Table Of ContentStereoselective Synthesis in Organic Chemistry
Atta-ur-Rahman Zahir Shah
Stereoselective Synthesis in
Organic Chemistry
With 85 Figures
Springer-Verlag
New York Berlin Heidelberg London Paris
Tokyo Hong Kong Barcelona Budapest
Atta-ur-Rahman Zahir Shah
H.E.J. Research Institute H.E.J. Research Institute
of Chemistry of Chemistry
University of Karachi University of Karachi
Karachi-75270, Pakistan Karachi-75270, Pakistan
Library of Congress Cataloging-in-Publication Data
Rahman, Atta-ur-, 1942-
Stereoselective synthesis in organic chemistry / Atta-ur-Rahman,
Zahir Shah.
p. cm.
Includes bibliographical references and index.
ISBN-13: 978-1-4613-8329-1 e-ISBN-13: 978-1-4613-8327-7
DOl: 10.1007/978-1-4613-8327-7
1. Stereochemistry. 2. Organic compounds-Synthesis. I. Shah,
Zahir. II. Title.
QD481.R23 1993
547' .2-dc20 93-284
Printed on acid-free paper.
© 1993 Springer-Verlag New York, Inc.
Softcover reprint of the hardcover 1st edition 1993
All rights reserved. This work may not be translated or copied in whole or in part without the
written permission of the publisher (Springer-Verlag New York, Inc., 175 Fifth Avenue, New
York, NY 10010, USA), except for brief excerpts in connection with reviews or scholarly
analysis. Use in connection with any form of information storage and retrieval, electronic
adaptation, computer software, or by sitnilar or dissimilar methodology now known or hereaf
ter developed is forbidden.
The use of general descriptive names, trade names, trademarks, etc., in this publication, even
if the former are not especially identified, is not to be taken as a sign that such names, as
understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely
by anyone.
Production managed by Hal Henglein; manufacturing supervised by Vincent R. Scelta.
Camera-ready copy prepared by the authors.
987654321
ISBN-13: 978-1-4613-8329-1
Foreword
This monumental tome by Prof. Atta-ur-Rahman and Dr. Zahir Shah pres
ents a broad overall perspective of stereo selectivity in the synthesis of or
ganic molecules. Thus it treats a problem that is of fundamental importance
and will be even more important in the future as the drug industry is
required to supply 1000/0 optically pure compounds.
After an exposition of general principles, the following subjects are
treated: Catalytic Reductions, Heterogeneous Catalytic Hydrogenations,
Stereoselective Non-Catalytic Reductions, Stereos elective Carbon-Carbon
Bond Forming Reactions, Asymmetric Oxidations, Asymmetric Carbon
Heteroatom Bond Formations, Enzyme Catalyzed Reactions, Stereo
selective Free Radical Reactions, and finally Miscellaneous Stereoselective
Reactions. For each subject, a wealth of examples are given. The highly
selective reactions are mentioned along with reactions that are not. This is
helpful as it will teach the practical chemist what to avoid.
Much progress has been made in the last two decades in the design of
new, very stereoselective reactions which can be applied in industry. For
example, and in alphabetical order, we can mention (among other peers):
H.C. Brown (hydroboration), D.C. Evans (carbon-carbon bond forma
tion), R. Noyori (BINAP reagents for hydrogenation), and K.B. Sharpless
(epoxidation and dihydroxylation of double bonds). Thus the field has
completely changed since the 1950s, when optically pure compounds were
always obtained by difficult resolutions of racemates and not by stereoselec
tive reactions.
The book will provide a very useful introduction to stereoselective pro
cesses in organic synthesis. The large number of examples with the appro
priate references will lead the practitioner, at any scientific level, to a rapid
evaluation of his problem. From the point of view of all types of organic
chemists, this book will be their first choice for information about stereose
lective reactions.
------
~ ........
D.H.R. Barton
Texas A&M University
October 7,1992
Preface
The marvellous chemistry evident in living processes is largely enzyme
controlled stereoselective synthesis of highly complex organic molecules,
designed to fulfill specific tasks in living organisms. Man continues to learn
from nature, and in many fields he tries to mimic it. Stereos elective synthe
sis is one such area where organic chemists have tried to develop new
reaction methodologies to transform substrates in stereos elective or enanti
oselective fashions.
There has been an explosive growth in the area of stereos elective synthe
sis in the last few decades, and the field has taxed the genius of some of the
most distinguished chemists of today. These developments have created the
need for a textbook that could present the salient features of the major
developments in the field of stereoselective synthesis. The vast and rapidly
growing literature in this important area prevents one from writing a "com
prehensive" treatise on all the stereos elective synthetic methods developed
to date, but it is hoped that the readers will find that the more important
developments in the field up to mid-1992 are adequately covered.
We are grateful for the help extended to us by a number of persons in
the writing of this book. Our thanks go to Mr. M. Rais Hussain and Mr.
M. Asif for diligently typing the manuscript. We are also indebted to Mr.
Abdul Hafeez and Mr. Ahmadullah Khan for structure drawing and to Mr.
S. Ejaz Ahmed Soofi and Miss Farzana Akhtar for their assistance in
preparing the subject index. Last, but not least, we are thankful to Mr.
Mahmood Alam for secretarial assistance.
The first author dedicates this book to a magic lake in Dera Ismail Khan,
and to a shining star which has given him eternal hope and enriched his life
in a million ways.
Atta-ur-Rahman
Zahir Shah
Karachi
October, 1992
Contents
Foreword v
Preface vii
1 Stereochemical Principles 1
1.1 Introduction................................................................... 1
1.2 Chirality........................................................................ 1
1.3 Diastereotopic Groups and Faces ........................................ 10
1.4 Enantiotopic Groups and Faces.......................................... 10
1.5 Homotopic Groups and Faces ............................................ 11
1.6 Homochiral Relationships................................................. 12
1.7 Selectivity in Organic Synthesis........................................... 13
1.7.1 Chemoselectivity........................................................ 13
1.7.2 Regioselectivity .......................................................... 14
1.7.3 Diastereoselectivity..................................................... 16
1.7.4 Enantioselectivity....................................................... 20
1. 7.4.1 Reactions in Presence of Chiral Additives........ ........... 21
1.7.4.2 Reactions Involving Covalent Linkages of Chiral
Auxiliary Groups with Substrates............................. 22
1. 7 .4.3 Reactions with Chiral Reagents................................ 23
1.7.4.4 Reactions with Enzymes......................................... 23
1.8 References ..................................................................... 24
2 Stereoselective Catalytic Reductions 26
2.1 Homogeneous Catalytic Hydrogenations ............................... 27
2.1.1 Hydrogenation of Olefins ............................................ 27
2.1.1.1 Hydrogenation with Rh-complexes ........................... 28
2.1.1.1.1 Tetrasubstituted Olefins ................................... 36
2.1.1.1.2 Substituted Itaconate Esters............................... 37
2.1.1.2 Hydrogenation with Ru-complexes ........................... 40
2.1.1.2.1 Allylic and Homoallylic Alcohols ........................ 41
2.1.1.2.2 Unsaturated Carboxylic Acids ............................ 42
2.1.1.2.3 Dicarboxylic Acids.......................................... 42
2.1.1.2.4 Dehydroamino Acids....................................... 43
2.1.1.2.5 Prochiral Ketones ........................................... 43
2.1.1.3 Hydrogenation with Ti-complexes ............................ 45
2.1.1.4 Hydrogenation with Co-complexes........................... 46
2.1.1.5 Hydrogenation with Heterobimetallic Complexes...... ... 49
x Contents
2.1.2 Catalytic Hydrosilylation ............................................. 50
2.1.2.1 Catalytic Hydrosilylation of Olefins.......................... 50
2.1.2.2 Catalytic Hydrosilylation of Imines .......................... 54
2.1.3 Catalytic Hydrogenation of Ketones............................... 57
2.1.3.1 Direct Hydrogenation of Simple Ketones................... 58
2.1.3.2 Direct Hydrogenation of Functionalized Ketones ......... 59
2.1.3.2.1 With Rhodium-Diphosphine Catalysts................. 62
2.1.3.2.2 With Ruthenium Complexes .............................. 62
2.1.3.2.3 With Copper Complexes ................................... 64
2.1.3.3 Hydrogenation of Ketones via Derivatization .............. 65
2.1.3.3.1 Hydrogenation of Simple Ketones
via Hydrosilylation ................ .......................... 65
2.1.3.3.2 Hydrogenation of Functionalized Ketones
via Hydrosilylation.......................................... 72
2.1.3.3.3 Hydrogenation of Ketones via Enol Phosphinates ... 78
2.2 Heterogeneous Catalytic Hydrogenations.............................. 78
2.2.1 Enantioselective Heterogeneous Catalytic Hydrogenations... 80
2.2.2 Diastereoselective Heterogeneous Catalytic
Hydrogenations......................................................... 83
2.2.2.1 Asymmetric Hydrogenation of Carbon-Carbon
Double Bonds...................................................... 83
2.2.2.1.1 Hydrogenation of N-Acyl-a,{3-Dehydroamino
Acids ........................................................... 84
2.2.2.1.2 Asymmetric Hydrogenation of Cyclic
Dehydropeptides ............................................. 91
2.2.2.2 Asymmetric Hydrogenation of other Carbonyl
Compounds ........................................................ 93
2.2.2.2.1 Asymmetric Hydrogenation of Benzoylformic
Acid Esters.......................... .......................... 93
2.2.2.2.2 Asymmetric Hydrogenation of a-Keto Amides ....... 96
2.2.2.3 Asymmetric Hydrogenation of Carbon-Nitrogen
Double Bonds...................................................... 99
2.2.2.3.1 Hydrogenation of Imines, Oximes and
Hydrazones ................................................... 99
2.3 References ..................................................................... 105
3 Stereoselective Non-Catalytic Reductions 115
3.1 Enantioselective Non-Catalytic Reductions ............................ 115
3.1.1 Chiral Metal-hydride Complexes .................................... 115
3.1.1.1 Lithium Aluminium Hydride Modified with
Chiral Groups ...................................................... 115
3.1.1.1.1 LAH Modified with Alcohols ............................ 116
3.1.1.1.2 LAH Modified with Amino Alcohols ................... 121
3.1.1.2 Chiral Boranes and Borohydrides ............................. 127
Contents xi
3.1.1.2.1 Chiral Alkylboranes ........................................ 127
3.1.1.2.2 Chiral Borohydride Reagents ............................. 136
3.1.1.2.2.1 NaBH4-derived Reagents ............................. 136
3.1.1.2.2.1.1 Phase Transfer Catalyzed Reductions ....... 138
3.1.1.2.2.1.2 LiBH4 Reductions ................................ 141
3.1.1.2.2.2 Super Hydrides ......................................... 141
3.1.2 Chiral Metal Alkyls and Alkoxides ................................. 146
3.1.3 Chiral Dihydropyridine Reagents ................................... 152
3.2 Diastereoselective Non-Catalytic Reductions .......................... 159
3.2.1 Cyclic Substrates ........................................................ 159
3.2.2 Acyclic Substrates ...................................................... 162
3.2.2.1 1,2-Induction ...................................................... 164
3.2.2.2 1,3-, 1,4-and 1,6-Inductions .................................. 165
3.2.2.2.1 Cyclic Ketones ................................................ 171
3.3 References ..................................................................... 174
4 Stereoselective Carbon-Carbon Bond Forming Reactions 185
4.1 Nucleophilic Additions to Aldehydes and Ketones ................... 185
4.1.1 Enantioselective Addition Reactions ............................... 185
4.1.2 Diastereoselective Addition Reactions ............................. 195
4.1.2.1 Diastereoselective Additions to Carbonyl Compounds ... 195
4.1.2.2 Diastereoselective Additions to Cyclic Ketones ............ 198
4.1.3 Addition of Chiral Reagents ......................................... 199
4.1.4 Stereo selectivity of Nucleophilic Addition Reactions .......... 202
4.2 Asymmetric Catalytic Hydrocarbonylations ........................... 207
4.2.1 Asymmetric Hydroformylations .................................... 207
4.2.1.1 Asymmetric Hydroformylation with
Homogeneous Catalysts ......................................... 208
4.2.1.2 Asymmetric Hydroformylations with
Heterogeneous Catalysts ........................................ 214
4.2.2 Asymmetric Hydroesterification .................................... 216
4.3 Asymmetric Aldol Reactions .............................................. 217
4.3.1 Stereochemistry of the Aldol Reaction ............................ 218
4.3.1.1 Transition State Models in the Aldol Reaction ............. 219
4.3.2 Addition of Enolates to Achiral Aldehydes ...................... 222
4.3.2.1 Generation and Aldol Reactions of Enolates ............... 222
4.3.2.1.1 Li Enolates in Aldol Reactions ........................... 222
4.3.2.1.1.1 Ketone Enolates ........................................ 224
4.3.2.1.1.2 Ester and Lactone Enolates .......................... 226
4.3.2.1.1.3 Amide and Lactam Enolates ........................ 228
4.3.2.1.1.4 Thioester and Thioamide Enolates ................. 229
4.3.2.1.1.5 Carboxylic Acid Dianions ............................ 231
4.3.2.1.2 Boron Enolates in Aldol Reactions ...................... 232
4.3.2.1.3. Magnesium Enolates in Aldol Reactions .............. 235
xii Contents
4.3.2.1.4 Titanium Enolates in Aldol Reactions .................. 236
4.3.2.1.5 Zinc Enolates in Aldol Reactions ........................ 237
4.3.2.1.6 Tin Enolates in Aldol Reactions ......................... 238
4.3.2.1.7 Silicon Enolates in Aldol Reactions ..................... 239
4.3.2.1.8 Zirconium Enolates in Aldol Reactions ................ 241
4.3.3 Addition of Chiral Enolates to Achiral Aldehydes and
Unsymmetric Ketones (the Cross Aldol Reaction) .............. 242
4.3.3.1 Metal Atoms as Chiral Centres in Aldol Reactions ....... 244
4.3.3.2 Chiral Ketone Enolates in Aldol Reactions ................. 246
4.3.3.3 Chiral Azaenolates in Aldol Reactions ....................... 247
4.3.4 Addition of Achiral Enolates to Chiral Aldehydes ............. 250
4.3.5 Reactions of Chiral Aldehydes with Chiral Enolates ........... 253
4.4 Allylmetal and Allylboron Additions .................................... 259
4.4.1 Configurational Stability of Allylmetal Compounds ........... 260
4.4.2 Stereochemistry of Allylmetal Additions .......................... 261
4.4.3 Addition of Allylboron Compounds ............................... 263
4.4.4 Addition of Allyltitanium Compounds ............................ 269
4.4.5 Addition of Allylstannanes ........................................... 275
4.4.6 Addition of Allylsilanes ............................................... 279
4.4.7 Palladium-Catalyzed Asymmetric Allylation .................... 284
4.4.8 Chromium (II)-Catalyzed Allylic Additions ...................... 285
4.4.9 Addition of other Allylmetals ....................................... 287
4.5 Asymmetric Alkylation Reactions ........................................ 290
4.5.1 Alkylation of Chiral Enolates ....................................... 290
4.5.1.1 Exocyclic Enolates ................................................ 292
4.5.1.2 Endocyclic Enolates .............................................. 294
4.5.1.3 Norbornyl Enolates ............................................... 297
4.5.2 Alkylation of Imine and Enamine Salts ........................... 299
4.5.3 Alkylation of Chiral Hydrazones ................................... 304
4.5.4 Alkylation of Chiral Oxazolines .................................... 308
4.5.4.1 Synthesis of Alkyl Alkanoic Acids ............................ 309
4.5.4.2 Synthesis of a-Hydroxyacids ................................... 311
4.5.4.3 Synthesis of Butyrolactones and Valerolactones ........... 311
4.5.4.4 Synthesis of ,B-Alkylalkanoic Acid ............................ 313
4.5.4.5 Synthesis of Un substituted 1,4-Dihydropyridines ......... 314
4.5.4.6 Synthesis of Resin-Bound Oxazolines ........................ 316
4.5.4.7 Alkylation via Diketopiperazines .............................. 317
4.5.5 Alkylation of Sulfoxides and Dithianes ........................... 318
4.5.6 Michael Addition Reactions .......................................... 322
4.5.6.1 Addition of Chiral Anions ...................................... 322
4.5.6.2 Addition of Achiral Anions Complexed with Chiral
Ligands to Prochiral Michael Acceptors ..................... 322
4.5.6.3 Addition of Achiral Anions to Michael Acceptors
Having One or More Chiral Centres .......................... 323
Contents xiii
4.5.6.4 Addition with Optically Active Transition
Metal-Ligand Catalysts .......................................... 325
4.6 Pericyclic Reactions ......................................................... 326
4.6.1 Asymmetric Cycloaddition Reactions .............................. 326
4.6.1.1 Asymmetric Diels-Alder Reactions ........................... 326
4.6.1.1.1 Addition to Chiral Dienophiles ........................... 327
4.6.1.1.2 Addition to Chiral Dienes ................................. 332
4.6.1.1.3 Chiral Catalysts .............................................. 334
4.6.2 Asymmetric [2 + 2] Cycloadditions ................................. 338
4.6.3 Asymmetric 1,3-Dipolar [3 + 2] Cycloadditions ................. 342
4.6.4 Sigmatropic Rearrangements ........................................ 345
4.6.4.1 [3,3] Sigmatropic Rearrangements ............................ 348
4.6.4.2 [2,3] Sigmatropic (Wittig) Rearrangements ................. 352
4.6.4.2.1 Allylsulfenate Rearrangements ........................... 357
4.6.5 Ene Reactions ........................................................... 360
4.6.5.1 Intermolecular Ene Reactions .................................. 361
4.6.5.2 Intramolecular Ene Reactions .................................. 362
4.7 References ..................................................................... 365
5 Asymmetric Oxidations 397
5.1 Asymmetric Epoxidation ................................................... 397
5.1.1 Asymmetric Epoxidation of Allylic Alcohols .................... 397
5.1.1.1 Katsuki-Sharpless Epoxidation ................................ 397
5.1.2 Asymmetric Epoxidation of other Substrates .................... 402
5.2 Asymmetric Oxidation of Sulfides ....................................... 405
5.3 Asymmetric Oxidation of Selenides ...................................... 405
5.4 Asymmetric Hydroxylations ............................................... 406
5.4.1 Vicinal Hydroxylations ................................................ 408
5.5 Asymmetric Oxidation of Aromatic Substrates via
Donor-Acceptor Interaction .............................................. 411
5.6 References ..................................................................... 412
6 Asymmetric Carbon-Heteroatom Bond Formations 416
6.1 Carbon-Oxygen Bond Formation ........................................ 416
6.1.1 Asymmetric Halolactonization ...................................... 416
6.1.2 Asymmetric Hydroboration .......................................... 420
6.2 Carbon-Nitrogen Bond Formation ...................................... 423
6.2.1 Halocyclization ......................................................... 423
6.2.1.1 Iodolactamization ................................................. 424
6.2.2 Mercuricyclization ...................................................... 424
6.3 Carbon-Sulfur Bond Formation ......................................... 426
6.4 Carbon-Phosphorus Bond Formation .................................. 428
6.5 Stereos elective C-H Bond Formation and Proton Migration ...... 429
6.6 References ..................................................................... 431
