Hydroboration and Organic Synthesis

9-Borabicyclo[331]nonane (9-BBN)

Ranjit S Dhillon

Hydroboration and Organic Synthesis9-Borabicyclo[331]nonane (9-BBN)

With 196 Figures and 260 Tables

123

Prof Dr Ranjit S DhillonDepartment of Biochemistry and ChemistryPunjab Agricultural UniversityLudhiana-141 004India

e-mail dhillonrrediffmailcom

Library of Congress Control Number 2006935689

ISBN 978-3-540-49075-3 Springer Berlin Heidelberg New YorkDOI 101007978-3-540-49076-0

This work is subject to copyright All rights are reserved whether the whole or part of the material is concerned specifically the rights of translation reprinting reuse of illustrations recitation broad-casting reproduction on microfilms or in any other way and storage in data banks Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9 1965 in its current version and permission for use must always be obtained from Springer-Verlag Violations are liable for prosecution under the German Copyright Law

Springer is a part of Springer Science + Business Mediaspringeronlinecomcopy Springer-Verlag Berlin Heidelberg 2007Printed in Germany

The use of general descriptive names registered names trademarks etc in this publication does not imply even in the absence of a specific statement that such names are exempt from the relevant protective laws and regulations and therefore free for general useProduct liability The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book In every individual case the user must check such information by consulting the relevant literature

Coverdesign WMXDesign GmbH HeidelbergTypesetting amp production LE-TEX Jelonek Schmidt amp Voumlckler GbR Leipzig Germany Printed on acid-freepaper 23141YL - 543210

This book is dedicated to

Prof Akira Suzuki Professor EmeritusHokkaido University Sapporo Japan

Organoborane chemistry expanded very rapidly after the hydroboration pro-cess developed by Nobel Laureate Late Prof Herbert C Brown Organoboraneintermediates can be converted to almost every class of functionality present inorganic molecules This continent has contributed immensely for the welfare ofmankind and is continuing to do so

Among the various hydroborating reagents 9-borabicyclo[331]nonane di-mer (9-BBN)2 has found the most extensive use because of its unique proper-ties convenient preparation commercial availability and enormous syntheticapplications

Many research papers and some review articles have been published on thesynthetic importance of 9-BBN and its derivatives B-R-9-BBN However nosingle manuscript is available on the burgeoning literature of B-R-9-BBN for theconvenient access to working chemists teachers and students

The aim of the book is to provide organoborane chemistry of B-R-9-BBN in afast organized and illustrated easily readable and introductory fashion

The second aim to prepare this book is to classify a variety of organic reac-tions of B-R-9-BBN and describe these reactions in a clear manner so that or-ganic chemists can use for the synthesis of intricate molecules

I hope the book will stimulate the chemists to explore further the potentialof B-R-9-BBN intermediates for developing new synthetic methodologies andin designing organic syntheses It is my opinion that organization of topics ofthe book will attract advanced organic chemistry students industrial and aca-demic chemists

I am grateful to Prof Akira Suzuki Professor Emeritus Hokkaido UniversitySapporo Japan who introduced me to this subject and without his help it wouldnot have been possible to complete this book I thank Prof S Hara of HokkaidoUniversity Dr (Ms) VK Gautam Dr (Ms) Shikha Ms Urvashi and my wifeSukhjinder for their help I also thank Editorial Board of Springer-Verlag fortheir help and suggestions

Ludhiana January 2007 Ranjit S Dhillon

Preface

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Ranjit S Dhillon

Hydroboration and Organic Synthesis9-Borabicyclo[331]nonane (9-BBN)

With 196 Figures and 260 Tables

123

Prof Dr Ranjit S DhillonDepartment of Biochemistry and ChemistryPunjab Agricultural UniversityLudhiana-141 004India

e-mail dhillonrrediffmailcom

Library of Congress Control Number 2006935689

ISBN 978-3-540-49075-3 Springer Berlin Heidelberg New YorkDOI 101007978-3-540-49076-0

This work is subject to copyright All rights are reserved whether the whole or part of the material is concerned specifically the rights of translation reprinting reuse of illustrations recitation broad-casting reproduction on microfilms or in any other way and storage in data banks Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9 1965 in its current version and permission for use must always be obtained from Springer-Verlag Violations are liable for prosecution under the German Copyright Law

Springer is a part of Springer Science + Business Mediaspringeronlinecomcopy Springer-Verlag Berlin Heidelberg 2007Printed in Germany

The use of general descriptive names registered names trademarks etc in this publication does not imply even in the absence of a specific statement that such names are exempt from the relevant protective laws and regulations and therefore free for general useProduct liability The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book In every individual case the user must check such information by consulting the relevant literature

Coverdesign WMXDesign GmbH HeidelbergTypesetting amp production LE-TEX Jelonek Schmidt amp Voumlckler GbR Leipzig Germany Printed on acid-freepaper 23141YL - 543210

This book is dedicated to

Prof Akira Suzuki Professor EmeritusHokkaido University Sapporo Japan

Organoborane chemistry expanded very rapidly after the hydroboration pro-cess developed by Nobel Laureate Late Prof Herbert C Brown Organoboraneintermediates can be converted to almost every class of functionality present inorganic molecules This continent has contributed immensely for the welfare ofmankind and is continuing to do so

Among the various hydroborating reagents 9-borabicyclo[331]nonane di-mer (9-BBN)2 has found the most extensive use because of its unique proper-ties convenient preparation commercial availability and enormous syntheticapplications

Many research papers and some review articles have been published on thesynthetic importance of 9-BBN and its derivatives B-R-9-BBN However nosingle manuscript is available on the burgeoning literature of B-R-9-BBN for theconvenient access to working chemists teachers and students

The aim of the book is to provide organoborane chemistry of B-R-9-BBN in afast organized and illustrated easily readable and introductory fashion

The second aim to prepare this book is to classify a variety of organic reac-tions of B-R-9-BBN and describe these reactions in a clear manner so that or-ganic chemists can use for the synthesis of intricate molecules

I hope the book will stimulate the chemists to explore further the potentialof B-R-9-BBN intermediates for developing new synthetic methodologies andin designing organic syntheses It is my opinion that organization of topics ofthe book will attract advanced organic chemistry students industrial and aca-demic chemists

I am grateful to Prof Akira Suzuki Professor Emeritus Hokkaido UniversitySapporo Japan who introduced me to this subject and without his help it wouldnot have been possible to complete this book I thank Prof S Hara of HokkaidoUniversity Dr (Ms) VK Gautam Dr (Ms) Shikha Ms Urvashi and my wifeSukhjinder for their help I also thank Editorial Board of Springer-Verlag fortheir help and suggestions

Ludhiana January 2007 Ranjit S Dhillon

Preface

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Prof Dr Ranjit S DhillonDepartment of Biochemistry and ChemistryPunjab Agricultural UniversityLudhiana-141 004India

e-mail dhillonrrediffmailcom

Library of Congress Control Number 2006935689

ISBN 978-3-540-49075-3 Springer Berlin Heidelberg New YorkDOI 101007978-3-540-49076-0

This work is subject to copyright All rights are reserved whether the whole or part of the material is concerned specifically the rights of translation reprinting reuse of illustrations recitation broad-casting reproduction on microfilms or in any other way and storage in data banks Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9 1965 in its current version and permission for use must always be obtained from Springer-Verlag Violations are liable for prosecution under the German Copyright Law

Springer is a part of Springer Science + Business Mediaspringeronlinecomcopy Springer-Verlag Berlin Heidelberg 2007Printed in Germany

The use of general descriptive names registered names trademarks etc in this publication does not imply even in the absence of a specific statement that such names are exempt from the relevant protective laws and regulations and therefore free for general useProduct liability The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book In every individual case the user must check such information by consulting the relevant literature

Coverdesign WMXDesign GmbH HeidelbergTypesetting amp production LE-TEX Jelonek Schmidt amp Voumlckler GbR Leipzig Germany Printed on acid-freepaper 23141YL - 543210

This book is dedicated to

Prof Akira Suzuki Professor EmeritusHokkaido University Sapporo Japan

Organoborane chemistry expanded very rapidly after the hydroboration pro-cess developed by Nobel Laureate Late Prof Herbert C Brown Organoboraneintermediates can be converted to almost every class of functionality present inorganic molecules This continent has contributed immensely for the welfare ofmankind and is continuing to do so

Among the various hydroborating reagents 9-borabicyclo[331]nonane di-mer (9-BBN)2 has found the most extensive use because of its unique proper-ties convenient preparation commercial availability and enormous syntheticapplications

Many research papers and some review articles have been published on thesynthetic importance of 9-BBN and its derivatives B-R-9-BBN However nosingle manuscript is available on the burgeoning literature of B-R-9-BBN for theconvenient access to working chemists teachers and students

The aim of the book is to provide organoborane chemistry of B-R-9-BBN in afast organized and illustrated easily readable and introductory fashion

The second aim to prepare this book is to classify a variety of organic reac-tions of B-R-9-BBN and describe these reactions in a clear manner so that or-ganic chemists can use for the synthesis of intricate molecules

I hope the book will stimulate the chemists to explore further the potentialof B-R-9-BBN intermediates for developing new synthetic methodologies andin designing organic syntheses It is my opinion that organization of topics ofthe book will attract advanced organic chemistry students industrial and aca-demic chemists

I am grateful to Prof Akira Suzuki Professor Emeritus Hokkaido UniversitySapporo Japan who introduced me to this subject and without his help it wouldnot have been possible to complete this book I thank Prof S Hara of HokkaidoUniversity Dr (Ms) VK Gautam Dr (Ms) Shikha Ms Urvashi and my wifeSukhjinder for their help I also thank Editorial Board of Springer-Verlag fortheir help and suggestions

Ludhiana January 2007 Ranjit S Dhillon

Preface

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

This book is dedicated to

Prof Akira Suzuki Professor EmeritusHokkaido University Sapporo Japan

Organoborane chemistry expanded very rapidly after the hydroboration pro-cess developed by Nobel Laureate Late Prof Herbert C Brown Organoboraneintermediates can be converted to almost every class of functionality present inorganic molecules This continent has contributed immensely for the welfare ofmankind and is continuing to do so

Among the various hydroborating reagents 9-borabicyclo[331]nonane di-mer (9-BBN)2 has found the most extensive use because of its unique proper-ties convenient preparation commercial availability and enormous syntheticapplications

Many research papers and some review articles have been published on thesynthetic importance of 9-BBN and its derivatives B-R-9-BBN However nosingle manuscript is available on the burgeoning literature of B-R-9-BBN for theconvenient access to working chemists teachers and students

The aim of the book is to provide organoborane chemistry of B-R-9-BBN in afast organized and illustrated easily readable and introductory fashion

The second aim to prepare this book is to classify a variety of organic reac-tions of B-R-9-BBN and describe these reactions in a clear manner so that or-ganic chemists can use for the synthesis of intricate molecules

I hope the book will stimulate the chemists to explore further the potentialof B-R-9-BBN intermediates for developing new synthetic methodologies andin designing organic syntheses It is my opinion that organization of topics ofthe book will attract advanced organic chemistry students industrial and aca-demic chemists

I am grateful to Prof Akira Suzuki Professor Emeritus Hokkaido UniversitySapporo Japan who introduced me to this subject and without his help it wouldnot have been possible to complete this book I thank Prof S Hara of HokkaidoUniversity Dr (Ms) VK Gautam Dr (Ms) Shikha Ms Urvashi and my wifeSukhjinder for their help I also thank Editorial Board of Springer-Verlag fortheir help and suggestions

Ludhiana January 2007 Ranjit S Dhillon

Preface

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Organoborane chemistry expanded very rapidly after the hydroboration pro-cess developed by Nobel Laureate Late Prof Herbert C Brown Organoboraneintermediates can be converted to almost every class of functionality present inorganic molecules This continent has contributed immensely for the welfare ofmankind and is continuing to do so

Among the various hydroborating reagents 9-borabicyclo[331]nonane di-mer (9-BBN)2 has found the most extensive use because of its unique proper-ties convenient preparation commercial availability and enormous syntheticapplications

Many research papers and some review articles have been published on thesynthetic importance of 9-BBN and its derivatives B-R-9-BBN However nosingle manuscript is available on the burgeoning literature of B-R-9-BBN for theconvenient access to working chemists teachers and students

The aim of the book is to provide organoborane chemistry of B-R-9-BBN in afast organized and illustrated easily readable and introductory fashion

The second aim to prepare this book is to classify a variety of organic reac-tions of B-R-9-BBN and describe these reactions in a clear manner so that or-ganic chemists can use for the synthesis of intricate molecules

I hope the book will stimulate the chemists to explore further the potentialof B-R-9-BBN intermediates for developing new synthetic methodologies andin designing organic syntheses It is my opinion that organization of topics ofthe book will attract advanced organic chemistry students industrial and aca-demic chemists

I am grateful to Prof Akira Suzuki Professor Emeritus Hokkaido UniversitySapporo Japan who introduced me to this subject and without his help it wouldnot have been possible to complete this book I thank Prof S Hara of HokkaidoUniversity Dr (Ms) VK Gautam Dr (Ms) Shikha Ms Urvashi and my wifeSukhjinder for their help I also thank Editorial Board of Springer-Verlag fortheir help and suggestions

Ludhiana January 2007 Ranjit S Dhillon

Preface

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

1 Introduction 1

2 General Remarks 3

3 Preparation and Properties 5

4 Kinetic Studies 1741 Hydroboration Kinetics of Alkenes 1842 Hydroboration Kinetics of Alkynes 27421 Relative Rates between Monohydroboration and Dihydroboration

of Alkynes 3043 Hydroboration Kinetics of Haloalkenes 3144 Hydroboration Kinetics of Haloalkynes 3845 Reduction Kinetics 4146 Kinetics of Complex Formation 4847 Kinetics of Protonolysis 51

5 Hydroboration 5951 Hydroboration of Alkenes 59511 Hydroboration of Acyclic Alkenes 595111 Terminal Olefins 615112 Internal Olefins 615113 cis and trans Isomers 625114 Effect of α-Methyl Substituents 645115 Effect of α-Conjugated Substituents 65512 Hydroboration of Cyclic Alkenes 68513 Hydroboration of Chloro- Acetate- and Acetal-Functionalized

Alkenes 73514 Hydroboration of Allylsilanes 76515 Hydroboration of Chiral Allyl Amines and Chiral Allyl Alcohols 78516 Hydroboration of Alkenylheterocycles 84517 Hydroboration of Enamines 96518 Hydroboration of Heterocyclic Olefins 9952 Hydroboration of Alkynes 111521 Hydroboration of 1-Alkynes 112

Contents

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

ContentsX

522 Hydroboration of 1-Silyl-2-Alkyl-1-Alkynes 116523 Hydroboration of 1-Halo-1-Alkynes 12053 Hydroboration of Dienes 12654 Hydroboration of Allenes 13055 Hydroboration of Enynes and Diynes 136

6 Synthesis of Alcohols 14361 Synthesis of Saturated Alcohols 14362 Synthesis of Allylic Alcohols 15363 Synthesis of Homoallylic Alcohols 15564 Synthesis of Propargylic Alcohols 16365 Synthesis of Homopropargylic Alcohols 16666 Synthesis of Silyl Alcohols 172661 Saturated Alcohols 173662 Allylic Alcohols 175663 Homoallylic Alcohols 177664 Homopropargylic Alcohols 179665 Diyne Alcohols 180666 Endiyne Alcohols 181667 Diendiyne Alcohols 181668 Allenic Alcohols 183669 Allenene Alcohols 1866610 Allenyne Alcohols 1876611 Allendienyne Alcohols 18867 Synthesis of Heterocyclic Alcohols 18868 Synthesis of Amino Alcohols 19369 Asymmetric Synthesis of Alcohols 194

7 Synthesis of Aldehydes and Ketones 21371 Synthesis of Aldehydes 21372 Synthesis of Ketones 219721 Synthesis of Saturated and Aromatic Ketones 219722 Synthesis of Enones 2277221 Synthesis of (E)-β-γ-Enones 2277222 Synthesis of γδ-Enones 227723 Synthesis of γδ-Ynones 229724 Synthesis of Dienones 231725 Synthesis of Conjugated Enynones 231726 Synthesis of β-Ketosilanes 233727 Synthesis of 1-Metallacyclohexan-4-ones 233728 Synthesis of Chiral Ketones 234

8 Synthesis of Carboxylic Acids 23781 Synthesis of Unsaturated Acids 23782 Synthesis of β-Amino Acids 237

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Contents XI

9 Synthesis of Esters 24191 Synthesis of Achiral Esters 24192 Synthesis of Chiral Esters 24293 Synthesis of (E)-βγ-Unsaturated Esters 24694 Synthesis of α-Amino Acid Esters 248

10 Synthesis of Nitriles 253101 Synthesis of Achiral Nitriles 253102 Synthesis of Chiral Nitriles 255103 Synthesis of (E)-βγ-Unsaturated Nitriles 257

11 Synthesis of (E)-βγ-Unsaturated Amides 259

12 Synthesis of Amines 261121 Synthesis of Chiral Amines 261122 Synthesis of Homopropargylic Amines 266123 Synthesis of Secondary Amines 267

13 Synthesis of Halides 271131 Synthesis of Halides via Hydroboration 271132 Synthesis of Halides via Haloboration 2731321 Synthesis of 2-Halo-1-Alkenes 2731322 Synthesis of (Z)-1-Alkynyl-2-Halo-1-Alkenes 2761323 Synthesis of (Z)-δ-Halo-γδ-Unsaturated Ketones 277

14 Synthesis of Dialkylsulfides 283

15 Synthesis of Thiophene Oligomers 285

16 Synthesis of Cyclopropanes and Cyclobutanes 287

17 Synthesis of Borinanes 291

18 Synthesis and Transformations of Butterflyboranes cis-Bicyclo[330]oct-1-yldialkylboranes 297

19 Synthesis of α-Bromoboranes 303

20 Synthesis of Borinates 307201 Enol Borinates 3072011 Synthesis of (E)- and (Z)-Enolborinates from Saturated Ketones 3072012 Stereoselective Synthesis of (Z)-Enol Borinates from αβ-

Unsaturated Ketones 3122013 Synthesis of Stable cis-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane

(cis-B-Vinyl-OBBD) Derivatives 313

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

ContentsXII

2014 Synthesis of Stable trans-B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (trans-B-Vinyl-OBBD) 314

2015 Markovnikov Vinylborinates Synthesis of B-Vinyl-9-Oxa-10-Borabicyclo[332]decane (Vinyl-10-OBBD) 314

202 Synthesis of Alkynylborinates 316

21 Synthesis and Transformation of Polymers 321

22 Synthesis of Alkali Metal 9-Boratabicyclo[331]nonane (Li K and Na 9-BBNH) 323

23 Synthesis of B-R-9-BBN Not Available via Hydroboration 327

24 Synthesis of Unsaturated Compounds 337241 Synthesis of Alkenes 3372411 Synthesis of Acyclic Cyclic and Heterocyclic Alkenes 3372412 Synthesis of (Z)-Alkenylsilane and (Z)-Alkenyltin 3472413 Synthesis of (Z)-1-Halo-1-Alkenes 351242 Synthesis of Dienes 3522421 Synthesis of 1ω-Dienes 3522422 Synthesis of Internal 13-Dienes 3612423 Synthesis of Nitrogen-Containing Heterocyclic (Z)-13-Dienes 3642424 Synthesis of Sulfur-Substituted 13-Dienes 3662425 Synthesis of Stannyl Dienes 3682426 Synthesis of B-Isoprenyl Derivatives 369243 Synthesis of Enynes 3702431 Stereoselective Synthesis of Conjugated (E)- and (Z)-Enynes 3702432 Stereoselective Synthesis of Silylated (E)- and (Z)-Enynes 371244 Synthesis of Endiynes 3732441 Stereoselective Synthesis of (E)- and (Z)-Endiynes 3732442 Stereoselective Synthesis of (E)- and (Z)-Silylated Endiynes 373245 Synthesis of 5-Methylene-13-Cyclohexadienes (o-Isotoluenes) and

1246-Heptatetraenes (Diene-Allenes) 375246 Synthesis of Enyne-Allenes Dienyne-Allenes and Trienyne-

Allenes and Their Cycloisomerization 376247 Synthesis of Silylated ZZ-Diendiynes and ZZZZ-

Tetraentetraynes and Their Cycloisomerization 381

25 Reduction 397251 With 9-BBNmiddotTHF 397252 With 9-BBNPy 408253 With Li 9-BBNH 410254 With B-Siamyl-9-BBN 414255 With Lithium 99-Di-n-Butyl-9-Borabicyclo[331]nonanate 415256 With 9-BBN Derivatives (as Catalysts) 422

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Contents XIII

26 Asymmetric Reduction 427261 Alpine-Borane 4282611 Reduction of Aldehydes 4282612 Reduction of Ketones 43326121 Reduction with Alpine-Borane under Pressure 43326122 Reduction with Alpine-Borane as Neat or in Excess 43726123 Reduction of Prochiral Ketones 43726124 Reduction of α-Haloketones 44126125 Reduction of Ketoesters 44226126 Reduction of αβ-Unsaturated Ketones 44426127 Reduction of Propargyl Ketones 44526128 Reduction of Propargylic Ketones with α-Chiral Centers 44926129 Reduction of Acylcyanide 451262 NB-Enantrane 452263 Eapine-Borane and Prapine-Borane 453264 NB-Enantride 459265 Eapine-Hydride 461266 K-Glucoride 462267 K-Xylide 468268 K9-OThx-9-BBNH 472269 Lithium Di-n-Butyl Ate Complex of 9-BBN 4732610 Li 9-BBNH 4752611 Comparative Data of Asymmetric Reducing Agents 476

27 Cleavage of Ethers 487

28 trans-Metalation 491

29 Separation of Isomers 499

30 Diels-Alder Reaction 501

31 Suzuki Reaction 523311 Mechanism of the Suzuki Catalytic Cycle 554

32 Miscellaneous Reactions 559

Subject Index 573

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Hydroboration constitutes one of the most important and facile methods for thesynthesis of organoboranes from unsaturated compounds [1] The organobo-ranes serve as valuable intermediates for the synthesis of a wide variety of organiccompounds Thus there is a huge interest in exploring their chemistry and thehydroboration reactions of major significance in synthetic organic chemistryhave been reviewed [1ndash15] Selective hydroboration with various hydroboratingagents and their application in organic synthesis has also been reviewed [16]

References

1 (a) Brown HC (1969) Hydroboration Benjamin New York (b) Brown HC (1972) Boranesin organic chemistry Cornell University Press Ithaca New York (c) Cragg GML (1973)Organoboranes in organic synthesis Dekker New York (d) Pelter A Smith K Brown HC(1988) Borane reagents Academic London (e) Onak TK (1975) Organoborane chemistryAcademic London

2 (a) Brown HC (1975) Organic syntheses via boranes Wiley New York [reprinted as vol 1by Aldrich (1999) Catalog no Z 40094-7] (b) Brown HC Zaidlewicz M (2001) Organicsynthesis via boranes vol 2 recent developments Aldrich Milwaukee (c) Suzuki A BrownHC (2002) Organic synthesis via boranes vol 3 Suzuki coupling Aldrich Milwaukee (d)Mikhailov BM Bubnov YN (1984) Organoboron compounds in organic synthesis (Englishtranslation) Harwood Utrecht

3 Matteson DS (1995) Stereodefined synthesis with organoboranes Springer Berlin HeidelbergNew York

4 Ramachandran PV Brown HC (2001) ACS Symp Ser 7835 Brown HC (1974) Aldrichim Acta 7436 Pelter A Smith K (1979) In Barton DHR Ollis WD (eds) Comprehensive organic chemistry

vol 3 Pergamon Oxford p 6897 Brown HC Zaidlewicz M Negishi E (1982) In Wilkinson G Stone FGA Abel EW (eds)

Comprehensive organometallic chemistry Pergamon Oxford8 Negishi EJ (1976) Organomet Chem 1082819 Weill-Raynal J (1976) Synthesis 63310 Brown HC Campbell JB Jr (1981) Aldrichim Acta 14311 Pelter A (1982) Chem Soc Rev 11191

1 Introduction

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

1 Introduction2

12 Suzuki A (1982) Acc Chem Res 1517813 Suzuki A (1983) Topics Curr Chem 1126914 Smith K Pelter A (1991) In Trost BM Fleming I (eds) Comprehensive organic synthesis

vol8 Pergamon Oxford p 70315 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 62216 Suzuki A Dhillon RS (1986) Topics Curr Chem 13023

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

The hydroboration of unhindered carbonndashcarbon double bonds with diboraneleads conveniently to trialkylboranes (Eq 21)

(21)

The presence of another unhindered carbonndashcarbon double or triple bondor functional group often affords a complex mixture of products resulting fromcompeting hydroboration As a result the hydroboration of dienes enynes orfunctionally substituted alkenes produces a considerable amount of other prod-ucts which is highly undesirable for the subsequent utilization of the resultingorganoborane In addition the stereoselective addition of borane is very poor inthe absence of steric bulk as shown

Moreover the regiochemistry of hydroboration of terminal unhindered al-kene is only 946 in favor of the terminal position The regioselectivity furtherdrops in cases where the carbonndashcarbon double bond is not surrounded by largesteric bulk

2 General Remarks

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

2 General Remarks4

In addition in many synthetic reactions that involve trialkylboron only oneor two alkyl groups are utilized and this results in the loss of valuable alkylgroups

The competitive reduction of functional groups and the formation of minorhydroboration products can be minimized by the use of disiamylborane (Sia2BH)or other dialkylboranes as hydroborating agents instead of diborane [1ndash3] How-ever these reagents are relatively unstable and must be freshly prepared priorto use a serious handicap for their utilization The 9-borabicyclo[331]nonanedimer (9-BBN)2 which was first identified by Koumlster [4] has been found to bean unusual dialkylborane with some valuable properties [5ndash8] The utility of thisunusual heterocyclic dialkylborane and the rearrangement of ate complexes ofit have been reviewed [6 7] Since then 9-BBN has been extensively studied andutilized by synthetic organic chemists It has also been converted into variousderivatives for asymmetric reduction and other reactions Among the varioushydroborating agents 9-BBN has found the most extensive use in various reac-tions due to its unique properties thermal stability and convenient prepara-tion

References

1 Brown HC Unni MK (1968) J Am Chem Soc 9029022 Brown HC Gallivan RM Jr (1968)J Am Chem Soc 9029063 Brown HC Sharp RL (1968) J Am Chem Soc 9029154 Koumlster R (1960) Angew Chem 726265 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 (a) Brown HC Lane CF (1977) Heterocycles 7453 (b) Kramer GW Brown HC (1977) ibid

74877 Koumlster R Yalpani M (1991) Pure Appl Chem 633878 Soderquist JA (1995) In Paquette LA (ed) Encyclopedia of reagents for organic synthesis vol

1 Wiley New York p 622

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Koumlster [1] was the first to report the preparation isolation and characterizationof 9-borabicyclo[331]nonane as a dimer (9-BBN)2 has been obtained from thethermal disproportionation of tetra-n-propyldiborane and B-n-propyl-9-BBN(Eq 31) B-alkyl-9-BBN preparation is itself a two-step process thus restrictingthe utility of the 9-BBN for synthetic purposes

(31)

However the direct and convenient synthesis of (9-BBN)2 has been reportedby Knights and Brown [2] and this development opened the door for its appli-cation in hydroboration [2ndash5] The synthesis involves the cyclic hydroborationof 15-cyclooctadiene with a boranendashtetrahydrofuran (THF) complex [2 3] in a11 ratio followed by refluxing the mixture at 65 degC thus producing a solutioncontaining (9-BBN)2 in ca 90 yield

In fact the borane adds to 15-cyclooctadiene to afford 14- and 15-isomersin a 3070 mixture With simple thermodynamic considerations it is apparentthat the 14-isomer which has a seven-membered ring fused to a five-memberedring is less stable Consequently the 14-addition product is easily isomerized tothe 15-isomer at 65 degC (Eq 32) This process affords a microcrystalline prod-uct with a melting point (mp) of 142 degC This material is further purified byvacuum sublimation with an increase in mp to 152ndash155 degC [5]

9-BBN exists as the dimer [A] both in the vapor state and in a crystallinesolid state The chairndashchair conformation of the dimer and the BndashH bridge hasbeen confirmed by spectral studies [5] and crystal structure determination [6]

IR (THF)5 1490 (w) 1567 (s) cmndash1 The IR of (9-BBN)2 exhibits a strongabsorption at 1567 cmndash1 either as a mineral oil mull of the solid or in solution(THF benzene hexane) indicating a BndashH bridge This confirms that 9-BBNmust exist as the dimer [A] 1H NMR (benzenendashTMS) exhibits a broad singlet atδ 18 11B NMR (THF)5 shows absorption at δ ndash28 relative to external BF3middotOEt2(benzene) at δ ndash28 relative to external BF3middotOEt2 (broad singlet) The mass spec-

3 Preparation and Properties

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

3 Preparation and Properties6

trum [5] (70 eV) shows a prominent cluster of peaks (me 242 243 244) in theapproximate ratio 1816 This is the expected ratio of molecules containing twoboron atoms since the natural abundance of 10B is 20 and that of 11B is 80

In solvents like carbon tetrachloride hexane benzene and diethylether9-BBN exists exclusively as the dimer However in THF and Me2S an equilib-rium between the (9-BBN)2 dimer and solvent-complexed 9-BBN monomer(9-BBN-solvent) is observed [7] From the kinetic studies (vide infra) it hasbeen proved that the 9-BBN monomer is actually the hydroborating agent Forconvenience 9-BBN is represented in the shorthand notation as shown in [B]

(32)

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

7

The preparation of (9-BBN)2 from BH3-THF suffers from some practical diffi-culties1 The choice of BH3-THF as the reagent used for hydroboration necessarily

requires that THF be used as the reaction solvent2 (9-BBN)2 is significantly soluble in THF and exists in an equilibrium with a

9-BBN-THF complex (Eq 33)

(33)

3 The microcrystalline product (9-BBN)2 obtained from THF solvent occasion-ally contains minor amounts of impurities which render it pyrophoric Thesefactors thus diminish the yield and purity of 9-BBNThe complexation of 9-BBN with basic solvents is summarized in Table 31 [8]

Table 31 Complexation of 9-BBN with basic solvents [8]

Base Complex () 11B chemical shift (J11BndashH)

THF 14 139 (~90 Hz)SMe2 46 39 (107 Hz)NC5H5 100 ndash07 (88 Hz)

The molar solubility of 9-BBN dimer is summarized in Table 32 [8]

Table 32 Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCMonoglyme 001 007Diglyme lt001 00414-Dioxane 003 00713-Dioxolane lt001 004Diethyl ether 009 018THF 012 029CH2Cl2 011 028CHCl3 021 050CCl4 015 036Pentane 013 023

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

3 Preparation and Properties8

These studies also reveal that the hydroboration of 15-cyclooctadiene usingboranendashdimethylsulfide to prepare a solution of 9-BBN can be carried out insolvents other than THF [9]

Consequently an efficient route for the synthesis of a high purity crystalline(9-BBN)2 dimer has been reported [8] and it has been found that 12-dime-thoxyethane (monoglyme) possesses a major advantage as the reaction solventover THF Accordingly the cyclic hydroboration of 15-cyclooctadiene is car-ried out in this solvent using a boranendashmethylsulfide complex as a hydrobo-rating agent Removal of dimethylsulfide yields 88 of 9-BBN dimer in largecrystal form with more than 99 purity (mp 153ndash155 degC)

Brown and Mandal [10] have reported another convenient procedure for thepreparation of (9-BBN)2 using borane-14-thioxane (BOT) as the hydroborat-ing reagent BOT is readily synthesized [11] by adding diborane to 14-thioxane(Eq 34) It is a stable liquid at 25 degC and crystallizes out at 0 degC with a mpof 11ndash15 degC Neat BOT is 8 M in borane 11B NMR of BOT exhibits only oneabsorption at δ ndash23 (relative to BF3middotOEt2) supporting the boronndashsulfur coordi-nation (BH3middotSMe2 δ ndash203 BH3middotTHF δ +1) [10] BOT as a neat reagent is indefi-nitely stable at 0 degC

(34)

The hydroboration with BOT can be carried out in a wide variety of solventssuch as THF diethylether methylene chloride and pentane or with neat re-agents at 0 or 25 degC

15-Cyclooctadiene undergoes hydroboration in a 2-M THF solution of BOTThe hydroboration is complete after 05 h at 25 degC and thermal isomerization

Table 32 (Continued) Molar solubility of dimeric 9-BBN in representative solvents [8]

Solvent Temperature

0 degC 25 degCHexane 011 025Benzene 019 036Cyclohexane 003 008Toluene 014 033Dimethylsulfide ndash 06

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

9

in refluxing THF leads to complete formation of 9-borabicyclo[331]nonaneafter 1 h (Eq 35) After completion of the reaction the supernatant liquid is re-moved crystals are washed with pentane and recrystallization from THF givespure (9-BBN)2 dimer (mp 153 degC)

(35)

The neat reaction is performed by the addition of 15-cyclooctadiene to BOTat 0 degC Hydroboration is complete after 025 h at 0 degC and after 025 h at 25 degCAfter thermal isomerization at 165ndash170 degC for 1 h 14-thioxane is distilled com-pletely from the reaction mixture leaving (9-BBN)2 as a pure stable crystallinesolid Both procedures afford (9-BBN)2 almost as a pure solid which on recrys-tallization from THF affords (9-BBN)2 crystals mp of 153 degC Moreover it isnow commercially available [12] in crystalline and in solution forms

In an indirect method for the synthesis of 9-BBN Brown and Kulkarni [13]have revealed that exchange between borane-methylsulfide (BMS) and B-MeO-9-BBN is effected to get 9-BBN and B(OMe)3 as the reaction products (Eq 36)

(36)

12-Dimethoxyethane (MG) is a superior solvent for crystallization [8] of9-BBN Soderquist and Negron [14] reported the reaction of B-MeO-9-BBNwith H3B-SMe2 in a 21 stoichiometry employing MG as the reaction solvent toafford 9-BBN in 93 yield (mp of 154ndash156 degC Eq 37)

(37)

Both crystalline 9-BBN and its solutions are indefinitely stable when storedunder an inert atmosphere and no noticeable change in activity has been re-corded even after more than 4 years The stability of colorless crystalline(9-BBN)2 toward air oxidation is unique among dialkyl boranes As a conse-quence a fresh unopened bottle of commercial crystalline (9-BBN)2 can be

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

3 Preparation and Properties10

opened in the air and the entire contents can be transferred rapidly to a nitrogen-flushed flask with minor loss of activity However small amounts should not beremoved in air at frequent intervals but must be weighed out and transferredwith approximately the same precautions and relative convenience accompany-ing the utilization of sodium borohydride and lithium aluminum hydride Onthe other hand 9-BBN in the solution form is very reactive to both water andoxygen Such a solution must be rigorously protected from the atmosphere forboth preparative and quantitative studies in the manner utilized in handling air-sensitive reagents [15]

The inertness of crystalline (9-BBN)2 toward oxygen is due to the unusualstability of the BndashHndashB bridge in the dimer and is supported by the observa-tion that neat B-methoxy-9-BBN solid B-chloro-9-BBN and solid B-hydroxy-9-BBN are all pyrophoric Moreover it is found that B-alkyl-9-BBN derivativesare very reactive toward oxygen more so than the corresponding trialkylbo-ranes [16] Hence with the BndashHndashB bridge no longer present the exposed boronatom makes these derivatives of 9-BBN unusually reactive toward oxygen

The boiling point of 9-BBN 195 degC (12 mm) is unusually high in contrastto dialkylboranes Simple dialkylboranes dissociate and distill as the monomerwhereas 9-BBN must distill as the dimer Dissociation of the dimer is accom-panied by an increase in CndashBndashC angle from 1118 to 120deg Such an increase isreadily accommodated in acyclic dialkylboranes but would be resisted in therigid bicyclic structure The unusual stability of the (9-BBN)2 is reflected in thechemistry of 9-BBN

Another remarkable property of 9-BBN where it distinguishes itself fromother dialkylboranes is its thermal stability 9-BBN can be distilled at 195 degC(12 mm) or heated for 24 h at 200 degC under nitrogen without loss of hydrideactivity [2 5] in sharp contrast to other dialkylboranes For instance dicyclo-hexylborane decomposes at 180ndash200 degC yielding cyclohexene and polymericboranes and disiamylborane undergoes isomerization [5 17] at 75 degC

The 9-BBN and its 10 B-substituted derivatives have been examined and hadtheir structures confirmed by their 13C NMR data [18] 9-BBN B-Cl-9-BBNB-OMe-9-BBN B-t-Bu-9-BBN and B-CH2-CH2SiMe3-9-BBN exhibit 13C NMRsignals that confirm that C-2 C-4 C-6 and C-8 ring carbon of the bicyclic sys-tem are identical and a separate second signal for C-3 and C-7 of the ring re-veals the symmetric structure of these derivatives The bulkier B-alkyl groupscontaining a chiral center reveal different signals one for C-2 and C-6 and thesecond for C-4 and C-8 corresponding to the asymmetric environment of thebicyclic structure (Table 33) [18]

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

11

Table 33 11B and 13C NMR spectral data for B-substituted derivatives of 9-BBN [18] Spectra arerecorded in CDCl3 solvent No attempt is made to determine the chemical shifts of the very broadsignals attributed to B-bonded carbons

11B 13C

X (Compound) C-2468 C-37 Other carbonsa

H (1) 28 334 239Cl (2) 815 342 23OCH3 (3) 532 331 232 533CH2CH3 (4) 88 332 234 8CH3CHCH2CH3 (5) 873 334 232 253 139CH3CHCH(CH3)2 (6) 884 338

336233 30 237

212 109C(CH3)3 (7) 858 336 232 259C6H5CHCH2CH3 (8) 839 339

337231 1313 1291

1284 1257143 11

CH2CH2Si(CH3)3 (9) 864 334 233 86 ndash2CH(CH3)Si(CH3)3 (10) 859 332

327232 103 ndash09

CH2CH(CH3)Si(CH3)3(11) 889 336333

234 179 152ndash36

aAssignments for the ldquootherrdquo carbons are made based on decoupling experiments In the ordergiven in the table they are the following 3 OCH3 4 CH3 5 CH2CH3 (coincident signals) 6 CH3-CH2 3-CH3 1-CH3 7 CH3 8 aromatic (1 3 2 4) CH2 CH3 9 2-CH2 Si(CH3)3 10 CH3Si(CH3)3 11 CH3 CH Si(CH3)3

9-BBN forms a stable isolable 11 complex with pyridine and exhibits in its13C spectrum the nonequivalence of two halves of the bicyclic ring system

One of the two halves is syn to the pyridine ring and the other is anti tothe pyridine ring The C-2 and C-4 positions occupy a gauche relationship tothe pyridine and these carbons correspond to the upfield signal at 29 ppm [19](Table 34)

Similarly the B-Cl-9-BBN derivative also forms a 11 complex with pyridineand gives separate signals for syn and anti halves (relative to pyridine [Py]) of

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

3 Preparation and Properties12

the 9-BBN ring system Quaternary nitrogen exerts a slightly greater upfield ef-fect than does chlorine thus the C-2 and C-4 positions are assigned to 308-ppmabsorbance[19] (Table 34) [18]The 13C NMR spectrum of B-OCH3-9-BBN andpyridine reveals incomplete formation of a 11 complex but full equivalence ofthe two halves of the 9-BBN ring The spectrum of B-Et-9-BBN shows the com-plete formation of a 11 complex and the 13C spectrum reveals full equivalenceof the two halves which is attributed to rapid dissociation and recombinationof the complex

Table 34 11B and 13C NMR spectral data for pyridine complexes of B-substituted derivatives of9-BBN [18] Spectra are recorded in CDCl3 solvent No attempt is made to determine the chemicalshifts of the very broad signals attributed to boron-bonded carbons

11B 13Ca

X (Compound) C-2468 C-37 Pyb

H (12) ndash07c 35129

254248

1459 1388 1253

Cl (13) 95 319308

239237

145 1417 1263

CH2CH3 (14) 13 316 25 1463 1383 1248CH3CHCH2CH3 (15) 14 312 247 147 1379 1241CH3CHCH(CH3)2 (16) ndash01 316

312246 1471 1382 1244

CH2CH2Si(CH3)3 (17) 21 316 251 1461 1383 1248aAlkyl carbons are assigned as in Table 33 The corresponding signals (parts per million) areobserved at 85 (14) 247 142 (1-CH3) 129 (4-CH3) (15) 263 261 181 78 (16) 94 ndash17 (17)bOrder follows α β γcDoublet J = 88 Hz

However with bulky groups such as t-Bu and 1-trimethylsilylethyl the com-plex formation with pyridine is incomplete even with excess pyridine

The 13C NMR spectra of the interaction of 9-BBN with two series of amineswith regular increasing steric requirements are studied (1) for the role of strainas a factor (2) for the stability of addition compounds formed and (3) for theirexchange with an amine One set of a Py bases includes Py and 2-methyl-2-ethyl 2-isopropyl- and 2-tert butylpyridine the second set is aliphatic aminessuch as n-propylamine isopropylamine diethylamine diisopropylamine andtriethylamine which are of increasing steric requirements and are examined fortheir interaction with 9-BBN Quinuclidine (QN) a base with relatively low ste-ric requirements is compared with triethylamine a base with very large stericrequirements

These two families of amines reveal four types of behavior (1) formationof stable complexes with no observable exchange even with excess amine (Pyn-PrNH2 i-PrNH2 Et2NH QN) (2) formation of stable complexes with rapid

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

13

exchange of amine (2-MePy) (3) formation of partially dissociated complexeswith rapid exchange (2-EtPy 2-i-PrPy i-Pr2NH) and (4) no detectable interac-tion of 9-BBN with amine (2-t-BuPy Et3N) These results are summarized inTable 35 [20]

Table 35 Summary of 13C NMR observations on the interaction of 9-BBN with amines [20]

Associated 100no exchange

Associated 100rapid exchange

Partially associatedrapid exchange

Not associated

Py 2-MePy 2-EtPy2-i-PrPy

2-t-BuPy

n-PrNH2

i-PrNH2

Et2NHQN

i-Pr2NH Et3N

In general there is a regular progression from (1) to (2) to (3) to (4) alongthese four types of behavior with increasing steric requirements in both series ofamines Consequently triethylamine fails to show any interaction with 9-BBNwhereas QN forms a stable that does not exchange with excess amine Thesestudies confirm the earlier results of the stabilities of these addition compoundsconducted with IR spectroscopic methods [21] However the 13C NMR providesconsiderable additional information about the exchange or lack of exchange inaddition compounds that are completely associated under the experimental con-ditions Consequently the 13C NMR method separates these compounds intotwo separate classes (1) and (2) providing a more sensitive probe into the effectsof steric strains over in systems where association is essentially complete

Soderquist and Najafi [22] have reported the selective monoxidation ofB-substituted derivatives of 9-BBN to afford in good yield the exclusive forma-tion of 9-oxa-10-borabicyclo[332]decane products (Eq 38 Table 36) The re-action proceeds smoothly using 1 equiv of anhydrous trimethylamine N-oxide(TMANO) in CHCl3 at 0 degC

(38)

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

3 Preparation and Properties14

Table 36 Oxidation of B-substituted 9-BBN derivatives with 1 equiv of TMANO [22]

R of B-R-9-BBN Yield of isolated9-oxa-10-borabicy-clo[332] seriesa

Reaction temp ( degC) Time (h)

Me 81 0 1n-Hx 84 0 1c-Hx 84 0 1t-Bu 80 25 20CH2SiMe3 93 0 1C(SiMe3)=CHMe(Z)

87 0 1

OMe 85 0 1O-(n-Hx) 86 0 1

aReactions are carried out by the dropwise addition of a solution of TMANO in CHCl3 to theorganoborane

The reaction involves the exclusive ring BndashC bond oxidation and this specificprocess has a conformational dependence The selectivities are rationalized interms of the required antiperiplanar relationship of the BndashC ring bond whichundergoes oxidation (case 1)

It is significant to mention that 9-oxa-10-borabicyclo[332]decane deriva-tives selectively transfer only the alkyl group of B-alkyl and consequently arevaluable intermediates in the syntheses of variety of compounds (vide infra)

Matos and Soderquist [23] reported the synthesis of (9-BBN-D)2 throughthe reduction of MeO-9-BBN with LiAl(OEt)D3 and the latter facilitates theseparation of the 9-borata complex from the insoluble [AlD(OMe)(OEt)]x(Eq 39) [24] The treatment of the borohydride with TMSCl affords crystalline(9-BBN-D)2 in a 31 yield

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

15

(39)

References

1 (a) Koumlster R (1960) Angew Chem 72626 (b) Koumlster R Griaznov G (1961) Angew Chem73171

2 Knights EF Brown HC (1968) J Am Chem Soc 9052803 Soderquist JA Negron A (1991) Org Synth 701694 In sharp contrast 15-cyclooctadiene on hydroboration with equimolar amount of thexylbo-

rane followed by oxidation gives an 8020 mixture of cis-14- and cis-15-cyclooctanediols in93 yield Brown HC Neigishi E J (1972) Am Chem Soc 943567

5 Brown HC Knights EF Scouten CG (1974) J Am Chem Soc 9677656 Brauer DJ Kruger C (1973) Acta Crystallogr B 2916847 Brown HC Wang KK Scouten CG (1980) Proc Natl Acad Sci USA 776988 Soderquist JA Brown HC (1981) J Org Chem 4645999 Brown HC Mandal AK Kulkarni SU (1977) J Org Chem 42139210 Brown HC Mandal AK (1992) J Org Chem 57497011 Brown HC Mandal AK (1980) Synthesis 15312 Aldrich Chemical Milwaukee Wisconsin13 Brown HC Kulkarni SU (1979) J Organomet Chem 16828114 Soderquist JA Negron A (1987) J Org Chem 52344115 Lane CF Kramer GW (1977) Aldrichim Acta 101116 Brown HC Midland MM (1971) Chem Commun 69917 Brown HC Zweifel G (1966) J Am Chem Soc 88143318 Brown HC Soderquist JA (1980) J Org Chem 4584619 Wehrli FW Wirthlin T (1976) Interpretation of carbon-13 NMR spectra Heyden London20 Brown HC Wang KK (1980) J Org Chem 45174821 Brown HC Wang KK (1979) Recl Trav Chim Pays Bas 9811722 Soderquist JA Najafi MR (1986) J Org Chem 51133023 Matos K Soderquist JA (1998) J Org Chem 6346124 Singaram B Cole TE Brown HC (1984) Organometallics 31520

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

Kinetic studies provide valuable information in the areas of both mechanisticand synthetic chemistry concerning the effects of substituents in alkenes andalkynes The effects of substituents that donate or withdraw or polarize electronsof C=C or C C provide information regarding the mechanism of hydrobora-tion On the other hand relative rates of hydroboration of substituted or un-substituted C=C or C C give synthetic chemists improved means of predictingthe selective hydroboration of C=C or C C or their functionalized derivatives9-BBN has proven to be the best candidate for the investigation of mechanismand kinetics of hydroboration because1 It has high thermal stability and purity2 It is convenient to handle compared to other boranes as it has lower sensitiv-

ity to oxygen and water vapors3 With only one center per boron its overall reaction with an alkene involves

only one dissociation step and one hydroboration step in contrast borane(BH3) has three consecutive addition reactions three redistribution equilib-ria and five monomerndashdimer equilibria [1]

4 9-BBN reactions can be studied in solvents such as carbon tetrachloridecyclohexane and benzene whereas 9-BBN exists exclusively as dimer thuseliminating complexation [2] with solvents and simplifying the kinetics

5 9-BBN is highly regio- and stereoselective which assures the study of onlyone reaction

6 In addition the progress of the reaction can easily be monitored via IRwhere disappearance of the 1570 cmndash1 absorption of bridged BndashH bondsoccurs

Consequently kinetic studies of 9-BBN have yielded very useful data for itsrelative reactivity toward various types of unsaturation and the effect of solventon the reaction

It is significant to mention that in compounds that display first-order kinet-ics the values differ in THF and CCl4 solvents The first-order rate constant inTHF is about 10 times that in CCl4 solvent This is due to the catalytic effect ofTHF [3] on the (9-BBN)2 dimer that breaks the BndashH bridge bond [4]

4 Kinetic Studies

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies18

41 Hydroboration Kinetics of Alkenes

The hydroboration reactions of (9-BBN)2 with more reactive olefins have beenfound to be the first-order kinetics (Eq 41) [1]

(41)

and three-halves kinetics with less reactive olefins (Eq 42) [2]

(42)

The kinetics for hydroboration of alkenes are conducted in various solventssuch as carbon tetrachloride hexane cyclohexane benzene and THF 9-BBNexists predominantly as the dimer (9-BBN)2 [2] After the addition of olefinsat 25 degC the aliquots from the reaction mixture are removed after appropri-ate intervals of time quenched with an excess methanol and analyzed by GLCfor residual olefin All operations are performed under nitrogen until identicalrates are observed for more reactive olefins such as 1-hexene 2-methyl-1-pen-tene 33-dimethyl-1-butene and cyclopentene and variation of olefin concen-tration does not alter the rate These results establish that the reaction is firstorder (Eq 41) Typical data for cyclopentene and cyclohexene are presented inTable 41 [1]

Table 41 Rate data and rate constants for the hydroboration of cyclopentene (0400 M) and cyclo-hexene (0400 M) with (9-BBN)2 (0200 M) in carbon tetrachloride at 25 degC [1]

Time (s) Cyclopentenea

(M)104 k1

bsndash1 Time (s) Cyclohexenea

(M)104 k32

b

l12

molndash12 sndash1

0 0400 0 0400298 0382 150 6001 0339 0321

1205 0332 154 15380 0262 03432713 0263 155 21605 0225 03444540 0202 151 42494 0148 03386297 0153 152 61769 0108 03369001 0102 152 72007 0096 0324

a Concentration of (9-BBN)2 is one half that of olefinb Calculated from the equations

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

19

(43)

where b is the initial concentration of olefin and bndash2x is the concentration attime (t)

The first-order rate constants are quite similar in solvents other than THFwhich are 152 in CCl4 197 in hexane 152 in cyclohexane and 195 in benzeneand 2 in diethylether However in THF k1 is considerably larger at 108

The less reactive olefins such as cyclohexene 1-methylcyclohexene and 23-dimethyl-2-butene exhibit rates that are slower and vary with concentration andthe structure of individual olefins The kinetics establishes these reactions tobe first order in olefins and one-half order in the 9-BBN dimer (Eq 42) Thecalculated three-halves-order rate constants also do not change as the reactionproceeds The rate constants observed both for the first-order and three-halves-order kinetics are summarized in Table 42 [1]

These studies unequivocally establish that the hydroboration of alkenes with(9-BBN)2 proceeds through the prior dissociation of the dimer to the monomer(Eq 44) followed by the reaction of monomer with the unsaturated substrate(Eq 45)

(44)

(45)

Table 42 First-order- and three-halves-order rate constants for the hydroboration of representa-tive olefins with (9-BBN)2 in carbon tetrachloride at 25 degC [1]

Olefina 104k1 sndash1 104 k32 l12 Mndash12 sndash1

1-Hexene 1542-Methyl-1-pentene 15333-Dimethyl-1-butene 145Cyclopenteneb 152Cyclohexeneb 03231-Methylcyclohexene 005123-Dimethyl-2-butene 002

a Rate constants in table are for initial concentration of olefin (04 M) and (9-BBN)2 (02 M)b Variation of the initial concentrations of the olefin and (9-BBN)2 do not change the observed

rate constants significantly cyclopentene (04 M) (9-BBN)2 (01 M) 104 k1 158 cyclopentene(02 M) (9-BBN)2 (01 M) 104 k1 158 cyclohexene (04 M) (9-BBN)2 (01 M) 104 k32 0324cyclohexene (02 M) (9-BBN)2 (01 M) 104 k32 0345

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

4 Kinetic Studies20

This mechanism leads to the following kinetic expression (Eq 46) utilizingthe usual steady state approximation

(46)

If 12 k2 [olefin] gtgt kndash1 [9-BBN] Eq 46 reduces to Eq 41 the reaction be-haves like a unimolecular reaction and exhibits first-order kinetics However if12 k2 [olefin] ltlt kndash1 [9-BBN] Eq 46 reduces to Eq 42 The reaction exhibitsthree-halves-order kinetics Consequently kinetics reveals that the hydrobora-tion with dimeric 9-BBN of representative alkenes proceeds through prior dis-sociation of the dimer to the monomer leading to simplified kinetic expressionas expressed in Eqs 41 and 42 for reactive alkenes and for less reactive alkenesrespectively However for olefins like 2-methyl-2-butene and cis-3-hexene 12 k2[olefin]asympkndash1 [9-BBN]2 and the kinetics fail to follow the simplified rate expres-sion Eqs 41 and 42

To test the proposed dissociation mechanism with (9-BBN)2 a detailed studyis conducted using quantitative IR spectrometry [3] (9-BBN)2 exhibits a verystrong IR absorption at 1570 cmndash1 due to BndashH bridges [4]This method is conve-nient and more reliable and thus has an advantage over tedious GLC analyses

The hydroboration kinetics are studied by addition of alkenes to the solu-tion of (9-BBN)2 in the solvent maintained at 25 degC The reaction mixtures arepumped through a sodium chloride IR cell The rates of the disappearance ofBndashH bridges of (9-BBN)2 at 1570 cmndash1 are monitored by quantitative IR spec-trometry The absorbance is recorded on chart paper

In IR studies an exponentially decaying curve of the absorbance of BndashHbridges is noticed which also reveals that the reaction follows first-order kinet-ics Six representative points on the exponentially decaying curve are calculated(Table 43) [3]

(47)

where [(9-BBN)2]o is the initial concentration of (9-BBN)2 and [(9-BBN)2]t is itsconcentration at time t a is the initial absorbance c is the absorbance at time tand b is the background absorbance

(48)

where b is the initial concentration of cyclopentene and bndash2x is the concentra-tion at time t

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes

21

The first-order constants remain essentially the same with varying initialconcentrations of (9-BBN)2 and cyclopentene (Table 44) [3]

The IR exponentially decaying curve for various more reactive alkenes in dif-ferent solvents (Table 45) [3] also shows a good agreement with the correspond-ing first-order rate constants realized by the quenching method

Table 43 Rate data and rate constants for the hydroboration of cyclopentene (04 M) with (9-BBN)2(02 M) in CCl4 at 25 degC [3]

t(s)

[(9-BBN)2]a

(M)[Cyclopentene](M)

104 k1b

(sndash1)0 02 04 ndash

500 0185 0370 1551000 0173 0346 1463000 0131 0262 1425000 0096 0191 1487000 007 0139 159000 005 01 154

a Calculated from Eq 47b Calculated by Eq 48c The three-halves-order rate constant obtained by the quenching method is 0323times10ndash4 Mndash12 sndash1

Table 44 Effect of concentration on the rate constants for the hydroboration of cyclopentene cy-clohexene and cis-3-hexene with (9-BBN)2 in carbon tetrachloride at 25 degC [3]

Initial concentration(M)

104 k1

(sndash1)104 k32

(Mndash12 sndash1)104 k2

b

(Mndash1 sndash1)

Alkene (9-BBN)2

Cyclopentene 04 02 154 241 77604 01 158 121 48102 01 158 354 164

Cyclohexene 04 02 0194 0314 10504 01 0456 0324 15802 01 0176 0345 137

cis-3-Hexenea 04 02 107 169 55204 01 145 108 47502 01 0925 207 949

a The kinetic data do not fit well to any of the integrated kinetic expressionsb The second-order rate constants

41 Hydroboration Kinetics of Alkenes