B NMR (192 MHz CD2Cl2) δ 337 (Bpin) -66 (B(C6F5)2)
13C1H NMR (151 MHz CD2Cl2) partial δ 1362 (d 2JC-P = 91 Hz o-Ph) 1318 (d 4JC-P = 29
Hz p-Ph) 1314 (d 2JC-P = 81 Hz o-Ph) 1313 (d 4JC-P = 28 Hz p-Ph) 1285 (d 3JC-P = 95
Hz m-Ph) 1279 (d 3JC-P = 10 Hz m-Ph) 1279 (d 1JC-P = 332 Hz ipso-Ph) 1238 (d 1JC-P =
179
34 Hz ipso-Ph) 824 (C(CH3)2) 346 (d 1JC-P = 37 Hz CHP) 301 (d 2JC-P = 80 Hz CH2CHP)
290 (d 3JC-P = 49 Hz CH2) 246 (BpinCH3) 242 (BpinCH3) 224 (CH2) 158 (CHB) 079
(CH3) Anal calcd () for C36H33B2F10O2P C 5841 H 449 Found 5808 H 437
Synthesis of Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin (442) CH2=C(CH3)CequivCBpin (567
mg 0289 mmol) product (153 mg 0211 mmol 73) Crystals suitable for X-ray diffraction
were grown from pentane at -30 ordmC
1H31P NMR (600 MHz CD2Cl2) δ 764 (tt 3JH-H = 73 Hz 4JH-H = 14 Hz 1H p-Ph) 755 (d 3JH-H = 73 Hz 2H o-Ph) 749 (t 3JH-H = 75 Hz 2H m-Ph) 727 (tt 3JH-H = 75 Hz 4JH-H = 12
Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 680 (d 3JH-H = 75 Hz 2H o-Ph) 645 (br 1H
=CH) 320 (d 2JH-H = 14 Hz 1H PCH2) 307 (d 2JH-H = 14 Hz 1H PCH2) 190 (s 3H CH3)
149 (br m 1H CHB) 106 (s 6H CH3) 104 (s 6H CH3) 19F NMR (564 MHz CD2Cl2)
partial δ -1254 (br 2F o-C6F5) -1665 (m 2F m-C6F5) (p-C6F5 was not observed) 31P1H
NMR (242 MHz CD2Cl2) δ 63 (br) 11B NMR (192 MHz CD2Cl2) δ 342 (Bpin) -104
(B(C6F5)2) 13C1H NMR (151 MHz CD2Cl2) partial δ 1481 (H3CC=CH) 1359 (=CH) 1329
(m o-Ph) 1323 (d 4JC-P = 39 Hz p-Ph) 1317 (d 2JC-P = 71 Hz o-Ph) 1311 (d 4JC-P = 30
Hz p-Ph) 1300 (d 3JC-P = 94 Hz m-Ph) 1291 (d 1JC-P = 54 Hz ipso-Ph) 1282 (d 3JC-P = 94
Hz m-Ph) 1251 (d 1JC-P = 54 Hz ipso-Ph) 821 (C(CH3)2) 268 (d 1JC-P = 33 Hz CH2P) 256
(d 3JC-P = 53 Hz H3CC=CH) 245 (BpinCH3) 244 (BpinCH3) 178 (br CHB) Anal calcd ()
for C35H29B2F10O2P C 5805 H 404 Found 5776 H 397
443 X-Ray Crystallography
4431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
Universitaumlt Muumlnster data sets were collected with a Nonius KappaCCD diffractometer
Programs used data collection COLLECT351 data reduction Denzo-SMN352 absorption
180
correction Denzo353 structure solution SHELXS-97354 structure refinement SHELXL-97355
Thermals ellipsoids are shown with 30 probability R-values are given for observed reflections
and wR2 values are given for all reflections
4432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
4433 Platon Squeeze details
During the refinement of structure 413 electron density peaks were located that were believed
to be highly disordered dichloromethane and 12-dichloroethane molecules Attempts made to
model the solvent molecule were not successful The SQUEEZE option in PLATON356 indicated
there was a large solvent cavity 160 A3 in the asymmetric unit In the final cycles of refinement
this contribution (39 electrons) to the electron density was removed from the observed data The
density the F(000) value the molecular weight and the formula are given taking into account the
results obtained with the SQUEEZE option PLATON
181
4434 Selected crystallographic data
Table 44 ndash Selected crystallographic data for 41 47 and 48
41 47 48
Formula C46H23B1F15N1 C62H31B1F15N1 C37H25B1F15N1
Formula wt 88546 108572 77939
Crystal system monoclinic triclinic triclinic
Space group P2(1)n P-1 P-1
a(Aring) 91451(8) 120520(8) 99293(9)
b(Aring) 20583(2) 122120(8) 115709(11)
c(Aring) 20738(2) 184965(12) 168258(15)
α(ordm) 9000 103236(4) 75826(4)
β(ordm) 96295(4) 104461(4) 77700(4)
γ(ordm) 9000 104447(4) 65591(4)
V(Aring3) 38800(6) 24264(3) 16930(3)
Z 4 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1516 1482 1529
Abs coeff μ mm-1 0138 0126 0146
Data collected 35905 34295 21194
Rint 00444 00308 00308
Data used 8910 11131 5899
Variables 569 712 490
R (gt2σ) 00420 00532 00488
wR2 00964 01380 01380
GOF 1018 1028 1026
182
Table 45 ndash Selected crystallographic data for 49 410 and 413
49 410
(+05 C5H12)
413
(+1 C2H4Cl2)
Formula C39H21B1F15N1S2 C425H23B1F15N1 C48H29B1Cl2F15N1
Formula wt 86350 85145 98643
Crystal system monoclinic triclinic monoclinic
Space group P2(1)c P-1 P2(1)c
a(Aring) 174202(13) 113739(5) 138815(4)
b(Aring) 135941(10) 115489(6) 242842(7)
c(Aring) 174144(13) 158094(7) 146750(4)
α(ordm) 9000 92979(2) 9000
β(ordm) 118149(3) 97298(2) 1108840(10)
γ(ordm) 9000 116865(3) 9000
V(Aring3) 36362(5) 182343(15) 46220(2)
Z 4 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1577 1536 1418
Abs coeff μ mm-1 0256 0143 0236
Data collected 27739 30840 34544
Rint 00299 00352 00437
Data used 6409 8342 8147
Variables 506 560 600
R (gt2σ) 00570 00504 00687
wR2 01537 01410 02122
GOF 1045 1021 1092
183
Table 46 ndash Selected crystallographic data for 414 432 and 439
414
(+05 CH2Cl2 +1 C5H12)
432
(+05 C5H12) 439
Formula C485H36B1Cl1F15N1 C325H21B1F15N1 C58H46B1F15P2
Formula wt 96404 72131 110070
Crystal system monoclinic triclinic triclinic
Space group C2c P-1 P-1
a(Aring) 309455(12) 80774(6) 117846(13)
b(Aring) 193567(7) 117730(8) 159017(19)
c(Aring) 182668(6) 158569(11) 16349(2)
α(ordm) 9000 79707(3) 108194(4)
β(ordm) 123002(2) 86387(3) 107588(4)
γ(ordm) 9000 87902(3) 104551(4)
V(Aring3) 91764(6) 148021(18) 25646(5)
Z 8 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1397 1620 1425
Abs coeff μ mm-1 0179 0160 0179
Data collected 34220 24071 37635
Rint 00476 00352 00284
Data used 8097 6615 9023
Variables 570 445 698
R (gt2σ) 00716 00560 00339
wR2 02417 01703 00880
GOF 1047 1096 1019
184
Table 47 ndash Selected crystallographic data for 440 and 442
440 442
Formula C38H38B1F15P2 C35H29B2F10O2P1
Formula wt 85243 72417
Crystal system monoclinic monoclinic
Space group C2c P2(1)n
a(Aring) 329294(17) 114236(2)
b(Aring) 118317(6) 151074(3)
c(Aring) 206088(10) 192749(4)
α(ordm) 9000 9000
β(ordm) 107535(5) 93553(1)
γ(ordm) 9000 9000
V(Aring3) 76563(7) 332009(11)
Z 8 4
Temp (K) 150(2) 223(2)
d(calc) gcm-3 1479 1449
Abs coeff μ mm-1 0215 0172
Data collected 63283 23294
Rint 00316 0055
Data used 8776 6697
Variables 517 456
R (gt2σ) 00365 00672
wR2 01017 01623
GOF 1021 1048
185
Chapter 5 Conclusion
51 Thesis Summary
The results presented in this thesis demonstrate the application of B(C6F5)3 and other
electrophilic boranes in metal-free synthetic methodologies thereby extending FLP reactivity
beyond the commonly reported stoichiometric activation of small molecules These findings
have also provided metal-free and catalytic routes to transformations typically performed using
transition-metal complexes or stoichiometric main group reagents
Initial results presented herein describe the aromatic reduction of N-phenyl amines in the
presence of an equivalent of B(C6F5)3 using H2 to yield the corresponding cyclohexylammonium
derivatives A reaction mechanism based on experimental evidence and theoretical calculations
has been proposed Elaborating the scope of these metal-free aromatic reductions a p-methoxy
substituted aniline was found to undergo tandem hydrogenation and intramolecular cyclization
with B(C6F5)3 presenting a unique route to a 7-azabicyclo[221]heptane derivative Aromatic
hydrogenations were further probed with pyridines quinolines and other N-heterocycles
Findings within this study were in agreement with the mechanism postulated for the arene
reduction of N-phenyl amines Although these reductions require an equimolar combination of
the aromatic amine and borane in certain cases the reactions take up eight equivalents of H2
Continued interest in FLP hydrogenation of aromatic rings was illustrated by subsequent reports
demonstrating borane-catalyzed stereoselective hydrogenation of pyridines by the Du group264
and catalytic hydrogenation of polyaromatic hydrocarbons by the Stephan group263
The second project discussed in this thesis was directly inspired by findings in the synthesis of a
7-azabicyclo[221]heptane derivative from a p-methoxy substituted aniline Detailed
mechanistic studies showed the B(C6F5)3-methoxide bond is labile under specific reaction
conditions These findings were applied to uncover a catalytic approach to the hydrogenation of
ketones and aldehydes yielding alcohols This method uses FLPs derived from B(C6F5)3 and
ether in which the ether is used as the solvent playing a pivotal role in hydrogen-bonding
interaction with the carbonyl substrate The catalysis was further studied in toluene using
B(C6F5)3 in combination with oxygen containing materials such as cyclodextrins or molecular
sieves Application of these materials provides an avenue to H2 activation and hydrogen-bonding
186
interactions necessary to facilitate hydrogenation In the particular case of aryl ketones the use
of molecular sieves promoted reductive deoxygenation of the substrate to give the aromatic
hydrocarbon product Hydrogenation of carbonyl substrates had perennially remained a
challenging problem since the discovery of FLP chemistry The results reported in this thesis
represent the first successful report of catalytic carbonyl hydrogenation using FLPs It should be
noted that the group of Ashley simultaneously reported the hydrogenation of ketones and
aldehydes using 14-dioxaneB(C6F5) as the FLP catalyst260
Lastly interest in expanding FLP catalysis beyond hydrogenations amineborane FLPs were
applied in the hydroamination of terminal alkynes The stoichiometric reaction of aniline
B(C6F5)3 and two equivalents of alkyne gave a series of iminium alkynylborate complexes
prepared through sequential intermolecular hydroamination and deprotonation reactions This
latter reaction results in the formation of the alkynylborate anion thus preventing participation of
B(C6F5)3 in catalysis Adjustment of the protocol by slow addition of the alkyne prevents the
deprotonation pathway thus allowing B(C6F5)3 to catalyze the Markovnikov hydroamination of
alkynes by a variety of secondary aryl amines affording enamines products This metal-free
route was also amenable to subsequent use of the catalyst in hydrogenation catalysis allowing
for the single-pot and stepwise conversion of the enamine products to the corresponding amines
Further expansion of the reactivity led to catalytic intramolecular hydroaminations affording a
one-pot strategy to N-heterocycles A stoichiometric approach to FLP hydrophosphinations was
also described
52 Future Work
While the reactivities presented in this thesis have typically been the purview of precious metals
research efforts motivated by cost toxicity and low abundance have provided alternative
strategies using main group compounds In 1961 the first metal-free catalytic hydrogenation was
reported displaying the reduction of benzophenone however this reaction required high
temperatures of about 200 degC and H2 pressures greater than 100 atm175 Since then dramatic
progress has been made in the advancement of metal-free catalysis Numerous metal-free
systems with particular emphasis on FLPs have been reported to effect the hydrogenation of an
elaborate list of substrates under mild conditions
187
An important direction to progress the chemistry found during this graduate research work would
be to design a borane reagent that will be suitable for the catalytic hydrogenation of N-phenyl
amines and N-heterocycles Such a direction will allow for a more atom-economic
transformation Ultimately the catalysis could be pursued using chiral boranes that may provide
a stereoselective process to cyclohexylamine derivatives (Scheme 51) Generally aromatic
hydrogenation of nitrogen substrates is a challenging transformation for transition-metal systems
due to deactivation of the catalyst by coordination of the substrate357
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
An interesting and obvious extension of carbonyl hydrogenations presented in Chapter 3 would
certainly be a FLP route to optically active alcohols Although such products were not obtained
when performing the reductions in the presence of chiral heterogeneous Lewis bases the
application of a chiral borane should be investigated The Du group recently presented the use of
chiral boranes in the asymmetric hydrogenation of silyl enol ethers to give chiral alcohol
products after appropriate work-up procedures97
Furthermore the use of cyclodextrins and molecular sieves in catalysis has presented the
possible notion of expanding homogeneous FLP chemistry to surface chemistry by designing
heterogeneous FLP catalysts that could be readily recycled (Scheme 52) Such a system may be
particularly attractive for industrial applicability Solid catalyst supports such as B(C6F5)3 grafted
onto silica have been used by the Scott group as a co-catalyst for the activation of metal
complexes used in olefin polymerization358 Although this system may not be sufficiently Lewis
acidic for carbonyl reductions further exploration and modification of Lewis acid and base
components could potentially lead to such a system
188
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations
The final chapter of this thesis outlined the consecutive hydroamination and hydrogenation of
ethynyl fragments catalyzed by B(C6F5)3 The novelty of this reactivity by FLP systems certainly
demands further explorations Catalytic hydroamination using FLPs could be extended to include
olefins and internal alkynes Furthermore the pursuit of an effective chiral borane catalyst may
provide a potential synthetic route to chiral amines of pharmaceutical and industrial interest
189
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Chem 1996 61 3849-3862
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Chem 1978 43 374-375
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204
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Commun 2007 0 278-279
205
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206
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ii
Hydrogenation and Hydroamination Reactions Using
Boron-Based Frustrated Lewis Pairs
Tayseer Mahdi
Doctor of Philosophy
Department of Chemistry University of Toronto
2015
Abstract
New main group systems that provide avenues for small molecule activation have been
illustrated using frustrated Lewis pairs (FLPs) ndash combinations of sterically encumbered Lewis
acids and bases which cannot form adducts The research presented herein expands the small
molecule activation and transformation of FLPs using B(C6F5)3
Combination of the aryl amine tBuNHPh and B(C6F5)3 under H2 at room temperature leads to its
heterolytic splitting forming the complex [tBuNH2Ph][HB(C6F5)3] Exposing the salt to elevated
temperatures is found to follow an alternative mechanism resulting in hydrogenation of the N-
bound phenyl ring affording the isolable cyclohexylammonium salt [tBuNH2Cy][HB(C6F5)3]
This finding is extended to include a series of N-phenyl amines in addition to mono- and di-
substituted pyridines quinolines and several other N-heterocycles
The reaction of B(C6F5)3 and H2 with other substrates namely ketones and aldehydes are also
investigated Catalytic hydrogenation of the carbonyl functional group is achieved in an ethereal
solvent to give alcohol products In these cases the borane and ether behave as a FLP to activate
H2 and effect the reduction Similar reductions are also achieved in toluene using B(C6F5)3 in
iii
combination with cyclodextrins or molecular sieves Reductive deoxygenation occurs in the
particular case of aryl ketones
Finally the Lewis acid B(C6F5)3 is found to enable the intermolecular hydroamination of various
terminal alkynes giving iminium alkynylborate complexes of the general formula
[RPhN=C(CH3)R1][R1CequivCB(C6F5)3] The three-component reaction can also be performed
catalytically generating enamine products which are amenable to subsequent hydrogenation
reactions giving their corresponding amines The chemistry is expanded to intramolecular
systems forming N-heterocyclic compounds Furthermore a FLP route to stoichiometric
hydrophosphination of alkynes is developed
iv
Acknowledgments
Graduate school is not a journey taken alone rather it is one travelled with companions I have a
large group of wonderful people to thank for travelling by my side continuously supporting me
and putting a smile on my face
First and foremost I would like to take this opportunity to express my sincere gratitude to my
supervisor Prof Doug Stephan Thank you for your support you were always positive and open
to discussions Aside from developing my knowledge in chemistry you provided me with the
opportunity to build relationships and grow professionally I have also had the honour of having
very helpful committee members over the past few years Profs Bob Morris and Datong Song I
would like to thank you for your guidance and feedback through the seminar series and
committee meetings Prof Andrew Ashley I truly appreciate the time you took to provide me
with feedback for this thesis and attend my examination Thank you to Prof Erker at the
University of Muumlnster for accepting me to do an exchange in his research group
Of course the results in this thesis would not be publishable without the hard work of the staff at
the University of Toronto I would like to thank you all especially Darcy Burns Dmitry
Pichugin Rose Balazs and Matthew Forbes Also I would like to thank Chris Caputo Peter
Mirtchev Conor Prankevicius Alex Pulis and Adam Ruddy for your time in editing this thesis
All of the past and present Stephan group members thank you for the great times and of course
for doing your lab jobs and keeping the lab functional I definitely have to thank you Shanna for
keeping us in check
I want to give a big shout out to all my Athletic Centre gym buddies rock-climbing fellows
Chem Club soccer team champions and amazing Argon crossfitters I cannot express how much I
enjoyed every moment spent doing these outside-the-lab activities
A big I love you to my most amazing siblings Maithem Christina Jacob and Hoda I do not have
enough room here to express how much you guys mean to me but through it all we have stuck
together and this is how we will continue until the end To my future baby niece you have put a
smile on my face even while you are still inside the womb I cannot wait to meet you Finally to
the most supportive and kind-hearted person I have ever met Renan you have been there for me
from the start of this journey until the end Thank you all
v
Table of Contents
Abstract ii
Acknowledgments iv
Table of Contents v
List of Figures xi
List of Schemes xiv
List of Tables xix
List of Symbols and Abbreviations xxi
Chapter 1 Introduction 1
11 Science and Technology 1
111 Boron properties production and uses 2
112 Boron chemistry 3
12 Catalysis 4
13 Frustrated Lewis Pairs 5
131 Early discovery 5
132 Hydrogen activation and mechanism 6
133 Substrate hydrogenation 9
134 Activation of other small molecules 10
1341 Unsaturated hydrocarbons 10
1342 Alkenes 11
1343 Alkynes 11
1344 11-Carboboration 12
1345 CO2 and SO2 13
1346 FLP activation of carbonyl bonds 14
1347 Carbonyl hydrogenation 15
vi
1348 Carbonyl hydrosilylation 16
14 Scope of Thesis 17
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines and N-Heterocyclic Compounds 19
21 Introduction 19
211 Hydrogenation 19
212 Transfer hydrogenation 20
213 Main group catalysts 21
214 Hydrogenation of aromatic and heteroaromatic substrates 22
2141 Transition metal catalysts 22
2142 Metal-free catalysts 23
215 Reactivity of FLPs with H2 23
22 Results and Discussion 24
221 H2 activation by amineborane FLPs 24
222 Aromatic hydrogenation of N-phenyl amines 25
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates 30
223 Mechanistic studies for aromatic hydrogenation reactions 31
2231 Deuterium studies 31
2232 Variable temperature NMR studies 32
2233 Theoretical calculations 33
224 Aromatic hydrogenation of substituted N-bound phenyl rings 35
2241 Fluoro-substituted rings and C-F bond transformations 35
2242 Methoxy-substituted rings and C-O bond transformations 38
22421 Mechanistic studies for C-O and B-O bond cleavage 40
225 Aromatic hydrogenation of N-heterocyclic compounds 45
vii
2251 Hydrogenation of substituted pyridines 45
2252 Hydrogenation of substituted N-heterocycles 49
2253 Proposed mechanism for aromatic hydrogenation 55
2254 Approaches to dehydrogenation 55
23 Conclusions 56
24 Experimental Section 56
241 General considerations 56
242 Synthesis of compounds 57
243 X-Ray Crystallography 79
2431 X-Ray data collection and reduction 79
2432 X-Ray data solution and refinement 79
2433 Selected crystallographic data 81
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation with Frustrated Lewis Pairs 88
31 Introduction 88
311 FLP reactivity with unsaturated C-O bonds 88
32 Results and Discussion 92
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions 92
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents 93
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents 96
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism 97
325 Other hydrogen-bond acceptors for carbonyl hydrogenations 99
326 Other boron-based catalysts for carbonyl hydrogenations 99
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism 100
viii
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system 102
328 Attempted hydrogenation of other carbonyl substrates and epoxides 102
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases 103
3291 Polysaccharides as heterogeneous Lewis bases 104
3292 Molecular sieves as heterogeneous Lewis bases 107
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones 107
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation 110
32101 Verifying the reductive deoxygenation mechanism 111
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins 113
33 Conclusions 113
34 Experimental Section 114
341 General Considerations 114
342 Synthesis of Compounds 116
3421 Procedures for reactions in ethereal solvents 116
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3] 119
3423 Procedures for reactions using heterogeneous Lewis bases 120
3424 Procedures for reductive deoxygenation reactions 121
3425 Spectroscopic data of products in Table 31 121
3426 Spectroscopic data of products in Table 32 125
3427 Spectroscopic data of products in Table 33 125
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a) 127
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b) 128
343 X-Ray Crystallography 130
3431 X-Ray data collection and reduction 130
ix
3432 X-Ray data solution and refinement 130
3433 Selected crystallographic data 131
Chapter 4 Hydroamination and Hydrophosphination Reactions Using Frustrated Lewis Pairs 132
41 Introduction 132
411 Hydroamination 132
412 Reactions of main group FLPs with alkynes 133
4121 12-Addition or deprotonation reactions 133
4122 11-Carboboration reactions 134
4123 Hydroelementation reactions 135
413 Reactions of transition metal FLPs with alkynes 135
42 Results and Discussion 136
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes 136
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes 140
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates 141
4213 Reactivity of the iminium alkynylborate products with nucleophiles 141
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3 142
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes 144
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions 146
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes 147
424 Intramolecular hydroamination reactions using FLPs 148
4241 Stoichiometric hydroamination 148
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines 150
x
425 Reaction of B(C6F5)3 with ethynylphosphines 151
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines 153
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs 154
427 Proposed mechanism for the hydroborationhydrophosphination reactions 156
43 Conclusions 157
44 Experimental Section 157
441 General Considerations 157
442 Synthesis of Compounds 158
4421 Procedures for stoichiometric intermolecular hydroamination reactions 158
4422 Procedures for hydroarylation of phenylacetylene 165
4423 Procedures for catalytic intermolecular hydroamination reactions 167
4424 Procedures for tandem hydroamination and hydrogenation reactions 172
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions 173
4426 Procedures for reactions with ethynylphosphines 177
443 X-Ray Crystallography 179
4431 X-Ray data collection and reduction 179
4432 X-Ray data solution and refinement 180
4433 Platon Squeeze details 180
4434 Selected crystallographic data 181
Chapter 5 Conclusion 185
51 Thesis Summary 185
52 Future Work 186
References 189
xi
List of Figures
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage 8
Figure 12 ndash A highly efficient borenium hydrogenation catalyst 10
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis 21
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates 23
Figure 23 ndash POV-Ray depiction of 24rsquo 26
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+ 27
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($) 27
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right) 28
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right) 31
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-) 33
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol) 34
Figure 210 ndash POV-Ray drawing of 216a 36
xii
Figure 211 ndash POV-Ray drawing of 218 37
Figure 212 ndash POV-Ray drawing of 219 39
Figure 213 ndash POV-Ray drawing of trans-220 40
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c) 42
Figure 215 ndash POV-Ray drawing of 222 43
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right) 46
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring 48
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups 49
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring 49
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c) 50
Figure 221 ndash POV-Ray depiction of the cation for compound 231a 51
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring 52
Figure 223 ndash POV-Ray depiction of the cation for compound 233 52
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right) 53
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine 54
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol () 94
xiii
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol 95
Figure 33 ndash POV-Ray depiction of 31 98
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted 100
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
104
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD) 104
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased 112
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
136
Figure 42 ndash POV-Ray depiction of 47 137
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b) 139
Figure 44 ndash POV-Ray depiction of 410 139
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg 143
Figure 46 ndash POV-Ray depiction of 432 149
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons 152
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b) 153
Figure 49 ndash POV-Ray depictions of 442 155
xiv
List of Schemes
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3 4
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe) 4
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP 6
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c) 7
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K 9
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines 9
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom) 11
Scheme 18 ndash Reaction of FLPs with phenylacetylene 12
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom) 12
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base 13
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I) 14
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs 15
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP 16
xv
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom) 17
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine 20
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b) 24
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom) 25
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23 26
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD 32
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23 32
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts 35
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a 36
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218 37
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219 39
Scheme 211 ndash Synthesis of 220 and 212 40
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b) 41
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3 43
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3 44
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane 45
Scheme 216 ndash Proposed reaction pathway for the formation of 235 54
xvi
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom) 89
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b) 90
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols 90
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom) 91
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH 92
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation 93
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents 97
Scheme 38 ndash Synthesis of 31 98
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond 100
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation 102
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone 108
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b) 110
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones 111
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al) 133
xvii
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c) 134
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes 134
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes 135
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes 135
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
136
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts 140
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3 141
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4] 141
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right) 142
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3 142
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond 144
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes 147
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430 148
xviii
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432 149
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433 150
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH 151
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439 152
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440 154
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH 155
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments 156
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
187
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations 188
xix
List of Tables
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts 29
Table 22 ndash Hydrogenation of substituted pyridines 47
Table 23 ndash Hydrogenation of substituted N-heterocycles 51
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25 81
Table 25 ndash Selected crystallographic data for 216a 218 and 219 82
Table 26 ndash Selected crystallographic data for 220 222 and 224 83
Table 27 ndash Selected crystallographic data for 225 227 and 228 84
Table 28 ndash Selected crystallographic data for 229 230 and 231a 85
Table 29 ndash Selected crystallographic data for 231b 233 and 234a 86
Table 210 ndash Selected crystallographic data for 234b and 235 87
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents 96
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3] 101
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
106
Table 34 ndash Deoxygenation of aryl alkyl ketones 108
Table 35 ndash Deoxygenation of diaryl ketones 109
Table 36 ndash Selected crystallographic data for 31 131
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
138
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3 145
xx
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines 151
Table 44 ndash Selected crystallographic data for 41 47 and 48 181
Table 45 ndash Selected crystallographic data for 49 410 and 413 182
Table 46 ndash Selected crystallographic data for 414 432 and 439 183
Table 47 ndash Selected crystallographic data for 440 and 442 184
xxi
List of Symbols and Abbreviations
9-BBN 9-borabicyclo[331]nonane
α alpha
Aring angstrom 10-10 m
atm atmosphere
β beta
Bpin pinacolborane (4455-tetramethyl-132-dioxaborolane)
br broad
Boc tert-butyloxycarbonyl
Bu butyl
C Celsius
ca circa
calcd calculated
CD cyclodextrin
C6D6 deuterated benzene
C6H5Br bromobenzene
C6D5Br deuterated bromobenzene
CD2Cl2 deuterated dichloromethane
Cy cyclohexyl
δ chemical shift
xxii
deg degrees
d doublet
Da Dalton
DART direct analysis in real time
DEPT Distortionless Enhancement by Polarization Transfer
dd doublet of doublets
de diastereomeric excess
DFT density functional theory
dt doublet of triplets
ee enantiomeric excess
eq equivalent(s)
ESI electrospray ionization
Et ethyl
Et2O diethyl ether
FLP frustrated Lewis pair
γ gamma
ΔG Gibbs free energy
g gram
GC gas chromatography
GOF goodness of fit
xxiii
h hour
HRMS high resolution mass spectroscopy
HMBC heteronuclear multiple bond correlation
HOESY heteronuclear Overhauser effect NMR spectroscopy
HSQC heteronuclear single quantum correlation
Hz Hertz
iPr2O diisopropyl ether
nJxy n-scalar coupling constant between X and Y atoms
K Kelvin
kcal kilocalories
m meta
m multiplet
M molar concentration
Me methyl
Mes mesityl 246-trimethylphenyl
MHz megahertz
μL microliter
μmol micromole
mg milligram
min minute
xxiv
mL milliliter
mmol millimole
MS mass spectroscopy
MS molecular sieves
nPr n-propyl
iPr iso-propyl (CH(CH3)2)
NHC N-heterocyclic carbene
NMR Nuclear Magnetic Resonance
NOE Nuclear Overhauser Effect
o ortho
π pi
p para
POV-Ray Persistence of Vision Raytracer
PGM Platinum Group Metals
Ph phenyl
Ph2O diphenyl ether
ppb parts per billion 10-9
ppm parts per million 10-6
q quartet
quint quintet
xxv
rpm rotations per minute
RT room temperature
σ sigma
s singlet
t triplet
tBu tert-butyl
THF tetrahydrofuran
TMP 2266-tetramethylpiperidine
TMS trimethylsilyl
TMS2O hexamethyldisiloxane
tol toluene
wt weight
1
Chapter 1 Introduction
11 Science and Technology
The advent of the scientific revolution and the scientific method in early modern Europe
dramatically transformed the way scientists viewed the universe as they attempted to explain the
physical world through experimental investigation The long-term effects of the revolution can
be felt today with our dependence upon science to improve the quality of our lives and advance a
globally interconnected world Some scientific discoveries which have paved the way for such
enterprising technologies include the Haber-Bosch process used for the production of ammonia
essential to the synthesis of nitrogen fertilizers1-3 This discovery has dramatically increased food
production globally and allowed for the explosive population growth observed in the past
century Research also intensified to change the world of medicine through discovery of antiviral
agents for treatment of the HIVAIDS pandemic4-5 Ziegler-Natta catalysts have become central
to the polymer industry manufacturing the largest volumes of commodity plastics and
chemicals6-8
While many chemical breakthroughs have had significant benefits on public health their initial
application or even long-term impact on the environment may be detrimental For example
chlorine was used as a weapon during World War I9 while today it plays a vital role in
disinfecting drinking water and sanitation processes10 A more significant example is the
industrial revolution when manufacturing transitioned from manual labour to machines resulting
in unprecedented growth in population and standards of living Our continued reliance on
factories and mass production has led to depletion of natural resources and emission of
greenhouse gases resulting in anthropogenic climate change11-15
Scientists have acknowledged the need to remediate environmental impacts and to find more
environmentally acceptable technologies for the chemical industry To this end chemical
research has focused on implementing the principles of green chemistry16-17 to develop benign
processes which will sustain the growing energy demands of our society18-19 Central to the green
concept is the application of catalysis in chemical transformations in addition to using readily
available non-toxic raw materials in cost effective procedures
2
Rare precious metals such as the Platinum Group Metals (PGM) are extracted by mining of non-
renewable resources normally resulting in negative social and environmental impacts on the
area20 The metals are used in industrial chemical syntheses where they are regularly recovered
and recycled back into production It is essential however to gradually replace these reagents
with more environmentally benign and readily available transition metals in order to reduce
waste processing costs and eliminate the possibility of their release into the environment In this
aspect chemists are actively seeking innovations to advance more green chemical processes21-24
A vast majority of d-block transition metals have energetically accessible valence d-orbitals
allowing for oxidation state changes which are pivotal to substrate activation and accessing
stabilized transition states Additional factors including the steric and electronic tunability of the
ligand framework have led to the development of a broad range of metal catalysts applied in
numerous chemical transformations25-26 Nonetheless a growing number of advancements
involving the use of main group s and p-block elements have also shown reactivities similar to
those of transition metal complexes27-30
Main group elements are relatively abundant on Earth and over the last decade have experienced
a renaissance in chemical transformations Notably frustrated Lewis pair (FLP) systems which
involve the combination of Lewis acids and bases that are sterically and electronically prohibited
from forming a classical adduct have been at the forefront31 The unquenched reactivity of FLPs
has been explored in the activation of numerous small molecules The majority of FLP systems
incorporate boron Lewis acids and phosphorus Lewis bases32 In this thesis the potential to
expand FLP reactivity to nitrogenboron and oxygenboron pairs is explored
111 Boron properties production and uses
Boron (B) is a non-metallic element always found in nature bound to oxygen as orthoboric acid
alkali metal and alkaline earth metal borates33 Prominent sources of boron include the sodium
borate minerals rasorite and kernite found in deposits at the Mojave Desert of California and in
Turkey which is the largest producer of boron minerals33-34 Boron is vastly spread in Nature
however it constitutes only about 3 ppm of the Earthrsquos crust35-36
Industrially the production of pure boron is very difficult as it tends to form refractory materials
containing small amounts of carbon and other elements The method typically used for
3
commercial production of amorphous boron (up to 97 purity) is by reduction of B2O3 with Mg
in a thermite-like reaction Higher purity (gt99) boron is obtained by the reduction of boron
halides with H2 whereas ultra-purity can be achieved by thermal decomposition of boron
halideshydrides or diboranes on tungsten wires followed by zone melting purification37
Regardless of the production method different allotropic forms of boron can be accessed Short
reaction times at temperatures below 900 degC produce amorphous boron longer reaction times
above 1400 degC afford β-rhombohedral and optimal conditions in between the two give α-
rhombohedral36
Amorphous boron consisting of 90 - 92 purity costs approximately $100kg Relatively large
quantities of the material are used as additives in pyrotechnic mixtures Ultrapure (gt9999)
boron costs about $3500kg and is applied in electronics such as a dopant for germanium and
silicon p-type semiconductors Furthermore as the second hardest element inferior only to
diamond there is a growing demand for boron as a light-weight hardenability additive for glass
ceramics and boron filaments used in high-strength materials for the aerospace and steel
industries35-36
112 Boron chemistry
Boron has a valence shell electron configuration of 2s22p1 representing a typical formal
oxidation state of 3+ although due to its high ionization potentials simple B3+ ions do not exist
Boron can form three sp2 hybridized bonds resulting in trigonal planar geometry with a non-
bonding vacant p-orbital orthogonal to the plane susceptible towards electron donation giving
rise to its noted Lewis acidic properties38-40 Scales to quantify Lewis acidity have been designed
by studying the acceptor-donor interactions between Lewis acid and base complexes using NMR
spectroscopy data based on the Gutmann-Beckett41 and Childs42 methods43 IR spectroscopy X-
ray diffraction44 and density functional calculations45
The most common use of Lewis acids are the boron trihalides particularly BF3 and BCl3 in
conjunction with a co-initiator Lewis base such as water initiating cationic polymerization The
unsaturated olefin monomer is protonated generating the [BF3OH]- counterion along with a
carbenium ion which reacts with olefin molecules leading to propagation of the polymer46 With
Lewis acidity comparable to BF3 the Lewis acid B(C6F5)3 was lsquorediscoveredrsquo in the 1990s as an
ideal activator component for Ziegler-Natta olefin polymerization catalysts47 Treatment of a
4
Group 4 dialkyl-metallocene catalyst precursor with one equivalent of B(C6F5)3 results in alkyl
anion abstraction forming the active alkyl-metallocene cation (eg [Cp2ZrMe]+) stabilized by the
weakly coordinating [MeB(C6F5)3]- anion (Scheme 11)48-51
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3
Hydroboration the addition of B-H across multiple bonds of organic substrates such as alkenes
and alkynes provides the most common route to alkyl or alkenyl organoborane reagents
respectively52 The products obtained can be employed as intermediates for further synthetic
derivatization One powerful and general methodology used for the modification of
organoboranes53 is the Suzuki-Miyaura cross-coupling reaction (Scheme 12) These C(sp2)-B
and C(sp3)-B organoboranes readily undergo transmetalation with an electrophilic organo- Cu
Pd Ni or Fe catalyst to give coupled products with new C-C bonds54-55 Other applications of
boron reagents include metal borohydrides as reducing agents transferring hydride nucleophiles
to versatile functional groups56-59 Operating in a similar manner anionic borates consisting of
polarized B-C bonds transfer an organic group to an electrophilic centre38 60
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe)
Of particular relevance to this thesis recent advances in boron chemistry particularly involving
the activation and reactivity of small molecules with FLP systems will be discussed
12 Catalysis
In the early part of the 20th century catalysis developed into a scientific discipline and has
evolved to underlie numerous chemical technologies that benefit human life worldwide61 The
5
function of a catalyst substance added in a sub-stoichiometric amount is to lower the reaction
activation energy and affect selectivity for chemical transformations without being consumed62
Homogeneous catalysts have a long prevalence in industry with applications ranging from bulk
chemicals to complex multi-step processes Among the most prominent examples are the
Monsanto and Cativa processes for the carbonylation of methanol to produce acetic acid and the
oxo process for hydroformylation of olefins to yield aldehydes63 Only touching the tip of the
iceberg other commercial processes include the Wacker process for the oxidation of ethylene
aforementioned Ziegler-Natta olefin polymerization based on immobilized TiCl3 and substrate
hydrogenations using Wilkinsonrsquos Rh and Ru catalysts64-65 Other noteworthy discoveries
essential to the advancement of catalysis include Fischer-Tropsch production of liquid
hydrocarbons asymmetric catalysis olefin metathesis and Pd-catalyzed cross couplings66
The significance of catalysis for the development of chemistry has been recognized by the Nobel
Prize Committee with the earliest accreditation in the field awarded in 1909 to W Ostwald
Shortly thereafter Nobel Prizes were awarded for important contributions by P Sabatier (1912)
F Haber (1918) and C Bosch and F Bergius (1931) Since the turn of the millennium catalysis
has been recognized with four Chemistry Nobel Prizes awarded to 10 laureates66
13 Frustrated Lewis Pairs
131 Early discovery
The acid-base theory proposed by G N Lewis in 1923 is arguably one of the most important
theories in chemistry describing Lewis acid and base species as electron pair acceptors and
electron pair donors respectively67 According to the theory sterically unhindered Lewis acid-
base pairs react to form a Lewis adduct quenching subsequent reactivity This concept is
fundamental in most areas of chemistry involving the interaction of a doubly occupied orbital
(nucleophile) with an empty orbital (electrophile) forming a favourable overlap
Recent advances involving sterically encumbered Lewis pairs preclude such adduct formation
thereby rendering the individual components available for unique reactivity68-70 Astonishingly
in 1942 H C Brown reported that the ldquosteric strainrdquo between the Lewis acid trimethylborane
and the bulky Lewis base 26-lutidine does not result in adduct formation71 These early results
predate the recently popularized concept of frustrated Lewis pairs (FLPs) describing the
6
combination of Lewis acids and bases with sterically and electronically frustrated substituents
which prevent formal adduct formation32 The cooperative behaviour of these frustrated Lewis
centres has been evidenced to activate small molecules72
132 Hydrogen activation and mechanism
The first FLP reactivity was discovered by Stephan et al in 2006 while investigating the
chemistry of phosphonium borate linked zwitterions R2P(H)(C6F4)B(F)(C6F5)2 (R = alkyl or
aryl) generated from nucleophilic aromatic substitution of B(C6F5)3 by bulky secondary
phosphines31 Treatment with Me2SiHCl easily converts the linked zwitterion to the
phosphonium borohydride species containing both protic and hydridic hydrogen atoms In a
remarkable example the linked PHndashBH zwitterion (R = Mes) was found to liberate and rapidly
activate H2 representing the first example of reversible H2 activation using main group
compounds (Scheme 13)
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP
Hydrogen activation by main group compounds is rare the first example was reported in 2005
by the group of Power and co-workers describing the addition of H2 to heavier main group
digermyne compounds RGeequivGeR (R = aryl)30 The seminal finding was followed by the work of
Bertrand using bulky (alkyl)(amino)carbenes displaying both nucleophilic and electrophilic
characteristics to split and add H2 at a single carbon centre28 In a succeeding report by Piers the
antiaromatic Lewis acid perfluoropentaphenylborole was exclusively employed in H2 activation
to yield boracyclopent-3-ene products resulting from H2 addition to the two carbon atoms alpha
to boron73
After the initial breakthrough with FLPs their unique reactivity attracted immediate attention of
the scientific community Erker and co-workers have synthesized intramolecular PB FLPs
derived by the anti-Markovnikov addition of HB(C6F5)2 to vinyl phosphines (Scheme 14 a)74-75
Additionally Rieger and Repo have reported the nitrogen-based intramolecular FLP ansa-
7
aminoborane shown in Scheme 14 (b)76-78 These systems heterolytically split H2 albeit
reversible H2 activation was only demonstrated for the ansa-aminoborane
Hydrogen activation has also been extended to bimolecular systems Combinations of B(C6F5)3
and sterically encumbered tertiary phosphines were found to effect H2 activation (Scheme 14
c)32 In one example the weaker Lewis acid B(p-HC6F4)3 and o-tolyl3P were found to liberate H2
under vacuum79-80
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c)
The initial mechanism proposed for heterolytic splitting of H2 was speculated to be a ldquoside-onrdquo
or ldquoend-onrdquo coordination of H2 to either the boron or phosphorus moiety followed by approach
of the respective FLP partner effecting H-H bond cleavage This mechanism was not found to be
computationally supported despite earlier evidence for the ldquoside-onrdquo mechanism based on BH3-
H2 adducts81-84 While mechanistic details remain debated theoretical investigations by the
groups of Paacutepai85-87 and Grimme88 were performed on the prototype tBu3PB(C6F5)3 FLP Both
groups agree on the formation of an ldquoencounter complexrdquo stabilized by CndashH---F dispersion
interactions between the phosphine methyl groups and C6F5 borane rings As a result the Lewis
pair orient such that the boron is in close proximity to the phosphorus centre The electron
transfer model proposed by Paacutepai89 explains hydrogen activation by synergistic interaction of the
8
Lewis pair inducing polarization on the H2 molecule effecting heterolytic cleavage In this case
donation from the σ orbital of H2 into the empty orbital on the Lewis acid occurs in conjunction
with lone pair donation from the Lewis base to the σ orbital of H2 representing a process
similar to metal-based heterolytic cleavage of H2 (Figure 11 a) In contrast the electric field
model reported by Grimme suggests heterolytic H2 activation is a barrierless process resulting
from the exposure of H2 to a sufficiently strong homogeneous electric field pocket created by the
FLP complex Interpretation of this model does not consider electron donation or the orbitals of
the FLP or H2 (Figure 11 b)
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage
Direct investigation of H2 activation intermediates by standard experimental techniques has been
unquestionably demanding Experimental evidence of an encounter complex has been observed
by 19F1H HOESY NMR studies revealing contacts between all protons of R3P (R = tBu Mes)
and fluorine nuclei of B(C6F5)3 although only a rough orientation of the molecules was
reported90 Examination of a related system has recently been reported by the Piers group In this
case combination of a highly electrophilic boraindene and Et3SiH gave an isolable borane-silane
complex affirming details of adduct formation in FLP hydrosilylation and to a certain extent
extrapolated to the closely related H2 activation reaction (Scheme 15)91
9
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K
133 Substrate hydrogenation
Reversible H2 activation by the initial FLP Mes2P(H)(C6F4)B(H)(C6F5)2 was a landmark
discovery that shed light onto potential important applications of such systems Most significant
of these efforts was demonstrated by employing R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) in the
catalytic reduction of unsaturated substrates specifically bulky imines and N-protected nitriles to
corresponding amines using 5 mol catalyst 5 atm of H2 and temperatures ranging from 80 -
100 degC Concerted investigations in the field revealed that sterically hindered substrates could
also serve as the Lewis base in splitting hydrogen92-93 To this end catalytic amounts of B(C6F5)3
in combination with various bulky aldimines and ketimines were reduced under 5 atm of H2 at
120 degC with isolated yields in the range of 89 - 99 Based on experimental observations the
proposed mechanism suggests H2 is cleaved between the bulky imine and B(C6F5)3 followed by
hydride delivery to the iminium cation (Scheme 16)
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines
10
Following the early reports on metal-free catalytic hydrogenation the reduction of various other
substrates has been demonstrated to include aziridines92 94 enamines93 enones95 silyl enol
ethers96-97 N-heterocycles98 olefins99 and most recently alkynes have been reduced to cis-
alkenes100 Asymmetric hydrogenation by chiral FLPs was first demonstrated in 2008 by
Klankermayer and co-workers to give a chiral amine with 13 ee and later improvements up to
83 were obtained using a camphor derived catalyst101-102 Rieger and Repo saw ee values of
3776 103 while significant improvements up to 89 were achieved by the Du group104
Recently borenium cations have been used as Lewis acids in FLP chemistry with remarkable
catalytic activity for the hydrogenation of imines and enamines at room temperature (Figure
12)105
Figure 12 ndash A highly efficient borenium hydrogenation catalyst
134 Activation of other small molecules
FLP-mediated bond activations have been explored for a multitude of small molecules including
CO2106-107 N2O108-112 SO2113-114 NO115-116 CO107 117-119 NSO120 fluoroalkanes121 ether122
disulfides123 alkenes124-125 and alkynes126-128 FLPs have also been exploited in radical
polymerizations116 and more recently in materials and surface science129 Efforts have also
continued to exploit FLP chemistry in synthetic organic applications130 Beyond here small
molecule transformations that are relevant to the chemistry presented in this thesis will be
discussed
1341 Unsaturated hydrocarbons
Reactivity of unsaturated hydrocarbons has been a field traditionally associated with transition
metal chemistry and has found particular use for organic synthesis131-138 The dramatic evolution
in FLP systems has raised interest in probing the reactivity of main group complexes with
alkenes and alkynes100 139-140 This reactivity is reminiscent of related findings by Wittig and
Benz in 1959 involving the addition of Ph3P and BPh3 to benzyne affording zwitterionic
11
phosphonium-borates141 In the same context Tochtermann showed the addition of the bulky
carbanion [Ph3C]- and Lewis acid BPh3 across the double bond of 13-butadiene rather than
anionic polymerization of the conjugated diene142
1342 Alkenes
The reaction of FLPs with alkenes is particularly intriguing as the individual Lewis components
do not react with the substrate rather the three component combination of R3P B(C6F5)3 and
alkene exhibited intermolecular 12-addition reactions (Scheme 17 top)143-144 Similar activation
results were also observed upon exposure to the ethylene-linked FLP Mes2PCH2CH2B(C6F5)2145-
147 In two remarkable examples the Stephan group provided spectroscopic theoretical148 and
crystallographic149 evidence for Lewis acid-olefin van der Waals complexes forming prior to
FLP additions (Scheme 17 bottom)
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom)
1343 Alkynes
Initial reactivity of FLPs with terminal alkynes featured the facile deprotonation or addition of
phosphineLewis acid (B Al) combinations to afford alkynylborate (aluminate) salts or
zwitterions with selectivity of the reaction correlated to the basicity of the phosphine (Scheme
18)126 128 In a joint report by the Stephan and Erker groups the B(C6F5)3-mediated
intramolecular cyclization of an ortho-ethynylaniline to access a cyclic anilinium borate was
presented150-151 In an analogous fashion Stephan and co-workers showed the cyclization of
alkyne- and alkene-tethered pyridines and quinolines using B(C6F5)3152 The groups of Berke
12
Erker Stephan and Uhl expanded the chemistry by varying the Lewis acid to BPh3 and alanes153
as well as the Lewis base to include phosphines154 polyphosphines155 thioethers amines and
pyridines156 carbenes157 and pyrroles158
Scheme 18 ndash Reaction of FLPs with phenylacetylene
1344 11-Carboboration
Particularly prolific in the research area of FLP reactivity with alkynes the groups of Erker and
Berke separately unravelled the 11-carboboration reaction resulting from the electrophilic
attack of the CequivC triple bond of an alkyne by highly electrophilic boranes RB(C6F5)2 generating
alkenylborane products (Scheme 19)156 159-160
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom)
In the absence of a Lewis base the combination of electrophilic boranes and terminal alkynes are
postulated to generate a vinylidene intermediate stabilized by 12-hydride migration to the
carbocation Subsequently scission of a BndashC bond transfers a substituent from the borane to the
same carbon of the alkyne generating the alkenylborane (Scheme 110 left)159 This simple yet
elegant strategy demonstrates a facile route to borane derivatives with a C(sp2)-B centre that
could be further treated under Suzuki cross-coupling conditions161 In the presence of a Lewis
13
base deprotonation of the vinylidene or nucleophilic addition at the carbocation takes place
(Scheme 110 right)
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base
1345 CO2 and SO2
Following the reactivity of FLPs with olefins successful joint efforts by the Stephan and Erker
groups showed the activation of the greenhouse gas CO2 and acid rain contributor SO2 using the
FLP tBu3PB(C6F5)3 and ethylene-linked PB system Mes2PCH2CH2B(C6F5)2 (Scheme 111 a
and b)113-114 Key differences were observed in the reactivity of the two gases For example the
reversible nature of binding CO2 was not observed with the SO2 bound species Furthermore the
six-membered SO2 adducts derived from linked PB FLPs gave a stereogenic sulphur centre
resulting in a pair of isomers (Scheme 111 b) The Stephan group extended the activation of
CO2 beyond borane Lewis acids To this end 12 combinations of bulky phosphines and AlX3 (X
= halide or C6F5) react with CO2 rapidly leading to the formation of R3P(CO2)(AlX3)2 (Scheme
111 c)
14
Mes2P B(C6F5)2
EO2Mes2P B(C6F5)2
E O
O
R R
gt -20 degC- CO2
tBu3P B(C6F5)3EO2
80 degC- CO2
PB(C6F5)3E
O
O
tBu3
Mes3P 2 AlX3 Mes3PAlX3E
O
O
AlX3
CO2
b)
a)
c)
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I)
In the case of CO2 further chemical transformation of the activated molecule has been
presented107 111 153 162-164 including efforts to reduce CO2 to CH3OH The groups of Ashley and
OrsquoHare presented this reactivity using H2 as the reducing source Stephan et al used ammonia
borane165 and this process has been achieved catalytically by Fontaine using hydroboranes166-168
Additionally Piers reported the catalytic deoxygenative reduction of CO2 to CH4 using silanes169
and Stephan showed the stoichiometric reduction of CO2 to CO using R3PAlX3 FLPs170
1346 FLP activation of carbonyl bonds
Efforts to include oxygen-based substrates in FLP-mediated catalytic transformations have found
limited success due to the high affinity of electrophilic boranes towards oxygen species72 171
Investigations by Erker and co-workers described the irreversible capture of benzaldehyde and
trans-cinnamaldehyde at the C=O functional group by the intramolecular FLP
Mes2PCH2CH2B(C6F5)2 (Scheme 112 top)172-173 Similar alkoxyborate products were obtained
in the reaction of NB FLPs with benzaldehyde (Scheme 112 bottom)174
15
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs
1347 Carbonyl hydrogenation
Metal-free hydrogenation of carbonyl substrates was reported as early as 1961 by Walling and
Bollyky for the homogeneous hydrogenation of ketones catalyzed by alkali metal alkoxides175
About 40 years later Berkessel and co-workers communicated mechanistic studies on the
process which were supported thereafter by computational investigations176 The authors
elucidated mechanistic analogies between base-catalyzed ketone hydrogenation and Ru-
catalyzed transfer hydrogenation by Noyori whereby a Broslashnsted base participates in H2
heterolysis177 Although this is the first example of metal-free reduction of ketone the reactions
are performed at relatively harsh conditions requiring 100 atm of H2 and 200 degC Moreover the
substrate scope was limited to the non-enolizable ketone benzophenone
The reaction of benzaldehyde with the intramolecular H2-activated FLP
R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) was found to proceed in a stoichiometric fashion
reducing the C=O double bond formulating the zwitterion R2P(H)(C6F4)B(C6F5)2OCH2Ph
(Scheme 113) Chemical intuition would perhaps point to proton transfer from the phosphonium
centre this is however prevented by the lower basicity of the oxygen atom contrasting
hydrogenation reactions with nitrogen substrates
16
B(C6F5)2R2P
FF
F F
H
H
O
HPhB(C6F5)2R2P
FF
F F
H O
Ph
R = tBu Mes
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP
Based on the principle for catalytic hydrogenation of imines Repo and co-workers explored
C=O hydrogenations using the aromatic carbonyl substrates benzophenone and benzaldehyde as
Lewis bases along with the Lewis acid B(C6F5)3 Experimental results indicated the reaction to
be challenging generating only sub-stoichiometric amounts of the alcohol products due to rapid
decomposition of the borane178
1348 Carbonyl hydrosilylation
Hydrosilylation is one of the most commonly applied processes within the chemical industry
today New catalytic technologies providing avenues for metal-free SindashH bond activation have
become appealing alternatives to traditional transition metal catalysts179 Impressively in 1996
the Piers group reported 1 - 4 mol of B(C6F5)3 to effect the catalytic hydrosilylation of
aromatic aldehydes ketones and esters at room temperature (Scheme 114 top)180-182 Clever
analysis of the mechanism by Oestreich using a stereochemically pure silane found inversion of
stereochemistry at silicon after hydrosilylation This finding rationalized a concerted SN2 type
displacement at the silicon centre of a (C6F5)3Bδ-middotmiddotmiddotHmiddotmiddotmiddot SiR3δ+ transition state by the substrate
carbonyl oxygen (Scheme 114 bottom)183
17
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom)
14 Scope of Thesis
The objective of this graduate research was to expand the scope of FLP reactions using the Lewis
acid B(C6F5)3 Although previous studies have documented the reactivity of B(C6F5)3 with small
molecules further transformation of the activated species in organic syntheses remains limited
In this work FLP hydrogenation reactions were extended to include the aromatic rings of N-
phenyl amines and N-heterocyclic compounds as described in Chapter 2 Tandem hydrogenation
and transannulation reactions occurred with a para-methoxy substituted aniline affording a 7-
azabicyclo[221]heptane derivative Mechanistic studies of this reactivity provided insight to a
viable approach achieving the catalytic hydrogenation of ketones and aldehydes to form alcohol
products presented in Chapter 3 In addition the reductive deoxygenation of aryl ketones to
aromatic hydrocarbons was investigated Finally Chapter 4 expands FLP catalytic reactions
beyond hydrogenations In this chapter B(C6F5)3 catalyzed hydroamination of terminal alkynes
is investigated with extension to intramolecular systems and stoichiometric hydrophosphination
reactions
All synthetic work and characterizations were performed by the author with the exception of
elemental analyses high resolution mass spectroscopy and X-ray experiments DFT calculations
for the aromatic hydrogenations described in Chapter 2 were performed by Professor Stefan
Grimme at Universitaumlt Bonn Germany Compounds 216 - 218 were initially synthesized by an
undergraduate student Jon Nathaniel del Castillo under the authorrsquos supervision The synthesis
of compounds 439 and 440 were initially performed by the author at the University of Toronto
18
and repeated during a four month research opportunity program in the laboratory of Professor
Gerhard Erker at Universitaumlt Muumlnster Germany Compounds 441 and 442 were prepared at
Universitaumlt Muumlnster and the structure of 442 was obtained and solved by Dr Constantin
Daniliuc All other molecular structures were solved by the author and the authorrsquos supervisor
Professor Douglas Stephan
Portions of each chapter have been published or accepted at the time of writing
Chapter 2 1) Voss T Mahdi T Otten E Froumlhlich R Kehr G Stephan D W Erker G
ldquoFrustrated Lewis Pair Behavior of Intermolecular AmineB(C6F5)3 Pairsrdquo Organometallics
2012 31 2367-2378 2) Mahdi T Heiden Z M Grimme S Stephan D W ldquoMetal-Free
Aromatic Hydrogenation Aniline to Cyclohexylamine Derivativesrdquo J Am Chem Soc 2012
134 4088-4091 3) Mahdi T Castillo J N Stephan D W ldquoMetal-Free Hydrogenation of N-
based Heterocyclesrdquo Organometallics 2013 32 1971-1978 4) Longobardi L E Mahdi T
Stephan D W ldquoB(C6F5)3 Mediated Arene HydrogenationTransannulation of para-
Methoxyanilinesrdquo Dalton Trans 2015 44 7114-7117
Chapter 3 5) Mahdi T Stephan D W ldquoEnabling Catalytic Ketone Hydrogenation by
Frustrated Lewis Pairsrdquo J Am Chem Soc 2014 136 15809-15812 6) Mahdi T Stephan D
W ldquoFacile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive
Deoxygenation of Ketones and Aldehydesrdquo Angew Chem Int Ed 2015 DOI
101002anie201503087
Chapter 4 7) Mahdi T Stephan D W ldquoFrustrated Lewis Pair Catalysed Hydroamination of
Terminal Alkynesrdquo Angew Chem Int Ed 2013 52 12418-12421 8) Mahdi T Stephan D
W ldquoInter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairsrdquo
Chem Eur J 2015 accepted
19
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines
and N-Heterocyclic Compounds
21 Introduction
211 Hydrogenation
Hydrogenation the addition of hydrogen (H2) to unsaturated compounds is one of the simplest
and most attractive chemical processes performed today26 The reaction is employed for the
production of commodity chemicals with widespread application in the petrochemical
pharmaceutical and foods industries One of the largest industrial applications of hydrogenation
is in the Haber-Bosch process63 66 184 This method uses N2 and H2 to produce ammonia which is
essential for the synthesis of nitrogen fertilizers currently sustaining about one-third of the
worldrsquos population Additionally significant is the Fischer-Tropsch process used to generate
liquid hydrocarbons from the chemical reaction of H2 and CO (synthesis gas)185-186
In the early part of the 20th century P Sabatier discovered the catalytic hydrogenation of organic
substrates over finely divided nickel thereby greatly advancing the field of organic chemistry187-
193 Approximately 60 years later Wilkinson uncovered the homogeneous hydrogenation of
olefins using Ru and Rh catalysts a development that was crowned initiator of organometallic
chemistry (Scheme 21 a)194-197 Further developments in metal-based hydrogenations were
made in the 1980s including the Nobel Prize winning work of asymmetric hydrogenations by
Noyori and Knowles (Scheme 21 b)198-207 While precious metal catalysts208-209 are known to
carry out this reactivity (Scheme 21 c) the high cost and low abundance of these metals
necessitates the development of more cost-efficient procedures New technologies providing
avenues for greener transformations have recently been illustrated using first-row transition
metals Fe and Co (Scheme 21 d)136 210-214
20
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine
212 Transfer hydrogenation
A variety of insightful strategies have provided alternative avenues to direct hydrogenation One
such example is transfer hydrogenation the addition of hydrogen to an unsaturated substrate
from a source other than gaseous H2 In the 1920s Meerwein Ponndorf and Verley (MPV)
demonstrated the first example of hydrogen transfer from a sacrificial alcohol to ketone using an
aluminum alkoxide catalyst215-217 Nonetheless interest in using organocatalysts for
hydrogenation reactions increased spectacularly due to novelty of the concept efficiency and
selectivity in organic reactions Particularly recognized are chiral amine catalysts in combination
with Hantzsch ester dihydropyridines which act as mild organic sources of H2218-219 Extensive
research has also focused on new transition metal catalysts for efficient dehydrocoupling of
ammonia borane (H3NBH3) and related amine borane compounds220
Although transfer hydrogenation is a process dominated by precious transition metal catalysts
Earth abundant less toxic Fe-based catalysts have proven remarkably active effecting high
enantioselectivity (Figure 21 a)221 Moreover catalyst-free strategies by Berke and co-workers
have promoted transfer hydrogenation of imines and polarized olefins222 Stephan et al
underscored extension of metal-free catalysis reporting a highly electrophilic phosphonium
cation catalyst for application in dehydrocoupling of protic compounds with silanes and transfer
hydrogenation to olefins (Figure 21 b)223
RhPh3P
Ph3P Cl
PPh3
(a) (b) (c)
(d)
21
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis
213 Main group catalysts
The discovery of sodium borohydride and lithium aluminum hydride in the 1940s introduced
new stoichiometric methods for the hydrogenation of unsaturated functional groups56 59 224 A
variety of these metal hydride reagents possessing a high degree of chemoselectivity have made
the reduction of a broad range of functional groups possible although catalytic procedures are
evidently more desirable In this vein the first non-transition metal catalyst for ketone
hydrogenation employing tBuOK and H2 is regarded as a breakthrough175-176 Early main group
metal catalysts have followed with highlights on a well-defined organocalcium catalyst
developed by Harder225 and the first cationic calcium hydrides by Okuda capable of catalytic
hydrogenation of 11-diphenylethylene226
Renaissance in main group chemistry emerged with the discovery of frustrated Lewis pairs
(FLPs) These relatively common main group reagents have been applied in the hydrogenation of
imines nitriles aziridines enamines silyl enol ethers olefins and alkynes typically using boron
Lewis acids relying on perfluoroaryl substituents227-228 More recently Lewis acidic borenium
ions based on an [NHC-9-BBN]+ framework have also proven ideal for hydrogenation of imine
and enamine substrates105 Du et al described the highly enantioselective hydrogenation of
imines using a chiral borane catalyst derived from the hydroboration of chiral diene
substituents104 Alkyl229 and aryl149 aluminum compounds in addition to metal-activated carbon-
based Lewis acids have been shown to participate in similar reactivity230
(a) (b)
22
214 Hydrogenation of aromatic and heteroaromatic substrates
2141 Transition metal catalysts
Despite advancements in hydrogenation catalysis the reduction of arenes and heteroaromatics to
saturated cyclic hydrocarbons remains challenging and is typically performed in the
heterogeneous phase using transition metal catalysts Such hydrogenations find particular use in
the petrochemical industry to convert alkene and aromatic fossil fuels into liquid hydrocarbons
before application in commodities such as synthetic fuel26 231 The number of complexes capable
of this catalysis is scarce mainly due to the high energy barrier required to disrupt aromaticity
Catalytic hydrogenation of aromatic systems was first demonstrated for phenols anilines and
benzene in the early 1900s by P Sabatier using powdered nickel189-193 Soon after the 14-
reduction of anisole was observed using dissolved alkali metals in liquid ammonia with major
developments emerging to include benzene and naphthalene derivatives232-233 Historically
significant accomplishments include the work of R Adams using finely divided platinum oxide
(Adamrsquos catalyst)234 and M Raney based on digestion of alloys to form finely divided metal
samples (Raney nickel)235 Other highly efficient catalysts include organometallic compounds
particularly Co Ni Ru and Rh deposited on to oxide surfaces236-239
The number of homogeneous systems capable of hydrogenating arene substrates lags well behind
heterogeneous systems The first well-documented homogeneous catalyst is a simple allylcobalt
complex η3-C3H5Co[P(OMe)3]3 reported by Muetterties and co-workers operating at room
temperature (Figure 22 left)240 shadowed by a new generation of TaV and NbV hydride catalysts
featuring bulky ancillary aryloxide ligands by Rothwell (Figure 22 right)241-243 It is noteworthy
that metal complexes of the cobalt group have provided valuable mechanistic information on this
transformation231 Ziegler type catalysts consisting of Ni or Co alkoxides acetylacetonates or
carboxylates with trialkylaluminum activators have also been demonstrated in the large scale
Institut Francais du Petrole (IFP) process231
23
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates
2142 Metal-free catalysts
Non-metal mediated routes such as the facile addition of borohydrides to unsaturated bonds
were developed early on by Brown and co-workers244 To this extent Koumlster has reported the
hydroboration and subsequent hydrogenolysis to convert naphthalenes to tetralins and
anthracenes to coronenes at 170 - 200 degC and 25 - 100 atm of H2245-246 Alternative efforts
demonstrated trialkylborane and tetraalkyldiborane catalysts in hydrogenating olefins and
polycyclic aromatic hydrocarbons including coal tar pitch In another finding homogeneous
iodine and borane catalysts were shown to hydrogenate the aromatic units of high-rank
bituminous coals at temperatures above 250 degC and 150 - 250 atm of H226 In a recent report the
Wang group has demonstrated the hydrogenation of unfunctionalized olefins catalyzed by
HB(C6F5)2247
215 Reactivity of FLPs with H2
The feasibility of FLP systems to activate H2 and hydrogenate unsaturated substrates
particularly heteroaromatic rings has been examined In this respect 26-lutidine and B(C6F5)3
exhibit reversible dissociation of the Lewis acid-base adduct providing a FLP-mode to H2
activation (Scheme 22 a)248-249 Similar acid-base equilibria were observed with N-heterocycles
nonetheless a catalytic amount of B(C6F5)3 and H2 results in reduction of the N-heterocyclic ring
(Scheme 22 b)98 Research by the Sooacutes group extended the scope of such catalytic reductions
using specifically designed Lewis acids250
24
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b)
Following these reports the commercially available Lewis acid B(C6F5)3251-252 was explored in
the hydrogenation of aromatic rings This chapter will describe results in metal-free aromatic
hydrogenation of N-bound phenyl rings of amines imines and aziridines in addition to pyridines
and N-heterocycles While these reductions are stoichiometric they represent rare examples of
homogeneous aromatic reductions that are metal-free and performed under comparatively mild
conditions Moreover the tandem hydrogenation and intramolecular cyclization of a para-
methoxy substituted aniline is presented This reaction provides a unique route to a 7-
azabicyclo[221]heptane derivative
22 Results and Discussion
221 H2 activation by amineborane FLPs
Phosphine-based FLPs have been thoroughly investigated in the activation of small molecules
and particularly revolutionizing is the first demonstration of reversible heterolytic H2 activation
by Mes2P(C6F4)B(C6F5)231 The corresponding chemistry with amineborane FLP systems has
been less explored Combination of the bulky amine tBuNHPh and an equivalent of B(C6F5)3 in
C6D5Br or pentane solutions do not result an apparent interaction by 1H 11B and 19F NMR
spectroscopy indeed supporting the ldquofrustratedrdquo nature of the system Following exposure of this
solution to H2 (4 atm) at 25 degC the gradual precipitation of a white solid was observed and after
12 h the H2 activated species [tBuNH2Ph][HB(C6F5)3] 21 was isolated in 82 yield (Scheme
23 top) The 1H NMR spectrum obtained in C6D5Br showed a broad resonance at 715 ppm
attributable to an NH2 fragment integrating to two protons as well as signals assignable to the
25
phenyl and tBu groups In addition 11B NMR spectroscopy revealed a doublet at -240 ppm (1JB-
H = 78 Hz) and 19F resonances were observed at -1335 -1613 and -1650 ppm These data
along with elemental analysis were consistent with the formulation of 21 Similar treatment of
the diamine 14-C6H4(CH2NHtBu)2 with two equivalents of B(C6F5)3 in toluene and exposure to
H2 (4 atm) resulted in formation of a precipitate at 25 degC Subsequent isolation of the product
afforded quantitative yield of the salt [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 22 (Scheme 23
bottom) The 1H NMR data showed signals at 595 ppm and 339 ppm attributable to the NH2
and BH fragments respectively The 11B and 19F NMR signals were consistent with the presence
of the [HB(C6F5)3]- anion
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom)
222 Aromatic hydrogenation of N-phenyl amines
Repetition of the H2 activation reaction between tBuNHPh and B(C6F5)3 in toluene with heating
at 110 degC for 48 h led to formation of a new product 23 Subsequent workup and
characterization by NMR spectroscopy revealed the presence of the [HB(C6F5)3]- anion The 1H
NMR spectrum displayed a broad resonance at 507 ppm attributed to an NH2 moiety while
aromatic resonances were notably absent Instead multiplets between 272 and 090 ppm along
with a sharp singlet at 091 ppm were observed This data was consistent with the identity of 23
as the cyclohexylamine product [tBuNH2Cy][HB(C6F5)3] (Scheme 24) By 1H NMR
spectroscopy after 48 h at 110 degC the reaction constituted approximately complete conversion
to 23 and was isolated in 84 yield (Table 21 entry 1)
26
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23
Treatment of iPrNHPh with an equivalent of B(C6F5)3 in toluene at 25 degC gave the
crystallographically characterized adduct (iPrNHPh)B(C6F5)3 24rsquo (Figure 23) This compound
exhibited broad resonances in the 1H 11B 13C and 19F NMR spectra at RT indicating a
fluxional adduct Upon cooling the sample to 193 K NMR signals coalesce giving distinct
resonances assignable to the adduct along with 15 inequivalent 19F resonances that are consistent
with a barrier of rotation of the pentafluorophenyl rings
Figure 23 ndash POV-Ray depiction of 24rsquo
Introducing the amine-borane adduct 24rsquo to H2 (4 atm) does not result in any noticeable changes
in the NMR spectra at RT Although thermolysis of the sample up to 70 degC eventually reveals
dissociation of the adduct with concurrent hydrogenation giving products of complete and partial
reduction of the phenyl ring The partially reduced product observed in trace amounts consisted
of olefinic resonances at 577 and 553 ppm and corresponding aliphatic signals at 256 and 222
ppm (Figure 24 insets) Extensive 1H1H COSY and 1H13C HSQC NMR studies confirmed
the compound as the partially hydrogenated 3-cyclohexenyl derivative [3-
(C6H9)NH2iPr][HB(C6F5)3] the cation is depicted in Figure 24
27
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+
Repeating the reaction at 110 degC for 36 h resulted in complete reduction of the aromatic ring
affording the salt [iPrNH2Cy][HB(C6F5)3] 24 in 93 yield (Table 21 entry 1) Monitoring the
reaction in a J-Young tube by 1H NMR spectroscopy at 110 degC showed the gradual growth of the
cyclohexyl methylene resonances with the corresponding consumption of aromatic signals
(Figure 25)
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($)
12 h
9 h
6 h
3 h
15 h
05 h
$
HB HA
28
The hydrogenation protocol was applied to PhCyNH and Ph2NH affording [Cy2NH2][HB(C6F5)3]
25 in yields of 88 and 65 respectively (Table 21 entry 2) Monitoring the reaction of Ph2NH
at 24 h intervals by 1H NMR spectroscopy did not show evidence for formation of PhCyNH
presumably this indicates that complete hydrogenation of both arene rings occurs prior to
addition of the first equivalent of hydrogen to another molecule of Ph2NH In addition to the
NMR spectroscopy data formulation of 24 and 25 were determined via X-ray crystallography
(Figure 26)
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right)
In an analogous fashion further substrates explored in such reductions included iPrNH(2-
MeC6H4) iPrNH(4-RC6H4) (R = Me OMe) iPrNH(3-MeC6H4) and iPrNH(35-Me2C6H3)
affording the arene-reduced products [iPrNH2(2-MeC6H10)][HB(C6F5)3] 26 [iPrNH2(4-
RC6H10)][HB(C6F5)3] (R = Me 27 OMe 28) [iPrNH2(3-MeC6H10)][HB(C6F5)3] 29 and
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] 210 in yields of 77 73 61 82 and 48 respectively (Table
21 entries 3 - 5) In cases where the hydrogenation reactions yield a chiral centre a mixture of
diastereomers was observed
Previously the Stephan group reported the catalytic hydrogenative ring-opening of cis-123-
triphenylaziridine using 5 mol B(C6F5)3 and H2 (4 atm) to give PhNHCHPhCH2Ph in 15 h at
120 degC94 In the following case however employing one equivalent of B(C6F5)3 at 110 ordmC for 96
h resulted in reduction of the N-bound phenyl ring yielding the salt
[CyNH2CHPhCH2Ph][HB(C6F5)3] 211 (Table 21 entry 6) The 1H NMR data were in
agreement with formulation of the cation fragment with notable resonances at 588 and 461
ppm ascribed to the NH2 and methine groups respectively in addition to the phenyl
29
cyclohexyl methylene and BH signals 11B and 19F NMR spectra displayed resonances
characteristic of the [HB(C6F5)3]- anion
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts
30
Reduction of the imine PhN=CMePh to the corresponding amine has also been previously
reported to occur upon exposure of the imine to H2 using 10 mol B(C6F5)392 Under the same
conditions heating the substrate in the presence of one equivalent of B(C6F5)3 for 96 h gave
reduction of the N-bound aromatic ring affording the species [PhCH(Me)NH2Cy][HB(C6F5)3]
212 (Table 21 entry 7) Similarly reduction of 14-C6H4(N=CMe2)2 was observed on heating
for 72 h in the presence of two equivalents of B(C6F5)3 yielding 64 of the product [14-
C6H10(iPrNH2)2][HB(C6F5)3]2 213 (Table 21 entry 8) Aromatic reduction of the bis-arene (14-
C6H4iPrNH)2CH2 with two equivalents of B(C6F5)3 was also achieved affording [(14-
C6H10iPrNH2)2CH2][HB(C6F5)3]2 214 in 76 yield (Table 21 entry 9)
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates
Although this reaction is stoichiometric in B(C6F5)3 hydrogenation of one arene ring takes up
three equivalents of H2 In an attempt to effect reactivity using sub-stoichiometric combinations
of the Lewis acid 5 mol B(C6F5)3 was combined with iPrNHPh pressurized with H2 (4 atm)
and heated at 120 degC After 24 h 1H NMR data yielded complete conversion of the borane to the
[HB(C6F5)3]- anion with only 5 mol conversion of the aniline to the [iPrNH2Cy]+ cation The
remaining 95 of the initial aniline was unaltered Increasing the H2 pressure to 80 atm did not
improve reactivity The inability of the system to turnover could be explained by pKa values of
the conjugate acid for example iPrNHPh has a pKa value of 58 in H2O while the hydrogenated
product has a pKa of about 10 - 11 in H2O (iPr2NH2 pKa 1105 in H2O) thus preventing
reversible activation of H2253-254
Furthermore efforts to hydrogenate the arene ring of iPrNHPh using pre-H2 activated FLPs
[tBu3PH][HB(C6F5)3] [Mes3PH][HB(C6F5)3] and tBu2P(H)(C6F4)B(H)(C6F5)2 did not result in
any observable reactivity by NMR spectroscopy However the stoichiometric combination of the
zwitterion Mes2P(H)(C6F4)B(H)(C6F5)2 evolved H2 at elevated temperatures and ca 10 of
[iPrNH2Cy]+ was observed Similarly 10 mol of the catalyst combination 18-
bis(diphenylphosphino)naphthalene and B(C6F5)3 gave 10 of aromatic reduction as a result of
the borane
Stoichiometric reactions of B(C6F5)3 and the anilines (p-CH3PhO2S)NHPh tBuNH(C6F5) Boc-
NHPh EtNHPh imines 26-(Me2C6H3)N=C(H)Ph PhN=CMe(p-EtOPh) phenols TMSOPh
31
tBuOPh tBuO(p-CF3C6H4) tBuO(p-FC6H4) hydrazine PhNH-NHPh 18-naphthosultam Ph3P
ethers (p-FPh)2O and CF3SPh did not evidence hydrogenation of the arene ring under the
optimized reaction conditions Furthermore the reactivity of iPrNHPh with the boranes BPh3
MesB(C6F5)2 MesB(p-C6F4H)2 PhB(C6F5)2 B(p-C6H4F)3 and B(o-C6H4CF3)3 did not activate
H2 or hydrogenate the aniline arene ring
223 Mechanistic studies for aromatic hydrogenation reactions
2231 Deuterium studies
To gain mechanistic insight into the presented transformation tBuNHPh was combined in a J-
Young tube with an equivalent of B(C6F5)3 in C6H5Br and exposed to D2 (2 atm) at 25 degC After
standing for 12 h multinuclear NMR data certainly indicated heterolytic activation of D2 The 2H
NMR spectrum gave a broad singlet at 658 ppm assigned to a N-D bond and a broad resonance
at 326 ppm attributed to a B-D bond (Figure 27 bottom-left) In addition to the 11B and 19F
NMR spectra these data supported formation of [tBuNHDPh][DB(C6F5)3] 21-d2 After heating
the sample for 3 h at 110 degC the 2H NMR revealed significant diminishing in the B-D resonance
while the N-D resonance was visibly unaltered (Figure 27 top-left) The 1H NMR spectrum of
the corresponding sample evidenced a broad quartet at 325 ppm (1JB-H = 78 Hz) representative
of a B-H bond (Figure 27 top-right) This B-H resonance is absent in the 1H NMR spectrum of
the sample at RT after 24 h (Figure 27 bottom-right)
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right)
Overall the following NMR studies are suggestive of reversible D2 activation in which at
elevated temperatures proton and deuteride from the nitrogen and boron centres of 21-d2
110 degC ND 110 degC BH (3 h) (3h) BD
RT ND BD RT (24 h) (24 h)
32
respectively combine releasing H-D The H-D gas is subsequently reactivated by the free amine-
borane FLP giving rise to [tBuND2Ph][HB(C6F5)3] (Scheme 25)
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD
2232 Variable temperature NMR studies
As supported by the aforementioned deuterium studies the reversible nature of H2 activation by
the aromatic amines and B(C6F5)3 is consistent with observation of species 21 as the initial
product of hydrogenation This is followed by evolution and reactivation of H2 allowing access
to the arene reduced species 23 at elevated temperatures (Scheme 26)
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23
This aspect of reversible H2 acitvation was further verified by variable temperature NMR studies
of the adduct (iPrNHPh)B(C6F5)3 24rsquo under H2 from 45 degC to 115 degC in C6D5Br As temperature
was increased both 11B and 19F NMR spectra displayed resonances pertaining to gradually
dissociating B(C6F5)3 and formation of the [HB(C6F5)3]- anion This is evidenced in Figure 28
by 11B NMR spectroscopy showing liberated B(C6F5)3 at 115 degC (11B δ 53 ppm) and progression
of the resonance at -25 ppm assignable to [HB(C6F5)3]- indicating formation of 24 It is
important to note that the [HB(C6F5)3]- resonance observed at the initiation of the reaction is
attributable to reversible hydride abstraction from the iPr substituent on the aniline
33
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-)
2233 Theoretical calculations
The mechanism of this study is proposed based on quantum chemical calculations performed by
Professor Stefan Grimme at Universitaumlt Bonn Germany Quantum chemical calculations were
performed at the dispersion-corrected meta-double hybrid level (PW6P95 functional) employing
large triple-zeta type basis sets and TPSS-D3 optimized geometries This final theoretical level
denoted as PWP95-D3def2-TZVPPTPSS-D3def-TZVP provides reaction energies with an
estimated accuracy of about 1 - 2 kcalmol Solvation effects of toluene were considered using
the COSMO-RS continuum solvation model255
Theoretical studies indicate a mechanism that supports reactivity to initiate by dissociation of the
weak amine-borane adduct At this stage the FLP could follow two reaction pathways (Figure
29) At moderate temperatures the FLP undergoes splitting of H2 to yield the salt 21 computed
to be 97 kcalmol lower in energy than the amine-borane adduct However the free enthalpy
difference for this species is close to zero hence under equilibrium conditions it can be
considered as a resting state of the reaction This minor difference in free enthalpy is in
agreement with reversible D2 activation results presented earlier using tBuNHPh and B(C6F5)3
45 degC
75 degC
95 degC
65 degC
115 degC
55 degC
85 degC
105 degC
34
An alternative reaction pathway follows at elevated reaction temperatures In this case the
dissociated amine rotates to position the arene para-carbon towards the boron atom creating a
van der Waals complex that is stabilized by significant pi-stacking with a C6F5 group This
complex creates a classical FLP with an electric field to polarize the entrapped H2 and effect
heterolytic splitting at a relatively low energy barrier of 87 kcalmol The free enthalpy for H2
activation relative to the resting state is computed to be 212 kcalmol certainly supporting the
elevated temperatures required to effect this reactivity
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol)
At the transition state the H-H distance is calculated to be about 097 Aring This bond is
significantly elongated compared with PB FLPs where the bond distance ranges between 078
and 080 Aring thus signifying a delayed transition state The corresponding H-H and C-H covalent
Wiberg bond orders are 033 and 041 respectively The B-H bond order is 063 indicating
approximately half-broken and half-formed bonds in the transition state88 256
21
23
35
The resulting intermediate [tBuNHC6H6][HB(C6F5)3] (CH-intermediate) is an ion pair showing
an sp3 hybridized para-carbon and an almost planar tBuNH=C unit in the cation shown in Figure
29 This species has similar energy and free enthalpy to the arene-B(C6F5)3 van der Waals
compound The complexity of subsequent hydrogenation steps to yield 23 has limited further
computations
It is noteworthy that prolonged heating of the more basic amine iPr2NPh with B(C6F5)3 under H2
only yields [iPr2NHPh][HB(C6F5)3] 215 This suggests that the greater basicity of the nitrogen
centre in iPr2NPh (Et2NHPh pKa 66 in H2O) stabilizes 215 thereby inhibiting access to the
amine-borane FLP and subsequent arene reduction (iPrNHPh pKa 58 in H2O)253-254 The overall
proposed reaction mechanism has been summarized in Scheme 27 Observation of the partially
hydrogenated cation [3-(C6H9)NH2iPr]+ illustrated in Figure 24 is presumed to be a result of H2
activation at the ortho-carbon of the arene ring
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts
224 Aromatic hydrogenation of substituted N-bound phenyl rings
2241 Fluoro-substituted rings and C-F bond transformations
Determining functional group tolerance of the demonstrated aromatic hydrogenations reaction
of the fluoro-substituted aniline (2-FPh)NHiPr with B(C6F5)3 under H2 indicated approximately
30 of the salt [(2-FPh)NH2iPr][HB(C6F5)3] after 31 h at RT Heating the sample at 110 degC for
36
24 h afforded a white solid 216a isolated in 59 yield (Scheme 28 a) Multinuclear NMR
spectroscopy revealed approximately 95 of the product consisted of [CyNH2iPr][FB(C6F5)3]
216a Spectral parameters of the cation were in agreement with that of compound 24 The
fluoroborate [FB(C6F5)3]- anionic fragment gave a broad signal at 055 ppm in the 11B NMR
spectrum and four 19F resonances were observed by 19F NMR spectroscopy at -1370 -1612 -
1669 and -1796 ppm The remaining 5 of the reaction mixture consisted of [(2-
FC6H10)NH2iPr][HB(C6F5)3] 216b Single crystals of 216a suitable for X-ray diffraction were
obtained and the structure is shown in Figure 210
Figure 210 ndash POV-Ray drawing of 216a
In a similar fashion heating the reaction of (3-FPh)NHiPr with B(C6F5)3 under H2 after 72 h
afforded the reduced product in 77 yield Approximately 95 of the salt consisted of 216a
and the remainder as [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b (Scheme 28 b) Indeed these
examples illustrate tandem B(C6F5)3 mediated arene hydrogenation and C-F bond activation
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a
37
Analogous reactivity with (4-FPh)NHiPr gave partial hydrogenation of the ring after 72 h
forming the 3-cyclohexenyl derivative [(4-FC6H8)NH2iPr][HB(C6F5)3] 218 in 62 yield
(Scheme 29) In addition to the expected resonances a diagnostic doublet of triplets in the 1H
NMR at 495 ppm and doublet at 1584 ppm (1JC-F = 255 Hz) in the 13C1H NMR spectra
certainly indicate an unsaturated C=C bond with the fluorine atom still intact This was
unambiguously confirmed by X-ray crystallography (Figure 211) It is important to note that
approximately 20 of the isolated product consisted of 216a indicating a much reduced rate of
arene hydrogenation and C-F bond activation in comparison to ortho- or meta-F substituted
anilines In these two cases intial H2 activation is expected to occur through the resonance form
in which the lone pair is at the para carbon (Scheme 27) However in the case of para-F
substituted aniline H2 activation is speculated to preferentially occur through the resonance
structure in which the negative charge is at an ortho carbon This proposal is ascribed to the
electron-withdrawing fluoro substituent which removes electron density from the para position
The partially hydrogenated product 218 is analogous to the cation [3-(C6H9)NH2iPr]+ presented
in Figure 24 in which H2 activation is suggested to initiate at the ortho carbon
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218
Figure 211 ndash POV-Ray drawing of 218
38
In light of recent findings121 a postulated mechanism implies that after reduction of the aromatic
ring B(C6F5)3 activates the C-F bond provoking nucleophilic addition of hydride from a
[HB(C6F5)3]- anion and liberating B(C6F5)3 for further reactivity Interaction of B(C6F5)3 with C-
F bonds were spectroscopically observed in a 11 combination of B(C6F5)3 and CF3-subtituted
anilines In this respect separate combinations of ortho- or para-F3CPhNH(iPr) and B(C6F5)3 in
C6D5Br gave a 19F NMR spectrum showing four broad resonances with a para-meta gap of 86
ppm and a diagnostic broad singlet assignable to a B-F resonance at -1800 ppm The broad
nature of these resonances and absence of a boron resonance in the 11B NMR spectrum do not
indicate formal C-F bond cleavage rather the data supports reversible B(C6F5)3-CF3
interaction121
2242 Methoxy-substituted rings and C-O bond transformations
Reactivity of FLP systems with oxygen-based substituents is noticeably limited due to high
oxophilicity of electrophilic boranes72 171 However recent findings have been reported on
lability of B-O adducts Stephan et al reported that the ethereal oxygen of the borane-oxyborate
(C6F5)2BCH(C6F5)OB(C6F5)3 derived from the reaction of FLPs with syn-gas activates H2 with
the B(C6F5)2 fragment117 Furthermore Et2O effects H2 activation with B(C6F5)3 and was shown
to be an efficient catalyst in the hydrogenation of olefins257 In an effort to further explore the
scope of the presented metal-free aromatic reductions the arene hydrogenation of anilines with
methoxy substituents was attempted
The combined toluene solution of B(C6F5)3 and the para-methoxy substituted imine (p-
CH3OC6H4)N=CCH3Ph was pressurized with H2 (4 atm) and heated at 110 degC for 48 h This
resulted in the formation of a new white crystalline product assigned to
[(C6H10)NHCH(CH3)Ph][HB(C6F5)3] 219 isolated in 30 yield (Scheme 210) Indeed the 1H
NMR spectrum indicated consumption of N-bound aromatic resonances concomitant with the
appearance of two inequivalent doublet of doublets observed at 447 and 374 ppm with the
corresponding 13C1H NMR resonances observed at 652 and 647 ppm respectively These
peaks are assignable to two inequivalent bridgehead CH groups of the resulting bicyclic
ammonium cation The 11B and 19F NMR spectra were in accordance with the presence of
[HB(C6F5)3]- as the anion X-ray diffraction studies further confirmed the bicyclic structure of
the product and the identity of the anion (Figure 212)
39
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219
Figure 212 ndash POV-Ray drawing of 219
In an effort to appreciate the importance of the position of the methoxy substituent on the arene
ring the separate reactions of ortho- and meta-methoxy substituted (CH3OC6H4)NHCH(CH3)Ph
with B(C6F5)3 were attempted under the established hydrogenationtransannulation protocol In
both cases hydrogenation of the N-bound phenyl group was observed although no
transannulation was achieved The amine (o-CH3OC6H4)NHCH(CH3)Ph gave cis and trans
mixtures of [(2-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 220 isolated in 92 yield In contrast
to fluorine abstraction from the ortho carbon position shown in Scheme 28 the methoxy
substituent in this case is not abstracted from the reduced ring due to steric effects preventing
B(C6F5)3 from binding to the substituent However the meta-substituted analogue resulted in C-
O bond cleavage yielding [(C6H11)NH2CH(CH3)Ph][HB(C6F5)3] 212 in 65 isolated yield
(Scheme 211) Ring closure was not obtained for this particular case due to ring strain of the
anticipated product Crystals of 220 suitable for X-ray crystallography were obtained and shown
in Figure 213
40
HB(C6F5)3
NH
OCH3
B(C6F5)3
Ph
+ CH3OH
NH2
OCH3
Ph
NH2Ph
HB(C6F5)3
NHPh
OCH3
220
212
H2
B(C6F5)3
H2
Scheme 211 ndash Synthesis of 220 and 212
Figure 213 ndash POV-Ray drawing of trans-220
In the case of the para-methoxy substituted imine B(C6F5)3 has participated in tandem arene
hydrogenation and transannulation to ultimately afford a 7-azabicyclo[221]heptane derivative a
bicyclic substructure of biological importance258 Unfortunately further expansion of the
substrate scope was not successful giving only the H2 activation product or arene hydrogenation
Such substrate examples include para-methoxyanilines with a methyl substituent at either the
ortho or meta position other para substituents such as HCF2O PhO2S and Br tertiary amine 4-
methoxy-N-phenyl-N-(1-phenylethyl)aniline
22421 Mechanistic studies for C-O and B-O bond cleavage
Studying the mechanism to form the 7-azabicyclo[221]heptane ammonium hydridoborate salt
219 the possibility of an intra- or intermolecular protonation of the methoxy group was initially
41
disproved by heating a toluene sample of the independently synthesized ammonium borate salt
trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] 221a at 110 degC (Scheme 212) No reaction
was evidenced by 1H 11B and 19F NMR spectroscopy However similar treatment of trans-[(4-
CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 221b at 110 degC prompted release of H2 as evidenced
by the 1H NMR signal at 45 ppm eventually giving compound 219 after 12 h at 110 degC
(Scheme 212)
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b)
To verify the liberation of CH3OH in the presented reactions the synthesis of 219 was repeated
starting from the free amine trans-[(4-CH3OC6H10)NHCH(CH3)Ph and B(C6F5)3 under H2
(Figure 214 a) After one week at RT the volatiles were transferred under vacuum from the
reaction vessel into a J-Young tube and the 1H NMR spectrum showed evidence of CH3OH
although a yield was not obtained
42
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c)
This observation implies that ring closing to yield the 7-azabicyclo[221]heptane ammonium
cation does not proceed by intra- or intermolecular protonation of the methoxy group rather
transannulation proceeds via intramolecular nucleophilic attack of the para-carbon by the amine
nitrogen while B(C6F5)3 captures the methoxide fragment To further support this proposed
mechanism the independently synthesized amine trans-(4-CH3OC6H10)NHiPr was treated with
an equivalent of B(C6F5)3 in the absence of H2 (Scheme 213) Interestingly after heating for 2 h
the reaction resulted in quantitative formation of a new product 222 with a sharp 11B resonance
at -242 ppm and 19F resonances at -1354 -1626 and -1668 ppm consistent with the formation
of the borane-methoxide anion [CH3OB(C6F5)3]- The 1H NMR data signified formation of the
diagnostic bridgehead CH protons at 413 ppm The combination of NMR spectroscopy
elemental analysis and X-ray diffraction studies evidenced the formation of compound 222 as
the bicyclic salt [(C6H10)NHiPr][CH3OB(C6F5)3] (Figure 215)
a)
b)
c)
43
Figure 215 ndash POV-Ray drawing of 222
Heating 222 at 110 degC in the absence of H2 eventually results in CH3OH liberation and rapid
degradation of the borane to CH3OB(C6F5)2 and C6F5H In the presence of H2 however 222 is
transformed to 223 with the liberation of CH3OH (Scheme 213) This observation implies that
the ammonium cation of 222 protonates the methoxide bound to boron liberating methanol and
regenerating B(C6F5)3 which undergoes FLP type H2 activation with the bicyclic amine
generating 223 Compound 223 was also prepared from the aniline p-CH3OC6H4NHiPr The
liberated CH3OH was isolated although not quantified and observed by 1H NMR spectroscopy
(Figure 214 b) Interestingly a similar protonation pathway has been previously proposed in a
study by Ashley and OrsquoHare whereby the stoichiometric hydrogenation of CO2 using 2266-
tetramethylpiperidine (TMP) and B(C6F5)3 was reported The authors proposed B-O bond
cleavage of [CH3OB(C6F5)3]- to occur through protonation by the 2266-
tetramethylpiperidinium counter cation259 Additionally most recently Ashley et al proposed
the metal-free carbonyl reduction of aldehydes to possibly proceed through oxonium protonation
of the boron-alkoxide anion [ROB(C6F5)3]-260
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3
44
Despite evidence for the protonation pathway contribution by a second pathway involving the
[CH3OB(C6F5)3]- anion and B(C6F5)3 acting as a FLP to activate H2 cannot be disregarded In
this respect a toluene solution of [NEt4][CH3OB(C6F5)3] and 5 mol B(C6F5)3 were exposed to
H2 (4 atm) at 110 degC After heating for 2 h the 11B and 19F NMR spectra revealed complete
consumption of the [CH3OB(C6F5)3]- anion along with emergence of peaks corresponding to the
H2 activation product [NEt4][HB(C6F5)3] and CH3OH (Scheme 214) This latter mechanism
provides an alternative path to the anion of 223 This type of system draws analogy to H2
activation by the earlier mentioned BO FLP (C6F5)2BCH(C6F5)OB(C6F5)3 suggesting H2
cleavage gives protonated oxygen and borohydride117
Gradual decomposition of the borane catalyst due to CH3OH was also observed as the amine is
not present to displace CH3OH from B(C6F5)3 consequently hindering its decomposition The
pKa of hydroxylic substrates have been shown to be significantly activated by coordination to
B(C6F5)3 generating strong Broslashnsted acids with pKa values comparable with HCl (84 in
acetonitrile)261
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3
Collectively it may be read that compound 219 is formed by initial hydrogenation of the imine
(p-CH3OC6H4)N=CCH3Ph C=N double bond followed by reduction of the arene ring affording
the cyclohexylamine The amine and borane can activate H2 to give the ammonium salt albeit at
elevated temperatures this is reversible allowing the borane to activate the methoxy substituent
and induce transannulation effecting C-O bond cleavage (Scheme 215) Subsequent conversion
of the generated methoxy-borate anion to the hydridoborate anion proceeds under H2 following
the pathways presented in Schemes 213 and 214
45
NH2
R
OCH3
110 oC
NHR
OCH3
NHR
OCH3
(F5C6)3B
+ H2
B(C6F5)3
H2
HB(C6F5)3
- H2HN
R
CH3OB(C6F5)3
+ H2
HB(C6F5)3
HNR
- CH3OH
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane
225 Aromatic hydrogenation of N-heterocyclic compounds
While seeking to extend the scope of aromatic reductions attention was focused on a series of
mono- and di-substituted pyridines quinolines and several other N-heterocycles In this regard
the aromatic hydrogenation of a variety of N-based heterocycles was explored using
stoichiometric combinations of B(C6F5)3 in the presence of H2 (4 atm)
2251 Hydrogenation of substituted pyridines
Detailed studies on the effects of increased steric bulk on pyridine249 and their reactivity with
B(C6F5)3 to activate H2248 at room temperature have been previously reported Stoichiometric
combination of the Lewis base 26-diphenylpyridine and the Lewis acid B(C6F5)3 do not show
evidence of a donor-acceptor interaction by NMR spectroscopy in contrast a reversible adduct is
observed with 26-lutidine Exposure of either combination of 26-diphenylpyridine or 26-
lutidine and B(C6F5)3 under H2 (4 atm) at room temperature activate H2 affording the
corresponding pyridinium hydridoborate salts
Nonetheless heating a mixture of 26-diphenylpyridine and B(C6F5)3 under H2 (4 atm) at 115 degC
for 16 h gives a new product isolated in 92 yield (Table 22 entry 1) The 11B NMR data in
CD2Cl2 displayed a doublet at -246 ppm and three resonances in the 19F NMR spectrum
observed at -1340 -1634 and -1666 ppm confirmed the presence of the [HB(C6F5)3]- anion
The 1H NMR spectrum showed a broad singlet at 590 ppm attributable to the NH2 group
multiplets at 453 and 226 - 189 ppm in addition to signals assignable to the phenyl and BH
46
groups These data were consistent with the formulation of the salt [26-
Ph2C5H8NH2][HB(C6F5)3] 224 Furthermore the 1H NMR data revealed a de of 91 favouring
the meso-diastereomer an assignment that was confirmed via NMR spectroscopy and the
molecular structure shown in Figure 216 (left) In a similar fashion the reaction of 26-lutidine
with B(C6F5)3 under H2 at 115 degC for 60 h afforded the corresponding salt [26-
Me2C5H8NH2][HB(C6F5)3] 225 in 84 yield (Table 22 entry 1) with a de of 80 also
favouring the meso-diastereomer (Figure 216 right) The preferred diastereoselectivity is
consistent with the known ability of B(C6F5)3 to effect epimerization of chiral carbon centres
adjacent to nitrogen by a process previously described to involve hydride abstraction and
redelivery262
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right)
The substrate ethyl 2-picolinate was exposed to the hydrogenation conditions giving a B(C6F5)3
adduct of the reduced substrate (2-(EtOCO)C5H9NH)B(C6F5)3 226 isolated in 74 yield after
36 h (Table 22 entry 2) The 11B NMR spectrum in CD2Cl2 showed a broad singlet at -486 ppm
and 15 inequivalent 19F resonances which were consistent with adduct formation between the
boron and nitrogen centres inhibiting rotation about the bond
47
Table 22 ndash Hydrogenation of substituted pyridines
Multinuclear NMR spectra of 226 displayed the presence of two diastereomers in a 11 ratio
Most distinguishable were the 13C1H resonances at 1674 and 1712 ppm attributable to the
OCO-ester groups and the 1H NMR signals at 418 and 424 ppm arising from the methine
protons Furthermore 1H1H NOESY experiments confirmed the assignment of these peaks to
the respective RSSR and RRSS diastereomers Independent reaction of B(C6F5)3 with the
optically pure piperidine S-2-(EtOCO)C5H9NH at -30 degC in CD2Cl2 afforded the preferential
formation of the SS-diastereomer of 226 However on warming to room temperature over 18 h
racemization at nitrogen eventually afforded a 11 mixture of the SS and SR diastereomers
Even though the pyridine-borane adduct of 2-phenylpyridine has been isolated and characterized
this adduct is reversed at 115 degC Reduction of the substrate using B(C6F5)3 and H2 gave a
mixture of two products isolated in 54 overall yield after 48 h (Table 22 entry 3) A broad 11B
NMR signal at -391 ppm together with a doublet at -240 ppm were consistent with the
48
presence of the adduct (2-PhC5H9NH)B(C6F5)3 227a and the ionic pair [2-
PhC5H9NH2][HB(C6F5)3] 227b in a 41 ratio respectively
The formulation of 227a is further supported by NMR data revealing two distinctively broad
NH singlets in the 1H NMR spectrum at 555 and 581 ppm attributable to a 71 ratio of the
RSSR and RRSS diastereomers The RSSR diastereomer was the more abundant form as
evidenced by NMR and X-ray crystallographic data (Figure 217)
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring
Interestingly the preferential formation of this diastereomer was evidenced by 1H19F HOESY
NMR spectroscopy through intramolecular π-π stacking interactions of the Ph and C6F5 groups
in addition to interactions between the C-H and N-H groups of piperidine and ortho-fluoro
groups of B(C6F5)3 (Figure 218) Identity of compound 227b was confirmed based on
agreement of spectral parameters with the NH2 methine and methylene groups
49
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups
The presence of adduct 227a raised the question about dissociation of the B-N bond and
possible participation of the liberated borane in further pyridine hydrogenation To probe this a
toluene solution of 2-phenylpyridine and 10 mol of 227 was exposed to H2 (4 atm) at 110 degC
After heating for 24 h 1H NMR spectroscopy did not indicate consumption of the pyridine
reagent Similarly repeating the hydrogenation of 2-phenylpyridine with 10 mol B(C6F5)3 did
not result in catalysis
2252 Hydrogenation of substituted N-heterocycles
Attempting to extend the aromatic hydrogenation of N-heterocycles beyond pyridine substrates
attention was focused to 1234-tetrahydroquinoline derivatives which have been reported to
result from the catalytic hydrogenation of N-heterocycles98 In examining the structure of
tetrahydroquinoline the carbocyclic ring fused to the N-heterocycle was observed to be similar
to a secondary aniline (Figure 219) Thus emerging the avenues of previous reports on catalytic
hydrogenation of substituted quinolines and most recent findings on the stoichiometric reduction
of anilines the complete homogeneous hydrogenation of N-heteroaromatic compounds was
explored
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring
50
Exposure of 2-methylquinoline and B(C6F5)3 to H2 (4 atm) at 115 degC for 48 h was found to effect
hydrogenation of not only the N-heterocycle but also the carbocyclic ring to yield [2-
MeC9H15NH2][HB(C6F5)3] 228 in 67 (Table 23 entry 1) In a similar fashion both rings of 2-
phenylquinoline were reduced in the same time frame to give [2-PhC9H15NH2][HB(C6F5)3] 229
in 95 yield (Table 23 entry 1)
The 1H NMR spectra for 228 and 229 exhibited characteristic chemical shifts corresponding to
NH2 methine and methylene groups Both compounds 228 and 229 were produced as mixtures
of diastereomers although in both cases the major isomer was crystallized and found to comprise
of 60 and 73 of the isolated products respectively The molecular structures show both
compounds exhibit SSSRRR stereochemistries in which one of the ring junctions adopts an
equatorial disposition while the other is axially disposed (Figure 220 a and b) Analogous
treatment of 8-methylquinoline with H2 and B(C6F5)3 in toluene for 48 h yielded [8-
MeC9H15NH2][HB(C6F5)3] 230 in 76 (Table 23 entry 1) 1H and 13C1H NMR data suggest
only the presence of the RRRSSS diastereomers (Figure 220 c)
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c)
a) b) c)
51
Table 23 ndash Hydrogenation of substituted N-heterocycles
The corresponding reduction of acridine results in isolation of the fully reduced tricyclic species
in 76 yield (Table 23 entry 2) The isolated product is obtained as a mixture of two isomers
one of which was characterized crystallographically as the salt [C13H22NH2][HB(C6F5)3] 231a
As shown in Figure 221 all ring junctions are equatorially positioned and thus the SRSRRSRS
diastereomers are assigned
Figure 221 ndash POV-Ray depiction of the cation for compound 231a
52
Interestingly a second product was isolated from the pentane work-up crystallographic data
showed it to be the adduct (C13H22NH)B(C6F5)3 231b (Figure 222) In this case however the
stereochemistries of the ring junctions adjacent to nitrogen are inverted affording the RRSSSSRR
diastereomers of the reduced acridine heterocycle Compound 231b was also independently
synthesized in 73 yield from a mixture of isomers of the neutral amine C13H22NH and
B(C6F5)3
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring
Although the substrates 23-dimethyl and 23-diphenylquinoxaline have two Lewis basic
nitrogen centres the reduction reactions required only one equivalent of B(C6F5)3 yielding the
piperazinium derivatives [23-(C4H6Me)2NHNH2][HB(C6F5)3] 232 and [23-
(C4H6Ph)2NHNH2][HB(C6F5)3] 233 in 59 and 55 yield respectively (Table 23 entry 3) In
the case of 232 a single set of diastereomers was observed and the NMR data were consistent
with ring junctions and methyl groups adopting equatorial dispositions In contrast the isolated
product 233 comprised of two diastereomers Crystallographic characterization of one
diastereomer showed the phenyl rings adopt equatorial positions while the ring junctions are
axial and equatorially disposed (Figure 223)
Figure 223 ndash POV-Ray depiction of the cation for compound 233
53
It is noteworthy that while the aromatic ring of the quinoxaline fragment is fully reduced the
phenyl substituents remain intact In a similar situation reduction of 78-benzoquinoline resulted
in the formation of [(C6H4)C7H12NH2][HB(C6F5)3] 234 in 55 yield (Table 23 entry 4) 1H
NMR spectroscopy evidenced a 41 mixture of two diastereomers in which reduction of the
pyridyl and adjacent carbocyclic ring were achieved while aromaticity of the ring remote from
the nitrogen atom was retained X-ray crystallography unambiguously confirmed the dominant
diastereomer 234a to have SRRS stereochemistry while the less abundant diastereomer 234b
showed SSRR stereochemistry (Figure 224)
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right)
Efforts to reduce the related heterocycle 110-phenanthroline in which a pyridyl ring is fused at
the 7 and 8 position of quinoline were undertaken employing one equivalent of B(C6F5)3 After
heating the solution for 14 h at 115 degC under H2 (4 atm) 1H NMR spectroscopy indicated
complete hydrogenation of the N-heterocycle in addition to loss of C6F5H and formation of a
four-coordinate boron centre with a 11B resonance observed at 302 ppm The [HB(C6F5)3]- anion
was not observed and further heating did not reveal hydrogenation of the carbocyclic ring
A second equivalent of B(C6F5)3 was added and the reaction was re-exposed to H2 (4 atm) for a
total of 96 h at 115 degC This resulted in isolation of [(C5H3N)(CH2)2(C5H8NH)B(C6F5)2]
[HB(C6F5)3] 235 in 73 yield (Table 23 entry 5) The 11B NMR spectrum revealed the
presence of two four-coordinate boron centres with resonances at 302 and -254 ppm The
former boron species exhibited six inequivalent fluorine atoms evidenced by 19F NMR
spectroscopy inferring the presence of two inequivalent fluoroarene rings where steric
congestion is inhibiting ring rotation at the B-N and B-C bonds The latter 11B NMR signal
together with the three corresponding 19F resonances arise from the [HB(C6F5)3]- anion X-ray
crystallography confirmed the formulation of 235 as the SRSRSR diastereomer present as 65
of the isolated reaction mixture (Figure 225)
54
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine
In the cationic fragment of compound 235 the boron centre is bound to two perfluoroarene rings
and is chelated by the pyridine and amine nitrogen atoms of partially reduced 110-
phenanthroline The B-N distances in the cation were found for B(1)-N(1)amine to be 1615(3) and
B(1)-N(2)pyridine 1598(3) Aring In this unique case as reduction of the heterocycle proceeds a
single pyridyl ring is initially reduced in which the resulting amine coordinates B(C6F5)3
resulting in loss of C6F5H and chelation of B(C6F5)2 by the pyridyl nitrogen centre affording the
cation (Scheme 216) The second equivalent of the borane remains intact and partakes in partial
hydrogenation of the carbocyclic ring Elimination of C6F5H followed by ring closure is
thermodynamically favoured due to formation of the five-membered borocycle
NN NN
B
B(C6F5)3
(C6F5)3B H
- C6F5H H2
235
(C6F5)2
Scheme 216 ndash Proposed reaction pathway for the formation of 235
Although this arene hydrogenation method is applicable to the presented N-heteroaromatic
substrates the reactivity was not successfully extended to 46-dimethyl-1-phenylpyrimidin-
2(1H)-one 2-methylindoline 3-methylindole 1-methylisoquinoline and carbazole
55
2253 Proposed mechanism for aromatic hydrogenation
The reductions described demonstrate the ability of B(C6F5)3 to mediate the complete aromatic
hydrogenation of a number of N-heterocycles It is clear that the products arise from reduction of
pyridyl andor aniline-type rings and in some cases affording a preferred set of diastereomers as
demonstrated by the ability of B(C6F5)3 to epimerize chiral centers alpha to nitrogen262 Efforts
to monitor several of the mixtures over the course of the reactions failed to provide unambiguous
mechanistic insight By analogy to computational studies presented for aniline hydrogenations
the need for elevated temperatures presumably reflects the fact that hybridizing the para-carbon
of the N-heterocycle is energetically uphill however once this is achieved there is an exothermic
route to the saturated amine Subsequent activation of H2 by the reduced amine and borane
affords the corresponding ammonium salt which is irreversible under the reaction conditions
thus precluding catalytic reduction This could simply be explained by Broslashnsted basicity of the
nitrogen centre An sp2 hybridized nitrogen has the lone pair in a p-orbital therefore it can
participate in resonance making it less basic as opposed to sp3 hybridization which does not have
a p-orbital (pyridine pKa 52 quinoline pKa 492 piperidine pKa 112 all values are in H2O)
While the reactions are nominally stoichiometric multiple turnovers of H2 activation are
achieved For example eight equivalents of H2 are taken up by acridine in the formation of 231
2254 Approaches to dehydrogenation
Although hydrogenation of aromatic substrates is appealing the reversible reaction
dehydrogenation of the products with aim at obtaining a molecular dihydrogen storage device
became a topic of interest Heating compound 231 at 115 degC in a vacuum sealed J-Young tube
did not evolve H2 As an alternative approach the neutral amine C13H22NH was combined with
the electrophilic boranes B(C6F5)3 B(p-C6F4H)3 or (12-C12F9)B(C6F5)2 and heated under
vacuum After 24 h trace amounts of aromatic resonances corresponding to dehydrogenation of
the N-heterocycle and a single carbocyclic ring (five equivalents of H2) was observed by 1H
NMR spectroscopy It is important to note that this process did not liberate H2 rather amine and
B(C6F5)3 abstracted proton and hydride respectively regenerating 231 One can envision this
dehydrogenation process could possibly be applied to transfer hydrogenation of imines similar
to an earlier report by the Stephan group262
56
23 Conclusions
This chapter provides an account on the discovery of N-phenyl amine reductions under H2 using
an equivalent of B(C6F5)3 to yield the corresponding cyclohexylamine derivatives In these
reactions B(C6F5)3 mediates uptake of four equivalents of H2 terminating with a final FLP
activation of H2 affording the cyclohexylammonium salts A possible reaction pathway is
proposed based on experimental evidence and theoretical calculations The substrate scope is
extended to a variety of pyridyl- and aniline-type rings of N-heterocyclic compounds These
reductions represent the first example of homogeneous metal-free hydrogenation of aromatic
rings
Shortly after publishing the presented data on aromatic hydrogenations in two separate reports
the Stephan group communicated the partial reduction of polycyclic aromatic hydrocarbons
using catalysts derived from weakly basic phosphines263 or ethers257 with B(C6F5)3 Additionally
the Du group showed a borane catalyzed route to the stereoselective hydrogenation of
pyridines264
24 Experimental Section
241 General considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane hexane tetrahydrofuran dichloromethane and toluene (Sigma Aldrich) were
dried employing a Grubbs-type column system (Innovative Technology) degassed and stored
over molecular sieves (4 Aring) in the glovebox Bromobenzene (-H5 and -D5) were purchased from
Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring molecular
sieves prior to use Dichloromethane-d2 was purchased from Sigma Aldrich dried over CaH2 and
vacuum distilled onto 4 Aring molecular sieves prior to use Tetrahydrofuran-d8 and toluene-d8 were
purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to use Molecular
sieves (4 Aring) were purchased from Sigma Aldrich and dried at 140 ordmC under vacuum for 24 h
prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at 80 degC under high
vacuum before use Sodium methoxide and tetraethylammonium chloride were purchased from
Sigma Aldrich and dried under vacuum at 140 ordmC for 12 h prior to use
57
All substituted amines anilines quinolines pyridines and other N-heterocycles were purchased
from Sigma Aldrich Alfa Aesar or TCI Potassium tetrakis(pentafluorophenyl)borate and
hydrogen chloride (40 M in 14-dioxane) were purchased from Alfa Aesar The oils were
distilled over CaH2 and solids were sublimed under high vacuum prior to use The following
compounds were independently synthesized following the cited procedure265 unless indicated
otherwise N-tert-butylaniline266 NN-(14-phenylenebis(methylene))bis(tert-butylamine) N-
isopropyl-2-methylaniline N-isopropyl-4-methylaniline N-isopropyl-4-methoxyaniline N-
isopropyl-3-methylaniline N-isopropyl-35-dimethylaniline N-(1-phenylethylidene)aniline
N1N4-di(propan-2-ylidene)benzene-14-diamine 44-methylenebis(N-isopropylaniline) 2-
fluoro-N-isopropylaniline 3-fluoro-N-isopropylaniline 4-fluoro-N-isopropylaniline 4-methoxy-
N-(1-phenylethylidene)aniline 2-methoxy-N-(1-phenylethyl)aniline266 3-methoxy-N-(1-
phenylethyl)aniline266 and alkylation methods267 to prepare trans-(4-
CH3OC6H10)NHCH(CH3)Ph and trans-(4-CH3OC6H10)NHiPr
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Varian 400 MHz spectrometer equipped with an HFX AutoX triple resonance indirect
probe (used for 13C1H 19F experiments) or an Agilent DD2 500 MHz spectrometer Spectra
were referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm
for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) d8-tol (1H = 208 ppm for CH3 13C
= 13748 ppm for ipso carbon) d8-THF (1H = 358 ppm for OCH2 13C = 6721 ppm for OCH2)
or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in ppm and the
absolute values of the coupling constants (J) are in Hz NMR assignments are supported by 2D
and DEPT-135 experiments
Elemental analyses (C H N) were performed in-house employing a Perkin Elmer 2400 Series II
CHNS Analyzer H2 (grade 50) was purchased from Linde and dried through a Nanochem
Weldassure purifier column prior to use High resolution mass spectra (HRMS) were obtained
using an ABSciex QStar Mass Spectrometer with an ESI source MSMS and accurate mass
capabilities
242 Synthesis of compounds
Synthesis of [NEt4][CH3OB(C6F5)3] In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (100 mg 0195 mmol) in CH2Cl2 (10 mL) To the vial
58
Na OCH3 (105 mg 0195 mmol) was added and the reaction was allowed to mix for 3 h at RT
The salt Na CH3OB(C6F5)3 was isolated as a white solid and dried under vacuum (110 mg 0195
mmol gt99) Na CH3OB(C6F5)3 (110 mg 0195 mmol) in CH2Cl2 (10 mL) was subsequently
added to a 4 dram vial containing NEt4 Cl (323 mg 0195 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT for 16 h and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (125 mg
0186 mmol 95)
1H NMR (400 MHz CD2Cl2) δ 322 (q 3JH-H = 73 Hz 8H Et) 311 (s 3H OCH3) 142 (tm 3JH-H = 73 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 3JF-F = 20 Hz 2F o-C6F5)
-1636 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
256 (s BOCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1480 (dm 1JC-F = 240 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1364 (dm 1JC-F = 248 Hz CF) 1246 (br ipso-C6F5) 529 (Et) 519
(OCH3) 710 (Et) Elemental analysis was not successful after numerous attempts
Synthesis of [tBuNH2Ph][HB(C6F5)3] (21) In the glove box a 100 mL Teflon screw cap
Schlenk tube equipped with a stir bar was charged with a yellow solution of B(C6F5)3 (100 mg
0195 mmol) in pentane (7 mL) To the reaction tube N-tert-butylaniline (291 mg 0195 mmol)
was added immediately resulting in a pale orange cloudy solution The reaction tube was
degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2
(4 atm) at -196 ordmC After about 10 min of reaction time at RT white precipitate was observed in
the reaction vessel and the solution became colourless The tube was left to stir at RT for 12 h
The solvent was decanted and the white precipitate was washed with pentane (3 mL) dried under
vacuum and isolated (106 mg 0160 mmol 82)
1H NMR (400 MHz C6D5Br) δ 715 (br s 2H NH2) 712 (t 3JH-H = 73 Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 682 (d 3JH-H = 76 Hz 2H o-Ph) 369 (br q 1JB-H = 78 Hz 1H BH)
102 (s 9H tBu) 19F NMR (377 MHz C6D5Br) δ -1335 (br 2F o-C6F5) -1613 (br 1F p-
C6F5) -1650 (br 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 78 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1494 (dm 1JC-F = 238 Hz CF) 1382 (dm 1JC-F = 244
Hz CF) 1369 (dm 1JC-F = 247 Hz CF) 1309 (p-Ph) 1299 (m-Ph) 1237 (o-Ph) 1244 (ipso-
C6F5) 659 (tBu) 255 (tBu) (ipso-Ph was not observed) Anal calcd () for C28H17BF15N C
5071 H 258 N 211 Found C 5027 H 287 N 219
59
[tBuNHDPh][DB(C6F5)3] (21-d2) This compound was prepared similar to 21 using D2
19F NMR (377 MHz C6H5Br) δ -1332 (m 2F o-C6F5) -1609 (br 1F p-C6F5) -1646 (m 2F
m-C6F5) 11B NMR (128 MHz C6H5Br) δ -238 (s BD)
Synthesis of [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 (22) In a glove box a 100 mL Teflon
screw cap Schlenk tube equipped with a stir bar was charged with a solution of B(C6F5)3 (304
mg 0594 mmol) and NN-(14-phenylenebis(methylene))bis(tert-butylamine) (725 mg 0297
mmol) in toluene (4 mL) The reaction was degassed three times with a freeze-pump-thaw cycle
on the vacuumH2 line The reaction flask was cooled to -196 ordmC and filled with H2 (4 atm)
Immediate precipitation of a white solid was observed at RT The reaction mixture was stirred
overnight at 70 ordmC Pentane (10 mL) was added after which the supernatant was decanted The
residue was washed with pentane (5 mL) and dried in vacuo to give the product as a white
powder (374 mg 0297 mmol gt99)
1H NMR (400 MHz CD2Cl2) δ 727 (s 4H Ph) 595 (br s 4H NH2) 438 (s 4H CH2) 339
(br q 1JB-H = 83 Hz 2H BH) 162 (s 18H tBu) 19F NMR (377 MHz CD2Cl2) δ -1349 (m 3JF-F = 21 Hz 2F o-C6F5) -1635 (t 3JF-F = 21 Hz 1F p-C6F5) -1670 (m 2F m-C6F5) 11B
NMR (128 MHz CD2Cl2) δ -243 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz d8-THF )
δ 1493 (dm 1JC-F = 236 Hz CF) 1461 (quaternary C for C6H4) 1385 (dm 1JC-F = 243 Hz CF)
1374 (dm 1JC-F = 246 Hz CF) 1345 (br ipso-C6F5) 1314 (Ph) 595 (tBu) 461 (CH2) 259
(tBu) Anal calcd () for C51H30B2F30N2 C 4852 H 240 N 222 Found C 4882 H 269 N
252
Compounds 23 ndash 214 were prepared following a common procedure In the glove box a 25 mL
Teflon screw cap Schlenk tube equipped with a stir bar was charged with a yellow solution of
B(C6F5)3 (379 mg 740 μmol) and N-phenyl amine (740 μmol) in toluene (2 mL) The reaction
tube was degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and
filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube was placed in a 110
ordmC oil bath After the appropriate reaction time the toluene was removed under reduced pressure
resulting in crude pale yellow oil The oil was washed with pentane (6 mL) affording the product
as a white powder
60
[tBuNH2Cy][HB(C6F5)3] (23) N-tert-butylaniline (110 mg 740 μmol) reaction time 48 h
product (415 mg 620 μmol 84)
1H NMR (400 MHz C6D5Br) δ 507 (br 2H NH2) 355 (br q 1JB-H = 83 Hz 1H BH) 272 (m
1H N-Cy) 155 (m 2H Cy) 145 (m 2H Cy) 131 (m 1H Cy) 117 (m 3H Cy) 091 (s 9H
tBu) 090 (m 2H Cy) 19F NMR (377 MHz C6D5Br) δ -1327 (m 3JF-F = 21 Hz 2F o-C6F5)
1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1645 (m 2F m-C6F5) 11 B NMR (128 MHz C6D5Br) δ -
240 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 238 Hz
CF) 1382 (dm 1JC-F = 247 Hz CF) 1368 (dm 1JC-F = 247 Hz CF) 1354 (ipso-C6F5) 610
(tBu) 561 (N-Cy) 319 (Cy) 258 (tBu) 244 (Cy) 236 (Cy) Anal calcd () for
C28H23BF15N C 5025 H 346 N 209 Found C 4985 H 357 N 219
Synthesis of PhNHiPrB(C6F5)3 (24rsquo) In a glove box a 20 mL dram vial equipped with a
magnetic stir bar was charged with B(C6F5)3 (176 mg 0344 mmol) and N-isopropylaniline (465
mg 0344 mmol) in toluene (4 mL) All volatiles were removed and the crude oil was washed
with hexane (2 mL) The hexane portion was reduced in volume and placed in a -30 ordmC freezer
Colourless crystals were obtained (122 mg 0192 mmol 55)
1H NMR (400 MHz CD2Cl2 193K) δ 740 - 726 (m 5H Ph) 696 (br 1H NH) 416 (br m
1H iPr) 123 (br 3H iPr) 072 (br 3H iPr) 19F NMR (367 MHz CD2Cl2 193K) δ -1219 (m
1F o-C6F5) -1272 (m 1F o-C6F5) -1279 (m 2F o-C6F5) -1315 (m 1F o-C6F5) -1388 (m
1F o-C6F5) -1543 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F p-C6F5) -1575 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1625 (m 1F m-
C6F5) -1627 (m 1F m-C6F5) -1629 (m 1F m-C6F5) -1636 (m 1F m-C6F5) 11B NMR (128
MHz CD2Cl2 193K) δ -323 (s B-N) 13C1H NMR (101 MHz CD2Cl2 298K) δ 1478 (dm 1JC-F = 246 Hz CF) 1390 (dm 1JC-F = 242 Hz CF) 1365 (dm 1JC-F = 236 Hz CF) 1328
(ipso-Ph) 1301 (o-Ph) 1295 (p-Ph) 1227 (m-Ph) 556 (iPr) 195 (iPr) (ipso-C6F5 was not
observed) Anal calcd () for C27H13BF15N C 5011 H 202 N 216 Found C 4961 H 246
N 209
[iPrNH2Cy][HB(C6F5)3] (24) N-Isopropylaniline (100 mg 740 μmol) reaction time 36 h
product (481 mg 730 μmol 93) Crystals suitable for X-ray diffraction were grown from a
layered dichloromethanepentane solution at -30 ordmC
61
1H NMR (400 MHz C6D5Br) δ 510 (s 2H NH2) 356 (br q 1JB-H = 84 Hz 1H BH) 303 (m 1JH-H = 65 Hz 1H iPr) 276 (m 1H N-Cy) 156 (m 2H Cy) 147 (m 2H Cy) 134 (m 1H
Cy) 099 - 086 (m 5H Cy) 091 (d 1JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1330 (m 3JF-F = 21 Hz 2F o-C6F5) -1609 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-
C6F5) 11 B NMR (128 MHz C6D5Br) δ -239 (d 1JB-H = 84 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1483 (dm 1JC-F = 238 Hz CF) 1384 (dm 1JC-F = 247 Hz CF) 1369 (dm 1JC-F =
248 Hz CF) 1288 (ipso-C6F5) 567 (N-Cy) 498 (iPr) 294 (Cy) 241 (Cy) 240 (Cy) 189
(iPr) Anal calcd () for C27H21BF15N C 4949 H 323 N 214 Found C 4952 H 345 N
219
[Cy2NH2][HB(C6F5)3] (25) Method 1 N-Cyclohexylaniline (130 mg 740 μmol) reaction
time 36 h product (452 mg 650 μmol 88) Method 2 Diphenylamine (125 mg 740 μmol)
reaction time 96 h product (334 mg 480 μmol 65) Crystals suitable for X-ray diffraction
were grown from a concentrated solution in C6D5Br at RT
1H NMR (400 MHz C6D5Br) δ 498 (br s 2H NH2) 317 (br q 1JB-H = 86 Hz 1H BH) 247
(m 2H N-Cy) 122 (m 4H Cy) 111 (m 4H Cy) 099 (m 2H Cy) 070 - 046 (m 10H Cy)
19F NMR (377 MHz C6D5Br) δ -1332 (m 3JF-F = 20 Hz 2F o-C6F5) -1608 (t 3JF-F = 20 Hz
1F p-C6F5) -1648 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 86 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 241 Hz CF) 1380 (dm 1JC-F =
247 Hz CF) 1365 (dm 1JC-F = 248 Hz CF) 1264 (ipso-C6F5) 558 (N-Cy) 293 (Cy) 238
(Cy) 237 (Cy) Anal calcd () for C30H25BF15N C 5182 H 362 N 201 Found C 5217 H
386 N 212
[iPrNH2(2-MeC6H10)][HB(C6F5)3] (26) N-Isopropyl-2-methylaniline (111 mg 740 μmol)
reaction time 36 h product (398 mg 570 μmol 77) NMR data is reported for one isomer
1H NMR (400 MHz C6D5Br) δ 587 (br 2H NH2) 375 (br q 1JB-H = 82 Hz 1H BH) 318 (m
1H N-Cy) 313 (m 3JH-H = 62 Hz 1H iPr) 180 - 118 (m 9H Cy) 113 (d 3JH-H = 64 Hz
6H iPr) 086 (d 3JH-H = 62 Hz 3H Me) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21
Hz 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -237 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) partial δ
1485 (dm 1JC-F = 235 Hz CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF)
1236 (ipso-C6F5) 638 (N-Cy) 593 (iPr) 347 (Cy) 319 (Cy) 304 (CMeH) 291 (Cy) 210
62
(Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C 5021 H
359 N 214
[iPrNH2(4-MeC6H10)][HB(C6F5)3] (27) N-isopropyl-4-methylaniline (111 mg 740 μmol)
reaction time 36 h product (377 mg 540 μmol 73)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 83 Hz 1H BH) 317 (m 3JH-H = 64 Hz 1H iPr) 290 (m 1H N-Cy) 171 (m 2H Cy) 162 (m 2H Cy) 120 (m 3H
Cy) 110 (d 3JH-H = 64 Hz 6H iPr) 086 (d 3JH-H = 66 Hz 3H Me) 077 (m 2H Cy) 19F
NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1613 (t 3JF-F = 21 Hz 1F
p-C6F5) -1652 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -236 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 247
Hz CF) 1367 (dm 1JC-F = 250 Hz CF) 562 (N-Cy) 495 (iPr) 319 (Cy) 304 (CMeH) 291
(Cy) 210 (Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found
C 5014 H 348 N 209
[iPrNH2(4-MeOC6H10)][HB(C6F5)3] (28) N-Isopropyl-4-methoxyaniline (122 mg 740
μmol) reaction time 36 h product (308 mg 450 μmol 61)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 346 (br
4H OMe and CHOMe) 299 (br m 1H N-Cy) 237 (m 1H iPr) 162 (m 2H Cy) 129 (m
2H Cy) 107 (m 4H Cy) 081 (d 3JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1338 (m 3JF-F = 21 Hz 2F o-C6F5) -1623 (t 3JF-F = 21 Hz 1F p-C6F5) -1659 (m 2F m-
C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1484 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 247 Hz CF) 1367 (dm 1JC-F =
247 Hz CF) 1243 (ipso-C6F5) 636 (OMe) 583 (CHOMe) 551 (N-Cy) 497 (iPr) 267 (Cy)
246 (Cy) 183 (iPr) Anal calcd () for C28H23BF15NO C 4908 H 338 N 204 Found C
4945 H 329 N 230
[iPrNH2(3-MeC6H10)][HB(C6F5)3] (29) N-Isopropyl-3-methylaniline (111 mg 740 μmol)
reaction time 36 h product (406 mg 610 μmol 82)
1H NMR (400 MHz C6D5Br) δ 547 (br 2H NH2) 369 (br q 1JB-H = 80 Hz 1H BH) 320 (m
1H iPr) 297 (m 1H N-Cy) 171 (m 3H Cy) 153 (m 1H Cy) 112 (m 1H CMeH) 112 (d
63
3JH-H = 60 Hz 3H iPr) 111 (d 3JH-H = 60 Hz 3H iPr) 104 (m 2H Cy) 086 (d 3JH-H = 66
Hz 3H Me) 078 (m 1H Cy) 068 (m 1H Cy) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1611 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5) 11B
NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ
1488 (dm 1JC-F = 237 Hz CF) 1390 (dm 1JC-F = 250 Hz CF) 1372 (dm 1JC-F = 247 Hz CF)
571 (N-Cy) 503 (iPr) 381 (Cy) 330 (Cy) 315 (CMeH) 293 (Cy) 241 (Cy) 219 (Me)
196 (iPr) 192 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C
5011 H 350 N 216
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] (210) N-Isoporpyl-35-dimethylaniline (121 mg 740
μmol) reaction time 72 h product (243 mg 360 μmol 48) Mixture of isomers was obtained
NMR data for one isomer is reported
1H NMR (400 MHz C6D5Br) δ 555 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 300 -
280 (br m 2H iPr N-Cy) 182 (br m 1H Cy) 149 - 100 (m 5H Cy) 093 (m 6H iPr) 077
- 072 (m 1H Cy) 068 - 062 (m 6H Me) 059 - 048 (m 1H Cy) 19F NMR (377 MHz
C6D5Br) δ -1337 (m 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5)
11B NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 82 Hz BH) 13C1H NMR (100 MHz
C6D5Br) partial δ 1479 (dm 1JC-F = 240 Hz CF) 1378 (dm 1JC-F = 249 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1227 (ipso-C6F5) 560 (N-Cy) 494 (iPr) 410 (Cy) 378 (Cy) 270 (Cy)
212 (Me) 188 (iPr) Anal calcd () for C29H25BF15N C 5097 H 369 N 205 Found C
5087 H 399 N 212
[CyNH2CHPhCH2Ph][HB(C6F5)3] (211) cis-123-Triphenylaziridine (201 mg 740 μmol)
reaction time 96 h product (293 mg 370 μmol 50)
1H NMR (400 MHz CD2Cl2) δ 755 (m 1H p-Ph) 745 (m 4H Ph) 740 (m 3H Ph) 720
(m 2H Ph) 588 (br 2H NH2) 461 (t 3JH-H = 77 Hz 1H PhCH) 369 (br q 1JB-H = 85 Hz
1H BH) 344 (d 2H 3JH-H = 77 Hz PhCH2) 306 (m 1H N-Cy) 203 (m 1H Cy) 168 (m
4H Cy) 137 - 115 (br m 5H Cy) 19F NMR (377 MHz CD2Cl2) δ -1338 (m 3JF-F = 20 Hz
2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1662 (m 2F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -239 (d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F
= 245 Hz CF) 1382 (dm 1JC-F = 248 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1333 (ipso-Ph)
1321 (ipso-Ph) 1310 (p-Ph) 1301 (Ph) 1298 (Ph) 1289 (Ph) 1287 (p-Ph) 1273 (Ph) 1235
64
(ipso-C6F5) 641 (PhCH) 582 (N-Cy) 403 (PhCH2) 306 (Cy) 289 (Cy) 241 (Cy) 238
(Cy) 236 (Cy) Anal calcd () for C38H27BF15N C 5752 H 343 N 177 Found C 5762 H
395 N 187
[PhCH(Me)NH2Cy][HB(C6F5)3] (212) Method 1 N-(1-Phenylethylidene)aniline (144 mg
740 μmol) reaction time 96 h product (303 mg 420 μmol 57) Method 2 B(C6F5) (379 mg
0740 mmol) 3-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol) toluene (5 mL)
product (347 mg 0481 mmol 65)
1H NMR (400 MHz C6D5Br) δ 735 (m 3H o p-Ph) 721 (m 2H m-Ph) 618 (br 1H NH2)
566 (br 1H NH2) 428 (m 1H NH2CHMe) 383 (br q 1JB-H = 83 Hz 1H BH) 288 (m 1H
N-Cy) 190 (m 1H Cy) 166 (m 2H Cy) 157 (m 1H Cy) 154 (d 3JH-H = 69 Hz 3H Me)
146 (m 1H Cy) 126 (m 2H Cy) 098 (m 3H Cy) 19F NMR (377 MHz C6D5Br) δ -1336
(m 2F o-C6F5) -1613 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -234 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 241 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1334
(ipso-Ph) 1296 (o-Ph) 1260 (m-Ph) 574 (NH2CHMe) 573 (N-Cy) 295 (Cy) 288 (Cy)
236 (Cy) 236 (Cy) 188 (Me) (p-Ph was not observed) Anal calcd () for C32H23BF15N C
5358 H 323 N 195 Found C 5374 H 300 N 189
[14-C6H10(iPrNH2)2][HB(C6F5)3]2 (213) N1N4-Di(propan-2-ylidene)benzene-14-diamine (70
mg 0037 mmol) reaction time 36 h product (293 mg 240 μmol 64)
1H NMR (400 MHz d8-THF) δ 784 (br 2H NH2) 376 (br q 1JB-H = 92 Hz 1H BH) 364 (m 3JH-H = 65 Hz 1H iPr) 335 (br m 1H N-Cy) 238 (m 2H Cy) 159 (m 2H Cy) 138 (d 3JH-
H = 65 Hz 6H iPr) 19F NMR (377 MHz d8-THF) δ -1346 (m 3JF-F = 20 Hz 2F o-C6F5) -
1670 (t 3JF-F = 20 Hz 1F p-C6F5) -1697 (m 2F m-C6F5) 11B NMR (128 MHz d8-THF) δ -
254 (d 1JB-H = 92 Hz BH) 13C1H NMR (101 MHz d8-THF) δ 1483 (dm 1JC-F = 237 Hz
CF) 1375 (dm 1JC-F = 242 Hz CF) 1362 (dm 1JC-F = 246 Hz CF) 1259 (ipso-C6F5) 528 (N-
Cy) 486 (iPr) 274 (Cy) 184 (iPr) Anal calcd () for C48H30B2F30N2 C 4701 H 247 N
228 Found C 4686 H 247 N 232
[(14-C6H10(iPrNH2))2CH2][HB(C6F5)3]2 (214) 44-Methylenebis(N-isopropylaniline) (104
mg 370 μmol) reaction time 76 h product (372 mg 280 μmol 76)
65
1H NMR (400 MHz C6D5Br) δ 513 (br 2H NH2) 359 (br q 1JB-H = 81 Hz 1H BH) 301 (m
1H iPr) 276 (m 1H N-Cy) 168 (m 1H Cy) 151 (m 2H Cy) 145 (m 1H CH2) 132 (m
2H Cy) 091 (m 2H Cy) 089 (m 2H Cy) 089 (d 3JH-H = 68 Hz 6H iPr) 19F NMR (377
MHz C6D5Br) δ -1331 (m 3JF-F = 20 Hz 2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -
1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 81 Hz BH) 13C1H
NMR (101 MHz C6D5Br) δ 1486 (dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF)
1385 (dm 1JC-F = 247 Hz CF) 569 (iPr) 500 (N-Cy) 432 (CH2) 296 (Cy) 272 (CH2-Cy)
242 (Cy) 190 (iPr) Anal calcd () for C55H42B2F30N2 C 4995 H 320 N 212 Found C
4973 H 333 N 221
[iPr2NHPh][HB(C6F5)3] (215) In a glove box B(C6F5)3 (379 mg 740 μmol) and NN-
diisopropylaniline (131 mg 740 μmol) were dissolved in C6D5Br (05 mL) and added into a
Teflon capped sealed J-Young tube The J-Young tube was degassed three times through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC and placed
in a 110 ordmC oil bath for 16 h To the C6D5Br solution pentane was added drop wise until the
product precipitated The white solid was isolated (442 mg 640 μmol 87) Crystals suitable
for X-ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H o p-Ph) 693 (m 2H m-Ph) 670 (br 1H NH)
371 (br q 1JB-H = 85 Hz 1H BH) 358 (m 3JH-H = 63 Hz 2H iPr) 093 (d 3JH-H = 63 Hz 6H
iPr) 077 (d 3JH-H = 63 Hz 6H iPr) 19F NMR (377 Hz C6D5Br) δ -1326 (m 3JF-F = 20 Hz
2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -245 ppm (br d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484
(dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1322
(ipso-Ph) 1304 (m-Ph) 1231 (p-Ph) 1211 (o-Ph) 584 (iPr) 188 (iPr) 168 (iPr) Anal calcd
() for C30H21BF15N C 5212 H 306 N 203 Found C 5183 H 329 N 211
Synthesis of 216 - 218 is similar to the general procedure used for compounds 23 - 214 Since
compounds [(2-FC6H10)NH2iPr][HB(C6F5)3] 216b and [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b
were present in trace amounts (5) isolation and characterization proved difficult therefore
spectroscopic data for the two compounds has not been reported
[iPrNH2Cy][FB(C6F5)3] (216a) B(C6F5)3 (379 mg 0740 mmol) 2-fluoro-N-isopropylaniline
(115 mg 0740 mmol) or 3-fluoro-N-isopropylaniline (115 mg 0740 mmol) toluene (5mL)
66
reaction time 72 h product from 2-fluoro-N-isopropylaniline (294 mg 0440 mmol 59)
product from 3-fluoro-N-isopropylaniline (381 mg 0570 mmol 77) Crystals suitable for x-
ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 561 (br 2H NH2) 288 (m 3JH-H = 64 Hz 1H iPr) 262 (br
m 1H N-Cy) 149 (m 2H Cy) 144 (m 2H Cy) 135 (m 1H Cy) 092 - 083 (m 5H Cy)
085 (d 1JH-H = 63 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1370 (m 6F o-C6F5) -1616
(t 3JF-F = 22 Hz 3F p-C6F5) -1669 (m 6F m-C6F5) -1795 (br s 1F BF) 11B NMR (128
MHz CD2Cl2) δ 051 (br s BF) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 239
Hz CF) 1394 (dm 1JC-F = 241 Hz CF) 1373 (dm 1JC-F = 249 Hz CF) 560 (N-Cy) 489
(iPr) 293 (Cy) 245 (Cy) 241 (Cy) 188 (iPr) Anal calcd () for C27H20BF16N C 4817 H
299 N 208 Found C 4804 H 307 N 210
[(4-FC6H8)NH2iPr][HB(C6F5)3] (218) B(C6F5)3 (379 mg 074 mmol) 4-fluoro-N-
isopropylaniline (113 mg 074 mmol) toluene (5 mL) reaction time 72 h product (308 mg
0460 mmol 62) Crystals suitable for X-ray diffraction were obtained from a layered solution
of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 582 (br s 2H NH2) 477 (dm 3JF-H = 14 Hz 1H CH=CF)
355 (br q 1JB-H = 81 Hz 1H BH) 345 (m 1H iPr) 293 (m 1H N-Cy) 192 - 133 (m 6H
CH2 groups of Cy) 081 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -9903
(dm 3JF-H = 14 Hz 1F FC=CH) -1331 (m 3JF-F = 23 Hz 6F o-C6F5) -1606 (t 3JF-F = 21 Hz
3F p-C6F5) -16398 (m 6F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 81 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1584 (d 1JC-F = 255 Hz CF=CH) 1484 (dm 1JC-F =
224 Hz C6F5)1385 (dm 1JC-F = 247 Hz C6F5)1369 (dm 1JC-F = 247 Hz C6F5) 1230 (ipso-
C6F5) 974 (d 2JC-F = 20 Hz CF=CH) 518 (iPr) 504 (N-Cy) 254 (d 2JC-F = 81 Hz CH2CF)
247 (d 3JC-F = 90 Hz CH2CH=CF) 228 (CH2) Anal calcd () for C27H18BF16N C 4831 H
270 N 209 Found C 4793 H 282 N 203
Synthesis of 219 and 220 is similar to the general procedure used for compounds 23 - 214
Synthesis of [C6H10NHCH(CH3)Ph][HB(C6F5)3] (219) Method 1 B(C6F5) (358 mg 0700
mmol) 4-methoxy-N-(1-phenylethylidene)aniline (113 mg 0500 mmol) toluene (4 mL) (107
67
mg 0150 mmol 30) Crystals suitable for X-ray diffraction were obtained from a layered
solution of dichloromethanepentane at -30 degC
Method 2 In the glovebox trans-(4-CH3OC6H10)NHCH(CH3)Ph (81 mg 340 μmol) and
B(C6F5)3 (17 mg 340 μmol) were dissolved in d8-toluene (04 mL) and added into a Teflon
capped J-Young tube The tube was degassed once through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at
110 degC The solvent was removed under vacuum and the residue was washed with pentane (2
mL) The product was dried under vacuum and collected (82 mg 110 μmol 33)
1H NMR (500 MHz CD2Cl2) δ 752 (tm 3JH-H = 77 Hz 1H p-Ph)
746 (tm 3JH-H = 77 Hz 2H m-Ph) 735 (dm 3JH-H = 77 Hz 2H o-
Ph) 555 (br m 1H NH) 447 (dd 3JH-H = 95 Hz 48 Hz 1H H1)
415 (dq 3JH-H = 102 Hz 68 Hz 1H CH(CH3)Ph) 374 (m JH-H = 95
Hz 48 Hz 1H H5) 363 (br q 1JB-H = 83 Hz 1H BH) 229 (m 1H
H3) 223 (m 1H H4) 215 (m 1H H2) 201 (m 1H H3) 196 (m 1H H6) 190 (m 1H H2)
188 (m 1H H4) 177 (d 3JH-H = 68 Hz 3H CH3) 176 (m 1H H6) 19F NMR (377 MHz
CD2Cl2) δ -1304 (m 2F o-C6F5) -1638 (t 1F 3JF-F = 21 Hz p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -249 (d 1JB-H = 83 Hz BH) 13C1H NMR (125 MHz
CD2Cl2) δ 1482 (dm 1JC-F = 236 Hz C6F5) 1378 (dm 1JC-F = 245 Hz C6F5) 1364 (dm 1JC-F
= 249 Hz C6F5) 1346 (ipso-Ph) 1308 (p-Ph) 1301 (m-Ph) 1266 (o-Ph) 1246 (ipso-C6F5)
652 (C5) 647 (C1) 586 (CH(CH3)Ph) 277 (C2) 273 (C6) 254 (C3 C4) 188 (CH3) Anal
calcd () for C32H21BF15N C 5373 H 296 N 196 Found 5384 H 321 N 200
[(o-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (220) Ratio of cis and trans isomers = 11
determined by 1H NMR spectroscopy The trans isomer has been isolated and characterized
B(C6F5) (379 mg 0740 mmol) 2-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol)
toluene (5 mL) product (508 mg 0680 mmol 92) Crystals suitable for X-ray diffraction were
obtained from a layered solution of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H m p-Ph) 691 (m 2H o-
Ph) 655 (br s 2H NH2) 413 (q 3JH-H = 64 Hz 1H CH(Me)Ph) 365
(br q 1JB-H = 92 Hz 1H BH) 313 (ddd 3JH-H = 107 Hz 43 Hz 1H
CHOCH3) 298 (s 3H OCH3) 237 (td 3JH-H = 107 Hz 1H CH2CHNH2) 180 (m 1H DCH2)
68
173 (dm 3JH-H = 136 Hz 1H ACH2) 140 (m 2H DCCH2) 128 (d 3JH-H = 64 Hz 3H
CH(CH3)Ph) 120 (m 1H BCH2) 095 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H BCH2)
066 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H CCH2) 039 (pseudo qd JH-H = 136 Hz 3JH-
H = 31 Hz 1H ACH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -1634 (t 3JF-F =
21 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -246 (d 1JB-H = 92
Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 235 Hz C6F5) 1381 (dm 1JC-F = 246 Hz C6F5) 1367 (dm 1JC-F = 247 Hz C6F5) 1334 (ipso-Ph) 1304 (p-Ph) 1299 (m-
Ph) 1264 (o-Ph) 1239 (ipso-C6F5) 778 (CHOCH3) 611 (CH2CHNH2) 571 (CH(CH3)Ph)
554 (OCH3) 279 (ACH2) 257 (DCH2) 236 (CCH2) 224 (BCH2) 202 (CH3) Anal calcd ()
for C33H25BF15NO C 5303 H 337 N 187 Found 5288 H 357 N 190
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] (221a) Part 1 In a Schlenk
tube trans-(4-CH3OC6H10)NHCH(CH3)Ph (16 mg 680 μmol) was dissolved in pentane (2 mL)
and hydrogen chloride (68 μL 027 mmol 40 M in 14-dioxane) was added drop wise White
precipitate was immediately formed The solvent was decanted and the solid was washed with
pentane (2 mL) and dried in vacuo to yield trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (163 mg
610 μmol 89)
Part 2 In the glovebox a 4 dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph
HCl (61 mg 0026 mmol) in dichloromethane (8 mL) and K B(C6F5)4 (162 mg 260 mmol)
was added at once The reaction was allowed to stir for 16 h at room temperature The mixture
was filtered through Celite and the solvent was removed under vacuum The product was
obtained as a white solid (209 mg 230 μmol 88)
1H NMR (400 MHz C6D5Br) δ 719 (m 2H m-Ph) 690 (m 3H o p-Ph) 510 (br s 2H NH2)
402 (q 3JH-H = 69 Hz 1H CH(CH3)Ph) 310 (s 3H OCH3) 272 (m 2H CyCHOCH3 CyCHN) 174 (m 3H CyCH2) 156 (m 1H CyCH2) 127 (d 3JH-H = 69 Hz 3H CH(CH3)Ph
093 - 084 (m 4H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1318 (m 2F o-C6F5) -1610 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -164 (s
B(C6F5)4)
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (221b) In the glovebox a 4
dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (93 mg 0034 mmol) in
dichloromethane (8 mL) and Na HB(C6F5)3 (185 mg 340 μmol) was added at once The
69
reaction was allowed to stir for 16 h at room temperature The mixture was filtered through
Celite and the solvent was removed under vacuum The product was obtained as a white solid
(193 mg 260 μmol 76) Preparation of Na HB(C6F5)3 is reported in Chapter 3
1H NMR (400 MHz C6D5Br) δ 716 (m 3H Ph) 702 (m 2H Ph) 546 (br 2H NH2) 407 (q 3JH-H = 68 Hz 1H CH(CH3)Ph) 347 (br q 1JB-H = 78 Hz 1H BH) 307 (s 3H OCH3) 283
(tt 3JH-H = 106 Hz 46 Hz 1H CyCHOCH3) 268 (tt 3JH-H = 117 Hz 39 Hz 1H CyCHN) 183
(m 3H CyCH2) 156 (dm 3JH-H = 128 Hz 1H CyCH2) 132 (d 3JH-H = 68 Hz CH(CH3)Ph)
121 (m 2H CyCH2) 084 (m 2H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1334 (m 2F o-
C6F5) -1604 (t 3JF-F = 22 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -238 (d 1JB-H = 78 Hz BH)
Synthesis of [C6H10NH(iPr)][CH3OB(C6F5)3] (222) In the glovebox a Schlenk tube (25 mL)
was charged with trans-(4-CH3OC6H10)NH(iPr) (253 mg 0148 mmol) in toluene (05 mL) and
B(C6F5) (758 mg 0148 mmol) dissolved in toluene (05 mL) was added at once The Schlenk
was sealed and heated at 110 degC for 2 h and the solvent was removed under vacuum The crude
solid was washed with pentane (2 mL) to yield the product as a white solid (991 mg 0145
mmol 98) Crystals suitable for X-ray diffraction were obtained from a layered solution of
dichloromethanepentane at -30 degC
1H NMR (500 MHz CD2Cl2) δ 810 (s 1H NH) 413 (m 2H CH2CH) 315 (m 3JH-H = 66
Hz 1H iPr) 302 (s 3H BOCH3) 222 (dm 1JH-H = 93 Hz 2H ACH2) 205 (dm 1JH-H = 100
Hz 2H BCH2) 181 (dm 1JH-H = 100 Hz 2H BCH2) 172 (dm 1JH-H = 93 Hz 2H ACH2) 136
(d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1351 (br 2F o-C6F5) -1620 (t 3JF-F = 20 Hz 1F p-C6F5) -1664 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -242 (s
BOCH3) 13C1H NMR (125 MHz CD2Cl2) δ 1482 (dm 1JC-F = 241 Hz C6F5) 1388 (dm 1JC-F = 262 Hz C6F5) 1370 (dm 1JC-F = 252 Hz C6F5) 1231 (ipso-C6F5) 634 (CH2CH) 522
(BOCH3) 502 (iPr) 274 (ACH2) 258 (BCH2) 185 (iPr) Anal calcd () for C28H21BF15N05
CH2Cl2 C 4717 H 306 N 193 Found 4674 H 327 N 199 HRMS-DART mz [M] calcd
for C9H18N+ 1401 Found 1401
Synthesis of [C6H10NH(iPr)][HB(C6F5)3] (223) Method 1 In the glovebox trans-(4-
CH3OC6H10)NH(iPr) (250 mg 0150 mmol) and B(C6F5)3 (760 mg 0150 mmol) were
dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The tube was
70
degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4
atm) at -196 ordmC The reaction was complete after 12 h at 110 degC The solvent was removed under
vacuum and the residue was washed with pentane (2 mL) The product was collected as a white
powder (607 mg 930 μmol 62)
Method 2 In the glovebox compound [C6H10NH(iPr)][CH3OB(C6F5)3] (222) (200 mg 290
μmol) was dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The
tube was degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with
H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at 110 degC
1H NMR (400 MHz C6D5Br) δ 510 (br m 1H NH) 367 (br q 1JB-H = 76 Hz 1H BH) 347
(br s 2H CH) 242 (m 1H iPr) 162 (m 2H CH2) 131 (m 2H CH2) 111 (m 2H CH2) 093
(m 2H CH2) 138 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -1338 (m 3JF-F
= 21 Hz 2F o-C6F5) -1622 (t 3JF-F = 21 Hz 1F p-C6F5) -1658 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -239 (d 1JB-H = 76 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483
(dm 1JC-F = 235 Hz CF) 1381 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 248 Hz CF) 1242
(ipso-C6F5) 636 (CHCH2) 500 (iPr) 271 (CH2) 248 (CH2) 186 (iPr) Anal calcd () for
C27H19BF15N C 4964 H 293 N 214 Found C 4924 H 300 N 214
Compounds 224 - 235 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 50 mL Teflon screw cap Schlenk tube equipped with a stir bar was charged
with a solution of B(C6F5)3 (0379 g 0740 mmol) and the respective N-heterocycle in toluene (5
mL) The reaction tube was degassed three times through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube
was placed in a 115 ordmC oil bath for the indicated reaction time The solvent was then removed
under vacuum and the crude product was washed with pentane to yield the product as a white
solid
[26-Ph2C5H8NH2][HB(C6F5)3] (224) 26-Diphenylpyridine (171 mg 0740 mmol) reaction
time 16 h product (511 g 0680 mmol 92) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC Isomer ratio by 1HNMR
spectroscopy meso 91 rac 9
71
meso-[26-Ph2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 734 (tt 3JH-H = 70 Hz
4JH-H = 24 Hz 2H p-Ph) 726 (m 8H o m-Ph) 590 (br 2H NH2) 453 (m 3JH-H = 122 Hz 3JH-H = 24 Hz 2H C(H)Ph) 339 (br q 1JB-H = 90 Hz 1H BH) 226 (br m 3H CH2) 212 (m
2H CH2) 189 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1340 (m 2F o-C6F5) -1634 (t 3JF-F = 20 Hz 1F p-C6F5) -1666 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -246 (d 1JB-H = 90 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1483 (dm 1JC-F = 237 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1367 (dm 1JC-F = 246 Hz CF) 1338 (ipso-Ph) 1313 (p-Ph) 1271
(Ph) 1264 (Ph) 1241 (ipso-C6F5) 657 (C(H)(Ph)) 297 (CH2) 233 (CH2) Anal calcd ()
for C35H21BF15N C 5595 H 282 N 186 Found C 5547 H 303 N 186
[26-Me2C5H8NH2][HB(C6F5)3] (225) 26-Dimethylpyridine (793 mg 0740 mmol) reaction
time 60 h product (390 mg 0621 mmol 84) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC over 48 h Isomer ratio by 1HNMR spectroscopy meso 80 rac 20
meso-[26-Me2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 508 (br 2H NH2) 345
(br q 1JB-H = 83 Hz 1H BH) 268 (m 2H NC(H)Me) 137 (m 4H CH2) 086 (d 3JH-H = 64
Hz 6H CH3) 077 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -
1617 (t 3JF-F = 20 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1485 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF) 1236 (ipso-C6F5) 567
(NCH) 303 (CH2) 220 (CH2) 193 (CH3) Anal calcd () for C25H17BF15N C 4787 H 273
N 223 Found C 4764 H 290 N 222
(2-(EtOCO)C5H9NH)B(C6F5)3 (226) Ethyl 2-picolinate (112 mg 0740 mmol) reaction time
36 h product (366 mg 0547 mmol 74) The isolated product consisted of an equal ratio of
both diastereomers Anal calcd () for C26H15BF15NO2 C 4667 H 226 N 209 Found C
4660 H 247 N 211
RSSR-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2)
δ 590 (m 1H NH) 430 (m 1H CH(H)NH) 418 (br m 1H
CHOCOEt) 393 (dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 373
(dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 320 (dm 2JH-H = 126 Hz 1H CH(H)NH) 217
(m 2H CH2) 204 (dm 2JH-H = 134 Hz 1H CH2) 184 (m 1H CH2) 175 (m 1H CH2) 119
72
(t 3JH-H = 72 Hz 3H Et) 103 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1264 (m 1F o-
C6F5) -1280 (m 1F o-C6F5) -1295 (m 1F o-C6F5) -1297 (m 1F o-C6F5) -1404 (m 1F o-
C6F5) -1433 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F
p-C6F5) -1575 (t 3JF-F = - 21 Hz 1F p-C6F5) -1616 (m 1F m-C6F5) -1621 (m 1F m-C6F5) -
1628 (m 1F m-C6F5) -1631 (m 1F m-C6F5) -1640 (m 1F m-C6F5) -1649 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -486 (s BNH) 13C1H NMR (101 MHz CD2Cl2) δ 1674
(OCO) 636 (Et) 568 (CHOCOEt) 445 (CH(H)NH) 305 (CH2) 208 (CH2) 181 (CH2) 134
(Et)
RRSS-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ
743 (br m 1H NH) 440 (dq 2JH-H = 107 Hz 3JH-H = 71 Hz 1H Et)
438 (dq 2JH-H = 91 Hz 3JH-H = 71 Hz 1H Et) 424 (br m 1H
CHOCOEt) 350 (ddd 2JH-H = 134 Hz 3JH-H = 89 Hz 3JH-H = 49 Hz 1H CH(H)NH) 333
(dm JH-H = 133 Hz 1H CH(H)NH) 218 (m 1H CH2) 208 (m 1H CH2) 185 (m 1H CH2)
154 (m 1H CH2) 151 (m 1H CH2) 135 (t 3JH-H = 71 Hz 3H Et) 124 (m 1H CH2) 19F
NMR (377 MHz CD2Cl2) δ -1276 (m 1F o-C6F5) -1285 (m 2F o-C6F5) -1291 (m 1F o-
C6F5) -1371 (m 1F o-C6F5) -1421 (m 1F o-C6F5) -1549 (t 3JF-F = 21 Hz 1F p-C6F5) -
1572 (t 3JF-F = 21 Hz 1F p-C6F5) -1578 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5)
-1626 (m 1F m-C6F5) -1630 (m 3F m-C6F5) -1633 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -486 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1712 (OCO) 616 (Et) 581
(CHOCOEt) 457 (CH(H)NH) 259 (CH2) 235 (CH2) 171 (CH2) 139 (Et)
(2-PhC5H9NH)B(C6F5)3 (227a) and [2-PhC5H9NH2][HB(C6F5)3] (227b) 2-Phenylpyridine
(115 mg 0740 mmol) reaction time 48 h product (269 mg 0400 mmol 54) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC The isolated product consisted of 227a (RSSR 70) 227a (SSRR 10) 227b (20)
Anal calcd () for C29H15BF15N C 5158 H 254 N 209 Found C 5209 H 258 N 210
RSSR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 727
(m 2H Ph) 714 (m 3H Ph) 555 (br s 1H NH) 415 (ddd 3JH-H = 111
Hz 3JH-H = 94 Hz 36 Hz 1H CHPh) 356 (dm 2JH-H = 132 Hz 1H CH(H)NH) 257 (ddd 2JH-H = 132 Hz 3JH-H = 103 Hz 3JH-H = 31 Hz 1H CH(H)NH) 199 - 135 (m 6H CH2) 19F
NMR (377 MHz C6D5Br) δ -1216 (m 1F o-C6F5) -1236 (m 1F o-C6F5) -1274 (m 1F o-
73
C6F5) -1286 (m 1F o-C6F5) -1312 (m 1F o-C6F5) -1426 (m 1F o-C6F5) -1534 (t 3JF-F =
22 Hz 1F p-C6F5) -1566 (t 3JF-F = 21 Hz 1F p-C6F5) -1567 (t 3JF-F = 21 Hz 1F p-C6F5) -
1615 (m 2F m-C6F5) -1620 (m 3F m-C6F5) -1624 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -391 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1385 (ipso-Ph) 1297 (p-Ph)
1291 (Ph) 1285 (Ph) 646 (CHPh) 521 (NCH2) 355 (CH2) 248 (CH2) 219 (CH2)
SSRR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 710 -
681 (m 5H Ph) 581 (br s 1H NH) 449 (m 1H CHPh) 347 (dm 2JH-H = 125 Hz 1H CH(H)NH) 321 (m 2JH-H = 125 Hz 1H CH(H)NH) 185 (m 2H CH2)
176 (m 2H CH2) 128 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1249 (m 1F o-C6F5)
-1263 (m 1F o-C6F5) -1268 (m 1F o-C6F5) -1287 (m 1F o-C6F5) -1390 (m 1F o-C6F5) -
1431 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1559 (t 3JF-F = 21 Hz 1F p-C6F5)
-1562 (t 3JF-F = 21 Hz 1F p-C6F5) -1598 (m 1F m-C6F5) -1610 (m 1F m-C6F5) -1617 (m
1F m-C6F5) -1620 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1643 (m 1F m-C6F5) 11B NMR
(128 MHz CD2Cl2) δ -39 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1365 (ipso-Ph)1294
(p-Ph) 1283 (Ph) 1256 (Ph) 629 (CHPh) 454 (NCH2) 350 (CH2) 297 (CH2) 260 (CH2)
[2-PhC5H9NH2][HB(C6F5)3] (227b) 1H NMR (400 MHz CD2Cl2) δ 710 - 681 (m 5H Ph)
557 (br s 2H NH2) 355 (dd 3JH-H = 117 Hz 28 Hz 1H CHPh) 330 (br q 1JB-H = 86 Hz
1H BH) 295 (dm JH-H = 124 Hz 1H CH(H)NH2) 244 (pseudo td JH-H = 124 Hz 3JH-H = 30
Hz 1H CH(H)NH2) 186 (m 2H CH2) 165 (m 1H CH2) 157 (m 1H CH2) 141 (m 1H
CH2) 137 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 2F o-C6F5) -1610 (t 3JF-
F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -248 (d 1JB-H
= 86 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1399 (ipso-Ph) 1297 (Ph) 1295 (p-Ph)
1267 (Ph) 625 (CHPh) 471 (NCH2) 327 (CH2) 242 (CH2) 240 (CH2)
[2-MeC9H15NH2][HB(C6F5)3] (228) 2-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (331 mg 500 mmol 67) Crystals suitable for X-ray diffraction were grown from
a layered solution of dichloromethanepentane at -30 ordmC About 60 of the isolated reaction
product consisted of the SSSRRR diastereomer
1H NMR (400 MHz C6D5Br) δ 602 (br 1H NH2) 460 (br 1H NH2) 336 (br q 1JB-H = 83
Hz 1H BH) 315 (dt 3JH-H = 100 Hz 52 Hz 1H NCHCH) 276 (m 1H CHMe) 145 - 096
(m 8H CH2) 110 (m 1H CHCHN) 093 - 067 (m 4H CH2) 081 (d 3JH-H = 64 Hz 3H
74
Me) 19F NMR (377 MHz C6D5Br) δ -1335 (m 2F o-C6F5) -1607 (t 3JF-F = 22 Hz 1F p-
C6F5) -1646 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1384 (dm 1JC-F = 246
Hz CF) 1369 (dm 1JC-F = 249 Hz CF) 1233 (ipso-C6F5) 577 (NCH) 493 (CHMe) 322
(CHCHN) 281 (CH2) 272 (CH2) 255 (CH2) 240 (CH2) 236 (CH2) 211 (CH2) 189 (Me)
Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C 5021 H 331 N 212
[2-PhC9H15NH2][HB(C6F5)3] (229) B(C6F5)3 (289 mg 0564 mmol) 2-phenylquinoline (116
mg 0564 mmol) reaction time 48 h product (391 mg 536 mmol 95) Crystals suitable for
X-ray diffraction were grown from a layered solution of dichloromethanepentane at -30 ordmC
About 73 of the reaction mixture consisted of the reported SSSRRR diastereomer
1H NMR (400 MHz CD2Cl2) δ 733 (tm 3JH-H = 73 Hz 1H p-Ph) 726 (tm 3JH-H = 73 Hz
2H m-Ph) 720 (dm 3JH-H = 73 Hz 2H o-Ph) 646 (br 1H NH2) 501 (br t 1H NH2) 433
(dm 3JH-H = 105 Hz 33 Hz 1H C(H)Ph) 380 (br m 1H CH2C(H)NH2) 320 (br q 1JB-H = 87
Hz 1H BH) 218 - 108 (m 13H CH2C(H)CH2 and CH2) 19F NMR (377 MHz C6D5Br) δ -
1334 (m 2F o-C6F5) -1612 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -242 (d 1JB-H = 87 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1342
(ipso-Ph) 1312 (p-Ph) 1301 (m-Ph) 1269 (o-Ph) 647 (CH2C(H)NH2) 601 (C(H)Ph) 345
(CH2C(H)CH2) 291 (CH2) 285 (CH2) 251 (CH2) 249 (CH2) 248 (CH2) 197 (CH2) Anal
calcd () for C33H23BF15N C 5434 H 318 N 192 Found C 5431 H 331 N 192
[8-MeC9H15NH2][HB(C6F5)3] (230) 8-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (375 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC The reported SSSRRR
diastereomer was only observed
1H NMR (400 MHz C6D5Br) δ 555 (br 1H NH2) 497 (br 1H NH2) 352 (br q 1JB-H = 80
Hz 1H BH) 327 (dm 2JH-H = 121 Hz 1H NH2CH(H)) 263 (dm 3JH-H = 112 Hz coupling to
NH2 is observed in 1H1H-cosy 1H CHN) 252 (qt 2JH-H = 121 Hz 3JH-H = 27 Hz 1H
NH2CH(H)) 141 - 133 (br m 2H CH2) 134 (m 1H CH2CHCH2) 125 - 114 (br m 4H
CH2) 122 (m 1H CHMe) 102 (m 1H CH2) 089 (m 2H CH2) 063 (d 3JH-H = 75 Hz 3H
Me) 058 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1343 (m 2F o-C6F5) -1618 (t 3JF-F
= 21 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -242 (d 1JB-H =
75
80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 249 Hz CF) 1237 (ipso-C6F5) 632 (CHN) 478
(NH2CH(H)) 339 (CH2CHCH2) 337 (CHMe) 271 (CH2) 268 (CH2) 243 (CH2) 231 (CH2)
178 (CH2) 163 (Me) Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C
5026 H 330 N 209
[C13H22NH2][HB(C6F5)3] (231a) Acridine (132 mg 0740 mmol) reaction time 36 h product
(398 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at 25 ordmC The isolated product is a mixture of the SRSRRSRS
and RRSSSSRR isomers in a 11 ratio The SRSRRSRS was separated by crystallization
1H NMR (400 MHz CD2Cl2) δ 626 (br m 1H NH2) 513 (br m 1H NH2) 327 (br q 1JB-H =
86 Hz 1H BH) 285 (dm 3JH-H = 111 Hz 40 Hz 2H CHN) 182 (m 2H NH2CHCH2) 176
(m 2H CyCH2) 175 (m 1H CHCH2CH) 171 (m 2H CyCH2) 167 (m 2H CyCH2) 144 (qt 3JH-H = 111 Hz 3JH-H = 40 Hz 2H CH2CHCH2) 123 (m 2H CyCH2) 122 (m 2H
NH2CHCH2) 118 (m 2H CyCH2) 101 (m 2H CyCH2) 100 (m 1H CHCH2CH) 19F NMR
(377 MHz CD2Cl2) δ -1345 (m 2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -244 (d 1JB-H = 86 Hz BH) 13C1H NMR (101
MHz CD2Cl2) partial δ 639 (CHN) 406 (CH2CHCH2) 371 (CHCH2CH) 318 (CyCH2) 307
(NH2CHCH2) 249 (CyCH2) 248 (CyCH2) Anal calcd () for C31H25BF15N C 5264 H 356
N 198 Found C 5214 H 358 N 196
Synthesis of RRSSSSRR and SRSRRSRS-[(C13H22NH)B(C6F5)3] (231b) Compound 231b
was initially isolated from the pentane wash work-up for the synthesis of 231a Independent
synthesis of 231b was performed and the procedure is described
In a 4 dram vial tetradecahydroacridine (366 mg 0189 mmol) was dissolved in pentane (5
mL) at room temperature To the vial B(C6F5)3 (965 mg 0189 mmol) was added at once and
allowed to mix for 2 minutes The solution was filtered through a bed of Celite to yield a
colourless solution The vial was placed in a -30 ordmC freezer for 3 h and colourless crystals were
collected (973 mg 138 mmol 73) The isolated mixture of compound 231b consisted of a 11
mixture of RRSSSSRR and SRSRRSRS (C13H22NH)B(C6F5)3 only the diagnostic resonances of
RRSSSSRR-(C13H22NH)B(C6F5)3 have been reported
76
RRSSSSRR-[(C13H22NH)B(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 503 (br 1H NH) 353
(dm 3JH-H = 123 Hz 2H NCH) 214 (dm JH-H = 123 Hz 2H NH2CHCH2) 196 - 160 (m
6H CH2) 188 (m 2H CH2CHCH2) 177 (m 4H NH2CHCH2 and CHCH2CH) 149 - 111 (m
6H CH2) 19F NMR (377 MHz CD2Cl2) δ -1270 (m 1F o-C6F5) -1277 (m 1F o-C6F5) -
1281 (m 1F o-C6F5) -1291 (m 2F o-C6F5) -1302 (m 1F o-C6F5) -1558 (t 3JH-H = 21 Hz
1F p-C6F5) -1579 (t 3JH-H = 21 Hz 1F p-C6F5) -1589 (t 3JH-H = 21 Hz 1F p-C6F5) -1624
(m 1F m-C6F5) -1637 (m 3F m-C6F5) -1641 8 (m 1F m-C6F5) -1644 8 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -318 (s BN) 13C1H NMR (101 MHz CD2Cl2) partial δ
630 (NCH) 359 (CHCH2CH) 356 (CH2CHCH2) 299 (NH2CHCH2) Anal calcd () for
C31H23BF15N C 5279 H 329 N 199 Found C 5266 H 328 N 196
[23-(C4H6Me)2NHNH2][HB(C6F5)3] (232) 23-Dimethylquinoxaline (0117 g 0740 mmol)
reaction time 96 h product (402 mg 437 mmol 59) The SRSSRSRR diastereomer was only
observed
1H NMR (400 MHz CD2Cl2) δ 643 (br 1H NH2) 592 (br 1H NH2) 349 (dm 3JH-H = 128
Hz 1H CH2CHN) 334 (br q 1JB-H = 94 Hz 1H BH) 326 (br m 2H NCHMe CH2CHN)
281 (dq 3JH-H = 123 Hz 64 Hz 1H NCHMe) 223 (dm JH-H = 128 Hz 1H CH2) 189 (dm
JH-H = 134 Hz 1H CH2) 179 (dm JH-H = 134 Hz 1H CH2) 162 (dm JH-H = 134 Hz 2H
CH2) 147 (m 1H CH2) 131 (m 1H CH2) 128 (d 3JH-H = 64 Hz 3H Me) 121 (d 3JH-H =
62 Hz 3H Me) 120 (m 1H CH2) (NH was not observed) 19F NMR (377 MHz C6D5Br) δ -
1336 (m 2F o-C6F5) -1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1646 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -241 (d 1JB-H = 94 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481
(dm 1JC-F = 234 Hz C6F5) 1384 (dm 1JC-F = 246 Hz C6F5) 1368 (dm 1JC-F = 247 Hz C6F5)
1232 (ipso-C6F5) 576 (CH2CHN) 563 (NCHMe) 541 (NCHMe) 519 (CH2CHN) 304
(CH2) 242 (CH2) 224 (CH2) 185 (CH2) 178 (Me) 151 (Me) Anal calcd () for
C28H22BF15N C 4929 H 325 N 411 Found C 4909 H 333 N 421
[23-(C4H6Ph)2NHNH2][HB(C6F5)3] (233) 23-Diphenylquinoxaline (0209 g 0740 mmol)
reaction time 96 h product (328 mg 0407 mmol 55) Crystals suitable for X-ray diffraction
were grown from a layered solution of dichloromethanepentane at RT Diastereomers
SRSSRSRR and RRRSSSSR are present in equal ratios The assigned diastereomers were
77
supported by 1H1H NOESY NMR spectroscopy Anal calcd () for C38H26BF15N2 C 5660
H 325 N 347 Found C 5611 H 313 N 321
SRSSRSRR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 763 (m 4H
Ph) 699 - 684 (m 6H Ph) 572 (br 2H NH2) 476 (d 3JH-H = 34 Hz 1H CHPh) 441 (d 3JH-H = 34 Hz 1H CHPh) 407 (br 1H NH) 356 (br q 1JB-H = 82 Hz 1H BH) 314 (td 3JH-H
= 102 Hz 3JH-H = 34 Hz 1H CH2CHN) 260 (m 3JH-H = 102 Hz 34 Hz 1H CH2CHN) 167
(m 1H CH2) 159 (m 1H CH2) 153 (m 1H CH2) 129 (m 1H CH2) 122 (m 2H CH2)
121 (m 1H CH2) 086 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1331 (m 2F o-C6F5)
-1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1362 (ipso-Ph) 1313
(Ph) 1301 (Ph) 1267 (Ph) 637 (CHPh) 619 (CHPh) 597 (CH2CHN) 561 (CH2CHN) 314
(CH2) 282 (CH2) 242 (CH2) 233 (CH2) (ipso-C6F5 was not observed)
RRRSSSSR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (500 MHz CD2Cl2) δ 729 - 708
(m 10H Ph) 657 (br 2H NH2) 451 (dm 3JH-H = 102 Hz 1H CHPh) 429 (dm 3JH-H = 102
Hz 1H CHPh) 386 (dm 3JH-H = 107 Hz 1H CH2CHN) 366 (br 1H NH) 328 (br q 1JB-H =
82 Hz 1H BH) 268 (dm 3JH-H = 107 Hz 1H CH2CHN) 205 (m 1H CH2) 188 (m 2H
CH2) 178 (m 2H CH2) 157 (m 1H CH2) 145 (m 1H CH2) 130 (m 1H CH2) 19F NMR
(377 MHz C6D5Br) δ -1331 (m 2F o-C6F5) -1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 82 Hz BH) 13C1H NMR (125
MHz CD2Cl2) δ 1479 (dm 1JC-F = 235 Hz CF) 1382 (dm 1JC-F = 246 Hz CF) 1366 (dm 1JC-F = 248 Hz CF) 1314 (ipso-Ph) 1304 (Ph) 1301 (ipso-Ph) 1293 (Ph) 1290 (Ph) 1286
(Ph) 1277 (Ph) 1274 (Ph) 1226 (ipso-C6F5) 655 (CHPh) 621 (CHPh) 581 (CH2CHN)
526 (CH2CHN) 308 (CH2) 245 (CH2) 229 (CH2) 188 (CH2)
[(C6H4)C7H12NH2][HB(C6F5)3] (234) 78-Benzoquinoline (133 mg 0740 mmol) reaction
time 48 h product (285 mg 407 mmol 55) Crystals of the SRRS isomer suitable for X-ray
diffraction were grown from a layered solution of bromobenzenepentane at -30 ordmC Crystals of
the SSRR isomer suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC Anal calcd () for C31H19BF15N C 5309 H 273 N 200
Found C 5347 H 291 N 209
78
Isomer ratio by 1HNMR spectroscopy SRRS 80 (pale orange crystals) SSRR 20 (colourless
crystals)
SRRS-[(C6H4)C7H12NH2][HB(C6F5)3] (234a) 1H NMR (400 MHz CD2Cl2) δ 725 (td 3JH-H
= 77 Hz 4JH-H = 14 Hz 1H C6H4) 715 (d 3JH-H = 77 Hz 1H C6H4) 707 (d 3JH-H = 77 Hz
1H C6H4) 700 (t 3JH-H = 77 Hz 1H C6H4) 597 (br 2H NH2) 440 (d 3JH-H = 38 Hz 1H
NCH) 361 (dt JH-H = 131 Hz 3JH-H = 35 Hz 1H NCH(H)) 328 (m 1H NCH(H)) 314 (br q 1JB-H = 80 Hz 1H BH) 294 (dm 2JH-H = 172 Hz 1H C6H4-CH(H)) 285 (dm 2JH-H = 172 Hz
1H C6H4-CH(H)) 239 (m 1H CH2CHCH2) 200 - 188 (br m 6H PiperidineCyCH2) 19F NMR
(377 MHz C6D5Br) δ -1345 (m 2F o-C6F5) -1621 (t 3JF-F = 21 Hz 1F p-C6F5) -1657 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 80 Hz BH) 13C1H NMR (101
MHz CD2Cl2) δ 1483 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1378
(quaternary C for C6H4-CHN) 1368 (dm 1JC-F = 248 CF) 1311 (C6H4) 1307 (C6H4) 1292
(C6H4) 1288 (quaternary C for C6H4-CH2) 1277 (C6H4) 1234 (ipso-C6F5) 605 (NCH) 479
(NCH2) 320 (CH2CHCH2) 286 (C6H4-CH(H)) 274 (PiperidineCH2) 225 (CyCH2) 184
(PiperidineCH2)
SSRR-[(C6H4)C7H12NH2][HB(C6F5)3] (234b) 1H NMR (400 MHz C6D5Br) partial δ 701
(m 1H C6H4) 699 (m 1H C6H4) 685 (m 1H C6H4) 675 (d 3JH-H = 77 Hz 1H C6H4) 350
(d 3JH-H = 104 Hz 1H NCH) 324 (br dm JH-H = 124 Hz 1H NCH(H)) 279 (m 1H
NCH(H)) 254 (m 1H C6H4-CH(H)) 242 (m 1H C6H4-CH(H)) 142 (m 2H CH2) 128 (m
2H CH2) 105 (m 1H CH2CHCH2) 083 (m 2H CH2) (NH2 was not observed) 13C1H
NMR (101 MHz C6D5Br) δ 1370 (quaternary C for C6H4-CHN) 1304 (C6H4) 1291 (C6H4)
1284 (quaternary C for C6H4-CH2) 1264 (C6H4) 1226 (C6H4) 629 (NCH) 474 (NCH2) 378
(CH2CHCH2) 291 (CH2) 288 (C6H4-CH(H)) 276 (CH2) 229 (CH2)
[(C5H3N)(CH2)2(C5H8NH)B(C6F5)2][HB(C6F5)3] (235) B(C6F5)3 (379 mg 0740 mmol) 110-
phenanthroline (667 mg 0370 mmol) reaction time 96 h product (283 mg 0270 mmol 73)
Crystals suitable for X-ray diffraction were grown from a layered solution of
tetrahydrofuranpentane at -30 ordmC Approximately 65 of the reaction mixture consisted of the
SRSRSR diastereomer
1H NMR (400 MHz CD2Cl2) δ 944 (br s 1H NH) 850 (dd JH-H = 47 Hz JH-H = 15 Hz 1H
C5H3N) 744 (dd JH-H = 78 Hz JH-H = 15 Hz 1H C5H3N) 722 (dd JH-H = 78 Hz JH-H = 47
79
Hz 1H C5H3N) 442 (d 3JH-H = 43 Hz 1H NCyCH) 342 (br 1H BH) 322 (dm 2JH-H = 138
Hz 1H NC(H)H) 291 (ddd 2JH-H = 138 Hz 3JH-H = 87 Hz 53 Hz 1H NC(H)H) 276 - 272
(m 2H C6H4-CH(H)) 212 (dm 3JH-H = 121 Hz 38 Hz 1H CH2CHCH2) 196 (m 1H CH2)
188 (m 1H CH2) 173 (m 1H CH2) 132 (dt 2JH-H = 140 Hz 3JH-H = 32 Hz 1H CH2) 091
(qd JH-H = 131 Hz 3JH-H = 38 Hz 1H CH2) 071 (qt JH-H = 137 Hz 3JH-H = 40 Hz 1H CH2)
19F NMR (377 MHz CD2Cl2) δ -1289 (m 2F B(C6F5)2o-C6F5) -1343 (m 6F HB(C6F5)3o-C6F5) -
1348 (m 2F B(C6F5)2o-C6F5) -1491 (t 3JF-F = 20 Hz 1F B(C6F5)2p-C6F5) -1511 (t 3JF-F = 20 Hz
1F B(C6F5)2p-C6F5) -1596 (m 4F B(C6F5)2m-C6F5) -1645 (t 3JF-F = 20 Hz 3F HB(C6F5)3p-C6F5) -
1676 (m 6F HB(C6F5)3m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 391 (s BN) -254 (d 1JB-H =
93 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1484 (quaternary C for C5H3N) 1466
(quaternary C for C5H3N) 1448 (C5H3N) 1354 (C5H3N) 1260 (C5H3N) 581 (CyNCH) 451
(NC(H)H) 296 (CH2C(H)CH2) 241 (CH2) 218 (CH2) 210 (CH2) 206 (CH2) Anal calcd
() for C42H17B2F25N2 C 4822 H 164 N 268 Found C 4783 H 197 N 269
243 X-Ray Crystallography
2431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
2432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
80
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
81
2433 Selected crystallographic data
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25
24 24rsquo 25
Formula C27H21B1F15N1 C27H13B1F15N1 C30H25B1F15N1
Formula wt 65526 64719 69532
Crystal system monoclinic orthorhombic monoclinic
Space group P2(1)c P2(1)2(1)2(1) P2(1)n
a(Aring) 97241(8) 116228(4) 126342(6)
b(Aring) 147348(12) 181284(7) 181939(8)
c(Aring) 188022(15) 236578(9) 128612(6)
α(ordm) 9000 9000 9000
β(ordm) 98826(4) 9000 90269(2)
γ(ordm) 9000 9000 9000
V(Aring3) 26621(4) 49848(3) 29563(2)
Z 4 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1635 1725 1562
Abs coeff μ mm-1 0169 0179 0157
Data collected 18591 28169 50674
Rint 00336 00297 00369
Data used 4685 8773 5207
Variables 401 793 424
R (gt2σ) 00361 00315 00352
wR2 00898 00758 00947
GOF 1007 1021 1024
82
Table 25 ndash Selected crystallographic data for 216a 218 and 219
216a 218 219
Formula C27H20B1F16N1 C27H18B1F16N1 C32H21B1F15N1
Formula wt 67325 67123 71533
Crystal system monoclinic monoclinic orthorhombic
Space group P2(1)c P2(1)n Pbca
a(Aring) 97677(6) 104368(7) 18886(4)
b(Aring) 147079(11) 93382(7) 16050(3)
c(Aring) 190576(14) 273881(18) 19128(4)
α(ordm) 9000 9000 9000
β(ordm) 98934(2) 96910(3) 9000
γ(ordm) 9000 9000 9000
V(Aring3) 27046(3) 26499(3) 5798(2)
Z 4 4 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1653 1683 16388
Abs coeff μ mm-1 0174 0177 0163
Data collected 23565 17203 50412
Rint 00432 00404 00662
Data used 6164 4676 6654
Variables 406 408 442
R (gt2σ) 00522 00496 00687
wR2 01387 01462 01912
GOF 1032 1041 10743
83
Table 26 ndash Selected crystallographic data for 220 222 and 224
220 222 (+05 CH2Cl2) 224 (+05 CH2Cl2)
Formula C33H25B1F15N1O1 C285H22B1Cl1F15N1O1 C355H22B1ClF15N1
Formula wt 74737 72573 79380
Crystal system orthorhombic orthorhombic monoclinic
Space group Pbca Pbca P2(1)n
a(Aring) 173531(15) 17750(5) 109902(9)
b(Aring) 161365(15) 16032(4) 151213(11)
c(Aring) 227522(17) 20783(6) 194765(15)
α(ordm) 9000 9000 90
β(ordm) 9000 96910(3) 92062(3)
γ(ordm) 9000 9000 90
V(Aring3) 63710(9) 5914(3) 32346(4)
Z 8 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 15582 16278 1630
Abs coeff μ mm-1 0154 0250 0235
Data collected 56289 47407 22409
Rint 00406 01159 00306
Data used 7321 5198 5688
Variables 461 440 495
R (gt2σ) 00413 00811 00495
wR2 01112 02505 01363
GOF 10647 10628 0936
84
Table 27 ndash Selected crystallographic data for 225 227 and 228
225 227 (+1 C5H12) 228
Formula C25H17B1F15N1 C63H42B2F30N2 C28H21B1F15N1
Formula wt 62721 141861 66727
Crystal system triclinic monoclinic triclinic
Space group P-1 P2(1)n P-1
a(Aring) 101339(5) 137416(4) 95967(15)
b(Aring) 112923(6) 119983(4) 108364(15)
c(Aring) 118209(6) 191036(7) 14143(2)
α(ordm) 98563(2) 9000 75929(5)
β(ordm) 109751(2) 109317(2) 80009(6)
γ(ordm) 94983(2) 9000 76629(5)
V(Aring3) 124520(11) 297240(17) 13772(4)
Z 2 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1673 1585 1609
Abs coeff μ mm-1 0176 0158 0235
Data collected 18038 22150 16105
Rint 00211 00246 00351
Data used 4357 5230 4743
Variables 379 436 406
R (gt2σ) 00371 00324 00546
wR2 00964 00816 01728
GOF 1044 1014 1028
85
Table 28 ndash Selected crystallographic data for 229 230 and 231a
229 (+05 C6H5Br) 230 231a
Formula C36H255B1Br05F15N1 C28H21B1F15N1 C31H25B1F15N1
Formula wt 80784 66727 70733
Crystal system monoclinic triclinic monoclinic
Space group C2c P-1 P2(1)n
a(Aring) 201550(11) 97752(4) 112914(4)
b(Aring) 133628(11) 120580(4) 183705(7)
c(Aring) 266328(18) 121120(5) 145648(5)
α(ordm) 9000 102296(2) 9000
β(ordm) 111905(6) 100079(2) 90480(2)
γ(ordm) 9000 90901(2) 9000
V(Aring3) 66551(8) 137127(9) 302105(19)
Z 8 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1613 1616 1555
Abs coeff μ mm-1 0749 0165 0155
Data collected 54940 20198 62113
Rint 00530 00245 00383
Data used 7644 4841 7630
Variables 484 406 533
R (gt2σ) 00651 00362 00778
wR2 01802 00971 02335
GOF 1037 1036 1007
86
Table 29 ndash Selected crystallographic data for 231b 233 and 234a
231b (+05 C6H14) 233 234a (+1 CH2Cl2)
Formula C34H30B1F15N1 C38H26B1F15N2 C32H21B1Cl2F15N1
Formula wt 74840 80642 78621
Crystal system triclinic monoclinic monoclinic
Space group P-1 Pn C2c
a(Aring) 107250(6) 99895(4) 181314(6)
b(Aring) 112916(7) 115666(5) 135137(5)
c(Aring) 136756(8) 155410(6) 253612(9)
α(ordm) 70523(2) 9000 9000
β(ordm) 88868(2) 105054(2) 92594(2)
γ(ordm) 86934(2) 9000 9000
V(Aring3) 155914(16) 173405(12) 62077(4)
Z 2 2 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1594 1544 1677
Abs coeff μ mm-1 0155 0147 0327
Data collected 22650 31226 22749
Rint 00233 00381 00512
Data used 5479 8395 7383
Variables 460 517 475
R (gt2σ) 00371 00400 00816
wR2 01066 00893 02554
GOF 0926 1011 1024
87
Table 210 ndash Selected crystallographic data for 234b and 235
234b 235 (+1 C4H8O +1 CH2Cl2)
Formula C31H19B1F15N1 C47H27B2Cl2F25N2O1
Formula wt 70128 120323
Crystal system monoclinic triclinic
Space group P2(1)c P-1
a(Aring) 100455(5) 113115(7)
b(Aring) 118185(5) 117849(8)
c(Aring) 245940(11) 188035(12)
α(ordm) 9000 83850(3)
β(ordm) 96724(2) 88364(3)
γ(ordm) 9000 69766(3)
V(Aring3) 28998(2) 23383(3)
Z 4 2
Temp (K) 150(2) 150(2)
d(calc) gcm-3 1606 1709
Abs coeff μ mm-1 0161 0281
Data collected 20742 36083
Rint 00342 00265
Data used 5101 8235
Variables 433 712
R (gt2σ) 00438 00473
wR2 01153 01198
GOF 1012 1015
88
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation
with Frustrated Lewis Pairs
31 Introduction
The reduction of carbonyl substrates such as aldehydes ketones esters acids and anhydrides to
alcohols is one of the most fundamental and widely used reactions in synthetic chemistry269
Sodium borohydride lithium aluminum hydride and other stoichiometric reducing agents56 224
serve adequately for laboratory scale syntheses however in an industrial setting the process
demands for a more clean environmentally benign and cost-effective procedure More desirable
methods involving H2 gas or transfer hydrogenation have proven practical and circumvent the
work-up operations required for stoichiometric reagents
Heterogeneous catalysts based on PdC and PtC are certainly atom economic however some of
these catalysts are not suitable in cases where mild conditions functional group tolerance and
chemoselectivity are required Therefore substantial research has been directed towards
homogeneous catalysts involving Ir237 Rh239 Ru238 Cu269 and Os238 complexes including metal-
immobilized systems269
Despite the power of these technologies research efforts motivated by cost toxicity and low
abundance have focused on the development of first-row transition metal catalysts based on Fe
and Co210 221 Also on-going interest in the field has been devoted to the discovery of new
asymmetric hydrogenation catalysts131 208-209 263-264136 213-214 270-271 in addition to transfer
hydrogenation via the Meerwein-Ponndorf-Verley reduction procedure216
311 FLP reactivity with unsaturated C-O bonds
In 1961 Walling and Bollyky reported the first metal-free hydrogenation system demonstrating
the reduction of the non-enolizable ketone benzophenone using H2 (100 atm) and tBuOK as the
catalyst at 200 degC175-176 While more recently metal-free reductions have been demonstrated
under more mild conditions using frustrated Lewis pairs (FLPs) These combinations of
sterically encumbered main group Lewis acids and bases have been shown to effect the catalytic
hydrogenation of a variety of unsaturated organic substrates Noticeably absent from these
substrates are ketones and aldehydes This is perhaps surprising given the precedence of catalytic
89
hydrosilylation of ketones established by Piers182 Moreover a number of groups have
demonstrated the ability of FLPs to effect the reduction of CO2 using H2259 silanes169 180 182
boranes111 163 272 or ammonia-borane273 as sources of the reducing equivalents The limited
attention to hydrogenation of ketones and aldehydes has been attributed to the high oxophilicity
of electrophilic boranes72 171 Indeed in an earlier report Erker and co-workers described the
irreversible capture of benzaldehyde and trans-cinnamaldehyde (Scheme 31 top) as well as the
14-addition of conjugated ynones by the intramolecular PB FLP Mes2PCH2CH2B(C6F5)2173 A
number of stoichiometric reductions have also been reported using H2 activated PB FLPs with
an example shown in Scheme 31 (bottom)94 173
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom)
Nonetheless the group of Privalov has computed an energetically viable mechanism for ketone
reduction suggesting a process analogous to imine hydrogenation and carbonyl hydrosilylation
using B(C6F5)3 as the catalyst274 Attempts to realize this prediction experimentally have been
unsuccessful Repo et al described the stoichiometric reaction of aromatic ketones with B(C6F5)3
effecting deoxygenation of the ketone to afford (C6F5)2BOH C6F5H and the corresponding aryl
alkane (Scheme 32 a)178 Furthermore the Stephan group found that similar reduction of alkyl
ketones gave borinic esters via H2 activation hydride delivery and protonation of a C6F5 group
(Scheme 32 b)275
90
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b)
Similar degradation of B(C6F5)3 via B-C bond cleavage affording CH3OB(C6F5)2 and C6F5H was
reported by Ashley and OrsquoHare in their efforts to reduce CO2 in the presence of H2 to CH3OH259
Due to the instability of B(C6F5)3 in these transformations Wang et al approached the catalytic
ketone hydrogenation challenge computationally suggesting that a bifunctional amine-borane
FLP catalyst would be viable276 Interestingly Du et al have taken a detour from direct FLP
hydrogenation of carbonyl groups reporting the catalytic hydrogenation of silyl enol ethers using
a chiral borane to obtain a variety of optically active secondary alcohols after workup (Scheme
33)277
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols
Reaction of main group species with other unsaturated C-O functionalities namely carbon
monoxide is also limited H C Brown established the synthesis of tertiary alcohols by
91
carbonylation of trialkylboranes using carbon monoxide278 although the analogous reactivity by
B-H boranes proved challenging279-282
Recently however Erker et al described the stoichiometric reduction of carbon monoxide by the
reaction of intramolecular PB FLPs and the hydroboration reagent HB(C6F5)2 to yield epoxy-
borate species (Scheme 34 top)118-119 283 Simultaneously the Stephan group exploited the
reaction of a 12 mixture of tBu3P and B(C6F5)3 with syn-gas (CO and H2) to result in sequences
of stoichiometric reactions eventually affording the borane-oxyborate derivative
(C6F5)2BCH(C6F5)OB(C6F5)3 a product of C-O bond cleavage (Scheme 34 bottom)117
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom)
The main group reduction of carbonyl groups has been limited to stoichiometric reactions with
classic hydride reagents In this chapter a remarkably simple approach to the metal-free
hydrogenation of ketones and aldehydes is reported using FLP catalysts derived from B(C6F5)3
and ether The hydrogenation concept was extended towards a heterogeneous avenue using
catalysts derived from the combination of polysaccharides or molecular sieves with B(C6F5)3
Moreover the catalytic reductive deoxygenation of aryl ketones is achieved in the case of
molecular sieves
92
32 Results and Discussion
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions
Heating a toluene solution of 5 mol B(C6F5)3 and 4-heptanone under H2 (60 atm) at 80 degC
yielded complete conversion of B(C6F5)3 to the borinic ester Pr2CHOB(C6F5)2 with concurrent
liberation of C6F5H The remaining 95 of the initial ketone was unaltered This observation
illustrates that borane and ketone act as a FLP to heterolytically cleave H2 affording nominally
[Pr2COH][HB(C6F5)3] At this stage the hydride is presumed to reduce the carbonyl fragment to
generate 4-heptanol which subsequently decomposes B(C6F5)3 to Pr2CHOB(C6F5)2 and C6F5H
It is important to note that the above example of rapid and facile decomposition of B(C6F5)3 to
borinic ester stands in contrast to an observation illustrated in Chapter 2 In this case the CH3OH
generated from ammonium protonation of [CH3OB(C6F5)3]- does not decompose B(C6F5)3 rather
under an atmosphere of H2 the resulting amine and B(C6F5)3 heterolytically split H2 to give the
ammonium [HB(C6F5)3] product (Scheme 35) Thus this observation led to the proposal of two
plausible borane decomposition pathways in ketone hydrogenation reactions
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH
In both pathways the reaction initiates with heterolytic H2 splitting by the ketone and B(C6F5)3
to give the ionic pair [R2COH][HB(C6F5)3] (Scheme 36) At this point the reaction could follow
a pathway in which hydride is transferred from the [HB(C6F5)3]- anion to the activated carbonyl
group generating alcohol and B(C6F5)3 both of which further react to give borinic ester and
C6F5H (Scheme 36 Pathway 1) The second pathway suggests the borane undergoes
protonolysis by the [R2COH]+ cation cleaving a C6F5 group to form HB(C6F5)2 and C6F5H whilst
regenerating the ketone The borane then undergoes hydroboration of the carbonyl group to
afford the borinic ester (Scheme 36 Pathway 2)
93
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation
To test Pathway 1 B(C6F5)3 was added to excess 4-heptanol (10 eq) and heated to 80 degC for 12
h This resulted in no reaction beyond formation of the alcohol-borane adduct
Pr2CHOHmiddotB(C6F5)3 as evidenced by the 11B and 19F NMR spectra (11B δ 197 ppm 19F δ -
1326 -1552 -1628 ppm) On the other hand stoichiometric and 5 mol combinations of
HB(C6F5)2 with 4-heptanone formed the new hydroboration species Pr2CHOB(C6F5)2 after 10
min at RT In addition to the characteristic methine multiplet observed at 405 ppm in the 1H
NMR spectrum 11B NMR spectroscopy gave a broad resonance at 394 ppm with 19F NMR
signals at -1325 -1498 and -1613 ppm representing the three-coordinate boron centre These
experiments provide evidence for Pathway 2 resulting in decomposition of B(C6F5)3 during
ketone hydrogenation
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents
To avoid this degradation pathway an alternative FLP is required This system must be basic
enough to effect H2 activation and stabilize the acidic proton by electrostatic interactions In this
regard the Stephan group previously reported that the ethereal oxygen of the borane-oxyborate
derivative (C6F5)2BCH(C6F5)OB(C6F5)3 is sufficiently Lewis basic to activate H2 with the
coordinating B(C6F5)2 group117 Subsequently the combination of weak Lewis bases such as
Et2O electron deficient triarylphosphines and diaryl amines were shown to be sufficiently basic
for both H2 activation and catalytic reduction of olefins99 257 In the case of Et2O DFT
calculations highlighted that solvation of the protonated ether by a second equivalent of Et2O can
significantly stabilize the proton by hydrogen-bonding interactions
94
To probe the viability of using Et2O in carbonyl reductions a d8-toluene solution of 5 mol
B(C6F5)3 was combined with a 51 ratio of Et2O4-heptanone and heated to 70 degC under H2 (4
atm) Monitoring the J-Young experiment by high temperature 1H NMR spectroscopy showed
gradual hydrogenation of the ketone yielding approximately 50 of 4-heptanol after 12 h The 1H NMR spectrum shows a distinct quintet at 345 ppm diagnostic of the hydrogenated C=O
fragment forming a C-H bond in addition to the multiplets at 128 and 080 ppm (Figure 31)
Increasing the H2 pressure to 60 atm improved the yield of 4-heptanol to 70
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol ()
Alternatively incrementing the ratio of Et2O to 4-heptanone resulted in increased yields in
which case a 81 ratio of Et2O4-heptanone in toluene gave 97 conversion to 4-heptanol after
12 h (Figure 32) The continuous improvement in alcohol yield was a direct result of gradual
preservation of the borane catalyst in the reaction as the Et2O concentration was increased
Employing identical conditions but using Et2O as the solvent resulted in the quantitative
formation of 4-heptanol after 12 h Similarly employing iPr2O as the solvent in analogous
$ $ 12
11
10
9
8
7
6
5
4
3
2
1
95
hydrogenations gave quantitative yields of 4-heptanol The use of Ph2O and TMS2O resulted in
yields of 44 and 42 in the same time frame (Table 31 entry 1)
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol
Using this FLP hydrogenation protocol a range of ketone substrates were treated with 5 mol
B(C6F5)3 in Et2O iPr2O Ph2O or TMS2O and heated for 12 h at 70 degC under H2 (60 atm) The
substrates investigated included several alkyl ketones (Table 31 entries 1 - 9) an aryl ketone
(Table 31 entry 10) benzyl ketones with substituents including F and CF3 groups (Table 31
entry 11 - 15) cyclic ketones including L-menthone and cyclohexanone (Table 31 entries 16
and 17) as well as the aldehyde cyclohexanal (Table 31 entry 18) Evaluating these reductions
by 1H NMR spectroscopy showed yields ranging between 32 - gt99 and isolated yields up to
91 for the reactions carried out in Et2O and iPr2O (Table 31) 1H NMR spectra of the alcohols
displayed characteristic multiplets at about 4 ppm assignable to the distinctive methine protons
with corresponding 13C1H resonances observed at ca 70 ppm as expected
These reactions could also be performed on a larger scale For example 100 g of 4-heptanone
was quantitatively converted to 4-heptanol using 5 mol B(C6F5)3 in Et2O and the alcohol
product was isolated in 87 yield
96
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents
Conversion (Isolated yields)
Entry R R1 Et2O iPr2O Ph2O TMS2O
1 n-C3H7 n-C3H7 gt99 (91) gt99 70 52
2 Me iPr gt99 (76) gt99 44 42
3 Me CH2tBu gt99 gt99 (90) 22 14
4 Me n-C5H11 93 (85) 50 (43) 58 41
5 Me CH2Cl gt99 (85) gt99 91 82
6 Me Cy 77 - - -
7 Et iPr gt99 gt99 (89) - trace
8 Et n-C4H9 gt99 (87) 95 44 38
9 Et CH2iPr 40 47 - -
10 Me Ph 90 69 (52) trace trace
11 Et CH2Ph gt99 (84) 97 trace trace
12 Me n-CH2CH2Ph gt99 (84) 69 58 24
13 Me CH2(o-FC6H4) 97 gt99 (90) trace trace
14 Me CH2(p-FC6H4) gt99 gt99 (90) trace trace
15 Me CH2(m-CF3C6H4) gt99 gt99 (88) 55 trace
16 -(CH2)5- 53 41 - -
17 -(2-iPr-5-Me)C5H8- gt99 (88) 89 47 45
18 Cy H 32 - - -
(-) Reaction was not performed
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents
The mechanism of these reactions is thought to be analogous to that previously described for
imine hydrogenations92 In the present case ether combines with the borane in equilibrium
97
between the classical Lewis acid-base adduct and the corresponding FLP in which the latter
effects the heterolytic cleavage of H2 The resulting protonated ether then associates with ketone
via a hydrogen-bonding interaction284-285 activating the carbonyl fragment for hydride transfer
from the [HB(C6F5)3]- anion Subsequent protonation of the generated alkoxide yields the
product alcohol while liberating etherB(C6F5)3 to further activate H2 (Scheme 37) It has been
experimentally proven that activation of the carbonyl fragment is required prior to hydride
delivery as a 11 combination of 4-heptanone and [NEt4][HB(C6F5)3] do not result in reactivity
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents
The possibility of initial H2 activation by ketoneborane combinations cannot be dismissed
however the proposed mechanism is based on the large excess of ether in comparison to ketone
In support of this proposed mechanism the activation of H2 by ethereal oxygen Lewis bases and
boranes have been described to protonate imines and alkenes en route to the corresponding
hydrogenated products257 286
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism
The proposed H-bonding ether-ketone intermediate was further probed by the stoichiometric
reaction of a toluene solution of Jutzirsquos acid [(Et2O)2H][B(C6F5)4]287 with 1-phenyl-2-butanone
and iPr2O After heating the reaction at 70 degC for 2 h a white crystalline solid 31 was isolated in
87 yield (Scheme 38) The 1H NMR spectrum of 31 showed a broad singlet at 1152 ppm
suggesting a proton involved in hydrogen-bonding Resonances attributable to both 1-phenyl-2-
butanone and iPr2O were unambiguously present although these shifts were deshielded in
98
comparison to the individual components These data in addition to the definite presence of the
[B(C6F5)4]- anion as evidenced by 11B and 19F NMR spectroscopy lead to the assignment of 31
as [(iPr2O)H(O=C(CH2Ph)CH2CH3)][B(C6F5)4]
Scheme 38 ndash Synthesis of 31
The structure of 31 was unambiguously confirmed by single crystal X-ray crystallography
(Figure 33) The molecular structure of this salt shows the proximity of the ketone and ether in
the cation with an O-O separation of 2534(3) Aring Location and complete refinement of the proton
in the cation shows it is associated with the ether oxygen and hydrogen-bonded to the ketone
with O-H distances of 104(2) and 154(2) Aring respectively The resulting angle at H is 1581(3)deg
consistent with that typically seen for hydrogen-bonding interactions288-289 The isolation of 31
provides a direct structural analogue of the proposed intermediate in the ketone hydrogenation
mechanism
The equilibrium position of the generated proton is predicted to favour the ether oxygen atom
where the unshared electron pair is sp3 hybridized making the ether oxygen more basic than the
carbonyl where the unshared pair is sp2 hybridized This is also in agreement with predicted pKa
values of protonated ether and ketone289
Figure 33 ndash POV-Ray depiction of 31
99
325 Other hydrogen-bond acceptors for carbonyl hydrogenations
By analogy to the proposed mechanism with ethereal solvents ketone hydrogenations were
explored with crown ethers in toluene To this end combinations of 5 and 10 mol of 12-crown-
4 18-crown-6 and benzo-12-crown-4 were used with 5 mol B(C6F5)3 and 4-heptanone
However in all cases only trace amounts of 4-heptanol was observed Similar to the results in
ethereal solvents these hydrogenation results could possibly be improved by using an excess of
the crown ether On the other hand inefficient hydrogenation could result due to the multiple
stabilizing hydrogen bonds with the crown (OCH2)n groups
Alternative oxygen containing solvents THF and tetrahydropyran were tested using the
hydrogenation protocol in both cases however catalysis was not observed This result could be
explained by the difference in steric hindrance of the two solvents in comparison to Et2O and
iPr2O Nonetheless performing the hydrogenations in 24-dimethylpentan-3-ol gave the
quantitative reduction of 4-heptanone after 12 h at 70 degC This result led to the proposal that
chiral alcohols could possibly be used as the solvent to induce asymmetric reduction of ketones
Thus testing this theory using enantiomerically pure alcohols (S)-2-octanol (R)-2-octanol (R)-
(+)-1-phenyl-1-butanol (S)-(+)-12-propanediol and (R)-(+)-11rsquo-bi(2-naphthol) the prochiral
ketone substrates in Table 31 entries 2 - 10 were hydrogenated although in all cases the
products were obtained as racemic mixtures
326 Other boron-based catalysts for carbonyl hydrogenations
While exploring other boron-based catalysts in carbonyl reductions borenium cation-based FLP
hydrogenation catalysts105 derived from carbene-stabilized 9-borabicyclo[331]nonane (9-
BBN) were tested in lieu of B(C6F5)3 (Figure 34) However at 70 degC (temperature required for
hydrogenation when using B(C6F5)3) the borenium cation catalysts were found to decompose to
unknown products thereby not resulting in any reactivity
100
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism
Reflecting back on a key result presented in Chapter 2 an alternative mechanism was applied to
successfully achieve B(C6F5)3 catalyzed ketone hydrogenation This finding demonstrates the
participation of the [CH3OB(C6F5)3]- anion and B(C6F5)3 in H2 activation forming CH3OH and
[HB(C6F5)3]- (Scheme 39) thereby signifying the lability of B(C6F5)3-alkoxide bonds
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond
Taking lability of the presented B-O bond into consideration a two component catalyst system
comprising of B(C6F5)3 and [NEt4][HB(C6F5)3] was conceptualized for ketone hydrogenation In
this regard the B(C6F5)3 catalyst is expected to coordinate to the carbonyl group activating it for
hydride delivery from [NEt4][HB(C6F5)3] This will consequently generate B(C6F5)3 and
B(C6F5)3-alkoxide wherein similar to Scheme 39 will react with H2 to form alcohol and
regenerate the catalysts
The proposed catalytic system was examined by combining 5 mol B(C6F5)3 and 5 mol
[NEt4][HB(C6F5)3] with 4-heptanone in toluene and heating at 80 degC under H2 (60 atm) After 12
h 1H NMR data revealed catalyst turnover giving 92 conversion to the product 4-heptanol
(Table 32 entry 1) It is important to note that under similar reaction conditions the
combination of ketone with [NEt4][HB(C6F5)3] does not give any reactivity while B(C6F5)3 alone
is decomposed to the borinic ester
101
Using this hydrogenation protocol dialkyl substituted ketones gave the corresponding alcohols
in 40 - 99 conversions by 1H NMR spectroscopy (Table 32 entries 2 - 6) Conversions were
dramatically reduced for methyl cyclohexyl ketone (Table 32 entry 7) aryl and benzyl
substituted ketones (Table 32 entries 8 - 10) benzylacetone (Table 32 entry 11) in addition to
the cyclic ketones cyclohexanone and 2-cyclohexen-1-one (Table 32 12 and 13) Interestingly
reduction of L-menthone produced the respective alcohol product in 62 by 1H NMR
spectroscopy (Table 32 entry 14)
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3]
Entry R R1 Conversion
1 n-C3H7 n-C3H7 92
2 Me iPr 57
3 Me CH2Cl gt99
4 Me 2-butyl 53
5 Et iPr gt99
6 Et CH2iPr 40
7 Me Cy 18
8 Me Ph 20
9 Ph Ph 20
10 Et CH2Ph 25
11 Me n-CH2CH2Ph 25
12 -(CH2)5- 28
13 -(CH2)3CH=CH- 0
14 -(2-iPr-5-Me)C5H8- 62
All conversions are determined by 1H NMR spectroscopy
102
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system
The mechanism of this reaction is thought to proceed by initial coordination of the Lewis acid
B(C6F5)3 to the carbonyl group assisting hydride transfer from [NEt4][HB(C6F5)3] resulting in
liberation of B(C6F5)3 and generation of [NEt4][RR1C(H)OB(C6F5)3] in which the alkoxide
anion is coordinated to B(C6F5)3 (Scheme 310) This combination of [RR1C(H)OB(C6F5)3]-
anion and B(C6F5)3 act as a FLP to activate H2 and dissociate the alcohol while simultaneously
regenerating B(C6F5)3 and [NEt4][HB(C6F5)3] By 1H NMR spectroscopy the [NEt4]+ cation
does not appear to participate in the reaction
R R1
OH
H
B(C6F5)3
R R1
O
+
B(C6F5)3
R R1
O NEt4
HB(C6F5)3
NEt4
B(C6F5)3
B(C6F5)3
R R1
O
05 H2
05 H2
H+ from H2 activation
H- from H2 activation
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation
In comparison to carbonyl hydrogenations in ethereal solvents the presented Lewis acid-assisted
mechanism has resulted in lower alcohol yields due to steric hindrance of the substrate Lewis
base preventing adequate coordination to the Lewis acid and consequently inefficient activation
of the carbonyl bond Additionally the steric hindrance of the alkoxyborate anion resulting from
hydride delivery slows down the H2 activation step allowing unreacted B(C6F5)3 and ketone to
activate H2 giving the corresponding borinic ester
328 Attempted hydrogenation of other carbonyl substrates and epoxides
Carbonyl reductions employing either the etherB(C6F5)3 FLP catalyst or the two component
catalyst species B(C6F5)3[NEt4][HB(C6F5)3] were unsuccessful for the ketones
diphenylcyclopropenone (ndash)-fenchone 25-hexanedione 6-methyl-35-heptadien-2-one
103
cyclohexane-14-dione 1-acetyl-1-cyclohexene 13-difluoroacetone 2-acetylthiophene 44-
dimethoxybutan-2-one aldehydes 5-methylthiophene-2-carboxaldehyde esters ethyl acetate
ethylchloroformate methylbenzoate ethylpyruvate phenyl acetate carboxylic acids isobutyric
acid pivalic acid 3-phenylpropanoic acid carbonates ethylene carbonate diethyl carbonate
and NN-diethylpropionamide Exposure of diethylmaleate to the hydrogenation conditions only
led to reduction of the C=C double bond
Similar treatment of the epoxides styrene oxide and trans-stilbene oxide were found to undergo
the well-documented Lewis acid catalyzed Meinwald rearrangement forming 2-
phenylacetaldehyde and 22-diphenylacetaldehyde respectively Selectivity of the aldehyde
products is determined by formation of the most stable carbenium intermediate followed by a
hydride shift (2-phenylacetaldehyde) or substituent shift (22-diphenylacetaldehyde)290-291
Moreover an attempt at extending this reduction procedure to the greenhouse gas CO2 was not
successful In this sense a J-Young tube consisting of B(C6F5)3 and 10 eq of Et2O was
pressurized with CO2H2 and heated at temperatures up to 80 degC Multinuclear NMR data only
revealed resonances corresponding to the Et2O-B(C6F5)3 adduct
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases
As presented in Section 322 judicious choice of the FLP catalyst derived from ether and
B(C6F5)3 gives catalytic hydrogenation of carbonyl substrates to their corresponding alcohols
The protonated ether solvent is proposed to hydrogen bond with the ketone substrate stabilizing
the Broslashnsted acidic proton while activating the carbonyl fragment to accept hydride from the
[HB(C6F5)3]- anion (Scheme 37)
Continued interest in ketone and aldehyde hydrogenation reactions led to the investigation of
potential oxygen-rich materials that will mimic ethereal solvents permitting catalytic
hydrogenation in a non-polar solvent To this end FLP hydrogenations were performed in
toluene using the Lewis acid B(C6F5)3 with the addition of heterogeneous Lewis bases including
cyclodextrins (poly)saccharides or molecular sieves (MS) with the formula
Na12[(AlO2)12(SiO2)12] (Figure 35)
104
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
3291 Polysaccharides as heterogeneous Lewis bases
In probing this investigation α-cyclodextrin (α-CD) an oligosaccharide formed of six
glucopyranose units (Figure 35 a) was initially tested in H2 activation In this regard 5 mol
B(C6F5)3 and α-CD were combined in d8-toluene and exposed to HD gas (1 atm) in a J-Young
tube at 60 degC (Figure 36 a) 1H NMR analysis after 1 h revealed signals for H2 resulting from
isotope equilibration thereby signifying the viability of H2 activation between B(C6F5)3 and the
oxygen donors of α-CD (Figure 36 b) Furthermore the 11B and 19F NMR spectra indicated
signals corresponding to unaltered B(C6F5)3 thus suggesting a remarkably simple and
inexpensive H2 activation FLP catalyst It is important to note that B(C6F5)3 or α-CD alone do not
effect HD activation
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD)
To assess the unprecedented FLP system in carbonyl hydrogenation catalysis the ketone 3-
methyl-2-butanone was combined with an equivalent of α-CD and 5 mol B(C6F5)3 in toluene
and heated at 60 degC under H2 (60 atm) After 12 h quantitative reduction to the product 3-
methyl-2-butanol was evidenced by 1H NMR spectroscopy revealing a diagnostic multiplet at
327 ppm corresponding to the product CH group and broad singlet at 182 ppm assignable to the
a) b)
a)
b)
105
OH group (Table 33 entry 1) Repeating the reaction in the absence of H2 does not lead to
reduction of the substrate thus eliminating the possibility of transfer hydrogenation from α-CD
Under similar conditions a series of methyl alkyl (Table 33 entries 2 - 6) and dialkyl ketones
(Table 33 entries 7 - 9) aryl (Table 33 entries 10 - 14) benzyl (Table 33 entries 15 - 19) and
cyclic ketones (Table 33 entries 20 - 22) were hydrogenated in high yields In addition the
catalytic reduction of aldehydes was similarly performed to give the corresponding primary
alcohols (Table 33 entries 23 - 25) The 1H NMR spectra for all products displayed a
characteristic resonance at about 4 ppm diagnostic of CH and CH2 protons for ketone and
aldehyde reductions respectively and the corresponding 13C1H resonances were observed at
ca 70 ppm
The efficient nature of these catalytic reactions imply that B(C6F5)3 and the oxygen atoms of α-
CD act as a FLP to activate H2 initiating hydrogenation catalysis Selective silylation of α-CD at
the 2- and 6-hydroxy positions of the glucose units gave the toluene soluble product hexakis[26-
O-(tert-butyldimethylsilyl)]-α-cyclodextrin292 This derivatization was found to have a marginal
influence on catalysis forming 3-methyl-2-butanol in 70 yield after 12 h at 60 degC Moreover
the hydrogenation protocol was further investigated using the heterogeneous Lewis bases β and
γ-CD oligosaccharides of seven and eight glucopyranose units respectively and the
(poly)saccharides maltitol and dextrin Hydrogenation results are summarized in Table 33
Taking into account that cyclodextrins are used as chiral stationary phases in separation of
enantiomers the prochiral substrates of Table 33 were analyzed by chiral GC However in all
cases the products were found as racemic mixtures
106
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
Entry R R1 α-CD β-CD γ-CD Maltitol Dextrin MS
1 Me iPr gt99 79 77 62 81 gt99
2 Me 2-butyl gt99 74 72 46 75 gt99
3 Me CH2tBu gt99 52 41 40 53 gt99
4 Me CH2Cl gt99 gt99 trace 51 trace 80
5 Me Cy gt99 81 62 31 64 gt99
6 Me n-C5H11 gt99 63 56 36 73 gt99
7 Et iPr gt99 75 75 69 80 gt99
8 Et n-C4H9 95 93 95 58 gt99 93
9 n-C3H7 n-C3H7 gt99 - - - - 92
10a Me Ph 30 13 15 10 27 trace
11 CH2CH2Cl Ph 54 - - - - 50
12 CF3 Ph 20 - - - - 20
13 Me o-CF3C6H4 trace - - - - 25
14 Me p-MeSO2C6H4 60 - - - - 97
15 Me n-CH2CH2Ph gt99 58 90 38 trace gt99
16 Me CH2(o-FC6H4) 75 70 69 66 34 gt99
17 Me CH2(p-FC6H4) gt99 49 31 55 48 gt99
18 Me CH2(m-CF3C6H4) gt99 gt99 62 43 92 gt99
19 Et CH2Ph gt68 20 31 28 46 gt99
20 -(CH2)5- gt99 72 65 68 90 gt99
21b -(CH2)3CH=CH- 67 trace trace trace trace 82
22 -(2-iPr-5-Me)C5H8- gt99 70 60 60 80 gt99
23 Cy H 10 - - - - 44
24 Ph2CH H 47 - - - - 86
25 PhCH(Me) H 20 - - - - 35
a Reported yields are for phenylethanol b Product is cyclohexanol Isolated yields are reported for α-CD and MS
107
3292 Molecular sieves as heterogeneous Lewis bases
The presented (poly)saccharides could be conveniently replaced with the ubiquitous laboratory
drying agent MS293 as HD isotope equilibration experiments evidenced the formation of H2
when exposed to a d8-toluene suspension of MS and B(C6F5)3 It is noteworthy however that
such equilibration was not observed in the absence of B(C6F5)3
Using MS as the heterogeneous Lewis base 5 mol B(C6F5)3 catalyzed the hydrogenation of
ketone and aldehyde substrates reported in Table 33 These reductions could also be performed
on an increased scale with consecutive recycling of the MS For example 100 g of 4-heptanone
in toluene was treated with 5 mol of the catalyst B(C6F5)3 and MS yielding quantitative
conversion to 4-heptanol which was isolated in 95 yield The sieves were washed with solvent
and recombined with borane and ketone in three successive hydrogenations without loss of
activity
Speculation of physisorbed B(C6F5)3 onto MS was probed by reusing filtered sieves that were
washed with toluene without further addition of B(C6F5)3 This gave 30 reduction of 4-
heptanone suggesting that while there is some physisorption it is not sufficient to provide a
significant degree of catalysis
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones
In an effort to reduce the aryl alkyl ketone acetophenone the above protocol using α-CD was
employed for 12 h at 70 degC under H2 (60 atm) 1H NMR data revealed ca 60 consumption of
acetophenone resulting in the formation of two products in almost equal ratios The distinct
quartet at 424 ppm broad singlet at 342 ppm and doublet at 102 ppm were consistent with the
hydrogenated product phenylethanol (Scheme 311) The 1H NMR spectrum of the second
product gave three separate doublet of doublets with olefinic chemical shifts observed at 652
556 and 504 ppm with each signal integrating to one proton Mass spectroscopy confirmed this
species to be styrene derived from reductive deoxygenation (Scheme 311) The reaction was
repeated using MS giving styrene in a significantly improved 92 yield (Table 34 entry 1)
108
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone
To probe this deoxygenation further the ketone 3rsquo-(trifluoromethyl)acetophenone was treated
with 5 mol B(C6F5)3 in toluene and added to a suspension of MS and heated for 12 h at 70 degC
under H2 (60 atm) This resulted in formation of the deoxygenated product 3-
(trifluoromethyl)styrene in 95 yield (Table 34 entry 2) while remainder of the reaction
mixture consisted of the alcohol 3rsquo-(trifluoromethyl)phenyl ethanol Similar treatment of
propiophenone gave trans-β-methylstyrene in 96 yield with trace amounts of the cis isomer
(Table 34 entry 3) In a similar timeframe the deoxygenation of isobutyrophenone was
performed giving 75 of the hydrocarbon 2-methyl-1-phenyl-propene while 10 of the mixture
consisted of the alcohol 1-phenyl-1-propanol (Table 34 entry 4) In this case the comparatively
slower deoxygenation rate is presumably due to increased steric hindrance about the carbonyl
functionality Indeed these effects are more pronounced with 222-trimethylacetophenone as no
reaction was observed Finally the bicyclic ketone 1-tetralone gave 12-dihydronaphthalene in
88 yield (Scheme 312 a)
Table 34 ndash Deoxygenation of aryl alkyl ketones
Entry R R1 R2 Isolated yield
1 H Me CH2 92
2 CF3 Me CH2 95
3 H Et CHCH3 trans 96
cis 4
4 H iPr C(Me)2 75
109
In light of the established tandem hydrogenation and deoxygenation protocol under these
conditions benzophenone is deoxygenated to give diphenylmethane in 81 yield (Table 35
entry 1) Similarly the diaryl ketone derivatives with substituents including CH3O Br tBu and
CH3 groups were reduced affording the corresponding diarylmethane products in yields ranging
from 67 - 99 (Table 35 entries 2 - 5) In the case of p-CF3 substituted benzophenone the
reaction gave 10 of the deoxygenation and 50 of the alcohol products (Table 35 entry 6)
Analogous treatment of 2-methylbenzophenone resulted in only 20 conversion to the aromatic
hydrocarbon (Table 35 entry 7) This example including the result for 2rsquo-
(trifluoromethyl)acetophenone (25 yield) (Table 33 entry 13) certainly infer that increased
steric hindrance about the carbonyl group has a negative impact on reactivity
Finally the tricyclic ketone dibenzosuberone afforded the reduced aryl alkane
dibenzocycloheptene in 73 yield (Scheme 312 b) It is noteworthy that Repo et al have
previously reported B(C6F5)3 mediated reductive deoxygenation of acetophenone in CD2Cl2
however in their case concurrent hydration of the borane affords (C6F5)2BOH and C6F5H178 In
the present system MS preclude this degradation pathway allowing deoxygenation to proceed
catalytically
Table 35 ndash Deoxygenation of diaryl ketones
Entry R R1 Isolated yield
1 H Ph 81
2 CH3O Ph 85
3 Br Ph 67
4 tBu Ph gt99
5 CH3 p-CH3C6H4 75
6 CF3 Ph 10
7 H o-CH3C6H4 20
110
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b)
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation
The mechanism of these ketone and aldehyde reductions is thought to be analogous to the FLP
reductions described earlier in ethereal solvents In the present case the FLP initiating
heterolytic H2 activation is believed to be the Lewis basic oxygen atoms on the surface of the α-
CD or MS and the Lewis acid B(C6F5)3 (Scheme 313) although H2 activation by ketone
B(C6F5)3 cannot be dismissed Proceeding from the former activation method similar to the case
in ethereal solvents the protonated surface hydrogen bonds to the carbonyl fragment polarizing
the bond for hydride transfer from the [HB(C6F5)3]- anion The generated alkoxide anion is then
sufficiently basic to accept proton from the surface thus regenerating the heterogeneous Lewis
base This H2 activation is in agreement with HD equilibration experiments presented for α-CD
and MS
The ease of deoxygenating the ketones Ph2C=O gt PhCH3C=O gave insight to postulate the
reductive deoxygenation mechanism Heterolytic H2 activation occurs between the MS and
B(C6F5)3 although activation between ketoneB(C6F5)3 and alcoholB(C6F5)3 cannot be
dismissed ultimately resulting in protonated alcohol which is hydrogen-bonded to ketone
(Scheme 313) At this stage it appears that C-O bond cleavage with hydride delivery and loss
of H2O affords the aromatic alkene or alkane products Evidence of the alcohol-H-ketone
intermediate proposed in the mechanism is investigated in the following section
111
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones
Experimental results have demonstrated electronic effects directly impact the deoxygenation
mechanism It appears that C-O bond cleavage and loss of H2O is governed by stability of an
alcohol carbocation intermediate Aryl alcohols readily stabilize such an intermediate through
delocalization by the neighbouring π-system while this effect is clearly absent with dialkyl and
primary alcohols Moreover electron withdrawing groups prevent formation of the carbocation
as demonstrated by the reduction results of 222-trifluoroacetophenone and 4-
(methylsulfonyl)acetophenone These compounds exclusively gave the corresponding alcohol
products (Table 33 entries 12 and 14)
32101 Verifying the reductive deoxygenation mechanism
To validate the proposed reductive deoxygenation mechanism treatment of diphenylmethanol
with 5 mol B(C6F5)3 and MS was carried out at 70 degC under H2 (60 atm) (Figure 37)
Surprisingly the reaction only gave 10 mol of diphenylmethane and complete degradation of
B(C6F5)3 Modification of the study to include 5 10 and 50 mol of benzophenone gradually
increased consumption of diphenylmethanol indicating participation of ketone in the
deoxygenation process (Figure 37) Such a mechanism accounts for necessity of a strong
112
Broslashnsted acid to initiate the deoxygenation process by protonating the hydroxyl group
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased
The conversion of carbonyl substrates to hydrocarbons is an important and rather broad area of
research in modern organic chemistry with extensive contribution to the production of fuels
Replacement of an oxo group by two hydrogen atoms is generally carried out through
hydrogenolysis although hydrogenation methods are also well studied Prominent procedures for
this transformation include the Clemmensen reduction294-295 Wolff-Kishner reduction296 and
stoichiometric methods involving LiAlH4-AlCl3 NaBH4-CF3CO2H297 Et3SiH-BF3 or
CF3CO2H298-299 and HI-Phosphorus combinations300-301 in addition to metal-catalyzed
approaches62
From the perspective of FLP systems reductive deoxygenation of carbonyl groups has been
previously achieved using silanes boranes or ammonia borane165 as sacrificial reducing agents
0 mol
5 mol
10 mol
50 mol
Diphenylmethanol (CH) Diphenylmethane (CH2)
113
The Piers group showed the B(C6F5)3 catalyzed deoxygenative hydrosilylation of CO2 to CH4
using TMP B(C6F5)3 and excess Et3SiH169 Such transformations have also been reported using
N-heterocyclic carbenes and hydrosilanes302 The Fontaine group among others111 163 have
shown the hydroboration of CO2 to methanol using FLPs167-168 Significantly more challenging is
H2 as the reducing reagent In a unique example Ashley and OrsquoHare reported the reduction of
CO2 by H2 using a stoichiometric combination of B(C6F5)3 and TMP at 160 degC to give methanol
in 17 - 25 yield259
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins
In the experiments presented 4 Aring pellet MS purchased from Sigma Aldrich were used in
combination with B(C6F5)3 To explore the efficacy of other materials the same hydrogenation
protocol was applied in the reduction of 4-heptanone to give 4-heptanol in the following yields 5
Aring MS pellets (gt99) 4 Aring MS powder (69) 3 Aring MS pellets (68) acidic alumina (30)
silicic acid (15) while no reactivity was observed in the case of silica gel sodium aluminate
neutral and basic alumina
The hydrogenation protocol using 4 Aring MS was also attempted in the reduction of olefins
including 1-hexene cyclohexene 11-diphenylethylene and αp-dimethylstyrene however no
reactivity was observed in either case
33 Conclusions
The following chapter provides an account on the discovery of a metal-free route for the
hydrogenation of ketone and aldehyde substrates to form alcohol products The FLP catalyst is
derived from ether and B(C6F5)3 in which the protonated ether participates in hydrogen-bonding
interactions with the substrate affording an efficient catalyst to mediate the transformations
Moreover B(C6F5)3-assisted ketone hydrogenations using a two component catalyst system
derived from B(C6F5)3 and [NEt4][HB(C6F5)3] has also proven viable
Simultaneous with communicating this finding Ashley et al reported an analogous
hydrogenation catalyst derived from 14-dioxaneB(C6F5)3 that is effective for the hydrogenation
of ketones and aldehydes at 4 atm of H2 and temperatures ranging between 80 and 100 degC260
114
Also an air stable catalyst derived from THFB(C6Cl5)(C6F5)2 was shown to be particularly
effective for the hydrogenation of weakly Lewis basic substrates286
Continuing to explore modifications and applications of this new metal-free carbonyl reduction
protocol catalytic reductions were achieved in toluene using B(C6F5)3 and a heterogeneous
Lewis base including CDs (poly)saccharides or MS This combination of soluble borane and
insoluble materials provided a facile route to alcohol products In the case of aryl ketones and
MS further reactivity of the alcohol resulted in deoxygenation of the carbonyl group affording
either the aromatic alkane or alkene products
34 Experimental Section
341 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane tetrahydrofuran toluene (Sigma Aldrich) were dried employing a Grubbs-type
column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring) in the
glovebox Bromobenzene (-H5 and -D5) were purchased from Sigma Aldrich and dried over
CaH2 for several days and vacuum distilled onto 4 Aring molecular sieves prior to use
Dichloromethane-d2 benzene-d6 and chloroform-d were purchased from Sigma Aldrich
Toluene-d8 was purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to
use Molecular sieves (4 Aring) were purchased from Sigma Aldrich and dried at 120 ordmC under
vacuum for 12 h prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at
80 degC under high vacuum before use
Tetrahydropyran 14-dioxane and hexamethyldisiloxane were purchased from Sigma Aldrich
and distilled over sodiumbenzophenone prior to use Diphenyl ether (ReagentPlusreg ge99) was
purchased from Sigma Aldrich and distilled under high vacuum at 80 degC over anhydrous
calcium chloride prior to use Diethyl ether (anhydrous 99) was purchased from Caledon
Laboratories Ltd and passed through a Grubbs-type column system manufactured by Innovative
Technology and stored over 4 Aring molecular sieves overnight prior to use Diisopropyl ether
(anhydrous 99 contains either BHT or hydroquinone as stabilizer) was purchased from Sigma
Aldrich and used without purification Cyclodextrins (α β and γ) maltitol dextrin from maize
starch and molecular sieves (pellets 32 mm diameter 4 Aring) were purchased from Sigma Aldrich
115
dried under vacuum at 120 degC for 12 h prior to use Deuterium hydride (extent of labeling 96
mol HD 98 atom D) was purchased from Sigma Aldrich Potassium
tetrakis(pentafluorophenyl)borate was purchased from Alfa Aesar Sodium triethylborohydride
(1M in toluene) was purchased from Sigma Aldrich Borenium cation-based FLP catalysts were
prepared by Dr Jeffrey M Farrell and Mr Roy Posaratnanathan following the literature
protocol105
All ketones and alcohols were purchased from Alfa Aesar Sigma Aldrich or TCI The liquids
were stored over 4 Aring molecular sieves and used without purification The solids were placed
under dynamic vacuum overnight prior to use H2 (grade 50) was purchased from Linde and
dried through a Nanochem Weldassure purifier column prior to use For the high pressure Parr
reactor the H2 was dried through a Matheson TRI-GAS purifier (type 452)
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D6 (1H = 716 ppm 13C = 1284 ppm) C6D5Br (1H = 728
ppm for meta proton 13C = 1224 ppm for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384
ppm) d8-tol (1H = 208 ppm for CH3 13C = 13748 ppm for ipso carbon) CDCl3 (1H = 726 ppm 13C = 7716 ppm) or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in
ppm and the absolute values of the coupling constants (J) are in Hz NMR assignments are
supported by additional 2D and DEPT-135 experiments
High Resolution Mass Spectroscopy (HRMS) was obtained using JMS T100-LC AccuTOF
DART with ion source Direct Analysis in Real Time (DART) Ionsense Inc Saugus MA GC-
MS spectra were obtained on an Agilent Technologies 5975C VL MSD with Triple-Axis
Detector and 7890A GC System Column Agilent 19091S-433 (30 m times 250 μm times 025 μm)
Oven 40 degC for first 10 min 10 degCmin to 300 degC for 10 min Injection volume 1 μL The pro-
chiral samples were analyzed using a Perkin Elmer Autosystem CL chromatograph with a chiral
column (CP Chirasil-Dex CB 25 m times 25 mm)
Jutzi acid [(Et2O)2H][B(C6F5)4]287 and silylation of α-CD with tert-butyldimethylsilyl chloride292
were prepared according to literature procedures
116
Solid materials were purchased from commercial sources 5 Aring molecular sieves (pellets 32 mm
Aldrich) 4 Aring molecular sieves (powder Aldrich) 3 Aring molecular sieves (rod 116 inches
Aldrich) aluminum oxide (weakly acidic 150 mesh 58 Aring SA = 155 m2g Aldrich) sodium
metasilicate (18 mesh granular Alfa Aesar) silicic acid (80 mesh powder Aldrich) silica gel
(200-425 mesh 60 Aring high purity grade Silicycle) sodium aluminate (powder Aldrich)
aluminum oxide (basic 150 mesh 58 Aring SA = 155 m2g Aldrich) aluminum oxide (neutral
150 mesh 58 Aring SA = 155 m2g Aldrich)
342 Synthesis of Compounds
3421 Procedures for reactions in ethereal solvents
4-Heptanol-B(C6F5)3 adduct experiment In the glove box an NMR tube was charged with a
d8-toluene (04 mL) solution of B(C6F5)3 (122 mg 240 μmol 100 mol) and 4-heptanol (279
mg 0240 mmol) The NMR tube was sealed with Parafilm and placed in an 80 degC oil bath for
12 h 19F and 11B NMR spectra were obtained No evidence for the formation of C6F5H was
observed
19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1552 (t 3JF-F = 22 Hz 1F p-C6F5) -
1628 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 197 (br s 4-heptanol-B(C6F5)3)
Synthesis of (CH3CH2CH2)2CHOB(C6F5)2from the reaction of 4-heptanone and HB(C6F5)2
In the glove box an NMR tube was charged with a d8-toluene (04 mL) solution of HB(C6F5)2
(834 mg 0240 mmol) and 4-heptanone (274 mg 0240 mmol) A second NMR tube was
charged with a d8-toluene (04 mL) solution of HB(C6F5)2 (83 mg 24 μmol 10 mol) and 4-
heptanone (274 mg 0240 mmol) After 10 min at RT the samples were analyzed by 1H 19F
and 11B NMR spectroscopy
1H NMR (400 MHz d8-tol) δ 405 (tt 3JH-H = 76 38 Hz 1H CH) 168-151 (m 2H CH2)
150 - 134 (m 4H CH2) 133 - 115 (m 2H CH2) 086 (t 3JH-H = 76 Hz 6H CH3) 19F NMR
(377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1498 (t 3JF-F = 20 Hz 1F p-C6F5) -1613 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 394 (br s (CH3CH2CH2)2CHOB(C6F5)2)
High temperature NMR study for the reduction of 4-heptanone using 5 equivalent of Et2O
(J-Young Experiment) In the glove box a 1 dram vial was charged with a d8-toluene (03 mL)
117
solution of B(C6F5)3 (61 mg 12 μmol 50 mol) 4-heptanone (274 mg 0240 mmol) and Et2O
(890 mg 125 μL 120 mmol) The reaction mixture was transferred into an oven-dried Teflon
screw cap J-Young tube The reaction tube was degassed once through a freeze-pump-thaw cycle
on the vacuumH2 line and filled with H2 (4 atm) at -196 degC The reaction was monitored by high
temperature 1H NMR spectroscopy at 70 degC with 15 minute acquisitions (Figure 31)
General procedure for reactions in ethereal solvents (Table 31) The following procedure is
common to the ketone hydrogenation reactions in Et2O iPr2O Ph2O and TMS2O In the glove
box a 2 dram vial equipped with a stir bar was charged with the respective ketone or aldehyde
(048 mmol) and B(C6F5)3 (122 mg 240 μmol 500 mol) To each vial the appropriate ether
(96 mmol 20 eq) was added using a syringe Et2O (10 mL) iPr2O (13 mL) Ph2O (15 mL) and
TMS2O (20 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glove box to be pressurized with hydrogen gas
The hydrogen gas line was thoroughly purged and the reactor was attached to it and purged 10
times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at 70 degC 540 rpm
and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time the reactor was
vented and the vials were exposed to the atmosphere In the case of Et2O and iPr2O the entire
reaction mixture was transferred to a round bottom flask and all the volatiles were collected by
vacuum distillation while cooling the collected distillate with liquid nitrogen The solvent was
then removed by applying a gentle stream of N2 gas The alcohol yields were recorded and the
products were characterized by NMR spectroscopy and GC-MS
General procedure for 100 gram reaction of 4-heptanone in Et2O In the glove box 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol 500 mol) dissolved in Et2O (143 mg 200 mL 0190 mol)
was added to the bottle The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glove box and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 540 rpm After the indicated reaction time the reactor was slowly
vented and all the volatiles were collected by vacuum distillation while cooling the collected
distillate with liquid nitrogen The solvent was removed by applying a gentle stream of N2 gas
118
By 1H NMR spectroscopy the product displayed complete conversion to 4-heptanol and was
isolated in 87 yield
Dependence of Et2O equivalents on the reduction of 4-heptanone (Figure 32) In the glove
box a stock solution consisting of 4-heptanone (192 mg 235 μL 167 mmol) and B(C6F5)3 (427
mg 800 μmol 500 mol) in toluene (35 mL) was prepared in a 2 dram vial The solution was
distributed evenly between seven 2-dram vials (053 mLvial) and each vial was equipped with a
stir bar To each vial the appropriate volume of Et2O was added using a (micro)syringe
Et2O volume 12 μL (005 eq) 25 μL (01 eq) 125 μL (05 eq) 252 μL (10 eq) 504 μL (20
eq) 756 μL (30 eq) 101 μL (40 eq) 126 μL (50 eq) 151 μL (60 eq) 176 μL (70 eq) 202 μL
(80 eq)
The vial was loosely capped and loaded in a Parr pressure reactor sealed carefully and removed
from the glove box to be pressurized with hydrogen gas The hydrogen gas line was thoroughly
purged and the reactor was attached to it and purged 10 times at 15 atm of hydrogen gas The
reactor was then placed in an oil bath set at 70 degC 540 rpm and sealed at 60 atm of hydrogen gas
for 12 h After the indicated reaction time the reactor was vented and the reactions were analyzed
by 1H NMR spectroscopy Percent conversion to 4-heptanol was obtained by integration relative
to the remaining starting material 4-heptanone
Synthesis of [iPr2O-HmiddotmiddotmiddotO=C(CH2Ph)CH2CH3][B(C6F5)4] (31) In the glove box to a 2 dram
vial was added [(Et2O)2H][B(C6F5)4] (130 mg 0157 mmol) 4-phenyl-2-butanone (349 mg
0235 mmol) iPr2O (1284 mg 126 mmol) and toluene (05 mL) The solution was transferred
into a Teflon-sealed Schlenk bomb (25 mL) equipped with a stir bar and heated at 70 degC for 2 h
The solvent was removed under vacuum and pentane (5 mL) was added to result in immediate
precipitation of a white solid that was washed again with pentane (3 mL) and dried under
vacuum (127 g 136 mmol 87) Crystals suitable for X-ray crystallographic studies were
obtained from a layered bromobenzenepentane solution at RT
1H NMR (400 MHz CD2Cl2) δ 1152 (br s 1H iPr2O-HmiddotmiddotmiddotO=C) 741 (m 3H m p-Ph) 718
(m 2H o-Ph) 468 (m 3JH-H = 68 Hz 2H iPr) 403 (s 2H PhCH2) 281 (q 3JH-H = 71 Hz
2H CH2CH3) 146 (d 3JH-H = 68 Hz 12H iPr) 117 (t 3JH-H = 71 Hz 3H CH2CH3) 19F NMR
(377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1617 (t 3JF-F = 22 Hz 1F p-C6F5) -1658 (m
119
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -168 (s B(C6F5)4) 13C1H NMR (125 MHz
CD2Cl2) δ 1480 (dm 1JC-F = 238 Hz CF) 1379 (dm 1JC-F = 243 Hz CF) 1362 (dm 1JC-F =
246 Hz CF5) 1319 (ipso-Ph) 1301 (m-Ph) 1298 (o-Ph) 1288 (p-Ph) 1240 (ipso-C6F5) 828
(iPr) 498 (CH2Ph) 373 (CH2CH3) 197 (iPr) 799 (CH2CH3) (C=O was not observed)
HRMS (DART-TOF+) mass [M]+ calcd for [C16H27O2]+ 25120110 Da Found 25120127 Da
mass [M]- calcd for [C24BF20]- 67897736 Da Found 67897745 Da
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3]
Synthesis of [NEt4][HB(C6F5)3] Part 1 In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (200 mg 0391 mmol) in toluene (10 mL) To the vial
sodium triethylborohydride (1M in toluene) (036 mL 036 mmol) was added drop wise over 15
min The reaction was allowed to mix overnight prior to removing the volatiles under vacuum
The crude mixture was washed with pentane (5 mL) to give the product Na HB(C6F5)3 as a white
solid (187 mg 0348 mmol 89)
Part 2 Na HB(C6F5)3 (187 mg 0348 mmol) was subsequently added to CH2Cl2 (10 mL) and
added to a 4 dram vial containing NEt4 Cl (576 mg 0348 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT overnight and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (206 mg
0320 mmol 92)
1H NMR (400 MHz d8-tol) δ 415 (br q 1JB-H = 91 Hz 1H BH) 211 (q 3JH-H = 74 Hz 8H
Et) 046 (tm 3JH-H = 74 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -13361 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
247 (d 1JB-H = 91 Hz BH)
General procedure for reactions in toluene using B(C6F5)3 and [NEt4][HB(C6F5)3] (Table
32) In the glovebox a 2 dram vial equipped with a stir bar was charged with the respective
ketone (048 mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and [NEt4][HB(C6F5)3] (154
mg 240 μmol 500 mol) in toluene (10 mL) The vial was loosely capped and loaded in a
Parr pressure reactor sealed carefully and removed from the glovebox to be pressurized with
hydrogen gas The hydrogen gas line was thoroughly purged and the reactor was attached to it
and purged 10 times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at
80 degC 540 rpm and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time
120
the reactor was vented and the reactions were analyzed by 1H NMR spectroscopy Percent
conversion to the alcohol product was obtained by integration relative to the remaining starting
material ketone
3423 Procedures for reactions using heterogeneous Lewis bases
General procedure for reactions in toluene using heterogeneous Lewis bases (Table 33) In
the glovebox a 2 dram vial equipped with a stir bar was charged with the respective ketone (048
mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and the respective heterogeneous Lewis base
in toluene (10 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glovebox to be pressurized with hydrogen gas The hydrogen gas
line was thoroughly purged and the reactor was attached to it and purged 10 times at 15 atm of
hydrogen gas The reactor was then placed in an oil bath set at 60 degC 430 rpm and sealed at 60
atm of hydrogen gas for 12 h Products were isolated by appropriate work-up methods The
alcohol yields were recorded and the products were characterized by NMR spectroscopy and
GC-MS
Heterogeneous Lewis bases α-CD (467 mg 0480 mmol) β-CD (467 mg 0410 mmol) γ-CD
(467 mg 0360 mmol) maltitol (168 mg 0480 mmol) dextrin (350 mg) MS (100 mg)
General procedure 100 g scale reduction of 4-heptanone using MS In the glovebox 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol) dissolved in toluene (7 mL ) was added to the bottle in addition
to 302 g of 4 Aring MS The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glovebox and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 430 rpm The reactor was slowly vented and an aliquot was taken in
d8-toluene and complete conversion of 4-heptanone to 4-heptanol was determined by 1H NMR
spectroscopy The reaction mixture was filtered through a frit and washed with dichloromethane
(2 times 10 mL) The collected molecular sieves were extracted with dichloromethane (3 times 10 mL)
and water (20 mL) The organic fraction was dried over magnesium sulfate and combined with
the toluene fraction The two solvents dichloromethane and toluene were removed by fractional
121
distillation 4-Heptanol was then collected under vacuum in a liquid nitrogen cooled Schlenk
flask The product was collected as a colourless liquid (0885 g 762 mmol 87)
3424 Procedures for reductive deoxygenation reactions
General procedure for deoxygenation reactions using molecular sieves (Table 34 and Table
35) This method follows the same procedure for reactions in Table 33 using 4 Aring MS The
reactor was placed in an oil bath set at 70 degC 340 rpm and sealed at 60 atm of hydrogen gas for
12 h Products were isolated by appropriate work-up methods The aromatic hydrocarbon yields
were recorded and the products were characterized by NMR spectroscopy and GC-MS
Verifying the deoxygenation mechanism In the glovebox four separate 2-dram vials were
loaded with diphenylmethanol (442 mg 0240 mmol) and B(C6F5)3 (61 mg 12 μmol 50
mol) To each vial the indicated equivalents of benzophenone were added (21 mg 12 μmol
50 mol 44 mg 24 μmol 10 mol 218 mg 0120 mmol 50 mol) followed by the
addition of d8-toluene (05 mL) and 4 Aring MS (100 mg) The reaction vials were equipped with a
stir bar loosely capped and placed inside a Parr pressure reactor The reactor was sealed
removed from the glovebox and attached to a purged hydrogen gas line The reactor was purged
ten times at 15 atm with hydrogen gas The reactor was then pressurized with 60 atm hydrogen
gas and placed in an oil bath for 12 h at 70 degC and 340 rpm After the indicated reaction time the
reactor was slowly vented and an aliquot was taken in d8-toluene and conversion of the
diphenylmethanol to diphenylmethane was determined by 1H NMR spectroscopy
3425 Spectroscopic data of products in Table 31
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
4-Heptanol (Entry 1) 1H NMR (500 MHz C6D5Br) δ 472 (br s 1H OH) 341 (tt 3JH-H = 70
Hz 46 Hz 1H CH) 124 (m 4H CHCH2) 114 (m 4H CH2CH3) 082 (t 3JH-H = 67 Hz 6H
CH3) 13C1H NMR (125 MHz C6D5Br) δ 721 (CH) 390 (CHCH2) 184 (CH2CH3) 135
(CH3) GC-MS 11928 min mz = 981 [M-H2O] 730 [M-C3H7] 550 [M-C3H9O]
3-Methylbutan-2-ol (Entry 2) 1H NMR (500 MHz C6D5Br) δ 339 (qd 3JH-H = 63 Hz 53
Hz 1H CHOH) 145 (m 1H iPr) 115 (br s 1H OH) 100 (d 3JH-H = 63 Hz 3H CH3) 083
122
(d 3JH-H = 68 Hz 3H iPr) 080 (d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz
C6D5Br) δ 719 (CHOH) 347 (iPr) 200 (CH3) 180 (iPr) 175 (iPr) GC-MS 3150 min mz
= 731 [M-CH3] 551 [M-CH5O]
44-Dimethylpentan-2-ol (Entry 3) 1H NMR (500 MHz C6D5Br) δ 380 (m 1H CH) 368
(br s 1H OH) 127 (dd 2JH-H = 143 Hz 3JH-H = 79 Hz 1H CH2) 116 (dd 2JH-H = 143 Hz 3JH-H = 33 Hz 1H CH2) 105 (d 3JH-H = 62 Hz 3H CH3) 087 (s 9H tBu) 13C1H NMR
(125 MHz C6D5Br) δ 660 (CH) 526 (CH2) 300 (tBu) 299 (tBu) 258 (CH3) GC-MS 6776
min mz = 1011 [M-CH3] 831 [M-CH5O] 701 [M-C2H6O] 571 [M-C3H7O]
Heptan-2-ol (Entry 4) 1H NMR (500 MHz d8-tol) δ 424 (br s 1H OH)
348 (m 3JH-H = 60 Hz 1H H2) 126 (m 2H H6) 123 (m 2H H3 H4)
118 - 114 (m 4H H3 H4 H5) 097 (d 3JH-H = 60 Hz 3H H1) 090 (t 3JH-H = 71 Hz 3H
H7) 13C1H NMR (125 MHz d8-tol) δ 684 (C2) 392 (C3) 319 (C5) 255 (C4) 228 (C1
C6) 139 (C7) GC-MS 12395 min mz = 1011 [M-CH3] 981 [M-H2O] 871 [M-C2H5]
1-Chloropropan-2-ol (Entry 5) 1H NMR (500 MHz C6D5Br) δ 432 (br s 1H OH) 362 (m 3JH-H = 68 Hz 1H CH) 316 (dd 2JH-H = 113 Hz 3JH-H = 35 Hz 1H CH2Cl) 304 (dd 2JH-H =
113 Hz 3JH-H = 68 Hz 1H CH2Cl) 090 (d 3JH-H = 61 Hz 3H CH3) 13C1H NMR (125
MHz C6D5Br) δ 692 (CH) 502 (CH2Cl) 222 (CH3) GC-MS 3383 min mz = 810 [(M+2)-
CH3] 790 [M-CH3]
1-Cyclohexylethan-1-ol (Entry 6) 1H NMR (400 MHz d8-tol) δ 330 (quint 3JH-H = 74 Hz
1H CH) 182 - 147 (m 5H Cy) 131 (br s 1H OH) 125 - 102 (m 4H Cy) 098 (d 3JH-H =
74 Hz 3H CH3) 087 (m 2H Cy) 13C1H NMR (125 MHz d8-tol) δ 721 (CHOH) 452
(CyCH) 287 (Cy) 268 (Cy) 267 (Cy) 205 (CH3) GC-MS 14245 min mz = 1131 [M-CH3]
1101 [M- H2O] 831 [M-C2H5O]
2-Methylpentan-3-ol (Entry 7) 1H NMR (500 MHz C6D5Br) δ 410 (br s 1H OH) 308
(ddd 3JH-H = 88 Hz 52 Hz 38 Hz 1H CHOH) 146 (m 3JH-H = 68 Hz 52 Hz 1H iPr) 133
(dqd 2JH-H = 140 Hz 3JH-H = 75 Hz 39 Hz 1H CH2) 120 (ddq 2JH-H = 140 Hz 3JH-H = 86
Hz 75 Hz 1H CH2) 081 (t 3JH-H = 75 Hz 3H CH3) 077 (d 3JH-H = 68 Hz 3H iPr) 076
(d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz C6D5Br) δ 783 (CHOH) 326 (iPr) 264
123
(CH2) 184 (iPr) 167 (iPr) 994 (CH3) GC-MS 5663 min mz = 841 [M-H2O] 731 [M-
C2H5] 591 [M-C3H7]
Heptan-3-ol (Entry 8) 1H NMR (500 MHz C6D5Br) δ 450 (br s 1H
OH) 335 (tt 3JH-H = 73 Hz 47 Hz 1H H3) 136-130 (m 2H H2) 128-
121 (m 5H H4 H5 H6) 115 (m 1H H5) 084 (t 3JH-H = 57 Hz 3H H7) 083 (t 3JH-H = 57
Hz 3H H1) 13C1H NMR (125 MHz C6D5Br) δ 732 (C3) 362 (C4) 295 (C2) 275 (C5)
226 (C6) 138 (C7) 961 (C1) GC-MS 12171 min mz = 981 [M-H2O] 831 [M-CH5O]
691 [M-C2H7O] 590 [M-C4H9]
5-Methylhexan-3-ol (Entry 9) 1H NMR (400 MHz d8-tol) δ (tt 3JH-H = 87 51 Hz 1H
CHOH) 201 (m 2H CH2CH3) 148 (m 3JH-H = 69 51 Hz 1H iPr) 130 (m 1H CH2iPr)
126 (m 1H CH2iPr) 089 (d 3JH-H = 69 Hz 6H iPr) 085 (t 3JH-H = 72 Hz 3H CH3)
13C1H NMR (101 MHz d8-tol) δ 785 (CHOH) 337 (iPr CH2CH3) 273 (CH2iPr) 188
(iPr) 171 (iPr) 104 (CH3) GC-MS 9458 min mz = 871 [M-Et] 691 [M-C2H7O] 591 [M-
CH2iPr]
1-Phenylethan-1-ol (Entry 10) 1H NMR (400 MHz C6D6) δ 702 (m 5H Ph) 428 (q 3JH-H =
65 Hz 1H CH) 342 (br s 1H OH) 102 (d 3JH-H = 65 Hz 3H CH3) 13C1H NMR (125
MHz CDCl3) δ 1460 (ipso-Ph) 1286 (m-Ph) 1283 (p-Ph) 1254 (o-Ph) 703 (CH) 252
(CH3) GC-MS 17207 min mz = 1221 [M] 1071 [M-CH3] 1040 [M-H2O] 910 [M-CH3O]
770 [M-C2H5O]
1-Phenylbutan-2-ol (Entry 11) 1H NMR (500 MHz CD2Cl2) δ 755 (m 1H OH) 733 (tm 3JH-H = 76 Hz 2H m-Ph) 729 (dm 3JH-H = 76 Hz 2H o-Ph) 725 (tm 3JH-H = 76 Hz 1H p-
Ph) 376 (dq 3JH-H = 81 Hz 42 Hz 1H CH) 286 (dd 2JH-H = 136 Hz 3JH-H = 43 Hz 1H
CH2Ph) 266 (dd 2JH-H = 136 Hz 3JH-H = 81 Hz 1H CH2Ph) 152 (q 3JH-H = 77 Hz 2H
CH2CH3) 102 (t 3JH-H = 77 Hz 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1391 (ipso-
Ph) 1295 (m-Ph) 1284 (o-Ph) 1263 (p-Ph) 739 (CH) 437 (CH2Ph) 303 (CH2CH3) 960
(CH3) GC-MS 20079 min mz = 1321 [M-H2O] 1030 [M-C2H7O] 911 [M-C3H7O]
591[M-C7H7]
4-Phenylbutan-2-ol (Entry 12) 1H NMR (500 MHz C6D5Br) δ 720 (t 3JH-H = 74 Hz 2H m-
Ph) 710 (t 3JH-H = 74 Hz 1H p-Ph) 706 (d 3JH-H = 74 Hz 2H o-Ph) 373 (br s 1H OH)
124
362 (dqd 3JH-H = 74 Hz 62 Hz 50 Hz 1H CH) 255 (m 2H PhCH2) 160 (m 2H CH2CH)
103 (d 3JH-H = 62 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1411 (ipso-Ph) 1281
(m-Ph) 1280 (o-Ph) 1255 (p-Ph) 673 (CH) 403 (PhCH2) 317 (CH2CH) 229 (CH3) GC-
MS 20438 min mz = 1501 [M] 1321 [M-H2O] 1170 [M-CH5O] 1051 [M-C2H5O] 911
[M-C3H7O]
1-(2-Fluorophenyl)propan-2-ol (Entry 13) 1H NMR (500 MHz CD2Cl2) δ
753 (m 1H OH) 733 - 705 (m 4H C6H4F) 406 (m 1H CH) 284 (dd 2JH-
H = 139 Hz 3JH-H = 51 Hz 1H CH2) 276 (dd 2JH-H = 139 Hz 3JH-H = 77
Hz 1H CH2) 124 (d 3JH-H = 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1178 (m
CF) 13C1H NMR (125 MHz CD2Cl2) δ 1611 (d 1JC-F = 240 Hz C1) 1318 (d 3JC-F = 59
Hz C3) 1285 (d 4JC-F = 88 Hz C4) 1257 (d 2JC-F = 16 Hz C2) 1240 (d 3JC-F = 37 Hz C5)
1152 (d 2JC-F = 22 Hz C6) 678 (d 4JC-F = 11 Hz CH) 388 (d 3JC-F = 14 Hz CH2) 229
(CH3) GC-MS 18697 min mz = 1360 [M-H2O] 960 [M-C3H6O]
1-(4-Fluorophenyl)propan-2-ol (Entry 14) 1H NMR (500 MHz CD2Cl2) δ 722 (m 2H o of
C6H4F) 705 (m 2H m of C6H4F) 399 (m 1H CH) 278 (dd 2JH-H = 137 Hz 3JH-H = 48 Hz
1H CH2) 269 (dd 2JH-H = 137 Hz 3JH-H = 78 Hz 1H CH2) 161 (br s 1H OH) 122 (d 3JH-H
= 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1177 (m p-C6H4F) 13C1H NMR (125
MHz CD2Cl2) δ 1616 (d 1JC-F = 243 Hz p of C6H4F) 1348 (d 4JC-F = 46 Hz ipso-C6H4F)
1307 (d 3JC-F = 82 Hz o of C6H4F) 1149 (d 2JC-F = 22 Hz m of C6H4F) 690 (CH) 449
(CH2) 227 (CH3) GC-MS 18697 min mz = 1361 [M-H2O] 960 [M-C3H6O]
1-(3-(Trifluoromethyl)phenyl)propan-2-ol (Entry 15) 1H NMR (500
MHz CD2Cl2) δ 751 (m 2H H1 H5) 744 (m 2H H3 H4) 408 (m 1H
CH) 283 (dd 2JH-H = 136 Hz 3JH-H = 49 Hz 1H CH2) 276 (dd 2JH-H =
136 Hz 3JH-H = 78 Hz 1H CH2) 181 (br s 1H OH) 123 (t 3JH-H = 62
Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -628 (CF3) 13C1H NMR (125 MHz CD2Cl2)
δ 1399 (C2) 1330 (q 4JC-F = 13 Hz C3) 1303 (q 2JC-F = 30 Hz C6) 1288 (C4) 1260 (q 3JC-F = 41 Hz C1) 1242 (q 1JC-F = 277 Hz CF3) 1230 (q 3JC-F = 41 Hz C5) 687 (CH) 447
(CH2) 228 (CH3) GC-MS 19011 min mz = 1861 [M-H2O] 1601 [M-C2H4O] 1171 [M-
CH2F3O]
125
Cyclohexanol (Entry 16) 1H NMR (400 MHz d8-tol) δ 324 (tt 3JH-H = 90 Hz 37 Hz 1H
CH) 177 (m 2H Cy) 168 (m 2H Cy) 142- 130 (m 3H Cy) 126- 115 (m 3H Cy)
13C1H NMR (101 MHz CD2Cl2) δ 706 (CH) 360 (CHCH2) 260 (Cy) 245 (Cy) GC-MS
4029 min mz = 1001 [M] 821 [M-H2O]
2-Isopropyl-5-methylcyclohexan-1-ol (Entry 17) 1H NMR (500 MHz
C6D5Br) δ 390 (q 3JH-H = 29 Hz 1H H1) 346 (br s 1H OH) 168 (ddd 2JH-H = 139 Hz 3JH-H = 36 Hz 24 Hz 1H H2) 164 (m 2H H3 H4) 153
(dm 2JH-H = 132 Hz 1H H5) 143 (dm 3JH-H = 92 Hz 67 Hz 1H H7) 118 (dm 2JH-H = 132
Hz 1H H5) 091 (m 1H H2) 087 (d 3JH-H = 67 Hz 3H H8) 083 (d 3JH-H = 67 Hz 3H
H9) 080 (d 3JH-H = 64 Hz 3H H10) 075 (m 1H H4) 070 (m 1H H6) 13C1H NMR (125
MHz C6D5Br) δ 675 (C1) 473 (C6) 421 (C2) 346 (C4) 288 (C7) 254 (C3) 238 (C5)
221 (C10) 208 (C9) 203 (C8) GC-MS 18912 min mz = 1381 [M-H2O] 1231 [M-CH5O]
951 [M-C3H9O] 811 [M-C4H12O]
Cyclohexylmethanol (Entry 18) 1H NMR (500 MHz CD2Cl2) δ 556 (br s 1H OH) 404 (d 3JH-H = 75 Hz 2H CH2OH) 212-182 (m 1H CyCH2) 180 (m 1H CyCH) 163 - 117 (m 1H CyCH2) 13C1H NMR (125 MHz CD2Cl2) δ 693 (CH2OH) 374 (CyCH) 301 (CyCH2) 262
(CyCH2) 252 (CyCH2) GC-MS 5538 min mz = 1141 [M] 961 [M-H2O] 831 [M-CH3O]
3426 Spectroscopic data of products in Table 32
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
3-Methylpentan-2-ol (Entry 4) 1H NMR (400 MHz CDCl3) δ 376 (m 1H CHOH) 223 (br
s 1H OH) 175 - 142 (m 3H CH(Et) Et) 118 (d 3JH-H = 69 Hz 3H CH3CHOH) 098 (m
6H CH(Et)CH3 Et) 13C1H NMR (125 MHz CD2Cl2) δ 713 (CHOH) 406 (CH(Et)) 223
(Et) 198 (OHCHCH3) 120 (CH(Et)CH3) 111 (Et) GC-MS 10215 min mz = 871 [M-CH3]
561 [M-C2H6O] 450 [C2H5O]
3427 Spectroscopic data of products in Table 33
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
126
222-Trifluoro-1-phenylethan-1-ol (Entry 12) 1H NMR (500 MHz d8-tol) δ 745 (m 2H m-
Ph) 717 (dm 3JH-H = 70 Hz 2H o-Ph) 711 (m 1H p-Ph) 432 (d 3JF-H = 77 Hz 1H CH)
306 (br s 1H OH) 19F NMR (470 MHz d8-tol) δ -783 (d 3JF-H = 77 Hz CF3) 13C1H NMR
(125 MHz d8-tol) δ 1341 (ipso-Ph) 1289 (m-Ph) 1276 (p-Ph) 1272 (q 4JC-F = 12 Hz o-Ph)
1234 (q 1JC-F = 297 Hz CF3) 726 (CH) GC-MS 6130 min mz = 1760 [M] 1701 [M-CF3]
3-Chloro-1-phenylpropan-1-ol (Entry 11) 1H NMR (600 MHz d8-tol) δ 712 (m 3H m p-
Ph) 703 (m 2H o-Ph) 399 (t 3JH-H = 78 Hz 1H CHOH) 312 (t 3JH-H = 67 Hz 2H CH2Cl)
251 (br s 1H OH) 218 (dt 3JH-H = 78 Hz 67 Hz 2H CHCH2CH2) 13C1H NMR (151
MHz d8-tol) δ 1440 (ipso-Ph) 1282 (m-Ph) 1275 (o-Ph) 1260 (p-Ph) 476 (CHOH) 432
(CH2Cl) 387 (CHCH2CH2) GC-MS 11210 min mz = 1701 [M] 1521 [M-H2O] 1070 [M-
C2H4Cl]
1-(2-(Trifluoromethyl)phenyl)ethan-1-ol (Entry 13) 1H NMR (500 MHz
d8-tol) δ 759 (d 3JH-H = 81 Hz 1H H2) 732 (d 3JH-H = 81 Hz 1H H5)
711 (t 3JH-H = 81 Hz 1H H3) 685 (t 3JH-H = 81 Hz 1H H4) 508 (qm 3JH-
H = 67 Hz 1H CHOH) 221 (br s 1H OH) 125 (d 3JH-H = 67 Hz 3H CH3)
19F NMR (470 MHz d8-tol) δ -582 (s CF3) 13C1H NMR (125 MHz d8-tol) δ 1455 (ipso-
C6H4CF3) 1315 (C3) 1314 (C1) 1294 (C4) 1264 (C2) 1244 (C5) 1240 (CF3) 653
(CHOH) 253 (CH3) (JC-F not reported) GC-MS 6453 min mz = 1901 [M] 1750 [M-CH3]
1720 [M-H2O] 1450 [M-C2H5O]
1-(4-(Methylsulfonyl)phenyl)ethan-1-ol (Entry 14) 1H NMR (500 MHz d8-tol) δ 763 (d 3JH-H = 86 Hz 2H o of C6H4SO2CH3) 705 (d 3JH-H = 86 Hz 2H m of C6H4SO2CH3) 437 (m
1H CHOH) 228 (s 3H SO2CH3) 141 (br s 1H OH) 112 (d 3JH-H = 66 Hz 3H CHCH3)
13C1H NMR (125 MHz d8-tol) δ 1522 (p of C6H4SO2CH3) 1402 (ipso-C6H4SO2CH3) 1270
(o of C6H4SO2CH3) 1257 (m of C6H4SO2CH3) 689 (CHOH) 436 (SO2CH3) 252 (CHCH3)
HRMS-DART+ mz [M+NH4]+ calcd for C9H16NO3S 21808509 Found 21808554
22-Diphenylethan-1-ol (Entry 24) 1H NMR (500 MHz d8-tol) δ 704 (m 1H p-Ph) 703 (m
2H m -Ph) 693 (d 3JH-H = 75 Hz 2H o-Ph) 405 (dd 3JH-H = 83 Hz 61 Hz 1H CH) 400
(m 2H CH2) (OH was not observed) 13C1H NMR (125 MHz d8-tol) δ 1418 (ipso-Ph)
1293 (m-Ph) 1287 (o-Ph) 1274 (p-Ph) 763 (CH2) 512 (CH) GC-MS 15178 min mz =
1811 [M-OH] 1671 [M-CH3O]
127
2-Phenylpropan-1-ol (Entry 25) 1H NMR (500 MHz d8-tol) δ 722 (d 3JH-H = 78 Hz 2H o-
Ph) 718 ndash 713 (m 3H m p-Ph) 362 (dd 2JH-H = 100 Hz 3JH-H = 62 Hz 1H CH2) 354 (dd 2JH-H = 100 Hz 3JH-H = 78 Hz 1H CH2) 342 (br s 1H OH) 288 (m 3JH-H = 69 Hz 1H CH)
121 (d 3JH-H = 69 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1459 (ipso-Ph) 1289 (p-
Ph) 1283 (m-Ph) 1274 (o-Ph) 780 (CH2) 435 (CH) 181 (CH3) GC-MS 6462 min mz =
1211 [M-CH3] 1051 [M-CH3O]
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Styrene (Entry 1)1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 77 Hz 2H o-Ph) 708 (t 3JH-
H = 77 Hz 2H m-Ph) 706 (t 3JH-H = 77 Hz 1H p-Ph) 653 (dd 3JH-H = 176 Hz 109 Hz 1H
CH) 556 (dd 3JH-H = 176 Hz 11 Hz 1H CH2) 505 (dd 3JH-H = 109 Hz 11 Hz 1H CH2)
13C1H NMR (125 MHz d8-tol) δ 1379 (CH) 1372 (ipso-Ph) 1286 (o m-Ph) 1284 (p-Ph)
1140 (CH2) GC-MS 4038 min mz = 1041 [M] 911 [C7H7] 781 [C6H6]
1-(Trifluoromethyl)-3-vinylbenzene (Entry 2) 1H NMR (500 MHz d8-
tol) δ 744 (s 1H H1) 718 (d 3JH-H = 77 Hz 1H H5) 706 (d 3JH-H = 77
Hz 1H H3) 686 (t 3JH-H = 75 Hz 1H H4) 631 (dd 3JH-H = 173 Hz 102
Hz 1H CH=CH2) 544 (d 3JH-H = 173 Hz 1H CH=CH2) 504 (d 3JH-H = 102 Hz 1H
CH=CH2) 19F NMR (470 MHz d8-tol) δ -626 (s CF3) 13C1H NMR (125 MHz d8-tol) δ
1379 (ipso-C6H4CF3) 1354 (CH=CH2) 1309 (C2) 1284 (C5) 1245 (CF3) 1237 (C3) 1225
(C1) 1151 (CH=CH2) (JC-F not reported) GC-MS 4290 min mz = 1721 [M] 1531 [M-F]
1451 [M-C2H3] 1031 [M-CF3]
(E)-Prop-1-en-1-ylbenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 73 Hz
2H o-Ph) 712 (t 3JH-H = 73 Hz 2H m-Ph) 702 (t 3JH-H = 73 Hz 1H p-Ph) 626 (dq 3JH-H =
156 Hz 4JH-H = 18 Hz 1H PhCH=CH) 600 (dq 3JH-H = 156 Hz 66 Hz 1H PhCH=CH)
168 (dd 3JH-H = 66 Hz 4JH-H = 18 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1378
(ipso-Ph) 1314 (PhCH=CH) 1283 (m-Ph) 1265 (p-Ph) 1258 (o-Ph) 1248 (PhCH=CH)
1800 (CH3) GC-MS 5888 min mz = 1181 [M] 1171 [M-H] 1031 [M-CH3]
128
(2-Methylprop-1-en-1-yl)benzene (Entry 4) 1H NMR (500 MHz d8-tol) δ 717 (m 4H o m-
Ph) 705 (m 1H p-Ph) 624 (m 4JH-H = 15 Hz 1H CH=C(CH3)2) 180 (d 4JH-H = 15 Hz 3H
CH=C(CH3)2) 175 (d 4JH-H = 15 Hz 3H CH=C(CH3)2) 13C1H NMR (125 MHz d8-tol) δ
1386 (C(CH3)2) 1345 (ipso-Ph) 1287 (o-Ph) 1279 (m-Ph) 1257 (CH=C(CH3)2) 1256 (p-
Ph) 264 (CH3) 188 (CH3) GC-MS 5780 min mz = 1321 [M] 1171 [M-CH3]
12-Dihydronaphthalene (Scheme 312a) 1H NMR (600 MHz CD2Cl2) δ 746 - 731 (m 4H
C6H4) 678 (dm 3JH-H = 96 Hz 1H CH=CHCH2) 632 (m 1H CH=CHCH2) 308 (m 2H
CH2CH2CH) 258 (m 2H CH2CH=CH) 13C1H NMR (125 MHz CD2Cl2) δ 1358
(quaternary C for C6H4) 1344 (quaternary C for C6H4) 1288 (CH=CHCH2) 1280
(CH=CHCH2) 1277 (C6H4) 1271 (C6H4) 1266 (C6H4) 1261 (C6H4) 278 (CHCH2CH2) 236
(CH=CHCH2) GC-MS 7943 min mz = 1301 [M] 1151 [M-CH3] 1021 [M-C2H4]
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Diphenylmethane (Entry 1) 1H NMR (500 MHz d8-tol) δ 708 (t 3JH-H = 75 Hz 2H m-Ph)
701 (t 3JH-H = 75 Hz 1H p-Ph) 700 (d 3JH-H = 75 Hz 2H o-Ph) 372 (s 1H CH2) 13C1H
NMR (125 MHz d8-tol) δ 1413 (ipso-Ph) 1293 (o-Ph) 1286 (m-Ph) 1263 (p-Ph) 422
(CH2) GC-MS 11686 min mz = 1681 [M] 1671 [M-H] 911 [C7H7]
1-Benzyl-4-methoxybenzene (Entry 2) 1H NMR (500 MHz d8-tol) δ 712 (m 2H m-Ph)
711 (m 1H p-Ph) 705 (d 3JH-H = 67 Hz 2H o-Ph) 693 (d 3JH-H = 76 Hz 2H o of
C6H4OCH3) 670 (d 3JH-H = 76 Hz 2H m of C6H4OCH3) 372 (s 2H CH2) 334 (s 3H
OCH3) 13C1H NMR (125 MHz d8-tol) δ 1581 (p of C6H4OCH3) 1416 (ipso-C6H4OCH3)
1328 (ipso-Ph) 1295 (o of C6H4OCH3) 1287 (o-Ph) 1283 (m-Ph) 1278 (p-Ph) 1137 (m of
C6H4OCH3) 542 (OCH3) 410 (CH2) GC-MS 14801 min mz = 1981 [M] 1671 [M-OCH3]
1211 [M-C6H5] 911 [M-C7H7O] 771 [M-C8H9O]
1-Benzyl-4-bromobenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 719 (m 1H p-Ph) 716
(d 3JH-H = 78 Hz 2H m of C6H4Br) 710 (t 3JH-H = 77 Hz 2H m-Ph) 691 (d 3JH-H = 77 Hz
2H o-Ph) 665 (d 3JH-H = 77 Hz 2H o of C6H4Br) 355 (s 2H CH2) 13C1H NMR (125
MHz d8-tol) δ 1407 (ipso-C6H4Br) 1403 (ipso-Ph) 1317 (m of C6H4Br) 1316 (p-Ph) 1308
129
(o of C6H4Br) 1289 (o-Ph) 1285 (m-Ph) 1204 (p-C6H4Br) 414 (CH2) GC-MS 15250 min
mz = 2480 [M+2] 2460 [M] 1671 [M-Br] 911 [M-C6H4Br]
1-Benzyl-4-(tert-butyl)benzene (Entry 4) 1H NMR (500 MHz CD2Cl2) δ 774 (t 3JH-H = 86
Hz 2H m of C6H4tBu) 768 (t 3JH-H = 76 Hz 1H p-Ph) 761 (t 3JH-H = 76 Hz 2H m-Ph)
759 (d 3JH-H = 76 Hz 2H o-Ph) 755 (d 3JH-H = 86 Hz 2H o of C6H4tBu) 435 (s 2H CH2)
178 (s 9H tBu) 13C1H NMR (125 MHz CD2Cl2) δ 1493 (p of C6H4tBu) 1420 (ipso-Ph)
1387 (ipso-C6H4tBu) 1294 (m-Ph o of C6H4tBu) 1286 (p-Ph) 1263 (o-Ph) 1255 (m of
C6H4tBu) 415 (CH2) 347 (tBu) 315 (tBu) GC-MS 15429 min mz = 2242 [M] 2092 [M-
CH3) 911 [C7H7]
Di-p-tolylmethane (Entry 5) 1H NMR (500 MHz d8-tol) δ 699 (d 3JH-H = 78 Hz 2H o of
C6H4CH3) 694 (d 3JH-H = 78 Hz 2H m of C6H4CH3) 375 (s 1H CH2) 215 (s 3H CH3)
13C1H NMR (125 MHz d8-tol) δ 1383 (ipso-C6H4CH3) 1350 (p of C6H4CH3) 1289 (m of
C6H4CH3) 1287 (o of C6H4CH3) 408 (CH2) 206 (CH3) GC-MS 14226 min mz = 1961
[M] 1811 [M-CH3) 1661 [M-2(CH3)] 1051 [M-C7H7] 911 [M- C8H9]
1-Benzyl-4-(trifluoromethyl)benzene (Entry 6) 1H NMR (600 MHz CD2Cl2) δ 800 (d 3JH-H
= 73 Hz 2H o-Ph) 788 (d 3JH-H = 74 Hz 2H m of C6H4CF3) 778 (t 3JH-H = 73 Hz 1H p-
Ph) 767 (t 3JH-H = 73 Hz 2H m-Ph) 751 (d 3JH-H = 74 Hz 2H o of C6H4CF3) 430 (s 2H
CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1458 (ipso-C6H4CF3) 1404 (ipso-Ph) 1296 (p-Ph
o of C6H4CF3) 1285 (m-Ph) 1258 (p of C6H4CF3) 1256 (o-Ph) 1255 (m of C6H4CF3) 1239
(CF3) 415 (CH2) (JC-F not reported) GC-MS 11767 min mz = 2361 [M] 1671 [M-CF3]
1591 [M-C6H5] 911 [C7H7]
1-Benzyl-2-methylbenzene (Entry 7) 1H NMR (600 MHz CD2Cl2) δ
776 (m 2H o-Ph) 767 - 761 (m 3H m p-Ph) 759 - 754 (m 4H
C6H4CH3) 438 (s 2H CH2) 270 (s 3H CH3) 13C1H NMR (151
MHz CD2Cl2) δ 1410 (ipso-Ph) 1393 (ipso-C6H4CH3) 1370 (C-CH3) 1307 (C1) 1303 (m-
Ph) 1292 (o-Ph) 1287 (C4) 1268 (p-Ph) 1263 (C3) 1262 (C2) 395 (CH2) 197 (CH3)
GC-MS 12844 min mz = 1821 [M] 1671 [M-CH3]
130
1011-Dihydro-5H-dibenzo[ad][7]annulene (Scheme 312 b) 1H NMR
(600 MHz CD2Cl2) δ 745 (m 1H H2) 742 (m 1H H4) 740 (m 2H
H3 H5) 438 (s 1H CH2) 342 (s 2H CH2) 13C1H NMR (125 MHz
CD2Cl2) δ 1423 (C6) 1395 (C1) 1298 (C5) 1291 (C2) 1268 (C4) 1263 (C3) GC-MS
15761 min mz = 1941 [M] 1791 [M-CH3] 1651 [M-C2H5]
343 X-Ray Crystallography
3431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
3432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
131
3433 Selected crystallographic data
Table 36 ndash Selected crystallographic data for 31
31 (+05 C6D5Br)
Formula C43H295B1Br05F20O2
Formula wt 100893
Crystal system monoclinic
Space group P2(1)c
a(Aring) 127865(6)
b(Aring) 199241(9)
c(Aring) 170110(7)
α(ordm) 9000
β(ordm) 1067440(10)
γ(ordm) 9000
V(Aring3) 41500(3)
Z 4
Temp (K) 150(2)
d(calc) gcm-3 1607
Abs coeff μ mm-1 0606
Data collected 37469
Rint 00368
Data used 9534
Variables 596
R (gt2σ) 00458
wR2 01145
GOF 1020
132
Chapter 4 Hydroamination and Hydrophosphination Reactions Using
Frustrated Lewis Pairs
41 Introduction
411 Hydroamination
The direct addition of N-H bonds to unsaturated organic compounds provides an atom-economic
route to valuable nitrogen-containing molecules Pursuit of such reactivity is largely motivated
by the ubiquitous nature of substituted amines in the pharmaceutical industry303-306 The
intermolecular hydroamination of alkynes represents an attractive single-step approach to
convert inexpensive and readily available starting materials to synthetic building blocks such as
imines and enamines
Intermolecular hydroamination of alkynes was initially carried out using Hg and Tl salts307-308
however toxicity concerns prompted subsequent development of a wide variety of other catalysts
based on rare-earth metals309 early- and late-transition metals303 310 as well as lanthanides311-312
and actinides313 Based on the pioneering work of Bergman314-316 and Doye317-318 group IV metal
derivatives have become popular catalysts in these reactions More recently the groups of
Richeson319 Odom320-321 Schafer322 Mountford323 and others311 313 321 324 have made significant
contributions to further the development of these catalysts
Nonetheless to date transition metal-free routes remain relatively less explored The Broslashnsted
acid tungstophosphoric acid has been reported by Lingaiah325 to catalyze the hydroamination of
alkynes However in order for this catalyst to operate harsh conditions and electronically
deactivated amines are required An alternative approach using a strong base such as cesium
hydroxide was reported by Knochel although this strategy only tolerated functional groups less
acidic than the amines309 More recently metal-free approaches have been demonstrated in the
work by Beauchemin on the Cope-type inter- and intramolecular hydroaminations326-329
133
412 Reactions of main group FLPs with alkynes
4121 12-Addition or deprotonation reactions
Recent research has been devoted to effect metal-free stoichiometric and catalytic
transformations using frustrated Lewis pairs (FLPs) These main group combinations of bulky
Lewis acids and bases have become the focus of a number of research groups worldwide330-331
Shortly after the discovery of FLP chemistry several reports communicated the organic
manipulation of alkynes analogous to the pioneering hydroboration reactions by H C Brown60
Initial studies showed that FLPs comprised of B(C6F5)3 or Al(C6F5)3(PhMe) and phosphines react
to yield either zwitterionic vinyl phosphonium borate or aluminate salts resulting from a 12-
addition reaction or phosphonium alkynylborates resulting from alkyne deprotonation126 128 The
course of the reaction was found to depend on the basicity of the phosphine donor with less
basic aryl phosphines favouring 12-addition (Scheme 41)
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al)
Berke and co-workers investigated related intermolecular reactions of terminal alkynes and
B(C6F5)3 with 26-lutidine and TMP demonstrating that these systems effect deprotonation of the
alkyne affording ammonium alkynylborates156 Alternatively the groups of Erker and Stephan
reported the intramolecular cyclization of pendant alkyne substituted anilines151 and N-
heterocycles152 via 12-addition reactions using B(C6F5)3 (Scheme 42 a and b) In a similar
fashion ethylene-linked sulphurborane systems were found to add to alkynes with subsequent
elimination of ethylene affording a single-step route to SB alkenyl-FLPs (Scheme 42 c)332
134
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c)
4122 11-Carboboration reactions
The groups of Berke and Erker separately studied the reactivity of Lewis acids with alkynes in
the absence of a Lewis base (Scheme 43) To this extent they identified the 11-carboboration
reaction to generate alkenylboranes156 159-160 Moreover the reaction of propargyl esters with
B(C6F5)3 have been shown to generate boron allylation reagents333
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes
135
4123 Hydroelementation reactions
Catalytic hydroelementation reactions have been reported for alkynes In the presence of 5 - 10
mol B(C6F5)3 internal alkynes have been shown to undergo both hydrostannylation334 (Scheme
44 a) and hydrogermylation335 reactions (Scheme 44 b)
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes
413 Reactions of transition metal FLPs with alkynes
The FLP paradigm has also been studied using transition metal systems in combination with
alkynes Some examples include metalation through the 11-carbozirconation336 and
boroauration337 reactions Additionally the Wass group developed cationic zirconocene
phosphinoaryloxide complexes that selectively deprotonate terminal alkynes (Scheme 45)338 In
a recent paper the Stephan group has shown that Ru-acetylides act as carbon nucleophiles in
combination with Lewis acids to effect trans-addition to alkynes162
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes
Inspired by the reactivity of FLPs with alkynes in this chapter the intermolecular reaction of
amines B(C6F5)3 and a versatile group of terminal alkynes is explored in hydroamination
reactions A catalytic approach to yield enamines and corresponding amines is described In
addition related systems are probed to accomplish stoichiometric and catalytic intramolecular
hydroaminations affording N-heterocycles Finally stoichiometric approaches to
hydrophosphination reactions are discussed
136
42 Results and Discussion
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
With the objective of initiating hydroamination reactivity the three component stoichiometric
reaction of Ph2NH B(C6F5)3 and phenylacetylene was performed in CD2Cl2 The 1H 11B and 19F
NMR spectra revealed consumption of two equivalents of phenylacetylene to afford the salt
[Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] 41 while leaving a portion of the starting materials Ph2NH
and B(C6F5)3 unreacted (Scheme 46) Adjustment of the alkyne stoichiometry to two equivalents
afforded 41 in 90 yield (Table 41 entry 1) This new species results from the sequential
hydroamination and deprotonation reaction of phenylacetylene
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
The 1H NMR spectrum displayed a diagnostic methyl singlet at 289 ppm with the corresponding 13C1H resonance at 283 ppm In addition a downfield 13C1H resonance at 1901 ppm is
attributable to the iminium N=C group The alkynylborate anion [PhCequivCB(C6F5)3]- gave rise to
the 11B NMR signal at -208 ppm and 19F resonances at -1327 -1638 and -1673 ppm The
nature of compound 41 was unambiguously confirmed by X-ray crystallography (Figure 41)
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
137
To probe the generality of this reaction the corresponding reactivity of various substituted
secondary anilines with two equivalents of phenylacetylene were explored In this fashion the
species [RPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (R = iPr 42 Cy 43 PhCH2 44 p-CH3O 45) were
isolated in 88 91 82 and 90 yield respectively (Table 41 entry 1) 1H NMR spectra
showed the iminium cations were formed as a mixture of the E and Z isomers in a 71 ratio for
compounds 42 and 43 41 ratio for 44 and 11 ratio for 45
Analogous reactions of Ph2NH B(C6F5)3 and two equivalents of 1-hexyne revealed two
competitive reaction pathways In addition to the hydroaminationdeprotonation product
[Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] 46 (Table 41 entry 2) the alkenylboranes resulting from
the 11-carboboration of 1-hexyne were also observed by NMR spectroscopy Exposing the same
anilineB(C6F5)3 combination to 9-ethynylphenanthrene produced [Ph2N=C(CH3)C14H9]
[C14H9CequivCB(C6F5)3] 47 in 75 isolated yield (Table 41 entry 3) The molecular structure of
47 was unambiguously characterized by X-ray crystallography (Figure 42)
Figure 42 ndash POV-Ray depiction of 47
138
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
139
In a similar fashion the reaction of two equivalents of ethynylcyclopropane with B(C6F5)3 and
iPrPhNH at room temperature afforded the yellow crystalline solid formulated as
[iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] 48 in 88 yield (Table 41 entry 4) In this case
the 1H NMR spectrum showed the iminium cation is formed as a mixture of the E and Z isomers
in a 17 ratio Furthermore the reaction of iPrPhNHB(C6F5)3 with 2-ethynylthiophene
proceeded cleanly to give the product [iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] 49
obtained as a 71 mixture of EZ isomers and isolated in 78 yield (Table 41 entry 5) Single
crystals suitable for X-ray diffraction were obtained for Z-48 and Z-49 and the structures are
shown in Figure 43 (a) and (b) respectively
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b)
Interestingly addition 14-diethynylbenzene to the stoichiometric combination of Ph2NH
B(C6F5)3 resulted in an instant color change from pale orange to deep red affording the
zwitterionic product [Ph2N=C(CH3)C6H4CequivCB(C6F5)3] 410 in 85 yield (Table 41 entry 6)
The molecular structure of 410 was confirmed by X-ray crystallography (Figure 44)
Figure 44 ndash POV-Ray depiction of 410
(a) (b)
140
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes
The three component reaction is thought to proceed via Lewis acid polarization of the alkyne by
B(C6F5)3 prompting nucleophilic addition of the aniline and generating a zwitterionic
intermediate (Scheme 47) Analogous 12-additions to alkynes have been previously reported for
phosphineborane126 128 thioetherborane339 and pyrroleborane127 FLPs However in the present
study the arylammonium intermediate provides an acidic proton which cleaved the B-C bond
yielding enamine with concurrent release of B(C6F5)3 Subsequent to this hydroamination the
FLP derived from enamine and B(C6F5)3 deprotonate a second equivalent of the alkyne affording
the isolated iminium alkynylborate salts (Scheme 47)
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts
Analogous stoichiometric combination of tert-butylaniline or diisopropylamine and B(C6F5)3
with either one or two equivalents of phenylacetylene resulted exclusively in deprotonation of
the terminal alkyne affording the ammonium alkynylborate salts [tBuPhNH2][PhCequivCB(C6F5)3]
411 and [iPr2NH2][PhCequivCB(C6F5)3] 412 in 99 and 76 yield respectively (Scheme 48) In
these cases the amines are sufficiently bulky to form a FLP with B(C6F5)3 and relatively basic to
preferentially effect deprotonation of the alkyne This reaction pathway has been previously
observed for basic phosphines and B(C6F5)3 with numerous alkynes
141
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates
In separate reactions FLPs comprised of iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 were
combined with the internal alkynes 3-hexyne diphenylacetylene and 1-phenyl-1-propyne At
RT multinuclear NMR data only revealed signals for the FLP and unaltered alkyne Heating
the reactions up to 80 degC did not display signals for hydroamination rather only products of 11-
carboboration were observed
Also interested in extending the unsaturated substrates scope the hydroamination of the olefins
1-hexene cyclohexene styrene αp-dimethylstyrene and 3-(trifluoromethyl)styrene were tested
using the FLPs iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 Thermolysis of the individual samples
up to 100 degC only revealed signals for the starting materials
4213 Reactivity of the iminium alkynylborate products with nucleophiles
An attractive feature of the iminium cation is the unsaturated N=C fragment since it could be
reacted with nucleophiles to give amines and this transformation could potentially be extended to
generate enantioselective variants of the amines Introducing simple fluoride sources such as
[NBu4][Si(Ph)3F2] NBu4F and CsF to compounds 42 and 46 resulted in deprotonation of the
methyl group losing HF and generating the corresponding enamine Nonetheless addition of the
H+ source [(Et2O)2H][B(C6F5)4]287 regenerated the iminium cation (Scheme 49)
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4]
142
Furthermore addition of the organolithium reagents methyl lithium and ethyl lithium at -30 degC
gave a 11 mixture of the alkylation and deprotonation products as evidenced by 1H NMR
spectroscopy while phenyl lithium did not result in any reactivity (Scheme 410 left)
Combinations of stoichiometric hydride sources [tBu3PH][HB(C6F5)3] NaBHEt3 and LiAlH4
only gave saturation of the N=C bond with the lithium reducing agent (Scheme 410 right)
Overall while hydride delivery to the N=C bond was successfully achieved inefficient delivery
of the presented alkyl and aryl nucleophiles shifted focus towards other types of reactivities
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right)
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3
The equimolar reaction of the tertiary amine dibenzylaniline B(C6F5)3 and phenylacetylene was
investigated with the aim of isolating a zwitterionic intermediate analogous to the compound
proposed en route to hydroamination in Scheme 47 In this case however the nucleophilic
centre for this reaction proved to be the para-carbon of the N-bound phenyl ring undergoing
hydroarylation of phenylacetylene to generate the zwitterionic species
(PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 413 in 96 yield (Scheme 411) Single crystal X-ray
diffraction confirmed the structure of 413 and it is shown in Figure 45 (a)
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3
143
Examining the secondary amine N-isopropylanthracen-9-amine in similar reactivity also gave the
hydroarylation of phenylacetylene and this was demonstrated at the C10 position of the
anthracene ring forming iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 414 in 95 yield In this unique
case however a N=C double bond is generated between nitrogen and the anthracene ring as well
as saturation of the C10 centre giving the tetrahedral geometry observed in the solid state
structure of 414 shown in Figure 45 (b) Generally aromatic substitution reactions in the
presence of Lewis acids have been used for the synthesis of numerous aromatic molecules340
Particularly relevant to this thesis the para-carbon of N-bound phenyl rings has been proposed
as the Lewis basic centre to heterolytically split H2 and generate a sp3-hybridized carbon centre
in the arene hydrogenation reactions presented in Chapter 2
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg
Stability of the B-C bond towards acidic conditions was tested In this regard combinations of
413 with the protic salts [(Et2O)2H][B(C6F5)4] or [Ph2NH2][B(C6F5)4] were found to readily
cleave the B-C bond liberating B(C6F5)3 and generating the diphenylethylene-ammonium
derivative as evidenced by the geminal protons at 508 and 504 ppm in the 1H NMR spectrum
(Scheme 412)
(a) (b)
144
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes
With the exception of catalytic hydrogenations the majority of FLPs reported to date react with
small molecules in a stoichiometric fashion Thus seeking to expand the application of FLPs in
catalysis beyond hydrogenations attention was turned to the development of catalytic
hydroamination reactions This motivation was inspired by the hydroaminationdeprotonation
mechanism proposed in Scheme 47 Realizing that deprotonation of alkyne eliminates the
possibility for catalysis the reaction protocol was adjusted in which the alkyne is added slowly
in order to achieve hydroamination and prevent deprotonation by enamine and B(C6F5)3
The slow addition of the terminal alkyne 2-ethynylanisole to a RT solution of Ph2NH and 10
mol of B(C6F5)3 in toluene over 10 h afforded the catalytic hydroamination product 2-
methoxyphenyl substituted enamine Ph2N(2-MeOC6H4)C=CH2 415 in 84 isolated yield (Table
42) The 1H NMR spectrum of 415 displayed two diagnostic singlets at 501 and 490 ppm
characteristic of the inequivalent geminal hydrogen atoms The corresponding carbon centre
gives rise to a 13C1H NMR signal at 108 ppm Further NMR studies of the compound were
consistent with formation of the Markovnikov isomer in which the nitrogen is added to the
substituted carbon of the terminal alkyne
The analogous treatment of Ph2NH with 2-ethynyltoluene in the presence of 10 mol B(C6F5)3
afforded Ph2N(2-MeC6H4)C=CH2 416 in 69 isolated yield while the alkyne 1-
ethynylnaphthalene yielded Ph2N(C10H7)C=CH2 417 in 62 yield (Table 42) The
corresponding reaction of Ph2NH with phenylacetylene and 2-bromo-phenylacetylene afforded
Ph2N(C6H5)C=CH2 418 and Ph2N(2-BrC6H4)C=CH2 419 in yields of 74 and 52 respectively
(Table 42) Similar to 415 the 1H and 13C1H NMR data for these products were in agreement
with the proposed product formulations
145
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3
This hydroamination strategy also proved effective for substituted diphenylamines For example
(p-FC6H4)2NH in combination with 10 mol B(C6F5)3 reacted with halogenated
phenylacetylenes to afford the species (p-FC6H4)2N(2-BrC6H4)C=CH2 420 and (p-FC6H4)2N(2-
146
FC6H4)C=CH2 421 while the corresponding reactivity with 2-thiophenylacetylene gave (p-
FC6H4)2N(2-SC4H3)C=CH2 422 and iPrPhN(2-SC4H3)C=CH2 423 when reacted with iPrNHPh
(Table 42)
The reaction of Ph2NH with 9-ethynylphenanthrene gave Ph2N(C14H9)C=CH2 424 and (p-
FC6H4)2NH was used to prepare (p-FC6H4)2N(C14H9)C=CH2 425 Similarly reactions of the
appropriate combinations of amine and alkyne using 10 mol B(C6F5)3 afforded (p-FC6H4)2N(3-
FC6H4)C=CH2 426 Ph2N(35-F2C6H3)C=CH2 427 and Ph2N(3-CF3C6H4)C=CH2 428 although
in these cases cooling to -30 degC was necessary to maximize yields obtained between 68 - 77
(Table 42) This impact of temperature was most dramatically demonstrated in the case of 426
where performing the reaction at 25 degC gave the product in 19 yield while at -30 degC the yield
was significantly enhanced to 74
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions
The success of these hydroamination reactions strongly depends on the electronic and steric
nature of the amineborane FLP combination thereby preventing 11-carboboration and
deprotonation of the alkyne Interaction of the borane with the terminal alkyne prompts amine
addition to generate a zwitterionic intermediate In the present case the acidic proton of the
anilinium centre migrates to the carbon adjacent to boron cleaving the B-C bond and forming the
enamine product (Scheme 413) The released B(C6F5)3 is then available to participate in further
hydroamination catalysis It is noteworthy that the postulated zwitterion accounts for the
Markovnikov addition of amines to alkynes and thus the nature of the observed enamine
products341
As stated earlier catalytic formation of enamine requires the slow addition of alkyne over 10 h
This is a result of deprotonation of the alkyne by the FLP derived from enamine and borane
consequently generating iminium alkynylborate salts analogous to 42 - 410 The observed
catalytic hydroaminations imply that amine addition to alkyne is faster than enamine
deprotonation of alkyne
147
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes
The catalytic generation of these enamines together with previously established FLP
hydrogenation of enamines93 prompted interest in a one-pot catalytic
hydroaminationhydrogenation protocol
Following the hydroamination procedure described above reaction mixtures generating the two
enamines 421 and 427 were exposed to H2 (4 atm) and heated at 80 degC for 14 h Pleasingly the
B(C6F5)3 catalyst successfully completed hydrogenation of the C=C double bond giving the
amines (p-FC6H4)2N(2-FC6H4)C(H)CH3 429 and Ph2N(35-F2C6H3)C(H)CH3 430 in 77 and
64 overall isolated yields respectively (Scheme 414) Monitoring the hydrogenation portion
of the reactions by 1H NMR spectroscopy revealed in both cases demise of the signals
attributable to the geminal protons of the enamines with simultaneous appearance of a quartet
attributable to the methine proton and a doublet assignable to the methyl group of the respective
amine In an alternative approach to the hydrogenation catalysis subsequent to hydroamination
5 mol of the known hydrogenation catalyst Mes2PH(C6F4)BH(C6F5)294 was added to the
reaction mixture pressurized with H2 (4 atm) and heated to 80 degC In both cases complete
hydrogenation was achieved after 3 h
148
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430
Experimental evidence demonstrated the catalytic hydroaminations are restricted to aryl
acetylenes Examples of other terminal alkynes that were examined include
trimethylsilylacetylene which resulted in 11-carboboration while the acetylene carboxylates
methyl propiolate ethyl propiolate 2-naphthyl propiolate and tert-butyl propiolate did not react
due to formation of a B-O adduct Extending the chemistry to hydrothiolation using thiophenol
was not successful
424 Intramolecular hydroamination reactions using FLPs
4241 Stoichiometric hydroamination
The potential of the above hydroamination reactions to access N-heterocycles was also probed
To this end the alkynyl-substituted aniline C6H5NH(CH2)3CequivCH was prepared and exposed to
an equivalent of B(C6F5)3 in toluene 11B NMR spectroscopy indicated the formation of a B-N
adduct verified by the resonance at -25 ppm although heating the reaction for 2 h at 50 degC
yielded the cyclized zwitterion C6H5N(CH2)3CCH2B(C6F5)3 431 isolated as a white solid in 94
yield (Scheme 415) The 1H NMR spectrum was consistent with consumption of the NH proton
revealing a diagnostic broad quartet at 333 ppm with geminal B-H coupling of 54 Hz indicative
of the B(C6F5)3 bound methylene group In addition a diagnostic sharp singlet at -134 ppm in
149
the 11B NMR spectrum and the N=C iminium 13C1H resonance at 192 ppm were consistent
with the formulation of 431
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432
The analogous 6-membered ring was prepared from the precursor C6H5NH(CH2)4CequivCH and an
equivalent of B(C6F5)3 giving the zwitterion C6H5N(CH2)4CCH2B(C6F5)3 432 in 99 yield The
formulation of 432 was affirmed by NMR spectroscopy in addition to elemental analysis and X-
ray crystallography (Figure 46)
Figure 46 ndash POV-Ray depiction of 432
Similarly substituted isoindoline species are accessible from the reaction of the precursor
C6H5NHCH2(C6H4)CequivCH with B(C6F5)3 in toluene Stoichiometric combination of the two
reagents resulted in a white precipitate believed to be the intramolecular hydroamination product
after 10 min at RT However this compound was sparingly soluble in toluene bromobenzene
and CD2Cl2 not allowing its comprehensive characterization by NMR spectroscopy As such H2
(4 atm) was added to the reaction and heated at 80 degC for 16 h in an effort to synthesize the H2
activated salt which was presumed to be more soluble than the zwitterion The 1H NMR
150
spectrum of this reaction displayed a quartet at 556 ppm and a triplet at 289 ppm with a four-
bond coupling constant of 26 Hz 13C1H NMR data showed a resonance at 182 ppm
attributable to a N=C bond Collectively these data are consistent with the successive
hydroamination and hydrogenation product [2-MeC8H6N(Ph)][HB(C6F5)3] 433 isolated in 54
yield (Scheme 416)
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433
While species 433 is isolated as an insoluble solid from pentane in CD2Cl2 the [HB(C6F5)3]-
anion appears to reversibly deliver hydride to the N=C carbon centre generating isoindoline and
B(C6F5)3 in about 25 This was evidenced by 1H NMR spectroscopy revealing a diagnostic
quartet at 518 ppm two diastereotopic doublets at 472 and 455 ppm and an upfield doublet at
151 ppm data that is collectively assignable to the isoindoline species This was further
supported by 11B and 19F NMR spectroscopy which provided evidence of free B(C6F5)3 Presence
of this equilibrium is consistent with a previous report on reversible hydride abstraction and
redelivery from carbon centres alpha to nitrogen262
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines
This hydroaminationhydrogenation protocol was further adapted for catalytic cyclization
reactions In this fashion the alkynyl substituted aniline C6H5NH(CH2)3CequivCH was treated with
10 mol B(C6F5)3 at 80 degC under H2 (4 atm) for 16 h This gave the desired product 2-methyl-1-
phenyl pyrrolidine 434 in 68 isolated yield (Table 43 entry 1) In a similar fashion the
catalytic hydroaminationhydrogenation of C6H5NH(CH2)4CequivCH gave 2-methyl-1-
phenylpiperidine 435 in 66 yield (Table 43 entry 2) The following protocol was also
applicable to p-fluoro and p-methoxy substituted substrates giving the respective cyclized
products 436 and 437 in 72 and 52 yield respectively (Table 43 entries 3 and 4) Finally
151
similar reactivity with C6H5NHCH2(C6H4)CequivCH gave 1-methyl-2-phenylisoindoline 438 in 70
yield (Scheme 417)
The yields obtained for compounds 436 and 437 strongly reflect the balance of Broslashnsted acidity
required by the amine proton to effect hydroamination In this case the p-fluoro substituent
proved more effective in hydroamination than p-methoxy
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines
Entry R n Isolated yield
1 H 0 68 434
2 H 1 66 435
3 F 1 72 436
4 CH3O 1 52 437
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH
425 Reaction of B(C6F5)3 with ethynylphosphines
The stoichiometric reaction of B(C6F5)3 with the ethynylphosphine tBu2PCequivCH has previously
been shown to give the deprotonation product tBu2P(H)CequivCB(C6F5)3342 Conversely analogous
treatment of Mes2PCequivCH required addition of tBu3P to effect deprotonation of the ethynyl group
due to diminished Lewis basicity of the phosphine Moreover the Erker group reported the
152
reaction of Ph2PCequivCH with B(C6F5)3 to generate a dimeric product formed by a sequential series
of 12-PB additions to the ethynyl unit343
While interested in hydroamination of ethynylphosphines the FLP iPrNHPhB(C6F5)3 was added
to two equivalents of Mes2PCequivCH giving the pale yellow solid 439 in 88 yield (Scheme 418)
The 1H NMR spectrum did not indicate incorporation of aniline into the product rather two
inequivalent vinylic protons with characteristic P-H and H-H coupling were observed at 771 and
574 ppm (Figure 47)
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons
The 31P NMR spectrum revealed two resonances with chemical shifts at -115 and -143 ppm
while the 11B and 19F NMR spectra were in agreement with formation of an alkynylborate
species (11B δ -211 ppm 19F δ -1329 -1616 and -1663 ppm) These data together with
elemental analysis confirm the formulation of the zwitterionic species trans-
Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 439 An X-ray crystallographic study confirmed the
1H
1H31P
153
molecular structure of 439 and it is shown in Figure 48 (a) In the absence of aniline the
reaction leads to the previously reported 11-carboboration product344-345
On another account the same reaction was obtained with 2 equivalents of tBu2PCequivCH and
B(C6F5)3 to give cis and trans isomers of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 440 The cis
isomer was crystallized and characterized by X-ray diffraction studies (Figure 48 b) In this
case the phosphorus centre was basic enough to effect deprotonation thus the reaction proceeded
in the absence of iPrNHPh Monitoring the reaction by 31P NMR spectroscopy the spectrum
indicated the simultaneous presence of tBu2PCequivCH and the deprotonation zwitterion
tBu2P(H)CequivCB(C6F5)3 giving insight to a plausible mechanism en route to the formation of
compounds 439 and 440
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b)
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines
The reaction is proposed to proceed through the mechanism highlighted in Scheme 419 wherein
the mixture of B(C6F5)3 and R2PCequivCH initially effect deprotonation of the ethynyl group
formulating the zwitterion R2P(H)CequivCB(C6F5)3 Under equilibrium conditions a second
equivalent of the ethynylphosphine is protonated consequently prompting nucleophilic addition
of the [R2PCequivCB(C6F5)3]- anion to the terminal carbon followed by proton transfer to generate
the isolated zwitterionic products In the case of Mes2PCequivCH the deprotonation step required a
stronger base therefore iPrNHPh was added to effect reactivity
(a) (b)
154
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs
An earlier report showed the three component reaction of p-tolyl2PH B(C6F5)3 and
phenylacetylene gave the 12-addition phosphonium borate zwitterion p-
tolyl2PH(Ph)C=C(H)B(C6F5)3128 Realizing the acidic hydrogen on the phosphorus atom a
sample of this compound was treated by UV radiation or heated to prompt hydrophosphination
of phenylacetylene in a mechanism analogous to that presented for the hydroamination reaction
In this regard however the zwitterion proved robust and further reactivity was not observed
Similar results were obtained when using Mes2PH or exchanging the borane for the slightly less
Lewis acidic B(p-C6F4H)3
Turning attention towards the borane HB(C6F5)2 the hydrophosphination reaction was attempted
following an alternative approach In this regard Ph2PH was added to a stoichiometric
combination of HB(C6F5)2 and Bpin-substituted 1-hexyne (Scheme 420 a) After 16 h at RT
the acetylenic unit of Bpin was reduced to a C-C single bond as illustrated by a characteristic
multiplet at 353 ppm and a very broad singlet at 148 ppm in the 1H NMR spectrum The
product Bu(H)Ph2PC-C(H)B(C6F5)2Bpin 441 resulting from the sequential hydroboration and
hydrophosphination reactions was isolated in 82 yield NMR spectroscopy data indeed showed
incorporation of all reactants into the isolated product
155
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH
Investigating similar reactivity of 2-methyl-1-buten-3-yne substituted Bpin with HB(C6F5)2 and
Ph2PH a colourless solid was obtained in 73 yield The 1H NMR data unambiguously showed
saturation of the acetylenic fragment however the spectrum consisted of an olefinic proton at
646 ppm in addition to a methylene group at 307 ppm Further spectroscopic data revealed the
product as Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin 442 resulting from nucleophilic addition of
the phosphine at the terminal double bond (Scheme 420) Single crystals suitable for X-Ray
diffraction were obtained and the structure is shown in Figure 49 (b)
Figure 49 ndash POV-Ray depictions of 442
156
427 Proposed mechanism for the hydroborationhydrophosphination reactions
The mechanism of this reaction is envisaged to initiate following the well-documented
hydroboration of the acetylenic group generating the corresponding alkenyl-bisborane species
(Scheme 421)346 At this point the phosphine coordinates to B(C6F5)2 rendering its proton more
Broslashnsted acidic and prompting protonation of the C=C double bond This is followed by
nucleophilic attack of the phosphine at the C2 position of alkynyl-substituted Bpin (441) or C4
position of the enyne-substituted Bpin (442) The 14-addition reaction to conjugated enynes has
been previously investigated using the ethylene-linked PB FLP to give eight membered cyclic
allenes147
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments
Since evidence for the P-B intermediate is not observed by 11B or 31P NMR spectroscopy an
alternative mechanism could be speculated In this case the nucleophilic phosphine could add to
the vinyl bisborane followed by proton transfer However this later mechanism is not highly
supported as the more Lewis basic secondary phosphines tBu2PH and iPr2PH only gave the P-B
adduct with HB(C6F5)2 consistent with retro-hydroboration after coordination of the phosphine
to the vinyl bisborane This adduct remained intact even at elevated temperatures of 80 degC
Similar N-B adducts were observed when the analogous reactivity was explored with the alkyl
and aryl amines iPr2NH iPrNHPh and Ph2NH
157
43 Conclusions
This chapter provides an account on the discovery of consecutive hydroamination and
deprotonation reactions of various terminal alkynes by anilineB(C6F5)3 FLPs to form a series of
iminium alkynylborate complexes The reaction procedure was modified to eliminate the
deprotonation step in order to achieve B(C6F5)3 catalyzed Markovnikov hydroamination of
alkynes yielding enamine products Subsequent to hydroamination catalysis the borane catalyst
was also used for catalytic hydrogenation of the enamine providing a one-pot avenue to the
corresponding amine derivatives Related systems were probed to accomplish the stoichiometric
and catalytic intramolecular hydroamination of alkynyl-substituted anilines generating cyclic
amines While this hydroamination protocol was not extendable to effect hydrophosphination a
new stoichiometric approach using HB(C6F5)2 and Ph2PH was found to result in the sequential
hydroboration and hydrophosphination reactions of an alkynyl- and enynyl-substituted
pinacolborane generating novel PB FLPs
44 Experimental Section
441 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane dichloromethane and toluene (Sigma Aldrich) were dried employing a Grubbs-
type column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring)
in the glovebox Dichloromethane-d2 bromobenzene-d5 and bromobenzene-H5 were purchased
from Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring
molecular sieves prior to use Hexane and ethyl acetate were purchased from Caledon
Laboratories Silica gel was purchased from Silicycle Molecular sieves (4 Aring) were purchased
from Sigma Aldrich and dried at 120 ordmC under vacuum for 24 h prior to use B(C6F5)3 was
purchased from Boulder Scientific and sublimed at 80 degC under high vacuum before use H2
(grade 50) was purchased from Linde and dried through a Nanochem Weldassure purifier
column prior to use
Substituted amines alkynes and phosphines were purchased from Sigma Aldrich Alfa Aesar
Apollo Scientific Strem Chemicals Inc and TCI The oils were distilled over CaH2 and solids
were sublimed under high vacuum prior to use The following reagents were prepared following
158
literature procedures 1-ethynylnaphthalene347 (p-C6H4F)2NH (p-CH3OC6H4)PhNH tBuNHPh
and N-isopropylanthracen-9-amine266 N-(2-ethynylbenzyl)aniline N-(pent-4-ynyl)aniline N-
(hex-5-ynyl)aniline 4-fluoro-N-(hex-5-yn-1-yl)aniline and 4-methoxy-N-(hex-5-yn-1-
yl)aniline348 N-(2-ethynylbenzyl)aniline349 tBu2PCequivCH and Mes2PCequivCH342
CH3(CH2)3CequivCBpin and CH2=C(CH3)CequivCBpin350
Compounds 439 - 442 were prepared by the author during a four month research opportunity in
the group of Professor Gerhard Erker at Universitaumlt Muumlnster Germany Molecular structures and
elemental analyses for 439 and 440 were obtained at the University of Toronto Molecular
structure for 442 was obtained at Universitaumlt Muumlnster and elemental analyses for 441 and 442
were obtained at the University of Toronto
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm for
ipso carbon) and CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) or externally (11B (Et2O)BF3 19F
CFCl3) Chemical Shifts (δ) are reported in ppm and the absolute values of the coupling
constants (J) are in Hz NMR assignments are supported by additional 2D and DEPT-135
experiments
High resolution mass spectra (HRMS) were obtained using an ABSciex QStar Mass
Spectrometer with an ESI source MSMS and accurate mass capabilities Elemental analyses (C
H N) were performed in-house employing a Perkin Elmer 2400 Series II CHNS Analyzer
442 Synthesis of Compounds
4421 Procedures for stoichiometric intermolecular hydroamination reactions
Compounds 41 - 45 were prepared in a similar fashion thus only one preparation is detailed In
the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial phenylacetylene (151
mg 148 mmol) was added drop wise over 1 min In the case where pentane was used as the
solvent the reaction was worked up as follows the solvent was decanted and the product was
washed with pentane (3 times 5 mL) to yield the product as a solid In the case where toluene or
159
dichloromethane was used as the as solvent the reaction was worked up as follows the solvent
was removed under reduced pressure and the crude product was washed with pentane to yield the
product as a solid
Synthesis of [Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] (41) Diphenylamine (0125 g 0740
mmol) pentane (20 mL) reaction time 2 h yellow solid (588 mg 0666 mmol 90) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC
1H NMR (400 MHz CD2Cl2) δ 768 (m 3H H4 H5) 761 (m 1H p-Ph)
745 (m 5H o m p-Ph) 739 (m 4H H3 m-Ph) 728 (dm 3JH-H = 75
Hz 2H H7) 717 (tm 3JH-H = 75 Hz 2H H8) 711 (tm 3JH-H = 75 Hz
1H H9) 710 (dm 3JH-H = 77 Hz 2H o-Ph) 289 (s 3H Me) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F
p-C6F5) -1673 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s
equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1901 (C1) 1352 (p-Ph) 1320 (C5) 1315 (C4)
1312 (p-Ph) 1310 (C7) 1307 (m-Ph) 1298 (Ph) 1293 (Ph) 1277 (C8) 1257 (C9) 1254 (o-
Ph) 1241 (C3) 283 (Me) (C2 C6 ipso-Ph and all carbons for CequivCB(C6F5)3 were not
observed) Elemental analysis was not successful after numerous attempts
Synthesis of E-[iPrPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (42) N-Isopropylaniline (100 mg
0740 mmol) pentane (10 mL) reaction time 1 h pale yellow solid (566 mg 0651 mmol 88)
EZ ratio 71
42 1H NMR (400 MHz CD2Cl2) δ 773 (tm 3JH-H = 77 Hz 1H H5)
772 (m 6H H4 H9 H10) 746 (dm 3JH-H = 77 Hz 2H H3) 728 (dm 3JH-H = 76 Hz 2H H12) 720 (m 2H H8) 716 (t 3JH-H = 76 Hz 2H
H13) 713 (t 3JH-H = 76 Hz 1H H14) 491 (m 3JH-H = 66 Hz 1H H6)
244 (s 3H Me) 126 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1637 (t 3JF-F = 20 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1913
(C1) 1482 (dm 1JC-F = 236 Hz CF) 1381 (dm 1JC-F = 243 Hz CF) 1365 (dm 1JC-F = 245 Hz
CF) 1346 (C2) 1339 (C5) 1319 (C10) 1318 (C7) 1311 (C12) 1310 (C4) 1303 (C9) 1278
(C13) 1274 (C11) 1258 (C14) 1253 (C3 C8) 937 (C15) 619 (C6) 288 (Me) 208 (iPr)
160
(CequivCB(C6F5)3 and ipso-C6F5 were not observed) Anal calcd () for C43H25BF15N C 6066 H
296 N 165 Found 6037 H 317 N 173
Synthesis of E-[CyPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (43) N-Cyclohexylaniline (135 mg
0740 mmol) pentane (10 mL) reaction time 1 h off-white solid (599 mg 0674 mmol 91)
EZ ratio 71
43 1H NMR (400 MHz CD2Cl2) δ 769 (tt 3JH-H = 74 Hz 4JH-H = 24
Hz 1H H5) 762 (m 5H H4 H12 H13) 737 (dm 3JH-H = 74 Hz 2H H3)
720 (dm 3JH-H = 77 Hz 2H H15) 711 (m 4H H11 H16) 703 (tm 3JH-H
= 77 Hz 1H H17) 439 (tt 3JH-H = 119 Hz 3JH-H = 35 Hz 1H H6) 235
(s 3H Me) 184 (dm JH-H = 117 Hz 1H H7) 170 (dm 2JH-H = 145 Hz
2H H8) 145 (dm 2JH-H = 132 Hz 2H H9) 133 (m 1H H7) 104 (pseudo qt JH-H = 138 Hz 3JH-H = 37 Hz 2H H8) 080 (pseudo qt 2JH-H = 132 Hz 3JH-H = 37 Hz 2H H9) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F p-C6F5) -1673 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (101 MHz
CD2Cl2) δ 1916 (C1) 1341 (C5) 1323 (C13) 1315 (C15) 1313 (C4) 1307 (C12) 1282 (C16)
1262 (C17) 1257 (C3) 1254 (C11) 699 (C6) 320 (C7) 291 (Me) 249 (C8) 244 (C9) (C2
C10 C14 and all carbons for CequivCB(C6F5)3 were not observed) Anal calcd () for C46H29BF15N
C 6197 H 328 N 157 Found 6158 H 354 N 153
Synthesis of E-[(PhCH2)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (44) N-Benzylaniline (135 mg
0740 mmol) dichloromethane (10 mL) reaction time 2 h pale yellow solid (544 mg 0607
mmol 82) EZ ratio 41
44 1H NMR (600 MHz CD2Cl2) δ 782 (t 3JH-H = 73 Hz 1H H5) 777
(t 3JH-H = 73 Hz 2H H4) 764 (d 3JH-H = 73 Hz 2H H3) 760 (t 3JH-H =
76 Hz 1H H14) 753 (t 3JH-H = 76 Hz 2H H13) 738 (m 1H H10) 728
(m 4H H9 H16) 716 (t 3JH-H = 73 Hz 2H H17) 710 (t 3JH-H = 73 Hz
1H H18) 699 (d 3JH-H = 76 Hz 2H H12) 679 (d 3JH-H = 76 Hz 2H
H8) 526 (s 2H H6) 259 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
207 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1912 (C1) 1386 (C7) 1342 (C5) 1339
(C2) 1317 (C11 C14) 1311 (C9) 1309 (C13 C15) 1304 (C4 C10) 1296 (C8) 1294 (C16) 1278
B(C6F5)3
N1
2
3
45
7
8
9
10
14
1516
17
18
6
11
12
13
B(C6F5)3
N1
2
3
45
7
8 9
10
11 12
13
14
1617
1815
6
19
161
(C17) 1263 (C3) 1258 (C18) 1241 (C8) 938 (C19) 645 (C6) 286 (Me) (CequivCB(C6F5)3 and all
carbons of B(C6F5)3 were not observed) Anal calcd () for C47H25BF15N C 6276 H 280 N
156 Found 6259 H 296 N 171
Synthesis of [(p-C6H4OMe)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (45) (p-CH3OC6H4)PhNH
(147 mg 0740 mmol) pentane (15 mL) room temperature reaction time 3 h yellow solid (493
mg 0540 mmol 73) Anal calcd () for C47H25BF15NO C 6166 H 275 N 153 Found C
6106 H 262 N 142 EZ ratio 11
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 748 (m 1H H5) 735
(m 2H H3) 730 (m 2H H4) 726 (m 2H H8) 717 (m 2H H15) 707
(tm 3JH-H = 72 Hz 2H H16) 702 (m 1H H17) 696 (m 1H H9) 688
(dm 3JH-H = 87 Hz 2H H11) 670 (dm 3JH-H = 87 Hz 2H H12) 365 (s
3H OMe) 273 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1327 (m
2F o-C6F5) -1637 (t 3JF-F = 21 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (125 MHz CD2Cl2) δ 1884
(C1) 1613 (C13) 1481 (dm 1JC-F = 241 Hz CF) 1421 (C6) 1381 (dm 1JC-F = 244 Hz CF)
1364 1 (dm 1JC-F = 246 Hz CF) 1356 (C10) 1348 (C5) 1325 (C2) 1313 (C7) 1310 (C15)
1305(C8) 1297 (C4) 1292 (C3) 1278 (C16) 1274 (C14) 1269 (C11) 1257 (C17) 1255 (C9)
1155 (C12) 937 (C18) 557 (OMe) 283 (Me)
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 750 (m 1H H5) 735
(m 2H H4) 730 (m 2H H3) 726 (m 2H H8) 717 (m 2H H12) 702 (m
2H H11) 696 (m 1H H9) 378 (s 3H OMe) 279 (s 3H Me) 13C1H
NMR (125 MHz CD2Cl2) δ 1892 (C1) 1620 (C13) 1432 (C6) 1348 (C5)
1345 (C10) 1325 (C2) 1319 (C7) 1310 (C3) 1297 (C4) 1257 (C11) 1255
(C9) 1242 (C8) 1162 (C12) 557 (OMe) 283 (Me) 19F and 11B NMR are the same as above
Compounds 46 - 410 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and either diphenylamine (125 mg 0740 mmol) or N-isopropylaniline
(100 mg 0740 mmol) To the vial the respective alkyne was added over 1 min In the case
where pentane was used as the solvent the reaction was worked up as follows the solvent was
decanted and the product was washed with pentane (3 times 5 mL) to yield the product as a solid In
162
the case where toluene or dichloromethane was used as the as solvent the reaction was worked
up as follows the solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as a solid
Synthesis of [Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] (46) 1-Hexyne (122 mg 148 mmol)
pentane (20 mL) -30 degC to room temperature reaction time 2 h yellow solid (350 mg 414
mmol 56) The reaction also yielded alkenylboranes resulting from 11-carboboration which
were separated from the reaction mixture through the pentane washes during work-up
1H NMR (400 MHz CD2Cl2) δ 768 (m 6H Ph) 738 (m 4H Ph) 282
(m 2H H2) 262 (s 3H Me) 211 (t 3JH-H = 67 Hz 2H H7) 180 (quint
of t 3JH-H = 77 Hz 4JH-H = 28 Hz 2H H3) 141 (m 6H H4 H8 H9) 092
(t 3JH-H = 73 Hz 3H H5) 087 (t 3JH-H = 72 Hz 3H H10) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1643 (t 3JF-F = 21 Hz 1F
p-C6F5) -1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211
(s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1992 (C1) 1482 (dm 1JC-F = 237 Hz CF)
1411 (ipso-Ph) 1407 (ipso-Ph) 1382 (dm 1JC-F = 242 Hz CF) 1363 (dm 1JC-F = 246 Hz
CF) 1319 (Ph) 1315 (Ph) 1314 (Ph) 1236 (Ph) 1234 (Ph) 932 (C6) 389 (C2) 320 (C8)
295 (C3) 248 (Me) 227 (C4) 219 (C9) 199 (C7) 135 (C10) 130 (C5) (CequivCB(C6F5)3 and
ipso-C6F5 were not observed) Anal calcd () for C42H31BF15N C 5966 H 370 N 166
Found 5885 H 366 N 154
Synthesis of [Ph2N=C(CH3)C14H9][C14H9CequivCB(C6F5)3] (47) 9-Ethynylphenanthrene (299
mg 148 mmol) pentane (15 mL) room temperature reaction time 3 h pale yellow solid (602
mg 0555 mmol 75) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 859 (dm 3JH-H = 82 Hz 1H ArH) 853 (dm 3JH-H = 82 Hz
1H ArH) 849 (m 2H ArH) 845 (dm 3JH-H = 82 Hz 1H ArH) 776 (dm 3JH-H = 76 Hz 1H ArH) 773 (tm 3JH-H = 76 Hz 1H ArH) 767 (s 1H borateArH) 765 (tm 3JH-H = 82 Hz 1H ArH) 763 (s 1H amineArH) 760 (m 3JH-H = 82 Hz 1H ArH) 757 (m 3H m p-Ph) 755 (m
2H o-Ph) 753 (dm 3JH-H = 76 Hz 1H ArH) 748 (m 2H ArH) 744 (tm 3JH-H = 76 Hz 1H ArH) 737 (tm 3JH-H = 76 Hz 1H ArH) 732 (m 2H ArH) 703 (tt 3JH-H = 70 Hz 4JH-H = 10
Hz 1H ArH) 696 (tm 3JH-H = 70 Hz 2H m-Ph) 691 (dm 3JH-H = 70 Hz 2H o-Ph) 284
163
(Me) 19F NMR (377 MHz CD2Cl2) δ -1324 (m 2F o-C6F5) -1636 (t 3JF-F = 21 Hz 1F p-
C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -206 (s equivCB) 13C1H NMR
(125 MHz CD2Cl2) δ 1943 (C=N) 1500 (dm 1JC-F = 242 CF) 1444 (ipso-Ph) 1430 (ipso-
Ph) 1400 (dm 1JC-F = 245 CF) 1386 (dm 1JC-F = 250 CF) 1342 (ArC) 1342 (m-Ph) 1337
(p-Ph) 1336 (ArC) 1334 (o-Ph) 1330 (p-Ph) 1326 (ArC) 1325 (ArC) 1321 (ArC) 1320 (m-
Ph) 1319 (ArC) 1317 (ArC) 1315 (ArC) 1313 (ArC) 1310 (ArC) 1307 (ArC) 1306 (ArC)
1303 (ArC) 1301 (ArC) 1298 (ArC) 1297 (ArC) 1286 (ArC) 1284 (ArC) 1284 (ArC) 1280
(ArC) 1272 (ArC) 1261 (o-Ph) 1250 (o-Ph) 1259 (ArC) 1259 (ArC) 1248 (ArC) 1242 (ArC)
1241 (ArC) 937 (CequivCB) 3096 (Me) Anal calcd () for C62H31BF15N C 6859 H 288 N
129 Found C 6812 H 306 N 134
Synthesis of [iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] (48) Cyclopropylacetylene (125 μL
148 mmol) dichloromethane (10 mL) and pentane (5 mL) room temperature reaction time 2 h
pale yellow solid (507 mg 651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 17
48 1H NMR (400 MHz CD2Cl2) δ 765 (m 3H m p-Ph) 717 (m 2H
o-Ph) 483 (m 3JH-H = 66 Hz 1H iPr) 222 (s 3H CH3) 158 (m 1H
H1) 146 (m 4H H2) 131 (d 3JH-H = 66 Hz 6H iPr) 112 (tt 3JH-H = 81
Hz 3JH-H = 51 Hz 1H H4) 057 - 050 (m 4H H5) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1642 (t 3JF-F = 20 Hz 1F p-C6F5) -
1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211(s equivCB)
13C1H NMR (101 MHz CD2Cl2) δ 1937 (N=C) 1486 (dm 1JC-F = 236 Hz CF) 1383 (dm 1JC-F = 243 Hz CF) 1368 (dm 1JC-F = 245 Hz CF) 1356 (ipso-Ph) 1320 (p-Ph) 1313 (m-
Ph) 1266 (o-Ph) 1258 (ipso-C6F5) 958 (C3) 599 (iPr) 218 (C1) 208 (iPr) 161 (CH3) 153
(C2) 84 (C5) 149 (C4) (CequivCB(C6F5)3 was not observed) Anal calcd () for C37H25BF15N C
5702 H 323 N 180 Found 5667 H 330 N 179
Synthesis of E-[iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] (49) 2-Ethynylthiophene (160
mg 148 mmol) dichloromethane (4 mL) and pentane (10 mL) room temperature reaction time
1 h pale pink solid (498 mg 0577 mmol 78) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 71
164
49 1H NMR (400 MHz C6D5Br) δ 738 (d 3JH-H = 45 Hz 1H H3)
733 (t 3JH-H = 72 Hz 1H H10) 731 (d 3JH-H = 45 Hz 1H H5) 726 (t 3JH-H = 72 Hz 2H H9) 693 (d 3JH-H = 38 Hz 1H H12) 674 (d 3JH-H =
53 Hz 1H H14) 667 (t 3JH-H = 45 Hz 1H H4) 664 (dd 3JH-H = 53
Hz 3JH-H = 38 Hz 1H H13) 660 (d 3JH-H = 72 Hz 2H H8) 436 (m 3JH-H = 66 Hz 1H H6) 256 (s 3H Me) 081 (d 3JH-H = 66 Hz 6H
iPr) 19F NMR (377 MHz C6D5Br) δ -1312 (m 2F o-C6F5) -1619 (t 3JF-F = 21 Hz 1F p-
C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -203 (s equivCB) 13C1H NMR
(101 MHz C6D5Br) δ 1724 (C1) 1486 (dm 1JC-F = 240 Hz CF) 1446 (C5) 1438 (C3) 1384
(dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 267 Hz CF) 1346 (C7) 1330 (C2) 1324 (C10)
1312 (C9) 1290 (C12) 1286 (C4) 1272 (C8) 1269 (C13) 1239 (C14) 593 (C6) 214 (Me)
201 (iPr) (C11 C15 ipso-C6F5 and CequivCB(C6F5)3 were not observed) Anal calcd () for
C39H21BF15NS2 C 5425 H 245 N 162 Found 5415 H 259 N 168
Synthesis of (C6F5)3BCequivC(C6H4)C(Me)=NPh2 (410) 14-Diethynylbenzene (934 mg 0740
mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 2 h orange solid
(508 mg 0629 mmol 85) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 760 (m 3H m p-Ph) 735 (m 4H o m-Ph) 729 (m 5H
C6H4 p-Ph) 706 (dm 3JH-H = 77 Hz 2H o-Ph) 277 (s 3H Me) 19F NMR (377 MHz
CD2Cl2) δ -1329 (m 2F o-C6F5) -1630 (t 3JF-F = 20 Hz 1F p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1877
(C=N) 1482 (dm 1JC-F = 236 Hz CF) 1433 (ipso-Ph) 1425 (ipso-Ph) 1383 (dm 1JC-F = 243
Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1364 (quaternary C for C6H4) 1322 (C6H4) 1317 (p-
Ph) 1314 (m-Ph) 1311 (p-Ph) 1308 (m-Ph) 1302 (C6H4) 1282 (quaternary C for C6H4)
1255 (o-Ph) 1244 (o-Ph) 1228 (ipso-C6F5) 937 (CequivCB(C6F5)3) 276 (Me) (CequivCB(C6F5)3
was not observed) Elemental analysis for this compound did not pass after repeated attempts
Synthesis of [tBu(Ph)NH2][PhCequivCB(C6F5)3] (411) tert-Butylaniline (111 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) pentane (10 mL) reaction time 16 h off-white solid
(560 mg 0733 mmol 99)
165
1H NMR (400 MHz CD2Cl2) δ 751 (tm 3JH-H = 77 Hz 1H H4) 741
(tm 3JH-H = 77 Hz 2H H3) 728 (m 2H H7) 727 (m 2H H6) 725 (m
1H H8) 684 (dm 3JH-H = 77 Hz 2H H2) 677 (br s 2H NH2) 113 (s
9H tBu) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5) -1622
(t 3JF-F = 21 Hz 1F p-C6F5) -1661 (m 2F m-C6F5) 11B NMR (128
MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1479 (dm 1JC-F =
236 Hz CF) 1384 (dm 1JC-F = 241 Hz CF) 1366 (dm 1JC-F = 243 Hz CF) 1319 (C7) 1314
(C4) 1310 (C1) 1307 (C3) 1296 (C6) 1283 (C8) 1258 (C5) 1237 (C2) 941 (C9) 654 (tBu)
262 (tBu) Anal calcd () for C36H21BF15N C 5664 H 277 N 183 Found 5608 H 297 N
174
Synthesis of [iPr2NH2][PhCequivCB(C6F5)3] (412) Diisopropylamine (750 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) toluene (10 mL) reaction time 4 h white solid (405
mg 566 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered solution
of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 727 (tm 3JH-H = 76 Hz 2H m-Ph) 721 (dm 3JH-H = 76 Hz
2H o-Ph) 718 (tm 3JH-H = 76 Hz 1H p-Ph) 505 (m 2H NH2) 332 (m 3JH-H = 64 Hz 2H
iPr) 114 (d 3JH-H = 64 Hz 12H iPr) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5)
-1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
208 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1317 (m-Ph) 1292 (o-Ph) 1276
(p-Ph) 511 (iPr) 197 (iPr) Anal calcd () for C32H21BF15N C 5373 H 296 N 196 Found
5318 H 304 N 194
4422 Procedures for hydroarylation of phenylacetylene
Compounds 413 and 414 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of
B(C6F5)3 (0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial
phenylacetylene (756 mg 0740 mol) was added over 1 min The solvent was then removed
under reduced pressure and the crude product was washed with pentane to yield the product as a
solid
166
Synthesis of (PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 (413) NN-Dibenzylaniline (202 mg
0740 mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 1 h yellow
solid (630 mg 0710 mmol 96) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 753 (t 3JH-H = 76 Hz 2H m-Ph) 746 (t 3JH-H = 73 Hz 4H benzylm-Ph) 741 (s 1H =CH) 734 (d 3JH-H = 76 Hz 2H o-Ph) 715 (d 3JH-H = 74 Hz 4H benzylo-Ph) 700 (m 3H p-Ph benzylp-Ph) 691 (d 3JH-H = 86 Hz 2H C6H4) 680 (d 3JH-H = 86
Hz 2H C6H4) 617 (br s 1H NH) 484 (dm JH-H = 126 Hz 2H CH2Ph) 472 (dm JH-H = 126
Hz 2H CH2Ph) 19F NMR (377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1644 (t 3JF-F = 19
Hz 1F p-C6F5) -1680 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -158 (s equivCB)
13C1H NMR (101 MHz CD2Cl2) partial δ 1521 (=CH) 1387 (ipso-Ph) 1317 (m-Ph) 1316
(benzylipso-Ph) 1302 (benzylo-Ph) 1300 (benzylm-Ph) 1292 (o-Ph) 1291 (C6H4) 1271 (benzylp-
Ph) 1206 (C6H4) 1256 (p-Ph) 647 (CH2Ph) Elemental analysis was not successful after
numerous attempts
Synthesis of iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 (414) N-isopropylanthracen-9-amine (170
mg 0740 mmol) dichloromethane (10 mL) room temperature reaction time 5 h bright yellow
solid (597 mg 0704 mmol 95) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 795 (s 1H C=NH) 785 (m 2H m-Ph) 778 (m 2H o-Ph)
773 (d 3JH-H = 83 Hz 1H C14H9) 762 (d 3JH-H = 83 Hz 1H C14H9) 759 (t 3JH-H = 83 Hz
1H C14H9) 758 (m 1H p-Ph) 689 (t 3JH-H = 83 Hz 1H C14H9) 680 (s 1H =CH) 671 (t 3JH-H = 83 Hz 2H C14H9) 603 (d 3JH-H = 83 Hz 2H C14H9) 544 (s 1H CHC(Ph)=CH) 454
(m 1H iPr) 178 (d 3JH-H = 66 Hz 3H iPr) 126 (d 3JH-H = 66 Hz 3H iPr) 19F NMR (377
MHz CD2Cl2) δ -1322 (m 2F o-C6F5) -1645 (t 3JF-F = 20 Hz 1F p-C6F5) -1681 (m 2F m-
C6F5) 11B NMR (128 MHz CD2Cl2) δ -163 (s equivCB) 13C1H NMR (125 MHz CD2Cl2)
partial δ 1707 (C=CH) 1503 (=CH) 1353 (m-Ph) 1308 (o-Ph) 1290 (C14H9) 1284 (p-Ph)
1276 (C14H9) 1274 (C14H9) 1265 (C14H9) 1255 (C14H9) 1224 (C14H9) 599 (CHC(Ph)=CH)
530 (iPr) 233 (iPr) 228 (iPr) Anal calcd () for C43H23BF15N C 6080 H 273 N 165
Found 6059 H 281 N 197
167
4423 Procedures for catalytic intermolecular hydroamination reactions
Compounds 415 - 425 were prepared in a similar fashion thus only one preparation is detailed
In the glovebox a 4 dram vial equipped with a stir bar was charged with diphenylamine (125
mg 740 μmol) (p-C6H4F)2NH (152 mg 740 μmol) or N-isopropylaniline (100 mg 740 μmol)
and B(C6F5)3 (38 mg 74 μmol) in toluene (4 mL) The respective alkyne (740 μmol) was added
at a rate of 10 molh via microsyringe (oils) or by weighing into a vial (solids) Total reaction
time was 10 h after which the reaction was worked up outside of the glovebox The solvent was
removed under vacuum and the crude mixture was dissolved in ethyl acetate (5 mL) and passed
through a short (4 cm) silica column previously treated with Et2NH The crude reaction mixtures
consisted of the starting materials (amine and alkyne) and the product The product was purified
by column chromatography using hexaneethyl acetate (61) as eluent
Compounds 426 - 428 were prepared with slight modifications to the procedure above The
reaction vial was cooled to -30 degC then placed in a pre-cooled -30 degC brass-well before addition
of the alkyne via microsyringe or by weighing into a vial The reaction vial was kept in the brass-
well and warmed up to RT before cooling down the reaction vial again and adding the
subsequent aliquot of alkyne Each addition of alkyne was made in a pre-cooled brass-well The
reactions were worked up similar to the procedure above
(415) Yellow solid (187 mg 620 μmol 84) 1H NMR (400 MHz
CD2Cl2) δ 744 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H5) 721 -713
(m 5H m-C6H5 H3) 712 - 706 (m 4H o-C6H5) 691 (tt 3JH-H = 72 Hz 4JH-H = 11 Hz 2H p-C6H5) 685 (td 3JH-H = 75 Hz 4JH-H = 18 Hz 1H
H4) 679 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H2) 501 (s 1H =CH2) 490 (s 1H =CH2)
376 (s 3H OCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1577 (C6) 1498 (C=CH2) 1481
(ipso-C6H5) 1312 (C5) 1296 (C3) 1290 (m-C6H5) 1283 (C1) 1248 (o-C6H5) 1227 (p-C6H5)
1205 (C4) 1112 (C2) 1077 (=CH2) 558 (OCH3) HRMS-ESI+ mz [M+H]+ calcd for
C21H20NO 30215449 Found 30215453
168
(416) Off-while solid (146 mg 510 μmol 69) 1H NMR (600 MHz
CD2Cl2) δ 750 -743 (m 1H H5) 724 - 716 (tm 3JH-H = 74 Hz 4H m-
C6H5) 715 - 708 (m 6H o-C6H5 H3 H4) 706 -701 (m 1H H2) 700-
692 (tm 3JH-H = 74 Hz 2H p-C6H5) 484 (s 1H =CH2) 470 (s 1H
=CH2) 252 (s 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1526 (C=CH2) 1476 (ipso-
C6H5) 1390 (C1) 1364 (C6) 1309 (C5 C2) 1291 (m-C6H5) 1281 (C4) 1259 (C3) 1255 (o-
C6H5) 1233 (p-C6H5) 1051 (=CH2) 206 (CH3) HRMS-ESI+ mz [M+H]+ calcd for C21H20N
28615957 Found 28615986
(417) Orange solid (147 mg 460 μmol 62) 1H NMR (400 MHz
CD2Cl2) δ 870 (d 3JH-H = 85 Hz 1H H10) 777 (d 3JH-H = 85 Hz 1H
H7) 771 - 768 (m 2H H2 H4) 752 (tm 3JH-H = 85 Hz 1H H9) 743
(tm 3JH-H = 85 Hz 1H H8) 736 (tm 3JH-H = 85 Hz 1H H3) 722 -
709 (m 8H o m-C6H5) 692 (m 2H p-C6H5) 507 (s 1H =CH2)
494 (s 1H =CH2) 13C1H NMR (101 MHz CD2Cl2) δ 1513 (C=CH2) 1478 (ipso-C6H5)
1371 (C1) 1341 (C6) 1319 (C5) 1292 (m-C6H5) 1288 (C7 C2) 1281 (C4) 1266 (C9) 1260
(C8) 1256 (C10) 1254 (C3) 1253 (o-C6H5) 1229 (p-C6H5) 1067 (=CH2) HRMS-ESI+ mz
[M+H]+ calcd for C24H20N 32215957 Found 32216049
(418) Yellow oil (148 mg 550 μmol 74) 1H NMR (500 MHz
CD2Cl2) δ 757 (dm 3JH-H = 73 Hz 2H H2) 728 - 726 (m 3H H3 H4)
720 (tm 3JH-H = 74 Hz 4H m-C6H5) 709 (dm 3JH-H = 74 Hz 4H o-
C6H5) 695 (tm 3JH-H = 74 Hz 2H p-C6H5) 523 (s 1H =CH2) 486 (s
1H =CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1533 (C=CH2) 1482 (ipso-C6H5) 1394 (C1)
1293 (m-C6H5) 1286 (C3) 1285 (C4) 1276 (C2) 1243 (o-C6H5) 1228 (p-C6H5) 1082
(=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H18N 2721433 Found 2721443
(419) Orange solid (134 mg 390 μmol 52)1H NMR (500 MHz
CD2Cl2) δ 753 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H
H2) 744 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H H5)
723 (td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H3) 720 - 715 (m 8H om-
C6H5) 706 (pseudo td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H4) 697 (tt 3JH-H = 70 Hz 4JH-H =
16 Hz 2H p-C6H5) 493 (d 2JH-H = 04 Hz 1H =CH2) 483 (d 2JH-H = 04 Hz 1H =CH2)
169
13C1H NMR (125 MHz CD2Cl2) δ 1513 (C=CH2) 1473 (ipso-C6H5) 1399 (C1) 1337 (C5)
1327 (C2) 1296 (C4) 1291 (m-C6H5) 1275 (C3) 1256 (o-C6H5) 1235 (p-C6H5) 1224 (C6)
1059 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H17BrN 35005444 Found 35005379
(420) Orange solid (191 mg 500 μmol 67) 1H NMR (500 MHz
CD2Cl2) δ 750 (ddm 3JH-H = 78 Hz 4JH-H = 18 Hz 1H H2) 743
(ddm 3JH-H = 78 Hz 4JH-H = 12 Hz 1H H5) 724 (tdm 3JH-H = 78
Hz 4JH-H = 12 Hz 1H H4) 712 (dm 3JH-H = 80 Hz 4H H8) 707
(dm 3JH-H = 78 Hz 1H H3) 690 (tm 3JH-H = 80 Hz 4H H9) 479 (s
1H =CH2) 471 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1202 (tt 3JF-H = 88 Hz 4JF-H
= 52 Hz p-C6H4F) 13C1H NMR (125 MHz CD2Cl2) δ 1593 (d 1JC-F = 242 Hz C10) 1518
(C=CH2) 1433 (d 4JCF = 29 Hz C7) 1395 (C1) 1337 (C5) 1328 (C2) 1298 (C3) 1276 (C4)
1272 (d 3JC-F = 79 Hz C8) 1223 (C6) 1159 (d 2JC-F = 22 Hz C9) 1041 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C20H15BrF2N 38603559 Found 38603477
(421) Yellow oil (188 mg 580 μmol 78) 1H NMR (400 MHz
CD2Cl2) δ 748 (pseudo td 3JH-H = 77 Hz J = 19 Hz 1H H2) 721
(m 1H H4) 707 - 702 (m 5H H3 H8) 697 (m 1H H5) 691 (m
4H H9) 500 (d 5JF-H = 15 Hz 1H =CH2) 488 (s 1H =CH2) 19F
NMR (377 MHz CD2Cl2) δ -1162 (dm 3JF-H = 119 Hz 1F CF of
C6) -1207 (tm 3JF-H = 97 Hz 2F p-C6H4F) 13C1H NMR (101 MHz CD2Cl2) δ 1605 (d 1JC-F = 249 Hz CF of C6) 1591 (d 1JC-F = 244 Hz C10) 1475 (C=CH2) 1438 (d 4JC-F = 28
Hz C7) 1311 (d 3JC-F = 30 Hz C2) 1302 (d 3JC-F = 85 Hz C4) 1271 (d 2JC-F = 116 Hz C1)
1264 (d 3JC-F = 81 Hz C8) 1244 (d 4JC-F = 37 Hz C3) 1162 (d 2JC-F = 22 Hz C5) 1160 (d 2JC-F = 22 Hz C9) 1077 (d 4JC-F = 36 Hz =CH2) HRMS-ESI+ mz [M+H]+ calcd for
C20H15F3N 32611566 Found 32611576
(422) Yellow oil (125 mg 400 μmol 54) 1H NMR (400 MHz
CD2Cl2) δ 718 (dd 3JH-H = 51 4JH-H = 12 Hz 1H H4) 712 (dd 3JH-H
= 36 Hz 4JH-H = 12 Hz 1H H2) 705 - 701 (m 4H H6) 695 - 689
(m 5H H3 H7) 526 (s 1H =CH2) 469 (s 1H =CH2) 19F NMR (377
MHz CD2Cl2) δ -1209 (m 3JF-H = 90 Hz p-C6H4F) 13C1H NMR
(101 MHz CD2Cl2) δ 1589 (d 1JC-F = 241 Hz C8) 1473 (C=CH2) 1442 (d 4JC-F = 26 Hz
170
C5) 1436 (C1) 1276 (C3) 1265 (C2) 1258 (C4) 1257 (d 3JC-F = 80 Hz C6) 1162 (d 2JC-F =
22 Hz C7) 1068 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 31408150 Found
31408200
(423) Yellow oil (104 mg 430 μmol 58) 1H NMR (400 MHz
CD2Cl2) δ 715 (tm 3JH-H = 79 Hz 2H m-C6H5) 712 (dd 3JH-H = 53 Hz 4JH-H = 13 Hz 1H H4) 701 (dd 3JH-H = 35 Hz 4JH-H = 13 Hz 1H H2)
693 (dm 3JH-H = 79 Hz 2H o-C6H5) 685 (m 1H H3) 681 (tm 3JH-H =
79 Hz 1H p-C6H5) 531 (s 1H =CH2) 484 (s 1H =CH2) 426 (m 3JH-H = 66 Hz 1H iPr)
125 (d 3JH-H = 66 Hz 6H iPr) 13C1H NMR (101 MHz CD2Cl2) δ 1466 (ipso-C6H5) 1456
(C1) 1446 (C=CH2) 1296 (m-C6H5) 1274 (C2) 1260 (C3) 1253 (C4) 1208 (o-C6H5) 1206
(p-C6H5) 502 (iPr) 211 (iPr) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 2441154
Found 2441166
(424) Pale yellow solid (206 mg 560 μmol 75) 1H NMR (600
MHz CD2Cl2) δ 881 (dm 3JH-H = 78 Hz 1H H14) 865 (dm 3JH-H =
78 Hz 1H H11) 860 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H10)
797 (s 1H H2) 787 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H7)
766-761 (m 3H H9 H12 H13) 757 (pseudo td 3JH-H = 78 Hz 4JH-H
= 14 Hz 1H H8) 723 (m 4H o-C6H5) 715 (t 3JH-H = 73 Hz 4H m-C6H5) 692 (tt 3JH-H =
73 Hz 4JH-H = 12 Hz 2H p-C6H5) 512 (s 1H =CH2) 503 (s 1H =CH2) 13C1H NMR (125
MHz CD2Cl2) δ 1516 (C=CH2) 1476 (ipso-C6H5) 1357 (C1) 1317 (C3) 1309 (C6) 1307
(C5) 1306 (C4) 1294 (C2) 1292 (m-C6H5) 1291 (C7) 1273 (C9) 1271 (C8 C13) 1268 (C12)
1264 (C14) 1255 (o-C6H5) 1235 (p-C6H5) 1232 (C11) 1228 (C10) 1060 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C28H22N 37217522 Found 37217485
(425) Pale yellow solid (228 mg 560 μmol 75) 1H NMR (400
MHz CD2Cl2) δ 874 (dm 3JH-H = 74 Hz 1H H14) 866 (dm 3JH-H
= 74 Hz 1H H11) 861 (dm 3JH-H = 74 Hz 1H H10) 795 (s 1H
H2) 788 (dm 3JH-H = 74 Hz 1H H7) 767- 762 (m 3H H9 H12
H13) 759 (pseudo td 3JH-H = 74 Hz 4JH-H = 12 Hz 1H H8) 718
(m 4H H16) 686 (m 4H H17) 499 (s 1H =CH2) 495 (s 1H =CH2) 19F NMR (377 MHz
CD2Cl2) δ -1200 (tt 3JF-H = 84 Hz 4JF-H = 42 Hz p-C6H4F) 13C1H NMR (125 MHz
171
CD2Cl2) δ 1592 (d 1JC-F = 240 Hz C18) 1519 (C=CH2) 1437 (d 4JC-F = 26 Hz C15) 1353
(C1) 1316 (C3) 1308 (C6) 1307 (C5) 1306 (C4) 1296 (C2) 1291 (C7) 1274 (C9) 1272 (C8
C12) 1271 (d 3JC-F = 83 Hz C16) 1269 (C13) 1262 (C14) 1233 (C11) 1228 (C10) 1161 (d 2JCF = 219 Hz C17) 1043 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C28H20F2N 40815638
Found 40815576
(426) Yellow oil (178 mg 550 μmol 74) 1H NMR (400 MHz
CD2Cl2) δ 735 (dm 3JH-H = 77 Hz 1H H2) 727- 723 (m 2H H3
H6) 701 (m 4H H8) 697- 691 (m 5H H4 H9) 516 (s 1H =CH2)
478 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1141 (m 1F
CF of C5) -1205 (m 2F p-C6H4F) 13C1H NMR (101 MHz
CD2Cl2) δ 1632 (d 1JC-F = 245 Hz C5) 1592 (d 1JC-F = 244 Hz C10) 1522 (d 4JC-F = 25 Hz
C=CH2) 1442 (d 4JC-F = 28 Hz C7) 1417 (d 3JC-F = 76 Hz C1) 1303 (d 3JC-F = 84 Hz C3)
1261 (d 3JC-F = 81 Hz C8) 1235 (d 4JC-F = 28 Hz C2) 1162 (d 2JC-F = 22 Hz C9) 1154 (d 2JC-F = 21 Hz C4) 1145 (d 2JC-F = 21 Hz C6) 1074 (=CH2) HRMS-ESI+ mz [M+H]+ calcd
for C20H15F3N 32611566 Found 32611485
(427) White solid (154 mg 500 μmol 68) 1H NMR (500 MHz
CD2Cl2) δ 722 (tm 3JH-H = 73 Hz 4H m-C6H5) 710 (m 2H H2) 705
(dm 3JH-H = 73 Hz 4H o-C6H5) 699 (tm 3JH-H = 73 Hz 2H p-C6H5)
670 (tt 3JH-H = 89 Hz 4JH-H = 24 Hz 1H H4) 525 (s 1H =CH2) 490
(s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1107 (t 3JF-H = 81 Hz m-C6H3F2) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (d 1JC-F = 248 Hz C3) 1515 (t 4JC-F = 28 Hz C=CH2)
1477 (ipso-C6H5) 1435 (d 3JC-F = 92 Hz C1) 1295 (m-C6H5) 1244 (o-C6H5) 1234 (p-
C6H5) 1105 (d 2JC-F = 21 Hz C2) 1093 (s =CH2) 1037 (t 2JC-F = 25 Hz C4) HRMS-ESI+
mz [M+H]+ calcd for C20H16F2N 30812508 Found 30812511
(428) Yellow oil (193 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 783 (ddq 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H6)
774 (ddq 3JH-H = 78 Hz 4JH-H = 12 Hz 6JF-H = 06 Hz 1H H2) 749
(dddq 3JH-H = 78 Hz 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H4)
739 (pseudo tq 3JH-H = 78 Hz 5JF-H = 07 Hz 1H H3) 721 (tm 3JH-H = 78 Hz 4H m-C6H5)
707 (dm 3JH-H = 78 Hz 4H o-C6H5) 697 (tm 3JH-H = 78 Hz 2H p-C6H5) 526 (d 1H 2JH-H
172
= 07 Hz =CH2) 493 (d 2JH-H = 07 Hz =CH2) 19F NMR (377 MHz CD2Cl2) δ -630 (s CF3)
13C1H NMR (125 MHz CD2Cl2) δ 1517 (C=CH2) 1474 (ipso-C6H5) 1400 (C1) 1304 (q 5JC-F = 13 Hz C2) 1304 (q 2JC-F = 32 Hz C5) 1290 (m-C6H5) 1287 (C3) 1247 (q 3JC-F = 38
Hz C4) 1242 (o-C6H5) 1241 (q 1JC-F = 271 Hz CF3) 1239 (q 3JC-F = 38 Hz C6) 1228 (p-
C6H5) 1083 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C21H17F3N 34013131 Found
34013065
4424 Procedures for tandem hydroamination and hydrogenation reactions
A general procedure is provided for the preparation of compounds 429 and 430 Following the
10 h catalytic hydroamination reaction in the glovebox the reaction mixture was transferred into
an oven-dried Teflon screw cap glass tube The reaction tube was degassed once through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The tube
was placed in an 80 ordmC oil bath for 14 h The solvent was removed under vacuum and the
mixture was dissolved in ethyl acetate (5 mL) and passed through a short (4 cm) silica column
previously treated with Et2NH The crude reaction mixtures consisted of the starting materials
(amine and alkyne) and the product The product was purified by column chromatography using
hexaneethyl acetate (61) as eluent
Alternative hydrogenation procedure using 5 mol Mes2PH(C6F4)BH(C6F5)2
Mes2PH(C6F4)BH(C6F5)2 (28 mg 37 μmol) was added to the reaction mixture before being
transferred into the glass tube The tube was filled with H2 and placed in an 80 ordmC oil bath The
reaction was stopped after 3 h at 80 ordmC and worked up similar to the procedure above
(429) Yellow oil (186 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 728 - 720 (m 2H H2 H5) 708 - 700 (m 2H H3 H4)
692 (m 4H H9) 680 (m 4H H8) 545 (q 3JH-H = 70 Hz C(CH3)H)
138 (d 3JH-H = 70 Hz C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -
1186 (m 1F F of C6) -1224 (m 2F F of C10) 13C1H NMR (125
MHz CD2Cl2) δ 1610 (d 1JC-F = 247 Hz C6) 1588 (d 1JC-F = 241 Hz C10) 1436 (d 4JC-F =
26 Hz C7) 1310 (d 2JC-F = 131 Hz C1) 1291 (d 2JC-F = 85 Hz C5) 1284 (d 3JC-F = 43 Hz
C2) 1249 (d 3JC-F = 79 Hz C8) 1244 (d 4JC-F = 35 Hz C3) 1159 (d 2JC-F = 22 Hz C9) 1157
173
(d 3JC-F = 22 Hz C4) 517 (C(CH3)H) 197 (C(CH3)H) HRMS-ESI+ mz [M+H]+ calcd for
C20H17F3N 32813131 Found 32813189
(430) Yellow oil (146 mg 470 μmol 64) 1H NMR (500 MHz
CD2Cl2) δ 724 (tm 3JH-H = 78 Hz 4H m-C6H5) 699 (m 4H H2 p-
C6H5) 688 (dm 3JH-H = 78 Hz 4H o-C6H5) 671 (tt 3JF-H = 89 Hz 4JH-H = 24 Hz 1H H4) 524 (d 3JH-H =70 Hz 1H C(CH3)H) 145 (d
3JH-H = 70 Hz 3H C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -1105 (m F of C3) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (dd 1JC-F = 248 Hz 3JC-F = 13 Hz C3) 1496 (t 3JC-F = 79
Hz C1) 1472 (ipso-C6H5) 1297 (m-C6H5) 1235 (o-C6H5) 1212 (p-C6H5) 1100 (dd 2JC-F =
20 Hz 4JC-F = 47 Hz C2) 1202 (t 2JC-F = 27 Hz C4) 579 (C(CH3)H) 203 (C(CH3)H)
HRMS-ESI+ mz [M+H]+ calcd for C20H18F2N 31014073 Found 31014081
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions
Compounds 431 and 432 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 25 mL Schlenk flask equipped with a stir bar was charged with a
toluene (5 mL) solution of B(C6F5)3 (0100 g 0190 mmol) and the respective alkynyl aniline
(0190 mmol) The solution was heated for 2 h at 50 degC and the solvent was subsequently
removed under reduced pressure The crude oil was washed with pentane (2 times 5 mL) to yield the
product as a white solid
Synthesis of C6H5N(CH2)3CCH2B(C6F5)3 (431) N-(Pent-4-ynyl)aniline (300 mg 0190
mmol) product (120 mg 0179 mmol 94)
1H NMR (400 MHz CD2Cl2) δ 746 (m 3H m p-Ph) 691 (dm 3JH-H =
86 Hz 2H o-Ph) 416 (t 3JH-H = 78 Hz 2H H3) 333 (br q 2JB-H = 54
Hz 2H CH2B) 311 (t 3JH-H = 78 Hz 2H H1) 215 (quint 3JH-H = 78 Hz
2H H2) 19F NMR (377 MHz CD2Cl2) δ -1325 (m 2F o-C6F5) -1601 (t 3JF-F = 21 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -134 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 1942 (C=N) 1476 (dm 1JC-F = 241 Hz CF)
1392 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1348 (ipso-Ph) 1324 (p-Ph)
174
1311 (m-Ph) 1231 (o-Ph) 1189 (ipso-C6F5) 651 (C3) 411 (C1) 185 (CH2B C2) Anal
calcd () for C29H13BF15N C 5189 H 195 N 209 Found 5140 H 219 N 191
Synthesis of C6H5N(CH2)4CCH2B(C6F5)3 (432) N-(Hex-5-ynyl)aniline (340 mg 0190
mmol) product (129 mg 0188 mmol 99) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC
1H NMR (600 MHz CD2Cl2) δ 745 (tt 3JH-H = 75 Hz 4JH-H = 22 Hz
1H p-Ph) 740 (tm 3JH-H = 75 Hz 2H m-Ph) 663 (dm 3JH-H = 75 Hz
2H o-Ph) 372 (t 3JH-H = 73 Hz 2H H4) 316 (br q 2JB-H = 63 Hz 2H
CH2B) 275 (t 3JH-H = 73 Hz 2H H1) 197 (m 2H H3) 176 (m 2H
H2) 19F NMR (377 MHz CD2Cl2) δ -1320 (m 2F o-C6F5) -1611 (t 3JF-
F = 20 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -130 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 2005 (C=N) 1481 (dm 1JC-F = 241 Hz CF)
1420 (ipso-Ph) 1384 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1301 (m p-
Ph) 1226 (ipso-C6F5) 1237 (o-Ph) 574 (C4) 380 (CH2B) 326 (C1) 213 (C3) 175 (C2)
Anal calcd () for C30H15BF15N C 5228 H 221 N 204 Found 5206 H 272 N 177
Synthesis of [2-MeC8H6N(Ph)][HB(C6F5)3] (433) In the glovebox a 25 mL Schlenk flask
equipped with a stir bar was charged with a toluene (5 mL) solution of B(C6F5)3 (0100 g 0190
mmol) and N-(2-ethynylbenzyl)aniline (390 mg 0190 mmol) The solution was heated for 16 h
under H2 (4 atm) at 80 degC The solvent was subsequently removed under reduced pressure The
crude oil was washed with pentane (2 times 5 mL) to yield the product as a white solid (740 mg
0103 mmol 54)
1H NMR (600 MHz CD2Cl2) δ 812 (dm 3JH-H = 79 Hz JH-H = 10
Hz 1H H9) 799 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H H8) 786 (dm 3JH-H = 79 Hz 1H H6) 782 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H
H7) 773 - 769 (m 3H H2 and H3) 745 (dm 3JH-H = 76 Hz H1) 556
(q JH-H = 26 Hz 2H H4) 353 (br 1H HB) 289 (t JH-H = 26 Hz Me) 19F NMR (564 MHz
CD2Cl2) δ -1341 (br 2F o-C6F5) -1644 (br 1F p-C6F5) -1674 (br 2F m-C6F5) 11B1H
NMR (192 MHz CD2Cl2) δ -252 (s HB) 13C1H NMR (151 MHz CD2Cl2) 1820 (N=C)
1480 (dm 1JC-F = 247 Hz CF) 1437 (C10) 1373 (C7) 1366 (dm 1JC-F = 241 Hz CF) 1362
(dm 1JC-F = 241 Hz CF) 1347 (ipso-Ph) 1337 (C5) 1322 (C3) 1308 (C2) 1306 (C8) 1266
NB(C6F5)3
4
3
2
1
175
(C9) 1247 (C1) 1234 (C6) 657 (C4) 149 (Me) (ipso-C6F5 was not observed) Anal calcd ()
for C33H15BF15N C 5495 H 210 N 194 Found C 5502 H 212 N 218
Compounds 434 - 438 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 25 mL Schlenk bomb equipped with a stir bar was charged with a toluene (2
mL) solution of B(C6F5)3 (20 mg 40 μmol) and the alkynyl aniline (039 mmol) The solution
was heated for 16 h under H2 (4 atm) at 80 degC The solvent was subsequently removed under
reduced pressure The crude oil was washed with pentane (2 times 5 mL) and purified by column
chromatography using hexaneethyl acetate (61) as eluent
Synthesis of 2-MeC4H7N(Ph) (434) N-(Pent-4-ynyl)aniline (600 mg 0390 mmol) product
(427 mg 0265 mmol 68)
1H NMR (500 MHz CD2Cl2) δ 718 (t 3JH-H = 78 Hz 2H m-Ph) 660 (tt 3JH-H =
78 Hz 4JH-H = 11 H 1H p-Ph) 657 (d 3JH-H = 78 Hz 2H o-Ph) 286 (m 3JH-H =
61 Hz 1H NCHCH3) 282 (ddd 2JH-H = 88 Hz 3JH-H = 78 Hz 35 Hz 1H H3)
254 (pseudo q 3JH-H = 83 Hz 1H H3) 211 - 162 (m 4H H1 and H2) 099 (d 3JH-H
= 61 Hz 3H Me) 13C1H NMR (151 MHz CD2Cl2) δ 1474 (ipso-Ph) 1289 (m-Ph) 1148
(p-Ph) 1116 (o-Ph) 540 (NCHCH3) 478 (C3) 330 (C1) 265 (C2) 197 (Me) HRMS-
DART+ mz [M+H]+ calcd for C11H15N 16212827 Found 16212755
Synthesis of 2-MeC5H9N(Ph) (435) N-(Hex-5-ynyl)aniline (682 mg 0390 mmol) product
(451 mg 0257 mmol 66)
1H NMR (500 MHz CD2Cl2) δ 723 (t 3JH-H = 81 Hz 2H m-Ph) 693 (d 3JH-H =
81 Hz 2H o-Ph) 680 (tt 3JH-H = 81 Hz 4JH-H = 11 H 1H p-Ph) 394 (m 1H
NCHCH3) 323 (dt 2JH-H = 121 Hz 3JH-H = 44 Hz 1H H4) 297 (dm 2JH-H = 121
Hz 1H H4) 190 - 160 (m 6H H1 H2 H3) 100 (d 3JH-H = 672 3H Me) 13C1H
NMR (151 MHz CD2Cl2) δ 1516 (ipso-Ph) 1288 (m-Ph) 1187 (p-Ph) 1173 (o-
Ph) 512 (NCHCH3) 446 (C4) 317 (C1) 261 (C3) 198 (C2) 134 (Me) HRMS- DART+ mz
[M+H]+ calcd for C12H17NO 17614392 Found 17614338
176
Synthesis of 2-MeC5H9N(p-FC6H4) (436) 4-Fluoro-N-(hex-5-yn-1-yl)aniline (745 mg 0390
mmol) product (542 mg 0281 mmol 72)
1H NMR (400 MHz C6D5Br) δ 652 (t JH-H = 88 Hz 2H m-H of C6H4F) 637 (dd 3JH-H = 88 Hz 4JH-F = 48 Hz 2H o-H of C6H4F) 306 (m 1H NCHCH3) 241 (m
1H H4) 135 (m 1H H1) 121 (m 1H H3) 113 (m 2H H23) 102 (m 1H H2)
101 (m 1H H2) 045 (d 3JH-H = 65 Hz 3H CH3) 19F NMR (377 MHz C6D5Br)
δ -1235 (s 1F C6H4F) 13C1H NMR (100 MHz C6D5Br) δ 1582 (q 1JC-F = 297
Hz p-C6H4F) 1479 (ipso-C6H4F) 1202 (d 3JC-F = 77 Hz o-C of C6H4F) 1150 (d 3JC-F = 227 Hz m-C of C6H4F) 518 (NCHCH3) 470 (C4) 321 (C1) 260 (C3) 203 (C2) 146
(CH3) HRMS- ESI + mz [M+H]+ calcd for C12H16NF 1941340 Found 1941337
Synthesis of 2-MeC5H9N(p-CH3OC6H4) (437) N-(Hex-5-yn-1-yl)-4-methoxyaniline (792 mg
0390 mmol) product (416 mg 0203 mmol 52)
1H NMR (500 MHz C6D5Br) δ 712 (d 3JH-H = 85 Hz 2H m-H of C6H4OCH3)
700 (d 3JH-H = 85 Hz 2H o-H of C6H4OCH3) 374 (s 3H OCH3) 349 (m 1H
NCHCH3) 309 (m 1H H4) 302 (m 1H H4) 194 (m 1H H1) 184 (m 1H H3)
178 (m 1H H2) 176 (m 1H H3) 161 (m 1H H1) 158 (m 1H H2) 106 (d 3JH-
H = 65 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1542 (p-C6H4OCH3)
1457 (ipso-C6H4OCH3) 1221 (m-C of C6H4OCH3) 1139 (o-C of C6H4OCH3) 546
(OCH3) 534 (NCHCH3) 496 (C4) 331 (C1) 264 (C3) 214 (C2) 160 (CH3) HRMS-ESI+
mz [M+H]+ calcd for C13H19NO 2061539 Found 2061539
Synthesis of 2-MeC8H7N(Ph) (438) N-(2-Ethynylbenzyl)aniline (808 mg 0390 mmol)
product (571 mg 0273 mmol 70)
1H NMR (400 MHz CD2Cl2) δ 778 (d 3JH-H = 77 Hz 1H C6H4) 745 - 737 (m
5H m-Ph C6H4) 707 (t 3JH-H = 77 Hz 1H p-Ph) 703 (d 3JH-H = 77 Hz 2H o-
Ph) 510 (q 3JH-H = 66 Hz 1H NCH(CH3)) 483 (d 2JH-H = 138 Hz 1H CH2)
463 (d 2JH-H = 138 Hz 1H CH2) 154 (d 3JH-H = 66 Hz 3H CH3) 13C1H NMR
(151 MHz CD2Cl2) δ 1435 (ipso-Ph) 1376 (C1) 1343 (C6) 1297 (m-Ph) 1283
177
(C34) 1245 (C2) 1226 (p-Ph) 1222 (C5) 1161 (o-Ph) 641 (NCH(CH3) 563 (CH2) 182
(CH3) HRMS-DART+ mz [M+H]+ calcd for C15H15N 21012827 Found 21012767
4426 Procedures for reactions with ethynylphosphines
Synthesis of trans-Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 (439) In the glove box a 4 dram
vial equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg
0740 mmol) and iPrNHPh (100 mg 0740 mmol) To the vial Mes2PCequivCH (440 mg 0148
mmol) was added and the reaction was left at RT for 16 h The solvent was removed under
reduced pressure and the crude product was washed with pentane to yield the product as a pale
yellow solid (717 mg 0651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 771 (td JP-H = 286 Hz 3JH-H = 172 Hz 1H =CH) 698 (d 4JPH = 49 Hz 4H Mes) 689 (d 4JPH = 32 Hz 4H Mes) 574 (ddd 2JP-H = 273 Hz 3JH-H =
172 3JP-H = 44 Hz 1H =CH) 235 (s 6H Mes) 229 (s 6H Mes) 223 (s 12H Mes) 218 (s
12H Mes) 19F NMR (377 MHz CD2Cl2) δ -1329(m 2F o-C6F5) -1616 (t 3JF-F = 21 Hz 1F
p-C6F5) -1663 (m 2F m-C6F5) 31P1H NMR (162 MHz CD2Cl2) δ -115 (br s PMes2) -143
(d JP-P = 82 Hz PMes2) 11B NMR (128 MHz CD2Cl2) δ -211 (CB) 13C1H NMR (101
MHz CD2Cl2) partial δ 1540 (d 1JC-P = 31 Hz Mes) 1470 (d 1JC-F = 248 Hz CF) 1437 (d
JC-P = 28 Hz Mes) 1417 (d JC-P = 150 Hz Mes) 1413 (d JC-P = 113 Hz Mes) 1393 (Mes)
1321 (d 3JC-P = 14 Hz Mes) 1303 (d 3JC-P = 56 Hz Mes) 1260 (d JC-P = 11 Hz Mes) 1178
(dd 2JC-P = 99 Hz 3JC-P = 27 Hz =CH) 1120 (dd 2JC-P = 85 Hz 3JC-P = 121 Hz =CH) 219 (d 3JC-P = 68 Hz Mes) 218 (d 3JC-P = 14 Hz Mes) 201 (d 5JC-P = 18 Hz Mes) 198 (Mes)
Anal calcd () for C58H46BF15P2 C 6329 H 421 Found C 6282 H 411
Synthesis of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 (440) In the glove box a 4 dram vial
equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg 0144
mmol) To the vial tBu2PCequivCH (250 mg 0148 mmol) was added and the reaction was left at
RT for 16 h The solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as an off-white solid (580 mg 0570 mmol 77)
Crystals suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC
178
1H NMR (600 MHz CD2Cl2) δ 777 (ddd 2JP-H = 46 Hz 3JH-H =15 Hz 3JP-H = 36 Hz 1H
=CH) 650 (ddd 2JP-H = 28 Hz 3JP-H = 19 Hz 3JH-H =15 Hz 1H =CH) 144 (d 3JP-H = 17 Hz
18H tBu) 101 (d 3JP-H = 11 Hz 18H tBu) 19F NMR (564 MHz CD2Cl2) δ -1322 (m 2F o-
C6F5) -1618 (t 3JF-F = 20 Hz 1F p-C6F5) -1665 (m 2F m-C6F5) 31P1H NMR (242 MHz
CD2Cl2) δ 215 (PtBu2) 251 (PtBu2) 11B NMR (192 MHz CD2Cl2) -212 (CB) 13C1H
NMR (151 MHz CD2Cl2) partial δ 1620 (dd 1JC-P = 42 Hz 2JC-P = 32 Hz =CH) 1210 (dd 1JC-P = 82 Hz 2JC-P = 21 Hz =CH) 371 (d 1JC-P = 48 Hz tBu) 325 (d 1JC-P = 22 Hz tBu) 292
(d 2JC-P = 14 Hz tBu) 266 (tBu) Anal calcd () for C38H38BF15P2 C 5354 H 449 Found C
5314 H 432
Compounds 441 and 442 were prepared following the same procedure In the glove box a
Schlenk tube equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of HB(C6F5)2
(100 mg 0289 mmol) and the appropriate alkynyl-substituted pinacolborane (0289 mmol) was
added at once After 5 minutes Ph2PH (538 mg 0289 mmol) was added to the vial The
reaction was left at RT for 16 h The solvent was then removed under reduced pressure and
pentane (5 mL) was added to the crude oil resulting in precipitate The pentane soluble fraction
was separated from the precipitate concentrated and placed in a -30 degC freezer to give the
product as colourless crystals
Synthesis of Bu(H)Ph2PC-C(H)B(C6F5)2Bpin (441) CH3(CH2)3CequivCBpin (606 mg 0289
mmol) product (175 mg 0237 mmol 82)
1H NMR (600 MHz CD2Cl2) δ 766 (m 2H o-Ph) 757 (tm 3JH-H = 77 Hz 1H p-Ph) 747
(tm 3JH-H = 72 Hz 1H p-Ph) 742 (m 2H m-Ph) 736 (m 2H m-Ph) 733 (m 2H o-Ph) 353
(m 1H CHP) 290 (d 2JH-H = 116 Hz 1H CH2CHP) 278 (d 2JH-H = 116 Hz 1H CH2CHP)
148 (m 1H CHB) 133 (m 2H CH2) 118 (m 2H CH2) 102 (s 6H CH3) 098 (s 6H CH3)
078 (t 3JH-H = 72 Hz 3H CH3) 19F NMR (564 MHz CD2Cl2) δ -1292 (m 2F o-C6F5) -
1328 (m 2F o-C6F5) -1665 (m 2F m-C6F5) -1585 (t 3JF-F = 20 Hz 1F p-C6F5) -1605 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) -1653 (m 2F m-C6F5) 31P1H NMR (242
MHz CD2Cl2) δ 322 (br) 11B NMR (192 MHz CD2Cl2) δ 337 (Bpin) -66 (B(C6F5)2)
13C1H NMR (151 MHz CD2Cl2) partial δ 1362 (d 2JC-P = 91 Hz o-Ph) 1318 (d 4JC-P = 29
Hz p-Ph) 1314 (d 2JC-P = 81 Hz o-Ph) 1313 (d 4JC-P = 28 Hz p-Ph) 1285 (d 3JC-P = 95
Hz m-Ph) 1279 (d 3JC-P = 10 Hz m-Ph) 1279 (d 1JC-P = 332 Hz ipso-Ph) 1238 (d 1JC-P =
179
34 Hz ipso-Ph) 824 (C(CH3)2) 346 (d 1JC-P = 37 Hz CHP) 301 (d 2JC-P = 80 Hz CH2CHP)
290 (d 3JC-P = 49 Hz CH2) 246 (BpinCH3) 242 (BpinCH3) 224 (CH2) 158 (CHB) 079
(CH3) Anal calcd () for C36H33B2F10O2P C 5841 H 449 Found 5808 H 437
Synthesis of Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin (442) CH2=C(CH3)CequivCBpin (567
mg 0289 mmol) product (153 mg 0211 mmol 73) Crystals suitable for X-ray diffraction
were grown from pentane at -30 ordmC
1H31P NMR (600 MHz CD2Cl2) δ 764 (tt 3JH-H = 73 Hz 4JH-H = 14 Hz 1H p-Ph) 755 (d 3JH-H = 73 Hz 2H o-Ph) 749 (t 3JH-H = 75 Hz 2H m-Ph) 727 (tt 3JH-H = 75 Hz 4JH-H = 12
Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 680 (d 3JH-H = 75 Hz 2H o-Ph) 645 (br 1H
=CH) 320 (d 2JH-H = 14 Hz 1H PCH2) 307 (d 2JH-H = 14 Hz 1H PCH2) 190 (s 3H CH3)
149 (br m 1H CHB) 106 (s 6H CH3) 104 (s 6H CH3) 19F NMR (564 MHz CD2Cl2)
partial δ -1254 (br 2F o-C6F5) -1665 (m 2F m-C6F5) (p-C6F5 was not observed) 31P1H
NMR (242 MHz CD2Cl2) δ 63 (br) 11B NMR (192 MHz CD2Cl2) δ 342 (Bpin) -104
(B(C6F5)2) 13C1H NMR (151 MHz CD2Cl2) partial δ 1481 (H3CC=CH) 1359 (=CH) 1329
(m o-Ph) 1323 (d 4JC-P = 39 Hz p-Ph) 1317 (d 2JC-P = 71 Hz o-Ph) 1311 (d 4JC-P = 30
Hz p-Ph) 1300 (d 3JC-P = 94 Hz m-Ph) 1291 (d 1JC-P = 54 Hz ipso-Ph) 1282 (d 3JC-P = 94
Hz m-Ph) 1251 (d 1JC-P = 54 Hz ipso-Ph) 821 (C(CH3)2) 268 (d 1JC-P = 33 Hz CH2P) 256
(d 3JC-P = 53 Hz H3CC=CH) 245 (BpinCH3) 244 (BpinCH3) 178 (br CHB) Anal calcd ()
for C35H29B2F10O2P C 5805 H 404 Found 5776 H 397
443 X-Ray Crystallography
4431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
Universitaumlt Muumlnster data sets were collected with a Nonius KappaCCD diffractometer
Programs used data collection COLLECT351 data reduction Denzo-SMN352 absorption
180
correction Denzo353 structure solution SHELXS-97354 structure refinement SHELXL-97355
Thermals ellipsoids are shown with 30 probability R-values are given for observed reflections
and wR2 values are given for all reflections
4432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
4433 Platon Squeeze details
During the refinement of structure 413 electron density peaks were located that were believed
to be highly disordered dichloromethane and 12-dichloroethane molecules Attempts made to
model the solvent molecule were not successful The SQUEEZE option in PLATON356 indicated
there was a large solvent cavity 160 A3 in the asymmetric unit In the final cycles of refinement
this contribution (39 electrons) to the electron density was removed from the observed data The
density the F(000) value the molecular weight and the formula are given taking into account the
results obtained with the SQUEEZE option PLATON
181
4434 Selected crystallographic data
Table 44 ndash Selected crystallographic data for 41 47 and 48
41 47 48
Formula C46H23B1F15N1 C62H31B1F15N1 C37H25B1F15N1
Formula wt 88546 108572 77939
Crystal system monoclinic triclinic triclinic
Space group P2(1)n P-1 P-1
a(Aring) 91451(8) 120520(8) 99293(9)
b(Aring) 20583(2) 122120(8) 115709(11)
c(Aring) 20738(2) 184965(12) 168258(15)
α(ordm) 9000 103236(4) 75826(4)
β(ordm) 96295(4) 104461(4) 77700(4)
γ(ordm) 9000 104447(4) 65591(4)
V(Aring3) 38800(6) 24264(3) 16930(3)
Z 4 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1516 1482 1529
Abs coeff μ mm-1 0138 0126 0146
Data collected 35905 34295 21194
Rint 00444 00308 00308
Data used 8910 11131 5899
Variables 569 712 490
R (gt2σ) 00420 00532 00488
wR2 00964 01380 01380
GOF 1018 1028 1026
182
Table 45 ndash Selected crystallographic data for 49 410 and 413
49 410
(+05 C5H12)
413
(+1 C2H4Cl2)
Formula C39H21B1F15N1S2 C425H23B1F15N1 C48H29B1Cl2F15N1
Formula wt 86350 85145 98643
Crystal system monoclinic triclinic monoclinic
Space group P2(1)c P-1 P2(1)c
a(Aring) 174202(13) 113739(5) 138815(4)
b(Aring) 135941(10) 115489(6) 242842(7)
c(Aring) 174144(13) 158094(7) 146750(4)
α(ordm) 9000 92979(2) 9000
β(ordm) 118149(3) 97298(2) 1108840(10)
γ(ordm) 9000 116865(3) 9000
V(Aring3) 36362(5) 182343(15) 46220(2)
Z 4 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1577 1536 1418
Abs coeff μ mm-1 0256 0143 0236
Data collected 27739 30840 34544
Rint 00299 00352 00437
Data used 6409 8342 8147
Variables 506 560 600
R (gt2σ) 00570 00504 00687
wR2 01537 01410 02122
GOF 1045 1021 1092
183
Table 46 ndash Selected crystallographic data for 414 432 and 439
414
(+05 CH2Cl2 +1 C5H12)
432
(+05 C5H12) 439
Formula C485H36B1Cl1F15N1 C325H21B1F15N1 C58H46B1F15P2
Formula wt 96404 72131 110070
Crystal system monoclinic triclinic triclinic
Space group C2c P-1 P-1
a(Aring) 309455(12) 80774(6) 117846(13)
b(Aring) 193567(7) 117730(8) 159017(19)
c(Aring) 182668(6) 158569(11) 16349(2)
α(ordm) 9000 79707(3) 108194(4)
β(ordm) 123002(2) 86387(3) 107588(4)
γ(ordm) 9000 87902(3) 104551(4)
V(Aring3) 91764(6) 148021(18) 25646(5)
Z 8 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1397 1620 1425
Abs coeff μ mm-1 0179 0160 0179
Data collected 34220 24071 37635
Rint 00476 00352 00284
Data used 8097 6615 9023
Variables 570 445 698
R (gt2σ) 00716 00560 00339
wR2 02417 01703 00880
GOF 1047 1096 1019
184
Table 47 ndash Selected crystallographic data for 440 and 442
440 442
Formula C38H38B1F15P2 C35H29B2F10O2P1
Formula wt 85243 72417
Crystal system monoclinic monoclinic
Space group C2c P2(1)n
a(Aring) 329294(17) 114236(2)
b(Aring) 118317(6) 151074(3)
c(Aring) 206088(10) 192749(4)
α(ordm) 9000 9000
β(ordm) 107535(5) 93553(1)
γ(ordm) 9000 9000
V(Aring3) 76563(7) 332009(11)
Z 8 4
Temp (K) 150(2) 223(2)
d(calc) gcm-3 1479 1449
Abs coeff μ mm-1 0215 0172
Data collected 63283 23294
Rint 00316 0055
Data used 8776 6697
Variables 517 456
R (gt2σ) 00365 00672
wR2 01017 01623
GOF 1021 1048
185
Chapter 5 Conclusion
51 Thesis Summary
The results presented in this thesis demonstrate the application of B(C6F5)3 and other
electrophilic boranes in metal-free synthetic methodologies thereby extending FLP reactivity
beyond the commonly reported stoichiometric activation of small molecules These findings
have also provided metal-free and catalytic routes to transformations typically performed using
transition-metal complexes or stoichiometric main group reagents
Initial results presented herein describe the aromatic reduction of N-phenyl amines in the
presence of an equivalent of B(C6F5)3 using H2 to yield the corresponding cyclohexylammonium
derivatives A reaction mechanism based on experimental evidence and theoretical calculations
has been proposed Elaborating the scope of these metal-free aromatic reductions a p-methoxy
substituted aniline was found to undergo tandem hydrogenation and intramolecular cyclization
with B(C6F5)3 presenting a unique route to a 7-azabicyclo[221]heptane derivative Aromatic
hydrogenations were further probed with pyridines quinolines and other N-heterocycles
Findings within this study were in agreement with the mechanism postulated for the arene
reduction of N-phenyl amines Although these reductions require an equimolar combination of
the aromatic amine and borane in certain cases the reactions take up eight equivalents of H2
Continued interest in FLP hydrogenation of aromatic rings was illustrated by subsequent reports
demonstrating borane-catalyzed stereoselective hydrogenation of pyridines by the Du group264
and catalytic hydrogenation of polyaromatic hydrocarbons by the Stephan group263
The second project discussed in this thesis was directly inspired by findings in the synthesis of a
7-azabicyclo[221]heptane derivative from a p-methoxy substituted aniline Detailed
mechanistic studies showed the B(C6F5)3-methoxide bond is labile under specific reaction
conditions These findings were applied to uncover a catalytic approach to the hydrogenation of
ketones and aldehydes yielding alcohols This method uses FLPs derived from B(C6F5)3 and
ether in which the ether is used as the solvent playing a pivotal role in hydrogen-bonding
interaction with the carbonyl substrate The catalysis was further studied in toluene using
B(C6F5)3 in combination with oxygen containing materials such as cyclodextrins or molecular
sieves Application of these materials provides an avenue to H2 activation and hydrogen-bonding
186
interactions necessary to facilitate hydrogenation In the particular case of aryl ketones the use
of molecular sieves promoted reductive deoxygenation of the substrate to give the aromatic
hydrocarbon product Hydrogenation of carbonyl substrates had perennially remained a
challenging problem since the discovery of FLP chemistry The results reported in this thesis
represent the first successful report of catalytic carbonyl hydrogenation using FLPs It should be
noted that the group of Ashley simultaneously reported the hydrogenation of ketones and
aldehydes using 14-dioxaneB(C6F5) as the FLP catalyst260
Lastly interest in expanding FLP catalysis beyond hydrogenations amineborane FLPs were
applied in the hydroamination of terminal alkynes The stoichiometric reaction of aniline
B(C6F5)3 and two equivalents of alkyne gave a series of iminium alkynylborate complexes
prepared through sequential intermolecular hydroamination and deprotonation reactions This
latter reaction results in the formation of the alkynylborate anion thus preventing participation of
B(C6F5)3 in catalysis Adjustment of the protocol by slow addition of the alkyne prevents the
deprotonation pathway thus allowing B(C6F5)3 to catalyze the Markovnikov hydroamination of
alkynes by a variety of secondary aryl amines affording enamines products This metal-free
route was also amenable to subsequent use of the catalyst in hydrogenation catalysis allowing
for the single-pot and stepwise conversion of the enamine products to the corresponding amines
Further expansion of the reactivity led to catalytic intramolecular hydroaminations affording a
one-pot strategy to N-heterocycles A stoichiometric approach to FLP hydrophosphinations was
also described
52 Future Work
While the reactivities presented in this thesis have typically been the purview of precious metals
research efforts motivated by cost toxicity and low abundance have provided alternative
strategies using main group compounds In 1961 the first metal-free catalytic hydrogenation was
reported displaying the reduction of benzophenone however this reaction required high
temperatures of about 200 degC and H2 pressures greater than 100 atm175 Since then dramatic
progress has been made in the advancement of metal-free catalysis Numerous metal-free
systems with particular emphasis on FLPs have been reported to effect the hydrogenation of an
elaborate list of substrates under mild conditions
187
An important direction to progress the chemistry found during this graduate research work would
be to design a borane reagent that will be suitable for the catalytic hydrogenation of N-phenyl
amines and N-heterocycles Such a direction will allow for a more atom-economic
transformation Ultimately the catalysis could be pursued using chiral boranes that may provide
a stereoselective process to cyclohexylamine derivatives (Scheme 51) Generally aromatic
hydrogenation of nitrogen substrates is a challenging transformation for transition-metal systems
due to deactivation of the catalyst by coordination of the substrate357
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
An interesting and obvious extension of carbonyl hydrogenations presented in Chapter 3 would
certainly be a FLP route to optically active alcohols Although such products were not obtained
when performing the reductions in the presence of chiral heterogeneous Lewis bases the
application of a chiral borane should be investigated The Du group recently presented the use of
chiral boranes in the asymmetric hydrogenation of silyl enol ethers to give chiral alcohol
products after appropriate work-up procedures97
Furthermore the use of cyclodextrins and molecular sieves in catalysis has presented the
possible notion of expanding homogeneous FLP chemistry to surface chemistry by designing
heterogeneous FLP catalysts that could be readily recycled (Scheme 52) Such a system may be
particularly attractive for industrial applicability Solid catalyst supports such as B(C6F5)3 grafted
onto silica have been used by the Scott group as a co-catalyst for the activation of metal
complexes used in olefin polymerization358 Although this system may not be sufficiently Lewis
acidic for carbonyl reductions further exploration and modification of Lewis acid and base
components could potentially lead to such a system
188
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations
The final chapter of this thesis outlined the consecutive hydroamination and hydrogenation of
ethynyl fragments catalyzed by B(C6F5)3 The novelty of this reactivity by FLP systems certainly
demands further explorations Catalytic hydroamination using FLPs could be extended to include
olefins and internal alkynes Furthermore the pursuit of an effective chiral borane catalyst may
provide a potential synthetic route to chiral amines of pharmaceutical and industrial interest
189
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iii
combination with cyclodextrins or molecular sieves Reductive deoxygenation occurs in the
particular case of aryl ketones
Finally the Lewis acid B(C6F5)3 is found to enable the intermolecular hydroamination of various
terminal alkynes giving iminium alkynylborate complexes of the general formula
[RPhN=C(CH3)R1][R1CequivCB(C6F5)3] The three-component reaction can also be performed
catalytically generating enamine products which are amenable to subsequent hydrogenation
reactions giving their corresponding amines The chemistry is expanded to intramolecular
systems forming N-heterocyclic compounds Furthermore a FLP route to stoichiometric
hydrophosphination of alkynes is developed
iv
Acknowledgments
Graduate school is not a journey taken alone rather it is one travelled with companions I have a
large group of wonderful people to thank for travelling by my side continuously supporting me
and putting a smile on my face
First and foremost I would like to take this opportunity to express my sincere gratitude to my
supervisor Prof Doug Stephan Thank you for your support you were always positive and open
to discussions Aside from developing my knowledge in chemistry you provided me with the
opportunity to build relationships and grow professionally I have also had the honour of having
very helpful committee members over the past few years Profs Bob Morris and Datong Song I
would like to thank you for your guidance and feedback through the seminar series and
committee meetings Prof Andrew Ashley I truly appreciate the time you took to provide me
with feedback for this thesis and attend my examination Thank you to Prof Erker at the
University of Muumlnster for accepting me to do an exchange in his research group
Of course the results in this thesis would not be publishable without the hard work of the staff at
the University of Toronto I would like to thank you all especially Darcy Burns Dmitry
Pichugin Rose Balazs and Matthew Forbes Also I would like to thank Chris Caputo Peter
Mirtchev Conor Prankevicius Alex Pulis and Adam Ruddy for your time in editing this thesis
All of the past and present Stephan group members thank you for the great times and of course
for doing your lab jobs and keeping the lab functional I definitely have to thank you Shanna for
keeping us in check
I want to give a big shout out to all my Athletic Centre gym buddies rock-climbing fellows
Chem Club soccer team champions and amazing Argon crossfitters I cannot express how much I
enjoyed every moment spent doing these outside-the-lab activities
A big I love you to my most amazing siblings Maithem Christina Jacob and Hoda I do not have
enough room here to express how much you guys mean to me but through it all we have stuck
together and this is how we will continue until the end To my future baby niece you have put a
smile on my face even while you are still inside the womb I cannot wait to meet you Finally to
the most supportive and kind-hearted person I have ever met Renan you have been there for me
from the start of this journey until the end Thank you all
v
Table of Contents
Abstract ii
Acknowledgments iv
Table of Contents v
List of Figures xi
List of Schemes xiv
List of Tables xix
List of Symbols and Abbreviations xxi
Chapter 1 Introduction 1
11 Science and Technology 1
111 Boron properties production and uses 2
112 Boron chemistry 3
12 Catalysis 4
13 Frustrated Lewis Pairs 5
131 Early discovery 5
132 Hydrogen activation and mechanism 6
133 Substrate hydrogenation 9
134 Activation of other small molecules 10
1341 Unsaturated hydrocarbons 10
1342 Alkenes 11
1343 Alkynes 11
1344 11-Carboboration 12
1345 CO2 and SO2 13
1346 FLP activation of carbonyl bonds 14
1347 Carbonyl hydrogenation 15
vi
1348 Carbonyl hydrosilylation 16
14 Scope of Thesis 17
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines and N-Heterocyclic Compounds 19
21 Introduction 19
211 Hydrogenation 19
212 Transfer hydrogenation 20
213 Main group catalysts 21
214 Hydrogenation of aromatic and heteroaromatic substrates 22
2141 Transition metal catalysts 22
2142 Metal-free catalysts 23
215 Reactivity of FLPs with H2 23
22 Results and Discussion 24
221 H2 activation by amineborane FLPs 24
222 Aromatic hydrogenation of N-phenyl amines 25
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates 30
223 Mechanistic studies for aromatic hydrogenation reactions 31
2231 Deuterium studies 31
2232 Variable temperature NMR studies 32
2233 Theoretical calculations 33
224 Aromatic hydrogenation of substituted N-bound phenyl rings 35
2241 Fluoro-substituted rings and C-F bond transformations 35
2242 Methoxy-substituted rings and C-O bond transformations 38
22421 Mechanistic studies for C-O and B-O bond cleavage 40
225 Aromatic hydrogenation of N-heterocyclic compounds 45
vii
2251 Hydrogenation of substituted pyridines 45
2252 Hydrogenation of substituted N-heterocycles 49
2253 Proposed mechanism for aromatic hydrogenation 55
2254 Approaches to dehydrogenation 55
23 Conclusions 56
24 Experimental Section 56
241 General considerations 56
242 Synthesis of compounds 57
243 X-Ray Crystallography 79
2431 X-Ray data collection and reduction 79
2432 X-Ray data solution and refinement 79
2433 Selected crystallographic data 81
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation with Frustrated Lewis Pairs 88
31 Introduction 88
311 FLP reactivity with unsaturated C-O bonds 88
32 Results and Discussion 92
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions 92
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents 93
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents 96
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism 97
325 Other hydrogen-bond acceptors for carbonyl hydrogenations 99
326 Other boron-based catalysts for carbonyl hydrogenations 99
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism 100
viii
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system 102
328 Attempted hydrogenation of other carbonyl substrates and epoxides 102
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases 103
3291 Polysaccharides as heterogeneous Lewis bases 104
3292 Molecular sieves as heterogeneous Lewis bases 107
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones 107
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation 110
32101 Verifying the reductive deoxygenation mechanism 111
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins 113
33 Conclusions 113
34 Experimental Section 114
341 General Considerations 114
342 Synthesis of Compounds 116
3421 Procedures for reactions in ethereal solvents 116
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3] 119
3423 Procedures for reactions using heterogeneous Lewis bases 120
3424 Procedures for reductive deoxygenation reactions 121
3425 Spectroscopic data of products in Table 31 121
3426 Spectroscopic data of products in Table 32 125
3427 Spectroscopic data of products in Table 33 125
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a) 127
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b) 128
343 X-Ray Crystallography 130
3431 X-Ray data collection and reduction 130
ix
3432 X-Ray data solution and refinement 130
3433 Selected crystallographic data 131
Chapter 4 Hydroamination and Hydrophosphination Reactions Using Frustrated Lewis Pairs 132
41 Introduction 132
411 Hydroamination 132
412 Reactions of main group FLPs with alkynes 133
4121 12-Addition or deprotonation reactions 133
4122 11-Carboboration reactions 134
4123 Hydroelementation reactions 135
413 Reactions of transition metal FLPs with alkynes 135
42 Results and Discussion 136
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes 136
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes 140
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates 141
4213 Reactivity of the iminium alkynylborate products with nucleophiles 141
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3 142
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes 144
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions 146
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes 147
424 Intramolecular hydroamination reactions using FLPs 148
4241 Stoichiometric hydroamination 148
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines 150
x
425 Reaction of B(C6F5)3 with ethynylphosphines 151
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines 153
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs 154
427 Proposed mechanism for the hydroborationhydrophosphination reactions 156
43 Conclusions 157
44 Experimental Section 157
441 General Considerations 157
442 Synthesis of Compounds 158
4421 Procedures for stoichiometric intermolecular hydroamination reactions 158
4422 Procedures for hydroarylation of phenylacetylene 165
4423 Procedures for catalytic intermolecular hydroamination reactions 167
4424 Procedures for tandem hydroamination and hydrogenation reactions 172
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions 173
4426 Procedures for reactions with ethynylphosphines 177
443 X-Ray Crystallography 179
4431 X-Ray data collection and reduction 179
4432 X-Ray data solution and refinement 180
4433 Platon Squeeze details 180
4434 Selected crystallographic data 181
Chapter 5 Conclusion 185
51 Thesis Summary 185
52 Future Work 186
References 189
xi
List of Figures
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage 8
Figure 12 ndash A highly efficient borenium hydrogenation catalyst 10
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis 21
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates 23
Figure 23 ndash POV-Ray depiction of 24rsquo 26
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+ 27
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($) 27
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right) 28
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right) 31
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-) 33
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol) 34
Figure 210 ndash POV-Ray drawing of 216a 36
xii
Figure 211 ndash POV-Ray drawing of 218 37
Figure 212 ndash POV-Ray drawing of 219 39
Figure 213 ndash POV-Ray drawing of trans-220 40
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c) 42
Figure 215 ndash POV-Ray drawing of 222 43
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right) 46
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring 48
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups 49
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring 49
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c) 50
Figure 221 ndash POV-Ray depiction of the cation for compound 231a 51
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring 52
Figure 223 ndash POV-Ray depiction of the cation for compound 233 52
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right) 53
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine 54
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol () 94
xiii
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol 95
Figure 33 ndash POV-Ray depiction of 31 98
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted 100
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
104
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD) 104
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased 112
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
136
Figure 42 ndash POV-Ray depiction of 47 137
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b) 139
Figure 44 ndash POV-Ray depiction of 410 139
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg 143
Figure 46 ndash POV-Ray depiction of 432 149
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons 152
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b) 153
Figure 49 ndash POV-Ray depictions of 442 155
xiv
List of Schemes
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3 4
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe) 4
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP 6
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c) 7
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K 9
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines 9
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom) 11
Scheme 18 ndash Reaction of FLPs with phenylacetylene 12
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom) 12
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base 13
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I) 14
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs 15
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP 16
xv
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom) 17
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine 20
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b) 24
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom) 25
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23 26
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD 32
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23 32
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts 35
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a 36
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218 37
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219 39
Scheme 211 ndash Synthesis of 220 and 212 40
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b) 41
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3 43
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3 44
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane 45
Scheme 216 ndash Proposed reaction pathway for the formation of 235 54
xvi
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom) 89
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b) 90
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols 90
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom) 91
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH 92
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation 93
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents 97
Scheme 38 ndash Synthesis of 31 98
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond 100
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation 102
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone 108
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b) 110
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones 111
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al) 133
xvii
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c) 134
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes 134
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes 135
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes 135
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
136
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts 140
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3 141
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4] 141
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right) 142
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3 142
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond 144
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes 147
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430 148
xviii
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432 149
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433 150
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH 151
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439 152
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440 154
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH 155
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments 156
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
187
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations 188
xix
List of Tables
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts 29
Table 22 ndash Hydrogenation of substituted pyridines 47
Table 23 ndash Hydrogenation of substituted N-heterocycles 51
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25 81
Table 25 ndash Selected crystallographic data for 216a 218 and 219 82
Table 26 ndash Selected crystallographic data for 220 222 and 224 83
Table 27 ndash Selected crystallographic data for 225 227 and 228 84
Table 28 ndash Selected crystallographic data for 229 230 and 231a 85
Table 29 ndash Selected crystallographic data for 231b 233 and 234a 86
Table 210 ndash Selected crystallographic data for 234b and 235 87
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents 96
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3] 101
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
106
Table 34 ndash Deoxygenation of aryl alkyl ketones 108
Table 35 ndash Deoxygenation of diaryl ketones 109
Table 36 ndash Selected crystallographic data for 31 131
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
138
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3 145
xx
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines 151
Table 44 ndash Selected crystallographic data for 41 47 and 48 181
Table 45 ndash Selected crystallographic data for 49 410 and 413 182
Table 46 ndash Selected crystallographic data for 414 432 and 439 183
Table 47 ndash Selected crystallographic data for 440 and 442 184
xxi
List of Symbols and Abbreviations
9-BBN 9-borabicyclo[331]nonane
α alpha
Aring angstrom 10-10 m
atm atmosphere
β beta
Bpin pinacolborane (4455-tetramethyl-132-dioxaborolane)
br broad
Boc tert-butyloxycarbonyl
Bu butyl
C Celsius
ca circa
calcd calculated
CD cyclodextrin
C6D6 deuterated benzene
C6H5Br bromobenzene
C6D5Br deuterated bromobenzene
CD2Cl2 deuterated dichloromethane
Cy cyclohexyl
δ chemical shift
xxii
deg degrees
d doublet
Da Dalton
DART direct analysis in real time
DEPT Distortionless Enhancement by Polarization Transfer
dd doublet of doublets
de diastereomeric excess
DFT density functional theory
dt doublet of triplets
ee enantiomeric excess
eq equivalent(s)
ESI electrospray ionization
Et ethyl
Et2O diethyl ether
FLP frustrated Lewis pair
γ gamma
ΔG Gibbs free energy
g gram
GC gas chromatography
GOF goodness of fit
xxiii
h hour
HRMS high resolution mass spectroscopy
HMBC heteronuclear multiple bond correlation
HOESY heteronuclear Overhauser effect NMR spectroscopy
HSQC heteronuclear single quantum correlation
Hz Hertz
iPr2O diisopropyl ether
nJxy n-scalar coupling constant between X and Y atoms
K Kelvin
kcal kilocalories
m meta
m multiplet
M molar concentration
Me methyl
Mes mesityl 246-trimethylphenyl
MHz megahertz
μL microliter
μmol micromole
mg milligram
min minute
xxiv
mL milliliter
mmol millimole
MS mass spectroscopy
MS molecular sieves
nPr n-propyl
iPr iso-propyl (CH(CH3)2)
NHC N-heterocyclic carbene
NMR Nuclear Magnetic Resonance
NOE Nuclear Overhauser Effect
o ortho
π pi
p para
POV-Ray Persistence of Vision Raytracer
PGM Platinum Group Metals
Ph phenyl
Ph2O diphenyl ether
ppb parts per billion 10-9
ppm parts per million 10-6
q quartet
quint quintet
xxv
rpm rotations per minute
RT room temperature
σ sigma
s singlet
t triplet
tBu tert-butyl
THF tetrahydrofuran
TMP 2266-tetramethylpiperidine
TMS trimethylsilyl
TMS2O hexamethyldisiloxane
tol toluene
wt weight
1
Chapter 1 Introduction
11 Science and Technology
The advent of the scientific revolution and the scientific method in early modern Europe
dramatically transformed the way scientists viewed the universe as they attempted to explain the
physical world through experimental investigation The long-term effects of the revolution can
be felt today with our dependence upon science to improve the quality of our lives and advance a
globally interconnected world Some scientific discoveries which have paved the way for such
enterprising technologies include the Haber-Bosch process used for the production of ammonia
essential to the synthesis of nitrogen fertilizers1-3 This discovery has dramatically increased food
production globally and allowed for the explosive population growth observed in the past
century Research also intensified to change the world of medicine through discovery of antiviral
agents for treatment of the HIVAIDS pandemic4-5 Ziegler-Natta catalysts have become central
to the polymer industry manufacturing the largest volumes of commodity plastics and
chemicals6-8
While many chemical breakthroughs have had significant benefits on public health their initial
application or even long-term impact on the environment may be detrimental For example
chlorine was used as a weapon during World War I9 while today it plays a vital role in
disinfecting drinking water and sanitation processes10 A more significant example is the
industrial revolution when manufacturing transitioned from manual labour to machines resulting
in unprecedented growth in population and standards of living Our continued reliance on
factories and mass production has led to depletion of natural resources and emission of
greenhouse gases resulting in anthropogenic climate change11-15
Scientists have acknowledged the need to remediate environmental impacts and to find more
environmentally acceptable technologies for the chemical industry To this end chemical
research has focused on implementing the principles of green chemistry16-17 to develop benign
processes which will sustain the growing energy demands of our society18-19 Central to the green
concept is the application of catalysis in chemical transformations in addition to using readily
available non-toxic raw materials in cost effective procedures
2
Rare precious metals such as the Platinum Group Metals (PGM) are extracted by mining of non-
renewable resources normally resulting in negative social and environmental impacts on the
area20 The metals are used in industrial chemical syntheses where they are regularly recovered
and recycled back into production It is essential however to gradually replace these reagents
with more environmentally benign and readily available transition metals in order to reduce
waste processing costs and eliminate the possibility of their release into the environment In this
aspect chemists are actively seeking innovations to advance more green chemical processes21-24
A vast majority of d-block transition metals have energetically accessible valence d-orbitals
allowing for oxidation state changes which are pivotal to substrate activation and accessing
stabilized transition states Additional factors including the steric and electronic tunability of the
ligand framework have led to the development of a broad range of metal catalysts applied in
numerous chemical transformations25-26 Nonetheless a growing number of advancements
involving the use of main group s and p-block elements have also shown reactivities similar to
those of transition metal complexes27-30
Main group elements are relatively abundant on Earth and over the last decade have experienced
a renaissance in chemical transformations Notably frustrated Lewis pair (FLP) systems which
involve the combination of Lewis acids and bases that are sterically and electronically prohibited
from forming a classical adduct have been at the forefront31 The unquenched reactivity of FLPs
has been explored in the activation of numerous small molecules The majority of FLP systems
incorporate boron Lewis acids and phosphorus Lewis bases32 In this thesis the potential to
expand FLP reactivity to nitrogenboron and oxygenboron pairs is explored
111 Boron properties production and uses
Boron (B) is a non-metallic element always found in nature bound to oxygen as orthoboric acid
alkali metal and alkaline earth metal borates33 Prominent sources of boron include the sodium
borate minerals rasorite and kernite found in deposits at the Mojave Desert of California and in
Turkey which is the largest producer of boron minerals33-34 Boron is vastly spread in Nature
however it constitutes only about 3 ppm of the Earthrsquos crust35-36
Industrially the production of pure boron is very difficult as it tends to form refractory materials
containing small amounts of carbon and other elements The method typically used for
3
commercial production of amorphous boron (up to 97 purity) is by reduction of B2O3 with Mg
in a thermite-like reaction Higher purity (gt99) boron is obtained by the reduction of boron
halides with H2 whereas ultra-purity can be achieved by thermal decomposition of boron
halideshydrides or diboranes on tungsten wires followed by zone melting purification37
Regardless of the production method different allotropic forms of boron can be accessed Short
reaction times at temperatures below 900 degC produce amorphous boron longer reaction times
above 1400 degC afford β-rhombohedral and optimal conditions in between the two give α-
rhombohedral36
Amorphous boron consisting of 90 - 92 purity costs approximately $100kg Relatively large
quantities of the material are used as additives in pyrotechnic mixtures Ultrapure (gt9999)
boron costs about $3500kg and is applied in electronics such as a dopant for germanium and
silicon p-type semiconductors Furthermore as the second hardest element inferior only to
diamond there is a growing demand for boron as a light-weight hardenability additive for glass
ceramics and boron filaments used in high-strength materials for the aerospace and steel
industries35-36
112 Boron chemistry
Boron has a valence shell electron configuration of 2s22p1 representing a typical formal
oxidation state of 3+ although due to its high ionization potentials simple B3+ ions do not exist
Boron can form three sp2 hybridized bonds resulting in trigonal planar geometry with a non-
bonding vacant p-orbital orthogonal to the plane susceptible towards electron donation giving
rise to its noted Lewis acidic properties38-40 Scales to quantify Lewis acidity have been designed
by studying the acceptor-donor interactions between Lewis acid and base complexes using NMR
spectroscopy data based on the Gutmann-Beckett41 and Childs42 methods43 IR spectroscopy X-
ray diffraction44 and density functional calculations45
The most common use of Lewis acids are the boron trihalides particularly BF3 and BCl3 in
conjunction with a co-initiator Lewis base such as water initiating cationic polymerization The
unsaturated olefin monomer is protonated generating the [BF3OH]- counterion along with a
carbenium ion which reacts with olefin molecules leading to propagation of the polymer46 With
Lewis acidity comparable to BF3 the Lewis acid B(C6F5)3 was lsquorediscoveredrsquo in the 1990s as an
ideal activator component for Ziegler-Natta olefin polymerization catalysts47 Treatment of a
4
Group 4 dialkyl-metallocene catalyst precursor with one equivalent of B(C6F5)3 results in alkyl
anion abstraction forming the active alkyl-metallocene cation (eg [Cp2ZrMe]+) stabilized by the
weakly coordinating [MeB(C6F5)3]- anion (Scheme 11)48-51
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3
Hydroboration the addition of B-H across multiple bonds of organic substrates such as alkenes
and alkynes provides the most common route to alkyl or alkenyl organoborane reagents
respectively52 The products obtained can be employed as intermediates for further synthetic
derivatization One powerful and general methodology used for the modification of
organoboranes53 is the Suzuki-Miyaura cross-coupling reaction (Scheme 12) These C(sp2)-B
and C(sp3)-B organoboranes readily undergo transmetalation with an electrophilic organo- Cu
Pd Ni or Fe catalyst to give coupled products with new C-C bonds54-55 Other applications of
boron reagents include metal borohydrides as reducing agents transferring hydride nucleophiles
to versatile functional groups56-59 Operating in a similar manner anionic borates consisting of
polarized B-C bonds transfer an organic group to an electrophilic centre38 60
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe)
Of particular relevance to this thesis recent advances in boron chemistry particularly involving
the activation and reactivity of small molecules with FLP systems will be discussed
12 Catalysis
In the early part of the 20th century catalysis developed into a scientific discipline and has
evolved to underlie numerous chemical technologies that benefit human life worldwide61 The
5
function of a catalyst substance added in a sub-stoichiometric amount is to lower the reaction
activation energy and affect selectivity for chemical transformations without being consumed62
Homogeneous catalysts have a long prevalence in industry with applications ranging from bulk
chemicals to complex multi-step processes Among the most prominent examples are the
Monsanto and Cativa processes for the carbonylation of methanol to produce acetic acid and the
oxo process for hydroformylation of olefins to yield aldehydes63 Only touching the tip of the
iceberg other commercial processes include the Wacker process for the oxidation of ethylene
aforementioned Ziegler-Natta olefin polymerization based on immobilized TiCl3 and substrate
hydrogenations using Wilkinsonrsquos Rh and Ru catalysts64-65 Other noteworthy discoveries
essential to the advancement of catalysis include Fischer-Tropsch production of liquid
hydrocarbons asymmetric catalysis olefin metathesis and Pd-catalyzed cross couplings66
The significance of catalysis for the development of chemistry has been recognized by the Nobel
Prize Committee with the earliest accreditation in the field awarded in 1909 to W Ostwald
Shortly thereafter Nobel Prizes were awarded for important contributions by P Sabatier (1912)
F Haber (1918) and C Bosch and F Bergius (1931) Since the turn of the millennium catalysis
has been recognized with four Chemistry Nobel Prizes awarded to 10 laureates66
13 Frustrated Lewis Pairs
131 Early discovery
The acid-base theory proposed by G N Lewis in 1923 is arguably one of the most important
theories in chemistry describing Lewis acid and base species as electron pair acceptors and
electron pair donors respectively67 According to the theory sterically unhindered Lewis acid-
base pairs react to form a Lewis adduct quenching subsequent reactivity This concept is
fundamental in most areas of chemistry involving the interaction of a doubly occupied orbital
(nucleophile) with an empty orbital (electrophile) forming a favourable overlap
Recent advances involving sterically encumbered Lewis pairs preclude such adduct formation
thereby rendering the individual components available for unique reactivity68-70 Astonishingly
in 1942 H C Brown reported that the ldquosteric strainrdquo between the Lewis acid trimethylborane
and the bulky Lewis base 26-lutidine does not result in adduct formation71 These early results
predate the recently popularized concept of frustrated Lewis pairs (FLPs) describing the
6
combination of Lewis acids and bases with sterically and electronically frustrated substituents
which prevent formal adduct formation32 The cooperative behaviour of these frustrated Lewis
centres has been evidenced to activate small molecules72
132 Hydrogen activation and mechanism
The first FLP reactivity was discovered by Stephan et al in 2006 while investigating the
chemistry of phosphonium borate linked zwitterions R2P(H)(C6F4)B(F)(C6F5)2 (R = alkyl or
aryl) generated from nucleophilic aromatic substitution of B(C6F5)3 by bulky secondary
phosphines31 Treatment with Me2SiHCl easily converts the linked zwitterion to the
phosphonium borohydride species containing both protic and hydridic hydrogen atoms In a
remarkable example the linked PHndashBH zwitterion (R = Mes) was found to liberate and rapidly
activate H2 representing the first example of reversible H2 activation using main group
compounds (Scheme 13)
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP
Hydrogen activation by main group compounds is rare the first example was reported in 2005
by the group of Power and co-workers describing the addition of H2 to heavier main group
digermyne compounds RGeequivGeR (R = aryl)30 The seminal finding was followed by the work of
Bertrand using bulky (alkyl)(amino)carbenes displaying both nucleophilic and electrophilic
characteristics to split and add H2 at a single carbon centre28 In a succeeding report by Piers the
antiaromatic Lewis acid perfluoropentaphenylborole was exclusively employed in H2 activation
to yield boracyclopent-3-ene products resulting from H2 addition to the two carbon atoms alpha
to boron73
After the initial breakthrough with FLPs their unique reactivity attracted immediate attention of
the scientific community Erker and co-workers have synthesized intramolecular PB FLPs
derived by the anti-Markovnikov addition of HB(C6F5)2 to vinyl phosphines (Scheme 14 a)74-75
Additionally Rieger and Repo have reported the nitrogen-based intramolecular FLP ansa-
7
aminoborane shown in Scheme 14 (b)76-78 These systems heterolytically split H2 albeit
reversible H2 activation was only demonstrated for the ansa-aminoborane
Hydrogen activation has also been extended to bimolecular systems Combinations of B(C6F5)3
and sterically encumbered tertiary phosphines were found to effect H2 activation (Scheme 14
c)32 In one example the weaker Lewis acid B(p-HC6F4)3 and o-tolyl3P were found to liberate H2
under vacuum79-80
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c)
The initial mechanism proposed for heterolytic splitting of H2 was speculated to be a ldquoside-onrdquo
or ldquoend-onrdquo coordination of H2 to either the boron or phosphorus moiety followed by approach
of the respective FLP partner effecting H-H bond cleavage This mechanism was not found to be
computationally supported despite earlier evidence for the ldquoside-onrdquo mechanism based on BH3-
H2 adducts81-84 While mechanistic details remain debated theoretical investigations by the
groups of Paacutepai85-87 and Grimme88 were performed on the prototype tBu3PB(C6F5)3 FLP Both
groups agree on the formation of an ldquoencounter complexrdquo stabilized by CndashH---F dispersion
interactions between the phosphine methyl groups and C6F5 borane rings As a result the Lewis
pair orient such that the boron is in close proximity to the phosphorus centre The electron
transfer model proposed by Paacutepai89 explains hydrogen activation by synergistic interaction of the
8
Lewis pair inducing polarization on the H2 molecule effecting heterolytic cleavage In this case
donation from the σ orbital of H2 into the empty orbital on the Lewis acid occurs in conjunction
with lone pair donation from the Lewis base to the σ orbital of H2 representing a process
similar to metal-based heterolytic cleavage of H2 (Figure 11 a) In contrast the electric field
model reported by Grimme suggests heterolytic H2 activation is a barrierless process resulting
from the exposure of H2 to a sufficiently strong homogeneous electric field pocket created by the
FLP complex Interpretation of this model does not consider electron donation or the orbitals of
the FLP or H2 (Figure 11 b)
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage
Direct investigation of H2 activation intermediates by standard experimental techniques has been
unquestionably demanding Experimental evidence of an encounter complex has been observed
by 19F1H HOESY NMR studies revealing contacts between all protons of R3P (R = tBu Mes)
and fluorine nuclei of B(C6F5)3 although only a rough orientation of the molecules was
reported90 Examination of a related system has recently been reported by the Piers group In this
case combination of a highly electrophilic boraindene and Et3SiH gave an isolable borane-silane
complex affirming details of adduct formation in FLP hydrosilylation and to a certain extent
extrapolated to the closely related H2 activation reaction (Scheme 15)91
9
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K
133 Substrate hydrogenation
Reversible H2 activation by the initial FLP Mes2P(H)(C6F4)B(H)(C6F5)2 was a landmark
discovery that shed light onto potential important applications of such systems Most significant
of these efforts was demonstrated by employing R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) in the
catalytic reduction of unsaturated substrates specifically bulky imines and N-protected nitriles to
corresponding amines using 5 mol catalyst 5 atm of H2 and temperatures ranging from 80 -
100 degC Concerted investigations in the field revealed that sterically hindered substrates could
also serve as the Lewis base in splitting hydrogen92-93 To this end catalytic amounts of B(C6F5)3
in combination with various bulky aldimines and ketimines were reduced under 5 atm of H2 at
120 degC with isolated yields in the range of 89 - 99 Based on experimental observations the
proposed mechanism suggests H2 is cleaved between the bulky imine and B(C6F5)3 followed by
hydride delivery to the iminium cation (Scheme 16)
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines
10
Following the early reports on metal-free catalytic hydrogenation the reduction of various other
substrates has been demonstrated to include aziridines92 94 enamines93 enones95 silyl enol
ethers96-97 N-heterocycles98 olefins99 and most recently alkynes have been reduced to cis-
alkenes100 Asymmetric hydrogenation by chiral FLPs was first demonstrated in 2008 by
Klankermayer and co-workers to give a chiral amine with 13 ee and later improvements up to
83 were obtained using a camphor derived catalyst101-102 Rieger and Repo saw ee values of
3776 103 while significant improvements up to 89 were achieved by the Du group104
Recently borenium cations have been used as Lewis acids in FLP chemistry with remarkable
catalytic activity for the hydrogenation of imines and enamines at room temperature (Figure
12)105
Figure 12 ndash A highly efficient borenium hydrogenation catalyst
134 Activation of other small molecules
FLP-mediated bond activations have been explored for a multitude of small molecules including
CO2106-107 N2O108-112 SO2113-114 NO115-116 CO107 117-119 NSO120 fluoroalkanes121 ether122
disulfides123 alkenes124-125 and alkynes126-128 FLPs have also been exploited in radical
polymerizations116 and more recently in materials and surface science129 Efforts have also
continued to exploit FLP chemistry in synthetic organic applications130 Beyond here small
molecule transformations that are relevant to the chemistry presented in this thesis will be
discussed
1341 Unsaturated hydrocarbons
Reactivity of unsaturated hydrocarbons has been a field traditionally associated with transition
metal chemistry and has found particular use for organic synthesis131-138 The dramatic evolution
in FLP systems has raised interest in probing the reactivity of main group complexes with
alkenes and alkynes100 139-140 This reactivity is reminiscent of related findings by Wittig and
Benz in 1959 involving the addition of Ph3P and BPh3 to benzyne affording zwitterionic
11
phosphonium-borates141 In the same context Tochtermann showed the addition of the bulky
carbanion [Ph3C]- and Lewis acid BPh3 across the double bond of 13-butadiene rather than
anionic polymerization of the conjugated diene142
1342 Alkenes
The reaction of FLPs with alkenes is particularly intriguing as the individual Lewis components
do not react with the substrate rather the three component combination of R3P B(C6F5)3 and
alkene exhibited intermolecular 12-addition reactions (Scheme 17 top)143-144 Similar activation
results were also observed upon exposure to the ethylene-linked FLP Mes2PCH2CH2B(C6F5)2145-
147 In two remarkable examples the Stephan group provided spectroscopic theoretical148 and
crystallographic149 evidence for Lewis acid-olefin van der Waals complexes forming prior to
FLP additions (Scheme 17 bottom)
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom)
1343 Alkynes
Initial reactivity of FLPs with terminal alkynes featured the facile deprotonation or addition of
phosphineLewis acid (B Al) combinations to afford alkynylborate (aluminate) salts or
zwitterions with selectivity of the reaction correlated to the basicity of the phosphine (Scheme
18)126 128 In a joint report by the Stephan and Erker groups the B(C6F5)3-mediated
intramolecular cyclization of an ortho-ethynylaniline to access a cyclic anilinium borate was
presented150-151 In an analogous fashion Stephan and co-workers showed the cyclization of
alkyne- and alkene-tethered pyridines and quinolines using B(C6F5)3152 The groups of Berke
12
Erker Stephan and Uhl expanded the chemistry by varying the Lewis acid to BPh3 and alanes153
as well as the Lewis base to include phosphines154 polyphosphines155 thioethers amines and
pyridines156 carbenes157 and pyrroles158
Scheme 18 ndash Reaction of FLPs with phenylacetylene
1344 11-Carboboration
Particularly prolific in the research area of FLP reactivity with alkynes the groups of Erker and
Berke separately unravelled the 11-carboboration reaction resulting from the electrophilic
attack of the CequivC triple bond of an alkyne by highly electrophilic boranes RB(C6F5)2 generating
alkenylborane products (Scheme 19)156 159-160
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom)
In the absence of a Lewis base the combination of electrophilic boranes and terminal alkynes are
postulated to generate a vinylidene intermediate stabilized by 12-hydride migration to the
carbocation Subsequently scission of a BndashC bond transfers a substituent from the borane to the
same carbon of the alkyne generating the alkenylborane (Scheme 110 left)159 This simple yet
elegant strategy demonstrates a facile route to borane derivatives with a C(sp2)-B centre that
could be further treated under Suzuki cross-coupling conditions161 In the presence of a Lewis
13
base deprotonation of the vinylidene or nucleophilic addition at the carbocation takes place
(Scheme 110 right)
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base
1345 CO2 and SO2
Following the reactivity of FLPs with olefins successful joint efforts by the Stephan and Erker
groups showed the activation of the greenhouse gas CO2 and acid rain contributor SO2 using the
FLP tBu3PB(C6F5)3 and ethylene-linked PB system Mes2PCH2CH2B(C6F5)2 (Scheme 111 a
and b)113-114 Key differences were observed in the reactivity of the two gases For example the
reversible nature of binding CO2 was not observed with the SO2 bound species Furthermore the
six-membered SO2 adducts derived from linked PB FLPs gave a stereogenic sulphur centre
resulting in a pair of isomers (Scheme 111 b) The Stephan group extended the activation of
CO2 beyond borane Lewis acids To this end 12 combinations of bulky phosphines and AlX3 (X
= halide or C6F5) react with CO2 rapidly leading to the formation of R3P(CO2)(AlX3)2 (Scheme
111 c)
14
Mes2P B(C6F5)2
EO2Mes2P B(C6F5)2
E O
O
R R
gt -20 degC- CO2
tBu3P B(C6F5)3EO2
80 degC- CO2
PB(C6F5)3E
O
O
tBu3
Mes3P 2 AlX3 Mes3PAlX3E
O
O
AlX3
CO2
b)
a)
c)
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I)
In the case of CO2 further chemical transformation of the activated molecule has been
presented107 111 153 162-164 including efforts to reduce CO2 to CH3OH The groups of Ashley and
OrsquoHare presented this reactivity using H2 as the reducing source Stephan et al used ammonia
borane165 and this process has been achieved catalytically by Fontaine using hydroboranes166-168
Additionally Piers reported the catalytic deoxygenative reduction of CO2 to CH4 using silanes169
and Stephan showed the stoichiometric reduction of CO2 to CO using R3PAlX3 FLPs170
1346 FLP activation of carbonyl bonds
Efforts to include oxygen-based substrates in FLP-mediated catalytic transformations have found
limited success due to the high affinity of electrophilic boranes towards oxygen species72 171
Investigations by Erker and co-workers described the irreversible capture of benzaldehyde and
trans-cinnamaldehyde at the C=O functional group by the intramolecular FLP
Mes2PCH2CH2B(C6F5)2 (Scheme 112 top)172-173 Similar alkoxyborate products were obtained
in the reaction of NB FLPs with benzaldehyde (Scheme 112 bottom)174
15
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs
1347 Carbonyl hydrogenation
Metal-free hydrogenation of carbonyl substrates was reported as early as 1961 by Walling and
Bollyky for the homogeneous hydrogenation of ketones catalyzed by alkali metal alkoxides175
About 40 years later Berkessel and co-workers communicated mechanistic studies on the
process which were supported thereafter by computational investigations176 The authors
elucidated mechanistic analogies between base-catalyzed ketone hydrogenation and Ru-
catalyzed transfer hydrogenation by Noyori whereby a Broslashnsted base participates in H2
heterolysis177 Although this is the first example of metal-free reduction of ketone the reactions
are performed at relatively harsh conditions requiring 100 atm of H2 and 200 degC Moreover the
substrate scope was limited to the non-enolizable ketone benzophenone
The reaction of benzaldehyde with the intramolecular H2-activated FLP
R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) was found to proceed in a stoichiometric fashion
reducing the C=O double bond formulating the zwitterion R2P(H)(C6F4)B(C6F5)2OCH2Ph
(Scheme 113) Chemical intuition would perhaps point to proton transfer from the phosphonium
centre this is however prevented by the lower basicity of the oxygen atom contrasting
hydrogenation reactions with nitrogen substrates
16
B(C6F5)2R2P
FF
F F
H
H
O
HPhB(C6F5)2R2P
FF
F F
H O
Ph
R = tBu Mes
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP
Based on the principle for catalytic hydrogenation of imines Repo and co-workers explored
C=O hydrogenations using the aromatic carbonyl substrates benzophenone and benzaldehyde as
Lewis bases along with the Lewis acid B(C6F5)3 Experimental results indicated the reaction to
be challenging generating only sub-stoichiometric amounts of the alcohol products due to rapid
decomposition of the borane178
1348 Carbonyl hydrosilylation
Hydrosilylation is one of the most commonly applied processes within the chemical industry
today New catalytic technologies providing avenues for metal-free SindashH bond activation have
become appealing alternatives to traditional transition metal catalysts179 Impressively in 1996
the Piers group reported 1 - 4 mol of B(C6F5)3 to effect the catalytic hydrosilylation of
aromatic aldehydes ketones and esters at room temperature (Scheme 114 top)180-182 Clever
analysis of the mechanism by Oestreich using a stereochemically pure silane found inversion of
stereochemistry at silicon after hydrosilylation This finding rationalized a concerted SN2 type
displacement at the silicon centre of a (C6F5)3Bδ-middotmiddotmiddotHmiddotmiddotmiddot SiR3δ+ transition state by the substrate
carbonyl oxygen (Scheme 114 bottom)183
17
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom)
14 Scope of Thesis
The objective of this graduate research was to expand the scope of FLP reactions using the Lewis
acid B(C6F5)3 Although previous studies have documented the reactivity of B(C6F5)3 with small
molecules further transformation of the activated species in organic syntheses remains limited
In this work FLP hydrogenation reactions were extended to include the aromatic rings of N-
phenyl amines and N-heterocyclic compounds as described in Chapter 2 Tandem hydrogenation
and transannulation reactions occurred with a para-methoxy substituted aniline affording a 7-
azabicyclo[221]heptane derivative Mechanistic studies of this reactivity provided insight to a
viable approach achieving the catalytic hydrogenation of ketones and aldehydes to form alcohol
products presented in Chapter 3 In addition the reductive deoxygenation of aryl ketones to
aromatic hydrocarbons was investigated Finally Chapter 4 expands FLP catalytic reactions
beyond hydrogenations In this chapter B(C6F5)3 catalyzed hydroamination of terminal alkynes
is investigated with extension to intramolecular systems and stoichiometric hydrophosphination
reactions
All synthetic work and characterizations were performed by the author with the exception of
elemental analyses high resolution mass spectroscopy and X-ray experiments DFT calculations
for the aromatic hydrogenations described in Chapter 2 were performed by Professor Stefan
Grimme at Universitaumlt Bonn Germany Compounds 216 - 218 were initially synthesized by an
undergraduate student Jon Nathaniel del Castillo under the authorrsquos supervision The synthesis
of compounds 439 and 440 were initially performed by the author at the University of Toronto
18
and repeated during a four month research opportunity program in the laboratory of Professor
Gerhard Erker at Universitaumlt Muumlnster Germany Compounds 441 and 442 were prepared at
Universitaumlt Muumlnster and the structure of 442 was obtained and solved by Dr Constantin
Daniliuc All other molecular structures were solved by the author and the authorrsquos supervisor
Professor Douglas Stephan
Portions of each chapter have been published or accepted at the time of writing
Chapter 2 1) Voss T Mahdi T Otten E Froumlhlich R Kehr G Stephan D W Erker G
ldquoFrustrated Lewis Pair Behavior of Intermolecular AmineB(C6F5)3 Pairsrdquo Organometallics
2012 31 2367-2378 2) Mahdi T Heiden Z M Grimme S Stephan D W ldquoMetal-Free
Aromatic Hydrogenation Aniline to Cyclohexylamine Derivativesrdquo J Am Chem Soc 2012
134 4088-4091 3) Mahdi T Castillo J N Stephan D W ldquoMetal-Free Hydrogenation of N-
based Heterocyclesrdquo Organometallics 2013 32 1971-1978 4) Longobardi L E Mahdi T
Stephan D W ldquoB(C6F5)3 Mediated Arene HydrogenationTransannulation of para-
Methoxyanilinesrdquo Dalton Trans 2015 44 7114-7117
Chapter 3 5) Mahdi T Stephan D W ldquoEnabling Catalytic Ketone Hydrogenation by
Frustrated Lewis Pairsrdquo J Am Chem Soc 2014 136 15809-15812 6) Mahdi T Stephan D
W ldquoFacile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive
Deoxygenation of Ketones and Aldehydesrdquo Angew Chem Int Ed 2015 DOI
101002anie201503087
Chapter 4 7) Mahdi T Stephan D W ldquoFrustrated Lewis Pair Catalysed Hydroamination of
Terminal Alkynesrdquo Angew Chem Int Ed 2013 52 12418-12421 8) Mahdi T Stephan D
W ldquoInter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairsrdquo
Chem Eur J 2015 accepted
19
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines
and N-Heterocyclic Compounds
21 Introduction
211 Hydrogenation
Hydrogenation the addition of hydrogen (H2) to unsaturated compounds is one of the simplest
and most attractive chemical processes performed today26 The reaction is employed for the
production of commodity chemicals with widespread application in the petrochemical
pharmaceutical and foods industries One of the largest industrial applications of hydrogenation
is in the Haber-Bosch process63 66 184 This method uses N2 and H2 to produce ammonia which is
essential for the synthesis of nitrogen fertilizers currently sustaining about one-third of the
worldrsquos population Additionally significant is the Fischer-Tropsch process used to generate
liquid hydrocarbons from the chemical reaction of H2 and CO (synthesis gas)185-186
In the early part of the 20th century P Sabatier discovered the catalytic hydrogenation of organic
substrates over finely divided nickel thereby greatly advancing the field of organic chemistry187-
193 Approximately 60 years later Wilkinson uncovered the homogeneous hydrogenation of
olefins using Ru and Rh catalysts a development that was crowned initiator of organometallic
chemistry (Scheme 21 a)194-197 Further developments in metal-based hydrogenations were
made in the 1980s including the Nobel Prize winning work of asymmetric hydrogenations by
Noyori and Knowles (Scheme 21 b)198-207 While precious metal catalysts208-209 are known to
carry out this reactivity (Scheme 21 c) the high cost and low abundance of these metals
necessitates the development of more cost-efficient procedures New technologies providing
avenues for greener transformations have recently been illustrated using first-row transition
metals Fe and Co (Scheme 21 d)136 210-214
20
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine
212 Transfer hydrogenation
A variety of insightful strategies have provided alternative avenues to direct hydrogenation One
such example is transfer hydrogenation the addition of hydrogen to an unsaturated substrate
from a source other than gaseous H2 In the 1920s Meerwein Ponndorf and Verley (MPV)
demonstrated the first example of hydrogen transfer from a sacrificial alcohol to ketone using an
aluminum alkoxide catalyst215-217 Nonetheless interest in using organocatalysts for
hydrogenation reactions increased spectacularly due to novelty of the concept efficiency and
selectivity in organic reactions Particularly recognized are chiral amine catalysts in combination
with Hantzsch ester dihydropyridines which act as mild organic sources of H2218-219 Extensive
research has also focused on new transition metal catalysts for efficient dehydrocoupling of
ammonia borane (H3NBH3) and related amine borane compounds220
Although transfer hydrogenation is a process dominated by precious transition metal catalysts
Earth abundant less toxic Fe-based catalysts have proven remarkably active effecting high
enantioselectivity (Figure 21 a)221 Moreover catalyst-free strategies by Berke and co-workers
have promoted transfer hydrogenation of imines and polarized olefins222 Stephan et al
underscored extension of metal-free catalysis reporting a highly electrophilic phosphonium
cation catalyst for application in dehydrocoupling of protic compounds with silanes and transfer
hydrogenation to olefins (Figure 21 b)223
RhPh3P
Ph3P Cl
PPh3
(a) (b) (c)
(d)
21
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis
213 Main group catalysts
The discovery of sodium borohydride and lithium aluminum hydride in the 1940s introduced
new stoichiometric methods for the hydrogenation of unsaturated functional groups56 59 224 A
variety of these metal hydride reagents possessing a high degree of chemoselectivity have made
the reduction of a broad range of functional groups possible although catalytic procedures are
evidently more desirable In this vein the first non-transition metal catalyst for ketone
hydrogenation employing tBuOK and H2 is regarded as a breakthrough175-176 Early main group
metal catalysts have followed with highlights on a well-defined organocalcium catalyst
developed by Harder225 and the first cationic calcium hydrides by Okuda capable of catalytic
hydrogenation of 11-diphenylethylene226
Renaissance in main group chemistry emerged with the discovery of frustrated Lewis pairs
(FLPs) These relatively common main group reagents have been applied in the hydrogenation of
imines nitriles aziridines enamines silyl enol ethers olefins and alkynes typically using boron
Lewis acids relying on perfluoroaryl substituents227-228 More recently Lewis acidic borenium
ions based on an [NHC-9-BBN]+ framework have also proven ideal for hydrogenation of imine
and enamine substrates105 Du et al described the highly enantioselective hydrogenation of
imines using a chiral borane catalyst derived from the hydroboration of chiral diene
substituents104 Alkyl229 and aryl149 aluminum compounds in addition to metal-activated carbon-
based Lewis acids have been shown to participate in similar reactivity230
(a) (b)
22
214 Hydrogenation of aromatic and heteroaromatic substrates
2141 Transition metal catalysts
Despite advancements in hydrogenation catalysis the reduction of arenes and heteroaromatics to
saturated cyclic hydrocarbons remains challenging and is typically performed in the
heterogeneous phase using transition metal catalysts Such hydrogenations find particular use in
the petrochemical industry to convert alkene and aromatic fossil fuels into liquid hydrocarbons
before application in commodities such as synthetic fuel26 231 The number of complexes capable
of this catalysis is scarce mainly due to the high energy barrier required to disrupt aromaticity
Catalytic hydrogenation of aromatic systems was first demonstrated for phenols anilines and
benzene in the early 1900s by P Sabatier using powdered nickel189-193 Soon after the 14-
reduction of anisole was observed using dissolved alkali metals in liquid ammonia with major
developments emerging to include benzene and naphthalene derivatives232-233 Historically
significant accomplishments include the work of R Adams using finely divided platinum oxide
(Adamrsquos catalyst)234 and M Raney based on digestion of alloys to form finely divided metal
samples (Raney nickel)235 Other highly efficient catalysts include organometallic compounds
particularly Co Ni Ru and Rh deposited on to oxide surfaces236-239
The number of homogeneous systems capable of hydrogenating arene substrates lags well behind
heterogeneous systems The first well-documented homogeneous catalyst is a simple allylcobalt
complex η3-C3H5Co[P(OMe)3]3 reported by Muetterties and co-workers operating at room
temperature (Figure 22 left)240 shadowed by a new generation of TaV and NbV hydride catalysts
featuring bulky ancillary aryloxide ligands by Rothwell (Figure 22 right)241-243 It is noteworthy
that metal complexes of the cobalt group have provided valuable mechanistic information on this
transformation231 Ziegler type catalysts consisting of Ni or Co alkoxides acetylacetonates or
carboxylates with trialkylaluminum activators have also been demonstrated in the large scale
Institut Francais du Petrole (IFP) process231
23
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates
2142 Metal-free catalysts
Non-metal mediated routes such as the facile addition of borohydrides to unsaturated bonds
were developed early on by Brown and co-workers244 To this extent Koumlster has reported the
hydroboration and subsequent hydrogenolysis to convert naphthalenes to tetralins and
anthracenes to coronenes at 170 - 200 degC and 25 - 100 atm of H2245-246 Alternative efforts
demonstrated trialkylborane and tetraalkyldiborane catalysts in hydrogenating olefins and
polycyclic aromatic hydrocarbons including coal tar pitch In another finding homogeneous
iodine and borane catalysts were shown to hydrogenate the aromatic units of high-rank
bituminous coals at temperatures above 250 degC and 150 - 250 atm of H226 In a recent report the
Wang group has demonstrated the hydrogenation of unfunctionalized olefins catalyzed by
HB(C6F5)2247
215 Reactivity of FLPs with H2
The feasibility of FLP systems to activate H2 and hydrogenate unsaturated substrates
particularly heteroaromatic rings has been examined In this respect 26-lutidine and B(C6F5)3
exhibit reversible dissociation of the Lewis acid-base adduct providing a FLP-mode to H2
activation (Scheme 22 a)248-249 Similar acid-base equilibria were observed with N-heterocycles
nonetheless a catalytic amount of B(C6F5)3 and H2 results in reduction of the N-heterocyclic ring
(Scheme 22 b)98 Research by the Sooacutes group extended the scope of such catalytic reductions
using specifically designed Lewis acids250
24
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b)
Following these reports the commercially available Lewis acid B(C6F5)3251-252 was explored in
the hydrogenation of aromatic rings This chapter will describe results in metal-free aromatic
hydrogenation of N-bound phenyl rings of amines imines and aziridines in addition to pyridines
and N-heterocycles While these reductions are stoichiometric they represent rare examples of
homogeneous aromatic reductions that are metal-free and performed under comparatively mild
conditions Moreover the tandem hydrogenation and intramolecular cyclization of a para-
methoxy substituted aniline is presented This reaction provides a unique route to a 7-
azabicyclo[221]heptane derivative
22 Results and Discussion
221 H2 activation by amineborane FLPs
Phosphine-based FLPs have been thoroughly investigated in the activation of small molecules
and particularly revolutionizing is the first demonstration of reversible heterolytic H2 activation
by Mes2P(C6F4)B(C6F5)231 The corresponding chemistry with amineborane FLP systems has
been less explored Combination of the bulky amine tBuNHPh and an equivalent of B(C6F5)3 in
C6D5Br or pentane solutions do not result an apparent interaction by 1H 11B and 19F NMR
spectroscopy indeed supporting the ldquofrustratedrdquo nature of the system Following exposure of this
solution to H2 (4 atm) at 25 degC the gradual precipitation of a white solid was observed and after
12 h the H2 activated species [tBuNH2Ph][HB(C6F5)3] 21 was isolated in 82 yield (Scheme
23 top) The 1H NMR spectrum obtained in C6D5Br showed a broad resonance at 715 ppm
attributable to an NH2 fragment integrating to two protons as well as signals assignable to the
25
phenyl and tBu groups In addition 11B NMR spectroscopy revealed a doublet at -240 ppm (1JB-
H = 78 Hz) and 19F resonances were observed at -1335 -1613 and -1650 ppm These data
along with elemental analysis were consistent with the formulation of 21 Similar treatment of
the diamine 14-C6H4(CH2NHtBu)2 with two equivalents of B(C6F5)3 in toluene and exposure to
H2 (4 atm) resulted in formation of a precipitate at 25 degC Subsequent isolation of the product
afforded quantitative yield of the salt [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 22 (Scheme 23
bottom) The 1H NMR data showed signals at 595 ppm and 339 ppm attributable to the NH2
and BH fragments respectively The 11B and 19F NMR signals were consistent with the presence
of the [HB(C6F5)3]- anion
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom)
222 Aromatic hydrogenation of N-phenyl amines
Repetition of the H2 activation reaction between tBuNHPh and B(C6F5)3 in toluene with heating
at 110 degC for 48 h led to formation of a new product 23 Subsequent workup and
characterization by NMR spectroscopy revealed the presence of the [HB(C6F5)3]- anion The 1H
NMR spectrum displayed a broad resonance at 507 ppm attributed to an NH2 moiety while
aromatic resonances were notably absent Instead multiplets between 272 and 090 ppm along
with a sharp singlet at 091 ppm were observed This data was consistent with the identity of 23
as the cyclohexylamine product [tBuNH2Cy][HB(C6F5)3] (Scheme 24) By 1H NMR
spectroscopy after 48 h at 110 degC the reaction constituted approximately complete conversion
to 23 and was isolated in 84 yield (Table 21 entry 1)
26
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23
Treatment of iPrNHPh with an equivalent of B(C6F5)3 in toluene at 25 degC gave the
crystallographically characterized adduct (iPrNHPh)B(C6F5)3 24rsquo (Figure 23) This compound
exhibited broad resonances in the 1H 11B 13C and 19F NMR spectra at RT indicating a
fluxional adduct Upon cooling the sample to 193 K NMR signals coalesce giving distinct
resonances assignable to the adduct along with 15 inequivalent 19F resonances that are consistent
with a barrier of rotation of the pentafluorophenyl rings
Figure 23 ndash POV-Ray depiction of 24rsquo
Introducing the amine-borane adduct 24rsquo to H2 (4 atm) does not result in any noticeable changes
in the NMR spectra at RT Although thermolysis of the sample up to 70 degC eventually reveals
dissociation of the adduct with concurrent hydrogenation giving products of complete and partial
reduction of the phenyl ring The partially reduced product observed in trace amounts consisted
of olefinic resonances at 577 and 553 ppm and corresponding aliphatic signals at 256 and 222
ppm (Figure 24 insets) Extensive 1H1H COSY and 1H13C HSQC NMR studies confirmed
the compound as the partially hydrogenated 3-cyclohexenyl derivative [3-
(C6H9)NH2iPr][HB(C6F5)3] the cation is depicted in Figure 24
27
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+
Repeating the reaction at 110 degC for 36 h resulted in complete reduction of the aromatic ring
affording the salt [iPrNH2Cy][HB(C6F5)3] 24 in 93 yield (Table 21 entry 1) Monitoring the
reaction in a J-Young tube by 1H NMR spectroscopy at 110 degC showed the gradual growth of the
cyclohexyl methylene resonances with the corresponding consumption of aromatic signals
(Figure 25)
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($)
12 h
9 h
6 h
3 h
15 h
05 h
$
HB HA
28
The hydrogenation protocol was applied to PhCyNH and Ph2NH affording [Cy2NH2][HB(C6F5)3]
25 in yields of 88 and 65 respectively (Table 21 entry 2) Monitoring the reaction of Ph2NH
at 24 h intervals by 1H NMR spectroscopy did not show evidence for formation of PhCyNH
presumably this indicates that complete hydrogenation of both arene rings occurs prior to
addition of the first equivalent of hydrogen to another molecule of Ph2NH In addition to the
NMR spectroscopy data formulation of 24 and 25 were determined via X-ray crystallography
(Figure 26)
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right)
In an analogous fashion further substrates explored in such reductions included iPrNH(2-
MeC6H4) iPrNH(4-RC6H4) (R = Me OMe) iPrNH(3-MeC6H4) and iPrNH(35-Me2C6H3)
affording the arene-reduced products [iPrNH2(2-MeC6H10)][HB(C6F5)3] 26 [iPrNH2(4-
RC6H10)][HB(C6F5)3] (R = Me 27 OMe 28) [iPrNH2(3-MeC6H10)][HB(C6F5)3] 29 and
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] 210 in yields of 77 73 61 82 and 48 respectively (Table
21 entries 3 - 5) In cases where the hydrogenation reactions yield a chiral centre a mixture of
diastereomers was observed
Previously the Stephan group reported the catalytic hydrogenative ring-opening of cis-123-
triphenylaziridine using 5 mol B(C6F5)3 and H2 (4 atm) to give PhNHCHPhCH2Ph in 15 h at
120 degC94 In the following case however employing one equivalent of B(C6F5)3 at 110 ordmC for 96
h resulted in reduction of the N-bound phenyl ring yielding the salt
[CyNH2CHPhCH2Ph][HB(C6F5)3] 211 (Table 21 entry 6) The 1H NMR data were in
agreement with formulation of the cation fragment with notable resonances at 588 and 461
ppm ascribed to the NH2 and methine groups respectively in addition to the phenyl
29
cyclohexyl methylene and BH signals 11B and 19F NMR spectra displayed resonances
characteristic of the [HB(C6F5)3]- anion
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts
30
Reduction of the imine PhN=CMePh to the corresponding amine has also been previously
reported to occur upon exposure of the imine to H2 using 10 mol B(C6F5)392 Under the same
conditions heating the substrate in the presence of one equivalent of B(C6F5)3 for 96 h gave
reduction of the N-bound aromatic ring affording the species [PhCH(Me)NH2Cy][HB(C6F5)3]
212 (Table 21 entry 7) Similarly reduction of 14-C6H4(N=CMe2)2 was observed on heating
for 72 h in the presence of two equivalents of B(C6F5)3 yielding 64 of the product [14-
C6H10(iPrNH2)2][HB(C6F5)3]2 213 (Table 21 entry 8) Aromatic reduction of the bis-arene (14-
C6H4iPrNH)2CH2 with two equivalents of B(C6F5)3 was also achieved affording [(14-
C6H10iPrNH2)2CH2][HB(C6F5)3]2 214 in 76 yield (Table 21 entry 9)
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates
Although this reaction is stoichiometric in B(C6F5)3 hydrogenation of one arene ring takes up
three equivalents of H2 In an attempt to effect reactivity using sub-stoichiometric combinations
of the Lewis acid 5 mol B(C6F5)3 was combined with iPrNHPh pressurized with H2 (4 atm)
and heated at 120 degC After 24 h 1H NMR data yielded complete conversion of the borane to the
[HB(C6F5)3]- anion with only 5 mol conversion of the aniline to the [iPrNH2Cy]+ cation The
remaining 95 of the initial aniline was unaltered Increasing the H2 pressure to 80 atm did not
improve reactivity The inability of the system to turnover could be explained by pKa values of
the conjugate acid for example iPrNHPh has a pKa value of 58 in H2O while the hydrogenated
product has a pKa of about 10 - 11 in H2O (iPr2NH2 pKa 1105 in H2O) thus preventing
reversible activation of H2253-254
Furthermore efforts to hydrogenate the arene ring of iPrNHPh using pre-H2 activated FLPs
[tBu3PH][HB(C6F5)3] [Mes3PH][HB(C6F5)3] and tBu2P(H)(C6F4)B(H)(C6F5)2 did not result in
any observable reactivity by NMR spectroscopy However the stoichiometric combination of the
zwitterion Mes2P(H)(C6F4)B(H)(C6F5)2 evolved H2 at elevated temperatures and ca 10 of
[iPrNH2Cy]+ was observed Similarly 10 mol of the catalyst combination 18-
bis(diphenylphosphino)naphthalene and B(C6F5)3 gave 10 of aromatic reduction as a result of
the borane
Stoichiometric reactions of B(C6F5)3 and the anilines (p-CH3PhO2S)NHPh tBuNH(C6F5) Boc-
NHPh EtNHPh imines 26-(Me2C6H3)N=C(H)Ph PhN=CMe(p-EtOPh) phenols TMSOPh
31
tBuOPh tBuO(p-CF3C6H4) tBuO(p-FC6H4) hydrazine PhNH-NHPh 18-naphthosultam Ph3P
ethers (p-FPh)2O and CF3SPh did not evidence hydrogenation of the arene ring under the
optimized reaction conditions Furthermore the reactivity of iPrNHPh with the boranes BPh3
MesB(C6F5)2 MesB(p-C6F4H)2 PhB(C6F5)2 B(p-C6H4F)3 and B(o-C6H4CF3)3 did not activate
H2 or hydrogenate the aniline arene ring
223 Mechanistic studies for aromatic hydrogenation reactions
2231 Deuterium studies
To gain mechanistic insight into the presented transformation tBuNHPh was combined in a J-
Young tube with an equivalent of B(C6F5)3 in C6H5Br and exposed to D2 (2 atm) at 25 degC After
standing for 12 h multinuclear NMR data certainly indicated heterolytic activation of D2 The 2H
NMR spectrum gave a broad singlet at 658 ppm assigned to a N-D bond and a broad resonance
at 326 ppm attributed to a B-D bond (Figure 27 bottom-left) In addition to the 11B and 19F
NMR spectra these data supported formation of [tBuNHDPh][DB(C6F5)3] 21-d2 After heating
the sample for 3 h at 110 degC the 2H NMR revealed significant diminishing in the B-D resonance
while the N-D resonance was visibly unaltered (Figure 27 top-left) The 1H NMR spectrum of
the corresponding sample evidenced a broad quartet at 325 ppm (1JB-H = 78 Hz) representative
of a B-H bond (Figure 27 top-right) This B-H resonance is absent in the 1H NMR spectrum of
the sample at RT after 24 h (Figure 27 bottom-right)
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right)
Overall the following NMR studies are suggestive of reversible D2 activation in which at
elevated temperatures proton and deuteride from the nitrogen and boron centres of 21-d2
110 degC ND 110 degC BH (3 h) (3h) BD
RT ND BD RT (24 h) (24 h)
32
respectively combine releasing H-D The H-D gas is subsequently reactivated by the free amine-
borane FLP giving rise to [tBuND2Ph][HB(C6F5)3] (Scheme 25)
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD
2232 Variable temperature NMR studies
As supported by the aforementioned deuterium studies the reversible nature of H2 activation by
the aromatic amines and B(C6F5)3 is consistent with observation of species 21 as the initial
product of hydrogenation This is followed by evolution and reactivation of H2 allowing access
to the arene reduced species 23 at elevated temperatures (Scheme 26)
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23
This aspect of reversible H2 acitvation was further verified by variable temperature NMR studies
of the adduct (iPrNHPh)B(C6F5)3 24rsquo under H2 from 45 degC to 115 degC in C6D5Br As temperature
was increased both 11B and 19F NMR spectra displayed resonances pertaining to gradually
dissociating B(C6F5)3 and formation of the [HB(C6F5)3]- anion This is evidenced in Figure 28
by 11B NMR spectroscopy showing liberated B(C6F5)3 at 115 degC (11B δ 53 ppm) and progression
of the resonance at -25 ppm assignable to [HB(C6F5)3]- indicating formation of 24 It is
important to note that the [HB(C6F5)3]- resonance observed at the initiation of the reaction is
attributable to reversible hydride abstraction from the iPr substituent on the aniline
33
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-)
2233 Theoretical calculations
The mechanism of this study is proposed based on quantum chemical calculations performed by
Professor Stefan Grimme at Universitaumlt Bonn Germany Quantum chemical calculations were
performed at the dispersion-corrected meta-double hybrid level (PW6P95 functional) employing
large triple-zeta type basis sets and TPSS-D3 optimized geometries This final theoretical level
denoted as PWP95-D3def2-TZVPPTPSS-D3def-TZVP provides reaction energies with an
estimated accuracy of about 1 - 2 kcalmol Solvation effects of toluene were considered using
the COSMO-RS continuum solvation model255
Theoretical studies indicate a mechanism that supports reactivity to initiate by dissociation of the
weak amine-borane adduct At this stage the FLP could follow two reaction pathways (Figure
29) At moderate temperatures the FLP undergoes splitting of H2 to yield the salt 21 computed
to be 97 kcalmol lower in energy than the amine-borane adduct However the free enthalpy
difference for this species is close to zero hence under equilibrium conditions it can be
considered as a resting state of the reaction This minor difference in free enthalpy is in
agreement with reversible D2 activation results presented earlier using tBuNHPh and B(C6F5)3
45 degC
75 degC
95 degC
65 degC
115 degC
55 degC
85 degC
105 degC
34
An alternative reaction pathway follows at elevated reaction temperatures In this case the
dissociated amine rotates to position the arene para-carbon towards the boron atom creating a
van der Waals complex that is stabilized by significant pi-stacking with a C6F5 group This
complex creates a classical FLP with an electric field to polarize the entrapped H2 and effect
heterolytic splitting at a relatively low energy barrier of 87 kcalmol The free enthalpy for H2
activation relative to the resting state is computed to be 212 kcalmol certainly supporting the
elevated temperatures required to effect this reactivity
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol)
At the transition state the H-H distance is calculated to be about 097 Aring This bond is
significantly elongated compared with PB FLPs where the bond distance ranges between 078
and 080 Aring thus signifying a delayed transition state The corresponding H-H and C-H covalent
Wiberg bond orders are 033 and 041 respectively The B-H bond order is 063 indicating
approximately half-broken and half-formed bonds in the transition state88 256
21
23
35
The resulting intermediate [tBuNHC6H6][HB(C6F5)3] (CH-intermediate) is an ion pair showing
an sp3 hybridized para-carbon and an almost planar tBuNH=C unit in the cation shown in Figure
29 This species has similar energy and free enthalpy to the arene-B(C6F5)3 van der Waals
compound The complexity of subsequent hydrogenation steps to yield 23 has limited further
computations
It is noteworthy that prolonged heating of the more basic amine iPr2NPh with B(C6F5)3 under H2
only yields [iPr2NHPh][HB(C6F5)3] 215 This suggests that the greater basicity of the nitrogen
centre in iPr2NPh (Et2NHPh pKa 66 in H2O) stabilizes 215 thereby inhibiting access to the
amine-borane FLP and subsequent arene reduction (iPrNHPh pKa 58 in H2O)253-254 The overall
proposed reaction mechanism has been summarized in Scheme 27 Observation of the partially
hydrogenated cation [3-(C6H9)NH2iPr]+ illustrated in Figure 24 is presumed to be a result of H2
activation at the ortho-carbon of the arene ring
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts
224 Aromatic hydrogenation of substituted N-bound phenyl rings
2241 Fluoro-substituted rings and C-F bond transformations
Determining functional group tolerance of the demonstrated aromatic hydrogenations reaction
of the fluoro-substituted aniline (2-FPh)NHiPr with B(C6F5)3 under H2 indicated approximately
30 of the salt [(2-FPh)NH2iPr][HB(C6F5)3] after 31 h at RT Heating the sample at 110 degC for
36
24 h afforded a white solid 216a isolated in 59 yield (Scheme 28 a) Multinuclear NMR
spectroscopy revealed approximately 95 of the product consisted of [CyNH2iPr][FB(C6F5)3]
216a Spectral parameters of the cation were in agreement with that of compound 24 The
fluoroborate [FB(C6F5)3]- anionic fragment gave a broad signal at 055 ppm in the 11B NMR
spectrum and four 19F resonances were observed by 19F NMR spectroscopy at -1370 -1612 -
1669 and -1796 ppm The remaining 5 of the reaction mixture consisted of [(2-
FC6H10)NH2iPr][HB(C6F5)3] 216b Single crystals of 216a suitable for X-ray diffraction were
obtained and the structure is shown in Figure 210
Figure 210 ndash POV-Ray drawing of 216a
In a similar fashion heating the reaction of (3-FPh)NHiPr with B(C6F5)3 under H2 after 72 h
afforded the reduced product in 77 yield Approximately 95 of the salt consisted of 216a
and the remainder as [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b (Scheme 28 b) Indeed these
examples illustrate tandem B(C6F5)3 mediated arene hydrogenation and C-F bond activation
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a
37
Analogous reactivity with (4-FPh)NHiPr gave partial hydrogenation of the ring after 72 h
forming the 3-cyclohexenyl derivative [(4-FC6H8)NH2iPr][HB(C6F5)3] 218 in 62 yield
(Scheme 29) In addition to the expected resonances a diagnostic doublet of triplets in the 1H
NMR at 495 ppm and doublet at 1584 ppm (1JC-F = 255 Hz) in the 13C1H NMR spectra
certainly indicate an unsaturated C=C bond with the fluorine atom still intact This was
unambiguously confirmed by X-ray crystallography (Figure 211) It is important to note that
approximately 20 of the isolated product consisted of 216a indicating a much reduced rate of
arene hydrogenation and C-F bond activation in comparison to ortho- or meta-F substituted
anilines In these two cases intial H2 activation is expected to occur through the resonance form
in which the lone pair is at the para carbon (Scheme 27) However in the case of para-F
substituted aniline H2 activation is speculated to preferentially occur through the resonance
structure in which the negative charge is at an ortho carbon This proposal is ascribed to the
electron-withdrawing fluoro substituent which removes electron density from the para position
The partially hydrogenated product 218 is analogous to the cation [3-(C6H9)NH2iPr]+ presented
in Figure 24 in which H2 activation is suggested to initiate at the ortho carbon
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218
Figure 211 ndash POV-Ray drawing of 218
38
In light of recent findings121 a postulated mechanism implies that after reduction of the aromatic
ring B(C6F5)3 activates the C-F bond provoking nucleophilic addition of hydride from a
[HB(C6F5)3]- anion and liberating B(C6F5)3 for further reactivity Interaction of B(C6F5)3 with C-
F bonds were spectroscopically observed in a 11 combination of B(C6F5)3 and CF3-subtituted
anilines In this respect separate combinations of ortho- or para-F3CPhNH(iPr) and B(C6F5)3 in
C6D5Br gave a 19F NMR spectrum showing four broad resonances with a para-meta gap of 86
ppm and a diagnostic broad singlet assignable to a B-F resonance at -1800 ppm The broad
nature of these resonances and absence of a boron resonance in the 11B NMR spectrum do not
indicate formal C-F bond cleavage rather the data supports reversible B(C6F5)3-CF3
interaction121
2242 Methoxy-substituted rings and C-O bond transformations
Reactivity of FLP systems with oxygen-based substituents is noticeably limited due to high
oxophilicity of electrophilic boranes72 171 However recent findings have been reported on
lability of B-O adducts Stephan et al reported that the ethereal oxygen of the borane-oxyborate
(C6F5)2BCH(C6F5)OB(C6F5)3 derived from the reaction of FLPs with syn-gas activates H2 with
the B(C6F5)2 fragment117 Furthermore Et2O effects H2 activation with B(C6F5)3 and was shown
to be an efficient catalyst in the hydrogenation of olefins257 In an effort to further explore the
scope of the presented metal-free aromatic reductions the arene hydrogenation of anilines with
methoxy substituents was attempted
The combined toluene solution of B(C6F5)3 and the para-methoxy substituted imine (p-
CH3OC6H4)N=CCH3Ph was pressurized with H2 (4 atm) and heated at 110 degC for 48 h This
resulted in the formation of a new white crystalline product assigned to
[(C6H10)NHCH(CH3)Ph][HB(C6F5)3] 219 isolated in 30 yield (Scheme 210) Indeed the 1H
NMR spectrum indicated consumption of N-bound aromatic resonances concomitant with the
appearance of two inequivalent doublet of doublets observed at 447 and 374 ppm with the
corresponding 13C1H NMR resonances observed at 652 and 647 ppm respectively These
peaks are assignable to two inequivalent bridgehead CH groups of the resulting bicyclic
ammonium cation The 11B and 19F NMR spectra were in accordance with the presence of
[HB(C6F5)3]- as the anion X-ray diffraction studies further confirmed the bicyclic structure of
the product and the identity of the anion (Figure 212)
39
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219
Figure 212 ndash POV-Ray drawing of 219
In an effort to appreciate the importance of the position of the methoxy substituent on the arene
ring the separate reactions of ortho- and meta-methoxy substituted (CH3OC6H4)NHCH(CH3)Ph
with B(C6F5)3 were attempted under the established hydrogenationtransannulation protocol In
both cases hydrogenation of the N-bound phenyl group was observed although no
transannulation was achieved The amine (o-CH3OC6H4)NHCH(CH3)Ph gave cis and trans
mixtures of [(2-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 220 isolated in 92 yield In contrast
to fluorine abstraction from the ortho carbon position shown in Scheme 28 the methoxy
substituent in this case is not abstracted from the reduced ring due to steric effects preventing
B(C6F5)3 from binding to the substituent However the meta-substituted analogue resulted in C-
O bond cleavage yielding [(C6H11)NH2CH(CH3)Ph][HB(C6F5)3] 212 in 65 isolated yield
(Scheme 211) Ring closure was not obtained for this particular case due to ring strain of the
anticipated product Crystals of 220 suitable for X-ray crystallography were obtained and shown
in Figure 213
40
HB(C6F5)3
NH
OCH3
B(C6F5)3
Ph
+ CH3OH
NH2
OCH3
Ph
NH2Ph
HB(C6F5)3
NHPh
OCH3
220
212
H2
B(C6F5)3
H2
Scheme 211 ndash Synthesis of 220 and 212
Figure 213 ndash POV-Ray drawing of trans-220
In the case of the para-methoxy substituted imine B(C6F5)3 has participated in tandem arene
hydrogenation and transannulation to ultimately afford a 7-azabicyclo[221]heptane derivative a
bicyclic substructure of biological importance258 Unfortunately further expansion of the
substrate scope was not successful giving only the H2 activation product or arene hydrogenation
Such substrate examples include para-methoxyanilines with a methyl substituent at either the
ortho or meta position other para substituents such as HCF2O PhO2S and Br tertiary amine 4-
methoxy-N-phenyl-N-(1-phenylethyl)aniline
22421 Mechanistic studies for C-O and B-O bond cleavage
Studying the mechanism to form the 7-azabicyclo[221]heptane ammonium hydridoborate salt
219 the possibility of an intra- or intermolecular protonation of the methoxy group was initially
41
disproved by heating a toluene sample of the independently synthesized ammonium borate salt
trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] 221a at 110 degC (Scheme 212) No reaction
was evidenced by 1H 11B and 19F NMR spectroscopy However similar treatment of trans-[(4-
CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 221b at 110 degC prompted release of H2 as evidenced
by the 1H NMR signal at 45 ppm eventually giving compound 219 after 12 h at 110 degC
(Scheme 212)
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b)
To verify the liberation of CH3OH in the presented reactions the synthesis of 219 was repeated
starting from the free amine trans-[(4-CH3OC6H10)NHCH(CH3)Ph and B(C6F5)3 under H2
(Figure 214 a) After one week at RT the volatiles were transferred under vacuum from the
reaction vessel into a J-Young tube and the 1H NMR spectrum showed evidence of CH3OH
although a yield was not obtained
42
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c)
This observation implies that ring closing to yield the 7-azabicyclo[221]heptane ammonium
cation does not proceed by intra- or intermolecular protonation of the methoxy group rather
transannulation proceeds via intramolecular nucleophilic attack of the para-carbon by the amine
nitrogen while B(C6F5)3 captures the methoxide fragment To further support this proposed
mechanism the independently synthesized amine trans-(4-CH3OC6H10)NHiPr was treated with
an equivalent of B(C6F5)3 in the absence of H2 (Scheme 213) Interestingly after heating for 2 h
the reaction resulted in quantitative formation of a new product 222 with a sharp 11B resonance
at -242 ppm and 19F resonances at -1354 -1626 and -1668 ppm consistent with the formation
of the borane-methoxide anion [CH3OB(C6F5)3]- The 1H NMR data signified formation of the
diagnostic bridgehead CH protons at 413 ppm The combination of NMR spectroscopy
elemental analysis and X-ray diffraction studies evidenced the formation of compound 222 as
the bicyclic salt [(C6H10)NHiPr][CH3OB(C6F5)3] (Figure 215)
a)
b)
c)
43
Figure 215 ndash POV-Ray drawing of 222
Heating 222 at 110 degC in the absence of H2 eventually results in CH3OH liberation and rapid
degradation of the borane to CH3OB(C6F5)2 and C6F5H In the presence of H2 however 222 is
transformed to 223 with the liberation of CH3OH (Scheme 213) This observation implies that
the ammonium cation of 222 protonates the methoxide bound to boron liberating methanol and
regenerating B(C6F5)3 which undergoes FLP type H2 activation with the bicyclic amine
generating 223 Compound 223 was also prepared from the aniline p-CH3OC6H4NHiPr The
liberated CH3OH was isolated although not quantified and observed by 1H NMR spectroscopy
(Figure 214 b) Interestingly a similar protonation pathway has been previously proposed in a
study by Ashley and OrsquoHare whereby the stoichiometric hydrogenation of CO2 using 2266-
tetramethylpiperidine (TMP) and B(C6F5)3 was reported The authors proposed B-O bond
cleavage of [CH3OB(C6F5)3]- to occur through protonation by the 2266-
tetramethylpiperidinium counter cation259 Additionally most recently Ashley et al proposed
the metal-free carbonyl reduction of aldehydes to possibly proceed through oxonium protonation
of the boron-alkoxide anion [ROB(C6F5)3]-260
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3
44
Despite evidence for the protonation pathway contribution by a second pathway involving the
[CH3OB(C6F5)3]- anion and B(C6F5)3 acting as a FLP to activate H2 cannot be disregarded In
this respect a toluene solution of [NEt4][CH3OB(C6F5)3] and 5 mol B(C6F5)3 were exposed to
H2 (4 atm) at 110 degC After heating for 2 h the 11B and 19F NMR spectra revealed complete
consumption of the [CH3OB(C6F5)3]- anion along with emergence of peaks corresponding to the
H2 activation product [NEt4][HB(C6F5)3] and CH3OH (Scheme 214) This latter mechanism
provides an alternative path to the anion of 223 This type of system draws analogy to H2
activation by the earlier mentioned BO FLP (C6F5)2BCH(C6F5)OB(C6F5)3 suggesting H2
cleavage gives protonated oxygen and borohydride117
Gradual decomposition of the borane catalyst due to CH3OH was also observed as the amine is
not present to displace CH3OH from B(C6F5)3 consequently hindering its decomposition The
pKa of hydroxylic substrates have been shown to be significantly activated by coordination to
B(C6F5)3 generating strong Broslashnsted acids with pKa values comparable with HCl (84 in
acetonitrile)261
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3
Collectively it may be read that compound 219 is formed by initial hydrogenation of the imine
(p-CH3OC6H4)N=CCH3Ph C=N double bond followed by reduction of the arene ring affording
the cyclohexylamine The amine and borane can activate H2 to give the ammonium salt albeit at
elevated temperatures this is reversible allowing the borane to activate the methoxy substituent
and induce transannulation effecting C-O bond cleavage (Scheme 215) Subsequent conversion
of the generated methoxy-borate anion to the hydridoborate anion proceeds under H2 following
the pathways presented in Schemes 213 and 214
45
NH2
R
OCH3
110 oC
NHR
OCH3
NHR
OCH3
(F5C6)3B
+ H2
B(C6F5)3
H2
HB(C6F5)3
- H2HN
R
CH3OB(C6F5)3
+ H2
HB(C6F5)3
HNR
- CH3OH
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane
225 Aromatic hydrogenation of N-heterocyclic compounds
While seeking to extend the scope of aromatic reductions attention was focused on a series of
mono- and di-substituted pyridines quinolines and several other N-heterocycles In this regard
the aromatic hydrogenation of a variety of N-based heterocycles was explored using
stoichiometric combinations of B(C6F5)3 in the presence of H2 (4 atm)
2251 Hydrogenation of substituted pyridines
Detailed studies on the effects of increased steric bulk on pyridine249 and their reactivity with
B(C6F5)3 to activate H2248 at room temperature have been previously reported Stoichiometric
combination of the Lewis base 26-diphenylpyridine and the Lewis acid B(C6F5)3 do not show
evidence of a donor-acceptor interaction by NMR spectroscopy in contrast a reversible adduct is
observed with 26-lutidine Exposure of either combination of 26-diphenylpyridine or 26-
lutidine and B(C6F5)3 under H2 (4 atm) at room temperature activate H2 affording the
corresponding pyridinium hydridoborate salts
Nonetheless heating a mixture of 26-diphenylpyridine and B(C6F5)3 under H2 (4 atm) at 115 degC
for 16 h gives a new product isolated in 92 yield (Table 22 entry 1) The 11B NMR data in
CD2Cl2 displayed a doublet at -246 ppm and three resonances in the 19F NMR spectrum
observed at -1340 -1634 and -1666 ppm confirmed the presence of the [HB(C6F5)3]- anion
The 1H NMR spectrum showed a broad singlet at 590 ppm attributable to the NH2 group
multiplets at 453 and 226 - 189 ppm in addition to signals assignable to the phenyl and BH
46
groups These data were consistent with the formulation of the salt [26-
Ph2C5H8NH2][HB(C6F5)3] 224 Furthermore the 1H NMR data revealed a de of 91 favouring
the meso-diastereomer an assignment that was confirmed via NMR spectroscopy and the
molecular structure shown in Figure 216 (left) In a similar fashion the reaction of 26-lutidine
with B(C6F5)3 under H2 at 115 degC for 60 h afforded the corresponding salt [26-
Me2C5H8NH2][HB(C6F5)3] 225 in 84 yield (Table 22 entry 1) with a de of 80 also
favouring the meso-diastereomer (Figure 216 right) The preferred diastereoselectivity is
consistent with the known ability of B(C6F5)3 to effect epimerization of chiral carbon centres
adjacent to nitrogen by a process previously described to involve hydride abstraction and
redelivery262
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right)
The substrate ethyl 2-picolinate was exposed to the hydrogenation conditions giving a B(C6F5)3
adduct of the reduced substrate (2-(EtOCO)C5H9NH)B(C6F5)3 226 isolated in 74 yield after
36 h (Table 22 entry 2) The 11B NMR spectrum in CD2Cl2 showed a broad singlet at -486 ppm
and 15 inequivalent 19F resonances which were consistent with adduct formation between the
boron and nitrogen centres inhibiting rotation about the bond
47
Table 22 ndash Hydrogenation of substituted pyridines
Multinuclear NMR spectra of 226 displayed the presence of two diastereomers in a 11 ratio
Most distinguishable were the 13C1H resonances at 1674 and 1712 ppm attributable to the
OCO-ester groups and the 1H NMR signals at 418 and 424 ppm arising from the methine
protons Furthermore 1H1H NOESY experiments confirmed the assignment of these peaks to
the respective RSSR and RRSS diastereomers Independent reaction of B(C6F5)3 with the
optically pure piperidine S-2-(EtOCO)C5H9NH at -30 degC in CD2Cl2 afforded the preferential
formation of the SS-diastereomer of 226 However on warming to room temperature over 18 h
racemization at nitrogen eventually afforded a 11 mixture of the SS and SR diastereomers
Even though the pyridine-borane adduct of 2-phenylpyridine has been isolated and characterized
this adduct is reversed at 115 degC Reduction of the substrate using B(C6F5)3 and H2 gave a
mixture of two products isolated in 54 overall yield after 48 h (Table 22 entry 3) A broad 11B
NMR signal at -391 ppm together with a doublet at -240 ppm were consistent with the
48
presence of the adduct (2-PhC5H9NH)B(C6F5)3 227a and the ionic pair [2-
PhC5H9NH2][HB(C6F5)3] 227b in a 41 ratio respectively
The formulation of 227a is further supported by NMR data revealing two distinctively broad
NH singlets in the 1H NMR spectrum at 555 and 581 ppm attributable to a 71 ratio of the
RSSR and RRSS diastereomers The RSSR diastereomer was the more abundant form as
evidenced by NMR and X-ray crystallographic data (Figure 217)
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring
Interestingly the preferential formation of this diastereomer was evidenced by 1H19F HOESY
NMR spectroscopy through intramolecular π-π stacking interactions of the Ph and C6F5 groups
in addition to interactions between the C-H and N-H groups of piperidine and ortho-fluoro
groups of B(C6F5)3 (Figure 218) Identity of compound 227b was confirmed based on
agreement of spectral parameters with the NH2 methine and methylene groups
49
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups
The presence of adduct 227a raised the question about dissociation of the B-N bond and
possible participation of the liberated borane in further pyridine hydrogenation To probe this a
toluene solution of 2-phenylpyridine and 10 mol of 227 was exposed to H2 (4 atm) at 110 degC
After heating for 24 h 1H NMR spectroscopy did not indicate consumption of the pyridine
reagent Similarly repeating the hydrogenation of 2-phenylpyridine with 10 mol B(C6F5)3 did
not result in catalysis
2252 Hydrogenation of substituted N-heterocycles
Attempting to extend the aromatic hydrogenation of N-heterocycles beyond pyridine substrates
attention was focused to 1234-tetrahydroquinoline derivatives which have been reported to
result from the catalytic hydrogenation of N-heterocycles98 In examining the structure of
tetrahydroquinoline the carbocyclic ring fused to the N-heterocycle was observed to be similar
to a secondary aniline (Figure 219) Thus emerging the avenues of previous reports on catalytic
hydrogenation of substituted quinolines and most recent findings on the stoichiometric reduction
of anilines the complete homogeneous hydrogenation of N-heteroaromatic compounds was
explored
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring
50
Exposure of 2-methylquinoline and B(C6F5)3 to H2 (4 atm) at 115 degC for 48 h was found to effect
hydrogenation of not only the N-heterocycle but also the carbocyclic ring to yield [2-
MeC9H15NH2][HB(C6F5)3] 228 in 67 (Table 23 entry 1) In a similar fashion both rings of 2-
phenylquinoline were reduced in the same time frame to give [2-PhC9H15NH2][HB(C6F5)3] 229
in 95 yield (Table 23 entry 1)
The 1H NMR spectra for 228 and 229 exhibited characteristic chemical shifts corresponding to
NH2 methine and methylene groups Both compounds 228 and 229 were produced as mixtures
of diastereomers although in both cases the major isomer was crystallized and found to comprise
of 60 and 73 of the isolated products respectively The molecular structures show both
compounds exhibit SSSRRR stereochemistries in which one of the ring junctions adopts an
equatorial disposition while the other is axially disposed (Figure 220 a and b) Analogous
treatment of 8-methylquinoline with H2 and B(C6F5)3 in toluene for 48 h yielded [8-
MeC9H15NH2][HB(C6F5)3] 230 in 76 (Table 23 entry 1) 1H and 13C1H NMR data suggest
only the presence of the RRRSSS diastereomers (Figure 220 c)
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c)
a) b) c)
51
Table 23 ndash Hydrogenation of substituted N-heterocycles
The corresponding reduction of acridine results in isolation of the fully reduced tricyclic species
in 76 yield (Table 23 entry 2) The isolated product is obtained as a mixture of two isomers
one of which was characterized crystallographically as the salt [C13H22NH2][HB(C6F5)3] 231a
As shown in Figure 221 all ring junctions are equatorially positioned and thus the SRSRRSRS
diastereomers are assigned
Figure 221 ndash POV-Ray depiction of the cation for compound 231a
52
Interestingly a second product was isolated from the pentane work-up crystallographic data
showed it to be the adduct (C13H22NH)B(C6F5)3 231b (Figure 222) In this case however the
stereochemistries of the ring junctions adjacent to nitrogen are inverted affording the RRSSSSRR
diastereomers of the reduced acridine heterocycle Compound 231b was also independently
synthesized in 73 yield from a mixture of isomers of the neutral amine C13H22NH and
B(C6F5)3
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring
Although the substrates 23-dimethyl and 23-diphenylquinoxaline have two Lewis basic
nitrogen centres the reduction reactions required only one equivalent of B(C6F5)3 yielding the
piperazinium derivatives [23-(C4H6Me)2NHNH2][HB(C6F5)3] 232 and [23-
(C4H6Ph)2NHNH2][HB(C6F5)3] 233 in 59 and 55 yield respectively (Table 23 entry 3) In
the case of 232 a single set of diastereomers was observed and the NMR data were consistent
with ring junctions and methyl groups adopting equatorial dispositions In contrast the isolated
product 233 comprised of two diastereomers Crystallographic characterization of one
diastereomer showed the phenyl rings adopt equatorial positions while the ring junctions are
axial and equatorially disposed (Figure 223)
Figure 223 ndash POV-Ray depiction of the cation for compound 233
53
It is noteworthy that while the aromatic ring of the quinoxaline fragment is fully reduced the
phenyl substituents remain intact In a similar situation reduction of 78-benzoquinoline resulted
in the formation of [(C6H4)C7H12NH2][HB(C6F5)3] 234 in 55 yield (Table 23 entry 4) 1H
NMR spectroscopy evidenced a 41 mixture of two diastereomers in which reduction of the
pyridyl and adjacent carbocyclic ring were achieved while aromaticity of the ring remote from
the nitrogen atom was retained X-ray crystallography unambiguously confirmed the dominant
diastereomer 234a to have SRRS stereochemistry while the less abundant diastereomer 234b
showed SSRR stereochemistry (Figure 224)
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right)
Efforts to reduce the related heterocycle 110-phenanthroline in which a pyridyl ring is fused at
the 7 and 8 position of quinoline were undertaken employing one equivalent of B(C6F5)3 After
heating the solution for 14 h at 115 degC under H2 (4 atm) 1H NMR spectroscopy indicated
complete hydrogenation of the N-heterocycle in addition to loss of C6F5H and formation of a
four-coordinate boron centre with a 11B resonance observed at 302 ppm The [HB(C6F5)3]- anion
was not observed and further heating did not reveal hydrogenation of the carbocyclic ring
A second equivalent of B(C6F5)3 was added and the reaction was re-exposed to H2 (4 atm) for a
total of 96 h at 115 degC This resulted in isolation of [(C5H3N)(CH2)2(C5H8NH)B(C6F5)2]
[HB(C6F5)3] 235 in 73 yield (Table 23 entry 5) The 11B NMR spectrum revealed the
presence of two four-coordinate boron centres with resonances at 302 and -254 ppm The
former boron species exhibited six inequivalent fluorine atoms evidenced by 19F NMR
spectroscopy inferring the presence of two inequivalent fluoroarene rings where steric
congestion is inhibiting ring rotation at the B-N and B-C bonds The latter 11B NMR signal
together with the three corresponding 19F resonances arise from the [HB(C6F5)3]- anion X-ray
crystallography confirmed the formulation of 235 as the SRSRSR diastereomer present as 65
of the isolated reaction mixture (Figure 225)
54
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine
In the cationic fragment of compound 235 the boron centre is bound to two perfluoroarene rings
and is chelated by the pyridine and amine nitrogen atoms of partially reduced 110-
phenanthroline The B-N distances in the cation were found for B(1)-N(1)amine to be 1615(3) and
B(1)-N(2)pyridine 1598(3) Aring In this unique case as reduction of the heterocycle proceeds a
single pyridyl ring is initially reduced in which the resulting amine coordinates B(C6F5)3
resulting in loss of C6F5H and chelation of B(C6F5)2 by the pyridyl nitrogen centre affording the
cation (Scheme 216) The second equivalent of the borane remains intact and partakes in partial
hydrogenation of the carbocyclic ring Elimination of C6F5H followed by ring closure is
thermodynamically favoured due to formation of the five-membered borocycle
NN NN
B
B(C6F5)3
(C6F5)3B H
- C6F5H H2
235
(C6F5)2
Scheme 216 ndash Proposed reaction pathway for the formation of 235
Although this arene hydrogenation method is applicable to the presented N-heteroaromatic
substrates the reactivity was not successfully extended to 46-dimethyl-1-phenylpyrimidin-
2(1H)-one 2-methylindoline 3-methylindole 1-methylisoquinoline and carbazole
55
2253 Proposed mechanism for aromatic hydrogenation
The reductions described demonstrate the ability of B(C6F5)3 to mediate the complete aromatic
hydrogenation of a number of N-heterocycles It is clear that the products arise from reduction of
pyridyl andor aniline-type rings and in some cases affording a preferred set of diastereomers as
demonstrated by the ability of B(C6F5)3 to epimerize chiral centers alpha to nitrogen262 Efforts
to monitor several of the mixtures over the course of the reactions failed to provide unambiguous
mechanistic insight By analogy to computational studies presented for aniline hydrogenations
the need for elevated temperatures presumably reflects the fact that hybridizing the para-carbon
of the N-heterocycle is energetically uphill however once this is achieved there is an exothermic
route to the saturated amine Subsequent activation of H2 by the reduced amine and borane
affords the corresponding ammonium salt which is irreversible under the reaction conditions
thus precluding catalytic reduction This could simply be explained by Broslashnsted basicity of the
nitrogen centre An sp2 hybridized nitrogen has the lone pair in a p-orbital therefore it can
participate in resonance making it less basic as opposed to sp3 hybridization which does not have
a p-orbital (pyridine pKa 52 quinoline pKa 492 piperidine pKa 112 all values are in H2O)
While the reactions are nominally stoichiometric multiple turnovers of H2 activation are
achieved For example eight equivalents of H2 are taken up by acridine in the formation of 231
2254 Approaches to dehydrogenation
Although hydrogenation of aromatic substrates is appealing the reversible reaction
dehydrogenation of the products with aim at obtaining a molecular dihydrogen storage device
became a topic of interest Heating compound 231 at 115 degC in a vacuum sealed J-Young tube
did not evolve H2 As an alternative approach the neutral amine C13H22NH was combined with
the electrophilic boranes B(C6F5)3 B(p-C6F4H)3 or (12-C12F9)B(C6F5)2 and heated under
vacuum After 24 h trace amounts of aromatic resonances corresponding to dehydrogenation of
the N-heterocycle and a single carbocyclic ring (five equivalents of H2) was observed by 1H
NMR spectroscopy It is important to note that this process did not liberate H2 rather amine and
B(C6F5)3 abstracted proton and hydride respectively regenerating 231 One can envision this
dehydrogenation process could possibly be applied to transfer hydrogenation of imines similar
to an earlier report by the Stephan group262
56
23 Conclusions
This chapter provides an account on the discovery of N-phenyl amine reductions under H2 using
an equivalent of B(C6F5)3 to yield the corresponding cyclohexylamine derivatives In these
reactions B(C6F5)3 mediates uptake of four equivalents of H2 terminating with a final FLP
activation of H2 affording the cyclohexylammonium salts A possible reaction pathway is
proposed based on experimental evidence and theoretical calculations The substrate scope is
extended to a variety of pyridyl- and aniline-type rings of N-heterocyclic compounds These
reductions represent the first example of homogeneous metal-free hydrogenation of aromatic
rings
Shortly after publishing the presented data on aromatic hydrogenations in two separate reports
the Stephan group communicated the partial reduction of polycyclic aromatic hydrocarbons
using catalysts derived from weakly basic phosphines263 or ethers257 with B(C6F5)3 Additionally
the Du group showed a borane catalyzed route to the stereoselective hydrogenation of
pyridines264
24 Experimental Section
241 General considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane hexane tetrahydrofuran dichloromethane and toluene (Sigma Aldrich) were
dried employing a Grubbs-type column system (Innovative Technology) degassed and stored
over molecular sieves (4 Aring) in the glovebox Bromobenzene (-H5 and -D5) were purchased from
Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring molecular
sieves prior to use Dichloromethane-d2 was purchased from Sigma Aldrich dried over CaH2 and
vacuum distilled onto 4 Aring molecular sieves prior to use Tetrahydrofuran-d8 and toluene-d8 were
purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to use Molecular
sieves (4 Aring) were purchased from Sigma Aldrich and dried at 140 ordmC under vacuum for 24 h
prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at 80 degC under high
vacuum before use Sodium methoxide and tetraethylammonium chloride were purchased from
Sigma Aldrich and dried under vacuum at 140 ordmC for 12 h prior to use
57
All substituted amines anilines quinolines pyridines and other N-heterocycles were purchased
from Sigma Aldrich Alfa Aesar or TCI Potassium tetrakis(pentafluorophenyl)borate and
hydrogen chloride (40 M in 14-dioxane) were purchased from Alfa Aesar The oils were
distilled over CaH2 and solids were sublimed under high vacuum prior to use The following
compounds were independently synthesized following the cited procedure265 unless indicated
otherwise N-tert-butylaniline266 NN-(14-phenylenebis(methylene))bis(tert-butylamine) N-
isopropyl-2-methylaniline N-isopropyl-4-methylaniline N-isopropyl-4-methoxyaniline N-
isopropyl-3-methylaniline N-isopropyl-35-dimethylaniline N-(1-phenylethylidene)aniline
N1N4-di(propan-2-ylidene)benzene-14-diamine 44-methylenebis(N-isopropylaniline) 2-
fluoro-N-isopropylaniline 3-fluoro-N-isopropylaniline 4-fluoro-N-isopropylaniline 4-methoxy-
N-(1-phenylethylidene)aniline 2-methoxy-N-(1-phenylethyl)aniline266 3-methoxy-N-(1-
phenylethyl)aniline266 and alkylation methods267 to prepare trans-(4-
CH3OC6H10)NHCH(CH3)Ph and trans-(4-CH3OC6H10)NHiPr
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Varian 400 MHz spectrometer equipped with an HFX AutoX triple resonance indirect
probe (used for 13C1H 19F experiments) or an Agilent DD2 500 MHz spectrometer Spectra
were referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm
for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) d8-tol (1H = 208 ppm for CH3 13C
= 13748 ppm for ipso carbon) d8-THF (1H = 358 ppm for OCH2 13C = 6721 ppm for OCH2)
or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in ppm and the
absolute values of the coupling constants (J) are in Hz NMR assignments are supported by 2D
and DEPT-135 experiments
Elemental analyses (C H N) were performed in-house employing a Perkin Elmer 2400 Series II
CHNS Analyzer H2 (grade 50) was purchased from Linde and dried through a Nanochem
Weldassure purifier column prior to use High resolution mass spectra (HRMS) were obtained
using an ABSciex QStar Mass Spectrometer with an ESI source MSMS and accurate mass
capabilities
242 Synthesis of compounds
Synthesis of [NEt4][CH3OB(C6F5)3] In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (100 mg 0195 mmol) in CH2Cl2 (10 mL) To the vial
58
Na OCH3 (105 mg 0195 mmol) was added and the reaction was allowed to mix for 3 h at RT
The salt Na CH3OB(C6F5)3 was isolated as a white solid and dried under vacuum (110 mg 0195
mmol gt99) Na CH3OB(C6F5)3 (110 mg 0195 mmol) in CH2Cl2 (10 mL) was subsequently
added to a 4 dram vial containing NEt4 Cl (323 mg 0195 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT for 16 h and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (125 mg
0186 mmol 95)
1H NMR (400 MHz CD2Cl2) δ 322 (q 3JH-H = 73 Hz 8H Et) 311 (s 3H OCH3) 142 (tm 3JH-H = 73 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 3JF-F = 20 Hz 2F o-C6F5)
-1636 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
256 (s BOCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1480 (dm 1JC-F = 240 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1364 (dm 1JC-F = 248 Hz CF) 1246 (br ipso-C6F5) 529 (Et) 519
(OCH3) 710 (Et) Elemental analysis was not successful after numerous attempts
Synthesis of [tBuNH2Ph][HB(C6F5)3] (21) In the glove box a 100 mL Teflon screw cap
Schlenk tube equipped with a stir bar was charged with a yellow solution of B(C6F5)3 (100 mg
0195 mmol) in pentane (7 mL) To the reaction tube N-tert-butylaniline (291 mg 0195 mmol)
was added immediately resulting in a pale orange cloudy solution The reaction tube was
degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2
(4 atm) at -196 ordmC After about 10 min of reaction time at RT white precipitate was observed in
the reaction vessel and the solution became colourless The tube was left to stir at RT for 12 h
The solvent was decanted and the white precipitate was washed with pentane (3 mL) dried under
vacuum and isolated (106 mg 0160 mmol 82)
1H NMR (400 MHz C6D5Br) δ 715 (br s 2H NH2) 712 (t 3JH-H = 73 Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 682 (d 3JH-H = 76 Hz 2H o-Ph) 369 (br q 1JB-H = 78 Hz 1H BH)
102 (s 9H tBu) 19F NMR (377 MHz C6D5Br) δ -1335 (br 2F o-C6F5) -1613 (br 1F p-
C6F5) -1650 (br 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 78 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1494 (dm 1JC-F = 238 Hz CF) 1382 (dm 1JC-F = 244
Hz CF) 1369 (dm 1JC-F = 247 Hz CF) 1309 (p-Ph) 1299 (m-Ph) 1237 (o-Ph) 1244 (ipso-
C6F5) 659 (tBu) 255 (tBu) (ipso-Ph was not observed) Anal calcd () for C28H17BF15N C
5071 H 258 N 211 Found C 5027 H 287 N 219
59
[tBuNHDPh][DB(C6F5)3] (21-d2) This compound was prepared similar to 21 using D2
19F NMR (377 MHz C6H5Br) δ -1332 (m 2F o-C6F5) -1609 (br 1F p-C6F5) -1646 (m 2F
m-C6F5) 11B NMR (128 MHz C6H5Br) δ -238 (s BD)
Synthesis of [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 (22) In a glove box a 100 mL Teflon
screw cap Schlenk tube equipped with a stir bar was charged with a solution of B(C6F5)3 (304
mg 0594 mmol) and NN-(14-phenylenebis(methylene))bis(tert-butylamine) (725 mg 0297
mmol) in toluene (4 mL) The reaction was degassed three times with a freeze-pump-thaw cycle
on the vacuumH2 line The reaction flask was cooled to -196 ordmC and filled with H2 (4 atm)
Immediate precipitation of a white solid was observed at RT The reaction mixture was stirred
overnight at 70 ordmC Pentane (10 mL) was added after which the supernatant was decanted The
residue was washed with pentane (5 mL) and dried in vacuo to give the product as a white
powder (374 mg 0297 mmol gt99)
1H NMR (400 MHz CD2Cl2) δ 727 (s 4H Ph) 595 (br s 4H NH2) 438 (s 4H CH2) 339
(br q 1JB-H = 83 Hz 2H BH) 162 (s 18H tBu) 19F NMR (377 MHz CD2Cl2) δ -1349 (m 3JF-F = 21 Hz 2F o-C6F5) -1635 (t 3JF-F = 21 Hz 1F p-C6F5) -1670 (m 2F m-C6F5) 11B
NMR (128 MHz CD2Cl2) δ -243 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz d8-THF )
δ 1493 (dm 1JC-F = 236 Hz CF) 1461 (quaternary C for C6H4) 1385 (dm 1JC-F = 243 Hz CF)
1374 (dm 1JC-F = 246 Hz CF) 1345 (br ipso-C6F5) 1314 (Ph) 595 (tBu) 461 (CH2) 259
(tBu) Anal calcd () for C51H30B2F30N2 C 4852 H 240 N 222 Found C 4882 H 269 N
252
Compounds 23 ndash 214 were prepared following a common procedure In the glove box a 25 mL
Teflon screw cap Schlenk tube equipped with a stir bar was charged with a yellow solution of
B(C6F5)3 (379 mg 740 μmol) and N-phenyl amine (740 μmol) in toluene (2 mL) The reaction
tube was degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and
filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube was placed in a 110
ordmC oil bath After the appropriate reaction time the toluene was removed under reduced pressure
resulting in crude pale yellow oil The oil was washed with pentane (6 mL) affording the product
as a white powder
60
[tBuNH2Cy][HB(C6F5)3] (23) N-tert-butylaniline (110 mg 740 μmol) reaction time 48 h
product (415 mg 620 μmol 84)
1H NMR (400 MHz C6D5Br) δ 507 (br 2H NH2) 355 (br q 1JB-H = 83 Hz 1H BH) 272 (m
1H N-Cy) 155 (m 2H Cy) 145 (m 2H Cy) 131 (m 1H Cy) 117 (m 3H Cy) 091 (s 9H
tBu) 090 (m 2H Cy) 19F NMR (377 MHz C6D5Br) δ -1327 (m 3JF-F = 21 Hz 2F o-C6F5)
1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1645 (m 2F m-C6F5) 11 B NMR (128 MHz C6D5Br) δ -
240 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 238 Hz
CF) 1382 (dm 1JC-F = 247 Hz CF) 1368 (dm 1JC-F = 247 Hz CF) 1354 (ipso-C6F5) 610
(tBu) 561 (N-Cy) 319 (Cy) 258 (tBu) 244 (Cy) 236 (Cy) Anal calcd () for
C28H23BF15N C 5025 H 346 N 209 Found C 4985 H 357 N 219
Synthesis of PhNHiPrB(C6F5)3 (24rsquo) In a glove box a 20 mL dram vial equipped with a
magnetic stir bar was charged with B(C6F5)3 (176 mg 0344 mmol) and N-isopropylaniline (465
mg 0344 mmol) in toluene (4 mL) All volatiles were removed and the crude oil was washed
with hexane (2 mL) The hexane portion was reduced in volume and placed in a -30 ordmC freezer
Colourless crystals were obtained (122 mg 0192 mmol 55)
1H NMR (400 MHz CD2Cl2 193K) δ 740 - 726 (m 5H Ph) 696 (br 1H NH) 416 (br m
1H iPr) 123 (br 3H iPr) 072 (br 3H iPr) 19F NMR (367 MHz CD2Cl2 193K) δ -1219 (m
1F o-C6F5) -1272 (m 1F o-C6F5) -1279 (m 2F o-C6F5) -1315 (m 1F o-C6F5) -1388 (m
1F o-C6F5) -1543 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F p-C6F5) -1575 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1625 (m 1F m-
C6F5) -1627 (m 1F m-C6F5) -1629 (m 1F m-C6F5) -1636 (m 1F m-C6F5) 11B NMR (128
MHz CD2Cl2 193K) δ -323 (s B-N) 13C1H NMR (101 MHz CD2Cl2 298K) δ 1478 (dm 1JC-F = 246 Hz CF) 1390 (dm 1JC-F = 242 Hz CF) 1365 (dm 1JC-F = 236 Hz CF) 1328
(ipso-Ph) 1301 (o-Ph) 1295 (p-Ph) 1227 (m-Ph) 556 (iPr) 195 (iPr) (ipso-C6F5 was not
observed) Anal calcd () for C27H13BF15N C 5011 H 202 N 216 Found C 4961 H 246
N 209
[iPrNH2Cy][HB(C6F5)3] (24) N-Isopropylaniline (100 mg 740 μmol) reaction time 36 h
product (481 mg 730 μmol 93) Crystals suitable for X-ray diffraction were grown from a
layered dichloromethanepentane solution at -30 ordmC
61
1H NMR (400 MHz C6D5Br) δ 510 (s 2H NH2) 356 (br q 1JB-H = 84 Hz 1H BH) 303 (m 1JH-H = 65 Hz 1H iPr) 276 (m 1H N-Cy) 156 (m 2H Cy) 147 (m 2H Cy) 134 (m 1H
Cy) 099 - 086 (m 5H Cy) 091 (d 1JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1330 (m 3JF-F = 21 Hz 2F o-C6F5) -1609 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-
C6F5) 11 B NMR (128 MHz C6D5Br) δ -239 (d 1JB-H = 84 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1483 (dm 1JC-F = 238 Hz CF) 1384 (dm 1JC-F = 247 Hz CF) 1369 (dm 1JC-F =
248 Hz CF) 1288 (ipso-C6F5) 567 (N-Cy) 498 (iPr) 294 (Cy) 241 (Cy) 240 (Cy) 189
(iPr) Anal calcd () for C27H21BF15N C 4949 H 323 N 214 Found C 4952 H 345 N
219
[Cy2NH2][HB(C6F5)3] (25) Method 1 N-Cyclohexylaniline (130 mg 740 μmol) reaction
time 36 h product (452 mg 650 μmol 88) Method 2 Diphenylamine (125 mg 740 μmol)
reaction time 96 h product (334 mg 480 μmol 65) Crystals suitable for X-ray diffraction
were grown from a concentrated solution in C6D5Br at RT
1H NMR (400 MHz C6D5Br) δ 498 (br s 2H NH2) 317 (br q 1JB-H = 86 Hz 1H BH) 247
(m 2H N-Cy) 122 (m 4H Cy) 111 (m 4H Cy) 099 (m 2H Cy) 070 - 046 (m 10H Cy)
19F NMR (377 MHz C6D5Br) δ -1332 (m 3JF-F = 20 Hz 2F o-C6F5) -1608 (t 3JF-F = 20 Hz
1F p-C6F5) -1648 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 86 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 241 Hz CF) 1380 (dm 1JC-F =
247 Hz CF) 1365 (dm 1JC-F = 248 Hz CF) 1264 (ipso-C6F5) 558 (N-Cy) 293 (Cy) 238
(Cy) 237 (Cy) Anal calcd () for C30H25BF15N C 5182 H 362 N 201 Found C 5217 H
386 N 212
[iPrNH2(2-MeC6H10)][HB(C6F5)3] (26) N-Isopropyl-2-methylaniline (111 mg 740 μmol)
reaction time 36 h product (398 mg 570 μmol 77) NMR data is reported for one isomer
1H NMR (400 MHz C6D5Br) δ 587 (br 2H NH2) 375 (br q 1JB-H = 82 Hz 1H BH) 318 (m
1H N-Cy) 313 (m 3JH-H = 62 Hz 1H iPr) 180 - 118 (m 9H Cy) 113 (d 3JH-H = 64 Hz
6H iPr) 086 (d 3JH-H = 62 Hz 3H Me) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21
Hz 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -237 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) partial δ
1485 (dm 1JC-F = 235 Hz CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF)
1236 (ipso-C6F5) 638 (N-Cy) 593 (iPr) 347 (Cy) 319 (Cy) 304 (CMeH) 291 (Cy) 210
62
(Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C 5021 H
359 N 214
[iPrNH2(4-MeC6H10)][HB(C6F5)3] (27) N-isopropyl-4-methylaniline (111 mg 740 μmol)
reaction time 36 h product (377 mg 540 μmol 73)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 83 Hz 1H BH) 317 (m 3JH-H = 64 Hz 1H iPr) 290 (m 1H N-Cy) 171 (m 2H Cy) 162 (m 2H Cy) 120 (m 3H
Cy) 110 (d 3JH-H = 64 Hz 6H iPr) 086 (d 3JH-H = 66 Hz 3H Me) 077 (m 2H Cy) 19F
NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1613 (t 3JF-F = 21 Hz 1F
p-C6F5) -1652 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -236 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 247
Hz CF) 1367 (dm 1JC-F = 250 Hz CF) 562 (N-Cy) 495 (iPr) 319 (Cy) 304 (CMeH) 291
(Cy) 210 (Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found
C 5014 H 348 N 209
[iPrNH2(4-MeOC6H10)][HB(C6F5)3] (28) N-Isopropyl-4-methoxyaniline (122 mg 740
μmol) reaction time 36 h product (308 mg 450 μmol 61)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 346 (br
4H OMe and CHOMe) 299 (br m 1H N-Cy) 237 (m 1H iPr) 162 (m 2H Cy) 129 (m
2H Cy) 107 (m 4H Cy) 081 (d 3JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1338 (m 3JF-F = 21 Hz 2F o-C6F5) -1623 (t 3JF-F = 21 Hz 1F p-C6F5) -1659 (m 2F m-
C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1484 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 247 Hz CF) 1367 (dm 1JC-F =
247 Hz CF) 1243 (ipso-C6F5) 636 (OMe) 583 (CHOMe) 551 (N-Cy) 497 (iPr) 267 (Cy)
246 (Cy) 183 (iPr) Anal calcd () for C28H23BF15NO C 4908 H 338 N 204 Found C
4945 H 329 N 230
[iPrNH2(3-MeC6H10)][HB(C6F5)3] (29) N-Isopropyl-3-methylaniline (111 mg 740 μmol)
reaction time 36 h product (406 mg 610 μmol 82)
1H NMR (400 MHz C6D5Br) δ 547 (br 2H NH2) 369 (br q 1JB-H = 80 Hz 1H BH) 320 (m
1H iPr) 297 (m 1H N-Cy) 171 (m 3H Cy) 153 (m 1H Cy) 112 (m 1H CMeH) 112 (d
63
3JH-H = 60 Hz 3H iPr) 111 (d 3JH-H = 60 Hz 3H iPr) 104 (m 2H Cy) 086 (d 3JH-H = 66
Hz 3H Me) 078 (m 1H Cy) 068 (m 1H Cy) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1611 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5) 11B
NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ
1488 (dm 1JC-F = 237 Hz CF) 1390 (dm 1JC-F = 250 Hz CF) 1372 (dm 1JC-F = 247 Hz CF)
571 (N-Cy) 503 (iPr) 381 (Cy) 330 (Cy) 315 (CMeH) 293 (Cy) 241 (Cy) 219 (Me)
196 (iPr) 192 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C
5011 H 350 N 216
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] (210) N-Isoporpyl-35-dimethylaniline (121 mg 740
μmol) reaction time 72 h product (243 mg 360 μmol 48) Mixture of isomers was obtained
NMR data for one isomer is reported
1H NMR (400 MHz C6D5Br) δ 555 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 300 -
280 (br m 2H iPr N-Cy) 182 (br m 1H Cy) 149 - 100 (m 5H Cy) 093 (m 6H iPr) 077
- 072 (m 1H Cy) 068 - 062 (m 6H Me) 059 - 048 (m 1H Cy) 19F NMR (377 MHz
C6D5Br) δ -1337 (m 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5)
11B NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 82 Hz BH) 13C1H NMR (100 MHz
C6D5Br) partial δ 1479 (dm 1JC-F = 240 Hz CF) 1378 (dm 1JC-F = 249 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1227 (ipso-C6F5) 560 (N-Cy) 494 (iPr) 410 (Cy) 378 (Cy) 270 (Cy)
212 (Me) 188 (iPr) Anal calcd () for C29H25BF15N C 5097 H 369 N 205 Found C
5087 H 399 N 212
[CyNH2CHPhCH2Ph][HB(C6F5)3] (211) cis-123-Triphenylaziridine (201 mg 740 μmol)
reaction time 96 h product (293 mg 370 μmol 50)
1H NMR (400 MHz CD2Cl2) δ 755 (m 1H p-Ph) 745 (m 4H Ph) 740 (m 3H Ph) 720
(m 2H Ph) 588 (br 2H NH2) 461 (t 3JH-H = 77 Hz 1H PhCH) 369 (br q 1JB-H = 85 Hz
1H BH) 344 (d 2H 3JH-H = 77 Hz PhCH2) 306 (m 1H N-Cy) 203 (m 1H Cy) 168 (m
4H Cy) 137 - 115 (br m 5H Cy) 19F NMR (377 MHz CD2Cl2) δ -1338 (m 3JF-F = 20 Hz
2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1662 (m 2F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -239 (d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F
= 245 Hz CF) 1382 (dm 1JC-F = 248 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1333 (ipso-Ph)
1321 (ipso-Ph) 1310 (p-Ph) 1301 (Ph) 1298 (Ph) 1289 (Ph) 1287 (p-Ph) 1273 (Ph) 1235
64
(ipso-C6F5) 641 (PhCH) 582 (N-Cy) 403 (PhCH2) 306 (Cy) 289 (Cy) 241 (Cy) 238
(Cy) 236 (Cy) Anal calcd () for C38H27BF15N C 5752 H 343 N 177 Found C 5762 H
395 N 187
[PhCH(Me)NH2Cy][HB(C6F5)3] (212) Method 1 N-(1-Phenylethylidene)aniline (144 mg
740 μmol) reaction time 96 h product (303 mg 420 μmol 57) Method 2 B(C6F5) (379 mg
0740 mmol) 3-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol) toluene (5 mL)
product (347 mg 0481 mmol 65)
1H NMR (400 MHz C6D5Br) δ 735 (m 3H o p-Ph) 721 (m 2H m-Ph) 618 (br 1H NH2)
566 (br 1H NH2) 428 (m 1H NH2CHMe) 383 (br q 1JB-H = 83 Hz 1H BH) 288 (m 1H
N-Cy) 190 (m 1H Cy) 166 (m 2H Cy) 157 (m 1H Cy) 154 (d 3JH-H = 69 Hz 3H Me)
146 (m 1H Cy) 126 (m 2H Cy) 098 (m 3H Cy) 19F NMR (377 MHz C6D5Br) δ -1336
(m 2F o-C6F5) -1613 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -234 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 241 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1334
(ipso-Ph) 1296 (o-Ph) 1260 (m-Ph) 574 (NH2CHMe) 573 (N-Cy) 295 (Cy) 288 (Cy)
236 (Cy) 236 (Cy) 188 (Me) (p-Ph was not observed) Anal calcd () for C32H23BF15N C
5358 H 323 N 195 Found C 5374 H 300 N 189
[14-C6H10(iPrNH2)2][HB(C6F5)3]2 (213) N1N4-Di(propan-2-ylidene)benzene-14-diamine (70
mg 0037 mmol) reaction time 36 h product (293 mg 240 μmol 64)
1H NMR (400 MHz d8-THF) δ 784 (br 2H NH2) 376 (br q 1JB-H = 92 Hz 1H BH) 364 (m 3JH-H = 65 Hz 1H iPr) 335 (br m 1H N-Cy) 238 (m 2H Cy) 159 (m 2H Cy) 138 (d 3JH-
H = 65 Hz 6H iPr) 19F NMR (377 MHz d8-THF) δ -1346 (m 3JF-F = 20 Hz 2F o-C6F5) -
1670 (t 3JF-F = 20 Hz 1F p-C6F5) -1697 (m 2F m-C6F5) 11B NMR (128 MHz d8-THF) δ -
254 (d 1JB-H = 92 Hz BH) 13C1H NMR (101 MHz d8-THF) δ 1483 (dm 1JC-F = 237 Hz
CF) 1375 (dm 1JC-F = 242 Hz CF) 1362 (dm 1JC-F = 246 Hz CF) 1259 (ipso-C6F5) 528 (N-
Cy) 486 (iPr) 274 (Cy) 184 (iPr) Anal calcd () for C48H30B2F30N2 C 4701 H 247 N
228 Found C 4686 H 247 N 232
[(14-C6H10(iPrNH2))2CH2][HB(C6F5)3]2 (214) 44-Methylenebis(N-isopropylaniline) (104
mg 370 μmol) reaction time 76 h product (372 mg 280 μmol 76)
65
1H NMR (400 MHz C6D5Br) δ 513 (br 2H NH2) 359 (br q 1JB-H = 81 Hz 1H BH) 301 (m
1H iPr) 276 (m 1H N-Cy) 168 (m 1H Cy) 151 (m 2H Cy) 145 (m 1H CH2) 132 (m
2H Cy) 091 (m 2H Cy) 089 (m 2H Cy) 089 (d 3JH-H = 68 Hz 6H iPr) 19F NMR (377
MHz C6D5Br) δ -1331 (m 3JF-F = 20 Hz 2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -
1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 81 Hz BH) 13C1H
NMR (101 MHz C6D5Br) δ 1486 (dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF)
1385 (dm 1JC-F = 247 Hz CF) 569 (iPr) 500 (N-Cy) 432 (CH2) 296 (Cy) 272 (CH2-Cy)
242 (Cy) 190 (iPr) Anal calcd () for C55H42B2F30N2 C 4995 H 320 N 212 Found C
4973 H 333 N 221
[iPr2NHPh][HB(C6F5)3] (215) In a glove box B(C6F5)3 (379 mg 740 μmol) and NN-
diisopropylaniline (131 mg 740 μmol) were dissolved in C6D5Br (05 mL) and added into a
Teflon capped sealed J-Young tube The J-Young tube was degassed three times through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC and placed
in a 110 ordmC oil bath for 16 h To the C6D5Br solution pentane was added drop wise until the
product precipitated The white solid was isolated (442 mg 640 μmol 87) Crystals suitable
for X-ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H o p-Ph) 693 (m 2H m-Ph) 670 (br 1H NH)
371 (br q 1JB-H = 85 Hz 1H BH) 358 (m 3JH-H = 63 Hz 2H iPr) 093 (d 3JH-H = 63 Hz 6H
iPr) 077 (d 3JH-H = 63 Hz 6H iPr) 19F NMR (377 Hz C6D5Br) δ -1326 (m 3JF-F = 20 Hz
2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -245 ppm (br d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484
(dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1322
(ipso-Ph) 1304 (m-Ph) 1231 (p-Ph) 1211 (o-Ph) 584 (iPr) 188 (iPr) 168 (iPr) Anal calcd
() for C30H21BF15N C 5212 H 306 N 203 Found C 5183 H 329 N 211
Synthesis of 216 - 218 is similar to the general procedure used for compounds 23 - 214 Since
compounds [(2-FC6H10)NH2iPr][HB(C6F5)3] 216b and [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b
were present in trace amounts (5) isolation and characterization proved difficult therefore
spectroscopic data for the two compounds has not been reported
[iPrNH2Cy][FB(C6F5)3] (216a) B(C6F5)3 (379 mg 0740 mmol) 2-fluoro-N-isopropylaniline
(115 mg 0740 mmol) or 3-fluoro-N-isopropylaniline (115 mg 0740 mmol) toluene (5mL)
66
reaction time 72 h product from 2-fluoro-N-isopropylaniline (294 mg 0440 mmol 59)
product from 3-fluoro-N-isopropylaniline (381 mg 0570 mmol 77) Crystals suitable for x-
ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 561 (br 2H NH2) 288 (m 3JH-H = 64 Hz 1H iPr) 262 (br
m 1H N-Cy) 149 (m 2H Cy) 144 (m 2H Cy) 135 (m 1H Cy) 092 - 083 (m 5H Cy)
085 (d 1JH-H = 63 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1370 (m 6F o-C6F5) -1616
(t 3JF-F = 22 Hz 3F p-C6F5) -1669 (m 6F m-C6F5) -1795 (br s 1F BF) 11B NMR (128
MHz CD2Cl2) δ 051 (br s BF) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 239
Hz CF) 1394 (dm 1JC-F = 241 Hz CF) 1373 (dm 1JC-F = 249 Hz CF) 560 (N-Cy) 489
(iPr) 293 (Cy) 245 (Cy) 241 (Cy) 188 (iPr) Anal calcd () for C27H20BF16N C 4817 H
299 N 208 Found C 4804 H 307 N 210
[(4-FC6H8)NH2iPr][HB(C6F5)3] (218) B(C6F5)3 (379 mg 074 mmol) 4-fluoro-N-
isopropylaniline (113 mg 074 mmol) toluene (5 mL) reaction time 72 h product (308 mg
0460 mmol 62) Crystals suitable for X-ray diffraction were obtained from a layered solution
of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 582 (br s 2H NH2) 477 (dm 3JF-H = 14 Hz 1H CH=CF)
355 (br q 1JB-H = 81 Hz 1H BH) 345 (m 1H iPr) 293 (m 1H N-Cy) 192 - 133 (m 6H
CH2 groups of Cy) 081 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -9903
(dm 3JF-H = 14 Hz 1F FC=CH) -1331 (m 3JF-F = 23 Hz 6F o-C6F5) -1606 (t 3JF-F = 21 Hz
3F p-C6F5) -16398 (m 6F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 81 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1584 (d 1JC-F = 255 Hz CF=CH) 1484 (dm 1JC-F =
224 Hz C6F5)1385 (dm 1JC-F = 247 Hz C6F5)1369 (dm 1JC-F = 247 Hz C6F5) 1230 (ipso-
C6F5) 974 (d 2JC-F = 20 Hz CF=CH) 518 (iPr) 504 (N-Cy) 254 (d 2JC-F = 81 Hz CH2CF)
247 (d 3JC-F = 90 Hz CH2CH=CF) 228 (CH2) Anal calcd () for C27H18BF16N C 4831 H
270 N 209 Found C 4793 H 282 N 203
Synthesis of 219 and 220 is similar to the general procedure used for compounds 23 - 214
Synthesis of [C6H10NHCH(CH3)Ph][HB(C6F5)3] (219) Method 1 B(C6F5) (358 mg 0700
mmol) 4-methoxy-N-(1-phenylethylidene)aniline (113 mg 0500 mmol) toluene (4 mL) (107
67
mg 0150 mmol 30) Crystals suitable for X-ray diffraction were obtained from a layered
solution of dichloromethanepentane at -30 degC
Method 2 In the glovebox trans-(4-CH3OC6H10)NHCH(CH3)Ph (81 mg 340 μmol) and
B(C6F5)3 (17 mg 340 μmol) were dissolved in d8-toluene (04 mL) and added into a Teflon
capped J-Young tube The tube was degassed once through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at
110 degC The solvent was removed under vacuum and the residue was washed with pentane (2
mL) The product was dried under vacuum and collected (82 mg 110 μmol 33)
1H NMR (500 MHz CD2Cl2) δ 752 (tm 3JH-H = 77 Hz 1H p-Ph)
746 (tm 3JH-H = 77 Hz 2H m-Ph) 735 (dm 3JH-H = 77 Hz 2H o-
Ph) 555 (br m 1H NH) 447 (dd 3JH-H = 95 Hz 48 Hz 1H H1)
415 (dq 3JH-H = 102 Hz 68 Hz 1H CH(CH3)Ph) 374 (m JH-H = 95
Hz 48 Hz 1H H5) 363 (br q 1JB-H = 83 Hz 1H BH) 229 (m 1H
H3) 223 (m 1H H4) 215 (m 1H H2) 201 (m 1H H3) 196 (m 1H H6) 190 (m 1H H2)
188 (m 1H H4) 177 (d 3JH-H = 68 Hz 3H CH3) 176 (m 1H H6) 19F NMR (377 MHz
CD2Cl2) δ -1304 (m 2F o-C6F5) -1638 (t 1F 3JF-F = 21 Hz p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -249 (d 1JB-H = 83 Hz BH) 13C1H NMR (125 MHz
CD2Cl2) δ 1482 (dm 1JC-F = 236 Hz C6F5) 1378 (dm 1JC-F = 245 Hz C6F5) 1364 (dm 1JC-F
= 249 Hz C6F5) 1346 (ipso-Ph) 1308 (p-Ph) 1301 (m-Ph) 1266 (o-Ph) 1246 (ipso-C6F5)
652 (C5) 647 (C1) 586 (CH(CH3)Ph) 277 (C2) 273 (C6) 254 (C3 C4) 188 (CH3) Anal
calcd () for C32H21BF15N C 5373 H 296 N 196 Found 5384 H 321 N 200
[(o-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (220) Ratio of cis and trans isomers = 11
determined by 1H NMR spectroscopy The trans isomer has been isolated and characterized
B(C6F5) (379 mg 0740 mmol) 2-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol)
toluene (5 mL) product (508 mg 0680 mmol 92) Crystals suitable for X-ray diffraction were
obtained from a layered solution of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H m p-Ph) 691 (m 2H o-
Ph) 655 (br s 2H NH2) 413 (q 3JH-H = 64 Hz 1H CH(Me)Ph) 365
(br q 1JB-H = 92 Hz 1H BH) 313 (ddd 3JH-H = 107 Hz 43 Hz 1H
CHOCH3) 298 (s 3H OCH3) 237 (td 3JH-H = 107 Hz 1H CH2CHNH2) 180 (m 1H DCH2)
68
173 (dm 3JH-H = 136 Hz 1H ACH2) 140 (m 2H DCCH2) 128 (d 3JH-H = 64 Hz 3H
CH(CH3)Ph) 120 (m 1H BCH2) 095 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H BCH2)
066 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H CCH2) 039 (pseudo qd JH-H = 136 Hz 3JH-
H = 31 Hz 1H ACH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -1634 (t 3JF-F =
21 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -246 (d 1JB-H = 92
Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 235 Hz C6F5) 1381 (dm 1JC-F = 246 Hz C6F5) 1367 (dm 1JC-F = 247 Hz C6F5) 1334 (ipso-Ph) 1304 (p-Ph) 1299 (m-
Ph) 1264 (o-Ph) 1239 (ipso-C6F5) 778 (CHOCH3) 611 (CH2CHNH2) 571 (CH(CH3)Ph)
554 (OCH3) 279 (ACH2) 257 (DCH2) 236 (CCH2) 224 (BCH2) 202 (CH3) Anal calcd ()
for C33H25BF15NO C 5303 H 337 N 187 Found 5288 H 357 N 190
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] (221a) Part 1 In a Schlenk
tube trans-(4-CH3OC6H10)NHCH(CH3)Ph (16 mg 680 μmol) was dissolved in pentane (2 mL)
and hydrogen chloride (68 μL 027 mmol 40 M in 14-dioxane) was added drop wise White
precipitate was immediately formed The solvent was decanted and the solid was washed with
pentane (2 mL) and dried in vacuo to yield trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (163 mg
610 μmol 89)
Part 2 In the glovebox a 4 dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph
HCl (61 mg 0026 mmol) in dichloromethane (8 mL) and K B(C6F5)4 (162 mg 260 mmol)
was added at once The reaction was allowed to stir for 16 h at room temperature The mixture
was filtered through Celite and the solvent was removed under vacuum The product was
obtained as a white solid (209 mg 230 μmol 88)
1H NMR (400 MHz C6D5Br) δ 719 (m 2H m-Ph) 690 (m 3H o p-Ph) 510 (br s 2H NH2)
402 (q 3JH-H = 69 Hz 1H CH(CH3)Ph) 310 (s 3H OCH3) 272 (m 2H CyCHOCH3 CyCHN) 174 (m 3H CyCH2) 156 (m 1H CyCH2) 127 (d 3JH-H = 69 Hz 3H CH(CH3)Ph
093 - 084 (m 4H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1318 (m 2F o-C6F5) -1610 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -164 (s
B(C6F5)4)
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (221b) In the glovebox a 4
dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (93 mg 0034 mmol) in
dichloromethane (8 mL) and Na HB(C6F5)3 (185 mg 340 μmol) was added at once The
69
reaction was allowed to stir for 16 h at room temperature The mixture was filtered through
Celite and the solvent was removed under vacuum The product was obtained as a white solid
(193 mg 260 μmol 76) Preparation of Na HB(C6F5)3 is reported in Chapter 3
1H NMR (400 MHz C6D5Br) δ 716 (m 3H Ph) 702 (m 2H Ph) 546 (br 2H NH2) 407 (q 3JH-H = 68 Hz 1H CH(CH3)Ph) 347 (br q 1JB-H = 78 Hz 1H BH) 307 (s 3H OCH3) 283
(tt 3JH-H = 106 Hz 46 Hz 1H CyCHOCH3) 268 (tt 3JH-H = 117 Hz 39 Hz 1H CyCHN) 183
(m 3H CyCH2) 156 (dm 3JH-H = 128 Hz 1H CyCH2) 132 (d 3JH-H = 68 Hz CH(CH3)Ph)
121 (m 2H CyCH2) 084 (m 2H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1334 (m 2F o-
C6F5) -1604 (t 3JF-F = 22 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -238 (d 1JB-H = 78 Hz BH)
Synthesis of [C6H10NH(iPr)][CH3OB(C6F5)3] (222) In the glovebox a Schlenk tube (25 mL)
was charged with trans-(4-CH3OC6H10)NH(iPr) (253 mg 0148 mmol) in toluene (05 mL) and
B(C6F5) (758 mg 0148 mmol) dissolved in toluene (05 mL) was added at once The Schlenk
was sealed and heated at 110 degC for 2 h and the solvent was removed under vacuum The crude
solid was washed with pentane (2 mL) to yield the product as a white solid (991 mg 0145
mmol 98) Crystals suitable for X-ray diffraction were obtained from a layered solution of
dichloromethanepentane at -30 degC
1H NMR (500 MHz CD2Cl2) δ 810 (s 1H NH) 413 (m 2H CH2CH) 315 (m 3JH-H = 66
Hz 1H iPr) 302 (s 3H BOCH3) 222 (dm 1JH-H = 93 Hz 2H ACH2) 205 (dm 1JH-H = 100
Hz 2H BCH2) 181 (dm 1JH-H = 100 Hz 2H BCH2) 172 (dm 1JH-H = 93 Hz 2H ACH2) 136
(d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1351 (br 2F o-C6F5) -1620 (t 3JF-F = 20 Hz 1F p-C6F5) -1664 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -242 (s
BOCH3) 13C1H NMR (125 MHz CD2Cl2) δ 1482 (dm 1JC-F = 241 Hz C6F5) 1388 (dm 1JC-F = 262 Hz C6F5) 1370 (dm 1JC-F = 252 Hz C6F5) 1231 (ipso-C6F5) 634 (CH2CH) 522
(BOCH3) 502 (iPr) 274 (ACH2) 258 (BCH2) 185 (iPr) Anal calcd () for C28H21BF15N05
CH2Cl2 C 4717 H 306 N 193 Found 4674 H 327 N 199 HRMS-DART mz [M] calcd
for C9H18N+ 1401 Found 1401
Synthesis of [C6H10NH(iPr)][HB(C6F5)3] (223) Method 1 In the glovebox trans-(4-
CH3OC6H10)NH(iPr) (250 mg 0150 mmol) and B(C6F5)3 (760 mg 0150 mmol) were
dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The tube was
70
degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4
atm) at -196 ordmC The reaction was complete after 12 h at 110 degC The solvent was removed under
vacuum and the residue was washed with pentane (2 mL) The product was collected as a white
powder (607 mg 930 μmol 62)
Method 2 In the glovebox compound [C6H10NH(iPr)][CH3OB(C6F5)3] (222) (200 mg 290
μmol) was dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The
tube was degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with
H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at 110 degC
1H NMR (400 MHz C6D5Br) δ 510 (br m 1H NH) 367 (br q 1JB-H = 76 Hz 1H BH) 347
(br s 2H CH) 242 (m 1H iPr) 162 (m 2H CH2) 131 (m 2H CH2) 111 (m 2H CH2) 093
(m 2H CH2) 138 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -1338 (m 3JF-F
= 21 Hz 2F o-C6F5) -1622 (t 3JF-F = 21 Hz 1F p-C6F5) -1658 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -239 (d 1JB-H = 76 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483
(dm 1JC-F = 235 Hz CF) 1381 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 248 Hz CF) 1242
(ipso-C6F5) 636 (CHCH2) 500 (iPr) 271 (CH2) 248 (CH2) 186 (iPr) Anal calcd () for
C27H19BF15N C 4964 H 293 N 214 Found C 4924 H 300 N 214
Compounds 224 - 235 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 50 mL Teflon screw cap Schlenk tube equipped with a stir bar was charged
with a solution of B(C6F5)3 (0379 g 0740 mmol) and the respective N-heterocycle in toluene (5
mL) The reaction tube was degassed three times through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube
was placed in a 115 ordmC oil bath for the indicated reaction time The solvent was then removed
under vacuum and the crude product was washed with pentane to yield the product as a white
solid
[26-Ph2C5H8NH2][HB(C6F5)3] (224) 26-Diphenylpyridine (171 mg 0740 mmol) reaction
time 16 h product (511 g 0680 mmol 92) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC Isomer ratio by 1HNMR
spectroscopy meso 91 rac 9
71
meso-[26-Ph2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 734 (tt 3JH-H = 70 Hz
4JH-H = 24 Hz 2H p-Ph) 726 (m 8H o m-Ph) 590 (br 2H NH2) 453 (m 3JH-H = 122 Hz 3JH-H = 24 Hz 2H C(H)Ph) 339 (br q 1JB-H = 90 Hz 1H BH) 226 (br m 3H CH2) 212 (m
2H CH2) 189 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1340 (m 2F o-C6F5) -1634 (t 3JF-F = 20 Hz 1F p-C6F5) -1666 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -246 (d 1JB-H = 90 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1483 (dm 1JC-F = 237 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1367 (dm 1JC-F = 246 Hz CF) 1338 (ipso-Ph) 1313 (p-Ph) 1271
(Ph) 1264 (Ph) 1241 (ipso-C6F5) 657 (C(H)(Ph)) 297 (CH2) 233 (CH2) Anal calcd ()
for C35H21BF15N C 5595 H 282 N 186 Found C 5547 H 303 N 186
[26-Me2C5H8NH2][HB(C6F5)3] (225) 26-Dimethylpyridine (793 mg 0740 mmol) reaction
time 60 h product (390 mg 0621 mmol 84) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC over 48 h Isomer ratio by 1HNMR spectroscopy meso 80 rac 20
meso-[26-Me2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 508 (br 2H NH2) 345
(br q 1JB-H = 83 Hz 1H BH) 268 (m 2H NC(H)Me) 137 (m 4H CH2) 086 (d 3JH-H = 64
Hz 6H CH3) 077 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -
1617 (t 3JF-F = 20 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1485 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF) 1236 (ipso-C6F5) 567
(NCH) 303 (CH2) 220 (CH2) 193 (CH3) Anal calcd () for C25H17BF15N C 4787 H 273
N 223 Found C 4764 H 290 N 222
(2-(EtOCO)C5H9NH)B(C6F5)3 (226) Ethyl 2-picolinate (112 mg 0740 mmol) reaction time
36 h product (366 mg 0547 mmol 74) The isolated product consisted of an equal ratio of
both diastereomers Anal calcd () for C26H15BF15NO2 C 4667 H 226 N 209 Found C
4660 H 247 N 211
RSSR-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2)
δ 590 (m 1H NH) 430 (m 1H CH(H)NH) 418 (br m 1H
CHOCOEt) 393 (dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 373
(dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 320 (dm 2JH-H = 126 Hz 1H CH(H)NH) 217
(m 2H CH2) 204 (dm 2JH-H = 134 Hz 1H CH2) 184 (m 1H CH2) 175 (m 1H CH2) 119
72
(t 3JH-H = 72 Hz 3H Et) 103 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1264 (m 1F o-
C6F5) -1280 (m 1F o-C6F5) -1295 (m 1F o-C6F5) -1297 (m 1F o-C6F5) -1404 (m 1F o-
C6F5) -1433 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F
p-C6F5) -1575 (t 3JF-F = - 21 Hz 1F p-C6F5) -1616 (m 1F m-C6F5) -1621 (m 1F m-C6F5) -
1628 (m 1F m-C6F5) -1631 (m 1F m-C6F5) -1640 (m 1F m-C6F5) -1649 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -486 (s BNH) 13C1H NMR (101 MHz CD2Cl2) δ 1674
(OCO) 636 (Et) 568 (CHOCOEt) 445 (CH(H)NH) 305 (CH2) 208 (CH2) 181 (CH2) 134
(Et)
RRSS-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ
743 (br m 1H NH) 440 (dq 2JH-H = 107 Hz 3JH-H = 71 Hz 1H Et)
438 (dq 2JH-H = 91 Hz 3JH-H = 71 Hz 1H Et) 424 (br m 1H
CHOCOEt) 350 (ddd 2JH-H = 134 Hz 3JH-H = 89 Hz 3JH-H = 49 Hz 1H CH(H)NH) 333
(dm JH-H = 133 Hz 1H CH(H)NH) 218 (m 1H CH2) 208 (m 1H CH2) 185 (m 1H CH2)
154 (m 1H CH2) 151 (m 1H CH2) 135 (t 3JH-H = 71 Hz 3H Et) 124 (m 1H CH2) 19F
NMR (377 MHz CD2Cl2) δ -1276 (m 1F o-C6F5) -1285 (m 2F o-C6F5) -1291 (m 1F o-
C6F5) -1371 (m 1F o-C6F5) -1421 (m 1F o-C6F5) -1549 (t 3JF-F = 21 Hz 1F p-C6F5) -
1572 (t 3JF-F = 21 Hz 1F p-C6F5) -1578 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5)
-1626 (m 1F m-C6F5) -1630 (m 3F m-C6F5) -1633 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -486 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1712 (OCO) 616 (Et) 581
(CHOCOEt) 457 (CH(H)NH) 259 (CH2) 235 (CH2) 171 (CH2) 139 (Et)
(2-PhC5H9NH)B(C6F5)3 (227a) and [2-PhC5H9NH2][HB(C6F5)3] (227b) 2-Phenylpyridine
(115 mg 0740 mmol) reaction time 48 h product (269 mg 0400 mmol 54) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC The isolated product consisted of 227a (RSSR 70) 227a (SSRR 10) 227b (20)
Anal calcd () for C29H15BF15N C 5158 H 254 N 209 Found C 5209 H 258 N 210
RSSR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 727
(m 2H Ph) 714 (m 3H Ph) 555 (br s 1H NH) 415 (ddd 3JH-H = 111
Hz 3JH-H = 94 Hz 36 Hz 1H CHPh) 356 (dm 2JH-H = 132 Hz 1H CH(H)NH) 257 (ddd 2JH-H = 132 Hz 3JH-H = 103 Hz 3JH-H = 31 Hz 1H CH(H)NH) 199 - 135 (m 6H CH2) 19F
NMR (377 MHz C6D5Br) δ -1216 (m 1F o-C6F5) -1236 (m 1F o-C6F5) -1274 (m 1F o-
73
C6F5) -1286 (m 1F o-C6F5) -1312 (m 1F o-C6F5) -1426 (m 1F o-C6F5) -1534 (t 3JF-F =
22 Hz 1F p-C6F5) -1566 (t 3JF-F = 21 Hz 1F p-C6F5) -1567 (t 3JF-F = 21 Hz 1F p-C6F5) -
1615 (m 2F m-C6F5) -1620 (m 3F m-C6F5) -1624 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -391 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1385 (ipso-Ph) 1297 (p-Ph)
1291 (Ph) 1285 (Ph) 646 (CHPh) 521 (NCH2) 355 (CH2) 248 (CH2) 219 (CH2)
SSRR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 710 -
681 (m 5H Ph) 581 (br s 1H NH) 449 (m 1H CHPh) 347 (dm 2JH-H = 125 Hz 1H CH(H)NH) 321 (m 2JH-H = 125 Hz 1H CH(H)NH) 185 (m 2H CH2)
176 (m 2H CH2) 128 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1249 (m 1F o-C6F5)
-1263 (m 1F o-C6F5) -1268 (m 1F o-C6F5) -1287 (m 1F o-C6F5) -1390 (m 1F o-C6F5) -
1431 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1559 (t 3JF-F = 21 Hz 1F p-C6F5)
-1562 (t 3JF-F = 21 Hz 1F p-C6F5) -1598 (m 1F m-C6F5) -1610 (m 1F m-C6F5) -1617 (m
1F m-C6F5) -1620 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1643 (m 1F m-C6F5) 11B NMR
(128 MHz CD2Cl2) δ -39 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1365 (ipso-Ph)1294
(p-Ph) 1283 (Ph) 1256 (Ph) 629 (CHPh) 454 (NCH2) 350 (CH2) 297 (CH2) 260 (CH2)
[2-PhC5H9NH2][HB(C6F5)3] (227b) 1H NMR (400 MHz CD2Cl2) δ 710 - 681 (m 5H Ph)
557 (br s 2H NH2) 355 (dd 3JH-H = 117 Hz 28 Hz 1H CHPh) 330 (br q 1JB-H = 86 Hz
1H BH) 295 (dm JH-H = 124 Hz 1H CH(H)NH2) 244 (pseudo td JH-H = 124 Hz 3JH-H = 30
Hz 1H CH(H)NH2) 186 (m 2H CH2) 165 (m 1H CH2) 157 (m 1H CH2) 141 (m 1H
CH2) 137 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 2F o-C6F5) -1610 (t 3JF-
F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -248 (d 1JB-H
= 86 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1399 (ipso-Ph) 1297 (Ph) 1295 (p-Ph)
1267 (Ph) 625 (CHPh) 471 (NCH2) 327 (CH2) 242 (CH2) 240 (CH2)
[2-MeC9H15NH2][HB(C6F5)3] (228) 2-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (331 mg 500 mmol 67) Crystals suitable for X-ray diffraction were grown from
a layered solution of dichloromethanepentane at -30 ordmC About 60 of the isolated reaction
product consisted of the SSSRRR diastereomer
1H NMR (400 MHz C6D5Br) δ 602 (br 1H NH2) 460 (br 1H NH2) 336 (br q 1JB-H = 83
Hz 1H BH) 315 (dt 3JH-H = 100 Hz 52 Hz 1H NCHCH) 276 (m 1H CHMe) 145 - 096
(m 8H CH2) 110 (m 1H CHCHN) 093 - 067 (m 4H CH2) 081 (d 3JH-H = 64 Hz 3H
74
Me) 19F NMR (377 MHz C6D5Br) δ -1335 (m 2F o-C6F5) -1607 (t 3JF-F = 22 Hz 1F p-
C6F5) -1646 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1384 (dm 1JC-F = 246
Hz CF) 1369 (dm 1JC-F = 249 Hz CF) 1233 (ipso-C6F5) 577 (NCH) 493 (CHMe) 322
(CHCHN) 281 (CH2) 272 (CH2) 255 (CH2) 240 (CH2) 236 (CH2) 211 (CH2) 189 (Me)
Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C 5021 H 331 N 212
[2-PhC9H15NH2][HB(C6F5)3] (229) B(C6F5)3 (289 mg 0564 mmol) 2-phenylquinoline (116
mg 0564 mmol) reaction time 48 h product (391 mg 536 mmol 95) Crystals suitable for
X-ray diffraction were grown from a layered solution of dichloromethanepentane at -30 ordmC
About 73 of the reaction mixture consisted of the reported SSSRRR diastereomer
1H NMR (400 MHz CD2Cl2) δ 733 (tm 3JH-H = 73 Hz 1H p-Ph) 726 (tm 3JH-H = 73 Hz
2H m-Ph) 720 (dm 3JH-H = 73 Hz 2H o-Ph) 646 (br 1H NH2) 501 (br t 1H NH2) 433
(dm 3JH-H = 105 Hz 33 Hz 1H C(H)Ph) 380 (br m 1H CH2C(H)NH2) 320 (br q 1JB-H = 87
Hz 1H BH) 218 - 108 (m 13H CH2C(H)CH2 and CH2) 19F NMR (377 MHz C6D5Br) δ -
1334 (m 2F o-C6F5) -1612 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -242 (d 1JB-H = 87 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1342
(ipso-Ph) 1312 (p-Ph) 1301 (m-Ph) 1269 (o-Ph) 647 (CH2C(H)NH2) 601 (C(H)Ph) 345
(CH2C(H)CH2) 291 (CH2) 285 (CH2) 251 (CH2) 249 (CH2) 248 (CH2) 197 (CH2) Anal
calcd () for C33H23BF15N C 5434 H 318 N 192 Found C 5431 H 331 N 192
[8-MeC9H15NH2][HB(C6F5)3] (230) 8-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (375 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC The reported SSSRRR
diastereomer was only observed
1H NMR (400 MHz C6D5Br) δ 555 (br 1H NH2) 497 (br 1H NH2) 352 (br q 1JB-H = 80
Hz 1H BH) 327 (dm 2JH-H = 121 Hz 1H NH2CH(H)) 263 (dm 3JH-H = 112 Hz coupling to
NH2 is observed in 1H1H-cosy 1H CHN) 252 (qt 2JH-H = 121 Hz 3JH-H = 27 Hz 1H
NH2CH(H)) 141 - 133 (br m 2H CH2) 134 (m 1H CH2CHCH2) 125 - 114 (br m 4H
CH2) 122 (m 1H CHMe) 102 (m 1H CH2) 089 (m 2H CH2) 063 (d 3JH-H = 75 Hz 3H
Me) 058 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1343 (m 2F o-C6F5) -1618 (t 3JF-F
= 21 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -242 (d 1JB-H =
75
80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 249 Hz CF) 1237 (ipso-C6F5) 632 (CHN) 478
(NH2CH(H)) 339 (CH2CHCH2) 337 (CHMe) 271 (CH2) 268 (CH2) 243 (CH2) 231 (CH2)
178 (CH2) 163 (Me) Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C
5026 H 330 N 209
[C13H22NH2][HB(C6F5)3] (231a) Acridine (132 mg 0740 mmol) reaction time 36 h product
(398 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at 25 ordmC The isolated product is a mixture of the SRSRRSRS
and RRSSSSRR isomers in a 11 ratio The SRSRRSRS was separated by crystallization
1H NMR (400 MHz CD2Cl2) δ 626 (br m 1H NH2) 513 (br m 1H NH2) 327 (br q 1JB-H =
86 Hz 1H BH) 285 (dm 3JH-H = 111 Hz 40 Hz 2H CHN) 182 (m 2H NH2CHCH2) 176
(m 2H CyCH2) 175 (m 1H CHCH2CH) 171 (m 2H CyCH2) 167 (m 2H CyCH2) 144 (qt 3JH-H = 111 Hz 3JH-H = 40 Hz 2H CH2CHCH2) 123 (m 2H CyCH2) 122 (m 2H
NH2CHCH2) 118 (m 2H CyCH2) 101 (m 2H CyCH2) 100 (m 1H CHCH2CH) 19F NMR
(377 MHz CD2Cl2) δ -1345 (m 2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -244 (d 1JB-H = 86 Hz BH) 13C1H NMR (101
MHz CD2Cl2) partial δ 639 (CHN) 406 (CH2CHCH2) 371 (CHCH2CH) 318 (CyCH2) 307
(NH2CHCH2) 249 (CyCH2) 248 (CyCH2) Anal calcd () for C31H25BF15N C 5264 H 356
N 198 Found C 5214 H 358 N 196
Synthesis of RRSSSSRR and SRSRRSRS-[(C13H22NH)B(C6F5)3] (231b) Compound 231b
was initially isolated from the pentane wash work-up for the synthesis of 231a Independent
synthesis of 231b was performed and the procedure is described
In a 4 dram vial tetradecahydroacridine (366 mg 0189 mmol) was dissolved in pentane (5
mL) at room temperature To the vial B(C6F5)3 (965 mg 0189 mmol) was added at once and
allowed to mix for 2 minutes The solution was filtered through a bed of Celite to yield a
colourless solution The vial was placed in a -30 ordmC freezer for 3 h and colourless crystals were
collected (973 mg 138 mmol 73) The isolated mixture of compound 231b consisted of a 11
mixture of RRSSSSRR and SRSRRSRS (C13H22NH)B(C6F5)3 only the diagnostic resonances of
RRSSSSRR-(C13H22NH)B(C6F5)3 have been reported
76
RRSSSSRR-[(C13H22NH)B(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 503 (br 1H NH) 353
(dm 3JH-H = 123 Hz 2H NCH) 214 (dm JH-H = 123 Hz 2H NH2CHCH2) 196 - 160 (m
6H CH2) 188 (m 2H CH2CHCH2) 177 (m 4H NH2CHCH2 and CHCH2CH) 149 - 111 (m
6H CH2) 19F NMR (377 MHz CD2Cl2) δ -1270 (m 1F o-C6F5) -1277 (m 1F o-C6F5) -
1281 (m 1F o-C6F5) -1291 (m 2F o-C6F5) -1302 (m 1F o-C6F5) -1558 (t 3JH-H = 21 Hz
1F p-C6F5) -1579 (t 3JH-H = 21 Hz 1F p-C6F5) -1589 (t 3JH-H = 21 Hz 1F p-C6F5) -1624
(m 1F m-C6F5) -1637 (m 3F m-C6F5) -1641 8 (m 1F m-C6F5) -1644 8 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -318 (s BN) 13C1H NMR (101 MHz CD2Cl2) partial δ
630 (NCH) 359 (CHCH2CH) 356 (CH2CHCH2) 299 (NH2CHCH2) Anal calcd () for
C31H23BF15N C 5279 H 329 N 199 Found C 5266 H 328 N 196
[23-(C4H6Me)2NHNH2][HB(C6F5)3] (232) 23-Dimethylquinoxaline (0117 g 0740 mmol)
reaction time 96 h product (402 mg 437 mmol 59) The SRSSRSRR diastereomer was only
observed
1H NMR (400 MHz CD2Cl2) δ 643 (br 1H NH2) 592 (br 1H NH2) 349 (dm 3JH-H = 128
Hz 1H CH2CHN) 334 (br q 1JB-H = 94 Hz 1H BH) 326 (br m 2H NCHMe CH2CHN)
281 (dq 3JH-H = 123 Hz 64 Hz 1H NCHMe) 223 (dm JH-H = 128 Hz 1H CH2) 189 (dm
JH-H = 134 Hz 1H CH2) 179 (dm JH-H = 134 Hz 1H CH2) 162 (dm JH-H = 134 Hz 2H
CH2) 147 (m 1H CH2) 131 (m 1H CH2) 128 (d 3JH-H = 64 Hz 3H Me) 121 (d 3JH-H =
62 Hz 3H Me) 120 (m 1H CH2) (NH was not observed) 19F NMR (377 MHz C6D5Br) δ -
1336 (m 2F o-C6F5) -1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1646 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -241 (d 1JB-H = 94 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481
(dm 1JC-F = 234 Hz C6F5) 1384 (dm 1JC-F = 246 Hz C6F5) 1368 (dm 1JC-F = 247 Hz C6F5)
1232 (ipso-C6F5) 576 (CH2CHN) 563 (NCHMe) 541 (NCHMe) 519 (CH2CHN) 304
(CH2) 242 (CH2) 224 (CH2) 185 (CH2) 178 (Me) 151 (Me) Anal calcd () for
C28H22BF15N C 4929 H 325 N 411 Found C 4909 H 333 N 421
[23-(C4H6Ph)2NHNH2][HB(C6F5)3] (233) 23-Diphenylquinoxaline (0209 g 0740 mmol)
reaction time 96 h product (328 mg 0407 mmol 55) Crystals suitable for X-ray diffraction
were grown from a layered solution of dichloromethanepentane at RT Diastereomers
SRSSRSRR and RRRSSSSR are present in equal ratios The assigned diastereomers were
77
supported by 1H1H NOESY NMR spectroscopy Anal calcd () for C38H26BF15N2 C 5660
H 325 N 347 Found C 5611 H 313 N 321
SRSSRSRR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 763 (m 4H
Ph) 699 - 684 (m 6H Ph) 572 (br 2H NH2) 476 (d 3JH-H = 34 Hz 1H CHPh) 441 (d 3JH-H = 34 Hz 1H CHPh) 407 (br 1H NH) 356 (br q 1JB-H = 82 Hz 1H BH) 314 (td 3JH-H
= 102 Hz 3JH-H = 34 Hz 1H CH2CHN) 260 (m 3JH-H = 102 Hz 34 Hz 1H CH2CHN) 167
(m 1H CH2) 159 (m 1H CH2) 153 (m 1H CH2) 129 (m 1H CH2) 122 (m 2H CH2)
121 (m 1H CH2) 086 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1331 (m 2F o-C6F5)
-1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1362 (ipso-Ph) 1313
(Ph) 1301 (Ph) 1267 (Ph) 637 (CHPh) 619 (CHPh) 597 (CH2CHN) 561 (CH2CHN) 314
(CH2) 282 (CH2) 242 (CH2) 233 (CH2) (ipso-C6F5 was not observed)
RRRSSSSR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (500 MHz CD2Cl2) δ 729 - 708
(m 10H Ph) 657 (br 2H NH2) 451 (dm 3JH-H = 102 Hz 1H CHPh) 429 (dm 3JH-H = 102
Hz 1H CHPh) 386 (dm 3JH-H = 107 Hz 1H CH2CHN) 366 (br 1H NH) 328 (br q 1JB-H =
82 Hz 1H BH) 268 (dm 3JH-H = 107 Hz 1H CH2CHN) 205 (m 1H CH2) 188 (m 2H
CH2) 178 (m 2H CH2) 157 (m 1H CH2) 145 (m 1H CH2) 130 (m 1H CH2) 19F NMR
(377 MHz C6D5Br) δ -1331 (m 2F o-C6F5) -1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 82 Hz BH) 13C1H NMR (125
MHz CD2Cl2) δ 1479 (dm 1JC-F = 235 Hz CF) 1382 (dm 1JC-F = 246 Hz CF) 1366 (dm 1JC-F = 248 Hz CF) 1314 (ipso-Ph) 1304 (Ph) 1301 (ipso-Ph) 1293 (Ph) 1290 (Ph) 1286
(Ph) 1277 (Ph) 1274 (Ph) 1226 (ipso-C6F5) 655 (CHPh) 621 (CHPh) 581 (CH2CHN)
526 (CH2CHN) 308 (CH2) 245 (CH2) 229 (CH2) 188 (CH2)
[(C6H4)C7H12NH2][HB(C6F5)3] (234) 78-Benzoquinoline (133 mg 0740 mmol) reaction
time 48 h product (285 mg 407 mmol 55) Crystals of the SRRS isomer suitable for X-ray
diffraction were grown from a layered solution of bromobenzenepentane at -30 ordmC Crystals of
the SSRR isomer suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC Anal calcd () for C31H19BF15N C 5309 H 273 N 200
Found C 5347 H 291 N 209
78
Isomer ratio by 1HNMR spectroscopy SRRS 80 (pale orange crystals) SSRR 20 (colourless
crystals)
SRRS-[(C6H4)C7H12NH2][HB(C6F5)3] (234a) 1H NMR (400 MHz CD2Cl2) δ 725 (td 3JH-H
= 77 Hz 4JH-H = 14 Hz 1H C6H4) 715 (d 3JH-H = 77 Hz 1H C6H4) 707 (d 3JH-H = 77 Hz
1H C6H4) 700 (t 3JH-H = 77 Hz 1H C6H4) 597 (br 2H NH2) 440 (d 3JH-H = 38 Hz 1H
NCH) 361 (dt JH-H = 131 Hz 3JH-H = 35 Hz 1H NCH(H)) 328 (m 1H NCH(H)) 314 (br q 1JB-H = 80 Hz 1H BH) 294 (dm 2JH-H = 172 Hz 1H C6H4-CH(H)) 285 (dm 2JH-H = 172 Hz
1H C6H4-CH(H)) 239 (m 1H CH2CHCH2) 200 - 188 (br m 6H PiperidineCyCH2) 19F NMR
(377 MHz C6D5Br) δ -1345 (m 2F o-C6F5) -1621 (t 3JF-F = 21 Hz 1F p-C6F5) -1657 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 80 Hz BH) 13C1H NMR (101
MHz CD2Cl2) δ 1483 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1378
(quaternary C for C6H4-CHN) 1368 (dm 1JC-F = 248 CF) 1311 (C6H4) 1307 (C6H4) 1292
(C6H4) 1288 (quaternary C for C6H4-CH2) 1277 (C6H4) 1234 (ipso-C6F5) 605 (NCH) 479
(NCH2) 320 (CH2CHCH2) 286 (C6H4-CH(H)) 274 (PiperidineCH2) 225 (CyCH2) 184
(PiperidineCH2)
SSRR-[(C6H4)C7H12NH2][HB(C6F5)3] (234b) 1H NMR (400 MHz C6D5Br) partial δ 701
(m 1H C6H4) 699 (m 1H C6H4) 685 (m 1H C6H4) 675 (d 3JH-H = 77 Hz 1H C6H4) 350
(d 3JH-H = 104 Hz 1H NCH) 324 (br dm JH-H = 124 Hz 1H NCH(H)) 279 (m 1H
NCH(H)) 254 (m 1H C6H4-CH(H)) 242 (m 1H C6H4-CH(H)) 142 (m 2H CH2) 128 (m
2H CH2) 105 (m 1H CH2CHCH2) 083 (m 2H CH2) (NH2 was not observed) 13C1H
NMR (101 MHz C6D5Br) δ 1370 (quaternary C for C6H4-CHN) 1304 (C6H4) 1291 (C6H4)
1284 (quaternary C for C6H4-CH2) 1264 (C6H4) 1226 (C6H4) 629 (NCH) 474 (NCH2) 378
(CH2CHCH2) 291 (CH2) 288 (C6H4-CH(H)) 276 (CH2) 229 (CH2)
[(C5H3N)(CH2)2(C5H8NH)B(C6F5)2][HB(C6F5)3] (235) B(C6F5)3 (379 mg 0740 mmol) 110-
phenanthroline (667 mg 0370 mmol) reaction time 96 h product (283 mg 0270 mmol 73)
Crystals suitable for X-ray diffraction were grown from a layered solution of
tetrahydrofuranpentane at -30 ordmC Approximately 65 of the reaction mixture consisted of the
SRSRSR diastereomer
1H NMR (400 MHz CD2Cl2) δ 944 (br s 1H NH) 850 (dd JH-H = 47 Hz JH-H = 15 Hz 1H
C5H3N) 744 (dd JH-H = 78 Hz JH-H = 15 Hz 1H C5H3N) 722 (dd JH-H = 78 Hz JH-H = 47
79
Hz 1H C5H3N) 442 (d 3JH-H = 43 Hz 1H NCyCH) 342 (br 1H BH) 322 (dm 2JH-H = 138
Hz 1H NC(H)H) 291 (ddd 2JH-H = 138 Hz 3JH-H = 87 Hz 53 Hz 1H NC(H)H) 276 - 272
(m 2H C6H4-CH(H)) 212 (dm 3JH-H = 121 Hz 38 Hz 1H CH2CHCH2) 196 (m 1H CH2)
188 (m 1H CH2) 173 (m 1H CH2) 132 (dt 2JH-H = 140 Hz 3JH-H = 32 Hz 1H CH2) 091
(qd JH-H = 131 Hz 3JH-H = 38 Hz 1H CH2) 071 (qt JH-H = 137 Hz 3JH-H = 40 Hz 1H CH2)
19F NMR (377 MHz CD2Cl2) δ -1289 (m 2F B(C6F5)2o-C6F5) -1343 (m 6F HB(C6F5)3o-C6F5) -
1348 (m 2F B(C6F5)2o-C6F5) -1491 (t 3JF-F = 20 Hz 1F B(C6F5)2p-C6F5) -1511 (t 3JF-F = 20 Hz
1F B(C6F5)2p-C6F5) -1596 (m 4F B(C6F5)2m-C6F5) -1645 (t 3JF-F = 20 Hz 3F HB(C6F5)3p-C6F5) -
1676 (m 6F HB(C6F5)3m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 391 (s BN) -254 (d 1JB-H =
93 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1484 (quaternary C for C5H3N) 1466
(quaternary C for C5H3N) 1448 (C5H3N) 1354 (C5H3N) 1260 (C5H3N) 581 (CyNCH) 451
(NC(H)H) 296 (CH2C(H)CH2) 241 (CH2) 218 (CH2) 210 (CH2) 206 (CH2) Anal calcd
() for C42H17B2F25N2 C 4822 H 164 N 268 Found C 4783 H 197 N 269
243 X-Ray Crystallography
2431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
2432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
80
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
81
2433 Selected crystallographic data
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25
24 24rsquo 25
Formula C27H21B1F15N1 C27H13B1F15N1 C30H25B1F15N1
Formula wt 65526 64719 69532
Crystal system monoclinic orthorhombic monoclinic
Space group P2(1)c P2(1)2(1)2(1) P2(1)n
a(Aring) 97241(8) 116228(4) 126342(6)
b(Aring) 147348(12) 181284(7) 181939(8)
c(Aring) 188022(15) 236578(9) 128612(6)
α(ordm) 9000 9000 9000
β(ordm) 98826(4) 9000 90269(2)
γ(ordm) 9000 9000 9000
V(Aring3) 26621(4) 49848(3) 29563(2)
Z 4 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1635 1725 1562
Abs coeff μ mm-1 0169 0179 0157
Data collected 18591 28169 50674
Rint 00336 00297 00369
Data used 4685 8773 5207
Variables 401 793 424
R (gt2σ) 00361 00315 00352
wR2 00898 00758 00947
GOF 1007 1021 1024
82
Table 25 ndash Selected crystallographic data for 216a 218 and 219
216a 218 219
Formula C27H20B1F16N1 C27H18B1F16N1 C32H21B1F15N1
Formula wt 67325 67123 71533
Crystal system monoclinic monoclinic orthorhombic
Space group P2(1)c P2(1)n Pbca
a(Aring) 97677(6) 104368(7) 18886(4)
b(Aring) 147079(11) 93382(7) 16050(3)
c(Aring) 190576(14) 273881(18) 19128(4)
α(ordm) 9000 9000 9000
β(ordm) 98934(2) 96910(3) 9000
γ(ordm) 9000 9000 9000
V(Aring3) 27046(3) 26499(3) 5798(2)
Z 4 4 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1653 1683 16388
Abs coeff μ mm-1 0174 0177 0163
Data collected 23565 17203 50412
Rint 00432 00404 00662
Data used 6164 4676 6654
Variables 406 408 442
R (gt2σ) 00522 00496 00687
wR2 01387 01462 01912
GOF 1032 1041 10743
83
Table 26 ndash Selected crystallographic data for 220 222 and 224
220 222 (+05 CH2Cl2) 224 (+05 CH2Cl2)
Formula C33H25B1F15N1O1 C285H22B1Cl1F15N1O1 C355H22B1ClF15N1
Formula wt 74737 72573 79380
Crystal system orthorhombic orthorhombic monoclinic
Space group Pbca Pbca P2(1)n
a(Aring) 173531(15) 17750(5) 109902(9)
b(Aring) 161365(15) 16032(4) 151213(11)
c(Aring) 227522(17) 20783(6) 194765(15)
α(ordm) 9000 9000 90
β(ordm) 9000 96910(3) 92062(3)
γ(ordm) 9000 9000 90
V(Aring3) 63710(9) 5914(3) 32346(4)
Z 8 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 15582 16278 1630
Abs coeff μ mm-1 0154 0250 0235
Data collected 56289 47407 22409
Rint 00406 01159 00306
Data used 7321 5198 5688
Variables 461 440 495
R (gt2σ) 00413 00811 00495
wR2 01112 02505 01363
GOF 10647 10628 0936
84
Table 27 ndash Selected crystallographic data for 225 227 and 228
225 227 (+1 C5H12) 228
Formula C25H17B1F15N1 C63H42B2F30N2 C28H21B1F15N1
Formula wt 62721 141861 66727
Crystal system triclinic monoclinic triclinic
Space group P-1 P2(1)n P-1
a(Aring) 101339(5) 137416(4) 95967(15)
b(Aring) 112923(6) 119983(4) 108364(15)
c(Aring) 118209(6) 191036(7) 14143(2)
α(ordm) 98563(2) 9000 75929(5)
β(ordm) 109751(2) 109317(2) 80009(6)
γ(ordm) 94983(2) 9000 76629(5)
V(Aring3) 124520(11) 297240(17) 13772(4)
Z 2 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1673 1585 1609
Abs coeff μ mm-1 0176 0158 0235
Data collected 18038 22150 16105
Rint 00211 00246 00351
Data used 4357 5230 4743
Variables 379 436 406
R (gt2σ) 00371 00324 00546
wR2 00964 00816 01728
GOF 1044 1014 1028
85
Table 28 ndash Selected crystallographic data for 229 230 and 231a
229 (+05 C6H5Br) 230 231a
Formula C36H255B1Br05F15N1 C28H21B1F15N1 C31H25B1F15N1
Formula wt 80784 66727 70733
Crystal system monoclinic triclinic monoclinic
Space group C2c P-1 P2(1)n
a(Aring) 201550(11) 97752(4) 112914(4)
b(Aring) 133628(11) 120580(4) 183705(7)
c(Aring) 266328(18) 121120(5) 145648(5)
α(ordm) 9000 102296(2) 9000
β(ordm) 111905(6) 100079(2) 90480(2)
γ(ordm) 9000 90901(2) 9000
V(Aring3) 66551(8) 137127(9) 302105(19)
Z 8 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1613 1616 1555
Abs coeff μ mm-1 0749 0165 0155
Data collected 54940 20198 62113
Rint 00530 00245 00383
Data used 7644 4841 7630
Variables 484 406 533
R (gt2σ) 00651 00362 00778
wR2 01802 00971 02335
GOF 1037 1036 1007
86
Table 29 ndash Selected crystallographic data for 231b 233 and 234a
231b (+05 C6H14) 233 234a (+1 CH2Cl2)
Formula C34H30B1F15N1 C38H26B1F15N2 C32H21B1Cl2F15N1
Formula wt 74840 80642 78621
Crystal system triclinic monoclinic monoclinic
Space group P-1 Pn C2c
a(Aring) 107250(6) 99895(4) 181314(6)
b(Aring) 112916(7) 115666(5) 135137(5)
c(Aring) 136756(8) 155410(6) 253612(9)
α(ordm) 70523(2) 9000 9000
β(ordm) 88868(2) 105054(2) 92594(2)
γ(ordm) 86934(2) 9000 9000
V(Aring3) 155914(16) 173405(12) 62077(4)
Z 2 2 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1594 1544 1677
Abs coeff μ mm-1 0155 0147 0327
Data collected 22650 31226 22749
Rint 00233 00381 00512
Data used 5479 8395 7383
Variables 460 517 475
R (gt2σ) 00371 00400 00816
wR2 01066 00893 02554
GOF 0926 1011 1024
87
Table 210 ndash Selected crystallographic data for 234b and 235
234b 235 (+1 C4H8O +1 CH2Cl2)
Formula C31H19B1F15N1 C47H27B2Cl2F25N2O1
Formula wt 70128 120323
Crystal system monoclinic triclinic
Space group P2(1)c P-1
a(Aring) 100455(5) 113115(7)
b(Aring) 118185(5) 117849(8)
c(Aring) 245940(11) 188035(12)
α(ordm) 9000 83850(3)
β(ordm) 96724(2) 88364(3)
γ(ordm) 9000 69766(3)
V(Aring3) 28998(2) 23383(3)
Z 4 2
Temp (K) 150(2) 150(2)
d(calc) gcm-3 1606 1709
Abs coeff μ mm-1 0161 0281
Data collected 20742 36083
Rint 00342 00265
Data used 5101 8235
Variables 433 712
R (gt2σ) 00438 00473
wR2 01153 01198
GOF 1012 1015
88
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation
with Frustrated Lewis Pairs
31 Introduction
The reduction of carbonyl substrates such as aldehydes ketones esters acids and anhydrides to
alcohols is one of the most fundamental and widely used reactions in synthetic chemistry269
Sodium borohydride lithium aluminum hydride and other stoichiometric reducing agents56 224
serve adequately for laboratory scale syntheses however in an industrial setting the process
demands for a more clean environmentally benign and cost-effective procedure More desirable
methods involving H2 gas or transfer hydrogenation have proven practical and circumvent the
work-up operations required for stoichiometric reagents
Heterogeneous catalysts based on PdC and PtC are certainly atom economic however some of
these catalysts are not suitable in cases where mild conditions functional group tolerance and
chemoselectivity are required Therefore substantial research has been directed towards
homogeneous catalysts involving Ir237 Rh239 Ru238 Cu269 and Os238 complexes including metal-
immobilized systems269
Despite the power of these technologies research efforts motivated by cost toxicity and low
abundance have focused on the development of first-row transition metal catalysts based on Fe
and Co210 221 Also on-going interest in the field has been devoted to the discovery of new
asymmetric hydrogenation catalysts131 208-209 263-264136 213-214 270-271 in addition to transfer
hydrogenation via the Meerwein-Ponndorf-Verley reduction procedure216
311 FLP reactivity with unsaturated C-O bonds
In 1961 Walling and Bollyky reported the first metal-free hydrogenation system demonstrating
the reduction of the non-enolizable ketone benzophenone using H2 (100 atm) and tBuOK as the
catalyst at 200 degC175-176 While more recently metal-free reductions have been demonstrated
under more mild conditions using frustrated Lewis pairs (FLPs) These combinations of
sterically encumbered main group Lewis acids and bases have been shown to effect the catalytic
hydrogenation of a variety of unsaturated organic substrates Noticeably absent from these
substrates are ketones and aldehydes This is perhaps surprising given the precedence of catalytic
89
hydrosilylation of ketones established by Piers182 Moreover a number of groups have
demonstrated the ability of FLPs to effect the reduction of CO2 using H2259 silanes169 180 182
boranes111 163 272 or ammonia-borane273 as sources of the reducing equivalents The limited
attention to hydrogenation of ketones and aldehydes has been attributed to the high oxophilicity
of electrophilic boranes72 171 Indeed in an earlier report Erker and co-workers described the
irreversible capture of benzaldehyde and trans-cinnamaldehyde (Scheme 31 top) as well as the
14-addition of conjugated ynones by the intramolecular PB FLP Mes2PCH2CH2B(C6F5)2173 A
number of stoichiometric reductions have also been reported using H2 activated PB FLPs with
an example shown in Scheme 31 (bottom)94 173
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom)
Nonetheless the group of Privalov has computed an energetically viable mechanism for ketone
reduction suggesting a process analogous to imine hydrogenation and carbonyl hydrosilylation
using B(C6F5)3 as the catalyst274 Attempts to realize this prediction experimentally have been
unsuccessful Repo et al described the stoichiometric reaction of aromatic ketones with B(C6F5)3
effecting deoxygenation of the ketone to afford (C6F5)2BOH C6F5H and the corresponding aryl
alkane (Scheme 32 a)178 Furthermore the Stephan group found that similar reduction of alkyl
ketones gave borinic esters via H2 activation hydride delivery and protonation of a C6F5 group
(Scheme 32 b)275
90
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b)
Similar degradation of B(C6F5)3 via B-C bond cleavage affording CH3OB(C6F5)2 and C6F5H was
reported by Ashley and OrsquoHare in their efforts to reduce CO2 in the presence of H2 to CH3OH259
Due to the instability of B(C6F5)3 in these transformations Wang et al approached the catalytic
ketone hydrogenation challenge computationally suggesting that a bifunctional amine-borane
FLP catalyst would be viable276 Interestingly Du et al have taken a detour from direct FLP
hydrogenation of carbonyl groups reporting the catalytic hydrogenation of silyl enol ethers using
a chiral borane to obtain a variety of optically active secondary alcohols after workup (Scheme
33)277
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols
Reaction of main group species with other unsaturated C-O functionalities namely carbon
monoxide is also limited H C Brown established the synthesis of tertiary alcohols by
91
carbonylation of trialkylboranes using carbon monoxide278 although the analogous reactivity by
B-H boranes proved challenging279-282
Recently however Erker et al described the stoichiometric reduction of carbon monoxide by the
reaction of intramolecular PB FLPs and the hydroboration reagent HB(C6F5)2 to yield epoxy-
borate species (Scheme 34 top)118-119 283 Simultaneously the Stephan group exploited the
reaction of a 12 mixture of tBu3P and B(C6F5)3 with syn-gas (CO and H2) to result in sequences
of stoichiometric reactions eventually affording the borane-oxyborate derivative
(C6F5)2BCH(C6F5)OB(C6F5)3 a product of C-O bond cleavage (Scheme 34 bottom)117
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom)
The main group reduction of carbonyl groups has been limited to stoichiometric reactions with
classic hydride reagents In this chapter a remarkably simple approach to the metal-free
hydrogenation of ketones and aldehydes is reported using FLP catalysts derived from B(C6F5)3
and ether The hydrogenation concept was extended towards a heterogeneous avenue using
catalysts derived from the combination of polysaccharides or molecular sieves with B(C6F5)3
Moreover the catalytic reductive deoxygenation of aryl ketones is achieved in the case of
molecular sieves
92
32 Results and Discussion
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions
Heating a toluene solution of 5 mol B(C6F5)3 and 4-heptanone under H2 (60 atm) at 80 degC
yielded complete conversion of B(C6F5)3 to the borinic ester Pr2CHOB(C6F5)2 with concurrent
liberation of C6F5H The remaining 95 of the initial ketone was unaltered This observation
illustrates that borane and ketone act as a FLP to heterolytically cleave H2 affording nominally
[Pr2COH][HB(C6F5)3] At this stage the hydride is presumed to reduce the carbonyl fragment to
generate 4-heptanol which subsequently decomposes B(C6F5)3 to Pr2CHOB(C6F5)2 and C6F5H
It is important to note that the above example of rapid and facile decomposition of B(C6F5)3 to
borinic ester stands in contrast to an observation illustrated in Chapter 2 In this case the CH3OH
generated from ammonium protonation of [CH3OB(C6F5)3]- does not decompose B(C6F5)3 rather
under an atmosphere of H2 the resulting amine and B(C6F5)3 heterolytically split H2 to give the
ammonium [HB(C6F5)3] product (Scheme 35) Thus this observation led to the proposal of two
plausible borane decomposition pathways in ketone hydrogenation reactions
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH
In both pathways the reaction initiates with heterolytic H2 splitting by the ketone and B(C6F5)3
to give the ionic pair [R2COH][HB(C6F5)3] (Scheme 36) At this point the reaction could follow
a pathway in which hydride is transferred from the [HB(C6F5)3]- anion to the activated carbonyl
group generating alcohol and B(C6F5)3 both of which further react to give borinic ester and
C6F5H (Scheme 36 Pathway 1) The second pathway suggests the borane undergoes
protonolysis by the [R2COH]+ cation cleaving a C6F5 group to form HB(C6F5)2 and C6F5H whilst
regenerating the ketone The borane then undergoes hydroboration of the carbonyl group to
afford the borinic ester (Scheme 36 Pathway 2)
93
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation
To test Pathway 1 B(C6F5)3 was added to excess 4-heptanol (10 eq) and heated to 80 degC for 12
h This resulted in no reaction beyond formation of the alcohol-borane adduct
Pr2CHOHmiddotB(C6F5)3 as evidenced by the 11B and 19F NMR spectra (11B δ 197 ppm 19F δ -
1326 -1552 -1628 ppm) On the other hand stoichiometric and 5 mol combinations of
HB(C6F5)2 with 4-heptanone formed the new hydroboration species Pr2CHOB(C6F5)2 after 10
min at RT In addition to the characteristic methine multiplet observed at 405 ppm in the 1H
NMR spectrum 11B NMR spectroscopy gave a broad resonance at 394 ppm with 19F NMR
signals at -1325 -1498 and -1613 ppm representing the three-coordinate boron centre These
experiments provide evidence for Pathway 2 resulting in decomposition of B(C6F5)3 during
ketone hydrogenation
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents
To avoid this degradation pathway an alternative FLP is required This system must be basic
enough to effect H2 activation and stabilize the acidic proton by electrostatic interactions In this
regard the Stephan group previously reported that the ethereal oxygen of the borane-oxyborate
derivative (C6F5)2BCH(C6F5)OB(C6F5)3 is sufficiently Lewis basic to activate H2 with the
coordinating B(C6F5)2 group117 Subsequently the combination of weak Lewis bases such as
Et2O electron deficient triarylphosphines and diaryl amines were shown to be sufficiently basic
for both H2 activation and catalytic reduction of olefins99 257 In the case of Et2O DFT
calculations highlighted that solvation of the protonated ether by a second equivalent of Et2O can
significantly stabilize the proton by hydrogen-bonding interactions
94
To probe the viability of using Et2O in carbonyl reductions a d8-toluene solution of 5 mol
B(C6F5)3 was combined with a 51 ratio of Et2O4-heptanone and heated to 70 degC under H2 (4
atm) Monitoring the J-Young experiment by high temperature 1H NMR spectroscopy showed
gradual hydrogenation of the ketone yielding approximately 50 of 4-heptanol after 12 h The 1H NMR spectrum shows a distinct quintet at 345 ppm diagnostic of the hydrogenated C=O
fragment forming a C-H bond in addition to the multiplets at 128 and 080 ppm (Figure 31)
Increasing the H2 pressure to 60 atm improved the yield of 4-heptanol to 70
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol ()
Alternatively incrementing the ratio of Et2O to 4-heptanone resulted in increased yields in
which case a 81 ratio of Et2O4-heptanone in toluene gave 97 conversion to 4-heptanol after
12 h (Figure 32) The continuous improvement in alcohol yield was a direct result of gradual
preservation of the borane catalyst in the reaction as the Et2O concentration was increased
Employing identical conditions but using Et2O as the solvent resulted in the quantitative
formation of 4-heptanol after 12 h Similarly employing iPr2O as the solvent in analogous
$ $ 12
11
10
9
8
7
6
5
4
3
2
1
95
hydrogenations gave quantitative yields of 4-heptanol The use of Ph2O and TMS2O resulted in
yields of 44 and 42 in the same time frame (Table 31 entry 1)
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol
Using this FLP hydrogenation protocol a range of ketone substrates were treated with 5 mol
B(C6F5)3 in Et2O iPr2O Ph2O or TMS2O and heated for 12 h at 70 degC under H2 (60 atm) The
substrates investigated included several alkyl ketones (Table 31 entries 1 - 9) an aryl ketone
(Table 31 entry 10) benzyl ketones with substituents including F and CF3 groups (Table 31
entry 11 - 15) cyclic ketones including L-menthone and cyclohexanone (Table 31 entries 16
and 17) as well as the aldehyde cyclohexanal (Table 31 entry 18) Evaluating these reductions
by 1H NMR spectroscopy showed yields ranging between 32 - gt99 and isolated yields up to
91 for the reactions carried out in Et2O and iPr2O (Table 31) 1H NMR spectra of the alcohols
displayed characteristic multiplets at about 4 ppm assignable to the distinctive methine protons
with corresponding 13C1H resonances observed at ca 70 ppm as expected
These reactions could also be performed on a larger scale For example 100 g of 4-heptanone
was quantitatively converted to 4-heptanol using 5 mol B(C6F5)3 in Et2O and the alcohol
product was isolated in 87 yield
96
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents
Conversion (Isolated yields)
Entry R R1 Et2O iPr2O Ph2O TMS2O
1 n-C3H7 n-C3H7 gt99 (91) gt99 70 52
2 Me iPr gt99 (76) gt99 44 42
3 Me CH2tBu gt99 gt99 (90) 22 14
4 Me n-C5H11 93 (85) 50 (43) 58 41
5 Me CH2Cl gt99 (85) gt99 91 82
6 Me Cy 77 - - -
7 Et iPr gt99 gt99 (89) - trace
8 Et n-C4H9 gt99 (87) 95 44 38
9 Et CH2iPr 40 47 - -
10 Me Ph 90 69 (52) trace trace
11 Et CH2Ph gt99 (84) 97 trace trace
12 Me n-CH2CH2Ph gt99 (84) 69 58 24
13 Me CH2(o-FC6H4) 97 gt99 (90) trace trace
14 Me CH2(p-FC6H4) gt99 gt99 (90) trace trace
15 Me CH2(m-CF3C6H4) gt99 gt99 (88) 55 trace
16 -(CH2)5- 53 41 - -
17 -(2-iPr-5-Me)C5H8- gt99 (88) 89 47 45
18 Cy H 32 - - -
(-) Reaction was not performed
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents
The mechanism of these reactions is thought to be analogous to that previously described for
imine hydrogenations92 In the present case ether combines with the borane in equilibrium
97
between the classical Lewis acid-base adduct and the corresponding FLP in which the latter
effects the heterolytic cleavage of H2 The resulting protonated ether then associates with ketone
via a hydrogen-bonding interaction284-285 activating the carbonyl fragment for hydride transfer
from the [HB(C6F5)3]- anion Subsequent protonation of the generated alkoxide yields the
product alcohol while liberating etherB(C6F5)3 to further activate H2 (Scheme 37) It has been
experimentally proven that activation of the carbonyl fragment is required prior to hydride
delivery as a 11 combination of 4-heptanone and [NEt4][HB(C6F5)3] do not result in reactivity
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents
The possibility of initial H2 activation by ketoneborane combinations cannot be dismissed
however the proposed mechanism is based on the large excess of ether in comparison to ketone
In support of this proposed mechanism the activation of H2 by ethereal oxygen Lewis bases and
boranes have been described to protonate imines and alkenes en route to the corresponding
hydrogenated products257 286
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism
The proposed H-bonding ether-ketone intermediate was further probed by the stoichiometric
reaction of a toluene solution of Jutzirsquos acid [(Et2O)2H][B(C6F5)4]287 with 1-phenyl-2-butanone
and iPr2O After heating the reaction at 70 degC for 2 h a white crystalline solid 31 was isolated in
87 yield (Scheme 38) The 1H NMR spectrum of 31 showed a broad singlet at 1152 ppm
suggesting a proton involved in hydrogen-bonding Resonances attributable to both 1-phenyl-2-
butanone and iPr2O were unambiguously present although these shifts were deshielded in
98
comparison to the individual components These data in addition to the definite presence of the
[B(C6F5)4]- anion as evidenced by 11B and 19F NMR spectroscopy lead to the assignment of 31
as [(iPr2O)H(O=C(CH2Ph)CH2CH3)][B(C6F5)4]
Scheme 38 ndash Synthesis of 31
The structure of 31 was unambiguously confirmed by single crystal X-ray crystallography
(Figure 33) The molecular structure of this salt shows the proximity of the ketone and ether in
the cation with an O-O separation of 2534(3) Aring Location and complete refinement of the proton
in the cation shows it is associated with the ether oxygen and hydrogen-bonded to the ketone
with O-H distances of 104(2) and 154(2) Aring respectively The resulting angle at H is 1581(3)deg
consistent with that typically seen for hydrogen-bonding interactions288-289 The isolation of 31
provides a direct structural analogue of the proposed intermediate in the ketone hydrogenation
mechanism
The equilibrium position of the generated proton is predicted to favour the ether oxygen atom
where the unshared electron pair is sp3 hybridized making the ether oxygen more basic than the
carbonyl where the unshared pair is sp2 hybridized This is also in agreement with predicted pKa
values of protonated ether and ketone289
Figure 33 ndash POV-Ray depiction of 31
99
325 Other hydrogen-bond acceptors for carbonyl hydrogenations
By analogy to the proposed mechanism with ethereal solvents ketone hydrogenations were
explored with crown ethers in toluene To this end combinations of 5 and 10 mol of 12-crown-
4 18-crown-6 and benzo-12-crown-4 were used with 5 mol B(C6F5)3 and 4-heptanone
However in all cases only trace amounts of 4-heptanol was observed Similar to the results in
ethereal solvents these hydrogenation results could possibly be improved by using an excess of
the crown ether On the other hand inefficient hydrogenation could result due to the multiple
stabilizing hydrogen bonds with the crown (OCH2)n groups
Alternative oxygen containing solvents THF and tetrahydropyran were tested using the
hydrogenation protocol in both cases however catalysis was not observed This result could be
explained by the difference in steric hindrance of the two solvents in comparison to Et2O and
iPr2O Nonetheless performing the hydrogenations in 24-dimethylpentan-3-ol gave the
quantitative reduction of 4-heptanone after 12 h at 70 degC This result led to the proposal that
chiral alcohols could possibly be used as the solvent to induce asymmetric reduction of ketones
Thus testing this theory using enantiomerically pure alcohols (S)-2-octanol (R)-2-octanol (R)-
(+)-1-phenyl-1-butanol (S)-(+)-12-propanediol and (R)-(+)-11rsquo-bi(2-naphthol) the prochiral
ketone substrates in Table 31 entries 2 - 10 were hydrogenated although in all cases the
products were obtained as racemic mixtures
326 Other boron-based catalysts for carbonyl hydrogenations
While exploring other boron-based catalysts in carbonyl reductions borenium cation-based FLP
hydrogenation catalysts105 derived from carbene-stabilized 9-borabicyclo[331]nonane (9-
BBN) were tested in lieu of B(C6F5)3 (Figure 34) However at 70 degC (temperature required for
hydrogenation when using B(C6F5)3) the borenium cation catalysts were found to decompose to
unknown products thereby not resulting in any reactivity
100
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism
Reflecting back on a key result presented in Chapter 2 an alternative mechanism was applied to
successfully achieve B(C6F5)3 catalyzed ketone hydrogenation This finding demonstrates the
participation of the [CH3OB(C6F5)3]- anion and B(C6F5)3 in H2 activation forming CH3OH and
[HB(C6F5)3]- (Scheme 39) thereby signifying the lability of B(C6F5)3-alkoxide bonds
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond
Taking lability of the presented B-O bond into consideration a two component catalyst system
comprising of B(C6F5)3 and [NEt4][HB(C6F5)3] was conceptualized for ketone hydrogenation In
this regard the B(C6F5)3 catalyst is expected to coordinate to the carbonyl group activating it for
hydride delivery from [NEt4][HB(C6F5)3] This will consequently generate B(C6F5)3 and
B(C6F5)3-alkoxide wherein similar to Scheme 39 will react with H2 to form alcohol and
regenerate the catalysts
The proposed catalytic system was examined by combining 5 mol B(C6F5)3 and 5 mol
[NEt4][HB(C6F5)3] with 4-heptanone in toluene and heating at 80 degC under H2 (60 atm) After 12
h 1H NMR data revealed catalyst turnover giving 92 conversion to the product 4-heptanol
(Table 32 entry 1) It is important to note that under similar reaction conditions the
combination of ketone with [NEt4][HB(C6F5)3] does not give any reactivity while B(C6F5)3 alone
is decomposed to the borinic ester
101
Using this hydrogenation protocol dialkyl substituted ketones gave the corresponding alcohols
in 40 - 99 conversions by 1H NMR spectroscopy (Table 32 entries 2 - 6) Conversions were
dramatically reduced for methyl cyclohexyl ketone (Table 32 entry 7) aryl and benzyl
substituted ketones (Table 32 entries 8 - 10) benzylacetone (Table 32 entry 11) in addition to
the cyclic ketones cyclohexanone and 2-cyclohexen-1-one (Table 32 12 and 13) Interestingly
reduction of L-menthone produced the respective alcohol product in 62 by 1H NMR
spectroscopy (Table 32 entry 14)
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3]
Entry R R1 Conversion
1 n-C3H7 n-C3H7 92
2 Me iPr 57
3 Me CH2Cl gt99
4 Me 2-butyl 53
5 Et iPr gt99
6 Et CH2iPr 40
7 Me Cy 18
8 Me Ph 20
9 Ph Ph 20
10 Et CH2Ph 25
11 Me n-CH2CH2Ph 25
12 -(CH2)5- 28
13 -(CH2)3CH=CH- 0
14 -(2-iPr-5-Me)C5H8- 62
All conversions are determined by 1H NMR spectroscopy
102
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system
The mechanism of this reaction is thought to proceed by initial coordination of the Lewis acid
B(C6F5)3 to the carbonyl group assisting hydride transfer from [NEt4][HB(C6F5)3] resulting in
liberation of B(C6F5)3 and generation of [NEt4][RR1C(H)OB(C6F5)3] in which the alkoxide
anion is coordinated to B(C6F5)3 (Scheme 310) This combination of [RR1C(H)OB(C6F5)3]-
anion and B(C6F5)3 act as a FLP to activate H2 and dissociate the alcohol while simultaneously
regenerating B(C6F5)3 and [NEt4][HB(C6F5)3] By 1H NMR spectroscopy the [NEt4]+ cation
does not appear to participate in the reaction
R R1
OH
H
B(C6F5)3
R R1
O
+
B(C6F5)3
R R1
O NEt4
HB(C6F5)3
NEt4
B(C6F5)3
B(C6F5)3
R R1
O
05 H2
05 H2
H+ from H2 activation
H- from H2 activation
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation
In comparison to carbonyl hydrogenations in ethereal solvents the presented Lewis acid-assisted
mechanism has resulted in lower alcohol yields due to steric hindrance of the substrate Lewis
base preventing adequate coordination to the Lewis acid and consequently inefficient activation
of the carbonyl bond Additionally the steric hindrance of the alkoxyborate anion resulting from
hydride delivery slows down the H2 activation step allowing unreacted B(C6F5)3 and ketone to
activate H2 giving the corresponding borinic ester
328 Attempted hydrogenation of other carbonyl substrates and epoxides
Carbonyl reductions employing either the etherB(C6F5)3 FLP catalyst or the two component
catalyst species B(C6F5)3[NEt4][HB(C6F5)3] were unsuccessful for the ketones
diphenylcyclopropenone (ndash)-fenchone 25-hexanedione 6-methyl-35-heptadien-2-one
103
cyclohexane-14-dione 1-acetyl-1-cyclohexene 13-difluoroacetone 2-acetylthiophene 44-
dimethoxybutan-2-one aldehydes 5-methylthiophene-2-carboxaldehyde esters ethyl acetate
ethylchloroformate methylbenzoate ethylpyruvate phenyl acetate carboxylic acids isobutyric
acid pivalic acid 3-phenylpropanoic acid carbonates ethylene carbonate diethyl carbonate
and NN-diethylpropionamide Exposure of diethylmaleate to the hydrogenation conditions only
led to reduction of the C=C double bond
Similar treatment of the epoxides styrene oxide and trans-stilbene oxide were found to undergo
the well-documented Lewis acid catalyzed Meinwald rearrangement forming 2-
phenylacetaldehyde and 22-diphenylacetaldehyde respectively Selectivity of the aldehyde
products is determined by formation of the most stable carbenium intermediate followed by a
hydride shift (2-phenylacetaldehyde) or substituent shift (22-diphenylacetaldehyde)290-291
Moreover an attempt at extending this reduction procedure to the greenhouse gas CO2 was not
successful In this sense a J-Young tube consisting of B(C6F5)3 and 10 eq of Et2O was
pressurized with CO2H2 and heated at temperatures up to 80 degC Multinuclear NMR data only
revealed resonances corresponding to the Et2O-B(C6F5)3 adduct
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases
As presented in Section 322 judicious choice of the FLP catalyst derived from ether and
B(C6F5)3 gives catalytic hydrogenation of carbonyl substrates to their corresponding alcohols
The protonated ether solvent is proposed to hydrogen bond with the ketone substrate stabilizing
the Broslashnsted acidic proton while activating the carbonyl fragment to accept hydride from the
[HB(C6F5)3]- anion (Scheme 37)
Continued interest in ketone and aldehyde hydrogenation reactions led to the investigation of
potential oxygen-rich materials that will mimic ethereal solvents permitting catalytic
hydrogenation in a non-polar solvent To this end FLP hydrogenations were performed in
toluene using the Lewis acid B(C6F5)3 with the addition of heterogeneous Lewis bases including
cyclodextrins (poly)saccharides or molecular sieves (MS) with the formula
Na12[(AlO2)12(SiO2)12] (Figure 35)
104
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
3291 Polysaccharides as heterogeneous Lewis bases
In probing this investigation α-cyclodextrin (α-CD) an oligosaccharide formed of six
glucopyranose units (Figure 35 a) was initially tested in H2 activation In this regard 5 mol
B(C6F5)3 and α-CD were combined in d8-toluene and exposed to HD gas (1 atm) in a J-Young
tube at 60 degC (Figure 36 a) 1H NMR analysis after 1 h revealed signals for H2 resulting from
isotope equilibration thereby signifying the viability of H2 activation between B(C6F5)3 and the
oxygen donors of α-CD (Figure 36 b) Furthermore the 11B and 19F NMR spectra indicated
signals corresponding to unaltered B(C6F5)3 thus suggesting a remarkably simple and
inexpensive H2 activation FLP catalyst It is important to note that B(C6F5)3 or α-CD alone do not
effect HD activation
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD)
To assess the unprecedented FLP system in carbonyl hydrogenation catalysis the ketone 3-
methyl-2-butanone was combined with an equivalent of α-CD and 5 mol B(C6F5)3 in toluene
and heated at 60 degC under H2 (60 atm) After 12 h quantitative reduction to the product 3-
methyl-2-butanol was evidenced by 1H NMR spectroscopy revealing a diagnostic multiplet at
327 ppm corresponding to the product CH group and broad singlet at 182 ppm assignable to the
a) b)
a)
b)
105
OH group (Table 33 entry 1) Repeating the reaction in the absence of H2 does not lead to
reduction of the substrate thus eliminating the possibility of transfer hydrogenation from α-CD
Under similar conditions a series of methyl alkyl (Table 33 entries 2 - 6) and dialkyl ketones
(Table 33 entries 7 - 9) aryl (Table 33 entries 10 - 14) benzyl (Table 33 entries 15 - 19) and
cyclic ketones (Table 33 entries 20 - 22) were hydrogenated in high yields In addition the
catalytic reduction of aldehydes was similarly performed to give the corresponding primary
alcohols (Table 33 entries 23 - 25) The 1H NMR spectra for all products displayed a
characteristic resonance at about 4 ppm diagnostic of CH and CH2 protons for ketone and
aldehyde reductions respectively and the corresponding 13C1H resonances were observed at
ca 70 ppm
The efficient nature of these catalytic reactions imply that B(C6F5)3 and the oxygen atoms of α-
CD act as a FLP to activate H2 initiating hydrogenation catalysis Selective silylation of α-CD at
the 2- and 6-hydroxy positions of the glucose units gave the toluene soluble product hexakis[26-
O-(tert-butyldimethylsilyl)]-α-cyclodextrin292 This derivatization was found to have a marginal
influence on catalysis forming 3-methyl-2-butanol in 70 yield after 12 h at 60 degC Moreover
the hydrogenation protocol was further investigated using the heterogeneous Lewis bases β and
γ-CD oligosaccharides of seven and eight glucopyranose units respectively and the
(poly)saccharides maltitol and dextrin Hydrogenation results are summarized in Table 33
Taking into account that cyclodextrins are used as chiral stationary phases in separation of
enantiomers the prochiral substrates of Table 33 were analyzed by chiral GC However in all
cases the products were found as racemic mixtures
106
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
Entry R R1 α-CD β-CD γ-CD Maltitol Dextrin MS
1 Me iPr gt99 79 77 62 81 gt99
2 Me 2-butyl gt99 74 72 46 75 gt99
3 Me CH2tBu gt99 52 41 40 53 gt99
4 Me CH2Cl gt99 gt99 trace 51 trace 80
5 Me Cy gt99 81 62 31 64 gt99
6 Me n-C5H11 gt99 63 56 36 73 gt99
7 Et iPr gt99 75 75 69 80 gt99
8 Et n-C4H9 95 93 95 58 gt99 93
9 n-C3H7 n-C3H7 gt99 - - - - 92
10a Me Ph 30 13 15 10 27 trace
11 CH2CH2Cl Ph 54 - - - - 50
12 CF3 Ph 20 - - - - 20
13 Me o-CF3C6H4 trace - - - - 25
14 Me p-MeSO2C6H4 60 - - - - 97
15 Me n-CH2CH2Ph gt99 58 90 38 trace gt99
16 Me CH2(o-FC6H4) 75 70 69 66 34 gt99
17 Me CH2(p-FC6H4) gt99 49 31 55 48 gt99
18 Me CH2(m-CF3C6H4) gt99 gt99 62 43 92 gt99
19 Et CH2Ph gt68 20 31 28 46 gt99
20 -(CH2)5- gt99 72 65 68 90 gt99
21b -(CH2)3CH=CH- 67 trace trace trace trace 82
22 -(2-iPr-5-Me)C5H8- gt99 70 60 60 80 gt99
23 Cy H 10 - - - - 44
24 Ph2CH H 47 - - - - 86
25 PhCH(Me) H 20 - - - - 35
a Reported yields are for phenylethanol b Product is cyclohexanol Isolated yields are reported for α-CD and MS
107
3292 Molecular sieves as heterogeneous Lewis bases
The presented (poly)saccharides could be conveniently replaced with the ubiquitous laboratory
drying agent MS293 as HD isotope equilibration experiments evidenced the formation of H2
when exposed to a d8-toluene suspension of MS and B(C6F5)3 It is noteworthy however that
such equilibration was not observed in the absence of B(C6F5)3
Using MS as the heterogeneous Lewis base 5 mol B(C6F5)3 catalyzed the hydrogenation of
ketone and aldehyde substrates reported in Table 33 These reductions could also be performed
on an increased scale with consecutive recycling of the MS For example 100 g of 4-heptanone
in toluene was treated with 5 mol of the catalyst B(C6F5)3 and MS yielding quantitative
conversion to 4-heptanol which was isolated in 95 yield The sieves were washed with solvent
and recombined with borane and ketone in three successive hydrogenations without loss of
activity
Speculation of physisorbed B(C6F5)3 onto MS was probed by reusing filtered sieves that were
washed with toluene without further addition of B(C6F5)3 This gave 30 reduction of 4-
heptanone suggesting that while there is some physisorption it is not sufficient to provide a
significant degree of catalysis
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones
In an effort to reduce the aryl alkyl ketone acetophenone the above protocol using α-CD was
employed for 12 h at 70 degC under H2 (60 atm) 1H NMR data revealed ca 60 consumption of
acetophenone resulting in the formation of two products in almost equal ratios The distinct
quartet at 424 ppm broad singlet at 342 ppm and doublet at 102 ppm were consistent with the
hydrogenated product phenylethanol (Scheme 311) The 1H NMR spectrum of the second
product gave three separate doublet of doublets with olefinic chemical shifts observed at 652
556 and 504 ppm with each signal integrating to one proton Mass spectroscopy confirmed this
species to be styrene derived from reductive deoxygenation (Scheme 311) The reaction was
repeated using MS giving styrene in a significantly improved 92 yield (Table 34 entry 1)
108
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone
To probe this deoxygenation further the ketone 3rsquo-(trifluoromethyl)acetophenone was treated
with 5 mol B(C6F5)3 in toluene and added to a suspension of MS and heated for 12 h at 70 degC
under H2 (60 atm) This resulted in formation of the deoxygenated product 3-
(trifluoromethyl)styrene in 95 yield (Table 34 entry 2) while remainder of the reaction
mixture consisted of the alcohol 3rsquo-(trifluoromethyl)phenyl ethanol Similar treatment of
propiophenone gave trans-β-methylstyrene in 96 yield with trace amounts of the cis isomer
(Table 34 entry 3) In a similar timeframe the deoxygenation of isobutyrophenone was
performed giving 75 of the hydrocarbon 2-methyl-1-phenyl-propene while 10 of the mixture
consisted of the alcohol 1-phenyl-1-propanol (Table 34 entry 4) In this case the comparatively
slower deoxygenation rate is presumably due to increased steric hindrance about the carbonyl
functionality Indeed these effects are more pronounced with 222-trimethylacetophenone as no
reaction was observed Finally the bicyclic ketone 1-tetralone gave 12-dihydronaphthalene in
88 yield (Scheme 312 a)
Table 34 ndash Deoxygenation of aryl alkyl ketones
Entry R R1 R2 Isolated yield
1 H Me CH2 92
2 CF3 Me CH2 95
3 H Et CHCH3 trans 96
cis 4
4 H iPr C(Me)2 75
109
In light of the established tandem hydrogenation and deoxygenation protocol under these
conditions benzophenone is deoxygenated to give diphenylmethane in 81 yield (Table 35
entry 1) Similarly the diaryl ketone derivatives with substituents including CH3O Br tBu and
CH3 groups were reduced affording the corresponding diarylmethane products in yields ranging
from 67 - 99 (Table 35 entries 2 - 5) In the case of p-CF3 substituted benzophenone the
reaction gave 10 of the deoxygenation and 50 of the alcohol products (Table 35 entry 6)
Analogous treatment of 2-methylbenzophenone resulted in only 20 conversion to the aromatic
hydrocarbon (Table 35 entry 7) This example including the result for 2rsquo-
(trifluoromethyl)acetophenone (25 yield) (Table 33 entry 13) certainly infer that increased
steric hindrance about the carbonyl group has a negative impact on reactivity
Finally the tricyclic ketone dibenzosuberone afforded the reduced aryl alkane
dibenzocycloheptene in 73 yield (Scheme 312 b) It is noteworthy that Repo et al have
previously reported B(C6F5)3 mediated reductive deoxygenation of acetophenone in CD2Cl2
however in their case concurrent hydration of the borane affords (C6F5)2BOH and C6F5H178 In
the present system MS preclude this degradation pathway allowing deoxygenation to proceed
catalytically
Table 35 ndash Deoxygenation of diaryl ketones
Entry R R1 Isolated yield
1 H Ph 81
2 CH3O Ph 85
3 Br Ph 67
4 tBu Ph gt99
5 CH3 p-CH3C6H4 75
6 CF3 Ph 10
7 H o-CH3C6H4 20
110
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b)
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation
The mechanism of these ketone and aldehyde reductions is thought to be analogous to the FLP
reductions described earlier in ethereal solvents In the present case the FLP initiating
heterolytic H2 activation is believed to be the Lewis basic oxygen atoms on the surface of the α-
CD or MS and the Lewis acid B(C6F5)3 (Scheme 313) although H2 activation by ketone
B(C6F5)3 cannot be dismissed Proceeding from the former activation method similar to the case
in ethereal solvents the protonated surface hydrogen bonds to the carbonyl fragment polarizing
the bond for hydride transfer from the [HB(C6F5)3]- anion The generated alkoxide anion is then
sufficiently basic to accept proton from the surface thus regenerating the heterogeneous Lewis
base This H2 activation is in agreement with HD equilibration experiments presented for α-CD
and MS
The ease of deoxygenating the ketones Ph2C=O gt PhCH3C=O gave insight to postulate the
reductive deoxygenation mechanism Heterolytic H2 activation occurs between the MS and
B(C6F5)3 although activation between ketoneB(C6F5)3 and alcoholB(C6F5)3 cannot be
dismissed ultimately resulting in protonated alcohol which is hydrogen-bonded to ketone
(Scheme 313) At this stage it appears that C-O bond cleavage with hydride delivery and loss
of H2O affords the aromatic alkene or alkane products Evidence of the alcohol-H-ketone
intermediate proposed in the mechanism is investigated in the following section
111
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones
Experimental results have demonstrated electronic effects directly impact the deoxygenation
mechanism It appears that C-O bond cleavage and loss of H2O is governed by stability of an
alcohol carbocation intermediate Aryl alcohols readily stabilize such an intermediate through
delocalization by the neighbouring π-system while this effect is clearly absent with dialkyl and
primary alcohols Moreover electron withdrawing groups prevent formation of the carbocation
as demonstrated by the reduction results of 222-trifluoroacetophenone and 4-
(methylsulfonyl)acetophenone These compounds exclusively gave the corresponding alcohol
products (Table 33 entries 12 and 14)
32101 Verifying the reductive deoxygenation mechanism
To validate the proposed reductive deoxygenation mechanism treatment of diphenylmethanol
with 5 mol B(C6F5)3 and MS was carried out at 70 degC under H2 (60 atm) (Figure 37)
Surprisingly the reaction only gave 10 mol of diphenylmethane and complete degradation of
B(C6F5)3 Modification of the study to include 5 10 and 50 mol of benzophenone gradually
increased consumption of diphenylmethanol indicating participation of ketone in the
deoxygenation process (Figure 37) Such a mechanism accounts for necessity of a strong
112
Broslashnsted acid to initiate the deoxygenation process by protonating the hydroxyl group
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased
The conversion of carbonyl substrates to hydrocarbons is an important and rather broad area of
research in modern organic chemistry with extensive contribution to the production of fuels
Replacement of an oxo group by two hydrogen atoms is generally carried out through
hydrogenolysis although hydrogenation methods are also well studied Prominent procedures for
this transformation include the Clemmensen reduction294-295 Wolff-Kishner reduction296 and
stoichiometric methods involving LiAlH4-AlCl3 NaBH4-CF3CO2H297 Et3SiH-BF3 or
CF3CO2H298-299 and HI-Phosphorus combinations300-301 in addition to metal-catalyzed
approaches62
From the perspective of FLP systems reductive deoxygenation of carbonyl groups has been
previously achieved using silanes boranes or ammonia borane165 as sacrificial reducing agents
0 mol
5 mol
10 mol
50 mol
Diphenylmethanol (CH) Diphenylmethane (CH2)
113
The Piers group showed the B(C6F5)3 catalyzed deoxygenative hydrosilylation of CO2 to CH4
using TMP B(C6F5)3 and excess Et3SiH169 Such transformations have also been reported using
N-heterocyclic carbenes and hydrosilanes302 The Fontaine group among others111 163 have
shown the hydroboration of CO2 to methanol using FLPs167-168 Significantly more challenging is
H2 as the reducing reagent In a unique example Ashley and OrsquoHare reported the reduction of
CO2 by H2 using a stoichiometric combination of B(C6F5)3 and TMP at 160 degC to give methanol
in 17 - 25 yield259
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins
In the experiments presented 4 Aring pellet MS purchased from Sigma Aldrich were used in
combination with B(C6F5)3 To explore the efficacy of other materials the same hydrogenation
protocol was applied in the reduction of 4-heptanone to give 4-heptanol in the following yields 5
Aring MS pellets (gt99) 4 Aring MS powder (69) 3 Aring MS pellets (68) acidic alumina (30)
silicic acid (15) while no reactivity was observed in the case of silica gel sodium aluminate
neutral and basic alumina
The hydrogenation protocol using 4 Aring MS was also attempted in the reduction of olefins
including 1-hexene cyclohexene 11-diphenylethylene and αp-dimethylstyrene however no
reactivity was observed in either case
33 Conclusions
The following chapter provides an account on the discovery of a metal-free route for the
hydrogenation of ketone and aldehyde substrates to form alcohol products The FLP catalyst is
derived from ether and B(C6F5)3 in which the protonated ether participates in hydrogen-bonding
interactions with the substrate affording an efficient catalyst to mediate the transformations
Moreover B(C6F5)3-assisted ketone hydrogenations using a two component catalyst system
derived from B(C6F5)3 and [NEt4][HB(C6F5)3] has also proven viable
Simultaneous with communicating this finding Ashley et al reported an analogous
hydrogenation catalyst derived from 14-dioxaneB(C6F5)3 that is effective for the hydrogenation
of ketones and aldehydes at 4 atm of H2 and temperatures ranging between 80 and 100 degC260
114
Also an air stable catalyst derived from THFB(C6Cl5)(C6F5)2 was shown to be particularly
effective for the hydrogenation of weakly Lewis basic substrates286
Continuing to explore modifications and applications of this new metal-free carbonyl reduction
protocol catalytic reductions were achieved in toluene using B(C6F5)3 and a heterogeneous
Lewis base including CDs (poly)saccharides or MS This combination of soluble borane and
insoluble materials provided a facile route to alcohol products In the case of aryl ketones and
MS further reactivity of the alcohol resulted in deoxygenation of the carbonyl group affording
either the aromatic alkane or alkene products
34 Experimental Section
341 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane tetrahydrofuran toluene (Sigma Aldrich) were dried employing a Grubbs-type
column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring) in the
glovebox Bromobenzene (-H5 and -D5) were purchased from Sigma Aldrich and dried over
CaH2 for several days and vacuum distilled onto 4 Aring molecular sieves prior to use
Dichloromethane-d2 benzene-d6 and chloroform-d were purchased from Sigma Aldrich
Toluene-d8 was purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to
use Molecular sieves (4 Aring) were purchased from Sigma Aldrich and dried at 120 ordmC under
vacuum for 12 h prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at
80 degC under high vacuum before use
Tetrahydropyran 14-dioxane and hexamethyldisiloxane were purchased from Sigma Aldrich
and distilled over sodiumbenzophenone prior to use Diphenyl ether (ReagentPlusreg ge99) was
purchased from Sigma Aldrich and distilled under high vacuum at 80 degC over anhydrous
calcium chloride prior to use Diethyl ether (anhydrous 99) was purchased from Caledon
Laboratories Ltd and passed through a Grubbs-type column system manufactured by Innovative
Technology and stored over 4 Aring molecular sieves overnight prior to use Diisopropyl ether
(anhydrous 99 contains either BHT or hydroquinone as stabilizer) was purchased from Sigma
Aldrich and used without purification Cyclodextrins (α β and γ) maltitol dextrin from maize
starch and molecular sieves (pellets 32 mm diameter 4 Aring) were purchased from Sigma Aldrich
115
dried under vacuum at 120 degC for 12 h prior to use Deuterium hydride (extent of labeling 96
mol HD 98 atom D) was purchased from Sigma Aldrich Potassium
tetrakis(pentafluorophenyl)borate was purchased from Alfa Aesar Sodium triethylborohydride
(1M in toluene) was purchased from Sigma Aldrich Borenium cation-based FLP catalysts were
prepared by Dr Jeffrey M Farrell and Mr Roy Posaratnanathan following the literature
protocol105
All ketones and alcohols were purchased from Alfa Aesar Sigma Aldrich or TCI The liquids
were stored over 4 Aring molecular sieves and used without purification The solids were placed
under dynamic vacuum overnight prior to use H2 (grade 50) was purchased from Linde and
dried through a Nanochem Weldassure purifier column prior to use For the high pressure Parr
reactor the H2 was dried through a Matheson TRI-GAS purifier (type 452)
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D6 (1H = 716 ppm 13C = 1284 ppm) C6D5Br (1H = 728
ppm for meta proton 13C = 1224 ppm for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384
ppm) d8-tol (1H = 208 ppm for CH3 13C = 13748 ppm for ipso carbon) CDCl3 (1H = 726 ppm 13C = 7716 ppm) or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in
ppm and the absolute values of the coupling constants (J) are in Hz NMR assignments are
supported by additional 2D and DEPT-135 experiments
High Resolution Mass Spectroscopy (HRMS) was obtained using JMS T100-LC AccuTOF
DART with ion source Direct Analysis in Real Time (DART) Ionsense Inc Saugus MA GC-
MS spectra were obtained on an Agilent Technologies 5975C VL MSD with Triple-Axis
Detector and 7890A GC System Column Agilent 19091S-433 (30 m times 250 μm times 025 μm)
Oven 40 degC for first 10 min 10 degCmin to 300 degC for 10 min Injection volume 1 μL The pro-
chiral samples were analyzed using a Perkin Elmer Autosystem CL chromatograph with a chiral
column (CP Chirasil-Dex CB 25 m times 25 mm)
Jutzi acid [(Et2O)2H][B(C6F5)4]287 and silylation of α-CD with tert-butyldimethylsilyl chloride292
were prepared according to literature procedures
116
Solid materials were purchased from commercial sources 5 Aring molecular sieves (pellets 32 mm
Aldrich) 4 Aring molecular sieves (powder Aldrich) 3 Aring molecular sieves (rod 116 inches
Aldrich) aluminum oxide (weakly acidic 150 mesh 58 Aring SA = 155 m2g Aldrich) sodium
metasilicate (18 mesh granular Alfa Aesar) silicic acid (80 mesh powder Aldrich) silica gel
(200-425 mesh 60 Aring high purity grade Silicycle) sodium aluminate (powder Aldrich)
aluminum oxide (basic 150 mesh 58 Aring SA = 155 m2g Aldrich) aluminum oxide (neutral
150 mesh 58 Aring SA = 155 m2g Aldrich)
342 Synthesis of Compounds
3421 Procedures for reactions in ethereal solvents
4-Heptanol-B(C6F5)3 adduct experiment In the glove box an NMR tube was charged with a
d8-toluene (04 mL) solution of B(C6F5)3 (122 mg 240 μmol 100 mol) and 4-heptanol (279
mg 0240 mmol) The NMR tube was sealed with Parafilm and placed in an 80 degC oil bath for
12 h 19F and 11B NMR spectra were obtained No evidence for the formation of C6F5H was
observed
19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1552 (t 3JF-F = 22 Hz 1F p-C6F5) -
1628 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 197 (br s 4-heptanol-B(C6F5)3)
Synthesis of (CH3CH2CH2)2CHOB(C6F5)2from the reaction of 4-heptanone and HB(C6F5)2
In the glove box an NMR tube was charged with a d8-toluene (04 mL) solution of HB(C6F5)2
(834 mg 0240 mmol) and 4-heptanone (274 mg 0240 mmol) A second NMR tube was
charged with a d8-toluene (04 mL) solution of HB(C6F5)2 (83 mg 24 μmol 10 mol) and 4-
heptanone (274 mg 0240 mmol) After 10 min at RT the samples were analyzed by 1H 19F
and 11B NMR spectroscopy
1H NMR (400 MHz d8-tol) δ 405 (tt 3JH-H = 76 38 Hz 1H CH) 168-151 (m 2H CH2)
150 - 134 (m 4H CH2) 133 - 115 (m 2H CH2) 086 (t 3JH-H = 76 Hz 6H CH3) 19F NMR
(377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1498 (t 3JF-F = 20 Hz 1F p-C6F5) -1613 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 394 (br s (CH3CH2CH2)2CHOB(C6F5)2)
High temperature NMR study for the reduction of 4-heptanone using 5 equivalent of Et2O
(J-Young Experiment) In the glove box a 1 dram vial was charged with a d8-toluene (03 mL)
117
solution of B(C6F5)3 (61 mg 12 μmol 50 mol) 4-heptanone (274 mg 0240 mmol) and Et2O
(890 mg 125 μL 120 mmol) The reaction mixture was transferred into an oven-dried Teflon
screw cap J-Young tube The reaction tube was degassed once through a freeze-pump-thaw cycle
on the vacuumH2 line and filled with H2 (4 atm) at -196 degC The reaction was monitored by high
temperature 1H NMR spectroscopy at 70 degC with 15 minute acquisitions (Figure 31)
General procedure for reactions in ethereal solvents (Table 31) The following procedure is
common to the ketone hydrogenation reactions in Et2O iPr2O Ph2O and TMS2O In the glove
box a 2 dram vial equipped with a stir bar was charged with the respective ketone or aldehyde
(048 mmol) and B(C6F5)3 (122 mg 240 μmol 500 mol) To each vial the appropriate ether
(96 mmol 20 eq) was added using a syringe Et2O (10 mL) iPr2O (13 mL) Ph2O (15 mL) and
TMS2O (20 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glove box to be pressurized with hydrogen gas
The hydrogen gas line was thoroughly purged and the reactor was attached to it and purged 10
times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at 70 degC 540 rpm
and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time the reactor was
vented and the vials were exposed to the atmosphere In the case of Et2O and iPr2O the entire
reaction mixture was transferred to a round bottom flask and all the volatiles were collected by
vacuum distillation while cooling the collected distillate with liquid nitrogen The solvent was
then removed by applying a gentle stream of N2 gas The alcohol yields were recorded and the
products were characterized by NMR spectroscopy and GC-MS
General procedure for 100 gram reaction of 4-heptanone in Et2O In the glove box 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol 500 mol) dissolved in Et2O (143 mg 200 mL 0190 mol)
was added to the bottle The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glove box and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 540 rpm After the indicated reaction time the reactor was slowly
vented and all the volatiles were collected by vacuum distillation while cooling the collected
distillate with liquid nitrogen The solvent was removed by applying a gentle stream of N2 gas
118
By 1H NMR spectroscopy the product displayed complete conversion to 4-heptanol and was
isolated in 87 yield
Dependence of Et2O equivalents on the reduction of 4-heptanone (Figure 32) In the glove
box a stock solution consisting of 4-heptanone (192 mg 235 μL 167 mmol) and B(C6F5)3 (427
mg 800 μmol 500 mol) in toluene (35 mL) was prepared in a 2 dram vial The solution was
distributed evenly between seven 2-dram vials (053 mLvial) and each vial was equipped with a
stir bar To each vial the appropriate volume of Et2O was added using a (micro)syringe
Et2O volume 12 μL (005 eq) 25 μL (01 eq) 125 μL (05 eq) 252 μL (10 eq) 504 μL (20
eq) 756 μL (30 eq) 101 μL (40 eq) 126 μL (50 eq) 151 μL (60 eq) 176 μL (70 eq) 202 μL
(80 eq)
The vial was loosely capped and loaded in a Parr pressure reactor sealed carefully and removed
from the glove box to be pressurized with hydrogen gas The hydrogen gas line was thoroughly
purged and the reactor was attached to it and purged 10 times at 15 atm of hydrogen gas The
reactor was then placed in an oil bath set at 70 degC 540 rpm and sealed at 60 atm of hydrogen gas
for 12 h After the indicated reaction time the reactor was vented and the reactions were analyzed
by 1H NMR spectroscopy Percent conversion to 4-heptanol was obtained by integration relative
to the remaining starting material 4-heptanone
Synthesis of [iPr2O-HmiddotmiddotmiddotO=C(CH2Ph)CH2CH3][B(C6F5)4] (31) In the glove box to a 2 dram
vial was added [(Et2O)2H][B(C6F5)4] (130 mg 0157 mmol) 4-phenyl-2-butanone (349 mg
0235 mmol) iPr2O (1284 mg 126 mmol) and toluene (05 mL) The solution was transferred
into a Teflon-sealed Schlenk bomb (25 mL) equipped with a stir bar and heated at 70 degC for 2 h
The solvent was removed under vacuum and pentane (5 mL) was added to result in immediate
precipitation of a white solid that was washed again with pentane (3 mL) and dried under
vacuum (127 g 136 mmol 87) Crystals suitable for X-ray crystallographic studies were
obtained from a layered bromobenzenepentane solution at RT
1H NMR (400 MHz CD2Cl2) δ 1152 (br s 1H iPr2O-HmiddotmiddotmiddotO=C) 741 (m 3H m p-Ph) 718
(m 2H o-Ph) 468 (m 3JH-H = 68 Hz 2H iPr) 403 (s 2H PhCH2) 281 (q 3JH-H = 71 Hz
2H CH2CH3) 146 (d 3JH-H = 68 Hz 12H iPr) 117 (t 3JH-H = 71 Hz 3H CH2CH3) 19F NMR
(377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1617 (t 3JF-F = 22 Hz 1F p-C6F5) -1658 (m
119
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -168 (s B(C6F5)4) 13C1H NMR (125 MHz
CD2Cl2) δ 1480 (dm 1JC-F = 238 Hz CF) 1379 (dm 1JC-F = 243 Hz CF) 1362 (dm 1JC-F =
246 Hz CF5) 1319 (ipso-Ph) 1301 (m-Ph) 1298 (o-Ph) 1288 (p-Ph) 1240 (ipso-C6F5) 828
(iPr) 498 (CH2Ph) 373 (CH2CH3) 197 (iPr) 799 (CH2CH3) (C=O was not observed)
HRMS (DART-TOF+) mass [M]+ calcd for [C16H27O2]+ 25120110 Da Found 25120127 Da
mass [M]- calcd for [C24BF20]- 67897736 Da Found 67897745 Da
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3]
Synthesis of [NEt4][HB(C6F5)3] Part 1 In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (200 mg 0391 mmol) in toluene (10 mL) To the vial
sodium triethylborohydride (1M in toluene) (036 mL 036 mmol) was added drop wise over 15
min The reaction was allowed to mix overnight prior to removing the volatiles under vacuum
The crude mixture was washed with pentane (5 mL) to give the product Na HB(C6F5)3 as a white
solid (187 mg 0348 mmol 89)
Part 2 Na HB(C6F5)3 (187 mg 0348 mmol) was subsequently added to CH2Cl2 (10 mL) and
added to a 4 dram vial containing NEt4 Cl (576 mg 0348 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT overnight and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (206 mg
0320 mmol 92)
1H NMR (400 MHz d8-tol) δ 415 (br q 1JB-H = 91 Hz 1H BH) 211 (q 3JH-H = 74 Hz 8H
Et) 046 (tm 3JH-H = 74 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -13361 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
247 (d 1JB-H = 91 Hz BH)
General procedure for reactions in toluene using B(C6F5)3 and [NEt4][HB(C6F5)3] (Table
32) In the glovebox a 2 dram vial equipped with a stir bar was charged with the respective
ketone (048 mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and [NEt4][HB(C6F5)3] (154
mg 240 μmol 500 mol) in toluene (10 mL) The vial was loosely capped and loaded in a
Parr pressure reactor sealed carefully and removed from the glovebox to be pressurized with
hydrogen gas The hydrogen gas line was thoroughly purged and the reactor was attached to it
and purged 10 times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at
80 degC 540 rpm and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time
120
the reactor was vented and the reactions were analyzed by 1H NMR spectroscopy Percent
conversion to the alcohol product was obtained by integration relative to the remaining starting
material ketone
3423 Procedures for reactions using heterogeneous Lewis bases
General procedure for reactions in toluene using heterogeneous Lewis bases (Table 33) In
the glovebox a 2 dram vial equipped with a stir bar was charged with the respective ketone (048
mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and the respective heterogeneous Lewis base
in toluene (10 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glovebox to be pressurized with hydrogen gas The hydrogen gas
line was thoroughly purged and the reactor was attached to it and purged 10 times at 15 atm of
hydrogen gas The reactor was then placed in an oil bath set at 60 degC 430 rpm and sealed at 60
atm of hydrogen gas for 12 h Products were isolated by appropriate work-up methods The
alcohol yields were recorded and the products were characterized by NMR spectroscopy and
GC-MS
Heterogeneous Lewis bases α-CD (467 mg 0480 mmol) β-CD (467 mg 0410 mmol) γ-CD
(467 mg 0360 mmol) maltitol (168 mg 0480 mmol) dextrin (350 mg) MS (100 mg)
General procedure 100 g scale reduction of 4-heptanone using MS In the glovebox 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol) dissolved in toluene (7 mL ) was added to the bottle in addition
to 302 g of 4 Aring MS The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glovebox and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 430 rpm The reactor was slowly vented and an aliquot was taken in
d8-toluene and complete conversion of 4-heptanone to 4-heptanol was determined by 1H NMR
spectroscopy The reaction mixture was filtered through a frit and washed with dichloromethane
(2 times 10 mL) The collected molecular sieves were extracted with dichloromethane (3 times 10 mL)
and water (20 mL) The organic fraction was dried over magnesium sulfate and combined with
the toluene fraction The two solvents dichloromethane and toluene were removed by fractional
121
distillation 4-Heptanol was then collected under vacuum in a liquid nitrogen cooled Schlenk
flask The product was collected as a colourless liquid (0885 g 762 mmol 87)
3424 Procedures for reductive deoxygenation reactions
General procedure for deoxygenation reactions using molecular sieves (Table 34 and Table
35) This method follows the same procedure for reactions in Table 33 using 4 Aring MS The
reactor was placed in an oil bath set at 70 degC 340 rpm and sealed at 60 atm of hydrogen gas for
12 h Products were isolated by appropriate work-up methods The aromatic hydrocarbon yields
were recorded and the products were characterized by NMR spectroscopy and GC-MS
Verifying the deoxygenation mechanism In the glovebox four separate 2-dram vials were
loaded with diphenylmethanol (442 mg 0240 mmol) and B(C6F5)3 (61 mg 12 μmol 50
mol) To each vial the indicated equivalents of benzophenone were added (21 mg 12 μmol
50 mol 44 mg 24 μmol 10 mol 218 mg 0120 mmol 50 mol) followed by the
addition of d8-toluene (05 mL) and 4 Aring MS (100 mg) The reaction vials were equipped with a
stir bar loosely capped and placed inside a Parr pressure reactor The reactor was sealed
removed from the glovebox and attached to a purged hydrogen gas line The reactor was purged
ten times at 15 atm with hydrogen gas The reactor was then pressurized with 60 atm hydrogen
gas and placed in an oil bath for 12 h at 70 degC and 340 rpm After the indicated reaction time the
reactor was slowly vented and an aliquot was taken in d8-toluene and conversion of the
diphenylmethanol to diphenylmethane was determined by 1H NMR spectroscopy
3425 Spectroscopic data of products in Table 31
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
4-Heptanol (Entry 1) 1H NMR (500 MHz C6D5Br) δ 472 (br s 1H OH) 341 (tt 3JH-H = 70
Hz 46 Hz 1H CH) 124 (m 4H CHCH2) 114 (m 4H CH2CH3) 082 (t 3JH-H = 67 Hz 6H
CH3) 13C1H NMR (125 MHz C6D5Br) δ 721 (CH) 390 (CHCH2) 184 (CH2CH3) 135
(CH3) GC-MS 11928 min mz = 981 [M-H2O] 730 [M-C3H7] 550 [M-C3H9O]
3-Methylbutan-2-ol (Entry 2) 1H NMR (500 MHz C6D5Br) δ 339 (qd 3JH-H = 63 Hz 53
Hz 1H CHOH) 145 (m 1H iPr) 115 (br s 1H OH) 100 (d 3JH-H = 63 Hz 3H CH3) 083
122
(d 3JH-H = 68 Hz 3H iPr) 080 (d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz
C6D5Br) δ 719 (CHOH) 347 (iPr) 200 (CH3) 180 (iPr) 175 (iPr) GC-MS 3150 min mz
= 731 [M-CH3] 551 [M-CH5O]
44-Dimethylpentan-2-ol (Entry 3) 1H NMR (500 MHz C6D5Br) δ 380 (m 1H CH) 368
(br s 1H OH) 127 (dd 2JH-H = 143 Hz 3JH-H = 79 Hz 1H CH2) 116 (dd 2JH-H = 143 Hz 3JH-H = 33 Hz 1H CH2) 105 (d 3JH-H = 62 Hz 3H CH3) 087 (s 9H tBu) 13C1H NMR
(125 MHz C6D5Br) δ 660 (CH) 526 (CH2) 300 (tBu) 299 (tBu) 258 (CH3) GC-MS 6776
min mz = 1011 [M-CH3] 831 [M-CH5O] 701 [M-C2H6O] 571 [M-C3H7O]
Heptan-2-ol (Entry 4) 1H NMR (500 MHz d8-tol) δ 424 (br s 1H OH)
348 (m 3JH-H = 60 Hz 1H H2) 126 (m 2H H6) 123 (m 2H H3 H4)
118 - 114 (m 4H H3 H4 H5) 097 (d 3JH-H = 60 Hz 3H H1) 090 (t 3JH-H = 71 Hz 3H
H7) 13C1H NMR (125 MHz d8-tol) δ 684 (C2) 392 (C3) 319 (C5) 255 (C4) 228 (C1
C6) 139 (C7) GC-MS 12395 min mz = 1011 [M-CH3] 981 [M-H2O] 871 [M-C2H5]
1-Chloropropan-2-ol (Entry 5) 1H NMR (500 MHz C6D5Br) δ 432 (br s 1H OH) 362 (m 3JH-H = 68 Hz 1H CH) 316 (dd 2JH-H = 113 Hz 3JH-H = 35 Hz 1H CH2Cl) 304 (dd 2JH-H =
113 Hz 3JH-H = 68 Hz 1H CH2Cl) 090 (d 3JH-H = 61 Hz 3H CH3) 13C1H NMR (125
MHz C6D5Br) δ 692 (CH) 502 (CH2Cl) 222 (CH3) GC-MS 3383 min mz = 810 [(M+2)-
CH3] 790 [M-CH3]
1-Cyclohexylethan-1-ol (Entry 6) 1H NMR (400 MHz d8-tol) δ 330 (quint 3JH-H = 74 Hz
1H CH) 182 - 147 (m 5H Cy) 131 (br s 1H OH) 125 - 102 (m 4H Cy) 098 (d 3JH-H =
74 Hz 3H CH3) 087 (m 2H Cy) 13C1H NMR (125 MHz d8-tol) δ 721 (CHOH) 452
(CyCH) 287 (Cy) 268 (Cy) 267 (Cy) 205 (CH3) GC-MS 14245 min mz = 1131 [M-CH3]
1101 [M- H2O] 831 [M-C2H5O]
2-Methylpentan-3-ol (Entry 7) 1H NMR (500 MHz C6D5Br) δ 410 (br s 1H OH) 308
(ddd 3JH-H = 88 Hz 52 Hz 38 Hz 1H CHOH) 146 (m 3JH-H = 68 Hz 52 Hz 1H iPr) 133
(dqd 2JH-H = 140 Hz 3JH-H = 75 Hz 39 Hz 1H CH2) 120 (ddq 2JH-H = 140 Hz 3JH-H = 86
Hz 75 Hz 1H CH2) 081 (t 3JH-H = 75 Hz 3H CH3) 077 (d 3JH-H = 68 Hz 3H iPr) 076
(d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz C6D5Br) δ 783 (CHOH) 326 (iPr) 264
123
(CH2) 184 (iPr) 167 (iPr) 994 (CH3) GC-MS 5663 min mz = 841 [M-H2O] 731 [M-
C2H5] 591 [M-C3H7]
Heptan-3-ol (Entry 8) 1H NMR (500 MHz C6D5Br) δ 450 (br s 1H
OH) 335 (tt 3JH-H = 73 Hz 47 Hz 1H H3) 136-130 (m 2H H2) 128-
121 (m 5H H4 H5 H6) 115 (m 1H H5) 084 (t 3JH-H = 57 Hz 3H H7) 083 (t 3JH-H = 57
Hz 3H H1) 13C1H NMR (125 MHz C6D5Br) δ 732 (C3) 362 (C4) 295 (C2) 275 (C5)
226 (C6) 138 (C7) 961 (C1) GC-MS 12171 min mz = 981 [M-H2O] 831 [M-CH5O]
691 [M-C2H7O] 590 [M-C4H9]
5-Methylhexan-3-ol (Entry 9) 1H NMR (400 MHz d8-tol) δ (tt 3JH-H = 87 51 Hz 1H
CHOH) 201 (m 2H CH2CH3) 148 (m 3JH-H = 69 51 Hz 1H iPr) 130 (m 1H CH2iPr)
126 (m 1H CH2iPr) 089 (d 3JH-H = 69 Hz 6H iPr) 085 (t 3JH-H = 72 Hz 3H CH3)
13C1H NMR (101 MHz d8-tol) δ 785 (CHOH) 337 (iPr CH2CH3) 273 (CH2iPr) 188
(iPr) 171 (iPr) 104 (CH3) GC-MS 9458 min mz = 871 [M-Et] 691 [M-C2H7O] 591 [M-
CH2iPr]
1-Phenylethan-1-ol (Entry 10) 1H NMR (400 MHz C6D6) δ 702 (m 5H Ph) 428 (q 3JH-H =
65 Hz 1H CH) 342 (br s 1H OH) 102 (d 3JH-H = 65 Hz 3H CH3) 13C1H NMR (125
MHz CDCl3) δ 1460 (ipso-Ph) 1286 (m-Ph) 1283 (p-Ph) 1254 (o-Ph) 703 (CH) 252
(CH3) GC-MS 17207 min mz = 1221 [M] 1071 [M-CH3] 1040 [M-H2O] 910 [M-CH3O]
770 [M-C2H5O]
1-Phenylbutan-2-ol (Entry 11) 1H NMR (500 MHz CD2Cl2) δ 755 (m 1H OH) 733 (tm 3JH-H = 76 Hz 2H m-Ph) 729 (dm 3JH-H = 76 Hz 2H o-Ph) 725 (tm 3JH-H = 76 Hz 1H p-
Ph) 376 (dq 3JH-H = 81 Hz 42 Hz 1H CH) 286 (dd 2JH-H = 136 Hz 3JH-H = 43 Hz 1H
CH2Ph) 266 (dd 2JH-H = 136 Hz 3JH-H = 81 Hz 1H CH2Ph) 152 (q 3JH-H = 77 Hz 2H
CH2CH3) 102 (t 3JH-H = 77 Hz 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1391 (ipso-
Ph) 1295 (m-Ph) 1284 (o-Ph) 1263 (p-Ph) 739 (CH) 437 (CH2Ph) 303 (CH2CH3) 960
(CH3) GC-MS 20079 min mz = 1321 [M-H2O] 1030 [M-C2H7O] 911 [M-C3H7O]
591[M-C7H7]
4-Phenylbutan-2-ol (Entry 12) 1H NMR (500 MHz C6D5Br) δ 720 (t 3JH-H = 74 Hz 2H m-
Ph) 710 (t 3JH-H = 74 Hz 1H p-Ph) 706 (d 3JH-H = 74 Hz 2H o-Ph) 373 (br s 1H OH)
124
362 (dqd 3JH-H = 74 Hz 62 Hz 50 Hz 1H CH) 255 (m 2H PhCH2) 160 (m 2H CH2CH)
103 (d 3JH-H = 62 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1411 (ipso-Ph) 1281
(m-Ph) 1280 (o-Ph) 1255 (p-Ph) 673 (CH) 403 (PhCH2) 317 (CH2CH) 229 (CH3) GC-
MS 20438 min mz = 1501 [M] 1321 [M-H2O] 1170 [M-CH5O] 1051 [M-C2H5O] 911
[M-C3H7O]
1-(2-Fluorophenyl)propan-2-ol (Entry 13) 1H NMR (500 MHz CD2Cl2) δ
753 (m 1H OH) 733 - 705 (m 4H C6H4F) 406 (m 1H CH) 284 (dd 2JH-
H = 139 Hz 3JH-H = 51 Hz 1H CH2) 276 (dd 2JH-H = 139 Hz 3JH-H = 77
Hz 1H CH2) 124 (d 3JH-H = 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1178 (m
CF) 13C1H NMR (125 MHz CD2Cl2) δ 1611 (d 1JC-F = 240 Hz C1) 1318 (d 3JC-F = 59
Hz C3) 1285 (d 4JC-F = 88 Hz C4) 1257 (d 2JC-F = 16 Hz C2) 1240 (d 3JC-F = 37 Hz C5)
1152 (d 2JC-F = 22 Hz C6) 678 (d 4JC-F = 11 Hz CH) 388 (d 3JC-F = 14 Hz CH2) 229
(CH3) GC-MS 18697 min mz = 1360 [M-H2O] 960 [M-C3H6O]
1-(4-Fluorophenyl)propan-2-ol (Entry 14) 1H NMR (500 MHz CD2Cl2) δ 722 (m 2H o of
C6H4F) 705 (m 2H m of C6H4F) 399 (m 1H CH) 278 (dd 2JH-H = 137 Hz 3JH-H = 48 Hz
1H CH2) 269 (dd 2JH-H = 137 Hz 3JH-H = 78 Hz 1H CH2) 161 (br s 1H OH) 122 (d 3JH-H
= 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1177 (m p-C6H4F) 13C1H NMR (125
MHz CD2Cl2) δ 1616 (d 1JC-F = 243 Hz p of C6H4F) 1348 (d 4JC-F = 46 Hz ipso-C6H4F)
1307 (d 3JC-F = 82 Hz o of C6H4F) 1149 (d 2JC-F = 22 Hz m of C6H4F) 690 (CH) 449
(CH2) 227 (CH3) GC-MS 18697 min mz = 1361 [M-H2O] 960 [M-C3H6O]
1-(3-(Trifluoromethyl)phenyl)propan-2-ol (Entry 15) 1H NMR (500
MHz CD2Cl2) δ 751 (m 2H H1 H5) 744 (m 2H H3 H4) 408 (m 1H
CH) 283 (dd 2JH-H = 136 Hz 3JH-H = 49 Hz 1H CH2) 276 (dd 2JH-H =
136 Hz 3JH-H = 78 Hz 1H CH2) 181 (br s 1H OH) 123 (t 3JH-H = 62
Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -628 (CF3) 13C1H NMR (125 MHz CD2Cl2)
δ 1399 (C2) 1330 (q 4JC-F = 13 Hz C3) 1303 (q 2JC-F = 30 Hz C6) 1288 (C4) 1260 (q 3JC-F = 41 Hz C1) 1242 (q 1JC-F = 277 Hz CF3) 1230 (q 3JC-F = 41 Hz C5) 687 (CH) 447
(CH2) 228 (CH3) GC-MS 19011 min mz = 1861 [M-H2O] 1601 [M-C2H4O] 1171 [M-
CH2F3O]
125
Cyclohexanol (Entry 16) 1H NMR (400 MHz d8-tol) δ 324 (tt 3JH-H = 90 Hz 37 Hz 1H
CH) 177 (m 2H Cy) 168 (m 2H Cy) 142- 130 (m 3H Cy) 126- 115 (m 3H Cy)
13C1H NMR (101 MHz CD2Cl2) δ 706 (CH) 360 (CHCH2) 260 (Cy) 245 (Cy) GC-MS
4029 min mz = 1001 [M] 821 [M-H2O]
2-Isopropyl-5-methylcyclohexan-1-ol (Entry 17) 1H NMR (500 MHz
C6D5Br) δ 390 (q 3JH-H = 29 Hz 1H H1) 346 (br s 1H OH) 168 (ddd 2JH-H = 139 Hz 3JH-H = 36 Hz 24 Hz 1H H2) 164 (m 2H H3 H4) 153
(dm 2JH-H = 132 Hz 1H H5) 143 (dm 3JH-H = 92 Hz 67 Hz 1H H7) 118 (dm 2JH-H = 132
Hz 1H H5) 091 (m 1H H2) 087 (d 3JH-H = 67 Hz 3H H8) 083 (d 3JH-H = 67 Hz 3H
H9) 080 (d 3JH-H = 64 Hz 3H H10) 075 (m 1H H4) 070 (m 1H H6) 13C1H NMR (125
MHz C6D5Br) δ 675 (C1) 473 (C6) 421 (C2) 346 (C4) 288 (C7) 254 (C3) 238 (C5)
221 (C10) 208 (C9) 203 (C8) GC-MS 18912 min mz = 1381 [M-H2O] 1231 [M-CH5O]
951 [M-C3H9O] 811 [M-C4H12O]
Cyclohexylmethanol (Entry 18) 1H NMR (500 MHz CD2Cl2) δ 556 (br s 1H OH) 404 (d 3JH-H = 75 Hz 2H CH2OH) 212-182 (m 1H CyCH2) 180 (m 1H CyCH) 163 - 117 (m 1H CyCH2) 13C1H NMR (125 MHz CD2Cl2) δ 693 (CH2OH) 374 (CyCH) 301 (CyCH2) 262
(CyCH2) 252 (CyCH2) GC-MS 5538 min mz = 1141 [M] 961 [M-H2O] 831 [M-CH3O]
3426 Spectroscopic data of products in Table 32
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
3-Methylpentan-2-ol (Entry 4) 1H NMR (400 MHz CDCl3) δ 376 (m 1H CHOH) 223 (br
s 1H OH) 175 - 142 (m 3H CH(Et) Et) 118 (d 3JH-H = 69 Hz 3H CH3CHOH) 098 (m
6H CH(Et)CH3 Et) 13C1H NMR (125 MHz CD2Cl2) δ 713 (CHOH) 406 (CH(Et)) 223
(Et) 198 (OHCHCH3) 120 (CH(Et)CH3) 111 (Et) GC-MS 10215 min mz = 871 [M-CH3]
561 [M-C2H6O] 450 [C2H5O]
3427 Spectroscopic data of products in Table 33
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
126
222-Trifluoro-1-phenylethan-1-ol (Entry 12) 1H NMR (500 MHz d8-tol) δ 745 (m 2H m-
Ph) 717 (dm 3JH-H = 70 Hz 2H o-Ph) 711 (m 1H p-Ph) 432 (d 3JF-H = 77 Hz 1H CH)
306 (br s 1H OH) 19F NMR (470 MHz d8-tol) δ -783 (d 3JF-H = 77 Hz CF3) 13C1H NMR
(125 MHz d8-tol) δ 1341 (ipso-Ph) 1289 (m-Ph) 1276 (p-Ph) 1272 (q 4JC-F = 12 Hz o-Ph)
1234 (q 1JC-F = 297 Hz CF3) 726 (CH) GC-MS 6130 min mz = 1760 [M] 1701 [M-CF3]
3-Chloro-1-phenylpropan-1-ol (Entry 11) 1H NMR (600 MHz d8-tol) δ 712 (m 3H m p-
Ph) 703 (m 2H o-Ph) 399 (t 3JH-H = 78 Hz 1H CHOH) 312 (t 3JH-H = 67 Hz 2H CH2Cl)
251 (br s 1H OH) 218 (dt 3JH-H = 78 Hz 67 Hz 2H CHCH2CH2) 13C1H NMR (151
MHz d8-tol) δ 1440 (ipso-Ph) 1282 (m-Ph) 1275 (o-Ph) 1260 (p-Ph) 476 (CHOH) 432
(CH2Cl) 387 (CHCH2CH2) GC-MS 11210 min mz = 1701 [M] 1521 [M-H2O] 1070 [M-
C2H4Cl]
1-(2-(Trifluoromethyl)phenyl)ethan-1-ol (Entry 13) 1H NMR (500 MHz
d8-tol) δ 759 (d 3JH-H = 81 Hz 1H H2) 732 (d 3JH-H = 81 Hz 1H H5)
711 (t 3JH-H = 81 Hz 1H H3) 685 (t 3JH-H = 81 Hz 1H H4) 508 (qm 3JH-
H = 67 Hz 1H CHOH) 221 (br s 1H OH) 125 (d 3JH-H = 67 Hz 3H CH3)
19F NMR (470 MHz d8-tol) δ -582 (s CF3) 13C1H NMR (125 MHz d8-tol) δ 1455 (ipso-
C6H4CF3) 1315 (C3) 1314 (C1) 1294 (C4) 1264 (C2) 1244 (C5) 1240 (CF3) 653
(CHOH) 253 (CH3) (JC-F not reported) GC-MS 6453 min mz = 1901 [M] 1750 [M-CH3]
1720 [M-H2O] 1450 [M-C2H5O]
1-(4-(Methylsulfonyl)phenyl)ethan-1-ol (Entry 14) 1H NMR (500 MHz d8-tol) δ 763 (d 3JH-H = 86 Hz 2H o of C6H4SO2CH3) 705 (d 3JH-H = 86 Hz 2H m of C6H4SO2CH3) 437 (m
1H CHOH) 228 (s 3H SO2CH3) 141 (br s 1H OH) 112 (d 3JH-H = 66 Hz 3H CHCH3)
13C1H NMR (125 MHz d8-tol) δ 1522 (p of C6H4SO2CH3) 1402 (ipso-C6H4SO2CH3) 1270
(o of C6H4SO2CH3) 1257 (m of C6H4SO2CH3) 689 (CHOH) 436 (SO2CH3) 252 (CHCH3)
HRMS-DART+ mz [M+NH4]+ calcd for C9H16NO3S 21808509 Found 21808554
22-Diphenylethan-1-ol (Entry 24) 1H NMR (500 MHz d8-tol) δ 704 (m 1H p-Ph) 703 (m
2H m -Ph) 693 (d 3JH-H = 75 Hz 2H o-Ph) 405 (dd 3JH-H = 83 Hz 61 Hz 1H CH) 400
(m 2H CH2) (OH was not observed) 13C1H NMR (125 MHz d8-tol) δ 1418 (ipso-Ph)
1293 (m-Ph) 1287 (o-Ph) 1274 (p-Ph) 763 (CH2) 512 (CH) GC-MS 15178 min mz =
1811 [M-OH] 1671 [M-CH3O]
127
2-Phenylpropan-1-ol (Entry 25) 1H NMR (500 MHz d8-tol) δ 722 (d 3JH-H = 78 Hz 2H o-
Ph) 718 ndash 713 (m 3H m p-Ph) 362 (dd 2JH-H = 100 Hz 3JH-H = 62 Hz 1H CH2) 354 (dd 2JH-H = 100 Hz 3JH-H = 78 Hz 1H CH2) 342 (br s 1H OH) 288 (m 3JH-H = 69 Hz 1H CH)
121 (d 3JH-H = 69 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1459 (ipso-Ph) 1289 (p-
Ph) 1283 (m-Ph) 1274 (o-Ph) 780 (CH2) 435 (CH) 181 (CH3) GC-MS 6462 min mz =
1211 [M-CH3] 1051 [M-CH3O]
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Styrene (Entry 1)1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 77 Hz 2H o-Ph) 708 (t 3JH-
H = 77 Hz 2H m-Ph) 706 (t 3JH-H = 77 Hz 1H p-Ph) 653 (dd 3JH-H = 176 Hz 109 Hz 1H
CH) 556 (dd 3JH-H = 176 Hz 11 Hz 1H CH2) 505 (dd 3JH-H = 109 Hz 11 Hz 1H CH2)
13C1H NMR (125 MHz d8-tol) δ 1379 (CH) 1372 (ipso-Ph) 1286 (o m-Ph) 1284 (p-Ph)
1140 (CH2) GC-MS 4038 min mz = 1041 [M] 911 [C7H7] 781 [C6H6]
1-(Trifluoromethyl)-3-vinylbenzene (Entry 2) 1H NMR (500 MHz d8-
tol) δ 744 (s 1H H1) 718 (d 3JH-H = 77 Hz 1H H5) 706 (d 3JH-H = 77
Hz 1H H3) 686 (t 3JH-H = 75 Hz 1H H4) 631 (dd 3JH-H = 173 Hz 102
Hz 1H CH=CH2) 544 (d 3JH-H = 173 Hz 1H CH=CH2) 504 (d 3JH-H = 102 Hz 1H
CH=CH2) 19F NMR (470 MHz d8-tol) δ -626 (s CF3) 13C1H NMR (125 MHz d8-tol) δ
1379 (ipso-C6H4CF3) 1354 (CH=CH2) 1309 (C2) 1284 (C5) 1245 (CF3) 1237 (C3) 1225
(C1) 1151 (CH=CH2) (JC-F not reported) GC-MS 4290 min mz = 1721 [M] 1531 [M-F]
1451 [M-C2H3] 1031 [M-CF3]
(E)-Prop-1-en-1-ylbenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 73 Hz
2H o-Ph) 712 (t 3JH-H = 73 Hz 2H m-Ph) 702 (t 3JH-H = 73 Hz 1H p-Ph) 626 (dq 3JH-H =
156 Hz 4JH-H = 18 Hz 1H PhCH=CH) 600 (dq 3JH-H = 156 Hz 66 Hz 1H PhCH=CH)
168 (dd 3JH-H = 66 Hz 4JH-H = 18 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1378
(ipso-Ph) 1314 (PhCH=CH) 1283 (m-Ph) 1265 (p-Ph) 1258 (o-Ph) 1248 (PhCH=CH)
1800 (CH3) GC-MS 5888 min mz = 1181 [M] 1171 [M-H] 1031 [M-CH3]
128
(2-Methylprop-1-en-1-yl)benzene (Entry 4) 1H NMR (500 MHz d8-tol) δ 717 (m 4H o m-
Ph) 705 (m 1H p-Ph) 624 (m 4JH-H = 15 Hz 1H CH=C(CH3)2) 180 (d 4JH-H = 15 Hz 3H
CH=C(CH3)2) 175 (d 4JH-H = 15 Hz 3H CH=C(CH3)2) 13C1H NMR (125 MHz d8-tol) δ
1386 (C(CH3)2) 1345 (ipso-Ph) 1287 (o-Ph) 1279 (m-Ph) 1257 (CH=C(CH3)2) 1256 (p-
Ph) 264 (CH3) 188 (CH3) GC-MS 5780 min mz = 1321 [M] 1171 [M-CH3]
12-Dihydronaphthalene (Scheme 312a) 1H NMR (600 MHz CD2Cl2) δ 746 - 731 (m 4H
C6H4) 678 (dm 3JH-H = 96 Hz 1H CH=CHCH2) 632 (m 1H CH=CHCH2) 308 (m 2H
CH2CH2CH) 258 (m 2H CH2CH=CH) 13C1H NMR (125 MHz CD2Cl2) δ 1358
(quaternary C for C6H4) 1344 (quaternary C for C6H4) 1288 (CH=CHCH2) 1280
(CH=CHCH2) 1277 (C6H4) 1271 (C6H4) 1266 (C6H4) 1261 (C6H4) 278 (CHCH2CH2) 236
(CH=CHCH2) GC-MS 7943 min mz = 1301 [M] 1151 [M-CH3] 1021 [M-C2H4]
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Diphenylmethane (Entry 1) 1H NMR (500 MHz d8-tol) δ 708 (t 3JH-H = 75 Hz 2H m-Ph)
701 (t 3JH-H = 75 Hz 1H p-Ph) 700 (d 3JH-H = 75 Hz 2H o-Ph) 372 (s 1H CH2) 13C1H
NMR (125 MHz d8-tol) δ 1413 (ipso-Ph) 1293 (o-Ph) 1286 (m-Ph) 1263 (p-Ph) 422
(CH2) GC-MS 11686 min mz = 1681 [M] 1671 [M-H] 911 [C7H7]
1-Benzyl-4-methoxybenzene (Entry 2) 1H NMR (500 MHz d8-tol) δ 712 (m 2H m-Ph)
711 (m 1H p-Ph) 705 (d 3JH-H = 67 Hz 2H o-Ph) 693 (d 3JH-H = 76 Hz 2H o of
C6H4OCH3) 670 (d 3JH-H = 76 Hz 2H m of C6H4OCH3) 372 (s 2H CH2) 334 (s 3H
OCH3) 13C1H NMR (125 MHz d8-tol) δ 1581 (p of C6H4OCH3) 1416 (ipso-C6H4OCH3)
1328 (ipso-Ph) 1295 (o of C6H4OCH3) 1287 (o-Ph) 1283 (m-Ph) 1278 (p-Ph) 1137 (m of
C6H4OCH3) 542 (OCH3) 410 (CH2) GC-MS 14801 min mz = 1981 [M] 1671 [M-OCH3]
1211 [M-C6H5] 911 [M-C7H7O] 771 [M-C8H9O]
1-Benzyl-4-bromobenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 719 (m 1H p-Ph) 716
(d 3JH-H = 78 Hz 2H m of C6H4Br) 710 (t 3JH-H = 77 Hz 2H m-Ph) 691 (d 3JH-H = 77 Hz
2H o-Ph) 665 (d 3JH-H = 77 Hz 2H o of C6H4Br) 355 (s 2H CH2) 13C1H NMR (125
MHz d8-tol) δ 1407 (ipso-C6H4Br) 1403 (ipso-Ph) 1317 (m of C6H4Br) 1316 (p-Ph) 1308
129
(o of C6H4Br) 1289 (o-Ph) 1285 (m-Ph) 1204 (p-C6H4Br) 414 (CH2) GC-MS 15250 min
mz = 2480 [M+2] 2460 [M] 1671 [M-Br] 911 [M-C6H4Br]
1-Benzyl-4-(tert-butyl)benzene (Entry 4) 1H NMR (500 MHz CD2Cl2) δ 774 (t 3JH-H = 86
Hz 2H m of C6H4tBu) 768 (t 3JH-H = 76 Hz 1H p-Ph) 761 (t 3JH-H = 76 Hz 2H m-Ph)
759 (d 3JH-H = 76 Hz 2H o-Ph) 755 (d 3JH-H = 86 Hz 2H o of C6H4tBu) 435 (s 2H CH2)
178 (s 9H tBu) 13C1H NMR (125 MHz CD2Cl2) δ 1493 (p of C6H4tBu) 1420 (ipso-Ph)
1387 (ipso-C6H4tBu) 1294 (m-Ph o of C6H4tBu) 1286 (p-Ph) 1263 (o-Ph) 1255 (m of
C6H4tBu) 415 (CH2) 347 (tBu) 315 (tBu) GC-MS 15429 min mz = 2242 [M] 2092 [M-
CH3) 911 [C7H7]
Di-p-tolylmethane (Entry 5) 1H NMR (500 MHz d8-tol) δ 699 (d 3JH-H = 78 Hz 2H o of
C6H4CH3) 694 (d 3JH-H = 78 Hz 2H m of C6H4CH3) 375 (s 1H CH2) 215 (s 3H CH3)
13C1H NMR (125 MHz d8-tol) δ 1383 (ipso-C6H4CH3) 1350 (p of C6H4CH3) 1289 (m of
C6H4CH3) 1287 (o of C6H4CH3) 408 (CH2) 206 (CH3) GC-MS 14226 min mz = 1961
[M] 1811 [M-CH3) 1661 [M-2(CH3)] 1051 [M-C7H7] 911 [M- C8H9]
1-Benzyl-4-(trifluoromethyl)benzene (Entry 6) 1H NMR (600 MHz CD2Cl2) δ 800 (d 3JH-H
= 73 Hz 2H o-Ph) 788 (d 3JH-H = 74 Hz 2H m of C6H4CF3) 778 (t 3JH-H = 73 Hz 1H p-
Ph) 767 (t 3JH-H = 73 Hz 2H m-Ph) 751 (d 3JH-H = 74 Hz 2H o of C6H4CF3) 430 (s 2H
CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1458 (ipso-C6H4CF3) 1404 (ipso-Ph) 1296 (p-Ph
o of C6H4CF3) 1285 (m-Ph) 1258 (p of C6H4CF3) 1256 (o-Ph) 1255 (m of C6H4CF3) 1239
(CF3) 415 (CH2) (JC-F not reported) GC-MS 11767 min mz = 2361 [M] 1671 [M-CF3]
1591 [M-C6H5] 911 [C7H7]
1-Benzyl-2-methylbenzene (Entry 7) 1H NMR (600 MHz CD2Cl2) δ
776 (m 2H o-Ph) 767 - 761 (m 3H m p-Ph) 759 - 754 (m 4H
C6H4CH3) 438 (s 2H CH2) 270 (s 3H CH3) 13C1H NMR (151
MHz CD2Cl2) δ 1410 (ipso-Ph) 1393 (ipso-C6H4CH3) 1370 (C-CH3) 1307 (C1) 1303 (m-
Ph) 1292 (o-Ph) 1287 (C4) 1268 (p-Ph) 1263 (C3) 1262 (C2) 395 (CH2) 197 (CH3)
GC-MS 12844 min mz = 1821 [M] 1671 [M-CH3]
130
1011-Dihydro-5H-dibenzo[ad][7]annulene (Scheme 312 b) 1H NMR
(600 MHz CD2Cl2) δ 745 (m 1H H2) 742 (m 1H H4) 740 (m 2H
H3 H5) 438 (s 1H CH2) 342 (s 2H CH2) 13C1H NMR (125 MHz
CD2Cl2) δ 1423 (C6) 1395 (C1) 1298 (C5) 1291 (C2) 1268 (C4) 1263 (C3) GC-MS
15761 min mz = 1941 [M] 1791 [M-CH3] 1651 [M-C2H5]
343 X-Ray Crystallography
3431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
3432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
131
3433 Selected crystallographic data
Table 36 ndash Selected crystallographic data for 31
31 (+05 C6D5Br)
Formula C43H295B1Br05F20O2
Formula wt 100893
Crystal system monoclinic
Space group P2(1)c
a(Aring) 127865(6)
b(Aring) 199241(9)
c(Aring) 170110(7)
α(ordm) 9000
β(ordm) 1067440(10)
γ(ordm) 9000
V(Aring3) 41500(3)
Z 4
Temp (K) 150(2)
d(calc) gcm-3 1607
Abs coeff μ mm-1 0606
Data collected 37469
Rint 00368
Data used 9534
Variables 596
R (gt2σ) 00458
wR2 01145
GOF 1020
132
Chapter 4 Hydroamination and Hydrophosphination Reactions Using
Frustrated Lewis Pairs
41 Introduction
411 Hydroamination
The direct addition of N-H bonds to unsaturated organic compounds provides an atom-economic
route to valuable nitrogen-containing molecules Pursuit of such reactivity is largely motivated
by the ubiquitous nature of substituted amines in the pharmaceutical industry303-306 The
intermolecular hydroamination of alkynes represents an attractive single-step approach to
convert inexpensive and readily available starting materials to synthetic building blocks such as
imines and enamines
Intermolecular hydroamination of alkynes was initially carried out using Hg and Tl salts307-308
however toxicity concerns prompted subsequent development of a wide variety of other catalysts
based on rare-earth metals309 early- and late-transition metals303 310 as well as lanthanides311-312
and actinides313 Based on the pioneering work of Bergman314-316 and Doye317-318 group IV metal
derivatives have become popular catalysts in these reactions More recently the groups of
Richeson319 Odom320-321 Schafer322 Mountford323 and others311 313 321 324 have made significant
contributions to further the development of these catalysts
Nonetheless to date transition metal-free routes remain relatively less explored The Broslashnsted
acid tungstophosphoric acid has been reported by Lingaiah325 to catalyze the hydroamination of
alkynes However in order for this catalyst to operate harsh conditions and electronically
deactivated amines are required An alternative approach using a strong base such as cesium
hydroxide was reported by Knochel although this strategy only tolerated functional groups less
acidic than the amines309 More recently metal-free approaches have been demonstrated in the
work by Beauchemin on the Cope-type inter- and intramolecular hydroaminations326-329
133
412 Reactions of main group FLPs with alkynes
4121 12-Addition or deprotonation reactions
Recent research has been devoted to effect metal-free stoichiometric and catalytic
transformations using frustrated Lewis pairs (FLPs) These main group combinations of bulky
Lewis acids and bases have become the focus of a number of research groups worldwide330-331
Shortly after the discovery of FLP chemistry several reports communicated the organic
manipulation of alkynes analogous to the pioneering hydroboration reactions by H C Brown60
Initial studies showed that FLPs comprised of B(C6F5)3 or Al(C6F5)3(PhMe) and phosphines react
to yield either zwitterionic vinyl phosphonium borate or aluminate salts resulting from a 12-
addition reaction or phosphonium alkynylborates resulting from alkyne deprotonation126 128 The
course of the reaction was found to depend on the basicity of the phosphine donor with less
basic aryl phosphines favouring 12-addition (Scheme 41)
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al)
Berke and co-workers investigated related intermolecular reactions of terminal alkynes and
B(C6F5)3 with 26-lutidine and TMP demonstrating that these systems effect deprotonation of the
alkyne affording ammonium alkynylborates156 Alternatively the groups of Erker and Stephan
reported the intramolecular cyclization of pendant alkyne substituted anilines151 and N-
heterocycles152 via 12-addition reactions using B(C6F5)3 (Scheme 42 a and b) In a similar
fashion ethylene-linked sulphurborane systems were found to add to alkynes with subsequent
elimination of ethylene affording a single-step route to SB alkenyl-FLPs (Scheme 42 c)332
134
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c)
4122 11-Carboboration reactions
The groups of Berke and Erker separately studied the reactivity of Lewis acids with alkynes in
the absence of a Lewis base (Scheme 43) To this extent they identified the 11-carboboration
reaction to generate alkenylboranes156 159-160 Moreover the reaction of propargyl esters with
B(C6F5)3 have been shown to generate boron allylation reagents333
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes
135
4123 Hydroelementation reactions
Catalytic hydroelementation reactions have been reported for alkynes In the presence of 5 - 10
mol B(C6F5)3 internal alkynes have been shown to undergo both hydrostannylation334 (Scheme
44 a) and hydrogermylation335 reactions (Scheme 44 b)
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes
413 Reactions of transition metal FLPs with alkynes
The FLP paradigm has also been studied using transition metal systems in combination with
alkynes Some examples include metalation through the 11-carbozirconation336 and
boroauration337 reactions Additionally the Wass group developed cationic zirconocene
phosphinoaryloxide complexes that selectively deprotonate terminal alkynes (Scheme 45)338 In
a recent paper the Stephan group has shown that Ru-acetylides act as carbon nucleophiles in
combination with Lewis acids to effect trans-addition to alkynes162
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes
Inspired by the reactivity of FLPs with alkynes in this chapter the intermolecular reaction of
amines B(C6F5)3 and a versatile group of terminal alkynes is explored in hydroamination
reactions A catalytic approach to yield enamines and corresponding amines is described In
addition related systems are probed to accomplish stoichiometric and catalytic intramolecular
hydroaminations affording N-heterocycles Finally stoichiometric approaches to
hydrophosphination reactions are discussed
136
42 Results and Discussion
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
With the objective of initiating hydroamination reactivity the three component stoichiometric
reaction of Ph2NH B(C6F5)3 and phenylacetylene was performed in CD2Cl2 The 1H 11B and 19F
NMR spectra revealed consumption of two equivalents of phenylacetylene to afford the salt
[Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] 41 while leaving a portion of the starting materials Ph2NH
and B(C6F5)3 unreacted (Scheme 46) Adjustment of the alkyne stoichiometry to two equivalents
afforded 41 in 90 yield (Table 41 entry 1) This new species results from the sequential
hydroamination and deprotonation reaction of phenylacetylene
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
The 1H NMR spectrum displayed a diagnostic methyl singlet at 289 ppm with the corresponding 13C1H resonance at 283 ppm In addition a downfield 13C1H resonance at 1901 ppm is
attributable to the iminium N=C group The alkynylborate anion [PhCequivCB(C6F5)3]- gave rise to
the 11B NMR signal at -208 ppm and 19F resonances at -1327 -1638 and -1673 ppm The
nature of compound 41 was unambiguously confirmed by X-ray crystallography (Figure 41)
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
137
To probe the generality of this reaction the corresponding reactivity of various substituted
secondary anilines with two equivalents of phenylacetylene were explored In this fashion the
species [RPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (R = iPr 42 Cy 43 PhCH2 44 p-CH3O 45) were
isolated in 88 91 82 and 90 yield respectively (Table 41 entry 1) 1H NMR spectra
showed the iminium cations were formed as a mixture of the E and Z isomers in a 71 ratio for
compounds 42 and 43 41 ratio for 44 and 11 ratio for 45
Analogous reactions of Ph2NH B(C6F5)3 and two equivalents of 1-hexyne revealed two
competitive reaction pathways In addition to the hydroaminationdeprotonation product
[Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] 46 (Table 41 entry 2) the alkenylboranes resulting from
the 11-carboboration of 1-hexyne were also observed by NMR spectroscopy Exposing the same
anilineB(C6F5)3 combination to 9-ethynylphenanthrene produced [Ph2N=C(CH3)C14H9]
[C14H9CequivCB(C6F5)3] 47 in 75 isolated yield (Table 41 entry 3) The molecular structure of
47 was unambiguously characterized by X-ray crystallography (Figure 42)
Figure 42 ndash POV-Ray depiction of 47
138
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
139
In a similar fashion the reaction of two equivalents of ethynylcyclopropane with B(C6F5)3 and
iPrPhNH at room temperature afforded the yellow crystalline solid formulated as
[iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] 48 in 88 yield (Table 41 entry 4) In this case
the 1H NMR spectrum showed the iminium cation is formed as a mixture of the E and Z isomers
in a 17 ratio Furthermore the reaction of iPrPhNHB(C6F5)3 with 2-ethynylthiophene
proceeded cleanly to give the product [iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] 49
obtained as a 71 mixture of EZ isomers and isolated in 78 yield (Table 41 entry 5) Single
crystals suitable for X-ray diffraction were obtained for Z-48 and Z-49 and the structures are
shown in Figure 43 (a) and (b) respectively
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b)
Interestingly addition 14-diethynylbenzene to the stoichiometric combination of Ph2NH
B(C6F5)3 resulted in an instant color change from pale orange to deep red affording the
zwitterionic product [Ph2N=C(CH3)C6H4CequivCB(C6F5)3] 410 in 85 yield (Table 41 entry 6)
The molecular structure of 410 was confirmed by X-ray crystallography (Figure 44)
Figure 44 ndash POV-Ray depiction of 410
(a) (b)
140
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes
The three component reaction is thought to proceed via Lewis acid polarization of the alkyne by
B(C6F5)3 prompting nucleophilic addition of the aniline and generating a zwitterionic
intermediate (Scheme 47) Analogous 12-additions to alkynes have been previously reported for
phosphineborane126 128 thioetherborane339 and pyrroleborane127 FLPs However in the present
study the arylammonium intermediate provides an acidic proton which cleaved the B-C bond
yielding enamine with concurrent release of B(C6F5)3 Subsequent to this hydroamination the
FLP derived from enamine and B(C6F5)3 deprotonate a second equivalent of the alkyne affording
the isolated iminium alkynylborate salts (Scheme 47)
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts
Analogous stoichiometric combination of tert-butylaniline or diisopropylamine and B(C6F5)3
with either one or two equivalents of phenylacetylene resulted exclusively in deprotonation of
the terminal alkyne affording the ammonium alkynylborate salts [tBuPhNH2][PhCequivCB(C6F5)3]
411 and [iPr2NH2][PhCequivCB(C6F5)3] 412 in 99 and 76 yield respectively (Scheme 48) In
these cases the amines are sufficiently bulky to form a FLP with B(C6F5)3 and relatively basic to
preferentially effect deprotonation of the alkyne This reaction pathway has been previously
observed for basic phosphines and B(C6F5)3 with numerous alkynes
141
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates
In separate reactions FLPs comprised of iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 were
combined with the internal alkynes 3-hexyne diphenylacetylene and 1-phenyl-1-propyne At
RT multinuclear NMR data only revealed signals for the FLP and unaltered alkyne Heating
the reactions up to 80 degC did not display signals for hydroamination rather only products of 11-
carboboration were observed
Also interested in extending the unsaturated substrates scope the hydroamination of the olefins
1-hexene cyclohexene styrene αp-dimethylstyrene and 3-(trifluoromethyl)styrene were tested
using the FLPs iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 Thermolysis of the individual samples
up to 100 degC only revealed signals for the starting materials
4213 Reactivity of the iminium alkynylborate products with nucleophiles
An attractive feature of the iminium cation is the unsaturated N=C fragment since it could be
reacted with nucleophiles to give amines and this transformation could potentially be extended to
generate enantioselective variants of the amines Introducing simple fluoride sources such as
[NBu4][Si(Ph)3F2] NBu4F and CsF to compounds 42 and 46 resulted in deprotonation of the
methyl group losing HF and generating the corresponding enamine Nonetheless addition of the
H+ source [(Et2O)2H][B(C6F5)4]287 regenerated the iminium cation (Scheme 49)
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4]
142
Furthermore addition of the organolithium reagents methyl lithium and ethyl lithium at -30 degC
gave a 11 mixture of the alkylation and deprotonation products as evidenced by 1H NMR
spectroscopy while phenyl lithium did not result in any reactivity (Scheme 410 left)
Combinations of stoichiometric hydride sources [tBu3PH][HB(C6F5)3] NaBHEt3 and LiAlH4
only gave saturation of the N=C bond with the lithium reducing agent (Scheme 410 right)
Overall while hydride delivery to the N=C bond was successfully achieved inefficient delivery
of the presented alkyl and aryl nucleophiles shifted focus towards other types of reactivities
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right)
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3
The equimolar reaction of the tertiary amine dibenzylaniline B(C6F5)3 and phenylacetylene was
investigated with the aim of isolating a zwitterionic intermediate analogous to the compound
proposed en route to hydroamination in Scheme 47 In this case however the nucleophilic
centre for this reaction proved to be the para-carbon of the N-bound phenyl ring undergoing
hydroarylation of phenylacetylene to generate the zwitterionic species
(PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 413 in 96 yield (Scheme 411) Single crystal X-ray
diffraction confirmed the structure of 413 and it is shown in Figure 45 (a)
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3
143
Examining the secondary amine N-isopropylanthracen-9-amine in similar reactivity also gave the
hydroarylation of phenylacetylene and this was demonstrated at the C10 position of the
anthracene ring forming iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 414 in 95 yield In this unique
case however a N=C double bond is generated between nitrogen and the anthracene ring as well
as saturation of the C10 centre giving the tetrahedral geometry observed in the solid state
structure of 414 shown in Figure 45 (b) Generally aromatic substitution reactions in the
presence of Lewis acids have been used for the synthesis of numerous aromatic molecules340
Particularly relevant to this thesis the para-carbon of N-bound phenyl rings has been proposed
as the Lewis basic centre to heterolytically split H2 and generate a sp3-hybridized carbon centre
in the arene hydrogenation reactions presented in Chapter 2
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg
Stability of the B-C bond towards acidic conditions was tested In this regard combinations of
413 with the protic salts [(Et2O)2H][B(C6F5)4] or [Ph2NH2][B(C6F5)4] were found to readily
cleave the B-C bond liberating B(C6F5)3 and generating the diphenylethylene-ammonium
derivative as evidenced by the geminal protons at 508 and 504 ppm in the 1H NMR spectrum
(Scheme 412)
(a) (b)
144
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes
With the exception of catalytic hydrogenations the majority of FLPs reported to date react with
small molecules in a stoichiometric fashion Thus seeking to expand the application of FLPs in
catalysis beyond hydrogenations attention was turned to the development of catalytic
hydroamination reactions This motivation was inspired by the hydroaminationdeprotonation
mechanism proposed in Scheme 47 Realizing that deprotonation of alkyne eliminates the
possibility for catalysis the reaction protocol was adjusted in which the alkyne is added slowly
in order to achieve hydroamination and prevent deprotonation by enamine and B(C6F5)3
The slow addition of the terminal alkyne 2-ethynylanisole to a RT solution of Ph2NH and 10
mol of B(C6F5)3 in toluene over 10 h afforded the catalytic hydroamination product 2-
methoxyphenyl substituted enamine Ph2N(2-MeOC6H4)C=CH2 415 in 84 isolated yield (Table
42) The 1H NMR spectrum of 415 displayed two diagnostic singlets at 501 and 490 ppm
characteristic of the inequivalent geminal hydrogen atoms The corresponding carbon centre
gives rise to a 13C1H NMR signal at 108 ppm Further NMR studies of the compound were
consistent with formation of the Markovnikov isomer in which the nitrogen is added to the
substituted carbon of the terminal alkyne
The analogous treatment of Ph2NH with 2-ethynyltoluene in the presence of 10 mol B(C6F5)3
afforded Ph2N(2-MeC6H4)C=CH2 416 in 69 isolated yield while the alkyne 1-
ethynylnaphthalene yielded Ph2N(C10H7)C=CH2 417 in 62 yield (Table 42) The
corresponding reaction of Ph2NH with phenylacetylene and 2-bromo-phenylacetylene afforded
Ph2N(C6H5)C=CH2 418 and Ph2N(2-BrC6H4)C=CH2 419 in yields of 74 and 52 respectively
(Table 42) Similar to 415 the 1H and 13C1H NMR data for these products were in agreement
with the proposed product formulations
145
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3
This hydroamination strategy also proved effective for substituted diphenylamines For example
(p-FC6H4)2NH in combination with 10 mol B(C6F5)3 reacted with halogenated
phenylacetylenes to afford the species (p-FC6H4)2N(2-BrC6H4)C=CH2 420 and (p-FC6H4)2N(2-
146
FC6H4)C=CH2 421 while the corresponding reactivity with 2-thiophenylacetylene gave (p-
FC6H4)2N(2-SC4H3)C=CH2 422 and iPrPhN(2-SC4H3)C=CH2 423 when reacted with iPrNHPh
(Table 42)
The reaction of Ph2NH with 9-ethynylphenanthrene gave Ph2N(C14H9)C=CH2 424 and (p-
FC6H4)2NH was used to prepare (p-FC6H4)2N(C14H9)C=CH2 425 Similarly reactions of the
appropriate combinations of amine and alkyne using 10 mol B(C6F5)3 afforded (p-FC6H4)2N(3-
FC6H4)C=CH2 426 Ph2N(35-F2C6H3)C=CH2 427 and Ph2N(3-CF3C6H4)C=CH2 428 although
in these cases cooling to -30 degC was necessary to maximize yields obtained between 68 - 77
(Table 42) This impact of temperature was most dramatically demonstrated in the case of 426
where performing the reaction at 25 degC gave the product in 19 yield while at -30 degC the yield
was significantly enhanced to 74
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions
The success of these hydroamination reactions strongly depends on the electronic and steric
nature of the amineborane FLP combination thereby preventing 11-carboboration and
deprotonation of the alkyne Interaction of the borane with the terminal alkyne prompts amine
addition to generate a zwitterionic intermediate In the present case the acidic proton of the
anilinium centre migrates to the carbon adjacent to boron cleaving the B-C bond and forming the
enamine product (Scheme 413) The released B(C6F5)3 is then available to participate in further
hydroamination catalysis It is noteworthy that the postulated zwitterion accounts for the
Markovnikov addition of amines to alkynes and thus the nature of the observed enamine
products341
As stated earlier catalytic formation of enamine requires the slow addition of alkyne over 10 h
This is a result of deprotonation of the alkyne by the FLP derived from enamine and borane
consequently generating iminium alkynylborate salts analogous to 42 - 410 The observed
catalytic hydroaminations imply that amine addition to alkyne is faster than enamine
deprotonation of alkyne
147
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes
The catalytic generation of these enamines together with previously established FLP
hydrogenation of enamines93 prompted interest in a one-pot catalytic
hydroaminationhydrogenation protocol
Following the hydroamination procedure described above reaction mixtures generating the two
enamines 421 and 427 were exposed to H2 (4 atm) and heated at 80 degC for 14 h Pleasingly the
B(C6F5)3 catalyst successfully completed hydrogenation of the C=C double bond giving the
amines (p-FC6H4)2N(2-FC6H4)C(H)CH3 429 and Ph2N(35-F2C6H3)C(H)CH3 430 in 77 and
64 overall isolated yields respectively (Scheme 414) Monitoring the hydrogenation portion
of the reactions by 1H NMR spectroscopy revealed in both cases demise of the signals
attributable to the geminal protons of the enamines with simultaneous appearance of a quartet
attributable to the methine proton and a doublet assignable to the methyl group of the respective
amine In an alternative approach to the hydrogenation catalysis subsequent to hydroamination
5 mol of the known hydrogenation catalyst Mes2PH(C6F4)BH(C6F5)294 was added to the
reaction mixture pressurized with H2 (4 atm) and heated to 80 degC In both cases complete
hydrogenation was achieved after 3 h
148
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430
Experimental evidence demonstrated the catalytic hydroaminations are restricted to aryl
acetylenes Examples of other terminal alkynes that were examined include
trimethylsilylacetylene which resulted in 11-carboboration while the acetylene carboxylates
methyl propiolate ethyl propiolate 2-naphthyl propiolate and tert-butyl propiolate did not react
due to formation of a B-O adduct Extending the chemistry to hydrothiolation using thiophenol
was not successful
424 Intramolecular hydroamination reactions using FLPs
4241 Stoichiometric hydroamination
The potential of the above hydroamination reactions to access N-heterocycles was also probed
To this end the alkynyl-substituted aniline C6H5NH(CH2)3CequivCH was prepared and exposed to
an equivalent of B(C6F5)3 in toluene 11B NMR spectroscopy indicated the formation of a B-N
adduct verified by the resonance at -25 ppm although heating the reaction for 2 h at 50 degC
yielded the cyclized zwitterion C6H5N(CH2)3CCH2B(C6F5)3 431 isolated as a white solid in 94
yield (Scheme 415) The 1H NMR spectrum was consistent with consumption of the NH proton
revealing a diagnostic broad quartet at 333 ppm with geminal B-H coupling of 54 Hz indicative
of the B(C6F5)3 bound methylene group In addition a diagnostic sharp singlet at -134 ppm in
149
the 11B NMR spectrum and the N=C iminium 13C1H resonance at 192 ppm were consistent
with the formulation of 431
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432
The analogous 6-membered ring was prepared from the precursor C6H5NH(CH2)4CequivCH and an
equivalent of B(C6F5)3 giving the zwitterion C6H5N(CH2)4CCH2B(C6F5)3 432 in 99 yield The
formulation of 432 was affirmed by NMR spectroscopy in addition to elemental analysis and X-
ray crystallography (Figure 46)
Figure 46 ndash POV-Ray depiction of 432
Similarly substituted isoindoline species are accessible from the reaction of the precursor
C6H5NHCH2(C6H4)CequivCH with B(C6F5)3 in toluene Stoichiometric combination of the two
reagents resulted in a white precipitate believed to be the intramolecular hydroamination product
after 10 min at RT However this compound was sparingly soluble in toluene bromobenzene
and CD2Cl2 not allowing its comprehensive characterization by NMR spectroscopy As such H2
(4 atm) was added to the reaction and heated at 80 degC for 16 h in an effort to synthesize the H2
activated salt which was presumed to be more soluble than the zwitterion The 1H NMR
150
spectrum of this reaction displayed a quartet at 556 ppm and a triplet at 289 ppm with a four-
bond coupling constant of 26 Hz 13C1H NMR data showed a resonance at 182 ppm
attributable to a N=C bond Collectively these data are consistent with the successive
hydroamination and hydrogenation product [2-MeC8H6N(Ph)][HB(C6F5)3] 433 isolated in 54
yield (Scheme 416)
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433
While species 433 is isolated as an insoluble solid from pentane in CD2Cl2 the [HB(C6F5)3]-
anion appears to reversibly deliver hydride to the N=C carbon centre generating isoindoline and
B(C6F5)3 in about 25 This was evidenced by 1H NMR spectroscopy revealing a diagnostic
quartet at 518 ppm two diastereotopic doublets at 472 and 455 ppm and an upfield doublet at
151 ppm data that is collectively assignable to the isoindoline species This was further
supported by 11B and 19F NMR spectroscopy which provided evidence of free B(C6F5)3 Presence
of this equilibrium is consistent with a previous report on reversible hydride abstraction and
redelivery from carbon centres alpha to nitrogen262
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines
This hydroaminationhydrogenation protocol was further adapted for catalytic cyclization
reactions In this fashion the alkynyl substituted aniline C6H5NH(CH2)3CequivCH was treated with
10 mol B(C6F5)3 at 80 degC under H2 (4 atm) for 16 h This gave the desired product 2-methyl-1-
phenyl pyrrolidine 434 in 68 isolated yield (Table 43 entry 1) In a similar fashion the
catalytic hydroaminationhydrogenation of C6H5NH(CH2)4CequivCH gave 2-methyl-1-
phenylpiperidine 435 in 66 yield (Table 43 entry 2) The following protocol was also
applicable to p-fluoro and p-methoxy substituted substrates giving the respective cyclized
products 436 and 437 in 72 and 52 yield respectively (Table 43 entries 3 and 4) Finally
151
similar reactivity with C6H5NHCH2(C6H4)CequivCH gave 1-methyl-2-phenylisoindoline 438 in 70
yield (Scheme 417)
The yields obtained for compounds 436 and 437 strongly reflect the balance of Broslashnsted acidity
required by the amine proton to effect hydroamination In this case the p-fluoro substituent
proved more effective in hydroamination than p-methoxy
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines
Entry R n Isolated yield
1 H 0 68 434
2 H 1 66 435
3 F 1 72 436
4 CH3O 1 52 437
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH
425 Reaction of B(C6F5)3 with ethynylphosphines
The stoichiometric reaction of B(C6F5)3 with the ethynylphosphine tBu2PCequivCH has previously
been shown to give the deprotonation product tBu2P(H)CequivCB(C6F5)3342 Conversely analogous
treatment of Mes2PCequivCH required addition of tBu3P to effect deprotonation of the ethynyl group
due to diminished Lewis basicity of the phosphine Moreover the Erker group reported the
152
reaction of Ph2PCequivCH with B(C6F5)3 to generate a dimeric product formed by a sequential series
of 12-PB additions to the ethynyl unit343
While interested in hydroamination of ethynylphosphines the FLP iPrNHPhB(C6F5)3 was added
to two equivalents of Mes2PCequivCH giving the pale yellow solid 439 in 88 yield (Scheme 418)
The 1H NMR spectrum did not indicate incorporation of aniline into the product rather two
inequivalent vinylic protons with characteristic P-H and H-H coupling were observed at 771 and
574 ppm (Figure 47)
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons
The 31P NMR spectrum revealed two resonances with chemical shifts at -115 and -143 ppm
while the 11B and 19F NMR spectra were in agreement with formation of an alkynylborate
species (11B δ -211 ppm 19F δ -1329 -1616 and -1663 ppm) These data together with
elemental analysis confirm the formulation of the zwitterionic species trans-
Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 439 An X-ray crystallographic study confirmed the
1H
1H31P
153
molecular structure of 439 and it is shown in Figure 48 (a) In the absence of aniline the
reaction leads to the previously reported 11-carboboration product344-345
On another account the same reaction was obtained with 2 equivalents of tBu2PCequivCH and
B(C6F5)3 to give cis and trans isomers of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 440 The cis
isomer was crystallized and characterized by X-ray diffraction studies (Figure 48 b) In this
case the phosphorus centre was basic enough to effect deprotonation thus the reaction proceeded
in the absence of iPrNHPh Monitoring the reaction by 31P NMR spectroscopy the spectrum
indicated the simultaneous presence of tBu2PCequivCH and the deprotonation zwitterion
tBu2P(H)CequivCB(C6F5)3 giving insight to a plausible mechanism en route to the formation of
compounds 439 and 440
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b)
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines
The reaction is proposed to proceed through the mechanism highlighted in Scheme 419 wherein
the mixture of B(C6F5)3 and R2PCequivCH initially effect deprotonation of the ethynyl group
formulating the zwitterion R2P(H)CequivCB(C6F5)3 Under equilibrium conditions a second
equivalent of the ethynylphosphine is protonated consequently prompting nucleophilic addition
of the [R2PCequivCB(C6F5)3]- anion to the terminal carbon followed by proton transfer to generate
the isolated zwitterionic products In the case of Mes2PCequivCH the deprotonation step required a
stronger base therefore iPrNHPh was added to effect reactivity
(a) (b)
154
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs
An earlier report showed the three component reaction of p-tolyl2PH B(C6F5)3 and
phenylacetylene gave the 12-addition phosphonium borate zwitterion p-
tolyl2PH(Ph)C=C(H)B(C6F5)3128 Realizing the acidic hydrogen on the phosphorus atom a
sample of this compound was treated by UV radiation or heated to prompt hydrophosphination
of phenylacetylene in a mechanism analogous to that presented for the hydroamination reaction
In this regard however the zwitterion proved robust and further reactivity was not observed
Similar results were obtained when using Mes2PH or exchanging the borane for the slightly less
Lewis acidic B(p-C6F4H)3
Turning attention towards the borane HB(C6F5)2 the hydrophosphination reaction was attempted
following an alternative approach In this regard Ph2PH was added to a stoichiometric
combination of HB(C6F5)2 and Bpin-substituted 1-hexyne (Scheme 420 a) After 16 h at RT
the acetylenic unit of Bpin was reduced to a C-C single bond as illustrated by a characteristic
multiplet at 353 ppm and a very broad singlet at 148 ppm in the 1H NMR spectrum The
product Bu(H)Ph2PC-C(H)B(C6F5)2Bpin 441 resulting from the sequential hydroboration and
hydrophosphination reactions was isolated in 82 yield NMR spectroscopy data indeed showed
incorporation of all reactants into the isolated product
155
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH
Investigating similar reactivity of 2-methyl-1-buten-3-yne substituted Bpin with HB(C6F5)2 and
Ph2PH a colourless solid was obtained in 73 yield The 1H NMR data unambiguously showed
saturation of the acetylenic fragment however the spectrum consisted of an olefinic proton at
646 ppm in addition to a methylene group at 307 ppm Further spectroscopic data revealed the
product as Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin 442 resulting from nucleophilic addition of
the phosphine at the terminal double bond (Scheme 420) Single crystals suitable for X-Ray
diffraction were obtained and the structure is shown in Figure 49 (b)
Figure 49 ndash POV-Ray depictions of 442
156
427 Proposed mechanism for the hydroborationhydrophosphination reactions
The mechanism of this reaction is envisaged to initiate following the well-documented
hydroboration of the acetylenic group generating the corresponding alkenyl-bisborane species
(Scheme 421)346 At this point the phosphine coordinates to B(C6F5)2 rendering its proton more
Broslashnsted acidic and prompting protonation of the C=C double bond This is followed by
nucleophilic attack of the phosphine at the C2 position of alkynyl-substituted Bpin (441) or C4
position of the enyne-substituted Bpin (442) The 14-addition reaction to conjugated enynes has
been previously investigated using the ethylene-linked PB FLP to give eight membered cyclic
allenes147
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments
Since evidence for the P-B intermediate is not observed by 11B or 31P NMR spectroscopy an
alternative mechanism could be speculated In this case the nucleophilic phosphine could add to
the vinyl bisborane followed by proton transfer However this later mechanism is not highly
supported as the more Lewis basic secondary phosphines tBu2PH and iPr2PH only gave the P-B
adduct with HB(C6F5)2 consistent with retro-hydroboration after coordination of the phosphine
to the vinyl bisborane This adduct remained intact even at elevated temperatures of 80 degC
Similar N-B adducts were observed when the analogous reactivity was explored with the alkyl
and aryl amines iPr2NH iPrNHPh and Ph2NH
157
43 Conclusions
This chapter provides an account on the discovery of consecutive hydroamination and
deprotonation reactions of various terminal alkynes by anilineB(C6F5)3 FLPs to form a series of
iminium alkynylborate complexes The reaction procedure was modified to eliminate the
deprotonation step in order to achieve B(C6F5)3 catalyzed Markovnikov hydroamination of
alkynes yielding enamine products Subsequent to hydroamination catalysis the borane catalyst
was also used for catalytic hydrogenation of the enamine providing a one-pot avenue to the
corresponding amine derivatives Related systems were probed to accomplish the stoichiometric
and catalytic intramolecular hydroamination of alkynyl-substituted anilines generating cyclic
amines While this hydroamination protocol was not extendable to effect hydrophosphination a
new stoichiometric approach using HB(C6F5)2 and Ph2PH was found to result in the sequential
hydroboration and hydrophosphination reactions of an alkynyl- and enynyl-substituted
pinacolborane generating novel PB FLPs
44 Experimental Section
441 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane dichloromethane and toluene (Sigma Aldrich) were dried employing a Grubbs-
type column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring)
in the glovebox Dichloromethane-d2 bromobenzene-d5 and bromobenzene-H5 were purchased
from Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring
molecular sieves prior to use Hexane and ethyl acetate were purchased from Caledon
Laboratories Silica gel was purchased from Silicycle Molecular sieves (4 Aring) were purchased
from Sigma Aldrich and dried at 120 ordmC under vacuum for 24 h prior to use B(C6F5)3 was
purchased from Boulder Scientific and sublimed at 80 degC under high vacuum before use H2
(grade 50) was purchased from Linde and dried through a Nanochem Weldassure purifier
column prior to use
Substituted amines alkynes and phosphines were purchased from Sigma Aldrich Alfa Aesar
Apollo Scientific Strem Chemicals Inc and TCI The oils were distilled over CaH2 and solids
were sublimed under high vacuum prior to use The following reagents were prepared following
158
literature procedures 1-ethynylnaphthalene347 (p-C6H4F)2NH (p-CH3OC6H4)PhNH tBuNHPh
and N-isopropylanthracen-9-amine266 N-(2-ethynylbenzyl)aniline N-(pent-4-ynyl)aniline N-
(hex-5-ynyl)aniline 4-fluoro-N-(hex-5-yn-1-yl)aniline and 4-methoxy-N-(hex-5-yn-1-
yl)aniline348 N-(2-ethynylbenzyl)aniline349 tBu2PCequivCH and Mes2PCequivCH342
CH3(CH2)3CequivCBpin and CH2=C(CH3)CequivCBpin350
Compounds 439 - 442 were prepared by the author during a four month research opportunity in
the group of Professor Gerhard Erker at Universitaumlt Muumlnster Germany Molecular structures and
elemental analyses for 439 and 440 were obtained at the University of Toronto Molecular
structure for 442 was obtained at Universitaumlt Muumlnster and elemental analyses for 441 and 442
were obtained at the University of Toronto
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm for
ipso carbon) and CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) or externally (11B (Et2O)BF3 19F
CFCl3) Chemical Shifts (δ) are reported in ppm and the absolute values of the coupling
constants (J) are in Hz NMR assignments are supported by additional 2D and DEPT-135
experiments
High resolution mass spectra (HRMS) were obtained using an ABSciex QStar Mass
Spectrometer with an ESI source MSMS and accurate mass capabilities Elemental analyses (C
H N) were performed in-house employing a Perkin Elmer 2400 Series II CHNS Analyzer
442 Synthesis of Compounds
4421 Procedures for stoichiometric intermolecular hydroamination reactions
Compounds 41 - 45 were prepared in a similar fashion thus only one preparation is detailed In
the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial phenylacetylene (151
mg 148 mmol) was added drop wise over 1 min In the case where pentane was used as the
solvent the reaction was worked up as follows the solvent was decanted and the product was
washed with pentane (3 times 5 mL) to yield the product as a solid In the case where toluene or
159
dichloromethane was used as the as solvent the reaction was worked up as follows the solvent
was removed under reduced pressure and the crude product was washed with pentane to yield the
product as a solid
Synthesis of [Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] (41) Diphenylamine (0125 g 0740
mmol) pentane (20 mL) reaction time 2 h yellow solid (588 mg 0666 mmol 90) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC
1H NMR (400 MHz CD2Cl2) δ 768 (m 3H H4 H5) 761 (m 1H p-Ph)
745 (m 5H o m p-Ph) 739 (m 4H H3 m-Ph) 728 (dm 3JH-H = 75
Hz 2H H7) 717 (tm 3JH-H = 75 Hz 2H H8) 711 (tm 3JH-H = 75 Hz
1H H9) 710 (dm 3JH-H = 77 Hz 2H o-Ph) 289 (s 3H Me) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F
p-C6F5) -1673 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s
equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1901 (C1) 1352 (p-Ph) 1320 (C5) 1315 (C4)
1312 (p-Ph) 1310 (C7) 1307 (m-Ph) 1298 (Ph) 1293 (Ph) 1277 (C8) 1257 (C9) 1254 (o-
Ph) 1241 (C3) 283 (Me) (C2 C6 ipso-Ph and all carbons for CequivCB(C6F5)3 were not
observed) Elemental analysis was not successful after numerous attempts
Synthesis of E-[iPrPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (42) N-Isopropylaniline (100 mg
0740 mmol) pentane (10 mL) reaction time 1 h pale yellow solid (566 mg 0651 mmol 88)
EZ ratio 71
42 1H NMR (400 MHz CD2Cl2) δ 773 (tm 3JH-H = 77 Hz 1H H5)
772 (m 6H H4 H9 H10) 746 (dm 3JH-H = 77 Hz 2H H3) 728 (dm 3JH-H = 76 Hz 2H H12) 720 (m 2H H8) 716 (t 3JH-H = 76 Hz 2H
H13) 713 (t 3JH-H = 76 Hz 1H H14) 491 (m 3JH-H = 66 Hz 1H H6)
244 (s 3H Me) 126 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1637 (t 3JF-F = 20 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1913
(C1) 1482 (dm 1JC-F = 236 Hz CF) 1381 (dm 1JC-F = 243 Hz CF) 1365 (dm 1JC-F = 245 Hz
CF) 1346 (C2) 1339 (C5) 1319 (C10) 1318 (C7) 1311 (C12) 1310 (C4) 1303 (C9) 1278
(C13) 1274 (C11) 1258 (C14) 1253 (C3 C8) 937 (C15) 619 (C6) 288 (Me) 208 (iPr)
160
(CequivCB(C6F5)3 and ipso-C6F5 were not observed) Anal calcd () for C43H25BF15N C 6066 H
296 N 165 Found 6037 H 317 N 173
Synthesis of E-[CyPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (43) N-Cyclohexylaniline (135 mg
0740 mmol) pentane (10 mL) reaction time 1 h off-white solid (599 mg 0674 mmol 91)
EZ ratio 71
43 1H NMR (400 MHz CD2Cl2) δ 769 (tt 3JH-H = 74 Hz 4JH-H = 24
Hz 1H H5) 762 (m 5H H4 H12 H13) 737 (dm 3JH-H = 74 Hz 2H H3)
720 (dm 3JH-H = 77 Hz 2H H15) 711 (m 4H H11 H16) 703 (tm 3JH-H
= 77 Hz 1H H17) 439 (tt 3JH-H = 119 Hz 3JH-H = 35 Hz 1H H6) 235
(s 3H Me) 184 (dm JH-H = 117 Hz 1H H7) 170 (dm 2JH-H = 145 Hz
2H H8) 145 (dm 2JH-H = 132 Hz 2H H9) 133 (m 1H H7) 104 (pseudo qt JH-H = 138 Hz 3JH-H = 37 Hz 2H H8) 080 (pseudo qt 2JH-H = 132 Hz 3JH-H = 37 Hz 2H H9) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F p-C6F5) -1673 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (101 MHz
CD2Cl2) δ 1916 (C1) 1341 (C5) 1323 (C13) 1315 (C15) 1313 (C4) 1307 (C12) 1282 (C16)
1262 (C17) 1257 (C3) 1254 (C11) 699 (C6) 320 (C7) 291 (Me) 249 (C8) 244 (C9) (C2
C10 C14 and all carbons for CequivCB(C6F5)3 were not observed) Anal calcd () for C46H29BF15N
C 6197 H 328 N 157 Found 6158 H 354 N 153
Synthesis of E-[(PhCH2)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (44) N-Benzylaniline (135 mg
0740 mmol) dichloromethane (10 mL) reaction time 2 h pale yellow solid (544 mg 0607
mmol 82) EZ ratio 41
44 1H NMR (600 MHz CD2Cl2) δ 782 (t 3JH-H = 73 Hz 1H H5) 777
(t 3JH-H = 73 Hz 2H H4) 764 (d 3JH-H = 73 Hz 2H H3) 760 (t 3JH-H =
76 Hz 1H H14) 753 (t 3JH-H = 76 Hz 2H H13) 738 (m 1H H10) 728
(m 4H H9 H16) 716 (t 3JH-H = 73 Hz 2H H17) 710 (t 3JH-H = 73 Hz
1H H18) 699 (d 3JH-H = 76 Hz 2H H12) 679 (d 3JH-H = 76 Hz 2H
H8) 526 (s 2H H6) 259 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
207 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1912 (C1) 1386 (C7) 1342 (C5) 1339
(C2) 1317 (C11 C14) 1311 (C9) 1309 (C13 C15) 1304 (C4 C10) 1296 (C8) 1294 (C16) 1278
B(C6F5)3
N1
2
3
45
7
8
9
10
14
1516
17
18
6
11
12
13
B(C6F5)3
N1
2
3
45
7
8 9
10
11 12
13
14
1617
1815
6
19
161
(C17) 1263 (C3) 1258 (C18) 1241 (C8) 938 (C19) 645 (C6) 286 (Me) (CequivCB(C6F5)3 and all
carbons of B(C6F5)3 were not observed) Anal calcd () for C47H25BF15N C 6276 H 280 N
156 Found 6259 H 296 N 171
Synthesis of [(p-C6H4OMe)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (45) (p-CH3OC6H4)PhNH
(147 mg 0740 mmol) pentane (15 mL) room temperature reaction time 3 h yellow solid (493
mg 0540 mmol 73) Anal calcd () for C47H25BF15NO C 6166 H 275 N 153 Found C
6106 H 262 N 142 EZ ratio 11
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 748 (m 1H H5) 735
(m 2H H3) 730 (m 2H H4) 726 (m 2H H8) 717 (m 2H H15) 707
(tm 3JH-H = 72 Hz 2H H16) 702 (m 1H H17) 696 (m 1H H9) 688
(dm 3JH-H = 87 Hz 2H H11) 670 (dm 3JH-H = 87 Hz 2H H12) 365 (s
3H OMe) 273 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1327 (m
2F o-C6F5) -1637 (t 3JF-F = 21 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (125 MHz CD2Cl2) δ 1884
(C1) 1613 (C13) 1481 (dm 1JC-F = 241 Hz CF) 1421 (C6) 1381 (dm 1JC-F = 244 Hz CF)
1364 1 (dm 1JC-F = 246 Hz CF) 1356 (C10) 1348 (C5) 1325 (C2) 1313 (C7) 1310 (C15)
1305(C8) 1297 (C4) 1292 (C3) 1278 (C16) 1274 (C14) 1269 (C11) 1257 (C17) 1255 (C9)
1155 (C12) 937 (C18) 557 (OMe) 283 (Me)
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 750 (m 1H H5) 735
(m 2H H4) 730 (m 2H H3) 726 (m 2H H8) 717 (m 2H H12) 702 (m
2H H11) 696 (m 1H H9) 378 (s 3H OMe) 279 (s 3H Me) 13C1H
NMR (125 MHz CD2Cl2) δ 1892 (C1) 1620 (C13) 1432 (C6) 1348 (C5)
1345 (C10) 1325 (C2) 1319 (C7) 1310 (C3) 1297 (C4) 1257 (C11) 1255
(C9) 1242 (C8) 1162 (C12) 557 (OMe) 283 (Me) 19F and 11B NMR are the same as above
Compounds 46 - 410 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and either diphenylamine (125 mg 0740 mmol) or N-isopropylaniline
(100 mg 0740 mmol) To the vial the respective alkyne was added over 1 min In the case
where pentane was used as the solvent the reaction was worked up as follows the solvent was
decanted and the product was washed with pentane (3 times 5 mL) to yield the product as a solid In
162
the case where toluene or dichloromethane was used as the as solvent the reaction was worked
up as follows the solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as a solid
Synthesis of [Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] (46) 1-Hexyne (122 mg 148 mmol)
pentane (20 mL) -30 degC to room temperature reaction time 2 h yellow solid (350 mg 414
mmol 56) The reaction also yielded alkenylboranes resulting from 11-carboboration which
were separated from the reaction mixture through the pentane washes during work-up
1H NMR (400 MHz CD2Cl2) δ 768 (m 6H Ph) 738 (m 4H Ph) 282
(m 2H H2) 262 (s 3H Me) 211 (t 3JH-H = 67 Hz 2H H7) 180 (quint
of t 3JH-H = 77 Hz 4JH-H = 28 Hz 2H H3) 141 (m 6H H4 H8 H9) 092
(t 3JH-H = 73 Hz 3H H5) 087 (t 3JH-H = 72 Hz 3H H10) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1643 (t 3JF-F = 21 Hz 1F
p-C6F5) -1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211
(s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1992 (C1) 1482 (dm 1JC-F = 237 Hz CF)
1411 (ipso-Ph) 1407 (ipso-Ph) 1382 (dm 1JC-F = 242 Hz CF) 1363 (dm 1JC-F = 246 Hz
CF) 1319 (Ph) 1315 (Ph) 1314 (Ph) 1236 (Ph) 1234 (Ph) 932 (C6) 389 (C2) 320 (C8)
295 (C3) 248 (Me) 227 (C4) 219 (C9) 199 (C7) 135 (C10) 130 (C5) (CequivCB(C6F5)3 and
ipso-C6F5 were not observed) Anal calcd () for C42H31BF15N C 5966 H 370 N 166
Found 5885 H 366 N 154
Synthesis of [Ph2N=C(CH3)C14H9][C14H9CequivCB(C6F5)3] (47) 9-Ethynylphenanthrene (299
mg 148 mmol) pentane (15 mL) room temperature reaction time 3 h pale yellow solid (602
mg 0555 mmol 75) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 859 (dm 3JH-H = 82 Hz 1H ArH) 853 (dm 3JH-H = 82 Hz
1H ArH) 849 (m 2H ArH) 845 (dm 3JH-H = 82 Hz 1H ArH) 776 (dm 3JH-H = 76 Hz 1H ArH) 773 (tm 3JH-H = 76 Hz 1H ArH) 767 (s 1H borateArH) 765 (tm 3JH-H = 82 Hz 1H ArH) 763 (s 1H amineArH) 760 (m 3JH-H = 82 Hz 1H ArH) 757 (m 3H m p-Ph) 755 (m
2H o-Ph) 753 (dm 3JH-H = 76 Hz 1H ArH) 748 (m 2H ArH) 744 (tm 3JH-H = 76 Hz 1H ArH) 737 (tm 3JH-H = 76 Hz 1H ArH) 732 (m 2H ArH) 703 (tt 3JH-H = 70 Hz 4JH-H = 10
Hz 1H ArH) 696 (tm 3JH-H = 70 Hz 2H m-Ph) 691 (dm 3JH-H = 70 Hz 2H o-Ph) 284
163
(Me) 19F NMR (377 MHz CD2Cl2) δ -1324 (m 2F o-C6F5) -1636 (t 3JF-F = 21 Hz 1F p-
C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -206 (s equivCB) 13C1H NMR
(125 MHz CD2Cl2) δ 1943 (C=N) 1500 (dm 1JC-F = 242 CF) 1444 (ipso-Ph) 1430 (ipso-
Ph) 1400 (dm 1JC-F = 245 CF) 1386 (dm 1JC-F = 250 CF) 1342 (ArC) 1342 (m-Ph) 1337
(p-Ph) 1336 (ArC) 1334 (o-Ph) 1330 (p-Ph) 1326 (ArC) 1325 (ArC) 1321 (ArC) 1320 (m-
Ph) 1319 (ArC) 1317 (ArC) 1315 (ArC) 1313 (ArC) 1310 (ArC) 1307 (ArC) 1306 (ArC)
1303 (ArC) 1301 (ArC) 1298 (ArC) 1297 (ArC) 1286 (ArC) 1284 (ArC) 1284 (ArC) 1280
(ArC) 1272 (ArC) 1261 (o-Ph) 1250 (o-Ph) 1259 (ArC) 1259 (ArC) 1248 (ArC) 1242 (ArC)
1241 (ArC) 937 (CequivCB) 3096 (Me) Anal calcd () for C62H31BF15N C 6859 H 288 N
129 Found C 6812 H 306 N 134
Synthesis of [iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] (48) Cyclopropylacetylene (125 μL
148 mmol) dichloromethane (10 mL) and pentane (5 mL) room temperature reaction time 2 h
pale yellow solid (507 mg 651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 17
48 1H NMR (400 MHz CD2Cl2) δ 765 (m 3H m p-Ph) 717 (m 2H
o-Ph) 483 (m 3JH-H = 66 Hz 1H iPr) 222 (s 3H CH3) 158 (m 1H
H1) 146 (m 4H H2) 131 (d 3JH-H = 66 Hz 6H iPr) 112 (tt 3JH-H = 81
Hz 3JH-H = 51 Hz 1H H4) 057 - 050 (m 4H H5) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1642 (t 3JF-F = 20 Hz 1F p-C6F5) -
1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211(s equivCB)
13C1H NMR (101 MHz CD2Cl2) δ 1937 (N=C) 1486 (dm 1JC-F = 236 Hz CF) 1383 (dm 1JC-F = 243 Hz CF) 1368 (dm 1JC-F = 245 Hz CF) 1356 (ipso-Ph) 1320 (p-Ph) 1313 (m-
Ph) 1266 (o-Ph) 1258 (ipso-C6F5) 958 (C3) 599 (iPr) 218 (C1) 208 (iPr) 161 (CH3) 153
(C2) 84 (C5) 149 (C4) (CequivCB(C6F5)3 was not observed) Anal calcd () for C37H25BF15N C
5702 H 323 N 180 Found 5667 H 330 N 179
Synthesis of E-[iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] (49) 2-Ethynylthiophene (160
mg 148 mmol) dichloromethane (4 mL) and pentane (10 mL) room temperature reaction time
1 h pale pink solid (498 mg 0577 mmol 78) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 71
164
49 1H NMR (400 MHz C6D5Br) δ 738 (d 3JH-H = 45 Hz 1H H3)
733 (t 3JH-H = 72 Hz 1H H10) 731 (d 3JH-H = 45 Hz 1H H5) 726 (t 3JH-H = 72 Hz 2H H9) 693 (d 3JH-H = 38 Hz 1H H12) 674 (d 3JH-H =
53 Hz 1H H14) 667 (t 3JH-H = 45 Hz 1H H4) 664 (dd 3JH-H = 53
Hz 3JH-H = 38 Hz 1H H13) 660 (d 3JH-H = 72 Hz 2H H8) 436 (m 3JH-H = 66 Hz 1H H6) 256 (s 3H Me) 081 (d 3JH-H = 66 Hz 6H
iPr) 19F NMR (377 MHz C6D5Br) δ -1312 (m 2F o-C6F5) -1619 (t 3JF-F = 21 Hz 1F p-
C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -203 (s equivCB) 13C1H NMR
(101 MHz C6D5Br) δ 1724 (C1) 1486 (dm 1JC-F = 240 Hz CF) 1446 (C5) 1438 (C3) 1384
(dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 267 Hz CF) 1346 (C7) 1330 (C2) 1324 (C10)
1312 (C9) 1290 (C12) 1286 (C4) 1272 (C8) 1269 (C13) 1239 (C14) 593 (C6) 214 (Me)
201 (iPr) (C11 C15 ipso-C6F5 and CequivCB(C6F5)3 were not observed) Anal calcd () for
C39H21BF15NS2 C 5425 H 245 N 162 Found 5415 H 259 N 168
Synthesis of (C6F5)3BCequivC(C6H4)C(Me)=NPh2 (410) 14-Diethynylbenzene (934 mg 0740
mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 2 h orange solid
(508 mg 0629 mmol 85) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 760 (m 3H m p-Ph) 735 (m 4H o m-Ph) 729 (m 5H
C6H4 p-Ph) 706 (dm 3JH-H = 77 Hz 2H o-Ph) 277 (s 3H Me) 19F NMR (377 MHz
CD2Cl2) δ -1329 (m 2F o-C6F5) -1630 (t 3JF-F = 20 Hz 1F p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1877
(C=N) 1482 (dm 1JC-F = 236 Hz CF) 1433 (ipso-Ph) 1425 (ipso-Ph) 1383 (dm 1JC-F = 243
Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1364 (quaternary C for C6H4) 1322 (C6H4) 1317 (p-
Ph) 1314 (m-Ph) 1311 (p-Ph) 1308 (m-Ph) 1302 (C6H4) 1282 (quaternary C for C6H4)
1255 (o-Ph) 1244 (o-Ph) 1228 (ipso-C6F5) 937 (CequivCB(C6F5)3) 276 (Me) (CequivCB(C6F5)3
was not observed) Elemental analysis for this compound did not pass after repeated attempts
Synthesis of [tBu(Ph)NH2][PhCequivCB(C6F5)3] (411) tert-Butylaniline (111 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) pentane (10 mL) reaction time 16 h off-white solid
(560 mg 0733 mmol 99)
165
1H NMR (400 MHz CD2Cl2) δ 751 (tm 3JH-H = 77 Hz 1H H4) 741
(tm 3JH-H = 77 Hz 2H H3) 728 (m 2H H7) 727 (m 2H H6) 725 (m
1H H8) 684 (dm 3JH-H = 77 Hz 2H H2) 677 (br s 2H NH2) 113 (s
9H tBu) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5) -1622
(t 3JF-F = 21 Hz 1F p-C6F5) -1661 (m 2F m-C6F5) 11B NMR (128
MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1479 (dm 1JC-F =
236 Hz CF) 1384 (dm 1JC-F = 241 Hz CF) 1366 (dm 1JC-F = 243 Hz CF) 1319 (C7) 1314
(C4) 1310 (C1) 1307 (C3) 1296 (C6) 1283 (C8) 1258 (C5) 1237 (C2) 941 (C9) 654 (tBu)
262 (tBu) Anal calcd () for C36H21BF15N C 5664 H 277 N 183 Found 5608 H 297 N
174
Synthesis of [iPr2NH2][PhCequivCB(C6F5)3] (412) Diisopropylamine (750 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) toluene (10 mL) reaction time 4 h white solid (405
mg 566 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered solution
of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 727 (tm 3JH-H = 76 Hz 2H m-Ph) 721 (dm 3JH-H = 76 Hz
2H o-Ph) 718 (tm 3JH-H = 76 Hz 1H p-Ph) 505 (m 2H NH2) 332 (m 3JH-H = 64 Hz 2H
iPr) 114 (d 3JH-H = 64 Hz 12H iPr) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5)
-1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
208 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1317 (m-Ph) 1292 (o-Ph) 1276
(p-Ph) 511 (iPr) 197 (iPr) Anal calcd () for C32H21BF15N C 5373 H 296 N 196 Found
5318 H 304 N 194
4422 Procedures for hydroarylation of phenylacetylene
Compounds 413 and 414 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of
B(C6F5)3 (0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial
phenylacetylene (756 mg 0740 mol) was added over 1 min The solvent was then removed
under reduced pressure and the crude product was washed with pentane to yield the product as a
solid
166
Synthesis of (PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 (413) NN-Dibenzylaniline (202 mg
0740 mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 1 h yellow
solid (630 mg 0710 mmol 96) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 753 (t 3JH-H = 76 Hz 2H m-Ph) 746 (t 3JH-H = 73 Hz 4H benzylm-Ph) 741 (s 1H =CH) 734 (d 3JH-H = 76 Hz 2H o-Ph) 715 (d 3JH-H = 74 Hz 4H benzylo-Ph) 700 (m 3H p-Ph benzylp-Ph) 691 (d 3JH-H = 86 Hz 2H C6H4) 680 (d 3JH-H = 86
Hz 2H C6H4) 617 (br s 1H NH) 484 (dm JH-H = 126 Hz 2H CH2Ph) 472 (dm JH-H = 126
Hz 2H CH2Ph) 19F NMR (377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1644 (t 3JF-F = 19
Hz 1F p-C6F5) -1680 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -158 (s equivCB)
13C1H NMR (101 MHz CD2Cl2) partial δ 1521 (=CH) 1387 (ipso-Ph) 1317 (m-Ph) 1316
(benzylipso-Ph) 1302 (benzylo-Ph) 1300 (benzylm-Ph) 1292 (o-Ph) 1291 (C6H4) 1271 (benzylp-
Ph) 1206 (C6H4) 1256 (p-Ph) 647 (CH2Ph) Elemental analysis was not successful after
numerous attempts
Synthesis of iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 (414) N-isopropylanthracen-9-amine (170
mg 0740 mmol) dichloromethane (10 mL) room temperature reaction time 5 h bright yellow
solid (597 mg 0704 mmol 95) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 795 (s 1H C=NH) 785 (m 2H m-Ph) 778 (m 2H o-Ph)
773 (d 3JH-H = 83 Hz 1H C14H9) 762 (d 3JH-H = 83 Hz 1H C14H9) 759 (t 3JH-H = 83 Hz
1H C14H9) 758 (m 1H p-Ph) 689 (t 3JH-H = 83 Hz 1H C14H9) 680 (s 1H =CH) 671 (t 3JH-H = 83 Hz 2H C14H9) 603 (d 3JH-H = 83 Hz 2H C14H9) 544 (s 1H CHC(Ph)=CH) 454
(m 1H iPr) 178 (d 3JH-H = 66 Hz 3H iPr) 126 (d 3JH-H = 66 Hz 3H iPr) 19F NMR (377
MHz CD2Cl2) δ -1322 (m 2F o-C6F5) -1645 (t 3JF-F = 20 Hz 1F p-C6F5) -1681 (m 2F m-
C6F5) 11B NMR (128 MHz CD2Cl2) δ -163 (s equivCB) 13C1H NMR (125 MHz CD2Cl2)
partial δ 1707 (C=CH) 1503 (=CH) 1353 (m-Ph) 1308 (o-Ph) 1290 (C14H9) 1284 (p-Ph)
1276 (C14H9) 1274 (C14H9) 1265 (C14H9) 1255 (C14H9) 1224 (C14H9) 599 (CHC(Ph)=CH)
530 (iPr) 233 (iPr) 228 (iPr) Anal calcd () for C43H23BF15N C 6080 H 273 N 165
Found 6059 H 281 N 197
167
4423 Procedures for catalytic intermolecular hydroamination reactions
Compounds 415 - 425 were prepared in a similar fashion thus only one preparation is detailed
In the glovebox a 4 dram vial equipped with a stir bar was charged with diphenylamine (125
mg 740 μmol) (p-C6H4F)2NH (152 mg 740 μmol) or N-isopropylaniline (100 mg 740 μmol)
and B(C6F5)3 (38 mg 74 μmol) in toluene (4 mL) The respective alkyne (740 μmol) was added
at a rate of 10 molh via microsyringe (oils) or by weighing into a vial (solids) Total reaction
time was 10 h after which the reaction was worked up outside of the glovebox The solvent was
removed under vacuum and the crude mixture was dissolved in ethyl acetate (5 mL) and passed
through a short (4 cm) silica column previously treated with Et2NH The crude reaction mixtures
consisted of the starting materials (amine and alkyne) and the product The product was purified
by column chromatography using hexaneethyl acetate (61) as eluent
Compounds 426 - 428 were prepared with slight modifications to the procedure above The
reaction vial was cooled to -30 degC then placed in a pre-cooled -30 degC brass-well before addition
of the alkyne via microsyringe or by weighing into a vial The reaction vial was kept in the brass-
well and warmed up to RT before cooling down the reaction vial again and adding the
subsequent aliquot of alkyne Each addition of alkyne was made in a pre-cooled brass-well The
reactions were worked up similar to the procedure above
(415) Yellow solid (187 mg 620 μmol 84) 1H NMR (400 MHz
CD2Cl2) δ 744 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H5) 721 -713
(m 5H m-C6H5 H3) 712 - 706 (m 4H o-C6H5) 691 (tt 3JH-H = 72 Hz 4JH-H = 11 Hz 2H p-C6H5) 685 (td 3JH-H = 75 Hz 4JH-H = 18 Hz 1H
H4) 679 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H2) 501 (s 1H =CH2) 490 (s 1H =CH2)
376 (s 3H OCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1577 (C6) 1498 (C=CH2) 1481
(ipso-C6H5) 1312 (C5) 1296 (C3) 1290 (m-C6H5) 1283 (C1) 1248 (o-C6H5) 1227 (p-C6H5)
1205 (C4) 1112 (C2) 1077 (=CH2) 558 (OCH3) HRMS-ESI+ mz [M+H]+ calcd for
C21H20NO 30215449 Found 30215453
168
(416) Off-while solid (146 mg 510 μmol 69) 1H NMR (600 MHz
CD2Cl2) δ 750 -743 (m 1H H5) 724 - 716 (tm 3JH-H = 74 Hz 4H m-
C6H5) 715 - 708 (m 6H o-C6H5 H3 H4) 706 -701 (m 1H H2) 700-
692 (tm 3JH-H = 74 Hz 2H p-C6H5) 484 (s 1H =CH2) 470 (s 1H
=CH2) 252 (s 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1526 (C=CH2) 1476 (ipso-
C6H5) 1390 (C1) 1364 (C6) 1309 (C5 C2) 1291 (m-C6H5) 1281 (C4) 1259 (C3) 1255 (o-
C6H5) 1233 (p-C6H5) 1051 (=CH2) 206 (CH3) HRMS-ESI+ mz [M+H]+ calcd for C21H20N
28615957 Found 28615986
(417) Orange solid (147 mg 460 μmol 62) 1H NMR (400 MHz
CD2Cl2) δ 870 (d 3JH-H = 85 Hz 1H H10) 777 (d 3JH-H = 85 Hz 1H
H7) 771 - 768 (m 2H H2 H4) 752 (tm 3JH-H = 85 Hz 1H H9) 743
(tm 3JH-H = 85 Hz 1H H8) 736 (tm 3JH-H = 85 Hz 1H H3) 722 -
709 (m 8H o m-C6H5) 692 (m 2H p-C6H5) 507 (s 1H =CH2)
494 (s 1H =CH2) 13C1H NMR (101 MHz CD2Cl2) δ 1513 (C=CH2) 1478 (ipso-C6H5)
1371 (C1) 1341 (C6) 1319 (C5) 1292 (m-C6H5) 1288 (C7 C2) 1281 (C4) 1266 (C9) 1260
(C8) 1256 (C10) 1254 (C3) 1253 (o-C6H5) 1229 (p-C6H5) 1067 (=CH2) HRMS-ESI+ mz
[M+H]+ calcd for C24H20N 32215957 Found 32216049
(418) Yellow oil (148 mg 550 μmol 74) 1H NMR (500 MHz
CD2Cl2) δ 757 (dm 3JH-H = 73 Hz 2H H2) 728 - 726 (m 3H H3 H4)
720 (tm 3JH-H = 74 Hz 4H m-C6H5) 709 (dm 3JH-H = 74 Hz 4H o-
C6H5) 695 (tm 3JH-H = 74 Hz 2H p-C6H5) 523 (s 1H =CH2) 486 (s
1H =CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1533 (C=CH2) 1482 (ipso-C6H5) 1394 (C1)
1293 (m-C6H5) 1286 (C3) 1285 (C4) 1276 (C2) 1243 (o-C6H5) 1228 (p-C6H5) 1082
(=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H18N 2721433 Found 2721443
(419) Orange solid (134 mg 390 μmol 52)1H NMR (500 MHz
CD2Cl2) δ 753 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H
H2) 744 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H H5)
723 (td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H3) 720 - 715 (m 8H om-
C6H5) 706 (pseudo td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H4) 697 (tt 3JH-H = 70 Hz 4JH-H =
16 Hz 2H p-C6H5) 493 (d 2JH-H = 04 Hz 1H =CH2) 483 (d 2JH-H = 04 Hz 1H =CH2)
169
13C1H NMR (125 MHz CD2Cl2) δ 1513 (C=CH2) 1473 (ipso-C6H5) 1399 (C1) 1337 (C5)
1327 (C2) 1296 (C4) 1291 (m-C6H5) 1275 (C3) 1256 (o-C6H5) 1235 (p-C6H5) 1224 (C6)
1059 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H17BrN 35005444 Found 35005379
(420) Orange solid (191 mg 500 μmol 67) 1H NMR (500 MHz
CD2Cl2) δ 750 (ddm 3JH-H = 78 Hz 4JH-H = 18 Hz 1H H2) 743
(ddm 3JH-H = 78 Hz 4JH-H = 12 Hz 1H H5) 724 (tdm 3JH-H = 78
Hz 4JH-H = 12 Hz 1H H4) 712 (dm 3JH-H = 80 Hz 4H H8) 707
(dm 3JH-H = 78 Hz 1H H3) 690 (tm 3JH-H = 80 Hz 4H H9) 479 (s
1H =CH2) 471 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1202 (tt 3JF-H = 88 Hz 4JF-H
= 52 Hz p-C6H4F) 13C1H NMR (125 MHz CD2Cl2) δ 1593 (d 1JC-F = 242 Hz C10) 1518
(C=CH2) 1433 (d 4JCF = 29 Hz C7) 1395 (C1) 1337 (C5) 1328 (C2) 1298 (C3) 1276 (C4)
1272 (d 3JC-F = 79 Hz C8) 1223 (C6) 1159 (d 2JC-F = 22 Hz C9) 1041 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C20H15BrF2N 38603559 Found 38603477
(421) Yellow oil (188 mg 580 μmol 78) 1H NMR (400 MHz
CD2Cl2) δ 748 (pseudo td 3JH-H = 77 Hz J = 19 Hz 1H H2) 721
(m 1H H4) 707 - 702 (m 5H H3 H8) 697 (m 1H H5) 691 (m
4H H9) 500 (d 5JF-H = 15 Hz 1H =CH2) 488 (s 1H =CH2) 19F
NMR (377 MHz CD2Cl2) δ -1162 (dm 3JF-H = 119 Hz 1F CF of
C6) -1207 (tm 3JF-H = 97 Hz 2F p-C6H4F) 13C1H NMR (101 MHz CD2Cl2) δ 1605 (d 1JC-F = 249 Hz CF of C6) 1591 (d 1JC-F = 244 Hz C10) 1475 (C=CH2) 1438 (d 4JC-F = 28
Hz C7) 1311 (d 3JC-F = 30 Hz C2) 1302 (d 3JC-F = 85 Hz C4) 1271 (d 2JC-F = 116 Hz C1)
1264 (d 3JC-F = 81 Hz C8) 1244 (d 4JC-F = 37 Hz C3) 1162 (d 2JC-F = 22 Hz C5) 1160 (d 2JC-F = 22 Hz C9) 1077 (d 4JC-F = 36 Hz =CH2) HRMS-ESI+ mz [M+H]+ calcd for
C20H15F3N 32611566 Found 32611576
(422) Yellow oil (125 mg 400 μmol 54) 1H NMR (400 MHz
CD2Cl2) δ 718 (dd 3JH-H = 51 4JH-H = 12 Hz 1H H4) 712 (dd 3JH-H
= 36 Hz 4JH-H = 12 Hz 1H H2) 705 - 701 (m 4H H6) 695 - 689
(m 5H H3 H7) 526 (s 1H =CH2) 469 (s 1H =CH2) 19F NMR (377
MHz CD2Cl2) δ -1209 (m 3JF-H = 90 Hz p-C6H4F) 13C1H NMR
(101 MHz CD2Cl2) δ 1589 (d 1JC-F = 241 Hz C8) 1473 (C=CH2) 1442 (d 4JC-F = 26 Hz
170
C5) 1436 (C1) 1276 (C3) 1265 (C2) 1258 (C4) 1257 (d 3JC-F = 80 Hz C6) 1162 (d 2JC-F =
22 Hz C7) 1068 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 31408150 Found
31408200
(423) Yellow oil (104 mg 430 μmol 58) 1H NMR (400 MHz
CD2Cl2) δ 715 (tm 3JH-H = 79 Hz 2H m-C6H5) 712 (dd 3JH-H = 53 Hz 4JH-H = 13 Hz 1H H4) 701 (dd 3JH-H = 35 Hz 4JH-H = 13 Hz 1H H2)
693 (dm 3JH-H = 79 Hz 2H o-C6H5) 685 (m 1H H3) 681 (tm 3JH-H =
79 Hz 1H p-C6H5) 531 (s 1H =CH2) 484 (s 1H =CH2) 426 (m 3JH-H = 66 Hz 1H iPr)
125 (d 3JH-H = 66 Hz 6H iPr) 13C1H NMR (101 MHz CD2Cl2) δ 1466 (ipso-C6H5) 1456
(C1) 1446 (C=CH2) 1296 (m-C6H5) 1274 (C2) 1260 (C3) 1253 (C4) 1208 (o-C6H5) 1206
(p-C6H5) 502 (iPr) 211 (iPr) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 2441154
Found 2441166
(424) Pale yellow solid (206 mg 560 μmol 75) 1H NMR (600
MHz CD2Cl2) δ 881 (dm 3JH-H = 78 Hz 1H H14) 865 (dm 3JH-H =
78 Hz 1H H11) 860 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H10)
797 (s 1H H2) 787 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H7)
766-761 (m 3H H9 H12 H13) 757 (pseudo td 3JH-H = 78 Hz 4JH-H
= 14 Hz 1H H8) 723 (m 4H o-C6H5) 715 (t 3JH-H = 73 Hz 4H m-C6H5) 692 (tt 3JH-H =
73 Hz 4JH-H = 12 Hz 2H p-C6H5) 512 (s 1H =CH2) 503 (s 1H =CH2) 13C1H NMR (125
MHz CD2Cl2) δ 1516 (C=CH2) 1476 (ipso-C6H5) 1357 (C1) 1317 (C3) 1309 (C6) 1307
(C5) 1306 (C4) 1294 (C2) 1292 (m-C6H5) 1291 (C7) 1273 (C9) 1271 (C8 C13) 1268 (C12)
1264 (C14) 1255 (o-C6H5) 1235 (p-C6H5) 1232 (C11) 1228 (C10) 1060 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C28H22N 37217522 Found 37217485
(425) Pale yellow solid (228 mg 560 μmol 75) 1H NMR (400
MHz CD2Cl2) δ 874 (dm 3JH-H = 74 Hz 1H H14) 866 (dm 3JH-H
= 74 Hz 1H H11) 861 (dm 3JH-H = 74 Hz 1H H10) 795 (s 1H
H2) 788 (dm 3JH-H = 74 Hz 1H H7) 767- 762 (m 3H H9 H12
H13) 759 (pseudo td 3JH-H = 74 Hz 4JH-H = 12 Hz 1H H8) 718
(m 4H H16) 686 (m 4H H17) 499 (s 1H =CH2) 495 (s 1H =CH2) 19F NMR (377 MHz
CD2Cl2) δ -1200 (tt 3JF-H = 84 Hz 4JF-H = 42 Hz p-C6H4F) 13C1H NMR (125 MHz
171
CD2Cl2) δ 1592 (d 1JC-F = 240 Hz C18) 1519 (C=CH2) 1437 (d 4JC-F = 26 Hz C15) 1353
(C1) 1316 (C3) 1308 (C6) 1307 (C5) 1306 (C4) 1296 (C2) 1291 (C7) 1274 (C9) 1272 (C8
C12) 1271 (d 3JC-F = 83 Hz C16) 1269 (C13) 1262 (C14) 1233 (C11) 1228 (C10) 1161 (d 2JCF = 219 Hz C17) 1043 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C28H20F2N 40815638
Found 40815576
(426) Yellow oil (178 mg 550 μmol 74) 1H NMR (400 MHz
CD2Cl2) δ 735 (dm 3JH-H = 77 Hz 1H H2) 727- 723 (m 2H H3
H6) 701 (m 4H H8) 697- 691 (m 5H H4 H9) 516 (s 1H =CH2)
478 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1141 (m 1F
CF of C5) -1205 (m 2F p-C6H4F) 13C1H NMR (101 MHz
CD2Cl2) δ 1632 (d 1JC-F = 245 Hz C5) 1592 (d 1JC-F = 244 Hz C10) 1522 (d 4JC-F = 25 Hz
C=CH2) 1442 (d 4JC-F = 28 Hz C7) 1417 (d 3JC-F = 76 Hz C1) 1303 (d 3JC-F = 84 Hz C3)
1261 (d 3JC-F = 81 Hz C8) 1235 (d 4JC-F = 28 Hz C2) 1162 (d 2JC-F = 22 Hz C9) 1154 (d 2JC-F = 21 Hz C4) 1145 (d 2JC-F = 21 Hz C6) 1074 (=CH2) HRMS-ESI+ mz [M+H]+ calcd
for C20H15F3N 32611566 Found 32611485
(427) White solid (154 mg 500 μmol 68) 1H NMR (500 MHz
CD2Cl2) δ 722 (tm 3JH-H = 73 Hz 4H m-C6H5) 710 (m 2H H2) 705
(dm 3JH-H = 73 Hz 4H o-C6H5) 699 (tm 3JH-H = 73 Hz 2H p-C6H5)
670 (tt 3JH-H = 89 Hz 4JH-H = 24 Hz 1H H4) 525 (s 1H =CH2) 490
(s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1107 (t 3JF-H = 81 Hz m-C6H3F2) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (d 1JC-F = 248 Hz C3) 1515 (t 4JC-F = 28 Hz C=CH2)
1477 (ipso-C6H5) 1435 (d 3JC-F = 92 Hz C1) 1295 (m-C6H5) 1244 (o-C6H5) 1234 (p-
C6H5) 1105 (d 2JC-F = 21 Hz C2) 1093 (s =CH2) 1037 (t 2JC-F = 25 Hz C4) HRMS-ESI+
mz [M+H]+ calcd for C20H16F2N 30812508 Found 30812511
(428) Yellow oil (193 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 783 (ddq 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H6)
774 (ddq 3JH-H = 78 Hz 4JH-H = 12 Hz 6JF-H = 06 Hz 1H H2) 749
(dddq 3JH-H = 78 Hz 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H4)
739 (pseudo tq 3JH-H = 78 Hz 5JF-H = 07 Hz 1H H3) 721 (tm 3JH-H = 78 Hz 4H m-C6H5)
707 (dm 3JH-H = 78 Hz 4H o-C6H5) 697 (tm 3JH-H = 78 Hz 2H p-C6H5) 526 (d 1H 2JH-H
172
= 07 Hz =CH2) 493 (d 2JH-H = 07 Hz =CH2) 19F NMR (377 MHz CD2Cl2) δ -630 (s CF3)
13C1H NMR (125 MHz CD2Cl2) δ 1517 (C=CH2) 1474 (ipso-C6H5) 1400 (C1) 1304 (q 5JC-F = 13 Hz C2) 1304 (q 2JC-F = 32 Hz C5) 1290 (m-C6H5) 1287 (C3) 1247 (q 3JC-F = 38
Hz C4) 1242 (o-C6H5) 1241 (q 1JC-F = 271 Hz CF3) 1239 (q 3JC-F = 38 Hz C6) 1228 (p-
C6H5) 1083 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C21H17F3N 34013131 Found
34013065
4424 Procedures for tandem hydroamination and hydrogenation reactions
A general procedure is provided for the preparation of compounds 429 and 430 Following the
10 h catalytic hydroamination reaction in the glovebox the reaction mixture was transferred into
an oven-dried Teflon screw cap glass tube The reaction tube was degassed once through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The tube
was placed in an 80 ordmC oil bath for 14 h The solvent was removed under vacuum and the
mixture was dissolved in ethyl acetate (5 mL) and passed through a short (4 cm) silica column
previously treated with Et2NH The crude reaction mixtures consisted of the starting materials
(amine and alkyne) and the product The product was purified by column chromatography using
hexaneethyl acetate (61) as eluent
Alternative hydrogenation procedure using 5 mol Mes2PH(C6F4)BH(C6F5)2
Mes2PH(C6F4)BH(C6F5)2 (28 mg 37 μmol) was added to the reaction mixture before being
transferred into the glass tube The tube was filled with H2 and placed in an 80 ordmC oil bath The
reaction was stopped after 3 h at 80 ordmC and worked up similar to the procedure above
(429) Yellow oil (186 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 728 - 720 (m 2H H2 H5) 708 - 700 (m 2H H3 H4)
692 (m 4H H9) 680 (m 4H H8) 545 (q 3JH-H = 70 Hz C(CH3)H)
138 (d 3JH-H = 70 Hz C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -
1186 (m 1F F of C6) -1224 (m 2F F of C10) 13C1H NMR (125
MHz CD2Cl2) δ 1610 (d 1JC-F = 247 Hz C6) 1588 (d 1JC-F = 241 Hz C10) 1436 (d 4JC-F =
26 Hz C7) 1310 (d 2JC-F = 131 Hz C1) 1291 (d 2JC-F = 85 Hz C5) 1284 (d 3JC-F = 43 Hz
C2) 1249 (d 3JC-F = 79 Hz C8) 1244 (d 4JC-F = 35 Hz C3) 1159 (d 2JC-F = 22 Hz C9) 1157
173
(d 3JC-F = 22 Hz C4) 517 (C(CH3)H) 197 (C(CH3)H) HRMS-ESI+ mz [M+H]+ calcd for
C20H17F3N 32813131 Found 32813189
(430) Yellow oil (146 mg 470 μmol 64) 1H NMR (500 MHz
CD2Cl2) δ 724 (tm 3JH-H = 78 Hz 4H m-C6H5) 699 (m 4H H2 p-
C6H5) 688 (dm 3JH-H = 78 Hz 4H o-C6H5) 671 (tt 3JF-H = 89 Hz 4JH-H = 24 Hz 1H H4) 524 (d 3JH-H =70 Hz 1H C(CH3)H) 145 (d
3JH-H = 70 Hz 3H C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -1105 (m F of C3) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (dd 1JC-F = 248 Hz 3JC-F = 13 Hz C3) 1496 (t 3JC-F = 79
Hz C1) 1472 (ipso-C6H5) 1297 (m-C6H5) 1235 (o-C6H5) 1212 (p-C6H5) 1100 (dd 2JC-F =
20 Hz 4JC-F = 47 Hz C2) 1202 (t 2JC-F = 27 Hz C4) 579 (C(CH3)H) 203 (C(CH3)H)
HRMS-ESI+ mz [M+H]+ calcd for C20H18F2N 31014073 Found 31014081
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions
Compounds 431 and 432 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 25 mL Schlenk flask equipped with a stir bar was charged with a
toluene (5 mL) solution of B(C6F5)3 (0100 g 0190 mmol) and the respective alkynyl aniline
(0190 mmol) The solution was heated for 2 h at 50 degC and the solvent was subsequently
removed under reduced pressure The crude oil was washed with pentane (2 times 5 mL) to yield the
product as a white solid
Synthesis of C6H5N(CH2)3CCH2B(C6F5)3 (431) N-(Pent-4-ynyl)aniline (300 mg 0190
mmol) product (120 mg 0179 mmol 94)
1H NMR (400 MHz CD2Cl2) δ 746 (m 3H m p-Ph) 691 (dm 3JH-H =
86 Hz 2H o-Ph) 416 (t 3JH-H = 78 Hz 2H H3) 333 (br q 2JB-H = 54
Hz 2H CH2B) 311 (t 3JH-H = 78 Hz 2H H1) 215 (quint 3JH-H = 78 Hz
2H H2) 19F NMR (377 MHz CD2Cl2) δ -1325 (m 2F o-C6F5) -1601 (t 3JF-F = 21 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -134 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 1942 (C=N) 1476 (dm 1JC-F = 241 Hz CF)
1392 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1348 (ipso-Ph) 1324 (p-Ph)
174
1311 (m-Ph) 1231 (o-Ph) 1189 (ipso-C6F5) 651 (C3) 411 (C1) 185 (CH2B C2) Anal
calcd () for C29H13BF15N C 5189 H 195 N 209 Found 5140 H 219 N 191
Synthesis of C6H5N(CH2)4CCH2B(C6F5)3 (432) N-(Hex-5-ynyl)aniline (340 mg 0190
mmol) product (129 mg 0188 mmol 99) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC
1H NMR (600 MHz CD2Cl2) δ 745 (tt 3JH-H = 75 Hz 4JH-H = 22 Hz
1H p-Ph) 740 (tm 3JH-H = 75 Hz 2H m-Ph) 663 (dm 3JH-H = 75 Hz
2H o-Ph) 372 (t 3JH-H = 73 Hz 2H H4) 316 (br q 2JB-H = 63 Hz 2H
CH2B) 275 (t 3JH-H = 73 Hz 2H H1) 197 (m 2H H3) 176 (m 2H
H2) 19F NMR (377 MHz CD2Cl2) δ -1320 (m 2F o-C6F5) -1611 (t 3JF-
F = 20 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -130 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 2005 (C=N) 1481 (dm 1JC-F = 241 Hz CF)
1420 (ipso-Ph) 1384 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1301 (m p-
Ph) 1226 (ipso-C6F5) 1237 (o-Ph) 574 (C4) 380 (CH2B) 326 (C1) 213 (C3) 175 (C2)
Anal calcd () for C30H15BF15N C 5228 H 221 N 204 Found 5206 H 272 N 177
Synthesis of [2-MeC8H6N(Ph)][HB(C6F5)3] (433) In the glovebox a 25 mL Schlenk flask
equipped with a stir bar was charged with a toluene (5 mL) solution of B(C6F5)3 (0100 g 0190
mmol) and N-(2-ethynylbenzyl)aniline (390 mg 0190 mmol) The solution was heated for 16 h
under H2 (4 atm) at 80 degC The solvent was subsequently removed under reduced pressure The
crude oil was washed with pentane (2 times 5 mL) to yield the product as a white solid (740 mg
0103 mmol 54)
1H NMR (600 MHz CD2Cl2) δ 812 (dm 3JH-H = 79 Hz JH-H = 10
Hz 1H H9) 799 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H H8) 786 (dm 3JH-H = 79 Hz 1H H6) 782 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H
H7) 773 - 769 (m 3H H2 and H3) 745 (dm 3JH-H = 76 Hz H1) 556
(q JH-H = 26 Hz 2H H4) 353 (br 1H HB) 289 (t JH-H = 26 Hz Me) 19F NMR (564 MHz
CD2Cl2) δ -1341 (br 2F o-C6F5) -1644 (br 1F p-C6F5) -1674 (br 2F m-C6F5) 11B1H
NMR (192 MHz CD2Cl2) δ -252 (s HB) 13C1H NMR (151 MHz CD2Cl2) 1820 (N=C)
1480 (dm 1JC-F = 247 Hz CF) 1437 (C10) 1373 (C7) 1366 (dm 1JC-F = 241 Hz CF) 1362
(dm 1JC-F = 241 Hz CF) 1347 (ipso-Ph) 1337 (C5) 1322 (C3) 1308 (C2) 1306 (C8) 1266
NB(C6F5)3
4
3
2
1
175
(C9) 1247 (C1) 1234 (C6) 657 (C4) 149 (Me) (ipso-C6F5 was not observed) Anal calcd ()
for C33H15BF15N C 5495 H 210 N 194 Found C 5502 H 212 N 218
Compounds 434 - 438 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 25 mL Schlenk bomb equipped with a stir bar was charged with a toluene (2
mL) solution of B(C6F5)3 (20 mg 40 μmol) and the alkynyl aniline (039 mmol) The solution
was heated for 16 h under H2 (4 atm) at 80 degC The solvent was subsequently removed under
reduced pressure The crude oil was washed with pentane (2 times 5 mL) and purified by column
chromatography using hexaneethyl acetate (61) as eluent
Synthesis of 2-MeC4H7N(Ph) (434) N-(Pent-4-ynyl)aniline (600 mg 0390 mmol) product
(427 mg 0265 mmol 68)
1H NMR (500 MHz CD2Cl2) δ 718 (t 3JH-H = 78 Hz 2H m-Ph) 660 (tt 3JH-H =
78 Hz 4JH-H = 11 H 1H p-Ph) 657 (d 3JH-H = 78 Hz 2H o-Ph) 286 (m 3JH-H =
61 Hz 1H NCHCH3) 282 (ddd 2JH-H = 88 Hz 3JH-H = 78 Hz 35 Hz 1H H3)
254 (pseudo q 3JH-H = 83 Hz 1H H3) 211 - 162 (m 4H H1 and H2) 099 (d 3JH-H
= 61 Hz 3H Me) 13C1H NMR (151 MHz CD2Cl2) δ 1474 (ipso-Ph) 1289 (m-Ph) 1148
(p-Ph) 1116 (o-Ph) 540 (NCHCH3) 478 (C3) 330 (C1) 265 (C2) 197 (Me) HRMS-
DART+ mz [M+H]+ calcd for C11H15N 16212827 Found 16212755
Synthesis of 2-MeC5H9N(Ph) (435) N-(Hex-5-ynyl)aniline (682 mg 0390 mmol) product
(451 mg 0257 mmol 66)
1H NMR (500 MHz CD2Cl2) δ 723 (t 3JH-H = 81 Hz 2H m-Ph) 693 (d 3JH-H =
81 Hz 2H o-Ph) 680 (tt 3JH-H = 81 Hz 4JH-H = 11 H 1H p-Ph) 394 (m 1H
NCHCH3) 323 (dt 2JH-H = 121 Hz 3JH-H = 44 Hz 1H H4) 297 (dm 2JH-H = 121
Hz 1H H4) 190 - 160 (m 6H H1 H2 H3) 100 (d 3JH-H = 672 3H Me) 13C1H
NMR (151 MHz CD2Cl2) δ 1516 (ipso-Ph) 1288 (m-Ph) 1187 (p-Ph) 1173 (o-
Ph) 512 (NCHCH3) 446 (C4) 317 (C1) 261 (C3) 198 (C2) 134 (Me) HRMS- DART+ mz
[M+H]+ calcd for C12H17NO 17614392 Found 17614338
176
Synthesis of 2-MeC5H9N(p-FC6H4) (436) 4-Fluoro-N-(hex-5-yn-1-yl)aniline (745 mg 0390
mmol) product (542 mg 0281 mmol 72)
1H NMR (400 MHz C6D5Br) δ 652 (t JH-H = 88 Hz 2H m-H of C6H4F) 637 (dd 3JH-H = 88 Hz 4JH-F = 48 Hz 2H o-H of C6H4F) 306 (m 1H NCHCH3) 241 (m
1H H4) 135 (m 1H H1) 121 (m 1H H3) 113 (m 2H H23) 102 (m 1H H2)
101 (m 1H H2) 045 (d 3JH-H = 65 Hz 3H CH3) 19F NMR (377 MHz C6D5Br)
δ -1235 (s 1F C6H4F) 13C1H NMR (100 MHz C6D5Br) δ 1582 (q 1JC-F = 297
Hz p-C6H4F) 1479 (ipso-C6H4F) 1202 (d 3JC-F = 77 Hz o-C of C6H4F) 1150 (d 3JC-F = 227 Hz m-C of C6H4F) 518 (NCHCH3) 470 (C4) 321 (C1) 260 (C3) 203 (C2) 146
(CH3) HRMS- ESI + mz [M+H]+ calcd for C12H16NF 1941340 Found 1941337
Synthesis of 2-MeC5H9N(p-CH3OC6H4) (437) N-(Hex-5-yn-1-yl)-4-methoxyaniline (792 mg
0390 mmol) product (416 mg 0203 mmol 52)
1H NMR (500 MHz C6D5Br) δ 712 (d 3JH-H = 85 Hz 2H m-H of C6H4OCH3)
700 (d 3JH-H = 85 Hz 2H o-H of C6H4OCH3) 374 (s 3H OCH3) 349 (m 1H
NCHCH3) 309 (m 1H H4) 302 (m 1H H4) 194 (m 1H H1) 184 (m 1H H3)
178 (m 1H H2) 176 (m 1H H3) 161 (m 1H H1) 158 (m 1H H2) 106 (d 3JH-
H = 65 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1542 (p-C6H4OCH3)
1457 (ipso-C6H4OCH3) 1221 (m-C of C6H4OCH3) 1139 (o-C of C6H4OCH3) 546
(OCH3) 534 (NCHCH3) 496 (C4) 331 (C1) 264 (C3) 214 (C2) 160 (CH3) HRMS-ESI+
mz [M+H]+ calcd for C13H19NO 2061539 Found 2061539
Synthesis of 2-MeC8H7N(Ph) (438) N-(2-Ethynylbenzyl)aniline (808 mg 0390 mmol)
product (571 mg 0273 mmol 70)
1H NMR (400 MHz CD2Cl2) δ 778 (d 3JH-H = 77 Hz 1H C6H4) 745 - 737 (m
5H m-Ph C6H4) 707 (t 3JH-H = 77 Hz 1H p-Ph) 703 (d 3JH-H = 77 Hz 2H o-
Ph) 510 (q 3JH-H = 66 Hz 1H NCH(CH3)) 483 (d 2JH-H = 138 Hz 1H CH2)
463 (d 2JH-H = 138 Hz 1H CH2) 154 (d 3JH-H = 66 Hz 3H CH3) 13C1H NMR
(151 MHz CD2Cl2) δ 1435 (ipso-Ph) 1376 (C1) 1343 (C6) 1297 (m-Ph) 1283
177
(C34) 1245 (C2) 1226 (p-Ph) 1222 (C5) 1161 (o-Ph) 641 (NCH(CH3) 563 (CH2) 182
(CH3) HRMS-DART+ mz [M+H]+ calcd for C15H15N 21012827 Found 21012767
4426 Procedures for reactions with ethynylphosphines
Synthesis of trans-Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 (439) In the glove box a 4 dram
vial equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg
0740 mmol) and iPrNHPh (100 mg 0740 mmol) To the vial Mes2PCequivCH (440 mg 0148
mmol) was added and the reaction was left at RT for 16 h The solvent was removed under
reduced pressure and the crude product was washed with pentane to yield the product as a pale
yellow solid (717 mg 0651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 771 (td JP-H = 286 Hz 3JH-H = 172 Hz 1H =CH) 698 (d 4JPH = 49 Hz 4H Mes) 689 (d 4JPH = 32 Hz 4H Mes) 574 (ddd 2JP-H = 273 Hz 3JH-H =
172 3JP-H = 44 Hz 1H =CH) 235 (s 6H Mes) 229 (s 6H Mes) 223 (s 12H Mes) 218 (s
12H Mes) 19F NMR (377 MHz CD2Cl2) δ -1329(m 2F o-C6F5) -1616 (t 3JF-F = 21 Hz 1F
p-C6F5) -1663 (m 2F m-C6F5) 31P1H NMR (162 MHz CD2Cl2) δ -115 (br s PMes2) -143
(d JP-P = 82 Hz PMes2) 11B NMR (128 MHz CD2Cl2) δ -211 (CB) 13C1H NMR (101
MHz CD2Cl2) partial δ 1540 (d 1JC-P = 31 Hz Mes) 1470 (d 1JC-F = 248 Hz CF) 1437 (d
JC-P = 28 Hz Mes) 1417 (d JC-P = 150 Hz Mes) 1413 (d JC-P = 113 Hz Mes) 1393 (Mes)
1321 (d 3JC-P = 14 Hz Mes) 1303 (d 3JC-P = 56 Hz Mes) 1260 (d JC-P = 11 Hz Mes) 1178
(dd 2JC-P = 99 Hz 3JC-P = 27 Hz =CH) 1120 (dd 2JC-P = 85 Hz 3JC-P = 121 Hz =CH) 219 (d 3JC-P = 68 Hz Mes) 218 (d 3JC-P = 14 Hz Mes) 201 (d 5JC-P = 18 Hz Mes) 198 (Mes)
Anal calcd () for C58H46BF15P2 C 6329 H 421 Found C 6282 H 411
Synthesis of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 (440) In the glove box a 4 dram vial
equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg 0144
mmol) To the vial tBu2PCequivCH (250 mg 0148 mmol) was added and the reaction was left at
RT for 16 h The solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as an off-white solid (580 mg 0570 mmol 77)
Crystals suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC
178
1H NMR (600 MHz CD2Cl2) δ 777 (ddd 2JP-H = 46 Hz 3JH-H =15 Hz 3JP-H = 36 Hz 1H
=CH) 650 (ddd 2JP-H = 28 Hz 3JP-H = 19 Hz 3JH-H =15 Hz 1H =CH) 144 (d 3JP-H = 17 Hz
18H tBu) 101 (d 3JP-H = 11 Hz 18H tBu) 19F NMR (564 MHz CD2Cl2) δ -1322 (m 2F o-
C6F5) -1618 (t 3JF-F = 20 Hz 1F p-C6F5) -1665 (m 2F m-C6F5) 31P1H NMR (242 MHz
CD2Cl2) δ 215 (PtBu2) 251 (PtBu2) 11B NMR (192 MHz CD2Cl2) -212 (CB) 13C1H
NMR (151 MHz CD2Cl2) partial δ 1620 (dd 1JC-P = 42 Hz 2JC-P = 32 Hz =CH) 1210 (dd 1JC-P = 82 Hz 2JC-P = 21 Hz =CH) 371 (d 1JC-P = 48 Hz tBu) 325 (d 1JC-P = 22 Hz tBu) 292
(d 2JC-P = 14 Hz tBu) 266 (tBu) Anal calcd () for C38H38BF15P2 C 5354 H 449 Found C
5314 H 432
Compounds 441 and 442 were prepared following the same procedure In the glove box a
Schlenk tube equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of HB(C6F5)2
(100 mg 0289 mmol) and the appropriate alkynyl-substituted pinacolborane (0289 mmol) was
added at once After 5 minutes Ph2PH (538 mg 0289 mmol) was added to the vial The
reaction was left at RT for 16 h The solvent was then removed under reduced pressure and
pentane (5 mL) was added to the crude oil resulting in precipitate The pentane soluble fraction
was separated from the precipitate concentrated and placed in a -30 degC freezer to give the
product as colourless crystals
Synthesis of Bu(H)Ph2PC-C(H)B(C6F5)2Bpin (441) CH3(CH2)3CequivCBpin (606 mg 0289
mmol) product (175 mg 0237 mmol 82)
1H NMR (600 MHz CD2Cl2) δ 766 (m 2H o-Ph) 757 (tm 3JH-H = 77 Hz 1H p-Ph) 747
(tm 3JH-H = 72 Hz 1H p-Ph) 742 (m 2H m-Ph) 736 (m 2H m-Ph) 733 (m 2H o-Ph) 353
(m 1H CHP) 290 (d 2JH-H = 116 Hz 1H CH2CHP) 278 (d 2JH-H = 116 Hz 1H CH2CHP)
148 (m 1H CHB) 133 (m 2H CH2) 118 (m 2H CH2) 102 (s 6H CH3) 098 (s 6H CH3)
078 (t 3JH-H = 72 Hz 3H CH3) 19F NMR (564 MHz CD2Cl2) δ -1292 (m 2F o-C6F5) -
1328 (m 2F o-C6F5) -1665 (m 2F m-C6F5) -1585 (t 3JF-F = 20 Hz 1F p-C6F5) -1605 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) -1653 (m 2F m-C6F5) 31P1H NMR (242
MHz CD2Cl2) δ 322 (br) 11B NMR (192 MHz CD2Cl2) δ 337 (Bpin) -66 (B(C6F5)2)
13C1H NMR (151 MHz CD2Cl2) partial δ 1362 (d 2JC-P = 91 Hz o-Ph) 1318 (d 4JC-P = 29
Hz p-Ph) 1314 (d 2JC-P = 81 Hz o-Ph) 1313 (d 4JC-P = 28 Hz p-Ph) 1285 (d 3JC-P = 95
Hz m-Ph) 1279 (d 3JC-P = 10 Hz m-Ph) 1279 (d 1JC-P = 332 Hz ipso-Ph) 1238 (d 1JC-P =
179
34 Hz ipso-Ph) 824 (C(CH3)2) 346 (d 1JC-P = 37 Hz CHP) 301 (d 2JC-P = 80 Hz CH2CHP)
290 (d 3JC-P = 49 Hz CH2) 246 (BpinCH3) 242 (BpinCH3) 224 (CH2) 158 (CHB) 079
(CH3) Anal calcd () for C36H33B2F10O2P C 5841 H 449 Found 5808 H 437
Synthesis of Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin (442) CH2=C(CH3)CequivCBpin (567
mg 0289 mmol) product (153 mg 0211 mmol 73) Crystals suitable for X-ray diffraction
were grown from pentane at -30 ordmC
1H31P NMR (600 MHz CD2Cl2) δ 764 (tt 3JH-H = 73 Hz 4JH-H = 14 Hz 1H p-Ph) 755 (d 3JH-H = 73 Hz 2H o-Ph) 749 (t 3JH-H = 75 Hz 2H m-Ph) 727 (tt 3JH-H = 75 Hz 4JH-H = 12
Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 680 (d 3JH-H = 75 Hz 2H o-Ph) 645 (br 1H
=CH) 320 (d 2JH-H = 14 Hz 1H PCH2) 307 (d 2JH-H = 14 Hz 1H PCH2) 190 (s 3H CH3)
149 (br m 1H CHB) 106 (s 6H CH3) 104 (s 6H CH3) 19F NMR (564 MHz CD2Cl2)
partial δ -1254 (br 2F o-C6F5) -1665 (m 2F m-C6F5) (p-C6F5 was not observed) 31P1H
NMR (242 MHz CD2Cl2) δ 63 (br) 11B NMR (192 MHz CD2Cl2) δ 342 (Bpin) -104
(B(C6F5)2) 13C1H NMR (151 MHz CD2Cl2) partial δ 1481 (H3CC=CH) 1359 (=CH) 1329
(m o-Ph) 1323 (d 4JC-P = 39 Hz p-Ph) 1317 (d 2JC-P = 71 Hz o-Ph) 1311 (d 4JC-P = 30
Hz p-Ph) 1300 (d 3JC-P = 94 Hz m-Ph) 1291 (d 1JC-P = 54 Hz ipso-Ph) 1282 (d 3JC-P = 94
Hz m-Ph) 1251 (d 1JC-P = 54 Hz ipso-Ph) 821 (C(CH3)2) 268 (d 1JC-P = 33 Hz CH2P) 256
(d 3JC-P = 53 Hz H3CC=CH) 245 (BpinCH3) 244 (BpinCH3) 178 (br CHB) Anal calcd ()
for C35H29B2F10O2P C 5805 H 404 Found 5776 H 397
443 X-Ray Crystallography
4431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
Universitaumlt Muumlnster data sets were collected with a Nonius KappaCCD diffractometer
Programs used data collection COLLECT351 data reduction Denzo-SMN352 absorption
180
correction Denzo353 structure solution SHELXS-97354 structure refinement SHELXL-97355
Thermals ellipsoids are shown with 30 probability R-values are given for observed reflections
and wR2 values are given for all reflections
4432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
4433 Platon Squeeze details
During the refinement of structure 413 electron density peaks were located that were believed
to be highly disordered dichloromethane and 12-dichloroethane molecules Attempts made to
model the solvent molecule were not successful The SQUEEZE option in PLATON356 indicated
there was a large solvent cavity 160 A3 in the asymmetric unit In the final cycles of refinement
this contribution (39 electrons) to the electron density was removed from the observed data The
density the F(000) value the molecular weight and the formula are given taking into account the
results obtained with the SQUEEZE option PLATON
181
4434 Selected crystallographic data
Table 44 ndash Selected crystallographic data for 41 47 and 48
41 47 48
Formula C46H23B1F15N1 C62H31B1F15N1 C37H25B1F15N1
Formula wt 88546 108572 77939
Crystal system monoclinic triclinic triclinic
Space group P2(1)n P-1 P-1
a(Aring) 91451(8) 120520(8) 99293(9)
b(Aring) 20583(2) 122120(8) 115709(11)
c(Aring) 20738(2) 184965(12) 168258(15)
α(ordm) 9000 103236(4) 75826(4)
β(ordm) 96295(4) 104461(4) 77700(4)
γ(ordm) 9000 104447(4) 65591(4)
V(Aring3) 38800(6) 24264(3) 16930(3)
Z 4 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1516 1482 1529
Abs coeff μ mm-1 0138 0126 0146
Data collected 35905 34295 21194
Rint 00444 00308 00308
Data used 8910 11131 5899
Variables 569 712 490
R (gt2σ) 00420 00532 00488
wR2 00964 01380 01380
GOF 1018 1028 1026
182
Table 45 ndash Selected crystallographic data for 49 410 and 413
49 410
(+05 C5H12)
413
(+1 C2H4Cl2)
Formula C39H21B1F15N1S2 C425H23B1F15N1 C48H29B1Cl2F15N1
Formula wt 86350 85145 98643
Crystal system monoclinic triclinic monoclinic
Space group P2(1)c P-1 P2(1)c
a(Aring) 174202(13) 113739(5) 138815(4)
b(Aring) 135941(10) 115489(6) 242842(7)
c(Aring) 174144(13) 158094(7) 146750(4)
α(ordm) 9000 92979(2) 9000
β(ordm) 118149(3) 97298(2) 1108840(10)
γ(ordm) 9000 116865(3) 9000
V(Aring3) 36362(5) 182343(15) 46220(2)
Z 4 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1577 1536 1418
Abs coeff μ mm-1 0256 0143 0236
Data collected 27739 30840 34544
Rint 00299 00352 00437
Data used 6409 8342 8147
Variables 506 560 600
R (gt2σ) 00570 00504 00687
wR2 01537 01410 02122
GOF 1045 1021 1092
183
Table 46 ndash Selected crystallographic data for 414 432 and 439
414
(+05 CH2Cl2 +1 C5H12)
432
(+05 C5H12) 439
Formula C485H36B1Cl1F15N1 C325H21B1F15N1 C58H46B1F15P2
Formula wt 96404 72131 110070
Crystal system monoclinic triclinic triclinic
Space group C2c P-1 P-1
a(Aring) 309455(12) 80774(6) 117846(13)
b(Aring) 193567(7) 117730(8) 159017(19)
c(Aring) 182668(6) 158569(11) 16349(2)
α(ordm) 9000 79707(3) 108194(4)
β(ordm) 123002(2) 86387(3) 107588(4)
γ(ordm) 9000 87902(3) 104551(4)
V(Aring3) 91764(6) 148021(18) 25646(5)
Z 8 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1397 1620 1425
Abs coeff μ mm-1 0179 0160 0179
Data collected 34220 24071 37635
Rint 00476 00352 00284
Data used 8097 6615 9023
Variables 570 445 698
R (gt2σ) 00716 00560 00339
wR2 02417 01703 00880
GOF 1047 1096 1019
184
Table 47 ndash Selected crystallographic data for 440 and 442
440 442
Formula C38H38B1F15P2 C35H29B2F10O2P1
Formula wt 85243 72417
Crystal system monoclinic monoclinic
Space group C2c P2(1)n
a(Aring) 329294(17) 114236(2)
b(Aring) 118317(6) 151074(3)
c(Aring) 206088(10) 192749(4)
α(ordm) 9000 9000
β(ordm) 107535(5) 93553(1)
γ(ordm) 9000 9000
V(Aring3) 76563(7) 332009(11)
Z 8 4
Temp (K) 150(2) 223(2)
d(calc) gcm-3 1479 1449
Abs coeff μ mm-1 0215 0172
Data collected 63283 23294
Rint 00316 0055
Data used 8776 6697
Variables 517 456
R (gt2σ) 00365 00672
wR2 01017 01623
GOF 1021 1048
185
Chapter 5 Conclusion
51 Thesis Summary
The results presented in this thesis demonstrate the application of B(C6F5)3 and other
electrophilic boranes in metal-free synthetic methodologies thereby extending FLP reactivity
beyond the commonly reported stoichiometric activation of small molecules These findings
have also provided metal-free and catalytic routes to transformations typically performed using
transition-metal complexes or stoichiometric main group reagents
Initial results presented herein describe the aromatic reduction of N-phenyl amines in the
presence of an equivalent of B(C6F5)3 using H2 to yield the corresponding cyclohexylammonium
derivatives A reaction mechanism based on experimental evidence and theoretical calculations
has been proposed Elaborating the scope of these metal-free aromatic reductions a p-methoxy
substituted aniline was found to undergo tandem hydrogenation and intramolecular cyclization
with B(C6F5)3 presenting a unique route to a 7-azabicyclo[221]heptane derivative Aromatic
hydrogenations were further probed with pyridines quinolines and other N-heterocycles
Findings within this study were in agreement with the mechanism postulated for the arene
reduction of N-phenyl amines Although these reductions require an equimolar combination of
the aromatic amine and borane in certain cases the reactions take up eight equivalents of H2
Continued interest in FLP hydrogenation of aromatic rings was illustrated by subsequent reports
demonstrating borane-catalyzed stereoselective hydrogenation of pyridines by the Du group264
and catalytic hydrogenation of polyaromatic hydrocarbons by the Stephan group263
The second project discussed in this thesis was directly inspired by findings in the synthesis of a
7-azabicyclo[221]heptane derivative from a p-methoxy substituted aniline Detailed
mechanistic studies showed the B(C6F5)3-methoxide bond is labile under specific reaction
conditions These findings were applied to uncover a catalytic approach to the hydrogenation of
ketones and aldehydes yielding alcohols This method uses FLPs derived from B(C6F5)3 and
ether in which the ether is used as the solvent playing a pivotal role in hydrogen-bonding
interaction with the carbonyl substrate The catalysis was further studied in toluene using
B(C6F5)3 in combination with oxygen containing materials such as cyclodextrins or molecular
sieves Application of these materials provides an avenue to H2 activation and hydrogen-bonding
186
interactions necessary to facilitate hydrogenation In the particular case of aryl ketones the use
of molecular sieves promoted reductive deoxygenation of the substrate to give the aromatic
hydrocarbon product Hydrogenation of carbonyl substrates had perennially remained a
challenging problem since the discovery of FLP chemistry The results reported in this thesis
represent the first successful report of catalytic carbonyl hydrogenation using FLPs It should be
noted that the group of Ashley simultaneously reported the hydrogenation of ketones and
aldehydes using 14-dioxaneB(C6F5) as the FLP catalyst260
Lastly interest in expanding FLP catalysis beyond hydrogenations amineborane FLPs were
applied in the hydroamination of terminal alkynes The stoichiometric reaction of aniline
B(C6F5)3 and two equivalents of alkyne gave a series of iminium alkynylborate complexes
prepared through sequential intermolecular hydroamination and deprotonation reactions This
latter reaction results in the formation of the alkynylborate anion thus preventing participation of
B(C6F5)3 in catalysis Adjustment of the protocol by slow addition of the alkyne prevents the
deprotonation pathway thus allowing B(C6F5)3 to catalyze the Markovnikov hydroamination of
alkynes by a variety of secondary aryl amines affording enamines products This metal-free
route was also amenable to subsequent use of the catalyst in hydrogenation catalysis allowing
for the single-pot and stepwise conversion of the enamine products to the corresponding amines
Further expansion of the reactivity led to catalytic intramolecular hydroaminations affording a
one-pot strategy to N-heterocycles A stoichiometric approach to FLP hydrophosphinations was
also described
52 Future Work
While the reactivities presented in this thesis have typically been the purview of precious metals
research efforts motivated by cost toxicity and low abundance have provided alternative
strategies using main group compounds In 1961 the first metal-free catalytic hydrogenation was
reported displaying the reduction of benzophenone however this reaction required high
temperatures of about 200 degC and H2 pressures greater than 100 atm175 Since then dramatic
progress has been made in the advancement of metal-free catalysis Numerous metal-free
systems with particular emphasis on FLPs have been reported to effect the hydrogenation of an
elaborate list of substrates under mild conditions
187
An important direction to progress the chemistry found during this graduate research work would
be to design a borane reagent that will be suitable for the catalytic hydrogenation of N-phenyl
amines and N-heterocycles Such a direction will allow for a more atom-economic
transformation Ultimately the catalysis could be pursued using chiral boranes that may provide
a stereoselective process to cyclohexylamine derivatives (Scheme 51) Generally aromatic
hydrogenation of nitrogen substrates is a challenging transformation for transition-metal systems
due to deactivation of the catalyst by coordination of the substrate357
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
An interesting and obvious extension of carbonyl hydrogenations presented in Chapter 3 would
certainly be a FLP route to optically active alcohols Although such products were not obtained
when performing the reductions in the presence of chiral heterogeneous Lewis bases the
application of a chiral borane should be investigated The Du group recently presented the use of
chiral boranes in the asymmetric hydrogenation of silyl enol ethers to give chiral alcohol
products after appropriate work-up procedures97
Furthermore the use of cyclodextrins and molecular sieves in catalysis has presented the
possible notion of expanding homogeneous FLP chemistry to surface chemistry by designing
heterogeneous FLP catalysts that could be readily recycled (Scheme 52) Such a system may be
particularly attractive for industrial applicability Solid catalyst supports such as B(C6F5)3 grafted
onto silica have been used by the Scott group as a co-catalyst for the activation of metal
complexes used in olefin polymerization358 Although this system may not be sufficiently Lewis
acidic for carbonyl reductions further exploration and modification of Lewis acid and base
components could potentially lead to such a system
188
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations
The final chapter of this thesis outlined the consecutive hydroamination and hydrogenation of
ethynyl fragments catalyzed by B(C6F5)3 The novelty of this reactivity by FLP systems certainly
demands further explorations Catalytic hydroamination using FLPs could be extended to include
olefins and internal alkynes Furthermore the pursuit of an effective chiral borane catalyst may
provide a potential synthetic route to chiral amines of pharmaceutical and industrial interest
189
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iv
Acknowledgments
Graduate school is not a journey taken alone rather it is one travelled with companions I have a
large group of wonderful people to thank for travelling by my side continuously supporting me
and putting a smile on my face
First and foremost I would like to take this opportunity to express my sincere gratitude to my
supervisor Prof Doug Stephan Thank you for your support you were always positive and open
to discussions Aside from developing my knowledge in chemistry you provided me with the
opportunity to build relationships and grow professionally I have also had the honour of having
very helpful committee members over the past few years Profs Bob Morris and Datong Song I
would like to thank you for your guidance and feedback through the seminar series and
committee meetings Prof Andrew Ashley I truly appreciate the time you took to provide me
with feedback for this thesis and attend my examination Thank you to Prof Erker at the
University of Muumlnster for accepting me to do an exchange in his research group
Of course the results in this thesis would not be publishable without the hard work of the staff at
the University of Toronto I would like to thank you all especially Darcy Burns Dmitry
Pichugin Rose Balazs and Matthew Forbes Also I would like to thank Chris Caputo Peter
Mirtchev Conor Prankevicius Alex Pulis and Adam Ruddy for your time in editing this thesis
All of the past and present Stephan group members thank you for the great times and of course
for doing your lab jobs and keeping the lab functional I definitely have to thank you Shanna for
keeping us in check
I want to give a big shout out to all my Athletic Centre gym buddies rock-climbing fellows
Chem Club soccer team champions and amazing Argon crossfitters I cannot express how much I
enjoyed every moment spent doing these outside-the-lab activities
A big I love you to my most amazing siblings Maithem Christina Jacob and Hoda I do not have
enough room here to express how much you guys mean to me but through it all we have stuck
together and this is how we will continue until the end To my future baby niece you have put a
smile on my face even while you are still inside the womb I cannot wait to meet you Finally to
the most supportive and kind-hearted person I have ever met Renan you have been there for me
from the start of this journey until the end Thank you all
v
Table of Contents
Abstract ii
Acknowledgments iv
Table of Contents v
List of Figures xi
List of Schemes xiv
List of Tables xix
List of Symbols and Abbreviations xxi
Chapter 1 Introduction 1
11 Science and Technology 1
111 Boron properties production and uses 2
112 Boron chemistry 3
12 Catalysis 4
13 Frustrated Lewis Pairs 5
131 Early discovery 5
132 Hydrogen activation and mechanism 6
133 Substrate hydrogenation 9
134 Activation of other small molecules 10
1341 Unsaturated hydrocarbons 10
1342 Alkenes 11
1343 Alkynes 11
1344 11-Carboboration 12
1345 CO2 and SO2 13
1346 FLP activation of carbonyl bonds 14
1347 Carbonyl hydrogenation 15
vi
1348 Carbonyl hydrosilylation 16
14 Scope of Thesis 17
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines and N-Heterocyclic Compounds 19
21 Introduction 19
211 Hydrogenation 19
212 Transfer hydrogenation 20
213 Main group catalysts 21
214 Hydrogenation of aromatic and heteroaromatic substrates 22
2141 Transition metal catalysts 22
2142 Metal-free catalysts 23
215 Reactivity of FLPs with H2 23
22 Results and Discussion 24
221 H2 activation by amineborane FLPs 24
222 Aromatic hydrogenation of N-phenyl amines 25
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates 30
223 Mechanistic studies for aromatic hydrogenation reactions 31
2231 Deuterium studies 31
2232 Variable temperature NMR studies 32
2233 Theoretical calculations 33
224 Aromatic hydrogenation of substituted N-bound phenyl rings 35
2241 Fluoro-substituted rings and C-F bond transformations 35
2242 Methoxy-substituted rings and C-O bond transformations 38
22421 Mechanistic studies for C-O and B-O bond cleavage 40
225 Aromatic hydrogenation of N-heterocyclic compounds 45
vii
2251 Hydrogenation of substituted pyridines 45
2252 Hydrogenation of substituted N-heterocycles 49
2253 Proposed mechanism for aromatic hydrogenation 55
2254 Approaches to dehydrogenation 55
23 Conclusions 56
24 Experimental Section 56
241 General considerations 56
242 Synthesis of compounds 57
243 X-Ray Crystallography 79
2431 X-Ray data collection and reduction 79
2432 X-Ray data solution and refinement 79
2433 Selected crystallographic data 81
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation with Frustrated Lewis Pairs 88
31 Introduction 88
311 FLP reactivity with unsaturated C-O bonds 88
32 Results and Discussion 92
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions 92
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents 93
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents 96
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism 97
325 Other hydrogen-bond acceptors for carbonyl hydrogenations 99
326 Other boron-based catalysts for carbonyl hydrogenations 99
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism 100
viii
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system 102
328 Attempted hydrogenation of other carbonyl substrates and epoxides 102
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases 103
3291 Polysaccharides as heterogeneous Lewis bases 104
3292 Molecular sieves as heterogeneous Lewis bases 107
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones 107
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation 110
32101 Verifying the reductive deoxygenation mechanism 111
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins 113
33 Conclusions 113
34 Experimental Section 114
341 General Considerations 114
342 Synthesis of Compounds 116
3421 Procedures for reactions in ethereal solvents 116
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3] 119
3423 Procedures for reactions using heterogeneous Lewis bases 120
3424 Procedures for reductive deoxygenation reactions 121
3425 Spectroscopic data of products in Table 31 121
3426 Spectroscopic data of products in Table 32 125
3427 Spectroscopic data of products in Table 33 125
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a) 127
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b) 128
343 X-Ray Crystallography 130
3431 X-Ray data collection and reduction 130
ix
3432 X-Ray data solution and refinement 130
3433 Selected crystallographic data 131
Chapter 4 Hydroamination and Hydrophosphination Reactions Using Frustrated Lewis Pairs 132
41 Introduction 132
411 Hydroamination 132
412 Reactions of main group FLPs with alkynes 133
4121 12-Addition or deprotonation reactions 133
4122 11-Carboboration reactions 134
4123 Hydroelementation reactions 135
413 Reactions of transition metal FLPs with alkynes 135
42 Results and Discussion 136
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes 136
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes 140
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates 141
4213 Reactivity of the iminium alkynylborate products with nucleophiles 141
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3 142
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes 144
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions 146
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes 147
424 Intramolecular hydroamination reactions using FLPs 148
4241 Stoichiometric hydroamination 148
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines 150
x
425 Reaction of B(C6F5)3 with ethynylphosphines 151
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines 153
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs 154
427 Proposed mechanism for the hydroborationhydrophosphination reactions 156
43 Conclusions 157
44 Experimental Section 157
441 General Considerations 157
442 Synthesis of Compounds 158
4421 Procedures for stoichiometric intermolecular hydroamination reactions 158
4422 Procedures for hydroarylation of phenylacetylene 165
4423 Procedures for catalytic intermolecular hydroamination reactions 167
4424 Procedures for tandem hydroamination and hydrogenation reactions 172
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions 173
4426 Procedures for reactions with ethynylphosphines 177
443 X-Ray Crystallography 179
4431 X-Ray data collection and reduction 179
4432 X-Ray data solution and refinement 180
4433 Platon Squeeze details 180
4434 Selected crystallographic data 181
Chapter 5 Conclusion 185
51 Thesis Summary 185
52 Future Work 186
References 189
xi
List of Figures
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage 8
Figure 12 ndash A highly efficient borenium hydrogenation catalyst 10
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis 21
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates 23
Figure 23 ndash POV-Ray depiction of 24rsquo 26
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+ 27
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($) 27
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right) 28
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right) 31
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-) 33
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol) 34
Figure 210 ndash POV-Ray drawing of 216a 36
xii
Figure 211 ndash POV-Ray drawing of 218 37
Figure 212 ndash POV-Ray drawing of 219 39
Figure 213 ndash POV-Ray drawing of trans-220 40
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c) 42
Figure 215 ndash POV-Ray drawing of 222 43
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right) 46
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring 48
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups 49
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring 49
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c) 50
Figure 221 ndash POV-Ray depiction of the cation for compound 231a 51
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring 52
Figure 223 ndash POV-Ray depiction of the cation for compound 233 52
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right) 53
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine 54
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol () 94
xiii
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol 95
Figure 33 ndash POV-Ray depiction of 31 98
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted 100
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
104
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD) 104
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased 112
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
136
Figure 42 ndash POV-Ray depiction of 47 137
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b) 139
Figure 44 ndash POV-Ray depiction of 410 139
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg 143
Figure 46 ndash POV-Ray depiction of 432 149
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons 152
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b) 153
Figure 49 ndash POV-Ray depictions of 442 155
xiv
List of Schemes
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3 4
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe) 4
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP 6
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c) 7
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K 9
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines 9
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom) 11
Scheme 18 ndash Reaction of FLPs with phenylacetylene 12
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom) 12
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base 13
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I) 14
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs 15
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP 16
xv
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom) 17
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine 20
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b) 24
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom) 25
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23 26
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD 32
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23 32
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts 35
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a 36
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218 37
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219 39
Scheme 211 ndash Synthesis of 220 and 212 40
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b) 41
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3 43
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3 44
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane 45
Scheme 216 ndash Proposed reaction pathway for the formation of 235 54
xvi
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom) 89
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b) 90
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols 90
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom) 91
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH 92
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation 93
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents 97
Scheme 38 ndash Synthesis of 31 98
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond 100
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation 102
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone 108
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b) 110
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones 111
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al) 133
xvii
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c) 134
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes 134
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes 135
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes 135
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
136
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts 140
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3 141
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4] 141
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right) 142
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3 142
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond 144
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes 147
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430 148
xviii
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432 149
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433 150
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH 151
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439 152
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440 154
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH 155
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments 156
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
187
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations 188
xix
List of Tables
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts 29
Table 22 ndash Hydrogenation of substituted pyridines 47
Table 23 ndash Hydrogenation of substituted N-heterocycles 51
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25 81
Table 25 ndash Selected crystallographic data for 216a 218 and 219 82
Table 26 ndash Selected crystallographic data for 220 222 and 224 83
Table 27 ndash Selected crystallographic data for 225 227 and 228 84
Table 28 ndash Selected crystallographic data for 229 230 and 231a 85
Table 29 ndash Selected crystallographic data for 231b 233 and 234a 86
Table 210 ndash Selected crystallographic data for 234b and 235 87
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents 96
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3] 101
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
106
Table 34 ndash Deoxygenation of aryl alkyl ketones 108
Table 35 ndash Deoxygenation of diaryl ketones 109
Table 36 ndash Selected crystallographic data for 31 131
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
138
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3 145
xx
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines 151
Table 44 ndash Selected crystallographic data for 41 47 and 48 181
Table 45 ndash Selected crystallographic data for 49 410 and 413 182
Table 46 ndash Selected crystallographic data for 414 432 and 439 183
Table 47 ndash Selected crystallographic data for 440 and 442 184
xxi
List of Symbols and Abbreviations
9-BBN 9-borabicyclo[331]nonane
α alpha
Aring angstrom 10-10 m
atm atmosphere
β beta
Bpin pinacolborane (4455-tetramethyl-132-dioxaborolane)
br broad
Boc tert-butyloxycarbonyl
Bu butyl
C Celsius
ca circa
calcd calculated
CD cyclodextrin
C6D6 deuterated benzene
C6H5Br bromobenzene
C6D5Br deuterated bromobenzene
CD2Cl2 deuterated dichloromethane
Cy cyclohexyl
δ chemical shift
xxii
deg degrees
d doublet
Da Dalton
DART direct analysis in real time
DEPT Distortionless Enhancement by Polarization Transfer
dd doublet of doublets
de diastereomeric excess
DFT density functional theory
dt doublet of triplets
ee enantiomeric excess
eq equivalent(s)
ESI electrospray ionization
Et ethyl
Et2O diethyl ether
FLP frustrated Lewis pair
γ gamma
ΔG Gibbs free energy
g gram
GC gas chromatography
GOF goodness of fit
xxiii
h hour
HRMS high resolution mass spectroscopy
HMBC heteronuclear multiple bond correlation
HOESY heteronuclear Overhauser effect NMR spectroscopy
HSQC heteronuclear single quantum correlation
Hz Hertz
iPr2O diisopropyl ether
nJxy n-scalar coupling constant between X and Y atoms
K Kelvin
kcal kilocalories
m meta
m multiplet
M molar concentration
Me methyl
Mes mesityl 246-trimethylphenyl
MHz megahertz
μL microliter
μmol micromole
mg milligram
min minute
xxiv
mL milliliter
mmol millimole
MS mass spectroscopy
MS molecular sieves
nPr n-propyl
iPr iso-propyl (CH(CH3)2)
NHC N-heterocyclic carbene
NMR Nuclear Magnetic Resonance
NOE Nuclear Overhauser Effect
o ortho
π pi
p para
POV-Ray Persistence of Vision Raytracer
PGM Platinum Group Metals
Ph phenyl
Ph2O diphenyl ether
ppb parts per billion 10-9
ppm parts per million 10-6
q quartet
quint quintet
xxv
rpm rotations per minute
RT room temperature
σ sigma
s singlet
t triplet
tBu tert-butyl
THF tetrahydrofuran
TMP 2266-tetramethylpiperidine
TMS trimethylsilyl
TMS2O hexamethyldisiloxane
tol toluene
wt weight
1
Chapter 1 Introduction
11 Science and Technology
The advent of the scientific revolution and the scientific method in early modern Europe
dramatically transformed the way scientists viewed the universe as they attempted to explain the
physical world through experimental investigation The long-term effects of the revolution can
be felt today with our dependence upon science to improve the quality of our lives and advance a
globally interconnected world Some scientific discoveries which have paved the way for such
enterprising technologies include the Haber-Bosch process used for the production of ammonia
essential to the synthesis of nitrogen fertilizers1-3 This discovery has dramatically increased food
production globally and allowed for the explosive population growth observed in the past
century Research also intensified to change the world of medicine through discovery of antiviral
agents for treatment of the HIVAIDS pandemic4-5 Ziegler-Natta catalysts have become central
to the polymer industry manufacturing the largest volumes of commodity plastics and
chemicals6-8
While many chemical breakthroughs have had significant benefits on public health their initial
application or even long-term impact on the environment may be detrimental For example
chlorine was used as a weapon during World War I9 while today it plays a vital role in
disinfecting drinking water and sanitation processes10 A more significant example is the
industrial revolution when manufacturing transitioned from manual labour to machines resulting
in unprecedented growth in population and standards of living Our continued reliance on
factories and mass production has led to depletion of natural resources and emission of
greenhouse gases resulting in anthropogenic climate change11-15
Scientists have acknowledged the need to remediate environmental impacts and to find more
environmentally acceptable technologies for the chemical industry To this end chemical
research has focused on implementing the principles of green chemistry16-17 to develop benign
processes which will sustain the growing energy demands of our society18-19 Central to the green
concept is the application of catalysis in chemical transformations in addition to using readily
available non-toxic raw materials in cost effective procedures
2
Rare precious metals such as the Platinum Group Metals (PGM) are extracted by mining of non-
renewable resources normally resulting in negative social and environmental impacts on the
area20 The metals are used in industrial chemical syntheses where they are regularly recovered
and recycled back into production It is essential however to gradually replace these reagents
with more environmentally benign and readily available transition metals in order to reduce
waste processing costs and eliminate the possibility of their release into the environment In this
aspect chemists are actively seeking innovations to advance more green chemical processes21-24
A vast majority of d-block transition metals have energetically accessible valence d-orbitals
allowing for oxidation state changes which are pivotal to substrate activation and accessing
stabilized transition states Additional factors including the steric and electronic tunability of the
ligand framework have led to the development of a broad range of metal catalysts applied in
numerous chemical transformations25-26 Nonetheless a growing number of advancements
involving the use of main group s and p-block elements have also shown reactivities similar to
those of transition metal complexes27-30
Main group elements are relatively abundant on Earth and over the last decade have experienced
a renaissance in chemical transformations Notably frustrated Lewis pair (FLP) systems which
involve the combination of Lewis acids and bases that are sterically and electronically prohibited
from forming a classical adduct have been at the forefront31 The unquenched reactivity of FLPs
has been explored in the activation of numerous small molecules The majority of FLP systems
incorporate boron Lewis acids and phosphorus Lewis bases32 In this thesis the potential to
expand FLP reactivity to nitrogenboron and oxygenboron pairs is explored
111 Boron properties production and uses
Boron (B) is a non-metallic element always found in nature bound to oxygen as orthoboric acid
alkali metal and alkaline earth metal borates33 Prominent sources of boron include the sodium
borate minerals rasorite and kernite found in deposits at the Mojave Desert of California and in
Turkey which is the largest producer of boron minerals33-34 Boron is vastly spread in Nature
however it constitutes only about 3 ppm of the Earthrsquos crust35-36
Industrially the production of pure boron is very difficult as it tends to form refractory materials
containing small amounts of carbon and other elements The method typically used for
3
commercial production of amorphous boron (up to 97 purity) is by reduction of B2O3 with Mg
in a thermite-like reaction Higher purity (gt99) boron is obtained by the reduction of boron
halides with H2 whereas ultra-purity can be achieved by thermal decomposition of boron
halideshydrides or diboranes on tungsten wires followed by zone melting purification37
Regardless of the production method different allotropic forms of boron can be accessed Short
reaction times at temperatures below 900 degC produce amorphous boron longer reaction times
above 1400 degC afford β-rhombohedral and optimal conditions in between the two give α-
rhombohedral36
Amorphous boron consisting of 90 - 92 purity costs approximately $100kg Relatively large
quantities of the material are used as additives in pyrotechnic mixtures Ultrapure (gt9999)
boron costs about $3500kg and is applied in electronics such as a dopant for germanium and
silicon p-type semiconductors Furthermore as the second hardest element inferior only to
diamond there is a growing demand for boron as a light-weight hardenability additive for glass
ceramics and boron filaments used in high-strength materials for the aerospace and steel
industries35-36
112 Boron chemistry
Boron has a valence shell electron configuration of 2s22p1 representing a typical formal
oxidation state of 3+ although due to its high ionization potentials simple B3+ ions do not exist
Boron can form three sp2 hybridized bonds resulting in trigonal planar geometry with a non-
bonding vacant p-orbital orthogonal to the plane susceptible towards electron donation giving
rise to its noted Lewis acidic properties38-40 Scales to quantify Lewis acidity have been designed
by studying the acceptor-donor interactions between Lewis acid and base complexes using NMR
spectroscopy data based on the Gutmann-Beckett41 and Childs42 methods43 IR spectroscopy X-
ray diffraction44 and density functional calculations45
The most common use of Lewis acids are the boron trihalides particularly BF3 and BCl3 in
conjunction with a co-initiator Lewis base such as water initiating cationic polymerization The
unsaturated olefin monomer is protonated generating the [BF3OH]- counterion along with a
carbenium ion which reacts with olefin molecules leading to propagation of the polymer46 With
Lewis acidity comparable to BF3 the Lewis acid B(C6F5)3 was lsquorediscoveredrsquo in the 1990s as an
ideal activator component for Ziegler-Natta olefin polymerization catalysts47 Treatment of a
4
Group 4 dialkyl-metallocene catalyst precursor with one equivalent of B(C6F5)3 results in alkyl
anion abstraction forming the active alkyl-metallocene cation (eg [Cp2ZrMe]+) stabilized by the
weakly coordinating [MeB(C6F5)3]- anion (Scheme 11)48-51
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3
Hydroboration the addition of B-H across multiple bonds of organic substrates such as alkenes
and alkynes provides the most common route to alkyl or alkenyl organoborane reagents
respectively52 The products obtained can be employed as intermediates for further synthetic
derivatization One powerful and general methodology used for the modification of
organoboranes53 is the Suzuki-Miyaura cross-coupling reaction (Scheme 12) These C(sp2)-B
and C(sp3)-B organoboranes readily undergo transmetalation with an electrophilic organo- Cu
Pd Ni or Fe catalyst to give coupled products with new C-C bonds54-55 Other applications of
boron reagents include metal borohydrides as reducing agents transferring hydride nucleophiles
to versatile functional groups56-59 Operating in a similar manner anionic borates consisting of
polarized B-C bonds transfer an organic group to an electrophilic centre38 60
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe)
Of particular relevance to this thesis recent advances in boron chemistry particularly involving
the activation and reactivity of small molecules with FLP systems will be discussed
12 Catalysis
In the early part of the 20th century catalysis developed into a scientific discipline and has
evolved to underlie numerous chemical technologies that benefit human life worldwide61 The
5
function of a catalyst substance added in a sub-stoichiometric amount is to lower the reaction
activation energy and affect selectivity for chemical transformations without being consumed62
Homogeneous catalysts have a long prevalence in industry with applications ranging from bulk
chemicals to complex multi-step processes Among the most prominent examples are the
Monsanto and Cativa processes for the carbonylation of methanol to produce acetic acid and the
oxo process for hydroformylation of olefins to yield aldehydes63 Only touching the tip of the
iceberg other commercial processes include the Wacker process for the oxidation of ethylene
aforementioned Ziegler-Natta olefin polymerization based on immobilized TiCl3 and substrate
hydrogenations using Wilkinsonrsquos Rh and Ru catalysts64-65 Other noteworthy discoveries
essential to the advancement of catalysis include Fischer-Tropsch production of liquid
hydrocarbons asymmetric catalysis olefin metathesis and Pd-catalyzed cross couplings66
The significance of catalysis for the development of chemistry has been recognized by the Nobel
Prize Committee with the earliest accreditation in the field awarded in 1909 to W Ostwald
Shortly thereafter Nobel Prizes were awarded for important contributions by P Sabatier (1912)
F Haber (1918) and C Bosch and F Bergius (1931) Since the turn of the millennium catalysis
has been recognized with four Chemistry Nobel Prizes awarded to 10 laureates66
13 Frustrated Lewis Pairs
131 Early discovery
The acid-base theory proposed by G N Lewis in 1923 is arguably one of the most important
theories in chemistry describing Lewis acid and base species as electron pair acceptors and
electron pair donors respectively67 According to the theory sterically unhindered Lewis acid-
base pairs react to form a Lewis adduct quenching subsequent reactivity This concept is
fundamental in most areas of chemistry involving the interaction of a doubly occupied orbital
(nucleophile) with an empty orbital (electrophile) forming a favourable overlap
Recent advances involving sterically encumbered Lewis pairs preclude such adduct formation
thereby rendering the individual components available for unique reactivity68-70 Astonishingly
in 1942 H C Brown reported that the ldquosteric strainrdquo between the Lewis acid trimethylborane
and the bulky Lewis base 26-lutidine does not result in adduct formation71 These early results
predate the recently popularized concept of frustrated Lewis pairs (FLPs) describing the
6
combination of Lewis acids and bases with sterically and electronically frustrated substituents
which prevent formal adduct formation32 The cooperative behaviour of these frustrated Lewis
centres has been evidenced to activate small molecules72
132 Hydrogen activation and mechanism
The first FLP reactivity was discovered by Stephan et al in 2006 while investigating the
chemistry of phosphonium borate linked zwitterions R2P(H)(C6F4)B(F)(C6F5)2 (R = alkyl or
aryl) generated from nucleophilic aromatic substitution of B(C6F5)3 by bulky secondary
phosphines31 Treatment with Me2SiHCl easily converts the linked zwitterion to the
phosphonium borohydride species containing both protic and hydridic hydrogen atoms In a
remarkable example the linked PHndashBH zwitterion (R = Mes) was found to liberate and rapidly
activate H2 representing the first example of reversible H2 activation using main group
compounds (Scheme 13)
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP
Hydrogen activation by main group compounds is rare the first example was reported in 2005
by the group of Power and co-workers describing the addition of H2 to heavier main group
digermyne compounds RGeequivGeR (R = aryl)30 The seminal finding was followed by the work of
Bertrand using bulky (alkyl)(amino)carbenes displaying both nucleophilic and electrophilic
characteristics to split and add H2 at a single carbon centre28 In a succeeding report by Piers the
antiaromatic Lewis acid perfluoropentaphenylborole was exclusively employed in H2 activation
to yield boracyclopent-3-ene products resulting from H2 addition to the two carbon atoms alpha
to boron73
After the initial breakthrough with FLPs their unique reactivity attracted immediate attention of
the scientific community Erker and co-workers have synthesized intramolecular PB FLPs
derived by the anti-Markovnikov addition of HB(C6F5)2 to vinyl phosphines (Scheme 14 a)74-75
Additionally Rieger and Repo have reported the nitrogen-based intramolecular FLP ansa-
7
aminoborane shown in Scheme 14 (b)76-78 These systems heterolytically split H2 albeit
reversible H2 activation was only demonstrated for the ansa-aminoborane
Hydrogen activation has also been extended to bimolecular systems Combinations of B(C6F5)3
and sterically encumbered tertiary phosphines were found to effect H2 activation (Scheme 14
c)32 In one example the weaker Lewis acid B(p-HC6F4)3 and o-tolyl3P were found to liberate H2
under vacuum79-80
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c)
The initial mechanism proposed for heterolytic splitting of H2 was speculated to be a ldquoside-onrdquo
or ldquoend-onrdquo coordination of H2 to either the boron or phosphorus moiety followed by approach
of the respective FLP partner effecting H-H bond cleavage This mechanism was not found to be
computationally supported despite earlier evidence for the ldquoside-onrdquo mechanism based on BH3-
H2 adducts81-84 While mechanistic details remain debated theoretical investigations by the
groups of Paacutepai85-87 and Grimme88 were performed on the prototype tBu3PB(C6F5)3 FLP Both
groups agree on the formation of an ldquoencounter complexrdquo stabilized by CndashH---F dispersion
interactions between the phosphine methyl groups and C6F5 borane rings As a result the Lewis
pair orient such that the boron is in close proximity to the phosphorus centre The electron
transfer model proposed by Paacutepai89 explains hydrogen activation by synergistic interaction of the
8
Lewis pair inducing polarization on the H2 molecule effecting heterolytic cleavage In this case
donation from the σ orbital of H2 into the empty orbital on the Lewis acid occurs in conjunction
with lone pair donation from the Lewis base to the σ orbital of H2 representing a process
similar to metal-based heterolytic cleavage of H2 (Figure 11 a) In contrast the electric field
model reported by Grimme suggests heterolytic H2 activation is a barrierless process resulting
from the exposure of H2 to a sufficiently strong homogeneous electric field pocket created by the
FLP complex Interpretation of this model does not consider electron donation or the orbitals of
the FLP or H2 (Figure 11 b)
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage
Direct investigation of H2 activation intermediates by standard experimental techniques has been
unquestionably demanding Experimental evidence of an encounter complex has been observed
by 19F1H HOESY NMR studies revealing contacts between all protons of R3P (R = tBu Mes)
and fluorine nuclei of B(C6F5)3 although only a rough orientation of the molecules was
reported90 Examination of a related system has recently been reported by the Piers group In this
case combination of a highly electrophilic boraindene and Et3SiH gave an isolable borane-silane
complex affirming details of adduct formation in FLP hydrosilylation and to a certain extent
extrapolated to the closely related H2 activation reaction (Scheme 15)91
9
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K
133 Substrate hydrogenation
Reversible H2 activation by the initial FLP Mes2P(H)(C6F4)B(H)(C6F5)2 was a landmark
discovery that shed light onto potential important applications of such systems Most significant
of these efforts was demonstrated by employing R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) in the
catalytic reduction of unsaturated substrates specifically bulky imines and N-protected nitriles to
corresponding amines using 5 mol catalyst 5 atm of H2 and temperatures ranging from 80 -
100 degC Concerted investigations in the field revealed that sterically hindered substrates could
also serve as the Lewis base in splitting hydrogen92-93 To this end catalytic amounts of B(C6F5)3
in combination with various bulky aldimines and ketimines were reduced under 5 atm of H2 at
120 degC with isolated yields in the range of 89 - 99 Based on experimental observations the
proposed mechanism suggests H2 is cleaved between the bulky imine and B(C6F5)3 followed by
hydride delivery to the iminium cation (Scheme 16)
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines
10
Following the early reports on metal-free catalytic hydrogenation the reduction of various other
substrates has been demonstrated to include aziridines92 94 enamines93 enones95 silyl enol
ethers96-97 N-heterocycles98 olefins99 and most recently alkynes have been reduced to cis-
alkenes100 Asymmetric hydrogenation by chiral FLPs was first demonstrated in 2008 by
Klankermayer and co-workers to give a chiral amine with 13 ee and later improvements up to
83 were obtained using a camphor derived catalyst101-102 Rieger and Repo saw ee values of
3776 103 while significant improvements up to 89 were achieved by the Du group104
Recently borenium cations have been used as Lewis acids in FLP chemistry with remarkable
catalytic activity for the hydrogenation of imines and enamines at room temperature (Figure
12)105
Figure 12 ndash A highly efficient borenium hydrogenation catalyst
134 Activation of other small molecules
FLP-mediated bond activations have been explored for a multitude of small molecules including
CO2106-107 N2O108-112 SO2113-114 NO115-116 CO107 117-119 NSO120 fluoroalkanes121 ether122
disulfides123 alkenes124-125 and alkynes126-128 FLPs have also been exploited in radical
polymerizations116 and more recently in materials and surface science129 Efforts have also
continued to exploit FLP chemistry in synthetic organic applications130 Beyond here small
molecule transformations that are relevant to the chemistry presented in this thesis will be
discussed
1341 Unsaturated hydrocarbons
Reactivity of unsaturated hydrocarbons has been a field traditionally associated with transition
metal chemistry and has found particular use for organic synthesis131-138 The dramatic evolution
in FLP systems has raised interest in probing the reactivity of main group complexes with
alkenes and alkynes100 139-140 This reactivity is reminiscent of related findings by Wittig and
Benz in 1959 involving the addition of Ph3P and BPh3 to benzyne affording zwitterionic
11
phosphonium-borates141 In the same context Tochtermann showed the addition of the bulky
carbanion [Ph3C]- and Lewis acid BPh3 across the double bond of 13-butadiene rather than
anionic polymerization of the conjugated diene142
1342 Alkenes
The reaction of FLPs with alkenes is particularly intriguing as the individual Lewis components
do not react with the substrate rather the three component combination of R3P B(C6F5)3 and
alkene exhibited intermolecular 12-addition reactions (Scheme 17 top)143-144 Similar activation
results were also observed upon exposure to the ethylene-linked FLP Mes2PCH2CH2B(C6F5)2145-
147 In two remarkable examples the Stephan group provided spectroscopic theoretical148 and
crystallographic149 evidence for Lewis acid-olefin van der Waals complexes forming prior to
FLP additions (Scheme 17 bottom)
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom)
1343 Alkynes
Initial reactivity of FLPs with terminal alkynes featured the facile deprotonation or addition of
phosphineLewis acid (B Al) combinations to afford alkynylborate (aluminate) salts or
zwitterions with selectivity of the reaction correlated to the basicity of the phosphine (Scheme
18)126 128 In a joint report by the Stephan and Erker groups the B(C6F5)3-mediated
intramolecular cyclization of an ortho-ethynylaniline to access a cyclic anilinium borate was
presented150-151 In an analogous fashion Stephan and co-workers showed the cyclization of
alkyne- and alkene-tethered pyridines and quinolines using B(C6F5)3152 The groups of Berke
12
Erker Stephan and Uhl expanded the chemistry by varying the Lewis acid to BPh3 and alanes153
as well as the Lewis base to include phosphines154 polyphosphines155 thioethers amines and
pyridines156 carbenes157 and pyrroles158
Scheme 18 ndash Reaction of FLPs with phenylacetylene
1344 11-Carboboration
Particularly prolific in the research area of FLP reactivity with alkynes the groups of Erker and
Berke separately unravelled the 11-carboboration reaction resulting from the electrophilic
attack of the CequivC triple bond of an alkyne by highly electrophilic boranes RB(C6F5)2 generating
alkenylborane products (Scheme 19)156 159-160
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom)
In the absence of a Lewis base the combination of electrophilic boranes and terminal alkynes are
postulated to generate a vinylidene intermediate stabilized by 12-hydride migration to the
carbocation Subsequently scission of a BndashC bond transfers a substituent from the borane to the
same carbon of the alkyne generating the alkenylborane (Scheme 110 left)159 This simple yet
elegant strategy demonstrates a facile route to borane derivatives with a C(sp2)-B centre that
could be further treated under Suzuki cross-coupling conditions161 In the presence of a Lewis
13
base deprotonation of the vinylidene or nucleophilic addition at the carbocation takes place
(Scheme 110 right)
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base
1345 CO2 and SO2
Following the reactivity of FLPs with olefins successful joint efforts by the Stephan and Erker
groups showed the activation of the greenhouse gas CO2 and acid rain contributor SO2 using the
FLP tBu3PB(C6F5)3 and ethylene-linked PB system Mes2PCH2CH2B(C6F5)2 (Scheme 111 a
and b)113-114 Key differences were observed in the reactivity of the two gases For example the
reversible nature of binding CO2 was not observed with the SO2 bound species Furthermore the
six-membered SO2 adducts derived from linked PB FLPs gave a stereogenic sulphur centre
resulting in a pair of isomers (Scheme 111 b) The Stephan group extended the activation of
CO2 beyond borane Lewis acids To this end 12 combinations of bulky phosphines and AlX3 (X
= halide or C6F5) react with CO2 rapidly leading to the formation of R3P(CO2)(AlX3)2 (Scheme
111 c)
14
Mes2P B(C6F5)2
EO2Mes2P B(C6F5)2
E O
O
R R
gt -20 degC- CO2
tBu3P B(C6F5)3EO2
80 degC- CO2
PB(C6F5)3E
O
O
tBu3
Mes3P 2 AlX3 Mes3PAlX3E
O
O
AlX3
CO2
b)
a)
c)
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I)
In the case of CO2 further chemical transformation of the activated molecule has been
presented107 111 153 162-164 including efforts to reduce CO2 to CH3OH The groups of Ashley and
OrsquoHare presented this reactivity using H2 as the reducing source Stephan et al used ammonia
borane165 and this process has been achieved catalytically by Fontaine using hydroboranes166-168
Additionally Piers reported the catalytic deoxygenative reduction of CO2 to CH4 using silanes169
and Stephan showed the stoichiometric reduction of CO2 to CO using R3PAlX3 FLPs170
1346 FLP activation of carbonyl bonds
Efforts to include oxygen-based substrates in FLP-mediated catalytic transformations have found
limited success due to the high affinity of electrophilic boranes towards oxygen species72 171
Investigations by Erker and co-workers described the irreversible capture of benzaldehyde and
trans-cinnamaldehyde at the C=O functional group by the intramolecular FLP
Mes2PCH2CH2B(C6F5)2 (Scheme 112 top)172-173 Similar alkoxyborate products were obtained
in the reaction of NB FLPs with benzaldehyde (Scheme 112 bottom)174
15
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs
1347 Carbonyl hydrogenation
Metal-free hydrogenation of carbonyl substrates was reported as early as 1961 by Walling and
Bollyky for the homogeneous hydrogenation of ketones catalyzed by alkali metal alkoxides175
About 40 years later Berkessel and co-workers communicated mechanistic studies on the
process which were supported thereafter by computational investigations176 The authors
elucidated mechanistic analogies between base-catalyzed ketone hydrogenation and Ru-
catalyzed transfer hydrogenation by Noyori whereby a Broslashnsted base participates in H2
heterolysis177 Although this is the first example of metal-free reduction of ketone the reactions
are performed at relatively harsh conditions requiring 100 atm of H2 and 200 degC Moreover the
substrate scope was limited to the non-enolizable ketone benzophenone
The reaction of benzaldehyde with the intramolecular H2-activated FLP
R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) was found to proceed in a stoichiometric fashion
reducing the C=O double bond formulating the zwitterion R2P(H)(C6F4)B(C6F5)2OCH2Ph
(Scheme 113) Chemical intuition would perhaps point to proton transfer from the phosphonium
centre this is however prevented by the lower basicity of the oxygen atom contrasting
hydrogenation reactions with nitrogen substrates
16
B(C6F5)2R2P
FF
F F
H
H
O
HPhB(C6F5)2R2P
FF
F F
H O
Ph
R = tBu Mes
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP
Based on the principle for catalytic hydrogenation of imines Repo and co-workers explored
C=O hydrogenations using the aromatic carbonyl substrates benzophenone and benzaldehyde as
Lewis bases along with the Lewis acid B(C6F5)3 Experimental results indicated the reaction to
be challenging generating only sub-stoichiometric amounts of the alcohol products due to rapid
decomposition of the borane178
1348 Carbonyl hydrosilylation
Hydrosilylation is one of the most commonly applied processes within the chemical industry
today New catalytic technologies providing avenues for metal-free SindashH bond activation have
become appealing alternatives to traditional transition metal catalysts179 Impressively in 1996
the Piers group reported 1 - 4 mol of B(C6F5)3 to effect the catalytic hydrosilylation of
aromatic aldehydes ketones and esters at room temperature (Scheme 114 top)180-182 Clever
analysis of the mechanism by Oestreich using a stereochemically pure silane found inversion of
stereochemistry at silicon after hydrosilylation This finding rationalized a concerted SN2 type
displacement at the silicon centre of a (C6F5)3Bδ-middotmiddotmiddotHmiddotmiddotmiddot SiR3δ+ transition state by the substrate
carbonyl oxygen (Scheme 114 bottom)183
17
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom)
14 Scope of Thesis
The objective of this graduate research was to expand the scope of FLP reactions using the Lewis
acid B(C6F5)3 Although previous studies have documented the reactivity of B(C6F5)3 with small
molecules further transformation of the activated species in organic syntheses remains limited
In this work FLP hydrogenation reactions were extended to include the aromatic rings of N-
phenyl amines and N-heterocyclic compounds as described in Chapter 2 Tandem hydrogenation
and transannulation reactions occurred with a para-methoxy substituted aniline affording a 7-
azabicyclo[221]heptane derivative Mechanistic studies of this reactivity provided insight to a
viable approach achieving the catalytic hydrogenation of ketones and aldehydes to form alcohol
products presented in Chapter 3 In addition the reductive deoxygenation of aryl ketones to
aromatic hydrocarbons was investigated Finally Chapter 4 expands FLP catalytic reactions
beyond hydrogenations In this chapter B(C6F5)3 catalyzed hydroamination of terminal alkynes
is investigated with extension to intramolecular systems and stoichiometric hydrophosphination
reactions
All synthetic work and characterizations were performed by the author with the exception of
elemental analyses high resolution mass spectroscopy and X-ray experiments DFT calculations
for the aromatic hydrogenations described in Chapter 2 were performed by Professor Stefan
Grimme at Universitaumlt Bonn Germany Compounds 216 - 218 were initially synthesized by an
undergraduate student Jon Nathaniel del Castillo under the authorrsquos supervision The synthesis
of compounds 439 and 440 were initially performed by the author at the University of Toronto
18
and repeated during a four month research opportunity program in the laboratory of Professor
Gerhard Erker at Universitaumlt Muumlnster Germany Compounds 441 and 442 were prepared at
Universitaumlt Muumlnster and the structure of 442 was obtained and solved by Dr Constantin
Daniliuc All other molecular structures were solved by the author and the authorrsquos supervisor
Professor Douglas Stephan
Portions of each chapter have been published or accepted at the time of writing
Chapter 2 1) Voss T Mahdi T Otten E Froumlhlich R Kehr G Stephan D W Erker G
ldquoFrustrated Lewis Pair Behavior of Intermolecular AmineB(C6F5)3 Pairsrdquo Organometallics
2012 31 2367-2378 2) Mahdi T Heiden Z M Grimme S Stephan D W ldquoMetal-Free
Aromatic Hydrogenation Aniline to Cyclohexylamine Derivativesrdquo J Am Chem Soc 2012
134 4088-4091 3) Mahdi T Castillo J N Stephan D W ldquoMetal-Free Hydrogenation of N-
based Heterocyclesrdquo Organometallics 2013 32 1971-1978 4) Longobardi L E Mahdi T
Stephan D W ldquoB(C6F5)3 Mediated Arene HydrogenationTransannulation of para-
Methoxyanilinesrdquo Dalton Trans 2015 44 7114-7117
Chapter 3 5) Mahdi T Stephan D W ldquoEnabling Catalytic Ketone Hydrogenation by
Frustrated Lewis Pairsrdquo J Am Chem Soc 2014 136 15809-15812 6) Mahdi T Stephan D
W ldquoFacile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive
Deoxygenation of Ketones and Aldehydesrdquo Angew Chem Int Ed 2015 DOI
101002anie201503087
Chapter 4 7) Mahdi T Stephan D W ldquoFrustrated Lewis Pair Catalysed Hydroamination of
Terminal Alkynesrdquo Angew Chem Int Ed 2013 52 12418-12421 8) Mahdi T Stephan D
W ldquoInter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairsrdquo
Chem Eur J 2015 accepted
19
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines
and N-Heterocyclic Compounds
21 Introduction
211 Hydrogenation
Hydrogenation the addition of hydrogen (H2) to unsaturated compounds is one of the simplest
and most attractive chemical processes performed today26 The reaction is employed for the
production of commodity chemicals with widespread application in the petrochemical
pharmaceutical and foods industries One of the largest industrial applications of hydrogenation
is in the Haber-Bosch process63 66 184 This method uses N2 and H2 to produce ammonia which is
essential for the synthesis of nitrogen fertilizers currently sustaining about one-third of the
worldrsquos population Additionally significant is the Fischer-Tropsch process used to generate
liquid hydrocarbons from the chemical reaction of H2 and CO (synthesis gas)185-186
In the early part of the 20th century P Sabatier discovered the catalytic hydrogenation of organic
substrates over finely divided nickel thereby greatly advancing the field of organic chemistry187-
193 Approximately 60 years later Wilkinson uncovered the homogeneous hydrogenation of
olefins using Ru and Rh catalysts a development that was crowned initiator of organometallic
chemistry (Scheme 21 a)194-197 Further developments in metal-based hydrogenations were
made in the 1980s including the Nobel Prize winning work of asymmetric hydrogenations by
Noyori and Knowles (Scheme 21 b)198-207 While precious metal catalysts208-209 are known to
carry out this reactivity (Scheme 21 c) the high cost and low abundance of these metals
necessitates the development of more cost-efficient procedures New technologies providing
avenues for greener transformations have recently been illustrated using first-row transition
metals Fe and Co (Scheme 21 d)136 210-214
20
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine
212 Transfer hydrogenation
A variety of insightful strategies have provided alternative avenues to direct hydrogenation One
such example is transfer hydrogenation the addition of hydrogen to an unsaturated substrate
from a source other than gaseous H2 In the 1920s Meerwein Ponndorf and Verley (MPV)
demonstrated the first example of hydrogen transfer from a sacrificial alcohol to ketone using an
aluminum alkoxide catalyst215-217 Nonetheless interest in using organocatalysts for
hydrogenation reactions increased spectacularly due to novelty of the concept efficiency and
selectivity in organic reactions Particularly recognized are chiral amine catalysts in combination
with Hantzsch ester dihydropyridines which act as mild organic sources of H2218-219 Extensive
research has also focused on new transition metal catalysts for efficient dehydrocoupling of
ammonia borane (H3NBH3) and related amine borane compounds220
Although transfer hydrogenation is a process dominated by precious transition metal catalysts
Earth abundant less toxic Fe-based catalysts have proven remarkably active effecting high
enantioselectivity (Figure 21 a)221 Moreover catalyst-free strategies by Berke and co-workers
have promoted transfer hydrogenation of imines and polarized olefins222 Stephan et al
underscored extension of metal-free catalysis reporting a highly electrophilic phosphonium
cation catalyst for application in dehydrocoupling of protic compounds with silanes and transfer
hydrogenation to olefins (Figure 21 b)223
RhPh3P
Ph3P Cl
PPh3
(a) (b) (c)
(d)
21
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis
213 Main group catalysts
The discovery of sodium borohydride and lithium aluminum hydride in the 1940s introduced
new stoichiometric methods for the hydrogenation of unsaturated functional groups56 59 224 A
variety of these metal hydride reagents possessing a high degree of chemoselectivity have made
the reduction of a broad range of functional groups possible although catalytic procedures are
evidently more desirable In this vein the first non-transition metal catalyst for ketone
hydrogenation employing tBuOK and H2 is regarded as a breakthrough175-176 Early main group
metal catalysts have followed with highlights on a well-defined organocalcium catalyst
developed by Harder225 and the first cationic calcium hydrides by Okuda capable of catalytic
hydrogenation of 11-diphenylethylene226
Renaissance in main group chemistry emerged with the discovery of frustrated Lewis pairs
(FLPs) These relatively common main group reagents have been applied in the hydrogenation of
imines nitriles aziridines enamines silyl enol ethers olefins and alkynes typically using boron
Lewis acids relying on perfluoroaryl substituents227-228 More recently Lewis acidic borenium
ions based on an [NHC-9-BBN]+ framework have also proven ideal for hydrogenation of imine
and enamine substrates105 Du et al described the highly enantioselective hydrogenation of
imines using a chiral borane catalyst derived from the hydroboration of chiral diene
substituents104 Alkyl229 and aryl149 aluminum compounds in addition to metal-activated carbon-
based Lewis acids have been shown to participate in similar reactivity230
(a) (b)
22
214 Hydrogenation of aromatic and heteroaromatic substrates
2141 Transition metal catalysts
Despite advancements in hydrogenation catalysis the reduction of arenes and heteroaromatics to
saturated cyclic hydrocarbons remains challenging and is typically performed in the
heterogeneous phase using transition metal catalysts Such hydrogenations find particular use in
the petrochemical industry to convert alkene and aromatic fossil fuels into liquid hydrocarbons
before application in commodities such as synthetic fuel26 231 The number of complexes capable
of this catalysis is scarce mainly due to the high energy barrier required to disrupt aromaticity
Catalytic hydrogenation of aromatic systems was first demonstrated for phenols anilines and
benzene in the early 1900s by P Sabatier using powdered nickel189-193 Soon after the 14-
reduction of anisole was observed using dissolved alkali metals in liquid ammonia with major
developments emerging to include benzene and naphthalene derivatives232-233 Historically
significant accomplishments include the work of R Adams using finely divided platinum oxide
(Adamrsquos catalyst)234 and M Raney based on digestion of alloys to form finely divided metal
samples (Raney nickel)235 Other highly efficient catalysts include organometallic compounds
particularly Co Ni Ru and Rh deposited on to oxide surfaces236-239
The number of homogeneous systems capable of hydrogenating arene substrates lags well behind
heterogeneous systems The first well-documented homogeneous catalyst is a simple allylcobalt
complex η3-C3H5Co[P(OMe)3]3 reported by Muetterties and co-workers operating at room
temperature (Figure 22 left)240 shadowed by a new generation of TaV and NbV hydride catalysts
featuring bulky ancillary aryloxide ligands by Rothwell (Figure 22 right)241-243 It is noteworthy
that metal complexes of the cobalt group have provided valuable mechanistic information on this
transformation231 Ziegler type catalysts consisting of Ni or Co alkoxides acetylacetonates or
carboxylates with trialkylaluminum activators have also been demonstrated in the large scale
Institut Francais du Petrole (IFP) process231
23
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates
2142 Metal-free catalysts
Non-metal mediated routes such as the facile addition of borohydrides to unsaturated bonds
were developed early on by Brown and co-workers244 To this extent Koumlster has reported the
hydroboration and subsequent hydrogenolysis to convert naphthalenes to tetralins and
anthracenes to coronenes at 170 - 200 degC and 25 - 100 atm of H2245-246 Alternative efforts
demonstrated trialkylborane and tetraalkyldiborane catalysts in hydrogenating olefins and
polycyclic aromatic hydrocarbons including coal tar pitch In another finding homogeneous
iodine and borane catalysts were shown to hydrogenate the aromatic units of high-rank
bituminous coals at temperatures above 250 degC and 150 - 250 atm of H226 In a recent report the
Wang group has demonstrated the hydrogenation of unfunctionalized olefins catalyzed by
HB(C6F5)2247
215 Reactivity of FLPs with H2
The feasibility of FLP systems to activate H2 and hydrogenate unsaturated substrates
particularly heteroaromatic rings has been examined In this respect 26-lutidine and B(C6F5)3
exhibit reversible dissociation of the Lewis acid-base adduct providing a FLP-mode to H2
activation (Scheme 22 a)248-249 Similar acid-base equilibria were observed with N-heterocycles
nonetheless a catalytic amount of B(C6F5)3 and H2 results in reduction of the N-heterocyclic ring
(Scheme 22 b)98 Research by the Sooacutes group extended the scope of such catalytic reductions
using specifically designed Lewis acids250
24
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b)
Following these reports the commercially available Lewis acid B(C6F5)3251-252 was explored in
the hydrogenation of aromatic rings This chapter will describe results in metal-free aromatic
hydrogenation of N-bound phenyl rings of amines imines and aziridines in addition to pyridines
and N-heterocycles While these reductions are stoichiometric they represent rare examples of
homogeneous aromatic reductions that are metal-free and performed under comparatively mild
conditions Moreover the tandem hydrogenation and intramolecular cyclization of a para-
methoxy substituted aniline is presented This reaction provides a unique route to a 7-
azabicyclo[221]heptane derivative
22 Results and Discussion
221 H2 activation by amineborane FLPs
Phosphine-based FLPs have been thoroughly investigated in the activation of small molecules
and particularly revolutionizing is the first demonstration of reversible heterolytic H2 activation
by Mes2P(C6F4)B(C6F5)231 The corresponding chemistry with amineborane FLP systems has
been less explored Combination of the bulky amine tBuNHPh and an equivalent of B(C6F5)3 in
C6D5Br or pentane solutions do not result an apparent interaction by 1H 11B and 19F NMR
spectroscopy indeed supporting the ldquofrustratedrdquo nature of the system Following exposure of this
solution to H2 (4 atm) at 25 degC the gradual precipitation of a white solid was observed and after
12 h the H2 activated species [tBuNH2Ph][HB(C6F5)3] 21 was isolated in 82 yield (Scheme
23 top) The 1H NMR spectrum obtained in C6D5Br showed a broad resonance at 715 ppm
attributable to an NH2 fragment integrating to two protons as well as signals assignable to the
25
phenyl and tBu groups In addition 11B NMR spectroscopy revealed a doublet at -240 ppm (1JB-
H = 78 Hz) and 19F resonances were observed at -1335 -1613 and -1650 ppm These data
along with elemental analysis were consistent with the formulation of 21 Similar treatment of
the diamine 14-C6H4(CH2NHtBu)2 with two equivalents of B(C6F5)3 in toluene and exposure to
H2 (4 atm) resulted in formation of a precipitate at 25 degC Subsequent isolation of the product
afforded quantitative yield of the salt [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 22 (Scheme 23
bottom) The 1H NMR data showed signals at 595 ppm and 339 ppm attributable to the NH2
and BH fragments respectively The 11B and 19F NMR signals were consistent with the presence
of the [HB(C6F5)3]- anion
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom)
222 Aromatic hydrogenation of N-phenyl amines
Repetition of the H2 activation reaction between tBuNHPh and B(C6F5)3 in toluene with heating
at 110 degC for 48 h led to formation of a new product 23 Subsequent workup and
characterization by NMR spectroscopy revealed the presence of the [HB(C6F5)3]- anion The 1H
NMR spectrum displayed a broad resonance at 507 ppm attributed to an NH2 moiety while
aromatic resonances were notably absent Instead multiplets between 272 and 090 ppm along
with a sharp singlet at 091 ppm were observed This data was consistent with the identity of 23
as the cyclohexylamine product [tBuNH2Cy][HB(C6F5)3] (Scheme 24) By 1H NMR
spectroscopy after 48 h at 110 degC the reaction constituted approximately complete conversion
to 23 and was isolated in 84 yield (Table 21 entry 1)
26
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23
Treatment of iPrNHPh with an equivalent of B(C6F5)3 in toluene at 25 degC gave the
crystallographically characterized adduct (iPrNHPh)B(C6F5)3 24rsquo (Figure 23) This compound
exhibited broad resonances in the 1H 11B 13C and 19F NMR spectra at RT indicating a
fluxional adduct Upon cooling the sample to 193 K NMR signals coalesce giving distinct
resonances assignable to the adduct along with 15 inequivalent 19F resonances that are consistent
with a barrier of rotation of the pentafluorophenyl rings
Figure 23 ndash POV-Ray depiction of 24rsquo
Introducing the amine-borane adduct 24rsquo to H2 (4 atm) does not result in any noticeable changes
in the NMR spectra at RT Although thermolysis of the sample up to 70 degC eventually reveals
dissociation of the adduct with concurrent hydrogenation giving products of complete and partial
reduction of the phenyl ring The partially reduced product observed in trace amounts consisted
of olefinic resonances at 577 and 553 ppm and corresponding aliphatic signals at 256 and 222
ppm (Figure 24 insets) Extensive 1H1H COSY and 1H13C HSQC NMR studies confirmed
the compound as the partially hydrogenated 3-cyclohexenyl derivative [3-
(C6H9)NH2iPr][HB(C6F5)3] the cation is depicted in Figure 24
27
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+
Repeating the reaction at 110 degC for 36 h resulted in complete reduction of the aromatic ring
affording the salt [iPrNH2Cy][HB(C6F5)3] 24 in 93 yield (Table 21 entry 1) Monitoring the
reaction in a J-Young tube by 1H NMR spectroscopy at 110 degC showed the gradual growth of the
cyclohexyl methylene resonances with the corresponding consumption of aromatic signals
(Figure 25)
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($)
12 h
9 h
6 h
3 h
15 h
05 h
$
HB HA
28
The hydrogenation protocol was applied to PhCyNH and Ph2NH affording [Cy2NH2][HB(C6F5)3]
25 in yields of 88 and 65 respectively (Table 21 entry 2) Monitoring the reaction of Ph2NH
at 24 h intervals by 1H NMR spectroscopy did not show evidence for formation of PhCyNH
presumably this indicates that complete hydrogenation of both arene rings occurs prior to
addition of the first equivalent of hydrogen to another molecule of Ph2NH In addition to the
NMR spectroscopy data formulation of 24 and 25 were determined via X-ray crystallography
(Figure 26)
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right)
In an analogous fashion further substrates explored in such reductions included iPrNH(2-
MeC6H4) iPrNH(4-RC6H4) (R = Me OMe) iPrNH(3-MeC6H4) and iPrNH(35-Me2C6H3)
affording the arene-reduced products [iPrNH2(2-MeC6H10)][HB(C6F5)3] 26 [iPrNH2(4-
RC6H10)][HB(C6F5)3] (R = Me 27 OMe 28) [iPrNH2(3-MeC6H10)][HB(C6F5)3] 29 and
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] 210 in yields of 77 73 61 82 and 48 respectively (Table
21 entries 3 - 5) In cases where the hydrogenation reactions yield a chiral centre a mixture of
diastereomers was observed
Previously the Stephan group reported the catalytic hydrogenative ring-opening of cis-123-
triphenylaziridine using 5 mol B(C6F5)3 and H2 (4 atm) to give PhNHCHPhCH2Ph in 15 h at
120 degC94 In the following case however employing one equivalent of B(C6F5)3 at 110 ordmC for 96
h resulted in reduction of the N-bound phenyl ring yielding the salt
[CyNH2CHPhCH2Ph][HB(C6F5)3] 211 (Table 21 entry 6) The 1H NMR data were in
agreement with formulation of the cation fragment with notable resonances at 588 and 461
ppm ascribed to the NH2 and methine groups respectively in addition to the phenyl
29
cyclohexyl methylene and BH signals 11B and 19F NMR spectra displayed resonances
characteristic of the [HB(C6F5)3]- anion
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts
30
Reduction of the imine PhN=CMePh to the corresponding amine has also been previously
reported to occur upon exposure of the imine to H2 using 10 mol B(C6F5)392 Under the same
conditions heating the substrate in the presence of one equivalent of B(C6F5)3 for 96 h gave
reduction of the N-bound aromatic ring affording the species [PhCH(Me)NH2Cy][HB(C6F5)3]
212 (Table 21 entry 7) Similarly reduction of 14-C6H4(N=CMe2)2 was observed on heating
for 72 h in the presence of two equivalents of B(C6F5)3 yielding 64 of the product [14-
C6H10(iPrNH2)2][HB(C6F5)3]2 213 (Table 21 entry 8) Aromatic reduction of the bis-arene (14-
C6H4iPrNH)2CH2 with two equivalents of B(C6F5)3 was also achieved affording [(14-
C6H10iPrNH2)2CH2][HB(C6F5)3]2 214 in 76 yield (Table 21 entry 9)
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates
Although this reaction is stoichiometric in B(C6F5)3 hydrogenation of one arene ring takes up
three equivalents of H2 In an attempt to effect reactivity using sub-stoichiometric combinations
of the Lewis acid 5 mol B(C6F5)3 was combined with iPrNHPh pressurized with H2 (4 atm)
and heated at 120 degC After 24 h 1H NMR data yielded complete conversion of the borane to the
[HB(C6F5)3]- anion with only 5 mol conversion of the aniline to the [iPrNH2Cy]+ cation The
remaining 95 of the initial aniline was unaltered Increasing the H2 pressure to 80 atm did not
improve reactivity The inability of the system to turnover could be explained by pKa values of
the conjugate acid for example iPrNHPh has a pKa value of 58 in H2O while the hydrogenated
product has a pKa of about 10 - 11 in H2O (iPr2NH2 pKa 1105 in H2O) thus preventing
reversible activation of H2253-254
Furthermore efforts to hydrogenate the arene ring of iPrNHPh using pre-H2 activated FLPs
[tBu3PH][HB(C6F5)3] [Mes3PH][HB(C6F5)3] and tBu2P(H)(C6F4)B(H)(C6F5)2 did not result in
any observable reactivity by NMR spectroscopy However the stoichiometric combination of the
zwitterion Mes2P(H)(C6F4)B(H)(C6F5)2 evolved H2 at elevated temperatures and ca 10 of
[iPrNH2Cy]+ was observed Similarly 10 mol of the catalyst combination 18-
bis(diphenylphosphino)naphthalene and B(C6F5)3 gave 10 of aromatic reduction as a result of
the borane
Stoichiometric reactions of B(C6F5)3 and the anilines (p-CH3PhO2S)NHPh tBuNH(C6F5) Boc-
NHPh EtNHPh imines 26-(Me2C6H3)N=C(H)Ph PhN=CMe(p-EtOPh) phenols TMSOPh
31
tBuOPh tBuO(p-CF3C6H4) tBuO(p-FC6H4) hydrazine PhNH-NHPh 18-naphthosultam Ph3P
ethers (p-FPh)2O and CF3SPh did not evidence hydrogenation of the arene ring under the
optimized reaction conditions Furthermore the reactivity of iPrNHPh with the boranes BPh3
MesB(C6F5)2 MesB(p-C6F4H)2 PhB(C6F5)2 B(p-C6H4F)3 and B(o-C6H4CF3)3 did not activate
H2 or hydrogenate the aniline arene ring
223 Mechanistic studies for aromatic hydrogenation reactions
2231 Deuterium studies
To gain mechanistic insight into the presented transformation tBuNHPh was combined in a J-
Young tube with an equivalent of B(C6F5)3 in C6H5Br and exposed to D2 (2 atm) at 25 degC After
standing for 12 h multinuclear NMR data certainly indicated heterolytic activation of D2 The 2H
NMR spectrum gave a broad singlet at 658 ppm assigned to a N-D bond and a broad resonance
at 326 ppm attributed to a B-D bond (Figure 27 bottom-left) In addition to the 11B and 19F
NMR spectra these data supported formation of [tBuNHDPh][DB(C6F5)3] 21-d2 After heating
the sample for 3 h at 110 degC the 2H NMR revealed significant diminishing in the B-D resonance
while the N-D resonance was visibly unaltered (Figure 27 top-left) The 1H NMR spectrum of
the corresponding sample evidenced a broad quartet at 325 ppm (1JB-H = 78 Hz) representative
of a B-H bond (Figure 27 top-right) This B-H resonance is absent in the 1H NMR spectrum of
the sample at RT after 24 h (Figure 27 bottom-right)
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right)
Overall the following NMR studies are suggestive of reversible D2 activation in which at
elevated temperatures proton and deuteride from the nitrogen and boron centres of 21-d2
110 degC ND 110 degC BH (3 h) (3h) BD
RT ND BD RT (24 h) (24 h)
32
respectively combine releasing H-D The H-D gas is subsequently reactivated by the free amine-
borane FLP giving rise to [tBuND2Ph][HB(C6F5)3] (Scheme 25)
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD
2232 Variable temperature NMR studies
As supported by the aforementioned deuterium studies the reversible nature of H2 activation by
the aromatic amines and B(C6F5)3 is consistent with observation of species 21 as the initial
product of hydrogenation This is followed by evolution and reactivation of H2 allowing access
to the arene reduced species 23 at elevated temperatures (Scheme 26)
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23
This aspect of reversible H2 acitvation was further verified by variable temperature NMR studies
of the adduct (iPrNHPh)B(C6F5)3 24rsquo under H2 from 45 degC to 115 degC in C6D5Br As temperature
was increased both 11B and 19F NMR spectra displayed resonances pertaining to gradually
dissociating B(C6F5)3 and formation of the [HB(C6F5)3]- anion This is evidenced in Figure 28
by 11B NMR spectroscopy showing liberated B(C6F5)3 at 115 degC (11B δ 53 ppm) and progression
of the resonance at -25 ppm assignable to [HB(C6F5)3]- indicating formation of 24 It is
important to note that the [HB(C6F5)3]- resonance observed at the initiation of the reaction is
attributable to reversible hydride abstraction from the iPr substituent on the aniline
33
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-)
2233 Theoretical calculations
The mechanism of this study is proposed based on quantum chemical calculations performed by
Professor Stefan Grimme at Universitaumlt Bonn Germany Quantum chemical calculations were
performed at the dispersion-corrected meta-double hybrid level (PW6P95 functional) employing
large triple-zeta type basis sets and TPSS-D3 optimized geometries This final theoretical level
denoted as PWP95-D3def2-TZVPPTPSS-D3def-TZVP provides reaction energies with an
estimated accuracy of about 1 - 2 kcalmol Solvation effects of toluene were considered using
the COSMO-RS continuum solvation model255
Theoretical studies indicate a mechanism that supports reactivity to initiate by dissociation of the
weak amine-borane adduct At this stage the FLP could follow two reaction pathways (Figure
29) At moderate temperatures the FLP undergoes splitting of H2 to yield the salt 21 computed
to be 97 kcalmol lower in energy than the amine-borane adduct However the free enthalpy
difference for this species is close to zero hence under equilibrium conditions it can be
considered as a resting state of the reaction This minor difference in free enthalpy is in
agreement with reversible D2 activation results presented earlier using tBuNHPh and B(C6F5)3
45 degC
75 degC
95 degC
65 degC
115 degC
55 degC
85 degC
105 degC
34
An alternative reaction pathway follows at elevated reaction temperatures In this case the
dissociated amine rotates to position the arene para-carbon towards the boron atom creating a
van der Waals complex that is stabilized by significant pi-stacking with a C6F5 group This
complex creates a classical FLP with an electric field to polarize the entrapped H2 and effect
heterolytic splitting at a relatively low energy barrier of 87 kcalmol The free enthalpy for H2
activation relative to the resting state is computed to be 212 kcalmol certainly supporting the
elevated temperatures required to effect this reactivity
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol)
At the transition state the H-H distance is calculated to be about 097 Aring This bond is
significantly elongated compared with PB FLPs where the bond distance ranges between 078
and 080 Aring thus signifying a delayed transition state The corresponding H-H and C-H covalent
Wiberg bond orders are 033 and 041 respectively The B-H bond order is 063 indicating
approximately half-broken and half-formed bonds in the transition state88 256
21
23
35
The resulting intermediate [tBuNHC6H6][HB(C6F5)3] (CH-intermediate) is an ion pair showing
an sp3 hybridized para-carbon and an almost planar tBuNH=C unit in the cation shown in Figure
29 This species has similar energy and free enthalpy to the arene-B(C6F5)3 van der Waals
compound The complexity of subsequent hydrogenation steps to yield 23 has limited further
computations
It is noteworthy that prolonged heating of the more basic amine iPr2NPh with B(C6F5)3 under H2
only yields [iPr2NHPh][HB(C6F5)3] 215 This suggests that the greater basicity of the nitrogen
centre in iPr2NPh (Et2NHPh pKa 66 in H2O) stabilizes 215 thereby inhibiting access to the
amine-borane FLP and subsequent arene reduction (iPrNHPh pKa 58 in H2O)253-254 The overall
proposed reaction mechanism has been summarized in Scheme 27 Observation of the partially
hydrogenated cation [3-(C6H9)NH2iPr]+ illustrated in Figure 24 is presumed to be a result of H2
activation at the ortho-carbon of the arene ring
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts
224 Aromatic hydrogenation of substituted N-bound phenyl rings
2241 Fluoro-substituted rings and C-F bond transformations
Determining functional group tolerance of the demonstrated aromatic hydrogenations reaction
of the fluoro-substituted aniline (2-FPh)NHiPr with B(C6F5)3 under H2 indicated approximately
30 of the salt [(2-FPh)NH2iPr][HB(C6F5)3] after 31 h at RT Heating the sample at 110 degC for
36
24 h afforded a white solid 216a isolated in 59 yield (Scheme 28 a) Multinuclear NMR
spectroscopy revealed approximately 95 of the product consisted of [CyNH2iPr][FB(C6F5)3]
216a Spectral parameters of the cation were in agreement with that of compound 24 The
fluoroborate [FB(C6F5)3]- anionic fragment gave a broad signal at 055 ppm in the 11B NMR
spectrum and four 19F resonances were observed by 19F NMR spectroscopy at -1370 -1612 -
1669 and -1796 ppm The remaining 5 of the reaction mixture consisted of [(2-
FC6H10)NH2iPr][HB(C6F5)3] 216b Single crystals of 216a suitable for X-ray diffraction were
obtained and the structure is shown in Figure 210
Figure 210 ndash POV-Ray drawing of 216a
In a similar fashion heating the reaction of (3-FPh)NHiPr with B(C6F5)3 under H2 after 72 h
afforded the reduced product in 77 yield Approximately 95 of the salt consisted of 216a
and the remainder as [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b (Scheme 28 b) Indeed these
examples illustrate tandem B(C6F5)3 mediated arene hydrogenation and C-F bond activation
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a
37
Analogous reactivity with (4-FPh)NHiPr gave partial hydrogenation of the ring after 72 h
forming the 3-cyclohexenyl derivative [(4-FC6H8)NH2iPr][HB(C6F5)3] 218 in 62 yield
(Scheme 29) In addition to the expected resonances a diagnostic doublet of triplets in the 1H
NMR at 495 ppm and doublet at 1584 ppm (1JC-F = 255 Hz) in the 13C1H NMR spectra
certainly indicate an unsaturated C=C bond with the fluorine atom still intact This was
unambiguously confirmed by X-ray crystallography (Figure 211) It is important to note that
approximately 20 of the isolated product consisted of 216a indicating a much reduced rate of
arene hydrogenation and C-F bond activation in comparison to ortho- or meta-F substituted
anilines In these two cases intial H2 activation is expected to occur through the resonance form
in which the lone pair is at the para carbon (Scheme 27) However in the case of para-F
substituted aniline H2 activation is speculated to preferentially occur through the resonance
structure in which the negative charge is at an ortho carbon This proposal is ascribed to the
electron-withdrawing fluoro substituent which removes electron density from the para position
The partially hydrogenated product 218 is analogous to the cation [3-(C6H9)NH2iPr]+ presented
in Figure 24 in which H2 activation is suggested to initiate at the ortho carbon
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218
Figure 211 ndash POV-Ray drawing of 218
38
In light of recent findings121 a postulated mechanism implies that after reduction of the aromatic
ring B(C6F5)3 activates the C-F bond provoking nucleophilic addition of hydride from a
[HB(C6F5)3]- anion and liberating B(C6F5)3 for further reactivity Interaction of B(C6F5)3 with C-
F bonds were spectroscopically observed in a 11 combination of B(C6F5)3 and CF3-subtituted
anilines In this respect separate combinations of ortho- or para-F3CPhNH(iPr) and B(C6F5)3 in
C6D5Br gave a 19F NMR spectrum showing four broad resonances with a para-meta gap of 86
ppm and a diagnostic broad singlet assignable to a B-F resonance at -1800 ppm The broad
nature of these resonances and absence of a boron resonance in the 11B NMR spectrum do not
indicate formal C-F bond cleavage rather the data supports reversible B(C6F5)3-CF3
interaction121
2242 Methoxy-substituted rings and C-O bond transformations
Reactivity of FLP systems with oxygen-based substituents is noticeably limited due to high
oxophilicity of electrophilic boranes72 171 However recent findings have been reported on
lability of B-O adducts Stephan et al reported that the ethereal oxygen of the borane-oxyborate
(C6F5)2BCH(C6F5)OB(C6F5)3 derived from the reaction of FLPs with syn-gas activates H2 with
the B(C6F5)2 fragment117 Furthermore Et2O effects H2 activation with B(C6F5)3 and was shown
to be an efficient catalyst in the hydrogenation of olefins257 In an effort to further explore the
scope of the presented metal-free aromatic reductions the arene hydrogenation of anilines with
methoxy substituents was attempted
The combined toluene solution of B(C6F5)3 and the para-methoxy substituted imine (p-
CH3OC6H4)N=CCH3Ph was pressurized with H2 (4 atm) and heated at 110 degC for 48 h This
resulted in the formation of a new white crystalline product assigned to
[(C6H10)NHCH(CH3)Ph][HB(C6F5)3] 219 isolated in 30 yield (Scheme 210) Indeed the 1H
NMR spectrum indicated consumption of N-bound aromatic resonances concomitant with the
appearance of two inequivalent doublet of doublets observed at 447 and 374 ppm with the
corresponding 13C1H NMR resonances observed at 652 and 647 ppm respectively These
peaks are assignable to two inequivalent bridgehead CH groups of the resulting bicyclic
ammonium cation The 11B and 19F NMR spectra were in accordance with the presence of
[HB(C6F5)3]- as the anion X-ray diffraction studies further confirmed the bicyclic structure of
the product and the identity of the anion (Figure 212)
39
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219
Figure 212 ndash POV-Ray drawing of 219
In an effort to appreciate the importance of the position of the methoxy substituent on the arene
ring the separate reactions of ortho- and meta-methoxy substituted (CH3OC6H4)NHCH(CH3)Ph
with B(C6F5)3 were attempted under the established hydrogenationtransannulation protocol In
both cases hydrogenation of the N-bound phenyl group was observed although no
transannulation was achieved The amine (o-CH3OC6H4)NHCH(CH3)Ph gave cis and trans
mixtures of [(2-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 220 isolated in 92 yield In contrast
to fluorine abstraction from the ortho carbon position shown in Scheme 28 the methoxy
substituent in this case is not abstracted from the reduced ring due to steric effects preventing
B(C6F5)3 from binding to the substituent However the meta-substituted analogue resulted in C-
O bond cleavage yielding [(C6H11)NH2CH(CH3)Ph][HB(C6F5)3] 212 in 65 isolated yield
(Scheme 211) Ring closure was not obtained for this particular case due to ring strain of the
anticipated product Crystals of 220 suitable for X-ray crystallography were obtained and shown
in Figure 213
40
HB(C6F5)3
NH
OCH3
B(C6F5)3
Ph
+ CH3OH
NH2
OCH3
Ph
NH2Ph
HB(C6F5)3
NHPh
OCH3
220
212
H2
B(C6F5)3
H2
Scheme 211 ndash Synthesis of 220 and 212
Figure 213 ndash POV-Ray drawing of trans-220
In the case of the para-methoxy substituted imine B(C6F5)3 has participated in tandem arene
hydrogenation and transannulation to ultimately afford a 7-azabicyclo[221]heptane derivative a
bicyclic substructure of biological importance258 Unfortunately further expansion of the
substrate scope was not successful giving only the H2 activation product or arene hydrogenation
Such substrate examples include para-methoxyanilines with a methyl substituent at either the
ortho or meta position other para substituents such as HCF2O PhO2S and Br tertiary amine 4-
methoxy-N-phenyl-N-(1-phenylethyl)aniline
22421 Mechanistic studies for C-O and B-O bond cleavage
Studying the mechanism to form the 7-azabicyclo[221]heptane ammonium hydridoborate salt
219 the possibility of an intra- or intermolecular protonation of the methoxy group was initially
41
disproved by heating a toluene sample of the independently synthesized ammonium borate salt
trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] 221a at 110 degC (Scheme 212) No reaction
was evidenced by 1H 11B and 19F NMR spectroscopy However similar treatment of trans-[(4-
CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 221b at 110 degC prompted release of H2 as evidenced
by the 1H NMR signal at 45 ppm eventually giving compound 219 after 12 h at 110 degC
(Scheme 212)
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b)
To verify the liberation of CH3OH in the presented reactions the synthesis of 219 was repeated
starting from the free amine trans-[(4-CH3OC6H10)NHCH(CH3)Ph and B(C6F5)3 under H2
(Figure 214 a) After one week at RT the volatiles were transferred under vacuum from the
reaction vessel into a J-Young tube and the 1H NMR spectrum showed evidence of CH3OH
although a yield was not obtained
42
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c)
This observation implies that ring closing to yield the 7-azabicyclo[221]heptane ammonium
cation does not proceed by intra- or intermolecular protonation of the methoxy group rather
transannulation proceeds via intramolecular nucleophilic attack of the para-carbon by the amine
nitrogen while B(C6F5)3 captures the methoxide fragment To further support this proposed
mechanism the independently synthesized amine trans-(4-CH3OC6H10)NHiPr was treated with
an equivalent of B(C6F5)3 in the absence of H2 (Scheme 213) Interestingly after heating for 2 h
the reaction resulted in quantitative formation of a new product 222 with a sharp 11B resonance
at -242 ppm and 19F resonances at -1354 -1626 and -1668 ppm consistent with the formation
of the borane-methoxide anion [CH3OB(C6F5)3]- The 1H NMR data signified formation of the
diagnostic bridgehead CH protons at 413 ppm The combination of NMR spectroscopy
elemental analysis and X-ray diffraction studies evidenced the formation of compound 222 as
the bicyclic salt [(C6H10)NHiPr][CH3OB(C6F5)3] (Figure 215)
a)
b)
c)
43
Figure 215 ndash POV-Ray drawing of 222
Heating 222 at 110 degC in the absence of H2 eventually results in CH3OH liberation and rapid
degradation of the borane to CH3OB(C6F5)2 and C6F5H In the presence of H2 however 222 is
transformed to 223 with the liberation of CH3OH (Scheme 213) This observation implies that
the ammonium cation of 222 protonates the methoxide bound to boron liberating methanol and
regenerating B(C6F5)3 which undergoes FLP type H2 activation with the bicyclic amine
generating 223 Compound 223 was also prepared from the aniline p-CH3OC6H4NHiPr The
liberated CH3OH was isolated although not quantified and observed by 1H NMR spectroscopy
(Figure 214 b) Interestingly a similar protonation pathway has been previously proposed in a
study by Ashley and OrsquoHare whereby the stoichiometric hydrogenation of CO2 using 2266-
tetramethylpiperidine (TMP) and B(C6F5)3 was reported The authors proposed B-O bond
cleavage of [CH3OB(C6F5)3]- to occur through protonation by the 2266-
tetramethylpiperidinium counter cation259 Additionally most recently Ashley et al proposed
the metal-free carbonyl reduction of aldehydes to possibly proceed through oxonium protonation
of the boron-alkoxide anion [ROB(C6F5)3]-260
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3
44
Despite evidence for the protonation pathway contribution by a second pathway involving the
[CH3OB(C6F5)3]- anion and B(C6F5)3 acting as a FLP to activate H2 cannot be disregarded In
this respect a toluene solution of [NEt4][CH3OB(C6F5)3] and 5 mol B(C6F5)3 were exposed to
H2 (4 atm) at 110 degC After heating for 2 h the 11B and 19F NMR spectra revealed complete
consumption of the [CH3OB(C6F5)3]- anion along with emergence of peaks corresponding to the
H2 activation product [NEt4][HB(C6F5)3] and CH3OH (Scheme 214) This latter mechanism
provides an alternative path to the anion of 223 This type of system draws analogy to H2
activation by the earlier mentioned BO FLP (C6F5)2BCH(C6F5)OB(C6F5)3 suggesting H2
cleavage gives protonated oxygen and borohydride117
Gradual decomposition of the borane catalyst due to CH3OH was also observed as the amine is
not present to displace CH3OH from B(C6F5)3 consequently hindering its decomposition The
pKa of hydroxylic substrates have been shown to be significantly activated by coordination to
B(C6F5)3 generating strong Broslashnsted acids with pKa values comparable with HCl (84 in
acetonitrile)261
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3
Collectively it may be read that compound 219 is formed by initial hydrogenation of the imine
(p-CH3OC6H4)N=CCH3Ph C=N double bond followed by reduction of the arene ring affording
the cyclohexylamine The amine and borane can activate H2 to give the ammonium salt albeit at
elevated temperatures this is reversible allowing the borane to activate the methoxy substituent
and induce transannulation effecting C-O bond cleavage (Scheme 215) Subsequent conversion
of the generated methoxy-borate anion to the hydridoborate anion proceeds under H2 following
the pathways presented in Schemes 213 and 214
45
NH2
R
OCH3
110 oC
NHR
OCH3
NHR
OCH3
(F5C6)3B
+ H2
B(C6F5)3
H2
HB(C6F5)3
- H2HN
R
CH3OB(C6F5)3
+ H2
HB(C6F5)3
HNR
- CH3OH
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane
225 Aromatic hydrogenation of N-heterocyclic compounds
While seeking to extend the scope of aromatic reductions attention was focused on a series of
mono- and di-substituted pyridines quinolines and several other N-heterocycles In this regard
the aromatic hydrogenation of a variety of N-based heterocycles was explored using
stoichiometric combinations of B(C6F5)3 in the presence of H2 (4 atm)
2251 Hydrogenation of substituted pyridines
Detailed studies on the effects of increased steric bulk on pyridine249 and their reactivity with
B(C6F5)3 to activate H2248 at room temperature have been previously reported Stoichiometric
combination of the Lewis base 26-diphenylpyridine and the Lewis acid B(C6F5)3 do not show
evidence of a donor-acceptor interaction by NMR spectroscopy in contrast a reversible adduct is
observed with 26-lutidine Exposure of either combination of 26-diphenylpyridine or 26-
lutidine and B(C6F5)3 under H2 (4 atm) at room temperature activate H2 affording the
corresponding pyridinium hydridoborate salts
Nonetheless heating a mixture of 26-diphenylpyridine and B(C6F5)3 under H2 (4 atm) at 115 degC
for 16 h gives a new product isolated in 92 yield (Table 22 entry 1) The 11B NMR data in
CD2Cl2 displayed a doublet at -246 ppm and three resonances in the 19F NMR spectrum
observed at -1340 -1634 and -1666 ppm confirmed the presence of the [HB(C6F5)3]- anion
The 1H NMR spectrum showed a broad singlet at 590 ppm attributable to the NH2 group
multiplets at 453 and 226 - 189 ppm in addition to signals assignable to the phenyl and BH
46
groups These data were consistent with the formulation of the salt [26-
Ph2C5H8NH2][HB(C6F5)3] 224 Furthermore the 1H NMR data revealed a de of 91 favouring
the meso-diastereomer an assignment that was confirmed via NMR spectroscopy and the
molecular structure shown in Figure 216 (left) In a similar fashion the reaction of 26-lutidine
with B(C6F5)3 under H2 at 115 degC for 60 h afforded the corresponding salt [26-
Me2C5H8NH2][HB(C6F5)3] 225 in 84 yield (Table 22 entry 1) with a de of 80 also
favouring the meso-diastereomer (Figure 216 right) The preferred diastereoselectivity is
consistent with the known ability of B(C6F5)3 to effect epimerization of chiral carbon centres
adjacent to nitrogen by a process previously described to involve hydride abstraction and
redelivery262
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right)
The substrate ethyl 2-picolinate was exposed to the hydrogenation conditions giving a B(C6F5)3
adduct of the reduced substrate (2-(EtOCO)C5H9NH)B(C6F5)3 226 isolated in 74 yield after
36 h (Table 22 entry 2) The 11B NMR spectrum in CD2Cl2 showed a broad singlet at -486 ppm
and 15 inequivalent 19F resonances which were consistent with adduct formation between the
boron and nitrogen centres inhibiting rotation about the bond
47
Table 22 ndash Hydrogenation of substituted pyridines
Multinuclear NMR spectra of 226 displayed the presence of two diastereomers in a 11 ratio
Most distinguishable were the 13C1H resonances at 1674 and 1712 ppm attributable to the
OCO-ester groups and the 1H NMR signals at 418 and 424 ppm arising from the methine
protons Furthermore 1H1H NOESY experiments confirmed the assignment of these peaks to
the respective RSSR and RRSS diastereomers Independent reaction of B(C6F5)3 with the
optically pure piperidine S-2-(EtOCO)C5H9NH at -30 degC in CD2Cl2 afforded the preferential
formation of the SS-diastereomer of 226 However on warming to room temperature over 18 h
racemization at nitrogen eventually afforded a 11 mixture of the SS and SR diastereomers
Even though the pyridine-borane adduct of 2-phenylpyridine has been isolated and characterized
this adduct is reversed at 115 degC Reduction of the substrate using B(C6F5)3 and H2 gave a
mixture of two products isolated in 54 overall yield after 48 h (Table 22 entry 3) A broad 11B
NMR signal at -391 ppm together with a doublet at -240 ppm were consistent with the
48
presence of the adduct (2-PhC5H9NH)B(C6F5)3 227a and the ionic pair [2-
PhC5H9NH2][HB(C6F5)3] 227b in a 41 ratio respectively
The formulation of 227a is further supported by NMR data revealing two distinctively broad
NH singlets in the 1H NMR spectrum at 555 and 581 ppm attributable to a 71 ratio of the
RSSR and RRSS diastereomers The RSSR diastereomer was the more abundant form as
evidenced by NMR and X-ray crystallographic data (Figure 217)
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring
Interestingly the preferential formation of this diastereomer was evidenced by 1H19F HOESY
NMR spectroscopy through intramolecular π-π stacking interactions of the Ph and C6F5 groups
in addition to interactions between the C-H and N-H groups of piperidine and ortho-fluoro
groups of B(C6F5)3 (Figure 218) Identity of compound 227b was confirmed based on
agreement of spectral parameters with the NH2 methine and methylene groups
49
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups
The presence of adduct 227a raised the question about dissociation of the B-N bond and
possible participation of the liberated borane in further pyridine hydrogenation To probe this a
toluene solution of 2-phenylpyridine and 10 mol of 227 was exposed to H2 (4 atm) at 110 degC
After heating for 24 h 1H NMR spectroscopy did not indicate consumption of the pyridine
reagent Similarly repeating the hydrogenation of 2-phenylpyridine with 10 mol B(C6F5)3 did
not result in catalysis
2252 Hydrogenation of substituted N-heterocycles
Attempting to extend the aromatic hydrogenation of N-heterocycles beyond pyridine substrates
attention was focused to 1234-tetrahydroquinoline derivatives which have been reported to
result from the catalytic hydrogenation of N-heterocycles98 In examining the structure of
tetrahydroquinoline the carbocyclic ring fused to the N-heterocycle was observed to be similar
to a secondary aniline (Figure 219) Thus emerging the avenues of previous reports on catalytic
hydrogenation of substituted quinolines and most recent findings on the stoichiometric reduction
of anilines the complete homogeneous hydrogenation of N-heteroaromatic compounds was
explored
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring
50
Exposure of 2-methylquinoline and B(C6F5)3 to H2 (4 atm) at 115 degC for 48 h was found to effect
hydrogenation of not only the N-heterocycle but also the carbocyclic ring to yield [2-
MeC9H15NH2][HB(C6F5)3] 228 in 67 (Table 23 entry 1) In a similar fashion both rings of 2-
phenylquinoline were reduced in the same time frame to give [2-PhC9H15NH2][HB(C6F5)3] 229
in 95 yield (Table 23 entry 1)
The 1H NMR spectra for 228 and 229 exhibited characteristic chemical shifts corresponding to
NH2 methine and methylene groups Both compounds 228 and 229 were produced as mixtures
of diastereomers although in both cases the major isomer was crystallized and found to comprise
of 60 and 73 of the isolated products respectively The molecular structures show both
compounds exhibit SSSRRR stereochemistries in which one of the ring junctions adopts an
equatorial disposition while the other is axially disposed (Figure 220 a and b) Analogous
treatment of 8-methylquinoline with H2 and B(C6F5)3 in toluene for 48 h yielded [8-
MeC9H15NH2][HB(C6F5)3] 230 in 76 (Table 23 entry 1) 1H and 13C1H NMR data suggest
only the presence of the RRRSSS diastereomers (Figure 220 c)
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c)
a) b) c)
51
Table 23 ndash Hydrogenation of substituted N-heterocycles
The corresponding reduction of acridine results in isolation of the fully reduced tricyclic species
in 76 yield (Table 23 entry 2) The isolated product is obtained as a mixture of two isomers
one of which was characterized crystallographically as the salt [C13H22NH2][HB(C6F5)3] 231a
As shown in Figure 221 all ring junctions are equatorially positioned and thus the SRSRRSRS
diastereomers are assigned
Figure 221 ndash POV-Ray depiction of the cation for compound 231a
52
Interestingly a second product was isolated from the pentane work-up crystallographic data
showed it to be the adduct (C13H22NH)B(C6F5)3 231b (Figure 222) In this case however the
stereochemistries of the ring junctions adjacent to nitrogen are inverted affording the RRSSSSRR
diastereomers of the reduced acridine heterocycle Compound 231b was also independently
synthesized in 73 yield from a mixture of isomers of the neutral amine C13H22NH and
B(C6F5)3
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring
Although the substrates 23-dimethyl and 23-diphenylquinoxaline have two Lewis basic
nitrogen centres the reduction reactions required only one equivalent of B(C6F5)3 yielding the
piperazinium derivatives [23-(C4H6Me)2NHNH2][HB(C6F5)3] 232 and [23-
(C4H6Ph)2NHNH2][HB(C6F5)3] 233 in 59 and 55 yield respectively (Table 23 entry 3) In
the case of 232 a single set of diastereomers was observed and the NMR data were consistent
with ring junctions and methyl groups adopting equatorial dispositions In contrast the isolated
product 233 comprised of two diastereomers Crystallographic characterization of one
diastereomer showed the phenyl rings adopt equatorial positions while the ring junctions are
axial and equatorially disposed (Figure 223)
Figure 223 ndash POV-Ray depiction of the cation for compound 233
53
It is noteworthy that while the aromatic ring of the quinoxaline fragment is fully reduced the
phenyl substituents remain intact In a similar situation reduction of 78-benzoquinoline resulted
in the formation of [(C6H4)C7H12NH2][HB(C6F5)3] 234 in 55 yield (Table 23 entry 4) 1H
NMR spectroscopy evidenced a 41 mixture of two diastereomers in which reduction of the
pyridyl and adjacent carbocyclic ring were achieved while aromaticity of the ring remote from
the nitrogen atom was retained X-ray crystallography unambiguously confirmed the dominant
diastereomer 234a to have SRRS stereochemistry while the less abundant diastereomer 234b
showed SSRR stereochemistry (Figure 224)
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right)
Efforts to reduce the related heterocycle 110-phenanthroline in which a pyridyl ring is fused at
the 7 and 8 position of quinoline were undertaken employing one equivalent of B(C6F5)3 After
heating the solution for 14 h at 115 degC under H2 (4 atm) 1H NMR spectroscopy indicated
complete hydrogenation of the N-heterocycle in addition to loss of C6F5H and formation of a
four-coordinate boron centre with a 11B resonance observed at 302 ppm The [HB(C6F5)3]- anion
was not observed and further heating did not reveal hydrogenation of the carbocyclic ring
A second equivalent of B(C6F5)3 was added and the reaction was re-exposed to H2 (4 atm) for a
total of 96 h at 115 degC This resulted in isolation of [(C5H3N)(CH2)2(C5H8NH)B(C6F5)2]
[HB(C6F5)3] 235 in 73 yield (Table 23 entry 5) The 11B NMR spectrum revealed the
presence of two four-coordinate boron centres with resonances at 302 and -254 ppm The
former boron species exhibited six inequivalent fluorine atoms evidenced by 19F NMR
spectroscopy inferring the presence of two inequivalent fluoroarene rings where steric
congestion is inhibiting ring rotation at the B-N and B-C bonds The latter 11B NMR signal
together with the three corresponding 19F resonances arise from the [HB(C6F5)3]- anion X-ray
crystallography confirmed the formulation of 235 as the SRSRSR diastereomer present as 65
of the isolated reaction mixture (Figure 225)
54
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine
In the cationic fragment of compound 235 the boron centre is bound to two perfluoroarene rings
and is chelated by the pyridine and amine nitrogen atoms of partially reduced 110-
phenanthroline The B-N distances in the cation were found for B(1)-N(1)amine to be 1615(3) and
B(1)-N(2)pyridine 1598(3) Aring In this unique case as reduction of the heterocycle proceeds a
single pyridyl ring is initially reduced in which the resulting amine coordinates B(C6F5)3
resulting in loss of C6F5H and chelation of B(C6F5)2 by the pyridyl nitrogen centre affording the
cation (Scheme 216) The second equivalent of the borane remains intact and partakes in partial
hydrogenation of the carbocyclic ring Elimination of C6F5H followed by ring closure is
thermodynamically favoured due to formation of the five-membered borocycle
NN NN
B
B(C6F5)3
(C6F5)3B H
- C6F5H H2
235
(C6F5)2
Scheme 216 ndash Proposed reaction pathway for the formation of 235
Although this arene hydrogenation method is applicable to the presented N-heteroaromatic
substrates the reactivity was not successfully extended to 46-dimethyl-1-phenylpyrimidin-
2(1H)-one 2-methylindoline 3-methylindole 1-methylisoquinoline and carbazole
55
2253 Proposed mechanism for aromatic hydrogenation
The reductions described demonstrate the ability of B(C6F5)3 to mediate the complete aromatic
hydrogenation of a number of N-heterocycles It is clear that the products arise from reduction of
pyridyl andor aniline-type rings and in some cases affording a preferred set of diastereomers as
demonstrated by the ability of B(C6F5)3 to epimerize chiral centers alpha to nitrogen262 Efforts
to monitor several of the mixtures over the course of the reactions failed to provide unambiguous
mechanistic insight By analogy to computational studies presented for aniline hydrogenations
the need for elevated temperatures presumably reflects the fact that hybridizing the para-carbon
of the N-heterocycle is energetically uphill however once this is achieved there is an exothermic
route to the saturated amine Subsequent activation of H2 by the reduced amine and borane
affords the corresponding ammonium salt which is irreversible under the reaction conditions
thus precluding catalytic reduction This could simply be explained by Broslashnsted basicity of the
nitrogen centre An sp2 hybridized nitrogen has the lone pair in a p-orbital therefore it can
participate in resonance making it less basic as opposed to sp3 hybridization which does not have
a p-orbital (pyridine pKa 52 quinoline pKa 492 piperidine pKa 112 all values are in H2O)
While the reactions are nominally stoichiometric multiple turnovers of H2 activation are
achieved For example eight equivalents of H2 are taken up by acridine in the formation of 231
2254 Approaches to dehydrogenation
Although hydrogenation of aromatic substrates is appealing the reversible reaction
dehydrogenation of the products with aim at obtaining a molecular dihydrogen storage device
became a topic of interest Heating compound 231 at 115 degC in a vacuum sealed J-Young tube
did not evolve H2 As an alternative approach the neutral amine C13H22NH was combined with
the electrophilic boranes B(C6F5)3 B(p-C6F4H)3 or (12-C12F9)B(C6F5)2 and heated under
vacuum After 24 h trace amounts of aromatic resonances corresponding to dehydrogenation of
the N-heterocycle and a single carbocyclic ring (five equivalents of H2) was observed by 1H
NMR spectroscopy It is important to note that this process did not liberate H2 rather amine and
B(C6F5)3 abstracted proton and hydride respectively regenerating 231 One can envision this
dehydrogenation process could possibly be applied to transfer hydrogenation of imines similar
to an earlier report by the Stephan group262
56
23 Conclusions
This chapter provides an account on the discovery of N-phenyl amine reductions under H2 using
an equivalent of B(C6F5)3 to yield the corresponding cyclohexylamine derivatives In these
reactions B(C6F5)3 mediates uptake of four equivalents of H2 terminating with a final FLP
activation of H2 affording the cyclohexylammonium salts A possible reaction pathway is
proposed based on experimental evidence and theoretical calculations The substrate scope is
extended to a variety of pyridyl- and aniline-type rings of N-heterocyclic compounds These
reductions represent the first example of homogeneous metal-free hydrogenation of aromatic
rings
Shortly after publishing the presented data on aromatic hydrogenations in two separate reports
the Stephan group communicated the partial reduction of polycyclic aromatic hydrocarbons
using catalysts derived from weakly basic phosphines263 or ethers257 with B(C6F5)3 Additionally
the Du group showed a borane catalyzed route to the stereoselective hydrogenation of
pyridines264
24 Experimental Section
241 General considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane hexane tetrahydrofuran dichloromethane and toluene (Sigma Aldrich) were
dried employing a Grubbs-type column system (Innovative Technology) degassed and stored
over molecular sieves (4 Aring) in the glovebox Bromobenzene (-H5 and -D5) were purchased from
Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring molecular
sieves prior to use Dichloromethane-d2 was purchased from Sigma Aldrich dried over CaH2 and
vacuum distilled onto 4 Aring molecular sieves prior to use Tetrahydrofuran-d8 and toluene-d8 were
purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to use Molecular
sieves (4 Aring) were purchased from Sigma Aldrich and dried at 140 ordmC under vacuum for 24 h
prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at 80 degC under high
vacuum before use Sodium methoxide and tetraethylammonium chloride were purchased from
Sigma Aldrich and dried under vacuum at 140 ordmC for 12 h prior to use
57
All substituted amines anilines quinolines pyridines and other N-heterocycles were purchased
from Sigma Aldrich Alfa Aesar or TCI Potassium tetrakis(pentafluorophenyl)borate and
hydrogen chloride (40 M in 14-dioxane) were purchased from Alfa Aesar The oils were
distilled over CaH2 and solids were sublimed under high vacuum prior to use The following
compounds were independently synthesized following the cited procedure265 unless indicated
otherwise N-tert-butylaniline266 NN-(14-phenylenebis(methylene))bis(tert-butylamine) N-
isopropyl-2-methylaniline N-isopropyl-4-methylaniline N-isopropyl-4-methoxyaniline N-
isopropyl-3-methylaniline N-isopropyl-35-dimethylaniline N-(1-phenylethylidene)aniline
N1N4-di(propan-2-ylidene)benzene-14-diamine 44-methylenebis(N-isopropylaniline) 2-
fluoro-N-isopropylaniline 3-fluoro-N-isopropylaniline 4-fluoro-N-isopropylaniline 4-methoxy-
N-(1-phenylethylidene)aniline 2-methoxy-N-(1-phenylethyl)aniline266 3-methoxy-N-(1-
phenylethyl)aniline266 and alkylation methods267 to prepare trans-(4-
CH3OC6H10)NHCH(CH3)Ph and trans-(4-CH3OC6H10)NHiPr
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Varian 400 MHz spectrometer equipped with an HFX AutoX triple resonance indirect
probe (used for 13C1H 19F experiments) or an Agilent DD2 500 MHz spectrometer Spectra
were referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm
for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) d8-tol (1H = 208 ppm for CH3 13C
= 13748 ppm for ipso carbon) d8-THF (1H = 358 ppm for OCH2 13C = 6721 ppm for OCH2)
or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in ppm and the
absolute values of the coupling constants (J) are in Hz NMR assignments are supported by 2D
and DEPT-135 experiments
Elemental analyses (C H N) were performed in-house employing a Perkin Elmer 2400 Series II
CHNS Analyzer H2 (grade 50) was purchased from Linde and dried through a Nanochem
Weldassure purifier column prior to use High resolution mass spectra (HRMS) were obtained
using an ABSciex QStar Mass Spectrometer with an ESI source MSMS and accurate mass
capabilities
242 Synthesis of compounds
Synthesis of [NEt4][CH3OB(C6F5)3] In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (100 mg 0195 mmol) in CH2Cl2 (10 mL) To the vial
58
Na OCH3 (105 mg 0195 mmol) was added and the reaction was allowed to mix for 3 h at RT
The salt Na CH3OB(C6F5)3 was isolated as a white solid and dried under vacuum (110 mg 0195
mmol gt99) Na CH3OB(C6F5)3 (110 mg 0195 mmol) in CH2Cl2 (10 mL) was subsequently
added to a 4 dram vial containing NEt4 Cl (323 mg 0195 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT for 16 h and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (125 mg
0186 mmol 95)
1H NMR (400 MHz CD2Cl2) δ 322 (q 3JH-H = 73 Hz 8H Et) 311 (s 3H OCH3) 142 (tm 3JH-H = 73 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 3JF-F = 20 Hz 2F o-C6F5)
-1636 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
256 (s BOCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1480 (dm 1JC-F = 240 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1364 (dm 1JC-F = 248 Hz CF) 1246 (br ipso-C6F5) 529 (Et) 519
(OCH3) 710 (Et) Elemental analysis was not successful after numerous attempts
Synthesis of [tBuNH2Ph][HB(C6F5)3] (21) In the glove box a 100 mL Teflon screw cap
Schlenk tube equipped with a stir bar was charged with a yellow solution of B(C6F5)3 (100 mg
0195 mmol) in pentane (7 mL) To the reaction tube N-tert-butylaniline (291 mg 0195 mmol)
was added immediately resulting in a pale orange cloudy solution The reaction tube was
degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2
(4 atm) at -196 ordmC After about 10 min of reaction time at RT white precipitate was observed in
the reaction vessel and the solution became colourless The tube was left to stir at RT for 12 h
The solvent was decanted and the white precipitate was washed with pentane (3 mL) dried under
vacuum and isolated (106 mg 0160 mmol 82)
1H NMR (400 MHz C6D5Br) δ 715 (br s 2H NH2) 712 (t 3JH-H = 73 Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 682 (d 3JH-H = 76 Hz 2H o-Ph) 369 (br q 1JB-H = 78 Hz 1H BH)
102 (s 9H tBu) 19F NMR (377 MHz C6D5Br) δ -1335 (br 2F o-C6F5) -1613 (br 1F p-
C6F5) -1650 (br 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 78 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1494 (dm 1JC-F = 238 Hz CF) 1382 (dm 1JC-F = 244
Hz CF) 1369 (dm 1JC-F = 247 Hz CF) 1309 (p-Ph) 1299 (m-Ph) 1237 (o-Ph) 1244 (ipso-
C6F5) 659 (tBu) 255 (tBu) (ipso-Ph was not observed) Anal calcd () for C28H17BF15N C
5071 H 258 N 211 Found C 5027 H 287 N 219
59
[tBuNHDPh][DB(C6F5)3] (21-d2) This compound was prepared similar to 21 using D2
19F NMR (377 MHz C6H5Br) δ -1332 (m 2F o-C6F5) -1609 (br 1F p-C6F5) -1646 (m 2F
m-C6F5) 11B NMR (128 MHz C6H5Br) δ -238 (s BD)
Synthesis of [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 (22) In a glove box a 100 mL Teflon
screw cap Schlenk tube equipped with a stir bar was charged with a solution of B(C6F5)3 (304
mg 0594 mmol) and NN-(14-phenylenebis(methylene))bis(tert-butylamine) (725 mg 0297
mmol) in toluene (4 mL) The reaction was degassed three times with a freeze-pump-thaw cycle
on the vacuumH2 line The reaction flask was cooled to -196 ordmC and filled with H2 (4 atm)
Immediate precipitation of a white solid was observed at RT The reaction mixture was stirred
overnight at 70 ordmC Pentane (10 mL) was added after which the supernatant was decanted The
residue was washed with pentane (5 mL) and dried in vacuo to give the product as a white
powder (374 mg 0297 mmol gt99)
1H NMR (400 MHz CD2Cl2) δ 727 (s 4H Ph) 595 (br s 4H NH2) 438 (s 4H CH2) 339
(br q 1JB-H = 83 Hz 2H BH) 162 (s 18H tBu) 19F NMR (377 MHz CD2Cl2) δ -1349 (m 3JF-F = 21 Hz 2F o-C6F5) -1635 (t 3JF-F = 21 Hz 1F p-C6F5) -1670 (m 2F m-C6F5) 11B
NMR (128 MHz CD2Cl2) δ -243 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz d8-THF )
δ 1493 (dm 1JC-F = 236 Hz CF) 1461 (quaternary C for C6H4) 1385 (dm 1JC-F = 243 Hz CF)
1374 (dm 1JC-F = 246 Hz CF) 1345 (br ipso-C6F5) 1314 (Ph) 595 (tBu) 461 (CH2) 259
(tBu) Anal calcd () for C51H30B2F30N2 C 4852 H 240 N 222 Found C 4882 H 269 N
252
Compounds 23 ndash 214 were prepared following a common procedure In the glove box a 25 mL
Teflon screw cap Schlenk tube equipped with a stir bar was charged with a yellow solution of
B(C6F5)3 (379 mg 740 μmol) and N-phenyl amine (740 μmol) in toluene (2 mL) The reaction
tube was degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and
filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube was placed in a 110
ordmC oil bath After the appropriate reaction time the toluene was removed under reduced pressure
resulting in crude pale yellow oil The oil was washed with pentane (6 mL) affording the product
as a white powder
60
[tBuNH2Cy][HB(C6F5)3] (23) N-tert-butylaniline (110 mg 740 μmol) reaction time 48 h
product (415 mg 620 μmol 84)
1H NMR (400 MHz C6D5Br) δ 507 (br 2H NH2) 355 (br q 1JB-H = 83 Hz 1H BH) 272 (m
1H N-Cy) 155 (m 2H Cy) 145 (m 2H Cy) 131 (m 1H Cy) 117 (m 3H Cy) 091 (s 9H
tBu) 090 (m 2H Cy) 19F NMR (377 MHz C6D5Br) δ -1327 (m 3JF-F = 21 Hz 2F o-C6F5)
1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1645 (m 2F m-C6F5) 11 B NMR (128 MHz C6D5Br) δ -
240 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 238 Hz
CF) 1382 (dm 1JC-F = 247 Hz CF) 1368 (dm 1JC-F = 247 Hz CF) 1354 (ipso-C6F5) 610
(tBu) 561 (N-Cy) 319 (Cy) 258 (tBu) 244 (Cy) 236 (Cy) Anal calcd () for
C28H23BF15N C 5025 H 346 N 209 Found C 4985 H 357 N 219
Synthesis of PhNHiPrB(C6F5)3 (24rsquo) In a glove box a 20 mL dram vial equipped with a
magnetic stir bar was charged with B(C6F5)3 (176 mg 0344 mmol) and N-isopropylaniline (465
mg 0344 mmol) in toluene (4 mL) All volatiles were removed and the crude oil was washed
with hexane (2 mL) The hexane portion was reduced in volume and placed in a -30 ordmC freezer
Colourless crystals were obtained (122 mg 0192 mmol 55)
1H NMR (400 MHz CD2Cl2 193K) δ 740 - 726 (m 5H Ph) 696 (br 1H NH) 416 (br m
1H iPr) 123 (br 3H iPr) 072 (br 3H iPr) 19F NMR (367 MHz CD2Cl2 193K) δ -1219 (m
1F o-C6F5) -1272 (m 1F o-C6F5) -1279 (m 2F o-C6F5) -1315 (m 1F o-C6F5) -1388 (m
1F o-C6F5) -1543 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F p-C6F5) -1575 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1625 (m 1F m-
C6F5) -1627 (m 1F m-C6F5) -1629 (m 1F m-C6F5) -1636 (m 1F m-C6F5) 11B NMR (128
MHz CD2Cl2 193K) δ -323 (s B-N) 13C1H NMR (101 MHz CD2Cl2 298K) δ 1478 (dm 1JC-F = 246 Hz CF) 1390 (dm 1JC-F = 242 Hz CF) 1365 (dm 1JC-F = 236 Hz CF) 1328
(ipso-Ph) 1301 (o-Ph) 1295 (p-Ph) 1227 (m-Ph) 556 (iPr) 195 (iPr) (ipso-C6F5 was not
observed) Anal calcd () for C27H13BF15N C 5011 H 202 N 216 Found C 4961 H 246
N 209
[iPrNH2Cy][HB(C6F5)3] (24) N-Isopropylaniline (100 mg 740 μmol) reaction time 36 h
product (481 mg 730 μmol 93) Crystals suitable for X-ray diffraction were grown from a
layered dichloromethanepentane solution at -30 ordmC
61
1H NMR (400 MHz C6D5Br) δ 510 (s 2H NH2) 356 (br q 1JB-H = 84 Hz 1H BH) 303 (m 1JH-H = 65 Hz 1H iPr) 276 (m 1H N-Cy) 156 (m 2H Cy) 147 (m 2H Cy) 134 (m 1H
Cy) 099 - 086 (m 5H Cy) 091 (d 1JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1330 (m 3JF-F = 21 Hz 2F o-C6F5) -1609 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-
C6F5) 11 B NMR (128 MHz C6D5Br) δ -239 (d 1JB-H = 84 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1483 (dm 1JC-F = 238 Hz CF) 1384 (dm 1JC-F = 247 Hz CF) 1369 (dm 1JC-F =
248 Hz CF) 1288 (ipso-C6F5) 567 (N-Cy) 498 (iPr) 294 (Cy) 241 (Cy) 240 (Cy) 189
(iPr) Anal calcd () for C27H21BF15N C 4949 H 323 N 214 Found C 4952 H 345 N
219
[Cy2NH2][HB(C6F5)3] (25) Method 1 N-Cyclohexylaniline (130 mg 740 μmol) reaction
time 36 h product (452 mg 650 μmol 88) Method 2 Diphenylamine (125 mg 740 μmol)
reaction time 96 h product (334 mg 480 μmol 65) Crystals suitable for X-ray diffraction
were grown from a concentrated solution in C6D5Br at RT
1H NMR (400 MHz C6D5Br) δ 498 (br s 2H NH2) 317 (br q 1JB-H = 86 Hz 1H BH) 247
(m 2H N-Cy) 122 (m 4H Cy) 111 (m 4H Cy) 099 (m 2H Cy) 070 - 046 (m 10H Cy)
19F NMR (377 MHz C6D5Br) δ -1332 (m 3JF-F = 20 Hz 2F o-C6F5) -1608 (t 3JF-F = 20 Hz
1F p-C6F5) -1648 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 86 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 241 Hz CF) 1380 (dm 1JC-F =
247 Hz CF) 1365 (dm 1JC-F = 248 Hz CF) 1264 (ipso-C6F5) 558 (N-Cy) 293 (Cy) 238
(Cy) 237 (Cy) Anal calcd () for C30H25BF15N C 5182 H 362 N 201 Found C 5217 H
386 N 212
[iPrNH2(2-MeC6H10)][HB(C6F5)3] (26) N-Isopropyl-2-methylaniline (111 mg 740 μmol)
reaction time 36 h product (398 mg 570 μmol 77) NMR data is reported for one isomer
1H NMR (400 MHz C6D5Br) δ 587 (br 2H NH2) 375 (br q 1JB-H = 82 Hz 1H BH) 318 (m
1H N-Cy) 313 (m 3JH-H = 62 Hz 1H iPr) 180 - 118 (m 9H Cy) 113 (d 3JH-H = 64 Hz
6H iPr) 086 (d 3JH-H = 62 Hz 3H Me) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21
Hz 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -237 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) partial δ
1485 (dm 1JC-F = 235 Hz CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF)
1236 (ipso-C6F5) 638 (N-Cy) 593 (iPr) 347 (Cy) 319 (Cy) 304 (CMeH) 291 (Cy) 210
62
(Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C 5021 H
359 N 214
[iPrNH2(4-MeC6H10)][HB(C6F5)3] (27) N-isopropyl-4-methylaniline (111 mg 740 μmol)
reaction time 36 h product (377 mg 540 μmol 73)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 83 Hz 1H BH) 317 (m 3JH-H = 64 Hz 1H iPr) 290 (m 1H N-Cy) 171 (m 2H Cy) 162 (m 2H Cy) 120 (m 3H
Cy) 110 (d 3JH-H = 64 Hz 6H iPr) 086 (d 3JH-H = 66 Hz 3H Me) 077 (m 2H Cy) 19F
NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1613 (t 3JF-F = 21 Hz 1F
p-C6F5) -1652 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -236 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 247
Hz CF) 1367 (dm 1JC-F = 250 Hz CF) 562 (N-Cy) 495 (iPr) 319 (Cy) 304 (CMeH) 291
(Cy) 210 (Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found
C 5014 H 348 N 209
[iPrNH2(4-MeOC6H10)][HB(C6F5)3] (28) N-Isopropyl-4-methoxyaniline (122 mg 740
μmol) reaction time 36 h product (308 mg 450 μmol 61)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 346 (br
4H OMe and CHOMe) 299 (br m 1H N-Cy) 237 (m 1H iPr) 162 (m 2H Cy) 129 (m
2H Cy) 107 (m 4H Cy) 081 (d 3JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1338 (m 3JF-F = 21 Hz 2F o-C6F5) -1623 (t 3JF-F = 21 Hz 1F p-C6F5) -1659 (m 2F m-
C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1484 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 247 Hz CF) 1367 (dm 1JC-F =
247 Hz CF) 1243 (ipso-C6F5) 636 (OMe) 583 (CHOMe) 551 (N-Cy) 497 (iPr) 267 (Cy)
246 (Cy) 183 (iPr) Anal calcd () for C28H23BF15NO C 4908 H 338 N 204 Found C
4945 H 329 N 230
[iPrNH2(3-MeC6H10)][HB(C6F5)3] (29) N-Isopropyl-3-methylaniline (111 mg 740 μmol)
reaction time 36 h product (406 mg 610 μmol 82)
1H NMR (400 MHz C6D5Br) δ 547 (br 2H NH2) 369 (br q 1JB-H = 80 Hz 1H BH) 320 (m
1H iPr) 297 (m 1H N-Cy) 171 (m 3H Cy) 153 (m 1H Cy) 112 (m 1H CMeH) 112 (d
63
3JH-H = 60 Hz 3H iPr) 111 (d 3JH-H = 60 Hz 3H iPr) 104 (m 2H Cy) 086 (d 3JH-H = 66
Hz 3H Me) 078 (m 1H Cy) 068 (m 1H Cy) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1611 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5) 11B
NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ
1488 (dm 1JC-F = 237 Hz CF) 1390 (dm 1JC-F = 250 Hz CF) 1372 (dm 1JC-F = 247 Hz CF)
571 (N-Cy) 503 (iPr) 381 (Cy) 330 (Cy) 315 (CMeH) 293 (Cy) 241 (Cy) 219 (Me)
196 (iPr) 192 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C
5011 H 350 N 216
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] (210) N-Isoporpyl-35-dimethylaniline (121 mg 740
μmol) reaction time 72 h product (243 mg 360 μmol 48) Mixture of isomers was obtained
NMR data for one isomer is reported
1H NMR (400 MHz C6D5Br) δ 555 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 300 -
280 (br m 2H iPr N-Cy) 182 (br m 1H Cy) 149 - 100 (m 5H Cy) 093 (m 6H iPr) 077
- 072 (m 1H Cy) 068 - 062 (m 6H Me) 059 - 048 (m 1H Cy) 19F NMR (377 MHz
C6D5Br) δ -1337 (m 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5)
11B NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 82 Hz BH) 13C1H NMR (100 MHz
C6D5Br) partial δ 1479 (dm 1JC-F = 240 Hz CF) 1378 (dm 1JC-F = 249 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1227 (ipso-C6F5) 560 (N-Cy) 494 (iPr) 410 (Cy) 378 (Cy) 270 (Cy)
212 (Me) 188 (iPr) Anal calcd () for C29H25BF15N C 5097 H 369 N 205 Found C
5087 H 399 N 212
[CyNH2CHPhCH2Ph][HB(C6F5)3] (211) cis-123-Triphenylaziridine (201 mg 740 μmol)
reaction time 96 h product (293 mg 370 μmol 50)
1H NMR (400 MHz CD2Cl2) δ 755 (m 1H p-Ph) 745 (m 4H Ph) 740 (m 3H Ph) 720
(m 2H Ph) 588 (br 2H NH2) 461 (t 3JH-H = 77 Hz 1H PhCH) 369 (br q 1JB-H = 85 Hz
1H BH) 344 (d 2H 3JH-H = 77 Hz PhCH2) 306 (m 1H N-Cy) 203 (m 1H Cy) 168 (m
4H Cy) 137 - 115 (br m 5H Cy) 19F NMR (377 MHz CD2Cl2) δ -1338 (m 3JF-F = 20 Hz
2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1662 (m 2F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -239 (d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F
= 245 Hz CF) 1382 (dm 1JC-F = 248 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1333 (ipso-Ph)
1321 (ipso-Ph) 1310 (p-Ph) 1301 (Ph) 1298 (Ph) 1289 (Ph) 1287 (p-Ph) 1273 (Ph) 1235
64
(ipso-C6F5) 641 (PhCH) 582 (N-Cy) 403 (PhCH2) 306 (Cy) 289 (Cy) 241 (Cy) 238
(Cy) 236 (Cy) Anal calcd () for C38H27BF15N C 5752 H 343 N 177 Found C 5762 H
395 N 187
[PhCH(Me)NH2Cy][HB(C6F5)3] (212) Method 1 N-(1-Phenylethylidene)aniline (144 mg
740 μmol) reaction time 96 h product (303 mg 420 μmol 57) Method 2 B(C6F5) (379 mg
0740 mmol) 3-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol) toluene (5 mL)
product (347 mg 0481 mmol 65)
1H NMR (400 MHz C6D5Br) δ 735 (m 3H o p-Ph) 721 (m 2H m-Ph) 618 (br 1H NH2)
566 (br 1H NH2) 428 (m 1H NH2CHMe) 383 (br q 1JB-H = 83 Hz 1H BH) 288 (m 1H
N-Cy) 190 (m 1H Cy) 166 (m 2H Cy) 157 (m 1H Cy) 154 (d 3JH-H = 69 Hz 3H Me)
146 (m 1H Cy) 126 (m 2H Cy) 098 (m 3H Cy) 19F NMR (377 MHz C6D5Br) δ -1336
(m 2F o-C6F5) -1613 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -234 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 241 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1334
(ipso-Ph) 1296 (o-Ph) 1260 (m-Ph) 574 (NH2CHMe) 573 (N-Cy) 295 (Cy) 288 (Cy)
236 (Cy) 236 (Cy) 188 (Me) (p-Ph was not observed) Anal calcd () for C32H23BF15N C
5358 H 323 N 195 Found C 5374 H 300 N 189
[14-C6H10(iPrNH2)2][HB(C6F5)3]2 (213) N1N4-Di(propan-2-ylidene)benzene-14-diamine (70
mg 0037 mmol) reaction time 36 h product (293 mg 240 μmol 64)
1H NMR (400 MHz d8-THF) δ 784 (br 2H NH2) 376 (br q 1JB-H = 92 Hz 1H BH) 364 (m 3JH-H = 65 Hz 1H iPr) 335 (br m 1H N-Cy) 238 (m 2H Cy) 159 (m 2H Cy) 138 (d 3JH-
H = 65 Hz 6H iPr) 19F NMR (377 MHz d8-THF) δ -1346 (m 3JF-F = 20 Hz 2F o-C6F5) -
1670 (t 3JF-F = 20 Hz 1F p-C6F5) -1697 (m 2F m-C6F5) 11B NMR (128 MHz d8-THF) δ -
254 (d 1JB-H = 92 Hz BH) 13C1H NMR (101 MHz d8-THF) δ 1483 (dm 1JC-F = 237 Hz
CF) 1375 (dm 1JC-F = 242 Hz CF) 1362 (dm 1JC-F = 246 Hz CF) 1259 (ipso-C6F5) 528 (N-
Cy) 486 (iPr) 274 (Cy) 184 (iPr) Anal calcd () for C48H30B2F30N2 C 4701 H 247 N
228 Found C 4686 H 247 N 232
[(14-C6H10(iPrNH2))2CH2][HB(C6F5)3]2 (214) 44-Methylenebis(N-isopropylaniline) (104
mg 370 μmol) reaction time 76 h product (372 mg 280 μmol 76)
65
1H NMR (400 MHz C6D5Br) δ 513 (br 2H NH2) 359 (br q 1JB-H = 81 Hz 1H BH) 301 (m
1H iPr) 276 (m 1H N-Cy) 168 (m 1H Cy) 151 (m 2H Cy) 145 (m 1H CH2) 132 (m
2H Cy) 091 (m 2H Cy) 089 (m 2H Cy) 089 (d 3JH-H = 68 Hz 6H iPr) 19F NMR (377
MHz C6D5Br) δ -1331 (m 3JF-F = 20 Hz 2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -
1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 81 Hz BH) 13C1H
NMR (101 MHz C6D5Br) δ 1486 (dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF)
1385 (dm 1JC-F = 247 Hz CF) 569 (iPr) 500 (N-Cy) 432 (CH2) 296 (Cy) 272 (CH2-Cy)
242 (Cy) 190 (iPr) Anal calcd () for C55H42B2F30N2 C 4995 H 320 N 212 Found C
4973 H 333 N 221
[iPr2NHPh][HB(C6F5)3] (215) In a glove box B(C6F5)3 (379 mg 740 μmol) and NN-
diisopropylaniline (131 mg 740 μmol) were dissolved in C6D5Br (05 mL) and added into a
Teflon capped sealed J-Young tube The J-Young tube was degassed three times through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC and placed
in a 110 ordmC oil bath for 16 h To the C6D5Br solution pentane was added drop wise until the
product precipitated The white solid was isolated (442 mg 640 μmol 87) Crystals suitable
for X-ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H o p-Ph) 693 (m 2H m-Ph) 670 (br 1H NH)
371 (br q 1JB-H = 85 Hz 1H BH) 358 (m 3JH-H = 63 Hz 2H iPr) 093 (d 3JH-H = 63 Hz 6H
iPr) 077 (d 3JH-H = 63 Hz 6H iPr) 19F NMR (377 Hz C6D5Br) δ -1326 (m 3JF-F = 20 Hz
2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -245 ppm (br d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484
(dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1322
(ipso-Ph) 1304 (m-Ph) 1231 (p-Ph) 1211 (o-Ph) 584 (iPr) 188 (iPr) 168 (iPr) Anal calcd
() for C30H21BF15N C 5212 H 306 N 203 Found C 5183 H 329 N 211
Synthesis of 216 - 218 is similar to the general procedure used for compounds 23 - 214 Since
compounds [(2-FC6H10)NH2iPr][HB(C6F5)3] 216b and [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b
were present in trace amounts (5) isolation and characterization proved difficult therefore
spectroscopic data for the two compounds has not been reported
[iPrNH2Cy][FB(C6F5)3] (216a) B(C6F5)3 (379 mg 0740 mmol) 2-fluoro-N-isopropylaniline
(115 mg 0740 mmol) or 3-fluoro-N-isopropylaniline (115 mg 0740 mmol) toluene (5mL)
66
reaction time 72 h product from 2-fluoro-N-isopropylaniline (294 mg 0440 mmol 59)
product from 3-fluoro-N-isopropylaniline (381 mg 0570 mmol 77) Crystals suitable for x-
ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 561 (br 2H NH2) 288 (m 3JH-H = 64 Hz 1H iPr) 262 (br
m 1H N-Cy) 149 (m 2H Cy) 144 (m 2H Cy) 135 (m 1H Cy) 092 - 083 (m 5H Cy)
085 (d 1JH-H = 63 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1370 (m 6F o-C6F5) -1616
(t 3JF-F = 22 Hz 3F p-C6F5) -1669 (m 6F m-C6F5) -1795 (br s 1F BF) 11B NMR (128
MHz CD2Cl2) δ 051 (br s BF) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 239
Hz CF) 1394 (dm 1JC-F = 241 Hz CF) 1373 (dm 1JC-F = 249 Hz CF) 560 (N-Cy) 489
(iPr) 293 (Cy) 245 (Cy) 241 (Cy) 188 (iPr) Anal calcd () for C27H20BF16N C 4817 H
299 N 208 Found C 4804 H 307 N 210
[(4-FC6H8)NH2iPr][HB(C6F5)3] (218) B(C6F5)3 (379 mg 074 mmol) 4-fluoro-N-
isopropylaniline (113 mg 074 mmol) toluene (5 mL) reaction time 72 h product (308 mg
0460 mmol 62) Crystals suitable for X-ray diffraction were obtained from a layered solution
of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 582 (br s 2H NH2) 477 (dm 3JF-H = 14 Hz 1H CH=CF)
355 (br q 1JB-H = 81 Hz 1H BH) 345 (m 1H iPr) 293 (m 1H N-Cy) 192 - 133 (m 6H
CH2 groups of Cy) 081 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -9903
(dm 3JF-H = 14 Hz 1F FC=CH) -1331 (m 3JF-F = 23 Hz 6F o-C6F5) -1606 (t 3JF-F = 21 Hz
3F p-C6F5) -16398 (m 6F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 81 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1584 (d 1JC-F = 255 Hz CF=CH) 1484 (dm 1JC-F =
224 Hz C6F5)1385 (dm 1JC-F = 247 Hz C6F5)1369 (dm 1JC-F = 247 Hz C6F5) 1230 (ipso-
C6F5) 974 (d 2JC-F = 20 Hz CF=CH) 518 (iPr) 504 (N-Cy) 254 (d 2JC-F = 81 Hz CH2CF)
247 (d 3JC-F = 90 Hz CH2CH=CF) 228 (CH2) Anal calcd () for C27H18BF16N C 4831 H
270 N 209 Found C 4793 H 282 N 203
Synthesis of 219 and 220 is similar to the general procedure used for compounds 23 - 214
Synthesis of [C6H10NHCH(CH3)Ph][HB(C6F5)3] (219) Method 1 B(C6F5) (358 mg 0700
mmol) 4-methoxy-N-(1-phenylethylidene)aniline (113 mg 0500 mmol) toluene (4 mL) (107
67
mg 0150 mmol 30) Crystals suitable for X-ray diffraction were obtained from a layered
solution of dichloromethanepentane at -30 degC
Method 2 In the glovebox trans-(4-CH3OC6H10)NHCH(CH3)Ph (81 mg 340 μmol) and
B(C6F5)3 (17 mg 340 μmol) were dissolved in d8-toluene (04 mL) and added into a Teflon
capped J-Young tube The tube was degassed once through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at
110 degC The solvent was removed under vacuum and the residue was washed with pentane (2
mL) The product was dried under vacuum and collected (82 mg 110 μmol 33)
1H NMR (500 MHz CD2Cl2) δ 752 (tm 3JH-H = 77 Hz 1H p-Ph)
746 (tm 3JH-H = 77 Hz 2H m-Ph) 735 (dm 3JH-H = 77 Hz 2H o-
Ph) 555 (br m 1H NH) 447 (dd 3JH-H = 95 Hz 48 Hz 1H H1)
415 (dq 3JH-H = 102 Hz 68 Hz 1H CH(CH3)Ph) 374 (m JH-H = 95
Hz 48 Hz 1H H5) 363 (br q 1JB-H = 83 Hz 1H BH) 229 (m 1H
H3) 223 (m 1H H4) 215 (m 1H H2) 201 (m 1H H3) 196 (m 1H H6) 190 (m 1H H2)
188 (m 1H H4) 177 (d 3JH-H = 68 Hz 3H CH3) 176 (m 1H H6) 19F NMR (377 MHz
CD2Cl2) δ -1304 (m 2F o-C6F5) -1638 (t 1F 3JF-F = 21 Hz p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -249 (d 1JB-H = 83 Hz BH) 13C1H NMR (125 MHz
CD2Cl2) δ 1482 (dm 1JC-F = 236 Hz C6F5) 1378 (dm 1JC-F = 245 Hz C6F5) 1364 (dm 1JC-F
= 249 Hz C6F5) 1346 (ipso-Ph) 1308 (p-Ph) 1301 (m-Ph) 1266 (o-Ph) 1246 (ipso-C6F5)
652 (C5) 647 (C1) 586 (CH(CH3)Ph) 277 (C2) 273 (C6) 254 (C3 C4) 188 (CH3) Anal
calcd () for C32H21BF15N C 5373 H 296 N 196 Found 5384 H 321 N 200
[(o-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (220) Ratio of cis and trans isomers = 11
determined by 1H NMR spectroscopy The trans isomer has been isolated and characterized
B(C6F5) (379 mg 0740 mmol) 2-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol)
toluene (5 mL) product (508 mg 0680 mmol 92) Crystals suitable for X-ray diffraction were
obtained from a layered solution of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H m p-Ph) 691 (m 2H o-
Ph) 655 (br s 2H NH2) 413 (q 3JH-H = 64 Hz 1H CH(Me)Ph) 365
(br q 1JB-H = 92 Hz 1H BH) 313 (ddd 3JH-H = 107 Hz 43 Hz 1H
CHOCH3) 298 (s 3H OCH3) 237 (td 3JH-H = 107 Hz 1H CH2CHNH2) 180 (m 1H DCH2)
68
173 (dm 3JH-H = 136 Hz 1H ACH2) 140 (m 2H DCCH2) 128 (d 3JH-H = 64 Hz 3H
CH(CH3)Ph) 120 (m 1H BCH2) 095 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H BCH2)
066 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H CCH2) 039 (pseudo qd JH-H = 136 Hz 3JH-
H = 31 Hz 1H ACH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -1634 (t 3JF-F =
21 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -246 (d 1JB-H = 92
Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 235 Hz C6F5) 1381 (dm 1JC-F = 246 Hz C6F5) 1367 (dm 1JC-F = 247 Hz C6F5) 1334 (ipso-Ph) 1304 (p-Ph) 1299 (m-
Ph) 1264 (o-Ph) 1239 (ipso-C6F5) 778 (CHOCH3) 611 (CH2CHNH2) 571 (CH(CH3)Ph)
554 (OCH3) 279 (ACH2) 257 (DCH2) 236 (CCH2) 224 (BCH2) 202 (CH3) Anal calcd ()
for C33H25BF15NO C 5303 H 337 N 187 Found 5288 H 357 N 190
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] (221a) Part 1 In a Schlenk
tube trans-(4-CH3OC6H10)NHCH(CH3)Ph (16 mg 680 μmol) was dissolved in pentane (2 mL)
and hydrogen chloride (68 μL 027 mmol 40 M in 14-dioxane) was added drop wise White
precipitate was immediately formed The solvent was decanted and the solid was washed with
pentane (2 mL) and dried in vacuo to yield trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (163 mg
610 μmol 89)
Part 2 In the glovebox a 4 dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph
HCl (61 mg 0026 mmol) in dichloromethane (8 mL) and K B(C6F5)4 (162 mg 260 mmol)
was added at once The reaction was allowed to stir for 16 h at room temperature The mixture
was filtered through Celite and the solvent was removed under vacuum The product was
obtained as a white solid (209 mg 230 μmol 88)
1H NMR (400 MHz C6D5Br) δ 719 (m 2H m-Ph) 690 (m 3H o p-Ph) 510 (br s 2H NH2)
402 (q 3JH-H = 69 Hz 1H CH(CH3)Ph) 310 (s 3H OCH3) 272 (m 2H CyCHOCH3 CyCHN) 174 (m 3H CyCH2) 156 (m 1H CyCH2) 127 (d 3JH-H = 69 Hz 3H CH(CH3)Ph
093 - 084 (m 4H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1318 (m 2F o-C6F5) -1610 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -164 (s
B(C6F5)4)
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (221b) In the glovebox a 4
dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (93 mg 0034 mmol) in
dichloromethane (8 mL) and Na HB(C6F5)3 (185 mg 340 μmol) was added at once The
69
reaction was allowed to stir for 16 h at room temperature The mixture was filtered through
Celite and the solvent was removed under vacuum The product was obtained as a white solid
(193 mg 260 μmol 76) Preparation of Na HB(C6F5)3 is reported in Chapter 3
1H NMR (400 MHz C6D5Br) δ 716 (m 3H Ph) 702 (m 2H Ph) 546 (br 2H NH2) 407 (q 3JH-H = 68 Hz 1H CH(CH3)Ph) 347 (br q 1JB-H = 78 Hz 1H BH) 307 (s 3H OCH3) 283
(tt 3JH-H = 106 Hz 46 Hz 1H CyCHOCH3) 268 (tt 3JH-H = 117 Hz 39 Hz 1H CyCHN) 183
(m 3H CyCH2) 156 (dm 3JH-H = 128 Hz 1H CyCH2) 132 (d 3JH-H = 68 Hz CH(CH3)Ph)
121 (m 2H CyCH2) 084 (m 2H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1334 (m 2F o-
C6F5) -1604 (t 3JF-F = 22 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -238 (d 1JB-H = 78 Hz BH)
Synthesis of [C6H10NH(iPr)][CH3OB(C6F5)3] (222) In the glovebox a Schlenk tube (25 mL)
was charged with trans-(4-CH3OC6H10)NH(iPr) (253 mg 0148 mmol) in toluene (05 mL) and
B(C6F5) (758 mg 0148 mmol) dissolved in toluene (05 mL) was added at once The Schlenk
was sealed and heated at 110 degC for 2 h and the solvent was removed under vacuum The crude
solid was washed with pentane (2 mL) to yield the product as a white solid (991 mg 0145
mmol 98) Crystals suitable for X-ray diffraction were obtained from a layered solution of
dichloromethanepentane at -30 degC
1H NMR (500 MHz CD2Cl2) δ 810 (s 1H NH) 413 (m 2H CH2CH) 315 (m 3JH-H = 66
Hz 1H iPr) 302 (s 3H BOCH3) 222 (dm 1JH-H = 93 Hz 2H ACH2) 205 (dm 1JH-H = 100
Hz 2H BCH2) 181 (dm 1JH-H = 100 Hz 2H BCH2) 172 (dm 1JH-H = 93 Hz 2H ACH2) 136
(d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1351 (br 2F o-C6F5) -1620 (t 3JF-F = 20 Hz 1F p-C6F5) -1664 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -242 (s
BOCH3) 13C1H NMR (125 MHz CD2Cl2) δ 1482 (dm 1JC-F = 241 Hz C6F5) 1388 (dm 1JC-F = 262 Hz C6F5) 1370 (dm 1JC-F = 252 Hz C6F5) 1231 (ipso-C6F5) 634 (CH2CH) 522
(BOCH3) 502 (iPr) 274 (ACH2) 258 (BCH2) 185 (iPr) Anal calcd () for C28H21BF15N05
CH2Cl2 C 4717 H 306 N 193 Found 4674 H 327 N 199 HRMS-DART mz [M] calcd
for C9H18N+ 1401 Found 1401
Synthesis of [C6H10NH(iPr)][HB(C6F5)3] (223) Method 1 In the glovebox trans-(4-
CH3OC6H10)NH(iPr) (250 mg 0150 mmol) and B(C6F5)3 (760 mg 0150 mmol) were
dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The tube was
70
degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4
atm) at -196 ordmC The reaction was complete after 12 h at 110 degC The solvent was removed under
vacuum and the residue was washed with pentane (2 mL) The product was collected as a white
powder (607 mg 930 μmol 62)
Method 2 In the glovebox compound [C6H10NH(iPr)][CH3OB(C6F5)3] (222) (200 mg 290
μmol) was dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The
tube was degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with
H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at 110 degC
1H NMR (400 MHz C6D5Br) δ 510 (br m 1H NH) 367 (br q 1JB-H = 76 Hz 1H BH) 347
(br s 2H CH) 242 (m 1H iPr) 162 (m 2H CH2) 131 (m 2H CH2) 111 (m 2H CH2) 093
(m 2H CH2) 138 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -1338 (m 3JF-F
= 21 Hz 2F o-C6F5) -1622 (t 3JF-F = 21 Hz 1F p-C6F5) -1658 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -239 (d 1JB-H = 76 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483
(dm 1JC-F = 235 Hz CF) 1381 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 248 Hz CF) 1242
(ipso-C6F5) 636 (CHCH2) 500 (iPr) 271 (CH2) 248 (CH2) 186 (iPr) Anal calcd () for
C27H19BF15N C 4964 H 293 N 214 Found C 4924 H 300 N 214
Compounds 224 - 235 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 50 mL Teflon screw cap Schlenk tube equipped with a stir bar was charged
with a solution of B(C6F5)3 (0379 g 0740 mmol) and the respective N-heterocycle in toluene (5
mL) The reaction tube was degassed three times through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube
was placed in a 115 ordmC oil bath for the indicated reaction time The solvent was then removed
under vacuum and the crude product was washed with pentane to yield the product as a white
solid
[26-Ph2C5H8NH2][HB(C6F5)3] (224) 26-Diphenylpyridine (171 mg 0740 mmol) reaction
time 16 h product (511 g 0680 mmol 92) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC Isomer ratio by 1HNMR
spectroscopy meso 91 rac 9
71
meso-[26-Ph2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 734 (tt 3JH-H = 70 Hz
4JH-H = 24 Hz 2H p-Ph) 726 (m 8H o m-Ph) 590 (br 2H NH2) 453 (m 3JH-H = 122 Hz 3JH-H = 24 Hz 2H C(H)Ph) 339 (br q 1JB-H = 90 Hz 1H BH) 226 (br m 3H CH2) 212 (m
2H CH2) 189 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1340 (m 2F o-C6F5) -1634 (t 3JF-F = 20 Hz 1F p-C6F5) -1666 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -246 (d 1JB-H = 90 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1483 (dm 1JC-F = 237 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1367 (dm 1JC-F = 246 Hz CF) 1338 (ipso-Ph) 1313 (p-Ph) 1271
(Ph) 1264 (Ph) 1241 (ipso-C6F5) 657 (C(H)(Ph)) 297 (CH2) 233 (CH2) Anal calcd ()
for C35H21BF15N C 5595 H 282 N 186 Found C 5547 H 303 N 186
[26-Me2C5H8NH2][HB(C6F5)3] (225) 26-Dimethylpyridine (793 mg 0740 mmol) reaction
time 60 h product (390 mg 0621 mmol 84) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC over 48 h Isomer ratio by 1HNMR spectroscopy meso 80 rac 20
meso-[26-Me2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 508 (br 2H NH2) 345
(br q 1JB-H = 83 Hz 1H BH) 268 (m 2H NC(H)Me) 137 (m 4H CH2) 086 (d 3JH-H = 64
Hz 6H CH3) 077 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -
1617 (t 3JF-F = 20 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1485 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF) 1236 (ipso-C6F5) 567
(NCH) 303 (CH2) 220 (CH2) 193 (CH3) Anal calcd () for C25H17BF15N C 4787 H 273
N 223 Found C 4764 H 290 N 222
(2-(EtOCO)C5H9NH)B(C6F5)3 (226) Ethyl 2-picolinate (112 mg 0740 mmol) reaction time
36 h product (366 mg 0547 mmol 74) The isolated product consisted of an equal ratio of
both diastereomers Anal calcd () for C26H15BF15NO2 C 4667 H 226 N 209 Found C
4660 H 247 N 211
RSSR-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2)
δ 590 (m 1H NH) 430 (m 1H CH(H)NH) 418 (br m 1H
CHOCOEt) 393 (dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 373
(dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 320 (dm 2JH-H = 126 Hz 1H CH(H)NH) 217
(m 2H CH2) 204 (dm 2JH-H = 134 Hz 1H CH2) 184 (m 1H CH2) 175 (m 1H CH2) 119
72
(t 3JH-H = 72 Hz 3H Et) 103 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1264 (m 1F o-
C6F5) -1280 (m 1F o-C6F5) -1295 (m 1F o-C6F5) -1297 (m 1F o-C6F5) -1404 (m 1F o-
C6F5) -1433 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F
p-C6F5) -1575 (t 3JF-F = - 21 Hz 1F p-C6F5) -1616 (m 1F m-C6F5) -1621 (m 1F m-C6F5) -
1628 (m 1F m-C6F5) -1631 (m 1F m-C6F5) -1640 (m 1F m-C6F5) -1649 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -486 (s BNH) 13C1H NMR (101 MHz CD2Cl2) δ 1674
(OCO) 636 (Et) 568 (CHOCOEt) 445 (CH(H)NH) 305 (CH2) 208 (CH2) 181 (CH2) 134
(Et)
RRSS-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ
743 (br m 1H NH) 440 (dq 2JH-H = 107 Hz 3JH-H = 71 Hz 1H Et)
438 (dq 2JH-H = 91 Hz 3JH-H = 71 Hz 1H Et) 424 (br m 1H
CHOCOEt) 350 (ddd 2JH-H = 134 Hz 3JH-H = 89 Hz 3JH-H = 49 Hz 1H CH(H)NH) 333
(dm JH-H = 133 Hz 1H CH(H)NH) 218 (m 1H CH2) 208 (m 1H CH2) 185 (m 1H CH2)
154 (m 1H CH2) 151 (m 1H CH2) 135 (t 3JH-H = 71 Hz 3H Et) 124 (m 1H CH2) 19F
NMR (377 MHz CD2Cl2) δ -1276 (m 1F o-C6F5) -1285 (m 2F o-C6F5) -1291 (m 1F o-
C6F5) -1371 (m 1F o-C6F5) -1421 (m 1F o-C6F5) -1549 (t 3JF-F = 21 Hz 1F p-C6F5) -
1572 (t 3JF-F = 21 Hz 1F p-C6F5) -1578 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5)
-1626 (m 1F m-C6F5) -1630 (m 3F m-C6F5) -1633 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -486 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1712 (OCO) 616 (Et) 581
(CHOCOEt) 457 (CH(H)NH) 259 (CH2) 235 (CH2) 171 (CH2) 139 (Et)
(2-PhC5H9NH)B(C6F5)3 (227a) and [2-PhC5H9NH2][HB(C6F5)3] (227b) 2-Phenylpyridine
(115 mg 0740 mmol) reaction time 48 h product (269 mg 0400 mmol 54) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC The isolated product consisted of 227a (RSSR 70) 227a (SSRR 10) 227b (20)
Anal calcd () for C29H15BF15N C 5158 H 254 N 209 Found C 5209 H 258 N 210
RSSR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 727
(m 2H Ph) 714 (m 3H Ph) 555 (br s 1H NH) 415 (ddd 3JH-H = 111
Hz 3JH-H = 94 Hz 36 Hz 1H CHPh) 356 (dm 2JH-H = 132 Hz 1H CH(H)NH) 257 (ddd 2JH-H = 132 Hz 3JH-H = 103 Hz 3JH-H = 31 Hz 1H CH(H)NH) 199 - 135 (m 6H CH2) 19F
NMR (377 MHz C6D5Br) δ -1216 (m 1F o-C6F5) -1236 (m 1F o-C6F5) -1274 (m 1F o-
73
C6F5) -1286 (m 1F o-C6F5) -1312 (m 1F o-C6F5) -1426 (m 1F o-C6F5) -1534 (t 3JF-F =
22 Hz 1F p-C6F5) -1566 (t 3JF-F = 21 Hz 1F p-C6F5) -1567 (t 3JF-F = 21 Hz 1F p-C6F5) -
1615 (m 2F m-C6F5) -1620 (m 3F m-C6F5) -1624 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -391 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1385 (ipso-Ph) 1297 (p-Ph)
1291 (Ph) 1285 (Ph) 646 (CHPh) 521 (NCH2) 355 (CH2) 248 (CH2) 219 (CH2)
SSRR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 710 -
681 (m 5H Ph) 581 (br s 1H NH) 449 (m 1H CHPh) 347 (dm 2JH-H = 125 Hz 1H CH(H)NH) 321 (m 2JH-H = 125 Hz 1H CH(H)NH) 185 (m 2H CH2)
176 (m 2H CH2) 128 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1249 (m 1F o-C6F5)
-1263 (m 1F o-C6F5) -1268 (m 1F o-C6F5) -1287 (m 1F o-C6F5) -1390 (m 1F o-C6F5) -
1431 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1559 (t 3JF-F = 21 Hz 1F p-C6F5)
-1562 (t 3JF-F = 21 Hz 1F p-C6F5) -1598 (m 1F m-C6F5) -1610 (m 1F m-C6F5) -1617 (m
1F m-C6F5) -1620 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1643 (m 1F m-C6F5) 11B NMR
(128 MHz CD2Cl2) δ -39 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1365 (ipso-Ph)1294
(p-Ph) 1283 (Ph) 1256 (Ph) 629 (CHPh) 454 (NCH2) 350 (CH2) 297 (CH2) 260 (CH2)
[2-PhC5H9NH2][HB(C6F5)3] (227b) 1H NMR (400 MHz CD2Cl2) δ 710 - 681 (m 5H Ph)
557 (br s 2H NH2) 355 (dd 3JH-H = 117 Hz 28 Hz 1H CHPh) 330 (br q 1JB-H = 86 Hz
1H BH) 295 (dm JH-H = 124 Hz 1H CH(H)NH2) 244 (pseudo td JH-H = 124 Hz 3JH-H = 30
Hz 1H CH(H)NH2) 186 (m 2H CH2) 165 (m 1H CH2) 157 (m 1H CH2) 141 (m 1H
CH2) 137 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 2F o-C6F5) -1610 (t 3JF-
F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -248 (d 1JB-H
= 86 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1399 (ipso-Ph) 1297 (Ph) 1295 (p-Ph)
1267 (Ph) 625 (CHPh) 471 (NCH2) 327 (CH2) 242 (CH2) 240 (CH2)
[2-MeC9H15NH2][HB(C6F5)3] (228) 2-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (331 mg 500 mmol 67) Crystals suitable for X-ray diffraction were grown from
a layered solution of dichloromethanepentane at -30 ordmC About 60 of the isolated reaction
product consisted of the SSSRRR diastereomer
1H NMR (400 MHz C6D5Br) δ 602 (br 1H NH2) 460 (br 1H NH2) 336 (br q 1JB-H = 83
Hz 1H BH) 315 (dt 3JH-H = 100 Hz 52 Hz 1H NCHCH) 276 (m 1H CHMe) 145 - 096
(m 8H CH2) 110 (m 1H CHCHN) 093 - 067 (m 4H CH2) 081 (d 3JH-H = 64 Hz 3H
74
Me) 19F NMR (377 MHz C6D5Br) δ -1335 (m 2F o-C6F5) -1607 (t 3JF-F = 22 Hz 1F p-
C6F5) -1646 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1384 (dm 1JC-F = 246
Hz CF) 1369 (dm 1JC-F = 249 Hz CF) 1233 (ipso-C6F5) 577 (NCH) 493 (CHMe) 322
(CHCHN) 281 (CH2) 272 (CH2) 255 (CH2) 240 (CH2) 236 (CH2) 211 (CH2) 189 (Me)
Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C 5021 H 331 N 212
[2-PhC9H15NH2][HB(C6F5)3] (229) B(C6F5)3 (289 mg 0564 mmol) 2-phenylquinoline (116
mg 0564 mmol) reaction time 48 h product (391 mg 536 mmol 95) Crystals suitable for
X-ray diffraction were grown from a layered solution of dichloromethanepentane at -30 ordmC
About 73 of the reaction mixture consisted of the reported SSSRRR diastereomer
1H NMR (400 MHz CD2Cl2) δ 733 (tm 3JH-H = 73 Hz 1H p-Ph) 726 (tm 3JH-H = 73 Hz
2H m-Ph) 720 (dm 3JH-H = 73 Hz 2H o-Ph) 646 (br 1H NH2) 501 (br t 1H NH2) 433
(dm 3JH-H = 105 Hz 33 Hz 1H C(H)Ph) 380 (br m 1H CH2C(H)NH2) 320 (br q 1JB-H = 87
Hz 1H BH) 218 - 108 (m 13H CH2C(H)CH2 and CH2) 19F NMR (377 MHz C6D5Br) δ -
1334 (m 2F o-C6F5) -1612 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -242 (d 1JB-H = 87 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1342
(ipso-Ph) 1312 (p-Ph) 1301 (m-Ph) 1269 (o-Ph) 647 (CH2C(H)NH2) 601 (C(H)Ph) 345
(CH2C(H)CH2) 291 (CH2) 285 (CH2) 251 (CH2) 249 (CH2) 248 (CH2) 197 (CH2) Anal
calcd () for C33H23BF15N C 5434 H 318 N 192 Found C 5431 H 331 N 192
[8-MeC9H15NH2][HB(C6F5)3] (230) 8-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (375 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC The reported SSSRRR
diastereomer was only observed
1H NMR (400 MHz C6D5Br) δ 555 (br 1H NH2) 497 (br 1H NH2) 352 (br q 1JB-H = 80
Hz 1H BH) 327 (dm 2JH-H = 121 Hz 1H NH2CH(H)) 263 (dm 3JH-H = 112 Hz coupling to
NH2 is observed in 1H1H-cosy 1H CHN) 252 (qt 2JH-H = 121 Hz 3JH-H = 27 Hz 1H
NH2CH(H)) 141 - 133 (br m 2H CH2) 134 (m 1H CH2CHCH2) 125 - 114 (br m 4H
CH2) 122 (m 1H CHMe) 102 (m 1H CH2) 089 (m 2H CH2) 063 (d 3JH-H = 75 Hz 3H
Me) 058 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1343 (m 2F o-C6F5) -1618 (t 3JF-F
= 21 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -242 (d 1JB-H =
75
80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 249 Hz CF) 1237 (ipso-C6F5) 632 (CHN) 478
(NH2CH(H)) 339 (CH2CHCH2) 337 (CHMe) 271 (CH2) 268 (CH2) 243 (CH2) 231 (CH2)
178 (CH2) 163 (Me) Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C
5026 H 330 N 209
[C13H22NH2][HB(C6F5)3] (231a) Acridine (132 mg 0740 mmol) reaction time 36 h product
(398 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at 25 ordmC The isolated product is a mixture of the SRSRRSRS
and RRSSSSRR isomers in a 11 ratio The SRSRRSRS was separated by crystallization
1H NMR (400 MHz CD2Cl2) δ 626 (br m 1H NH2) 513 (br m 1H NH2) 327 (br q 1JB-H =
86 Hz 1H BH) 285 (dm 3JH-H = 111 Hz 40 Hz 2H CHN) 182 (m 2H NH2CHCH2) 176
(m 2H CyCH2) 175 (m 1H CHCH2CH) 171 (m 2H CyCH2) 167 (m 2H CyCH2) 144 (qt 3JH-H = 111 Hz 3JH-H = 40 Hz 2H CH2CHCH2) 123 (m 2H CyCH2) 122 (m 2H
NH2CHCH2) 118 (m 2H CyCH2) 101 (m 2H CyCH2) 100 (m 1H CHCH2CH) 19F NMR
(377 MHz CD2Cl2) δ -1345 (m 2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -244 (d 1JB-H = 86 Hz BH) 13C1H NMR (101
MHz CD2Cl2) partial δ 639 (CHN) 406 (CH2CHCH2) 371 (CHCH2CH) 318 (CyCH2) 307
(NH2CHCH2) 249 (CyCH2) 248 (CyCH2) Anal calcd () for C31H25BF15N C 5264 H 356
N 198 Found C 5214 H 358 N 196
Synthesis of RRSSSSRR and SRSRRSRS-[(C13H22NH)B(C6F5)3] (231b) Compound 231b
was initially isolated from the pentane wash work-up for the synthesis of 231a Independent
synthesis of 231b was performed and the procedure is described
In a 4 dram vial tetradecahydroacridine (366 mg 0189 mmol) was dissolved in pentane (5
mL) at room temperature To the vial B(C6F5)3 (965 mg 0189 mmol) was added at once and
allowed to mix for 2 minutes The solution was filtered through a bed of Celite to yield a
colourless solution The vial was placed in a -30 ordmC freezer for 3 h and colourless crystals were
collected (973 mg 138 mmol 73) The isolated mixture of compound 231b consisted of a 11
mixture of RRSSSSRR and SRSRRSRS (C13H22NH)B(C6F5)3 only the diagnostic resonances of
RRSSSSRR-(C13H22NH)B(C6F5)3 have been reported
76
RRSSSSRR-[(C13H22NH)B(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 503 (br 1H NH) 353
(dm 3JH-H = 123 Hz 2H NCH) 214 (dm JH-H = 123 Hz 2H NH2CHCH2) 196 - 160 (m
6H CH2) 188 (m 2H CH2CHCH2) 177 (m 4H NH2CHCH2 and CHCH2CH) 149 - 111 (m
6H CH2) 19F NMR (377 MHz CD2Cl2) δ -1270 (m 1F o-C6F5) -1277 (m 1F o-C6F5) -
1281 (m 1F o-C6F5) -1291 (m 2F o-C6F5) -1302 (m 1F o-C6F5) -1558 (t 3JH-H = 21 Hz
1F p-C6F5) -1579 (t 3JH-H = 21 Hz 1F p-C6F5) -1589 (t 3JH-H = 21 Hz 1F p-C6F5) -1624
(m 1F m-C6F5) -1637 (m 3F m-C6F5) -1641 8 (m 1F m-C6F5) -1644 8 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -318 (s BN) 13C1H NMR (101 MHz CD2Cl2) partial δ
630 (NCH) 359 (CHCH2CH) 356 (CH2CHCH2) 299 (NH2CHCH2) Anal calcd () for
C31H23BF15N C 5279 H 329 N 199 Found C 5266 H 328 N 196
[23-(C4H6Me)2NHNH2][HB(C6F5)3] (232) 23-Dimethylquinoxaline (0117 g 0740 mmol)
reaction time 96 h product (402 mg 437 mmol 59) The SRSSRSRR diastereomer was only
observed
1H NMR (400 MHz CD2Cl2) δ 643 (br 1H NH2) 592 (br 1H NH2) 349 (dm 3JH-H = 128
Hz 1H CH2CHN) 334 (br q 1JB-H = 94 Hz 1H BH) 326 (br m 2H NCHMe CH2CHN)
281 (dq 3JH-H = 123 Hz 64 Hz 1H NCHMe) 223 (dm JH-H = 128 Hz 1H CH2) 189 (dm
JH-H = 134 Hz 1H CH2) 179 (dm JH-H = 134 Hz 1H CH2) 162 (dm JH-H = 134 Hz 2H
CH2) 147 (m 1H CH2) 131 (m 1H CH2) 128 (d 3JH-H = 64 Hz 3H Me) 121 (d 3JH-H =
62 Hz 3H Me) 120 (m 1H CH2) (NH was not observed) 19F NMR (377 MHz C6D5Br) δ -
1336 (m 2F o-C6F5) -1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1646 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -241 (d 1JB-H = 94 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481
(dm 1JC-F = 234 Hz C6F5) 1384 (dm 1JC-F = 246 Hz C6F5) 1368 (dm 1JC-F = 247 Hz C6F5)
1232 (ipso-C6F5) 576 (CH2CHN) 563 (NCHMe) 541 (NCHMe) 519 (CH2CHN) 304
(CH2) 242 (CH2) 224 (CH2) 185 (CH2) 178 (Me) 151 (Me) Anal calcd () for
C28H22BF15N C 4929 H 325 N 411 Found C 4909 H 333 N 421
[23-(C4H6Ph)2NHNH2][HB(C6F5)3] (233) 23-Diphenylquinoxaline (0209 g 0740 mmol)
reaction time 96 h product (328 mg 0407 mmol 55) Crystals suitable for X-ray diffraction
were grown from a layered solution of dichloromethanepentane at RT Diastereomers
SRSSRSRR and RRRSSSSR are present in equal ratios The assigned diastereomers were
77
supported by 1H1H NOESY NMR spectroscopy Anal calcd () for C38H26BF15N2 C 5660
H 325 N 347 Found C 5611 H 313 N 321
SRSSRSRR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 763 (m 4H
Ph) 699 - 684 (m 6H Ph) 572 (br 2H NH2) 476 (d 3JH-H = 34 Hz 1H CHPh) 441 (d 3JH-H = 34 Hz 1H CHPh) 407 (br 1H NH) 356 (br q 1JB-H = 82 Hz 1H BH) 314 (td 3JH-H
= 102 Hz 3JH-H = 34 Hz 1H CH2CHN) 260 (m 3JH-H = 102 Hz 34 Hz 1H CH2CHN) 167
(m 1H CH2) 159 (m 1H CH2) 153 (m 1H CH2) 129 (m 1H CH2) 122 (m 2H CH2)
121 (m 1H CH2) 086 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1331 (m 2F o-C6F5)
-1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1362 (ipso-Ph) 1313
(Ph) 1301 (Ph) 1267 (Ph) 637 (CHPh) 619 (CHPh) 597 (CH2CHN) 561 (CH2CHN) 314
(CH2) 282 (CH2) 242 (CH2) 233 (CH2) (ipso-C6F5 was not observed)
RRRSSSSR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (500 MHz CD2Cl2) δ 729 - 708
(m 10H Ph) 657 (br 2H NH2) 451 (dm 3JH-H = 102 Hz 1H CHPh) 429 (dm 3JH-H = 102
Hz 1H CHPh) 386 (dm 3JH-H = 107 Hz 1H CH2CHN) 366 (br 1H NH) 328 (br q 1JB-H =
82 Hz 1H BH) 268 (dm 3JH-H = 107 Hz 1H CH2CHN) 205 (m 1H CH2) 188 (m 2H
CH2) 178 (m 2H CH2) 157 (m 1H CH2) 145 (m 1H CH2) 130 (m 1H CH2) 19F NMR
(377 MHz C6D5Br) δ -1331 (m 2F o-C6F5) -1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 82 Hz BH) 13C1H NMR (125
MHz CD2Cl2) δ 1479 (dm 1JC-F = 235 Hz CF) 1382 (dm 1JC-F = 246 Hz CF) 1366 (dm 1JC-F = 248 Hz CF) 1314 (ipso-Ph) 1304 (Ph) 1301 (ipso-Ph) 1293 (Ph) 1290 (Ph) 1286
(Ph) 1277 (Ph) 1274 (Ph) 1226 (ipso-C6F5) 655 (CHPh) 621 (CHPh) 581 (CH2CHN)
526 (CH2CHN) 308 (CH2) 245 (CH2) 229 (CH2) 188 (CH2)
[(C6H4)C7H12NH2][HB(C6F5)3] (234) 78-Benzoquinoline (133 mg 0740 mmol) reaction
time 48 h product (285 mg 407 mmol 55) Crystals of the SRRS isomer suitable for X-ray
diffraction were grown from a layered solution of bromobenzenepentane at -30 ordmC Crystals of
the SSRR isomer suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC Anal calcd () for C31H19BF15N C 5309 H 273 N 200
Found C 5347 H 291 N 209
78
Isomer ratio by 1HNMR spectroscopy SRRS 80 (pale orange crystals) SSRR 20 (colourless
crystals)
SRRS-[(C6H4)C7H12NH2][HB(C6F5)3] (234a) 1H NMR (400 MHz CD2Cl2) δ 725 (td 3JH-H
= 77 Hz 4JH-H = 14 Hz 1H C6H4) 715 (d 3JH-H = 77 Hz 1H C6H4) 707 (d 3JH-H = 77 Hz
1H C6H4) 700 (t 3JH-H = 77 Hz 1H C6H4) 597 (br 2H NH2) 440 (d 3JH-H = 38 Hz 1H
NCH) 361 (dt JH-H = 131 Hz 3JH-H = 35 Hz 1H NCH(H)) 328 (m 1H NCH(H)) 314 (br q 1JB-H = 80 Hz 1H BH) 294 (dm 2JH-H = 172 Hz 1H C6H4-CH(H)) 285 (dm 2JH-H = 172 Hz
1H C6H4-CH(H)) 239 (m 1H CH2CHCH2) 200 - 188 (br m 6H PiperidineCyCH2) 19F NMR
(377 MHz C6D5Br) δ -1345 (m 2F o-C6F5) -1621 (t 3JF-F = 21 Hz 1F p-C6F5) -1657 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 80 Hz BH) 13C1H NMR (101
MHz CD2Cl2) δ 1483 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1378
(quaternary C for C6H4-CHN) 1368 (dm 1JC-F = 248 CF) 1311 (C6H4) 1307 (C6H4) 1292
(C6H4) 1288 (quaternary C for C6H4-CH2) 1277 (C6H4) 1234 (ipso-C6F5) 605 (NCH) 479
(NCH2) 320 (CH2CHCH2) 286 (C6H4-CH(H)) 274 (PiperidineCH2) 225 (CyCH2) 184
(PiperidineCH2)
SSRR-[(C6H4)C7H12NH2][HB(C6F5)3] (234b) 1H NMR (400 MHz C6D5Br) partial δ 701
(m 1H C6H4) 699 (m 1H C6H4) 685 (m 1H C6H4) 675 (d 3JH-H = 77 Hz 1H C6H4) 350
(d 3JH-H = 104 Hz 1H NCH) 324 (br dm JH-H = 124 Hz 1H NCH(H)) 279 (m 1H
NCH(H)) 254 (m 1H C6H4-CH(H)) 242 (m 1H C6H4-CH(H)) 142 (m 2H CH2) 128 (m
2H CH2) 105 (m 1H CH2CHCH2) 083 (m 2H CH2) (NH2 was not observed) 13C1H
NMR (101 MHz C6D5Br) δ 1370 (quaternary C for C6H4-CHN) 1304 (C6H4) 1291 (C6H4)
1284 (quaternary C for C6H4-CH2) 1264 (C6H4) 1226 (C6H4) 629 (NCH) 474 (NCH2) 378
(CH2CHCH2) 291 (CH2) 288 (C6H4-CH(H)) 276 (CH2) 229 (CH2)
[(C5H3N)(CH2)2(C5H8NH)B(C6F5)2][HB(C6F5)3] (235) B(C6F5)3 (379 mg 0740 mmol) 110-
phenanthroline (667 mg 0370 mmol) reaction time 96 h product (283 mg 0270 mmol 73)
Crystals suitable for X-ray diffraction were grown from a layered solution of
tetrahydrofuranpentane at -30 ordmC Approximately 65 of the reaction mixture consisted of the
SRSRSR diastereomer
1H NMR (400 MHz CD2Cl2) δ 944 (br s 1H NH) 850 (dd JH-H = 47 Hz JH-H = 15 Hz 1H
C5H3N) 744 (dd JH-H = 78 Hz JH-H = 15 Hz 1H C5H3N) 722 (dd JH-H = 78 Hz JH-H = 47
79
Hz 1H C5H3N) 442 (d 3JH-H = 43 Hz 1H NCyCH) 342 (br 1H BH) 322 (dm 2JH-H = 138
Hz 1H NC(H)H) 291 (ddd 2JH-H = 138 Hz 3JH-H = 87 Hz 53 Hz 1H NC(H)H) 276 - 272
(m 2H C6H4-CH(H)) 212 (dm 3JH-H = 121 Hz 38 Hz 1H CH2CHCH2) 196 (m 1H CH2)
188 (m 1H CH2) 173 (m 1H CH2) 132 (dt 2JH-H = 140 Hz 3JH-H = 32 Hz 1H CH2) 091
(qd JH-H = 131 Hz 3JH-H = 38 Hz 1H CH2) 071 (qt JH-H = 137 Hz 3JH-H = 40 Hz 1H CH2)
19F NMR (377 MHz CD2Cl2) δ -1289 (m 2F B(C6F5)2o-C6F5) -1343 (m 6F HB(C6F5)3o-C6F5) -
1348 (m 2F B(C6F5)2o-C6F5) -1491 (t 3JF-F = 20 Hz 1F B(C6F5)2p-C6F5) -1511 (t 3JF-F = 20 Hz
1F B(C6F5)2p-C6F5) -1596 (m 4F B(C6F5)2m-C6F5) -1645 (t 3JF-F = 20 Hz 3F HB(C6F5)3p-C6F5) -
1676 (m 6F HB(C6F5)3m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 391 (s BN) -254 (d 1JB-H =
93 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1484 (quaternary C for C5H3N) 1466
(quaternary C for C5H3N) 1448 (C5H3N) 1354 (C5H3N) 1260 (C5H3N) 581 (CyNCH) 451
(NC(H)H) 296 (CH2C(H)CH2) 241 (CH2) 218 (CH2) 210 (CH2) 206 (CH2) Anal calcd
() for C42H17B2F25N2 C 4822 H 164 N 268 Found C 4783 H 197 N 269
243 X-Ray Crystallography
2431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
2432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
80
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
81
2433 Selected crystallographic data
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25
24 24rsquo 25
Formula C27H21B1F15N1 C27H13B1F15N1 C30H25B1F15N1
Formula wt 65526 64719 69532
Crystal system monoclinic orthorhombic monoclinic
Space group P2(1)c P2(1)2(1)2(1) P2(1)n
a(Aring) 97241(8) 116228(4) 126342(6)
b(Aring) 147348(12) 181284(7) 181939(8)
c(Aring) 188022(15) 236578(9) 128612(6)
α(ordm) 9000 9000 9000
β(ordm) 98826(4) 9000 90269(2)
γ(ordm) 9000 9000 9000
V(Aring3) 26621(4) 49848(3) 29563(2)
Z 4 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1635 1725 1562
Abs coeff μ mm-1 0169 0179 0157
Data collected 18591 28169 50674
Rint 00336 00297 00369
Data used 4685 8773 5207
Variables 401 793 424
R (gt2σ) 00361 00315 00352
wR2 00898 00758 00947
GOF 1007 1021 1024
82
Table 25 ndash Selected crystallographic data for 216a 218 and 219
216a 218 219
Formula C27H20B1F16N1 C27H18B1F16N1 C32H21B1F15N1
Formula wt 67325 67123 71533
Crystal system monoclinic monoclinic orthorhombic
Space group P2(1)c P2(1)n Pbca
a(Aring) 97677(6) 104368(7) 18886(4)
b(Aring) 147079(11) 93382(7) 16050(3)
c(Aring) 190576(14) 273881(18) 19128(4)
α(ordm) 9000 9000 9000
β(ordm) 98934(2) 96910(3) 9000
γ(ordm) 9000 9000 9000
V(Aring3) 27046(3) 26499(3) 5798(2)
Z 4 4 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1653 1683 16388
Abs coeff μ mm-1 0174 0177 0163
Data collected 23565 17203 50412
Rint 00432 00404 00662
Data used 6164 4676 6654
Variables 406 408 442
R (gt2σ) 00522 00496 00687
wR2 01387 01462 01912
GOF 1032 1041 10743
83
Table 26 ndash Selected crystallographic data for 220 222 and 224
220 222 (+05 CH2Cl2) 224 (+05 CH2Cl2)
Formula C33H25B1F15N1O1 C285H22B1Cl1F15N1O1 C355H22B1ClF15N1
Formula wt 74737 72573 79380
Crystal system orthorhombic orthorhombic monoclinic
Space group Pbca Pbca P2(1)n
a(Aring) 173531(15) 17750(5) 109902(9)
b(Aring) 161365(15) 16032(4) 151213(11)
c(Aring) 227522(17) 20783(6) 194765(15)
α(ordm) 9000 9000 90
β(ordm) 9000 96910(3) 92062(3)
γ(ordm) 9000 9000 90
V(Aring3) 63710(9) 5914(3) 32346(4)
Z 8 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 15582 16278 1630
Abs coeff μ mm-1 0154 0250 0235
Data collected 56289 47407 22409
Rint 00406 01159 00306
Data used 7321 5198 5688
Variables 461 440 495
R (gt2σ) 00413 00811 00495
wR2 01112 02505 01363
GOF 10647 10628 0936
84
Table 27 ndash Selected crystallographic data for 225 227 and 228
225 227 (+1 C5H12) 228
Formula C25H17B1F15N1 C63H42B2F30N2 C28H21B1F15N1
Formula wt 62721 141861 66727
Crystal system triclinic monoclinic triclinic
Space group P-1 P2(1)n P-1
a(Aring) 101339(5) 137416(4) 95967(15)
b(Aring) 112923(6) 119983(4) 108364(15)
c(Aring) 118209(6) 191036(7) 14143(2)
α(ordm) 98563(2) 9000 75929(5)
β(ordm) 109751(2) 109317(2) 80009(6)
γ(ordm) 94983(2) 9000 76629(5)
V(Aring3) 124520(11) 297240(17) 13772(4)
Z 2 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1673 1585 1609
Abs coeff μ mm-1 0176 0158 0235
Data collected 18038 22150 16105
Rint 00211 00246 00351
Data used 4357 5230 4743
Variables 379 436 406
R (gt2σ) 00371 00324 00546
wR2 00964 00816 01728
GOF 1044 1014 1028
85
Table 28 ndash Selected crystallographic data for 229 230 and 231a
229 (+05 C6H5Br) 230 231a
Formula C36H255B1Br05F15N1 C28H21B1F15N1 C31H25B1F15N1
Formula wt 80784 66727 70733
Crystal system monoclinic triclinic monoclinic
Space group C2c P-1 P2(1)n
a(Aring) 201550(11) 97752(4) 112914(4)
b(Aring) 133628(11) 120580(4) 183705(7)
c(Aring) 266328(18) 121120(5) 145648(5)
α(ordm) 9000 102296(2) 9000
β(ordm) 111905(6) 100079(2) 90480(2)
γ(ordm) 9000 90901(2) 9000
V(Aring3) 66551(8) 137127(9) 302105(19)
Z 8 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1613 1616 1555
Abs coeff μ mm-1 0749 0165 0155
Data collected 54940 20198 62113
Rint 00530 00245 00383
Data used 7644 4841 7630
Variables 484 406 533
R (gt2σ) 00651 00362 00778
wR2 01802 00971 02335
GOF 1037 1036 1007
86
Table 29 ndash Selected crystallographic data for 231b 233 and 234a
231b (+05 C6H14) 233 234a (+1 CH2Cl2)
Formula C34H30B1F15N1 C38H26B1F15N2 C32H21B1Cl2F15N1
Formula wt 74840 80642 78621
Crystal system triclinic monoclinic monoclinic
Space group P-1 Pn C2c
a(Aring) 107250(6) 99895(4) 181314(6)
b(Aring) 112916(7) 115666(5) 135137(5)
c(Aring) 136756(8) 155410(6) 253612(9)
α(ordm) 70523(2) 9000 9000
β(ordm) 88868(2) 105054(2) 92594(2)
γ(ordm) 86934(2) 9000 9000
V(Aring3) 155914(16) 173405(12) 62077(4)
Z 2 2 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1594 1544 1677
Abs coeff μ mm-1 0155 0147 0327
Data collected 22650 31226 22749
Rint 00233 00381 00512
Data used 5479 8395 7383
Variables 460 517 475
R (gt2σ) 00371 00400 00816
wR2 01066 00893 02554
GOF 0926 1011 1024
87
Table 210 ndash Selected crystallographic data for 234b and 235
234b 235 (+1 C4H8O +1 CH2Cl2)
Formula C31H19B1F15N1 C47H27B2Cl2F25N2O1
Formula wt 70128 120323
Crystal system monoclinic triclinic
Space group P2(1)c P-1
a(Aring) 100455(5) 113115(7)
b(Aring) 118185(5) 117849(8)
c(Aring) 245940(11) 188035(12)
α(ordm) 9000 83850(3)
β(ordm) 96724(2) 88364(3)
γ(ordm) 9000 69766(3)
V(Aring3) 28998(2) 23383(3)
Z 4 2
Temp (K) 150(2) 150(2)
d(calc) gcm-3 1606 1709
Abs coeff μ mm-1 0161 0281
Data collected 20742 36083
Rint 00342 00265
Data used 5101 8235
Variables 433 712
R (gt2σ) 00438 00473
wR2 01153 01198
GOF 1012 1015
88
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation
with Frustrated Lewis Pairs
31 Introduction
The reduction of carbonyl substrates such as aldehydes ketones esters acids and anhydrides to
alcohols is one of the most fundamental and widely used reactions in synthetic chemistry269
Sodium borohydride lithium aluminum hydride and other stoichiometric reducing agents56 224
serve adequately for laboratory scale syntheses however in an industrial setting the process
demands for a more clean environmentally benign and cost-effective procedure More desirable
methods involving H2 gas or transfer hydrogenation have proven practical and circumvent the
work-up operations required for stoichiometric reagents
Heterogeneous catalysts based on PdC and PtC are certainly atom economic however some of
these catalysts are not suitable in cases where mild conditions functional group tolerance and
chemoselectivity are required Therefore substantial research has been directed towards
homogeneous catalysts involving Ir237 Rh239 Ru238 Cu269 and Os238 complexes including metal-
immobilized systems269
Despite the power of these technologies research efforts motivated by cost toxicity and low
abundance have focused on the development of first-row transition metal catalysts based on Fe
and Co210 221 Also on-going interest in the field has been devoted to the discovery of new
asymmetric hydrogenation catalysts131 208-209 263-264136 213-214 270-271 in addition to transfer
hydrogenation via the Meerwein-Ponndorf-Verley reduction procedure216
311 FLP reactivity with unsaturated C-O bonds
In 1961 Walling and Bollyky reported the first metal-free hydrogenation system demonstrating
the reduction of the non-enolizable ketone benzophenone using H2 (100 atm) and tBuOK as the
catalyst at 200 degC175-176 While more recently metal-free reductions have been demonstrated
under more mild conditions using frustrated Lewis pairs (FLPs) These combinations of
sterically encumbered main group Lewis acids and bases have been shown to effect the catalytic
hydrogenation of a variety of unsaturated organic substrates Noticeably absent from these
substrates are ketones and aldehydes This is perhaps surprising given the precedence of catalytic
89
hydrosilylation of ketones established by Piers182 Moreover a number of groups have
demonstrated the ability of FLPs to effect the reduction of CO2 using H2259 silanes169 180 182
boranes111 163 272 or ammonia-borane273 as sources of the reducing equivalents The limited
attention to hydrogenation of ketones and aldehydes has been attributed to the high oxophilicity
of electrophilic boranes72 171 Indeed in an earlier report Erker and co-workers described the
irreversible capture of benzaldehyde and trans-cinnamaldehyde (Scheme 31 top) as well as the
14-addition of conjugated ynones by the intramolecular PB FLP Mes2PCH2CH2B(C6F5)2173 A
number of stoichiometric reductions have also been reported using H2 activated PB FLPs with
an example shown in Scheme 31 (bottom)94 173
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom)
Nonetheless the group of Privalov has computed an energetically viable mechanism for ketone
reduction suggesting a process analogous to imine hydrogenation and carbonyl hydrosilylation
using B(C6F5)3 as the catalyst274 Attempts to realize this prediction experimentally have been
unsuccessful Repo et al described the stoichiometric reaction of aromatic ketones with B(C6F5)3
effecting deoxygenation of the ketone to afford (C6F5)2BOH C6F5H and the corresponding aryl
alkane (Scheme 32 a)178 Furthermore the Stephan group found that similar reduction of alkyl
ketones gave borinic esters via H2 activation hydride delivery and protonation of a C6F5 group
(Scheme 32 b)275
90
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b)
Similar degradation of B(C6F5)3 via B-C bond cleavage affording CH3OB(C6F5)2 and C6F5H was
reported by Ashley and OrsquoHare in their efforts to reduce CO2 in the presence of H2 to CH3OH259
Due to the instability of B(C6F5)3 in these transformations Wang et al approached the catalytic
ketone hydrogenation challenge computationally suggesting that a bifunctional amine-borane
FLP catalyst would be viable276 Interestingly Du et al have taken a detour from direct FLP
hydrogenation of carbonyl groups reporting the catalytic hydrogenation of silyl enol ethers using
a chiral borane to obtain a variety of optically active secondary alcohols after workup (Scheme
33)277
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols
Reaction of main group species with other unsaturated C-O functionalities namely carbon
monoxide is also limited H C Brown established the synthesis of tertiary alcohols by
91
carbonylation of trialkylboranes using carbon monoxide278 although the analogous reactivity by
B-H boranes proved challenging279-282
Recently however Erker et al described the stoichiometric reduction of carbon monoxide by the
reaction of intramolecular PB FLPs and the hydroboration reagent HB(C6F5)2 to yield epoxy-
borate species (Scheme 34 top)118-119 283 Simultaneously the Stephan group exploited the
reaction of a 12 mixture of tBu3P and B(C6F5)3 with syn-gas (CO and H2) to result in sequences
of stoichiometric reactions eventually affording the borane-oxyborate derivative
(C6F5)2BCH(C6F5)OB(C6F5)3 a product of C-O bond cleavage (Scheme 34 bottom)117
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom)
The main group reduction of carbonyl groups has been limited to stoichiometric reactions with
classic hydride reagents In this chapter a remarkably simple approach to the metal-free
hydrogenation of ketones and aldehydes is reported using FLP catalysts derived from B(C6F5)3
and ether The hydrogenation concept was extended towards a heterogeneous avenue using
catalysts derived from the combination of polysaccharides or molecular sieves with B(C6F5)3
Moreover the catalytic reductive deoxygenation of aryl ketones is achieved in the case of
molecular sieves
92
32 Results and Discussion
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions
Heating a toluene solution of 5 mol B(C6F5)3 and 4-heptanone under H2 (60 atm) at 80 degC
yielded complete conversion of B(C6F5)3 to the borinic ester Pr2CHOB(C6F5)2 with concurrent
liberation of C6F5H The remaining 95 of the initial ketone was unaltered This observation
illustrates that borane and ketone act as a FLP to heterolytically cleave H2 affording nominally
[Pr2COH][HB(C6F5)3] At this stage the hydride is presumed to reduce the carbonyl fragment to
generate 4-heptanol which subsequently decomposes B(C6F5)3 to Pr2CHOB(C6F5)2 and C6F5H
It is important to note that the above example of rapid and facile decomposition of B(C6F5)3 to
borinic ester stands in contrast to an observation illustrated in Chapter 2 In this case the CH3OH
generated from ammonium protonation of [CH3OB(C6F5)3]- does not decompose B(C6F5)3 rather
under an atmosphere of H2 the resulting amine and B(C6F5)3 heterolytically split H2 to give the
ammonium [HB(C6F5)3] product (Scheme 35) Thus this observation led to the proposal of two
plausible borane decomposition pathways in ketone hydrogenation reactions
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH
In both pathways the reaction initiates with heterolytic H2 splitting by the ketone and B(C6F5)3
to give the ionic pair [R2COH][HB(C6F5)3] (Scheme 36) At this point the reaction could follow
a pathway in which hydride is transferred from the [HB(C6F5)3]- anion to the activated carbonyl
group generating alcohol and B(C6F5)3 both of which further react to give borinic ester and
C6F5H (Scheme 36 Pathway 1) The second pathway suggests the borane undergoes
protonolysis by the [R2COH]+ cation cleaving a C6F5 group to form HB(C6F5)2 and C6F5H whilst
regenerating the ketone The borane then undergoes hydroboration of the carbonyl group to
afford the borinic ester (Scheme 36 Pathway 2)
93
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation
To test Pathway 1 B(C6F5)3 was added to excess 4-heptanol (10 eq) and heated to 80 degC for 12
h This resulted in no reaction beyond formation of the alcohol-borane adduct
Pr2CHOHmiddotB(C6F5)3 as evidenced by the 11B and 19F NMR spectra (11B δ 197 ppm 19F δ -
1326 -1552 -1628 ppm) On the other hand stoichiometric and 5 mol combinations of
HB(C6F5)2 with 4-heptanone formed the new hydroboration species Pr2CHOB(C6F5)2 after 10
min at RT In addition to the characteristic methine multiplet observed at 405 ppm in the 1H
NMR spectrum 11B NMR spectroscopy gave a broad resonance at 394 ppm with 19F NMR
signals at -1325 -1498 and -1613 ppm representing the three-coordinate boron centre These
experiments provide evidence for Pathway 2 resulting in decomposition of B(C6F5)3 during
ketone hydrogenation
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents
To avoid this degradation pathway an alternative FLP is required This system must be basic
enough to effect H2 activation and stabilize the acidic proton by electrostatic interactions In this
regard the Stephan group previously reported that the ethereal oxygen of the borane-oxyborate
derivative (C6F5)2BCH(C6F5)OB(C6F5)3 is sufficiently Lewis basic to activate H2 with the
coordinating B(C6F5)2 group117 Subsequently the combination of weak Lewis bases such as
Et2O electron deficient triarylphosphines and diaryl amines were shown to be sufficiently basic
for both H2 activation and catalytic reduction of olefins99 257 In the case of Et2O DFT
calculations highlighted that solvation of the protonated ether by a second equivalent of Et2O can
significantly stabilize the proton by hydrogen-bonding interactions
94
To probe the viability of using Et2O in carbonyl reductions a d8-toluene solution of 5 mol
B(C6F5)3 was combined with a 51 ratio of Et2O4-heptanone and heated to 70 degC under H2 (4
atm) Monitoring the J-Young experiment by high temperature 1H NMR spectroscopy showed
gradual hydrogenation of the ketone yielding approximately 50 of 4-heptanol after 12 h The 1H NMR spectrum shows a distinct quintet at 345 ppm diagnostic of the hydrogenated C=O
fragment forming a C-H bond in addition to the multiplets at 128 and 080 ppm (Figure 31)
Increasing the H2 pressure to 60 atm improved the yield of 4-heptanol to 70
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol ()
Alternatively incrementing the ratio of Et2O to 4-heptanone resulted in increased yields in
which case a 81 ratio of Et2O4-heptanone in toluene gave 97 conversion to 4-heptanol after
12 h (Figure 32) The continuous improvement in alcohol yield was a direct result of gradual
preservation of the borane catalyst in the reaction as the Et2O concentration was increased
Employing identical conditions but using Et2O as the solvent resulted in the quantitative
formation of 4-heptanol after 12 h Similarly employing iPr2O as the solvent in analogous
$ $ 12
11
10
9
8
7
6
5
4
3
2
1
95
hydrogenations gave quantitative yields of 4-heptanol The use of Ph2O and TMS2O resulted in
yields of 44 and 42 in the same time frame (Table 31 entry 1)
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol
Using this FLP hydrogenation protocol a range of ketone substrates were treated with 5 mol
B(C6F5)3 in Et2O iPr2O Ph2O or TMS2O and heated for 12 h at 70 degC under H2 (60 atm) The
substrates investigated included several alkyl ketones (Table 31 entries 1 - 9) an aryl ketone
(Table 31 entry 10) benzyl ketones with substituents including F and CF3 groups (Table 31
entry 11 - 15) cyclic ketones including L-menthone and cyclohexanone (Table 31 entries 16
and 17) as well as the aldehyde cyclohexanal (Table 31 entry 18) Evaluating these reductions
by 1H NMR spectroscopy showed yields ranging between 32 - gt99 and isolated yields up to
91 for the reactions carried out in Et2O and iPr2O (Table 31) 1H NMR spectra of the alcohols
displayed characteristic multiplets at about 4 ppm assignable to the distinctive methine protons
with corresponding 13C1H resonances observed at ca 70 ppm as expected
These reactions could also be performed on a larger scale For example 100 g of 4-heptanone
was quantitatively converted to 4-heptanol using 5 mol B(C6F5)3 in Et2O and the alcohol
product was isolated in 87 yield
96
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents
Conversion (Isolated yields)
Entry R R1 Et2O iPr2O Ph2O TMS2O
1 n-C3H7 n-C3H7 gt99 (91) gt99 70 52
2 Me iPr gt99 (76) gt99 44 42
3 Me CH2tBu gt99 gt99 (90) 22 14
4 Me n-C5H11 93 (85) 50 (43) 58 41
5 Me CH2Cl gt99 (85) gt99 91 82
6 Me Cy 77 - - -
7 Et iPr gt99 gt99 (89) - trace
8 Et n-C4H9 gt99 (87) 95 44 38
9 Et CH2iPr 40 47 - -
10 Me Ph 90 69 (52) trace trace
11 Et CH2Ph gt99 (84) 97 trace trace
12 Me n-CH2CH2Ph gt99 (84) 69 58 24
13 Me CH2(o-FC6H4) 97 gt99 (90) trace trace
14 Me CH2(p-FC6H4) gt99 gt99 (90) trace trace
15 Me CH2(m-CF3C6H4) gt99 gt99 (88) 55 trace
16 -(CH2)5- 53 41 - -
17 -(2-iPr-5-Me)C5H8- gt99 (88) 89 47 45
18 Cy H 32 - - -
(-) Reaction was not performed
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents
The mechanism of these reactions is thought to be analogous to that previously described for
imine hydrogenations92 In the present case ether combines with the borane in equilibrium
97
between the classical Lewis acid-base adduct and the corresponding FLP in which the latter
effects the heterolytic cleavage of H2 The resulting protonated ether then associates with ketone
via a hydrogen-bonding interaction284-285 activating the carbonyl fragment for hydride transfer
from the [HB(C6F5)3]- anion Subsequent protonation of the generated alkoxide yields the
product alcohol while liberating etherB(C6F5)3 to further activate H2 (Scheme 37) It has been
experimentally proven that activation of the carbonyl fragment is required prior to hydride
delivery as a 11 combination of 4-heptanone and [NEt4][HB(C6F5)3] do not result in reactivity
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents
The possibility of initial H2 activation by ketoneborane combinations cannot be dismissed
however the proposed mechanism is based on the large excess of ether in comparison to ketone
In support of this proposed mechanism the activation of H2 by ethereal oxygen Lewis bases and
boranes have been described to protonate imines and alkenes en route to the corresponding
hydrogenated products257 286
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism
The proposed H-bonding ether-ketone intermediate was further probed by the stoichiometric
reaction of a toluene solution of Jutzirsquos acid [(Et2O)2H][B(C6F5)4]287 with 1-phenyl-2-butanone
and iPr2O After heating the reaction at 70 degC for 2 h a white crystalline solid 31 was isolated in
87 yield (Scheme 38) The 1H NMR spectrum of 31 showed a broad singlet at 1152 ppm
suggesting a proton involved in hydrogen-bonding Resonances attributable to both 1-phenyl-2-
butanone and iPr2O were unambiguously present although these shifts were deshielded in
98
comparison to the individual components These data in addition to the definite presence of the
[B(C6F5)4]- anion as evidenced by 11B and 19F NMR spectroscopy lead to the assignment of 31
as [(iPr2O)H(O=C(CH2Ph)CH2CH3)][B(C6F5)4]
Scheme 38 ndash Synthesis of 31
The structure of 31 was unambiguously confirmed by single crystal X-ray crystallography
(Figure 33) The molecular structure of this salt shows the proximity of the ketone and ether in
the cation with an O-O separation of 2534(3) Aring Location and complete refinement of the proton
in the cation shows it is associated with the ether oxygen and hydrogen-bonded to the ketone
with O-H distances of 104(2) and 154(2) Aring respectively The resulting angle at H is 1581(3)deg
consistent with that typically seen for hydrogen-bonding interactions288-289 The isolation of 31
provides a direct structural analogue of the proposed intermediate in the ketone hydrogenation
mechanism
The equilibrium position of the generated proton is predicted to favour the ether oxygen atom
where the unshared electron pair is sp3 hybridized making the ether oxygen more basic than the
carbonyl where the unshared pair is sp2 hybridized This is also in agreement with predicted pKa
values of protonated ether and ketone289
Figure 33 ndash POV-Ray depiction of 31
99
325 Other hydrogen-bond acceptors for carbonyl hydrogenations
By analogy to the proposed mechanism with ethereal solvents ketone hydrogenations were
explored with crown ethers in toluene To this end combinations of 5 and 10 mol of 12-crown-
4 18-crown-6 and benzo-12-crown-4 were used with 5 mol B(C6F5)3 and 4-heptanone
However in all cases only trace amounts of 4-heptanol was observed Similar to the results in
ethereal solvents these hydrogenation results could possibly be improved by using an excess of
the crown ether On the other hand inefficient hydrogenation could result due to the multiple
stabilizing hydrogen bonds with the crown (OCH2)n groups
Alternative oxygen containing solvents THF and tetrahydropyran were tested using the
hydrogenation protocol in both cases however catalysis was not observed This result could be
explained by the difference in steric hindrance of the two solvents in comparison to Et2O and
iPr2O Nonetheless performing the hydrogenations in 24-dimethylpentan-3-ol gave the
quantitative reduction of 4-heptanone after 12 h at 70 degC This result led to the proposal that
chiral alcohols could possibly be used as the solvent to induce asymmetric reduction of ketones
Thus testing this theory using enantiomerically pure alcohols (S)-2-octanol (R)-2-octanol (R)-
(+)-1-phenyl-1-butanol (S)-(+)-12-propanediol and (R)-(+)-11rsquo-bi(2-naphthol) the prochiral
ketone substrates in Table 31 entries 2 - 10 were hydrogenated although in all cases the
products were obtained as racemic mixtures
326 Other boron-based catalysts for carbonyl hydrogenations
While exploring other boron-based catalysts in carbonyl reductions borenium cation-based FLP
hydrogenation catalysts105 derived from carbene-stabilized 9-borabicyclo[331]nonane (9-
BBN) were tested in lieu of B(C6F5)3 (Figure 34) However at 70 degC (temperature required for
hydrogenation when using B(C6F5)3) the borenium cation catalysts were found to decompose to
unknown products thereby not resulting in any reactivity
100
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism
Reflecting back on a key result presented in Chapter 2 an alternative mechanism was applied to
successfully achieve B(C6F5)3 catalyzed ketone hydrogenation This finding demonstrates the
participation of the [CH3OB(C6F5)3]- anion and B(C6F5)3 in H2 activation forming CH3OH and
[HB(C6F5)3]- (Scheme 39) thereby signifying the lability of B(C6F5)3-alkoxide bonds
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond
Taking lability of the presented B-O bond into consideration a two component catalyst system
comprising of B(C6F5)3 and [NEt4][HB(C6F5)3] was conceptualized for ketone hydrogenation In
this regard the B(C6F5)3 catalyst is expected to coordinate to the carbonyl group activating it for
hydride delivery from [NEt4][HB(C6F5)3] This will consequently generate B(C6F5)3 and
B(C6F5)3-alkoxide wherein similar to Scheme 39 will react with H2 to form alcohol and
regenerate the catalysts
The proposed catalytic system was examined by combining 5 mol B(C6F5)3 and 5 mol
[NEt4][HB(C6F5)3] with 4-heptanone in toluene and heating at 80 degC under H2 (60 atm) After 12
h 1H NMR data revealed catalyst turnover giving 92 conversion to the product 4-heptanol
(Table 32 entry 1) It is important to note that under similar reaction conditions the
combination of ketone with [NEt4][HB(C6F5)3] does not give any reactivity while B(C6F5)3 alone
is decomposed to the borinic ester
101
Using this hydrogenation protocol dialkyl substituted ketones gave the corresponding alcohols
in 40 - 99 conversions by 1H NMR spectroscopy (Table 32 entries 2 - 6) Conversions were
dramatically reduced for methyl cyclohexyl ketone (Table 32 entry 7) aryl and benzyl
substituted ketones (Table 32 entries 8 - 10) benzylacetone (Table 32 entry 11) in addition to
the cyclic ketones cyclohexanone and 2-cyclohexen-1-one (Table 32 12 and 13) Interestingly
reduction of L-menthone produced the respective alcohol product in 62 by 1H NMR
spectroscopy (Table 32 entry 14)
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3]
Entry R R1 Conversion
1 n-C3H7 n-C3H7 92
2 Me iPr 57
3 Me CH2Cl gt99
4 Me 2-butyl 53
5 Et iPr gt99
6 Et CH2iPr 40
7 Me Cy 18
8 Me Ph 20
9 Ph Ph 20
10 Et CH2Ph 25
11 Me n-CH2CH2Ph 25
12 -(CH2)5- 28
13 -(CH2)3CH=CH- 0
14 -(2-iPr-5-Me)C5H8- 62
All conversions are determined by 1H NMR spectroscopy
102
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system
The mechanism of this reaction is thought to proceed by initial coordination of the Lewis acid
B(C6F5)3 to the carbonyl group assisting hydride transfer from [NEt4][HB(C6F5)3] resulting in
liberation of B(C6F5)3 and generation of [NEt4][RR1C(H)OB(C6F5)3] in which the alkoxide
anion is coordinated to B(C6F5)3 (Scheme 310) This combination of [RR1C(H)OB(C6F5)3]-
anion and B(C6F5)3 act as a FLP to activate H2 and dissociate the alcohol while simultaneously
regenerating B(C6F5)3 and [NEt4][HB(C6F5)3] By 1H NMR spectroscopy the [NEt4]+ cation
does not appear to participate in the reaction
R R1
OH
H
B(C6F5)3
R R1
O
+
B(C6F5)3
R R1
O NEt4
HB(C6F5)3
NEt4
B(C6F5)3
B(C6F5)3
R R1
O
05 H2
05 H2
H+ from H2 activation
H- from H2 activation
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation
In comparison to carbonyl hydrogenations in ethereal solvents the presented Lewis acid-assisted
mechanism has resulted in lower alcohol yields due to steric hindrance of the substrate Lewis
base preventing adequate coordination to the Lewis acid and consequently inefficient activation
of the carbonyl bond Additionally the steric hindrance of the alkoxyborate anion resulting from
hydride delivery slows down the H2 activation step allowing unreacted B(C6F5)3 and ketone to
activate H2 giving the corresponding borinic ester
328 Attempted hydrogenation of other carbonyl substrates and epoxides
Carbonyl reductions employing either the etherB(C6F5)3 FLP catalyst or the two component
catalyst species B(C6F5)3[NEt4][HB(C6F5)3] were unsuccessful for the ketones
diphenylcyclopropenone (ndash)-fenchone 25-hexanedione 6-methyl-35-heptadien-2-one
103
cyclohexane-14-dione 1-acetyl-1-cyclohexene 13-difluoroacetone 2-acetylthiophene 44-
dimethoxybutan-2-one aldehydes 5-methylthiophene-2-carboxaldehyde esters ethyl acetate
ethylchloroformate methylbenzoate ethylpyruvate phenyl acetate carboxylic acids isobutyric
acid pivalic acid 3-phenylpropanoic acid carbonates ethylene carbonate diethyl carbonate
and NN-diethylpropionamide Exposure of diethylmaleate to the hydrogenation conditions only
led to reduction of the C=C double bond
Similar treatment of the epoxides styrene oxide and trans-stilbene oxide were found to undergo
the well-documented Lewis acid catalyzed Meinwald rearrangement forming 2-
phenylacetaldehyde and 22-diphenylacetaldehyde respectively Selectivity of the aldehyde
products is determined by formation of the most stable carbenium intermediate followed by a
hydride shift (2-phenylacetaldehyde) or substituent shift (22-diphenylacetaldehyde)290-291
Moreover an attempt at extending this reduction procedure to the greenhouse gas CO2 was not
successful In this sense a J-Young tube consisting of B(C6F5)3 and 10 eq of Et2O was
pressurized with CO2H2 and heated at temperatures up to 80 degC Multinuclear NMR data only
revealed resonances corresponding to the Et2O-B(C6F5)3 adduct
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases
As presented in Section 322 judicious choice of the FLP catalyst derived from ether and
B(C6F5)3 gives catalytic hydrogenation of carbonyl substrates to their corresponding alcohols
The protonated ether solvent is proposed to hydrogen bond with the ketone substrate stabilizing
the Broslashnsted acidic proton while activating the carbonyl fragment to accept hydride from the
[HB(C6F5)3]- anion (Scheme 37)
Continued interest in ketone and aldehyde hydrogenation reactions led to the investigation of
potential oxygen-rich materials that will mimic ethereal solvents permitting catalytic
hydrogenation in a non-polar solvent To this end FLP hydrogenations were performed in
toluene using the Lewis acid B(C6F5)3 with the addition of heterogeneous Lewis bases including
cyclodextrins (poly)saccharides or molecular sieves (MS) with the formula
Na12[(AlO2)12(SiO2)12] (Figure 35)
104
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
3291 Polysaccharides as heterogeneous Lewis bases
In probing this investigation α-cyclodextrin (α-CD) an oligosaccharide formed of six
glucopyranose units (Figure 35 a) was initially tested in H2 activation In this regard 5 mol
B(C6F5)3 and α-CD were combined in d8-toluene and exposed to HD gas (1 atm) in a J-Young
tube at 60 degC (Figure 36 a) 1H NMR analysis after 1 h revealed signals for H2 resulting from
isotope equilibration thereby signifying the viability of H2 activation between B(C6F5)3 and the
oxygen donors of α-CD (Figure 36 b) Furthermore the 11B and 19F NMR spectra indicated
signals corresponding to unaltered B(C6F5)3 thus suggesting a remarkably simple and
inexpensive H2 activation FLP catalyst It is important to note that B(C6F5)3 or α-CD alone do not
effect HD activation
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD)
To assess the unprecedented FLP system in carbonyl hydrogenation catalysis the ketone 3-
methyl-2-butanone was combined with an equivalent of α-CD and 5 mol B(C6F5)3 in toluene
and heated at 60 degC under H2 (60 atm) After 12 h quantitative reduction to the product 3-
methyl-2-butanol was evidenced by 1H NMR spectroscopy revealing a diagnostic multiplet at
327 ppm corresponding to the product CH group and broad singlet at 182 ppm assignable to the
a) b)
a)
b)
105
OH group (Table 33 entry 1) Repeating the reaction in the absence of H2 does not lead to
reduction of the substrate thus eliminating the possibility of transfer hydrogenation from α-CD
Under similar conditions a series of methyl alkyl (Table 33 entries 2 - 6) and dialkyl ketones
(Table 33 entries 7 - 9) aryl (Table 33 entries 10 - 14) benzyl (Table 33 entries 15 - 19) and
cyclic ketones (Table 33 entries 20 - 22) were hydrogenated in high yields In addition the
catalytic reduction of aldehydes was similarly performed to give the corresponding primary
alcohols (Table 33 entries 23 - 25) The 1H NMR spectra for all products displayed a
characteristic resonance at about 4 ppm diagnostic of CH and CH2 protons for ketone and
aldehyde reductions respectively and the corresponding 13C1H resonances were observed at
ca 70 ppm
The efficient nature of these catalytic reactions imply that B(C6F5)3 and the oxygen atoms of α-
CD act as a FLP to activate H2 initiating hydrogenation catalysis Selective silylation of α-CD at
the 2- and 6-hydroxy positions of the glucose units gave the toluene soluble product hexakis[26-
O-(tert-butyldimethylsilyl)]-α-cyclodextrin292 This derivatization was found to have a marginal
influence on catalysis forming 3-methyl-2-butanol in 70 yield after 12 h at 60 degC Moreover
the hydrogenation protocol was further investigated using the heterogeneous Lewis bases β and
γ-CD oligosaccharides of seven and eight glucopyranose units respectively and the
(poly)saccharides maltitol and dextrin Hydrogenation results are summarized in Table 33
Taking into account that cyclodextrins are used as chiral stationary phases in separation of
enantiomers the prochiral substrates of Table 33 were analyzed by chiral GC However in all
cases the products were found as racemic mixtures
106
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
Entry R R1 α-CD β-CD γ-CD Maltitol Dextrin MS
1 Me iPr gt99 79 77 62 81 gt99
2 Me 2-butyl gt99 74 72 46 75 gt99
3 Me CH2tBu gt99 52 41 40 53 gt99
4 Me CH2Cl gt99 gt99 trace 51 trace 80
5 Me Cy gt99 81 62 31 64 gt99
6 Me n-C5H11 gt99 63 56 36 73 gt99
7 Et iPr gt99 75 75 69 80 gt99
8 Et n-C4H9 95 93 95 58 gt99 93
9 n-C3H7 n-C3H7 gt99 - - - - 92
10a Me Ph 30 13 15 10 27 trace
11 CH2CH2Cl Ph 54 - - - - 50
12 CF3 Ph 20 - - - - 20
13 Me o-CF3C6H4 trace - - - - 25
14 Me p-MeSO2C6H4 60 - - - - 97
15 Me n-CH2CH2Ph gt99 58 90 38 trace gt99
16 Me CH2(o-FC6H4) 75 70 69 66 34 gt99
17 Me CH2(p-FC6H4) gt99 49 31 55 48 gt99
18 Me CH2(m-CF3C6H4) gt99 gt99 62 43 92 gt99
19 Et CH2Ph gt68 20 31 28 46 gt99
20 -(CH2)5- gt99 72 65 68 90 gt99
21b -(CH2)3CH=CH- 67 trace trace trace trace 82
22 -(2-iPr-5-Me)C5H8- gt99 70 60 60 80 gt99
23 Cy H 10 - - - - 44
24 Ph2CH H 47 - - - - 86
25 PhCH(Me) H 20 - - - - 35
a Reported yields are for phenylethanol b Product is cyclohexanol Isolated yields are reported for α-CD and MS
107
3292 Molecular sieves as heterogeneous Lewis bases
The presented (poly)saccharides could be conveniently replaced with the ubiquitous laboratory
drying agent MS293 as HD isotope equilibration experiments evidenced the formation of H2
when exposed to a d8-toluene suspension of MS and B(C6F5)3 It is noteworthy however that
such equilibration was not observed in the absence of B(C6F5)3
Using MS as the heterogeneous Lewis base 5 mol B(C6F5)3 catalyzed the hydrogenation of
ketone and aldehyde substrates reported in Table 33 These reductions could also be performed
on an increased scale with consecutive recycling of the MS For example 100 g of 4-heptanone
in toluene was treated with 5 mol of the catalyst B(C6F5)3 and MS yielding quantitative
conversion to 4-heptanol which was isolated in 95 yield The sieves were washed with solvent
and recombined with borane and ketone in three successive hydrogenations without loss of
activity
Speculation of physisorbed B(C6F5)3 onto MS was probed by reusing filtered sieves that were
washed with toluene without further addition of B(C6F5)3 This gave 30 reduction of 4-
heptanone suggesting that while there is some physisorption it is not sufficient to provide a
significant degree of catalysis
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones
In an effort to reduce the aryl alkyl ketone acetophenone the above protocol using α-CD was
employed for 12 h at 70 degC under H2 (60 atm) 1H NMR data revealed ca 60 consumption of
acetophenone resulting in the formation of two products in almost equal ratios The distinct
quartet at 424 ppm broad singlet at 342 ppm and doublet at 102 ppm were consistent with the
hydrogenated product phenylethanol (Scheme 311) The 1H NMR spectrum of the second
product gave three separate doublet of doublets with olefinic chemical shifts observed at 652
556 and 504 ppm with each signal integrating to one proton Mass spectroscopy confirmed this
species to be styrene derived from reductive deoxygenation (Scheme 311) The reaction was
repeated using MS giving styrene in a significantly improved 92 yield (Table 34 entry 1)
108
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone
To probe this deoxygenation further the ketone 3rsquo-(trifluoromethyl)acetophenone was treated
with 5 mol B(C6F5)3 in toluene and added to a suspension of MS and heated for 12 h at 70 degC
under H2 (60 atm) This resulted in formation of the deoxygenated product 3-
(trifluoromethyl)styrene in 95 yield (Table 34 entry 2) while remainder of the reaction
mixture consisted of the alcohol 3rsquo-(trifluoromethyl)phenyl ethanol Similar treatment of
propiophenone gave trans-β-methylstyrene in 96 yield with trace amounts of the cis isomer
(Table 34 entry 3) In a similar timeframe the deoxygenation of isobutyrophenone was
performed giving 75 of the hydrocarbon 2-methyl-1-phenyl-propene while 10 of the mixture
consisted of the alcohol 1-phenyl-1-propanol (Table 34 entry 4) In this case the comparatively
slower deoxygenation rate is presumably due to increased steric hindrance about the carbonyl
functionality Indeed these effects are more pronounced with 222-trimethylacetophenone as no
reaction was observed Finally the bicyclic ketone 1-tetralone gave 12-dihydronaphthalene in
88 yield (Scheme 312 a)
Table 34 ndash Deoxygenation of aryl alkyl ketones
Entry R R1 R2 Isolated yield
1 H Me CH2 92
2 CF3 Me CH2 95
3 H Et CHCH3 trans 96
cis 4
4 H iPr C(Me)2 75
109
In light of the established tandem hydrogenation and deoxygenation protocol under these
conditions benzophenone is deoxygenated to give diphenylmethane in 81 yield (Table 35
entry 1) Similarly the diaryl ketone derivatives with substituents including CH3O Br tBu and
CH3 groups were reduced affording the corresponding diarylmethane products in yields ranging
from 67 - 99 (Table 35 entries 2 - 5) In the case of p-CF3 substituted benzophenone the
reaction gave 10 of the deoxygenation and 50 of the alcohol products (Table 35 entry 6)
Analogous treatment of 2-methylbenzophenone resulted in only 20 conversion to the aromatic
hydrocarbon (Table 35 entry 7) This example including the result for 2rsquo-
(trifluoromethyl)acetophenone (25 yield) (Table 33 entry 13) certainly infer that increased
steric hindrance about the carbonyl group has a negative impact on reactivity
Finally the tricyclic ketone dibenzosuberone afforded the reduced aryl alkane
dibenzocycloheptene in 73 yield (Scheme 312 b) It is noteworthy that Repo et al have
previously reported B(C6F5)3 mediated reductive deoxygenation of acetophenone in CD2Cl2
however in their case concurrent hydration of the borane affords (C6F5)2BOH and C6F5H178 In
the present system MS preclude this degradation pathway allowing deoxygenation to proceed
catalytically
Table 35 ndash Deoxygenation of diaryl ketones
Entry R R1 Isolated yield
1 H Ph 81
2 CH3O Ph 85
3 Br Ph 67
4 tBu Ph gt99
5 CH3 p-CH3C6H4 75
6 CF3 Ph 10
7 H o-CH3C6H4 20
110
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b)
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation
The mechanism of these ketone and aldehyde reductions is thought to be analogous to the FLP
reductions described earlier in ethereal solvents In the present case the FLP initiating
heterolytic H2 activation is believed to be the Lewis basic oxygen atoms on the surface of the α-
CD or MS and the Lewis acid B(C6F5)3 (Scheme 313) although H2 activation by ketone
B(C6F5)3 cannot be dismissed Proceeding from the former activation method similar to the case
in ethereal solvents the protonated surface hydrogen bonds to the carbonyl fragment polarizing
the bond for hydride transfer from the [HB(C6F5)3]- anion The generated alkoxide anion is then
sufficiently basic to accept proton from the surface thus regenerating the heterogeneous Lewis
base This H2 activation is in agreement with HD equilibration experiments presented for α-CD
and MS
The ease of deoxygenating the ketones Ph2C=O gt PhCH3C=O gave insight to postulate the
reductive deoxygenation mechanism Heterolytic H2 activation occurs between the MS and
B(C6F5)3 although activation between ketoneB(C6F5)3 and alcoholB(C6F5)3 cannot be
dismissed ultimately resulting in protonated alcohol which is hydrogen-bonded to ketone
(Scheme 313) At this stage it appears that C-O bond cleavage with hydride delivery and loss
of H2O affords the aromatic alkene or alkane products Evidence of the alcohol-H-ketone
intermediate proposed in the mechanism is investigated in the following section
111
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones
Experimental results have demonstrated electronic effects directly impact the deoxygenation
mechanism It appears that C-O bond cleavage and loss of H2O is governed by stability of an
alcohol carbocation intermediate Aryl alcohols readily stabilize such an intermediate through
delocalization by the neighbouring π-system while this effect is clearly absent with dialkyl and
primary alcohols Moreover electron withdrawing groups prevent formation of the carbocation
as demonstrated by the reduction results of 222-trifluoroacetophenone and 4-
(methylsulfonyl)acetophenone These compounds exclusively gave the corresponding alcohol
products (Table 33 entries 12 and 14)
32101 Verifying the reductive deoxygenation mechanism
To validate the proposed reductive deoxygenation mechanism treatment of diphenylmethanol
with 5 mol B(C6F5)3 and MS was carried out at 70 degC under H2 (60 atm) (Figure 37)
Surprisingly the reaction only gave 10 mol of diphenylmethane and complete degradation of
B(C6F5)3 Modification of the study to include 5 10 and 50 mol of benzophenone gradually
increased consumption of diphenylmethanol indicating participation of ketone in the
deoxygenation process (Figure 37) Such a mechanism accounts for necessity of a strong
112
Broslashnsted acid to initiate the deoxygenation process by protonating the hydroxyl group
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased
The conversion of carbonyl substrates to hydrocarbons is an important and rather broad area of
research in modern organic chemistry with extensive contribution to the production of fuels
Replacement of an oxo group by two hydrogen atoms is generally carried out through
hydrogenolysis although hydrogenation methods are also well studied Prominent procedures for
this transformation include the Clemmensen reduction294-295 Wolff-Kishner reduction296 and
stoichiometric methods involving LiAlH4-AlCl3 NaBH4-CF3CO2H297 Et3SiH-BF3 or
CF3CO2H298-299 and HI-Phosphorus combinations300-301 in addition to metal-catalyzed
approaches62
From the perspective of FLP systems reductive deoxygenation of carbonyl groups has been
previously achieved using silanes boranes or ammonia borane165 as sacrificial reducing agents
0 mol
5 mol
10 mol
50 mol
Diphenylmethanol (CH) Diphenylmethane (CH2)
113
The Piers group showed the B(C6F5)3 catalyzed deoxygenative hydrosilylation of CO2 to CH4
using TMP B(C6F5)3 and excess Et3SiH169 Such transformations have also been reported using
N-heterocyclic carbenes and hydrosilanes302 The Fontaine group among others111 163 have
shown the hydroboration of CO2 to methanol using FLPs167-168 Significantly more challenging is
H2 as the reducing reagent In a unique example Ashley and OrsquoHare reported the reduction of
CO2 by H2 using a stoichiometric combination of B(C6F5)3 and TMP at 160 degC to give methanol
in 17 - 25 yield259
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins
In the experiments presented 4 Aring pellet MS purchased from Sigma Aldrich were used in
combination with B(C6F5)3 To explore the efficacy of other materials the same hydrogenation
protocol was applied in the reduction of 4-heptanone to give 4-heptanol in the following yields 5
Aring MS pellets (gt99) 4 Aring MS powder (69) 3 Aring MS pellets (68) acidic alumina (30)
silicic acid (15) while no reactivity was observed in the case of silica gel sodium aluminate
neutral and basic alumina
The hydrogenation protocol using 4 Aring MS was also attempted in the reduction of olefins
including 1-hexene cyclohexene 11-diphenylethylene and αp-dimethylstyrene however no
reactivity was observed in either case
33 Conclusions
The following chapter provides an account on the discovery of a metal-free route for the
hydrogenation of ketone and aldehyde substrates to form alcohol products The FLP catalyst is
derived from ether and B(C6F5)3 in which the protonated ether participates in hydrogen-bonding
interactions with the substrate affording an efficient catalyst to mediate the transformations
Moreover B(C6F5)3-assisted ketone hydrogenations using a two component catalyst system
derived from B(C6F5)3 and [NEt4][HB(C6F5)3] has also proven viable
Simultaneous with communicating this finding Ashley et al reported an analogous
hydrogenation catalyst derived from 14-dioxaneB(C6F5)3 that is effective for the hydrogenation
of ketones and aldehydes at 4 atm of H2 and temperatures ranging between 80 and 100 degC260
114
Also an air stable catalyst derived from THFB(C6Cl5)(C6F5)2 was shown to be particularly
effective for the hydrogenation of weakly Lewis basic substrates286
Continuing to explore modifications and applications of this new metal-free carbonyl reduction
protocol catalytic reductions were achieved in toluene using B(C6F5)3 and a heterogeneous
Lewis base including CDs (poly)saccharides or MS This combination of soluble borane and
insoluble materials provided a facile route to alcohol products In the case of aryl ketones and
MS further reactivity of the alcohol resulted in deoxygenation of the carbonyl group affording
either the aromatic alkane or alkene products
34 Experimental Section
341 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane tetrahydrofuran toluene (Sigma Aldrich) were dried employing a Grubbs-type
column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring) in the
glovebox Bromobenzene (-H5 and -D5) were purchased from Sigma Aldrich and dried over
CaH2 for several days and vacuum distilled onto 4 Aring molecular sieves prior to use
Dichloromethane-d2 benzene-d6 and chloroform-d were purchased from Sigma Aldrich
Toluene-d8 was purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to
use Molecular sieves (4 Aring) were purchased from Sigma Aldrich and dried at 120 ordmC under
vacuum for 12 h prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at
80 degC under high vacuum before use
Tetrahydropyran 14-dioxane and hexamethyldisiloxane were purchased from Sigma Aldrich
and distilled over sodiumbenzophenone prior to use Diphenyl ether (ReagentPlusreg ge99) was
purchased from Sigma Aldrich and distilled under high vacuum at 80 degC over anhydrous
calcium chloride prior to use Diethyl ether (anhydrous 99) was purchased from Caledon
Laboratories Ltd and passed through a Grubbs-type column system manufactured by Innovative
Technology and stored over 4 Aring molecular sieves overnight prior to use Diisopropyl ether
(anhydrous 99 contains either BHT or hydroquinone as stabilizer) was purchased from Sigma
Aldrich and used without purification Cyclodextrins (α β and γ) maltitol dextrin from maize
starch and molecular sieves (pellets 32 mm diameter 4 Aring) were purchased from Sigma Aldrich
115
dried under vacuum at 120 degC for 12 h prior to use Deuterium hydride (extent of labeling 96
mol HD 98 atom D) was purchased from Sigma Aldrich Potassium
tetrakis(pentafluorophenyl)borate was purchased from Alfa Aesar Sodium triethylborohydride
(1M in toluene) was purchased from Sigma Aldrich Borenium cation-based FLP catalysts were
prepared by Dr Jeffrey M Farrell and Mr Roy Posaratnanathan following the literature
protocol105
All ketones and alcohols were purchased from Alfa Aesar Sigma Aldrich or TCI The liquids
were stored over 4 Aring molecular sieves and used without purification The solids were placed
under dynamic vacuum overnight prior to use H2 (grade 50) was purchased from Linde and
dried through a Nanochem Weldassure purifier column prior to use For the high pressure Parr
reactor the H2 was dried through a Matheson TRI-GAS purifier (type 452)
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D6 (1H = 716 ppm 13C = 1284 ppm) C6D5Br (1H = 728
ppm for meta proton 13C = 1224 ppm for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384
ppm) d8-tol (1H = 208 ppm for CH3 13C = 13748 ppm for ipso carbon) CDCl3 (1H = 726 ppm 13C = 7716 ppm) or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in
ppm and the absolute values of the coupling constants (J) are in Hz NMR assignments are
supported by additional 2D and DEPT-135 experiments
High Resolution Mass Spectroscopy (HRMS) was obtained using JMS T100-LC AccuTOF
DART with ion source Direct Analysis in Real Time (DART) Ionsense Inc Saugus MA GC-
MS spectra were obtained on an Agilent Technologies 5975C VL MSD with Triple-Axis
Detector and 7890A GC System Column Agilent 19091S-433 (30 m times 250 μm times 025 μm)
Oven 40 degC for first 10 min 10 degCmin to 300 degC for 10 min Injection volume 1 μL The pro-
chiral samples were analyzed using a Perkin Elmer Autosystem CL chromatograph with a chiral
column (CP Chirasil-Dex CB 25 m times 25 mm)
Jutzi acid [(Et2O)2H][B(C6F5)4]287 and silylation of α-CD with tert-butyldimethylsilyl chloride292
were prepared according to literature procedures
116
Solid materials were purchased from commercial sources 5 Aring molecular sieves (pellets 32 mm
Aldrich) 4 Aring molecular sieves (powder Aldrich) 3 Aring molecular sieves (rod 116 inches
Aldrich) aluminum oxide (weakly acidic 150 mesh 58 Aring SA = 155 m2g Aldrich) sodium
metasilicate (18 mesh granular Alfa Aesar) silicic acid (80 mesh powder Aldrich) silica gel
(200-425 mesh 60 Aring high purity grade Silicycle) sodium aluminate (powder Aldrich)
aluminum oxide (basic 150 mesh 58 Aring SA = 155 m2g Aldrich) aluminum oxide (neutral
150 mesh 58 Aring SA = 155 m2g Aldrich)
342 Synthesis of Compounds
3421 Procedures for reactions in ethereal solvents
4-Heptanol-B(C6F5)3 adduct experiment In the glove box an NMR tube was charged with a
d8-toluene (04 mL) solution of B(C6F5)3 (122 mg 240 μmol 100 mol) and 4-heptanol (279
mg 0240 mmol) The NMR tube was sealed with Parafilm and placed in an 80 degC oil bath for
12 h 19F and 11B NMR spectra were obtained No evidence for the formation of C6F5H was
observed
19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1552 (t 3JF-F = 22 Hz 1F p-C6F5) -
1628 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 197 (br s 4-heptanol-B(C6F5)3)
Synthesis of (CH3CH2CH2)2CHOB(C6F5)2from the reaction of 4-heptanone and HB(C6F5)2
In the glove box an NMR tube was charged with a d8-toluene (04 mL) solution of HB(C6F5)2
(834 mg 0240 mmol) and 4-heptanone (274 mg 0240 mmol) A second NMR tube was
charged with a d8-toluene (04 mL) solution of HB(C6F5)2 (83 mg 24 μmol 10 mol) and 4-
heptanone (274 mg 0240 mmol) After 10 min at RT the samples were analyzed by 1H 19F
and 11B NMR spectroscopy
1H NMR (400 MHz d8-tol) δ 405 (tt 3JH-H = 76 38 Hz 1H CH) 168-151 (m 2H CH2)
150 - 134 (m 4H CH2) 133 - 115 (m 2H CH2) 086 (t 3JH-H = 76 Hz 6H CH3) 19F NMR
(377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1498 (t 3JF-F = 20 Hz 1F p-C6F5) -1613 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 394 (br s (CH3CH2CH2)2CHOB(C6F5)2)
High temperature NMR study for the reduction of 4-heptanone using 5 equivalent of Et2O
(J-Young Experiment) In the glove box a 1 dram vial was charged with a d8-toluene (03 mL)
117
solution of B(C6F5)3 (61 mg 12 μmol 50 mol) 4-heptanone (274 mg 0240 mmol) and Et2O
(890 mg 125 μL 120 mmol) The reaction mixture was transferred into an oven-dried Teflon
screw cap J-Young tube The reaction tube was degassed once through a freeze-pump-thaw cycle
on the vacuumH2 line and filled with H2 (4 atm) at -196 degC The reaction was monitored by high
temperature 1H NMR spectroscopy at 70 degC with 15 minute acquisitions (Figure 31)
General procedure for reactions in ethereal solvents (Table 31) The following procedure is
common to the ketone hydrogenation reactions in Et2O iPr2O Ph2O and TMS2O In the glove
box a 2 dram vial equipped with a stir bar was charged with the respective ketone or aldehyde
(048 mmol) and B(C6F5)3 (122 mg 240 μmol 500 mol) To each vial the appropriate ether
(96 mmol 20 eq) was added using a syringe Et2O (10 mL) iPr2O (13 mL) Ph2O (15 mL) and
TMS2O (20 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glove box to be pressurized with hydrogen gas
The hydrogen gas line was thoroughly purged and the reactor was attached to it and purged 10
times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at 70 degC 540 rpm
and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time the reactor was
vented and the vials were exposed to the atmosphere In the case of Et2O and iPr2O the entire
reaction mixture was transferred to a round bottom flask and all the volatiles were collected by
vacuum distillation while cooling the collected distillate with liquid nitrogen The solvent was
then removed by applying a gentle stream of N2 gas The alcohol yields were recorded and the
products were characterized by NMR spectroscopy and GC-MS
General procedure for 100 gram reaction of 4-heptanone in Et2O In the glove box 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol 500 mol) dissolved in Et2O (143 mg 200 mL 0190 mol)
was added to the bottle The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glove box and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 540 rpm After the indicated reaction time the reactor was slowly
vented and all the volatiles were collected by vacuum distillation while cooling the collected
distillate with liquid nitrogen The solvent was removed by applying a gentle stream of N2 gas
118
By 1H NMR spectroscopy the product displayed complete conversion to 4-heptanol and was
isolated in 87 yield
Dependence of Et2O equivalents on the reduction of 4-heptanone (Figure 32) In the glove
box a stock solution consisting of 4-heptanone (192 mg 235 μL 167 mmol) and B(C6F5)3 (427
mg 800 μmol 500 mol) in toluene (35 mL) was prepared in a 2 dram vial The solution was
distributed evenly between seven 2-dram vials (053 mLvial) and each vial was equipped with a
stir bar To each vial the appropriate volume of Et2O was added using a (micro)syringe
Et2O volume 12 μL (005 eq) 25 μL (01 eq) 125 μL (05 eq) 252 μL (10 eq) 504 μL (20
eq) 756 μL (30 eq) 101 μL (40 eq) 126 μL (50 eq) 151 μL (60 eq) 176 μL (70 eq) 202 μL
(80 eq)
The vial was loosely capped and loaded in a Parr pressure reactor sealed carefully and removed
from the glove box to be pressurized with hydrogen gas The hydrogen gas line was thoroughly
purged and the reactor was attached to it and purged 10 times at 15 atm of hydrogen gas The
reactor was then placed in an oil bath set at 70 degC 540 rpm and sealed at 60 atm of hydrogen gas
for 12 h After the indicated reaction time the reactor was vented and the reactions were analyzed
by 1H NMR spectroscopy Percent conversion to 4-heptanol was obtained by integration relative
to the remaining starting material 4-heptanone
Synthesis of [iPr2O-HmiddotmiddotmiddotO=C(CH2Ph)CH2CH3][B(C6F5)4] (31) In the glove box to a 2 dram
vial was added [(Et2O)2H][B(C6F5)4] (130 mg 0157 mmol) 4-phenyl-2-butanone (349 mg
0235 mmol) iPr2O (1284 mg 126 mmol) and toluene (05 mL) The solution was transferred
into a Teflon-sealed Schlenk bomb (25 mL) equipped with a stir bar and heated at 70 degC for 2 h
The solvent was removed under vacuum and pentane (5 mL) was added to result in immediate
precipitation of a white solid that was washed again with pentane (3 mL) and dried under
vacuum (127 g 136 mmol 87) Crystals suitable for X-ray crystallographic studies were
obtained from a layered bromobenzenepentane solution at RT
1H NMR (400 MHz CD2Cl2) δ 1152 (br s 1H iPr2O-HmiddotmiddotmiddotO=C) 741 (m 3H m p-Ph) 718
(m 2H o-Ph) 468 (m 3JH-H = 68 Hz 2H iPr) 403 (s 2H PhCH2) 281 (q 3JH-H = 71 Hz
2H CH2CH3) 146 (d 3JH-H = 68 Hz 12H iPr) 117 (t 3JH-H = 71 Hz 3H CH2CH3) 19F NMR
(377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1617 (t 3JF-F = 22 Hz 1F p-C6F5) -1658 (m
119
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -168 (s B(C6F5)4) 13C1H NMR (125 MHz
CD2Cl2) δ 1480 (dm 1JC-F = 238 Hz CF) 1379 (dm 1JC-F = 243 Hz CF) 1362 (dm 1JC-F =
246 Hz CF5) 1319 (ipso-Ph) 1301 (m-Ph) 1298 (o-Ph) 1288 (p-Ph) 1240 (ipso-C6F5) 828
(iPr) 498 (CH2Ph) 373 (CH2CH3) 197 (iPr) 799 (CH2CH3) (C=O was not observed)
HRMS (DART-TOF+) mass [M]+ calcd for [C16H27O2]+ 25120110 Da Found 25120127 Da
mass [M]- calcd for [C24BF20]- 67897736 Da Found 67897745 Da
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3]
Synthesis of [NEt4][HB(C6F5)3] Part 1 In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (200 mg 0391 mmol) in toluene (10 mL) To the vial
sodium triethylborohydride (1M in toluene) (036 mL 036 mmol) was added drop wise over 15
min The reaction was allowed to mix overnight prior to removing the volatiles under vacuum
The crude mixture was washed with pentane (5 mL) to give the product Na HB(C6F5)3 as a white
solid (187 mg 0348 mmol 89)
Part 2 Na HB(C6F5)3 (187 mg 0348 mmol) was subsequently added to CH2Cl2 (10 mL) and
added to a 4 dram vial containing NEt4 Cl (576 mg 0348 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT overnight and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (206 mg
0320 mmol 92)
1H NMR (400 MHz d8-tol) δ 415 (br q 1JB-H = 91 Hz 1H BH) 211 (q 3JH-H = 74 Hz 8H
Et) 046 (tm 3JH-H = 74 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -13361 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
247 (d 1JB-H = 91 Hz BH)
General procedure for reactions in toluene using B(C6F5)3 and [NEt4][HB(C6F5)3] (Table
32) In the glovebox a 2 dram vial equipped with a stir bar was charged with the respective
ketone (048 mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and [NEt4][HB(C6F5)3] (154
mg 240 μmol 500 mol) in toluene (10 mL) The vial was loosely capped and loaded in a
Parr pressure reactor sealed carefully and removed from the glovebox to be pressurized with
hydrogen gas The hydrogen gas line was thoroughly purged and the reactor was attached to it
and purged 10 times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at
80 degC 540 rpm and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time
120
the reactor was vented and the reactions were analyzed by 1H NMR spectroscopy Percent
conversion to the alcohol product was obtained by integration relative to the remaining starting
material ketone
3423 Procedures for reactions using heterogeneous Lewis bases
General procedure for reactions in toluene using heterogeneous Lewis bases (Table 33) In
the glovebox a 2 dram vial equipped with a stir bar was charged with the respective ketone (048
mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and the respective heterogeneous Lewis base
in toluene (10 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glovebox to be pressurized with hydrogen gas The hydrogen gas
line was thoroughly purged and the reactor was attached to it and purged 10 times at 15 atm of
hydrogen gas The reactor was then placed in an oil bath set at 60 degC 430 rpm and sealed at 60
atm of hydrogen gas for 12 h Products were isolated by appropriate work-up methods The
alcohol yields were recorded and the products were characterized by NMR spectroscopy and
GC-MS
Heterogeneous Lewis bases α-CD (467 mg 0480 mmol) β-CD (467 mg 0410 mmol) γ-CD
(467 mg 0360 mmol) maltitol (168 mg 0480 mmol) dextrin (350 mg) MS (100 mg)
General procedure 100 g scale reduction of 4-heptanone using MS In the glovebox 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol) dissolved in toluene (7 mL ) was added to the bottle in addition
to 302 g of 4 Aring MS The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glovebox and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 430 rpm The reactor was slowly vented and an aliquot was taken in
d8-toluene and complete conversion of 4-heptanone to 4-heptanol was determined by 1H NMR
spectroscopy The reaction mixture was filtered through a frit and washed with dichloromethane
(2 times 10 mL) The collected molecular sieves were extracted with dichloromethane (3 times 10 mL)
and water (20 mL) The organic fraction was dried over magnesium sulfate and combined with
the toluene fraction The two solvents dichloromethane and toluene were removed by fractional
121
distillation 4-Heptanol was then collected under vacuum in a liquid nitrogen cooled Schlenk
flask The product was collected as a colourless liquid (0885 g 762 mmol 87)
3424 Procedures for reductive deoxygenation reactions
General procedure for deoxygenation reactions using molecular sieves (Table 34 and Table
35) This method follows the same procedure for reactions in Table 33 using 4 Aring MS The
reactor was placed in an oil bath set at 70 degC 340 rpm and sealed at 60 atm of hydrogen gas for
12 h Products were isolated by appropriate work-up methods The aromatic hydrocarbon yields
were recorded and the products were characterized by NMR spectroscopy and GC-MS
Verifying the deoxygenation mechanism In the glovebox four separate 2-dram vials were
loaded with diphenylmethanol (442 mg 0240 mmol) and B(C6F5)3 (61 mg 12 μmol 50
mol) To each vial the indicated equivalents of benzophenone were added (21 mg 12 μmol
50 mol 44 mg 24 μmol 10 mol 218 mg 0120 mmol 50 mol) followed by the
addition of d8-toluene (05 mL) and 4 Aring MS (100 mg) The reaction vials were equipped with a
stir bar loosely capped and placed inside a Parr pressure reactor The reactor was sealed
removed from the glovebox and attached to a purged hydrogen gas line The reactor was purged
ten times at 15 atm with hydrogen gas The reactor was then pressurized with 60 atm hydrogen
gas and placed in an oil bath for 12 h at 70 degC and 340 rpm After the indicated reaction time the
reactor was slowly vented and an aliquot was taken in d8-toluene and conversion of the
diphenylmethanol to diphenylmethane was determined by 1H NMR spectroscopy
3425 Spectroscopic data of products in Table 31
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
4-Heptanol (Entry 1) 1H NMR (500 MHz C6D5Br) δ 472 (br s 1H OH) 341 (tt 3JH-H = 70
Hz 46 Hz 1H CH) 124 (m 4H CHCH2) 114 (m 4H CH2CH3) 082 (t 3JH-H = 67 Hz 6H
CH3) 13C1H NMR (125 MHz C6D5Br) δ 721 (CH) 390 (CHCH2) 184 (CH2CH3) 135
(CH3) GC-MS 11928 min mz = 981 [M-H2O] 730 [M-C3H7] 550 [M-C3H9O]
3-Methylbutan-2-ol (Entry 2) 1H NMR (500 MHz C6D5Br) δ 339 (qd 3JH-H = 63 Hz 53
Hz 1H CHOH) 145 (m 1H iPr) 115 (br s 1H OH) 100 (d 3JH-H = 63 Hz 3H CH3) 083
122
(d 3JH-H = 68 Hz 3H iPr) 080 (d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz
C6D5Br) δ 719 (CHOH) 347 (iPr) 200 (CH3) 180 (iPr) 175 (iPr) GC-MS 3150 min mz
= 731 [M-CH3] 551 [M-CH5O]
44-Dimethylpentan-2-ol (Entry 3) 1H NMR (500 MHz C6D5Br) δ 380 (m 1H CH) 368
(br s 1H OH) 127 (dd 2JH-H = 143 Hz 3JH-H = 79 Hz 1H CH2) 116 (dd 2JH-H = 143 Hz 3JH-H = 33 Hz 1H CH2) 105 (d 3JH-H = 62 Hz 3H CH3) 087 (s 9H tBu) 13C1H NMR
(125 MHz C6D5Br) δ 660 (CH) 526 (CH2) 300 (tBu) 299 (tBu) 258 (CH3) GC-MS 6776
min mz = 1011 [M-CH3] 831 [M-CH5O] 701 [M-C2H6O] 571 [M-C3H7O]
Heptan-2-ol (Entry 4) 1H NMR (500 MHz d8-tol) δ 424 (br s 1H OH)
348 (m 3JH-H = 60 Hz 1H H2) 126 (m 2H H6) 123 (m 2H H3 H4)
118 - 114 (m 4H H3 H4 H5) 097 (d 3JH-H = 60 Hz 3H H1) 090 (t 3JH-H = 71 Hz 3H
H7) 13C1H NMR (125 MHz d8-tol) δ 684 (C2) 392 (C3) 319 (C5) 255 (C4) 228 (C1
C6) 139 (C7) GC-MS 12395 min mz = 1011 [M-CH3] 981 [M-H2O] 871 [M-C2H5]
1-Chloropropan-2-ol (Entry 5) 1H NMR (500 MHz C6D5Br) δ 432 (br s 1H OH) 362 (m 3JH-H = 68 Hz 1H CH) 316 (dd 2JH-H = 113 Hz 3JH-H = 35 Hz 1H CH2Cl) 304 (dd 2JH-H =
113 Hz 3JH-H = 68 Hz 1H CH2Cl) 090 (d 3JH-H = 61 Hz 3H CH3) 13C1H NMR (125
MHz C6D5Br) δ 692 (CH) 502 (CH2Cl) 222 (CH3) GC-MS 3383 min mz = 810 [(M+2)-
CH3] 790 [M-CH3]
1-Cyclohexylethan-1-ol (Entry 6) 1H NMR (400 MHz d8-tol) δ 330 (quint 3JH-H = 74 Hz
1H CH) 182 - 147 (m 5H Cy) 131 (br s 1H OH) 125 - 102 (m 4H Cy) 098 (d 3JH-H =
74 Hz 3H CH3) 087 (m 2H Cy) 13C1H NMR (125 MHz d8-tol) δ 721 (CHOH) 452
(CyCH) 287 (Cy) 268 (Cy) 267 (Cy) 205 (CH3) GC-MS 14245 min mz = 1131 [M-CH3]
1101 [M- H2O] 831 [M-C2H5O]
2-Methylpentan-3-ol (Entry 7) 1H NMR (500 MHz C6D5Br) δ 410 (br s 1H OH) 308
(ddd 3JH-H = 88 Hz 52 Hz 38 Hz 1H CHOH) 146 (m 3JH-H = 68 Hz 52 Hz 1H iPr) 133
(dqd 2JH-H = 140 Hz 3JH-H = 75 Hz 39 Hz 1H CH2) 120 (ddq 2JH-H = 140 Hz 3JH-H = 86
Hz 75 Hz 1H CH2) 081 (t 3JH-H = 75 Hz 3H CH3) 077 (d 3JH-H = 68 Hz 3H iPr) 076
(d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz C6D5Br) δ 783 (CHOH) 326 (iPr) 264
123
(CH2) 184 (iPr) 167 (iPr) 994 (CH3) GC-MS 5663 min mz = 841 [M-H2O] 731 [M-
C2H5] 591 [M-C3H7]
Heptan-3-ol (Entry 8) 1H NMR (500 MHz C6D5Br) δ 450 (br s 1H
OH) 335 (tt 3JH-H = 73 Hz 47 Hz 1H H3) 136-130 (m 2H H2) 128-
121 (m 5H H4 H5 H6) 115 (m 1H H5) 084 (t 3JH-H = 57 Hz 3H H7) 083 (t 3JH-H = 57
Hz 3H H1) 13C1H NMR (125 MHz C6D5Br) δ 732 (C3) 362 (C4) 295 (C2) 275 (C5)
226 (C6) 138 (C7) 961 (C1) GC-MS 12171 min mz = 981 [M-H2O] 831 [M-CH5O]
691 [M-C2H7O] 590 [M-C4H9]
5-Methylhexan-3-ol (Entry 9) 1H NMR (400 MHz d8-tol) δ (tt 3JH-H = 87 51 Hz 1H
CHOH) 201 (m 2H CH2CH3) 148 (m 3JH-H = 69 51 Hz 1H iPr) 130 (m 1H CH2iPr)
126 (m 1H CH2iPr) 089 (d 3JH-H = 69 Hz 6H iPr) 085 (t 3JH-H = 72 Hz 3H CH3)
13C1H NMR (101 MHz d8-tol) δ 785 (CHOH) 337 (iPr CH2CH3) 273 (CH2iPr) 188
(iPr) 171 (iPr) 104 (CH3) GC-MS 9458 min mz = 871 [M-Et] 691 [M-C2H7O] 591 [M-
CH2iPr]
1-Phenylethan-1-ol (Entry 10) 1H NMR (400 MHz C6D6) δ 702 (m 5H Ph) 428 (q 3JH-H =
65 Hz 1H CH) 342 (br s 1H OH) 102 (d 3JH-H = 65 Hz 3H CH3) 13C1H NMR (125
MHz CDCl3) δ 1460 (ipso-Ph) 1286 (m-Ph) 1283 (p-Ph) 1254 (o-Ph) 703 (CH) 252
(CH3) GC-MS 17207 min mz = 1221 [M] 1071 [M-CH3] 1040 [M-H2O] 910 [M-CH3O]
770 [M-C2H5O]
1-Phenylbutan-2-ol (Entry 11) 1H NMR (500 MHz CD2Cl2) δ 755 (m 1H OH) 733 (tm 3JH-H = 76 Hz 2H m-Ph) 729 (dm 3JH-H = 76 Hz 2H o-Ph) 725 (tm 3JH-H = 76 Hz 1H p-
Ph) 376 (dq 3JH-H = 81 Hz 42 Hz 1H CH) 286 (dd 2JH-H = 136 Hz 3JH-H = 43 Hz 1H
CH2Ph) 266 (dd 2JH-H = 136 Hz 3JH-H = 81 Hz 1H CH2Ph) 152 (q 3JH-H = 77 Hz 2H
CH2CH3) 102 (t 3JH-H = 77 Hz 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1391 (ipso-
Ph) 1295 (m-Ph) 1284 (o-Ph) 1263 (p-Ph) 739 (CH) 437 (CH2Ph) 303 (CH2CH3) 960
(CH3) GC-MS 20079 min mz = 1321 [M-H2O] 1030 [M-C2H7O] 911 [M-C3H7O]
591[M-C7H7]
4-Phenylbutan-2-ol (Entry 12) 1H NMR (500 MHz C6D5Br) δ 720 (t 3JH-H = 74 Hz 2H m-
Ph) 710 (t 3JH-H = 74 Hz 1H p-Ph) 706 (d 3JH-H = 74 Hz 2H o-Ph) 373 (br s 1H OH)
124
362 (dqd 3JH-H = 74 Hz 62 Hz 50 Hz 1H CH) 255 (m 2H PhCH2) 160 (m 2H CH2CH)
103 (d 3JH-H = 62 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1411 (ipso-Ph) 1281
(m-Ph) 1280 (o-Ph) 1255 (p-Ph) 673 (CH) 403 (PhCH2) 317 (CH2CH) 229 (CH3) GC-
MS 20438 min mz = 1501 [M] 1321 [M-H2O] 1170 [M-CH5O] 1051 [M-C2H5O] 911
[M-C3H7O]
1-(2-Fluorophenyl)propan-2-ol (Entry 13) 1H NMR (500 MHz CD2Cl2) δ
753 (m 1H OH) 733 - 705 (m 4H C6H4F) 406 (m 1H CH) 284 (dd 2JH-
H = 139 Hz 3JH-H = 51 Hz 1H CH2) 276 (dd 2JH-H = 139 Hz 3JH-H = 77
Hz 1H CH2) 124 (d 3JH-H = 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1178 (m
CF) 13C1H NMR (125 MHz CD2Cl2) δ 1611 (d 1JC-F = 240 Hz C1) 1318 (d 3JC-F = 59
Hz C3) 1285 (d 4JC-F = 88 Hz C4) 1257 (d 2JC-F = 16 Hz C2) 1240 (d 3JC-F = 37 Hz C5)
1152 (d 2JC-F = 22 Hz C6) 678 (d 4JC-F = 11 Hz CH) 388 (d 3JC-F = 14 Hz CH2) 229
(CH3) GC-MS 18697 min mz = 1360 [M-H2O] 960 [M-C3H6O]
1-(4-Fluorophenyl)propan-2-ol (Entry 14) 1H NMR (500 MHz CD2Cl2) δ 722 (m 2H o of
C6H4F) 705 (m 2H m of C6H4F) 399 (m 1H CH) 278 (dd 2JH-H = 137 Hz 3JH-H = 48 Hz
1H CH2) 269 (dd 2JH-H = 137 Hz 3JH-H = 78 Hz 1H CH2) 161 (br s 1H OH) 122 (d 3JH-H
= 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1177 (m p-C6H4F) 13C1H NMR (125
MHz CD2Cl2) δ 1616 (d 1JC-F = 243 Hz p of C6H4F) 1348 (d 4JC-F = 46 Hz ipso-C6H4F)
1307 (d 3JC-F = 82 Hz o of C6H4F) 1149 (d 2JC-F = 22 Hz m of C6H4F) 690 (CH) 449
(CH2) 227 (CH3) GC-MS 18697 min mz = 1361 [M-H2O] 960 [M-C3H6O]
1-(3-(Trifluoromethyl)phenyl)propan-2-ol (Entry 15) 1H NMR (500
MHz CD2Cl2) δ 751 (m 2H H1 H5) 744 (m 2H H3 H4) 408 (m 1H
CH) 283 (dd 2JH-H = 136 Hz 3JH-H = 49 Hz 1H CH2) 276 (dd 2JH-H =
136 Hz 3JH-H = 78 Hz 1H CH2) 181 (br s 1H OH) 123 (t 3JH-H = 62
Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -628 (CF3) 13C1H NMR (125 MHz CD2Cl2)
δ 1399 (C2) 1330 (q 4JC-F = 13 Hz C3) 1303 (q 2JC-F = 30 Hz C6) 1288 (C4) 1260 (q 3JC-F = 41 Hz C1) 1242 (q 1JC-F = 277 Hz CF3) 1230 (q 3JC-F = 41 Hz C5) 687 (CH) 447
(CH2) 228 (CH3) GC-MS 19011 min mz = 1861 [M-H2O] 1601 [M-C2H4O] 1171 [M-
CH2F3O]
125
Cyclohexanol (Entry 16) 1H NMR (400 MHz d8-tol) δ 324 (tt 3JH-H = 90 Hz 37 Hz 1H
CH) 177 (m 2H Cy) 168 (m 2H Cy) 142- 130 (m 3H Cy) 126- 115 (m 3H Cy)
13C1H NMR (101 MHz CD2Cl2) δ 706 (CH) 360 (CHCH2) 260 (Cy) 245 (Cy) GC-MS
4029 min mz = 1001 [M] 821 [M-H2O]
2-Isopropyl-5-methylcyclohexan-1-ol (Entry 17) 1H NMR (500 MHz
C6D5Br) δ 390 (q 3JH-H = 29 Hz 1H H1) 346 (br s 1H OH) 168 (ddd 2JH-H = 139 Hz 3JH-H = 36 Hz 24 Hz 1H H2) 164 (m 2H H3 H4) 153
(dm 2JH-H = 132 Hz 1H H5) 143 (dm 3JH-H = 92 Hz 67 Hz 1H H7) 118 (dm 2JH-H = 132
Hz 1H H5) 091 (m 1H H2) 087 (d 3JH-H = 67 Hz 3H H8) 083 (d 3JH-H = 67 Hz 3H
H9) 080 (d 3JH-H = 64 Hz 3H H10) 075 (m 1H H4) 070 (m 1H H6) 13C1H NMR (125
MHz C6D5Br) δ 675 (C1) 473 (C6) 421 (C2) 346 (C4) 288 (C7) 254 (C3) 238 (C5)
221 (C10) 208 (C9) 203 (C8) GC-MS 18912 min mz = 1381 [M-H2O] 1231 [M-CH5O]
951 [M-C3H9O] 811 [M-C4H12O]
Cyclohexylmethanol (Entry 18) 1H NMR (500 MHz CD2Cl2) δ 556 (br s 1H OH) 404 (d 3JH-H = 75 Hz 2H CH2OH) 212-182 (m 1H CyCH2) 180 (m 1H CyCH) 163 - 117 (m 1H CyCH2) 13C1H NMR (125 MHz CD2Cl2) δ 693 (CH2OH) 374 (CyCH) 301 (CyCH2) 262
(CyCH2) 252 (CyCH2) GC-MS 5538 min mz = 1141 [M] 961 [M-H2O] 831 [M-CH3O]
3426 Spectroscopic data of products in Table 32
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
3-Methylpentan-2-ol (Entry 4) 1H NMR (400 MHz CDCl3) δ 376 (m 1H CHOH) 223 (br
s 1H OH) 175 - 142 (m 3H CH(Et) Et) 118 (d 3JH-H = 69 Hz 3H CH3CHOH) 098 (m
6H CH(Et)CH3 Et) 13C1H NMR (125 MHz CD2Cl2) δ 713 (CHOH) 406 (CH(Et)) 223
(Et) 198 (OHCHCH3) 120 (CH(Et)CH3) 111 (Et) GC-MS 10215 min mz = 871 [M-CH3]
561 [M-C2H6O] 450 [C2H5O]
3427 Spectroscopic data of products in Table 33
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
126
222-Trifluoro-1-phenylethan-1-ol (Entry 12) 1H NMR (500 MHz d8-tol) δ 745 (m 2H m-
Ph) 717 (dm 3JH-H = 70 Hz 2H o-Ph) 711 (m 1H p-Ph) 432 (d 3JF-H = 77 Hz 1H CH)
306 (br s 1H OH) 19F NMR (470 MHz d8-tol) δ -783 (d 3JF-H = 77 Hz CF3) 13C1H NMR
(125 MHz d8-tol) δ 1341 (ipso-Ph) 1289 (m-Ph) 1276 (p-Ph) 1272 (q 4JC-F = 12 Hz o-Ph)
1234 (q 1JC-F = 297 Hz CF3) 726 (CH) GC-MS 6130 min mz = 1760 [M] 1701 [M-CF3]
3-Chloro-1-phenylpropan-1-ol (Entry 11) 1H NMR (600 MHz d8-tol) δ 712 (m 3H m p-
Ph) 703 (m 2H o-Ph) 399 (t 3JH-H = 78 Hz 1H CHOH) 312 (t 3JH-H = 67 Hz 2H CH2Cl)
251 (br s 1H OH) 218 (dt 3JH-H = 78 Hz 67 Hz 2H CHCH2CH2) 13C1H NMR (151
MHz d8-tol) δ 1440 (ipso-Ph) 1282 (m-Ph) 1275 (o-Ph) 1260 (p-Ph) 476 (CHOH) 432
(CH2Cl) 387 (CHCH2CH2) GC-MS 11210 min mz = 1701 [M] 1521 [M-H2O] 1070 [M-
C2H4Cl]
1-(2-(Trifluoromethyl)phenyl)ethan-1-ol (Entry 13) 1H NMR (500 MHz
d8-tol) δ 759 (d 3JH-H = 81 Hz 1H H2) 732 (d 3JH-H = 81 Hz 1H H5)
711 (t 3JH-H = 81 Hz 1H H3) 685 (t 3JH-H = 81 Hz 1H H4) 508 (qm 3JH-
H = 67 Hz 1H CHOH) 221 (br s 1H OH) 125 (d 3JH-H = 67 Hz 3H CH3)
19F NMR (470 MHz d8-tol) δ -582 (s CF3) 13C1H NMR (125 MHz d8-tol) δ 1455 (ipso-
C6H4CF3) 1315 (C3) 1314 (C1) 1294 (C4) 1264 (C2) 1244 (C5) 1240 (CF3) 653
(CHOH) 253 (CH3) (JC-F not reported) GC-MS 6453 min mz = 1901 [M] 1750 [M-CH3]
1720 [M-H2O] 1450 [M-C2H5O]
1-(4-(Methylsulfonyl)phenyl)ethan-1-ol (Entry 14) 1H NMR (500 MHz d8-tol) δ 763 (d 3JH-H = 86 Hz 2H o of C6H4SO2CH3) 705 (d 3JH-H = 86 Hz 2H m of C6H4SO2CH3) 437 (m
1H CHOH) 228 (s 3H SO2CH3) 141 (br s 1H OH) 112 (d 3JH-H = 66 Hz 3H CHCH3)
13C1H NMR (125 MHz d8-tol) δ 1522 (p of C6H4SO2CH3) 1402 (ipso-C6H4SO2CH3) 1270
(o of C6H4SO2CH3) 1257 (m of C6H4SO2CH3) 689 (CHOH) 436 (SO2CH3) 252 (CHCH3)
HRMS-DART+ mz [M+NH4]+ calcd for C9H16NO3S 21808509 Found 21808554
22-Diphenylethan-1-ol (Entry 24) 1H NMR (500 MHz d8-tol) δ 704 (m 1H p-Ph) 703 (m
2H m -Ph) 693 (d 3JH-H = 75 Hz 2H o-Ph) 405 (dd 3JH-H = 83 Hz 61 Hz 1H CH) 400
(m 2H CH2) (OH was not observed) 13C1H NMR (125 MHz d8-tol) δ 1418 (ipso-Ph)
1293 (m-Ph) 1287 (o-Ph) 1274 (p-Ph) 763 (CH2) 512 (CH) GC-MS 15178 min mz =
1811 [M-OH] 1671 [M-CH3O]
127
2-Phenylpropan-1-ol (Entry 25) 1H NMR (500 MHz d8-tol) δ 722 (d 3JH-H = 78 Hz 2H o-
Ph) 718 ndash 713 (m 3H m p-Ph) 362 (dd 2JH-H = 100 Hz 3JH-H = 62 Hz 1H CH2) 354 (dd 2JH-H = 100 Hz 3JH-H = 78 Hz 1H CH2) 342 (br s 1H OH) 288 (m 3JH-H = 69 Hz 1H CH)
121 (d 3JH-H = 69 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1459 (ipso-Ph) 1289 (p-
Ph) 1283 (m-Ph) 1274 (o-Ph) 780 (CH2) 435 (CH) 181 (CH3) GC-MS 6462 min mz =
1211 [M-CH3] 1051 [M-CH3O]
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Styrene (Entry 1)1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 77 Hz 2H o-Ph) 708 (t 3JH-
H = 77 Hz 2H m-Ph) 706 (t 3JH-H = 77 Hz 1H p-Ph) 653 (dd 3JH-H = 176 Hz 109 Hz 1H
CH) 556 (dd 3JH-H = 176 Hz 11 Hz 1H CH2) 505 (dd 3JH-H = 109 Hz 11 Hz 1H CH2)
13C1H NMR (125 MHz d8-tol) δ 1379 (CH) 1372 (ipso-Ph) 1286 (o m-Ph) 1284 (p-Ph)
1140 (CH2) GC-MS 4038 min mz = 1041 [M] 911 [C7H7] 781 [C6H6]
1-(Trifluoromethyl)-3-vinylbenzene (Entry 2) 1H NMR (500 MHz d8-
tol) δ 744 (s 1H H1) 718 (d 3JH-H = 77 Hz 1H H5) 706 (d 3JH-H = 77
Hz 1H H3) 686 (t 3JH-H = 75 Hz 1H H4) 631 (dd 3JH-H = 173 Hz 102
Hz 1H CH=CH2) 544 (d 3JH-H = 173 Hz 1H CH=CH2) 504 (d 3JH-H = 102 Hz 1H
CH=CH2) 19F NMR (470 MHz d8-tol) δ -626 (s CF3) 13C1H NMR (125 MHz d8-tol) δ
1379 (ipso-C6H4CF3) 1354 (CH=CH2) 1309 (C2) 1284 (C5) 1245 (CF3) 1237 (C3) 1225
(C1) 1151 (CH=CH2) (JC-F not reported) GC-MS 4290 min mz = 1721 [M] 1531 [M-F]
1451 [M-C2H3] 1031 [M-CF3]
(E)-Prop-1-en-1-ylbenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 73 Hz
2H o-Ph) 712 (t 3JH-H = 73 Hz 2H m-Ph) 702 (t 3JH-H = 73 Hz 1H p-Ph) 626 (dq 3JH-H =
156 Hz 4JH-H = 18 Hz 1H PhCH=CH) 600 (dq 3JH-H = 156 Hz 66 Hz 1H PhCH=CH)
168 (dd 3JH-H = 66 Hz 4JH-H = 18 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1378
(ipso-Ph) 1314 (PhCH=CH) 1283 (m-Ph) 1265 (p-Ph) 1258 (o-Ph) 1248 (PhCH=CH)
1800 (CH3) GC-MS 5888 min mz = 1181 [M] 1171 [M-H] 1031 [M-CH3]
128
(2-Methylprop-1-en-1-yl)benzene (Entry 4) 1H NMR (500 MHz d8-tol) δ 717 (m 4H o m-
Ph) 705 (m 1H p-Ph) 624 (m 4JH-H = 15 Hz 1H CH=C(CH3)2) 180 (d 4JH-H = 15 Hz 3H
CH=C(CH3)2) 175 (d 4JH-H = 15 Hz 3H CH=C(CH3)2) 13C1H NMR (125 MHz d8-tol) δ
1386 (C(CH3)2) 1345 (ipso-Ph) 1287 (o-Ph) 1279 (m-Ph) 1257 (CH=C(CH3)2) 1256 (p-
Ph) 264 (CH3) 188 (CH3) GC-MS 5780 min mz = 1321 [M] 1171 [M-CH3]
12-Dihydronaphthalene (Scheme 312a) 1H NMR (600 MHz CD2Cl2) δ 746 - 731 (m 4H
C6H4) 678 (dm 3JH-H = 96 Hz 1H CH=CHCH2) 632 (m 1H CH=CHCH2) 308 (m 2H
CH2CH2CH) 258 (m 2H CH2CH=CH) 13C1H NMR (125 MHz CD2Cl2) δ 1358
(quaternary C for C6H4) 1344 (quaternary C for C6H4) 1288 (CH=CHCH2) 1280
(CH=CHCH2) 1277 (C6H4) 1271 (C6H4) 1266 (C6H4) 1261 (C6H4) 278 (CHCH2CH2) 236
(CH=CHCH2) GC-MS 7943 min mz = 1301 [M] 1151 [M-CH3] 1021 [M-C2H4]
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Diphenylmethane (Entry 1) 1H NMR (500 MHz d8-tol) δ 708 (t 3JH-H = 75 Hz 2H m-Ph)
701 (t 3JH-H = 75 Hz 1H p-Ph) 700 (d 3JH-H = 75 Hz 2H o-Ph) 372 (s 1H CH2) 13C1H
NMR (125 MHz d8-tol) δ 1413 (ipso-Ph) 1293 (o-Ph) 1286 (m-Ph) 1263 (p-Ph) 422
(CH2) GC-MS 11686 min mz = 1681 [M] 1671 [M-H] 911 [C7H7]
1-Benzyl-4-methoxybenzene (Entry 2) 1H NMR (500 MHz d8-tol) δ 712 (m 2H m-Ph)
711 (m 1H p-Ph) 705 (d 3JH-H = 67 Hz 2H o-Ph) 693 (d 3JH-H = 76 Hz 2H o of
C6H4OCH3) 670 (d 3JH-H = 76 Hz 2H m of C6H4OCH3) 372 (s 2H CH2) 334 (s 3H
OCH3) 13C1H NMR (125 MHz d8-tol) δ 1581 (p of C6H4OCH3) 1416 (ipso-C6H4OCH3)
1328 (ipso-Ph) 1295 (o of C6H4OCH3) 1287 (o-Ph) 1283 (m-Ph) 1278 (p-Ph) 1137 (m of
C6H4OCH3) 542 (OCH3) 410 (CH2) GC-MS 14801 min mz = 1981 [M] 1671 [M-OCH3]
1211 [M-C6H5] 911 [M-C7H7O] 771 [M-C8H9O]
1-Benzyl-4-bromobenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 719 (m 1H p-Ph) 716
(d 3JH-H = 78 Hz 2H m of C6H4Br) 710 (t 3JH-H = 77 Hz 2H m-Ph) 691 (d 3JH-H = 77 Hz
2H o-Ph) 665 (d 3JH-H = 77 Hz 2H o of C6H4Br) 355 (s 2H CH2) 13C1H NMR (125
MHz d8-tol) δ 1407 (ipso-C6H4Br) 1403 (ipso-Ph) 1317 (m of C6H4Br) 1316 (p-Ph) 1308
129
(o of C6H4Br) 1289 (o-Ph) 1285 (m-Ph) 1204 (p-C6H4Br) 414 (CH2) GC-MS 15250 min
mz = 2480 [M+2] 2460 [M] 1671 [M-Br] 911 [M-C6H4Br]
1-Benzyl-4-(tert-butyl)benzene (Entry 4) 1H NMR (500 MHz CD2Cl2) δ 774 (t 3JH-H = 86
Hz 2H m of C6H4tBu) 768 (t 3JH-H = 76 Hz 1H p-Ph) 761 (t 3JH-H = 76 Hz 2H m-Ph)
759 (d 3JH-H = 76 Hz 2H o-Ph) 755 (d 3JH-H = 86 Hz 2H o of C6H4tBu) 435 (s 2H CH2)
178 (s 9H tBu) 13C1H NMR (125 MHz CD2Cl2) δ 1493 (p of C6H4tBu) 1420 (ipso-Ph)
1387 (ipso-C6H4tBu) 1294 (m-Ph o of C6H4tBu) 1286 (p-Ph) 1263 (o-Ph) 1255 (m of
C6H4tBu) 415 (CH2) 347 (tBu) 315 (tBu) GC-MS 15429 min mz = 2242 [M] 2092 [M-
CH3) 911 [C7H7]
Di-p-tolylmethane (Entry 5) 1H NMR (500 MHz d8-tol) δ 699 (d 3JH-H = 78 Hz 2H o of
C6H4CH3) 694 (d 3JH-H = 78 Hz 2H m of C6H4CH3) 375 (s 1H CH2) 215 (s 3H CH3)
13C1H NMR (125 MHz d8-tol) δ 1383 (ipso-C6H4CH3) 1350 (p of C6H4CH3) 1289 (m of
C6H4CH3) 1287 (o of C6H4CH3) 408 (CH2) 206 (CH3) GC-MS 14226 min mz = 1961
[M] 1811 [M-CH3) 1661 [M-2(CH3)] 1051 [M-C7H7] 911 [M- C8H9]
1-Benzyl-4-(trifluoromethyl)benzene (Entry 6) 1H NMR (600 MHz CD2Cl2) δ 800 (d 3JH-H
= 73 Hz 2H o-Ph) 788 (d 3JH-H = 74 Hz 2H m of C6H4CF3) 778 (t 3JH-H = 73 Hz 1H p-
Ph) 767 (t 3JH-H = 73 Hz 2H m-Ph) 751 (d 3JH-H = 74 Hz 2H o of C6H4CF3) 430 (s 2H
CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1458 (ipso-C6H4CF3) 1404 (ipso-Ph) 1296 (p-Ph
o of C6H4CF3) 1285 (m-Ph) 1258 (p of C6H4CF3) 1256 (o-Ph) 1255 (m of C6H4CF3) 1239
(CF3) 415 (CH2) (JC-F not reported) GC-MS 11767 min mz = 2361 [M] 1671 [M-CF3]
1591 [M-C6H5] 911 [C7H7]
1-Benzyl-2-methylbenzene (Entry 7) 1H NMR (600 MHz CD2Cl2) δ
776 (m 2H o-Ph) 767 - 761 (m 3H m p-Ph) 759 - 754 (m 4H
C6H4CH3) 438 (s 2H CH2) 270 (s 3H CH3) 13C1H NMR (151
MHz CD2Cl2) δ 1410 (ipso-Ph) 1393 (ipso-C6H4CH3) 1370 (C-CH3) 1307 (C1) 1303 (m-
Ph) 1292 (o-Ph) 1287 (C4) 1268 (p-Ph) 1263 (C3) 1262 (C2) 395 (CH2) 197 (CH3)
GC-MS 12844 min mz = 1821 [M] 1671 [M-CH3]
130
1011-Dihydro-5H-dibenzo[ad][7]annulene (Scheme 312 b) 1H NMR
(600 MHz CD2Cl2) δ 745 (m 1H H2) 742 (m 1H H4) 740 (m 2H
H3 H5) 438 (s 1H CH2) 342 (s 2H CH2) 13C1H NMR (125 MHz
CD2Cl2) δ 1423 (C6) 1395 (C1) 1298 (C5) 1291 (C2) 1268 (C4) 1263 (C3) GC-MS
15761 min mz = 1941 [M] 1791 [M-CH3] 1651 [M-C2H5]
343 X-Ray Crystallography
3431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
3432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
131
3433 Selected crystallographic data
Table 36 ndash Selected crystallographic data for 31
31 (+05 C6D5Br)
Formula C43H295B1Br05F20O2
Formula wt 100893
Crystal system monoclinic
Space group P2(1)c
a(Aring) 127865(6)
b(Aring) 199241(9)
c(Aring) 170110(7)
α(ordm) 9000
β(ordm) 1067440(10)
γ(ordm) 9000
V(Aring3) 41500(3)
Z 4
Temp (K) 150(2)
d(calc) gcm-3 1607
Abs coeff μ mm-1 0606
Data collected 37469
Rint 00368
Data used 9534
Variables 596
R (gt2σ) 00458
wR2 01145
GOF 1020
132
Chapter 4 Hydroamination and Hydrophosphination Reactions Using
Frustrated Lewis Pairs
41 Introduction
411 Hydroamination
The direct addition of N-H bonds to unsaturated organic compounds provides an atom-economic
route to valuable nitrogen-containing molecules Pursuit of such reactivity is largely motivated
by the ubiquitous nature of substituted amines in the pharmaceutical industry303-306 The
intermolecular hydroamination of alkynes represents an attractive single-step approach to
convert inexpensive and readily available starting materials to synthetic building blocks such as
imines and enamines
Intermolecular hydroamination of alkynes was initially carried out using Hg and Tl salts307-308
however toxicity concerns prompted subsequent development of a wide variety of other catalysts
based on rare-earth metals309 early- and late-transition metals303 310 as well as lanthanides311-312
and actinides313 Based on the pioneering work of Bergman314-316 and Doye317-318 group IV metal
derivatives have become popular catalysts in these reactions More recently the groups of
Richeson319 Odom320-321 Schafer322 Mountford323 and others311 313 321 324 have made significant
contributions to further the development of these catalysts
Nonetheless to date transition metal-free routes remain relatively less explored The Broslashnsted
acid tungstophosphoric acid has been reported by Lingaiah325 to catalyze the hydroamination of
alkynes However in order for this catalyst to operate harsh conditions and electronically
deactivated amines are required An alternative approach using a strong base such as cesium
hydroxide was reported by Knochel although this strategy only tolerated functional groups less
acidic than the amines309 More recently metal-free approaches have been demonstrated in the
work by Beauchemin on the Cope-type inter- and intramolecular hydroaminations326-329
133
412 Reactions of main group FLPs with alkynes
4121 12-Addition or deprotonation reactions
Recent research has been devoted to effect metal-free stoichiometric and catalytic
transformations using frustrated Lewis pairs (FLPs) These main group combinations of bulky
Lewis acids and bases have become the focus of a number of research groups worldwide330-331
Shortly after the discovery of FLP chemistry several reports communicated the organic
manipulation of alkynes analogous to the pioneering hydroboration reactions by H C Brown60
Initial studies showed that FLPs comprised of B(C6F5)3 or Al(C6F5)3(PhMe) and phosphines react
to yield either zwitterionic vinyl phosphonium borate or aluminate salts resulting from a 12-
addition reaction or phosphonium alkynylborates resulting from alkyne deprotonation126 128 The
course of the reaction was found to depend on the basicity of the phosphine donor with less
basic aryl phosphines favouring 12-addition (Scheme 41)
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al)
Berke and co-workers investigated related intermolecular reactions of terminal alkynes and
B(C6F5)3 with 26-lutidine and TMP demonstrating that these systems effect deprotonation of the
alkyne affording ammonium alkynylborates156 Alternatively the groups of Erker and Stephan
reported the intramolecular cyclization of pendant alkyne substituted anilines151 and N-
heterocycles152 via 12-addition reactions using B(C6F5)3 (Scheme 42 a and b) In a similar
fashion ethylene-linked sulphurborane systems were found to add to alkynes with subsequent
elimination of ethylene affording a single-step route to SB alkenyl-FLPs (Scheme 42 c)332
134
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c)
4122 11-Carboboration reactions
The groups of Berke and Erker separately studied the reactivity of Lewis acids with alkynes in
the absence of a Lewis base (Scheme 43) To this extent they identified the 11-carboboration
reaction to generate alkenylboranes156 159-160 Moreover the reaction of propargyl esters with
B(C6F5)3 have been shown to generate boron allylation reagents333
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes
135
4123 Hydroelementation reactions
Catalytic hydroelementation reactions have been reported for alkynes In the presence of 5 - 10
mol B(C6F5)3 internal alkynes have been shown to undergo both hydrostannylation334 (Scheme
44 a) and hydrogermylation335 reactions (Scheme 44 b)
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes
413 Reactions of transition metal FLPs with alkynes
The FLP paradigm has also been studied using transition metal systems in combination with
alkynes Some examples include metalation through the 11-carbozirconation336 and
boroauration337 reactions Additionally the Wass group developed cationic zirconocene
phosphinoaryloxide complexes that selectively deprotonate terminal alkynes (Scheme 45)338 In
a recent paper the Stephan group has shown that Ru-acetylides act as carbon nucleophiles in
combination with Lewis acids to effect trans-addition to alkynes162
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes
Inspired by the reactivity of FLPs with alkynes in this chapter the intermolecular reaction of
amines B(C6F5)3 and a versatile group of terminal alkynes is explored in hydroamination
reactions A catalytic approach to yield enamines and corresponding amines is described In
addition related systems are probed to accomplish stoichiometric and catalytic intramolecular
hydroaminations affording N-heterocycles Finally stoichiometric approaches to
hydrophosphination reactions are discussed
136
42 Results and Discussion
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
With the objective of initiating hydroamination reactivity the three component stoichiometric
reaction of Ph2NH B(C6F5)3 and phenylacetylene was performed in CD2Cl2 The 1H 11B and 19F
NMR spectra revealed consumption of two equivalents of phenylacetylene to afford the salt
[Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] 41 while leaving a portion of the starting materials Ph2NH
and B(C6F5)3 unreacted (Scheme 46) Adjustment of the alkyne stoichiometry to two equivalents
afforded 41 in 90 yield (Table 41 entry 1) This new species results from the sequential
hydroamination and deprotonation reaction of phenylacetylene
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
The 1H NMR spectrum displayed a diagnostic methyl singlet at 289 ppm with the corresponding 13C1H resonance at 283 ppm In addition a downfield 13C1H resonance at 1901 ppm is
attributable to the iminium N=C group The alkynylborate anion [PhCequivCB(C6F5)3]- gave rise to
the 11B NMR signal at -208 ppm and 19F resonances at -1327 -1638 and -1673 ppm The
nature of compound 41 was unambiguously confirmed by X-ray crystallography (Figure 41)
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
137
To probe the generality of this reaction the corresponding reactivity of various substituted
secondary anilines with two equivalents of phenylacetylene were explored In this fashion the
species [RPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (R = iPr 42 Cy 43 PhCH2 44 p-CH3O 45) were
isolated in 88 91 82 and 90 yield respectively (Table 41 entry 1) 1H NMR spectra
showed the iminium cations were formed as a mixture of the E and Z isomers in a 71 ratio for
compounds 42 and 43 41 ratio for 44 and 11 ratio for 45
Analogous reactions of Ph2NH B(C6F5)3 and two equivalents of 1-hexyne revealed two
competitive reaction pathways In addition to the hydroaminationdeprotonation product
[Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] 46 (Table 41 entry 2) the alkenylboranes resulting from
the 11-carboboration of 1-hexyne were also observed by NMR spectroscopy Exposing the same
anilineB(C6F5)3 combination to 9-ethynylphenanthrene produced [Ph2N=C(CH3)C14H9]
[C14H9CequivCB(C6F5)3] 47 in 75 isolated yield (Table 41 entry 3) The molecular structure of
47 was unambiguously characterized by X-ray crystallography (Figure 42)
Figure 42 ndash POV-Ray depiction of 47
138
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
139
In a similar fashion the reaction of two equivalents of ethynylcyclopropane with B(C6F5)3 and
iPrPhNH at room temperature afforded the yellow crystalline solid formulated as
[iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] 48 in 88 yield (Table 41 entry 4) In this case
the 1H NMR spectrum showed the iminium cation is formed as a mixture of the E and Z isomers
in a 17 ratio Furthermore the reaction of iPrPhNHB(C6F5)3 with 2-ethynylthiophene
proceeded cleanly to give the product [iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] 49
obtained as a 71 mixture of EZ isomers and isolated in 78 yield (Table 41 entry 5) Single
crystals suitable for X-ray diffraction were obtained for Z-48 and Z-49 and the structures are
shown in Figure 43 (a) and (b) respectively
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b)
Interestingly addition 14-diethynylbenzene to the stoichiometric combination of Ph2NH
B(C6F5)3 resulted in an instant color change from pale orange to deep red affording the
zwitterionic product [Ph2N=C(CH3)C6H4CequivCB(C6F5)3] 410 in 85 yield (Table 41 entry 6)
The molecular structure of 410 was confirmed by X-ray crystallography (Figure 44)
Figure 44 ndash POV-Ray depiction of 410
(a) (b)
140
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes
The three component reaction is thought to proceed via Lewis acid polarization of the alkyne by
B(C6F5)3 prompting nucleophilic addition of the aniline and generating a zwitterionic
intermediate (Scheme 47) Analogous 12-additions to alkynes have been previously reported for
phosphineborane126 128 thioetherborane339 and pyrroleborane127 FLPs However in the present
study the arylammonium intermediate provides an acidic proton which cleaved the B-C bond
yielding enamine with concurrent release of B(C6F5)3 Subsequent to this hydroamination the
FLP derived from enamine and B(C6F5)3 deprotonate a second equivalent of the alkyne affording
the isolated iminium alkynylborate salts (Scheme 47)
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts
Analogous stoichiometric combination of tert-butylaniline or diisopropylamine and B(C6F5)3
with either one or two equivalents of phenylacetylene resulted exclusively in deprotonation of
the terminal alkyne affording the ammonium alkynylborate salts [tBuPhNH2][PhCequivCB(C6F5)3]
411 and [iPr2NH2][PhCequivCB(C6F5)3] 412 in 99 and 76 yield respectively (Scheme 48) In
these cases the amines are sufficiently bulky to form a FLP with B(C6F5)3 and relatively basic to
preferentially effect deprotonation of the alkyne This reaction pathway has been previously
observed for basic phosphines and B(C6F5)3 with numerous alkynes
141
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates
In separate reactions FLPs comprised of iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 were
combined with the internal alkynes 3-hexyne diphenylacetylene and 1-phenyl-1-propyne At
RT multinuclear NMR data only revealed signals for the FLP and unaltered alkyne Heating
the reactions up to 80 degC did not display signals for hydroamination rather only products of 11-
carboboration were observed
Also interested in extending the unsaturated substrates scope the hydroamination of the olefins
1-hexene cyclohexene styrene αp-dimethylstyrene and 3-(trifluoromethyl)styrene were tested
using the FLPs iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 Thermolysis of the individual samples
up to 100 degC only revealed signals for the starting materials
4213 Reactivity of the iminium alkynylborate products with nucleophiles
An attractive feature of the iminium cation is the unsaturated N=C fragment since it could be
reacted with nucleophiles to give amines and this transformation could potentially be extended to
generate enantioselective variants of the amines Introducing simple fluoride sources such as
[NBu4][Si(Ph)3F2] NBu4F and CsF to compounds 42 and 46 resulted in deprotonation of the
methyl group losing HF and generating the corresponding enamine Nonetheless addition of the
H+ source [(Et2O)2H][B(C6F5)4]287 regenerated the iminium cation (Scheme 49)
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4]
142
Furthermore addition of the organolithium reagents methyl lithium and ethyl lithium at -30 degC
gave a 11 mixture of the alkylation and deprotonation products as evidenced by 1H NMR
spectroscopy while phenyl lithium did not result in any reactivity (Scheme 410 left)
Combinations of stoichiometric hydride sources [tBu3PH][HB(C6F5)3] NaBHEt3 and LiAlH4
only gave saturation of the N=C bond with the lithium reducing agent (Scheme 410 right)
Overall while hydride delivery to the N=C bond was successfully achieved inefficient delivery
of the presented alkyl and aryl nucleophiles shifted focus towards other types of reactivities
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right)
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3
The equimolar reaction of the tertiary amine dibenzylaniline B(C6F5)3 and phenylacetylene was
investigated with the aim of isolating a zwitterionic intermediate analogous to the compound
proposed en route to hydroamination in Scheme 47 In this case however the nucleophilic
centre for this reaction proved to be the para-carbon of the N-bound phenyl ring undergoing
hydroarylation of phenylacetylene to generate the zwitterionic species
(PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 413 in 96 yield (Scheme 411) Single crystal X-ray
diffraction confirmed the structure of 413 and it is shown in Figure 45 (a)
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3
143
Examining the secondary amine N-isopropylanthracen-9-amine in similar reactivity also gave the
hydroarylation of phenylacetylene and this was demonstrated at the C10 position of the
anthracene ring forming iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 414 in 95 yield In this unique
case however a N=C double bond is generated between nitrogen and the anthracene ring as well
as saturation of the C10 centre giving the tetrahedral geometry observed in the solid state
structure of 414 shown in Figure 45 (b) Generally aromatic substitution reactions in the
presence of Lewis acids have been used for the synthesis of numerous aromatic molecules340
Particularly relevant to this thesis the para-carbon of N-bound phenyl rings has been proposed
as the Lewis basic centre to heterolytically split H2 and generate a sp3-hybridized carbon centre
in the arene hydrogenation reactions presented in Chapter 2
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg
Stability of the B-C bond towards acidic conditions was tested In this regard combinations of
413 with the protic salts [(Et2O)2H][B(C6F5)4] or [Ph2NH2][B(C6F5)4] were found to readily
cleave the B-C bond liberating B(C6F5)3 and generating the diphenylethylene-ammonium
derivative as evidenced by the geminal protons at 508 and 504 ppm in the 1H NMR spectrum
(Scheme 412)
(a) (b)
144
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes
With the exception of catalytic hydrogenations the majority of FLPs reported to date react with
small molecules in a stoichiometric fashion Thus seeking to expand the application of FLPs in
catalysis beyond hydrogenations attention was turned to the development of catalytic
hydroamination reactions This motivation was inspired by the hydroaminationdeprotonation
mechanism proposed in Scheme 47 Realizing that deprotonation of alkyne eliminates the
possibility for catalysis the reaction protocol was adjusted in which the alkyne is added slowly
in order to achieve hydroamination and prevent deprotonation by enamine and B(C6F5)3
The slow addition of the terminal alkyne 2-ethynylanisole to a RT solution of Ph2NH and 10
mol of B(C6F5)3 in toluene over 10 h afforded the catalytic hydroamination product 2-
methoxyphenyl substituted enamine Ph2N(2-MeOC6H4)C=CH2 415 in 84 isolated yield (Table
42) The 1H NMR spectrum of 415 displayed two diagnostic singlets at 501 and 490 ppm
characteristic of the inequivalent geminal hydrogen atoms The corresponding carbon centre
gives rise to a 13C1H NMR signal at 108 ppm Further NMR studies of the compound were
consistent with formation of the Markovnikov isomer in which the nitrogen is added to the
substituted carbon of the terminal alkyne
The analogous treatment of Ph2NH with 2-ethynyltoluene in the presence of 10 mol B(C6F5)3
afforded Ph2N(2-MeC6H4)C=CH2 416 in 69 isolated yield while the alkyne 1-
ethynylnaphthalene yielded Ph2N(C10H7)C=CH2 417 in 62 yield (Table 42) The
corresponding reaction of Ph2NH with phenylacetylene and 2-bromo-phenylacetylene afforded
Ph2N(C6H5)C=CH2 418 and Ph2N(2-BrC6H4)C=CH2 419 in yields of 74 and 52 respectively
(Table 42) Similar to 415 the 1H and 13C1H NMR data for these products were in agreement
with the proposed product formulations
145
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3
This hydroamination strategy also proved effective for substituted diphenylamines For example
(p-FC6H4)2NH in combination with 10 mol B(C6F5)3 reacted with halogenated
phenylacetylenes to afford the species (p-FC6H4)2N(2-BrC6H4)C=CH2 420 and (p-FC6H4)2N(2-
146
FC6H4)C=CH2 421 while the corresponding reactivity with 2-thiophenylacetylene gave (p-
FC6H4)2N(2-SC4H3)C=CH2 422 and iPrPhN(2-SC4H3)C=CH2 423 when reacted with iPrNHPh
(Table 42)
The reaction of Ph2NH with 9-ethynylphenanthrene gave Ph2N(C14H9)C=CH2 424 and (p-
FC6H4)2NH was used to prepare (p-FC6H4)2N(C14H9)C=CH2 425 Similarly reactions of the
appropriate combinations of amine and alkyne using 10 mol B(C6F5)3 afforded (p-FC6H4)2N(3-
FC6H4)C=CH2 426 Ph2N(35-F2C6H3)C=CH2 427 and Ph2N(3-CF3C6H4)C=CH2 428 although
in these cases cooling to -30 degC was necessary to maximize yields obtained between 68 - 77
(Table 42) This impact of temperature was most dramatically demonstrated in the case of 426
where performing the reaction at 25 degC gave the product in 19 yield while at -30 degC the yield
was significantly enhanced to 74
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions
The success of these hydroamination reactions strongly depends on the electronic and steric
nature of the amineborane FLP combination thereby preventing 11-carboboration and
deprotonation of the alkyne Interaction of the borane with the terminal alkyne prompts amine
addition to generate a zwitterionic intermediate In the present case the acidic proton of the
anilinium centre migrates to the carbon adjacent to boron cleaving the B-C bond and forming the
enamine product (Scheme 413) The released B(C6F5)3 is then available to participate in further
hydroamination catalysis It is noteworthy that the postulated zwitterion accounts for the
Markovnikov addition of amines to alkynes and thus the nature of the observed enamine
products341
As stated earlier catalytic formation of enamine requires the slow addition of alkyne over 10 h
This is a result of deprotonation of the alkyne by the FLP derived from enamine and borane
consequently generating iminium alkynylborate salts analogous to 42 - 410 The observed
catalytic hydroaminations imply that amine addition to alkyne is faster than enamine
deprotonation of alkyne
147
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes
The catalytic generation of these enamines together with previously established FLP
hydrogenation of enamines93 prompted interest in a one-pot catalytic
hydroaminationhydrogenation protocol
Following the hydroamination procedure described above reaction mixtures generating the two
enamines 421 and 427 were exposed to H2 (4 atm) and heated at 80 degC for 14 h Pleasingly the
B(C6F5)3 catalyst successfully completed hydrogenation of the C=C double bond giving the
amines (p-FC6H4)2N(2-FC6H4)C(H)CH3 429 and Ph2N(35-F2C6H3)C(H)CH3 430 in 77 and
64 overall isolated yields respectively (Scheme 414) Monitoring the hydrogenation portion
of the reactions by 1H NMR spectroscopy revealed in both cases demise of the signals
attributable to the geminal protons of the enamines with simultaneous appearance of a quartet
attributable to the methine proton and a doublet assignable to the methyl group of the respective
amine In an alternative approach to the hydrogenation catalysis subsequent to hydroamination
5 mol of the known hydrogenation catalyst Mes2PH(C6F4)BH(C6F5)294 was added to the
reaction mixture pressurized with H2 (4 atm) and heated to 80 degC In both cases complete
hydrogenation was achieved after 3 h
148
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430
Experimental evidence demonstrated the catalytic hydroaminations are restricted to aryl
acetylenes Examples of other terminal alkynes that were examined include
trimethylsilylacetylene which resulted in 11-carboboration while the acetylene carboxylates
methyl propiolate ethyl propiolate 2-naphthyl propiolate and tert-butyl propiolate did not react
due to formation of a B-O adduct Extending the chemistry to hydrothiolation using thiophenol
was not successful
424 Intramolecular hydroamination reactions using FLPs
4241 Stoichiometric hydroamination
The potential of the above hydroamination reactions to access N-heterocycles was also probed
To this end the alkynyl-substituted aniline C6H5NH(CH2)3CequivCH was prepared and exposed to
an equivalent of B(C6F5)3 in toluene 11B NMR spectroscopy indicated the formation of a B-N
adduct verified by the resonance at -25 ppm although heating the reaction for 2 h at 50 degC
yielded the cyclized zwitterion C6H5N(CH2)3CCH2B(C6F5)3 431 isolated as a white solid in 94
yield (Scheme 415) The 1H NMR spectrum was consistent with consumption of the NH proton
revealing a diagnostic broad quartet at 333 ppm with geminal B-H coupling of 54 Hz indicative
of the B(C6F5)3 bound methylene group In addition a diagnostic sharp singlet at -134 ppm in
149
the 11B NMR spectrum and the N=C iminium 13C1H resonance at 192 ppm were consistent
with the formulation of 431
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432
The analogous 6-membered ring was prepared from the precursor C6H5NH(CH2)4CequivCH and an
equivalent of B(C6F5)3 giving the zwitterion C6H5N(CH2)4CCH2B(C6F5)3 432 in 99 yield The
formulation of 432 was affirmed by NMR spectroscopy in addition to elemental analysis and X-
ray crystallography (Figure 46)
Figure 46 ndash POV-Ray depiction of 432
Similarly substituted isoindoline species are accessible from the reaction of the precursor
C6H5NHCH2(C6H4)CequivCH with B(C6F5)3 in toluene Stoichiometric combination of the two
reagents resulted in a white precipitate believed to be the intramolecular hydroamination product
after 10 min at RT However this compound was sparingly soluble in toluene bromobenzene
and CD2Cl2 not allowing its comprehensive characterization by NMR spectroscopy As such H2
(4 atm) was added to the reaction and heated at 80 degC for 16 h in an effort to synthesize the H2
activated salt which was presumed to be more soluble than the zwitterion The 1H NMR
150
spectrum of this reaction displayed a quartet at 556 ppm and a triplet at 289 ppm with a four-
bond coupling constant of 26 Hz 13C1H NMR data showed a resonance at 182 ppm
attributable to a N=C bond Collectively these data are consistent with the successive
hydroamination and hydrogenation product [2-MeC8H6N(Ph)][HB(C6F5)3] 433 isolated in 54
yield (Scheme 416)
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433
While species 433 is isolated as an insoluble solid from pentane in CD2Cl2 the [HB(C6F5)3]-
anion appears to reversibly deliver hydride to the N=C carbon centre generating isoindoline and
B(C6F5)3 in about 25 This was evidenced by 1H NMR spectroscopy revealing a diagnostic
quartet at 518 ppm two diastereotopic doublets at 472 and 455 ppm and an upfield doublet at
151 ppm data that is collectively assignable to the isoindoline species This was further
supported by 11B and 19F NMR spectroscopy which provided evidence of free B(C6F5)3 Presence
of this equilibrium is consistent with a previous report on reversible hydride abstraction and
redelivery from carbon centres alpha to nitrogen262
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines
This hydroaminationhydrogenation protocol was further adapted for catalytic cyclization
reactions In this fashion the alkynyl substituted aniline C6H5NH(CH2)3CequivCH was treated with
10 mol B(C6F5)3 at 80 degC under H2 (4 atm) for 16 h This gave the desired product 2-methyl-1-
phenyl pyrrolidine 434 in 68 isolated yield (Table 43 entry 1) In a similar fashion the
catalytic hydroaminationhydrogenation of C6H5NH(CH2)4CequivCH gave 2-methyl-1-
phenylpiperidine 435 in 66 yield (Table 43 entry 2) The following protocol was also
applicable to p-fluoro and p-methoxy substituted substrates giving the respective cyclized
products 436 and 437 in 72 and 52 yield respectively (Table 43 entries 3 and 4) Finally
151
similar reactivity with C6H5NHCH2(C6H4)CequivCH gave 1-methyl-2-phenylisoindoline 438 in 70
yield (Scheme 417)
The yields obtained for compounds 436 and 437 strongly reflect the balance of Broslashnsted acidity
required by the amine proton to effect hydroamination In this case the p-fluoro substituent
proved more effective in hydroamination than p-methoxy
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines
Entry R n Isolated yield
1 H 0 68 434
2 H 1 66 435
3 F 1 72 436
4 CH3O 1 52 437
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH
425 Reaction of B(C6F5)3 with ethynylphosphines
The stoichiometric reaction of B(C6F5)3 with the ethynylphosphine tBu2PCequivCH has previously
been shown to give the deprotonation product tBu2P(H)CequivCB(C6F5)3342 Conversely analogous
treatment of Mes2PCequivCH required addition of tBu3P to effect deprotonation of the ethynyl group
due to diminished Lewis basicity of the phosphine Moreover the Erker group reported the
152
reaction of Ph2PCequivCH with B(C6F5)3 to generate a dimeric product formed by a sequential series
of 12-PB additions to the ethynyl unit343
While interested in hydroamination of ethynylphosphines the FLP iPrNHPhB(C6F5)3 was added
to two equivalents of Mes2PCequivCH giving the pale yellow solid 439 in 88 yield (Scheme 418)
The 1H NMR spectrum did not indicate incorporation of aniline into the product rather two
inequivalent vinylic protons with characteristic P-H and H-H coupling were observed at 771 and
574 ppm (Figure 47)
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons
The 31P NMR spectrum revealed two resonances with chemical shifts at -115 and -143 ppm
while the 11B and 19F NMR spectra were in agreement with formation of an alkynylborate
species (11B δ -211 ppm 19F δ -1329 -1616 and -1663 ppm) These data together with
elemental analysis confirm the formulation of the zwitterionic species trans-
Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 439 An X-ray crystallographic study confirmed the
1H
1H31P
153
molecular structure of 439 and it is shown in Figure 48 (a) In the absence of aniline the
reaction leads to the previously reported 11-carboboration product344-345
On another account the same reaction was obtained with 2 equivalents of tBu2PCequivCH and
B(C6F5)3 to give cis and trans isomers of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 440 The cis
isomer was crystallized and characterized by X-ray diffraction studies (Figure 48 b) In this
case the phosphorus centre was basic enough to effect deprotonation thus the reaction proceeded
in the absence of iPrNHPh Monitoring the reaction by 31P NMR spectroscopy the spectrum
indicated the simultaneous presence of tBu2PCequivCH and the deprotonation zwitterion
tBu2P(H)CequivCB(C6F5)3 giving insight to a plausible mechanism en route to the formation of
compounds 439 and 440
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b)
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines
The reaction is proposed to proceed through the mechanism highlighted in Scheme 419 wherein
the mixture of B(C6F5)3 and R2PCequivCH initially effect deprotonation of the ethynyl group
formulating the zwitterion R2P(H)CequivCB(C6F5)3 Under equilibrium conditions a second
equivalent of the ethynylphosphine is protonated consequently prompting nucleophilic addition
of the [R2PCequivCB(C6F5)3]- anion to the terminal carbon followed by proton transfer to generate
the isolated zwitterionic products In the case of Mes2PCequivCH the deprotonation step required a
stronger base therefore iPrNHPh was added to effect reactivity
(a) (b)
154
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs
An earlier report showed the three component reaction of p-tolyl2PH B(C6F5)3 and
phenylacetylene gave the 12-addition phosphonium borate zwitterion p-
tolyl2PH(Ph)C=C(H)B(C6F5)3128 Realizing the acidic hydrogen on the phosphorus atom a
sample of this compound was treated by UV radiation or heated to prompt hydrophosphination
of phenylacetylene in a mechanism analogous to that presented for the hydroamination reaction
In this regard however the zwitterion proved robust and further reactivity was not observed
Similar results were obtained when using Mes2PH or exchanging the borane for the slightly less
Lewis acidic B(p-C6F4H)3
Turning attention towards the borane HB(C6F5)2 the hydrophosphination reaction was attempted
following an alternative approach In this regard Ph2PH was added to a stoichiometric
combination of HB(C6F5)2 and Bpin-substituted 1-hexyne (Scheme 420 a) After 16 h at RT
the acetylenic unit of Bpin was reduced to a C-C single bond as illustrated by a characteristic
multiplet at 353 ppm and a very broad singlet at 148 ppm in the 1H NMR spectrum The
product Bu(H)Ph2PC-C(H)B(C6F5)2Bpin 441 resulting from the sequential hydroboration and
hydrophosphination reactions was isolated in 82 yield NMR spectroscopy data indeed showed
incorporation of all reactants into the isolated product
155
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH
Investigating similar reactivity of 2-methyl-1-buten-3-yne substituted Bpin with HB(C6F5)2 and
Ph2PH a colourless solid was obtained in 73 yield The 1H NMR data unambiguously showed
saturation of the acetylenic fragment however the spectrum consisted of an olefinic proton at
646 ppm in addition to a methylene group at 307 ppm Further spectroscopic data revealed the
product as Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin 442 resulting from nucleophilic addition of
the phosphine at the terminal double bond (Scheme 420) Single crystals suitable for X-Ray
diffraction were obtained and the structure is shown in Figure 49 (b)
Figure 49 ndash POV-Ray depictions of 442
156
427 Proposed mechanism for the hydroborationhydrophosphination reactions
The mechanism of this reaction is envisaged to initiate following the well-documented
hydroboration of the acetylenic group generating the corresponding alkenyl-bisborane species
(Scheme 421)346 At this point the phosphine coordinates to B(C6F5)2 rendering its proton more
Broslashnsted acidic and prompting protonation of the C=C double bond This is followed by
nucleophilic attack of the phosphine at the C2 position of alkynyl-substituted Bpin (441) or C4
position of the enyne-substituted Bpin (442) The 14-addition reaction to conjugated enynes has
been previously investigated using the ethylene-linked PB FLP to give eight membered cyclic
allenes147
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments
Since evidence for the P-B intermediate is not observed by 11B or 31P NMR spectroscopy an
alternative mechanism could be speculated In this case the nucleophilic phosphine could add to
the vinyl bisborane followed by proton transfer However this later mechanism is not highly
supported as the more Lewis basic secondary phosphines tBu2PH and iPr2PH only gave the P-B
adduct with HB(C6F5)2 consistent with retro-hydroboration after coordination of the phosphine
to the vinyl bisborane This adduct remained intact even at elevated temperatures of 80 degC
Similar N-B adducts were observed when the analogous reactivity was explored with the alkyl
and aryl amines iPr2NH iPrNHPh and Ph2NH
157
43 Conclusions
This chapter provides an account on the discovery of consecutive hydroamination and
deprotonation reactions of various terminal alkynes by anilineB(C6F5)3 FLPs to form a series of
iminium alkynylborate complexes The reaction procedure was modified to eliminate the
deprotonation step in order to achieve B(C6F5)3 catalyzed Markovnikov hydroamination of
alkynes yielding enamine products Subsequent to hydroamination catalysis the borane catalyst
was also used for catalytic hydrogenation of the enamine providing a one-pot avenue to the
corresponding amine derivatives Related systems were probed to accomplish the stoichiometric
and catalytic intramolecular hydroamination of alkynyl-substituted anilines generating cyclic
amines While this hydroamination protocol was not extendable to effect hydrophosphination a
new stoichiometric approach using HB(C6F5)2 and Ph2PH was found to result in the sequential
hydroboration and hydrophosphination reactions of an alkynyl- and enynyl-substituted
pinacolborane generating novel PB FLPs
44 Experimental Section
441 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane dichloromethane and toluene (Sigma Aldrich) were dried employing a Grubbs-
type column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring)
in the glovebox Dichloromethane-d2 bromobenzene-d5 and bromobenzene-H5 were purchased
from Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring
molecular sieves prior to use Hexane and ethyl acetate were purchased from Caledon
Laboratories Silica gel was purchased from Silicycle Molecular sieves (4 Aring) were purchased
from Sigma Aldrich and dried at 120 ordmC under vacuum for 24 h prior to use B(C6F5)3 was
purchased from Boulder Scientific and sublimed at 80 degC under high vacuum before use H2
(grade 50) was purchased from Linde and dried through a Nanochem Weldassure purifier
column prior to use
Substituted amines alkynes and phosphines were purchased from Sigma Aldrich Alfa Aesar
Apollo Scientific Strem Chemicals Inc and TCI The oils were distilled over CaH2 and solids
were sublimed under high vacuum prior to use The following reagents were prepared following
158
literature procedures 1-ethynylnaphthalene347 (p-C6H4F)2NH (p-CH3OC6H4)PhNH tBuNHPh
and N-isopropylanthracen-9-amine266 N-(2-ethynylbenzyl)aniline N-(pent-4-ynyl)aniline N-
(hex-5-ynyl)aniline 4-fluoro-N-(hex-5-yn-1-yl)aniline and 4-methoxy-N-(hex-5-yn-1-
yl)aniline348 N-(2-ethynylbenzyl)aniline349 tBu2PCequivCH and Mes2PCequivCH342
CH3(CH2)3CequivCBpin and CH2=C(CH3)CequivCBpin350
Compounds 439 - 442 were prepared by the author during a four month research opportunity in
the group of Professor Gerhard Erker at Universitaumlt Muumlnster Germany Molecular structures and
elemental analyses for 439 and 440 were obtained at the University of Toronto Molecular
structure for 442 was obtained at Universitaumlt Muumlnster and elemental analyses for 441 and 442
were obtained at the University of Toronto
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm for
ipso carbon) and CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) or externally (11B (Et2O)BF3 19F
CFCl3) Chemical Shifts (δ) are reported in ppm and the absolute values of the coupling
constants (J) are in Hz NMR assignments are supported by additional 2D and DEPT-135
experiments
High resolution mass spectra (HRMS) were obtained using an ABSciex QStar Mass
Spectrometer with an ESI source MSMS and accurate mass capabilities Elemental analyses (C
H N) were performed in-house employing a Perkin Elmer 2400 Series II CHNS Analyzer
442 Synthesis of Compounds
4421 Procedures for stoichiometric intermolecular hydroamination reactions
Compounds 41 - 45 were prepared in a similar fashion thus only one preparation is detailed In
the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial phenylacetylene (151
mg 148 mmol) was added drop wise over 1 min In the case where pentane was used as the
solvent the reaction was worked up as follows the solvent was decanted and the product was
washed with pentane (3 times 5 mL) to yield the product as a solid In the case where toluene or
159
dichloromethane was used as the as solvent the reaction was worked up as follows the solvent
was removed under reduced pressure and the crude product was washed with pentane to yield the
product as a solid
Synthesis of [Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] (41) Diphenylamine (0125 g 0740
mmol) pentane (20 mL) reaction time 2 h yellow solid (588 mg 0666 mmol 90) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC
1H NMR (400 MHz CD2Cl2) δ 768 (m 3H H4 H5) 761 (m 1H p-Ph)
745 (m 5H o m p-Ph) 739 (m 4H H3 m-Ph) 728 (dm 3JH-H = 75
Hz 2H H7) 717 (tm 3JH-H = 75 Hz 2H H8) 711 (tm 3JH-H = 75 Hz
1H H9) 710 (dm 3JH-H = 77 Hz 2H o-Ph) 289 (s 3H Me) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F
p-C6F5) -1673 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s
equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1901 (C1) 1352 (p-Ph) 1320 (C5) 1315 (C4)
1312 (p-Ph) 1310 (C7) 1307 (m-Ph) 1298 (Ph) 1293 (Ph) 1277 (C8) 1257 (C9) 1254 (o-
Ph) 1241 (C3) 283 (Me) (C2 C6 ipso-Ph and all carbons for CequivCB(C6F5)3 were not
observed) Elemental analysis was not successful after numerous attempts
Synthesis of E-[iPrPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (42) N-Isopropylaniline (100 mg
0740 mmol) pentane (10 mL) reaction time 1 h pale yellow solid (566 mg 0651 mmol 88)
EZ ratio 71
42 1H NMR (400 MHz CD2Cl2) δ 773 (tm 3JH-H = 77 Hz 1H H5)
772 (m 6H H4 H9 H10) 746 (dm 3JH-H = 77 Hz 2H H3) 728 (dm 3JH-H = 76 Hz 2H H12) 720 (m 2H H8) 716 (t 3JH-H = 76 Hz 2H
H13) 713 (t 3JH-H = 76 Hz 1H H14) 491 (m 3JH-H = 66 Hz 1H H6)
244 (s 3H Me) 126 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1637 (t 3JF-F = 20 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1913
(C1) 1482 (dm 1JC-F = 236 Hz CF) 1381 (dm 1JC-F = 243 Hz CF) 1365 (dm 1JC-F = 245 Hz
CF) 1346 (C2) 1339 (C5) 1319 (C10) 1318 (C7) 1311 (C12) 1310 (C4) 1303 (C9) 1278
(C13) 1274 (C11) 1258 (C14) 1253 (C3 C8) 937 (C15) 619 (C6) 288 (Me) 208 (iPr)
160
(CequivCB(C6F5)3 and ipso-C6F5 were not observed) Anal calcd () for C43H25BF15N C 6066 H
296 N 165 Found 6037 H 317 N 173
Synthesis of E-[CyPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (43) N-Cyclohexylaniline (135 mg
0740 mmol) pentane (10 mL) reaction time 1 h off-white solid (599 mg 0674 mmol 91)
EZ ratio 71
43 1H NMR (400 MHz CD2Cl2) δ 769 (tt 3JH-H = 74 Hz 4JH-H = 24
Hz 1H H5) 762 (m 5H H4 H12 H13) 737 (dm 3JH-H = 74 Hz 2H H3)
720 (dm 3JH-H = 77 Hz 2H H15) 711 (m 4H H11 H16) 703 (tm 3JH-H
= 77 Hz 1H H17) 439 (tt 3JH-H = 119 Hz 3JH-H = 35 Hz 1H H6) 235
(s 3H Me) 184 (dm JH-H = 117 Hz 1H H7) 170 (dm 2JH-H = 145 Hz
2H H8) 145 (dm 2JH-H = 132 Hz 2H H9) 133 (m 1H H7) 104 (pseudo qt JH-H = 138 Hz 3JH-H = 37 Hz 2H H8) 080 (pseudo qt 2JH-H = 132 Hz 3JH-H = 37 Hz 2H H9) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F p-C6F5) -1673 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (101 MHz
CD2Cl2) δ 1916 (C1) 1341 (C5) 1323 (C13) 1315 (C15) 1313 (C4) 1307 (C12) 1282 (C16)
1262 (C17) 1257 (C3) 1254 (C11) 699 (C6) 320 (C7) 291 (Me) 249 (C8) 244 (C9) (C2
C10 C14 and all carbons for CequivCB(C6F5)3 were not observed) Anal calcd () for C46H29BF15N
C 6197 H 328 N 157 Found 6158 H 354 N 153
Synthesis of E-[(PhCH2)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (44) N-Benzylaniline (135 mg
0740 mmol) dichloromethane (10 mL) reaction time 2 h pale yellow solid (544 mg 0607
mmol 82) EZ ratio 41
44 1H NMR (600 MHz CD2Cl2) δ 782 (t 3JH-H = 73 Hz 1H H5) 777
(t 3JH-H = 73 Hz 2H H4) 764 (d 3JH-H = 73 Hz 2H H3) 760 (t 3JH-H =
76 Hz 1H H14) 753 (t 3JH-H = 76 Hz 2H H13) 738 (m 1H H10) 728
(m 4H H9 H16) 716 (t 3JH-H = 73 Hz 2H H17) 710 (t 3JH-H = 73 Hz
1H H18) 699 (d 3JH-H = 76 Hz 2H H12) 679 (d 3JH-H = 76 Hz 2H
H8) 526 (s 2H H6) 259 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
207 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1912 (C1) 1386 (C7) 1342 (C5) 1339
(C2) 1317 (C11 C14) 1311 (C9) 1309 (C13 C15) 1304 (C4 C10) 1296 (C8) 1294 (C16) 1278
B(C6F5)3
N1
2
3
45
7
8
9
10
14
1516
17
18
6
11
12
13
B(C6F5)3
N1
2
3
45
7
8 9
10
11 12
13
14
1617
1815
6
19
161
(C17) 1263 (C3) 1258 (C18) 1241 (C8) 938 (C19) 645 (C6) 286 (Me) (CequivCB(C6F5)3 and all
carbons of B(C6F5)3 were not observed) Anal calcd () for C47H25BF15N C 6276 H 280 N
156 Found 6259 H 296 N 171
Synthesis of [(p-C6H4OMe)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (45) (p-CH3OC6H4)PhNH
(147 mg 0740 mmol) pentane (15 mL) room temperature reaction time 3 h yellow solid (493
mg 0540 mmol 73) Anal calcd () for C47H25BF15NO C 6166 H 275 N 153 Found C
6106 H 262 N 142 EZ ratio 11
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 748 (m 1H H5) 735
(m 2H H3) 730 (m 2H H4) 726 (m 2H H8) 717 (m 2H H15) 707
(tm 3JH-H = 72 Hz 2H H16) 702 (m 1H H17) 696 (m 1H H9) 688
(dm 3JH-H = 87 Hz 2H H11) 670 (dm 3JH-H = 87 Hz 2H H12) 365 (s
3H OMe) 273 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1327 (m
2F o-C6F5) -1637 (t 3JF-F = 21 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (125 MHz CD2Cl2) δ 1884
(C1) 1613 (C13) 1481 (dm 1JC-F = 241 Hz CF) 1421 (C6) 1381 (dm 1JC-F = 244 Hz CF)
1364 1 (dm 1JC-F = 246 Hz CF) 1356 (C10) 1348 (C5) 1325 (C2) 1313 (C7) 1310 (C15)
1305(C8) 1297 (C4) 1292 (C3) 1278 (C16) 1274 (C14) 1269 (C11) 1257 (C17) 1255 (C9)
1155 (C12) 937 (C18) 557 (OMe) 283 (Me)
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 750 (m 1H H5) 735
(m 2H H4) 730 (m 2H H3) 726 (m 2H H8) 717 (m 2H H12) 702 (m
2H H11) 696 (m 1H H9) 378 (s 3H OMe) 279 (s 3H Me) 13C1H
NMR (125 MHz CD2Cl2) δ 1892 (C1) 1620 (C13) 1432 (C6) 1348 (C5)
1345 (C10) 1325 (C2) 1319 (C7) 1310 (C3) 1297 (C4) 1257 (C11) 1255
(C9) 1242 (C8) 1162 (C12) 557 (OMe) 283 (Me) 19F and 11B NMR are the same as above
Compounds 46 - 410 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and either diphenylamine (125 mg 0740 mmol) or N-isopropylaniline
(100 mg 0740 mmol) To the vial the respective alkyne was added over 1 min In the case
where pentane was used as the solvent the reaction was worked up as follows the solvent was
decanted and the product was washed with pentane (3 times 5 mL) to yield the product as a solid In
162
the case where toluene or dichloromethane was used as the as solvent the reaction was worked
up as follows the solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as a solid
Synthesis of [Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] (46) 1-Hexyne (122 mg 148 mmol)
pentane (20 mL) -30 degC to room temperature reaction time 2 h yellow solid (350 mg 414
mmol 56) The reaction also yielded alkenylboranes resulting from 11-carboboration which
were separated from the reaction mixture through the pentane washes during work-up
1H NMR (400 MHz CD2Cl2) δ 768 (m 6H Ph) 738 (m 4H Ph) 282
(m 2H H2) 262 (s 3H Me) 211 (t 3JH-H = 67 Hz 2H H7) 180 (quint
of t 3JH-H = 77 Hz 4JH-H = 28 Hz 2H H3) 141 (m 6H H4 H8 H9) 092
(t 3JH-H = 73 Hz 3H H5) 087 (t 3JH-H = 72 Hz 3H H10) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1643 (t 3JF-F = 21 Hz 1F
p-C6F5) -1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211
(s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1992 (C1) 1482 (dm 1JC-F = 237 Hz CF)
1411 (ipso-Ph) 1407 (ipso-Ph) 1382 (dm 1JC-F = 242 Hz CF) 1363 (dm 1JC-F = 246 Hz
CF) 1319 (Ph) 1315 (Ph) 1314 (Ph) 1236 (Ph) 1234 (Ph) 932 (C6) 389 (C2) 320 (C8)
295 (C3) 248 (Me) 227 (C4) 219 (C9) 199 (C7) 135 (C10) 130 (C5) (CequivCB(C6F5)3 and
ipso-C6F5 were not observed) Anal calcd () for C42H31BF15N C 5966 H 370 N 166
Found 5885 H 366 N 154
Synthesis of [Ph2N=C(CH3)C14H9][C14H9CequivCB(C6F5)3] (47) 9-Ethynylphenanthrene (299
mg 148 mmol) pentane (15 mL) room temperature reaction time 3 h pale yellow solid (602
mg 0555 mmol 75) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 859 (dm 3JH-H = 82 Hz 1H ArH) 853 (dm 3JH-H = 82 Hz
1H ArH) 849 (m 2H ArH) 845 (dm 3JH-H = 82 Hz 1H ArH) 776 (dm 3JH-H = 76 Hz 1H ArH) 773 (tm 3JH-H = 76 Hz 1H ArH) 767 (s 1H borateArH) 765 (tm 3JH-H = 82 Hz 1H ArH) 763 (s 1H amineArH) 760 (m 3JH-H = 82 Hz 1H ArH) 757 (m 3H m p-Ph) 755 (m
2H o-Ph) 753 (dm 3JH-H = 76 Hz 1H ArH) 748 (m 2H ArH) 744 (tm 3JH-H = 76 Hz 1H ArH) 737 (tm 3JH-H = 76 Hz 1H ArH) 732 (m 2H ArH) 703 (tt 3JH-H = 70 Hz 4JH-H = 10
Hz 1H ArH) 696 (tm 3JH-H = 70 Hz 2H m-Ph) 691 (dm 3JH-H = 70 Hz 2H o-Ph) 284
163
(Me) 19F NMR (377 MHz CD2Cl2) δ -1324 (m 2F o-C6F5) -1636 (t 3JF-F = 21 Hz 1F p-
C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -206 (s equivCB) 13C1H NMR
(125 MHz CD2Cl2) δ 1943 (C=N) 1500 (dm 1JC-F = 242 CF) 1444 (ipso-Ph) 1430 (ipso-
Ph) 1400 (dm 1JC-F = 245 CF) 1386 (dm 1JC-F = 250 CF) 1342 (ArC) 1342 (m-Ph) 1337
(p-Ph) 1336 (ArC) 1334 (o-Ph) 1330 (p-Ph) 1326 (ArC) 1325 (ArC) 1321 (ArC) 1320 (m-
Ph) 1319 (ArC) 1317 (ArC) 1315 (ArC) 1313 (ArC) 1310 (ArC) 1307 (ArC) 1306 (ArC)
1303 (ArC) 1301 (ArC) 1298 (ArC) 1297 (ArC) 1286 (ArC) 1284 (ArC) 1284 (ArC) 1280
(ArC) 1272 (ArC) 1261 (o-Ph) 1250 (o-Ph) 1259 (ArC) 1259 (ArC) 1248 (ArC) 1242 (ArC)
1241 (ArC) 937 (CequivCB) 3096 (Me) Anal calcd () for C62H31BF15N C 6859 H 288 N
129 Found C 6812 H 306 N 134
Synthesis of [iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] (48) Cyclopropylacetylene (125 μL
148 mmol) dichloromethane (10 mL) and pentane (5 mL) room temperature reaction time 2 h
pale yellow solid (507 mg 651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 17
48 1H NMR (400 MHz CD2Cl2) δ 765 (m 3H m p-Ph) 717 (m 2H
o-Ph) 483 (m 3JH-H = 66 Hz 1H iPr) 222 (s 3H CH3) 158 (m 1H
H1) 146 (m 4H H2) 131 (d 3JH-H = 66 Hz 6H iPr) 112 (tt 3JH-H = 81
Hz 3JH-H = 51 Hz 1H H4) 057 - 050 (m 4H H5) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1642 (t 3JF-F = 20 Hz 1F p-C6F5) -
1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211(s equivCB)
13C1H NMR (101 MHz CD2Cl2) δ 1937 (N=C) 1486 (dm 1JC-F = 236 Hz CF) 1383 (dm 1JC-F = 243 Hz CF) 1368 (dm 1JC-F = 245 Hz CF) 1356 (ipso-Ph) 1320 (p-Ph) 1313 (m-
Ph) 1266 (o-Ph) 1258 (ipso-C6F5) 958 (C3) 599 (iPr) 218 (C1) 208 (iPr) 161 (CH3) 153
(C2) 84 (C5) 149 (C4) (CequivCB(C6F5)3 was not observed) Anal calcd () for C37H25BF15N C
5702 H 323 N 180 Found 5667 H 330 N 179
Synthesis of E-[iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] (49) 2-Ethynylthiophene (160
mg 148 mmol) dichloromethane (4 mL) and pentane (10 mL) room temperature reaction time
1 h pale pink solid (498 mg 0577 mmol 78) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 71
164
49 1H NMR (400 MHz C6D5Br) δ 738 (d 3JH-H = 45 Hz 1H H3)
733 (t 3JH-H = 72 Hz 1H H10) 731 (d 3JH-H = 45 Hz 1H H5) 726 (t 3JH-H = 72 Hz 2H H9) 693 (d 3JH-H = 38 Hz 1H H12) 674 (d 3JH-H =
53 Hz 1H H14) 667 (t 3JH-H = 45 Hz 1H H4) 664 (dd 3JH-H = 53
Hz 3JH-H = 38 Hz 1H H13) 660 (d 3JH-H = 72 Hz 2H H8) 436 (m 3JH-H = 66 Hz 1H H6) 256 (s 3H Me) 081 (d 3JH-H = 66 Hz 6H
iPr) 19F NMR (377 MHz C6D5Br) δ -1312 (m 2F o-C6F5) -1619 (t 3JF-F = 21 Hz 1F p-
C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -203 (s equivCB) 13C1H NMR
(101 MHz C6D5Br) δ 1724 (C1) 1486 (dm 1JC-F = 240 Hz CF) 1446 (C5) 1438 (C3) 1384
(dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 267 Hz CF) 1346 (C7) 1330 (C2) 1324 (C10)
1312 (C9) 1290 (C12) 1286 (C4) 1272 (C8) 1269 (C13) 1239 (C14) 593 (C6) 214 (Me)
201 (iPr) (C11 C15 ipso-C6F5 and CequivCB(C6F5)3 were not observed) Anal calcd () for
C39H21BF15NS2 C 5425 H 245 N 162 Found 5415 H 259 N 168
Synthesis of (C6F5)3BCequivC(C6H4)C(Me)=NPh2 (410) 14-Diethynylbenzene (934 mg 0740
mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 2 h orange solid
(508 mg 0629 mmol 85) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 760 (m 3H m p-Ph) 735 (m 4H o m-Ph) 729 (m 5H
C6H4 p-Ph) 706 (dm 3JH-H = 77 Hz 2H o-Ph) 277 (s 3H Me) 19F NMR (377 MHz
CD2Cl2) δ -1329 (m 2F o-C6F5) -1630 (t 3JF-F = 20 Hz 1F p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1877
(C=N) 1482 (dm 1JC-F = 236 Hz CF) 1433 (ipso-Ph) 1425 (ipso-Ph) 1383 (dm 1JC-F = 243
Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1364 (quaternary C for C6H4) 1322 (C6H4) 1317 (p-
Ph) 1314 (m-Ph) 1311 (p-Ph) 1308 (m-Ph) 1302 (C6H4) 1282 (quaternary C for C6H4)
1255 (o-Ph) 1244 (o-Ph) 1228 (ipso-C6F5) 937 (CequivCB(C6F5)3) 276 (Me) (CequivCB(C6F5)3
was not observed) Elemental analysis for this compound did not pass after repeated attempts
Synthesis of [tBu(Ph)NH2][PhCequivCB(C6F5)3] (411) tert-Butylaniline (111 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) pentane (10 mL) reaction time 16 h off-white solid
(560 mg 0733 mmol 99)
165
1H NMR (400 MHz CD2Cl2) δ 751 (tm 3JH-H = 77 Hz 1H H4) 741
(tm 3JH-H = 77 Hz 2H H3) 728 (m 2H H7) 727 (m 2H H6) 725 (m
1H H8) 684 (dm 3JH-H = 77 Hz 2H H2) 677 (br s 2H NH2) 113 (s
9H tBu) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5) -1622
(t 3JF-F = 21 Hz 1F p-C6F5) -1661 (m 2F m-C6F5) 11B NMR (128
MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1479 (dm 1JC-F =
236 Hz CF) 1384 (dm 1JC-F = 241 Hz CF) 1366 (dm 1JC-F = 243 Hz CF) 1319 (C7) 1314
(C4) 1310 (C1) 1307 (C3) 1296 (C6) 1283 (C8) 1258 (C5) 1237 (C2) 941 (C9) 654 (tBu)
262 (tBu) Anal calcd () for C36H21BF15N C 5664 H 277 N 183 Found 5608 H 297 N
174
Synthesis of [iPr2NH2][PhCequivCB(C6F5)3] (412) Diisopropylamine (750 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) toluene (10 mL) reaction time 4 h white solid (405
mg 566 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered solution
of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 727 (tm 3JH-H = 76 Hz 2H m-Ph) 721 (dm 3JH-H = 76 Hz
2H o-Ph) 718 (tm 3JH-H = 76 Hz 1H p-Ph) 505 (m 2H NH2) 332 (m 3JH-H = 64 Hz 2H
iPr) 114 (d 3JH-H = 64 Hz 12H iPr) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5)
-1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
208 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1317 (m-Ph) 1292 (o-Ph) 1276
(p-Ph) 511 (iPr) 197 (iPr) Anal calcd () for C32H21BF15N C 5373 H 296 N 196 Found
5318 H 304 N 194
4422 Procedures for hydroarylation of phenylacetylene
Compounds 413 and 414 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of
B(C6F5)3 (0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial
phenylacetylene (756 mg 0740 mol) was added over 1 min The solvent was then removed
under reduced pressure and the crude product was washed with pentane to yield the product as a
solid
166
Synthesis of (PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 (413) NN-Dibenzylaniline (202 mg
0740 mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 1 h yellow
solid (630 mg 0710 mmol 96) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 753 (t 3JH-H = 76 Hz 2H m-Ph) 746 (t 3JH-H = 73 Hz 4H benzylm-Ph) 741 (s 1H =CH) 734 (d 3JH-H = 76 Hz 2H o-Ph) 715 (d 3JH-H = 74 Hz 4H benzylo-Ph) 700 (m 3H p-Ph benzylp-Ph) 691 (d 3JH-H = 86 Hz 2H C6H4) 680 (d 3JH-H = 86
Hz 2H C6H4) 617 (br s 1H NH) 484 (dm JH-H = 126 Hz 2H CH2Ph) 472 (dm JH-H = 126
Hz 2H CH2Ph) 19F NMR (377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1644 (t 3JF-F = 19
Hz 1F p-C6F5) -1680 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -158 (s equivCB)
13C1H NMR (101 MHz CD2Cl2) partial δ 1521 (=CH) 1387 (ipso-Ph) 1317 (m-Ph) 1316
(benzylipso-Ph) 1302 (benzylo-Ph) 1300 (benzylm-Ph) 1292 (o-Ph) 1291 (C6H4) 1271 (benzylp-
Ph) 1206 (C6H4) 1256 (p-Ph) 647 (CH2Ph) Elemental analysis was not successful after
numerous attempts
Synthesis of iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 (414) N-isopropylanthracen-9-amine (170
mg 0740 mmol) dichloromethane (10 mL) room temperature reaction time 5 h bright yellow
solid (597 mg 0704 mmol 95) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 795 (s 1H C=NH) 785 (m 2H m-Ph) 778 (m 2H o-Ph)
773 (d 3JH-H = 83 Hz 1H C14H9) 762 (d 3JH-H = 83 Hz 1H C14H9) 759 (t 3JH-H = 83 Hz
1H C14H9) 758 (m 1H p-Ph) 689 (t 3JH-H = 83 Hz 1H C14H9) 680 (s 1H =CH) 671 (t 3JH-H = 83 Hz 2H C14H9) 603 (d 3JH-H = 83 Hz 2H C14H9) 544 (s 1H CHC(Ph)=CH) 454
(m 1H iPr) 178 (d 3JH-H = 66 Hz 3H iPr) 126 (d 3JH-H = 66 Hz 3H iPr) 19F NMR (377
MHz CD2Cl2) δ -1322 (m 2F o-C6F5) -1645 (t 3JF-F = 20 Hz 1F p-C6F5) -1681 (m 2F m-
C6F5) 11B NMR (128 MHz CD2Cl2) δ -163 (s equivCB) 13C1H NMR (125 MHz CD2Cl2)
partial δ 1707 (C=CH) 1503 (=CH) 1353 (m-Ph) 1308 (o-Ph) 1290 (C14H9) 1284 (p-Ph)
1276 (C14H9) 1274 (C14H9) 1265 (C14H9) 1255 (C14H9) 1224 (C14H9) 599 (CHC(Ph)=CH)
530 (iPr) 233 (iPr) 228 (iPr) Anal calcd () for C43H23BF15N C 6080 H 273 N 165
Found 6059 H 281 N 197
167
4423 Procedures for catalytic intermolecular hydroamination reactions
Compounds 415 - 425 were prepared in a similar fashion thus only one preparation is detailed
In the glovebox a 4 dram vial equipped with a stir bar was charged with diphenylamine (125
mg 740 μmol) (p-C6H4F)2NH (152 mg 740 μmol) or N-isopropylaniline (100 mg 740 μmol)
and B(C6F5)3 (38 mg 74 μmol) in toluene (4 mL) The respective alkyne (740 μmol) was added
at a rate of 10 molh via microsyringe (oils) or by weighing into a vial (solids) Total reaction
time was 10 h after which the reaction was worked up outside of the glovebox The solvent was
removed under vacuum and the crude mixture was dissolved in ethyl acetate (5 mL) and passed
through a short (4 cm) silica column previously treated with Et2NH The crude reaction mixtures
consisted of the starting materials (amine and alkyne) and the product The product was purified
by column chromatography using hexaneethyl acetate (61) as eluent
Compounds 426 - 428 were prepared with slight modifications to the procedure above The
reaction vial was cooled to -30 degC then placed in a pre-cooled -30 degC brass-well before addition
of the alkyne via microsyringe or by weighing into a vial The reaction vial was kept in the brass-
well and warmed up to RT before cooling down the reaction vial again and adding the
subsequent aliquot of alkyne Each addition of alkyne was made in a pre-cooled brass-well The
reactions were worked up similar to the procedure above
(415) Yellow solid (187 mg 620 μmol 84) 1H NMR (400 MHz
CD2Cl2) δ 744 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H5) 721 -713
(m 5H m-C6H5 H3) 712 - 706 (m 4H o-C6H5) 691 (tt 3JH-H = 72 Hz 4JH-H = 11 Hz 2H p-C6H5) 685 (td 3JH-H = 75 Hz 4JH-H = 18 Hz 1H
H4) 679 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H2) 501 (s 1H =CH2) 490 (s 1H =CH2)
376 (s 3H OCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1577 (C6) 1498 (C=CH2) 1481
(ipso-C6H5) 1312 (C5) 1296 (C3) 1290 (m-C6H5) 1283 (C1) 1248 (o-C6H5) 1227 (p-C6H5)
1205 (C4) 1112 (C2) 1077 (=CH2) 558 (OCH3) HRMS-ESI+ mz [M+H]+ calcd for
C21H20NO 30215449 Found 30215453
168
(416) Off-while solid (146 mg 510 μmol 69) 1H NMR (600 MHz
CD2Cl2) δ 750 -743 (m 1H H5) 724 - 716 (tm 3JH-H = 74 Hz 4H m-
C6H5) 715 - 708 (m 6H o-C6H5 H3 H4) 706 -701 (m 1H H2) 700-
692 (tm 3JH-H = 74 Hz 2H p-C6H5) 484 (s 1H =CH2) 470 (s 1H
=CH2) 252 (s 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1526 (C=CH2) 1476 (ipso-
C6H5) 1390 (C1) 1364 (C6) 1309 (C5 C2) 1291 (m-C6H5) 1281 (C4) 1259 (C3) 1255 (o-
C6H5) 1233 (p-C6H5) 1051 (=CH2) 206 (CH3) HRMS-ESI+ mz [M+H]+ calcd for C21H20N
28615957 Found 28615986
(417) Orange solid (147 mg 460 μmol 62) 1H NMR (400 MHz
CD2Cl2) δ 870 (d 3JH-H = 85 Hz 1H H10) 777 (d 3JH-H = 85 Hz 1H
H7) 771 - 768 (m 2H H2 H4) 752 (tm 3JH-H = 85 Hz 1H H9) 743
(tm 3JH-H = 85 Hz 1H H8) 736 (tm 3JH-H = 85 Hz 1H H3) 722 -
709 (m 8H o m-C6H5) 692 (m 2H p-C6H5) 507 (s 1H =CH2)
494 (s 1H =CH2) 13C1H NMR (101 MHz CD2Cl2) δ 1513 (C=CH2) 1478 (ipso-C6H5)
1371 (C1) 1341 (C6) 1319 (C5) 1292 (m-C6H5) 1288 (C7 C2) 1281 (C4) 1266 (C9) 1260
(C8) 1256 (C10) 1254 (C3) 1253 (o-C6H5) 1229 (p-C6H5) 1067 (=CH2) HRMS-ESI+ mz
[M+H]+ calcd for C24H20N 32215957 Found 32216049
(418) Yellow oil (148 mg 550 μmol 74) 1H NMR (500 MHz
CD2Cl2) δ 757 (dm 3JH-H = 73 Hz 2H H2) 728 - 726 (m 3H H3 H4)
720 (tm 3JH-H = 74 Hz 4H m-C6H5) 709 (dm 3JH-H = 74 Hz 4H o-
C6H5) 695 (tm 3JH-H = 74 Hz 2H p-C6H5) 523 (s 1H =CH2) 486 (s
1H =CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1533 (C=CH2) 1482 (ipso-C6H5) 1394 (C1)
1293 (m-C6H5) 1286 (C3) 1285 (C4) 1276 (C2) 1243 (o-C6H5) 1228 (p-C6H5) 1082
(=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H18N 2721433 Found 2721443
(419) Orange solid (134 mg 390 μmol 52)1H NMR (500 MHz
CD2Cl2) δ 753 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H
H2) 744 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H H5)
723 (td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H3) 720 - 715 (m 8H om-
C6H5) 706 (pseudo td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H4) 697 (tt 3JH-H = 70 Hz 4JH-H =
16 Hz 2H p-C6H5) 493 (d 2JH-H = 04 Hz 1H =CH2) 483 (d 2JH-H = 04 Hz 1H =CH2)
169
13C1H NMR (125 MHz CD2Cl2) δ 1513 (C=CH2) 1473 (ipso-C6H5) 1399 (C1) 1337 (C5)
1327 (C2) 1296 (C4) 1291 (m-C6H5) 1275 (C3) 1256 (o-C6H5) 1235 (p-C6H5) 1224 (C6)
1059 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H17BrN 35005444 Found 35005379
(420) Orange solid (191 mg 500 μmol 67) 1H NMR (500 MHz
CD2Cl2) δ 750 (ddm 3JH-H = 78 Hz 4JH-H = 18 Hz 1H H2) 743
(ddm 3JH-H = 78 Hz 4JH-H = 12 Hz 1H H5) 724 (tdm 3JH-H = 78
Hz 4JH-H = 12 Hz 1H H4) 712 (dm 3JH-H = 80 Hz 4H H8) 707
(dm 3JH-H = 78 Hz 1H H3) 690 (tm 3JH-H = 80 Hz 4H H9) 479 (s
1H =CH2) 471 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1202 (tt 3JF-H = 88 Hz 4JF-H
= 52 Hz p-C6H4F) 13C1H NMR (125 MHz CD2Cl2) δ 1593 (d 1JC-F = 242 Hz C10) 1518
(C=CH2) 1433 (d 4JCF = 29 Hz C7) 1395 (C1) 1337 (C5) 1328 (C2) 1298 (C3) 1276 (C4)
1272 (d 3JC-F = 79 Hz C8) 1223 (C6) 1159 (d 2JC-F = 22 Hz C9) 1041 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C20H15BrF2N 38603559 Found 38603477
(421) Yellow oil (188 mg 580 μmol 78) 1H NMR (400 MHz
CD2Cl2) δ 748 (pseudo td 3JH-H = 77 Hz J = 19 Hz 1H H2) 721
(m 1H H4) 707 - 702 (m 5H H3 H8) 697 (m 1H H5) 691 (m
4H H9) 500 (d 5JF-H = 15 Hz 1H =CH2) 488 (s 1H =CH2) 19F
NMR (377 MHz CD2Cl2) δ -1162 (dm 3JF-H = 119 Hz 1F CF of
C6) -1207 (tm 3JF-H = 97 Hz 2F p-C6H4F) 13C1H NMR (101 MHz CD2Cl2) δ 1605 (d 1JC-F = 249 Hz CF of C6) 1591 (d 1JC-F = 244 Hz C10) 1475 (C=CH2) 1438 (d 4JC-F = 28
Hz C7) 1311 (d 3JC-F = 30 Hz C2) 1302 (d 3JC-F = 85 Hz C4) 1271 (d 2JC-F = 116 Hz C1)
1264 (d 3JC-F = 81 Hz C8) 1244 (d 4JC-F = 37 Hz C3) 1162 (d 2JC-F = 22 Hz C5) 1160 (d 2JC-F = 22 Hz C9) 1077 (d 4JC-F = 36 Hz =CH2) HRMS-ESI+ mz [M+H]+ calcd for
C20H15F3N 32611566 Found 32611576
(422) Yellow oil (125 mg 400 μmol 54) 1H NMR (400 MHz
CD2Cl2) δ 718 (dd 3JH-H = 51 4JH-H = 12 Hz 1H H4) 712 (dd 3JH-H
= 36 Hz 4JH-H = 12 Hz 1H H2) 705 - 701 (m 4H H6) 695 - 689
(m 5H H3 H7) 526 (s 1H =CH2) 469 (s 1H =CH2) 19F NMR (377
MHz CD2Cl2) δ -1209 (m 3JF-H = 90 Hz p-C6H4F) 13C1H NMR
(101 MHz CD2Cl2) δ 1589 (d 1JC-F = 241 Hz C8) 1473 (C=CH2) 1442 (d 4JC-F = 26 Hz
170
C5) 1436 (C1) 1276 (C3) 1265 (C2) 1258 (C4) 1257 (d 3JC-F = 80 Hz C6) 1162 (d 2JC-F =
22 Hz C7) 1068 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 31408150 Found
31408200
(423) Yellow oil (104 mg 430 μmol 58) 1H NMR (400 MHz
CD2Cl2) δ 715 (tm 3JH-H = 79 Hz 2H m-C6H5) 712 (dd 3JH-H = 53 Hz 4JH-H = 13 Hz 1H H4) 701 (dd 3JH-H = 35 Hz 4JH-H = 13 Hz 1H H2)
693 (dm 3JH-H = 79 Hz 2H o-C6H5) 685 (m 1H H3) 681 (tm 3JH-H =
79 Hz 1H p-C6H5) 531 (s 1H =CH2) 484 (s 1H =CH2) 426 (m 3JH-H = 66 Hz 1H iPr)
125 (d 3JH-H = 66 Hz 6H iPr) 13C1H NMR (101 MHz CD2Cl2) δ 1466 (ipso-C6H5) 1456
(C1) 1446 (C=CH2) 1296 (m-C6H5) 1274 (C2) 1260 (C3) 1253 (C4) 1208 (o-C6H5) 1206
(p-C6H5) 502 (iPr) 211 (iPr) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 2441154
Found 2441166
(424) Pale yellow solid (206 mg 560 μmol 75) 1H NMR (600
MHz CD2Cl2) δ 881 (dm 3JH-H = 78 Hz 1H H14) 865 (dm 3JH-H =
78 Hz 1H H11) 860 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H10)
797 (s 1H H2) 787 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H7)
766-761 (m 3H H9 H12 H13) 757 (pseudo td 3JH-H = 78 Hz 4JH-H
= 14 Hz 1H H8) 723 (m 4H o-C6H5) 715 (t 3JH-H = 73 Hz 4H m-C6H5) 692 (tt 3JH-H =
73 Hz 4JH-H = 12 Hz 2H p-C6H5) 512 (s 1H =CH2) 503 (s 1H =CH2) 13C1H NMR (125
MHz CD2Cl2) δ 1516 (C=CH2) 1476 (ipso-C6H5) 1357 (C1) 1317 (C3) 1309 (C6) 1307
(C5) 1306 (C4) 1294 (C2) 1292 (m-C6H5) 1291 (C7) 1273 (C9) 1271 (C8 C13) 1268 (C12)
1264 (C14) 1255 (o-C6H5) 1235 (p-C6H5) 1232 (C11) 1228 (C10) 1060 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C28H22N 37217522 Found 37217485
(425) Pale yellow solid (228 mg 560 μmol 75) 1H NMR (400
MHz CD2Cl2) δ 874 (dm 3JH-H = 74 Hz 1H H14) 866 (dm 3JH-H
= 74 Hz 1H H11) 861 (dm 3JH-H = 74 Hz 1H H10) 795 (s 1H
H2) 788 (dm 3JH-H = 74 Hz 1H H7) 767- 762 (m 3H H9 H12
H13) 759 (pseudo td 3JH-H = 74 Hz 4JH-H = 12 Hz 1H H8) 718
(m 4H H16) 686 (m 4H H17) 499 (s 1H =CH2) 495 (s 1H =CH2) 19F NMR (377 MHz
CD2Cl2) δ -1200 (tt 3JF-H = 84 Hz 4JF-H = 42 Hz p-C6H4F) 13C1H NMR (125 MHz
171
CD2Cl2) δ 1592 (d 1JC-F = 240 Hz C18) 1519 (C=CH2) 1437 (d 4JC-F = 26 Hz C15) 1353
(C1) 1316 (C3) 1308 (C6) 1307 (C5) 1306 (C4) 1296 (C2) 1291 (C7) 1274 (C9) 1272 (C8
C12) 1271 (d 3JC-F = 83 Hz C16) 1269 (C13) 1262 (C14) 1233 (C11) 1228 (C10) 1161 (d 2JCF = 219 Hz C17) 1043 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C28H20F2N 40815638
Found 40815576
(426) Yellow oil (178 mg 550 μmol 74) 1H NMR (400 MHz
CD2Cl2) δ 735 (dm 3JH-H = 77 Hz 1H H2) 727- 723 (m 2H H3
H6) 701 (m 4H H8) 697- 691 (m 5H H4 H9) 516 (s 1H =CH2)
478 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1141 (m 1F
CF of C5) -1205 (m 2F p-C6H4F) 13C1H NMR (101 MHz
CD2Cl2) δ 1632 (d 1JC-F = 245 Hz C5) 1592 (d 1JC-F = 244 Hz C10) 1522 (d 4JC-F = 25 Hz
C=CH2) 1442 (d 4JC-F = 28 Hz C7) 1417 (d 3JC-F = 76 Hz C1) 1303 (d 3JC-F = 84 Hz C3)
1261 (d 3JC-F = 81 Hz C8) 1235 (d 4JC-F = 28 Hz C2) 1162 (d 2JC-F = 22 Hz C9) 1154 (d 2JC-F = 21 Hz C4) 1145 (d 2JC-F = 21 Hz C6) 1074 (=CH2) HRMS-ESI+ mz [M+H]+ calcd
for C20H15F3N 32611566 Found 32611485
(427) White solid (154 mg 500 μmol 68) 1H NMR (500 MHz
CD2Cl2) δ 722 (tm 3JH-H = 73 Hz 4H m-C6H5) 710 (m 2H H2) 705
(dm 3JH-H = 73 Hz 4H o-C6H5) 699 (tm 3JH-H = 73 Hz 2H p-C6H5)
670 (tt 3JH-H = 89 Hz 4JH-H = 24 Hz 1H H4) 525 (s 1H =CH2) 490
(s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1107 (t 3JF-H = 81 Hz m-C6H3F2) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (d 1JC-F = 248 Hz C3) 1515 (t 4JC-F = 28 Hz C=CH2)
1477 (ipso-C6H5) 1435 (d 3JC-F = 92 Hz C1) 1295 (m-C6H5) 1244 (o-C6H5) 1234 (p-
C6H5) 1105 (d 2JC-F = 21 Hz C2) 1093 (s =CH2) 1037 (t 2JC-F = 25 Hz C4) HRMS-ESI+
mz [M+H]+ calcd for C20H16F2N 30812508 Found 30812511
(428) Yellow oil (193 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 783 (ddq 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H6)
774 (ddq 3JH-H = 78 Hz 4JH-H = 12 Hz 6JF-H = 06 Hz 1H H2) 749
(dddq 3JH-H = 78 Hz 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H4)
739 (pseudo tq 3JH-H = 78 Hz 5JF-H = 07 Hz 1H H3) 721 (tm 3JH-H = 78 Hz 4H m-C6H5)
707 (dm 3JH-H = 78 Hz 4H o-C6H5) 697 (tm 3JH-H = 78 Hz 2H p-C6H5) 526 (d 1H 2JH-H
172
= 07 Hz =CH2) 493 (d 2JH-H = 07 Hz =CH2) 19F NMR (377 MHz CD2Cl2) δ -630 (s CF3)
13C1H NMR (125 MHz CD2Cl2) δ 1517 (C=CH2) 1474 (ipso-C6H5) 1400 (C1) 1304 (q 5JC-F = 13 Hz C2) 1304 (q 2JC-F = 32 Hz C5) 1290 (m-C6H5) 1287 (C3) 1247 (q 3JC-F = 38
Hz C4) 1242 (o-C6H5) 1241 (q 1JC-F = 271 Hz CF3) 1239 (q 3JC-F = 38 Hz C6) 1228 (p-
C6H5) 1083 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C21H17F3N 34013131 Found
34013065
4424 Procedures for tandem hydroamination and hydrogenation reactions
A general procedure is provided for the preparation of compounds 429 and 430 Following the
10 h catalytic hydroamination reaction in the glovebox the reaction mixture was transferred into
an oven-dried Teflon screw cap glass tube The reaction tube was degassed once through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The tube
was placed in an 80 ordmC oil bath for 14 h The solvent was removed under vacuum and the
mixture was dissolved in ethyl acetate (5 mL) and passed through a short (4 cm) silica column
previously treated with Et2NH The crude reaction mixtures consisted of the starting materials
(amine and alkyne) and the product The product was purified by column chromatography using
hexaneethyl acetate (61) as eluent
Alternative hydrogenation procedure using 5 mol Mes2PH(C6F4)BH(C6F5)2
Mes2PH(C6F4)BH(C6F5)2 (28 mg 37 μmol) was added to the reaction mixture before being
transferred into the glass tube The tube was filled with H2 and placed in an 80 ordmC oil bath The
reaction was stopped after 3 h at 80 ordmC and worked up similar to the procedure above
(429) Yellow oil (186 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 728 - 720 (m 2H H2 H5) 708 - 700 (m 2H H3 H4)
692 (m 4H H9) 680 (m 4H H8) 545 (q 3JH-H = 70 Hz C(CH3)H)
138 (d 3JH-H = 70 Hz C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -
1186 (m 1F F of C6) -1224 (m 2F F of C10) 13C1H NMR (125
MHz CD2Cl2) δ 1610 (d 1JC-F = 247 Hz C6) 1588 (d 1JC-F = 241 Hz C10) 1436 (d 4JC-F =
26 Hz C7) 1310 (d 2JC-F = 131 Hz C1) 1291 (d 2JC-F = 85 Hz C5) 1284 (d 3JC-F = 43 Hz
C2) 1249 (d 3JC-F = 79 Hz C8) 1244 (d 4JC-F = 35 Hz C3) 1159 (d 2JC-F = 22 Hz C9) 1157
173
(d 3JC-F = 22 Hz C4) 517 (C(CH3)H) 197 (C(CH3)H) HRMS-ESI+ mz [M+H]+ calcd for
C20H17F3N 32813131 Found 32813189
(430) Yellow oil (146 mg 470 μmol 64) 1H NMR (500 MHz
CD2Cl2) δ 724 (tm 3JH-H = 78 Hz 4H m-C6H5) 699 (m 4H H2 p-
C6H5) 688 (dm 3JH-H = 78 Hz 4H o-C6H5) 671 (tt 3JF-H = 89 Hz 4JH-H = 24 Hz 1H H4) 524 (d 3JH-H =70 Hz 1H C(CH3)H) 145 (d
3JH-H = 70 Hz 3H C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -1105 (m F of C3) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (dd 1JC-F = 248 Hz 3JC-F = 13 Hz C3) 1496 (t 3JC-F = 79
Hz C1) 1472 (ipso-C6H5) 1297 (m-C6H5) 1235 (o-C6H5) 1212 (p-C6H5) 1100 (dd 2JC-F =
20 Hz 4JC-F = 47 Hz C2) 1202 (t 2JC-F = 27 Hz C4) 579 (C(CH3)H) 203 (C(CH3)H)
HRMS-ESI+ mz [M+H]+ calcd for C20H18F2N 31014073 Found 31014081
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions
Compounds 431 and 432 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 25 mL Schlenk flask equipped with a stir bar was charged with a
toluene (5 mL) solution of B(C6F5)3 (0100 g 0190 mmol) and the respective alkynyl aniline
(0190 mmol) The solution was heated for 2 h at 50 degC and the solvent was subsequently
removed under reduced pressure The crude oil was washed with pentane (2 times 5 mL) to yield the
product as a white solid
Synthesis of C6H5N(CH2)3CCH2B(C6F5)3 (431) N-(Pent-4-ynyl)aniline (300 mg 0190
mmol) product (120 mg 0179 mmol 94)
1H NMR (400 MHz CD2Cl2) δ 746 (m 3H m p-Ph) 691 (dm 3JH-H =
86 Hz 2H o-Ph) 416 (t 3JH-H = 78 Hz 2H H3) 333 (br q 2JB-H = 54
Hz 2H CH2B) 311 (t 3JH-H = 78 Hz 2H H1) 215 (quint 3JH-H = 78 Hz
2H H2) 19F NMR (377 MHz CD2Cl2) δ -1325 (m 2F o-C6F5) -1601 (t 3JF-F = 21 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -134 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 1942 (C=N) 1476 (dm 1JC-F = 241 Hz CF)
1392 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1348 (ipso-Ph) 1324 (p-Ph)
174
1311 (m-Ph) 1231 (o-Ph) 1189 (ipso-C6F5) 651 (C3) 411 (C1) 185 (CH2B C2) Anal
calcd () for C29H13BF15N C 5189 H 195 N 209 Found 5140 H 219 N 191
Synthesis of C6H5N(CH2)4CCH2B(C6F5)3 (432) N-(Hex-5-ynyl)aniline (340 mg 0190
mmol) product (129 mg 0188 mmol 99) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC
1H NMR (600 MHz CD2Cl2) δ 745 (tt 3JH-H = 75 Hz 4JH-H = 22 Hz
1H p-Ph) 740 (tm 3JH-H = 75 Hz 2H m-Ph) 663 (dm 3JH-H = 75 Hz
2H o-Ph) 372 (t 3JH-H = 73 Hz 2H H4) 316 (br q 2JB-H = 63 Hz 2H
CH2B) 275 (t 3JH-H = 73 Hz 2H H1) 197 (m 2H H3) 176 (m 2H
H2) 19F NMR (377 MHz CD2Cl2) δ -1320 (m 2F o-C6F5) -1611 (t 3JF-
F = 20 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -130 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 2005 (C=N) 1481 (dm 1JC-F = 241 Hz CF)
1420 (ipso-Ph) 1384 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1301 (m p-
Ph) 1226 (ipso-C6F5) 1237 (o-Ph) 574 (C4) 380 (CH2B) 326 (C1) 213 (C3) 175 (C2)
Anal calcd () for C30H15BF15N C 5228 H 221 N 204 Found 5206 H 272 N 177
Synthesis of [2-MeC8H6N(Ph)][HB(C6F5)3] (433) In the glovebox a 25 mL Schlenk flask
equipped with a stir bar was charged with a toluene (5 mL) solution of B(C6F5)3 (0100 g 0190
mmol) and N-(2-ethynylbenzyl)aniline (390 mg 0190 mmol) The solution was heated for 16 h
under H2 (4 atm) at 80 degC The solvent was subsequently removed under reduced pressure The
crude oil was washed with pentane (2 times 5 mL) to yield the product as a white solid (740 mg
0103 mmol 54)
1H NMR (600 MHz CD2Cl2) δ 812 (dm 3JH-H = 79 Hz JH-H = 10
Hz 1H H9) 799 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H H8) 786 (dm 3JH-H = 79 Hz 1H H6) 782 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H
H7) 773 - 769 (m 3H H2 and H3) 745 (dm 3JH-H = 76 Hz H1) 556
(q JH-H = 26 Hz 2H H4) 353 (br 1H HB) 289 (t JH-H = 26 Hz Me) 19F NMR (564 MHz
CD2Cl2) δ -1341 (br 2F o-C6F5) -1644 (br 1F p-C6F5) -1674 (br 2F m-C6F5) 11B1H
NMR (192 MHz CD2Cl2) δ -252 (s HB) 13C1H NMR (151 MHz CD2Cl2) 1820 (N=C)
1480 (dm 1JC-F = 247 Hz CF) 1437 (C10) 1373 (C7) 1366 (dm 1JC-F = 241 Hz CF) 1362
(dm 1JC-F = 241 Hz CF) 1347 (ipso-Ph) 1337 (C5) 1322 (C3) 1308 (C2) 1306 (C8) 1266
NB(C6F5)3
4
3
2
1
175
(C9) 1247 (C1) 1234 (C6) 657 (C4) 149 (Me) (ipso-C6F5 was not observed) Anal calcd ()
for C33H15BF15N C 5495 H 210 N 194 Found C 5502 H 212 N 218
Compounds 434 - 438 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 25 mL Schlenk bomb equipped with a stir bar was charged with a toluene (2
mL) solution of B(C6F5)3 (20 mg 40 μmol) and the alkynyl aniline (039 mmol) The solution
was heated for 16 h under H2 (4 atm) at 80 degC The solvent was subsequently removed under
reduced pressure The crude oil was washed with pentane (2 times 5 mL) and purified by column
chromatography using hexaneethyl acetate (61) as eluent
Synthesis of 2-MeC4H7N(Ph) (434) N-(Pent-4-ynyl)aniline (600 mg 0390 mmol) product
(427 mg 0265 mmol 68)
1H NMR (500 MHz CD2Cl2) δ 718 (t 3JH-H = 78 Hz 2H m-Ph) 660 (tt 3JH-H =
78 Hz 4JH-H = 11 H 1H p-Ph) 657 (d 3JH-H = 78 Hz 2H o-Ph) 286 (m 3JH-H =
61 Hz 1H NCHCH3) 282 (ddd 2JH-H = 88 Hz 3JH-H = 78 Hz 35 Hz 1H H3)
254 (pseudo q 3JH-H = 83 Hz 1H H3) 211 - 162 (m 4H H1 and H2) 099 (d 3JH-H
= 61 Hz 3H Me) 13C1H NMR (151 MHz CD2Cl2) δ 1474 (ipso-Ph) 1289 (m-Ph) 1148
(p-Ph) 1116 (o-Ph) 540 (NCHCH3) 478 (C3) 330 (C1) 265 (C2) 197 (Me) HRMS-
DART+ mz [M+H]+ calcd for C11H15N 16212827 Found 16212755
Synthesis of 2-MeC5H9N(Ph) (435) N-(Hex-5-ynyl)aniline (682 mg 0390 mmol) product
(451 mg 0257 mmol 66)
1H NMR (500 MHz CD2Cl2) δ 723 (t 3JH-H = 81 Hz 2H m-Ph) 693 (d 3JH-H =
81 Hz 2H o-Ph) 680 (tt 3JH-H = 81 Hz 4JH-H = 11 H 1H p-Ph) 394 (m 1H
NCHCH3) 323 (dt 2JH-H = 121 Hz 3JH-H = 44 Hz 1H H4) 297 (dm 2JH-H = 121
Hz 1H H4) 190 - 160 (m 6H H1 H2 H3) 100 (d 3JH-H = 672 3H Me) 13C1H
NMR (151 MHz CD2Cl2) δ 1516 (ipso-Ph) 1288 (m-Ph) 1187 (p-Ph) 1173 (o-
Ph) 512 (NCHCH3) 446 (C4) 317 (C1) 261 (C3) 198 (C2) 134 (Me) HRMS- DART+ mz
[M+H]+ calcd for C12H17NO 17614392 Found 17614338
176
Synthesis of 2-MeC5H9N(p-FC6H4) (436) 4-Fluoro-N-(hex-5-yn-1-yl)aniline (745 mg 0390
mmol) product (542 mg 0281 mmol 72)
1H NMR (400 MHz C6D5Br) δ 652 (t JH-H = 88 Hz 2H m-H of C6H4F) 637 (dd 3JH-H = 88 Hz 4JH-F = 48 Hz 2H o-H of C6H4F) 306 (m 1H NCHCH3) 241 (m
1H H4) 135 (m 1H H1) 121 (m 1H H3) 113 (m 2H H23) 102 (m 1H H2)
101 (m 1H H2) 045 (d 3JH-H = 65 Hz 3H CH3) 19F NMR (377 MHz C6D5Br)
δ -1235 (s 1F C6H4F) 13C1H NMR (100 MHz C6D5Br) δ 1582 (q 1JC-F = 297
Hz p-C6H4F) 1479 (ipso-C6H4F) 1202 (d 3JC-F = 77 Hz o-C of C6H4F) 1150 (d 3JC-F = 227 Hz m-C of C6H4F) 518 (NCHCH3) 470 (C4) 321 (C1) 260 (C3) 203 (C2) 146
(CH3) HRMS- ESI + mz [M+H]+ calcd for C12H16NF 1941340 Found 1941337
Synthesis of 2-MeC5H9N(p-CH3OC6H4) (437) N-(Hex-5-yn-1-yl)-4-methoxyaniline (792 mg
0390 mmol) product (416 mg 0203 mmol 52)
1H NMR (500 MHz C6D5Br) δ 712 (d 3JH-H = 85 Hz 2H m-H of C6H4OCH3)
700 (d 3JH-H = 85 Hz 2H o-H of C6H4OCH3) 374 (s 3H OCH3) 349 (m 1H
NCHCH3) 309 (m 1H H4) 302 (m 1H H4) 194 (m 1H H1) 184 (m 1H H3)
178 (m 1H H2) 176 (m 1H H3) 161 (m 1H H1) 158 (m 1H H2) 106 (d 3JH-
H = 65 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1542 (p-C6H4OCH3)
1457 (ipso-C6H4OCH3) 1221 (m-C of C6H4OCH3) 1139 (o-C of C6H4OCH3) 546
(OCH3) 534 (NCHCH3) 496 (C4) 331 (C1) 264 (C3) 214 (C2) 160 (CH3) HRMS-ESI+
mz [M+H]+ calcd for C13H19NO 2061539 Found 2061539
Synthesis of 2-MeC8H7N(Ph) (438) N-(2-Ethynylbenzyl)aniline (808 mg 0390 mmol)
product (571 mg 0273 mmol 70)
1H NMR (400 MHz CD2Cl2) δ 778 (d 3JH-H = 77 Hz 1H C6H4) 745 - 737 (m
5H m-Ph C6H4) 707 (t 3JH-H = 77 Hz 1H p-Ph) 703 (d 3JH-H = 77 Hz 2H o-
Ph) 510 (q 3JH-H = 66 Hz 1H NCH(CH3)) 483 (d 2JH-H = 138 Hz 1H CH2)
463 (d 2JH-H = 138 Hz 1H CH2) 154 (d 3JH-H = 66 Hz 3H CH3) 13C1H NMR
(151 MHz CD2Cl2) δ 1435 (ipso-Ph) 1376 (C1) 1343 (C6) 1297 (m-Ph) 1283
177
(C34) 1245 (C2) 1226 (p-Ph) 1222 (C5) 1161 (o-Ph) 641 (NCH(CH3) 563 (CH2) 182
(CH3) HRMS-DART+ mz [M+H]+ calcd for C15H15N 21012827 Found 21012767
4426 Procedures for reactions with ethynylphosphines
Synthesis of trans-Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 (439) In the glove box a 4 dram
vial equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg
0740 mmol) and iPrNHPh (100 mg 0740 mmol) To the vial Mes2PCequivCH (440 mg 0148
mmol) was added and the reaction was left at RT for 16 h The solvent was removed under
reduced pressure and the crude product was washed with pentane to yield the product as a pale
yellow solid (717 mg 0651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 771 (td JP-H = 286 Hz 3JH-H = 172 Hz 1H =CH) 698 (d 4JPH = 49 Hz 4H Mes) 689 (d 4JPH = 32 Hz 4H Mes) 574 (ddd 2JP-H = 273 Hz 3JH-H =
172 3JP-H = 44 Hz 1H =CH) 235 (s 6H Mes) 229 (s 6H Mes) 223 (s 12H Mes) 218 (s
12H Mes) 19F NMR (377 MHz CD2Cl2) δ -1329(m 2F o-C6F5) -1616 (t 3JF-F = 21 Hz 1F
p-C6F5) -1663 (m 2F m-C6F5) 31P1H NMR (162 MHz CD2Cl2) δ -115 (br s PMes2) -143
(d JP-P = 82 Hz PMes2) 11B NMR (128 MHz CD2Cl2) δ -211 (CB) 13C1H NMR (101
MHz CD2Cl2) partial δ 1540 (d 1JC-P = 31 Hz Mes) 1470 (d 1JC-F = 248 Hz CF) 1437 (d
JC-P = 28 Hz Mes) 1417 (d JC-P = 150 Hz Mes) 1413 (d JC-P = 113 Hz Mes) 1393 (Mes)
1321 (d 3JC-P = 14 Hz Mes) 1303 (d 3JC-P = 56 Hz Mes) 1260 (d JC-P = 11 Hz Mes) 1178
(dd 2JC-P = 99 Hz 3JC-P = 27 Hz =CH) 1120 (dd 2JC-P = 85 Hz 3JC-P = 121 Hz =CH) 219 (d 3JC-P = 68 Hz Mes) 218 (d 3JC-P = 14 Hz Mes) 201 (d 5JC-P = 18 Hz Mes) 198 (Mes)
Anal calcd () for C58H46BF15P2 C 6329 H 421 Found C 6282 H 411
Synthesis of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 (440) In the glove box a 4 dram vial
equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg 0144
mmol) To the vial tBu2PCequivCH (250 mg 0148 mmol) was added and the reaction was left at
RT for 16 h The solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as an off-white solid (580 mg 0570 mmol 77)
Crystals suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC
178
1H NMR (600 MHz CD2Cl2) δ 777 (ddd 2JP-H = 46 Hz 3JH-H =15 Hz 3JP-H = 36 Hz 1H
=CH) 650 (ddd 2JP-H = 28 Hz 3JP-H = 19 Hz 3JH-H =15 Hz 1H =CH) 144 (d 3JP-H = 17 Hz
18H tBu) 101 (d 3JP-H = 11 Hz 18H tBu) 19F NMR (564 MHz CD2Cl2) δ -1322 (m 2F o-
C6F5) -1618 (t 3JF-F = 20 Hz 1F p-C6F5) -1665 (m 2F m-C6F5) 31P1H NMR (242 MHz
CD2Cl2) δ 215 (PtBu2) 251 (PtBu2) 11B NMR (192 MHz CD2Cl2) -212 (CB) 13C1H
NMR (151 MHz CD2Cl2) partial δ 1620 (dd 1JC-P = 42 Hz 2JC-P = 32 Hz =CH) 1210 (dd 1JC-P = 82 Hz 2JC-P = 21 Hz =CH) 371 (d 1JC-P = 48 Hz tBu) 325 (d 1JC-P = 22 Hz tBu) 292
(d 2JC-P = 14 Hz tBu) 266 (tBu) Anal calcd () for C38H38BF15P2 C 5354 H 449 Found C
5314 H 432
Compounds 441 and 442 were prepared following the same procedure In the glove box a
Schlenk tube equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of HB(C6F5)2
(100 mg 0289 mmol) and the appropriate alkynyl-substituted pinacolborane (0289 mmol) was
added at once After 5 minutes Ph2PH (538 mg 0289 mmol) was added to the vial The
reaction was left at RT for 16 h The solvent was then removed under reduced pressure and
pentane (5 mL) was added to the crude oil resulting in precipitate The pentane soluble fraction
was separated from the precipitate concentrated and placed in a -30 degC freezer to give the
product as colourless crystals
Synthesis of Bu(H)Ph2PC-C(H)B(C6F5)2Bpin (441) CH3(CH2)3CequivCBpin (606 mg 0289
mmol) product (175 mg 0237 mmol 82)
1H NMR (600 MHz CD2Cl2) δ 766 (m 2H o-Ph) 757 (tm 3JH-H = 77 Hz 1H p-Ph) 747
(tm 3JH-H = 72 Hz 1H p-Ph) 742 (m 2H m-Ph) 736 (m 2H m-Ph) 733 (m 2H o-Ph) 353
(m 1H CHP) 290 (d 2JH-H = 116 Hz 1H CH2CHP) 278 (d 2JH-H = 116 Hz 1H CH2CHP)
148 (m 1H CHB) 133 (m 2H CH2) 118 (m 2H CH2) 102 (s 6H CH3) 098 (s 6H CH3)
078 (t 3JH-H = 72 Hz 3H CH3) 19F NMR (564 MHz CD2Cl2) δ -1292 (m 2F o-C6F5) -
1328 (m 2F o-C6F5) -1665 (m 2F m-C6F5) -1585 (t 3JF-F = 20 Hz 1F p-C6F5) -1605 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) -1653 (m 2F m-C6F5) 31P1H NMR (242
MHz CD2Cl2) δ 322 (br) 11B NMR (192 MHz CD2Cl2) δ 337 (Bpin) -66 (B(C6F5)2)
13C1H NMR (151 MHz CD2Cl2) partial δ 1362 (d 2JC-P = 91 Hz o-Ph) 1318 (d 4JC-P = 29
Hz p-Ph) 1314 (d 2JC-P = 81 Hz o-Ph) 1313 (d 4JC-P = 28 Hz p-Ph) 1285 (d 3JC-P = 95
Hz m-Ph) 1279 (d 3JC-P = 10 Hz m-Ph) 1279 (d 1JC-P = 332 Hz ipso-Ph) 1238 (d 1JC-P =
179
34 Hz ipso-Ph) 824 (C(CH3)2) 346 (d 1JC-P = 37 Hz CHP) 301 (d 2JC-P = 80 Hz CH2CHP)
290 (d 3JC-P = 49 Hz CH2) 246 (BpinCH3) 242 (BpinCH3) 224 (CH2) 158 (CHB) 079
(CH3) Anal calcd () for C36H33B2F10O2P C 5841 H 449 Found 5808 H 437
Synthesis of Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin (442) CH2=C(CH3)CequivCBpin (567
mg 0289 mmol) product (153 mg 0211 mmol 73) Crystals suitable for X-ray diffraction
were grown from pentane at -30 ordmC
1H31P NMR (600 MHz CD2Cl2) δ 764 (tt 3JH-H = 73 Hz 4JH-H = 14 Hz 1H p-Ph) 755 (d 3JH-H = 73 Hz 2H o-Ph) 749 (t 3JH-H = 75 Hz 2H m-Ph) 727 (tt 3JH-H = 75 Hz 4JH-H = 12
Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 680 (d 3JH-H = 75 Hz 2H o-Ph) 645 (br 1H
=CH) 320 (d 2JH-H = 14 Hz 1H PCH2) 307 (d 2JH-H = 14 Hz 1H PCH2) 190 (s 3H CH3)
149 (br m 1H CHB) 106 (s 6H CH3) 104 (s 6H CH3) 19F NMR (564 MHz CD2Cl2)
partial δ -1254 (br 2F o-C6F5) -1665 (m 2F m-C6F5) (p-C6F5 was not observed) 31P1H
NMR (242 MHz CD2Cl2) δ 63 (br) 11B NMR (192 MHz CD2Cl2) δ 342 (Bpin) -104
(B(C6F5)2) 13C1H NMR (151 MHz CD2Cl2) partial δ 1481 (H3CC=CH) 1359 (=CH) 1329
(m o-Ph) 1323 (d 4JC-P = 39 Hz p-Ph) 1317 (d 2JC-P = 71 Hz o-Ph) 1311 (d 4JC-P = 30
Hz p-Ph) 1300 (d 3JC-P = 94 Hz m-Ph) 1291 (d 1JC-P = 54 Hz ipso-Ph) 1282 (d 3JC-P = 94
Hz m-Ph) 1251 (d 1JC-P = 54 Hz ipso-Ph) 821 (C(CH3)2) 268 (d 1JC-P = 33 Hz CH2P) 256
(d 3JC-P = 53 Hz H3CC=CH) 245 (BpinCH3) 244 (BpinCH3) 178 (br CHB) Anal calcd ()
for C35H29B2F10O2P C 5805 H 404 Found 5776 H 397
443 X-Ray Crystallography
4431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
Universitaumlt Muumlnster data sets were collected with a Nonius KappaCCD diffractometer
Programs used data collection COLLECT351 data reduction Denzo-SMN352 absorption
180
correction Denzo353 structure solution SHELXS-97354 structure refinement SHELXL-97355
Thermals ellipsoids are shown with 30 probability R-values are given for observed reflections
and wR2 values are given for all reflections
4432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
4433 Platon Squeeze details
During the refinement of structure 413 electron density peaks were located that were believed
to be highly disordered dichloromethane and 12-dichloroethane molecules Attempts made to
model the solvent molecule were not successful The SQUEEZE option in PLATON356 indicated
there was a large solvent cavity 160 A3 in the asymmetric unit In the final cycles of refinement
this contribution (39 electrons) to the electron density was removed from the observed data The
density the F(000) value the molecular weight and the formula are given taking into account the
results obtained with the SQUEEZE option PLATON
181
4434 Selected crystallographic data
Table 44 ndash Selected crystallographic data for 41 47 and 48
41 47 48
Formula C46H23B1F15N1 C62H31B1F15N1 C37H25B1F15N1
Formula wt 88546 108572 77939
Crystal system monoclinic triclinic triclinic
Space group P2(1)n P-1 P-1
a(Aring) 91451(8) 120520(8) 99293(9)
b(Aring) 20583(2) 122120(8) 115709(11)
c(Aring) 20738(2) 184965(12) 168258(15)
α(ordm) 9000 103236(4) 75826(4)
β(ordm) 96295(4) 104461(4) 77700(4)
γ(ordm) 9000 104447(4) 65591(4)
V(Aring3) 38800(6) 24264(3) 16930(3)
Z 4 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1516 1482 1529
Abs coeff μ mm-1 0138 0126 0146
Data collected 35905 34295 21194
Rint 00444 00308 00308
Data used 8910 11131 5899
Variables 569 712 490
R (gt2σ) 00420 00532 00488
wR2 00964 01380 01380
GOF 1018 1028 1026
182
Table 45 ndash Selected crystallographic data for 49 410 and 413
49 410
(+05 C5H12)
413
(+1 C2H4Cl2)
Formula C39H21B1F15N1S2 C425H23B1F15N1 C48H29B1Cl2F15N1
Formula wt 86350 85145 98643
Crystal system monoclinic triclinic monoclinic
Space group P2(1)c P-1 P2(1)c
a(Aring) 174202(13) 113739(5) 138815(4)
b(Aring) 135941(10) 115489(6) 242842(7)
c(Aring) 174144(13) 158094(7) 146750(4)
α(ordm) 9000 92979(2) 9000
β(ordm) 118149(3) 97298(2) 1108840(10)
γ(ordm) 9000 116865(3) 9000
V(Aring3) 36362(5) 182343(15) 46220(2)
Z 4 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1577 1536 1418
Abs coeff μ mm-1 0256 0143 0236
Data collected 27739 30840 34544
Rint 00299 00352 00437
Data used 6409 8342 8147
Variables 506 560 600
R (gt2σ) 00570 00504 00687
wR2 01537 01410 02122
GOF 1045 1021 1092
183
Table 46 ndash Selected crystallographic data for 414 432 and 439
414
(+05 CH2Cl2 +1 C5H12)
432
(+05 C5H12) 439
Formula C485H36B1Cl1F15N1 C325H21B1F15N1 C58H46B1F15P2
Formula wt 96404 72131 110070
Crystal system monoclinic triclinic triclinic
Space group C2c P-1 P-1
a(Aring) 309455(12) 80774(6) 117846(13)
b(Aring) 193567(7) 117730(8) 159017(19)
c(Aring) 182668(6) 158569(11) 16349(2)
α(ordm) 9000 79707(3) 108194(4)
β(ordm) 123002(2) 86387(3) 107588(4)
γ(ordm) 9000 87902(3) 104551(4)
V(Aring3) 91764(6) 148021(18) 25646(5)
Z 8 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1397 1620 1425
Abs coeff μ mm-1 0179 0160 0179
Data collected 34220 24071 37635
Rint 00476 00352 00284
Data used 8097 6615 9023
Variables 570 445 698
R (gt2σ) 00716 00560 00339
wR2 02417 01703 00880
GOF 1047 1096 1019
184
Table 47 ndash Selected crystallographic data for 440 and 442
440 442
Formula C38H38B1F15P2 C35H29B2F10O2P1
Formula wt 85243 72417
Crystal system monoclinic monoclinic
Space group C2c P2(1)n
a(Aring) 329294(17) 114236(2)
b(Aring) 118317(6) 151074(3)
c(Aring) 206088(10) 192749(4)
α(ordm) 9000 9000
β(ordm) 107535(5) 93553(1)
γ(ordm) 9000 9000
V(Aring3) 76563(7) 332009(11)
Z 8 4
Temp (K) 150(2) 223(2)
d(calc) gcm-3 1479 1449
Abs coeff μ mm-1 0215 0172
Data collected 63283 23294
Rint 00316 0055
Data used 8776 6697
Variables 517 456
R (gt2σ) 00365 00672
wR2 01017 01623
GOF 1021 1048
185
Chapter 5 Conclusion
51 Thesis Summary
The results presented in this thesis demonstrate the application of B(C6F5)3 and other
electrophilic boranes in metal-free synthetic methodologies thereby extending FLP reactivity
beyond the commonly reported stoichiometric activation of small molecules These findings
have also provided metal-free and catalytic routes to transformations typically performed using
transition-metal complexes or stoichiometric main group reagents
Initial results presented herein describe the aromatic reduction of N-phenyl amines in the
presence of an equivalent of B(C6F5)3 using H2 to yield the corresponding cyclohexylammonium
derivatives A reaction mechanism based on experimental evidence and theoretical calculations
has been proposed Elaborating the scope of these metal-free aromatic reductions a p-methoxy
substituted aniline was found to undergo tandem hydrogenation and intramolecular cyclization
with B(C6F5)3 presenting a unique route to a 7-azabicyclo[221]heptane derivative Aromatic
hydrogenations were further probed with pyridines quinolines and other N-heterocycles
Findings within this study were in agreement with the mechanism postulated for the arene
reduction of N-phenyl amines Although these reductions require an equimolar combination of
the aromatic amine and borane in certain cases the reactions take up eight equivalents of H2
Continued interest in FLP hydrogenation of aromatic rings was illustrated by subsequent reports
demonstrating borane-catalyzed stereoselective hydrogenation of pyridines by the Du group264
and catalytic hydrogenation of polyaromatic hydrocarbons by the Stephan group263
The second project discussed in this thesis was directly inspired by findings in the synthesis of a
7-azabicyclo[221]heptane derivative from a p-methoxy substituted aniline Detailed
mechanistic studies showed the B(C6F5)3-methoxide bond is labile under specific reaction
conditions These findings were applied to uncover a catalytic approach to the hydrogenation of
ketones and aldehydes yielding alcohols This method uses FLPs derived from B(C6F5)3 and
ether in which the ether is used as the solvent playing a pivotal role in hydrogen-bonding
interaction with the carbonyl substrate The catalysis was further studied in toluene using
B(C6F5)3 in combination with oxygen containing materials such as cyclodextrins or molecular
sieves Application of these materials provides an avenue to H2 activation and hydrogen-bonding
186
interactions necessary to facilitate hydrogenation In the particular case of aryl ketones the use
of molecular sieves promoted reductive deoxygenation of the substrate to give the aromatic
hydrocarbon product Hydrogenation of carbonyl substrates had perennially remained a
challenging problem since the discovery of FLP chemistry The results reported in this thesis
represent the first successful report of catalytic carbonyl hydrogenation using FLPs It should be
noted that the group of Ashley simultaneously reported the hydrogenation of ketones and
aldehydes using 14-dioxaneB(C6F5) as the FLP catalyst260
Lastly interest in expanding FLP catalysis beyond hydrogenations amineborane FLPs were
applied in the hydroamination of terminal alkynes The stoichiometric reaction of aniline
B(C6F5)3 and two equivalents of alkyne gave a series of iminium alkynylborate complexes
prepared through sequential intermolecular hydroamination and deprotonation reactions This
latter reaction results in the formation of the alkynylborate anion thus preventing participation of
B(C6F5)3 in catalysis Adjustment of the protocol by slow addition of the alkyne prevents the
deprotonation pathway thus allowing B(C6F5)3 to catalyze the Markovnikov hydroamination of
alkynes by a variety of secondary aryl amines affording enamines products This metal-free
route was also amenable to subsequent use of the catalyst in hydrogenation catalysis allowing
for the single-pot and stepwise conversion of the enamine products to the corresponding amines
Further expansion of the reactivity led to catalytic intramolecular hydroaminations affording a
one-pot strategy to N-heterocycles A stoichiometric approach to FLP hydrophosphinations was
also described
52 Future Work
While the reactivities presented in this thesis have typically been the purview of precious metals
research efforts motivated by cost toxicity and low abundance have provided alternative
strategies using main group compounds In 1961 the first metal-free catalytic hydrogenation was
reported displaying the reduction of benzophenone however this reaction required high
temperatures of about 200 degC and H2 pressures greater than 100 atm175 Since then dramatic
progress has been made in the advancement of metal-free catalysis Numerous metal-free
systems with particular emphasis on FLPs have been reported to effect the hydrogenation of an
elaborate list of substrates under mild conditions
187
An important direction to progress the chemistry found during this graduate research work would
be to design a borane reagent that will be suitable for the catalytic hydrogenation of N-phenyl
amines and N-heterocycles Such a direction will allow for a more atom-economic
transformation Ultimately the catalysis could be pursued using chiral boranes that may provide
a stereoselective process to cyclohexylamine derivatives (Scheme 51) Generally aromatic
hydrogenation of nitrogen substrates is a challenging transformation for transition-metal systems
due to deactivation of the catalyst by coordination of the substrate357
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
An interesting and obvious extension of carbonyl hydrogenations presented in Chapter 3 would
certainly be a FLP route to optically active alcohols Although such products were not obtained
when performing the reductions in the presence of chiral heterogeneous Lewis bases the
application of a chiral borane should be investigated The Du group recently presented the use of
chiral boranes in the asymmetric hydrogenation of silyl enol ethers to give chiral alcohol
products after appropriate work-up procedures97
Furthermore the use of cyclodextrins and molecular sieves in catalysis has presented the
possible notion of expanding homogeneous FLP chemistry to surface chemistry by designing
heterogeneous FLP catalysts that could be readily recycled (Scheme 52) Such a system may be
particularly attractive for industrial applicability Solid catalyst supports such as B(C6F5)3 grafted
onto silica have been used by the Scott group as a co-catalyst for the activation of metal
complexes used in olefin polymerization358 Although this system may not be sufficiently Lewis
acidic for carbonyl reductions further exploration and modification of Lewis acid and base
components could potentially lead to such a system
188
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations
The final chapter of this thesis outlined the consecutive hydroamination and hydrogenation of
ethynyl fragments catalyzed by B(C6F5)3 The novelty of this reactivity by FLP systems certainly
demands further explorations Catalytic hydroamination using FLPs could be extended to include
olefins and internal alkynes Furthermore the pursuit of an effective chiral borane catalyst may
provide a potential synthetic route to chiral amines of pharmaceutical and industrial interest
189
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308 Barluenga J Aznar F Liz R Rodes R J Chem Soc Perkin Trans 1 1980 0 2732-2737
309 Tzalis D Koradin C Knochel P Tetrahedron Lett 1999 40 6193-6195
310 Chinchilla R Naacutejera C Chem Rev 2014 114 1783-1826
311 Li Y Marks T J Organometallics 1996 15 3770-3772
312 Li Y Marks T J J Am Chem Soc 1998 120 1757-1771
313 Haskel A Straub T Eisen M S Organometallics 1996 15 3773-3775
314 Johnson J S Bergman R G J Am Chem Soc 2001 123 2923-2924
315 Straub B F Bergman R G Angew Chem Int Ed 2001 40 4632-4635
316 Walsh P J Baranger A M Bergman R G J Am Chem Soc 1992 114 1708-1719
317 Haak E Bytschkov I Doye S Angew Chem Int Ed 1999 38 3389-3391
318 Pohlki F Doye S Angew Chem Int Ed 2001 40 2305-2308
319 Ong T-G Yap G P A Richeson D S Organometallics 2002 21 2839-2841
320 Cao C Ciszewski J T Odom A L Organometallics 2001 20 5011-5013
321 Shi Y Hall C Ciszewski J T Cao C Odom A L Chem Commun 2003 0 586-587
322 Zhang Z Leitch D C Lu M Patrick B O Schafer L L Chem Eur J 2007 13 2012-2022
323 Vujkovic N Ward B D Maisse-Franccedilois A Wadepohl H Mountford P Gade L H Organometallics 2007 26 5522-5534
324 Tillack A Garcia Castro I Hartung C G Beller M Angew Chem Int Ed 2002 41 2541-2543
325 Lingaiah N Babu N S Reddy K M Prasad P S S Suryanarayana I Chem
Commun 2007 0 278-279
205
326 Bourgeois J Dion I Cebrowski P H Loiseau F Beacutedard A-C Beauchemin A M J Am Chem Soc 2009 131 874-875
327 Moran J Gorelsky S I Dimitrijevic E Lebrun M-E Beacutedard A-C Seacuteguin C Beauchemin A M J Am Chem Soc 2008 130 17893-17906
328 Rizk T Bilodeau E J F Beauchemin A M Angew Chem Int Ed 2009 48 8325-8327
329 Clavette C Vincent Rocan J-F Beauchemin A M Angew Chem Int Ed 2013 52 12705-12708
330 Erker G Stephan D W Frustrated Lewis Pairs I Springer-Verlag Berlin Heidelberg 2013
331 Erker G Stephan D W Frustrated Lewis Pairs II Springer Berlin Heidelberg 2013
332 Eller C Bussmann K Kehr G Wibbeling B Daniliuc C G Erker G Chem
Commun 2014 50 1980-1982
333 Hansmann M M Melen R L Rominger F Hashmi A S K Stephan D W J Am
Chem Soc 2013 136 777-782
334 Gevorgyan V Liu J-X Yamamoto Y Chem Commun 1998 37-38
335 Schwier T Gevorgyan V Org Lett 2005 7 5191-5194
336 Xu X Kehr G Daniliuc C G Erker G Angew Chem Int Ed 2013 52 13629-13632
337 Ye H Lu Z You D Chen Z Li Z H Wang H Angew Chem Int Ed 2012 51 12047-12050
338 Chapman A M Haddow M F Wass D F J Am Chem Soc 2011 133 18463-18478
339 Tanur C A Stephan D W Organometallics 2011 30 3652-3657
340 Corey E J K L Enantioselective Chemical Synthesis Methods Logic and Practice Elsevier Science 2013 p 334
341 Utsunomiya M Hartwig J F J Am Chem Soc 2003 125 14286-14287
342 Zhao X Lough A J Stephan D W Chem Eur J 2011 17 6731-6743
343 Yu J Kehr G Daniliuc C G Erker G Inorg Chem 2013 52 11661-11668
344 Ekkert O Kehr G Frohlich R Erker G Chem Commun 2011 47 10482-10484
345 Ekkert O Kehr G Froumlhlich R Erker G J Am Chem Soc 2011 133 4610-4616
206
346 Parks D J Piers W E Yap G P A Organometallics 1998 17 5492-5503
347 Severin R Reimer J Doye S J Org Chem 2010 75 3518-3521
348 Han J Xu B Hammond G B Org Lett 2011 13 3450-3453
349 Das B Kundu P Chowdhury C Org Biomol Chem 2014 12 741-748
350 Gazić Smilović I Casas-Arceacute E Roseblade S J Nettekoven U Zanotti-Gerosa A Kovačevič M Časar Z Angew Chem Int Ed 2012 51 1014-1018
351 Hooft R W W Bruker AXS Delft The Netherlands 2008
352 Otwinowski Z Minor W [20] Processing of X-ray diffraction data collected in oscillation mode In Methods Enzymol Charles W Carter Jr Ed Academic Press 1997 Vol 276 pp 307-326
353 Otwinowski Z Borek D Majewski W Minor W Acta Cryst 2003 59 228-234
354 Sheldrick G Acta Cryst 1990 46 467-473
355 Sheldrick G Acta Cryst 2008 64 112-122
356 Spek A J Appl Crystallogr 2003 36 7-13
357 Fleury-Breacutegeot N de la Fuente V Castilloacuten S Claver C ChemCatChem 2010 2 1346-1371
358 Wanglee Y-J Hu J White R E Lee M-Y Stewart S M Perrotin P Scott S L J Am Chem Soc 2011 134 355-366
v
Table of Contents
Abstract ii
Acknowledgments iv
Table of Contents v
List of Figures xi
List of Schemes xiv
List of Tables xix
List of Symbols and Abbreviations xxi
Chapter 1 Introduction 1
11 Science and Technology 1
111 Boron properties production and uses 2
112 Boron chemistry 3
12 Catalysis 4
13 Frustrated Lewis Pairs 5
131 Early discovery 5
132 Hydrogen activation and mechanism 6
133 Substrate hydrogenation 9
134 Activation of other small molecules 10
1341 Unsaturated hydrocarbons 10
1342 Alkenes 11
1343 Alkynes 11
1344 11-Carboboration 12
1345 CO2 and SO2 13
1346 FLP activation of carbonyl bonds 14
1347 Carbonyl hydrogenation 15
vi
1348 Carbonyl hydrosilylation 16
14 Scope of Thesis 17
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines and N-Heterocyclic Compounds 19
21 Introduction 19
211 Hydrogenation 19
212 Transfer hydrogenation 20
213 Main group catalysts 21
214 Hydrogenation of aromatic and heteroaromatic substrates 22
2141 Transition metal catalysts 22
2142 Metal-free catalysts 23
215 Reactivity of FLPs with H2 23
22 Results and Discussion 24
221 H2 activation by amineborane FLPs 24
222 Aromatic hydrogenation of N-phenyl amines 25
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates 30
223 Mechanistic studies for aromatic hydrogenation reactions 31
2231 Deuterium studies 31
2232 Variable temperature NMR studies 32
2233 Theoretical calculations 33
224 Aromatic hydrogenation of substituted N-bound phenyl rings 35
2241 Fluoro-substituted rings and C-F bond transformations 35
2242 Methoxy-substituted rings and C-O bond transformations 38
22421 Mechanistic studies for C-O and B-O bond cleavage 40
225 Aromatic hydrogenation of N-heterocyclic compounds 45
vii
2251 Hydrogenation of substituted pyridines 45
2252 Hydrogenation of substituted N-heterocycles 49
2253 Proposed mechanism for aromatic hydrogenation 55
2254 Approaches to dehydrogenation 55
23 Conclusions 56
24 Experimental Section 56
241 General considerations 56
242 Synthesis of compounds 57
243 X-Ray Crystallography 79
2431 X-Ray data collection and reduction 79
2432 X-Ray data solution and refinement 79
2433 Selected crystallographic data 81
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation with Frustrated Lewis Pairs 88
31 Introduction 88
311 FLP reactivity with unsaturated C-O bonds 88
32 Results and Discussion 92
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions 92
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents 93
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents 96
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism 97
325 Other hydrogen-bond acceptors for carbonyl hydrogenations 99
326 Other boron-based catalysts for carbonyl hydrogenations 99
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism 100
viii
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system 102
328 Attempted hydrogenation of other carbonyl substrates and epoxides 102
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases 103
3291 Polysaccharides as heterogeneous Lewis bases 104
3292 Molecular sieves as heterogeneous Lewis bases 107
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones 107
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation 110
32101 Verifying the reductive deoxygenation mechanism 111
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins 113
33 Conclusions 113
34 Experimental Section 114
341 General Considerations 114
342 Synthesis of Compounds 116
3421 Procedures for reactions in ethereal solvents 116
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3] 119
3423 Procedures for reactions using heterogeneous Lewis bases 120
3424 Procedures for reductive deoxygenation reactions 121
3425 Spectroscopic data of products in Table 31 121
3426 Spectroscopic data of products in Table 32 125
3427 Spectroscopic data of products in Table 33 125
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a) 127
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b) 128
343 X-Ray Crystallography 130
3431 X-Ray data collection and reduction 130
ix
3432 X-Ray data solution and refinement 130
3433 Selected crystallographic data 131
Chapter 4 Hydroamination and Hydrophosphination Reactions Using Frustrated Lewis Pairs 132
41 Introduction 132
411 Hydroamination 132
412 Reactions of main group FLPs with alkynes 133
4121 12-Addition or deprotonation reactions 133
4122 11-Carboboration reactions 134
4123 Hydroelementation reactions 135
413 Reactions of transition metal FLPs with alkynes 135
42 Results and Discussion 136
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes 136
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes 140
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates 141
4213 Reactivity of the iminium alkynylborate products with nucleophiles 141
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3 142
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes 144
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions 146
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes 147
424 Intramolecular hydroamination reactions using FLPs 148
4241 Stoichiometric hydroamination 148
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines 150
x
425 Reaction of B(C6F5)3 with ethynylphosphines 151
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines 153
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs 154
427 Proposed mechanism for the hydroborationhydrophosphination reactions 156
43 Conclusions 157
44 Experimental Section 157
441 General Considerations 157
442 Synthesis of Compounds 158
4421 Procedures for stoichiometric intermolecular hydroamination reactions 158
4422 Procedures for hydroarylation of phenylacetylene 165
4423 Procedures for catalytic intermolecular hydroamination reactions 167
4424 Procedures for tandem hydroamination and hydrogenation reactions 172
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions 173
4426 Procedures for reactions with ethynylphosphines 177
443 X-Ray Crystallography 179
4431 X-Ray data collection and reduction 179
4432 X-Ray data solution and refinement 180
4433 Platon Squeeze details 180
4434 Selected crystallographic data 181
Chapter 5 Conclusion 185
51 Thesis Summary 185
52 Future Work 186
References 189
xi
List of Figures
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage 8
Figure 12 ndash A highly efficient borenium hydrogenation catalyst 10
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis 21
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates 23
Figure 23 ndash POV-Ray depiction of 24rsquo 26
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+ 27
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($) 27
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right) 28
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right) 31
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-) 33
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol) 34
Figure 210 ndash POV-Ray drawing of 216a 36
xii
Figure 211 ndash POV-Ray drawing of 218 37
Figure 212 ndash POV-Ray drawing of 219 39
Figure 213 ndash POV-Ray drawing of trans-220 40
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c) 42
Figure 215 ndash POV-Ray drawing of 222 43
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right) 46
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring 48
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups 49
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring 49
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c) 50
Figure 221 ndash POV-Ray depiction of the cation for compound 231a 51
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring 52
Figure 223 ndash POV-Ray depiction of the cation for compound 233 52
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right) 53
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine 54
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol () 94
xiii
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol 95
Figure 33 ndash POV-Ray depiction of 31 98
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted 100
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
104
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD) 104
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased 112
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
136
Figure 42 ndash POV-Ray depiction of 47 137
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b) 139
Figure 44 ndash POV-Ray depiction of 410 139
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg 143
Figure 46 ndash POV-Ray depiction of 432 149
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons 152
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b) 153
Figure 49 ndash POV-Ray depictions of 442 155
xiv
List of Schemes
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3 4
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe) 4
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP 6
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c) 7
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K 9
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines 9
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom) 11
Scheme 18 ndash Reaction of FLPs with phenylacetylene 12
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom) 12
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base 13
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I) 14
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs 15
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP 16
xv
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom) 17
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine 20
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b) 24
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom) 25
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23 26
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD 32
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23 32
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts 35
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a 36
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218 37
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219 39
Scheme 211 ndash Synthesis of 220 and 212 40
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b) 41
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3 43
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3 44
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane 45
Scheme 216 ndash Proposed reaction pathway for the formation of 235 54
xvi
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom) 89
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b) 90
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols 90
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom) 91
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH 92
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation 93
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents 97
Scheme 38 ndash Synthesis of 31 98
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond 100
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation 102
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone 108
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b) 110
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones 111
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al) 133
xvii
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c) 134
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes 134
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes 135
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes 135
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
136
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts 140
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3 141
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4] 141
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right) 142
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3 142
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond 144
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes 147
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430 148
xviii
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432 149
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433 150
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH 151
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439 152
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440 154
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH 155
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments 156
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
187
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations 188
xix
List of Tables
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts 29
Table 22 ndash Hydrogenation of substituted pyridines 47
Table 23 ndash Hydrogenation of substituted N-heterocycles 51
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25 81
Table 25 ndash Selected crystallographic data for 216a 218 and 219 82
Table 26 ndash Selected crystallographic data for 220 222 and 224 83
Table 27 ndash Selected crystallographic data for 225 227 and 228 84
Table 28 ndash Selected crystallographic data for 229 230 and 231a 85
Table 29 ndash Selected crystallographic data for 231b 233 and 234a 86
Table 210 ndash Selected crystallographic data for 234b and 235 87
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents 96
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3] 101
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
106
Table 34 ndash Deoxygenation of aryl alkyl ketones 108
Table 35 ndash Deoxygenation of diaryl ketones 109
Table 36 ndash Selected crystallographic data for 31 131
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
138
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3 145
xx
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines 151
Table 44 ndash Selected crystallographic data for 41 47 and 48 181
Table 45 ndash Selected crystallographic data for 49 410 and 413 182
Table 46 ndash Selected crystallographic data for 414 432 and 439 183
Table 47 ndash Selected crystallographic data for 440 and 442 184
xxi
List of Symbols and Abbreviations
9-BBN 9-borabicyclo[331]nonane
α alpha
Aring angstrom 10-10 m
atm atmosphere
β beta
Bpin pinacolborane (4455-tetramethyl-132-dioxaborolane)
br broad
Boc tert-butyloxycarbonyl
Bu butyl
C Celsius
ca circa
calcd calculated
CD cyclodextrin
C6D6 deuterated benzene
C6H5Br bromobenzene
C6D5Br deuterated bromobenzene
CD2Cl2 deuterated dichloromethane
Cy cyclohexyl
δ chemical shift
xxii
deg degrees
d doublet
Da Dalton
DART direct analysis in real time
DEPT Distortionless Enhancement by Polarization Transfer
dd doublet of doublets
de diastereomeric excess
DFT density functional theory
dt doublet of triplets
ee enantiomeric excess
eq equivalent(s)
ESI electrospray ionization
Et ethyl
Et2O diethyl ether
FLP frustrated Lewis pair
γ gamma
ΔG Gibbs free energy
g gram
GC gas chromatography
GOF goodness of fit
xxiii
h hour
HRMS high resolution mass spectroscopy
HMBC heteronuclear multiple bond correlation
HOESY heteronuclear Overhauser effect NMR spectroscopy
HSQC heteronuclear single quantum correlation
Hz Hertz
iPr2O diisopropyl ether
nJxy n-scalar coupling constant between X and Y atoms
K Kelvin
kcal kilocalories
m meta
m multiplet
M molar concentration
Me methyl
Mes mesityl 246-trimethylphenyl
MHz megahertz
μL microliter
μmol micromole
mg milligram
min minute
xxiv
mL milliliter
mmol millimole
MS mass spectroscopy
MS molecular sieves
nPr n-propyl
iPr iso-propyl (CH(CH3)2)
NHC N-heterocyclic carbene
NMR Nuclear Magnetic Resonance
NOE Nuclear Overhauser Effect
o ortho
π pi
p para
POV-Ray Persistence of Vision Raytracer
PGM Platinum Group Metals
Ph phenyl
Ph2O diphenyl ether
ppb parts per billion 10-9
ppm parts per million 10-6
q quartet
quint quintet
xxv
rpm rotations per minute
RT room temperature
σ sigma
s singlet
t triplet
tBu tert-butyl
THF tetrahydrofuran
TMP 2266-tetramethylpiperidine
TMS trimethylsilyl
TMS2O hexamethyldisiloxane
tol toluene
wt weight
1
Chapter 1 Introduction
11 Science and Technology
The advent of the scientific revolution and the scientific method in early modern Europe
dramatically transformed the way scientists viewed the universe as they attempted to explain the
physical world through experimental investigation The long-term effects of the revolution can
be felt today with our dependence upon science to improve the quality of our lives and advance a
globally interconnected world Some scientific discoveries which have paved the way for such
enterprising technologies include the Haber-Bosch process used for the production of ammonia
essential to the synthesis of nitrogen fertilizers1-3 This discovery has dramatically increased food
production globally and allowed for the explosive population growth observed in the past
century Research also intensified to change the world of medicine through discovery of antiviral
agents for treatment of the HIVAIDS pandemic4-5 Ziegler-Natta catalysts have become central
to the polymer industry manufacturing the largest volumes of commodity plastics and
chemicals6-8
While many chemical breakthroughs have had significant benefits on public health their initial
application or even long-term impact on the environment may be detrimental For example
chlorine was used as a weapon during World War I9 while today it plays a vital role in
disinfecting drinking water and sanitation processes10 A more significant example is the
industrial revolution when manufacturing transitioned from manual labour to machines resulting
in unprecedented growth in population and standards of living Our continued reliance on
factories and mass production has led to depletion of natural resources and emission of
greenhouse gases resulting in anthropogenic climate change11-15
Scientists have acknowledged the need to remediate environmental impacts and to find more
environmentally acceptable technologies for the chemical industry To this end chemical
research has focused on implementing the principles of green chemistry16-17 to develop benign
processes which will sustain the growing energy demands of our society18-19 Central to the green
concept is the application of catalysis in chemical transformations in addition to using readily
available non-toxic raw materials in cost effective procedures
2
Rare precious metals such as the Platinum Group Metals (PGM) are extracted by mining of non-
renewable resources normally resulting in negative social and environmental impacts on the
area20 The metals are used in industrial chemical syntheses where they are regularly recovered
and recycled back into production It is essential however to gradually replace these reagents
with more environmentally benign and readily available transition metals in order to reduce
waste processing costs and eliminate the possibility of their release into the environment In this
aspect chemists are actively seeking innovations to advance more green chemical processes21-24
A vast majority of d-block transition metals have energetically accessible valence d-orbitals
allowing for oxidation state changes which are pivotal to substrate activation and accessing
stabilized transition states Additional factors including the steric and electronic tunability of the
ligand framework have led to the development of a broad range of metal catalysts applied in
numerous chemical transformations25-26 Nonetheless a growing number of advancements
involving the use of main group s and p-block elements have also shown reactivities similar to
those of transition metal complexes27-30
Main group elements are relatively abundant on Earth and over the last decade have experienced
a renaissance in chemical transformations Notably frustrated Lewis pair (FLP) systems which
involve the combination of Lewis acids and bases that are sterically and electronically prohibited
from forming a classical adduct have been at the forefront31 The unquenched reactivity of FLPs
has been explored in the activation of numerous small molecules The majority of FLP systems
incorporate boron Lewis acids and phosphorus Lewis bases32 In this thesis the potential to
expand FLP reactivity to nitrogenboron and oxygenboron pairs is explored
111 Boron properties production and uses
Boron (B) is a non-metallic element always found in nature bound to oxygen as orthoboric acid
alkali metal and alkaline earth metal borates33 Prominent sources of boron include the sodium
borate minerals rasorite and kernite found in deposits at the Mojave Desert of California and in
Turkey which is the largest producer of boron minerals33-34 Boron is vastly spread in Nature
however it constitutes only about 3 ppm of the Earthrsquos crust35-36
Industrially the production of pure boron is very difficult as it tends to form refractory materials
containing small amounts of carbon and other elements The method typically used for
3
commercial production of amorphous boron (up to 97 purity) is by reduction of B2O3 with Mg
in a thermite-like reaction Higher purity (gt99) boron is obtained by the reduction of boron
halides with H2 whereas ultra-purity can be achieved by thermal decomposition of boron
halideshydrides or diboranes on tungsten wires followed by zone melting purification37
Regardless of the production method different allotropic forms of boron can be accessed Short
reaction times at temperatures below 900 degC produce amorphous boron longer reaction times
above 1400 degC afford β-rhombohedral and optimal conditions in between the two give α-
rhombohedral36
Amorphous boron consisting of 90 - 92 purity costs approximately $100kg Relatively large
quantities of the material are used as additives in pyrotechnic mixtures Ultrapure (gt9999)
boron costs about $3500kg and is applied in electronics such as a dopant for germanium and
silicon p-type semiconductors Furthermore as the second hardest element inferior only to
diamond there is a growing demand for boron as a light-weight hardenability additive for glass
ceramics and boron filaments used in high-strength materials for the aerospace and steel
industries35-36
112 Boron chemistry
Boron has a valence shell electron configuration of 2s22p1 representing a typical formal
oxidation state of 3+ although due to its high ionization potentials simple B3+ ions do not exist
Boron can form three sp2 hybridized bonds resulting in trigonal planar geometry with a non-
bonding vacant p-orbital orthogonal to the plane susceptible towards electron donation giving
rise to its noted Lewis acidic properties38-40 Scales to quantify Lewis acidity have been designed
by studying the acceptor-donor interactions between Lewis acid and base complexes using NMR
spectroscopy data based on the Gutmann-Beckett41 and Childs42 methods43 IR spectroscopy X-
ray diffraction44 and density functional calculations45
The most common use of Lewis acids are the boron trihalides particularly BF3 and BCl3 in
conjunction with a co-initiator Lewis base such as water initiating cationic polymerization The
unsaturated olefin monomer is protonated generating the [BF3OH]- counterion along with a
carbenium ion which reacts with olefin molecules leading to propagation of the polymer46 With
Lewis acidity comparable to BF3 the Lewis acid B(C6F5)3 was lsquorediscoveredrsquo in the 1990s as an
ideal activator component for Ziegler-Natta olefin polymerization catalysts47 Treatment of a
4
Group 4 dialkyl-metallocene catalyst precursor with one equivalent of B(C6F5)3 results in alkyl
anion abstraction forming the active alkyl-metallocene cation (eg [Cp2ZrMe]+) stabilized by the
weakly coordinating [MeB(C6F5)3]- anion (Scheme 11)48-51
Scheme 11 ndash Dimethyl zirconocene catalyst activation with B(C6F5)3
Hydroboration the addition of B-H across multiple bonds of organic substrates such as alkenes
and alkynes provides the most common route to alkyl or alkenyl organoborane reagents
respectively52 The products obtained can be employed as intermediates for further synthetic
derivatization One powerful and general methodology used for the modification of
organoboranes53 is the Suzuki-Miyaura cross-coupling reaction (Scheme 12) These C(sp2)-B
and C(sp3)-B organoboranes readily undergo transmetalation with an electrophilic organo- Cu
Pd Ni or Fe catalyst to give coupled products with new C-C bonds54-55 Other applications of
boron reagents include metal borohydrides as reducing agents transferring hydride nucleophiles
to versatile functional groups56-59 Operating in a similar manner anionic borates consisting of
polarized B-C bonds transfer an organic group to an electrophilic centre38 60
Scheme 12 ndash Hydroboration of terminal alkynes to give alkenylboranes followed by cross-
coupling with an alkyl or aryl halide (M = Cu Pd Ni or Fe)
Of particular relevance to this thesis recent advances in boron chemistry particularly involving
the activation and reactivity of small molecules with FLP systems will be discussed
12 Catalysis
In the early part of the 20th century catalysis developed into a scientific discipline and has
evolved to underlie numerous chemical technologies that benefit human life worldwide61 The
5
function of a catalyst substance added in a sub-stoichiometric amount is to lower the reaction
activation energy and affect selectivity for chemical transformations without being consumed62
Homogeneous catalysts have a long prevalence in industry with applications ranging from bulk
chemicals to complex multi-step processes Among the most prominent examples are the
Monsanto and Cativa processes for the carbonylation of methanol to produce acetic acid and the
oxo process for hydroformylation of olefins to yield aldehydes63 Only touching the tip of the
iceberg other commercial processes include the Wacker process for the oxidation of ethylene
aforementioned Ziegler-Natta olefin polymerization based on immobilized TiCl3 and substrate
hydrogenations using Wilkinsonrsquos Rh and Ru catalysts64-65 Other noteworthy discoveries
essential to the advancement of catalysis include Fischer-Tropsch production of liquid
hydrocarbons asymmetric catalysis olefin metathesis and Pd-catalyzed cross couplings66
The significance of catalysis for the development of chemistry has been recognized by the Nobel
Prize Committee with the earliest accreditation in the field awarded in 1909 to W Ostwald
Shortly thereafter Nobel Prizes were awarded for important contributions by P Sabatier (1912)
F Haber (1918) and C Bosch and F Bergius (1931) Since the turn of the millennium catalysis
has been recognized with four Chemistry Nobel Prizes awarded to 10 laureates66
13 Frustrated Lewis Pairs
131 Early discovery
The acid-base theory proposed by G N Lewis in 1923 is arguably one of the most important
theories in chemistry describing Lewis acid and base species as electron pair acceptors and
electron pair donors respectively67 According to the theory sterically unhindered Lewis acid-
base pairs react to form a Lewis adduct quenching subsequent reactivity This concept is
fundamental in most areas of chemistry involving the interaction of a doubly occupied orbital
(nucleophile) with an empty orbital (electrophile) forming a favourable overlap
Recent advances involving sterically encumbered Lewis pairs preclude such adduct formation
thereby rendering the individual components available for unique reactivity68-70 Astonishingly
in 1942 H C Brown reported that the ldquosteric strainrdquo between the Lewis acid trimethylborane
and the bulky Lewis base 26-lutidine does not result in adduct formation71 These early results
predate the recently popularized concept of frustrated Lewis pairs (FLPs) describing the
6
combination of Lewis acids and bases with sterically and electronically frustrated substituents
which prevent formal adduct formation32 The cooperative behaviour of these frustrated Lewis
centres has been evidenced to activate small molecules72
132 Hydrogen activation and mechanism
The first FLP reactivity was discovered by Stephan et al in 2006 while investigating the
chemistry of phosphonium borate linked zwitterions R2P(H)(C6F4)B(F)(C6F5)2 (R = alkyl or
aryl) generated from nucleophilic aromatic substitution of B(C6F5)3 by bulky secondary
phosphines31 Treatment with Me2SiHCl easily converts the linked zwitterion to the
phosphonium borohydride species containing both protic and hydridic hydrogen atoms In a
remarkable example the linked PHndashBH zwitterion (R = Mes) was found to liberate and rapidly
activate H2 representing the first example of reversible H2 activation using main group
compounds (Scheme 13)
Scheme 13 ndash Reversible H2 activation by linked phosphine-borane FLP
Hydrogen activation by main group compounds is rare the first example was reported in 2005
by the group of Power and co-workers describing the addition of H2 to heavier main group
digermyne compounds RGeequivGeR (R = aryl)30 The seminal finding was followed by the work of
Bertrand using bulky (alkyl)(amino)carbenes displaying both nucleophilic and electrophilic
characteristics to split and add H2 at a single carbon centre28 In a succeeding report by Piers the
antiaromatic Lewis acid perfluoropentaphenylborole was exclusively employed in H2 activation
to yield boracyclopent-3-ene products resulting from H2 addition to the two carbon atoms alpha
to boron73
After the initial breakthrough with FLPs their unique reactivity attracted immediate attention of
the scientific community Erker and co-workers have synthesized intramolecular PB FLPs
derived by the anti-Markovnikov addition of HB(C6F5)2 to vinyl phosphines (Scheme 14 a)74-75
Additionally Rieger and Repo have reported the nitrogen-based intramolecular FLP ansa-
7
aminoborane shown in Scheme 14 (b)76-78 These systems heterolytically split H2 albeit
reversible H2 activation was only demonstrated for the ansa-aminoborane
Hydrogen activation has also been extended to bimolecular systems Combinations of B(C6F5)3
and sterically encumbered tertiary phosphines were found to effect H2 activation (Scheme 14
c)32 In one example the weaker Lewis acid B(p-HC6F4)3 and o-tolyl3P were found to liberate H2
under vacuum79-80
Scheme 14 ndash Heterolytic H2 activation by an intramolecular PB FLP (a) reversible H2
activation by an NB FLP (b) and H2 activation by an intermolecular PB FLP (c)
The initial mechanism proposed for heterolytic splitting of H2 was speculated to be a ldquoside-onrdquo
or ldquoend-onrdquo coordination of H2 to either the boron or phosphorus moiety followed by approach
of the respective FLP partner effecting H-H bond cleavage This mechanism was not found to be
computationally supported despite earlier evidence for the ldquoside-onrdquo mechanism based on BH3-
H2 adducts81-84 While mechanistic details remain debated theoretical investigations by the
groups of Paacutepai85-87 and Grimme88 were performed on the prototype tBu3PB(C6F5)3 FLP Both
groups agree on the formation of an ldquoencounter complexrdquo stabilized by CndashH---F dispersion
interactions between the phosphine methyl groups and C6F5 borane rings As a result the Lewis
pair orient such that the boron is in close proximity to the phosphorus centre The electron
transfer model proposed by Paacutepai89 explains hydrogen activation by synergistic interaction of the
8
Lewis pair inducing polarization on the H2 molecule effecting heterolytic cleavage In this case
donation from the σ orbital of H2 into the empty orbital on the Lewis acid occurs in conjunction
with lone pair donation from the Lewis base to the σ orbital of H2 representing a process
similar to metal-based heterolytic cleavage of H2 (Figure 11 a) In contrast the electric field
model reported by Grimme suggests heterolytic H2 activation is a barrierless process resulting
from the exposure of H2 to a sufficiently strong homogeneous electric field pocket created by the
FLP complex Interpretation of this model does not consider electron donation or the orbitals of
the FLP or H2 (Figure 11 b)
Figure 11 ndash Proposed tBu3PB(C6F5)3 encounter complex with electron transfer (a) and electric
field (b) models representing H2 cleavage
Direct investigation of H2 activation intermediates by standard experimental techniques has been
unquestionably demanding Experimental evidence of an encounter complex has been observed
by 19F1H HOESY NMR studies revealing contacts between all protons of R3P (R = tBu Mes)
and fluorine nuclei of B(C6F5)3 although only a rough orientation of the molecules was
reported90 Examination of a related system has recently been reported by the Piers group In this
case combination of a highly electrophilic boraindene and Et3SiH gave an isolable borane-silane
complex affirming details of adduct formation in FLP hydrosilylation and to a certain extent
extrapolated to the closely related H2 activation reaction (Scheme 15)91
9
Scheme 15 ndash Schematic representation of equilibrium formation of the boraindene-Et3SiH
adduct at 195 K
133 Substrate hydrogenation
Reversible H2 activation by the initial FLP Mes2P(H)(C6F4)B(H)(C6F5)2 was a landmark
discovery that shed light onto potential important applications of such systems Most significant
of these efforts was demonstrated by employing R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) in the
catalytic reduction of unsaturated substrates specifically bulky imines and N-protected nitriles to
corresponding amines using 5 mol catalyst 5 atm of H2 and temperatures ranging from 80 -
100 degC Concerted investigations in the field revealed that sterically hindered substrates could
also serve as the Lewis base in splitting hydrogen92-93 To this end catalytic amounts of B(C6F5)3
in combination with various bulky aldimines and ketimines were reduced under 5 atm of H2 at
120 degC with isolated yields in the range of 89 - 99 Based on experimental observations the
proposed mechanism suggests H2 is cleaved between the bulky imine and B(C6F5)3 followed by
hydride delivery to the iminium cation (Scheme 16)
Scheme 16 ndash Proposed mechanism for B(C6F5)3 catalyzed reduction of imines
10
Following the early reports on metal-free catalytic hydrogenation the reduction of various other
substrates has been demonstrated to include aziridines92 94 enamines93 enones95 silyl enol
ethers96-97 N-heterocycles98 olefins99 and most recently alkynes have been reduced to cis-
alkenes100 Asymmetric hydrogenation by chiral FLPs was first demonstrated in 2008 by
Klankermayer and co-workers to give a chiral amine with 13 ee and later improvements up to
83 were obtained using a camphor derived catalyst101-102 Rieger and Repo saw ee values of
3776 103 while significant improvements up to 89 were achieved by the Du group104
Recently borenium cations have been used as Lewis acids in FLP chemistry with remarkable
catalytic activity for the hydrogenation of imines and enamines at room temperature (Figure
12)105
Figure 12 ndash A highly efficient borenium hydrogenation catalyst
134 Activation of other small molecules
FLP-mediated bond activations have been explored for a multitude of small molecules including
CO2106-107 N2O108-112 SO2113-114 NO115-116 CO107 117-119 NSO120 fluoroalkanes121 ether122
disulfides123 alkenes124-125 and alkynes126-128 FLPs have also been exploited in radical
polymerizations116 and more recently in materials and surface science129 Efforts have also
continued to exploit FLP chemistry in synthetic organic applications130 Beyond here small
molecule transformations that are relevant to the chemistry presented in this thesis will be
discussed
1341 Unsaturated hydrocarbons
Reactivity of unsaturated hydrocarbons has been a field traditionally associated with transition
metal chemistry and has found particular use for organic synthesis131-138 The dramatic evolution
in FLP systems has raised interest in probing the reactivity of main group complexes with
alkenes and alkynes100 139-140 This reactivity is reminiscent of related findings by Wittig and
Benz in 1959 involving the addition of Ph3P and BPh3 to benzyne affording zwitterionic
11
phosphonium-borates141 In the same context Tochtermann showed the addition of the bulky
carbanion [Ph3C]- and Lewis acid BPh3 across the double bond of 13-butadiene rather than
anionic polymerization of the conjugated diene142
1342 Alkenes
The reaction of FLPs with alkenes is particularly intriguing as the individual Lewis components
do not react with the substrate rather the three component combination of R3P B(C6F5)3 and
alkene exhibited intermolecular 12-addition reactions (Scheme 17 top)143-144 Similar activation
results were also observed upon exposure to the ethylene-linked FLP Mes2PCH2CH2B(C6F5)2145-
147 In two remarkable examples the Stephan group provided spectroscopic theoretical148 and
crystallographic149 evidence for Lewis acid-olefin van der Waals complexes forming prior to
FLP additions (Scheme 17 bottom)
Scheme 17 ndash Intermolecular addition of frustrated tBu3PB(C6F5)3 pairs to olefins (top)
equilibrium between ldquoopenrdquo and ldquoclosedrdquo form of a tethered olefin-borane species (bottom)
1343 Alkynes
Initial reactivity of FLPs with terminal alkynes featured the facile deprotonation or addition of
phosphineLewis acid (B Al) combinations to afford alkynylborate (aluminate) salts or
zwitterions with selectivity of the reaction correlated to the basicity of the phosphine (Scheme
18)126 128 In a joint report by the Stephan and Erker groups the B(C6F5)3-mediated
intramolecular cyclization of an ortho-ethynylaniline to access a cyclic anilinium borate was
presented150-151 In an analogous fashion Stephan and co-workers showed the cyclization of
alkyne- and alkene-tethered pyridines and quinolines using B(C6F5)3152 The groups of Berke
12
Erker Stephan and Uhl expanded the chemistry by varying the Lewis acid to BPh3 and alanes153
as well as the Lewis base to include phosphines154 polyphosphines155 thioethers amines and
pyridines156 carbenes157 and pyrroles158
Scheme 18 ndash Reaction of FLPs with phenylacetylene
1344 11-Carboboration
Particularly prolific in the research area of FLP reactivity with alkynes the groups of Erker and
Berke separately unravelled the 11-carboboration reaction resulting from the electrophilic
attack of the CequivC triple bond of an alkyne by highly electrophilic boranes RB(C6F5)2 generating
alkenylborane products (Scheme 19)156 159-160
Scheme 19 ndash 11-Carboboration reaction of terminal (top) and internal alkynes (bottom)
In the absence of a Lewis base the combination of electrophilic boranes and terminal alkynes are
postulated to generate a vinylidene intermediate stabilized by 12-hydride migration to the
carbocation Subsequently scission of a BndashC bond transfers a substituent from the borane to the
same carbon of the alkyne generating the alkenylborane (Scheme 110 left)159 This simple yet
elegant strategy demonstrates a facile route to borane derivatives with a C(sp2)-B centre that
could be further treated under Suzuki cross-coupling conditions161 In the presence of a Lewis
13
base deprotonation of the vinylidene or nucleophilic addition at the carbocation takes place
(Scheme 110 right)
Scheme 110 ndash Proposed reaction mechanism of B(C6F5)3 with terminal alkynes in the presence
(right) and absence (left) of a Lewis base
1345 CO2 and SO2
Following the reactivity of FLPs with olefins successful joint efforts by the Stephan and Erker
groups showed the activation of the greenhouse gas CO2 and acid rain contributor SO2 using the
FLP tBu3PB(C6F5)3 and ethylene-linked PB system Mes2PCH2CH2B(C6F5)2 (Scheme 111 a
and b)113-114 Key differences were observed in the reactivity of the two gases For example the
reversible nature of binding CO2 was not observed with the SO2 bound species Furthermore the
six-membered SO2 adducts derived from linked PB FLPs gave a stereogenic sulphur centre
resulting in a pair of isomers (Scheme 111 b) The Stephan group extended the activation of
CO2 beyond borane Lewis acids To this end 12 combinations of bulky phosphines and AlX3 (X
= halide or C6F5) react with CO2 rapidly leading to the formation of R3P(CO2)(AlX3)2 (Scheme
111 c)
14
Mes2P B(C6F5)2
EO2Mes2P B(C6F5)2
E O
O
R R
gt -20 degC- CO2
tBu3P B(C6F5)3EO2
80 degC- CO2
PB(C6F5)3E
O
O
tBu3
Mes3P 2 AlX3 Mes3PAlX3E
O
O
AlX3
CO2
b)
a)
c)
Scheme 111 ndashActivation of CO2 and SO2 using intermolecular (a) and intramolecular (b) PB
FLPs activation of CO2 using PAl FLP (c) (R = H Me E = C S X = Br I)
In the case of CO2 further chemical transformation of the activated molecule has been
presented107 111 153 162-164 including efforts to reduce CO2 to CH3OH The groups of Ashley and
OrsquoHare presented this reactivity using H2 as the reducing source Stephan et al used ammonia
borane165 and this process has been achieved catalytically by Fontaine using hydroboranes166-168
Additionally Piers reported the catalytic deoxygenative reduction of CO2 to CH4 using silanes169
and Stephan showed the stoichiometric reduction of CO2 to CO using R3PAlX3 FLPs170
1346 FLP activation of carbonyl bonds
Efforts to include oxygen-based substrates in FLP-mediated catalytic transformations have found
limited success due to the high affinity of electrophilic boranes towards oxygen species72 171
Investigations by Erker and co-workers described the irreversible capture of benzaldehyde and
trans-cinnamaldehyde at the C=O functional group by the intramolecular FLP
Mes2PCH2CH2B(C6F5)2 (Scheme 112 top)172-173 Similar alkoxyborate products were obtained
in the reaction of NB FLPs with benzaldehyde (Scheme 112 bottom)174
15
Scheme 112 ndash Stoichiometric reaction of benzaldehyde with the linked PB (top) and NB
(bottom) FLPs
1347 Carbonyl hydrogenation
Metal-free hydrogenation of carbonyl substrates was reported as early as 1961 by Walling and
Bollyky for the homogeneous hydrogenation of ketones catalyzed by alkali metal alkoxides175
About 40 years later Berkessel and co-workers communicated mechanistic studies on the
process which were supported thereafter by computational investigations176 The authors
elucidated mechanistic analogies between base-catalyzed ketone hydrogenation and Ru-
catalyzed transfer hydrogenation by Noyori whereby a Broslashnsted base participates in H2
heterolysis177 Although this is the first example of metal-free reduction of ketone the reactions
are performed at relatively harsh conditions requiring 100 atm of H2 and 200 degC Moreover the
substrate scope was limited to the non-enolizable ketone benzophenone
The reaction of benzaldehyde with the intramolecular H2-activated FLP
R2P(H)(C6F4)B(H)(C6F5)2 (R = tBu Mes) was found to proceed in a stoichiometric fashion
reducing the C=O double bond formulating the zwitterion R2P(H)(C6F4)B(C6F5)2OCH2Ph
(Scheme 113) Chemical intuition would perhaps point to proton transfer from the phosphonium
centre this is however prevented by the lower basicity of the oxygen atom contrasting
hydrogenation reactions with nitrogen substrates
16
B(C6F5)2R2P
FF
F F
H
H
O
HPhB(C6F5)2R2P
FF
F F
H O
Ph
R = tBu Mes
Scheme 113 ndash Stoichiometric reaction of benzaldehyde with the linked phosphonium
borohydride FLP
Based on the principle for catalytic hydrogenation of imines Repo and co-workers explored
C=O hydrogenations using the aromatic carbonyl substrates benzophenone and benzaldehyde as
Lewis bases along with the Lewis acid B(C6F5)3 Experimental results indicated the reaction to
be challenging generating only sub-stoichiometric amounts of the alcohol products due to rapid
decomposition of the borane178
1348 Carbonyl hydrosilylation
Hydrosilylation is one of the most commonly applied processes within the chemical industry
today New catalytic technologies providing avenues for metal-free SindashH bond activation have
become appealing alternatives to traditional transition metal catalysts179 Impressively in 1996
the Piers group reported 1 - 4 mol of B(C6F5)3 to effect the catalytic hydrosilylation of
aromatic aldehydes ketones and esters at room temperature (Scheme 114 top)180-182 Clever
analysis of the mechanism by Oestreich using a stereochemically pure silane found inversion of
stereochemistry at silicon after hydrosilylation This finding rationalized a concerted SN2 type
displacement at the silicon centre of a (C6F5)3Bδ-middotmiddotmiddotHmiddotmiddotmiddot SiR3δ+ transition state by the substrate
carbonyl oxygen (Scheme 114 bottom)183
17
Scheme 114 ndash B(C6F5)3 catalyzed hydrosilylation of aromatic aldehydes ketones and esters
using Ph3SiH (top) stereochemical analysis of the hydrosilylation mechanism (bottom)
14 Scope of Thesis
The objective of this graduate research was to expand the scope of FLP reactions using the Lewis
acid B(C6F5)3 Although previous studies have documented the reactivity of B(C6F5)3 with small
molecules further transformation of the activated species in organic syntheses remains limited
In this work FLP hydrogenation reactions were extended to include the aromatic rings of N-
phenyl amines and N-heterocyclic compounds as described in Chapter 2 Tandem hydrogenation
and transannulation reactions occurred with a para-methoxy substituted aniline affording a 7-
azabicyclo[221]heptane derivative Mechanistic studies of this reactivity provided insight to a
viable approach achieving the catalytic hydrogenation of ketones and aldehydes to form alcohol
products presented in Chapter 3 In addition the reductive deoxygenation of aryl ketones to
aromatic hydrocarbons was investigated Finally Chapter 4 expands FLP catalytic reactions
beyond hydrogenations In this chapter B(C6F5)3 catalyzed hydroamination of terminal alkynes
is investigated with extension to intramolecular systems and stoichiometric hydrophosphination
reactions
All synthetic work and characterizations were performed by the author with the exception of
elemental analyses high resolution mass spectroscopy and X-ray experiments DFT calculations
for the aromatic hydrogenations described in Chapter 2 were performed by Professor Stefan
Grimme at Universitaumlt Bonn Germany Compounds 216 - 218 were initially synthesized by an
undergraduate student Jon Nathaniel del Castillo under the authorrsquos supervision The synthesis
of compounds 439 and 440 were initially performed by the author at the University of Toronto
18
and repeated during a four month research opportunity program in the laboratory of Professor
Gerhard Erker at Universitaumlt Muumlnster Germany Compounds 441 and 442 were prepared at
Universitaumlt Muumlnster and the structure of 442 was obtained and solved by Dr Constantin
Daniliuc All other molecular structures were solved by the author and the authorrsquos supervisor
Professor Douglas Stephan
Portions of each chapter have been published or accepted at the time of writing
Chapter 2 1) Voss T Mahdi T Otten E Froumlhlich R Kehr G Stephan D W Erker G
ldquoFrustrated Lewis Pair Behavior of Intermolecular AmineB(C6F5)3 Pairsrdquo Organometallics
2012 31 2367-2378 2) Mahdi T Heiden Z M Grimme S Stephan D W ldquoMetal-Free
Aromatic Hydrogenation Aniline to Cyclohexylamine Derivativesrdquo J Am Chem Soc 2012
134 4088-4091 3) Mahdi T Castillo J N Stephan D W ldquoMetal-Free Hydrogenation of N-
based Heterocyclesrdquo Organometallics 2013 32 1971-1978 4) Longobardi L E Mahdi T
Stephan D W ldquoB(C6F5)3 Mediated Arene HydrogenationTransannulation of para-
Methoxyanilinesrdquo Dalton Trans 2015 44 7114-7117
Chapter 3 5) Mahdi T Stephan D W ldquoEnabling Catalytic Ketone Hydrogenation by
Frustrated Lewis Pairsrdquo J Am Chem Soc 2014 136 15809-15812 6) Mahdi T Stephan D
W ldquoFacile Protocol for Catalytic Frustrated Lewis Pair Hydrogenation and Reductive
Deoxygenation of Ketones and Aldehydesrdquo Angew Chem Int Ed 2015 DOI
101002anie201503087
Chapter 4 7) Mahdi T Stephan D W ldquoFrustrated Lewis Pair Catalysed Hydroamination of
Terminal Alkynesrdquo Angew Chem Int Ed 2013 52 12418-12421 8) Mahdi T Stephan D
W ldquoInter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairsrdquo
Chem Eur J 2015 accepted
19
Chapter 2 Metal-Free Aromatic Hydrogenation of N-Phenyl Amines
and N-Heterocyclic Compounds
21 Introduction
211 Hydrogenation
Hydrogenation the addition of hydrogen (H2) to unsaturated compounds is one of the simplest
and most attractive chemical processes performed today26 The reaction is employed for the
production of commodity chemicals with widespread application in the petrochemical
pharmaceutical and foods industries One of the largest industrial applications of hydrogenation
is in the Haber-Bosch process63 66 184 This method uses N2 and H2 to produce ammonia which is
essential for the synthesis of nitrogen fertilizers currently sustaining about one-third of the
worldrsquos population Additionally significant is the Fischer-Tropsch process used to generate
liquid hydrocarbons from the chemical reaction of H2 and CO (synthesis gas)185-186
In the early part of the 20th century P Sabatier discovered the catalytic hydrogenation of organic
substrates over finely divided nickel thereby greatly advancing the field of organic chemistry187-
193 Approximately 60 years later Wilkinson uncovered the homogeneous hydrogenation of
olefins using Ru and Rh catalysts a development that was crowned initiator of organometallic
chemistry (Scheme 21 a)194-197 Further developments in metal-based hydrogenations were
made in the 1980s including the Nobel Prize winning work of asymmetric hydrogenations by
Noyori and Knowles (Scheme 21 b)198-207 While precious metal catalysts208-209 are known to
carry out this reactivity (Scheme 21 c) the high cost and low abundance of these metals
necessitates the development of more cost-efficient procedures New technologies providing
avenues for greener transformations have recently been illustrated using first-row transition
metals Fe and Co (Scheme 21 d)136 210-214
20
Scheme 21 ndash Transition metal hydrogenation catalysts Wilkinson (a) Noyori (b) Crabtree (c)
and Chirik (d) py = pyridine
212 Transfer hydrogenation
A variety of insightful strategies have provided alternative avenues to direct hydrogenation One
such example is transfer hydrogenation the addition of hydrogen to an unsaturated substrate
from a source other than gaseous H2 In the 1920s Meerwein Ponndorf and Verley (MPV)
demonstrated the first example of hydrogen transfer from a sacrificial alcohol to ketone using an
aluminum alkoxide catalyst215-217 Nonetheless interest in using organocatalysts for
hydrogenation reactions increased spectacularly due to novelty of the concept efficiency and
selectivity in organic reactions Particularly recognized are chiral amine catalysts in combination
with Hantzsch ester dihydropyridines which act as mild organic sources of H2218-219 Extensive
research has also focused on new transition metal catalysts for efficient dehydrocoupling of
ammonia borane (H3NBH3) and related amine borane compounds220
Although transfer hydrogenation is a process dominated by precious transition metal catalysts
Earth abundant less toxic Fe-based catalysts have proven remarkably active effecting high
enantioselectivity (Figure 21 a)221 Moreover catalyst-free strategies by Berke and co-workers
have promoted transfer hydrogenation of imines and polarized olefins222 Stephan et al
underscored extension of metal-free catalysis reporting a highly electrophilic phosphonium
cation catalyst for application in dehydrocoupling of protic compounds with silanes and transfer
hydrogenation to olefins (Figure 21 b)223
RhPh3P
Ph3P Cl
PPh3
(a) (b) (c)
(d)
21
Figure 21 ndash An amine(imine)diphosphine iron complex (a) and an electrophilic phosphonium
cation (b) used for transfer hydrogenation catalysis
213 Main group catalysts
The discovery of sodium borohydride and lithium aluminum hydride in the 1940s introduced
new stoichiometric methods for the hydrogenation of unsaturated functional groups56 59 224 A
variety of these metal hydride reagents possessing a high degree of chemoselectivity have made
the reduction of a broad range of functional groups possible although catalytic procedures are
evidently more desirable In this vein the first non-transition metal catalyst for ketone
hydrogenation employing tBuOK and H2 is regarded as a breakthrough175-176 Early main group
metal catalysts have followed with highlights on a well-defined organocalcium catalyst
developed by Harder225 and the first cationic calcium hydrides by Okuda capable of catalytic
hydrogenation of 11-diphenylethylene226
Renaissance in main group chemistry emerged with the discovery of frustrated Lewis pairs
(FLPs) These relatively common main group reagents have been applied in the hydrogenation of
imines nitriles aziridines enamines silyl enol ethers olefins and alkynes typically using boron
Lewis acids relying on perfluoroaryl substituents227-228 More recently Lewis acidic borenium
ions based on an [NHC-9-BBN]+ framework have also proven ideal for hydrogenation of imine
and enamine substrates105 Du et al described the highly enantioselective hydrogenation of
imines using a chiral borane catalyst derived from the hydroboration of chiral diene
substituents104 Alkyl229 and aryl149 aluminum compounds in addition to metal-activated carbon-
based Lewis acids have been shown to participate in similar reactivity230
(a) (b)
22
214 Hydrogenation of aromatic and heteroaromatic substrates
2141 Transition metal catalysts
Despite advancements in hydrogenation catalysis the reduction of arenes and heteroaromatics to
saturated cyclic hydrocarbons remains challenging and is typically performed in the
heterogeneous phase using transition metal catalysts Such hydrogenations find particular use in
the petrochemical industry to convert alkene and aromatic fossil fuels into liquid hydrocarbons
before application in commodities such as synthetic fuel26 231 The number of complexes capable
of this catalysis is scarce mainly due to the high energy barrier required to disrupt aromaticity
Catalytic hydrogenation of aromatic systems was first demonstrated for phenols anilines and
benzene in the early 1900s by P Sabatier using powdered nickel189-193 Soon after the 14-
reduction of anisole was observed using dissolved alkali metals in liquid ammonia with major
developments emerging to include benzene and naphthalene derivatives232-233 Historically
significant accomplishments include the work of R Adams using finely divided platinum oxide
(Adamrsquos catalyst)234 and M Raney based on digestion of alloys to form finely divided metal
samples (Raney nickel)235 Other highly efficient catalysts include organometallic compounds
particularly Co Ni Ru and Rh deposited on to oxide surfaces236-239
The number of homogeneous systems capable of hydrogenating arene substrates lags well behind
heterogeneous systems The first well-documented homogeneous catalyst is a simple allylcobalt
complex η3-C3H5Co[P(OMe)3]3 reported by Muetterties and co-workers operating at room
temperature (Figure 22 left)240 shadowed by a new generation of TaV and NbV hydride catalysts
featuring bulky ancillary aryloxide ligands by Rothwell (Figure 22 right)241-243 It is noteworthy
that metal complexes of the cobalt group have provided valuable mechanistic information on this
transformation231 Ziegler type catalysts consisting of Ni or Co alkoxides acetylacetonates or
carboxylates with trialkylaluminum activators have also been demonstrated in the large scale
Institut Francais du Petrole (IFP) process231
23
Figure 22 ndash Allylcobalt (left) and TaV and NbV hydride (right) catalysts used for the
homogeneous hydrogenation of aromatic substrates
2142 Metal-free catalysts
Non-metal mediated routes such as the facile addition of borohydrides to unsaturated bonds
were developed early on by Brown and co-workers244 To this extent Koumlster has reported the
hydroboration and subsequent hydrogenolysis to convert naphthalenes to tetralins and
anthracenes to coronenes at 170 - 200 degC and 25 - 100 atm of H2245-246 Alternative efforts
demonstrated trialkylborane and tetraalkyldiborane catalysts in hydrogenating olefins and
polycyclic aromatic hydrocarbons including coal tar pitch In another finding homogeneous
iodine and borane catalysts were shown to hydrogenate the aromatic units of high-rank
bituminous coals at temperatures above 250 degC and 150 - 250 atm of H226 In a recent report the
Wang group has demonstrated the hydrogenation of unfunctionalized olefins catalyzed by
HB(C6F5)2247
215 Reactivity of FLPs with H2
The feasibility of FLP systems to activate H2 and hydrogenate unsaturated substrates
particularly heteroaromatic rings has been examined In this respect 26-lutidine and B(C6F5)3
exhibit reversible dissociation of the Lewis acid-base adduct providing a FLP-mode to H2
activation (Scheme 22 a)248-249 Similar acid-base equilibria were observed with N-heterocycles
nonetheless a catalytic amount of B(C6F5)3 and H2 results in reduction of the N-heterocyclic ring
(Scheme 22 b)98 Research by the Sooacutes group extended the scope of such catalytic reductions
using specifically designed Lewis acids250
24
Scheme 22 ndash H2 activation by 26-lutidine and B(C6F5)3 (a) partial hydrogenation of substituted
quinoline to 1234-tetrahydroquinoline (b)
Following these reports the commercially available Lewis acid B(C6F5)3251-252 was explored in
the hydrogenation of aromatic rings This chapter will describe results in metal-free aromatic
hydrogenation of N-bound phenyl rings of amines imines and aziridines in addition to pyridines
and N-heterocycles While these reductions are stoichiometric they represent rare examples of
homogeneous aromatic reductions that are metal-free and performed under comparatively mild
conditions Moreover the tandem hydrogenation and intramolecular cyclization of a para-
methoxy substituted aniline is presented This reaction provides a unique route to a 7-
azabicyclo[221]heptane derivative
22 Results and Discussion
221 H2 activation by amineborane FLPs
Phosphine-based FLPs have been thoroughly investigated in the activation of small molecules
and particularly revolutionizing is the first demonstration of reversible heterolytic H2 activation
by Mes2P(C6F4)B(C6F5)231 The corresponding chemistry with amineborane FLP systems has
been less explored Combination of the bulky amine tBuNHPh and an equivalent of B(C6F5)3 in
C6D5Br or pentane solutions do not result an apparent interaction by 1H 11B and 19F NMR
spectroscopy indeed supporting the ldquofrustratedrdquo nature of the system Following exposure of this
solution to H2 (4 atm) at 25 degC the gradual precipitation of a white solid was observed and after
12 h the H2 activated species [tBuNH2Ph][HB(C6F5)3] 21 was isolated in 82 yield (Scheme
23 top) The 1H NMR spectrum obtained in C6D5Br showed a broad resonance at 715 ppm
attributable to an NH2 fragment integrating to two protons as well as signals assignable to the
25
phenyl and tBu groups In addition 11B NMR spectroscopy revealed a doublet at -240 ppm (1JB-
H = 78 Hz) and 19F resonances were observed at -1335 -1613 and -1650 ppm These data
along with elemental analysis were consistent with the formulation of 21 Similar treatment of
the diamine 14-C6H4(CH2NHtBu)2 with two equivalents of B(C6F5)3 in toluene and exposure to
H2 (4 atm) resulted in formation of a precipitate at 25 degC Subsequent isolation of the product
afforded quantitative yield of the salt [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 22 (Scheme 23
bottom) The 1H NMR data showed signals at 595 ppm and 339 ppm attributable to the NH2
and BH fragments respectively The 11B and 19F NMR signals were consistent with the presence
of the [HB(C6F5)3]- anion
Scheme 23 ndash Reactions of B(C6F5)3 and H2 with tBuNHPh and 14-C6H4(CH2NHtBu)2 at 25 degC
to make 21 (top) and 22 (bottom)
222 Aromatic hydrogenation of N-phenyl amines
Repetition of the H2 activation reaction between tBuNHPh and B(C6F5)3 in toluene with heating
at 110 degC for 48 h led to formation of a new product 23 Subsequent workup and
characterization by NMR spectroscopy revealed the presence of the [HB(C6F5)3]- anion The 1H
NMR spectrum displayed a broad resonance at 507 ppm attributed to an NH2 moiety while
aromatic resonances were notably absent Instead multiplets between 272 and 090 ppm along
with a sharp singlet at 091 ppm were observed This data was consistent with the identity of 23
as the cyclohexylamine product [tBuNH2Cy][HB(C6F5)3] (Scheme 24) By 1H NMR
spectroscopy after 48 h at 110 degC the reaction constituted approximately complete conversion
to 23 and was isolated in 84 yield (Table 21 entry 1)
26
Scheme 24 ndash Aromatic hydrogenation of tBuNHPh to give 23
Treatment of iPrNHPh with an equivalent of B(C6F5)3 in toluene at 25 degC gave the
crystallographically characterized adduct (iPrNHPh)B(C6F5)3 24rsquo (Figure 23) This compound
exhibited broad resonances in the 1H 11B 13C and 19F NMR spectra at RT indicating a
fluxional adduct Upon cooling the sample to 193 K NMR signals coalesce giving distinct
resonances assignable to the adduct along with 15 inequivalent 19F resonances that are consistent
with a barrier of rotation of the pentafluorophenyl rings
Figure 23 ndash POV-Ray depiction of 24rsquo
Introducing the amine-borane adduct 24rsquo to H2 (4 atm) does not result in any noticeable changes
in the NMR spectra at RT Although thermolysis of the sample up to 70 degC eventually reveals
dissociation of the adduct with concurrent hydrogenation giving products of complete and partial
reduction of the phenyl ring The partially reduced product observed in trace amounts consisted
of olefinic resonances at 577 and 553 ppm and corresponding aliphatic signals at 256 and 222
ppm (Figure 24 insets) Extensive 1H1H COSY and 1H13C HSQC NMR studies confirmed
the compound as the partially hydrogenated 3-cyclohexenyl derivative [3-
(C6H9)NH2iPr][HB(C6F5)3] the cation is depicted in Figure 24
27
Figure 24 ndash 1H NMR (400 MHz CD2Cl2) spectrum with insets in specified regions showing the
partially hydrogenated cation [3-(C6H9)NH2iPr]+
Repeating the reaction at 110 degC for 36 h resulted in complete reduction of the aromatic ring
affording the salt [iPrNH2Cy][HB(C6F5)3] 24 in 93 yield (Table 21 entry 1) Monitoring the
reaction in a J-Young tube by 1H NMR spectroscopy at 110 degC showed the gradual growth of the
cyclohexyl methylene resonances with the corresponding consumption of aromatic signals
(Figure 25)
Figure 25 ndash High temperature 1H NMR (400 MHz C6D5Br 383 K) stack plot depicting
iPrNHPh consumption to form 24 iPr methine for iPrNHPh () and [iPrNH2Cy]+ ($)
12 h
9 h
6 h
3 h
15 h
05 h
$
HB HA
28
The hydrogenation protocol was applied to PhCyNH and Ph2NH affording [Cy2NH2][HB(C6F5)3]
25 in yields of 88 and 65 respectively (Table 21 entry 2) Monitoring the reaction of Ph2NH
at 24 h intervals by 1H NMR spectroscopy did not show evidence for formation of PhCyNH
presumably this indicates that complete hydrogenation of both arene rings occurs prior to
addition of the first equivalent of hydrogen to another molecule of Ph2NH In addition to the
NMR spectroscopy data formulation of 24 and 25 were determined via X-ray crystallography
(Figure 26)
Figure 26 ndash POV-Ray drawings of 24 (left) and 25 (right)
In an analogous fashion further substrates explored in such reductions included iPrNH(2-
MeC6H4) iPrNH(4-RC6H4) (R = Me OMe) iPrNH(3-MeC6H4) and iPrNH(35-Me2C6H3)
affording the arene-reduced products [iPrNH2(2-MeC6H10)][HB(C6F5)3] 26 [iPrNH2(4-
RC6H10)][HB(C6F5)3] (R = Me 27 OMe 28) [iPrNH2(3-MeC6H10)][HB(C6F5)3] 29 and
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] 210 in yields of 77 73 61 82 and 48 respectively (Table
21 entries 3 - 5) In cases where the hydrogenation reactions yield a chiral centre a mixture of
diastereomers was observed
Previously the Stephan group reported the catalytic hydrogenative ring-opening of cis-123-
triphenylaziridine using 5 mol B(C6F5)3 and H2 (4 atm) to give PhNHCHPhCH2Ph in 15 h at
120 degC94 In the following case however employing one equivalent of B(C6F5)3 at 110 ordmC for 96
h resulted in reduction of the N-bound phenyl ring yielding the salt
[CyNH2CHPhCH2Ph][HB(C6F5)3] 211 (Table 21 entry 6) The 1H NMR data were in
agreement with formulation of the cation fragment with notable resonances at 588 and 461
ppm ascribed to the NH2 and methine groups respectively in addition to the phenyl
29
cyclohexyl methylene and BH signals 11B and 19F NMR spectra displayed resonances
characteristic of the [HB(C6F5)3]- anion
Table 21 ndash Aromatic reduction of N-phenyl amine substrates to N-cyclohexylammonium salts
30
Reduction of the imine PhN=CMePh to the corresponding amine has also been previously
reported to occur upon exposure of the imine to H2 using 10 mol B(C6F5)392 Under the same
conditions heating the substrate in the presence of one equivalent of B(C6F5)3 for 96 h gave
reduction of the N-bound aromatic ring affording the species [PhCH(Me)NH2Cy][HB(C6F5)3]
212 (Table 21 entry 7) Similarly reduction of 14-C6H4(N=CMe2)2 was observed on heating
for 72 h in the presence of two equivalents of B(C6F5)3 yielding 64 of the product [14-
C6H10(iPrNH2)2][HB(C6F5)3]2 213 (Table 21 entry 8) Aromatic reduction of the bis-arene (14-
C6H4iPrNH)2CH2 with two equivalents of B(C6F5)3 was also achieved affording [(14-
C6H10iPrNH2)2CH2][HB(C6F5)3]2 214 in 76 yield (Table 21 entry 9)
2221 Attempts at catalytic aromatic hydrogenation and hydrogenation of other aromatic substrates
Although this reaction is stoichiometric in B(C6F5)3 hydrogenation of one arene ring takes up
three equivalents of H2 In an attempt to effect reactivity using sub-stoichiometric combinations
of the Lewis acid 5 mol B(C6F5)3 was combined with iPrNHPh pressurized with H2 (4 atm)
and heated at 120 degC After 24 h 1H NMR data yielded complete conversion of the borane to the
[HB(C6F5)3]- anion with only 5 mol conversion of the aniline to the [iPrNH2Cy]+ cation The
remaining 95 of the initial aniline was unaltered Increasing the H2 pressure to 80 atm did not
improve reactivity The inability of the system to turnover could be explained by pKa values of
the conjugate acid for example iPrNHPh has a pKa value of 58 in H2O while the hydrogenated
product has a pKa of about 10 - 11 in H2O (iPr2NH2 pKa 1105 in H2O) thus preventing
reversible activation of H2253-254
Furthermore efforts to hydrogenate the arene ring of iPrNHPh using pre-H2 activated FLPs
[tBu3PH][HB(C6F5)3] [Mes3PH][HB(C6F5)3] and tBu2P(H)(C6F4)B(H)(C6F5)2 did not result in
any observable reactivity by NMR spectroscopy However the stoichiometric combination of the
zwitterion Mes2P(H)(C6F4)B(H)(C6F5)2 evolved H2 at elevated temperatures and ca 10 of
[iPrNH2Cy]+ was observed Similarly 10 mol of the catalyst combination 18-
bis(diphenylphosphino)naphthalene and B(C6F5)3 gave 10 of aromatic reduction as a result of
the borane
Stoichiometric reactions of B(C6F5)3 and the anilines (p-CH3PhO2S)NHPh tBuNH(C6F5) Boc-
NHPh EtNHPh imines 26-(Me2C6H3)N=C(H)Ph PhN=CMe(p-EtOPh) phenols TMSOPh
31
tBuOPh tBuO(p-CF3C6H4) tBuO(p-FC6H4) hydrazine PhNH-NHPh 18-naphthosultam Ph3P
ethers (p-FPh)2O and CF3SPh did not evidence hydrogenation of the arene ring under the
optimized reaction conditions Furthermore the reactivity of iPrNHPh with the boranes BPh3
MesB(C6F5)2 MesB(p-C6F4H)2 PhB(C6F5)2 B(p-C6H4F)3 and B(o-C6H4CF3)3 did not activate
H2 or hydrogenate the aniline arene ring
223 Mechanistic studies for aromatic hydrogenation reactions
2231 Deuterium studies
To gain mechanistic insight into the presented transformation tBuNHPh was combined in a J-
Young tube with an equivalent of B(C6F5)3 in C6H5Br and exposed to D2 (2 atm) at 25 degC After
standing for 12 h multinuclear NMR data certainly indicated heterolytic activation of D2 The 2H
NMR spectrum gave a broad singlet at 658 ppm assigned to a N-D bond and a broad resonance
at 326 ppm attributed to a B-D bond (Figure 27 bottom-left) In addition to the 11B and 19F
NMR spectra these data supported formation of [tBuNHDPh][DB(C6F5)3] 21-d2 After heating
the sample for 3 h at 110 degC the 2H NMR revealed significant diminishing in the B-D resonance
while the N-D resonance was visibly unaltered (Figure 27 top-left) The 1H NMR spectrum of
the corresponding sample evidenced a broad quartet at 325 ppm (1JB-H = 78 Hz) representative
of a B-H bond (Figure 27 top-right) This B-H resonance is absent in the 1H NMR spectrum of
the sample at RT after 24 h (Figure 27 bottom-right)
Figure 27 ndash 2H NMR (615 MHz C6H5Br) stack plot representing reversible D2 activation
releasing HD at 110 degC (left) Corresponding 1H NMR (400 MHz C6H5Br) stack plot showing
activation of HD and formation of [HB(C6F5)3]- at 110 degC (right)
Overall the following NMR studies are suggestive of reversible D2 activation in which at
elevated temperatures proton and deuteride from the nitrogen and boron centres of 21-d2
110 degC ND 110 degC BH (3 h) (3h) BD
RT ND BD RT (24 h) (24 h)
32
respectively combine releasing H-D The H-D gas is subsequently reactivated by the free amine-
borane FLP giving rise to [tBuND2Ph][HB(C6F5)3] (Scheme 25)
Scheme 25 ndash Reversible D2 activation by tBuNHPh and B(C6F5)3 to give HD
2232 Variable temperature NMR studies
As supported by the aforementioned deuterium studies the reversible nature of H2 activation by
the aromatic amines and B(C6F5)3 is consistent with observation of species 21 as the initial
product of hydrogenation This is followed by evolution and reactivation of H2 allowing access
to the arene reduced species 23 at elevated temperatures (Scheme 26)
Scheme 26 ndash Aromatic hydrogenation of 21 to give 23
This aspect of reversible H2 acitvation was further verified by variable temperature NMR studies
of the adduct (iPrNHPh)B(C6F5)3 24rsquo under H2 from 45 degC to 115 degC in C6D5Br As temperature
was increased both 11B and 19F NMR spectra displayed resonances pertaining to gradually
dissociating B(C6F5)3 and formation of the [HB(C6F5)3]- anion This is evidenced in Figure 28
by 11B NMR spectroscopy showing liberated B(C6F5)3 at 115 degC (11B δ 53 ppm) and progression
of the resonance at -25 ppm assignable to [HB(C6F5)3]- indicating formation of 24 It is
important to note that the [HB(C6F5)3]- resonance observed at the initiation of the reaction is
attributable to reversible hydride abstraction from the iPr substituent on the aniline
33
Figure 28 ndash Variable temperature 11B NMR (128 MHz C6D5Br) stack plot of 24rsquo under H2
showing dissociation of B(C6F5)3 with increase in temperature (11B δ 53 ppm B(C6F5)3 -25
ppm [HB(C6F5)3]-)
2233 Theoretical calculations
The mechanism of this study is proposed based on quantum chemical calculations performed by
Professor Stefan Grimme at Universitaumlt Bonn Germany Quantum chemical calculations were
performed at the dispersion-corrected meta-double hybrid level (PW6P95 functional) employing
large triple-zeta type basis sets and TPSS-D3 optimized geometries This final theoretical level
denoted as PWP95-D3def2-TZVPPTPSS-D3def-TZVP provides reaction energies with an
estimated accuracy of about 1 - 2 kcalmol Solvation effects of toluene were considered using
the COSMO-RS continuum solvation model255
Theoretical studies indicate a mechanism that supports reactivity to initiate by dissociation of the
weak amine-borane adduct At this stage the FLP could follow two reaction pathways (Figure
29) At moderate temperatures the FLP undergoes splitting of H2 to yield the salt 21 computed
to be 97 kcalmol lower in energy than the amine-borane adduct However the free enthalpy
difference for this species is close to zero hence under equilibrium conditions it can be
considered as a resting state of the reaction This minor difference in free enthalpy is in
agreement with reversible D2 activation results presented earlier using tBuNHPh and B(C6F5)3
45 degC
75 degC
95 degC
65 degC
115 degC
55 degC
85 degC
105 degC
34
An alternative reaction pathway follows at elevated reaction temperatures In this case the
dissociated amine rotates to position the arene para-carbon towards the boron atom creating a
van der Waals complex that is stabilized by significant pi-stacking with a C6F5 group This
complex creates a classical FLP with an electric field to polarize the entrapped H2 and effect
heterolytic splitting at a relatively low energy barrier of 87 kcalmol The free enthalpy for H2
activation relative to the resting state is computed to be 212 kcalmol certainly supporting the
elevated temperatures required to effect this reactivity
Figure 29 ndash Proposed mechanism for aromatic hydrogenations based on quantum chemical
calculations Optimized structure energies are in parentheses and free enthalpies ΔG (298 K) are
relative to FLP + H2 (all data are in kcalmol)
At the transition state the H-H distance is calculated to be about 097 Aring This bond is
significantly elongated compared with PB FLPs where the bond distance ranges between 078
and 080 Aring thus signifying a delayed transition state The corresponding H-H and C-H covalent
Wiberg bond orders are 033 and 041 respectively The B-H bond order is 063 indicating
approximately half-broken and half-formed bonds in the transition state88 256
21
23
35
The resulting intermediate [tBuNHC6H6][HB(C6F5)3] (CH-intermediate) is an ion pair showing
an sp3 hybridized para-carbon and an almost planar tBuNH=C unit in the cation shown in Figure
29 This species has similar energy and free enthalpy to the arene-B(C6F5)3 van der Waals
compound The complexity of subsequent hydrogenation steps to yield 23 has limited further
computations
It is noteworthy that prolonged heating of the more basic amine iPr2NPh with B(C6F5)3 under H2
only yields [iPr2NHPh][HB(C6F5)3] 215 This suggests that the greater basicity of the nitrogen
centre in iPr2NPh (Et2NHPh pKa 66 in H2O) stabilizes 215 thereby inhibiting access to the
amine-borane FLP and subsequent arene reduction (iPrNHPh pKa 58 in H2O)253-254 The overall
proposed reaction mechanism has been summarized in Scheme 27 Observation of the partially
hydrogenated cation [3-(C6H9)NH2iPr]+ illustrated in Figure 24 is presumed to be a result of H2
activation at the ortho-carbon of the arene ring
Scheme 27 ndash Proposed reaction pathway to anilinium and cyclohexylammonium salts
224 Aromatic hydrogenation of substituted N-bound phenyl rings
2241 Fluoro-substituted rings and C-F bond transformations
Determining functional group tolerance of the demonstrated aromatic hydrogenations reaction
of the fluoro-substituted aniline (2-FPh)NHiPr with B(C6F5)3 under H2 indicated approximately
30 of the salt [(2-FPh)NH2iPr][HB(C6F5)3] after 31 h at RT Heating the sample at 110 degC for
36
24 h afforded a white solid 216a isolated in 59 yield (Scheme 28 a) Multinuclear NMR
spectroscopy revealed approximately 95 of the product consisted of [CyNH2iPr][FB(C6F5)3]
216a Spectral parameters of the cation were in agreement with that of compound 24 The
fluoroborate [FB(C6F5)3]- anionic fragment gave a broad signal at 055 ppm in the 11B NMR
spectrum and four 19F resonances were observed by 19F NMR spectroscopy at -1370 -1612 -
1669 and -1796 ppm The remaining 5 of the reaction mixture consisted of [(2-
FC6H10)NH2iPr][HB(C6F5)3] 216b Single crystals of 216a suitable for X-ray diffraction were
obtained and the structure is shown in Figure 210
Figure 210 ndash POV-Ray drawing of 216a
In a similar fashion heating the reaction of (3-FPh)NHiPr with B(C6F5)3 under H2 after 72 h
afforded the reduced product in 77 yield Approximately 95 of the salt consisted of 216a
and the remainder as [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b (Scheme 28 b) Indeed these
examples illustrate tandem B(C6F5)3 mediated arene hydrogenation and C-F bond activation
Scheme 28 ndash Arene hydrogenation of (2-FPh)NHiPr (a) and (3-FPh)NHiPr (b) to give 216a
37
Analogous reactivity with (4-FPh)NHiPr gave partial hydrogenation of the ring after 72 h
forming the 3-cyclohexenyl derivative [(4-FC6H8)NH2iPr][HB(C6F5)3] 218 in 62 yield
(Scheme 29) In addition to the expected resonances a diagnostic doublet of triplets in the 1H
NMR at 495 ppm and doublet at 1584 ppm (1JC-F = 255 Hz) in the 13C1H NMR spectra
certainly indicate an unsaturated C=C bond with the fluorine atom still intact This was
unambiguously confirmed by X-ray crystallography (Figure 211) It is important to note that
approximately 20 of the isolated product consisted of 216a indicating a much reduced rate of
arene hydrogenation and C-F bond activation in comparison to ortho- or meta-F substituted
anilines In these two cases intial H2 activation is expected to occur through the resonance form
in which the lone pair is at the para carbon (Scheme 27) However in the case of para-F
substituted aniline H2 activation is speculated to preferentially occur through the resonance
structure in which the negative charge is at an ortho carbon This proposal is ascribed to the
electron-withdrawing fluoro substituent which removes electron density from the para position
The partially hydrogenated product 218 is analogous to the cation [3-(C6H9)NH2iPr]+ presented
in Figure 24 in which H2 activation is suggested to initiate at the ortho carbon
Scheme 29 ndash Arene hydrogenation of (4-FPh)NHiPr to give 218
Figure 211 ndash POV-Ray drawing of 218
38
In light of recent findings121 a postulated mechanism implies that after reduction of the aromatic
ring B(C6F5)3 activates the C-F bond provoking nucleophilic addition of hydride from a
[HB(C6F5)3]- anion and liberating B(C6F5)3 for further reactivity Interaction of B(C6F5)3 with C-
F bonds were spectroscopically observed in a 11 combination of B(C6F5)3 and CF3-subtituted
anilines In this respect separate combinations of ortho- or para-F3CPhNH(iPr) and B(C6F5)3 in
C6D5Br gave a 19F NMR spectrum showing four broad resonances with a para-meta gap of 86
ppm and a diagnostic broad singlet assignable to a B-F resonance at -1800 ppm The broad
nature of these resonances and absence of a boron resonance in the 11B NMR spectrum do not
indicate formal C-F bond cleavage rather the data supports reversible B(C6F5)3-CF3
interaction121
2242 Methoxy-substituted rings and C-O bond transformations
Reactivity of FLP systems with oxygen-based substituents is noticeably limited due to high
oxophilicity of electrophilic boranes72 171 However recent findings have been reported on
lability of B-O adducts Stephan et al reported that the ethereal oxygen of the borane-oxyborate
(C6F5)2BCH(C6F5)OB(C6F5)3 derived from the reaction of FLPs with syn-gas activates H2 with
the B(C6F5)2 fragment117 Furthermore Et2O effects H2 activation with B(C6F5)3 and was shown
to be an efficient catalyst in the hydrogenation of olefins257 In an effort to further explore the
scope of the presented metal-free aromatic reductions the arene hydrogenation of anilines with
methoxy substituents was attempted
The combined toluene solution of B(C6F5)3 and the para-methoxy substituted imine (p-
CH3OC6H4)N=CCH3Ph was pressurized with H2 (4 atm) and heated at 110 degC for 48 h This
resulted in the formation of a new white crystalline product assigned to
[(C6H10)NHCH(CH3)Ph][HB(C6F5)3] 219 isolated in 30 yield (Scheme 210) Indeed the 1H
NMR spectrum indicated consumption of N-bound aromatic resonances concomitant with the
appearance of two inequivalent doublet of doublets observed at 447 and 374 ppm with the
corresponding 13C1H NMR resonances observed at 652 and 647 ppm respectively These
peaks are assignable to two inequivalent bridgehead CH groups of the resulting bicyclic
ammonium cation The 11B and 19F NMR spectra were in accordance with the presence of
[HB(C6F5)3]- as the anion X-ray diffraction studies further confirmed the bicyclic structure of
the product and the identity of the anion (Figure 212)
39
Scheme 210 ndash Reaction of (p-CH3OC6H4)N=CCH3Ph and B(C6F5)3 with H2 to give 219
Figure 212 ndash POV-Ray drawing of 219
In an effort to appreciate the importance of the position of the methoxy substituent on the arene
ring the separate reactions of ortho- and meta-methoxy substituted (CH3OC6H4)NHCH(CH3)Ph
with B(C6F5)3 were attempted under the established hydrogenationtransannulation protocol In
both cases hydrogenation of the N-bound phenyl group was observed although no
transannulation was achieved The amine (o-CH3OC6H4)NHCH(CH3)Ph gave cis and trans
mixtures of [(2-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 220 isolated in 92 yield In contrast
to fluorine abstraction from the ortho carbon position shown in Scheme 28 the methoxy
substituent in this case is not abstracted from the reduced ring due to steric effects preventing
B(C6F5)3 from binding to the substituent However the meta-substituted analogue resulted in C-
O bond cleavage yielding [(C6H11)NH2CH(CH3)Ph][HB(C6F5)3] 212 in 65 isolated yield
(Scheme 211) Ring closure was not obtained for this particular case due to ring strain of the
anticipated product Crystals of 220 suitable for X-ray crystallography were obtained and shown
in Figure 213
40
HB(C6F5)3
NH
OCH3
B(C6F5)3
Ph
+ CH3OH
NH2
OCH3
Ph
NH2Ph
HB(C6F5)3
NHPh
OCH3
220
212
H2
B(C6F5)3
H2
Scheme 211 ndash Synthesis of 220 and 212
Figure 213 ndash POV-Ray drawing of trans-220
In the case of the para-methoxy substituted imine B(C6F5)3 has participated in tandem arene
hydrogenation and transannulation to ultimately afford a 7-azabicyclo[221]heptane derivative a
bicyclic substructure of biological importance258 Unfortunately further expansion of the
substrate scope was not successful giving only the H2 activation product or arene hydrogenation
Such substrate examples include para-methoxyanilines with a methyl substituent at either the
ortho or meta position other para substituents such as HCF2O PhO2S and Br tertiary amine 4-
methoxy-N-phenyl-N-(1-phenylethyl)aniline
22421 Mechanistic studies for C-O and B-O bond cleavage
Studying the mechanism to form the 7-azabicyclo[221]heptane ammonium hydridoborate salt
219 the possibility of an intra- or intermolecular protonation of the methoxy group was initially
41
disproved by heating a toluene sample of the independently synthesized ammonium borate salt
trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] 221a at 110 degC (Scheme 212) No reaction
was evidenced by 1H 11B and 19F NMR spectroscopy However similar treatment of trans-[(4-
CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] 221b at 110 degC prompted release of H2 as evidenced
by the 1H NMR signal at 45 ppm eventually giving compound 219 after 12 h at 110 degC
(Scheme 212)
Scheme 212 ndash Thermolysis reactions of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][XB(C6F5)3] (X
= C6F5 221a and X = H 221b)
To verify the liberation of CH3OH in the presented reactions the synthesis of 219 was repeated
starting from the free amine trans-[(4-CH3OC6H10)NHCH(CH3)Ph and B(C6F5)3 under H2
(Figure 214 a) After one week at RT the volatiles were transferred under vacuum from the
reaction vessel into a J-Young tube and the 1H NMR spectrum showed evidence of CH3OH
although a yield was not obtained
42
Figure 214 ndash 1H NMR stack plot (d8-tol) of CH3OH isolated from independent synthesis of 219
(a) CH3OH isolated from synthesis of 223 starting from p-CH3OC6H4NHiPr (b) CH3OH in d8-
tol (c)
This observation implies that ring closing to yield the 7-azabicyclo[221]heptane ammonium
cation does not proceed by intra- or intermolecular protonation of the methoxy group rather
transannulation proceeds via intramolecular nucleophilic attack of the para-carbon by the amine
nitrogen while B(C6F5)3 captures the methoxide fragment To further support this proposed
mechanism the independently synthesized amine trans-(4-CH3OC6H10)NHiPr was treated with
an equivalent of B(C6F5)3 in the absence of H2 (Scheme 213) Interestingly after heating for 2 h
the reaction resulted in quantitative formation of a new product 222 with a sharp 11B resonance
at -242 ppm and 19F resonances at -1354 -1626 and -1668 ppm consistent with the formation
of the borane-methoxide anion [CH3OB(C6F5)3]- The 1H NMR data signified formation of the
diagnostic bridgehead CH protons at 413 ppm The combination of NMR spectroscopy
elemental analysis and X-ray diffraction studies evidenced the formation of compound 222 as
the bicyclic salt [(C6H10)NHiPr][CH3OB(C6F5)3] (Figure 215)
a)
b)
c)
43
Figure 215 ndash POV-Ray drawing of 222
Heating 222 at 110 degC in the absence of H2 eventually results in CH3OH liberation and rapid
degradation of the borane to CH3OB(C6F5)2 and C6F5H In the presence of H2 however 222 is
transformed to 223 with the liberation of CH3OH (Scheme 213) This observation implies that
the ammonium cation of 222 protonates the methoxide bound to boron liberating methanol and
regenerating B(C6F5)3 which undergoes FLP type H2 activation with the bicyclic amine
generating 223 Compound 223 was also prepared from the aniline p-CH3OC6H4NHiPr The
liberated CH3OH was isolated although not quantified and observed by 1H NMR spectroscopy
(Figure 214 b) Interestingly a similar protonation pathway has been previously proposed in a
study by Ashley and OrsquoHare whereby the stoichiometric hydrogenation of CO2 using 2266-
tetramethylpiperidine (TMP) and B(C6F5)3 was reported The authors proposed B-O bond
cleavage of [CH3OB(C6F5)3]- to occur through protonation by the 2266-
tetramethylpiperidinium counter cation259 Additionally most recently Ashley et al proposed
the metal-free carbonyl reduction of aldehydes to possibly proceed through oxonium protonation
of the boron-alkoxide anion [ROB(C6F5)3]-260
Scheme 213 ndash Thermolysis of trans-(4-CH3OC6H10)NHiPr and B(C6F5)3
44
Despite evidence for the protonation pathway contribution by a second pathway involving the
[CH3OB(C6F5)3]- anion and B(C6F5)3 acting as a FLP to activate H2 cannot be disregarded In
this respect a toluene solution of [NEt4][CH3OB(C6F5)3] and 5 mol B(C6F5)3 were exposed to
H2 (4 atm) at 110 degC After heating for 2 h the 11B and 19F NMR spectra revealed complete
consumption of the [CH3OB(C6F5)3]- anion along with emergence of peaks corresponding to the
H2 activation product [NEt4][HB(C6F5)3] and CH3OH (Scheme 214) This latter mechanism
provides an alternative path to the anion of 223 This type of system draws analogy to H2
activation by the earlier mentioned BO FLP (C6F5)2BCH(C6F5)OB(C6F5)3 suggesting H2
cleavage gives protonated oxygen and borohydride117
Gradual decomposition of the borane catalyst due to CH3OH was also observed as the amine is
not present to displace CH3OH from B(C6F5)3 consequently hindering its decomposition The
pKa of hydroxylic substrates have been shown to be significantly activated by coordination to
B(C6F5)3 generating strong Broslashnsted acids with pKa values comparable with HCl (84 in
acetonitrile)261
Scheme 214 ndash H2 activation between [CH3OB(C6F5)3]- anion and B(C6F5)3
Collectively it may be read that compound 219 is formed by initial hydrogenation of the imine
(p-CH3OC6H4)N=CCH3Ph C=N double bond followed by reduction of the arene ring affording
the cyclohexylamine The amine and borane can activate H2 to give the ammonium salt albeit at
elevated temperatures this is reversible allowing the borane to activate the methoxy substituent
and induce transannulation effecting C-O bond cleavage (Scheme 215) Subsequent conversion
of the generated methoxy-borate anion to the hydridoborate anion proceeds under H2 following
the pathways presented in Schemes 213 and 214
45
NH2
R
OCH3
110 oC
NHR
OCH3
NHR
OCH3
(F5C6)3B
+ H2
B(C6F5)3
H2
HB(C6F5)3
- H2HN
R
CH3OB(C6F5)3
+ H2
HB(C6F5)3
HNR
- CH3OH
Scheme 215 ndash Overall proposed mechanism for the formation of 7-azabicyclo[221] heptane
225 Aromatic hydrogenation of N-heterocyclic compounds
While seeking to extend the scope of aromatic reductions attention was focused on a series of
mono- and di-substituted pyridines quinolines and several other N-heterocycles In this regard
the aromatic hydrogenation of a variety of N-based heterocycles was explored using
stoichiometric combinations of B(C6F5)3 in the presence of H2 (4 atm)
2251 Hydrogenation of substituted pyridines
Detailed studies on the effects of increased steric bulk on pyridine249 and their reactivity with
B(C6F5)3 to activate H2248 at room temperature have been previously reported Stoichiometric
combination of the Lewis base 26-diphenylpyridine and the Lewis acid B(C6F5)3 do not show
evidence of a donor-acceptor interaction by NMR spectroscopy in contrast a reversible adduct is
observed with 26-lutidine Exposure of either combination of 26-diphenylpyridine or 26-
lutidine and B(C6F5)3 under H2 (4 atm) at room temperature activate H2 affording the
corresponding pyridinium hydridoborate salts
Nonetheless heating a mixture of 26-diphenylpyridine and B(C6F5)3 under H2 (4 atm) at 115 degC
for 16 h gives a new product isolated in 92 yield (Table 22 entry 1) The 11B NMR data in
CD2Cl2 displayed a doublet at -246 ppm and three resonances in the 19F NMR spectrum
observed at -1340 -1634 and -1666 ppm confirmed the presence of the [HB(C6F5)3]- anion
The 1H NMR spectrum showed a broad singlet at 590 ppm attributable to the NH2 group
multiplets at 453 and 226 - 189 ppm in addition to signals assignable to the phenyl and BH
46
groups These data were consistent with the formulation of the salt [26-
Ph2C5H8NH2][HB(C6F5)3] 224 Furthermore the 1H NMR data revealed a de of 91 favouring
the meso-diastereomer an assignment that was confirmed via NMR spectroscopy and the
molecular structure shown in Figure 216 (left) In a similar fashion the reaction of 26-lutidine
with B(C6F5)3 under H2 at 115 degC for 60 h afforded the corresponding salt [26-
Me2C5H8NH2][HB(C6F5)3] 225 in 84 yield (Table 22 entry 1) with a de of 80 also
favouring the meso-diastereomer (Figure 216 right) The preferred diastereoselectivity is
consistent with the known ability of B(C6F5)3 to effect epimerization of chiral carbon centres
adjacent to nitrogen by a process previously described to involve hydride abstraction and
redelivery262
Figure 216 ndash POV-Ray drawing of 224 (left) and 225 (right)
The substrate ethyl 2-picolinate was exposed to the hydrogenation conditions giving a B(C6F5)3
adduct of the reduced substrate (2-(EtOCO)C5H9NH)B(C6F5)3 226 isolated in 74 yield after
36 h (Table 22 entry 2) The 11B NMR spectrum in CD2Cl2 showed a broad singlet at -486 ppm
and 15 inequivalent 19F resonances which were consistent with adduct formation between the
boron and nitrogen centres inhibiting rotation about the bond
47
Table 22 ndash Hydrogenation of substituted pyridines
Multinuclear NMR spectra of 226 displayed the presence of two diastereomers in a 11 ratio
Most distinguishable were the 13C1H resonances at 1674 and 1712 ppm attributable to the
OCO-ester groups and the 1H NMR signals at 418 and 424 ppm arising from the methine
protons Furthermore 1H1H NOESY experiments confirmed the assignment of these peaks to
the respective RSSR and RRSS diastereomers Independent reaction of B(C6F5)3 with the
optically pure piperidine S-2-(EtOCO)C5H9NH at -30 degC in CD2Cl2 afforded the preferential
formation of the SS-diastereomer of 226 However on warming to room temperature over 18 h
racemization at nitrogen eventually afforded a 11 mixture of the SS and SR diastereomers
Even though the pyridine-borane adduct of 2-phenylpyridine has been isolated and characterized
this adduct is reversed at 115 degC Reduction of the substrate using B(C6F5)3 and H2 gave a
mixture of two products isolated in 54 overall yield after 48 h (Table 22 entry 3) A broad 11B
NMR signal at -391 ppm together with a doublet at -240 ppm were consistent with the
48
presence of the adduct (2-PhC5H9NH)B(C6F5)3 227a and the ionic pair [2-
PhC5H9NH2][HB(C6F5)3] 227b in a 41 ratio respectively
The formulation of 227a is further supported by NMR data revealing two distinctively broad
NH singlets in the 1H NMR spectrum at 555 and 581 ppm attributable to a 71 ratio of the
RSSR and RRSS diastereomers The RSSR diastereomer was the more abundant form as
evidenced by NMR and X-ray crystallographic data (Figure 217)
Figure 217 ndash POV-Ray depiction of 227a B-N 1662(2) Aring
Interestingly the preferential formation of this diastereomer was evidenced by 1H19F HOESY
NMR spectroscopy through intramolecular π-π stacking interactions of the Ph and C6F5 groups
in addition to interactions between the C-H and N-H groups of piperidine and ortho-fluoro
groups of B(C6F5)3 (Figure 218) Identity of compound 227b was confirmed based on
agreement of spectral parameters with the NH2 methine and methylene groups
49
Figure 218 ndash 2-Dimensional 1H19F HOESY NMR (400377 MHz C6D5Br) spectrum showing
cross peaks between Ph-piperidine (1H δ 415 CH 555 NH 720 Ph) and o-C6F5 groups
The presence of adduct 227a raised the question about dissociation of the B-N bond and
possible participation of the liberated borane in further pyridine hydrogenation To probe this a
toluene solution of 2-phenylpyridine and 10 mol of 227 was exposed to H2 (4 atm) at 110 degC
After heating for 24 h 1H NMR spectroscopy did not indicate consumption of the pyridine
reagent Similarly repeating the hydrogenation of 2-phenylpyridine with 10 mol B(C6F5)3 did
not result in catalysis
2252 Hydrogenation of substituted N-heterocycles
Attempting to extend the aromatic hydrogenation of N-heterocycles beyond pyridine substrates
attention was focused to 1234-tetrahydroquinoline derivatives which have been reported to
result from the catalytic hydrogenation of N-heterocycles98 In examining the structure of
tetrahydroquinoline the carbocyclic ring fused to the N-heterocycle was observed to be similar
to a secondary aniline (Figure 219) Thus emerging the avenues of previous reports on catalytic
hydrogenation of substituted quinolines and most recent findings on the stoichiometric reduction
of anilines the complete homogeneous hydrogenation of N-heteroaromatic compounds was
explored
Figure 219 ndash 1234-Tetrahydroquinoline with emphasis on the fused carbocyclic ring
50
Exposure of 2-methylquinoline and B(C6F5)3 to H2 (4 atm) at 115 degC for 48 h was found to effect
hydrogenation of not only the N-heterocycle but also the carbocyclic ring to yield [2-
MeC9H15NH2][HB(C6F5)3] 228 in 67 (Table 23 entry 1) In a similar fashion both rings of 2-
phenylquinoline were reduced in the same time frame to give [2-PhC9H15NH2][HB(C6F5)3] 229
in 95 yield (Table 23 entry 1)
The 1H NMR spectra for 228 and 229 exhibited characteristic chemical shifts corresponding to
NH2 methine and methylene groups Both compounds 228 and 229 were produced as mixtures
of diastereomers although in both cases the major isomer was crystallized and found to comprise
of 60 and 73 of the isolated products respectively The molecular structures show both
compounds exhibit SSSRRR stereochemistries in which one of the ring junctions adopts an
equatorial disposition while the other is axially disposed (Figure 220 a and b) Analogous
treatment of 8-methylquinoline with H2 and B(C6F5)3 in toluene for 48 h yielded [8-
MeC9H15NH2][HB(C6F5)3] 230 in 76 (Table 23 entry 1) 1H and 13C1H NMR data suggest
only the presence of the RRRSSS diastereomers (Figure 220 c)
Figure 220 ndash POV-Ray depiction of the cations for compounds 228 (a) 229 (b) and 230 (c)
a) b) c)
51
Table 23 ndash Hydrogenation of substituted N-heterocycles
The corresponding reduction of acridine results in isolation of the fully reduced tricyclic species
in 76 yield (Table 23 entry 2) The isolated product is obtained as a mixture of two isomers
one of which was characterized crystallographically as the salt [C13H22NH2][HB(C6F5)3] 231a
As shown in Figure 221 all ring junctions are equatorially positioned and thus the SRSRRSRS
diastereomers are assigned
Figure 221 ndash POV-Ray depiction of the cation for compound 231a
52
Interestingly a second product was isolated from the pentane work-up crystallographic data
showed it to be the adduct (C13H22NH)B(C6F5)3 231b (Figure 222) In this case however the
stereochemistries of the ring junctions adjacent to nitrogen are inverted affording the RRSSSSRR
diastereomers of the reduced acridine heterocycle Compound 231b was also independently
synthesized in 73 yield from a mixture of isomers of the neutral amine C13H22NH and
B(C6F5)3
Figure 222 ndash POV-Ray depiction of 231b B-N 1666(2) Aring
Although the substrates 23-dimethyl and 23-diphenylquinoxaline have two Lewis basic
nitrogen centres the reduction reactions required only one equivalent of B(C6F5)3 yielding the
piperazinium derivatives [23-(C4H6Me)2NHNH2][HB(C6F5)3] 232 and [23-
(C4H6Ph)2NHNH2][HB(C6F5)3] 233 in 59 and 55 yield respectively (Table 23 entry 3) In
the case of 232 a single set of diastereomers was observed and the NMR data were consistent
with ring junctions and methyl groups adopting equatorial dispositions In contrast the isolated
product 233 comprised of two diastereomers Crystallographic characterization of one
diastereomer showed the phenyl rings adopt equatorial positions while the ring junctions are
axial and equatorially disposed (Figure 223)
Figure 223 ndash POV-Ray depiction of the cation for compound 233
53
It is noteworthy that while the aromatic ring of the quinoxaline fragment is fully reduced the
phenyl substituents remain intact In a similar situation reduction of 78-benzoquinoline resulted
in the formation of [(C6H4)C7H12NH2][HB(C6F5)3] 234 in 55 yield (Table 23 entry 4) 1H
NMR spectroscopy evidenced a 41 mixture of two diastereomers in which reduction of the
pyridyl and adjacent carbocyclic ring were achieved while aromaticity of the ring remote from
the nitrogen atom was retained X-ray crystallography unambiguously confirmed the dominant
diastereomer 234a to have SRRS stereochemistry while the less abundant diastereomer 234b
showed SSRR stereochemistry (Figure 224)
Figure 224 ndash POV-Ray depiction of the cations for compounds 234a (left) and 234b (right)
Efforts to reduce the related heterocycle 110-phenanthroline in which a pyridyl ring is fused at
the 7 and 8 position of quinoline were undertaken employing one equivalent of B(C6F5)3 After
heating the solution for 14 h at 115 degC under H2 (4 atm) 1H NMR spectroscopy indicated
complete hydrogenation of the N-heterocycle in addition to loss of C6F5H and formation of a
four-coordinate boron centre with a 11B resonance observed at 302 ppm The [HB(C6F5)3]- anion
was not observed and further heating did not reveal hydrogenation of the carbocyclic ring
A second equivalent of B(C6F5)3 was added and the reaction was re-exposed to H2 (4 atm) for a
total of 96 h at 115 degC This resulted in isolation of [(C5H3N)(CH2)2(C5H8NH)B(C6F5)2]
[HB(C6F5)3] 235 in 73 yield (Table 23 entry 5) The 11B NMR spectrum revealed the
presence of two four-coordinate boron centres with resonances at 302 and -254 ppm The
former boron species exhibited six inequivalent fluorine atoms evidenced by 19F NMR
spectroscopy inferring the presence of two inequivalent fluoroarene rings where steric
congestion is inhibiting ring rotation at the B-N and B-C bonds The latter 11B NMR signal
together with the three corresponding 19F resonances arise from the [HB(C6F5)3]- anion X-ray
crystallography confirmed the formulation of 235 as the SRSRSR diastereomer present as 65
of the isolated reaction mixture (Figure 225)
54
Figure 225 ndash POV-Ray depiction of the cation for compound 235 Selected bond distances (Aring)
and angles (deg) B(1)-N(1) 1615(3) B(1)-N(2) 1598(3) N(1)-B(1)-N(2) 9663(19) N(1) amine
N(2) pyridine
In the cationic fragment of compound 235 the boron centre is bound to two perfluoroarene rings
and is chelated by the pyridine and amine nitrogen atoms of partially reduced 110-
phenanthroline The B-N distances in the cation were found for B(1)-N(1)amine to be 1615(3) and
B(1)-N(2)pyridine 1598(3) Aring In this unique case as reduction of the heterocycle proceeds a
single pyridyl ring is initially reduced in which the resulting amine coordinates B(C6F5)3
resulting in loss of C6F5H and chelation of B(C6F5)2 by the pyridyl nitrogen centre affording the
cation (Scheme 216) The second equivalent of the borane remains intact and partakes in partial
hydrogenation of the carbocyclic ring Elimination of C6F5H followed by ring closure is
thermodynamically favoured due to formation of the five-membered borocycle
NN NN
B
B(C6F5)3
(C6F5)3B H
- C6F5H H2
235
(C6F5)2
Scheme 216 ndash Proposed reaction pathway for the formation of 235
Although this arene hydrogenation method is applicable to the presented N-heteroaromatic
substrates the reactivity was not successfully extended to 46-dimethyl-1-phenylpyrimidin-
2(1H)-one 2-methylindoline 3-methylindole 1-methylisoquinoline and carbazole
55
2253 Proposed mechanism for aromatic hydrogenation
The reductions described demonstrate the ability of B(C6F5)3 to mediate the complete aromatic
hydrogenation of a number of N-heterocycles It is clear that the products arise from reduction of
pyridyl andor aniline-type rings and in some cases affording a preferred set of diastereomers as
demonstrated by the ability of B(C6F5)3 to epimerize chiral centers alpha to nitrogen262 Efforts
to monitor several of the mixtures over the course of the reactions failed to provide unambiguous
mechanistic insight By analogy to computational studies presented for aniline hydrogenations
the need for elevated temperatures presumably reflects the fact that hybridizing the para-carbon
of the N-heterocycle is energetically uphill however once this is achieved there is an exothermic
route to the saturated amine Subsequent activation of H2 by the reduced amine and borane
affords the corresponding ammonium salt which is irreversible under the reaction conditions
thus precluding catalytic reduction This could simply be explained by Broslashnsted basicity of the
nitrogen centre An sp2 hybridized nitrogen has the lone pair in a p-orbital therefore it can
participate in resonance making it less basic as opposed to sp3 hybridization which does not have
a p-orbital (pyridine pKa 52 quinoline pKa 492 piperidine pKa 112 all values are in H2O)
While the reactions are nominally stoichiometric multiple turnovers of H2 activation are
achieved For example eight equivalents of H2 are taken up by acridine in the formation of 231
2254 Approaches to dehydrogenation
Although hydrogenation of aromatic substrates is appealing the reversible reaction
dehydrogenation of the products with aim at obtaining a molecular dihydrogen storage device
became a topic of interest Heating compound 231 at 115 degC in a vacuum sealed J-Young tube
did not evolve H2 As an alternative approach the neutral amine C13H22NH was combined with
the electrophilic boranes B(C6F5)3 B(p-C6F4H)3 or (12-C12F9)B(C6F5)2 and heated under
vacuum After 24 h trace amounts of aromatic resonances corresponding to dehydrogenation of
the N-heterocycle and a single carbocyclic ring (five equivalents of H2) was observed by 1H
NMR spectroscopy It is important to note that this process did not liberate H2 rather amine and
B(C6F5)3 abstracted proton and hydride respectively regenerating 231 One can envision this
dehydrogenation process could possibly be applied to transfer hydrogenation of imines similar
to an earlier report by the Stephan group262
56
23 Conclusions
This chapter provides an account on the discovery of N-phenyl amine reductions under H2 using
an equivalent of B(C6F5)3 to yield the corresponding cyclohexylamine derivatives In these
reactions B(C6F5)3 mediates uptake of four equivalents of H2 terminating with a final FLP
activation of H2 affording the cyclohexylammonium salts A possible reaction pathway is
proposed based on experimental evidence and theoretical calculations The substrate scope is
extended to a variety of pyridyl- and aniline-type rings of N-heterocyclic compounds These
reductions represent the first example of homogeneous metal-free hydrogenation of aromatic
rings
Shortly after publishing the presented data on aromatic hydrogenations in two separate reports
the Stephan group communicated the partial reduction of polycyclic aromatic hydrocarbons
using catalysts derived from weakly basic phosphines263 or ethers257 with B(C6F5)3 Additionally
the Du group showed a borane catalyzed route to the stereoselective hydrogenation of
pyridines264
24 Experimental Section
241 General considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane hexane tetrahydrofuran dichloromethane and toluene (Sigma Aldrich) were
dried employing a Grubbs-type column system (Innovative Technology) degassed and stored
over molecular sieves (4 Aring) in the glovebox Bromobenzene (-H5 and -D5) were purchased from
Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring molecular
sieves prior to use Dichloromethane-d2 was purchased from Sigma Aldrich dried over CaH2 and
vacuum distilled onto 4 Aring molecular sieves prior to use Tetrahydrofuran-d8 and toluene-d8 were
purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to use Molecular
sieves (4 Aring) were purchased from Sigma Aldrich and dried at 140 ordmC under vacuum for 24 h
prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at 80 degC under high
vacuum before use Sodium methoxide and tetraethylammonium chloride were purchased from
Sigma Aldrich and dried under vacuum at 140 ordmC for 12 h prior to use
57
All substituted amines anilines quinolines pyridines and other N-heterocycles were purchased
from Sigma Aldrich Alfa Aesar or TCI Potassium tetrakis(pentafluorophenyl)borate and
hydrogen chloride (40 M in 14-dioxane) were purchased from Alfa Aesar The oils were
distilled over CaH2 and solids were sublimed under high vacuum prior to use The following
compounds were independently synthesized following the cited procedure265 unless indicated
otherwise N-tert-butylaniline266 NN-(14-phenylenebis(methylene))bis(tert-butylamine) N-
isopropyl-2-methylaniline N-isopropyl-4-methylaniline N-isopropyl-4-methoxyaniline N-
isopropyl-3-methylaniline N-isopropyl-35-dimethylaniline N-(1-phenylethylidene)aniline
N1N4-di(propan-2-ylidene)benzene-14-diamine 44-methylenebis(N-isopropylaniline) 2-
fluoro-N-isopropylaniline 3-fluoro-N-isopropylaniline 4-fluoro-N-isopropylaniline 4-methoxy-
N-(1-phenylethylidene)aniline 2-methoxy-N-(1-phenylethyl)aniline266 3-methoxy-N-(1-
phenylethyl)aniline266 and alkylation methods267 to prepare trans-(4-
CH3OC6H10)NHCH(CH3)Ph and trans-(4-CH3OC6H10)NHiPr
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Varian 400 MHz spectrometer equipped with an HFX AutoX triple resonance indirect
probe (used for 13C1H 19F experiments) or an Agilent DD2 500 MHz spectrometer Spectra
were referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm
for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) d8-tol (1H = 208 ppm for CH3 13C
= 13748 ppm for ipso carbon) d8-THF (1H = 358 ppm for OCH2 13C = 6721 ppm for OCH2)
or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in ppm and the
absolute values of the coupling constants (J) are in Hz NMR assignments are supported by 2D
and DEPT-135 experiments
Elemental analyses (C H N) were performed in-house employing a Perkin Elmer 2400 Series II
CHNS Analyzer H2 (grade 50) was purchased from Linde and dried through a Nanochem
Weldassure purifier column prior to use High resolution mass spectra (HRMS) were obtained
using an ABSciex QStar Mass Spectrometer with an ESI source MSMS and accurate mass
capabilities
242 Synthesis of compounds
Synthesis of [NEt4][CH3OB(C6F5)3] In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (100 mg 0195 mmol) in CH2Cl2 (10 mL) To the vial
58
Na OCH3 (105 mg 0195 mmol) was added and the reaction was allowed to mix for 3 h at RT
The salt Na CH3OB(C6F5)3 was isolated as a white solid and dried under vacuum (110 mg 0195
mmol gt99) Na CH3OB(C6F5)3 (110 mg 0195 mmol) in CH2Cl2 (10 mL) was subsequently
added to a 4 dram vial containing NEt4 Cl (323 mg 0195 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT for 16 h and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (125 mg
0186 mmol 95)
1H NMR (400 MHz CD2Cl2) δ 322 (q 3JH-H = 73 Hz 8H Et) 311 (s 3H OCH3) 142 (tm 3JH-H = 73 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 3JF-F = 20 Hz 2F o-C6F5)
-1636 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
256 (s BOCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1480 (dm 1JC-F = 240 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1364 (dm 1JC-F = 248 Hz CF) 1246 (br ipso-C6F5) 529 (Et) 519
(OCH3) 710 (Et) Elemental analysis was not successful after numerous attempts
Synthesis of [tBuNH2Ph][HB(C6F5)3] (21) In the glove box a 100 mL Teflon screw cap
Schlenk tube equipped with a stir bar was charged with a yellow solution of B(C6F5)3 (100 mg
0195 mmol) in pentane (7 mL) To the reaction tube N-tert-butylaniline (291 mg 0195 mmol)
was added immediately resulting in a pale orange cloudy solution The reaction tube was
degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2
(4 atm) at -196 ordmC After about 10 min of reaction time at RT white precipitate was observed in
the reaction vessel and the solution became colourless The tube was left to stir at RT for 12 h
The solvent was decanted and the white precipitate was washed with pentane (3 mL) dried under
vacuum and isolated (106 mg 0160 mmol 82)
1H NMR (400 MHz C6D5Br) δ 715 (br s 2H NH2) 712 (t 3JH-H = 73 Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 682 (d 3JH-H = 76 Hz 2H o-Ph) 369 (br q 1JB-H = 78 Hz 1H BH)
102 (s 9H tBu) 19F NMR (377 MHz C6D5Br) δ -1335 (br 2F o-C6F5) -1613 (br 1F p-
C6F5) -1650 (br 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 78 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1494 (dm 1JC-F = 238 Hz CF) 1382 (dm 1JC-F = 244
Hz CF) 1369 (dm 1JC-F = 247 Hz CF) 1309 (p-Ph) 1299 (m-Ph) 1237 (o-Ph) 1244 (ipso-
C6F5) 659 (tBu) 255 (tBu) (ipso-Ph was not observed) Anal calcd () for C28H17BF15N C
5071 H 258 N 211 Found C 5027 H 287 N 219
59
[tBuNHDPh][DB(C6F5)3] (21-d2) This compound was prepared similar to 21 using D2
19F NMR (377 MHz C6H5Br) δ -1332 (m 2F o-C6F5) -1609 (br 1F p-C6F5) -1646 (m 2F
m-C6F5) 11B NMR (128 MHz C6H5Br) δ -238 (s BD)
Synthesis of [14-C6H4(CH2NH2tBu)2][HB(C6F5)3]2 (22) In a glove box a 100 mL Teflon
screw cap Schlenk tube equipped with a stir bar was charged with a solution of B(C6F5)3 (304
mg 0594 mmol) and NN-(14-phenylenebis(methylene))bis(tert-butylamine) (725 mg 0297
mmol) in toluene (4 mL) The reaction was degassed three times with a freeze-pump-thaw cycle
on the vacuumH2 line The reaction flask was cooled to -196 ordmC and filled with H2 (4 atm)
Immediate precipitation of a white solid was observed at RT The reaction mixture was stirred
overnight at 70 ordmC Pentane (10 mL) was added after which the supernatant was decanted The
residue was washed with pentane (5 mL) and dried in vacuo to give the product as a white
powder (374 mg 0297 mmol gt99)
1H NMR (400 MHz CD2Cl2) δ 727 (s 4H Ph) 595 (br s 4H NH2) 438 (s 4H CH2) 339
(br q 1JB-H = 83 Hz 2H BH) 162 (s 18H tBu) 19F NMR (377 MHz CD2Cl2) δ -1349 (m 3JF-F = 21 Hz 2F o-C6F5) -1635 (t 3JF-F = 21 Hz 1F p-C6F5) -1670 (m 2F m-C6F5) 11B
NMR (128 MHz CD2Cl2) δ -243 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz d8-THF )
δ 1493 (dm 1JC-F = 236 Hz CF) 1461 (quaternary C for C6H4) 1385 (dm 1JC-F = 243 Hz CF)
1374 (dm 1JC-F = 246 Hz CF) 1345 (br ipso-C6F5) 1314 (Ph) 595 (tBu) 461 (CH2) 259
(tBu) Anal calcd () for C51H30B2F30N2 C 4852 H 240 N 222 Found C 4882 H 269 N
252
Compounds 23 ndash 214 were prepared following a common procedure In the glove box a 25 mL
Teflon screw cap Schlenk tube equipped with a stir bar was charged with a yellow solution of
B(C6F5)3 (379 mg 740 μmol) and N-phenyl amine (740 μmol) in toluene (2 mL) The reaction
tube was degassed three times through a freeze-pump-thaw cycle on the vacuumH2 line and
filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube was placed in a 110
ordmC oil bath After the appropriate reaction time the toluene was removed under reduced pressure
resulting in crude pale yellow oil The oil was washed with pentane (6 mL) affording the product
as a white powder
60
[tBuNH2Cy][HB(C6F5)3] (23) N-tert-butylaniline (110 mg 740 μmol) reaction time 48 h
product (415 mg 620 μmol 84)
1H NMR (400 MHz C6D5Br) δ 507 (br 2H NH2) 355 (br q 1JB-H = 83 Hz 1H BH) 272 (m
1H N-Cy) 155 (m 2H Cy) 145 (m 2H Cy) 131 (m 1H Cy) 117 (m 3H Cy) 091 (s 9H
tBu) 090 (m 2H Cy) 19F NMR (377 MHz C6D5Br) δ -1327 (m 3JF-F = 21 Hz 2F o-C6F5)
1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1645 (m 2F m-C6F5) 11 B NMR (128 MHz C6D5Br) δ -
240 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 238 Hz
CF) 1382 (dm 1JC-F = 247 Hz CF) 1368 (dm 1JC-F = 247 Hz CF) 1354 (ipso-C6F5) 610
(tBu) 561 (N-Cy) 319 (Cy) 258 (tBu) 244 (Cy) 236 (Cy) Anal calcd () for
C28H23BF15N C 5025 H 346 N 209 Found C 4985 H 357 N 219
Synthesis of PhNHiPrB(C6F5)3 (24rsquo) In a glove box a 20 mL dram vial equipped with a
magnetic stir bar was charged with B(C6F5)3 (176 mg 0344 mmol) and N-isopropylaniline (465
mg 0344 mmol) in toluene (4 mL) All volatiles were removed and the crude oil was washed
with hexane (2 mL) The hexane portion was reduced in volume and placed in a -30 ordmC freezer
Colourless crystals were obtained (122 mg 0192 mmol 55)
1H NMR (400 MHz CD2Cl2 193K) δ 740 - 726 (m 5H Ph) 696 (br 1H NH) 416 (br m
1H iPr) 123 (br 3H iPr) 072 (br 3H iPr) 19F NMR (367 MHz CD2Cl2 193K) δ -1219 (m
1F o-C6F5) -1272 (m 1F o-C6F5) -1279 (m 2F o-C6F5) -1315 (m 1F o-C6F5) -1388 (m
1F o-C6F5) -1543 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F p-C6F5) -1575 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1625 (m 1F m-
C6F5) -1627 (m 1F m-C6F5) -1629 (m 1F m-C6F5) -1636 (m 1F m-C6F5) 11B NMR (128
MHz CD2Cl2 193K) δ -323 (s B-N) 13C1H NMR (101 MHz CD2Cl2 298K) δ 1478 (dm 1JC-F = 246 Hz CF) 1390 (dm 1JC-F = 242 Hz CF) 1365 (dm 1JC-F = 236 Hz CF) 1328
(ipso-Ph) 1301 (o-Ph) 1295 (p-Ph) 1227 (m-Ph) 556 (iPr) 195 (iPr) (ipso-C6F5 was not
observed) Anal calcd () for C27H13BF15N C 5011 H 202 N 216 Found C 4961 H 246
N 209
[iPrNH2Cy][HB(C6F5)3] (24) N-Isopropylaniline (100 mg 740 μmol) reaction time 36 h
product (481 mg 730 μmol 93) Crystals suitable for X-ray diffraction were grown from a
layered dichloromethanepentane solution at -30 ordmC
61
1H NMR (400 MHz C6D5Br) δ 510 (s 2H NH2) 356 (br q 1JB-H = 84 Hz 1H BH) 303 (m 1JH-H = 65 Hz 1H iPr) 276 (m 1H N-Cy) 156 (m 2H Cy) 147 (m 2H Cy) 134 (m 1H
Cy) 099 - 086 (m 5H Cy) 091 (d 1JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1330 (m 3JF-F = 21 Hz 2F o-C6F5) -1609 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-
C6F5) 11 B NMR (128 MHz C6D5Br) δ -239 (d 1JB-H = 84 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1483 (dm 1JC-F = 238 Hz CF) 1384 (dm 1JC-F = 247 Hz CF) 1369 (dm 1JC-F =
248 Hz CF) 1288 (ipso-C6F5) 567 (N-Cy) 498 (iPr) 294 (Cy) 241 (Cy) 240 (Cy) 189
(iPr) Anal calcd () for C27H21BF15N C 4949 H 323 N 214 Found C 4952 H 345 N
219
[Cy2NH2][HB(C6F5)3] (25) Method 1 N-Cyclohexylaniline (130 mg 740 μmol) reaction
time 36 h product (452 mg 650 μmol 88) Method 2 Diphenylamine (125 mg 740 μmol)
reaction time 96 h product (334 mg 480 μmol 65) Crystals suitable for X-ray diffraction
were grown from a concentrated solution in C6D5Br at RT
1H NMR (400 MHz C6D5Br) δ 498 (br s 2H NH2) 317 (br q 1JB-H = 86 Hz 1H BH) 247
(m 2H N-Cy) 122 (m 4H Cy) 111 (m 4H Cy) 099 (m 2H Cy) 070 - 046 (m 10H Cy)
19F NMR (377 MHz C6D5Br) δ -1332 (m 3JF-F = 20 Hz 2F o-C6F5) -1608 (t 3JF-F = 20 Hz
1F p-C6F5) -1648 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 86 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 241 Hz CF) 1380 (dm 1JC-F =
247 Hz CF) 1365 (dm 1JC-F = 248 Hz CF) 1264 (ipso-C6F5) 558 (N-Cy) 293 (Cy) 238
(Cy) 237 (Cy) Anal calcd () for C30H25BF15N C 5182 H 362 N 201 Found C 5217 H
386 N 212
[iPrNH2(2-MeC6H10)][HB(C6F5)3] (26) N-Isopropyl-2-methylaniline (111 mg 740 μmol)
reaction time 36 h product (398 mg 570 μmol 77) NMR data is reported for one isomer
1H NMR (400 MHz C6D5Br) δ 587 (br 2H NH2) 375 (br q 1JB-H = 82 Hz 1H BH) 318 (m
1H N-Cy) 313 (m 3JH-H = 62 Hz 1H iPr) 180 - 118 (m 9H Cy) 113 (d 3JH-H = 64 Hz
6H iPr) 086 (d 3JH-H = 62 Hz 3H Me) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21
Hz 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -237 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) partial δ
1485 (dm 1JC-F = 235 Hz CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF)
1236 (ipso-C6F5) 638 (N-Cy) 593 (iPr) 347 (Cy) 319 (Cy) 304 (CMeH) 291 (Cy) 210
62
(Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C 5021 H
359 N 214
[iPrNH2(4-MeC6H10)][HB(C6F5)3] (27) N-isopropyl-4-methylaniline (111 mg 740 μmol)
reaction time 36 h product (377 mg 540 μmol 73)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 83 Hz 1H BH) 317 (m 3JH-H = 64 Hz 1H iPr) 290 (m 1H N-Cy) 171 (m 2H Cy) 162 (m 2H Cy) 120 (m 3H
Cy) 110 (d 3JH-H = 64 Hz 6H iPr) 086 (d 3JH-H = 66 Hz 3H Me) 077 (m 2H Cy) 19F
NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1613 (t 3JF-F = 21 Hz 1F
p-C6F5) -1652 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -236 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1480 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 247
Hz CF) 1367 (dm 1JC-F = 250 Hz CF) 562 (N-Cy) 495 (iPr) 319 (Cy) 304 (CMeH) 291
(Cy) 210 (Me) 186 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found
C 5014 H 348 N 209
[iPrNH2(4-MeOC6H10)][HB(C6F5)3] (28) N-Isopropyl-4-methoxyaniline (122 mg 740
μmol) reaction time 36 h product (308 mg 450 μmol 61)
1H NMR (400 MHz C6D5Br) δ 553 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 346 (br
4H OMe and CHOMe) 299 (br m 1H N-Cy) 237 (m 1H iPr) 162 (m 2H Cy) 129 (m
2H Cy) 107 (m 4H Cy) 081 (d 3JH-H = 65 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -
1338 (m 3JF-F = 21 Hz 2F o-C6F5) -1623 (t 3JF-F = 21 Hz 1F p-C6F5) -1659 (m 2F m-
C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz
C6D5Br) δ 1484 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 247 Hz CF) 1367 (dm 1JC-F =
247 Hz CF) 1243 (ipso-C6F5) 636 (OMe) 583 (CHOMe) 551 (N-Cy) 497 (iPr) 267 (Cy)
246 (Cy) 183 (iPr) Anal calcd () for C28H23BF15NO C 4908 H 338 N 204 Found C
4945 H 329 N 230
[iPrNH2(3-MeC6H10)][HB(C6F5)3] (29) N-Isopropyl-3-methylaniline (111 mg 740 μmol)
reaction time 36 h product (406 mg 610 μmol 82)
1H NMR (400 MHz C6D5Br) δ 547 (br 2H NH2) 369 (br q 1JB-H = 80 Hz 1H BH) 320 (m
1H iPr) 297 (m 1H N-Cy) 171 (m 3H Cy) 153 (m 1H Cy) 112 (m 1H CMeH) 112 (d
63
3JH-H = 60 Hz 3H iPr) 111 (d 3JH-H = 60 Hz 3H iPr) 104 (m 2H Cy) 086 (d 3JH-H = 66
Hz 3H Me) 078 (m 1H Cy) 068 (m 1H Cy) 19F NMR (377 MHz C6D5Br) δ -1337 (m 3JF-F = 21 Hz 2F o-C6F5) -1611 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5) 11B
NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ
1488 (dm 1JC-F = 237 Hz CF) 1390 (dm 1JC-F = 250 Hz CF) 1372 (dm 1JC-F = 247 Hz CF)
571 (N-Cy) 503 (iPr) 381 (Cy) 330 (Cy) 315 (CMeH) 293 (Cy) 241 (Cy) 219 (Me)
196 (iPr) 192 (iPr) Anal calcd () for C28H23BF15N C 5025 H 346 N 209 Found C
5011 H 350 N 216
[iPrNH2(35-Me2C6H9)][HB(C6F5)3] (210) N-Isoporpyl-35-dimethylaniline (121 mg 740
μmol) reaction time 72 h product (243 mg 360 μmol 48) Mixture of isomers was obtained
NMR data for one isomer is reported
1H NMR (400 MHz C6D5Br) δ 555 (br 2H NH2) 371 (br q 1JB-H = 82 Hz 1H BH) 300 -
280 (br m 2H iPr N-Cy) 182 (br m 1H Cy) 149 - 100 (m 5H Cy) 093 (m 6H iPr) 077
- 072 (m 1H Cy) 068 - 062 (m 6H Me) 059 - 048 (m 1H Cy) 19F NMR (377 MHz
C6D5Br) δ -1337 (m 2F o-C6F5) -1614 (t 3JF-F = 21 Hz 1F p-C6F5) -1652 (m 2F m-C6F5)
11B NMR (128 MHz C6D5Br) δ -235 (d 1JB-H = 82 Hz BH) 13C1H NMR (100 MHz
C6D5Br) partial δ 1479 (dm 1JC-F = 240 Hz CF) 1378 (dm 1JC-F = 249 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1227 (ipso-C6F5) 560 (N-Cy) 494 (iPr) 410 (Cy) 378 (Cy) 270 (Cy)
212 (Me) 188 (iPr) Anal calcd () for C29H25BF15N C 5097 H 369 N 205 Found C
5087 H 399 N 212
[CyNH2CHPhCH2Ph][HB(C6F5)3] (211) cis-123-Triphenylaziridine (201 mg 740 μmol)
reaction time 96 h product (293 mg 370 μmol 50)
1H NMR (400 MHz CD2Cl2) δ 755 (m 1H p-Ph) 745 (m 4H Ph) 740 (m 3H Ph) 720
(m 2H Ph) 588 (br 2H NH2) 461 (t 3JH-H = 77 Hz 1H PhCH) 369 (br q 1JB-H = 85 Hz
1H BH) 344 (d 2H 3JH-H = 77 Hz PhCH2) 306 (m 1H N-Cy) 203 (m 1H Cy) 168 (m
4H Cy) 137 - 115 (br m 5H Cy) 19F NMR (377 MHz CD2Cl2) δ -1338 (m 3JF-F = 20 Hz
2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1662 (m 2F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -239 (d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F
= 245 Hz CF) 1382 (dm 1JC-F = 248 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1333 (ipso-Ph)
1321 (ipso-Ph) 1310 (p-Ph) 1301 (Ph) 1298 (Ph) 1289 (Ph) 1287 (p-Ph) 1273 (Ph) 1235
64
(ipso-C6F5) 641 (PhCH) 582 (N-Cy) 403 (PhCH2) 306 (Cy) 289 (Cy) 241 (Cy) 238
(Cy) 236 (Cy) Anal calcd () for C38H27BF15N C 5752 H 343 N 177 Found C 5762 H
395 N 187
[PhCH(Me)NH2Cy][HB(C6F5)3] (212) Method 1 N-(1-Phenylethylidene)aniline (144 mg
740 μmol) reaction time 96 h product (303 mg 420 μmol 57) Method 2 B(C6F5) (379 mg
0740 mmol) 3-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol) toluene (5 mL)
product (347 mg 0481 mmol 65)
1H NMR (400 MHz C6D5Br) δ 735 (m 3H o p-Ph) 721 (m 2H m-Ph) 618 (br 1H NH2)
566 (br 1H NH2) 428 (m 1H NH2CHMe) 383 (br q 1JB-H = 83 Hz 1H BH) 288 (m 1H
N-Cy) 190 (m 1H Cy) 166 (m 2H Cy) 157 (m 1H Cy) 154 (d 3JH-H = 69 Hz 3H Me)
146 (m 1H Cy) 126 (m 2H Cy) 098 (m 3H Cy) 19F NMR (377 MHz C6D5Br) δ -1336
(m 2F o-C6F5) -1613 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) 11B NMR (128
MHz C6D5Br) δ -234 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481 (dm 1JC-F = 243 Hz CF) 1380 (dm 1JC-F = 241 Hz CF) 1365 (dm 1JC-F = 250 Hz CF) 1334
(ipso-Ph) 1296 (o-Ph) 1260 (m-Ph) 574 (NH2CHMe) 573 (N-Cy) 295 (Cy) 288 (Cy)
236 (Cy) 236 (Cy) 188 (Me) (p-Ph was not observed) Anal calcd () for C32H23BF15N C
5358 H 323 N 195 Found C 5374 H 300 N 189
[14-C6H10(iPrNH2)2][HB(C6F5)3]2 (213) N1N4-Di(propan-2-ylidene)benzene-14-diamine (70
mg 0037 mmol) reaction time 36 h product (293 mg 240 μmol 64)
1H NMR (400 MHz d8-THF) δ 784 (br 2H NH2) 376 (br q 1JB-H = 92 Hz 1H BH) 364 (m 3JH-H = 65 Hz 1H iPr) 335 (br m 1H N-Cy) 238 (m 2H Cy) 159 (m 2H Cy) 138 (d 3JH-
H = 65 Hz 6H iPr) 19F NMR (377 MHz d8-THF) δ -1346 (m 3JF-F = 20 Hz 2F o-C6F5) -
1670 (t 3JF-F = 20 Hz 1F p-C6F5) -1697 (m 2F m-C6F5) 11B NMR (128 MHz d8-THF) δ -
254 (d 1JB-H = 92 Hz BH) 13C1H NMR (101 MHz d8-THF) δ 1483 (dm 1JC-F = 237 Hz
CF) 1375 (dm 1JC-F = 242 Hz CF) 1362 (dm 1JC-F = 246 Hz CF) 1259 (ipso-C6F5) 528 (N-
Cy) 486 (iPr) 274 (Cy) 184 (iPr) Anal calcd () for C48H30B2F30N2 C 4701 H 247 N
228 Found C 4686 H 247 N 232
[(14-C6H10(iPrNH2))2CH2][HB(C6F5)3]2 (214) 44-Methylenebis(N-isopropylaniline) (104
mg 370 μmol) reaction time 76 h product (372 mg 280 μmol 76)
65
1H NMR (400 MHz C6D5Br) δ 513 (br 2H NH2) 359 (br q 1JB-H = 81 Hz 1H BH) 301 (m
1H iPr) 276 (m 1H N-Cy) 168 (m 1H Cy) 151 (m 2H Cy) 145 (m 1H CH2) 132 (m
2H Cy) 091 (m 2H Cy) 089 (m 2H Cy) 089 (d 3JH-H = 68 Hz 6H iPr) 19F NMR (377
MHz C6D5Br) δ -1331 (m 3JF-F = 20 Hz 2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -
1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -240 (d 1JB-H = 81 Hz BH) 13C1H
NMR (101 MHz C6D5Br) δ 1486 (dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF)
1385 (dm 1JC-F = 247 Hz CF) 569 (iPr) 500 (N-Cy) 432 (CH2) 296 (Cy) 272 (CH2-Cy)
242 (Cy) 190 (iPr) Anal calcd () for C55H42B2F30N2 C 4995 H 320 N 212 Found C
4973 H 333 N 221
[iPr2NHPh][HB(C6F5)3] (215) In a glove box B(C6F5)3 (379 mg 740 μmol) and NN-
diisopropylaniline (131 mg 740 μmol) were dissolved in C6D5Br (05 mL) and added into a
Teflon capped sealed J-Young tube The J-Young tube was degassed three times through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC and placed
in a 110 ordmC oil bath for 16 h To the C6D5Br solution pentane was added drop wise until the
product precipitated The white solid was isolated (442 mg 640 μmol 87) Crystals suitable
for X-ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H o p-Ph) 693 (m 2H m-Ph) 670 (br 1H NH)
371 (br q 1JB-H = 85 Hz 1H BH) 358 (m 3JH-H = 63 Hz 2H iPr) 093 (d 3JH-H = 63 Hz 6H
iPr) 077 (d 3JH-H = 63 Hz 6H iPr) 19F NMR (377 Hz C6D5Br) δ -1326 (m 3JF-F = 20 Hz
2F o-C6F5) -1619 (t 3JF-F = 20 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -245 ppm (br d 1JB-H = 85 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484
(dm 1JC-F = 243 Hz CF) 1381 (dm 1JC-F = 247 Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1322
(ipso-Ph) 1304 (m-Ph) 1231 (p-Ph) 1211 (o-Ph) 584 (iPr) 188 (iPr) 168 (iPr) Anal calcd
() for C30H21BF15N C 5212 H 306 N 203 Found C 5183 H 329 N 211
Synthesis of 216 - 218 is similar to the general procedure used for compounds 23 - 214 Since
compounds [(2-FC6H10)NH2iPr][HB(C6F5)3] 216b and [(3-FC6H10)NH2iPr][HB(C6F5)3] 217b
were present in trace amounts (5) isolation and characterization proved difficult therefore
spectroscopic data for the two compounds has not been reported
[iPrNH2Cy][FB(C6F5)3] (216a) B(C6F5)3 (379 mg 0740 mmol) 2-fluoro-N-isopropylaniline
(115 mg 0740 mmol) or 3-fluoro-N-isopropylaniline (115 mg 0740 mmol) toluene (5mL)
66
reaction time 72 h product from 2-fluoro-N-isopropylaniline (294 mg 0440 mmol 59)
product from 3-fluoro-N-isopropylaniline (381 mg 0570 mmol 77) Crystals suitable for x-
ray diffraction were grown from a layered C6D5Brpentane solution at -30 ordmC
1H NMR (400 MHz C6D5Br) δ 561 (br 2H NH2) 288 (m 3JH-H = 64 Hz 1H iPr) 262 (br
m 1H N-Cy) 149 (m 2H Cy) 144 (m 2H Cy) 135 (m 1H Cy) 092 - 083 (m 5H Cy)
085 (d 1JH-H = 63 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1370 (m 6F o-C6F5) -1616
(t 3JF-F = 22 Hz 3F p-C6F5) -1669 (m 6F m-C6F5) -1795 (br s 1F BF) 11B NMR (128
MHz CD2Cl2) δ 051 (br s BF) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 239
Hz CF) 1394 (dm 1JC-F = 241 Hz CF) 1373 (dm 1JC-F = 249 Hz CF) 560 (N-Cy) 489
(iPr) 293 (Cy) 245 (Cy) 241 (Cy) 188 (iPr) Anal calcd () for C27H20BF16N C 4817 H
299 N 208 Found C 4804 H 307 N 210
[(4-FC6H8)NH2iPr][HB(C6F5)3] (218) B(C6F5)3 (379 mg 074 mmol) 4-fluoro-N-
isopropylaniline (113 mg 074 mmol) toluene (5 mL) reaction time 72 h product (308 mg
0460 mmol 62) Crystals suitable for X-ray diffraction were obtained from a layered solution
of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 582 (br s 2H NH2) 477 (dm 3JF-H = 14 Hz 1H CH=CF)
355 (br q 1JB-H = 81 Hz 1H BH) 345 (m 1H iPr) 293 (m 1H N-Cy) 192 - 133 (m 6H
CH2 groups of Cy) 081 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -9903
(dm 3JF-H = 14 Hz 1F FC=CH) -1331 (m 3JF-F = 23 Hz 6F o-C6F5) -1606 (t 3JF-F = 21 Hz
3F p-C6F5) -16398 (m 6F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 81 Hz
BH) 13C1H NMR (101 MHz C6D5Br) δ 1584 (d 1JC-F = 255 Hz CF=CH) 1484 (dm 1JC-F =
224 Hz C6F5)1385 (dm 1JC-F = 247 Hz C6F5)1369 (dm 1JC-F = 247 Hz C6F5) 1230 (ipso-
C6F5) 974 (d 2JC-F = 20 Hz CF=CH) 518 (iPr) 504 (N-Cy) 254 (d 2JC-F = 81 Hz CH2CF)
247 (d 3JC-F = 90 Hz CH2CH=CF) 228 (CH2) Anal calcd () for C27H18BF16N C 4831 H
270 N 209 Found C 4793 H 282 N 203
Synthesis of 219 and 220 is similar to the general procedure used for compounds 23 - 214
Synthesis of [C6H10NHCH(CH3)Ph][HB(C6F5)3] (219) Method 1 B(C6F5) (358 mg 0700
mmol) 4-methoxy-N-(1-phenylethylidene)aniline (113 mg 0500 mmol) toluene (4 mL) (107
67
mg 0150 mmol 30) Crystals suitable for X-ray diffraction were obtained from a layered
solution of dichloromethanepentane at -30 degC
Method 2 In the glovebox trans-(4-CH3OC6H10)NHCH(CH3)Ph (81 mg 340 μmol) and
B(C6F5)3 (17 mg 340 μmol) were dissolved in d8-toluene (04 mL) and added into a Teflon
capped J-Young tube The tube was degassed once through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at
110 degC The solvent was removed under vacuum and the residue was washed with pentane (2
mL) The product was dried under vacuum and collected (82 mg 110 μmol 33)
1H NMR (500 MHz CD2Cl2) δ 752 (tm 3JH-H = 77 Hz 1H p-Ph)
746 (tm 3JH-H = 77 Hz 2H m-Ph) 735 (dm 3JH-H = 77 Hz 2H o-
Ph) 555 (br m 1H NH) 447 (dd 3JH-H = 95 Hz 48 Hz 1H H1)
415 (dq 3JH-H = 102 Hz 68 Hz 1H CH(CH3)Ph) 374 (m JH-H = 95
Hz 48 Hz 1H H5) 363 (br q 1JB-H = 83 Hz 1H BH) 229 (m 1H
H3) 223 (m 1H H4) 215 (m 1H H2) 201 (m 1H H3) 196 (m 1H H6) 190 (m 1H H2)
188 (m 1H H4) 177 (d 3JH-H = 68 Hz 3H CH3) 176 (m 1H H6) 19F NMR (377 MHz
CD2Cl2) δ -1304 (m 2F o-C6F5) -1638 (t 1F 3JF-F = 21 Hz p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -249 (d 1JB-H = 83 Hz BH) 13C1H NMR (125 MHz
CD2Cl2) δ 1482 (dm 1JC-F = 236 Hz C6F5) 1378 (dm 1JC-F = 245 Hz C6F5) 1364 (dm 1JC-F
= 249 Hz C6F5) 1346 (ipso-Ph) 1308 (p-Ph) 1301 (m-Ph) 1266 (o-Ph) 1246 (ipso-C6F5)
652 (C5) 647 (C1) 586 (CH(CH3)Ph) 277 (C2) 273 (C6) 254 (C3 C4) 188 (CH3) Anal
calcd () for C32H21BF15N C 5373 H 296 N 196 Found 5384 H 321 N 200
[(o-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (220) Ratio of cis and trans isomers = 11
determined by 1H NMR spectroscopy The trans isomer has been isolated and characterized
B(C6F5) (379 mg 0740 mmol) 2-methoxy-N-(1-phenylethyl)aniline (168 mg 0740 mmol)
toluene (5 mL) product (508 mg 0680 mmol 92) Crystals suitable for X-ray diffraction were
obtained from a layered solution of dichloromethanepentane at -30 degC
1H NMR (400 MHz C6D5Br) δ 716 (m 3H m p-Ph) 691 (m 2H o-
Ph) 655 (br s 2H NH2) 413 (q 3JH-H = 64 Hz 1H CH(Me)Ph) 365
(br q 1JB-H = 92 Hz 1H BH) 313 (ddd 3JH-H = 107 Hz 43 Hz 1H
CHOCH3) 298 (s 3H OCH3) 237 (td 3JH-H = 107 Hz 1H CH2CHNH2) 180 (m 1H DCH2)
68
173 (dm 3JH-H = 136 Hz 1H ACH2) 140 (m 2H DCCH2) 128 (d 3JH-H = 64 Hz 3H
CH(CH3)Ph) 120 (m 1H BCH2) 095 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H BCH2)
066 (pseudo qt JH-H = 136 Hz 3JH-H = 31 Hz 1H CCH2) 039 (pseudo qd JH-H = 136 Hz 3JH-
H = 31 Hz 1H ACH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -1634 (t 3JF-F =
21 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -246 (d 1JB-H = 92
Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 235 Hz C6F5) 1381 (dm 1JC-F = 246 Hz C6F5) 1367 (dm 1JC-F = 247 Hz C6F5) 1334 (ipso-Ph) 1304 (p-Ph) 1299 (m-
Ph) 1264 (o-Ph) 1239 (ipso-C6F5) 778 (CHOCH3) 611 (CH2CHNH2) 571 (CH(CH3)Ph)
554 (OCH3) 279 (ACH2) 257 (DCH2) 236 (CCH2) 224 (BCH2) 202 (CH3) Anal calcd ()
for C33H25BF15NO C 5303 H 337 N 187 Found 5288 H 357 N 190
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][B(C6F5)4] (221a) Part 1 In a Schlenk
tube trans-(4-CH3OC6H10)NHCH(CH3)Ph (16 mg 680 μmol) was dissolved in pentane (2 mL)
and hydrogen chloride (68 μL 027 mmol 40 M in 14-dioxane) was added drop wise White
precipitate was immediately formed The solvent was decanted and the solid was washed with
pentane (2 mL) and dried in vacuo to yield trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (163 mg
610 μmol 89)
Part 2 In the glovebox a 4 dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph
HCl (61 mg 0026 mmol) in dichloromethane (8 mL) and K B(C6F5)4 (162 mg 260 mmol)
was added at once The reaction was allowed to stir for 16 h at room temperature The mixture
was filtered through Celite and the solvent was removed under vacuum The product was
obtained as a white solid (209 mg 230 μmol 88)
1H NMR (400 MHz C6D5Br) δ 719 (m 2H m-Ph) 690 (m 3H o p-Ph) 510 (br s 2H NH2)
402 (q 3JH-H = 69 Hz 1H CH(CH3)Ph) 310 (s 3H OCH3) 272 (m 2H CyCHOCH3 CyCHN) 174 (m 3H CyCH2) 156 (m 1H CyCH2) 127 (d 3JH-H = 69 Hz 3H CH(CH3)Ph
093 - 084 (m 4H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1318 (m 2F o-C6F5) -1610 (t 3JF-F = 21 Hz 1F p-C6F5) -1653 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -164 (s
B(C6F5)4)
Synthesis of trans-[(4-CH3OC6H10)NH2CH(CH3)Ph][HB(C6F5)3] (221b) In the glovebox a 4
dram vial was charged with trans-4-(CH3OC6H10)NHCH(CH3)Ph HCl (93 mg 0034 mmol) in
dichloromethane (8 mL) and Na HB(C6F5)3 (185 mg 340 μmol) was added at once The
69
reaction was allowed to stir for 16 h at room temperature The mixture was filtered through
Celite and the solvent was removed under vacuum The product was obtained as a white solid
(193 mg 260 μmol 76) Preparation of Na HB(C6F5)3 is reported in Chapter 3
1H NMR (400 MHz C6D5Br) δ 716 (m 3H Ph) 702 (m 2H Ph) 546 (br 2H NH2) 407 (q 3JH-H = 68 Hz 1H CH(CH3)Ph) 347 (br q 1JB-H = 78 Hz 1H BH) 307 (s 3H OCH3) 283
(tt 3JH-H = 106 Hz 46 Hz 1H CyCHOCH3) 268 (tt 3JH-H = 117 Hz 39 Hz 1H CyCHN) 183
(m 3H CyCH2) 156 (dm 3JH-H = 128 Hz 1H CyCH2) 132 (d 3JH-H = 68 Hz CH(CH3)Ph)
121 (m 2H CyCH2) 084 (m 2H CyCH2) 19F NMR (377 MHz C6D5Br) δ -1334 (m 2F o-
C6F5) -1604 (t 3JF-F = 22 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz
C6D5Br) δ -238 (d 1JB-H = 78 Hz BH)
Synthesis of [C6H10NH(iPr)][CH3OB(C6F5)3] (222) In the glovebox a Schlenk tube (25 mL)
was charged with trans-(4-CH3OC6H10)NH(iPr) (253 mg 0148 mmol) in toluene (05 mL) and
B(C6F5) (758 mg 0148 mmol) dissolved in toluene (05 mL) was added at once The Schlenk
was sealed and heated at 110 degC for 2 h and the solvent was removed under vacuum The crude
solid was washed with pentane (2 mL) to yield the product as a white solid (991 mg 0145
mmol 98) Crystals suitable for X-ray diffraction were obtained from a layered solution of
dichloromethanepentane at -30 degC
1H NMR (500 MHz CD2Cl2) δ 810 (s 1H NH) 413 (m 2H CH2CH) 315 (m 3JH-H = 66
Hz 1H iPr) 302 (s 3H BOCH3) 222 (dm 1JH-H = 93 Hz 2H ACH2) 205 (dm 1JH-H = 100
Hz 2H BCH2) 181 (dm 1JH-H = 100 Hz 2H BCH2) 172 (dm 1JH-H = 93 Hz 2H ACH2) 136
(d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz CD2Cl2) δ -1351 (br 2F o-C6F5) -1620 (t 3JF-F = 20 Hz 1F p-C6F5) -1664 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -242 (s
BOCH3) 13C1H NMR (125 MHz CD2Cl2) δ 1482 (dm 1JC-F = 241 Hz C6F5) 1388 (dm 1JC-F = 262 Hz C6F5) 1370 (dm 1JC-F = 252 Hz C6F5) 1231 (ipso-C6F5) 634 (CH2CH) 522
(BOCH3) 502 (iPr) 274 (ACH2) 258 (BCH2) 185 (iPr) Anal calcd () for C28H21BF15N05
CH2Cl2 C 4717 H 306 N 193 Found 4674 H 327 N 199 HRMS-DART mz [M] calcd
for C9H18N+ 1401 Found 1401
Synthesis of [C6H10NH(iPr)][HB(C6F5)3] (223) Method 1 In the glovebox trans-(4-
CH3OC6H10)NH(iPr) (250 mg 0150 mmol) and B(C6F5)3 (760 mg 0150 mmol) were
dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The tube was
70
degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4
atm) at -196 ordmC The reaction was complete after 12 h at 110 degC The solvent was removed under
vacuum and the residue was washed with pentane (2 mL) The product was collected as a white
powder (607 mg 930 μmol 62)
Method 2 In the glovebox compound [C6H10NH(iPr)][CH3OB(C6F5)3] (222) (200 mg 290
μmol) was dissolved in d8-toluene (04 mL) and added into a Teflon capped J-Young tube The
tube was degassed once through a freeze-pump-thaw cycle on the vacuumH2 line and filled with
H2 (4 atm) at -196 ordmC The reaction was complete after 12 h at 110 degC
1H NMR (400 MHz C6D5Br) δ 510 (br m 1H NH) 367 (br q 1JB-H = 76 Hz 1H BH) 347
(br s 2H CH) 242 (m 1H iPr) 162 (m 2H CH2) 131 (m 2H CH2) 111 (m 2H CH2) 093
(m 2H CH2) 138 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz C6D5Br) δ -1338 (m 3JF-F
= 21 Hz 2F o-C6F5) -1622 (t 3JF-F = 21 Hz 1F p-C6F5) -1658 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -239 (d 1JB-H = 76 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483
(dm 1JC-F = 235 Hz CF) 1381 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 248 Hz CF) 1242
(ipso-C6F5) 636 (CHCH2) 500 (iPr) 271 (CH2) 248 (CH2) 186 (iPr) Anal calcd () for
C27H19BF15N C 4964 H 293 N 214 Found C 4924 H 300 N 214
Compounds 224 - 235 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 50 mL Teflon screw cap Schlenk tube equipped with a stir bar was charged
with a solution of B(C6F5)3 (0379 g 0740 mmol) and the respective N-heterocycle in toluene (5
mL) The reaction tube was degassed three times through a freeze-pump-thaw cycle on the
vacuumH2 line and filled with H2 (4 atm) at -196 ordmC After the addition of H2 the reaction tube
was placed in a 115 ordmC oil bath for the indicated reaction time The solvent was then removed
under vacuum and the crude product was washed with pentane to yield the product as a white
solid
[26-Ph2C5H8NH2][HB(C6F5)3] (224) 26-Diphenylpyridine (171 mg 0740 mmol) reaction
time 16 h product (511 g 0680 mmol 92) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC Isomer ratio by 1HNMR
spectroscopy meso 91 rac 9
71
meso-[26-Ph2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 734 (tt 3JH-H = 70 Hz
4JH-H = 24 Hz 2H p-Ph) 726 (m 8H o m-Ph) 590 (br 2H NH2) 453 (m 3JH-H = 122 Hz 3JH-H = 24 Hz 2H C(H)Ph) 339 (br q 1JB-H = 90 Hz 1H BH) 226 (br m 3H CH2) 212 (m
2H CH2) 189 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1340 (m 2F o-C6F5) -1634 (t 3JF-F = 20 Hz 1F p-C6F5) -1666 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -246 (d 1JB-H = 90 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1483 (dm 1JC-F = 237 Hz CF) 1380
(dm 1JC-F = 244 Hz CF) 1367 (dm 1JC-F = 246 Hz CF) 1338 (ipso-Ph) 1313 (p-Ph) 1271
(Ph) 1264 (Ph) 1241 (ipso-C6F5) 657 (C(H)(Ph)) 297 (CH2) 233 (CH2) Anal calcd ()
for C35H21BF15N C 5595 H 282 N 186 Found C 5547 H 303 N 186
[26-Me2C5H8NH2][HB(C6F5)3] (225) 26-Dimethylpyridine (793 mg 0740 mmol) reaction
time 60 h product (390 mg 0621 mmol 84) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC over 48 h Isomer ratio by 1HNMR spectroscopy meso 80 rac 20
meso-[26-Me2C5H8NH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 508 (br 2H NH2) 345
(br q 1JB-H = 83 Hz 1H BH) 268 (m 2H NC(H)Me) 137 (m 4H CH2) 086 (d 3JH-H = 64
Hz 6H CH3) 077 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1341 (m 2F o-C6F5) -
1617 (t 3JF-F = 20 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 83 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1485 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1370 (dm 1JC-F = 249 Hz CF) 1236 (ipso-C6F5) 567
(NCH) 303 (CH2) 220 (CH2) 193 (CH3) Anal calcd () for C25H17BF15N C 4787 H 273
N 223 Found C 4764 H 290 N 222
(2-(EtOCO)C5H9NH)B(C6F5)3 (226) Ethyl 2-picolinate (112 mg 0740 mmol) reaction time
36 h product (366 mg 0547 mmol 74) The isolated product consisted of an equal ratio of
both diastereomers Anal calcd () for C26H15BF15NO2 C 4667 H 226 N 209 Found C
4660 H 247 N 211
RSSR-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2)
δ 590 (m 1H NH) 430 (m 1H CH(H)NH) 418 (br m 1H
CHOCOEt) 393 (dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 373
(dq 2JH-H = 108 Hz 3JH-H = 71 Hz 1H Et) 320 (dm 2JH-H = 126 Hz 1H CH(H)NH) 217
(m 2H CH2) 204 (dm 2JH-H = 134 Hz 1H CH2) 184 (m 1H CH2) 175 (m 1H CH2) 119
72
(t 3JH-H = 72 Hz 3H Et) 103 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1264 (m 1F o-
C6F5) -1280 (m 1F o-C6F5) -1295 (m 1F o-C6F5) -1297 (m 1F o-C6F5) -1404 (m 1F o-
C6F5) -1433 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1573 (t 3JF-F = 21 Hz 1F
p-C6F5) -1575 (t 3JF-F = - 21 Hz 1F p-C6F5) -1616 (m 1F m-C6F5) -1621 (m 1F m-C6F5) -
1628 (m 1F m-C6F5) -1631 (m 1F m-C6F5) -1640 (m 1F m-C6F5) -1649 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -486 (s BNH) 13C1H NMR (101 MHz CD2Cl2) δ 1674
(OCO) 636 (Et) 568 (CHOCOEt) 445 (CH(H)NH) 305 (CH2) 208 (CH2) 181 (CH2) 134
(Et)
RRSS-[2-(OCOEt)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ
743 (br m 1H NH) 440 (dq 2JH-H = 107 Hz 3JH-H = 71 Hz 1H Et)
438 (dq 2JH-H = 91 Hz 3JH-H = 71 Hz 1H Et) 424 (br m 1H
CHOCOEt) 350 (ddd 2JH-H = 134 Hz 3JH-H = 89 Hz 3JH-H = 49 Hz 1H CH(H)NH) 333
(dm JH-H = 133 Hz 1H CH(H)NH) 218 (m 1H CH2) 208 (m 1H CH2) 185 (m 1H CH2)
154 (m 1H CH2) 151 (m 1H CH2) 135 (t 3JH-H = 71 Hz 3H Et) 124 (m 1H CH2) 19F
NMR (377 MHz CD2Cl2) δ -1276 (m 1F o-C6F5) -1285 (m 2F o-C6F5) -1291 (m 1F o-
C6F5) -1371 (m 1F o-C6F5) -1421 (m 1F o-C6F5) -1549 (t 3JF-F = 21 Hz 1F p-C6F5) -
1572 (t 3JF-F = 21 Hz 1F p-C6F5) -1578 (t 3JF-F = 21 Hz 1F p-C6F5) -1618 (m 1F m-C6F5)
-1626 (m 1F m-C6F5) -1630 (m 3F m-C6F5) -1633 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -486 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1712 (OCO) 616 (Et) 581
(CHOCOEt) 457 (CH(H)NH) 259 (CH2) 235 (CH2) 171 (CH2) 139 (Et)
(2-PhC5H9NH)B(C6F5)3 (227a) and [2-PhC5H9NH2][HB(C6F5)3] (227b) 2-Phenylpyridine
(115 mg 0740 mmol) reaction time 48 h product (269 mg 0400 mmol 54) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC The isolated product consisted of 227a (RSSR 70) 227a (SSRR 10) 227b (20)
Anal calcd () for C29H15BF15N C 5158 H 254 N 209 Found C 5209 H 258 N 210
RSSR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 727
(m 2H Ph) 714 (m 3H Ph) 555 (br s 1H NH) 415 (ddd 3JH-H = 111
Hz 3JH-H = 94 Hz 36 Hz 1H CHPh) 356 (dm 2JH-H = 132 Hz 1H CH(H)NH) 257 (ddd 2JH-H = 132 Hz 3JH-H = 103 Hz 3JH-H = 31 Hz 1H CH(H)NH) 199 - 135 (m 6H CH2) 19F
NMR (377 MHz C6D5Br) δ -1216 (m 1F o-C6F5) -1236 (m 1F o-C6F5) -1274 (m 1F o-
73
C6F5) -1286 (m 1F o-C6F5) -1312 (m 1F o-C6F5) -1426 (m 1F o-C6F5) -1534 (t 3JF-F =
22 Hz 1F p-C6F5) -1566 (t 3JF-F = 21 Hz 1F p-C6F5) -1567 (t 3JF-F = 21 Hz 1F p-C6F5) -
1615 (m 2F m-C6F5) -1620 (m 3F m-C6F5) -1624 (m 1F m-C6F5) 11B NMR (128 MHz
CD2Cl2) δ -391 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1385 (ipso-Ph) 1297 (p-Ph)
1291 (Ph) 1285 (Ph) 646 (CHPh) 521 (NCH2) 355 (CH2) 248 (CH2) 219 (CH2)
SSRR-[2-(Ph)C5H9NHB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 710 -
681 (m 5H Ph) 581 (br s 1H NH) 449 (m 1H CHPh) 347 (dm 2JH-H = 125 Hz 1H CH(H)NH) 321 (m 2JH-H = 125 Hz 1H CH(H)NH) 185 (m 2H CH2)
176 (m 2H CH2) 128 (m 2H CH2) 19F NMR (377 MHz C6D5Br) δ -1249 (m 1F o-C6F5)
-1263 (m 1F o-C6F5) -1268 (m 1F o-C6F5) -1287 (m 1F o-C6F5) -1390 (m 1F o-C6F5) -
1431 (m 1F o-C6F5) -1555 (t 3JF-F = 21 Hz 1F p-C6F5) -1559 (t 3JF-F = 21 Hz 1F p-C6F5)
-1562 (t 3JF-F = 21 Hz 1F p-C6F5) -1598 (m 1F m-C6F5) -1610 (m 1F m-C6F5) -1617 (m
1F m-C6F5) -1620 (m 1F m-C6F5) -1622 (m 1F m-C6F5) -1643 (m 1F m-C6F5) 11B NMR
(128 MHz CD2Cl2) δ -39 (s BN) 13C1H NMR (101 MHz CD2Cl2) δ 1365 (ipso-Ph)1294
(p-Ph) 1283 (Ph) 1256 (Ph) 629 (CHPh) 454 (NCH2) 350 (CH2) 297 (CH2) 260 (CH2)
[2-PhC5H9NH2][HB(C6F5)3] (227b) 1H NMR (400 MHz CD2Cl2) δ 710 - 681 (m 5H Ph)
557 (br s 2H NH2) 355 (dd 3JH-H = 117 Hz 28 Hz 1H CHPh) 330 (br q 1JB-H = 86 Hz
1H BH) 295 (dm JH-H = 124 Hz 1H CH(H)NH2) 244 (pseudo td JH-H = 124 Hz 3JH-H = 30
Hz 1H CH(H)NH2) 186 (m 2H CH2) 165 (m 1H CH2) 157 (m 1H CH2) 141 (m 1H
CH2) 137 (m 1H CH2) 19F NMR (377 MHz CD2Cl2) δ -1344 (m 2F o-C6F5) -1610 (t 3JF-
F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -248 (d 1JB-H
= 86 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1399 (ipso-Ph) 1297 (Ph) 1295 (p-Ph)
1267 (Ph) 625 (CHPh) 471 (NCH2) 327 (CH2) 242 (CH2) 240 (CH2)
[2-MeC9H15NH2][HB(C6F5)3] (228) 2-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (331 mg 500 mmol 67) Crystals suitable for X-ray diffraction were grown from
a layered solution of dichloromethanepentane at -30 ordmC About 60 of the isolated reaction
product consisted of the SSSRRR diastereomer
1H NMR (400 MHz C6D5Br) δ 602 (br 1H NH2) 460 (br 1H NH2) 336 (br q 1JB-H = 83
Hz 1H BH) 315 (dt 3JH-H = 100 Hz 52 Hz 1H NCHCH) 276 (m 1H CHMe) 145 - 096
(m 8H CH2) 110 (m 1H CHCHN) 093 - 067 (m 4H CH2) 081 (d 3JH-H = 64 Hz 3H
74
Me) 19F NMR (377 MHz C6D5Br) δ -1335 (m 2F o-C6F5) -1607 (t 3JF-F = 22 Hz 1F p-
C6F5) -1646 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 83 Hz BH)
13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1384 (dm 1JC-F = 246
Hz CF) 1369 (dm 1JC-F = 249 Hz CF) 1233 (ipso-C6F5) 577 (NCH) 493 (CHMe) 322
(CHCHN) 281 (CH2) 272 (CH2) 255 (CH2) 240 (CH2) 236 (CH2) 211 (CH2) 189 (Me)
Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C 5021 H 331 N 212
[2-PhC9H15NH2][HB(C6F5)3] (229) B(C6F5)3 (289 mg 0564 mmol) 2-phenylquinoline (116
mg 0564 mmol) reaction time 48 h product (391 mg 536 mmol 95) Crystals suitable for
X-ray diffraction were grown from a layered solution of dichloromethanepentane at -30 ordmC
About 73 of the reaction mixture consisted of the reported SSSRRR diastereomer
1H NMR (400 MHz CD2Cl2) δ 733 (tm 3JH-H = 73 Hz 1H p-Ph) 726 (tm 3JH-H = 73 Hz
2H m-Ph) 720 (dm 3JH-H = 73 Hz 2H o-Ph) 646 (br 1H NH2) 501 (br t 1H NH2) 433
(dm 3JH-H = 105 Hz 33 Hz 1H C(H)Ph) 380 (br m 1H CH2C(H)NH2) 320 (br q 1JB-H = 87
Hz 1H BH) 218 - 108 (m 13H CH2C(H)CH2 and CH2) 19F NMR (377 MHz C6D5Br) δ -
1334 (m 2F o-C6F5) -1612 (t 3JF-F = 21 Hz 1F p-C6F5) -1647 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -242 (d 1JB-H = 87 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1342
(ipso-Ph) 1312 (p-Ph) 1301 (m-Ph) 1269 (o-Ph) 647 (CH2C(H)NH2) 601 (C(H)Ph) 345
(CH2C(H)CH2) 291 (CH2) 285 (CH2) 251 (CH2) 249 (CH2) 248 (CH2) 197 (CH2) Anal
calcd () for C33H23BF15N C 5434 H 318 N 192 Found C 5431 H 331 N 192
[8-MeC9H15NH2][HB(C6F5)3] (230) 8-Methylquinoline (106 mg 0740 mmol) reaction time
48 h product (375 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC The reported SSSRRR
diastereomer was only observed
1H NMR (400 MHz C6D5Br) δ 555 (br 1H NH2) 497 (br 1H NH2) 352 (br q 1JB-H = 80
Hz 1H BH) 327 (dm 2JH-H = 121 Hz 1H NH2CH(H)) 263 (dm 3JH-H = 112 Hz coupling to
NH2 is observed in 1H1H-cosy 1H CHN) 252 (qt 2JH-H = 121 Hz 3JH-H = 27 Hz 1H
NH2CH(H)) 141 - 133 (br m 2H CH2) 134 (m 1H CH2CHCH2) 125 - 114 (br m 4H
CH2) 122 (m 1H CHMe) 102 (m 1H CH2) 089 (m 2H CH2) 063 (d 3JH-H = 75 Hz 3H
Me) 058 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1343 (m 2F o-C6F5) -1618 (t 3JF-F
= 21 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -242 (d 1JB-H =
75
80 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1484 (dm 1JC-F = 234 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1368 (dm 1JC-F = 249 Hz CF) 1237 (ipso-C6F5) 632 (CHN) 478
(NH2CH(H)) 339 (CH2CHCH2) 337 (CHMe) 271 (CH2) 268 (CH2) 243 (CH2) 231 (CH2)
178 (CH2) 163 (Me) Anal calcd () for C28H21BF15N C 5040 H 317 N 210 Found C
5026 H 330 N 209
[C13H22NH2][HB(C6F5)3] (231a) Acridine (132 mg 0740 mmol) reaction time 36 h product
(398 mg 0562 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at 25 ordmC The isolated product is a mixture of the SRSRRSRS
and RRSSSSRR isomers in a 11 ratio The SRSRRSRS was separated by crystallization
1H NMR (400 MHz CD2Cl2) δ 626 (br m 1H NH2) 513 (br m 1H NH2) 327 (br q 1JB-H =
86 Hz 1H BH) 285 (dm 3JH-H = 111 Hz 40 Hz 2H CHN) 182 (m 2H NH2CHCH2) 176
(m 2H CyCH2) 175 (m 1H CHCH2CH) 171 (m 2H CyCH2) 167 (m 2H CyCH2) 144 (qt 3JH-H = 111 Hz 3JH-H = 40 Hz 2H CH2CHCH2) 123 (m 2H CyCH2) 122 (m 2H
NH2CHCH2) 118 (m 2H CyCH2) 101 (m 2H CyCH2) 100 (m 1H CHCH2CH) 19F NMR
(377 MHz CD2Cl2) δ -1345 (m 2F o-C6F5) -1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -244 (d 1JB-H = 86 Hz BH) 13C1H NMR (101
MHz CD2Cl2) partial δ 639 (CHN) 406 (CH2CHCH2) 371 (CHCH2CH) 318 (CyCH2) 307
(NH2CHCH2) 249 (CyCH2) 248 (CyCH2) Anal calcd () for C31H25BF15N C 5264 H 356
N 198 Found C 5214 H 358 N 196
Synthesis of RRSSSSRR and SRSRRSRS-[(C13H22NH)B(C6F5)3] (231b) Compound 231b
was initially isolated from the pentane wash work-up for the synthesis of 231a Independent
synthesis of 231b was performed and the procedure is described
In a 4 dram vial tetradecahydroacridine (366 mg 0189 mmol) was dissolved in pentane (5
mL) at room temperature To the vial B(C6F5)3 (965 mg 0189 mmol) was added at once and
allowed to mix for 2 minutes The solution was filtered through a bed of Celite to yield a
colourless solution The vial was placed in a -30 ordmC freezer for 3 h and colourless crystals were
collected (973 mg 138 mmol 73) The isolated mixture of compound 231b consisted of a 11
mixture of RRSSSSRR and SRSRRSRS (C13H22NH)B(C6F5)3 only the diagnostic resonances of
RRSSSSRR-(C13H22NH)B(C6F5)3 have been reported
76
RRSSSSRR-[(C13H22NH)B(C6F5)3] 1H NMR (400 MHz CD2Cl2) δ 503 (br 1H NH) 353
(dm 3JH-H = 123 Hz 2H NCH) 214 (dm JH-H = 123 Hz 2H NH2CHCH2) 196 - 160 (m
6H CH2) 188 (m 2H CH2CHCH2) 177 (m 4H NH2CHCH2 and CHCH2CH) 149 - 111 (m
6H CH2) 19F NMR (377 MHz CD2Cl2) δ -1270 (m 1F o-C6F5) -1277 (m 1F o-C6F5) -
1281 (m 1F o-C6F5) -1291 (m 2F o-C6F5) -1302 (m 1F o-C6F5) -1558 (t 3JH-H = 21 Hz
1F p-C6F5) -1579 (t 3JH-H = 21 Hz 1F p-C6F5) -1589 (t 3JH-H = 21 Hz 1F p-C6F5) -1624
(m 1F m-C6F5) -1637 (m 3F m-C6F5) -1641 8 (m 1F m-C6F5) -1644 8 (m 1F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -318 (s BN) 13C1H NMR (101 MHz CD2Cl2) partial δ
630 (NCH) 359 (CHCH2CH) 356 (CH2CHCH2) 299 (NH2CHCH2) Anal calcd () for
C31H23BF15N C 5279 H 329 N 199 Found C 5266 H 328 N 196
[23-(C4H6Me)2NHNH2][HB(C6F5)3] (232) 23-Dimethylquinoxaline (0117 g 0740 mmol)
reaction time 96 h product (402 mg 437 mmol 59) The SRSSRSRR diastereomer was only
observed
1H NMR (400 MHz CD2Cl2) δ 643 (br 1H NH2) 592 (br 1H NH2) 349 (dm 3JH-H = 128
Hz 1H CH2CHN) 334 (br q 1JB-H = 94 Hz 1H BH) 326 (br m 2H NCHMe CH2CHN)
281 (dq 3JH-H = 123 Hz 64 Hz 1H NCHMe) 223 (dm JH-H = 128 Hz 1H CH2) 189 (dm
JH-H = 134 Hz 1H CH2) 179 (dm JH-H = 134 Hz 1H CH2) 162 (dm JH-H = 134 Hz 2H
CH2) 147 (m 1H CH2) 131 (m 1H CH2) 128 (d 3JH-H = 64 Hz 3H Me) 121 (d 3JH-H =
62 Hz 3H Me) 120 (m 1H CH2) (NH was not observed) 19F NMR (377 MHz C6D5Br) δ -
1336 (m 2F o-C6F5) -1607 (t 3JF-F = 21 Hz 1F p-C6F5) -1646 (m 2F m-C6F5) 11B NMR
(128 MHz C6D5Br) δ -241 (d 1JB-H = 94 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1481
(dm 1JC-F = 234 Hz C6F5) 1384 (dm 1JC-F = 246 Hz C6F5) 1368 (dm 1JC-F = 247 Hz C6F5)
1232 (ipso-C6F5) 576 (CH2CHN) 563 (NCHMe) 541 (NCHMe) 519 (CH2CHN) 304
(CH2) 242 (CH2) 224 (CH2) 185 (CH2) 178 (Me) 151 (Me) Anal calcd () for
C28H22BF15N C 4929 H 325 N 411 Found C 4909 H 333 N 421
[23-(C4H6Ph)2NHNH2][HB(C6F5)3] (233) 23-Diphenylquinoxaline (0209 g 0740 mmol)
reaction time 96 h product (328 mg 0407 mmol 55) Crystals suitable for X-ray diffraction
were grown from a layered solution of dichloromethanepentane at RT Diastereomers
SRSSRSRR and RRRSSSSR are present in equal ratios The assigned diastereomers were
77
supported by 1H1H NOESY NMR spectroscopy Anal calcd () for C38H26BF15N2 C 5660
H 325 N 347 Found C 5611 H 313 N 321
SRSSRSRR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (400 MHz C6D5Br) δ 763 (m 4H
Ph) 699 - 684 (m 6H Ph) 572 (br 2H NH2) 476 (d 3JH-H = 34 Hz 1H CHPh) 441 (d 3JH-H = 34 Hz 1H CHPh) 407 (br 1H NH) 356 (br q 1JB-H = 82 Hz 1H BH) 314 (td 3JH-H
= 102 Hz 3JH-H = 34 Hz 1H CH2CHN) 260 (m 3JH-H = 102 Hz 34 Hz 1H CH2CHN) 167
(m 1H CH2) 159 (m 1H CH2) 153 (m 1H CH2) 129 (m 1H CH2) 122 (m 2H CH2)
121 (m 1H CH2) 086 (m 1H CH2) 19F NMR (377 MHz C6D5Br) δ -1331 (m 2F o-C6F5)
-1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -
238 (d 1JB-H = 82 Hz BH) 13C1H NMR (101 MHz C6D5Br) δ 1483 (dm 1JC-F = 235 Hz
CF) 1385 (dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 248 Hz CF) 1362 (ipso-Ph) 1313
(Ph) 1301 (Ph) 1267 (Ph) 637 (CHPh) 619 (CHPh) 597 (CH2CHN) 561 (CH2CHN) 314
(CH2) 282 (CH2) 242 (CH2) 233 (CH2) (ipso-C6F5 was not observed)
RRRSSSSR-[23-(C4H6Ph)2NHNH2][HB(C6F5)3] 1H NMR (500 MHz CD2Cl2) δ 729 - 708
(m 10H Ph) 657 (br 2H NH2) 451 (dm 3JH-H = 102 Hz 1H CHPh) 429 (dm 3JH-H = 102
Hz 1H CHPh) 386 (dm 3JH-H = 107 Hz 1H CH2CHN) 366 (br 1H NH) 328 (br q 1JB-H =
82 Hz 1H BH) 268 (dm 3JH-H = 107 Hz 1H CH2CHN) 205 (m 1H CH2) 188 (m 2H
CH2) 178 (m 2H CH2) 157 (m 1H CH2) 145 (m 1H CH2) 130 (m 1H CH2) 19F NMR
(377 MHz C6D5Br) δ -1331 (m 2F o-C6F5) -1606 (t 3JF-F = 21 Hz 1F p-C6F5) -1643 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -238 (d 1JB-H = 82 Hz BH) 13C1H NMR (125
MHz CD2Cl2) δ 1479 (dm 1JC-F = 235 Hz CF) 1382 (dm 1JC-F = 246 Hz CF) 1366 (dm 1JC-F = 248 Hz CF) 1314 (ipso-Ph) 1304 (Ph) 1301 (ipso-Ph) 1293 (Ph) 1290 (Ph) 1286
(Ph) 1277 (Ph) 1274 (Ph) 1226 (ipso-C6F5) 655 (CHPh) 621 (CHPh) 581 (CH2CHN)
526 (CH2CHN) 308 (CH2) 245 (CH2) 229 (CH2) 188 (CH2)
[(C6H4)C7H12NH2][HB(C6F5)3] (234) 78-Benzoquinoline (133 mg 0740 mmol) reaction
time 48 h product (285 mg 407 mmol 55) Crystals of the SRRS isomer suitable for X-ray
diffraction were grown from a layered solution of bromobenzenepentane at -30 ordmC Crystals of
the SSRR isomer suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC Anal calcd () for C31H19BF15N C 5309 H 273 N 200
Found C 5347 H 291 N 209
78
Isomer ratio by 1HNMR spectroscopy SRRS 80 (pale orange crystals) SSRR 20 (colourless
crystals)
SRRS-[(C6H4)C7H12NH2][HB(C6F5)3] (234a) 1H NMR (400 MHz CD2Cl2) δ 725 (td 3JH-H
= 77 Hz 4JH-H = 14 Hz 1H C6H4) 715 (d 3JH-H = 77 Hz 1H C6H4) 707 (d 3JH-H = 77 Hz
1H C6H4) 700 (t 3JH-H = 77 Hz 1H C6H4) 597 (br 2H NH2) 440 (d 3JH-H = 38 Hz 1H
NCH) 361 (dt JH-H = 131 Hz 3JH-H = 35 Hz 1H NCH(H)) 328 (m 1H NCH(H)) 314 (br q 1JB-H = 80 Hz 1H BH) 294 (dm 2JH-H = 172 Hz 1H C6H4-CH(H)) 285 (dm 2JH-H = 172 Hz
1H C6H4-CH(H)) 239 (m 1H CH2CHCH2) 200 - 188 (br m 6H PiperidineCyCH2) 19F NMR
(377 MHz C6D5Br) δ -1345 (m 2F o-C6F5) -1621 (t 3JF-F = 21 Hz 1F p-C6F5) -1657 (m
2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -241 (d 1JB-H = 80 Hz BH) 13C1H NMR (101
MHz CD2Cl2) δ 1483 (dm 1JC-F = 235 Hz CF) 1383 (dm 1JC-F = 246 Hz CF) 1378
(quaternary C for C6H4-CHN) 1368 (dm 1JC-F = 248 CF) 1311 (C6H4) 1307 (C6H4) 1292
(C6H4) 1288 (quaternary C for C6H4-CH2) 1277 (C6H4) 1234 (ipso-C6F5) 605 (NCH) 479
(NCH2) 320 (CH2CHCH2) 286 (C6H4-CH(H)) 274 (PiperidineCH2) 225 (CyCH2) 184
(PiperidineCH2)
SSRR-[(C6H4)C7H12NH2][HB(C6F5)3] (234b) 1H NMR (400 MHz C6D5Br) partial δ 701
(m 1H C6H4) 699 (m 1H C6H4) 685 (m 1H C6H4) 675 (d 3JH-H = 77 Hz 1H C6H4) 350
(d 3JH-H = 104 Hz 1H NCH) 324 (br dm JH-H = 124 Hz 1H NCH(H)) 279 (m 1H
NCH(H)) 254 (m 1H C6H4-CH(H)) 242 (m 1H C6H4-CH(H)) 142 (m 2H CH2) 128 (m
2H CH2) 105 (m 1H CH2CHCH2) 083 (m 2H CH2) (NH2 was not observed) 13C1H
NMR (101 MHz C6D5Br) δ 1370 (quaternary C for C6H4-CHN) 1304 (C6H4) 1291 (C6H4)
1284 (quaternary C for C6H4-CH2) 1264 (C6H4) 1226 (C6H4) 629 (NCH) 474 (NCH2) 378
(CH2CHCH2) 291 (CH2) 288 (C6H4-CH(H)) 276 (CH2) 229 (CH2)
[(C5H3N)(CH2)2(C5H8NH)B(C6F5)2][HB(C6F5)3] (235) B(C6F5)3 (379 mg 0740 mmol) 110-
phenanthroline (667 mg 0370 mmol) reaction time 96 h product (283 mg 0270 mmol 73)
Crystals suitable for X-ray diffraction were grown from a layered solution of
tetrahydrofuranpentane at -30 ordmC Approximately 65 of the reaction mixture consisted of the
SRSRSR diastereomer
1H NMR (400 MHz CD2Cl2) δ 944 (br s 1H NH) 850 (dd JH-H = 47 Hz JH-H = 15 Hz 1H
C5H3N) 744 (dd JH-H = 78 Hz JH-H = 15 Hz 1H C5H3N) 722 (dd JH-H = 78 Hz JH-H = 47
79
Hz 1H C5H3N) 442 (d 3JH-H = 43 Hz 1H NCyCH) 342 (br 1H BH) 322 (dm 2JH-H = 138
Hz 1H NC(H)H) 291 (ddd 2JH-H = 138 Hz 3JH-H = 87 Hz 53 Hz 1H NC(H)H) 276 - 272
(m 2H C6H4-CH(H)) 212 (dm 3JH-H = 121 Hz 38 Hz 1H CH2CHCH2) 196 (m 1H CH2)
188 (m 1H CH2) 173 (m 1H CH2) 132 (dt 2JH-H = 140 Hz 3JH-H = 32 Hz 1H CH2) 091
(qd JH-H = 131 Hz 3JH-H = 38 Hz 1H CH2) 071 (qt JH-H = 137 Hz 3JH-H = 40 Hz 1H CH2)
19F NMR (377 MHz CD2Cl2) δ -1289 (m 2F B(C6F5)2o-C6F5) -1343 (m 6F HB(C6F5)3o-C6F5) -
1348 (m 2F B(C6F5)2o-C6F5) -1491 (t 3JF-F = 20 Hz 1F B(C6F5)2p-C6F5) -1511 (t 3JF-F = 20 Hz
1F B(C6F5)2p-C6F5) -1596 (m 4F B(C6F5)2m-C6F5) -1645 (t 3JF-F = 20 Hz 3F HB(C6F5)3p-C6F5) -
1676 (m 6F HB(C6F5)3m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 391 (s BN) -254 (d 1JB-H =
93 Hz BH) 13C1H NMR (101 MHz CD2Cl2) δ 1484 (quaternary C for C5H3N) 1466
(quaternary C for C5H3N) 1448 (C5H3N) 1354 (C5H3N) 1260 (C5H3N) 581 (CyNCH) 451
(NC(H)H) 296 (CH2C(H)CH2) 241 (CH2) 218 (CH2) 210 (CH2) 206 (CH2) Anal calcd
() for C42H17B2F25N2 C 4822 H 164 N 268 Found C 4783 H 197 N 269
243 X-Ray Crystallography
2431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
2432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
80
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
81
2433 Selected crystallographic data
Table 24 ndash Selected crystallographic data for 24 24rsquo and 25
24 24rsquo 25
Formula C27H21B1F15N1 C27H13B1F15N1 C30H25B1F15N1
Formula wt 65526 64719 69532
Crystal system monoclinic orthorhombic monoclinic
Space group P2(1)c P2(1)2(1)2(1) P2(1)n
a(Aring) 97241(8) 116228(4) 126342(6)
b(Aring) 147348(12) 181284(7) 181939(8)
c(Aring) 188022(15) 236578(9) 128612(6)
α(ordm) 9000 9000 9000
β(ordm) 98826(4) 9000 90269(2)
γ(ordm) 9000 9000 9000
V(Aring3) 26621(4) 49848(3) 29563(2)
Z 4 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1635 1725 1562
Abs coeff μ mm-1 0169 0179 0157
Data collected 18591 28169 50674
Rint 00336 00297 00369
Data used 4685 8773 5207
Variables 401 793 424
R (gt2σ) 00361 00315 00352
wR2 00898 00758 00947
GOF 1007 1021 1024
82
Table 25 ndash Selected crystallographic data for 216a 218 and 219
216a 218 219
Formula C27H20B1F16N1 C27H18B1F16N1 C32H21B1F15N1
Formula wt 67325 67123 71533
Crystal system monoclinic monoclinic orthorhombic
Space group P2(1)c P2(1)n Pbca
a(Aring) 97677(6) 104368(7) 18886(4)
b(Aring) 147079(11) 93382(7) 16050(3)
c(Aring) 190576(14) 273881(18) 19128(4)
α(ordm) 9000 9000 9000
β(ordm) 98934(2) 96910(3) 9000
γ(ordm) 9000 9000 9000
V(Aring3) 27046(3) 26499(3) 5798(2)
Z 4 4 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1653 1683 16388
Abs coeff μ mm-1 0174 0177 0163
Data collected 23565 17203 50412
Rint 00432 00404 00662
Data used 6164 4676 6654
Variables 406 408 442
R (gt2σ) 00522 00496 00687
wR2 01387 01462 01912
GOF 1032 1041 10743
83
Table 26 ndash Selected crystallographic data for 220 222 and 224
220 222 (+05 CH2Cl2) 224 (+05 CH2Cl2)
Formula C33H25B1F15N1O1 C285H22B1Cl1F15N1O1 C355H22B1ClF15N1
Formula wt 74737 72573 79380
Crystal system orthorhombic orthorhombic monoclinic
Space group Pbca Pbca P2(1)n
a(Aring) 173531(15) 17750(5) 109902(9)
b(Aring) 161365(15) 16032(4) 151213(11)
c(Aring) 227522(17) 20783(6) 194765(15)
α(ordm) 9000 9000 90
β(ordm) 9000 96910(3) 92062(3)
γ(ordm) 9000 9000 90
V(Aring3) 63710(9) 5914(3) 32346(4)
Z 8 8 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 15582 16278 1630
Abs coeff μ mm-1 0154 0250 0235
Data collected 56289 47407 22409
Rint 00406 01159 00306
Data used 7321 5198 5688
Variables 461 440 495
R (gt2σ) 00413 00811 00495
wR2 01112 02505 01363
GOF 10647 10628 0936
84
Table 27 ndash Selected crystallographic data for 225 227 and 228
225 227 (+1 C5H12) 228
Formula C25H17B1F15N1 C63H42B2F30N2 C28H21B1F15N1
Formula wt 62721 141861 66727
Crystal system triclinic monoclinic triclinic
Space group P-1 P2(1)n P-1
a(Aring) 101339(5) 137416(4) 95967(15)
b(Aring) 112923(6) 119983(4) 108364(15)
c(Aring) 118209(6) 191036(7) 14143(2)
α(ordm) 98563(2) 9000 75929(5)
β(ordm) 109751(2) 109317(2) 80009(6)
γ(ordm) 94983(2) 9000 76629(5)
V(Aring3) 124520(11) 297240(17) 13772(4)
Z 2 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1673 1585 1609
Abs coeff μ mm-1 0176 0158 0235
Data collected 18038 22150 16105
Rint 00211 00246 00351
Data used 4357 5230 4743
Variables 379 436 406
R (gt2σ) 00371 00324 00546
wR2 00964 00816 01728
GOF 1044 1014 1028
85
Table 28 ndash Selected crystallographic data for 229 230 and 231a
229 (+05 C6H5Br) 230 231a
Formula C36H255B1Br05F15N1 C28H21B1F15N1 C31H25B1F15N1
Formula wt 80784 66727 70733
Crystal system monoclinic triclinic monoclinic
Space group C2c P-1 P2(1)n
a(Aring) 201550(11) 97752(4) 112914(4)
b(Aring) 133628(11) 120580(4) 183705(7)
c(Aring) 266328(18) 121120(5) 145648(5)
α(ordm) 9000 102296(2) 9000
β(ordm) 111905(6) 100079(2) 90480(2)
γ(ordm) 9000 90901(2) 9000
V(Aring3) 66551(8) 137127(9) 302105(19)
Z 8 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1613 1616 1555
Abs coeff μ mm-1 0749 0165 0155
Data collected 54940 20198 62113
Rint 00530 00245 00383
Data used 7644 4841 7630
Variables 484 406 533
R (gt2σ) 00651 00362 00778
wR2 01802 00971 02335
GOF 1037 1036 1007
86
Table 29 ndash Selected crystallographic data for 231b 233 and 234a
231b (+05 C6H14) 233 234a (+1 CH2Cl2)
Formula C34H30B1F15N1 C38H26B1F15N2 C32H21B1Cl2F15N1
Formula wt 74840 80642 78621
Crystal system triclinic monoclinic monoclinic
Space group P-1 Pn C2c
a(Aring) 107250(6) 99895(4) 181314(6)
b(Aring) 112916(7) 115666(5) 135137(5)
c(Aring) 136756(8) 155410(6) 253612(9)
α(ordm) 70523(2) 9000 9000
β(ordm) 88868(2) 105054(2) 92594(2)
γ(ordm) 86934(2) 9000 9000
V(Aring3) 155914(16) 173405(12) 62077(4)
Z 2 2 8
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1594 1544 1677
Abs coeff μ mm-1 0155 0147 0327
Data collected 22650 31226 22749
Rint 00233 00381 00512
Data used 5479 8395 7383
Variables 460 517 475
R (gt2σ) 00371 00400 00816
wR2 01066 00893 02554
GOF 0926 1011 1024
87
Table 210 ndash Selected crystallographic data for 234b and 235
234b 235 (+1 C4H8O +1 CH2Cl2)
Formula C31H19B1F15N1 C47H27B2Cl2F25N2O1
Formula wt 70128 120323
Crystal system monoclinic triclinic
Space group P2(1)c P-1
a(Aring) 100455(5) 113115(7)
b(Aring) 118185(5) 117849(8)
c(Aring) 245940(11) 188035(12)
α(ordm) 9000 83850(3)
β(ordm) 96724(2) 88364(3)
γ(ordm) 9000 69766(3)
V(Aring3) 28998(2) 23383(3)
Z 4 2
Temp (K) 150(2) 150(2)
d(calc) gcm-3 1606 1709
Abs coeff μ mm-1 0161 0281
Data collected 20742 36083
Rint 00342 00265
Data used 5101 8235
Variables 433 712
R (gt2σ) 00438 00473
wR2 01153 01198
GOF 1012 1015
88
Chapter 3 Enabling Catalytic Ketone and Aldehyde Hydrogenation
with Frustrated Lewis Pairs
31 Introduction
The reduction of carbonyl substrates such as aldehydes ketones esters acids and anhydrides to
alcohols is one of the most fundamental and widely used reactions in synthetic chemistry269
Sodium borohydride lithium aluminum hydride and other stoichiometric reducing agents56 224
serve adequately for laboratory scale syntheses however in an industrial setting the process
demands for a more clean environmentally benign and cost-effective procedure More desirable
methods involving H2 gas or transfer hydrogenation have proven practical and circumvent the
work-up operations required for stoichiometric reagents
Heterogeneous catalysts based on PdC and PtC are certainly atom economic however some of
these catalysts are not suitable in cases where mild conditions functional group tolerance and
chemoselectivity are required Therefore substantial research has been directed towards
homogeneous catalysts involving Ir237 Rh239 Ru238 Cu269 and Os238 complexes including metal-
immobilized systems269
Despite the power of these technologies research efforts motivated by cost toxicity and low
abundance have focused on the development of first-row transition metal catalysts based on Fe
and Co210 221 Also on-going interest in the field has been devoted to the discovery of new
asymmetric hydrogenation catalysts131 208-209 263-264136 213-214 270-271 in addition to transfer
hydrogenation via the Meerwein-Ponndorf-Verley reduction procedure216
311 FLP reactivity with unsaturated C-O bonds
In 1961 Walling and Bollyky reported the first metal-free hydrogenation system demonstrating
the reduction of the non-enolizable ketone benzophenone using H2 (100 atm) and tBuOK as the
catalyst at 200 degC175-176 While more recently metal-free reductions have been demonstrated
under more mild conditions using frustrated Lewis pairs (FLPs) These combinations of
sterically encumbered main group Lewis acids and bases have been shown to effect the catalytic
hydrogenation of a variety of unsaturated organic substrates Noticeably absent from these
substrates are ketones and aldehydes This is perhaps surprising given the precedence of catalytic
89
hydrosilylation of ketones established by Piers182 Moreover a number of groups have
demonstrated the ability of FLPs to effect the reduction of CO2 using H2259 silanes169 180 182
boranes111 163 272 or ammonia-borane273 as sources of the reducing equivalents The limited
attention to hydrogenation of ketones and aldehydes has been attributed to the high oxophilicity
of electrophilic boranes72 171 Indeed in an earlier report Erker and co-workers described the
irreversible capture of benzaldehyde and trans-cinnamaldehyde (Scheme 31 top) as well as the
14-addition of conjugated ynones by the intramolecular PB FLP Mes2PCH2CH2B(C6F5)2173 A
number of stoichiometric reductions have also been reported using H2 activated PB FLPs with
an example shown in Scheme 31 (bottom)94 173
Scheme 31 ndash Reaction of Mes2PCH2CH2B(C6F5)2 with benzaldehyde and trans-cinnamaldehyde
(top) stoichiometric reduction of benzaldehyde using Mes2P(H)CH2CH2BH(C6F5)2 (bottom)
Nonetheless the group of Privalov has computed an energetically viable mechanism for ketone
reduction suggesting a process analogous to imine hydrogenation and carbonyl hydrosilylation
using B(C6F5)3 as the catalyst274 Attempts to realize this prediction experimentally have been
unsuccessful Repo et al described the stoichiometric reaction of aromatic ketones with B(C6F5)3
effecting deoxygenation of the ketone to afford (C6F5)2BOH C6F5H and the corresponding aryl
alkane (Scheme 32 a)178 Furthermore the Stephan group found that similar reduction of alkyl
ketones gave borinic esters via H2 activation hydride delivery and protonation of a C6F5 group
(Scheme 32 b)275
90
Scheme 32 minus Stoichiometric reduction of aryl ketones to aromatic hydrocarbons (a) and alkyl
ketones to borinic esters (b)
Similar degradation of B(C6F5)3 via B-C bond cleavage affording CH3OB(C6F5)2 and C6F5H was
reported by Ashley and OrsquoHare in their efforts to reduce CO2 in the presence of H2 to CH3OH259
Due to the instability of B(C6F5)3 in these transformations Wang et al approached the catalytic
ketone hydrogenation challenge computationally suggesting that a bifunctional amine-borane
FLP catalyst would be viable276 Interestingly Du et al have taken a detour from direct FLP
hydrogenation of carbonyl groups reporting the catalytic hydrogenation of silyl enol ethers using
a chiral borane to obtain a variety of optically active secondary alcohols after workup (Scheme
33)277
Scheme 33 ndash Asymmetric hydrogenation of silyl enol ethers to yield optically active secondary
alcohols
Reaction of main group species with other unsaturated C-O functionalities namely carbon
monoxide is also limited H C Brown established the synthesis of tertiary alcohols by
91
carbonylation of trialkylboranes using carbon monoxide278 although the analogous reactivity by
B-H boranes proved challenging279-282
Recently however Erker et al described the stoichiometric reduction of carbon monoxide by the
reaction of intramolecular PB FLPs and the hydroboration reagent HB(C6F5)2 to yield epoxy-
borate species (Scheme 34 top)118-119 283 Simultaneously the Stephan group exploited the
reaction of a 12 mixture of tBu3P and B(C6F5)3 with syn-gas (CO and H2) to result in sequences
of stoichiometric reactions eventually affording the borane-oxyborate derivative
(C6F5)2BCH(C6F5)OB(C6F5)3 a product of C-O bond cleavage (Scheme 34 bottom)117
Scheme 34 ndash Reaction of cyclopentenylphosphine with HB(C6F5)2 and carbon monoxide (top)
reaction of tBu3P and B(C6F5)3 with COH2 to generate (C6F5)2BCH(C6F5)OB(C6F5)3 (bottom)
The main group reduction of carbonyl groups has been limited to stoichiometric reactions with
classic hydride reagents In this chapter a remarkably simple approach to the metal-free
hydrogenation of ketones and aldehydes is reported using FLP catalysts derived from B(C6F5)3
and ether The hydrogenation concept was extended towards a heterogeneous avenue using
catalysts derived from the combination of polysaccharides or molecular sieves with B(C6F5)3
Moreover the catalytic reductive deoxygenation of aryl ketones is achieved in the case of
molecular sieves
92
32 Results and Discussion
321 B(C6F5)3 decomposition pathway in C=O hydrogenation reactions
Heating a toluene solution of 5 mol B(C6F5)3 and 4-heptanone under H2 (60 atm) at 80 degC
yielded complete conversion of B(C6F5)3 to the borinic ester Pr2CHOB(C6F5)2 with concurrent
liberation of C6F5H The remaining 95 of the initial ketone was unaltered This observation
illustrates that borane and ketone act as a FLP to heterolytically cleave H2 affording nominally
[Pr2COH][HB(C6F5)3] At this stage the hydride is presumed to reduce the carbonyl fragment to
generate 4-heptanol which subsequently decomposes B(C6F5)3 to Pr2CHOB(C6F5)2 and C6F5H
It is important to note that the above example of rapid and facile decomposition of B(C6F5)3 to
borinic ester stands in contrast to an observation illustrated in Chapter 2 In this case the CH3OH
generated from ammonium protonation of [CH3OB(C6F5)3]- does not decompose B(C6F5)3 rather
under an atmosphere of H2 the resulting amine and B(C6F5)3 heterolytically split H2 to give the
ammonium [HB(C6F5)3] product (Scheme 35) Thus this observation led to the proposal of two
plausible borane decomposition pathways in ketone hydrogenation reactions
Scheme 35 ndash Activation of H2 by amineborane FLP while in the presence of CH3OH
In both pathways the reaction initiates with heterolytic H2 splitting by the ketone and B(C6F5)3
to give the ionic pair [R2COH][HB(C6F5)3] (Scheme 36) At this point the reaction could follow
a pathway in which hydride is transferred from the [HB(C6F5)3]- anion to the activated carbonyl
group generating alcohol and B(C6F5)3 both of which further react to give borinic ester and
C6F5H (Scheme 36 Pathway 1) The second pathway suggests the borane undergoes
protonolysis by the [R2COH]+ cation cleaving a C6F5 group to form HB(C6F5)2 and C6F5H whilst
regenerating the ketone The borane then undergoes hydroboration of the carbonyl group to
afford the borinic ester (Scheme 36 Pathway 2)
93
Scheme 36 ndash Two pathways proposed in the decomposition of B(C6F5)3 during ketone
hydrogenation
To test Pathway 1 B(C6F5)3 was added to excess 4-heptanol (10 eq) and heated to 80 degC for 12
h This resulted in no reaction beyond formation of the alcohol-borane adduct
Pr2CHOHmiddotB(C6F5)3 as evidenced by the 11B and 19F NMR spectra (11B δ 197 ppm 19F δ -
1326 -1552 -1628 ppm) On the other hand stoichiometric and 5 mol combinations of
HB(C6F5)2 with 4-heptanone formed the new hydroboration species Pr2CHOB(C6F5)2 after 10
min at RT In addition to the characteristic methine multiplet observed at 405 ppm in the 1H
NMR spectrum 11B NMR spectroscopy gave a broad resonance at 394 ppm with 19F NMR
signals at -1325 -1498 and -1613 ppm representing the three-coordinate boron centre These
experiments provide evidence for Pathway 2 resulting in decomposition of B(C6F5)3 during
ketone hydrogenation
322 B(C6F5)3 catalyzed carbonyl hydrogenation in ethereal solvents
To avoid this degradation pathway an alternative FLP is required This system must be basic
enough to effect H2 activation and stabilize the acidic proton by electrostatic interactions In this
regard the Stephan group previously reported that the ethereal oxygen of the borane-oxyborate
derivative (C6F5)2BCH(C6F5)OB(C6F5)3 is sufficiently Lewis basic to activate H2 with the
coordinating B(C6F5)2 group117 Subsequently the combination of weak Lewis bases such as
Et2O electron deficient triarylphosphines and diaryl amines were shown to be sufficiently basic
for both H2 activation and catalytic reduction of olefins99 257 In the case of Et2O DFT
calculations highlighted that solvation of the protonated ether by a second equivalent of Et2O can
significantly stabilize the proton by hydrogen-bonding interactions
94
To probe the viability of using Et2O in carbonyl reductions a d8-toluene solution of 5 mol
B(C6F5)3 was combined with a 51 ratio of Et2O4-heptanone and heated to 70 degC under H2 (4
atm) Monitoring the J-Young experiment by high temperature 1H NMR spectroscopy showed
gradual hydrogenation of the ketone yielding approximately 50 of 4-heptanol after 12 h The 1H NMR spectrum shows a distinct quintet at 345 ppm diagnostic of the hydrogenated C=O
fragment forming a C-H bond in addition to the multiplets at 128 and 080 ppm (Figure 31)
Increasing the H2 pressure to 60 atm improved the yield of 4-heptanol to 70
Figure 31 ndash 1H NMR (600 MHz d8-tol 343 K) stack plot showing catalytic hydrogenation of 4-
heptanone resulting in gradual formation of 4-heptanol Acquisitions are obtained over 1 h time
intervals Starting material 4-heptanone ($) product 4-heptanol ()
Alternatively incrementing the ratio of Et2O to 4-heptanone resulted in increased yields in
which case a 81 ratio of Et2O4-heptanone in toluene gave 97 conversion to 4-heptanol after
12 h (Figure 32) The continuous improvement in alcohol yield was a direct result of gradual
preservation of the borane catalyst in the reaction as the Et2O concentration was increased
Employing identical conditions but using Et2O as the solvent resulted in the quantitative
formation of 4-heptanol after 12 h Similarly employing iPr2O as the solvent in analogous
$ $ 12
11
10
9
8
7
6
5
4
3
2
1
95
hydrogenations gave quantitative yields of 4-heptanol The use of Ph2O and TMS2O resulted in
yields of 44 and 42 in the same time frame (Table 31 entry 1)
Figure 32 ndash Plot representing the dependence of Et2O equivalents on the conversion of 4-
heptanone to 4-heptanol
Using this FLP hydrogenation protocol a range of ketone substrates were treated with 5 mol
B(C6F5)3 in Et2O iPr2O Ph2O or TMS2O and heated for 12 h at 70 degC under H2 (60 atm) The
substrates investigated included several alkyl ketones (Table 31 entries 1 - 9) an aryl ketone
(Table 31 entry 10) benzyl ketones with substituents including F and CF3 groups (Table 31
entry 11 - 15) cyclic ketones including L-menthone and cyclohexanone (Table 31 entries 16
and 17) as well as the aldehyde cyclohexanal (Table 31 entry 18) Evaluating these reductions
by 1H NMR spectroscopy showed yields ranging between 32 - gt99 and isolated yields up to
91 for the reactions carried out in Et2O and iPr2O (Table 31) 1H NMR spectra of the alcohols
displayed characteristic multiplets at about 4 ppm assignable to the distinctive methine protons
with corresponding 13C1H resonances observed at ca 70 ppm as expected
These reactions could also be performed on a larger scale For example 100 g of 4-heptanone
was quantitatively converted to 4-heptanol using 5 mol B(C6F5)3 in Et2O and the alcohol
product was isolated in 87 yield
96
Table 31 ndash Catalytic hydrogenation of ketones and aldehydes in ethereal solvents
Conversion (Isolated yields)
Entry R R1 Et2O iPr2O Ph2O TMS2O
1 n-C3H7 n-C3H7 gt99 (91) gt99 70 52
2 Me iPr gt99 (76) gt99 44 42
3 Me CH2tBu gt99 gt99 (90) 22 14
4 Me n-C5H11 93 (85) 50 (43) 58 41
5 Me CH2Cl gt99 (85) gt99 91 82
6 Me Cy 77 - - -
7 Et iPr gt99 gt99 (89) - trace
8 Et n-C4H9 gt99 (87) 95 44 38
9 Et CH2iPr 40 47 - -
10 Me Ph 90 69 (52) trace trace
11 Et CH2Ph gt99 (84) 97 trace trace
12 Me n-CH2CH2Ph gt99 (84) 69 58 24
13 Me CH2(o-FC6H4) 97 gt99 (90) trace trace
14 Me CH2(p-FC6H4) gt99 gt99 (90) trace trace
15 Me CH2(m-CF3C6H4) gt99 gt99 (88) 55 trace
16 -(CH2)5- 53 41 - -
17 -(2-iPr-5-Me)C5H8- gt99 (88) 89 47 45
18 Cy H 32 - - -
(-) Reaction was not performed
323 Proposed mechanism for the catalytic hydrogenation of ketones using B(C6F5)3 in ethereal solvents
The mechanism of these reactions is thought to be analogous to that previously described for
imine hydrogenations92 In the present case ether combines with the borane in equilibrium
97
between the classical Lewis acid-base adduct and the corresponding FLP in which the latter
effects the heterolytic cleavage of H2 The resulting protonated ether then associates with ketone
via a hydrogen-bonding interaction284-285 activating the carbonyl fragment for hydride transfer
from the [HB(C6F5)3]- anion Subsequent protonation of the generated alkoxide yields the
product alcohol while liberating etherB(C6F5)3 to further activate H2 (Scheme 37) It has been
experimentally proven that activation of the carbonyl fragment is required prior to hydride
delivery as a 11 combination of 4-heptanone and [NEt4][HB(C6F5)3] do not result in reactivity
Scheme 37 ndash Proposed mechanism for catalytic ketone hydrogenation in ethereal solvents
The possibility of initial H2 activation by ketoneborane combinations cannot be dismissed
however the proposed mechanism is based on the large excess of ether in comparison to ketone
In support of this proposed mechanism the activation of H2 by ethereal oxygen Lewis bases and
boranes have been described to protonate imines and alkenes en route to the corresponding
hydrogenated products257 286
324 Structural analogue of the proposed intermediate in the ketone hydrogenation mechanism
The proposed H-bonding ether-ketone intermediate was further probed by the stoichiometric
reaction of a toluene solution of Jutzirsquos acid [(Et2O)2H][B(C6F5)4]287 with 1-phenyl-2-butanone
and iPr2O After heating the reaction at 70 degC for 2 h a white crystalline solid 31 was isolated in
87 yield (Scheme 38) The 1H NMR spectrum of 31 showed a broad singlet at 1152 ppm
suggesting a proton involved in hydrogen-bonding Resonances attributable to both 1-phenyl-2-
butanone and iPr2O were unambiguously present although these shifts were deshielded in
98
comparison to the individual components These data in addition to the definite presence of the
[B(C6F5)4]- anion as evidenced by 11B and 19F NMR spectroscopy lead to the assignment of 31
as [(iPr2O)H(O=C(CH2Ph)CH2CH3)][B(C6F5)4]
Scheme 38 ndash Synthesis of 31
The structure of 31 was unambiguously confirmed by single crystal X-ray crystallography
(Figure 33) The molecular structure of this salt shows the proximity of the ketone and ether in
the cation with an O-O separation of 2534(3) Aring Location and complete refinement of the proton
in the cation shows it is associated with the ether oxygen and hydrogen-bonded to the ketone
with O-H distances of 104(2) and 154(2) Aring respectively The resulting angle at H is 1581(3)deg
consistent with that typically seen for hydrogen-bonding interactions288-289 The isolation of 31
provides a direct structural analogue of the proposed intermediate in the ketone hydrogenation
mechanism
The equilibrium position of the generated proton is predicted to favour the ether oxygen atom
where the unshared electron pair is sp3 hybridized making the ether oxygen more basic than the
carbonyl where the unshared pair is sp2 hybridized This is also in agreement with predicted pKa
values of protonated ether and ketone289
Figure 33 ndash POV-Ray depiction of 31
99
325 Other hydrogen-bond acceptors for carbonyl hydrogenations
By analogy to the proposed mechanism with ethereal solvents ketone hydrogenations were
explored with crown ethers in toluene To this end combinations of 5 and 10 mol of 12-crown-
4 18-crown-6 and benzo-12-crown-4 were used with 5 mol B(C6F5)3 and 4-heptanone
However in all cases only trace amounts of 4-heptanol was observed Similar to the results in
ethereal solvents these hydrogenation results could possibly be improved by using an excess of
the crown ether On the other hand inefficient hydrogenation could result due to the multiple
stabilizing hydrogen bonds with the crown (OCH2)n groups
Alternative oxygen containing solvents THF and tetrahydropyran were tested using the
hydrogenation protocol in both cases however catalysis was not observed This result could be
explained by the difference in steric hindrance of the two solvents in comparison to Et2O and
iPr2O Nonetheless performing the hydrogenations in 24-dimethylpentan-3-ol gave the
quantitative reduction of 4-heptanone after 12 h at 70 degC This result led to the proposal that
chiral alcohols could possibly be used as the solvent to induce asymmetric reduction of ketones
Thus testing this theory using enantiomerically pure alcohols (S)-2-octanol (R)-2-octanol (R)-
(+)-1-phenyl-1-butanol (S)-(+)-12-propanediol and (R)-(+)-11rsquo-bi(2-naphthol) the prochiral
ketone substrates in Table 31 entries 2 - 10 were hydrogenated although in all cases the
products were obtained as racemic mixtures
326 Other boron-based catalysts for carbonyl hydrogenations
While exploring other boron-based catalysts in carbonyl reductions borenium cation-based FLP
hydrogenation catalysts105 derived from carbene-stabilized 9-borabicyclo[331]nonane (9-
BBN) were tested in lieu of B(C6F5)3 (Figure 34) However at 70 degC (temperature required for
hydrogenation when using B(C6F5)3) the borenium cation catalysts were found to decompose to
unknown products thereby not resulting in any reactivity
100
Figure 34 ndash Borenium cation-based FLP hydrogenation catalysts tested in ketone hydrogenation
reactions [B(C6F5)4]- anions have been omitted
327 Alternative approach to catalytic ketone hydrogenation using a B(C6F5)3-assisted mechanism
Reflecting back on a key result presented in Chapter 2 an alternative mechanism was applied to
successfully achieve B(C6F5)3 catalyzed ketone hydrogenation This finding demonstrates the
participation of the [CH3OB(C6F5)3]- anion and B(C6F5)3 in H2 activation forming CH3OH and
[HB(C6F5)3]- (Scheme 39) thereby signifying the lability of B(C6F5)3-alkoxide bonds
Scheme 39 ndash Example demonstrating lability of a B(C6F5)3-alkoxide bond
Taking lability of the presented B-O bond into consideration a two component catalyst system
comprising of B(C6F5)3 and [NEt4][HB(C6F5)3] was conceptualized for ketone hydrogenation In
this regard the B(C6F5)3 catalyst is expected to coordinate to the carbonyl group activating it for
hydride delivery from [NEt4][HB(C6F5)3] This will consequently generate B(C6F5)3 and
B(C6F5)3-alkoxide wherein similar to Scheme 39 will react with H2 to form alcohol and
regenerate the catalysts
The proposed catalytic system was examined by combining 5 mol B(C6F5)3 and 5 mol
[NEt4][HB(C6F5)3] with 4-heptanone in toluene and heating at 80 degC under H2 (60 atm) After 12
h 1H NMR data revealed catalyst turnover giving 92 conversion to the product 4-heptanol
(Table 32 entry 1) It is important to note that under similar reaction conditions the
combination of ketone with [NEt4][HB(C6F5)3] does not give any reactivity while B(C6F5)3 alone
is decomposed to the borinic ester
101
Using this hydrogenation protocol dialkyl substituted ketones gave the corresponding alcohols
in 40 - 99 conversions by 1H NMR spectroscopy (Table 32 entries 2 - 6) Conversions were
dramatically reduced for methyl cyclohexyl ketone (Table 32 entry 7) aryl and benzyl
substituted ketones (Table 32 entries 8 - 10) benzylacetone (Table 32 entry 11) in addition to
the cyclic ketones cyclohexanone and 2-cyclohexen-1-one (Table 32 12 and 13) Interestingly
reduction of L-menthone produced the respective alcohol product in 62 by 1H NMR
spectroscopy (Table 32 entry 14)
Table 32 ndash FLP mediated catalytic ketone hydrogenation using B(C6F5)3[NEt4][HB(C6F5)3]
Entry R R1 Conversion
1 n-C3H7 n-C3H7 92
2 Me iPr 57
3 Me CH2Cl gt99
4 Me 2-butyl 53
5 Et iPr gt99
6 Et CH2iPr 40
7 Me Cy 18
8 Me Ph 20
9 Ph Ph 20
10 Et CH2Ph 25
11 Me n-CH2CH2Ph 25
12 -(CH2)5- 28
13 -(CH2)3CH=CH- 0
14 -(2-iPr-5-Me)C5H8- 62
All conversions are determined by 1H NMR spectroscopy
102
3271 Proposed mechanism for ketone hydrogenation using the B(C6F5)3[NEt4][HB(C6F5)3] catalyst system
The mechanism of this reaction is thought to proceed by initial coordination of the Lewis acid
B(C6F5)3 to the carbonyl group assisting hydride transfer from [NEt4][HB(C6F5)3] resulting in
liberation of B(C6F5)3 and generation of [NEt4][RR1C(H)OB(C6F5)3] in which the alkoxide
anion is coordinated to B(C6F5)3 (Scheme 310) This combination of [RR1C(H)OB(C6F5)3]-
anion and B(C6F5)3 act as a FLP to activate H2 and dissociate the alcohol while simultaneously
regenerating B(C6F5)3 and [NEt4][HB(C6F5)3] By 1H NMR spectroscopy the [NEt4]+ cation
does not appear to participate in the reaction
R R1
OH
H
B(C6F5)3
R R1
O
+
B(C6F5)3
R R1
O NEt4
HB(C6F5)3
NEt4
B(C6F5)3
B(C6F5)3
R R1
O
05 H2
05 H2
H+ from H2 activation
H- from H2 activation
Scheme 310 ndash Proposed mechanism for B(C6F5)3[NEt4][HB(C6F5)3] catalyst system used in
ketone hydrogenation
In comparison to carbonyl hydrogenations in ethereal solvents the presented Lewis acid-assisted
mechanism has resulted in lower alcohol yields due to steric hindrance of the substrate Lewis
base preventing adequate coordination to the Lewis acid and consequently inefficient activation
of the carbonyl bond Additionally the steric hindrance of the alkoxyborate anion resulting from
hydride delivery slows down the H2 activation step allowing unreacted B(C6F5)3 and ketone to
activate H2 giving the corresponding borinic ester
328 Attempted hydrogenation of other carbonyl substrates and epoxides
Carbonyl reductions employing either the etherB(C6F5)3 FLP catalyst or the two component
catalyst species B(C6F5)3[NEt4][HB(C6F5)3] were unsuccessful for the ketones
diphenylcyclopropenone (ndash)-fenchone 25-hexanedione 6-methyl-35-heptadien-2-one
103
cyclohexane-14-dione 1-acetyl-1-cyclohexene 13-difluoroacetone 2-acetylthiophene 44-
dimethoxybutan-2-one aldehydes 5-methylthiophene-2-carboxaldehyde esters ethyl acetate
ethylchloroformate methylbenzoate ethylpyruvate phenyl acetate carboxylic acids isobutyric
acid pivalic acid 3-phenylpropanoic acid carbonates ethylene carbonate diethyl carbonate
and NN-diethylpropionamide Exposure of diethylmaleate to the hydrogenation conditions only
led to reduction of the C=C double bond
Similar treatment of the epoxides styrene oxide and trans-stilbene oxide were found to undergo
the well-documented Lewis acid catalyzed Meinwald rearrangement forming 2-
phenylacetaldehyde and 22-diphenylacetaldehyde respectively Selectivity of the aldehyde
products is determined by formation of the most stable carbenium intermediate followed by a
hydride shift (2-phenylacetaldehyde) or substituent shift (22-diphenylacetaldehyde)290-291
Moreover an attempt at extending this reduction procedure to the greenhouse gas CO2 was not
successful In this sense a J-Young tube consisting of B(C6F5)3 and 10 eq of Et2O was
pressurized with CO2H2 and heated at temperatures up to 80 degC Multinuclear NMR data only
revealed resonances corresponding to the Et2O-B(C6F5)3 adduct
329 FLPs comprised of B(C6F5)3 with polysaccharides or molecular sieves as Lewis bases
As presented in Section 322 judicious choice of the FLP catalyst derived from ether and
B(C6F5)3 gives catalytic hydrogenation of carbonyl substrates to their corresponding alcohols
The protonated ether solvent is proposed to hydrogen bond with the ketone substrate stabilizing
the Broslashnsted acidic proton while activating the carbonyl fragment to accept hydride from the
[HB(C6F5)3]- anion (Scheme 37)
Continued interest in ketone and aldehyde hydrogenation reactions led to the investigation of
potential oxygen-rich materials that will mimic ethereal solvents permitting catalytic
hydrogenation in a non-polar solvent To this end FLP hydrogenations were performed in
toluene using the Lewis acid B(C6F5)3 with the addition of heterogeneous Lewis bases including
cyclodextrins (poly)saccharides or molecular sieves (MS) with the formula
Na12[(AlO2)12(SiO2)12] (Figure 35)
104
Figure 35 ndash Chemical structure of aluminosilicate framework of α-cyclodextrin (a) and MS (b)
3291 Polysaccharides as heterogeneous Lewis bases
In probing this investigation α-cyclodextrin (α-CD) an oligosaccharide formed of six
glucopyranose units (Figure 35 a) was initially tested in H2 activation In this regard 5 mol
B(C6F5)3 and α-CD were combined in d8-toluene and exposed to HD gas (1 atm) in a J-Young
tube at 60 degC (Figure 36 a) 1H NMR analysis after 1 h revealed signals for H2 resulting from
isotope equilibration thereby signifying the viability of H2 activation between B(C6F5)3 and the
oxygen donors of α-CD (Figure 36 b) Furthermore the 11B and 19F NMR spectra indicated
signals corresponding to unaltered B(C6F5)3 thus suggesting a remarkably simple and
inexpensive H2 activation FLP catalyst It is important to note that B(C6F5)3 or α-CD alone do not
effect HD activation
Figure 36 ndash 1H NMR (400 MHz d8-tol) stack plot showing HD (a) isotope equilibration by 5
mol B(C6F5)3 and α-CD after 12 h at 60 degC (b) 1H δ 456 (H2) 452 1JHD = 423 Hz (HD)
To assess the unprecedented FLP system in carbonyl hydrogenation catalysis the ketone 3-
methyl-2-butanone was combined with an equivalent of α-CD and 5 mol B(C6F5)3 in toluene
and heated at 60 degC under H2 (60 atm) After 12 h quantitative reduction to the product 3-
methyl-2-butanol was evidenced by 1H NMR spectroscopy revealing a diagnostic multiplet at
327 ppm corresponding to the product CH group and broad singlet at 182 ppm assignable to the
a) b)
a)
b)
105
OH group (Table 33 entry 1) Repeating the reaction in the absence of H2 does not lead to
reduction of the substrate thus eliminating the possibility of transfer hydrogenation from α-CD
Under similar conditions a series of methyl alkyl (Table 33 entries 2 - 6) and dialkyl ketones
(Table 33 entries 7 - 9) aryl (Table 33 entries 10 - 14) benzyl (Table 33 entries 15 - 19) and
cyclic ketones (Table 33 entries 20 - 22) were hydrogenated in high yields In addition the
catalytic reduction of aldehydes was similarly performed to give the corresponding primary
alcohols (Table 33 entries 23 - 25) The 1H NMR spectra for all products displayed a
characteristic resonance at about 4 ppm diagnostic of CH and CH2 protons for ketone and
aldehyde reductions respectively and the corresponding 13C1H resonances were observed at
ca 70 ppm
The efficient nature of these catalytic reactions imply that B(C6F5)3 and the oxygen atoms of α-
CD act as a FLP to activate H2 initiating hydrogenation catalysis Selective silylation of α-CD at
the 2- and 6-hydroxy positions of the glucose units gave the toluene soluble product hexakis[26-
O-(tert-butyldimethylsilyl)]-α-cyclodextrin292 This derivatization was found to have a marginal
influence on catalysis forming 3-methyl-2-butanol in 70 yield after 12 h at 60 degC Moreover
the hydrogenation protocol was further investigated using the heterogeneous Lewis bases β and
γ-CD oligosaccharides of seven and eight glucopyranose units respectively and the
(poly)saccharides maltitol and dextrin Hydrogenation results are summarized in Table 33
Taking into account that cyclodextrins are used as chiral stationary phases in separation of
enantiomers the prochiral substrates of Table 33 were analyzed by chiral GC However in all
cases the products were found as racemic mixtures
106
Table 33 ndash Catalytic hydrogenation of ketones and aldehydes using heterogeneous Lewis bases
Entry R R1 α-CD β-CD γ-CD Maltitol Dextrin MS
1 Me iPr gt99 79 77 62 81 gt99
2 Me 2-butyl gt99 74 72 46 75 gt99
3 Me CH2tBu gt99 52 41 40 53 gt99
4 Me CH2Cl gt99 gt99 trace 51 trace 80
5 Me Cy gt99 81 62 31 64 gt99
6 Me n-C5H11 gt99 63 56 36 73 gt99
7 Et iPr gt99 75 75 69 80 gt99
8 Et n-C4H9 95 93 95 58 gt99 93
9 n-C3H7 n-C3H7 gt99 - - - - 92
10a Me Ph 30 13 15 10 27 trace
11 CH2CH2Cl Ph 54 - - - - 50
12 CF3 Ph 20 - - - - 20
13 Me o-CF3C6H4 trace - - - - 25
14 Me p-MeSO2C6H4 60 - - - - 97
15 Me n-CH2CH2Ph gt99 58 90 38 trace gt99
16 Me CH2(o-FC6H4) 75 70 69 66 34 gt99
17 Me CH2(p-FC6H4) gt99 49 31 55 48 gt99
18 Me CH2(m-CF3C6H4) gt99 gt99 62 43 92 gt99
19 Et CH2Ph gt68 20 31 28 46 gt99
20 -(CH2)5- gt99 72 65 68 90 gt99
21b -(CH2)3CH=CH- 67 trace trace trace trace 82
22 -(2-iPr-5-Me)C5H8- gt99 70 60 60 80 gt99
23 Cy H 10 - - - - 44
24 Ph2CH H 47 - - - - 86
25 PhCH(Me) H 20 - - - - 35
a Reported yields are for phenylethanol b Product is cyclohexanol Isolated yields are reported for α-CD and MS
107
3292 Molecular sieves as heterogeneous Lewis bases
The presented (poly)saccharides could be conveniently replaced with the ubiquitous laboratory
drying agent MS293 as HD isotope equilibration experiments evidenced the formation of H2
when exposed to a d8-toluene suspension of MS and B(C6F5)3 It is noteworthy however that
such equilibration was not observed in the absence of B(C6F5)3
Using MS as the heterogeneous Lewis base 5 mol B(C6F5)3 catalyzed the hydrogenation of
ketone and aldehyde substrates reported in Table 33 These reductions could also be performed
on an increased scale with consecutive recycling of the MS For example 100 g of 4-heptanone
in toluene was treated with 5 mol of the catalyst B(C6F5)3 and MS yielding quantitative
conversion to 4-heptanol which was isolated in 95 yield The sieves were washed with solvent
and recombined with borane and ketone in three successive hydrogenations without loss of
activity
Speculation of physisorbed B(C6F5)3 onto MS was probed by reusing filtered sieves that were
washed with toluene without further addition of B(C6F5)3 This gave 30 reduction of 4-
heptanone suggesting that while there is some physisorption it is not sufficient to provide a
significant degree of catalysis
3293 Reductive deoxygenation of alkyl aryl ketones and diaryl ketones
In an effort to reduce the aryl alkyl ketone acetophenone the above protocol using α-CD was
employed for 12 h at 70 degC under H2 (60 atm) 1H NMR data revealed ca 60 consumption of
acetophenone resulting in the formation of two products in almost equal ratios The distinct
quartet at 424 ppm broad singlet at 342 ppm and doublet at 102 ppm were consistent with the
hydrogenated product phenylethanol (Scheme 311) The 1H NMR spectrum of the second
product gave three separate doublet of doublets with olefinic chemical shifts observed at 652
556 and 504 ppm with each signal integrating to one proton Mass spectroscopy confirmed this
species to be styrene derived from reductive deoxygenation (Scheme 311) The reaction was
repeated using MS giving styrene in a significantly improved 92 yield (Table 34 entry 1)
108
Scheme 311 ndash Catalytic hydrogenation and reductive deoxygenation of acetophenone
To probe this deoxygenation further the ketone 3rsquo-(trifluoromethyl)acetophenone was treated
with 5 mol B(C6F5)3 in toluene and added to a suspension of MS and heated for 12 h at 70 degC
under H2 (60 atm) This resulted in formation of the deoxygenated product 3-
(trifluoromethyl)styrene in 95 yield (Table 34 entry 2) while remainder of the reaction
mixture consisted of the alcohol 3rsquo-(trifluoromethyl)phenyl ethanol Similar treatment of
propiophenone gave trans-β-methylstyrene in 96 yield with trace amounts of the cis isomer
(Table 34 entry 3) In a similar timeframe the deoxygenation of isobutyrophenone was
performed giving 75 of the hydrocarbon 2-methyl-1-phenyl-propene while 10 of the mixture
consisted of the alcohol 1-phenyl-1-propanol (Table 34 entry 4) In this case the comparatively
slower deoxygenation rate is presumably due to increased steric hindrance about the carbonyl
functionality Indeed these effects are more pronounced with 222-trimethylacetophenone as no
reaction was observed Finally the bicyclic ketone 1-tetralone gave 12-dihydronaphthalene in
88 yield (Scheme 312 a)
Table 34 ndash Deoxygenation of aryl alkyl ketones
Entry R R1 R2 Isolated yield
1 H Me CH2 92
2 CF3 Me CH2 95
3 H Et CHCH3 trans 96
cis 4
4 H iPr C(Me)2 75
109
In light of the established tandem hydrogenation and deoxygenation protocol under these
conditions benzophenone is deoxygenated to give diphenylmethane in 81 yield (Table 35
entry 1) Similarly the diaryl ketone derivatives with substituents including CH3O Br tBu and
CH3 groups were reduced affording the corresponding diarylmethane products in yields ranging
from 67 - 99 (Table 35 entries 2 - 5) In the case of p-CF3 substituted benzophenone the
reaction gave 10 of the deoxygenation and 50 of the alcohol products (Table 35 entry 6)
Analogous treatment of 2-methylbenzophenone resulted in only 20 conversion to the aromatic
hydrocarbon (Table 35 entry 7) This example including the result for 2rsquo-
(trifluoromethyl)acetophenone (25 yield) (Table 33 entry 13) certainly infer that increased
steric hindrance about the carbonyl group has a negative impact on reactivity
Finally the tricyclic ketone dibenzosuberone afforded the reduced aryl alkane
dibenzocycloheptene in 73 yield (Scheme 312 b) It is noteworthy that Repo et al have
previously reported B(C6F5)3 mediated reductive deoxygenation of acetophenone in CD2Cl2
however in their case concurrent hydration of the borane affords (C6F5)2BOH and C6F5H178 In
the present system MS preclude this degradation pathway allowing deoxygenation to proceed
catalytically
Table 35 ndash Deoxygenation of diaryl ketones
Entry R R1 Isolated yield
1 H Ph 81
2 CH3O Ph 85
3 Br Ph 67
4 tBu Ph gt99
5 CH3 p-CH3C6H4 75
6 CF3 Ph 10
7 H o-CH3C6H4 20
110
Scheme 312 ndash Hydrogenation and deoxygenation of 1-tetralone (a) and dibenzosuberone (b)
3210 Proposed mechanism for catalytic carbonyl hydrogenation and reductive deoxygenation
The mechanism of these ketone and aldehyde reductions is thought to be analogous to the FLP
reductions described earlier in ethereal solvents In the present case the FLP initiating
heterolytic H2 activation is believed to be the Lewis basic oxygen atoms on the surface of the α-
CD or MS and the Lewis acid B(C6F5)3 (Scheme 313) although H2 activation by ketone
B(C6F5)3 cannot be dismissed Proceeding from the former activation method similar to the case
in ethereal solvents the protonated surface hydrogen bonds to the carbonyl fragment polarizing
the bond for hydride transfer from the [HB(C6F5)3]- anion The generated alkoxide anion is then
sufficiently basic to accept proton from the surface thus regenerating the heterogeneous Lewis
base This H2 activation is in agreement with HD equilibration experiments presented for α-CD
and MS
The ease of deoxygenating the ketones Ph2C=O gt PhCH3C=O gave insight to postulate the
reductive deoxygenation mechanism Heterolytic H2 activation occurs between the MS and
B(C6F5)3 although activation between ketoneB(C6F5)3 and alcoholB(C6F5)3 cannot be
dismissed ultimately resulting in protonated alcohol which is hydrogen-bonded to ketone
(Scheme 313) At this stage it appears that C-O bond cleavage with hydride delivery and loss
of H2O affords the aromatic alkene or alkane products Evidence of the alcohol-H-ketone
intermediate proposed in the mechanism is investigated in the following section
111
Scheme 313 ndash Proposed mechanism for hydrogenation of carbonyl substrates and reductive
deoxygenation of aryl ketones
Experimental results have demonstrated electronic effects directly impact the deoxygenation
mechanism It appears that C-O bond cleavage and loss of H2O is governed by stability of an
alcohol carbocation intermediate Aryl alcohols readily stabilize such an intermediate through
delocalization by the neighbouring π-system while this effect is clearly absent with dialkyl and
primary alcohols Moreover electron withdrawing groups prevent formation of the carbocation
as demonstrated by the reduction results of 222-trifluoroacetophenone and 4-
(methylsulfonyl)acetophenone These compounds exclusively gave the corresponding alcohol
products (Table 33 entries 12 and 14)
32101 Verifying the reductive deoxygenation mechanism
To validate the proposed reductive deoxygenation mechanism treatment of diphenylmethanol
with 5 mol B(C6F5)3 and MS was carried out at 70 degC under H2 (60 atm) (Figure 37)
Surprisingly the reaction only gave 10 mol of diphenylmethane and complete degradation of
B(C6F5)3 Modification of the study to include 5 10 and 50 mol of benzophenone gradually
increased consumption of diphenylmethanol indicating participation of ketone in the
deoxygenation process (Figure 37) Such a mechanism accounts for necessity of a strong
112
Broslashnsted acid to initiate the deoxygenation process by protonating the hydroxyl group
Figure 37 ndash 1H NMR (500 MHz d8-tol) stack plot showing consumption of diphenylmethanol
(530 ppm) and formation of diphenylmethane (372 ppm) as the equivalents of benzophenone
(749 and 722 ppm) is gradually increased
The conversion of carbonyl substrates to hydrocarbons is an important and rather broad area of
research in modern organic chemistry with extensive contribution to the production of fuels
Replacement of an oxo group by two hydrogen atoms is generally carried out through
hydrogenolysis although hydrogenation methods are also well studied Prominent procedures for
this transformation include the Clemmensen reduction294-295 Wolff-Kishner reduction296 and
stoichiometric methods involving LiAlH4-AlCl3 NaBH4-CF3CO2H297 Et3SiH-BF3 or
CF3CO2H298-299 and HI-Phosphorus combinations300-301 in addition to metal-catalyzed
approaches62
From the perspective of FLP systems reductive deoxygenation of carbonyl groups has been
previously achieved using silanes boranes or ammonia borane165 as sacrificial reducing agents
0 mol
5 mol
10 mol
50 mol
Diphenylmethanol (CH) Diphenylmethane (CH2)
113
The Piers group showed the B(C6F5)3 catalyzed deoxygenative hydrosilylation of CO2 to CH4
using TMP B(C6F5)3 and excess Et3SiH169 Such transformations have also been reported using
N-heterocyclic carbenes and hydrosilanes302 The Fontaine group among others111 163 have
shown the hydroboration of CO2 to methanol using FLPs167-168 Significantly more challenging is
H2 as the reducing reagent In a unique example Ashley and OrsquoHare reported the reduction of
CO2 by H2 using a stoichiometric combination of B(C6F5)3 and TMP at 160 degC to give methanol
in 17 - 25 yield259
3211 Other heterogeneous Lewis bases and attempting the hydrogenation of olefins
In the experiments presented 4 Aring pellet MS purchased from Sigma Aldrich were used in
combination with B(C6F5)3 To explore the efficacy of other materials the same hydrogenation
protocol was applied in the reduction of 4-heptanone to give 4-heptanol in the following yields 5
Aring MS pellets (gt99) 4 Aring MS powder (69) 3 Aring MS pellets (68) acidic alumina (30)
silicic acid (15) while no reactivity was observed in the case of silica gel sodium aluminate
neutral and basic alumina
The hydrogenation protocol using 4 Aring MS was also attempted in the reduction of olefins
including 1-hexene cyclohexene 11-diphenylethylene and αp-dimethylstyrene however no
reactivity was observed in either case
33 Conclusions
The following chapter provides an account on the discovery of a metal-free route for the
hydrogenation of ketone and aldehyde substrates to form alcohol products The FLP catalyst is
derived from ether and B(C6F5)3 in which the protonated ether participates in hydrogen-bonding
interactions with the substrate affording an efficient catalyst to mediate the transformations
Moreover B(C6F5)3-assisted ketone hydrogenations using a two component catalyst system
derived from B(C6F5)3 and [NEt4][HB(C6F5)3] has also proven viable
Simultaneous with communicating this finding Ashley et al reported an analogous
hydrogenation catalyst derived from 14-dioxaneB(C6F5)3 that is effective for the hydrogenation
of ketones and aldehydes at 4 atm of H2 and temperatures ranging between 80 and 100 degC260
114
Also an air stable catalyst derived from THFB(C6Cl5)(C6F5)2 was shown to be particularly
effective for the hydrogenation of weakly Lewis basic substrates286
Continuing to explore modifications and applications of this new metal-free carbonyl reduction
protocol catalytic reductions were achieved in toluene using B(C6F5)3 and a heterogeneous
Lewis base including CDs (poly)saccharides or MS This combination of soluble borane and
insoluble materials provided a facile route to alcohol products In the case of aryl ketones and
MS further reactivity of the alcohol resulted in deoxygenation of the carbonyl group affording
either the aromatic alkane or alkene products
34 Experimental Section
341 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane tetrahydrofuran toluene (Sigma Aldrich) were dried employing a Grubbs-type
column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring) in the
glovebox Bromobenzene (-H5 and -D5) were purchased from Sigma Aldrich and dried over
CaH2 for several days and vacuum distilled onto 4 Aring molecular sieves prior to use
Dichloromethane-d2 benzene-d6 and chloroform-d were purchased from Sigma Aldrich
Toluene-d8 was purchased from Sigma Aldrich and distilled over sodiumbenzophenone prior to
use Molecular sieves (4 Aring) were purchased from Sigma Aldrich and dried at 120 ordmC under
vacuum for 12 h prior to use B(C6F5)3 was purchased from Boulder Scientific and sublimed at
80 degC under high vacuum before use
Tetrahydropyran 14-dioxane and hexamethyldisiloxane were purchased from Sigma Aldrich
and distilled over sodiumbenzophenone prior to use Diphenyl ether (ReagentPlusreg ge99) was
purchased from Sigma Aldrich and distilled under high vacuum at 80 degC over anhydrous
calcium chloride prior to use Diethyl ether (anhydrous 99) was purchased from Caledon
Laboratories Ltd and passed through a Grubbs-type column system manufactured by Innovative
Technology and stored over 4 Aring molecular sieves overnight prior to use Diisopropyl ether
(anhydrous 99 contains either BHT or hydroquinone as stabilizer) was purchased from Sigma
Aldrich and used without purification Cyclodextrins (α β and γ) maltitol dextrin from maize
starch and molecular sieves (pellets 32 mm diameter 4 Aring) were purchased from Sigma Aldrich
115
dried under vacuum at 120 degC for 12 h prior to use Deuterium hydride (extent of labeling 96
mol HD 98 atom D) was purchased from Sigma Aldrich Potassium
tetrakis(pentafluorophenyl)borate was purchased from Alfa Aesar Sodium triethylborohydride
(1M in toluene) was purchased from Sigma Aldrich Borenium cation-based FLP catalysts were
prepared by Dr Jeffrey M Farrell and Mr Roy Posaratnanathan following the literature
protocol105
All ketones and alcohols were purchased from Alfa Aesar Sigma Aldrich or TCI The liquids
were stored over 4 Aring molecular sieves and used without purification The solids were placed
under dynamic vacuum overnight prior to use H2 (grade 50) was purchased from Linde and
dried through a Nanochem Weldassure purifier column prior to use For the high pressure Parr
reactor the H2 was dried through a Matheson TRI-GAS purifier (type 452)
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D6 (1H = 716 ppm 13C = 1284 ppm) C6D5Br (1H = 728
ppm for meta proton 13C = 1224 ppm for ipso carbon) CD2Cl2 (1H = 532 ppm 13C = 5384
ppm) d8-tol (1H = 208 ppm for CH3 13C = 13748 ppm for ipso carbon) CDCl3 (1H = 726 ppm 13C = 7716 ppm) or externally (11B (Et2O)BF3 19F CFCl3) Chemical Shifts (δ) are reported in
ppm and the absolute values of the coupling constants (J) are in Hz NMR assignments are
supported by additional 2D and DEPT-135 experiments
High Resolution Mass Spectroscopy (HRMS) was obtained using JMS T100-LC AccuTOF
DART with ion source Direct Analysis in Real Time (DART) Ionsense Inc Saugus MA GC-
MS spectra were obtained on an Agilent Technologies 5975C VL MSD with Triple-Axis
Detector and 7890A GC System Column Agilent 19091S-433 (30 m times 250 μm times 025 μm)
Oven 40 degC for first 10 min 10 degCmin to 300 degC for 10 min Injection volume 1 μL The pro-
chiral samples were analyzed using a Perkin Elmer Autosystem CL chromatograph with a chiral
column (CP Chirasil-Dex CB 25 m times 25 mm)
Jutzi acid [(Et2O)2H][B(C6F5)4]287 and silylation of α-CD with tert-butyldimethylsilyl chloride292
were prepared according to literature procedures
116
Solid materials were purchased from commercial sources 5 Aring molecular sieves (pellets 32 mm
Aldrich) 4 Aring molecular sieves (powder Aldrich) 3 Aring molecular sieves (rod 116 inches
Aldrich) aluminum oxide (weakly acidic 150 mesh 58 Aring SA = 155 m2g Aldrich) sodium
metasilicate (18 mesh granular Alfa Aesar) silicic acid (80 mesh powder Aldrich) silica gel
(200-425 mesh 60 Aring high purity grade Silicycle) sodium aluminate (powder Aldrich)
aluminum oxide (basic 150 mesh 58 Aring SA = 155 m2g Aldrich) aluminum oxide (neutral
150 mesh 58 Aring SA = 155 m2g Aldrich)
342 Synthesis of Compounds
3421 Procedures for reactions in ethereal solvents
4-Heptanol-B(C6F5)3 adduct experiment In the glove box an NMR tube was charged with a
d8-toluene (04 mL) solution of B(C6F5)3 (122 mg 240 μmol 100 mol) and 4-heptanol (279
mg 0240 mmol) The NMR tube was sealed with Parafilm and placed in an 80 degC oil bath for
12 h 19F and 11B NMR spectra were obtained No evidence for the formation of C6F5H was
observed
19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1552 (t 3JF-F = 22 Hz 1F p-C6F5) -
1628 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 197 (br s 4-heptanol-B(C6F5)3)
Synthesis of (CH3CH2CH2)2CHOB(C6F5)2from the reaction of 4-heptanone and HB(C6F5)2
In the glove box an NMR tube was charged with a d8-toluene (04 mL) solution of HB(C6F5)2
(834 mg 0240 mmol) and 4-heptanone (274 mg 0240 mmol) A second NMR tube was
charged with a d8-toluene (04 mL) solution of HB(C6F5)2 (83 mg 24 μmol 10 mol) and 4-
heptanone (274 mg 0240 mmol) After 10 min at RT the samples were analyzed by 1H 19F
and 11B NMR spectroscopy
1H NMR (400 MHz d8-tol) δ 405 (tt 3JH-H = 76 38 Hz 1H CH) 168-151 (m 2H CH2)
150 - 134 (m 4H CH2) 133 - 115 (m 2H CH2) 086 (t 3JH-H = 76 Hz 6H CH3) 19F NMR
(377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5) -1498 (t 3JF-F = 20 Hz 1F p-C6F5) -1613 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ 394 (br s (CH3CH2CH2)2CHOB(C6F5)2)
High temperature NMR study for the reduction of 4-heptanone using 5 equivalent of Et2O
(J-Young Experiment) In the glove box a 1 dram vial was charged with a d8-toluene (03 mL)
117
solution of B(C6F5)3 (61 mg 12 μmol 50 mol) 4-heptanone (274 mg 0240 mmol) and Et2O
(890 mg 125 μL 120 mmol) The reaction mixture was transferred into an oven-dried Teflon
screw cap J-Young tube The reaction tube was degassed once through a freeze-pump-thaw cycle
on the vacuumH2 line and filled with H2 (4 atm) at -196 degC The reaction was monitored by high
temperature 1H NMR spectroscopy at 70 degC with 15 minute acquisitions (Figure 31)
General procedure for reactions in ethereal solvents (Table 31) The following procedure is
common to the ketone hydrogenation reactions in Et2O iPr2O Ph2O and TMS2O In the glove
box a 2 dram vial equipped with a stir bar was charged with the respective ketone or aldehyde
(048 mmol) and B(C6F5)3 (122 mg 240 μmol 500 mol) To each vial the appropriate ether
(96 mmol 20 eq) was added using a syringe Et2O (10 mL) iPr2O (13 mL) Ph2O (15 mL) and
TMS2O (20 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glove box to be pressurized with hydrogen gas
The hydrogen gas line was thoroughly purged and the reactor was attached to it and purged 10
times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at 70 degC 540 rpm
and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time the reactor was
vented and the vials were exposed to the atmosphere In the case of Et2O and iPr2O the entire
reaction mixture was transferred to a round bottom flask and all the volatiles were collected by
vacuum distillation while cooling the collected distillate with liquid nitrogen The solvent was
then removed by applying a gentle stream of N2 gas The alcohol yields were recorded and the
products were characterized by NMR spectroscopy and GC-MS
General procedure for 100 gram reaction of 4-heptanone in Et2O In the glove box 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol 500 mol) dissolved in Et2O (143 mg 200 mL 0190 mol)
was added to the bottle The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glove box and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 540 rpm After the indicated reaction time the reactor was slowly
vented and all the volatiles were collected by vacuum distillation while cooling the collected
distillate with liquid nitrogen The solvent was removed by applying a gentle stream of N2 gas
118
By 1H NMR spectroscopy the product displayed complete conversion to 4-heptanol and was
isolated in 87 yield
Dependence of Et2O equivalents on the reduction of 4-heptanone (Figure 32) In the glove
box a stock solution consisting of 4-heptanone (192 mg 235 μL 167 mmol) and B(C6F5)3 (427
mg 800 μmol 500 mol) in toluene (35 mL) was prepared in a 2 dram vial The solution was
distributed evenly between seven 2-dram vials (053 mLvial) and each vial was equipped with a
stir bar To each vial the appropriate volume of Et2O was added using a (micro)syringe
Et2O volume 12 μL (005 eq) 25 μL (01 eq) 125 μL (05 eq) 252 μL (10 eq) 504 μL (20
eq) 756 μL (30 eq) 101 μL (40 eq) 126 μL (50 eq) 151 μL (60 eq) 176 μL (70 eq) 202 μL
(80 eq)
The vial was loosely capped and loaded in a Parr pressure reactor sealed carefully and removed
from the glove box to be pressurized with hydrogen gas The hydrogen gas line was thoroughly
purged and the reactor was attached to it and purged 10 times at 15 atm of hydrogen gas The
reactor was then placed in an oil bath set at 70 degC 540 rpm and sealed at 60 atm of hydrogen gas
for 12 h After the indicated reaction time the reactor was vented and the reactions were analyzed
by 1H NMR spectroscopy Percent conversion to 4-heptanol was obtained by integration relative
to the remaining starting material 4-heptanone
Synthesis of [iPr2O-HmiddotmiddotmiddotO=C(CH2Ph)CH2CH3][B(C6F5)4] (31) In the glove box to a 2 dram
vial was added [(Et2O)2H][B(C6F5)4] (130 mg 0157 mmol) 4-phenyl-2-butanone (349 mg
0235 mmol) iPr2O (1284 mg 126 mmol) and toluene (05 mL) The solution was transferred
into a Teflon-sealed Schlenk bomb (25 mL) equipped with a stir bar and heated at 70 degC for 2 h
The solvent was removed under vacuum and pentane (5 mL) was added to result in immediate
precipitation of a white solid that was washed again with pentane (3 mL) and dried under
vacuum (127 g 136 mmol 87) Crystals suitable for X-ray crystallographic studies were
obtained from a layered bromobenzenepentane solution at RT
1H NMR (400 MHz CD2Cl2) δ 1152 (br s 1H iPr2O-HmiddotmiddotmiddotO=C) 741 (m 3H m p-Ph) 718
(m 2H o-Ph) 468 (m 3JH-H = 68 Hz 2H iPr) 403 (s 2H PhCH2) 281 (q 3JH-H = 71 Hz
2H CH2CH3) 146 (d 3JH-H = 68 Hz 12H iPr) 117 (t 3JH-H = 71 Hz 3H CH2CH3) 19F NMR
(377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1617 (t 3JF-F = 22 Hz 1F p-C6F5) -1658 (m
119
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -168 (s B(C6F5)4) 13C1H NMR (125 MHz
CD2Cl2) δ 1480 (dm 1JC-F = 238 Hz CF) 1379 (dm 1JC-F = 243 Hz CF) 1362 (dm 1JC-F =
246 Hz CF5) 1319 (ipso-Ph) 1301 (m-Ph) 1298 (o-Ph) 1288 (p-Ph) 1240 (ipso-C6F5) 828
(iPr) 498 (CH2Ph) 373 (CH2CH3) 197 (iPr) 799 (CH2CH3) (C=O was not observed)
HRMS (DART-TOF+) mass [M]+ calcd for [C16H27O2]+ 25120110 Da Found 25120127 Da
mass [M]- calcd for [C24BF20]- 67897736 Da Found 67897745 Da
3422 Procedures for reactions using B(C6F5)3 and [NEt4][HB(C6F5)3]
Synthesis of [NEt4][HB(C6F5)3] Part 1 In the glove box a 4 dram vial equipped with a stir bar
was charged with a solution of B(C6F5)3 (200 mg 0391 mmol) in toluene (10 mL) To the vial
sodium triethylborohydride (1M in toluene) (036 mL 036 mmol) was added drop wise over 15
min The reaction was allowed to mix overnight prior to removing the volatiles under vacuum
The crude mixture was washed with pentane (5 mL) to give the product Na HB(C6F5)3 as a white
solid (187 mg 0348 mmol 89)
Part 2 Na HB(C6F5)3 (187 mg 0348 mmol) was subsequently added to CH2Cl2 (10 mL) and
added to a 4 dram vial containing NEt4 Cl (576 mg 0348 mmol) in CH2Cl2 (5 mL) The
reaction was allowed to mix at RT overnight and filtered through Celite The filtrate was
concentrated and placed in a -30 degC freezer giving the product as colourless needles (206 mg
0320 mmol 92)
1H NMR (400 MHz d8-tol) δ 415 (br q 1JB-H = 91 Hz 1H BH) 211 (q 3JH-H = 74 Hz 8H
Et) 046 (tm 3JH-H = 74 Hz 12H Et) 19F NMR (377 MHz CD2Cl2) δ -13361 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1663 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
247 (d 1JB-H = 91 Hz BH)
General procedure for reactions in toluene using B(C6F5)3 and [NEt4][HB(C6F5)3] (Table
32) In the glovebox a 2 dram vial equipped with a stir bar was charged with the respective
ketone (048 mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and [NEt4][HB(C6F5)3] (154
mg 240 μmol 500 mol) in toluene (10 mL) The vial was loosely capped and loaded in a
Parr pressure reactor sealed carefully and removed from the glovebox to be pressurized with
hydrogen gas The hydrogen gas line was thoroughly purged and the reactor was attached to it
and purged 10 times at 15 atm of hydrogen gas The reactor was then placed in an oil bath set at
80 degC 540 rpm and sealed at 60 atm of hydrogen gas for 12 h After the indicated reaction time
120
the reactor was vented and the reactions were analyzed by 1H NMR spectroscopy Percent
conversion to the alcohol product was obtained by integration relative to the remaining starting
material ketone
3423 Procedures for reactions using heterogeneous Lewis bases
General procedure for reactions in toluene using heterogeneous Lewis bases (Table 33) In
the glovebox a 2 dram vial equipped with a stir bar was charged with the respective ketone (048
mmol) B(C6F5)3 (122 mg 240 μmol 500 mol) and the respective heterogeneous Lewis base
in toluene (10 mL) The vial was loosely capped and loaded in a Parr pressure reactor sealed
carefully and removed from the glovebox to be pressurized with hydrogen gas The hydrogen gas
line was thoroughly purged and the reactor was attached to it and purged 10 times at 15 atm of
hydrogen gas The reactor was then placed in an oil bath set at 60 degC 430 rpm and sealed at 60
atm of hydrogen gas for 12 h Products were isolated by appropriate work-up methods The
alcohol yields were recorded and the products were characterized by NMR spectroscopy and
GC-MS
Heterogeneous Lewis bases α-CD (467 mg 0480 mmol) β-CD (467 mg 0410 mmol) γ-CD
(467 mg 0360 mmol) maltitol (168 mg 0480 mmol) dextrin (350 mg) MS (100 mg)
General procedure 100 g scale reduction of 4-heptanone using MS In the glovebox 4-
heptanone (100 g 876 mmol) was weighed into a 125 mL screw-capped bottle Subsequently
B(C6F5)3 (0224 g 0430 mmol) dissolved in toluene (7 mL ) was added to the bottle in addition
to 302 g of 4 Aring MS The reaction vessel was equipped with a stir bar loosely capped and
placed inside a Parr pressure reactor The reactor was sealed removed from the glovebox and
attached to a purged hydrogen gas line The reactor was purged ten times at 15 atm with
hydrogen gas The reactor was then pressurized with 60 atm hydrogen gas and placed in an oil
bath for 12 h at 70 degC and 430 rpm The reactor was slowly vented and an aliquot was taken in
d8-toluene and complete conversion of 4-heptanone to 4-heptanol was determined by 1H NMR
spectroscopy The reaction mixture was filtered through a frit and washed with dichloromethane
(2 times 10 mL) The collected molecular sieves were extracted with dichloromethane (3 times 10 mL)
and water (20 mL) The organic fraction was dried over magnesium sulfate and combined with
the toluene fraction The two solvents dichloromethane and toluene were removed by fractional
121
distillation 4-Heptanol was then collected under vacuum in a liquid nitrogen cooled Schlenk
flask The product was collected as a colourless liquid (0885 g 762 mmol 87)
3424 Procedures for reductive deoxygenation reactions
General procedure for deoxygenation reactions using molecular sieves (Table 34 and Table
35) This method follows the same procedure for reactions in Table 33 using 4 Aring MS The
reactor was placed in an oil bath set at 70 degC 340 rpm and sealed at 60 atm of hydrogen gas for
12 h Products were isolated by appropriate work-up methods The aromatic hydrocarbon yields
were recorded and the products were characterized by NMR spectroscopy and GC-MS
Verifying the deoxygenation mechanism In the glovebox four separate 2-dram vials were
loaded with diphenylmethanol (442 mg 0240 mmol) and B(C6F5)3 (61 mg 12 μmol 50
mol) To each vial the indicated equivalents of benzophenone were added (21 mg 12 μmol
50 mol 44 mg 24 μmol 10 mol 218 mg 0120 mmol 50 mol) followed by the
addition of d8-toluene (05 mL) and 4 Aring MS (100 mg) The reaction vials were equipped with a
stir bar loosely capped and placed inside a Parr pressure reactor The reactor was sealed
removed from the glovebox and attached to a purged hydrogen gas line The reactor was purged
ten times at 15 atm with hydrogen gas The reactor was then pressurized with 60 atm hydrogen
gas and placed in an oil bath for 12 h at 70 degC and 340 rpm After the indicated reaction time the
reactor was slowly vented and an aliquot was taken in d8-toluene and conversion of the
diphenylmethanol to diphenylmethane was determined by 1H NMR spectroscopy
3425 Spectroscopic data of products in Table 31
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
4-Heptanol (Entry 1) 1H NMR (500 MHz C6D5Br) δ 472 (br s 1H OH) 341 (tt 3JH-H = 70
Hz 46 Hz 1H CH) 124 (m 4H CHCH2) 114 (m 4H CH2CH3) 082 (t 3JH-H = 67 Hz 6H
CH3) 13C1H NMR (125 MHz C6D5Br) δ 721 (CH) 390 (CHCH2) 184 (CH2CH3) 135
(CH3) GC-MS 11928 min mz = 981 [M-H2O] 730 [M-C3H7] 550 [M-C3H9O]
3-Methylbutan-2-ol (Entry 2) 1H NMR (500 MHz C6D5Br) δ 339 (qd 3JH-H = 63 Hz 53
Hz 1H CHOH) 145 (m 1H iPr) 115 (br s 1H OH) 100 (d 3JH-H = 63 Hz 3H CH3) 083
122
(d 3JH-H = 68 Hz 3H iPr) 080 (d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz
C6D5Br) δ 719 (CHOH) 347 (iPr) 200 (CH3) 180 (iPr) 175 (iPr) GC-MS 3150 min mz
= 731 [M-CH3] 551 [M-CH5O]
44-Dimethylpentan-2-ol (Entry 3) 1H NMR (500 MHz C6D5Br) δ 380 (m 1H CH) 368
(br s 1H OH) 127 (dd 2JH-H = 143 Hz 3JH-H = 79 Hz 1H CH2) 116 (dd 2JH-H = 143 Hz 3JH-H = 33 Hz 1H CH2) 105 (d 3JH-H = 62 Hz 3H CH3) 087 (s 9H tBu) 13C1H NMR
(125 MHz C6D5Br) δ 660 (CH) 526 (CH2) 300 (tBu) 299 (tBu) 258 (CH3) GC-MS 6776
min mz = 1011 [M-CH3] 831 [M-CH5O] 701 [M-C2H6O] 571 [M-C3H7O]
Heptan-2-ol (Entry 4) 1H NMR (500 MHz d8-tol) δ 424 (br s 1H OH)
348 (m 3JH-H = 60 Hz 1H H2) 126 (m 2H H6) 123 (m 2H H3 H4)
118 - 114 (m 4H H3 H4 H5) 097 (d 3JH-H = 60 Hz 3H H1) 090 (t 3JH-H = 71 Hz 3H
H7) 13C1H NMR (125 MHz d8-tol) δ 684 (C2) 392 (C3) 319 (C5) 255 (C4) 228 (C1
C6) 139 (C7) GC-MS 12395 min mz = 1011 [M-CH3] 981 [M-H2O] 871 [M-C2H5]
1-Chloropropan-2-ol (Entry 5) 1H NMR (500 MHz C6D5Br) δ 432 (br s 1H OH) 362 (m 3JH-H = 68 Hz 1H CH) 316 (dd 2JH-H = 113 Hz 3JH-H = 35 Hz 1H CH2Cl) 304 (dd 2JH-H =
113 Hz 3JH-H = 68 Hz 1H CH2Cl) 090 (d 3JH-H = 61 Hz 3H CH3) 13C1H NMR (125
MHz C6D5Br) δ 692 (CH) 502 (CH2Cl) 222 (CH3) GC-MS 3383 min mz = 810 [(M+2)-
CH3] 790 [M-CH3]
1-Cyclohexylethan-1-ol (Entry 6) 1H NMR (400 MHz d8-tol) δ 330 (quint 3JH-H = 74 Hz
1H CH) 182 - 147 (m 5H Cy) 131 (br s 1H OH) 125 - 102 (m 4H Cy) 098 (d 3JH-H =
74 Hz 3H CH3) 087 (m 2H Cy) 13C1H NMR (125 MHz d8-tol) δ 721 (CHOH) 452
(CyCH) 287 (Cy) 268 (Cy) 267 (Cy) 205 (CH3) GC-MS 14245 min mz = 1131 [M-CH3]
1101 [M- H2O] 831 [M-C2H5O]
2-Methylpentan-3-ol (Entry 7) 1H NMR (500 MHz C6D5Br) δ 410 (br s 1H OH) 308
(ddd 3JH-H = 88 Hz 52 Hz 38 Hz 1H CHOH) 146 (m 3JH-H = 68 Hz 52 Hz 1H iPr) 133
(dqd 2JH-H = 140 Hz 3JH-H = 75 Hz 39 Hz 1H CH2) 120 (ddq 2JH-H = 140 Hz 3JH-H = 86
Hz 75 Hz 1H CH2) 081 (t 3JH-H = 75 Hz 3H CH3) 077 (d 3JH-H = 68 Hz 3H iPr) 076
(d 3JH-H = 68 Hz 3H iPr) 13C1H NMR (125 MHz C6D5Br) δ 783 (CHOH) 326 (iPr) 264
123
(CH2) 184 (iPr) 167 (iPr) 994 (CH3) GC-MS 5663 min mz = 841 [M-H2O] 731 [M-
C2H5] 591 [M-C3H7]
Heptan-3-ol (Entry 8) 1H NMR (500 MHz C6D5Br) δ 450 (br s 1H
OH) 335 (tt 3JH-H = 73 Hz 47 Hz 1H H3) 136-130 (m 2H H2) 128-
121 (m 5H H4 H5 H6) 115 (m 1H H5) 084 (t 3JH-H = 57 Hz 3H H7) 083 (t 3JH-H = 57
Hz 3H H1) 13C1H NMR (125 MHz C6D5Br) δ 732 (C3) 362 (C4) 295 (C2) 275 (C5)
226 (C6) 138 (C7) 961 (C1) GC-MS 12171 min mz = 981 [M-H2O] 831 [M-CH5O]
691 [M-C2H7O] 590 [M-C4H9]
5-Methylhexan-3-ol (Entry 9) 1H NMR (400 MHz d8-tol) δ (tt 3JH-H = 87 51 Hz 1H
CHOH) 201 (m 2H CH2CH3) 148 (m 3JH-H = 69 51 Hz 1H iPr) 130 (m 1H CH2iPr)
126 (m 1H CH2iPr) 089 (d 3JH-H = 69 Hz 6H iPr) 085 (t 3JH-H = 72 Hz 3H CH3)
13C1H NMR (101 MHz d8-tol) δ 785 (CHOH) 337 (iPr CH2CH3) 273 (CH2iPr) 188
(iPr) 171 (iPr) 104 (CH3) GC-MS 9458 min mz = 871 [M-Et] 691 [M-C2H7O] 591 [M-
CH2iPr]
1-Phenylethan-1-ol (Entry 10) 1H NMR (400 MHz C6D6) δ 702 (m 5H Ph) 428 (q 3JH-H =
65 Hz 1H CH) 342 (br s 1H OH) 102 (d 3JH-H = 65 Hz 3H CH3) 13C1H NMR (125
MHz CDCl3) δ 1460 (ipso-Ph) 1286 (m-Ph) 1283 (p-Ph) 1254 (o-Ph) 703 (CH) 252
(CH3) GC-MS 17207 min mz = 1221 [M] 1071 [M-CH3] 1040 [M-H2O] 910 [M-CH3O]
770 [M-C2H5O]
1-Phenylbutan-2-ol (Entry 11) 1H NMR (500 MHz CD2Cl2) δ 755 (m 1H OH) 733 (tm 3JH-H = 76 Hz 2H m-Ph) 729 (dm 3JH-H = 76 Hz 2H o-Ph) 725 (tm 3JH-H = 76 Hz 1H p-
Ph) 376 (dq 3JH-H = 81 Hz 42 Hz 1H CH) 286 (dd 2JH-H = 136 Hz 3JH-H = 43 Hz 1H
CH2Ph) 266 (dd 2JH-H = 136 Hz 3JH-H = 81 Hz 1H CH2Ph) 152 (q 3JH-H = 77 Hz 2H
CH2CH3) 102 (t 3JH-H = 77 Hz 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1391 (ipso-
Ph) 1295 (m-Ph) 1284 (o-Ph) 1263 (p-Ph) 739 (CH) 437 (CH2Ph) 303 (CH2CH3) 960
(CH3) GC-MS 20079 min mz = 1321 [M-H2O] 1030 [M-C2H7O] 911 [M-C3H7O]
591[M-C7H7]
4-Phenylbutan-2-ol (Entry 12) 1H NMR (500 MHz C6D5Br) δ 720 (t 3JH-H = 74 Hz 2H m-
Ph) 710 (t 3JH-H = 74 Hz 1H p-Ph) 706 (d 3JH-H = 74 Hz 2H o-Ph) 373 (br s 1H OH)
124
362 (dqd 3JH-H = 74 Hz 62 Hz 50 Hz 1H CH) 255 (m 2H PhCH2) 160 (m 2H CH2CH)
103 (d 3JH-H = 62 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1411 (ipso-Ph) 1281
(m-Ph) 1280 (o-Ph) 1255 (p-Ph) 673 (CH) 403 (PhCH2) 317 (CH2CH) 229 (CH3) GC-
MS 20438 min mz = 1501 [M] 1321 [M-H2O] 1170 [M-CH5O] 1051 [M-C2H5O] 911
[M-C3H7O]
1-(2-Fluorophenyl)propan-2-ol (Entry 13) 1H NMR (500 MHz CD2Cl2) δ
753 (m 1H OH) 733 - 705 (m 4H C6H4F) 406 (m 1H CH) 284 (dd 2JH-
H = 139 Hz 3JH-H = 51 Hz 1H CH2) 276 (dd 2JH-H = 139 Hz 3JH-H = 77
Hz 1H CH2) 124 (d 3JH-H = 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1178 (m
CF) 13C1H NMR (125 MHz CD2Cl2) δ 1611 (d 1JC-F = 240 Hz C1) 1318 (d 3JC-F = 59
Hz C3) 1285 (d 4JC-F = 88 Hz C4) 1257 (d 2JC-F = 16 Hz C2) 1240 (d 3JC-F = 37 Hz C5)
1152 (d 2JC-F = 22 Hz C6) 678 (d 4JC-F = 11 Hz CH) 388 (d 3JC-F = 14 Hz CH2) 229
(CH3) GC-MS 18697 min mz = 1360 [M-H2O] 960 [M-C3H6O]
1-(4-Fluorophenyl)propan-2-ol (Entry 14) 1H NMR (500 MHz CD2Cl2) δ 722 (m 2H o of
C6H4F) 705 (m 2H m of C6H4F) 399 (m 1H CH) 278 (dd 2JH-H = 137 Hz 3JH-H = 48 Hz
1H CH2) 269 (dd 2JH-H = 137 Hz 3JH-H = 78 Hz 1H CH2) 161 (br s 1H OH) 122 (d 3JH-H
= 62 Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -1177 (m p-C6H4F) 13C1H NMR (125
MHz CD2Cl2) δ 1616 (d 1JC-F = 243 Hz p of C6H4F) 1348 (d 4JC-F = 46 Hz ipso-C6H4F)
1307 (d 3JC-F = 82 Hz o of C6H4F) 1149 (d 2JC-F = 22 Hz m of C6H4F) 690 (CH) 449
(CH2) 227 (CH3) GC-MS 18697 min mz = 1361 [M-H2O] 960 [M-C3H6O]
1-(3-(Trifluoromethyl)phenyl)propan-2-ol (Entry 15) 1H NMR (500
MHz CD2Cl2) δ 751 (m 2H H1 H5) 744 (m 2H H3 H4) 408 (m 1H
CH) 283 (dd 2JH-H = 136 Hz 3JH-H = 49 Hz 1H CH2) 276 (dd 2JH-H =
136 Hz 3JH-H = 78 Hz 1H CH2) 181 (br s 1H OH) 123 (t 3JH-H = 62
Hz 3H CH3) 19F NMR (377 MHz CD2Cl2) δ -628 (CF3) 13C1H NMR (125 MHz CD2Cl2)
δ 1399 (C2) 1330 (q 4JC-F = 13 Hz C3) 1303 (q 2JC-F = 30 Hz C6) 1288 (C4) 1260 (q 3JC-F = 41 Hz C1) 1242 (q 1JC-F = 277 Hz CF3) 1230 (q 3JC-F = 41 Hz C5) 687 (CH) 447
(CH2) 228 (CH3) GC-MS 19011 min mz = 1861 [M-H2O] 1601 [M-C2H4O] 1171 [M-
CH2F3O]
125
Cyclohexanol (Entry 16) 1H NMR (400 MHz d8-tol) δ 324 (tt 3JH-H = 90 Hz 37 Hz 1H
CH) 177 (m 2H Cy) 168 (m 2H Cy) 142- 130 (m 3H Cy) 126- 115 (m 3H Cy)
13C1H NMR (101 MHz CD2Cl2) δ 706 (CH) 360 (CHCH2) 260 (Cy) 245 (Cy) GC-MS
4029 min mz = 1001 [M] 821 [M-H2O]
2-Isopropyl-5-methylcyclohexan-1-ol (Entry 17) 1H NMR (500 MHz
C6D5Br) δ 390 (q 3JH-H = 29 Hz 1H H1) 346 (br s 1H OH) 168 (ddd 2JH-H = 139 Hz 3JH-H = 36 Hz 24 Hz 1H H2) 164 (m 2H H3 H4) 153
(dm 2JH-H = 132 Hz 1H H5) 143 (dm 3JH-H = 92 Hz 67 Hz 1H H7) 118 (dm 2JH-H = 132
Hz 1H H5) 091 (m 1H H2) 087 (d 3JH-H = 67 Hz 3H H8) 083 (d 3JH-H = 67 Hz 3H
H9) 080 (d 3JH-H = 64 Hz 3H H10) 075 (m 1H H4) 070 (m 1H H6) 13C1H NMR (125
MHz C6D5Br) δ 675 (C1) 473 (C6) 421 (C2) 346 (C4) 288 (C7) 254 (C3) 238 (C5)
221 (C10) 208 (C9) 203 (C8) GC-MS 18912 min mz = 1381 [M-H2O] 1231 [M-CH5O]
951 [M-C3H9O] 811 [M-C4H12O]
Cyclohexylmethanol (Entry 18) 1H NMR (500 MHz CD2Cl2) δ 556 (br s 1H OH) 404 (d 3JH-H = 75 Hz 2H CH2OH) 212-182 (m 1H CyCH2) 180 (m 1H CyCH) 163 - 117 (m 1H CyCH2) 13C1H NMR (125 MHz CD2Cl2) δ 693 (CH2OH) 374 (CyCH) 301 (CyCH2) 262
(CyCH2) 252 (CyCH2) GC-MS 5538 min mz = 1141 [M] 961 [M-H2O] 831 [M-CH3O]
3426 Spectroscopic data of products in Table 32
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
3-Methylpentan-2-ol (Entry 4) 1H NMR (400 MHz CDCl3) δ 376 (m 1H CHOH) 223 (br
s 1H OH) 175 - 142 (m 3H CH(Et) Et) 118 (d 3JH-H = 69 Hz 3H CH3CHOH) 098 (m
6H CH(Et)CH3 Et) 13C1H NMR (125 MHz CD2Cl2) δ 713 (CHOH) 406 (CH(Et)) 223
(Et) 198 (OHCHCH3) 120 (CH(Et)CH3) 111 (Et) GC-MS 10215 min mz = 871 [M-CH3]
561 [M-C2H6O] 450 [C2H5O]
3427 Spectroscopic data of products in Table 33
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products NMR and GC-MS data of products not reported in previous sections are listed
126
222-Trifluoro-1-phenylethan-1-ol (Entry 12) 1H NMR (500 MHz d8-tol) δ 745 (m 2H m-
Ph) 717 (dm 3JH-H = 70 Hz 2H o-Ph) 711 (m 1H p-Ph) 432 (d 3JF-H = 77 Hz 1H CH)
306 (br s 1H OH) 19F NMR (470 MHz d8-tol) δ -783 (d 3JF-H = 77 Hz CF3) 13C1H NMR
(125 MHz d8-tol) δ 1341 (ipso-Ph) 1289 (m-Ph) 1276 (p-Ph) 1272 (q 4JC-F = 12 Hz o-Ph)
1234 (q 1JC-F = 297 Hz CF3) 726 (CH) GC-MS 6130 min mz = 1760 [M] 1701 [M-CF3]
3-Chloro-1-phenylpropan-1-ol (Entry 11) 1H NMR (600 MHz d8-tol) δ 712 (m 3H m p-
Ph) 703 (m 2H o-Ph) 399 (t 3JH-H = 78 Hz 1H CHOH) 312 (t 3JH-H = 67 Hz 2H CH2Cl)
251 (br s 1H OH) 218 (dt 3JH-H = 78 Hz 67 Hz 2H CHCH2CH2) 13C1H NMR (151
MHz d8-tol) δ 1440 (ipso-Ph) 1282 (m-Ph) 1275 (o-Ph) 1260 (p-Ph) 476 (CHOH) 432
(CH2Cl) 387 (CHCH2CH2) GC-MS 11210 min mz = 1701 [M] 1521 [M-H2O] 1070 [M-
C2H4Cl]
1-(2-(Trifluoromethyl)phenyl)ethan-1-ol (Entry 13) 1H NMR (500 MHz
d8-tol) δ 759 (d 3JH-H = 81 Hz 1H H2) 732 (d 3JH-H = 81 Hz 1H H5)
711 (t 3JH-H = 81 Hz 1H H3) 685 (t 3JH-H = 81 Hz 1H H4) 508 (qm 3JH-
H = 67 Hz 1H CHOH) 221 (br s 1H OH) 125 (d 3JH-H = 67 Hz 3H CH3)
19F NMR (470 MHz d8-tol) δ -582 (s CF3) 13C1H NMR (125 MHz d8-tol) δ 1455 (ipso-
C6H4CF3) 1315 (C3) 1314 (C1) 1294 (C4) 1264 (C2) 1244 (C5) 1240 (CF3) 653
(CHOH) 253 (CH3) (JC-F not reported) GC-MS 6453 min mz = 1901 [M] 1750 [M-CH3]
1720 [M-H2O] 1450 [M-C2H5O]
1-(4-(Methylsulfonyl)phenyl)ethan-1-ol (Entry 14) 1H NMR (500 MHz d8-tol) δ 763 (d 3JH-H = 86 Hz 2H o of C6H4SO2CH3) 705 (d 3JH-H = 86 Hz 2H m of C6H4SO2CH3) 437 (m
1H CHOH) 228 (s 3H SO2CH3) 141 (br s 1H OH) 112 (d 3JH-H = 66 Hz 3H CHCH3)
13C1H NMR (125 MHz d8-tol) δ 1522 (p of C6H4SO2CH3) 1402 (ipso-C6H4SO2CH3) 1270
(o of C6H4SO2CH3) 1257 (m of C6H4SO2CH3) 689 (CHOH) 436 (SO2CH3) 252 (CHCH3)
HRMS-DART+ mz [M+NH4]+ calcd for C9H16NO3S 21808509 Found 21808554
22-Diphenylethan-1-ol (Entry 24) 1H NMR (500 MHz d8-tol) δ 704 (m 1H p-Ph) 703 (m
2H m -Ph) 693 (d 3JH-H = 75 Hz 2H o-Ph) 405 (dd 3JH-H = 83 Hz 61 Hz 1H CH) 400
(m 2H CH2) (OH was not observed) 13C1H NMR (125 MHz d8-tol) δ 1418 (ipso-Ph)
1293 (m-Ph) 1287 (o-Ph) 1274 (p-Ph) 763 (CH2) 512 (CH) GC-MS 15178 min mz =
1811 [M-OH] 1671 [M-CH3O]
127
2-Phenylpropan-1-ol (Entry 25) 1H NMR (500 MHz d8-tol) δ 722 (d 3JH-H = 78 Hz 2H o-
Ph) 718 ndash 713 (m 3H m p-Ph) 362 (dd 2JH-H = 100 Hz 3JH-H = 62 Hz 1H CH2) 354 (dd 2JH-H = 100 Hz 3JH-H = 78 Hz 1H CH2) 342 (br s 1H OH) 288 (m 3JH-H = 69 Hz 1H CH)
121 (d 3JH-H = 69 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1459 (ipso-Ph) 1289 (p-
Ph) 1283 (m-Ph) 1274 (o-Ph) 780 (CH2) 435 (CH) 181 (CH3) GC-MS 6462 min mz =
1211 [M-CH3] 1051 [M-CH3O]
3428 Spectroscopic data of products in Table 34 and Scheme 312 (a)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Styrene (Entry 1)1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 77 Hz 2H o-Ph) 708 (t 3JH-
H = 77 Hz 2H m-Ph) 706 (t 3JH-H = 77 Hz 1H p-Ph) 653 (dd 3JH-H = 176 Hz 109 Hz 1H
CH) 556 (dd 3JH-H = 176 Hz 11 Hz 1H CH2) 505 (dd 3JH-H = 109 Hz 11 Hz 1H CH2)
13C1H NMR (125 MHz d8-tol) δ 1379 (CH) 1372 (ipso-Ph) 1286 (o m-Ph) 1284 (p-Ph)
1140 (CH2) GC-MS 4038 min mz = 1041 [M] 911 [C7H7] 781 [C6H6]
1-(Trifluoromethyl)-3-vinylbenzene (Entry 2) 1H NMR (500 MHz d8-
tol) δ 744 (s 1H H1) 718 (d 3JH-H = 77 Hz 1H H5) 706 (d 3JH-H = 77
Hz 1H H3) 686 (t 3JH-H = 75 Hz 1H H4) 631 (dd 3JH-H = 173 Hz 102
Hz 1H CH=CH2) 544 (d 3JH-H = 173 Hz 1H CH=CH2) 504 (d 3JH-H = 102 Hz 1H
CH=CH2) 19F NMR (470 MHz d8-tol) δ -626 (s CF3) 13C1H NMR (125 MHz d8-tol) δ
1379 (ipso-C6H4CF3) 1354 (CH=CH2) 1309 (C2) 1284 (C5) 1245 (CF3) 1237 (C3) 1225
(C1) 1151 (CH=CH2) (JC-F not reported) GC-MS 4290 min mz = 1721 [M] 1531 [M-F]
1451 [M-C2H3] 1031 [M-CF3]
(E)-Prop-1-en-1-ylbenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 718 (d 3JH-H = 73 Hz
2H o-Ph) 712 (t 3JH-H = 73 Hz 2H m-Ph) 702 (t 3JH-H = 73 Hz 1H p-Ph) 626 (dq 3JH-H =
156 Hz 4JH-H = 18 Hz 1H PhCH=CH) 600 (dq 3JH-H = 156 Hz 66 Hz 1H PhCH=CH)
168 (dd 3JH-H = 66 Hz 4JH-H = 18 Hz 3H CH3) 13C1H NMR (125 MHz d8-tol) δ 1378
(ipso-Ph) 1314 (PhCH=CH) 1283 (m-Ph) 1265 (p-Ph) 1258 (o-Ph) 1248 (PhCH=CH)
1800 (CH3) GC-MS 5888 min mz = 1181 [M] 1171 [M-H] 1031 [M-CH3]
128
(2-Methylprop-1-en-1-yl)benzene (Entry 4) 1H NMR (500 MHz d8-tol) δ 717 (m 4H o m-
Ph) 705 (m 1H p-Ph) 624 (m 4JH-H = 15 Hz 1H CH=C(CH3)2) 180 (d 4JH-H = 15 Hz 3H
CH=C(CH3)2) 175 (d 4JH-H = 15 Hz 3H CH=C(CH3)2) 13C1H NMR (125 MHz d8-tol) δ
1386 (C(CH3)2) 1345 (ipso-Ph) 1287 (o-Ph) 1279 (m-Ph) 1257 (CH=C(CH3)2) 1256 (p-
Ph) 264 (CH3) 188 (CH3) GC-MS 5780 min mz = 1321 [M] 1171 [M-CH3]
12-Dihydronaphthalene (Scheme 312a) 1H NMR (600 MHz CD2Cl2) δ 746 - 731 (m 4H
C6H4) 678 (dm 3JH-H = 96 Hz 1H CH=CHCH2) 632 (m 1H CH=CHCH2) 308 (m 2H
CH2CH2CH) 258 (m 2H CH2CH=CH) 13C1H NMR (125 MHz CD2Cl2) δ 1358
(quaternary C for C6H4) 1344 (quaternary C for C6H4) 1288 (CH=CHCH2) 1280
(CH=CHCH2) 1277 (C6H4) 1271 (C6H4) 1266 (C6H4) 1261 (C6H4) 278 (CHCH2CH2) 236
(CH=CHCH2) GC-MS 7943 min mz = 1301 [M] 1151 [M-CH3] 1021 [M-C2H4]
3429 Spectroscopic data of products in Table 35 and Scheme 312 (b)
All GC-MS results have been compared to starting materials and commercially purchased
alcohol products
Diphenylmethane (Entry 1) 1H NMR (500 MHz d8-tol) δ 708 (t 3JH-H = 75 Hz 2H m-Ph)
701 (t 3JH-H = 75 Hz 1H p-Ph) 700 (d 3JH-H = 75 Hz 2H o-Ph) 372 (s 1H CH2) 13C1H
NMR (125 MHz d8-tol) δ 1413 (ipso-Ph) 1293 (o-Ph) 1286 (m-Ph) 1263 (p-Ph) 422
(CH2) GC-MS 11686 min mz = 1681 [M] 1671 [M-H] 911 [C7H7]
1-Benzyl-4-methoxybenzene (Entry 2) 1H NMR (500 MHz d8-tol) δ 712 (m 2H m-Ph)
711 (m 1H p-Ph) 705 (d 3JH-H = 67 Hz 2H o-Ph) 693 (d 3JH-H = 76 Hz 2H o of
C6H4OCH3) 670 (d 3JH-H = 76 Hz 2H m of C6H4OCH3) 372 (s 2H CH2) 334 (s 3H
OCH3) 13C1H NMR (125 MHz d8-tol) δ 1581 (p of C6H4OCH3) 1416 (ipso-C6H4OCH3)
1328 (ipso-Ph) 1295 (o of C6H4OCH3) 1287 (o-Ph) 1283 (m-Ph) 1278 (p-Ph) 1137 (m of
C6H4OCH3) 542 (OCH3) 410 (CH2) GC-MS 14801 min mz = 1981 [M] 1671 [M-OCH3]
1211 [M-C6H5] 911 [M-C7H7O] 771 [M-C8H9O]
1-Benzyl-4-bromobenzene (Entry 3) 1H NMR (500 MHz d8-tol) δ 719 (m 1H p-Ph) 716
(d 3JH-H = 78 Hz 2H m of C6H4Br) 710 (t 3JH-H = 77 Hz 2H m-Ph) 691 (d 3JH-H = 77 Hz
2H o-Ph) 665 (d 3JH-H = 77 Hz 2H o of C6H4Br) 355 (s 2H CH2) 13C1H NMR (125
MHz d8-tol) δ 1407 (ipso-C6H4Br) 1403 (ipso-Ph) 1317 (m of C6H4Br) 1316 (p-Ph) 1308
129
(o of C6H4Br) 1289 (o-Ph) 1285 (m-Ph) 1204 (p-C6H4Br) 414 (CH2) GC-MS 15250 min
mz = 2480 [M+2] 2460 [M] 1671 [M-Br] 911 [M-C6H4Br]
1-Benzyl-4-(tert-butyl)benzene (Entry 4) 1H NMR (500 MHz CD2Cl2) δ 774 (t 3JH-H = 86
Hz 2H m of C6H4tBu) 768 (t 3JH-H = 76 Hz 1H p-Ph) 761 (t 3JH-H = 76 Hz 2H m-Ph)
759 (d 3JH-H = 76 Hz 2H o-Ph) 755 (d 3JH-H = 86 Hz 2H o of C6H4tBu) 435 (s 2H CH2)
178 (s 9H tBu) 13C1H NMR (125 MHz CD2Cl2) δ 1493 (p of C6H4tBu) 1420 (ipso-Ph)
1387 (ipso-C6H4tBu) 1294 (m-Ph o of C6H4tBu) 1286 (p-Ph) 1263 (o-Ph) 1255 (m of
C6H4tBu) 415 (CH2) 347 (tBu) 315 (tBu) GC-MS 15429 min mz = 2242 [M] 2092 [M-
CH3) 911 [C7H7]
Di-p-tolylmethane (Entry 5) 1H NMR (500 MHz d8-tol) δ 699 (d 3JH-H = 78 Hz 2H o of
C6H4CH3) 694 (d 3JH-H = 78 Hz 2H m of C6H4CH3) 375 (s 1H CH2) 215 (s 3H CH3)
13C1H NMR (125 MHz d8-tol) δ 1383 (ipso-C6H4CH3) 1350 (p of C6H4CH3) 1289 (m of
C6H4CH3) 1287 (o of C6H4CH3) 408 (CH2) 206 (CH3) GC-MS 14226 min mz = 1961
[M] 1811 [M-CH3) 1661 [M-2(CH3)] 1051 [M-C7H7] 911 [M- C8H9]
1-Benzyl-4-(trifluoromethyl)benzene (Entry 6) 1H NMR (600 MHz CD2Cl2) δ 800 (d 3JH-H
= 73 Hz 2H o-Ph) 788 (d 3JH-H = 74 Hz 2H m of C6H4CF3) 778 (t 3JH-H = 73 Hz 1H p-
Ph) 767 (t 3JH-H = 73 Hz 2H m-Ph) 751 (d 3JH-H = 74 Hz 2H o of C6H4CF3) 430 (s 2H
CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1458 (ipso-C6H4CF3) 1404 (ipso-Ph) 1296 (p-Ph
o of C6H4CF3) 1285 (m-Ph) 1258 (p of C6H4CF3) 1256 (o-Ph) 1255 (m of C6H4CF3) 1239
(CF3) 415 (CH2) (JC-F not reported) GC-MS 11767 min mz = 2361 [M] 1671 [M-CF3]
1591 [M-C6H5] 911 [C7H7]
1-Benzyl-2-methylbenzene (Entry 7) 1H NMR (600 MHz CD2Cl2) δ
776 (m 2H o-Ph) 767 - 761 (m 3H m p-Ph) 759 - 754 (m 4H
C6H4CH3) 438 (s 2H CH2) 270 (s 3H CH3) 13C1H NMR (151
MHz CD2Cl2) δ 1410 (ipso-Ph) 1393 (ipso-C6H4CH3) 1370 (C-CH3) 1307 (C1) 1303 (m-
Ph) 1292 (o-Ph) 1287 (C4) 1268 (p-Ph) 1263 (C3) 1262 (C2) 395 (CH2) 197 (CH3)
GC-MS 12844 min mz = 1821 [M] 1671 [M-CH3]
130
1011-Dihydro-5H-dibenzo[ad][7]annulene (Scheme 312 b) 1H NMR
(600 MHz CD2Cl2) δ 745 (m 1H H2) 742 (m 1H H4) 740 (m 2H
H3 H5) 438 (s 1H CH2) 342 (s 2H CH2) 13C1H NMR (125 MHz
CD2Cl2) δ 1423 (C6) 1395 (C1) 1298 (C5) 1291 (C2) 1268 (C4) 1263 (C3) GC-MS
15761 min mz = 1941 [M] 1791 [M-CH3] 1651 [M-C2H5]
343 X-Ray Crystallography
3431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
3432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
131
3433 Selected crystallographic data
Table 36 ndash Selected crystallographic data for 31
31 (+05 C6D5Br)
Formula C43H295B1Br05F20O2
Formula wt 100893
Crystal system monoclinic
Space group P2(1)c
a(Aring) 127865(6)
b(Aring) 199241(9)
c(Aring) 170110(7)
α(ordm) 9000
β(ordm) 1067440(10)
γ(ordm) 9000
V(Aring3) 41500(3)
Z 4
Temp (K) 150(2)
d(calc) gcm-3 1607
Abs coeff μ mm-1 0606
Data collected 37469
Rint 00368
Data used 9534
Variables 596
R (gt2σ) 00458
wR2 01145
GOF 1020
132
Chapter 4 Hydroamination and Hydrophosphination Reactions Using
Frustrated Lewis Pairs
41 Introduction
411 Hydroamination
The direct addition of N-H bonds to unsaturated organic compounds provides an atom-economic
route to valuable nitrogen-containing molecules Pursuit of such reactivity is largely motivated
by the ubiquitous nature of substituted amines in the pharmaceutical industry303-306 The
intermolecular hydroamination of alkynes represents an attractive single-step approach to
convert inexpensive and readily available starting materials to synthetic building blocks such as
imines and enamines
Intermolecular hydroamination of alkynes was initially carried out using Hg and Tl salts307-308
however toxicity concerns prompted subsequent development of a wide variety of other catalysts
based on rare-earth metals309 early- and late-transition metals303 310 as well as lanthanides311-312
and actinides313 Based on the pioneering work of Bergman314-316 and Doye317-318 group IV metal
derivatives have become popular catalysts in these reactions More recently the groups of
Richeson319 Odom320-321 Schafer322 Mountford323 and others311 313 321 324 have made significant
contributions to further the development of these catalysts
Nonetheless to date transition metal-free routes remain relatively less explored The Broslashnsted
acid tungstophosphoric acid has been reported by Lingaiah325 to catalyze the hydroamination of
alkynes However in order for this catalyst to operate harsh conditions and electronically
deactivated amines are required An alternative approach using a strong base such as cesium
hydroxide was reported by Knochel although this strategy only tolerated functional groups less
acidic than the amines309 More recently metal-free approaches have been demonstrated in the
work by Beauchemin on the Cope-type inter- and intramolecular hydroaminations326-329
133
412 Reactions of main group FLPs with alkynes
4121 12-Addition or deprotonation reactions
Recent research has been devoted to effect metal-free stoichiometric and catalytic
transformations using frustrated Lewis pairs (FLPs) These main group combinations of bulky
Lewis acids and bases have become the focus of a number of research groups worldwide330-331
Shortly after the discovery of FLP chemistry several reports communicated the organic
manipulation of alkynes analogous to the pioneering hydroboration reactions by H C Brown60
Initial studies showed that FLPs comprised of B(C6F5)3 or Al(C6F5)3(PhMe) and phosphines react
to yield either zwitterionic vinyl phosphonium borate or aluminate salts resulting from a 12-
addition reaction or phosphonium alkynylborates resulting from alkyne deprotonation126 128 The
course of the reaction was found to depend on the basicity of the phosphine donor with less
basic aryl phosphines favouring 12-addition (Scheme 41)
Scheme 41 ndash Reaction of sterically hindered tertiary phosphines and E(C6F5)3 with
phenylacetylene to give 12-addition or deprotonation products (E = B or Al)
Berke and co-workers investigated related intermolecular reactions of terminal alkynes and
B(C6F5)3 with 26-lutidine and TMP demonstrating that these systems effect deprotonation of the
alkyne affording ammonium alkynylborates156 Alternatively the groups of Erker and Stephan
reported the intramolecular cyclization of pendant alkyne substituted anilines151 and N-
heterocycles152 via 12-addition reactions using B(C6F5)3 (Scheme 42 a and b) In a similar
fashion ethylene-linked sulphurborane systems were found to add to alkynes with subsequent
elimination of ethylene affording a single-step route to SB alkenyl-FLPs (Scheme 42 c)332
134
Scheme 42 ndash FLP-type 12-addition reactions of B(C6F5)3 to pendant alkyne substituted anilines
(a) and N-heterocycles (b) 12-addition of ethylene-linked sulphurborane FLP to
phenylacetylene generating SB alkenyl-FLPs (c)
4122 11-Carboboration reactions
The groups of Berke and Erker separately studied the reactivity of Lewis acids with alkynes in
the absence of a Lewis base (Scheme 43) To this extent they identified the 11-carboboration
reaction to generate alkenylboranes156 159-160 Moreover the reaction of propargyl esters with
B(C6F5)3 have been shown to generate boron allylation reagents333
Scheme 43 ndash 11-Carboboration of terminal and internal alkynes to generate a series of
alkenylboranes
135
4123 Hydroelementation reactions
Catalytic hydroelementation reactions have been reported for alkynes In the presence of 5 - 10
mol B(C6F5)3 internal alkynes have been shown to undergo both hydrostannylation334 (Scheme
44 a) and hydrogermylation335 reactions (Scheme 44 b)
Scheme 44 ndash B(C6F5)3 catalyzed hydrostannylation (a) and hydrogermylation (b) of alkynes
413 Reactions of transition metal FLPs with alkynes
The FLP paradigm has also been studied using transition metal systems in combination with
alkynes Some examples include metalation through the 11-carbozirconation336 and
boroauration337 reactions Additionally the Wass group developed cationic zirconocene
phosphinoaryloxide complexes that selectively deprotonate terminal alkynes (Scheme 45)338 In
a recent paper the Stephan group has shown that Ru-acetylides act as carbon nucleophiles in
combination with Lewis acids to effect trans-addition to alkynes162
Scheme 45 ndash Reaction of zirconocene phosphinoaryloxide complexes with terminal alkynes
Inspired by the reactivity of FLPs with alkynes in this chapter the intermolecular reaction of
amines B(C6F5)3 and a versatile group of terminal alkynes is explored in hydroamination
reactions A catalytic approach to yield enamines and corresponding amines is described In
addition related systems are probed to accomplish stoichiometric and catalytic intramolecular
hydroaminations affording N-heterocycles Finally stoichiometric approaches to
hydrophosphination reactions are discussed
136
42 Results and Discussion
421 Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
With the objective of initiating hydroamination reactivity the three component stoichiometric
reaction of Ph2NH B(C6F5)3 and phenylacetylene was performed in CD2Cl2 The 1H 11B and 19F
NMR spectra revealed consumption of two equivalents of phenylacetylene to afford the salt
[Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] 41 while leaving a portion of the starting materials Ph2NH
and B(C6F5)3 unreacted (Scheme 46) Adjustment of the alkyne stoichiometry to two equivalents
afforded 41 in 90 yield (Table 41 entry 1) This new species results from the sequential
hydroamination and deprotonation reaction of phenylacetylene
Scheme 46 ndash Stoichiometric hydroamination and deprotonation of phenylacetylene yielding 41
The 1H NMR spectrum displayed a diagnostic methyl singlet at 289 ppm with the corresponding 13C1H resonance at 283 ppm In addition a downfield 13C1H resonance at 1901 ppm is
attributable to the iminium N=C group The alkynylborate anion [PhCequivCB(C6F5)3]- gave rise to
the 11B NMR signal at -208 ppm and 19F resonances at -1327 -1638 and -1673 ppm The
nature of compound 41 was unambiguously confirmed by X-ray crystallography (Figure 41)
Figure 41 ndash POV-Ray depiction of 41 N=C 1308(2) Aring sum of bond angles at nitrogen 3599deg
137
To probe the generality of this reaction the corresponding reactivity of various substituted
secondary anilines with two equivalents of phenylacetylene were explored In this fashion the
species [RPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (R = iPr 42 Cy 43 PhCH2 44 p-CH3O 45) were
isolated in 88 91 82 and 90 yield respectively (Table 41 entry 1) 1H NMR spectra
showed the iminium cations were formed as a mixture of the E and Z isomers in a 71 ratio for
compounds 42 and 43 41 ratio for 44 and 11 ratio for 45
Analogous reactions of Ph2NH B(C6F5)3 and two equivalents of 1-hexyne revealed two
competitive reaction pathways In addition to the hydroaminationdeprotonation product
[Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] 46 (Table 41 entry 2) the alkenylboranes resulting from
the 11-carboboration of 1-hexyne were also observed by NMR spectroscopy Exposing the same
anilineB(C6F5)3 combination to 9-ethynylphenanthrene produced [Ph2N=C(CH3)C14H9]
[C14H9CequivCB(C6F5)3] 47 in 75 isolated yield (Table 41 entry 3) The molecular structure of
47 was unambiguously characterized by X-ray crystallography (Figure 42)
Figure 42 ndash POV-Ray depiction of 47
138
Table 41 ndash Stoichiometric intermolecular hydroamination and deprotonation of terminal alkynes
139
In a similar fashion the reaction of two equivalents of ethynylcyclopropane with B(C6F5)3 and
iPrPhNH at room temperature afforded the yellow crystalline solid formulated as
[iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] 48 in 88 yield (Table 41 entry 4) In this case
the 1H NMR spectrum showed the iminium cation is formed as a mixture of the E and Z isomers
in a 17 ratio Furthermore the reaction of iPrPhNHB(C6F5)3 with 2-ethynylthiophene
proceeded cleanly to give the product [iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] 49
obtained as a 71 mixture of EZ isomers and isolated in 78 yield (Table 41 entry 5) Single
crystals suitable for X-ray diffraction were obtained for Z-48 and Z-49 and the structures are
shown in Figure 43 (a) and (b) respectively
Figure 43 ndash POV-Ray depiction of Z-48 (a) and Z-49 (b)
Interestingly addition 14-diethynylbenzene to the stoichiometric combination of Ph2NH
B(C6F5)3 resulted in an instant color change from pale orange to deep red affording the
zwitterionic product [Ph2N=C(CH3)C6H4CequivCB(C6F5)3] 410 in 85 yield (Table 41 entry 6)
The molecular structure of 410 was confirmed by X-ray crystallography (Figure 44)
Figure 44 ndash POV-Ray depiction of 410
(a) (b)
140
4211 Proposed mechanism for the hydroamination and deprotonation reactions of terminal alkynes
The three component reaction is thought to proceed via Lewis acid polarization of the alkyne by
B(C6F5)3 prompting nucleophilic addition of the aniline and generating a zwitterionic
intermediate (Scheme 47) Analogous 12-additions to alkynes have been previously reported for
phosphineborane126 128 thioetherborane339 and pyrroleborane127 FLPs However in the present
study the arylammonium intermediate provides an acidic proton which cleaved the B-C bond
yielding enamine with concurrent release of B(C6F5)3 Subsequent to this hydroamination the
FLP derived from enamine and B(C6F5)3 deprotonate a second equivalent of the alkyne affording
the isolated iminium alkynylborate salts (Scheme 47)
Scheme 47 ndash Proposed mechanism for the hydroamination and deprotonation reactions
generating iminium alkynylborate salts
Analogous stoichiometric combination of tert-butylaniline or diisopropylamine and B(C6F5)3
with either one or two equivalents of phenylacetylene resulted exclusively in deprotonation of
the terminal alkyne affording the ammonium alkynylborate salts [tBuPhNH2][PhCequivCB(C6F5)3]
411 and [iPr2NH2][PhCequivCB(C6F5)3] 412 in 99 and 76 yield respectively (Scheme 48) In
these cases the amines are sufficiently bulky to form a FLP with B(C6F5)3 and relatively basic to
preferentially effect deprotonation of the alkyne This reaction pathway has been previously
observed for basic phosphines and B(C6F5)3 with numerous alkynes
141
Scheme 48 ndash Deprotonation of phenylacetylene by diisopropylamine and B(C6F5)3
4212 Reactivity of amineborane FLPs with internal alkynes and other unsaturated substrates
In separate reactions FLPs comprised of iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 were
combined with the internal alkynes 3-hexyne diphenylacetylene and 1-phenyl-1-propyne At
RT multinuclear NMR data only revealed signals for the FLP and unaltered alkyne Heating
the reactions up to 80 degC did not display signals for hydroamination rather only products of 11-
carboboration were observed
Also interested in extending the unsaturated substrates scope the hydroamination of the olefins
1-hexene cyclohexene styrene αp-dimethylstyrene and 3-(trifluoromethyl)styrene were tested
using the FLPs iPrNHPhB(C6F5)3 and Ph2NHB(C6F5)3 Thermolysis of the individual samples
up to 100 degC only revealed signals for the starting materials
4213 Reactivity of the iminium alkynylborate products with nucleophiles
An attractive feature of the iminium cation is the unsaturated N=C fragment since it could be
reacted with nucleophiles to give amines and this transformation could potentially be extended to
generate enantioselective variants of the amines Introducing simple fluoride sources such as
[NBu4][Si(Ph)3F2] NBu4F and CsF to compounds 42 and 46 resulted in deprotonation of the
methyl group losing HF and generating the corresponding enamine Nonetheless addition of the
H+ source [(Et2O)2H][B(C6F5)4]287 regenerated the iminium cation (Scheme 49)
Scheme 49 ndash Deprotonation of 42-cation by fluoride sources and regeneration of the cation
with [(Et2O)2H][B(C6F5)4]
142
Furthermore addition of the organolithium reagents methyl lithium and ethyl lithium at -30 degC
gave a 11 mixture of the alkylation and deprotonation products as evidenced by 1H NMR
spectroscopy while phenyl lithium did not result in any reactivity (Scheme 410 left)
Combinations of stoichiometric hydride sources [tBu3PH][HB(C6F5)3] NaBHEt3 and LiAlH4
only gave saturation of the N=C bond with the lithium reducing agent (Scheme 410 right)
Overall while hydride delivery to the N=C bond was successfully achieved inefficient delivery
of the presented alkyl and aryl nucleophiles shifted focus towards other types of reactivities
Scheme 410 ndash Reaction of 42-cation with organolithium sources (left) and LiAlH4 (right)
422 Friedel-Crafts hydroarylation of phenylacetylene using aromatic amines and B(C6F5)3
The equimolar reaction of the tertiary amine dibenzylaniline B(C6F5)3 and phenylacetylene was
investigated with the aim of isolating a zwitterionic intermediate analogous to the compound
proposed en route to hydroamination in Scheme 47 In this case however the nucleophilic
centre for this reaction proved to be the para-carbon of the N-bound phenyl ring undergoing
hydroarylation of phenylacetylene to generate the zwitterionic species
(PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 413 in 96 yield (Scheme 411) Single crystal X-ray
diffraction confirmed the structure of 413 and it is shown in Figure 45 (a)
Scheme 411 ndash Hydroarylation of phenylacetylene using stoichiometric equivalents of
dibenzylaniline and B(C6F5)3
143
Examining the secondary amine N-isopropylanthracen-9-amine in similar reactivity also gave the
hydroarylation of phenylacetylene and this was demonstrated at the C10 position of the
anthracene ring forming iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 414 in 95 yield In this unique
case however a N=C double bond is generated between nitrogen and the anthracene ring as well
as saturation of the C10 centre giving the tetrahedral geometry observed in the solid state
structure of 414 shown in Figure 45 (b) Generally aromatic substitution reactions in the
presence of Lewis acids have been used for the synthesis of numerous aromatic molecules340
Particularly relevant to this thesis the para-carbon of N-bound phenyl rings has been proposed
as the Lewis basic centre to heterolytically split H2 and generate a sp3-hybridized carbon centre
in the arene hydrogenation reactions presented in Chapter 2
Figure 45 ndash POV-Ray depiction of 413 (a) and 414 (b) Compound 414 N=Canthracene bond
length 1305(5)Aring bond angle iPrC-N=Canthracene 1328deg
Stability of the B-C bond towards acidic conditions was tested In this regard combinations of
413 with the protic salts [(Et2O)2H][B(C6F5)4] or [Ph2NH2][B(C6F5)4] were found to readily
cleave the B-C bond liberating B(C6F5)3 and generating the diphenylethylene-ammonium
derivative as evidenced by the geminal protons at 508 and 504 ppm in the 1H NMR spectrum
(Scheme 412)
(a) (b)
144
Scheme 412 ndash Treatment of compound 413 with protic salts [(Et2O)2H][B(C6F5)4] or
[Ph2NH2][B(C6F5)4] to cleave the B-C bond
423 B(C6F5)3 catalyzed intermolecular hydroamination of terminal alkynes
With the exception of catalytic hydrogenations the majority of FLPs reported to date react with
small molecules in a stoichiometric fashion Thus seeking to expand the application of FLPs in
catalysis beyond hydrogenations attention was turned to the development of catalytic
hydroamination reactions This motivation was inspired by the hydroaminationdeprotonation
mechanism proposed in Scheme 47 Realizing that deprotonation of alkyne eliminates the
possibility for catalysis the reaction protocol was adjusted in which the alkyne is added slowly
in order to achieve hydroamination and prevent deprotonation by enamine and B(C6F5)3
The slow addition of the terminal alkyne 2-ethynylanisole to a RT solution of Ph2NH and 10
mol of B(C6F5)3 in toluene over 10 h afforded the catalytic hydroamination product 2-
methoxyphenyl substituted enamine Ph2N(2-MeOC6H4)C=CH2 415 in 84 isolated yield (Table
42) The 1H NMR spectrum of 415 displayed two diagnostic singlets at 501 and 490 ppm
characteristic of the inequivalent geminal hydrogen atoms The corresponding carbon centre
gives rise to a 13C1H NMR signal at 108 ppm Further NMR studies of the compound were
consistent with formation of the Markovnikov isomer in which the nitrogen is added to the
substituted carbon of the terminal alkyne
The analogous treatment of Ph2NH with 2-ethynyltoluene in the presence of 10 mol B(C6F5)3
afforded Ph2N(2-MeC6H4)C=CH2 416 in 69 isolated yield while the alkyne 1-
ethynylnaphthalene yielded Ph2N(C10H7)C=CH2 417 in 62 yield (Table 42) The
corresponding reaction of Ph2NH with phenylacetylene and 2-bromo-phenylacetylene afforded
Ph2N(C6H5)C=CH2 418 and Ph2N(2-BrC6H4)C=CH2 419 in yields of 74 and 52 respectively
(Table 42) Similar to 415 the 1H and 13C1H NMR data for these products were in agreement
with the proposed product formulations
145
Table 42 ndash Intermolecular hydroamination reactions catalyzed by B(C6F5)3
This hydroamination strategy also proved effective for substituted diphenylamines For example
(p-FC6H4)2NH in combination with 10 mol B(C6F5)3 reacted with halogenated
phenylacetylenes to afford the species (p-FC6H4)2N(2-BrC6H4)C=CH2 420 and (p-FC6H4)2N(2-
146
FC6H4)C=CH2 421 while the corresponding reactivity with 2-thiophenylacetylene gave (p-
FC6H4)2N(2-SC4H3)C=CH2 422 and iPrPhN(2-SC4H3)C=CH2 423 when reacted with iPrNHPh
(Table 42)
The reaction of Ph2NH with 9-ethynylphenanthrene gave Ph2N(C14H9)C=CH2 424 and (p-
FC6H4)2NH was used to prepare (p-FC6H4)2N(C14H9)C=CH2 425 Similarly reactions of the
appropriate combinations of amine and alkyne using 10 mol B(C6F5)3 afforded (p-FC6H4)2N(3-
FC6H4)C=CH2 426 Ph2N(35-F2C6H3)C=CH2 427 and Ph2N(3-CF3C6H4)C=CH2 428 although
in these cases cooling to -30 degC was necessary to maximize yields obtained between 68 - 77
(Table 42) This impact of temperature was most dramatically demonstrated in the case of 426
where performing the reaction at 25 degC gave the product in 19 yield while at -30 degC the yield
was significantly enhanced to 74
4231 Proposed mechanism for B(C6F5)3 catalyzed intermolecular hydroamination reactions
The success of these hydroamination reactions strongly depends on the electronic and steric
nature of the amineborane FLP combination thereby preventing 11-carboboration and
deprotonation of the alkyne Interaction of the borane with the terminal alkyne prompts amine
addition to generate a zwitterionic intermediate In the present case the acidic proton of the
anilinium centre migrates to the carbon adjacent to boron cleaving the B-C bond and forming the
enamine product (Scheme 413) The released B(C6F5)3 is then available to participate in further
hydroamination catalysis It is noteworthy that the postulated zwitterion accounts for the
Markovnikov addition of amines to alkynes and thus the nature of the observed enamine
products341
As stated earlier catalytic formation of enamine requires the slow addition of alkyne over 10 h
This is a result of deprotonation of the alkyne by the FLP derived from enamine and borane
consequently generating iminium alkynylborate salts analogous to 42 - 410 The observed
catalytic hydroaminations imply that amine addition to alkyne is faster than enamine
deprotonation of alkyne
147
Scheme 413 ndash Proposed mechanism for catalytic intermolecular hydroamination of terminal
alkynes
4232 One-pot catalytic hydroamination and hydrogenation reactions of terminal alkynes
The catalytic generation of these enamines together with previously established FLP
hydrogenation of enamines93 prompted interest in a one-pot catalytic
hydroaminationhydrogenation protocol
Following the hydroamination procedure described above reaction mixtures generating the two
enamines 421 and 427 were exposed to H2 (4 atm) and heated at 80 degC for 14 h Pleasingly the
B(C6F5)3 catalyst successfully completed hydrogenation of the C=C double bond giving the
amines (p-FC6H4)2N(2-FC6H4)C(H)CH3 429 and Ph2N(35-F2C6H3)C(H)CH3 430 in 77 and
64 overall isolated yields respectively (Scheme 414) Monitoring the hydrogenation portion
of the reactions by 1H NMR spectroscopy revealed in both cases demise of the signals
attributable to the geminal protons of the enamines with simultaneous appearance of a quartet
attributable to the methine proton and a doublet assignable to the methyl group of the respective
amine In an alternative approach to the hydrogenation catalysis subsequent to hydroamination
5 mol of the known hydrogenation catalyst Mes2PH(C6F4)BH(C6F5)294 was added to the
reaction mixture pressurized with H2 (4 atm) and heated to 80 degC In both cases complete
hydrogenation was achieved after 3 h
148
Scheme 414 ndash One-pot stepwise catalytic hydroamination and hydrogenation reactions giving
429 and 430
Experimental evidence demonstrated the catalytic hydroaminations are restricted to aryl
acetylenes Examples of other terminal alkynes that were examined include
trimethylsilylacetylene which resulted in 11-carboboration while the acetylene carboxylates
methyl propiolate ethyl propiolate 2-naphthyl propiolate and tert-butyl propiolate did not react
due to formation of a B-O adduct Extending the chemistry to hydrothiolation using thiophenol
was not successful
424 Intramolecular hydroamination reactions using FLPs
4241 Stoichiometric hydroamination
The potential of the above hydroamination reactions to access N-heterocycles was also probed
To this end the alkynyl-substituted aniline C6H5NH(CH2)3CequivCH was prepared and exposed to
an equivalent of B(C6F5)3 in toluene 11B NMR spectroscopy indicated the formation of a B-N
adduct verified by the resonance at -25 ppm although heating the reaction for 2 h at 50 degC
yielded the cyclized zwitterion C6H5N(CH2)3CCH2B(C6F5)3 431 isolated as a white solid in 94
yield (Scheme 415) The 1H NMR spectrum was consistent with consumption of the NH proton
revealing a diagnostic broad quartet at 333 ppm with geminal B-H coupling of 54 Hz indicative
of the B(C6F5)3 bound methylene group In addition a diagnostic sharp singlet at -134 ppm in
149
the 11B NMR spectrum and the N=C iminium 13C1H resonance at 192 ppm were consistent
with the formulation of 431
Scheme 415 ndash B(C6F5)3-mediated intramolecular cyclization of alkynyl-substituted anilines to
generate 431 and 432
The analogous 6-membered ring was prepared from the precursor C6H5NH(CH2)4CequivCH and an
equivalent of B(C6F5)3 giving the zwitterion C6H5N(CH2)4CCH2B(C6F5)3 432 in 99 yield The
formulation of 432 was affirmed by NMR spectroscopy in addition to elemental analysis and X-
ray crystallography (Figure 46)
Figure 46 ndash POV-Ray depiction of 432
Similarly substituted isoindoline species are accessible from the reaction of the precursor
C6H5NHCH2(C6H4)CequivCH with B(C6F5)3 in toluene Stoichiometric combination of the two
reagents resulted in a white precipitate believed to be the intramolecular hydroamination product
after 10 min at RT However this compound was sparingly soluble in toluene bromobenzene
and CD2Cl2 not allowing its comprehensive characterization by NMR spectroscopy As such H2
(4 atm) was added to the reaction and heated at 80 degC for 16 h in an effort to synthesize the H2
activated salt which was presumed to be more soluble than the zwitterion The 1H NMR
150
spectrum of this reaction displayed a quartet at 556 ppm and a triplet at 289 ppm with a four-
bond coupling constant of 26 Hz 13C1H NMR data showed a resonance at 182 ppm
attributable to a N=C bond Collectively these data are consistent with the successive
hydroamination and hydrogenation product [2-MeC8H6N(Ph)][HB(C6F5)3] 433 isolated in 54
yield (Scheme 416)
Scheme 416 ndash Successive hydroamination and hydrogenation reactions of
C6H5NHCH2(C6H4)CequivCH and B(C6F5)3 to generate 433
While species 433 is isolated as an insoluble solid from pentane in CD2Cl2 the [HB(C6F5)3]-
anion appears to reversibly deliver hydride to the N=C carbon centre generating isoindoline and
B(C6F5)3 in about 25 This was evidenced by 1H NMR spectroscopy revealing a diagnostic
quartet at 518 ppm two diastereotopic doublets at 472 and 455 ppm and an upfield doublet at
151 ppm data that is collectively assignable to the isoindoline species This was further
supported by 11B and 19F NMR spectroscopy which provided evidence of free B(C6F5)3 Presence
of this equilibrium is consistent with a previous report on reversible hydride abstraction and
redelivery from carbon centres alpha to nitrogen262
4242 B(C6F5)3 catalyzed intramolecular hydroamination to generate cyclized amines
This hydroaminationhydrogenation protocol was further adapted for catalytic cyclization
reactions In this fashion the alkynyl substituted aniline C6H5NH(CH2)3CequivCH was treated with
10 mol B(C6F5)3 at 80 degC under H2 (4 atm) for 16 h This gave the desired product 2-methyl-1-
phenyl pyrrolidine 434 in 68 isolated yield (Table 43 entry 1) In a similar fashion the
catalytic hydroaminationhydrogenation of C6H5NH(CH2)4CequivCH gave 2-methyl-1-
phenylpiperidine 435 in 66 yield (Table 43 entry 2) The following protocol was also
applicable to p-fluoro and p-methoxy substituted substrates giving the respective cyclized
products 436 and 437 in 72 and 52 yield respectively (Table 43 entries 3 and 4) Finally
151
similar reactivity with C6H5NHCH2(C6H4)CequivCH gave 1-methyl-2-phenylisoindoline 438 in 70
yield (Scheme 417)
The yields obtained for compounds 436 and 437 strongly reflect the balance of Broslashnsted acidity
required by the amine proton to effect hydroamination In this case the p-fluoro substituent
proved more effective in hydroamination than p-methoxy
Table 43 ndash Catalytic intramolecular hydroamination and hydrogenation of alkynyl-substituted
anilines generating cyclized amines
Entry R n Isolated yield
1 H 0 68 434
2 H 1 66 435
3 F 1 72 436
4 CH3O 1 52 437
Scheme 417 ndash Catalytic intramolecular hydroamination and hydrogenation of
C6H5NHCH2(C6H4)CequivCH
425 Reaction of B(C6F5)3 with ethynylphosphines
The stoichiometric reaction of B(C6F5)3 with the ethynylphosphine tBu2PCequivCH has previously
been shown to give the deprotonation product tBu2P(H)CequivCB(C6F5)3342 Conversely analogous
treatment of Mes2PCequivCH required addition of tBu3P to effect deprotonation of the ethynyl group
due to diminished Lewis basicity of the phosphine Moreover the Erker group reported the
152
reaction of Ph2PCequivCH with B(C6F5)3 to generate a dimeric product formed by a sequential series
of 12-PB additions to the ethynyl unit343
While interested in hydroamination of ethynylphosphines the FLP iPrNHPhB(C6F5)3 was added
to two equivalents of Mes2PCequivCH giving the pale yellow solid 439 in 88 yield (Scheme 418)
The 1H NMR spectrum did not indicate incorporation of aniline into the product rather two
inequivalent vinylic protons with characteristic P-H and H-H coupling were observed at 771 and
574 ppm (Figure 47)
Scheme 418 ndash Reaction of iPrNHPhB(C6F5)3 with two equivalents of Mes2PCequivCH generating
the zwitterion 439
Figure 47 ndash 1H (top) and 1H31P (bottom) NMR (400 MHz CD2Cl2) stack plot of compound
439 with insets focusing on the vinylic protons
The 31P NMR spectrum revealed two resonances with chemical shifts at -115 and -143 ppm
while the 11B and 19F NMR spectra were in agreement with formation of an alkynylborate
species (11B δ -211 ppm 19F δ -1329 -1616 and -1663 ppm) These data together with
elemental analysis confirm the formulation of the zwitterionic species trans-
Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 439 An X-ray crystallographic study confirmed the
1H
1H31P
153
molecular structure of 439 and it is shown in Figure 48 (a) In the absence of aniline the
reaction leads to the previously reported 11-carboboration product344-345
On another account the same reaction was obtained with 2 equivalents of tBu2PCequivCH and
B(C6F5)3 to give cis and trans isomers of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 440 The cis
isomer was crystallized and characterized by X-ray diffraction studies (Figure 48 b) In this
case the phosphorus centre was basic enough to effect deprotonation thus the reaction proceeded
in the absence of iPrNHPh Monitoring the reaction by 31P NMR spectroscopy the spectrum
indicated the simultaneous presence of tBu2PCequivCH and the deprotonation zwitterion
tBu2P(H)CequivCB(C6F5)3 giving insight to a plausible mechanism en route to the formation of
compounds 439 and 440
Figure 48 ndash POV-Ray depictions of 439 (a) and 440 (b)
4251 Proposed mechanism for reaction of B(C6F5)3 and ethynylphosphines
The reaction is proposed to proceed through the mechanism highlighted in Scheme 419 wherein
the mixture of B(C6F5)3 and R2PCequivCH initially effect deprotonation of the ethynyl group
formulating the zwitterion R2P(H)CequivCB(C6F5)3 Under equilibrium conditions a second
equivalent of the ethynylphosphine is protonated consequently prompting nucleophilic addition
of the [R2PCequivCB(C6F5)3]- anion to the terminal carbon followed by proton transfer to generate
the isolated zwitterionic products In the case of Mes2PCequivCH the deprotonation step required a
stronger base therefore iPrNHPh was added to effect reactivity
(a) (b)
154
Scheme 419 ndash Proposed mechanism for the 12 combination of B(C6F5)3 and R2PCequivCH to
generate the vinylic zwitterions 439 and 440
426 Stoichiometric hydrophosphination of acetylenic groups using FLPs
An earlier report showed the three component reaction of p-tolyl2PH B(C6F5)3 and
phenylacetylene gave the 12-addition phosphonium borate zwitterion p-
tolyl2PH(Ph)C=C(H)B(C6F5)3128 Realizing the acidic hydrogen on the phosphorus atom a
sample of this compound was treated by UV radiation or heated to prompt hydrophosphination
of phenylacetylene in a mechanism analogous to that presented for the hydroamination reaction
In this regard however the zwitterion proved robust and further reactivity was not observed
Similar results were obtained when using Mes2PH or exchanging the borane for the slightly less
Lewis acidic B(p-C6F4H)3
Turning attention towards the borane HB(C6F5)2 the hydrophosphination reaction was attempted
following an alternative approach In this regard Ph2PH was added to a stoichiometric
combination of HB(C6F5)2 and Bpin-substituted 1-hexyne (Scheme 420 a) After 16 h at RT
the acetylenic unit of Bpin was reduced to a C-C single bond as illustrated by a characteristic
multiplet at 353 ppm and a very broad singlet at 148 ppm in the 1H NMR spectrum The
product Bu(H)Ph2PC-C(H)B(C6F5)2Bpin 441 resulting from the sequential hydroboration and
hydrophosphination reactions was isolated in 82 yield NMR spectroscopy data indeed showed
incorporation of all reactants into the isolated product
155
Scheme 420 ndash Sequential hydroboration and hydrophosphination reactions of hexynyl-
substituted Bpin (a) and 2-methyl-1-buten-3-yne-substituted Bpin (b) using HB(C6F5)2 and
Ph2PH
Investigating similar reactivity of 2-methyl-1-buten-3-yne substituted Bpin with HB(C6F5)2 and
Ph2PH a colourless solid was obtained in 73 yield The 1H NMR data unambiguously showed
saturation of the acetylenic fragment however the spectrum consisted of an olefinic proton at
646 ppm in addition to a methylene group at 307 ppm Further spectroscopic data revealed the
product as Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin 442 resulting from nucleophilic addition of
the phosphine at the terminal double bond (Scheme 420) Single crystals suitable for X-Ray
diffraction were obtained and the structure is shown in Figure 49 (b)
Figure 49 ndash POV-Ray depictions of 442
156
427 Proposed mechanism for the hydroborationhydrophosphination reactions
The mechanism of this reaction is envisaged to initiate following the well-documented
hydroboration of the acetylenic group generating the corresponding alkenyl-bisborane species
(Scheme 421)346 At this point the phosphine coordinates to B(C6F5)2 rendering its proton more
Broslashnsted acidic and prompting protonation of the C=C double bond This is followed by
nucleophilic attack of the phosphine at the C2 position of alkynyl-substituted Bpin (441) or C4
position of the enyne-substituted Bpin (442) The 14-addition reaction to conjugated enynes has
been previously investigated using the ethylene-linked PB FLP to give eight membered cyclic
allenes147
Scheme 421 ndash Proposed reaction mechanism for the hydroboration and hydrophosphination
reactions of Bpin substrates consisting of acetylenic fragments
Since evidence for the P-B intermediate is not observed by 11B or 31P NMR spectroscopy an
alternative mechanism could be speculated In this case the nucleophilic phosphine could add to
the vinyl bisborane followed by proton transfer However this later mechanism is not highly
supported as the more Lewis basic secondary phosphines tBu2PH and iPr2PH only gave the P-B
adduct with HB(C6F5)2 consistent with retro-hydroboration after coordination of the phosphine
to the vinyl bisborane This adduct remained intact even at elevated temperatures of 80 degC
Similar N-B adducts were observed when the analogous reactivity was explored with the alkyl
and aryl amines iPr2NH iPrNHPh and Ph2NH
157
43 Conclusions
This chapter provides an account on the discovery of consecutive hydroamination and
deprotonation reactions of various terminal alkynes by anilineB(C6F5)3 FLPs to form a series of
iminium alkynylborate complexes The reaction procedure was modified to eliminate the
deprotonation step in order to achieve B(C6F5)3 catalyzed Markovnikov hydroamination of
alkynes yielding enamine products Subsequent to hydroamination catalysis the borane catalyst
was also used for catalytic hydrogenation of the enamine providing a one-pot avenue to the
corresponding amine derivatives Related systems were probed to accomplish the stoichiometric
and catalytic intramolecular hydroamination of alkynyl-substituted anilines generating cyclic
amines While this hydroamination protocol was not extendable to effect hydrophosphination a
new stoichiometric approach using HB(C6F5)2 and Ph2PH was found to result in the sequential
hydroboration and hydrophosphination reactions of an alkynyl- and enynyl-substituted
pinacolborane generating novel PB FLPs
44 Experimental Section
441 General Considerations
All manipulations were performed under an atmosphere of dry oxygen-free N2 by means of both
standard Schlenk line or glovebox techniques (MBraun glovebox equipped with a -30 degC
freezer) Pentane dichloromethane and toluene (Sigma Aldrich) were dried employing a Grubbs-
type column system (Innovative Technology) degassed and stored over molecular sieves (4 Aring)
in the glovebox Dichloromethane-d2 bromobenzene-d5 and bromobenzene-H5 were purchased
from Sigma Aldrich and dried over CaH2 for several days and vacuum distilled onto 4 Aring
molecular sieves prior to use Hexane and ethyl acetate were purchased from Caledon
Laboratories Silica gel was purchased from Silicycle Molecular sieves (4 Aring) were purchased
from Sigma Aldrich and dried at 120 ordmC under vacuum for 24 h prior to use B(C6F5)3 was
purchased from Boulder Scientific and sublimed at 80 degC under high vacuum before use H2
(grade 50) was purchased from Linde and dried through a Nanochem Weldassure purifier
column prior to use
Substituted amines alkynes and phosphines were purchased from Sigma Aldrich Alfa Aesar
Apollo Scientific Strem Chemicals Inc and TCI The oils were distilled over CaH2 and solids
were sublimed under high vacuum prior to use The following reagents were prepared following
158
literature procedures 1-ethynylnaphthalene347 (p-C6H4F)2NH (p-CH3OC6H4)PhNH tBuNHPh
and N-isopropylanthracen-9-amine266 N-(2-ethynylbenzyl)aniline N-(pent-4-ynyl)aniline N-
(hex-5-ynyl)aniline 4-fluoro-N-(hex-5-yn-1-yl)aniline and 4-methoxy-N-(hex-5-yn-1-
yl)aniline348 N-(2-ethynylbenzyl)aniline349 tBu2PCequivCH and Mes2PCequivCH342
CH3(CH2)3CequivCBpin and CH2=C(CH3)CequivCBpin350
Compounds 439 - 442 were prepared by the author during a four month research opportunity in
the group of Professor Gerhard Erker at Universitaumlt Muumlnster Germany Molecular structures and
elemental analyses for 439 and 440 were obtained at the University of Toronto Molecular
structure for 442 was obtained at Universitaumlt Muumlnster and elemental analyses for 441 and 442
were obtained at the University of Toronto
Nuclear magnetic resonance (NMR) spectroscopy spectra were recorded on a Bruker Avance III
400 MHz Agilent DD2 600 MHz or an Agilent DD2 500 MHz spectrometer Spectra were
referenced to residual solvent of C6D5Br (1H = 728 ppm for meta proton 13C = 1224 ppm for
ipso carbon) and CD2Cl2 (1H = 532 ppm 13C = 5384 ppm) or externally (11B (Et2O)BF3 19F
CFCl3) Chemical Shifts (δ) are reported in ppm and the absolute values of the coupling
constants (J) are in Hz NMR assignments are supported by additional 2D and DEPT-135
experiments
High resolution mass spectra (HRMS) were obtained using an ABSciex QStar Mass
Spectrometer with an ESI source MSMS and accurate mass capabilities Elemental analyses (C
H N) were performed in-house employing a Perkin Elmer 2400 Series II CHNS Analyzer
442 Synthesis of Compounds
4421 Procedures for stoichiometric intermolecular hydroamination reactions
Compounds 41 - 45 were prepared in a similar fashion thus only one preparation is detailed In
the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial phenylacetylene (151
mg 148 mmol) was added drop wise over 1 min In the case where pentane was used as the
solvent the reaction was worked up as follows the solvent was decanted and the product was
washed with pentane (3 times 5 mL) to yield the product as a solid In the case where toluene or
159
dichloromethane was used as the as solvent the reaction was worked up as follows the solvent
was removed under reduced pressure and the crude product was washed with pentane to yield the
product as a solid
Synthesis of [Ph2N=C(CH3)Ph][PhCequivCB(C6F5)3] (41) Diphenylamine (0125 g 0740
mmol) pentane (20 mL) reaction time 2 h yellow solid (588 mg 0666 mmol 90) Crystals
suitable for X-ray diffraction were grown from a layered solution of dichloromethanepentane at
-30 ordmC
1H NMR (400 MHz CD2Cl2) δ 768 (m 3H H4 H5) 761 (m 1H p-Ph)
745 (m 5H o m p-Ph) 739 (m 4H H3 m-Ph) 728 (dm 3JH-H = 75
Hz 2H H7) 717 (tm 3JH-H = 75 Hz 2H H8) 711 (tm 3JH-H = 75 Hz
1H H9) 710 (dm 3JH-H = 77 Hz 2H o-Ph) 289 (s 3H Me) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F
p-C6F5) -1673 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s
equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1901 (C1) 1352 (p-Ph) 1320 (C5) 1315 (C4)
1312 (p-Ph) 1310 (C7) 1307 (m-Ph) 1298 (Ph) 1293 (Ph) 1277 (C8) 1257 (C9) 1254 (o-
Ph) 1241 (C3) 283 (Me) (C2 C6 ipso-Ph and all carbons for CequivCB(C6F5)3 were not
observed) Elemental analysis was not successful after numerous attempts
Synthesis of E-[iPrPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (42) N-Isopropylaniline (100 mg
0740 mmol) pentane (10 mL) reaction time 1 h pale yellow solid (566 mg 0651 mmol 88)
EZ ratio 71
42 1H NMR (400 MHz CD2Cl2) δ 773 (tm 3JH-H = 77 Hz 1H H5)
772 (m 6H H4 H9 H10) 746 (dm 3JH-H = 77 Hz 2H H3) 728 (dm 3JH-H = 76 Hz 2H H12) 720 (m 2H H8) 716 (t 3JH-H = 76 Hz 2H
H13) 713 (t 3JH-H = 76 Hz 1H H14) 491 (m 3JH-H = 66 Hz 1H H6)
244 (s 3H Me) 126 (d 3JH-H = 66 Hz 6H iPr) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1637 (t 3JF-F = 20 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1913
(C1) 1482 (dm 1JC-F = 236 Hz CF) 1381 (dm 1JC-F = 243 Hz CF) 1365 (dm 1JC-F = 245 Hz
CF) 1346 (C2) 1339 (C5) 1319 (C10) 1318 (C7) 1311 (C12) 1310 (C4) 1303 (C9) 1278
(C13) 1274 (C11) 1258 (C14) 1253 (C3 C8) 937 (C15) 619 (C6) 288 (Me) 208 (iPr)
160
(CequivCB(C6F5)3 and ipso-C6F5 were not observed) Anal calcd () for C43H25BF15N C 6066 H
296 N 165 Found 6037 H 317 N 173
Synthesis of E-[CyPhN=C(CH3)Ph][PhCequivCB(C6F5)3] (43) N-Cyclohexylaniline (135 mg
0740 mmol) pentane (10 mL) reaction time 1 h off-white solid (599 mg 0674 mmol 91)
EZ ratio 71
43 1H NMR (400 MHz CD2Cl2) δ 769 (tt 3JH-H = 74 Hz 4JH-H = 24
Hz 1H H5) 762 (m 5H H4 H12 H13) 737 (dm 3JH-H = 74 Hz 2H H3)
720 (dm 3JH-H = 77 Hz 2H H15) 711 (m 4H H11 H16) 703 (tm 3JH-H
= 77 Hz 1H H17) 439 (tt 3JH-H = 119 Hz 3JH-H = 35 Hz 1H H6) 235
(s 3H Me) 184 (dm JH-H = 117 Hz 1H H7) 170 (dm 2JH-H = 145 Hz
2H H8) 145 (dm 2JH-H = 132 Hz 2H H9) 133 (m 1H H7) 104 (pseudo qt JH-H = 138 Hz 3JH-H = 37 Hz 2H H8) 080 (pseudo qt 2JH-H = 132 Hz 3JH-H = 37 Hz 2H H9) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1638 (t 3JF-F = 21 Hz 1F p-C6F5) -1673 (m
2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (101 MHz
CD2Cl2) δ 1916 (C1) 1341 (C5) 1323 (C13) 1315 (C15) 1313 (C4) 1307 (C12) 1282 (C16)
1262 (C17) 1257 (C3) 1254 (C11) 699 (C6) 320 (C7) 291 (Me) 249 (C8) 244 (C9) (C2
C10 C14 and all carbons for CequivCB(C6F5)3 were not observed) Anal calcd () for C46H29BF15N
C 6197 H 328 N 157 Found 6158 H 354 N 153
Synthesis of E-[(PhCH2)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (44) N-Benzylaniline (135 mg
0740 mmol) dichloromethane (10 mL) reaction time 2 h pale yellow solid (544 mg 0607
mmol 82) EZ ratio 41
44 1H NMR (600 MHz CD2Cl2) δ 782 (t 3JH-H = 73 Hz 1H H5) 777
(t 3JH-H = 73 Hz 2H H4) 764 (d 3JH-H = 73 Hz 2H H3) 760 (t 3JH-H =
76 Hz 1H H14) 753 (t 3JH-H = 76 Hz 2H H13) 738 (m 1H H10) 728
(m 4H H9 H16) 716 (t 3JH-H = 73 Hz 2H H17) 710 (t 3JH-H = 73 Hz
1H H18) 699 (d 3JH-H = 76 Hz 2H H12) 679 (d 3JH-H = 76 Hz 2H
H8) 526 (s 2H H6) 259 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1326 (m 2F o-C6F5)
-1635 (t 3JF-F = 20 Hz 1F p-C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
207 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1912 (C1) 1386 (C7) 1342 (C5) 1339
(C2) 1317 (C11 C14) 1311 (C9) 1309 (C13 C15) 1304 (C4 C10) 1296 (C8) 1294 (C16) 1278
B(C6F5)3
N1
2
3
45
7
8
9
10
14
1516
17
18
6
11
12
13
B(C6F5)3
N1
2
3
45
7
8 9
10
11 12
13
14
1617
1815
6
19
161
(C17) 1263 (C3) 1258 (C18) 1241 (C8) 938 (C19) 645 (C6) 286 (Me) (CequivCB(C6F5)3 and all
carbons of B(C6F5)3 were not observed) Anal calcd () for C47H25BF15N C 6276 H 280 N
156 Found 6259 H 296 N 171
Synthesis of [(p-C6H4OMe)PhN=C(CH3)Ph][PhCequivCB(C6F5)3] (45) (p-CH3OC6H4)PhNH
(147 mg 0740 mmol) pentane (15 mL) room temperature reaction time 3 h yellow solid (493
mg 0540 mmol 73) Anal calcd () for C47H25BF15NO C 6166 H 275 N 153 Found C
6106 H 262 N 142 EZ ratio 11
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 748 (m 1H H5) 735
(m 2H H3) 730 (m 2H H4) 726 (m 2H H8) 717 (m 2H H15) 707
(tm 3JH-H = 72 Hz 2H H16) 702 (m 1H H17) 696 (m 1H H9) 688
(dm 3JH-H = 87 Hz 2H H11) 670 (dm 3JH-H = 87 Hz 2H H12) 365 (s
3H OMe) 273 (s 3H Me) 19F NMR (377 MHz CD2Cl2) δ -1327 (m
2F o-C6F5) -1637 (t 3JF-F = 21 Hz 1F p-C6F5) -1672 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -208 (s equivCB) 13C1H NMR (125 MHz CD2Cl2) δ 1884
(C1) 1613 (C13) 1481 (dm 1JC-F = 241 Hz CF) 1421 (C6) 1381 (dm 1JC-F = 244 Hz CF)
1364 1 (dm 1JC-F = 246 Hz CF) 1356 (C10) 1348 (C5) 1325 (C2) 1313 (C7) 1310 (C15)
1305(C8) 1297 (C4) 1292 (C3) 1278 (C16) 1274 (C14) 1269 (C11) 1257 (C17) 1255 (C9)
1155 (C12) 937 (C18) 557 (OMe) 283 (Me)
1H NMR (500 MHz CD2Cl2) δ 756 (m 2H H7) 750 (m 1H H5) 735
(m 2H H4) 730 (m 2H H3) 726 (m 2H H8) 717 (m 2H H12) 702 (m
2H H11) 696 (m 1H H9) 378 (s 3H OMe) 279 (s 3H Me) 13C1H
NMR (125 MHz CD2Cl2) δ 1892 (C1) 1620 (C13) 1432 (C6) 1348 (C5)
1345 (C10) 1325 (C2) 1319 (C7) 1310 (C3) 1297 (C4) 1257 (C11) 1255
(C9) 1242 (C8) 1162 (C12) 557 (OMe) 283 (Me) 19F and 11B NMR are the same as above
Compounds 46 - 410 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of B(C6F5)3
(0379 g 0740 mmol) and either diphenylamine (125 mg 0740 mmol) or N-isopropylaniline
(100 mg 0740 mmol) To the vial the respective alkyne was added over 1 min In the case
where pentane was used as the solvent the reaction was worked up as follows the solvent was
decanted and the product was washed with pentane (3 times 5 mL) to yield the product as a solid In
162
the case where toluene or dichloromethane was used as the as solvent the reaction was worked
up as follows the solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as a solid
Synthesis of [Ph2N=C(CH3)Bu][BuCequivCB(C6F5)3] (46) 1-Hexyne (122 mg 148 mmol)
pentane (20 mL) -30 degC to room temperature reaction time 2 h yellow solid (350 mg 414
mmol 56) The reaction also yielded alkenylboranes resulting from 11-carboboration which
were separated from the reaction mixture through the pentane washes during work-up
1H NMR (400 MHz CD2Cl2) δ 768 (m 6H Ph) 738 (m 4H Ph) 282
(m 2H H2) 262 (s 3H Me) 211 (t 3JH-H = 67 Hz 2H H7) 180 (quint
of t 3JH-H = 77 Hz 4JH-H = 28 Hz 2H H3) 141 (m 6H H4 H8 H9) 092
(t 3JH-H = 73 Hz 3H H5) 087 (t 3JH-H = 72 Hz 3H H10) 19F NMR
(377 MHz CD2Cl2) δ -1327 (m 2F o-C6F5) -1643 (t 3JF-F = 21 Hz 1F
p-C6F5) -1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211
(s equivCB) 13C1H NMR (101 MHz CD2Cl2) δ 1992 (C1) 1482 (dm 1JC-F = 237 Hz CF)
1411 (ipso-Ph) 1407 (ipso-Ph) 1382 (dm 1JC-F = 242 Hz CF) 1363 (dm 1JC-F = 246 Hz
CF) 1319 (Ph) 1315 (Ph) 1314 (Ph) 1236 (Ph) 1234 (Ph) 932 (C6) 389 (C2) 320 (C8)
295 (C3) 248 (Me) 227 (C4) 219 (C9) 199 (C7) 135 (C10) 130 (C5) (CequivCB(C6F5)3 and
ipso-C6F5 were not observed) Anal calcd () for C42H31BF15N C 5966 H 370 N 166
Found 5885 H 366 N 154
Synthesis of [Ph2N=C(CH3)C14H9][C14H9CequivCB(C6F5)3] (47) 9-Ethynylphenanthrene (299
mg 148 mmol) pentane (15 mL) room temperature reaction time 3 h pale yellow solid (602
mg 0555 mmol 75) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 859 (dm 3JH-H = 82 Hz 1H ArH) 853 (dm 3JH-H = 82 Hz
1H ArH) 849 (m 2H ArH) 845 (dm 3JH-H = 82 Hz 1H ArH) 776 (dm 3JH-H = 76 Hz 1H ArH) 773 (tm 3JH-H = 76 Hz 1H ArH) 767 (s 1H borateArH) 765 (tm 3JH-H = 82 Hz 1H ArH) 763 (s 1H amineArH) 760 (m 3JH-H = 82 Hz 1H ArH) 757 (m 3H m p-Ph) 755 (m
2H o-Ph) 753 (dm 3JH-H = 76 Hz 1H ArH) 748 (m 2H ArH) 744 (tm 3JH-H = 76 Hz 1H ArH) 737 (tm 3JH-H = 76 Hz 1H ArH) 732 (m 2H ArH) 703 (tt 3JH-H = 70 Hz 4JH-H = 10
Hz 1H ArH) 696 (tm 3JH-H = 70 Hz 2H m-Ph) 691 (dm 3JH-H = 70 Hz 2H o-Ph) 284
163
(Me) 19F NMR (377 MHz CD2Cl2) δ -1324 (m 2F o-C6F5) -1636 (t 3JF-F = 21 Hz 1F p-
C6F5) -1671 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -206 (s equivCB) 13C1H NMR
(125 MHz CD2Cl2) δ 1943 (C=N) 1500 (dm 1JC-F = 242 CF) 1444 (ipso-Ph) 1430 (ipso-
Ph) 1400 (dm 1JC-F = 245 CF) 1386 (dm 1JC-F = 250 CF) 1342 (ArC) 1342 (m-Ph) 1337
(p-Ph) 1336 (ArC) 1334 (o-Ph) 1330 (p-Ph) 1326 (ArC) 1325 (ArC) 1321 (ArC) 1320 (m-
Ph) 1319 (ArC) 1317 (ArC) 1315 (ArC) 1313 (ArC) 1310 (ArC) 1307 (ArC) 1306 (ArC)
1303 (ArC) 1301 (ArC) 1298 (ArC) 1297 (ArC) 1286 (ArC) 1284 (ArC) 1284 (ArC) 1280
(ArC) 1272 (ArC) 1261 (o-Ph) 1250 (o-Ph) 1259 (ArC) 1259 (ArC) 1248 (ArC) 1242 (ArC)
1241 (ArC) 937 (CequivCB) 3096 (Me) Anal calcd () for C62H31BF15N C 6859 H 288 N
129 Found C 6812 H 306 N 134
Synthesis of [iPrPhN=C(CH3)C3H5][C3H5CequivCB(C6F5)3] (48) Cyclopropylacetylene (125 μL
148 mmol) dichloromethane (10 mL) and pentane (5 mL) room temperature reaction time 2 h
pale yellow solid (507 mg 651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 17
48 1H NMR (400 MHz CD2Cl2) δ 765 (m 3H m p-Ph) 717 (m 2H
o-Ph) 483 (m 3JH-H = 66 Hz 1H iPr) 222 (s 3H CH3) 158 (m 1H
H1) 146 (m 4H H2) 131 (d 3JH-H = 66 Hz 6H iPr) 112 (tt 3JH-H = 81
Hz 3JH-H = 51 Hz 1H H4) 057 - 050 (m 4H H5) 19F NMR (377 MHz
CD2Cl2) δ -1327 (m 2F o-C6F5) -1642 (t 3JF-F = 20 Hz 1F p-C6F5) -
1675 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -211(s equivCB)
13C1H NMR (101 MHz CD2Cl2) δ 1937 (N=C) 1486 (dm 1JC-F = 236 Hz CF) 1383 (dm 1JC-F = 243 Hz CF) 1368 (dm 1JC-F = 245 Hz CF) 1356 (ipso-Ph) 1320 (p-Ph) 1313 (m-
Ph) 1266 (o-Ph) 1258 (ipso-C6F5) 958 (C3) 599 (iPr) 218 (C1) 208 (iPr) 161 (CH3) 153
(C2) 84 (C5) 149 (C4) (CequivCB(C6F5)3 was not observed) Anal calcd () for C37H25BF15N C
5702 H 323 N 180 Found 5667 H 330 N 179
Synthesis of E-[iPrPhN=C(CH3)C4H3S][C4H3SCequivCB(C6F5)3] (49) 2-Ethynylthiophene (160
mg 148 mmol) dichloromethane (4 mL) and pentane (10 mL) room temperature reaction time
1 h pale pink solid (498 mg 0577 mmol 78) Crystals suitable for X-ray diffraction were
grown from a layered solution of bromobenzenepentane at -30 ordmC EZ ratio 71
164
49 1H NMR (400 MHz C6D5Br) δ 738 (d 3JH-H = 45 Hz 1H H3)
733 (t 3JH-H = 72 Hz 1H H10) 731 (d 3JH-H = 45 Hz 1H H5) 726 (t 3JH-H = 72 Hz 2H H9) 693 (d 3JH-H = 38 Hz 1H H12) 674 (d 3JH-H =
53 Hz 1H H14) 667 (t 3JH-H = 45 Hz 1H H4) 664 (dd 3JH-H = 53
Hz 3JH-H = 38 Hz 1H H13) 660 (d 3JH-H = 72 Hz 2H H8) 436 (m 3JH-H = 66 Hz 1H H6) 256 (s 3H Me) 081 (d 3JH-H = 66 Hz 6H
iPr) 19F NMR (377 MHz C6D5Br) δ -1312 (m 2F o-C6F5) -1619 (t 3JF-F = 21 Hz 1F p-
C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz C6D5Br) δ -203 (s equivCB) 13C1H NMR
(101 MHz C6D5Br) δ 1724 (C1) 1486 (dm 1JC-F = 240 Hz CF) 1446 (C5) 1438 (C3) 1384
(dm 1JC-F = 246 Hz CF) 1367 (dm 1JC-F = 267 Hz CF) 1346 (C7) 1330 (C2) 1324 (C10)
1312 (C9) 1290 (C12) 1286 (C4) 1272 (C8) 1269 (C13) 1239 (C14) 593 (C6) 214 (Me)
201 (iPr) (C11 C15 ipso-C6F5 and CequivCB(C6F5)3 were not observed) Anal calcd () for
C39H21BF15NS2 C 5425 H 245 N 162 Found 5415 H 259 N 168
Synthesis of (C6F5)3BCequivC(C6H4)C(Me)=NPh2 (410) 14-Diethynylbenzene (934 mg 0740
mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 2 h orange solid
(508 mg 0629 mmol 85) Crystals suitable for X-ray diffraction were grown from a layered
solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 760 (m 3H m p-Ph) 735 (m 4H o m-Ph) 729 (m 5H
C6H4 p-Ph) 706 (dm 3JH-H = 77 Hz 2H o-Ph) 277 (s 3H Me) 19F NMR (377 MHz
CD2Cl2) δ -1329 (m 2F o-C6F5) -1630 (t 3JF-F = 20 Hz 1F p-C6F5) -1670 (m 2F m-C6F5)
11B NMR (128 MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (151 MHz CD2Cl2) δ 1877
(C=N) 1482 (dm 1JC-F = 236 Hz CF) 1433 (ipso-Ph) 1425 (ipso-Ph) 1383 (dm 1JC-F = 243
Hz CF) 1365 (dm 1JC-F = 247 Hz CF) 1364 (quaternary C for C6H4) 1322 (C6H4) 1317 (p-
Ph) 1314 (m-Ph) 1311 (p-Ph) 1308 (m-Ph) 1302 (C6H4) 1282 (quaternary C for C6H4)
1255 (o-Ph) 1244 (o-Ph) 1228 (ipso-C6F5) 937 (CequivCB(C6F5)3) 276 (Me) (CequivCB(C6F5)3
was not observed) Elemental analysis for this compound did not pass after repeated attempts
Synthesis of [tBu(Ph)NH2][PhCequivCB(C6F5)3] (411) tert-Butylaniline (111 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) pentane (10 mL) reaction time 16 h off-white solid
(560 mg 0733 mmol 99)
165
1H NMR (400 MHz CD2Cl2) δ 751 (tm 3JH-H = 77 Hz 1H H4) 741
(tm 3JH-H = 77 Hz 2H H3) 728 (m 2H H7) 727 (m 2H H6) 725 (m
1H H8) 684 (dm 3JH-H = 77 Hz 2H H2) 677 (br s 2H NH2) 113 (s
9H tBu) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5) -1622
(t 3JF-F = 21 Hz 1F p-C6F5) -1661 (m 2F m-C6F5) 11B NMR (128
MHz CD2Cl2) δ -209 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1479 (dm 1JC-F =
236 Hz CF) 1384 (dm 1JC-F = 241 Hz CF) 1366 (dm 1JC-F = 243 Hz CF) 1319 (C7) 1314
(C4) 1310 (C1) 1307 (C3) 1296 (C6) 1283 (C8) 1258 (C5) 1237 (C2) 941 (C9) 654 (tBu)
262 (tBu) Anal calcd () for C36H21BF15N C 5664 H 277 N 183 Found 5608 H 297 N
174
Synthesis of [iPr2NH2][PhCequivCB(C6F5)3] (412) Diisopropylamine (750 mg 0741 mmol)
phenylacetylene (757 mg 0741 mmol) toluene (10 mL) reaction time 4 h white solid (405
mg 566 mmol 76) Crystals suitable for X-ray diffraction were grown from a layered solution
of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 727 (tm 3JH-H = 76 Hz 2H m-Ph) 721 (dm 3JH-H = 76 Hz
2H o-Ph) 718 (tm 3JH-H = 76 Hz 1H p-Ph) 505 (m 2H NH2) 332 (m 3JH-H = 64 Hz 2H
iPr) 114 (d 3JH-H = 64 Hz 12H iPr) 19F NMR (377 MHz CD2Cl2) δ -1329 (m 2F o-C6F5)
-1627 (t 3JF-F = 20 Hz 1F p-C6F5) -1667 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -
208 (s equivCB) 13C1H NMR (101 MHz CD2Cl2) partial δ 1317 (m-Ph) 1292 (o-Ph) 1276
(p-Ph) 511 (iPr) 197 (iPr) Anal calcd () for C32H21BF15N C 5373 H 296 N 196 Found
5318 H 304 N 194
4422 Procedures for hydroarylation of phenylacetylene
Compounds 413 and 414 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 4 dram vial equipped with a stir bar was charged with a solution of
B(C6F5)3 (0379 g 0740 mmol) and the respective amine (0740 mmol) To the vial
phenylacetylene (756 mg 0740 mol) was added over 1 min The solvent was then removed
under reduced pressure and the crude product was washed with pentane to yield the product as a
solid
166
Synthesis of (PhCH2)2NHC6H4C(Ph)=C(H)B(C6F5)3 (413) NN-Dibenzylaniline (202 mg
0740 mmol) dichloromethane (10 mL) -30 degC to room temperature reaction time 1 h yellow
solid (630 mg 0710 mmol 96) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 753 (t 3JH-H = 76 Hz 2H m-Ph) 746 (t 3JH-H = 73 Hz 4H benzylm-Ph) 741 (s 1H =CH) 734 (d 3JH-H = 76 Hz 2H o-Ph) 715 (d 3JH-H = 74 Hz 4H benzylo-Ph) 700 (m 3H p-Ph benzylp-Ph) 691 (d 3JH-H = 86 Hz 2H C6H4) 680 (d 3JH-H = 86
Hz 2H C6H4) 617 (br s 1H NH) 484 (dm JH-H = 126 Hz 2H CH2Ph) 472 (dm JH-H = 126
Hz 2H CH2Ph) 19F NMR (377 MHz CD2Cl2) δ -1319 (m 2F o-C6F5) -1644 (t 3JF-F = 19
Hz 1F p-C6F5) -1680 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -158 (s equivCB)
13C1H NMR (101 MHz CD2Cl2) partial δ 1521 (=CH) 1387 (ipso-Ph) 1317 (m-Ph) 1316
(benzylipso-Ph) 1302 (benzylo-Ph) 1300 (benzylm-Ph) 1292 (o-Ph) 1291 (C6H4) 1271 (benzylp-
Ph) 1206 (C6H4) 1256 (p-Ph) 647 (CH2Ph) Elemental analysis was not successful after
numerous attempts
Synthesis of iPr(H)N=C14H9C(Ph)=C(H)B(C6F5)3 (414) N-isopropylanthracen-9-amine (170
mg 0740 mmol) dichloromethane (10 mL) room temperature reaction time 5 h bright yellow
solid (597 mg 0704 mmol 95) Crystals suitable for X-ray diffraction were grown from a
layered solution of bromobenzenepentane at -30 ordmC
1H NMR (500 MHz CD2Cl2) δ 795 (s 1H C=NH) 785 (m 2H m-Ph) 778 (m 2H o-Ph)
773 (d 3JH-H = 83 Hz 1H C14H9) 762 (d 3JH-H = 83 Hz 1H C14H9) 759 (t 3JH-H = 83 Hz
1H C14H9) 758 (m 1H p-Ph) 689 (t 3JH-H = 83 Hz 1H C14H9) 680 (s 1H =CH) 671 (t 3JH-H = 83 Hz 2H C14H9) 603 (d 3JH-H = 83 Hz 2H C14H9) 544 (s 1H CHC(Ph)=CH) 454
(m 1H iPr) 178 (d 3JH-H = 66 Hz 3H iPr) 126 (d 3JH-H = 66 Hz 3H iPr) 19F NMR (377
MHz CD2Cl2) δ -1322 (m 2F o-C6F5) -1645 (t 3JF-F = 20 Hz 1F p-C6F5) -1681 (m 2F m-
C6F5) 11B NMR (128 MHz CD2Cl2) δ -163 (s equivCB) 13C1H NMR (125 MHz CD2Cl2)
partial δ 1707 (C=CH) 1503 (=CH) 1353 (m-Ph) 1308 (o-Ph) 1290 (C14H9) 1284 (p-Ph)
1276 (C14H9) 1274 (C14H9) 1265 (C14H9) 1255 (C14H9) 1224 (C14H9) 599 (CHC(Ph)=CH)
530 (iPr) 233 (iPr) 228 (iPr) Anal calcd () for C43H23BF15N C 6080 H 273 N 165
Found 6059 H 281 N 197
167
4423 Procedures for catalytic intermolecular hydroamination reactions
Compounds 415 - 425 were prepared in a similar fashion thus only one preparation is detailed
In the glovebox a 4 dram vial equipped with a stir bar was charged with diphenylamine (125
mg 740 μmol) (p-C6H4F)2NH (152 mg 740 μmol) or N-isopropylaniline (100 mg 740 μmol)
and B(C6F5)3 (38 mg 74 μmol) in toluene (4 mL) The respective alkyne (740 μmol) was added
at a rate of 10 molh via microsyringe (oils) or by weighing into a vial (solids) Total reaction
time was 10 h after which the reaction was worked up outside of the glovebox The solvent was
removed under vacuum and the crude mixture was dissolved in ethyl acetate (5 mL) and passed
through a short (4 cm) silica column previously treated with Et2NH The crude reaction mixtures
consisted of the starting materials (amine and alkyne) and the product The product was purified
by column chromatography using hexaneethyl acetate (61) as eluent
Compounds 426 - 428 were prepared with slight modifications to the procedure above The
reaction vial was cooled to -30 degC then placed in a pre-cooled -30 degC brass-well before addition
of the alkyne via microsyringe or by weighing into a vial The reaction vial was kept in the brass-
well and warmed up to RT before cooling down the reaction vial again and adding the
subsequent aliquot of alkyne Each addition of alkyne was made in a pre-cooled brass-well The
reactions were worked up similar to the procedure above
(415) Yellow solid (187 mg 620 μmol 84) 1H NMR (400 MHz
CD2Cl2) δ 744 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H5) 721 -713
(m 5H m-C6H5 H3) 712 - 706 (m 4H o-C6H5) 691 (tt 3JH-H = 72 Hz 4JH-H = 11 Hz 2H p-C6H5) 685 (td 3JH-H = 75 Hz 4JH-H = 18 Hz 1H
H4) 679 (dd 3JH-H = 75 Hz 4JH-H = 18 Hz 1H H2) 501 (s 1H =CH2) 490 (s 1H =CH2)
376 (s 3H OCH3) 13C1H NMR (101 MHz CD2Cl2) δ 1577 (C6) 1498 (C=CH2) 1481
(ipso-C6H5) 1312 (C5) 1296 (C3) 1290 (m-C6H5) 1283 (C1) 1248 (o-C6H5) 1227 (p-C6H5)
1205 (C4) 1112 (C2) 1077 (=CH2) 558 (OCH3) HRMS-ESI+ mz [M+H]+ calcd for
C21H20NO 30215449 Found 30215453
168
(416) Off-while solid (146 mg 510 μmol 69) 1H NMR (600 MHz
CD2Cl2) δ 750 -743 (m 1H H5) 724 - 716 (tm 3JH-H = 74 Hz 4H m-
C6H5) 715 - 708 (m 6H o-C6H5 H3 H4) 706 -701 (m 1H H2) 700-
692 (tm 3JH-H = 74 Hz 2H p-C6H5) 484 (s 1H =CH2) 470 (s 1H
=CH2) 252 (s 3H CH3) 13C1H NMR (125 MHz CD2Cl2) δ 1526 (C=CH2) 1476 (ipso-
C6H5) 1390 (C1) 1364 (C6) 1309 (C5 C2) 1291 (m-C6H5) 1281 (C4) 1259 (C3) 1255 (o-
C6H5) 1233 (p-C6H5) 1051 (=CH2) 206 (CH3) HRMS-ESI+ mz [M+H]+ calcd for C21H20N
28615957 Found 28615986
(417) Orange solid (147 mg 460 μmol 62) 1H NMR (400 MHz
CD2Cl2) δ 870 (d 3JH-H = 85 Hz 1H H10) 777 (d 3JH-H = 85 Hz 1H
H7) 771 - 768 (m 2H H2 H4) 752 (tm 3JH-H = 85 Hz 1H H9) 743
(tm 3JH-H = 85 Hz 1H H8) 736 (tm 3JH-H = 85 Hz 1H H3) 722 -
709 (m 8H o m-C6H5) 692 (m 2H p-C6H5) 507 (s 1H =CH2)
494 (s 1H =CH2) 13C1H NMR (101 MHz CD2Cl2) δ 1513 (C=CH2) 1478 (ipso-C6H5)
1371 (C1) 1341 (C6) 1319 (C5) 1292 (m-C6H5) 1288 (C7 C2) 1281 (C4) 1266 (C9) 1260
(C8) 1256 (C10) 1254 (C3) 1253 (o-C6H5) 1229 (p-C6H5) 1067 (=CH2) HRMS-ESI+ mz
[M+H]+ calcd for C24H20N 32215957 Found 32216049
(418) Yellow oil (148 mg 550 μmol 74) 1H NMR (500 MHz
CD2Cl2) δ 757 (dm 3JH-H = 73 Hz 2H H2) 728 - 726 (m 3H H3 H4)
720 (tm 3JH-H = 74 Hz 4H m-C6H5) 709 (dm 3JH-H = 74 Hz 4H o-
C6H5) 695 (tm 3JH-H = 74 Hz 2H p-C6H5) 523 (s 1H =CH2) 486 (s
1H =CH2) 13C1H NMR (125 MHz CD2Cl2) δ 1533 (C=CH2) 1482 (ipso-C6H5) 1394 (C1)
1293 (m-C6H5) 1286 (C3) 1285 (C4) 1276 (C2) 1243 (o-C6H5) 1228 (p-C6H5) 1082
(=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H18N 2721433 Found 2721443
(419) Orange solid (134 mg 390 μmol 52)1H NMR (500 MHz
CD2Cl2) δ 753 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H
H2) 744 (ddd 3JH-H = 77 Hz 4JH-H = 18 Hz 5JH-H = 04 Hz 1H H5)
723 (td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H3) 720 - 715 (m 8H om-
C6H5) 706 (pseudo td 3JH-H = 77 Hz 4JH-H = 18 Hz 1H H4) 697 (tt 3JH-H = 70 Hz 4JH-H =
16 Hz 2H p-C6H5) 493 (d 2JH-H = 04 Hz 1H =CH2) 483 (d 2JH-H = 04 Hz 1H =CH2)
169
13C1H NMR (125 MHz CD2Cl2) δ 1513 (C=CH2) 1473 (ipso-C6H5) 1399 (C1) 1337 (C5)
1327 (C2) 1296 (C4) 1291 (m-C6H5) 1275 (C3) 1256 (o-C6H5) 1235 (p-C6H5) 1224 (C6)
1059 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C20H17BrN 35005444 Found 35005379
(420) Orange solid (191 mg 500 μmol 67) 1H NMR (500 MHz
CD2Cl2) δ 750 (ddm 3JH-H = 78 Hz 4JH-H = 18 Hz 1H H2) 743
(ddm 3JH-H = 78 Hz 4JH-H = 12 Hz 1H H5) 724 (tdm 3JH-H = 78
Hz 4JH-H = 12 Hz 1H H4) 712 (dm 3JH-H = 80 Hz 4H H8) 707
(dm 3JH-H = 78 Hz 1H H3) 690 (tm 3JH-H = 80 Hz 4H H9) 479 (s
1H =CH2) 471 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1202 (tt 3JF-H = 88 Hz 4JF-H
= 52 Hz p-C6H4F) 13C1H NMR (125 MHz CD2Cl2) δ 1593 (d 1JC-F = 242 Hz C10) 1518
(C=CH2) 1433 (d 4JCF = 29 Hz C7) 1395 (C1) 1337 (C5) 1328 (C2) 1298 (C3) 1276 (C4)
1272 (d 3JC-F = 79 Hz C8) 1223 (C6) 1159 (d 2JC-F = 22 Hz C9) 1041 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C20H15BrF2N 38603559 Found 38603477
(421) Yellow oil (188 mg 580 μmol 78) 1H NMR (400 MHz
CD2Cl2) δ 748 (pseudo td 3JH-H = 77 Hz J = 19 Hz 1H H2) 721
(m 1H H4) 707 - 702 (m 5H H3 H8) 697 (m 1H H5) 691 (m
4H H9) 500 (d 5JF-H = 15 Hz 1H =CH2) 488 (s 1H =CH2) 19F
NMR (377 MHz CD2Cl2) δ -1162 (dm 3JF-H = 119 Hz 1F CF of
C6) -1207 (tm 3JF-H = 97 Hz 2F p-C6H4F) 13C1H NMR (101 MHz CD2Cl2) δ 1605 (d 1JC-F = 249 Hz CF of C6) 1591 (d 1JC-F = 244 Hz C10) 1475 (C=CH2) 1438 (d 4JC-F = 28
Hz C7) 1311 (d 3JC-F = 30 Hz C2) 1302 (d 3JC-F = 85 Hz C4) 1271 (d 2JC-F = 116 Hz C1)
1264 (d 3JC-F = 81 Hz C8) 1244 (d 4JC-F = 37 Hz C3) 1162 (d 2JC-F = 22 Hz C5) 1160 (d 2JC-F = 22 Hz C9) 1077 (d 4JC-F = 36 Hz =CH2) HRMS-ESI+ mz [M+H]+ calcd for
C20H15F3N 32611566 Found 32611576
(422) Yellow oil (125 mg 400 μmol 54) 1H NMR (400 MHz
CD2Cl2) δ 718 (dd 3JH-H = 51 4JH-H = 12 Hz 1H H4) 712 (dd 3JH-H
= 36 Hz 4JH-H = 12 Hz 1H H2) 705 - 701 (m 4H H6) 695 - 689
(m 5H H3 H7) 526 (s 1H =CH2) 469 (s 1H =CH2) 19F NMR (377
MHz CD2Cl2) δ -1209 (m 3JF-H = 90 Hz p-C6H4F) 13C1H NMR
(101 MHz CD2Cl2) δ 1589 (d 1JC-F = 241 Hz C8) 1473 (C=CH2) 1442 (d 4JC-F = 26 Hz
170
C5) 1436 (C1) 1276 (C3) 1265 (C2) 1258 (C4) 1257 (d 3JC-F = 80 Hz C6) 1162 (d 2JC-F =
22 Hz C7) 1068 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 31408150 Found
31408200
(423) Yellow oil (104 mg 430 μmol 58) 1H NMR (400 MHz
CD2Cl2) δ 715 (tm 3JH-H = 79 Hz 2H m-C6H5) 712 (dd 3JH-H = 53 Hz 4JH-H = 13 Hz 1H H4) 701 (dd 3JH-H = 35 Hz 4JH-H = 13 Hz 1H H2)
693 (dm 3JH-H = 79 Hz 2H o-C6H5) 685 (m 1H H3) 681 (tm 3JH-H =
79 Hz 1H p-C6H5) 531 (s 1H =CH2) 484 (s 1H =CH2) 426 (m 3JH-H = 66 Hz 1H iPr)
125 (d 3JH-H = 66 Hz 6H iPr) 13C1H NMR (101 MHz CD2Cl2) δ 1466 (ipso-C6H5) 1456
(C1) 1446 (C=CH2) 1296 (m-C6H5) 1274 (C2) 1260 (C3) 1253 (C4) 1208 (o-C6H5) 1206
(p-C6H5) 502 (iPr) 211 (iPr) HRMS-ESI+ mz [M+H]+ calcd for C18H14F2NS 2441154
Found 2441166
(424) Pale yellow solid (206 mg 560 μmol 75) 1H NMR (600
MHz CD2Cl2) δ 881 (dm 3JH-H = 78 Hz 1H H14) 865 (dm 3JH-H =
78 Hz 1H H11) 860 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H10)
797 (s 1H H2) 787 (dd 3JH-H = 78 Hz 4JH-H = 14 Hz 1H H7)
766-761 (m 3H H9 H12 H13) 757 (pseudo td 3JH-H = 78 Hz 4JH-H
= 14 Hz 1H H8) 723 (m 4H o-C6H5) 715 (t 3JH-H = 73 Hz 4H m-C6H5) 692 (tt 3JH-H =
73 Hz 4JH-H = 12 Hz 2H p-C6H5) 512 (s 1H =CH2) 503 (s 1H =CH2) 13C1H NMR (125
MHz CD2Cl2) δ 1516 (C=CH2) 1476 (ipso-C6H5) 1357 (C1) 1317 (C3) 1309 (C6) 1307
(C5) 1306 (C4) 1294 (C2) 1292 (m-C6H5) 1291 (C7) 1273 (C9) 1271 (C8 C13) 1268 (C12)
1264 (C14) 1255 (o-C6H5) 1235 (p-C6H5) 1232 (C11) 1228 (C10) 1060 (=CH2) HRMS-
ESI+ mz [M+H]+ calcd for C28H22N 37217522 Found 37217485
(425) Pale yellow solid (228 mg 560 μmol 75) 1H NMR (400
MHz CD2Cl2) δ 874 (dm 3JH-H = 74 Hz 1H H14) 866 (dm 3JH-H
= 74 Hz 1H H11) 861 (dm 3JH-H = 74 Hz 1H H10) 795 (s 1H
H2) 788 (dm 3JH-H = 74 Hz 1H H7) 767- 762 (m 3H H9 H12
H13) 759 (pseudo td 3JH-H = 74 Hz 4JH-H = 12 Hz 1H H8) 718
(m 4H H16) 686 (m 4H H17) 499 (s 1H =CH2) 495 (s 1H =CH2) 19F NMR (377 MHz
CD2Cl2) δ -1200 (tt 3JF-H = 84 Hz 4JF-H = 42 Hz p-C6H4F) 13C1H NMR (125 MHz
171
CD2Cl2) δ 1592 (d 1JC-F = 240 Hz C18) 1519 (C=CH2) 1437 (d 4JC-F = 26 Hz C15) 1353
(C1) 1316 (C3) 1308 (C6) 1307 (C5) 1306 (C4) 1296 (C2) 1291 (C7) 1274 (C9) 1272 (C8
C12) 1271 (d 3JC-F = 83 Hz C16) 1269 (C13) 1262 (C14) 1233 (C11) 1228 (C10) 1161 (d 2JCF = 219 Hz C17) 1043 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C28H20F2N 40815638
Found 40815576
(426) Yellow oil (178 mg 550 μmol 74) 1H NMR (400 MHz
CD2Cl2) δ 735 (dm 3JH-H = 77 Hz 1H H2) 727- 723 (m 2H H3
H6) 701 (m 4H H8) 697- 691 (m 5H H4 H9) 516 (s 1H =CH2)
478 (s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1141 (m 1F
CF of C5) -1205 (m 2F p-C6H4F) 13C1H NMR (101 MHz
CD2Cl2) δ 1632 (d 1JC-F = 245 Hz C5) 1592 (d 1JC-F = 244 Hz C10) 1522 (d 4JC-F = 25 Hz
C=CH2) 1442 (d 4JC-F = 28 Hz C7) 1417 (d 3JC-F = 76 Hz C1) 1303 (d 3JC-F = 84 Hz C3)
1261 (d 3JC-F = 81 Hz C8) 1235 (d 4JC-F = 28 Hz C2) 1162 (d 2JC-F = 22 Hz C9) 1154 (d 2JC-F = 21 Hz C4) 1145 (d 2JC-F = 21 Hz C6) 1074 (=CH2) HRMS-ESI+ mz [M+H]+ calcd
for C20H15F3N 32611566 Found 32611485
(427) White solid (154 mg 500 μmol 68) 1H NMR (500 MHz
CD2Cl2) δ 722 (tm 3JH-H = 73 Hz 4H m-C6H5) 710 (m 2H H2) 705
(dm 3JH-H = 73 Hz 4H o-C6H5) 699 (tm 3JH-H = 73 Hz 2H p-C6H5)
670 (tt 3JH-H = 89 Hz 4JH-H = 24 Hz 1H H4) 525 (s 1H =CH2) 490
(s 1H =CH2) 19F NMR (377 MHz CD2Cl2) δ -1107 (t 3JF-H = 81 Hz m-C6H3F2) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (d 1JC-F = 248 Hz C3) 1515 (t 4JC-F = 28 Hz C=CH2)
1477 (ipso-C6H5) 1435 (d 3JC-F = 92 Hz C1) 1295 (m-C6H5) 1244 (o-C6H5) 1234 (p-
C6H5) 1105 (d 2JC-F = 21 Hz C2) 1093 (s =CH2) 1037 (t 2JC-F = 25 Hz C4) HRMS-ESI+
mz [M+H]+ calcd for C20H16F2N 30812508 Found 30812511
(428) Yellow oil (193 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 783 (ddq 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H6)
774 (ddq 3JH-H = 78 Hz 4JH-H = 12 Hz 6JF-H = 06 Hz 1H H2) 749
(dddq 3JH-H = 78 Hz 4JH-H = 20 Hz 12 Hz 4JF-H = 07 Hz 1H H4)
739 (pseudo tq 3JH-H = 78 Hz 5JF-H = 07 Hz 1H H3) 721 (tm 3JH-H = 78 Hz 4H m-C6H5)
707 (dm 3JH-H = 78 Hz 4H o-C6H5) 697 (tm 3JH-H = 78 Hz 2H p-C6H5) 526 (d 1H 2JH-H
172
= 07 Hz =CH2) 493 (d 2JH-H = 07 Hz =CH2) 19F NMR (377 MHz CD2Cl2) δ -630 (s CF3)
13C1H NMR (125 MHz CD2Cl2) δ 1517 (C=CH2) 1474 (ipso-C6H5) 1400 (C1) 1304 (q 5JC-F = 13 Hz C2) 1304 (q 2JC-F = 32 Hz C5) 1290 (m-C6H5) 1287 (C3) 1247 (q 3JC-F = 38
Hz C4) 1242 (o-C6H5) 1241 (q 1JC-F = 271 Hz CF3) 1239 (q 3JC-F = 38 Hz C6) 1228 (p-
C6H5) 1083 (=CH2) HRMS-ESI+ mz [M+H]+ calcd for C21H17F3N 34013131 Found
34013065
4424 Procedures for tandem hydroamination and hydrogenation reactions
A general procedure is provided for the preparation of compounds 429 and 430 Following the
10 h catalytic hydroamination reaction in the glovebox the reaction mixture was transferred into
an oven-dried Teflon screw cap glass tube The reaction tube was degassed once through a
freeze-pump-thaw cycle on the vacuumH2 line and filled with H2 (4 atm) at -196 ordmC The tube
was placed in an 80 ordmC oil bath for 14 h The solvent was removed under vacuum and the
mixture was dissolved in ethyl acetate (5 mL) and passed through a short (4 cm) silica column
previously treated with Et2NH The crude reaction mixtures consisted of the starting materials
(amine and alkyne) and the product The product was purified by column chromatography using
hexaneethyl acetate (61) as eluent
Alternative hydrogenation procedure using 5 mol Mes2PH(C6F4)BH(C6F5)2
Mes2PH(C6F4)BH(C6F5)2 (28 mg 37 μmol) was added to the reaction mixture before being
transferred into the glass tube The tube was filled with H2 and placed in an 80 ordmC oil bath The
reaction was stopped after 3 h at 80 ordmC and worked up similar to the procedure above
(429) Yellow oil (186 mg 570 μmol 77) 1H NMR (500 MHz
CD2Cl2) δ 728 - 720 (m 2H H2 H5) 708 - 700 (m 2H H3 H4)
692 (m 4H H9) 680 (m 4H H8) 545 (q 3JH-H = 70 Hz C(CH3)H)
138 (d 3JH-H = 70 Hz C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -
1186 (m 1F F of C6) -1224 (m 2F F of C10) 13C1H NMR (125
MHz CD2Cl2) δ 1610 (d 1JC-F = 247 Hz C6) 1588 (d 1JC-F = 241 Hz C10) 1436 (d 4JC-F =
26 Hz C7) 1310 (d 2JC-F = 131 Hz C1) 1291 (d 2JC-F = 85 Hz C5) 1284 (d 3JC-F = 43 Hz
C2) 1249 (d 3JC-F = 79 Hz C8) 1244 (d 4JC-F = 35 Hz C3) 1159 (d 2JC-F = 22 Hz C9) 1157
173
(d 3JC-F = 22 Hz C4) 517 (C(CH3)H) 197 (C(CH3)H) HRMS-ESI+ mz [M+H]+ calcd for
C20H17F3N 32813131 Found 32813189
(430) Yellow oil (146 mg 470 μmol 64) 1H NMR (500 MHz
CD2Cl2) δ 724 (tm 3JH-H = 78 Hz 4H m-C6H5) 699 (m 4H H2 p-
C6H5) 688 (dm 3JH-H = 78 Hz 4H o-C6H5) 671 (tt 3JF-H = 89 Hz 4JH-H = 24 Hz 1H H4) 524 (d 3JH-H =70 Hz 1H C(CH3)H) 145 (d
3JH-H = 70 Hz 3H C(CH3)H) 19F NMR (377 MHz CD2Cl2) δ -1105 (m F of C3) 13C1H
NMR (125 MHz CD2Cl2) δ 1634 (dd 1JC-F = 248 Hz 3JC-F = 13 Hz C3) 1496 (t 3JC-F = 79
Hz C1) 1472 (ipso-C6H5) 1297 (m-C6H5) 1235 (o-C6H5) 1212 (p-C6H5) 1100 (dd 2JC-F =
20 Hz 4JC-F = 47 Hz C2) 1202 (t 2JC-F = 27 Hz C4) 579 (C(CH3)H) 203 (C(CH3)H)
HRMS-ESI+ mz [M+H]+ calcd for C20H18F2N 31014073 Found 31014081
4425 Procedures for stoichiometric and catalytic intramolecular hydroamination reactions
Compounds 431 and 432 were prepared in a similar fashion thus only one preparation is
detailed In the glove box a 25 mL Schlenk flask equipped with a stir bar was charged with a
toluene (5 mL) solution of B(C6F5)3 (0100 g 0190 mmol) and the respective alkynyl aniline
(0190 mmol) The solution was heated for 2 h at 50 degC and the solvent was subsequently
removed under reduced pressure The crude oil was washed with pentane (2 times 5 mL) to yield the
product as a white solid
Synthesis of C6H5N(CH2)3CCH2B(C6F5)3 (431) N-(Pent-4-ynyl)aniline (300 mg 0190
mmol) product (120 mg 0179 mmol 94)
1H NMR (400 MHz CD2Cl2) δ 746 (m 3H m p-Ph) 691 (dm 3JH-H =
86 Hz 2H o-Ph) 416 (t 3JH-H = 78 Hz 2H H3) 333 (br q 2JB-H = 54
Hz 2H CH2B) 311 (t 3JH-H = 78 Hz 2H H1) 215 (quint 3JH-H = 78 Hz
2H H2) 19F NMR (377 MHz CD2Cl2) δ -1325 (m 2F o-C6F5) -1601 (t 3JF-F = 21 Hz 1F p-C6F5) -1655 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -134 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 1942 (C=N) 1476 (dm 1JC-F = 241 Hz CF)
1392 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1348 (ipso-Ph) 1324 (p-Ph)
174
1311 (m-Ph) 1231 (o-Ph) 1189 (ipso-C6F5) 651 (C3) 411 (C1) 185 (CH2B C2) Anal
calcd () for C29H13BF15N C 5189 H 195 N 209 Found 5140 H 219 N 191
Synthesis of C6H5N(CH2)4CCH2B(C6F5)3 (432) N-(Hex-5-ynyl)aniline (340 mg 0190
mmol) product (129 mg 0188 mmol 99) Crystals suitable for X-ray diffraction were grown
from a layered solution of bromobenzenepentane at -30 ordmC
1H NMR (600 MHz CD2Cl2) δ 745 (tt 3JH-H = 75 Hz 4JH-H = 22 Hz
1H p-Ph) 740 (tm 3JH-H = 75 Hz 2H m-Ph) 663 (dm 3JH-H = 75 Hz
2H o-Ph) 372 (t 3JH-H = 73 Hz 2H H4) 316 (br q 2JB-H = 63 Hz 2H
CH2B) 275 (t 3JH-H = 73 Hz 2H H1) 197 (m 2H H3) 176 (m 2H
H2) 19F NMR (377 MHz CD2Cl2) δ -1320 (m 2F o-C6F5) -1611 (t 3JF-
F = 20 Hz 1F p-C6F5) -1656 (m 2F m-C6F5) 11B NMR (128 MHz CD2Cl2) δ -130 (s
CH2B) 13C1H NMR (151 MHz CD2Cl2) δ 2005 (C=N) 1481 (dm 1JC-F = 241 Hz CF)
1420 (ipso-Ph) 1384 (dm 1JC-F = 243 Hz CF) 1366 (dm 1JC-F = 247 Hz CF) 1301 (m p-
Ph) 1226 (ipso-C6F5) 1237 (o-Ph) 574 (C4) 380 (CH2B) 326 (C1) 213 (C3) 175 (C2)
Anal calcd () for C30H15BF15N C 5228 H 221 N 204 Found 5206 H 272 N 177
Synthesis of [2-MeC8H6N(Ph)][HB(C6F5)3] (433) In the glovebox a 25 mL Schlenk flask
equipped with a stir bar was charged with a toluene (5 mL) solution of B(C6F5)3 (0100 g 0190
mmol) and N-(2-ethynylbenzyl)aniline (390 mg 0190 mmol) The solution was heated for 16 h
under H2 (4 atm) at 80 degC The solvent was subsequently removed under reduced pressure The
crude oil was washed with pentane (2 times 5 mL) to yield the product as a white solid (740 mg
0103 mmol 54)
1H NMR (600 MHz CD2Cl2) δ 812 (dm 3JH-H = 79 Hz JH-H = 10
Hz 1H H9) 799 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H H8) 786 (dm 3JH-H = 79 Hz 1H H6) 782 (td 3JH-H = 79 Hz 4JH-H = 10 Hz 1H
H7) 773 - 769 (m 3H H2 and H3) 745 (dm 3JH-H = 76 Hz H1) 556
(q JH-H = 26 Hz 2H H4) 353 (br 1H HB) 289 (t JH-H = 26 Hz Me) 19F NMR (564 MHz
CD2Cl2) δ -1341 (br 2F o-C6F5) -1644 (br 1F p-C6F5) -1674 (br 2F m-C6F5) 11B1H
NMR (192 MHz CD2Cl2) δ -252 (s HB) 13C1H NMR (151 MHz CD2Cl2) 1820 (N=C)
1480 (dm 1JC-F = 247 Hz CF) 1437 (C10) 1373 (C7) 1366 (dm 1JC-F = 241 Hz CF) 1362
(dm 1JC-F = 241 Hz CF) 1347 (ipso-Ph) 1337 (C5) 1322 (C3) 1308 (C2) 1306 (C8) 1266
NB(C6F5)3
4
3
2
1
175
(C9) 1247 (C1) 1234 (C6) 657 (C4) 149 (Me) (ipso-C6F5 was not observed) Anal calcd ()
for C33H15BF15N C 5495 H 210 N 194 Found C 5502 H 212 N 218
Compounds 434 - 438 were prepared in a similar fashion thus only one preparation is detailed
In the glove box a 25 mL Schlenk bomb equipped with a stir bar was charged with a toluene (2
mL) solution of B(C6F5)3 (20 mg 40 μmol) and the alkynyl aniline (039 mmol) The solution
was heated for 16 h under H2 (4 atm) at 80 degC The solvent was subsequently removed under
reduced pressure The crude oil was washed with pentane (2 times 5 mL) and purified by column
chromatography using hexaneethyl acetate (61) as eluent
Synthesis of 2-MeC4H7N(Ph) (434) N-(Pent-4-ynyl)aniline (600 mg 0390 mmol) product
(427 mg 0265 mmol 68)
1H NMR (500 MHz CD2Cl2) δ 718 (t 3JH-H = 78 Hz 2H m-Ph) 660 (tt 3JH-H =
78 Hz 4JH-H = 11 H 1H p-Ph) 657 (d 3JH-H = 78 Hz 2H o-Ph) 286 (m 3JH-H =
61 Hz 1H NCHCH3) 282 (ddd 2JH-H = 88 Hz 3JH-H = 78 Hz 35 Hz 1H H3)
254 (pseudo q 3JH-H = 83 Hz 1H H3) 211 - 162 (m 4H H1 and H2) 099 (d 3JH-H
= 61 Hz 3H Me) 13C1H NMR (151 MHz CD2Cl2) δ 1474 (ipso-Ph) 1289 (m-Ph) 1148
(p-Ph) 1116 (o-Ph) 540 (NCHCH3) 478 (C3) 330 (C1) 265 (C2) 197 (Me) HRMS-
DART+ mz [M+H]+ calcd for C11H15N 16212827 Found 16212755
Synthesis of 2-MeC5H9N(Ph) (435) N-(Hex-5-ynyl)aniline (682 mg 0390 mmol) product
(451 mg 0257 mmol 66)
1H NMR (500 MHz CD2Cl2) δ 723 (t 3JH-H = 81 Hz 2H m-Ph) 693 (d 3JH-H =
81 Hz 2H o-Ph) 680 (tt 3JH-H = 81 Hz 4JH-H = 11 H 1H p-Ph) 394 (m 1H
NCHCH3) 323 (dt 2JH-H = 121 Hz 3JH-H = 44 Hz 1H H4) 297 (dm 2JH-H = 121
Hz 1H H4) 190 - 160 (m 6H H1 H2 H3) 100 (d 3JH-H = 672 3H Me) 13C1H
NMR (151 MHz CD2Cl2) δ 1516 (ipso-Ph) 1288 (m-Ph) 1187 (p-Ph) 1173 (o-
Ph) 512 (NCHCH3) 446 (C4) 317 (C1) 261 (C3) 198 (C2) 134 (Me) HRMS- DART+ mz
[M+H]+ calcd for C12H17NO 17614392 Found 17614338
176
Synthesis of 2-MeC5H9N(p-FC6H4) (436) 4-Fluoro-N-(hex-5-yn-1-yl)aniline (745 mg 0390
mmol) product (542 mg 0281 mmol 72)
1H NMR (400 MHz C6D5Br) δ 652 (t JH-H = 88 Hz 2H m-H of C6H4F) 637 (dd 3JH-H = 88 Hz 4JH-F = 48 Hz 2H o-H of C6H4F) 306 (m 1H NCHCH3) 241 (m
1H H4) 135 (m 1H H1) 121 (m 1H H3) 113 (m 2H H23) 102 (m 1H H2)
101 (m 1H H2) 045 (d 3JH-H = 65 Hz 3H CH3) 19F NMR (377 MHz C6D5Br)
δ -1235 (s 1F C6H4F) 13C1H NMR (100 MHz C6D5Br) δ 1582 (q 1JC-F = 297
Hz p-C6H4F) 1479 (ipso-C6H4F) 1202 (d 3JC-F = 77 Hz o-C of C6H4F) 1150 (d 3JC-F = 227 Hz m-C of C6H4F) 518 (NCHCH3) 470 (C4) 321 (C1) 260 (C3) 203 (C2) 146
(CH3) HRMS- ESI + mz [M+H]+ calcd for C12H16NF 1941340 Found 1941337
Synthesis of 2-MeC5H9N(p-CH3OC6H4) (437) N-(Hex-5-yn-1-yl)-4-methoxyaniline (792 mg
0390 mmol) product (416 mg 0203 mmol 52)
1H NMR (500 MHz C6D5Br) δ 712 (d 3JH-H = 85 Hz 2H m-H of C6H4OCH3)
700 (d 3JH-H = 85 Hz 2H o-H of C6H4OCH3) 374 (s 3H OCH3) 349 (m 1H
NCHCH3) 309 (m 1H H4) 302 (m 1H H4) 194 (m 1H H1) 184 (m 1H H3)
178 (m 1H H2) 176 (m 1H H3) 161 (m 1H H1) 158 (m 1H H2) 106 (d 3JH-
H = 65 Hz 3H CH3) 13C1H NMR (125 MHz C6D5Br) δ 1542 (p-C6H4OCH3)
1457 (ipso-C6H4OCH3) 1221 (m-C of C6H4OCH3) 1139 (o-C of C6H4OCH3) 546
(OCH3) 534 (NCHCH3) 496 (C4) 331 (C1) 264 (C3) 214 (C2) 160 (CH3) HRMS-ESI+
mz [M+H]+ calcd for C13H19NO 2061539 Found 2061539
Synthesis of 2-MeC8H7N(Ph) (438) N-(2-Ethynylbenzyl)aniline (808 mg 0390 mmol)
product (571 mg 0273 mmol 70)
1H NMR (400 MHz CD2Cl2) δ 778 (d 3JH-H = 77 Hz 1H C6H4) 745 - 737 (m
5H m-Ph C6H4) 707 (t 3JH-H = 77 Hz 1H p-Ph) 703 (d 3JH-H = 77 Hz 2H o-
Ph) 510 (q 3JH-H = 66 Hz 1H NCH(CH3)) 483 (d 2JH-H = 138 Hz 1H CH2)
463 (d 2JH-H = 138 Hz 1H CH2) 154 (d 3JH-H = 66 Hz 3H CH3) 13C1H NMR
(151 MHz CD2Cl2) δ 1435 (ipso-Ph) 1376 (C1) 1343 (C6) 1297 (m-Ph) 1283
177
(C34) 1245 (C2) 1226 (p-Ph) 1222 (C5) 1161 (o-Ph) 641 (NCH(CH3) 563 (CH2) 182
(CH3) HRMS-DART+ mz [M+H]+ calcd for C15H15N 21012827 Found 21012767
4426 Procedures for reactions with ethynylphosphines
Synthesis of trans-Mes2PC(H)=C(H)Mes2PCequivCB(C6F5)3 (439) In the glove box a 4 dram
vial equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg
0740 mmol) and iPrNHPh (100 mg 0740 mmol) To the vial Mes2PCequivCH (440 mg 0148
mmol) was added and the reaction was left at RT for 16 h The solvent was removed under
reduced pressure and the crude product was washed with pentane to yield the product as a pale
yellow solid (717 mg 0651 mmol 88) Crystals suitable for X-ray diffraction were grown
from a layered solution of dichloromethanepentane at -30 ordmC
1H NMR (400 MHz CD2Cl2) δ 771 (td JP-H = 286 Hz 3JH-H = 172 Hz 1H =CH) 698 (d 4JPH = 49 Hz 4H Mes) 689 (d 4JPH = 32 Hz 4H Mes) 574 (ddd 2JP-H = 273 Hz 3JH-H =
172 3JP-H = 44 Hz 1H =CH) 235 (s 6H Mes) 229 (s 6H Mes) 223 (s 12H Mes) 218 (s
12H Mes) 19F NMR (377 MHz CD2Cl2) δ -1329(m 2F o-C6F5) -1616 (t 3JF-F = 21 Hz 1F
p-C6F5) -1663 (m 2F m-C6F5) 31P1H NMR (162 MHz CD2Cl2) δ -115 (br s PMes2) -143
(d JP-P = 82 Hz PMes2) 11B NMR (128 MHz CD2Cl2) δ -211 (CB) 13C1H NMR (101
MHz CD2Cl2) partial δ 1540 (d 1JC-P = 31 Hz Mes) 1470 (d 1JC-F = 248 Hz CF) 1437 (d
JC-P = 28 Hz Mes) 1417 (d JC-P = 150 Hz Mes) 1413 (d JC-P = 113 Hz Mes) 1393 (Mes)
1321 (d 3JC-P = 14 Hz Mes) 1303 (d 3JC-P = 56 Hz Mes) 1260 (d JC-P = 11 Hz Mes) 1178
(dd 2JC-P = 99 Hz 3JC-P = 27 Hz =CH) 1120 (dd 2JC-P = 85 Hz 3JC-P = 121 Hz =CH) 219 (d 3JC-P = 68 Hz Mes) 218 (d 3JC-P = 14 Hz Mes) 201 (d 5JC-P = 18 Hz Mes) 198 (Mes)
Anal calcd () for C58H46BF15P2 C 6329 H 421 Found C 6282 H 411
Synthesis of tBu2PC(H)=C(H)tBu2PCequivCB(C6F5)3 (440) In the glove box a 4 dram vial
equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of B(C6F5)3 (379 mg 0144
mmol) To the vial tBu2PCequivCH (250 mg 0148 mmol) was added and the reaction was left at
RT for 16 h The solvent was removed under reduced pressure and the crude product was
washed with pentane to yield the product as an off-white solid (580 mg 0570 mmol 77)
Crystals suitable for X-ray diffraction were grown from a layered solution of
dichloromethanepentane at -30 ordmC
178
1H NMR (600 MHz CD2Cl2) δ 777 (ddd 2JP-H = 46 Hz 3JH-H =15 Hz 3JP-H = 36 Hz 1H
=CH) 650 (ddd 2JP-H = 28 Hz 3JP-H = 19 Hz 3JH-H =15 Hz 1H =CH) 144 (d 3JP-H = 17 Hz
18H tBu) 101 (d 3JP-H = 11 Hz 18H tBu) 19F NMR (564 MHz CD2Cl2) δ -1322 (m 2F o-
C6F5) -1618 (t 3JF-F = 20 Hz 1F p-C6F5) -1665 (m 2F m-C6F5) 31P1H NMR (242 MHz
CD2Cl2) δ 215 (PtBu2) 251 (PtBu2) 11B NMR (192 MHz CD2Cl2) -212 (CB) 13C1H
NMR (151 MHz CD2Cl2) partial δ 1620 (dd 1JC-P = 42 Hz 2JC-P = 32 Hz =CH) 1210 (dd 1JC-P = 82 Hz 2JC-P = 21 Hz =CH) 371 (d 1JC-P = 48 Hz tBu) 325 (d 1JC-P = 22 Hz tBu) 292
(d 2JC-P = 14 Hz tBu) 266 (tBu) Anal calcd () for C38H38BF15P2 C 5354 H 449 Found C
5314 H 432
Compounds 441 and 442 were prepared following the same procedure In the glove box a
Schlenk tube equipped with a stir bar was charged with a CH2Cl2 (10 mL) solution of HB(C6F5)2
(100 mg 0289 mmol) and the appropriate alkynyl-substituted pinacolborane (0289 mmol) was
added at once After 5 minutes Ph2PH (538 mg 0289 mmol) was added to the vial The
reaction was left at RT for 16 h The solvent was then removed under reduced pressure and
pentane (5 mL) was added to the crude oil resulting in precipitate The pentane soluble fraction
was separated from the precipitate concentrated and placed in a -30 degC freezer to give the
product as colourless crystals
Synthesis of Bu(H)Ph2PC-C(H)B(C6F5)2Bpin (441) CH3(CH2)3CequivCBpin (606 mg 0289
mmol) product (175 mg 0237 mmol 82)
1H NMR (600 MHz CD2Cl2) δ 766 (m 2H o-Ph) 757 (tm 3JH-H = 77 Hz 1H p-Ph) 747
(tm 3JH-H = 72 Hz 1H p-Ph) 742 (m 2H m-Ph) 736 (m 2H m-Ph) 733 (m 2H o-Ph) 353
(m 1H CHP) 290 (d 2JH-H = 116 Hz 1H CH2CHP) 278 (d 2JH-H = 116 Hz 1H CH2CHP)
148 (m 1H CHB) 133 (m 2H CH2) 118 (m 2H CH2) 102 (s 6H CH3) 098 (s 6H CH3)
078 (t 3JH-H = 72 Hz 3H CH3) 19F NMR (564 MHz CD2Cl2) δ -1292 (m 2F o-C6F5) -
1328 (m 2F o-C6F5) -1665 (m 2F m-C6F5) -1585 (t 3JF-F = 20 Hz 1F p-C6F5) -1605 (t 3JF-F = 20 Hz 1F p-C6F5) -1651 (m 2F m-C6F5) -1653 (m 2F m-C6F5) 31P1H NMR (242
MHz CD2Cl2) δ 322 (br) 11B NMR (192 MHz CD2Cl2) δ 337 (Bpin) -66 (B(C6F5)2)
13C1H NMR (151 MHz CD2Cl2) partial δ 1362 (d 2JC-P = 91 Hz o-Ph) 1318 (d 4JC-P = 29
Hz p-Ph) 1314 (d 2JC-P = 81 Hz o-Ph) 1313 (d 4JC-P = 28 Hz p-Ph) 1285 (d 3JC-P = 95
Hz m-Ph) 1279 (d 3JC-P = 10 Hz m-Ph) 1279 (d 1JC-P = 332 Hz ipso-Ph) 1238 (d 1JC-P =
179
34 Hz ipso-Ph) 824 (C(CH3)2) 346 (d 1JC-P = 37 Hz CHP) 301 (d 2JC-P = 80 Hz CH2CHP)
290 (d 3JC-P = 49 Hz CH2) 246 (BpinCH3) 242 (BpinCH3) 224 (CH2) 158 (CHB) 079
(CH3) Anal calcd () for C36H33B2F10O2P C 5841 H 449 Found 5808 H 437
Synthesis of Ph2PCH2(CH3)C=CHC(H)B(C6F5)2Bpin (442) CH2=C(CH3)CequivCBpin (567
mg 0289 mmol) product (153 mg 0211 mmol 73) Crystals suitable for X-ray diffraction
were grown from pentane at -30 ordmC
1H31P NMR (600 MHz CD2Cl2) δ 764 (tt 3JH-H = 73 Hz 4JH-H = 14 Hz 1H p-Ph) 755 (d 3JH-H = 73 Hz 2H o-Ph) 749 (t 3JH-H = 75 Hz 2H m-Ph) 727 (tt 3JH-H = 75 Hz 4JH-H = 12
Hz 1H p-Ph) 706 (t 3JH-H = 73 Hz 2H m-Ph) 680 (d 3JH-H = 75 Hz 2H o-Ph) 645 (br 1H
=CH) 320 (d 2JH-H = 14 Hz 1H PCH2) 307 (d 2JH-H = 14 Hz 1H PCH2) 190 (s 3H CH3)
149 (br m 1H CHB) 106 (s 6H CH3) 104 (s 6H CH3) 19F NMR (564 MHz CD2Cl2)
partial δ -1254 (br 2F o-C6F5) -1665 (m 2F m-C6F5) (p-C6F5 was not observed) 31P1H
NMR (242 MHz CD2Cl2) δ 63 (br) 11B NMR (192 MHz CD2Cl2) δ 342 (Bpin) -104
(B(C6F5)2) 13C1H NMR (151 MHz CD2Cl2) partial δ 1481 (H3CC=CH) 1359 (=CH) 1329
(m o-Ph) 1323 (d 4JC-P = 39 Hz p-Ph) 1317 (d 2JC-P = 71 Hz o-Ph) 1311 (d 4JC-P = 30
Hz p-Ph) 1300 (d 3JC-P = 94 Hz m-Ph) 1291 (d 1JC-P = 54 Hz ipso-Ph) 1282 (d 3JC-P = 94
Hz m-Ph) 1251 (d 1JC-P = 54 Hz ipso-Ph) 821 (C(CH3)2) 268 (d 1JC-P = 33 Hz CH2P) 256
(d 3JC-P = 53 Hz H3CC=CH) 245 (BpinCH3) 244 (BpinCH3) 178 (br CHB) Anal calcd ()
for C35H29B2F10O2P C 5805 H 404 Found 5776 H 397
443 X-Ray Crystallography
4431 X-Ray data collection and reduction
Crystals were coated in Paratone-N oil in the glovebox mounted on a MiTegen Micromount and
placed under an N2 stream thus maintaining a dry O2-free environment for each crystal The
data for crystals were collected on a Bruker Apex II diffractometer The data were collected at
150(plusmn2) K for all crystals The frames were integrated with the Bruker SAINT software package
using a narrow-frame algorithm Data were corrected for absorption effects using the empirical
multi-scan method (SADABS)
Universitaumlt Muumlnster data sets were collected with a Nonius KappaCCD diffractometer
Programs used data collection COLLECT351 data reduction Denzo-SMN352 absorption
180
correction Denzo353 structure solution SHELXS-97354 structure refinement SHELXL-97355
Thermals ellipsoids are shown with 30 probability R-values are given for observed reflections
and wR2 values are given for all reflections
4432 X-Ray data solution and refinement
Non-hydrogen atomic scattering factors were taken from the literature tabulations268 The heavy
atom positions were determined using direct methods employing the SHELXTL direct methods
routine The remaining non-hydrogen atoms were located from successive difference Fourier
map calculations The refinements were carried out by using full-matrix least squares techniques
on F minimizing the function ω (Fo-Fc)2 where the weight ω is defined as 4Fo22σ (Fo
2) and Fo
and Fc are the observed and calculated structure factor amplitudes respectively In the final
cycles of each refinement all non-hydrogen atoms were assigned anisotropic temperature factors
in the absence of disorder or insufficient data In the latter cases atoms were treated isotropically
C-H atom positions were calculated and allowed to ride on the carbon to which they are bonded
assuming a C-H bond length of 095 Aring H-atom temperature factors were fixed at 120 times the
isotropic temperature factor of the C-atom to which they are bonded The H-atom contributions
were calculated but not refined The locations of the largest peaks in the final difference Fourier
map calculation as well as the magnitude of the residual electron densities in each case were of
no chemical significance
4433 Platon Squeeze details
During the refinement of structure 413 electron density peaks were located that were believed
to be highly disordered dichloromethane and 12-dichloroethane molecules Attempts made to
model the solvent molecule were not successful The SQUEEZE option in PLATON356 indicated
there was a large solvent cavity 160 A3 in the asymmetric unit In the final cycles of refinement
this contribution (39 electrons) to the electron density was removed from the observed data The
density the F(000) value the molecular weight and the formula are given taking into account the
results obtained with the SQUEEZE option PLATON
181
4434 Selected crystallographic data
Table 44 ndash Selected crystallographic data for 41 47 and 48
41 47 48
Formula C46H23B1F15N1 C62H31B1F15N1 C37H25B1F15N1
Formula wt 88546 108572 77939
Crystal system monoclinic triclinic triclinic
Space group P2(1)n P-1 P-1
a(Aring) 91451(8) 120520(8) 99293(9)
b(Aring) 20583(2) 122120(8) 115709(11)
c(Aring) 20738(2) 184965(12) 168258(15)
α(ordm) 9000 103236(4) 75826(4)
β(ordm) 96295(4) 104461(4) 77700(4)
γ(ordm) 9000 104447(4) 65591(4)
V(Aring3) 38800(6) 24264(3) 16930(3)
Z 4 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1516 1482 1529
Abs coeff μ mm-1 0138 0126 0146
Data collected 35905 34295 21194
Rint 00444 00308 00308
Data used 8910 11131 5899
Variables 569 712 490
R (gt2σ) 00420 00532 00488
wR2 00964 01380 01380
GOF 1018 1028 1026
182
Table 45 ndash Selected crystallographic data for 49 410 and 413
49 410
(+05 C5H12)
413
(+1 C2H4Cl2)
Formula C39H21B1F15N1S2 C425H23B1F15N1 C48H29B1Cl2F15N1
Formula wt 86350 85145 98643
Crystal system monoclinic triclinic monoclinic
Space group P2(1)c P-1 P2(1)c
a(Aring) 174202(13) 113739(5) 138815(4)
b(Aring) 135941(10) 115489(6) 242842(7)
c(Aring) 174144(13) 158094(7) 146750(4)
α(ordm) 9000 92979(2) 9000
β(ordm) 118149(3) 97298(2) 1108840(10)
γ(ordm) 9000 116865(3) 9000
V(Aring3) 36362(5) 182343(15) 46220(2)
Z 4 2 4
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1577 1536 1418
Abs coeff μ mm-1 0256 0143 0236
Data collected 27739 30840 34544
Rint 00299 00352 00437
Data used 6409 8342 8147
Variables 506 560 600
R (gt2σ) 00570 00504 00687
wR2 01537 01410 02122
GOF 1045 1021 1092
183
Table 46 ndash Selected crystallographic data for 414 432 and 439
414
(+05 CH2Cl2 +1 C5H12)
432
(+05 C5H12) 439
Formula C485H36B1Cl1F15N1 C325H21B1F15N1 C58H46B1F15P2
Formula wt 96404 72131 110070
Crystal system monoclinic triclinic triclinic
Space group C2c P-1 P-1
a(Aring) 309455(12) 80774(6) 117846(13)
b(Aring) 193567(7) 117730(8) 159017(19)
c(Aring) 182668(6) 158569(11) 16349(2)
α(ordm) 9000 79707(3) 108194(4)
β(ordm) 123002(2) 86387(3) 107588(4)
γ(ordm) 9000 87902(3) 104551(4)
V(Aring3) 91764(6) 148021(18) 25646(5)
Z 8 2 2
Temp (K) 150(2) 150(2) 150(2)
d(calc) gcm-3 1397 1620 1425
Abs coeff μ mm-1 0179 0160 0179
Data collected 34220 24071 37635
Rint 00476 00352 00284
Data used 8097 6615 9023
Variables 570 445 698
R (gt2σ) 00716 00560 00339
wR2 02417 01703 00880
GOF 1047 1096 1019
184
Table 47 ndash Selected crystallographic data for 440 and 442
440 442
Formula C38H38B1F15P2 C35H29B2F10O2P1
Formula wt 85243 72417
Crystal system monoclinic monoclinic
Space group C2c P2(1)n
a(Aring) 329294(17) 114236(2)
b(Aring) 118317(6) 151074(3)
c(Aring) 206088(10) 192749(4)
α(ordm) 9000 9000
β(ordm) 107535(5) 93553(1)
γ(ordm) 9000 9000
V(Aring3) 76563(7) 332009(11)
Z 8 4
Temp (K) 150(2) 223(2)
d(calc) gcm-3 1479 1449
Abs coeff μ mm-1 0215 0172
Data collected 63283 23294
Rint 00316 0055
Data used 8776 6697
Variables 517 456
R (gt2σ) 00365 00672
wR2 01017 01623
GOF 1021 1048
185
Chapter 5 Conclusion
51 Thesis Summary
The results presented in this thesis demonstrate the application of B(C6F5)3 and other
electrophilic boranes in metal-free synthetic methodologies thereby extending FLP reactivity
beyond the commonly reported stoichiometric activation of small molecules These findings
have also provided metal-free and catalytic routes to transformations typically performed using
transition-metal complexes or stoichiometric main group reagents
Initial results presented herein describe the aromatic reduction of N-phenyl amines in the
presence of an equivalent of B(C6F5)3 using H2 to yield the corresponding cyclohexylammonium
derivatives A reaction mechanism based on experimental evidence and theoretical calculations
has been proposed Elaborating the scope of these metal-free aromatic reductions a p-methoxy
substituted aniline was found to undergo tandem hydrogenation and intramolecular cyclization
with B(C6F5)3 presenting a unique route to a 7-azabicyclo[221]heptane derivative Aromatic
hydrogenations were further probed with pyridines quinolines and other N-heterocycles
Findings within this study were in agreement with the mechanism postulated for the arene
reduction of N-phenyl amines Although these reductions require an equimolar combination of
the aromatic amine and borane in certain cases the reactions take up eight equivalents of H2
Continued interest in FLP hydrogenation of aromatic rings was illustrated by subsequent reports
demonstrating borane-catalyzed stereoselective hydrogenation of pyridines by the Du group264
and catalytic hydrogenation of polyaromatic hydrocarbons by the Stephan group263
The second project discussed in this thesis was directly inspired by findings in the synthesis of a
7-azabicyclo[221]heptane derivative from a p-methoxy substituted aniline Detailed
mechanistic studies showed the B(C6F5)3-methoxide bond is labile under specific reaction
conditions These findings were applied to uncover a catalytic approach to the hydrogenation of
ketones and aldehydes yielding alcohols This method uses FLPs derived from B(C6F5)3 and
ether in which the ether is used as the solvent playing a pivotal role in hydrogen-bonding
interaction with the carbonyl substrate The catalysis was further studied in toluene using
B(C6F5)3 in combination with oxygen containing materials such as cyclodextrins or molecular
sieves Application of these materials provides an avenue to H2 activation and hydrogen-bonding
186
interactions necessary to facilitate hydrogenation In the particular case of aryl ketones the use
of molecular sieves promoted reductive deoxygenation of the substrate to give the aromatic
hydrocarbon product Hydrogenation of carbonyl substrates had perennially remained a
challenging problem since the discovery of FLP chemistry The results reported in this thesis
represent the first successful report of catalytic carbonyl hydrogenation using FLPs It should be
noted that the group of Ashley simultaneously reported the hydrogenation of ketones and
aldehydes using 14-dioxaneB(C6F5) as the FLP catalyst260
Lastly interest in expanding FLP catalysis beyond hydrogenations amineborane FLPs were
applied in the hydroamination of terminal alkynes The stoichiometric reaction of aniline
B(C6F5)3 and two equivalents of alkyne gave a series of iminium alkynylborate complexes
prepared through sequential intermolecular hydroamination and deprotonation reactions This
latter reaction results in the formation of the alkynylborate anion thus preventing participation of
B(C6F5)3 in catalysis Adjustment of the protocol by slow addition of the alkyne prevents the
deprotonation pathway thus allowing B(C6F5)3 to catalyze the Markovnikov hydroamination of
alkynes by a variety of secondary aryl amines affording enamines products This metal-free
route was also amenable to subsequent use of the catalyst in hydrogenation catalysis allowing
for the single-pot and stepwise conversion of the enamine products to the corresponding amines
Further expansion of the reactivity led to catalytic intramolecular hydroaminations affording a
one-pot strategy to N-heterocycles A stoichiometric approach to FLP hydrophosphinations was
also described
52 Future Work
While the reactivities presented in this thesis have typically been the purview of precious metals
research efforts motivated by cost toxicity and low abundance have provided alternative
strategies using main group compounds In 1961 the first metal-free catalytic hydrogenation was
reported displaying the reduction of benzophenone however this reaction required high
temperatures of about 200 degC and H2 pressures greater than 100 atm175 Since then dramatic
progress has been made in the advancement of metal-free catalysis Numerous metal-free
systems with particular emphasis on FLPs have been reported to effect the hydrogenation of an
elaborate list of substrates under mild conditions
187
An important direction to progress the chemistry found during this graduate research work would
be to design a borane reagent that will be suitable for the catalytic hydrogenation of N-phenyl
amines and N-heterocycles Such a direction will allow for a more atom-economic
transformation Ultimately the catalysis could be pursued using chiral boranes that may provide
a stereoselective process to cyclohexylamine derivatives (Scheme 51) Generally aromatic
hydrogenation of nitrogen substrates is a challenging transformation for transition-metal systems
due to deactivation of the catalyst by coordination of the substrate357
Scheme 51 ndash Chiral borane catalyzed hydrogenation of N-phenyl bound amines with
substitution on the phenyl ring to generate enantiopure substituted cyclohexylamine derivatives
An interesting and obvious extension of carbonyl hydrogenations presented in Chapter 3 would
certainly be a FLP route to optically active alcohols Although such products were not obtained
when performing the reductions in the presence of chiral heterogeneous Lewis bases the
application of a chiral borane should be investigated The Du group recently presented the use of
chiral boranes in the asymmetric hydrogenation of silyl enol ethers to give chiral alcohol
products after appropriate work-up procedures97
Furthermore the use of cyclodextrins and molecular sieves in catalysis has presented the
possible notion of expanding homogeneous FLP chemistry to surface chemistry by designing
heterogeneous FLP catalysts that could be readily recycled (Scheme 52) Such a system may be
particularly attractive for industrial applicability Solid catalyst supports such as B(C6F5)3 grafted
onto silica have been used by the Scott group as a co-catalyst for the activation of metal
complexes used in olefin polymerization358 Although this system may not be sufficiently Lewis
acidic for carbonyl reductions further exploration and modification of Lewis acid and base
components could potentially lead to such a system
188
Scheme 52 ndash Proposed heterogeneous FLP catalyst for catalytic carbonyl hydrogenations
The final chapter of this thesis outlined the consecutive hydroamination and hydrogenation of
ethynyl fragments catalyzed by B(C6F5)3 The novelty of this reactivity by FLP systems certainly
demands further explorations Catalytic hydroamination using FLPs could be extended to include
olefins and internal alkynes Furthermore the pursuit of an effective chiral borane catalyst may
provide a potential synthetic route to chiral amines of pharmaceutical and industrial interest
189
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