Comprehensive asymmetric catalysis i III jacobsen, pfaltz yamamoto

Eric N. Jacobsen · Andreas Pfaltz · Hisashi Yamamoto (Eds.)

Comprehensive Asymmetric
Catalysis I–III
With contributions by numerous experts

123


ERIC N. JACOBSEN
Department of Chemistry and Chemical Biology
Harvard University
12 Oxford Street
MA 02138 Cambridge, USA
e-mail:
ANDREAS PFALTZ
Department of Chemistry
University of Basel
St. Johanns-Ring 19
CH-4056 Basel, Switzerland
e-mail:
HISASHI YAMAMOTO
School of Engineering
Nagoya University
Chikusa, 464-01 Nagoya, Japan
e-mail:

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Authors

Varinder K. Aggarwal

Klaus Breuer

Department of Chemistry
University of Sheffield
Sheffield S3 7HF, UK
e-mail: V.Aggarwal@Sheffield.ac.uk

Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

Susumu Akutagawa
Takasago International Corporation
Nissay Aroma Square 5–37–1
Kamata Ohta-ku
Tokyo 144–8721, Japan
e-mail:

Tadatoshi Aratani
Organic Synthesis Research Laboratory
Sumitomo Chemical Co., Ltd.
Takatsuki
Osaka 569-1093, Japan
e-mail:

Oliver Beckmann
Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

Hans-Ulrich Blaser
Novartis Services AG
Catalysis & Synthesis Services
R 1055.6.28
CH-4002 Basel, Switzerland
e-mail:

Carsten Bolm
Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

John M. Brown
Dyson Perrins Laboratory
South Parks Road
Oxford OX1 3QY, UK
e-mail:

Stephen L. Buchwald
Department of Chemistry
Massachusetts Institute of Technology
77 Massachusetts Ave.
Cambridge
MA 02139-4307, USA
e-mail:

Erick M. Carreira
Laboratorium für Organische Chemie
ETH Zürich
Universitätsstraße 16
CH-8092 Zürich, Switzerland
e-mail:

Albert L. Casalnuovo

DuPont Agricultural Products
Stine-Haskell Research Center
Newark
Delaware 19714, USA
e-mail: albert

André B. Charette
Département de Chimie
Université de Montréal
P.O. Box 6128, Station Downtown,
Montréal (Québec), Canada H3C 3J7
e-mail:


VI

Geoffrey W. Coates

Yujiro Hayashi

Department of Chemistry, Baker Laboratory
Cornell University, Ithaca
New York 14853-1301, USA
e-mail:

Department of Chemistry
School of Science
The University of Tokyo
Hongo, Bunkyo-ku
Tokyo 113-0033, Japan

e-mail:

Scott E. Denmark
Roger Adams Laboratory
Department of Chemistry
University of Illinois
Urbana, Illinois, 61801, USA
e-mail:

Dieter Enders
Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

David A. Evans
Department of Chemistry and Chemical
Biology
Harvard University
Cambridge
Massachusetts 02138, USA
e-mail:

Harald Gröger
Graduate School of Pharmaceutical Sciences
The University of Tokyo
Hongo 7-3-1, Bunkyo-ku
Tokyo 113, Japan

e-mail:

Ronald L. Halterman
Department of Chemistry and Biochemistry
University of Oklahoma
620 Parrington Oval
Norman, OK 73019, USA
e-mail:

Tamio Hayashi
Department of Chemistry
Faculty of Science
Kyoto University
Sakyo
Kyoto 606–8502, Japan
e-mail:
kyoto-u.ac.jp

Nicola M. Heron
Department of Chemistry
Merkert Chemistry Center
Boston College
Chestnut Hill
MA 02467, USA
e-mail:

Frederick A. Hicks
Department of Chemistry
Massachusetts Institute of Technology
Cambridge

77 Massachusetts Ave
MA 02139-4307, USA
e-mail:

Jens P. Hildebrand
Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

Amir H. Hoveyda
Department of Chemistry
Merkert Chemistry Center
Boston College
Chestnut Hill
MA 02467, USA
e-mail:

David L. Hughes
Merck and Co., Inc.
Mail Drop R80Y-250
Rahway, NJ 07065, USA
e-mail:

Shohei Inoue
Department of Industrial Chemistry
Faculty of Engineering
Science University of Tokyo

Kagurazaka, Shinjuku
Tokyo 162–8601, Japan
e-mail:


VII

Authors

Yoshihiko Ito
Department of Synthetic Chemistry and
Biological Chemistry
Graduate School of Engineering
Kyoto University
Sakyo-ku
Kyoto 606–8501, Japan
e-mail:

Shinichi Itsuno
Department of Materials Science
Toyohashi University of Technology
Tempaku-cho
Toyohashi 441-8580, Japan
e-mail:

Eric N. Jacobsen
Department of Chemistry and Chemical
Biology
Harvard University
12 Oxford Street

Cambridge, MA 02138, USA
e-mail:

Kim D. Janda
Department of Chemistry
The Scripps Research Institute and
The Skaggs Institute for Chemical Biology
10550 North Torrey Pines Road
La Jolla, CA 92037, USA
e-mail:

Jeffrey S. Johnson
Department of Chemistry and
Chemical Biology
Harvard University
Cambridge
Massachusetts 02138, USA
e-mail:

Henri B. Kagan
Laboratoire de Synthèse Asymétrique
Institut de Chimie Moléculaire d’ Orsay
Université Paris-Sud
F-91405 Orsay, France
e-mail:

Fukuoka 812–8581, Japan
e-mail:

Ryoichi Kuwano

Department of Synthetic Chemistry and
Biological Chemistry
Graduate School of Engineering
Kyoto University
Sakyo-ku
Kyoto 606–8501, Japan
e-mail:

Mark Lautens
Department of Chemistry
University of Toronto
Toronto, Ontario, Canada, M5 S 3H6
e-mail:

Hélène Lebel
Département de Chimie
Université de Montréal
P.O. Box 6128, Station Downtown
Montréal (Québec), Canada H3C 3J7
e-mail:

T. O. Luukas
Laboratoire de Synthèse Asymétrique
Institut de Chimie Moléculaire d’ Orsay
Université Paris-Sud
F-91405 Orsay, France
e-mail:

Kevin M. Lydon
School of Chemistry

The Queen’s University
David Keir Building
Stranmillis Road
Belfast BT9 5AG, Northern Ireland
e-mail:

Istvan E. Markó
Department of Chemistry
University of Louvain
Place Louis Pasteur 1
B-1348 Louvain-la-Neuve, Belgium
e-mail:

Keiji Maruoka
Tsutomu Katsuki
Department of Chemistry
Faculty of Science
Kyushu University 33
Hakozaki, Higashi-ku

Department of Chemistry
Graduate School of Science
Hokkaido University
Sapporo, 060–0810, Japan
e-mail:


VIII

M. Anthony McKervey

Hisao Nishiyama

School of Chemistry
The Queen’s University
David Keir Building
Stranmillis Road
Belfast BT9 5AG, Northern Ireland
e-mail:

School of Materials Science
Toyohashi University of Technology
Tempaku-cho,
Toyohashi 441, Japan
e-mail:

Koichi Mikami
Department of Chemical Technology
Tokyo Institute of Technology
Meguro-ku
Tokyo 152, Japan
e-mail:

Olivier J.-C. Nicaise
Monsanto Hall, Department of Chemistry
Saint Louis University
St. Louis, Missouri, 63103, USA
e-mail:

R. Noyori

Atsunori Mori
Research Laboratory of Resources
Utilization
Tokyo Institute of Technology
Nagatsuta
Yokohama 226–8503, Japan
e-mail:

Johann Mulzer

Department of Chemistry and Molecular
Chirality Research Unit
Nagoya University
Chikusa
Nagoya 464–8602, Japan
e-mail:

Kyoko Nozaki

Institut für Organische Chemie
Universität Wien
Währingerstrasse 38
A-1090 Wien, Austria
e-mail:

Department of Material Chemistry
Graduate School of Engineering
Kyoto University
Yoshida
Sakyo-ku, 606–8501, Japan

e-mail:

Kilian Muñiz

Günther Oehme

Institut für Organische Chemie
Rheinisch-Westfälische Technische
Hochschule
Professor-Pirlet-Straße 1
D-52074 Aachen, Germany
e-mail:

Yasuo Nagaoka
Graduate School of Pharmaceutical Sciences
Kyoto University
Yoshida, Sakyo-ku
Kyoto 606-8501, Japan
e-mail:

Koichi Narasaka
Department of Chemistry
School of Science
The University of Tokyo,
Hongo, Bunkyo-ku
Tokyo 113-0033, Japan
e-mail:

Institut für Organische Katalyseforschung
Universität Rostock e.V.

Buchbinderstr. 5–6
D-18055 Rostock, Germany
e-mail:

T. Ohkuma
Department of Chemistry and Molecular
Chirality Research Unit
Nagoya University
Chikusa
Nagoya 464–8602, Japan
e-mail:

Takashi Ooi
Department of Chemistry
Graduate School of Science
Hokkaido University
Sapporo, 060–0810, Japan
e-mail:


IX

Authors

Andreas Pfaltz
Department of Chemistry
University of Basel
St. Johanns-Ring 19,
CH-4056 Basel, Switzerland
e-mail:

Benoˆıt Pugin
Novartis Services AG
Catalysis and Synthesis Services
R-1055.6.29
CH-4002 Basel, Switzerland
e-mail:

T.V. RajanBabu
Department of Chemistry
The Ohio State University
100 W. 18th Avenue
Columbus, Ohio 43210, USA
e-mail:

Tomislav Rovis
Department of Chemistry
University of Toronto
Toronto, Ontario, Canada, M5 S 3H6
e-mail:

Michelangelo Scalone
Process Research and Catalysis Department
Pharmaceuticals Division
F. Hoffmann-La Roche AG
CH-4070 Basel, Switzerland
e-mail:

Rudolf Schmid
Process Research and Catalysis Department

Pharmaceuticals Division
F. Hoffmann-La Roche AG
CH-4070 Basel, Switzerland
e-mail:

Masakatsu Shibasaki
Graduate School of Pharmaceutical Sciences
The University of Tokyo
Hongo 7-3-1
Bunkyo-ku, Tokyo 113, Japan
e-mail:

Takanori Shibata
Department of Applied Chemistry
Faculty of Science
Science University of Tokyo
Kagurazaka, Shinjuku-ku

Tokyo 162–8601 Japan
e-mail:

Ken D. Shimizu
Department of Chemistry and Biochemistry
University of South Carolina
Columbia
South Carolina 29208, USA
e-mail:

Marc L. Snapper
Department of Chemistry

Merkert Chemistry Center
Boston College
Chestnut Hill
Massachusetts 02467, USA
e-mail:

Kenso Soai
Department of Applied Chemistry
Faculty of Science
Science University of Tokyo
Kagurazaka, Shinjuku-ku
Tokyo 162–8601, Japan
e-mail:

Felix Spindler
Novartis Services AG
Catalysis & Synthesis Services
R 1055.6.28
CH-4002 Basel, Switzerland
e-mail:

Martin Studer
Novartis Services AG
Catalysis & Synthesis Services
R 1055.6.28
CH-4002 Basel, Switzerland
e-mail:

John S. Svendsen
Department of Chemistry

University of Tromsø
N-9037 Tromsø, Norway
e-mail:

Masahiro Terada
Department of Chemical Technology
Tokyo Institute of Technology
Meguro-ku
Tokyo 152, Japan
e-mail:


X

Kiyoshi Tomioka

Masahiko Yamaguchi

Graduate School of Pharmaceutical Sciences
Kyoto University
Yoshida, Sakyo-ku
Kyoto 606-8501, Japan
e-mail:

Graduate School of Pharmaceutical Sciences
Tohoku University
Aoba
Sendai 980-8578, Japan
e-mail:

Erasmus M. Vogl

Hisashi Yamamoto

Graduate School of Pharmaceutical Sciences
The University of Tokyo
Hongo 7-3-1, Bunkyo-ku
Tokyo 113, Japan
e-mail:

Graduate School of Engineering
Nagoya University
CREST, Japan Science and Technology
Corporation (JST)
Chikusa
Nagoya 464–8603, Japan
e-mail:

Paul Wentworth Jr.
Department of Chemistry
The Scripps Research Institute and
The Skaggs Institute for Chemical Biology
10550 North Torrey Pines Road
La Jolla, CA 92037, USA
e-mail:

Michael H. Wu
Department of Chemistry and
Chemical Biology
Harvard University

Cambridge
MA 02138, USA
e-mail:

Akira Yanagisawa
Graduate School of Engineering
Nagoya University
CREST, Japan Science and Technology
Corporation (JST)
Chikusa
Nagoya 464–8603, Japan
e-mail:


Preface

The title of this collection is an accurate reflection of the goals we defined at the
outset of the project. Our intention was to bring together all important aspects
of the field of asymmetric catalysis and to present them in a format that would
be most useful to a wide range of scientists including students of chemistry, expert practitioners, and chemists contemplating the possibility of using an asymmetric catalytic reaction in their own research.
This project was initiated by Joe Richmond, who was one of many to recognize the need for an exhaustive and current treatment of the field of asymmetric
catalysis, but was unique in being willing and able to get such an ambitious effort
started. Considering that it is a field that is evolving in parallel in laboratories
throughout the world, he sought to select editors who were not only authoritative, but also as geographically distributed as the field itself. He approached each
of us separately, and in the end we were compelled equally by the significance of
the project, and by the exciting prospect of working together.
Given the dramatic growth of activity in the field of asymmetric catalysis over
the past few years in particular, it was apparent from the start that a comprehensive treatment would be a ambitious task, especially if we were to succeed in capturing the excitement and challenges in field, as well its basic principles. The
field is interdisciplinary by its nature, incorporating organic synthesis, coordination chemistry, homogeneous catalysis, kinetics and mechanism, and advanced stereochemical concepts all at its very heart. We realized that the project
would require authors who would be willing not only to commit the effort of

writing definitive and compelling chapters, but who would also be capable of analyzing their topic with absolute authority. At a hotel near the Frankfurt airport
in the Fall of 1996, we got together and constructed an exhaustive list of topics
in asymmetric catalysis, and then we devised a “dream list” of contributors.
These were individuals who contributed in defining ways to the topics in question. That this dream list came true hopefully should be evident by surveying the
names of the contributing authors. If we have succeeded to any extent in our effort to put forth a comprehensive and useful analysis of the field of asymmetric
catalysis, it is thanks to them.
Eric N. Jacobsen, Cambridge
Andreas Pfaltz, Basel
Hisashi Yamamoto, Nagoya

July 1999


Subject Index

Acetone cyanohydrin 983
Achiral proton sources 1295
Acid
–, α-Amino 923
–, 2-Arylpropanoic 367, 417
–, chiral Lewis 9, 1237
–, β-Hydroxy-α-amino 1067
–, Lewis 983, 1121, 1177
–, pantothenic 1439
–, polyamino 679
–, Raney-Ni/tartaric 1439
Activated olefin 1105
acyloin reaction 1093
Adsorption 1367
Alcohol 911

–, allylic 621
–, amino 911, 1451
–, chiral 199
–, epoxy 621
–, secondary 267, 319, 351, 887
Aldehydes 1237
Aldol 997
– condensation 1403
– reaction 1067
– type reaction 1143
Alkoxide 1121
Alkyl hydrides 121
Alkylation 431, 911, 923, 1105
Allenylboranes 351
Allyl alcohol 813
π-Allyl complexes 833
π-Allylnickel bromide 417
π-Allypalladium complexes 923
Allylamine 813, 1461
Allylation 833, 923, 965
Allylic alcohol hydrogenation 1439
Allylic
– alcohol 621
– alkylation 833, 1273
– oxidation 791
– substitution 833
Allylsilanes 319, 887, 965
Allylstannanes 965
Aluminum 1143

Amine 267, 923, 1105, 1121
α-Amino acid 923
Amino alcohol 911, 1451
α-Aminonitrile 983
Anionic polymerization 1329
Ansa-metallocene titanium complexes:
imine hydrogenation 247
Arylation 457
Arylphosphinites 367
2-Arylpropanoic acid 367, 417
Asymmetric 539
– activation 1143
– amplification 101
– arylation 1273
– autocatalysis 911
– catalysis 9, 101
– depletion 101
– deprotonation 1273
– dihydroxylation 713
– Heck reaction 457
– hydrocyanation 367
– hydrogenation 9, 183, 199
– hydrovinylation 417
– nitroaldol reaction 1075
– phase-transfer catalysis 1377
– synthesis 1389
– transfer hydrogenation 199
Atropisomeric polymer 1329
Autocatalysis 101
Auxiliary 923

Aza-allyl 813
Aziridine 607
Azomethine 813
– function 923
Baeyer-Villiger oxidation 803
Benzoin reaction 1093
Benzylic hydroxylation 791
Betaines 679
BINAP 199, 337, 813, 1461
Binaphthol 1143
Biphasic catalysis 1377
BIPHEMP 813


2
Bisoxazoline 607, 1143
Borane 289
Borohydride 289
C=N bond 923
C=N hydrogenation: historical
development 247
C=N reduction: assessment of catalysts 247
Carbenes 581, 679
Carbohydrate ligands 367
Carbon-Hydrogen Insertion 539
Carbon-metal bond 337
Carbonyl
– addition reaction 1143
– compounds 965
Carbonylation 381

Carbopalladation 457
Catalysis
–, asymmetric 9, 101
–, asymmetric phase-transfer 1377
–, Auto- 101
–, biphasic 1377
–, enantioselective 1177
–, ligand accelerated 713
–, micellar 1377
Catalyst 923
–, chiral 33, 1389
–, chiral titanium 1255
–, chiral Lewis acid 965
–, cinchona modified Pt 1353
–, copper 513
–, epoxidation 1353
–, heterobimetallic lanthanoid 1075
–, heterogeneous 1353
–, homogeneous 199
–, hybrid 33
–, hydrogenation 1353
–, Nickel 319, 337, 887
–, organic 9
–, organometallic 9
–, Palladium 319, 351, 887
–, phase transfer 1273
–, Platinum 319, 887
–, Rhodium 267, 319, 351, 887
–, Rhodium diphosphine 1439
–, Ruthenium diphosphine 1439

–, tartrate-modified Nickel 1353
–, Titanium 267
Catalyst recycle 1461
Catalytic antibody 9, 1403
Catalyzed cyclization 417
Cationic polymerization 1329
Cationic reactions 1403
C-H insertion 513, 581

C-H oxidation 791
Chiral 539
– alcohols 199
– amines 199
– auxiliary 33, 101, 491
– base 1273
– catalysts 33, 1389
– cyclopentadienyllanthanides 183
– drugs 1439
– enyne 491
– imprints 1353
– Lewis acid catalysts 965
– Lewis acids 9, 1237
– Lewis base catalysts 965
– ligand 9, 1273
– metal complexes 697
– metal surfaces 1353
– metallocenes 183
– phosphines 183, 199
– polymers 1353
– proton sources 1295

– switch 1427
– titanium catalyst 1255
– titanocenes 183
– zirconocene 183
Chiraphor and catalaphor 33
Cilazapril 1439
Cinchona
– alkaloid 713, 1255
– modified Pt catalysts 1353
Cinchonine 1273
Citronellal 813, 1461
Cobalt 813
Conjugate addition 1105
Controller 923
Copolymerization 1367
Copper 607, 803, 1105, 1143
– catalysts 513
– complexes 1451
Crown ether 1121
α-Cyanohydrin 983
Cyanohydrin formation 1353
Cyclic dipeptide 983, 1353
Cyclic imine hydrogenation: effective
catalysts 247
Cycloaddition 1177
–, [2+2] 1255
Cyclobutane 1255
Cyclocondensation 1237
Cycloheptenols 337
Cyclohexenols 337

Cyclopentenone 491
Cyclopropanation 539, 581, 1451
Cyclopropanes 513


3

Subject Index

Danishefsky’s diene 1237
Desymmetrization 1143, 1309
– of meso compound 791
Dextromethorphan 1439
Dialkylzinc 911
Diazo compounds 513, 581
Diazoacetate 1451
Diazocarbonyl Compounds 539
DIBALH 337
Diels-Alder
– cycloaddition 1403
– reaction 1177
1,6-Diene 417
1,3-Dienes 319, 887
Diene 417
Dihydrides 121
Diimine ligands 607
DIOP 813
Dioxirane 649
Diphenylsilane 267
Diphosphine 121, 1143

Disfavored cyclization 1403
Double stereodifferentiation 33
Electronic asymmetry 367
Electronic effects 367
Enamide 121
– hydrogenation 1439
Enamine 813, 1461
Enantiofacial 1403
Enantiomeric excess 101
Enantioselective 431, 539, 1403
– and diastereoselective reactions 1075
– catalysis 1177
– hydrogenation 1439
Enantioselectivity 1237
Ene
– cyclization 1143
– reaction 1143, 1439, 1461
Enol 813
– silane 997
Enolate alkylation 1273
Entrapment 1367
Enyne 491
Enzymes 9
Epoxidation 621, 679
– catalysts 1353
Epoxide 649, 1309
Epoxy alcohol 621
Ether 1105
Ethylene 417
Ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl (EBTHI) ligand 491

exo-endo-Diastereoselectivity 33

Ferrocenylphosphine 1067
β-Functionalized ketones 1353
Functionalized ketones 199
Glyoxylate-ene reaction 1439
Gold 1067
Grafting 1367
Grignard reagent 923, 1105
Hapten 1403
Hemilabile ligand 417
Henry reaction 1075
Heterobimetallic lanthanoid
catalysts 1075
Hetero-Diels-Alder reaction 1143
Heterogeneous catalysts 1353
Heterogenization 1367
High-throughput screening 1389
History 9
Homoallylic amine 923
Homogeneous catalysts 199
Hybrid catalysts 33
Hydroboration 289, 351
Hydrocarboxylation 381
Hydroformylation 381
Hydrogen cyanide 367, 983
Hydrogenation
–, N-Alkylimine 247
–, allylic alcohol 1439
–, N-Arylimine 247

–, asymmetric 9, 183, 199
–, asymmetric transfer 199
–, C=N 247
–, catalysts 1353
–, cyclic imine 247
–, enamide 1439
–, enantioselective 1439
–, imine 247, 1427, 1439
–, β-Ketoester 1439
–, α-Ketolactone 1439
–, γ-Oxo-olefin 1439
– α,β-Unsaturated acid 1439
Hydrometalation 337
Hydrosilylation 319, 887
β-Hydroxy-α-amino acid 1067
Imine 267, 813, 923
Imine hydrogenation 1427, 1439
–, mechanistic aspects 247
Immobilization 1367
Industrial application 1427
Insertion polymerization 1329
Intermolecular 539


4
Intramolecular 539
Ir
– complexes: imine hydrogenation 247
– diphosphine complexes 1427
– ferrocenyldiphosphine complexes 1427

Iridium 183, 833
Iron-porphyrin complex 791
Isocyanocarboxylate 1067
Isomerization 813, 1461
α-Keto acid derivatives 1353
α-Ketolactone hydrogenation 1439
β-Ketoester hydrogenation 1439
Ketone 267, 289
–, functionalized 199
–, β-Functionalized 1353
–, simple 199
Kharash-Sosnovsky reaction 791
Kinetic
– models 101
– resolution 431, 621, 813, 1143, 1309, 1329
Lanthanides 1143
Lewis acid 983, 1121, 1177
Ligand 923, 1105
– accelerated catalysis 713
– acceleration 621
– dibersity 1389
– tuning 417
Lithium enolates 923
Macromolecular stereochemistry 1329
Magnesium 1143
Main-chain chiral polymer 1329
Mannich reaction 923
MEA imine 1427
Mechanism control 33
Menthol 1461

Metal
– carbenes 513
– enolates 1295
– peroxides 679
Metallo-ene 1143
(S)-Metolachlor 1427
Mibefradil 1439
Micellar catalysis 1377
Michael addition 1121
Microheterogeneous systems 1377
Miscellaneous C=N-X reduction: effective
catalysts 247
Modified metal oxides 1353
Molybdenum 833
N-Alkylimine hydrogenation: effective
catalysts 247

Naproxen 367
N-Arylimine hydrogenation: effective
catalysts 247
Nickel 417, 431
–, catalyst 319, 337, 887
Nitrogen-triggered 813
Nitrone 923
Non-linear effect 9, 101, 1143
Norbornene 417
Nucleophilic
– acylation 1093
– addition 1105
– oxidation 679

Olefins 319, 351, 381, 887
Organic catalysts 9
Organoalane 337
Organoboron reagents 923
Organolithium 1105
– reagents 923
Organometallic
– catalysts 9
– compound 923
Organozinc 1105
– reagents 923
Orlistat 1439
Osmium tetroxide 713
Oxazaborolidine 289
Oxazaphospholidine 289
Oxime 923
γ-Oxo-olefin hydrogenation 1439
Palladium 417, 833, 1143
– catalyst 319, 351, 887
Pantolactone 1439
Pantothenic acid 1439
Pauson-Khand 491
Peptide-metal complex 983
Phase transfer 1273
– catalyst 1121
2-Phenyl-1-butene 183
Phosphanodihydrooxazole 183
Phosphine 1105
Phospholane 417
Phosphorus 1105

Platinum 803
– catalyst 319, 887
Polyamino acids 679
Polymerization
–, anionic 1329
–, cationic 1329
–, co- 1367
–, insertion 1329
Polypeptides 1353


5

Subject Index

Porphyrin 649
Pressure and temperature dependence 121
Propionolactone 1255
Protonation 1295
Pyrone derivatives 1237
Radical alkylation 1273
Raney-Ni/tartaric acid 1439
[1,2]-Rearrangement 803
reaction
–, acyloin 1093
–, aldol type 1067
–, asymmetric Heck 457
–, asymmetric nitroaldol 1075
–, benzoin 1093
–, carbonyl addition 1143

–, cationic 1403
–, diastereoselective 1075
–, Diels-Alder 1177
–, enantioselective 1075
–, Ene 1143, 1439, 1461
–, Glyoxylate-ene 1439
–, Henry 1075
–, Hetero-Diels-Alder 1143
–, Mannich 923
–, stereogenic 33
–, Stetter 1093
Reduction 289, 337
Reservoir effect 101
Rh diphosphine complexes 1427
–, C=N hydrogenation 247
Rh(BPPM) 1439
Rhodium 121, 183, 539, 813
– catalyst 267, 319, 351, 887
– complex 1461
– diphosphine catalysts 1439
Ring opening 1309
Ru Complexes: C=N reduction 247
Ru(MeOBIPHEP) 1439
Ruthenium 121, 183, 813
– diphosphine catalysts 1439
Salen complexes 649
(Salen)manganese(III) complex 791
Schiff base 1143, 1451
Secondary alcohols 267, 319, 351, 887
Silver 1067

Silyl
– enol ether 923
– ketene acetal 923
Simmons-Smith 581
Simple
– diastereoselectivity 33

– ketones 199
– olefins 183
Site isolation 1367
Solid phase chemistry 1389
Stereogenic reactions 33
Stereoselectivity 33
Stetter reaction 1093
Strecker synthesis 983
β-Substituted carbonyl compound 1105
Substrate and reagent control 33
Substrate chelation 121
Sulfimides 697
Sulfones 697
Sulfoxides 697
Sulfoximines 697
Sulfur ylides 679
Support 1367
syn-Selectivity 1075
TADDOL 1143
Tartrate-modified Nickel catalysts 1353
Technical process 1427
Telomerization 1461
Terpenoids 1461

Tetrahydrolipstatin 1439
thiazolium salts 1093
Ti(BINOL) 1439
Titanium 803, 1143
– catalysts 267
– -mediated epoxidation 621
– tartrate complex 621
Titanocene 491
TMSCN 983
(R,R,R)-α-Tocopherol 1439
Transient NMR 121
Transition metal 997
– complex 1121
Triazolium salts 1093
Tungsten 833
Unfunctionalized olefins 183
α,β-Unsaturated acid hydrogenation 1439
Vesicles 1377
Vinylarene 367, 417
Vinylation 457
Vitamin E 1439
Ylides 513
Zirconium 431


Contents

Volume I
1

Introduction
Andreas Pfaltz. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3

Historical Perspective
Henri B. Kagan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9

Basic Principles of Asymmetric Synthesis
Johann Mulzer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33

4
General Aspects of Asymmetric Catalysis
4.1 Non-Linear Effects and Autocatalysis
Henri B. Kagan, T. O. Luukas. . . . . . . . . . . . . . . . . . . . . . . .

101

2
3

5
Hydrogenation of Carbon-Carbon Double Bonds
5.1 Hydrogenation of Functionalized Carbon-Carbon Double Bonds
John M. Brown . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.2 Hydrogenation of Non-Functionalized Carbon-Carbon Double Bonds

Ronald L. Halterman . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
6
Reduction of Carbonyl and Imino Groups
6.1 Hydrogenation of Carbonyl Groups
T. Ohkuma · R. Noyori . . . . . . . . . . . . . . .
6.2 Hydrogenation of Imino Groups
Hans-Ulrich Blaser, Felix Spindler . . . . . . . .
6.3 Hydrosilylation of Carbonyl and Imino Groups
Hisao Nishiyama . . . . . . . . . . . . . . . . . .
6.4 Hydroboration of Carbonyl Groups
Shinichi Itsuno . . . . . . . . . . . . . . . . . . .
7
8
9

. . . . . . . . . . . .

199

. . . . . . . . . . . .

247

. . . . . . . . . . . .

267

. . . . . . . . . . . .

289

Hydrosilylation of Carbon-Carbon Double Bonds
Tamio Hayashi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

319

Hydroalumination of Carbon-Carbon Double Bonds
Mark Lautens, Tomislav Rovis. . . . . . . . . . . . . . . . . . . . . . .

337

Hydroboration of Carbon-Carbon Double Bonds
Tamio Hayashi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

351


XIV

10
11
12
13
14

Hydrocyanation of Carbon-Carbon Double Bonds
T.V. RajanBabu, Albert L. Casalnuovo. . . . . . . . . . . . . . . . . . .

367

Hydrocarbonylation of Carbon-Carbon Double Bonds
Kyoko Nozaki . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

381

Hydrovinylation of Carbon-Carbon Double Bonds
T.V. RajanBabu. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

417

Carbometalation of Carbon-Carbon Double Bonds
Amir H. Hoveyda, Nicola M. Heron . . . . . . . . . . . . . . . . . . . .

431

Heck Reaction
Masakatsu Shibasaki, Erasmus M. Vogl. . . . . . . . . . . . . . . . . .

457

Volume II
15

Pauson-Khand Type Reactions
Stephen L. Buchwald, Frederick A. Hicks . . . . . . . . . . . . . . . . .

16 Cyclopropanation and C-H Insertion Reactions
16.1 Cyclopropanation and C-H Insertion with Cu
Andreas Pfaltz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16.2 Cyclopropanation and C-H Insertion with Rh

Kevin M. Lydon, M. Anthony McKervey . . . . . . . . . . . . . . . . .
16.3 Cyclopropanation and C-H Insertion with Metals
Other Than Cu and Rh
André B. Charette, Hélène Lebel. . . . . . . . . . . . . . . . . . . . . .
17

Aziridination
Eric N. Jacobsen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

18 Epoxidation
18.1 Epoxidation of Allylic Alcohols
Tsutomu Katsuki . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18.2 Epoxidation of Alkenes Other than Allylic Alcohols
Eric N. Jacobsen, Michael H. Wu. . . . . . . . . . . . . . . . . . . . . .
18.3 Epoxide Formation of Enones and Aldehydes
Varinder K. Aggarwal . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19
20
21
22

491

513
539

581
607

621

649
679

Oxidation of Sulfides
Carsten Bolm, Kilian Muñiz, Jens P. Hildebrand . . . . . . . . . . . . .

697

Dihydroxylation of Carbon-Carbon Double Bonds
Istvan E. Markó, John S. Svendsen. . . . . . . . . . . . . . . . . . . . .

713

C-H Oxidation
Tsutomu Katsuki . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

791

Baeyer-Villiger Reaction
Carsten Bolm, Oliver Beckmann . . . . . . . . . . . . . . . . . . . . .

803


Contents

23
24
25

Isomerization of Carbon-Carbon Double Bonds
Susumu Akutagawa. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

813

Allylic Substitution Reactions
Andreas Pfaltz, Mark Lautens . . . . . . . . . . . . . . . . . . . . . . .

833

Cross-Coupling Reactions
Tamio Hayashi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

887

26 Alkylation of Carbonyl and Imino Groups
26.1 Alkylation of Carbonyl Groups
Kenso Soai, Takanori Shibata . . . . . . . . . . . . . . . . . . . . . . .
26.2 Alkylation of Imino Groups
Scott E. Denmark, Olivier J.-C. Nicaise . . . . . . . . . . . . . . . . . .
27
28

XV

911
923

Allylation of Carbonyl Groups
Akira Yanagisawa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

965

Cyanation of Carbonyl and Imino Groups
Atsunori Mori, Shohei Inoue . . . . . . . . . . . . . . . . . . . . . . .

983

Volume III
29 Aldol Reactions
29.1 Mukaiyama Aldol Reaction
Erick M. Carreira . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 997
29.2 Addition of Isocyanocarboxylates to Aldehydes
Ryoichi Kuwano, Yoshihiko Ito . . . . . . . . . . . . . . . . . . . . . . 1067
29.3 Nitroaldol Reaction
Masakatsu Shibasaki, Harald Gröger . . . . . . . . . . . . . . . . . . . 1075
30

Addition of Acyl Carbanion Equivalents to
Carbonyl Groups and Enones
Dieter Enders, Klaus Breuer . . . . . . . . . . . . . . . . . . . . . . . . 1093

31 Conjugate Addition Reactions
31.1 Conjugate Addition of Organometallic Reagents
Kiyoshi Tomioka, Yasuo Nagaoka . . . . . . . . . . . . . . . . . . . . . 1105
31.2 Conjugate Addition of Stabilized Carbanions
Masahiko Yamaguchi . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1121
32

Ene-Type Reactions

Koichi Mikami, Masahiro Terada . . . . . . . . . . . . . . . . . . . . . 1143

33 Cycloaddition Reactions
33.1 Diels-Alder Reactions
David A. Evans, Jeffrey S. Johnson . . . . . . . . . . . . . . . . . . . . 1177
33.2 Hetero-Diels-Alder and Related Reactions
Takashi Ooi, Keiji Maruoka . . . . . . . . . . . . . . . . . . . . . . . . 1237


XVI

33.3 [2+2] Cycloaddition Reactions
Yujiro Hayashi, Koichi Narasaka . . . . . . . . . . . . . . . . . . . . . 1255
34 Additions to Enolates
34.1 Alkylation of Enolates
David L. Hughes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1273
34.2 Protonation of Enolates
Akira Yanagisawa, Hisashi Yamamoto . . . . . . . . . . . . . . . . . . 1295
35

Ring Opening of Epoxides and Related Reactions
Eric N. Jacobsen, Michael H. Wu. . . . . . . . . . . . . . . . . . . . . . 1309

36

Polymerization Reactions
Geoffrey W. Coates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1329

37

Heterogeneous Catalysis
Hans-Ulrich Blaser, Martin Studer . . . . . . . . . . . . . . . . . . . . 1353

38 Catalyst Immobilization
38.1 Catalyst Immobilization: Solid Supports
Benoˆıt Pugin, Hans-Ulrich Blaser . . . . . . . . . . . . . . . . . . . . . 1367
38.2 Catalyst Immobilization: Two-Phase Systems
Günther Oehme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1377
39

Combinatorial Approaches
Ken D. Shimizu, Marc L. Snapper, Amir H. Hoveyda . . . . . . . . . . 1389

40

Catalytic Antibodies
Paul Wentworth Jr., Kim D. Janda . . . . . . . . . . . . . . . . . . . . . 1403

41 Industrial Applications
41.1 The Chiral Switch of Metolachlor
Hans-Ulrich Blaser, Felix Spindler . . . . . .
41.2 Process R&D of Pharmaceuticals, Vitamins,
and Fine Chemicals
Rudolf Schmid, Michelangelo Scalone . . . .
41.3 Cyclopropanation
Tadatoshi Aratani . . . . . . . . . . . . . . . .
41.4 Asymmetric Isomerization of Olefins
Susumu Akutagawa . . . . . . . . . . . . . . .
42

. . . . . . . . . . . . . . 1427

. . . . . . . . . . . . . . 1439
. . . . . . . . . . . . . . 1451
. . . . . . . . . . . . . . 1461

Future Perspectives in Asymmetric Catalysis
Eric N. Jacobsen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1473

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1479


Chapter 1
Introduction
Andreas Pfaltz
Department of Chemistry, University of Basel, St. Johanns-Ring 19,
CH-4056 Basel, Switzerland
e-mail:

In Morrison and Mosher’s classical book ‘Asymmetric Organic Reactions’, which
covered the literature up to 1968, asymmetric catalysis did not fill more than a
few pages and no special chapter was devoted to it. Apart from enzymatic processes, only a few examples of enantioselective catalytic reactions were known at
that that time, and in view of the generally low enantiomeric excesses, many
chemists doubted that synthetic chiral catalysts would ever play an important
role in asymmetric synthesis. Shortly after, the situation changed dramatically
as spectacular progress was made in the rhodium-catalyzed enantioselective hydrogenation of olefins, culminating in the famous Monsanto process for L-dopa.
Since then, asymmetric catalysis has undergone explosive growth, especially
during the last decade. Today, it has its standard place in the repertoire of asymmetric synthesis and the increasing number of industrial applications clearly
demonstrates its practicality. Although the remarkable development of this still
relatively young area has been documented in many excellent books and review

articles, an up-to-date comprehensive overview is lacking. This makes it difficult
for the newcomer, and even the specialist, to gather all the relevant information
on a particular method or catalyst.
With ‘Comprehensive Asymmetric Catalysis’ we hope to fill this gap. ‘Comprehensive’ means that all important classes of enantioselective catalytic transformations are covered but it does not imply an extensive lexicographic compilation of examples. The aim was a concise and readable overview of the field,
providing a clear picture of the state of the art. The reader should be able to recognize the scope and limitations of a specific catalyst or method and find the
pertinent references for a more detailed bibliographic study. The electronic version with reaction and substructure search options should be particularly useful
for this purpose.
Although enzymes are an important class of enantioselective catalysts, a systematic coverage of biocatalysis was beyond the scope of this work. However, the
reader should be aware that biocatalysts can be an attractive alternative to synthetic chiral catalysts and in many chapters, references to related enzymatic
transformations are given. An important new addition to biocatalysis are catalytic antibodies and their use for enantioselective transformations is summarized in chapter 40.


2

Andreas Pfaltz

The wide variety of chiral catalysts and the impressive number of enantioselective reactions that are listed in this reference work might lead to the impression that for most organic transformations efficient enantioselective catalysts
have been developed. However, a more critical evaluation reveals that the number
of truly useful enantioselective catalysts is still limited, especially catalysts that
can be employed in an industrial process. In addition to high enantioselectivity,
there are other criteria that count, such as catalytic efficiency (turnover number
and frequency), application range, reliability, accessibility of the catalyst, and
functional group tolerance. In this respect, many of the current methods still
need to be improved and the search for new and more efficient catalysts will continue. We feel that ‘Comprehensive Asymmetric Catalysis’ will allow one to recognize the gaps and weak points of current methodology and, in this way, serve
as a basis for future research.
It is interesting to compare and categorize the various catalysts discussed in
the individual chapters. Most enantioselective catalysts are metal complexes
containing chiral organic ligands. Obviously, the choice of a suitable chiral controller ligand is a crucial step in the development of a new catalyst. While originally chiral diphosphines dominated the field, an impressive variety of mono-,
bi-, and multidentate ligands with P, N, O, and other coordinating atoms is used
today. However, compilation of the most efficient ligands reveals that most of

them belong to a relatively small number of structural classes. Examples are
binaphthyl and other biaryl derivatives such as BINOL and BINAP, bisoxazolines, salens and the tartrate-derived TADDOLS, which are all C2-symmetric.
However, there are also important classes of non-symmetric ligands such as ferrocenylphosphines, phosphinooxazolines and cinchona alkaloid derivatives.
The concept of C2 symmetry, introduced by Kagan in the early seventies with
the diop ligand, had an important impact on the course of research in asymmetric catalysis. This is reflected in the remarkably high number of C2-symmetric
ligands developed so far. C2 symmetry is attractive because it reduces the number
of possible catalyst-substrate arrangements and, consequently, the number of
competing reaction pathways by a factor of two. This can have a beneficial effect
on the enantioselectivity and, moreover, facilitates a mechanistic analysis and
identification of the factors responsible for enantiocontrol. However, there is no
fundamental reason that nonsymmetrical ligands should necessarily be less effective and, indeed, there are many examples where nonsymmetrical ligands are
the better choice.
An ideal chiral ligand should not only be easily accessible but it should also
be possible to modify its structure systematically. In this way the catalyst structure can be optimized for a specific application or substrate structure. Therefore,
it is not surprising to see a clear trend toward modular ligands that can be readily assembled from a large selection of simple precursors. Good examples of such
modular ligands are salens, phosphinooxazolines or TADDOLS, which are derived from inexpensive chiral diamines, amino alcohols and tartrate, respectively.
In general, the current approach to finding new catalysts is still rather empirical. Chance and intuition as well as systematic screening play an important role.


Introduction

3

Although we can see a trend toward a more rationally based catalyst design, our
present, still limited mechanistic understanding and the complexity of most catalytic processes prevents a purely rational approach. Nevertheless, for certain
reactions such as rhodium-catalyzed hydrogenation or palladium-catalyzed allylic substitution, the mechanism and the structure of intermediates in the catalytic cycle are known in detail so that an at least semi-rational development of
new ligands seems possible (cf. chapters 5 and 24). Because rational design is so
difficult, an alternative approach based on combinatorial strategies has been
proposed. However, in contrast to biology or medicinal chemistry, where combinatorial chemistry is already well-established, the situation in asymmetric catalysis is rather different. Screening of large catalyst libraries for enantioselectivity and reactivity is much more difficult than testing for biological activity or for
binding to a specific receptor. Therefore, future progress in ‘combinatorial catalysis’ will crucially depend on the development of suitable high-throughput

screening methods. Nevertheless, first steps in this direction have been taken
and, in some cases, promising results have been obtained (cf. chapter 39).
It was our goal to find for each chapter an author who has been personally involved in the research described therein so that he would be able to provide an
insider’s view and a critical analysis of the state of the art. We are grateful to all
our colleagues who agreed to contribute to this ambitious project, despite their
busy schedules and many other obligations. The result, more than 40 chapters
written by well-known experts, is more than satisfying. We feel that this reference work is not only an authoritative up-to-date treatment of the field but, in
addition, provides a lively view on the many fascinating aspects of asymmetric
catalysis, the remarkable and often unexpected developments, as well as current
and future trends. We hope that ‘Comprehensive Asymmetric Catalysis’ will be a
useful tool for the practicing chemist and, at the same time, serve as a source of
inspiration for the specialists as well as those who are planning to enter this dynamic area of research.


Chapter 2
Historical Perspective
Henri B. Kagan
Laboratoire de Synthèse Asymétrique, Institut de Chimie Moléculaire d’ Orsay,
Université Paris-Sud 91405 Orsay, France
e-mail:

Keywords: Asymmetric catalysis, Asymmetric hydrogenation, Catalytic antibodies, Chiral
Lewis acids, Chiral ligands, Enzymes, Organometallic catalysts, Organic catalysts, Nonlinear
effects, History

1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

2

Some Early Examples of Bioorganic Enantioselective Catalysis . . .

3

3

The First Examples of Non-enzymatic Enantioselective Catalysis .

3

4
4.1
4.1.1
4.1.2
4.1.3
4.1.3.1
4.1.3.2
4.1.4
4.2

Enantioselective Catalysis Until 1980 . . . . . . .
Organometallic Catalysis . . . . . . . . . . . . . .
Asymmetric Polymerization . . . . . . . . . . . .
Asymmetric Cyclopropanation. . . . . . . . . . .
Asymmetric Hydrogenation . . . . . . . . . . . .
Early Stages (1968–1972) . . . . . . . . . . . . . .
The Period 1973–1979 . . . . . . . . . . . . . . . .

Miscellaneous . . . . . . . . . . . . . . . . . . . .
Organic Catalysts in Enantioselective Synthesis .

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5
5.1
5.2
5.3

Enantioselective Catalysis Between 1980 and 1990
Organometallic Catalysis . . . . . . . . . . . . . . .

Organic Catalysis. . . . . . . . . . . . . . . . . . . .
Nonlinear Effects. . . . . . . . . . . . . . . . . . . .

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6

Epilogue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

11
11
15

16

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1

Introduction
Catalysis is a process which was recognized early in the last century. It seems that
Michael Faraday was one of the first scientists to study a catalytic reaction,
namely the reaction of hydrogen and oxygen on platinum. This work was pub-


2

Henri B. Kagan

lished in 1834. Faraday understood that in this case of heterogeneous catalysis,
the platinum surface was involved and he explained the activity of platinum by
adsorption of the reactants on the surface. Apparently, this investigation originated from his association with sir Humphrey Davy who contributed to the development of the miner’s safety lamp in 1818. A year before Davy found that a
platinum or palladium wire became incandescent in a mixture of coal gas and
air. In 1823 in Germany Döbereiner set up a porous platinum which catalyzed
the combination of hydrogen and oxygen at room temperature. It was this experiment which became known to Faraday and encouraged him to study catalysis
over platinum. In 1835, Berzelius also investigated some catalytic reactions such
as gas combustion and coined the word “catalysis”, derived from an ancient
Greek word meaning dissolution, destruction or end. This choice of word is quite
unfortunate as catalysis is most of the time very productive, and in fact the opposite of destruction. Berthelot studied many cases of catalysis in organic transformations. In 1902, Ostwald defined catalysts as agents which accelerate chemical reactions without affecting the chemical equilibrium. This definition applies
to reversible systems and excludes autocatalytic reactions. P. Sabatier (Nobel
laureate in Chemistry in 1911) defined catalysis as a mechanism whereby some
compounds are intimately involved in the process of generating or accelerating
chemical reactions without being products of the reaction.
Catalysis may be divided into three branches:

1. Heterogeneous catalysis (chemical).
2. Homogeneous catalysis (chemical).
3. Enzymatic catalysis.
Historically, heterogeneous catalysis had a strong impact on the concept of catalysis (vide supra). It also gave powerful tools to the chemical industry and to
organic synthesis.
It is interesting to recall that the first catalytic asymmetric reaction was performed on a racemic mixture (kinetic resolution) in an enzymatic reaction carried out by Pasteur in 1858. The organism Penicillium glauca destroyed (d)-ammonium tartrate more rapidly from a solution of a racemic ammonium tartrate
[1]. The first use of a chiral non-enzymatic catalyst can be traced to the work of
Bredig and Fajans in 1908 [2]. They studied the decarboxylation of camphorcarboxylic acid catalyzed by nicotine or quinidine, and they established the basic
kinetic equations of kinetic resolution.
In this chapter, we intend to restrict the expression “asymmetric catalysis” to
the specific case of an enantioselective reaction controlled by a chiral catalyst.
We will not consider the diastereoselective reactions on a chiral substrate involving a chiral catalyst (double asymmetric induction with matched and mismatched pairs).
The concept itself of asymmetric synthesis, stoichiometric or catalytic, took
a long time appear. One important step was the investigations of Fischer in
1894–1899 on the structure and stereochemistry of sugars [3, 4, 5]. He observed
the formation of diastereomers on addition of HCN to the aldehyde function of


3

Historical Perspective

some sugars. He also recognized that enzymes acted as catalysts either in a living
organism or as an isolated species and proposed the “lock and key” analogy for
explaining the stereospecificity of the enzymes. Marckwald [6] gave, in 1904, a
definition of asymmetric synthesis which is still acceptable today, although it
has been modified since by Morrison and Mosher in order to include the various
cases of asymmetric induction [7].
2

Some Early Examples of Bioorganic Enantioselective Catalysis
It is difficult to localize in the literature the initial reports on enantioselective reactions. After Pasteur’s discoveries, many people tried to prepare optically active
compounds from inactive precursors, though without making much distinction
between racemic or prochiral starting materials. These attempts to generate enantiomerically enriched products were most of the time carried out by fermentation in presence of a microorganism. The synthesis of optically active mandelonitrile by addition of HCN to benzaldehyde, catalyzed by an isolated enzyme,
emulsin from almonds, was reported by Rosenthaler in 1908 [8]. It was clearly
recognized by the author as a case of asymmetric synthesis as defined by Marckwald. Another early example of bioorganic catalysis is the work of Hayashi in
1929, who rearranged phenylgloxal (hydrate) into mandelic acid (95% ee) in the
presence of B. proteus [9].
3

The First Examples of Non-enzymatic Enantioselective Catalysis
Bredig, in a pioneering investigation in 1908, was able to prepare mandelonitrile
1 from benzaldehyde and HCN in the presence of an alkaloid (quinine or quinidine) as catalyst (Scheme 1) [10]. The enantioselectivities were less than 10%,
however this work was conceptually important, though it did not lead to developments in other laboratories. It was only in 1955 that Prelog and Wilhelm reinvestigated this system and proposed a mechanistic picture [11].
Asymmetric catalysis in oxidation reactions by molecular oxygen with a chiral cobalt catalyst was studied by Shibata et al. in 1931 for the kinetic resolution

O
H

Scheme 1

+

HCN

Cat*

OH
CN
H

1

*

Cat* : emulsin

Rosenthaler, 1908 [8]

Cat* : alkaloids

Bredig, 1912 [10]


4

Henri B. Kagan

of a racemic mixture [12]. This interesting work will not be detailed here since
it is outside of the scope of this chapter.
Another approach to asymmetric catalysis was proposed in Japan in the late
1950s by Akabori, Izumi et al. [13]. It was based on heterogeneous catalysis, a
metal being modified by a chiral environment. The first attempt made was to impregnate silk with palladium dichloride which was subsequently reduced with
hydrogen. The resulting colloidal palladium being deposited on the silk. Asymmetric hydrogenation of some dehydroaminoacid derivatives gave rise to appreciable ee’s, for example phenylalanine was obtained in 25% ee. Unfortunately,
the experiments were not reproducible.
Izumi et al. then developed another type of catalyst, Raney nickel modified by
tartaric acid [14]. Using this, methyl acetoacetate could be hydrogenated into
methyl β-hydroxybutyrate with an ee of up to 80%. Unfortunately, only some
specific substrates were reduced enantioselectively. However, some interesting
developments were later realized (vide infra).
4

Enantioselective Catalysis Until 1980
4.1
Organometallic Catalysis
4.1.1
Asymmetric Polymerization
Organometallic catalysis was stimulated by industrial research, especially in
Germany before and during the last world war. Of course, there were no projects
devoted to asymmetric synthesis.
The discovery of the stereoregular polymerization of alkenes by Ziegler-Natta
catalysis opened a possible route to optically active polymers by a suitable modification of the catalyst. Indeed, Natta, in 1961, succeeded in polymerizing benzofurane 2 (Scheme 2) under the influence of a catalyst obtained by a combining
of AlCl3 and phenylalanine. Optical activity was detected for the polymer [15].
This reaction seems the first example of homogeneous asymmetric catalysis by
a metal complex, however it is difficult to estimate the efficiency of the process
from the specific rotation of the polymer. The asymmetric polymerization of
1,3-pentadiene was also studied by Natta et al. in 1963 [16]. The chiral catalysts
used were prepared by the combination of titanium tetramenthoxide with either
AlEt3 or AlEt2Cl. In both cases optically active polymers were isolated.