Modern Aldol Reactions, 2 Volume Set

1. Auflage 2004
ISBN: 978-3-527-30714-2
Verlag: WILEY-VCH

Buch, Englisch, 679 Seiten, Format (B × H): 175 mm x 249 mm, Gewicht: 1520 g

Das ganze Spektrum der Aldolreaktionen in zwei Bänden: Diese Monografie erspart Ihnen zeitraubende Recherchen in der weit verstreuten Originalliteratur! Ausgehend von den Grundlagen beantwortet Ihnen das praxiserfahrene Autorenteam alle denkbaren Fragen zu Enolaten, katalytischen und enzymatischen Aldolreaktionen sowie zu speziellen Namensreaktionen. Mit einem Vorwort von Professor D. A. Evans.

Zielgruppe

Organiker, Katalyse-Chemiker, Chemiker in der Industrie, Bibliotheken

Autoren/Hrsg.

Mahrwald, Rainer

Weitere Mitwirkende

Evans, David A.

Fachgebiete

• Naturwissenschaften Chemie Organische Chemie Biochemie
• Naturwissenschaften Chemie Chemie Allgemein Pharmazeutische Chemie, Medizinische Chemie
• Naturwissenschaften Chemie Chemie Allgemein Chemometrik, Chemoinformatik
• Naturwissenschaften Chemie Chemie Allgemein Chemische Labormethoden, Stöchiometrie
• Naturwissenschaften Chemie Chemie Allgemein Toxikologie, Gefahrstoffe, Sicherheit in der Chemie

Inhaltsverzeichnis

Fundamentals and Transition State Models
The Development of Titanium Enolate Based Aldol Reactions
Boron and Silicon Enolates in Crossed Aldol Reaction
Silver, Gold and Palladium Lewis-Acids
Boron and Silicon Lewis Acids for Mukaiyama Aldol Reactions
Copper Lewis Acids
Tin-promoted Aldol Reactions and Their Applications to Total Syntheses of Natural Products
Zirconium Alkoxides as Lewis Acids
Direct Catalytic Asymmetric Aldol Reaction Using Chiral Metal Complexes
Catalytic Enantioselective Aldol Additions with Chiral Lewis Bases
Amine-Catalyzed Aldol Reactions
Enzyme Catalyzed Aldol Additions
Antibody-Catalyzed Aldol Reactions
The Aldol-Tishchenko Reaction
The Aldol Reaction in Natural Product Synthesis: The Epothilone
Story

Volume 1

Preface xvii

List of Contributors xix

1 Fundamentals and Transition-state Models. Aldol Additions of Group 1 and 2 Enolates 1
Manfred Braun

1.1 Introduction 1

1.2 The Acid or Base-mediated ‘‘Traditional’’ Aldol Reaction 2

1.3 The Aldol Addition of Preformed Enolates – Stereoselectivity and Transition-state Models 9

1.4 Stereoselective Aldol Addition of Lithium, Magnesium and Sodium Enolates 25

1.4.1 Addition of Chiral Enolates to Achiral Carbonyl Compounds 26

1.4.1.1 a-Substituted Enolates 26

1.4.1.2 a-Unsubstituted Enolates 32

1.4.2 Addition of Achiral Enolates to Chiral Carbonyl Compounds 41

1.4.3 Addition of Chiral Enolates to Chiral Carbonyl Compounds 49

1.4.4 Addition of Achiral Enolates to Achiral Carbonyl Compounds in the Presence of Chiral Additives and Catalysts 51

1.5 Conclusion 52

References 53

2 The Development of Titanium Enolate-based Aldol Reactions 63
Arun K. Ghosh, M. Shevlin

2.1 Introduction 63

2.2 Additions of Enolates to Ketones 65

2.3 Addition of Enolates Without a-Substituents to Aldehydes 66

2.3.1 Stereoselective Acetate Aldol Reactions Using Chiral Auxiliaries 67

2.3.2 Stereoselective Acetate Aldol Reactions Involving Chiral Titanium Ligands 69

2.3.3 Alternative Approaches to Acetate Aldol Adducts 70

2.4 Addition of Enolates with a-Substituents to Aldehydes 72

2.4.1 Syn Diastereoselectivity 74

2.4.1.1 Synthesis of syn Aldols in Racemic Form 75

2.4.1.1.1 Reactions of Ketones 75

2.4.1.1.2 Reactions of Esters and Thiol Esters 77

2.4.1.1.3 Aldol Reactions of Aldehyde Hydrazones 78

2.4.1.2 Synthesis of Optically Active syn Aldols Using Chiral Auxiliaries 80

2.4.1.2.1 Amino Acid-derived Oxazolidinone and Related Auxiliaries 80

2.4.1.2.2 Camphor-derived Chiral Auxiliaries 84

2.4.1.2.3 Aminoindanol and Amino Acid-derived Chiral Auxiliaries 87

2.4.1.2.4 Other Chiral Auxiliaries 90

2.4.1.3 Synthesis of Optically Active syn Aldols Using Chiral Titanium Ligands 92

2.4.1.4 Synthesis of Optically Active syn Aldols with Chiral Enolates 95

2.4.2 Anti Diastereoselectivity 98

2.4.2.1 Synthesis of anti Aldols in Racemic Form 98

2.4.2.2 Synthesis of Optically Active anti Aldols by Use of Chiral Auxiliaries 99

2.4.2.2.1 Aminoindanol and Related Chiral Auxiliaries 99

2.4.2.2.2 Oxazolidinethione and Oxazolidineselone Chiral Auxiliaries 103

2.4.2.3 Synthesis of Optically Active anti Aldols by Use of Chiral Titanium Ligands 104

2.5 Natural Product Synthesis via Titanium Enolate Aldol Reactions 105

2.5.1 Lactone Natural Products 105

2.5.1.1 Tetrahydrolipstatin 106

2.5.1.2 Myxopyronins A and B 106

2.5.1.3 Callystatin A 107

2.5.1.4 Ai-77-B 108

2.5.2 Macrolide Natural Products 110

2.5.2.1 Epothilone 490 110

2.5.2.2 Cryptophycin B 110

2.5.2.3 Amphidinolide T1 111

2.5.2.4 Rapamycin 112

2.5.2.5 Spongistatins 1 and 2 113

2.5.3 Miscellaneous Natural Products 114

2.5.3.1 Tautomycin 114

2.5.3.2 Crocacin C 115

2.5.3.3 Stigmatellin A 116

2.5.3.4 Denticulatin B 117

2.5.3.5 Membrenone C 119

2.6 Typical Experimental Procedures for Generation of Titanium Enolates 120

2.6.1 Experimental Procedures 120

2.6.2 Alternative Approaches to Titanium Enolate Generation 121

2.7 Conclusion 121

References 122

3 Boron and Silicon Enolates in Crossed Aldol Reaction 127
Teruaki Mukaiyama and Jun-ichi Matsuo

3.1 Introduction 127

3.2 Crossed Aldol Reactions Using Boron Enolates 127

3.2.1 Discovery of Aldol Reaction Mediated by Boron Enolates 127

3.2.2 New Method for Direct Generation of Boron Enolates 129

3.2.3 Regioselectivity on Generation of Boron Enolates 130

3.2.4 Stereoselective Formation of (E) or (Z) Boron Enolates 131

3.2.5 syn-Selective Asymmetric Boron Aldol Reactions 134

3.2.6 anti-Selective Asymmetric Aldol Reaction 135

3.3 Crossed Aldol Reactions Using Silicon Enolates 137

3.3.1 Discovery of Silicon Enolate-mediated Crossed Aldol Reactions 137

3.3.2 Lewis Acid-catalyzed Aldol Reactions of Silicon Enolates 143

3.3.3 Non-catalyzed Aldol Reactions of Silicon Enolates 147

3.3.4 Lewis Base-catalyzed Aldol Reactions of Trimethylsilyl Enolates 148

3.3.5 Diastereoselective Synthesis of Polyoxygenated Compounds 149

3.3.6 Asymmetric Aldol Reactions Using Chiral Tin(II) Lewis Acid Catalysts 150

3.3.6.1 Stoichiometric Enantioselective Aldol Reaction 151

3.3.6.2 Catalytic Enantioselective Aldol Reaction 154

References 155

4 Amine-catalyzed Aldol Reactions 161
Benjamin List

4.1 Introduction 161

4.2 Aminocatalysis of the Aldol Reaction 162

4.2.1 Intermolecular Aldolizations 163

4.2.1.1 Aldehyde Donors 164

4.2.1.2 Ketone Donors 166

4.2.2 Intramolecular Aldolizations 167

4.2.2.1 Enolexo Aldolizations 167

4.2.2.2 Enolendo Aldolizations 171

4.3 Asymmetric Aminocatalysis of the Aldol Reaction 173

4.3.1 Intramolecular Aldolizations 173

4.3.1.1 Enolendo Aldolizations 173

4.3.1.2 Enolexo Aldolizations 177

4.3.2 Intermolecular Aldolizations 179

4.3.2.1 Ketone Donors 179

4.3.2.2 Aldehyde Donors 193

References 196

5 Enzyme-catalyzed Aldol Additions 201
Wolf-Dieter Fessner

5.1 Introduction 201

5.2 General Aspects 202

5.2.1 Classification of Lyases 202

5.2.2 Enzyme Structure and Mechanism 204

5.2.3 Practical Considerations 207

5.3 Pyruvate Aldolases 208

5.3.1 N-Acetylneuraminic Acid Aldolase 208

5.3.2 KDO Aldolase 216

5.3.3 DAHP Synthase 217

5.3.4 KDPG Aldolase and Related Enzymes 218

5.4 Dihydroxyacetone Phosphate Aldolases 221

5.4.1 FruA 222

5.4.2 TagA 224

5.4.3 RhuA and FucA 224

5.4.4 DHAP Synthesis 227

5.4.5 Applications 230

5.4.6 Aldol Transfer Enzymes 246

5.5 Transketolase and Related Enzymes 247

5.6 2-Deoxy-D-ribose 5-Phosphate Aldolase 250

5.7 Glycine Aldolases 254

5.8 Recent Developments 257

5.9 Summary and Conclusion 258

References 260

6 Antibody-catalyzed Aldol Reactions 273
Fujie Tanaka and Carlos F. Barbas, III

6.1 Introduction 273

6.2 Generation of Aldolase Antibodies 273

6.2.1 Antibody as Catalyst Scaffold 273

6.2.2 Generation of Aldolase Antibodies that Operate via an Enamine Mechanism 274

6.2.2.1 Reactive Immunization with the Simple Diketone Derivative 275

6.2.2.2 Combining Reactive Immunization with Transition-state Analogs 277

6.2.2.3 Reactive Immunization with other Diketones 279

6.3 Aldolase Antibody-catalyzed Aldol and Retro-aldol Reactions 279

6.3.1 Antibody 38C2-catalyzed Aldol Reactions 280

6.3.2 Antibody 38C2-Catalyzed Retro-aldol Reactions and their Application to Kinetic Resolution 283

6.3.3 Aldol and Retro-aldol Reactions Catalyzed by Antibodies 93F3 and 84G3 285

6.3.4 Preparative-scale Kinetic Resolution Using Aldolase Antibodies in a Biphasic Aqueous–Organic Solvent System 288

6.3.5 Aldolase Antibody-catalyzed Reactions in Natural Product Synthesis 290

6.3.6 Retro-aldol Reactions in Human Therapy: Prodrug Activation by Aldolase Antibody 291

6.4 Aldolase Antibodies for Reactions Related to an Enamine Mechanism and the Nucleophilic Lysine e-Amino Group 293

6.5 Concise Catalytic Assays for Aldolase Antibody-catalyzed Reactions 297

6.6 Structures of Aldolase Antibodies and Reaction Mechanism of Nucleophilic Lysine e-Amino Group 298

6.7 Evolution of Aldolase Antibodies In Vitro 302

6.8 Cofactor-mediated Antibody-catalyzed Aldol and/or Retro-aldol Reactions 305

6.9 Summary and Conclusion 305

6.10 Experimental Procedures 306

Acknowledgments 307

References 307

7 The Aldol Reaction in Natural Product Synthesis: The Epothilone Story 311
Dieter Schinzer

7.1 History of Epothilones: Biological Source, Isolation, and Structural Elucidation 311

7.2 History of Epothilones: The Total Synthesis Race 311

7.2.1 Different Strategies with Aldol Reactions: The Danishefsky Synthesis of Epothilone A Relying on Intramolecular Aldol Reaction 312

7.2.2 Different Strategies with Aldol Reactions: The Nicolaou Synthesis of Epothilone A Using an Unselective Aldol Reaction 313

7.2.3 Different Strategies with Aldol Reactions: The Schinzer Synthesis of Epothilone A with Complete Stereocontrol in the Aldol Reaction 314

7.3 Model Study via Chelation Control in the Aldol Reaction by Kalesse 319

7.3.1 Different Aldol Strategies: Mulzer’s Total Syntheses of Epothilones B and D 320

7.4 Long-range Structural Effects on the Stereochemistry of Aldol Reactions 322

7.5 Summary and Conclusion 326

References 326

Index 329

Volume 2

Preface xvii

List of Contributors xix

1 Silver, Gold, and Palladium Lewis Acids 1
Akira Yanagisawa

1.1 Introduction 1

1.2 Mukaiyama Aldol Reaction and Related Reactions 1

1.3 Asymmetric Aldol Reactions of a-Isocyanocarboxylates 8

1.4 Summary and Conclusions 15

1.5 Experimental Procedures 18

References 21

2 Boron and Silicon Lewis Acids for Mukaiyama Aldol Reactions 25
Kazuaki Ishihara and Hisashi Yamamoto

2.1 Achiral Boron Lewis Acids 25

2.1.1 Introduction 25

2.1.2 BF3 · Et2O 26

2.1.3 B(C6F5)3 29

2.1.4 Ar2BOH 30

2.2 Chiral Boron Lewis Acids 33

2.2.1 Introduction 33

2.2.2 Chiral Boron Lewis Acids as Stoichiometric Reagents 33

2.2.3 Chiral Boron Lewis Acids as Catalytic Reagents 40

2.3 Silicon Lewis Acids 53

2.3.1 Introduction 53

2.3.2 Lewis Acidity of Silicon Derivatives 54

2.3.3 Silicon Lewis Acids as Catalytic Reagents 55

2.3.4 Activation of Silicon Lewis Acids by Combination with Other Lewis Acids 60

References 65

3 Copper Lewis Acids 69
Jeffrey S. Johnson and David A. Nicewicz

3.1 Introduction 69

3.2 Early Examples 69

3.3 Mukaiyama Aldol Reactions with Cu(II) Complexes 70

3.3.1 Enolsilane Additions to (Benzyloxy)acetaldehyde 70

3.3.1.1 Scope and Application 70

3.3.1.2 Mechanism and Stereochemistry 75

3.3.2 Enolsilane Additions to a-Keto Esters 80

3.3.2.1 Scope and Application 80

3.3.2.2 Mechanism and Stereochemistry 85

3.3.3 Enolsilane Additions to Unfunctionalized Aldehydes 88

3.4 Additions Involving In-Situ Enolate Formation 90

3.4.1 Pyruvate Ester Dimerization 90

3.4.2 Addition of Nitromethane to a-Keto Esters 91

3.4.3 Malonic Acid Half Thioester Additions to Aldehydes 94

3.4.4 Dienolate Additions to Aldehydes 96

3.4.4.1 Scope and Application 96

3.4.4.2 Mechanistic Considerations 97

3.4.5 Enantioselective Cu(II) Enolate-Catalyzed Vinylogous Aldol Reactions 99

3.5 Conclusions 101

References 102

4 Tin-promoted Aldol Reactions and their Application to Total Syntheses of Natural Products 105
Isamu Shiina

4.1 Introduction 105

4.2 Tin-promoted Intermolecular Aldol Reactions 105

4.2.1 Achiral Aldol Reactions 105

4.2.2 The Reaction of Silyl Enolates with Aldehydes or Ketones 108

4.2.3 The Reaction of Silyl Enolates with Acetals 117

4.2.4 Reaction of Dienol Silyl Ethers 120

4.3 Tin-promoted Intramolecular Aldol Reactions 121

4.3.1 The Intramolecular Aldol Reaction of Silyl Enolates 121

4.3.2 Reaction of Dienol Si

Über Autor(innen)

Born in 1950, Rainer Mahrwald studied chemistry at MLU Halle and subsequently joined the "Manfred von Ardenne" Research Institute in Dresden, where he led the synthetics group. He gained his doctorate under G. Wagner in Leipzig in 1979, and went on to the Institute of Organic Chemistry at the Academy of Science in Berlin, where he remained until 1990. Following a stay at the Philipps-University in Marburg, Dr. Mahrwald qualified as a lecturer at the Humboldt University Berlin, where he is now a private lecturer.