Chapter-III, Section A 3.1 Introduction and applications ...shodhganga.inflibnet.ac.in/bitstream/10603/70860/12/12_chapter 3.pdf · Chapter-III, Section A 73 3.1 Introduction and

Chapter-III, Section A

73

3.1 Introduction and applications of B(C6F5)3 catalyst

Tris(pentafluorophenyl)boron [B (C6F5)3] is a Lewis acid catalyst, consists of

three pentafluorophenyl groups attached in a paddle-wheel manner to a central boron

atom. The BC3 core is planar in structure. It has been described as the ideal Lewis

acid because of its versatility and relative inertness of the B-C bonds. However,

special properties of B(C6F5)3 have made this a strong boron Lewis acid, an

increasingly preferable catalyst in organic and organometallic chemistry. This

includes catalytic hydrometallation reactions, alkylations and catalyzed aldol type

reactions. The Lewis acidity of B(C6F5)3 is somewhere between that of BF3 and BCl3,

as judged by the method of Childs et al.1 This property indicates that the

electronegativity of the C6F5 group and a halide are similar. It was found to be a

strong Lewis acid that formed adducts with triphenylphosphine and other Lewis

bases.

Figure 1: structure of Tris(pentafluorophenyl) borane

BF

F F

F F F

FF

F

FF

F

FF

F

Tris(pentafluorophenyl)borane was first prepared and described by Stone,

Massey and Park in 1963.2 It can be easily prepared by the addition of Grignard

reagent (C6F5MgBr) to BCl3 to give a white solid in good yields (Scheme 1).

(C6F5)3B + 3MgBrCl3 C6F5MgBr + BCl3

Scheme 1


74

The development of efficient and practically useful Lewis acid catalysts for

various organic transformations is of great importance. B(C6F5)3 was first known for

its role as an excellent activator component in homogeneous Ziegler–Natta olefin

polymerization catalyst and their related chemistry.3 A growing number of such

examples indicates an increasing application potential of Lewis acid B(C6F5)3 aside

from its established role in olefin polymerization catalysis (Scheme 2).

RCp2ZrB(C6F5)3

RCp2Zr

[H3CB(C6F5)3]Polyolefin

Scheme 2

Me

Me

Me

For many years, tris(pentafluorophenyl)borane was known to be synonymous

with homogeneous Ziegler-Natta catalyst activation, when recently an increasing

number of reactions from the literature enounced the special features of B(C6F5)3

other than in polymerization catalysis. Its high Lewis acidity combined with steric

bulk, its pronounced ability for anion, specially carbanion equivalent abstraction and

persistence of the resulting anions have made B(C6F5)3 as a useful catalyst to induce a

variety of specific reactions in organic and organometallic chemistry and to open

synthetic pathways to unusually structured new compounds. This interesting new

development will be illustrated by a number of selected examples in this perspective.

Yamamoto et. al., have used B(C6F5)3 for the first time as a catalyst in the

Mukaiyama aldol reactions of various silyl enol ethers and ketene silyl acetals with

aldehydes or other electrophiles, which proceeds smoothly in presence of 2 mol% of

catalyst.4 These aldol-type reactions do not proceed when triphenylborane is used as

catalyst (Scheme 3).

R1-CHOR2

R3TMSO

H

B(C6F5)3, 2 mol%

CH2Cl2, -78 oC, 12 h,65-96%

R1

O

R2

OH

R3

Scheme 3


75

Conjugate addition of silyl enol ethers to α, β-unsaturated ketones proceeds

regio selectively in presence of 2 mol% of B(C6F5)3. The products can be isolated as

synthetically valuable silyl enol ethers when the crude product is worked up without

exposure to acid (Scheme 4).

Scheme 4

R1 R2

O

R3

R4TMSO

H

B(C6F5)3 (2 mol%)

CH2Cl2, -78 oC, 12 h,85-94%

R3

O R1

R4

R2

O

B(C6F5)3 is a highly active catalyst for aldol-type reactions between ketenes

silyl acetals and imines because of its stability (comparatively low- N-B bond energy)

and affinity towards nitrogen-containing compounds.4b,4c N-Benzylimines are useful

substrates because β-benzylamino acid esters can be readily debenzylated by

hydrogenolysis on palladium/carbon. Catalysis is carried out using a 0.2 mol%

catalyst loading in toluene.

In most cases the condensation proceeds smoothly even with aliphatic

enolizable imines derived from primary or secondary aliphatic aldehydes. The

syn/anti stereo selectivity of N-benzylidenebenzylamine is dependent on the geometry

of the ketene silyl acetal double bond: (E) and (Z)-ketene silyl acetals gave anti and

syn products respectively, as the major diastereomers. The use of N-trialkylsilylimines

can be advantageous, since protected N-substituent can easily cleaved from the β-

[(trialkylsilyl) amino] acid esters produced in the reaction. Borane Lewis acid is an

effective catalyst for the reaction of N-trimethylsilylimines. The reaction of mono or

di-substituted ketene silyl acetals with N-(tri- methylsilyl)benzylideneamine proceeds

smoothly to give the corresponding β-amino acid esters in good yield (Scheme 5).4c

Scheme 5

R1 H

NBn

R4

R2TMSO

R3

B(C6F5)3, 0.2 -10 mol%

toluene, -78 oC, 13h,25 oC, 2 h, 55-99%

R1

NHBn

R2

OR4

O

R3


76

B(C6F5)3 was used as a versatile catalyst for several organic transformations

and recently explored as a non-conventional Lewis acid catalyst. This catalyst

operates via hyper co-ordination at the boron center.5 Allylation of the formyl group

in o-anisaldehyde is favored by a >20:1 margin over that in p-anisaldehyde, in a

competitive situation (Scheme 6).6

X

Y

O

1:1

X = OMe, Y = HX = H, Y = OMe

SnBu3

B(C6F5)3, -40 oCPhCH3, 2 h

OMe

H

O

B(C6F5)3X

Y

OH

> 20:1 selectivity

Scheme 6

B(C6F5)3 is a highly efficient catalyst in rearrangement of epoxides.7

Rearrangement of tri substituted epoxides readily takes place in presence of catalytic

amounts of B(C6F5)3, resulting in a highly selective alkyl shift to give the

corresponding aldehydes. Exceptional bulkiness of B(C6F5)3 may play a role in

ensuring high selectivity of this process (Scheme 7).

Scheme 7

B(C6F5)3 (1 mol%)

toluene, refluxC3H7

O CHO

C3H7C3H7

O

alkyl shift hydride shift98/2 ratio

Lewis acid mediated cleavage of epoxides with various nucleophiles such as

alcohols, amines and thiols is an important transformation in organic synthesis. Our

group has found B(C6F5)3 to be a highly efficient catalyst for ring opening of

epoxides.8 Ring opening reaction of epoxides in presence of this catalyst (5 mol%)

with various hetero atoms viz., O, N and S generated ß- hydroxy ethers, amines and

sulfides in high yield. Acid labile protecting groups like TBDMS and THP were


77

stable under these reaction conditions (Scheme 8). In presence of catalytic amount of

B(C6F5)3, optically active styrene oxide and its analogs are directly converted into

corresponding acetals such as acetonides or cyclopentylidene acetals to complete

optical purity on the treatment with ketones.9

Scheme 8

XH, B(C6F5)3,

CH2Cl2, rtRO

R= alkyl, aryl

R

OHX

X= OO

-NHPh, SHPh

B(C6F5)3 was also involved in ring opening reactions of non-activated

aziridines. There have been few reports on the ring opening of simple N-alkyl

aziridines. Ring opening of non-activated aziridines with amine nucleophiles in

presence of B(C6F5)3 (10 mol%) in acetonitrile at 65 oC yielded the corresponding

trans-diamine (Scheme 9).10

Scheme 9

B(C6F5)3, 10 mol%

HX, CH3CN, 65 oCR2

R3N

R1

NHR3XR1

R2

B(C6F5)3 is an effective catalyst for dehydrogenative silation of primary,

secondary, tertiary and phenolic alcohols with variety of silanes (R3SiH, R2SiH2,

R2R'SiH). Generally, the reaction occurs at room temperature using 2 mol% of

catalyst, clean and high yielding with hydrogen as the only by product (Scheme 10). 11

Scheme 10

B(C6F5)3, 2 mol%

R13SiH, toluene

R-OH R-OSiR13

R= Alkyl/ aryl R1 = Et, Ph

H2

Carbonyl compounds undergo partial reduction with R3SiH in the presence of

B(C6F5)3 as catalyst. In this method one equivalent of the silane reagent was essential


78

for clean reaction since further reduction of silyl ethers or silyl acetal products was

observed when excess of silane used. Exhaustive reduction of aliphatic carbonyl

function (aldehyde, acyl chloride, ester and carboxylic acid) to methyl group was

achieved using catalytic amount of B(C6F5)3 with stoichiometric amount of Et3SiH

(Scheme 11).12a

R X

O B(C6F5)3, 5 mol%

Et3SiH, CH2Cl2

R = alkyl, X = H, Cl, OMe, OH

R-CH3

Scheme 11

Reduction of aromatic carbonyl compounds was achieved even with an excess

of Et3SiH. It was found that aromatic carbonyl functions underwent smooth partial

reduction with Et3SiH to afford silyl ethers.12b Aromatic α- diketones also well

participated in this transformation to produce corresponding silyl-protected 1, 2-diols

(Scheme 12).12c

Scheme 12

B(C6F5)3, (5 mol%)

Et3SiH, CH2Cl2

R-CH2-OSiEt3

R= aryl X = H,Cl,OMe, OH

R X

O

B(C6F5)3O

O

Ph

Ph Me3Si

O

O

Ph

Ph SiMe3

SiMe3

B(C6F5)3

Ph3Si

O

O

Ph

Ph SiPh3

SiPh3

Our group has used B(C6F5)3 as an excellent catalyst for activation of

polymeric hydride source Polymethylhydrosiloxane (PMHS), a co-product of the

silicon industry. A combination of PMHS and catalytic amount of B(C6F5)3 efficiently

reduced carbonyl compounds to corresponding methelenes (Scheme 13).13 This

procedure has advantages such as, selective reduction of ketone in presence of olefins


79

and esters. Acid sensitive protecting groups like TBS and THP ethers are unaffected

during this transformation.

R R1

O B(C6F5)3, PMHS

CH2Cl2, rt

R = alkyl, aryl, R1 = H, alkyl, aryl

R-CH2 -R1

Scheme 13

B(C6F5)3 as a catalyst in conjunction with PhMe2SiH efficiently hydrosilated

benzaldimines and ketimines.14 B(C6F5)3 abstracts hydride from PhMe2SiH in

presence of imines and forms silyliminium cation with hydridoborate counterion. The

reaction proceeds via activation of imine by “PhMe2Si+”, spectral evidences support

intermediacy of a silyliminium cation. Reductive coupling of carbonyl compounds

with alkoxy silanes using Polymethylhydrosiloxane (PMHS) and catalytic amount of

B(C6F5)3 as the activator of the PMHS produce symmetrical and unsymmetrical ethers

(Scheme 14).15

R1 R2

O B(C6F5)3, PMHS

CH2Cl2, rt

Scheme 14

R3 R4

OTMS

R2 O

R1

R4

R3

A reaction between tri-O-acetyl-D-glucal and sulfonamides was effectively

promoted by 0.5 mol% B(C6F5)3 in acetonitrile at room temperature to produce aza-

pseudoglycals via Ferrier rearrangement in good yields and preferential anomeric

selectivity (Scheme 15).16 Extension of this to N-substitued sulfonamides (N-phenyl

and N-benzyl sulfonamides) and carbamates (benzyl carbamate and tert-butyl

carbamate) furnished corresponding N-pseudoglycals in moderate yields.


80

B(C6F5)3, PMHS

CH3CN, rt

Scheme 15

O

OAc

AcO

AcORNH2

O

OAc

AcO

AcO

NHR

R = ArSO2, Boc, Cbz

B(C6F5)3 was used as an efficient catalyst for synthesis of β –keto enol ethers

from various β-diketones in presence of 2 mol% of B(C6F5)3 at room temperatuere

under rapid and mild conditions (Scheme 16).17

O

O

O

OR

B(C6F5)3 (2 mol%)

ROH, rt, 5 -10 min

Scheme 16

O

OH

Synthesis of 1, 8-dioxo decahydroacridinediones was achieved under mild and

solvent free conditions in the presence of catalytic amount of B(C6F5)3 with moderate

to excellent yields (scheme 17).18

O

O

CHO NH2

B(C6F5)3 3 mol%

neat, rt,1 h N

O O

Scheme 17

B(C6F5)3 acts as a co-catalyst in metallocene mediated carbometalation of

olefins and cyclocarbometalation of diolefins19 or amino alkenes. 20 B(C6F5)3 catalyzes

tautomerization reactions and is able to very effectively stabilize otherwise disfavored

tautomeric isomers by adduct formation through N–B or O–B bond formation. The

reaction between α-naphthol and B(C6F5)3 is a typical example.


81

Scheme 18

OH

B(C6F5)3

O

H H

B(C6F5)3

Stirring of a suspension of the α-naphthol with borane for 12 h at rt in pentane

eventually gave a crystalline product which was shown to be the B(C6F5)3 adduct of

the benzoylclohexadienone tautomer. Several other phenolic derivatives behaved

similarly with B(C6F5)3, but some gave equilibrium mixtures (Scheme 18).21

A synthetically useful and convenient method for the B(C6F5)3-catalyzed

hydrostannylation of alkynes with tributyltin hydride, prepared in situ from easily

handled and inexpensive chlorostannane and hydrosilane has been developed by

Yamamoto et al.22 The hydrostannylation of mono- substituted alkynes proceeds in a

regio specific manner affording exclusively the β-hydrostannylation products. The

reaction is trans-stereo selective and can also be applied to the hydrostannylation of

alkenes and allenes (Scheme 19).

Scheme 19

R R1 Bu3SnCl Et3SiHB(C6F5)3 (10 mol%)

toluene, 0 oC-rt

RSnBu3

R1

Bu3SnCl Et3SiHB(C6F5)3 (10 mol%)

toluene, 0 oC-rt

SnBu3

B(C6F5)3 has found to be an efficient catalyst for Friedel-Crafts reactions

between activated arenes or heteroarenes and α-amidosulfones in dichloromethane at

room temperature. The products undergo further Friedel-Crafts reactions with

activated heteroarenes leading to the synthesis of unsymmetrical triarylmethanes

(Scheme 20).23


82

OMe

OMe

MeO

Ph SO2Tol-p

NHCbz B(C6F5)3

CH2Cl2, 2.5h

OMe

OMe

MeO

Ph

SO2Tol-p

Scheme 20

OMe

OMe

MeO

R

SO2Tol-p NH

R1

HN

R1

R OMe

OMeOMe

B(C6F5)3 (5 mol%)

CH2Cl2, reflux

The treatment of the imidazole and thiazole ring with highly Lewis acidic

borane B(C6F5)3 forms a B-N adduct, which further treated with a strong base, such as

methyllithium or LDA to form a cyclized skeletons via a Coordination/Cyclization

Protocol with B(C6F5)3 (Scheme 21). These cyclized imidazolyl and thiazolyl-

containing π-conjugated frameworks have several advantages as candidates for n-type

semiconductors and exhibits relatively high electron accepting properties.24

N

S

N

S

C6H13 C6H13

S S

N

S N

S N

S N

S

B(C6F5)3

B(C6F5)3

N

S N

S

BC6F5

C6F5

BC6F5 C6F5

=

B(C6F5)3

toluenert, 24h

LDA, toluene

60-65 oC

Scheme 21

1, 3- Dicarbonyl compounds undergo alkylation with various alcohols as

alkylating agents in the presence of B(C6F5)3 as a milder acid catalyst in

dichloromethane under reflux conditions gave corresponding α-alkylated- β-diketones

in good yields.25


83

Ph Ph

OH O O

PhPh

O O B(C6F5)3, (5 mol%)

CH2Cl2, reflux, 0.5h

Scheme 22

Gerhard Erker has used B(C6F5)3 catalyst as an alternative reagent for

hydroboration reactions. Strongly electrophilic boranes R-B(C6F5)2 react readily with

a variety of 1-alkynes by means of a 1, 1-carboboration/photochemical isomerization

sequence to yield alkenylborane products, which subsequently used as reagent in

metal catalyzed cross-coupling reactions in the presence of aryl halide and catalytic

amounts of Pd(PPh3)4 in basic medium to produce coupling product in good yields

(Scheme 23).26

R1 H

RB(C6F5)2

R= Ph, (CH2)2Ph

R

(C6F5)2B R1

H R

(C6F5)2B H

R1 R

Ar H

R1

CH2Cl2

rt, 3h

hv ArX

Pd (0)

Scheme 23

B(C6F5)3 promotes regio and stereo selective cyclizations of unsaturated

alkoxysilanes to generate oxasilinanes and oxasilepanes. These products are available

directly from alkenols via tandem silylation and hydrosilylation. Addition of B(C6F5)3

to a solution of unsaturated alkoxysilane resulted in regioselective formation of

oxasilinane with high 3, 5-trans diastereoselectivity. Oxidative desilylation of these

hindered siloxanes was attempted by various oxidation conditions provided

corresponding diols with high stereo selectivity (Scheme 24). 27

Hex

OH

Scheme 24

Ph2SiH2

B(C6F5)3 Hex

O

Hex

OSiHPh

PhSi

H

PhPh

HHex

OH CH3OH

[Ox]

Tris(pentafluorophenyl) borane was also used as a novel electrolyte additive

for silicon (Si) thin film anodes in lithium ion batteries. The introduction of B(C6F5)3


84

catalyst significantly enhances the capacity retention and coulombic efficiency.

Specifically, B(C6F5)3 enables the improved properties by forming stable solid-

electrolyte interphase (SEI) layers and suppressing surface pulverization.28 The

addition of 5 mol% boron catalyst enables almost a twofold capacity retention at the

100th cycle and higher coulombic efficiencies.

Dargaville and his co-workers have utilized borane catalyst in silicon

chemistry to prepare amphiphilic silicone architectures.29 B(C6F5)3-catalyzed

condensation of alkoxysilanes and vinyl functionalized hydrosilanes to give silicones

and alkane byproducts. The resulting pure silicones were coupled to thiol-terminated

PEG oligomers using photogenerated radicals under anaerobic conditions provided

thiol-ene coupling products. These products were much useful in cosmetics, paints,

coatings and for the stabilization of bubbles in polyurethane foam structures.30

Scheme 25

SiH

O OSiSi

EtOSiOEt

OEt

B(C6F5)3

HSO n

DMPA

SiO

OO S

O

Si

Si

SiO

OSi

OSi

nO

Si

Si

OO SiSi

DMPA = 2, 2-dimethoxy-2-phenylacetophenone


85

3.2 REFERENCES:

1. a) Doring, S.; Erker, G.; Frohlich, R.; Meyer, O.; Bergander, K.

Organometallics, 1998, 17, 2183. b) Childs, R. F.; Mulholland, D. L. Can. J.

Chem., 1982, 60, 801. c) Childs, R. F.; Mulholland, D. L. Can. J. Chem., 1982,

60, 809. d) Laszlo, P.; Teston, M. J. Am. Chem. Soc., 1990, 112, 8750.

2. a) Massey, A. G.; Park, A. J.; Stone, F. G, A. Proc. Chem. Soc., 1963, 212. b)

Massey, A. G.; Park, A. J. J. Organomet. Chem., 1964, 2, 245. c) Massey, A.

J.; Park, A, J. Organometallic Syntheses, 1986, 3, 461–462.

3. a) Marks, T. J. Acc. Chem. Res., 1992, 25, 57; (b) Yang, X.; Stern, C. L.;

Marks, T. J. J. Am. Chem. Soc., 1994, 116, 10015.

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Ishihara, K.; Funahashi, M.; Miyata, M; Yamamoto, H. Synlet.,t 1994, 963-

964. c) Ishihara, K.; Hanaki, N.; Funahashi, M.; Miyata, M.; Yamamoto, H.

Bull. Chem. Soc. Jpn., 1995, 68, 1721-1730.

5. Akiba, K. The Chemistry of HyperValent Compounds; John Wiley& Sons:

Chichester, 1999.

6. Blackwell, J. M.; Piers, W. E.; Parvez, M. Org. Lett. 2000, 2, 695-698.

7. Ishihara, K.; Hanaki, N.; Yamamoto, H. Synlett., 1995, 721-722.

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Tetrahedron lett., 2002, 43, 3801-3803.

9. Nagata, T.; Takai, T.; Yamada, T.; Imagawa, K.; Mukaiyama, T. Bull. Chem.

Soc. Jpn., 1994, 67, 2614-2616.

10. Watson, I. D. G.; Yudin, A. K.; J. Org. Chem., 2003, 68, 5160-5167.

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14. Blackwell, J. M.; Sonmor, E. R.; Scoccitti, T.; Piers, W. E. Org. Lett., 2000, 2,

3921- 3923.

15. Chandrasekhar, S.; Chandrashekar, G.; Babu, B, N.; Vijeender, K.; Reddy, K,

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45, 6481-6484.

17. Chandrasekhar, S.; Srinivasarao, Y.; Reddy, NRK. Synlett., 2005, 1471-1473.

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Reddy, Ch. Synthesis., 2008, 11, 1737-1740.

19. a) Molander, G. A.; Corrette, C. P. Tetrahedron Lett. 1998, 39, 5011-5014. b)

Shaughnessy, K. H.; Waymouth, R. M. J. Am. Chem. Soc., 1995, 117, 5873-

5874. c) Yang, X.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc., 1994, 116,

10015-10031.

20. a) Gribkov, D. V.; Hultzsch, K. C. Angew. Chem. Int. Ed. 2004, 43, 5542-

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Widenhoefer, R. A. J. Org.Chem. 2002, 67, 2778-2788.

21. a) Vagedes, D.; Frohlich, R.; Erker, G. Angew. Chem., 1999, 111, 3561; (b)

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23. Thirupathi, P.; Lok Nath, N.; Keun-Hyeung, L. Tetrahedron, 2011, 67, 7301-

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24. a) Andre J.; Atsushi W.; Gerald K.; Gerhard E.; Yamaguchi, S.; Org. Lett.,

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Frohlich, R.; Erker, G.; Muck-Lichtenfeld, C.; Grimme, S. Eur. J. Inorg.

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25. Rajireddy, Ch.; Vijaykumar, J.; Rene, G. Synthesis., 2010, 21, 3715-3723.

26. Chen, C.; Voss, T.; Frohlich, R.; Kehr, G.; Erker, G. Org. Lett., 2011, 13, 62-

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27. Roman Shchepin, Chunping Xu, Patrick Dussault. Org. Lett., 2010, 12, 4772-

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28. Beom, H. G.; Leea, L. J.; Choib, J. W.; Park, J. K. Electrochimica Acta., 2011,

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29. Keddie, D. J.; Grande, J. B.; Gonzaga, F.; Brook, M.A.; Dargaville, T. R.

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88

SYNTHESIS OF TRIARYL AND TRIHETEROARYL METHANES.

3.3 INTRODUCTION:

Friedel-Crafts alkylation of aromatic compounds is one of the most important

C-C bond-forming reactions in organic chemistry,1 which has found significant

applications in the synthesis of various biologically active compounds.2 Acid-

catalyzed Friedel–Crafts alkylation of arenes with aromatic aldehydes has been

known since 1886.3 Friedel-Crafts arylation reactions of carbonyl compounds,4

epoxides5 and electron-deficient olefins6 as substrates have been extensively studied.

Triaryl- and triheteroarylmethanes have attracted much attention from all fields of

chemists from last decade after discovery of triphenylmethyl radical by Gomberg in

1900.7 Many of these compounds have found widespread applications in synthetic,

medicinal and industrial chemistry.8 The triarylmethyl derivatives are useful as

protective groups9, photochromic agents10 and dyes.11 Ring hydroxylated

triarylmethanes have been reported to exhibit antitumor and antioxidant activities.12

Also, bisheteroarylmethanes are of interest to the food industry as natural components

of certain food and beverage items as well as flavor agents in coffee.13

Triarylmethanes and bis-heteroarylarylmethanes have been prepared by using Lewis

acid or protic acid-catalyzed Friedel-Crafts arylation reactions of aldehydes with

electron-rich arenes and heteroarenes.14 Triaryl methanes (TRAMs) including

triheteroaryl methanes have attracted the attention of chemists because of the

interesting properties associated with their derivatives. They have exhibited varied

biological activities as antiviral, antitumor, antitubercular, antifungal and anti-

inflammatory agents.15 Many of the important bisindolyl methanes and trisindolyl

methanes (BIMs and TIMs) were widely isolated from various terrestrial and marine

natural sources. These natural products have novel structures and exhibit a range of

important biological activities.16 A number of methods were reported in the literature

for the synthesis of trialkylmethanes with various electron rich arenes, most of which

are multistep processes and require harsh reaction conditions with longer reaction

timings.14 Some of the important previous approaches are discussed here.


89

3.4 PREVIOUS APPROACHES:

Vijay Nair’s approach:

Vijay Nair et al. prepared triaryl and triheteroaryl methanes using electron rich

arenes (Indole, 1, 3, 5-trimethoxy benzene, 2-methyl furan etc) with various aromatic

aldehydes under the influence of 1 mol% of AuCl3 in acetonoitrile solvent at rt for 12

h with 40-90% yield.17 An electron-rich arene, 1, 3, 5-trimethoxybenzene

additionallly required catalytic system of AuCl3/AgOTf and a slightly elevated

temperature (50 °C) to condense effectively with benzaldehyde. However, with a

more activated electrophile (4-nitro benzaldehyde), the reaction took place at room

temperature to afford the tris aryl adduct in good yield (Scheme 1).

O O O

AuCl3 (1 mol%)

CH3CN, rt, 12 h

O

O O

CHO

R

AuCl3/Ag(oTf)3 (1 mol%)

R

R= H, rt, 12 h, 45 %H, 50 oC, 12 h, 85%NO2, rt, 12 h, 80 %

R-CHO

R

R = H, Ph, 4-MeC6H4, 2-Naphth,4-CF3C6H4, 4-H2NC(O)C6H4

NH

CH3CN

R

R1-CHO

R= H, R1 = Phenyl, 2-Napth, 4-CF3C6H4, 4-BrC6H4

R= Me, R1 = 4-NH2C(O)C6H4, 4-BrC6H4

AuCl3 (1 mol%)

CH3CN, rt, 12 h

R1

HNNH

Scheme 1

O

O O OO

O


90

Kodomari’s approach:

Kodomari and his group have developed a method for the synthesis of

triarylmethanes and 9, 10-diarylanthracenes by Friedal-crafts alkylation of electron

rich arenes with aromatic aldehydes in presence of catalytic amount of silicagel

supported Zinc bromide (ZnBr2/SiO2) and acetyl bromide in benzene medium at room

temperature with moderate yields.18 Polymethylbenzene such as o- and m-xylene and

1, 2, 3-trimethylbenzene required a slightly elevated temperature (50 oC) to condense

effectively with benzaldehyde. The ratio of formation of arene:aldehyde is changed

from 4:1 to 1:3, disubstituted anthracenes were obtained in good yields. Veratrole (1

equiv) with benzaldehyde (3 equiv) and AcBr (4 equiv) in benzene was carried out in

the presence of ZnBr2/SiO2 at room temperature for 4 h to give anthracene in 77%

yield (scheme 2).

MeO OMe

OMe

CHO

CH3COBrZnBr2/ SiO2

benzene, rt

MeO

MeO

CHO

AcBr-ZnBr2/ SiO2

excess of aldehydeMeO OMe

MeO OMe

MeO OMe

AcBr-ZnBr2/ SiO2

excess of veratrole

MeO OMe

Scheme 2


91

Silveira’s approach:

Silveira and his co-workers have described a method for the synthesis of

bis(indolyl)methanes through a reaction of indoles with various aromatic and aliphatic

aldehydes in presence of catalytic amount of CeCl3.7H2O at 75 oC for 3 hours in

glycerin, used as recyclable solvent (scheme 3).19

NH

CeCl3.7H2O, 75 oC

Glycerin

CHO

HN NH

scheme 3

Genovese approach:

Salvatore Genovese et al have prepared various triarylmethanes and

triheteroarylmethanes with 2-methyl furan and anisole used as electron rich arenes in

presence of Yb(OTf)3 under solvent free conditions at room temperature for 3 hours

with 70-90% (scheme 4).20

CHO

F

OMe

Yb(OTf)3 (1 mol%)

rt, 3 h, 82%

MeO OMe

F

CHO

NO2O rt, 3 h, 74%

O O

O2N

Scheme 4

Yb(OTf)3 (1 mol%)

Cheng’s approach:

Jin-Pei Cheng and his co-workers have described a method for the synthesis of

bis(indolyl)methanes through the condensation of indole with aldehydes, ketones and


92

imines in presence of catalytic amount of Dy(OTf)3 immobilized in ionic liquid at

room temperature with 76-95% yield (scheme 5).21

Dy(OTf)3

[BMIM]BF4.rt, 3 h, 90%

NH

O

R

Cl

Cl

HN NH

NH

R1

N

R2

Dy(OTf)3

[BMIM]BF4.rt, 3 h

R1

HN NH

R1

NH

HN

R2

48%

52%

R= H, Me

R1= H, Cl, OMe

R2= H, Cl, Me

Scheme 5


93

3.5 PRESENT WORK:

To our knowledge, only few reports regarding the synthesis of triaryl and

triheteroaryl methanes in the literature was described.17-21 Reaction conditions

employed in some of these methods involve expensive reagents, harsh conditions and

lengthy reaction times. Hence, the development of new methods using mild Lewis

acid catalyst in catalytic amounts is of practical importance. In continuation of our

interest in Lewis acid catalyzed transformations herein, in the present work, we have

described an efficient and mild Lewis acid-catalyzed method for the synthesis of

triaryl and tri hetero arylmethanes with various electron rich arenes and variety of

aromatic aldehydes in presence of tris(pentafluorophenyl)borane in dichloromethane

at room temperature in good yields (Scheme 6).

Ar-CHO RB(C6F5)3 (5 mol%)

CH2Cl2, rt, 0.5 -3 h, 90% R

Ar

R

R= Indole, 2-Me-Furan, 1, 3, 5-trimethoxy benzene

Scheme 6

Initially, our attempts started from the treatment of commercially available 1,

3, 5-trimethoxybenzene (an electron rich arene) with 3, 4, 5-trifluorobenzaldehyde 1

(entry 1, table1) in CH2Cl2 in presence of 5 mol% tris(pentafluorophenyl) borane at

room temperature and observed the formation of corresponding triaryl methane 1a in

82% yield (scheme 7, entry 1, table 1). This process took 3 h before total conversion

was observed by TLC. 1H NMR of compound 1a revealed the presence of resonance

at 6.10 ppm as a singlet for four aromatic (-CH=CH) protons and triphenyl methyl

(Ph3CH) proton. Two more singlet peaks resonating at 3.79 ppm for 6H and 3.55 ppm

for 12H clearly indicated the presence of six aromatic methoxy (OCH3) protons. 13C

NMR spectrum of 1a showed a peak at 36.4 ppm for triphenyl methyl (Ph3CH)

carbon indicated the formation of product. The product was further confirmed by its

HRMS spectrum which showed [M+H]+ peak at 479.1675.


94

FF F

CHO

O

O O

B(C6F5)3 (5 mol%)

CH2Cl2, rt, 3 h, 82%

FF F

O

O O O O

O

Scheme 711a

This result prompted us to look for the reactivity of other aldehydes in this

transformation to produce corresponding triaryl methanes with 1, 3, 5-

trimethoxybenzene and we found that they all participating well in this transformation

and yielding the corresponding triaryl methanes. Accordingly, 2, 5-dimethoxy

benzaldehyde 2 (entry 2, table1) was used as aldehyde component and treated with 1,

3, 5-trimethoxybenzene in presence of 5 mol% B(C6F5)3at room temperature. The

reaction proceeded smoothly in 2.5 h and produced corresponding triaryl methane 2a

in 89% yield (scheme 8). 1H NMR of this compound 2a revealed the presence of

resonance at 6.23 ppm as singlet corresponding to triphenyl methyl (Ph3CH) proton

and resonance at 6.10 ppm as a singlet for four aromatic (-CH=CH) protons. 13C

NMR spectrum showed a peak at 32.5 ppm for triphenyl methyl (Ph3CH) carbon

which suggested the formation of product. The product 2a was further confirmed by

its HRMS spectrum which showed [M+H]+ peak at 485.2169.

CHO

O

O O

B(C6F5)3 (5 mol%)

CH2Cl2, rt, 2.5 h, 89%

O

O

O O O O

O

Scheme 82 2a

O

OO

Later we treated 1, 3, 5-trimethoxybenzene with other aldehydes such as p-

hydroxy bromo benzaldehyde 3 (entry 3, table1) and o-nitro benzaldehyde 4 (entry 4,

table1) were also participated in the similar manner and yielded the corresponding


95

triaryl methane 3a and 4a in 78 and 91% yield respectively. All the products were

fully characterized by IR, 1H NMR and 13C NMR spectroscopy and results are

summarized in table 1.

S.No Aldehyde Product Yielda (%)

1.

2.

3.

4.

CHO

OMe

MeO

CHO

OH

Br

CHONO2

1

2

3

4

FF F

CHO

FF F

1a

2a

3a

4a

[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

OMe

MeO

[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

Br

OH

[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

NO2

82%

89%

78%

91%

Table 1. B(C6F5)3 catalyzed alkylation of 1, 3, 5- trimethoxy benzene with various aldehydes

Time (h)

3

2.5

3

3

a isolated yield


96

Our next focus of interest was to prepare triheteroaryl methanes by the

condensation of various aromatic aldehydes with heteroarenes such as indole and 2-

methyl-furan. Interestingly, these heteroarenes were actively participated in this

transformation with high yields and in less reaction time. p-Nitrobenzaldehyde 5 was

condensed with 2-methyl-furan (entry 1, table 2) in dichloromethane in the presence

of (5 mol%) tris (pentafluorophenyl) borane at room temperature for 0.5 h to achieve

the corresponding triheteroarylmethane 5a in 85% yield (scheme 9). 1H NMR of 5a

revealed the presence of resonance at 5.37 ppm as a singlet for one proton

corresponding to triheteroaryl methane (Ph3CH) proton and resonance at 2.25 ppm as

singlet for six aromatic methyl (Ar-CH3) protons. 13C NMR spectrum showed a peak

at 44.7 ppm for triheteroaryl methyl (Ar3CH) carbon which suggested the formation

of product 5a. It was further confirmed by its EI-MS spectrum which showed

[M+Na]+ peak at m/z 297.3.

CHO

NO2

5

NO2

OO

5a

O

Scheme 9

B(C6F5)3 (5 mol%)

CH2Cl2, rt, 0.5 h, 85%

This result encouraged us to explore other aldehydes and to our delight

aldehyde 6 (entry 2, table 2) participated in this reaction to form the corresponding

triarylmethane 6a with 2-methyl-furan in the presence of 5 mol% of tris

(pentafluorophenyl) borane at room temperature. The reaction proceeded smoothly in

1h and produced corresponding triaryl methane 6a in 92% yield (scheme 10). 1H

NMR of 6a revealed the presence of resonance at 5.52 ppm for one proton as a singlet

corresponding to triheteroaryl methane (Ph3CH) proton and resonance at 2.25 ppm as

singlet for six aromatic methyl (Ar-CH3) protons. 13C NMR spectrum of 6a showed a

peak at 39.8 ppm for triheteroaryl methyl (Ar3CH) carbon confirmed the formation of

product.


97

6

OO

6a

O

Scheme 10

B(C6F5)3 (5 mol%)

CH2Cl2, rt, 0.5 h, 85%Br

OH

CHO

Br

OH

Later another electron rich arene, indole was explored by reaction with 3, 4,

5-trifluoro benzaldehyde 7 (entry 3, table 2) in presence of 5 mol% of borane catalyst

in dichloromethane at room temperature. The reaction proceeded smoothly in 30 min

and provided the corresponding triheteroarylmethane 7a in 93% yield (scheme 10). 1H

NMR spectra of compound 7a revealed the presence of resonance at 6.67 ppm as

singlet for two protons represents aromatic (CH=CH) protons of indole and resonance

at 5.82 ppm as a singlet for one proton corresponding to triheteroaryl methane

(Ph3CH) proton which suggested the formation of product 7a. It was further

confirmed by its 13C NMR spectrum which showed a peak at 39.5 ppm for

triheteroaryl methyl (Ar3CH) carbon.

CHO

F

7 7a

Scheme 10

F F

FF F

HN NH

NH

B(C6F5)3 (5 mol%)

CH2Cl2, 30 min, 93%

Similarly, the reaction between indole and benzaldehyde 8 (entry 3, table 2)

has also participated well in this transformation in presence of 5 mol% of tris

(pentafluorophenyl) borane in 30 min at room temperature and provided

corresponding triheteroaryl methane 8a in 86% yield. The results are summarized in

table 2.


98

S.No Aldehyde Product Yielda (%)

2.

3.

4.

1. 85%

92%

93%

86%

Table 2. B(C6F5)3 catalyzed alkylation of Indole, 2-methyl furan with aldehydes

Time (h)

0.5

1

0.5

0.5

a isolated yield

CHO

NO2

CHO

OH

Br

CHO

FF F

CHO

5

6

7

8

NO2

OO

OO

Br

OH

FF F

HN NH

HN NH

5a

6a

7a

8b

In summary, we have demonstrated an efficient and mild lewis acid B(C6F5)3-

catalyzed synthesis of triaryl and triheteroaryl methanes by condensation of electron-

rich arenes with various aldehydes at room temperature. The simple procedure, mild

reaction conditions and high yields of the products makes this methodology attractive

for applications in organic synthesis.


99

3.6 Experimental Section

Experimental procedure:

To a stirred solution of arene (1 mmol) in dichloromethane (10 mL), aromatic

aldehyde (0.5 mmol) and 5 mol% of B(C6F5)3 were added at room temperature and

the reaction progress was monitored by TLC analysis. After completion of the

reaction (0.5 h), solvent was evaporated under vacuum and residue was purified by

column chromatography on silica gel using ethyl acetate and hexanes (10:90 to 15:85)

as eluent to give triarylmethanes and triheteroarylmethanes in 93% yield.

2, 2'-((3, 4, 5-Trifluorophenyl) methylene) bis (1, 3, 5-trimethoxybenzene) (1a):

FF F

1a[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

Nature of the compound : Yellow solid.

Melting point : 168-170 oC.1H NMR (300 MHz, CDCl3) : δ 6.72-6.59 (m, 2H), 6.10 (s, 5H), 3.79 (s,

6H), 3.55 (s, 12H).13C NMR (75 MHz, CDCl3) : δ 159.5, 152.0, 151.8, 148.7, 148.6, 142.5,

112.1, 111.5, 111.2, 91.4, 55.8, 55.1, 36.4.

IR (KBr) : υmax 2934, 2838, 1593, 1225, 1124cm-1.

HRMS-ESI (m/z) : calcd for C25H26F3O6 [M+H]+: 479.1676,

found: 479.1675.


100

2, 2'-((2, 5-Dimethoxyphenyl) methylene) bis (1, 3, 5-trimethoxybenzene) (2a):

2a

[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

OMe

MeO

Nature of the compound : white solid.

Melting point : 172-174 oC1H NMR (300 MHz, CDCl3) : δ 6.68 (d, J = 8.7 Hz, 1H), 6.59 (dd, J =

2.8, 8.7 Hz, 1H), 6.52 (d, J = 2.8 Hz, 1H),

6.23 (s, 1H), 6.1 (s, 4H), 3.76 (s, 6H), 3.65

(s, 3H), 3.58 (s, 3H), 3.49 (s, 12H).13C NMR (75 MHz, CDCl3) : δ 159.3, 158.6, 153.1, 152.2, 135.6, 116.4,

114.6, 110.6, 108.9, 91.9, 56.6, 56.2, 55.4,

55.0, 32.5.

IR (KBr) : υmax 2938, 2931, 2832, 1594, 1223, 1122

cm-1.

HRMS-ESI (m/z) : calcd for C27H33O8 [M+H]+: 485.217,

found: 485.2169.

3-(bis (2, 4, 6-Trimethoxyphenyl) methyl)-4-bromophenol (3a):

3a[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

Br

OH


101

Nature of the compound : White solid.

Melting point : 188-189 oC.1H NMR (300 MHz, CDCl3) : δ 7.15-7.05 (m, 2H), 6.65 (d, J = 8.8 Hz,

1H), 6.13 (s, 1H), 6.10 (s, 4H), 3.77 (s,

6H), 3.57 (s, 12H).13C NMR (75 MHz, CDCl3) : δ 159.6, 159.3, 154.7, 132.8, 129.1, 117.3,

111.4, 91.7, 56.0, 55.1, 34.0.

IR (KBr) : υmax 2925, 2843, 1596, 1461, 1117 cm-1.

2, 2'-((2-Nitrophenyl) methylene) bis (1, 3, 5-trimethoxybenzene) (4a):

4a[2, 4, 6 (OMe)3] [2, 4, 6 (OMe)3]

NO2


Melting point : 202-205 oC.1H NMR (200 MHz, CDCl3) : δ 7.69 (d, J = 7.7 Hz, 1H), 7.33 (t, J = 7.7

Hz, 1H), 7.26-7.16 (m, 1H), 7.10 (d, J =

7.7 Hz, 1H), 6.84 (s, 1H), 6.08 (s, 4H),

3.76 (s, 6H), 3.51 (s, 12 H).13C NMR (75 MHz, CDCl3) : δ 159.5, 159.4, 149.5, 139.9, 131.3, 130.4,

125.1, 123.2, 123.0, 111.9, 91.6, 56.1,

55.0, 33.5.

IR (KBr) : υmax 2924, 2849, 1596, 1151, 1119 cm-1.

HRMS-ESI (m/z) : calcd for C25H28NO8 [M+H]+ : 470.1809,

found: 470.1806.


102

5, 5'-((4-Nitrophenyl) methylene) bis (2-methylfuran) (5a):

NO2

OO5a


Melting point : 85-88 oC.1H NMR (200 MHz, CDCl3) : δ 8.17 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.7

Hz, 2H), 5.90-5.85 (m, 4H), 5.37 (s, 1H),

2.25 (s, 6H).13C NMR (75 MHz, CDCl3) : δ 152.0, 150.0, 147.3, 129.2, 123.7, 108.7,

106.2, 44.7, 13.5.

IR (KBr) : υmax 3115, 2924, 2863, 2358, 1563, 1347,

790 cm-1.

3-(bis (5-Methylfuran-2-yl) methyl)-4-bromophenol (6a):

OO

Br

OH

6a

Nature of the compound : White solid

Melting point : 89-90 oC1H NMR (300 MHz, CDCl3) : δ 7.24 (dd, J = 2.4, 8.5 Hz, 1H), 7.19 (d, J

= 8.5 Hz, 1H), 6.69 (d, J = 8.5 Hz, 1H),

5.93 (dd, J = 3.0, 14.5 Hz, 4H), 5.57 (br,

1H), 5.52 (s, 1H), 2.25 (s, 6H).


103

13C NMR (75 MHz, CDCl3) : δ 152.7, 152.0, 150.6, 132.4, 131.2, 128.0,

118.2, 112.8, 108.7, 106.2, 77.4, 76.9,

76.5, 39.8, 13.6

IR (KBr) : υmax 3503, 2921, 2853, 1487, 1216, 782

cm-1.

3, 3'-((3, 4, 5-Trifluorophenyl) methylene) bis (1H-indole) (7a):

FF F

HN NH7a

Nature of the compound : White solid

Melting point : 92-94 oC1H NMR (200 MHz, CDCl3) : δ 7.97 (s, 2H), 7.44-7.29 (m, 4H), 7.28-

7.13 (m, 2H), 7.11-6.88 (m, 4H), 6.67 (s,

2H), 5.82 (s, 1H)13C NMR (75 MHz, CDCl3) : δ 136.6, 126.5, 123.4, 122.2, 119.6, 119.5,

118.1, 112.6, 112.3, 111.2, 39.5.

IR (KBr) : υmax 3415, 1627, 1523, 1342, 1093, 750

cm-1.

3, 3'-(Phenylmethylene) bis (1H-indole)(8b):

HN NH8b


104

Nature of the compound : White amorphous solid.

Melting point : 87-88 oC1H NMR (200 MHz, CDCl3) : δ 7.81 (s, 2H), 7.42-7.10 (m, 11H), 6.99 (t,

J = 7.3 Hz, 2H), 6.59 (s, 2H), 5.87 (s, 1H).13C NMR (75 MHz, CDCl3) : δ 143.9, 136.5, 128.6, 128.1, 126.9, 126.0,

123.5, 121.8, 119.8, 119.6, 119.1, 110.9,

40.1.

IR (KBr) : υmax 3412, 2922, 1453, 1122, 744 cm-1.

ESI-MS : m/z 321 [M-H]+.


105

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15. a) Mibu, N.; Yokomizo, K.; Uyeda, M.; Sumoto, K. Chem. Pharm. Bull. 2005,

53, 1171-1174. b) Mibu, N.; Yokomizo, K.; Uyeda, M.; Sumoto, K. Chem.

Pharm.Bull. 2003, 51, 1325-1327. c) Lewis, M. R.; Goland, P. P. Cancer Res.

1952, 12, 130-136. d) Parai, M. K.; Panda, G.; Chaturvedi, V.; Manju, Y. K.;


107

Sinha, S. Bioorg. Med. Chem. Lett. 2008, 18, 289-292. e) Panda, G.;

Shagufta; Mishra, J. K.; Chaturvedi, V.; Srivastava, A. K.; Srivastava, R.;

Srivastava, B. S. Bioorg. Med. Chem. 2004, 12, 269-5276. f) Podder, S.;

Choudhury, J.; Roy, U. K.; Roy, S. J. Org. Chem. 2007, 72, 3100-3103. g)

Nair, V.; Thomas, S.; Mathew, S. C.; Abhilash, K. G. Tetrahedron. 2006, 62,

6731.

16. Morteza Shiri,, Mohammad Ali Zolfigol, Hendrik Gerhardus Kruger, and

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Chapter III, section B

108

B(C6F5)3 - CATALYZED TRITYLATION OF ALCOHOLS

3.9 INTRODUCTION:

Masking of hydroxyl functionalities early in a synthetic route with different

protecting groups is often necessary to successfully perform subsequent multistep

synthetic reactions.The selection of suitable protecting group has still got ambiguity

in the field of synthetic organic chemistry, because of failures to fulfill many

requirements. It must react selectively in good yields and give protected compounds

which should be stable for next steps of the projected reactions. So one should

consider, in detail, about all the reactants, reagents, reaction conditions and

functionalities involved in the proposed synthetic scheme. The ability to easily install

the desired protecting group, followed by facile removal at the end of synthesis is

important for the selection of specific protecting group. Many protecting groups have

been reported till date and more are being developed for this purpose.1

In continuation of these efforts, we developed a facile method for the

protection of alcohols as its trityl ethers. The triphenylmethyl (trityl) group is a most

commonly used protecting group for alcohols especially in carbohydrate2 and

nucleoside chemistry.3Tritylation of other heterocyclics such as Nitrogen4a and

Sulfur4b is also known in literature. Trityl functionality represents an attractive

protecting group, because of its stability towards neutral and basic conditions.5

Moreover; it is readily removed under mild acidic conditions6 to regenerate the

alcohol. The advantage of suitably derivatizedtrityl moieties for the introduction of

various functional features on synthetic DNA without affecting the genetic integrity

of it becomes more attractive. Furthermore, additional chromophore in trityl group,

along with increased lipophilicity helps in purification of intermediate. With these

advantages, formation of trityl ethers is not always straightforward. Some procedures

require extensive preparation of tritylating reagents and harsh conditions,7, 8others

require lengthy reaction times.9, 10


109

3.10 PREVIOUS APPROACHES:

Hanessian’s approach:

Hanessian and Staub have described a method for tritylation of various

alcohols using N-triphenylmethylpyridiniumtetrafluoroborate (prepared from Trityl

chloride and pyridine) in CCl4 under reflux conditions for 3h to give corresponding

tritylethers in 88% overall yield (Scheme 1 ).7

NCPh3

BF4-

CCl4 , 5 0 oC

3 h, 88%

Scheme 1

O

OH

OH

OHOMe

HOO

OH

OH

OHOMe

TrO

NH BF4-

Noyori’s approach:

Noyori and Murata have described a method for tritylation of

trimethylsilylated hydroxyl compounds with trimethyltrityloxysilane and 1 mol% of

trimethylsilyltriflate in dichloromethane at 0 oC to achieve corresponding tritylated

ethers in 90% yield (Scheme 2).8The reaction timings varied from 30 min to 18 h

depending upon the hydroxyl moities.

Scheme 2

OSi

PhPh

Ph

OSi

cat. TMSOTf O

PhPh

Ph

14 oC, 18 h, 90%

PhPh

Ph

OSiO

SiO

cat. TMSOTf

0 oC, 6 h, 73%O Ph

O PhPh

Hernandez’s approach:

Hernandez et al.described tritylation of alcohol using 4- dimethylamino-N-

triphenylmethylpyridinium chloride (which was derived from trityl chloride) in

dichloromethane at 25 oC for 16 h to achieve corresponding trityl ethers in 65% yield

(Scheme3).9


110

DDQ, 70-75 oC

3 h, 65%

O

PhPh

PhOH

OH DDQ, 70-75 oC

4 h, 55%

O

PhPh

Ph

N

N

Ph3CCl

Ph3CCl

Scheme 3

Messager’s approach:

Messager et al. described a method for tritylation of primary and secondary

alcohols using trityl chloride and DBU as a base in dichloromethane at room

temperature for 2 days which gave corresponding trityl ethers in 90% yield

(Scheme 4).10

HO

C8H17

TrO

C8H17

TrClDBU, CH2Cl2

rt, 2 days, 90%

Scheme 4

OH DBU, CH2Cl2

rt, 2 days, 85%TrCl

OTr

Reddy’s approach:

Reddy et al. described solid phase tritylation of hydroxyl function of

nucleoside bound to controlled pore glass (CPG) using dimethoxytrityl chloride in the

presence of 2, 4, 6-collidine in dichloromethane to achieve corresponding trityl ether

in 90 % yield (Scheme 5).11


111

Cl

O

O

O

OHO

O

OO

O

O

nBu4NClO4

2, 4, 6 collidine

CH2Cl2,15 min, 90%

Scheme 5

Lundquist’s approach:

Lundquist and his coworkers have described silver triflate assisted method for

trityl protection of alcohols in solution phase in presence of 2, 6-di-tert butylpyridine

as a mild base with 70% yield (Scheme 6).12

BrR OR1R

R1-OH, AgOTf

2,6-di-tertbutylpyridine

CH2Cl2 , 0 °C, 1 h, 70 %

Scheme 6

Kusumoto’s approach:

Kusumoto et al. have described a method for tritylation of alcohols using

benzyl trityl ether as tritylating agent in presence of DDQ in dichloromethane and 4Ao

MS at 30-50 oC under anhydrous conditions for 36 h which gave corresponding trityl

ethers in 90% yield (Scheme 7).13

O

OHOH

OH

OH

ORO Ph

PhPh

O

OTrOH

OH

OH

ORDDQ, CH2Cl2

30-50 oC, 36 h, 90 %

Scheme 7


112

Iranpoor’s approach:

First generation:

Nasser Iranpoor and his co-workers have described a selective method for

catalytic conversion of allylic and tertiary benzylic alcohols into their corresponding

trityl ethers in presence of CAN (Ceric Ammonium Nitrate) under refluxed conditions

for 2 h in both solvolytic and non solvolytic conditions in good yields (Scheme 9).14

OH PhPh

PhOH

cat CAN, 70-75 oC

2 h, 85 %

O

PhPh

Ph

Scheme 8

Second generation:

Iranpoor group have described another method for tritylation of various

alcohols to tritylethers in presence of FeCl3 under reflux conditions which gave poor

to moderate yields (Scheme 9).15

FeCl3, 70-75 oC

2 h, 62%

Scheme 9

OH

OH FeCl3, 80-85 oC

30 min, 83%

HO

OH

OH O

Sarma’s approach:

Sarma and his group described tritylation of alcohols using p-

methoxybenzyltrityl ether (p-MBTE) or prenyltrityl ether (PTE) as tritylating agent in

presence of DDQ and Mn(OAc)3 at room temperature gave the protected alcohols in

65-85% yield (Scheme 11).16


113

Scheme 10

OH OTr

p-MBTE-DDQ-Mn(OAC)3

CH2Cl2, MS 4Ao, rt, 80 %

O O

Ph

OH

OH

O O

Ph

OH

OTr

PTE-DDQ, CH2Cl2

MS 4Ao, rt, 3 h, 67 %

Most of these tritylating agents are commercially not available and have to be

prepared from trityl chloride. To date, there are very limited examples known in

literature describing protection of alcohols as trityl ethers with triphenylmethanol (as

tritylating agent) in presence of an acid catalyst.14, 15 Reaction conditions employed in

some of these methods involve strong acidic conditions17 (H2SO4, FeCl3, etc.).

Furthermore, these catalysts were studied using only a few examples and no

systematic study on chemoselectivity has been carried out. Thus, development of a

new Lewis acid for chemoselective protection of alcohols as trityl ethers under mild

reaction conditions is of interest to synthetic organic chemists.


114

3.11 PRESENT WORK:

This section describes an efficient and mild acid-catalyzed protection of

alcohols as trityl ethers using triphenylmethanol (trityl alcohol) in presence of

tris(pentafluorophenyl) borane (3 mol%) in dichloromethane at room temperature

which gave moderate to good yields (Scheme 11).

PhPh

PhOH

R R1

OH

R R1

OPh Ph

Ph

R= alkyl, aryl; R1 = H, alkyl

R R1

OTror

B(C6F5)3 (3 mol%)

CH2Cl2, rt, 3-8 h

Scheme 11

Our attempts started with the treatment of 3-phenyl-1-propanol 1a, a

commercially available starting material, with triphenylmethanol in presence of 3 mol

% B(C6F5)3 in dichloromethane at room temperature. Reaction proceeded smoothly in

3 h and afforded the corresponding trityl ether 2a in 92% isolated yield (Table 1,

entry 1, scheme 12). 1HMR spectrum of 2a showed two multiplets resonating at δ 7.5-

7.41 for 6H and 7.35-7.06 for 14H which clearly indicated the formation of trityl

product. Product was further confirmed by its mass spectrum which showed

[M+H]+peak at m/z 379.5.

Ph OH Ph OTr3 mol % B(C6F5)3

CH2Cl2, rt, 3h, 92 %

Scheme 12

1a 2a

This result prompted us to look for other alcohols which can participate in

trityl ether formation with trityl alcohol in presence of tris(pentafluorophenyl)borane

and we found that they participated well in this transformation and results are

summarized in table 1. Accordingly, propargyl alcohol 1b (entry 2, Table 1, scheme

13) was used as alcohol component and found the product 2b was formed in 87%

yield. 1H NMR spectrum of compound 2b revealed peaks that resonates between δ


115

7.55-7.10 as a muliplet for 15H clearly indicated the presence of trityl group and

another singlet at δ 3.75 for 2H indicating presence of -CH2O attached to triple bond

of the product. This was further confirmed by its mass spectrum, which showed

[M+H]+ peak at m/z 299.2.

O3 mol % B(C6F5)3

CH2Cl2, rt, 3h, 87%

Scheme 13

PhPh

Ph

OH

1b 2b

All primary alcohols 1a-1c were participated in tritylation reaction to yielded

corresponding trityl ethers 2a-2c in quantitative yields (Table1). Secondary benzyl

alcohols 1d and 1e reacted slowly at room temperature, however, they reacted under

refluxing conditions to provide the corresponding trityl ethers 2d and 2e in 48 and

56% yields, respectively (Scheme 14, entries 4 and 5). Bulkiness of three phenyl rings

in trityl group creates steric hinderance and decreases reactivity of secondary alcohols

towards tritylation while compared to primary alcohols.

3 mol % B(C6F5)3

CH2Cl2, 8h, 35 oC

Scheme 141e 2e

Ph

OH

Ph

OTr

Ph

OH

Ph

OTr

1d 2d

3 mol % B(C6F5)3

CH2Cl2, 8h, 35 oC

Chemoselectivity of this protocol is demonstrated by studying tritylation of a

primary alcohol in presence of a secondary alcohol (entries 6 and 8). Scheme 15

clearly demonstrates the chemoselective protection of a primary benzylic alcohol in

presence of a phenolic hydroxyl group. Compound 1f reacts smoothly in 4.5 h and to

give the corresponding trityl ether 2f as a sole product.


116

Entry Substrate Time(h) Product Yield (%)a

Ph OH Ph OTr

OH OTr

OH OTr

Ph

OH

Ph

OTr

Ph

OTr

Ph

OH

OH

OH

OTr

OH

OHO

MeO O

O

OHO

BnO O

O

HO

OHO

BnO O

O

TrO

OTrO

MeO O

O

HO OBnOO

TrO OBnOO

NBoC

OH

NBoc

OTr

HOCOOMe

NHBoCTrO

COOMe

NHBoc

Table 1 B(C6F5)3 catalyzed tritylation of alcohols

1

2

3

4

5

6

7

8

9

10

11

1a 2a

1b 2b

1c 2c

1d 2d

1e 2e

1f 2f

1g 2g

1h 2h

1i 2i

1j 2j

1k 2k

3

3.5

4

8

8

4.5

4

4

4

4

3.5

92

87

93

48b

56b

88

90

90

94

87

95

a Isolated yields after column chromatography.b Yield from the reaction carried out at reflux.


117

1HMR spectrum of 2f showed a broad singlet at δ 5.25 and its IR spectrum

showed a peak at 3465 cm-1indicating the presence of phenolic OH. Chemoselectivity

was confirmed by its 1H NMR spectrum, which revealed a singlet at δ 4.13 for two

protons (deshielding region) clearly indicating the protection at benzyl alcoholic

function and not at phenolic function. Product was further confirmed by its mass

spectrum which showed (M+Na)+ peakat m/z 389.1.

3 mol % B(C6F5)3

CH2Cl2,4.5 h, rt

Scheme 151f 2f

OH

OH

OH

OTr

Chemoselective tritylation was also performed with other substrates 1g to 1i

which were selectively converted to trityl ethers 2g to 2i without effecting acid-labile

acetonide, ketal and benzyl protecting groups (Table 1, entries 7-9). Similarly,

reaction succeeded with alcohols 1j and 1k, keeping acid-sensitive tert-

butylcarbamate (NBoc) protecting group intact (Table 1, entries 10 and 11, scheme

16).

NBoc

OH

NBoc

OTr

3 mol% B(C6F5)3

CH2Cl2, 4 h, rt, 87%

Scheme 16

1j 2j

To check compatibility and to confirm the mildness of the reagent system, we

studied protection of 1, 3-propanediol mono ether substrates 3a to 3h having a free

hydroxyl group at one end and a hydroxyl-protecting group (particularly acid labile

protecting groups) at the other end. These substrates underwent tritylation at free

hydroxyl group without affecting protecting groups such as silyl (TBS, TBDPS),

methoxy methyl (MOM), benzyl (Bn), Tosyl (Ts) and other groups .The results are

summarized in Table 2 (entries 1–8).


118

Entry Substrate Time(h) Product Yield(%)a

1

2

3

4

5

6

7

8

3

3.5

4

4

4

3.5

4

4

90

92

94

85

92

90

93

95

HO OTHP

HO OTBDMS

HO OTBDPS

HO OMOM

HO OPMB

HO OBn

HO OTr

HO OTs

TrO OTHP

TrO OTBDMS

TrO OTBDPS

TrO OMOM

TrO OPMB

TrO OBn

TrO OTr

TrO OTs

3a

3b

3c

3d

3e

3f

3g

3h

4a

4b

4c

4d

4e

4f

4g

4h

Table 2 Tritylation of alcohols in the presence of other protecting groups

a Isolated yields after column chromatography.

Efficiency of other Lewis acids was also investigated for this transformation

using 3-phenylpropanol as a model substrate. Treatment of 3-phenylpropanol with

triphenylmethanol in presence of 3 mol% of BF3.Et2O led to a complex mixture.

Other acid catalysts such as ZnCl2, AlCl3, p-TSA, and I2 also participated in

tritylation reaction and gave trityl ethers, results are summarized in Table 3 (entries

1–5). Among these catalysts, B(C6F5)3 was found to be more effective in terms of

yield, reaction profile and selectivity (Table 3, entry 6).

Deprotection of the trityl group, which is well known under acidic

conditions18-21was also attempted using the same catalyst [B(C6F5)3] in methanol but

without success, even at refluxing temperature.


119

Entry Acid catalyst (3 mol %) Time (h) Yield (%)a

1

2

3

4

5

6

4

5

4

4

4

3

Complex mixture

86

84

88

74

92

Table 3 Tritylation of 3-phenylpropanol in the presence of different acid catalysts

ZnCl2

AlCl3

p TSA

I2

B(C6F5)3

BF3.Et2O

a Isolated yield

In conclusion, we have demonstrated an extremely facile and efficient method

for protection of alcohols as trityl ethers in presence of 3 mol% of

tris(pentafluorophenyl) borane. Using this procedure, primary alcohols were

selectively protected as trityl ethers in presence of secondary alcohols under mild

reaction conditions. Stability of acid-labile protecting groups is an added advantage of

this method. In addition, the protocol offers an opportunity to install a trityl protecting

group in presence of base-sensitive functionalities such as esters.


120

3.12 Experimental Section

Typical experimental procedure:

To a mixture of 3-phenyl-1-propanol 1a (1.0 mmol) and triphenylmethanol

(1.5 mmol) in dichloromethane (5 mL), 3 mol% of B(C6F5)3 was added and mixture

was allowed to stir for 3h at room temperature. After completion of reaction

(monitored by TLC), the mixture was diluted with dichloromethane (5 mL) and

washed with water (1 x 5 mL) and then with brine (1 x5 mL). Organic layer was

separated and dried over Na2SO4 and evaporated in vacuo. Residue was purified by

column chromatography on silica gel using ethyl acetate and hexanes (4:96) as eluent

to give corresponding trityl ethers 2a in 92% yield.

SPECTRAL DATA

((3-Phenylpropoxy)-methanetrityl)tribenzene(2a).

Ph OTr

2a


Melting point : 80-82 o C.1H NMR (200 MHz, CDCl3) : δ 7.5-7.41 (m, 6H), 7.35-7.06 (m, 14H),

3.15 (t, J = 5.8 Hz, 2H), 2.77 (t, J = 7.3

Hz, 2H), 2.05-1.89 (m, 2H).13C NMR (75 MHz, CDCl3) : δ 144.6, 142.3, 128.8, 128.6, 128.4, 127.9,

127.0, 125.8, 86.5, 62.9, 32.7, 31.9.

IR (KBr) : υmax 3018, 1215, 758 cm-1.

Triphenyl (prop-2-ynyloxy) methane (2b).


121

OTr

2b

Nature of the compound : white solidMelting point : 111-113 oC1H NMR (200 MHz, CDCl3) : δ 7.55-7.10 (m, 15H), 3.75 (s, 2H), 2.30 (s,

1H).13C NMR (75 MHz, CDCl3) : δ 143.5, 128.7, 128.0, 127.4, 87.5, 80.6,

73.4, 52.9.IR (KBr) : υ 3291, 3058, 1062, 760, 703 cm-1.EIMS (m/z) : 321.1 (M+Na)+.

((Cyclopropylmethoxy)-methanetriyl)tribenzene(2c).

OTr

2c



3.07 (d, J = 6.6 Hz, 2H), 1.30-1.09 (m,1H), 0.66-0.55 (m, 2H), 0.32-0.22 (m, 2H)

13C NMR (75 MHz, CDCl3) : δ 144.6, 128.9, 128.1, 127.0, 86.3, 68.4,11.1, 3.0

IR (KBr) : υmax 1488, 1445, 1216, 1058, 759 cm-1.

(1-Phenylethoxy)triphenylmethane (2d).

Ph

OTr

2d

Nature of the compound : Colorless liquid.1H NMR (300 MHz, CDCl3) : δ 7.51-7.41 (m, 6H), 7.26-7.01 (m, 14H),

4.65 (q, 1H), 1.14 (d, J = 6.2 Hz, 3H).


122

13C NMR (75 MHz, CDCl3) : δ 146.5, 145.2, 129.2, 128.0, 127.7, 127.0,

126.2, 125.7, 88.0, 77.6, 77.2, 76.8, 73.0,

26.0,

IR (KBr) : υmax 2985, 1741, 1242, 1047 cm-1.

EIMS (m/z) : calcd for C27H24ONa: 387.1736; found,

387.1738 (M+Na)+.

((1-Phenyl-but-3-enyloxy) methanetriyl)tribenzene(2e).

Ph

OTr

2e

Nature of the compound : Pale yellow liquid.1H NMR (300 MHz, CDCl3) : δ 7.49 (d, J = 6.7 Hz, 6H), 7.39-7.10 (m,

15H), 5.45- 5.28 (m, 1H), 4.82 (d, J = 10.5

Hz, 1H), 4.65 (d, J = 17.3 Hz, 1H), 4.54

(dd, J = 8.3, 3.7 Hz, 1H), 2.20- 2.07 (m,

1H), 1.94-1.83 (m, 1H).13C NMR (75 MHz, CDCl3) : δ 145.0, 143.7, 134.1, 129.2, 128.1, 127.8,

127.7, 127.1, 126.8, 126.5, 111.2, 88.1,

76.4, 43.0.

IR (KBr) : υmax 3060, 3029, 1447, 1215, 1044, 916,

759 cm-1

EIMS (m/z) : 413.2 (M+Na)+.

3-(Trityloxymethyl) phenol (2f).

OTr

OH

2f

Nature of the compound : Pale yellow liquid.


123

1H NMR (300 MHz, CDCl3) : δ 7.56-7.45 (m, 6H), 7.38-7.1 (m, 10H),

6.95-6.85 (m, 2H), 6.7 (dd, J = 7.0, 2.3 Hz,

1H), 5.25 (brs, 1H), 4.13 (s, 2H).13C NMR (75 MHz, CDCl3) : δ 155.7, 144.2, 141.2, 128.9, 128.1, 128.0,

127.4, 119.3, 114.9, 114.0, 87.2, 65.5,

65.2.

IR (KBr) : υmax 3465, 2923, 1445, 1326, 1155, 1008,

761cm-1

EIMS (m/z) : 389.10 (M+Na)+.

(3aR, 5R, 6S, 6aR)-6-Methoxy-2, 2-dimethyl-5 (trityloxymethyl)tetrahydrofuro[2,3-d][1, 3]dioxole (2g).

O

MeO O

O

2g

TrO

Nature of the compound : Pale yellow oil.1H NMR (300 MHz, CDCl3) : δ 7.50-7.41 (m, 6H), 7.34-7.17 (m, 9H),

5.85 (d, J = 3.7 Hz, 1H), 4.54 (d, J = 3.7

Hz, 1H), 4.38-4.29 (m, 1H), 3.79 (d, J =

3.2 Hz, 1H), 3.46-3.21 (m, 2H), 3.33 (s,

3H), 1.52 (s, 3H), 1.32 (s, 3H).13C NMR (75 MHz, CDCl3) : δ 144.1, 129.2, 128.8, 128.0, 127.6, 127.3,

127.1, 111.8, 105.1, 86.9, 84.0, 82.1, 79.4,

61.0, 58.1,26.9, 26.4.

IR (KBr) : υmax 3418, 1636, 1215, 757 cm-1.

HRMS-ESI (m/z) : calcd for C28H30O5Na: 469.1990; found,

469.1992. (M+Na)+.


124

1-((3aR, 5R, 6S, 6aR)-6-(benzyloxy)-tetrahydro-2, 2-dimethylfuro [2, 3-d][1,3]dioxol-5-yl)-2-(trityloxy)ethanol (2h).

OHO

BnO O

O

TrO

2h

Nature of the compound : white crystalline solid.

Melting point : 101-103 oC1H NMR (300 MHz, CDCl3) : δ 7.45-7.38 (m, 6H), 7.33-7.15 (m, 14H),

5.84 (d, J = 3.7 Hz, 1H), 4.54 (AB quartet,

2H), 4.50 (m, 1H), 4.28 (dd, J = 3.0 Hz,

1H), 4.09 (q, 2H), 4.01 ( d, J = 3.0 Hz,

1H), 3.42 (dd, J = 4.9 Hz, 1H), 3.22 (dd, J

= 3.2 Hz, 1H), 2.42 (brs, 1H), 1.47 (s,3H),

1.29 (s, 3H).13C NMR (75 MHz, CDCl3) : δ 144.0, 137.4, 128.9, 128.7, 128.2, 128.0,

127.3, 111.8, 105.3, 86.9, 82.6, 82.4, 79.7,

72.5, 68.5, 65.3, 60.6, 26.9, 26.5, 21.2,

14.4

IR (KBr) : υmax 2933, 1214, 1077, 763 cm-1.

EIMS (m/z) : calcd for C35H36ONa :575.2432 (M+Na)+.

found: 575.2430

2-(2-(Benzyloxy)ethyl)-2-(2-(trityloxy)ethyl)-1, 3-dioxolane (2i).

TrO OBnOO

2i


125

Nature of the compound : Pale yellow liquid.1H NMR (200 MHz, CDCl3) : δ 7.49-7.14 (m, 20H), 4.48 (d, J = 5.3 Hz,

2H), 3.85-3.67 (m, 4H), 3.60-3.15 (td, J =

7.3, 6.5 Hz, 2H), 3.40 (t, J = 7.3 Hz, 2H),

2.71 (q, 2H), 1.96 (m, 2H).13C NMR(75MHz, CDCl3) : δ 144.5, 138.6, 128.8, 128.7, 128.5, 128.4,

127.9, 127.8, 127.7, 127.6, 127.1, 127.0,

109.6, 87.0, 73.2, 65.3, 64.0, 44.0, 37.9,

37.6

IR (KBr) : υmax 2985, 1741, 1374, 1242, 1047, 937

cm-1.

EIMS (m/z) : 517.2 (M+Na)+.

tert-Butyl -3-(trityloxymethyl)-1H-indole-1-carboxylate(2j).

NBoC

OTr

2j

Nature of the compound : Pale yellow liquid.1H NMR (200 MHz, CDCl3) : δ 7.56-7.06 (m, 20H), 4.24 (s, 2H), 1.68 (s,

9H).13C NMR (75 MHz, CDCl3) : δ 150.0, 147.0, 144.3, 144.1, 135.7, 129.3,

27.9, 126.5, 124.9, 122.9, 119.8, 118.9,

87.2, 83.8, 58.8, 28.4.

IR (KBr) : υ 2972, 1731, 1450, 1359, 1152, 1087,

1039, 745 cm-1.

EIMS (m/z) : 512.2 (M+Na)+.

tert-Butyl (S)-1-(methoxycarbonyl)-2-(trityloxy)ethylcarbamate(2k).


126

TrOCOOMe

NHBoc2k

Nature of the compound : White sticky compound.1H NMR (300 MHz, CDCl3) : δ 7.5-7.1 (m, 15H), 5.39 (d, J = 17.6 Hz,

1H), .39 (m, 1H), 3.74 (s, 3H), 3.50 (dd, J

= 7.1, 14.2 Hz, 1H), 3.37 (dd, J = 7.1, 14.2

Hz, 1H), 1.47 (s, 9H).13C NMR (75 MHz, CDCl3) : δ 171.5, 155.5, 143.6, 86.7, 80.1, 64.1,

54.2, 52.5, 28.5.

IR (KBr) : υmax3495, 3094, 2958, 1794, 1556, 1210,

1110, 798 cm-1.

EIMS (m/z) : 484.2 (M+Na)+.

3-(3-(1, 1-Diphenyl-ethoxy)propoxy)tetrahydro-2H-pyran (4a).

TrO OTHP4a

Nature of the compound : Pale yellow liquid.1H NMR (200 MHz, CDCl3) : δ 7.45-7.20 (m, 15H), 4.59 (s, 1H), 4.0-

3.39 (m, 6H), 1.99-1.64 (m, 8H).13C NMR (75 MHz, CDCl3) : δ 144.6, 128.9, 127.9, 127.0, 98.9, 64.7,

62.3, 60.6, 30.8, 30.6, 25.7, 19.6.

IR (KBr) : υ 2924, 1447, 1213, 1018, 760 cm-1.

ESI (m/z) : 425.2.

(3-(Trityloxy)propoxy)(tert-butyl)dimethylsilane (4b).


127

TrO OTBDMS4b

Nature of the compound : Colorless liquid1H NMR (200 MHz, CDCl3) : δ 7.47-7.13 (m, 15H), 3.69 (t, J = 6.2 Hz,

2H), 3.15 (t, J = 6.2 Hz, 2H), 1.88-1.63

(m, 2H), 0.9 (s, 9H), 0.6 (s, 3H), 0.1 (s,

3H).13C NMR (75 MHz, CDCl3) : δ 144.6, 128.9, 127.9, 127.0, 86.6, 60.5,

59.9, 33.6, 26.1, 18.5, -5.1

IR (KBr) : υmax3449, 2928, 1636, 1088, 836, 702 cm-1.

ESI (m/z) : 455.2 (M+Na)+.

(3-(Trityloxy) tert-Butyldiphenylpropoxy)silane(4c).

TrO OTBDPS4c

Nature of the compound : Pale yellow liquid.1H NMR (300 MHz, CDCl3) : δ 8.05-7.88 (m, 4H), 7.82- 7.50 (m, 21H),

4.19 (t, J = 6.6 Hz, 2H), 3.58 (t, J = 6.6

Hz, 2H), 2.30-2.16 (m, 2H), 1.33 (s, 9H).13C NMR (75 MHz, CDCl3) : δ 144.6, 135.7, 134.1, 129.6, 128.9, 128.5,

127.97,127.91, 127.7, 127.0, 86.6, 61.1,

60.6, 33.3, 27.0, 19.3.

IR (KBr) : υmax 2925, 1644, 1218, 1101, 767 cm-1.

HRMS-ESI : calcd for C38H40O2SiNa :579.2672, found:

579.2671 (M+Na)+.

(3-(Methoxymethoxy)propoxy)triphenylmethane (4d).


128

TrO OMOM4d

Nature of the compound : Pale yellow liquid.1H NMR (300 MHz, CDCl3) : δ 7.49-7.20 (m, 15H), 4.60 (s, 2H), 3.70 (t,

J = 6.0 Hz, 2H), 3.31 (s. 3H), 3.20 (t, J =

6.0 Hz, 2H), 1.98-1.87 (m, 2H).13C NMR (75 MHz, CDCl3) : δ 144.5, 128.9, 128.1, 127.9, 127.4, 127.0,

96.6, 86.6, 65.3, 60.7, 55.3, 30.6

IR (KBr) : υmax 3019, 1215, 1042, 762 cm-1.

EIMS (m/z) : calcd for C24H26O3Na :385.1778, found:

385.1775 (M+Na)+.

1-Methoxy-4-((3-(trityloxy)propoxy)methyl) benzene(4e).

TrO OPMB4e

Nature of the compound : Pale yellow liquid.1H NMR (300 MHz, CDCl3) : δ 7.44 (d, J = 6.7 Hz, 6H), 7.31-7.11 (m,

11H), 6.83 (d, J = 8.0 Hz, 2H), 4.37 (s,

2H), 3.77 (s, 3H), 3.57 (t, J = 6.7 Hz, 2H),

3.15 (t, J = 6.7 Hz, 2H), 2.04-1.78 (m,

2H).13C NMR (75 MHz, CDCl3) : δ 159.0, 144.3, 129.1, 128.6, 127.6, 127.2,

126.8, 113.6, 86.3, 72.5, 67.2, 60.4, 55.2,

30.4.

IR (KBr) : υmax2987, 2934, 2361, 1216, 1077, 1025,

755, 702 cm-1.

EIMS (m/z) : 461.2 (M+Na)+.


129

3-(Benzyloxy)propoxy)methanetriyl)-tribenzene (4f).

TrO OBn4f

Nature of the compound : Pale yellow liquid.1H NMR (300 MHz, CDCl3) : δ7.42-7.36 (m, 6H), 7.31-7.14 (m, 14H),

4.46 (s, 2H), 3.61 (t, J = 6.7 Hz, 2H), 3.18

(t, J = 6.7 Hz, 2H), 1.94-1.84 (m, 2H).13C NMR (75 MHz, CDCl3) : δ144.3, 138.5, 128.6, 128.3, 127.8, 127.6,

126.8, 86.4, 72.8, 67.5, 60.4, 30.4.

IR (KBr) : υmax3020, 1215, 758, 670 cm-1.

EIMS (m/z) : 431.1 (M+Na)+.

1, 3-bis(Trityloxy)propane (4g).

TrO OTr4g



3.23 (t, J = 5.8 Hz, 4H), 1.98-1.80 (m,

2H).13C NMR (75 MHz, CDCl3) : δ 144.5, 128.9, 127.9, 126.9, 86.6, 60.6,

30.7.

IR (KBr) : υmax 2926, 1489, 1446, 1217, 1081, 753

cm-1.

EIMS (m/z) : 583.2 (M+Na)+.


130

3-(Trityloxy)-propyl-4-methylbenzene-sulfonate(4h).

TrO OTs4h

Nature of the compound : Pale yellow solid

Melting point : 96-98 oC1H NMR (200 MHz, CDCl3) : δ 7.75 (d, J = 8.3 Hz, 2H), 7.38-7.20 (m,

17H), 4.21 (t, J = 6.7 Hz, 2H), 3.12 (t, J =

6.0 Hz, 2H), 2.43 (s, 3H), 1.90 (q, J = 6.7,

6.0 Hz, 2H).13C NMR (75 MHz, CDCl3) : δ 144.8, 144.1, 133.1, 129.9, 128.7, 127.0,

127.9, 127.1, 86.7, 68.1, 59.3, 29.7, 21.8.

IR (KBr) : υmax 3058, 3027, 2957, 1447, 1361, 1178,

1095, 1068, 840, 860, 752, 704, 664 cm-1.

EIMS (m/z) : 495.1 (M+Na)+.


131

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133

LIST OF PUBLICATIONS:

1. Tris(pentafluorophenyl)borane: a mild and efficient catalyst for the

chemoselectivetritylation of alcohols. Ch.Raji Reddy, G. Rajesh, S.V.Balaji,

N.Chethan. Tetrahedron. Lett. 2008, 49, 970-973.

2. B(C6F5) 3: an efficient catalyst for reductive alkylation of alkoxy benzenes and

for synthesis of triarylmethanes using aldehydes: S. Chandrasekhar,

SanjidaKhatun, G. Rajesh, Ch. Raji Reddy. Tetrahedron Letters, 2009, 50,

6693–6697.

3. First total synthesis of achaetolide, S. Chandrasekhar, S.V. Balaji, G. Rajesh.

Tetrahedron Lett, 2010, 51, 5164-5166.

4. Enantioselective synthesis of the C5-C23 segment of biselyngbyaside.

S.Chandrasekhar, G. Rajesh. (To be communicated).

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