Science of Synthesis: Asymmetric Organocatalysis Vol. 2 (eBook)

Science of Synthesis: Asymmetric Organocatalysis 2 – Brønsted Base and Acid Catalysts, and Additional Topics 1
Organizational Structure of Science of Synthesis 2
Science of Synthesis Reference Library 3
Title page 5
Imprint 7
Preface 8
Asymmetric Organocatalysis Volumes 10
Abstracts 12
Overview 24
Table of Contents 26
2.1 Brønsted Bases 48
2.1.1 Chiral Guanidine and Amidine Organocatalysts 48
2.1.1.1 Synthesis of 2-Aminoacetonitriles 49
2.1.1.1.1 Catalytic Asymmetric Strecker Reactions 49
2.1.1.2 Synthesis of Chiral Alcohols 50
2.1.1.2.1 Catalytic Nitroaldol (Henry) Reactions 50
2.1.1.2.1.1 Nitroaldol Reactions with a-Chiral Aldehydes 53
2.1.1.2.1.2 Nitroaldol Reactions with a-Keto Esters 54
2.1.1.2.2 Catalytic Asymmetric Aldol Reactions 55
2.1.1.2.2.1 Aldol Reactions with Dihalofuran-2(5H)-ones 57
2.1.1.3 Synthesis of Chiral Amines 59
2.1.1.3.1 Catalytic Asymmetric Nitro-Mannich-Type Reactions 59
2.1.1.3.1.1 Nitro-Mannich-Type Reactions with Nitroacetates 63
2.1.1.3.1.2 Nitro-Mannich-Type Reactions with a-Substituted Nitroacetates 64
2.1.1.3.2 Catalytic Asymmetric Mannich-Type Reactions 65
2.1.1.4 Synthesis of Chiral Nitroalkanes 67
2.1.1.4.1 Catalytic Asymmetric Michael Reactions 67
2.1.1.4.1.1 Michael Reactions with ß-Keto Esters 69
2.1.1.4.1.2 Michael Reactions with Phenols 71
2.1.1.4.1.3 Michael Reactions with Nitroalkanes 72
2.1.1.4.1.4 Michael Reactions with 4,7-Dihydroindoles 73
2.1.1.5 Synthesis of Chiral Epoxy Ketones 75
2.1.1.5.1 Catalytic Asymmetric Nucleophilic Epoxidation Reactions 75
2.1.1.6 Synthesis of Chiral Hydrazines 76
2.1.1.6.1 Catalytic Asymmetric Amination Reactions 76
2.1.1.7 Synthesis of Chiral Phosphonates and Phosphine Oxides 78
2.1.1.7.1 Catalytic Asymmetric 1,4-Addition Reactions 78
2.1.1.7.1.1 1,4-Addition Reactions with Phosphites 78
2.1.1.7.1.2 1,4-Addition Reactions with Phosphine Oxides 79
2.1.1.8 Synthesis of Chiral d-Lactones 80
2.1.1.8.1 Catalytic Asymmetric Inverse-Electron-Demand Hetero-Diels--Alder Reactions 80
2.1.1.9 Synthesis of Chiral Pyrrolidines 83
2.1.1.9.1 Catalytic Asymmetric [3 + 2]-Cycloaddition Reactions 83
2.1.1.10 Synthesis of Chiral a-Keto Esters 84
2.1.1.10.1 Catalytic Asymmetric Claisen Rearrangement Reactions 84
2.1.2 Cinchona Alkaloid Organocatalysts 88
2.1.2.1 Nucleophilic Catalysis 89
2.1.2.1.1 Asymmetric Reactions with Ketenes 90
2.1.2.1.1.1 Synthesis of ß-Lactones 90
2.1.2.1.1.2 Intramolecular Synthesis of ß-Lactones 91
2.1.2.1.1.3 Synthesis of ß-Lactams 92
2.1.2.1.1.4 Synthesis of ß-Oxo Amides 93
2.1.2.1.1.5 Asymmetric Synthesis of a-Halogenated Esters 94
2.1.2.1.1.6 Cycloaddition of Ketenes and N-Thioacylimines 95
2.1.2.1.2 Asymmetric Morita--Baylis--Hillman Reactions 96
2.1.2.1.2.1 Synthesis of Hydroxy Acrylates 97
2.1.2.1.2.2 Synthesis of Sulfonamido Enones 98
2.1.2.1.3 Enantioselective Protonation 99
2.1.2.1.3.1 Thiol Addition to Alkyl(silyl)ketenes 99
2.1.2.1.4 Asymmetric Cyanation of Simple Ketones 100
2.1.2.1.4.1 Synthesis of Cyanohydrin Carbonates 100
2.1.2.1.5 Asymmetric Conjugate Additions 101
2.1.2.1.5.1 Synthesis of tert-Butyl Cyclopropanecarboxylates 102
2.1.2.1.5.2 Reaction of Indole with Morita--Baylis--Hillman Adducts 102
2.1.2.1.5.3 Reaction of Furan-2-ones with Morita--Baylis--Hillman Adducts 103
2.1.2.1.6 Asymmetric Electrophilic Halogenation of Alkenes 104
2.1.2.1.6.1 Chlorolactonization of Pent-4-enoic Acid 104
2.1.2.2 Enantioselective Base Catalysis 105
2.1.2.2.1 Asymmetric Brønsted Base Catalysis 105
2.1.2.2.1.1 Asymmetric Protonation of Silyl Enol Ethers 106
2.1.2.2.1.2 Alcoholysis of Anhydrides in the Presence of a Cinchona-Derived Catalyst 107
2.1.2.2.1.3 Alcoholysis in the Presence of a Substoichiometric Amount of Catalyst and a Stoichiometric Amount of an Achiral Base 108
2.1.2.2.1.4 Enantioselective Alcoholysis of Monosubstituted Succinic Anhydrides by Parallel Kinetic Resolution 109
2.1.2.2.1.5 Alcoholysis of Urethane-Protected a-Amino Acid N-Carboxyanhydrides by Kinetic Resolution 111
2.1.2.2.1.6 Alcoholysis of 1,3-Dioxolane-2,4-diones by Dynamic Kinetic Resolution 113
2.1.2.2.2 Asymmetric Lewis Base Catalysis 114
2.1.2.2.2.1 Asymmetric Sulfinyl Transfer Reactions via Dynamic Kinetic Resolution of Sulfinyl Chlorides: Synthesis of Sulfinates in the Presence of a Stoichiometric Amount of Catalyst 115
2.1.2.2.2.2 Synthesis of Sulfinates in the Presence of a Catalytic Amount of Catalyst and a Stoichiometric Amount of Achiral Base 116
2.1.2.2.2.3 Fluorodesilylation of Allylsilanes: Synthesis of Chiral Alkyl Fluorides 117
2.1.2.2.2.4 Conjugate Addition of Thiols to Cyclic Enones 118
2.1.2.2.2.5 Conjugate Addition of 1,3-Dicarbonyl Compounds to Alkynones 119
2.1.2.2.2.6 Conjugate Addition of 1,3-Dicarbonyl Compounds to Enones 120
2.1.2.2.2.7 Conjugate Addition of Alkylidenemalononitriles 121
2.1.2.2.2.8 Asymmetric Mannich Reaction of a-Substituted Cyanoacetates 122
2.1.2.2.2.9 Asymmetric Aldol Reaction of Oxindoles with Trifluoropyruvate 123
2.1.2.3 Acid--Base Cooperative Catalysis 124
2.1.2.3.1 Asymmetric 1,2-Addition to Carbonyl Compounds 124
2.1.2.3.1.1 Aldol Reaction of Cyclic Ketones 124
2.1.2.3.1.2 Aldol Reaction of Acyclic Ketones 125
2.1.2.3.1.3 Intramolecular Aldol Reaction of Diketones 127
2.1.2.3.2 Asymmetric 1,2-Addition to Imines 128
2.1.2.3.2.1 Hydrophosphonylation Reaction of Imines with Phosphites 128
2.1.2.3.2.2 Reaction of ß-Oxo Esters with Imines 129
2.1.2.3.3 Asymmetric Friedel--Crafts Reactions 130
2.1.2.3.3.1 Reaction of Indoles and Trifluoropyruvate 131
2.1.2.3.3.2 Reaction of Indoles with Aldehydes or Pyruvates 132
2.1.2.3.3.3 Reaction of Indoles and Imines 134
2.1.2.3.4 Asymmetric Fragmentation 135
2.1.2.3.4.1 Enantioselective Fragmentation of Cyclic meso-Peroxides 136
2.1.2.3.4.2 Desymmetrization of meso-Cyclopropane-Fused Cyclopentanones and Epoxycyclopentanones 137
2.1.2.3.5 Desymmetrization of meso-Diols 138
2.1.2.3.5.1 Monobenzoylation of meso-Diols 138
2.1.2.3.6 Asymmetric Halolactonization 139
2.1.2.3.6.1 Asymmetric Bromolactonization of Pentenoic Acids 139
2.1.2.3.6.2 Asymmetric Bromolactonization of Z-Enynes 140
2.1.2.4 Base--Iminium Catalysis 141
2.1.2.4.1 Asymmetric Conjugate Additions 141
2.1.2.4.1.1 Vinylogous Michael Addition of a,a-Dicyanoalkenes to Enones 142
2.1.2.4.1.2 Conjugate Addition of Benzannulated Cyclic 1,3-Dicarbonyl Compounds to Enones 143
2.1.2.4.1.3 Conjugate Addition of Nitrogen Nucleophiles to Enones 144
2.1.2.4.1.4 Aziridination of Enones 145
2.1.2.4.1.5 Epoxidation of Cyclic Enones 146
2.1.2.4.1.6 Epoxidation of Acyclic Enones 148
2.1.2.4.2 Asymmetric Conjugated Friedel--Crafts Alkylations 149
2.1.2.4.2.1 Friedel--Crafts Addition of Indoles to a,ß-Unsaturated Ketones 149
2.1.2.4.3 Asymmetric Diels--Alder Reactions 150
2.1.2.4.3.1 Diels--Alder Reaction of 2H-Pyran-2-ones with a,ß-Unsaturated Ketones 151
2.1.2.4.4 Semipinacol-Type 1,2-Carbon Migrations 152
2.1.2.4.4.1 a-Ketol Rearrangement of Cyclic Hydroxy Enones to Chiral Spirocyclic Diketones 152
2.1.2.5 Multifunctional Cooperative Catalysis 154
2.1.2.5.1 Catalytic Asymmetric Peroxidations 154
2.1.2.5.1.1 Reaction of a,ß-Unsaturated Ketones with Hydroperoxides 154
2.1.2.5.1.2 Synthesis of Cyclic Peroxyhemiketals 158
2.1.2.5.2 1,3-Dipolar Cycloadditions 158
2.1.2.5.2.1 Cycloaddition of Cyclic Enones and Azomethine Imines 159
2.1.2.6 Conclusion 160
2.1.3 Bifunctional Cinchona Alkaloid Organocatalysts 166
2.1.3.1 Bifunctional Cinchona Alkaloid Organocatalysts: Cooperative Catalysis 167
2.1.3.1.1 Bifunctional Catalysts Based on 9-Urea and 9-Thiourea Cinchona Alkaloids 167
2.1.3.1.2 Bifunctional Catalysts Based on 6'-Thiourea Cinchona Alkaloids 183
2.1.3.1.3 Bifunctional Catalysts Based on 9-Squaramide Cinchona Alkaloids 184
2.1.3.1.4 Cupreine and Cupreidine Derivatives as Bifunctional Catalysts 187
2.1.3.1.5 ß-Isocupreidine as a Bifunctional Catalyst 200
2.1.3.2 Bifunctional Cinchona Alkaloid Organocatalysts: Self-Association Problem 203
2.1.3.2.1 Self-Association Phenomena of Bifunctional Organocatalysts 203
2.1.3.2.2 Self-Association-Free Bifunctional Cinchona Alkaloid Organocatalysts 204
2.1.3.2.2.1 9-Squaramide Dimeric Cinchona Alkaloids 204
2.1.3.2.2.2 9-Sulfonamide Cinchona Alkaloids 207
2.1.3.3 Conclusions 212
2.2 Brønsted Acids 216
2.2.1 Phosphoric Acid Catalyzed Reactions of Imines 216
2.2.1.1 Nucleophilic Addition to Imines 217
2.2.1.1.1 Mannich and Related Reactions 218
2.2.1.1.2 Strecker Reaction 224
2.2.1.1.3 Friedel--Crafts Reactions 225
2.2.1.1.4 Ene-Type Reactions 234
2.2.1.1.5 Allylation Reactions 237
2.2.1.1.6 Carbon--Heteroatom Bond-Forming Reactions 238
2.2.1.2 Cycloaddition to Imines 243
2.2.1.2.1 Aza-Diels--Alder Reactions 243
2.2.1.2.2 1,3-Dipolar Cycloaddition 248
2.2.1.3 Transfer Hydrogenation of Imines 252
2.2.1.3.1 Reduction of Imines 252
2.2.1.3.2 Reduction of Quinolines 259
2.2.2 Phosphoric Acid Catalysis of Reactions Not Involving Imines 266
2.2.2.1 Reactions of Carbonyl Compounds 266
2.2.2.1.1 Reactions of a,ß-Unsaturated Carbonyl Compounds 267
2.2.2.1.1.1 Diels--Alder Reaction 267
2.2.2.1.1.2 Friedel--Crafts Reaction 269
2.2.2.1.1.3 Nazarov Cyclization 274
2.2.2.1.1.4 Epoxidation 276
2.2.2.1.1.5 Oxa-Michael Reaction 279
2.2.2.1.1.6 Aza-Michael Reaction 280
2.2.2.1.2 Reactions of Ketones and Aldehydes 281
2.2.2.1.2.1 Aza-Ene-Type Reaction 281
2.2.2.1.2.2 Carbonyl-Ene Reaction 283
2.2.2.1.2.3 Allylboration 284
2.2.2.1.2.4 Hetero-Diels--Alder Reaction 286
2.2.2.1.2.5 Intramolecular Aldol Reaction (Robinson-Type Annulation) 288
2.2.2.1.2.6 Baeyer--Villiger Oxidation 289
2.2.2.2 Reactions of Hemiaminal Ethers and Acetals 291
2.2.2.2.1 Reactions of Hemiaminal Ethers 291
2.2.2.2.1.1 Aza-Ene Type Reaction 291
2.2.2.2.1.2 Aza-Petasis--Ferrier Rearrangement 295
2.2.2.2.2 Reactions of Acetals 296
2.2.2.3 Reactions of Nitroalkenes 298
2.2.2.3.1 Friedel--Crafts Reaction 298
2.2.2.4 Reactions of Nitrones 301
2.2.2.4.1 1,3-Dipolar Cycloaddition 301
2.2.2.5 Reactions of Nitroso Compounds 302
2.2.2.5.1 a-Hydroxylation of 1,3-Dicarbonyl Compounds 302
2.2.2.5.2 a-Aminoxylation of Enecarbamates 304
2.2.2.6 Reactions of Strained Small-Ring Compounds 304
2.2.2.6.1 Ring Opening of Aziridines and Related Reactions 304
2.2.2.7 Reactions of Electron-Rich Alkenes 309
2.2.2.7.1 Reactions of Enecarbamates and Enamides 309
2.2.2.7.1.1 Friedel--Crafts Reaction 309
2.2.2.7.1.2 Aza-Ene-Type Reaction 311
2.2.2.7.2 Reactions of Vinyl Ethers and Analogues 312
2.2.2.7.2.1 Aldol-Type Reaction 312
2.2.2.7.2.2 Semipinacol Rearrangement 314
2.2.2.7.2.3 Protonation of Silyl Enol Ethers 316
2.2.2.7.2.4 Addition Reaction to Vinyl-1H-indoles 317
2.2.2.7.3 Reactions of Nonactivated Alkenes and Analogues 319
2.2.2.7.3.1 Hydroamination of Alkenes 319
2.2.2.7.3.2 Hydroamination of Dienes and Allenes 319
2.2.3 Brønsted Acid Catalysts Other than Phosphoric Acids 326
2.2.3.1 Carboxylic Acids 326
2.2.3.1.1 Imines as Electrophiles 326
2.2.3.1.1.1 Nucleophilic Additions of Diazo Compounds 326
2.2.3.1.1.2 Nucleophilic Additions of Aza-enamines (N,N-Dialkylhydrazones) 329
2.2.3.1.1.3 Alkynylation of Imines 331
2.2.3.1.1.4 Friedel--Crafts Reactions 332
2.2.3.1.2 O-Nitroso Aldol Reactions 333
2.2.3.2 Amides and Sulfonamides 333
2.2.3.2.1 Hetero-Diels--Alder Reactions 333
2.2.3.2.2 Double Michael Addition/Aromatization 335
2.2.3.3 1,1'-Bi-2-naphthol and Its Derivatives 336
2.2.3.3.1 Allyl-, Alkenyl-, Alkynyl-, and Arylborations 336
2.2.3.3.1.1 Allylboration of Ketones 336
2.2.3.3.1.2 Alkenyl- and Alkynylboration of Enones 337
2.2.3.3.1.3 Allyl-, Alkenyl-, Alkynyl-, and Arylboration of Imines 338
2.2.3.3.2 Enamine Mannich Reactions 341
2.2.3.4 Disulfonimides and Aryldisulfonylmethanes 341
2.2.3.4.1 Mukaiyama Aldol Reactions 341
2.2.3.4.2 Mannich-Type Reactions 342
2.2.4 Hydrogen-Bonding Catalysts: (Thio)urea Catalysis 344
2.2.4.1 On the Way to Thiourea Organocatalysts 344
2.2.4.2 Thiourea Derivatives as Organocatalysts in Organic Synthesis 346
2.2.4.2.1 Nonstereoselective Transformations with Achiral Thiourea Derivatives 346
2.2.4.2.2 Stereoselective Transformations with Chiral Thiourea Derivatives 347
2.2.4.3 Michael Addition 348
2.2.4.3.1 Michael Addition of 1,3-Dioxolan-4-ones to 1-Nitro-2-phenylethenes 348
2.2.4.3.2 Michael Addition of Aldehydes to Nitroalkenes 349
2.2.4.3.3 Michael Addition of a-Cyano Ketones to a,ß-Unsaturated Trifluoromethyl Ketones 350
2.2.4.3.4 Michael Addition of Diethyl Malonate to (E)-Chalcones 352
2.2.4.3.5 Michael Addition of Malononitriles to a,ß-Unsaturated 1-Acylpyrrolidinones 353
2.2.4.3.6 Michael Addition of Nitroalkanes to Nitroalkenes 354
2.2.4.3.7 Michael Addition of Oximes to Aliphatic Nitroalkenes 355
2.2.4.3.8 Michael Addition of 3-Substituted Oxindoles to Nitroalkenes 356
2.2.4.3.9 Michael Addition of Oxindoles to Maleimides 358
2.2.4.3.10 Phospha-Michael Addition of Diarylphosphine Oxides to a,ß-Unsaturated Ketones 359
2.2.4.3.11 Sulfa-Michael Addition of Alkanethiols to a,ß-Unsaturated N-Acylated Oxazolidin-2-ones 360
2.2.4.3.12 Michael Addition of Cyclohexanone to Nitroalkenes 362
2.2.4.3.13 Intramolecular Michael Addition of Nitronates to Conjugated Esters 363
2.2.4.3.14 Michael Addition of a,a-Disubstituted Aldehydes to Nitroalkenes 364
2.2.4.3.15 Michael Addition of 1,3-Dicarbonyl Compounds to Nitroalkenes 365
2.2.4.3.16 Nitrocyclopropanation of a,ß-Unsaturated a-Cyanoimides with Bromonitromethane 367
2.2.4.3.17 Michael Addition: Substrate Scope 368
2.2.4.4 Mannich Reaction 369
2.2.4.4.1 Mannich Reaction of Phosphorus Ylides with Imines 369
2.2.4.4.2 Mannich Reaction of Malonates with Imines 369
2.2.4.4.3 Mannich Reaction of Fluorinated ß-Keto Esters with Imines 370
2.2.4.4.4 Mannich Reactions of a-Amido Sulfones or Sulfonylimines 371
2.2.4.4.5 Mannich Reaction of Lactones with Imines 374
2.2.4.4.6 Mannich Reaction of Oxindoles with Imines 375
2.2.4.4.7 Mannich Reaction of Ketones with Hydrazones 376
2.2.4.4.8 Mannich Reaction of Ketene Silyl Acetals with Imines 377
2.2.4.4.9 Vinylogous Mannich Reaction 378
2.2.4.4.10 Nitro-Mannich Reaction/Aza-Henry Reaction 379
2.2.4.4.10.1 Nitro-Mannich/Aza-Henry Reaction of Nitroalkanes with Imines 379
2.2.4.4.10.2 Nitro-Mannich/Aza-Henry Reaction of Nitroalkanes with a-Amido Sulfones 381
2.2.4.4.10.3 Nitro-Mannich/Aza-Henry Reaction of Nitroacetates with Imines 382
2.2.4.4.11 Acyl-Mannich Reaction 383
2.2.4.4.12 anti-Mannich Reaction 385
2.2.4.5 Henry Reaction/Nitroaldol Reaction 386
2.2.4.6 Aldol Reaction 387
2.2.4.6.1 Aldol Reaction of a-Isothiocyanato Imides with Aldehydes 387
2.2.4.6.2 Aldol Reaction of a-Isothiocyanato Imides with a-Keto Esters 388
2.2.4.6.3 Aldol Reaction of Aromatic Aldehydes with Cyclohexanone 389
2.2.4.6.4 Vinylogous Aldol Reaction 390
2.2.4.6.5 Vinylogous Mukaiyama Aldol Reaction 391
2.2.4.7 Morita--Baylis--Hillman Reaction 393
2.2.4.7.1 Morita--Baylis--Hillman Reaction of Cyclohex-2-enone with Aldehydes 393
2.2.4.7.2 Morita--Baylis--Hillman Reaction of Methyl Vinyl Ketone with Aldehydes 396
2.2.4.7.3 Aza-Morita--Baylis--Hillman Reaction of Imines with Acrylates or Methyl Vinyl Ketone 397
2.2.4.7.4 Aza-Morita--Baylis--Hillman-Type Reactions of N-Tosylimines with Nitroalkenes 399
2.2.4.8 Strecker Reaction 400
2.2.4.8.1 Strecker Reaction: Catalytic Addition of Hydrogen Cyanide or Trimethylsilyl Cyanide to Aldimines 400
2.2.4.8.2 Strecker Reaction: Catalytic Addition of Hydrogen Cyanide or Trimethylsilyl Cyanide to Ketimines 405
2.2.4.8.3 Strecker Reaction: Acylcyanation of Imines 406
2.2.4.8.4 Acyl-Strecker Reaction in One Pot 407
2.2.4.9 Cyanosilylation 409
2.2.4.10 Hydrophosphonylation 410
2.2.4.10.1 Hydrophosphonylation of Imines 410
2.2.4.10.2 Hydrophosphonylation of a-Keto Esters 412
2.2.4.11 Friedel--Crafts Reaction 413
2.2.4.11.1 Friedel--Crafts Reaction of Indoles with Imines 413
2.2.4.11.2 Friedel--Crafts Reaction of Naphthols with Nitroalkenes 414
2.2.4.11.3 Friedel--Crafts Reaction of Naphthols with ß,.-Unsaturated a-Keto Esters 416
2.2.4.11.4 Friedel--Crafts Reactions of Sesamol with Nitrostyrenes 417
2.2.4.11.5 Friedel--Crafts Reaction of Indoles with Acylphosphonates 418
2.2.4.12 Desymmetrizations 420
2.2.4.12.1 meso-Anhydride Desymmetrization 420
2.2.4.12.2 Ring Opening of Aziridines 423
2.2.4.13 Kinetic Resolutions 424
2.2.4.13.1 Kinetic Resolution of Propargylic Amines 424
2.2.4.14 Cycloadditions 426
2.2.4.14.1 Diels--Alder Reaction 426
2.2.4.14.2 [3 + 2] Cycloaddition 428
2.2.4.14.3 1,3-Dipolar Cycloaddition 429
2.2.4.15 Pictet--Spengler Reaction 430
2.2.4.15.1 Cyclization of Hydroxy Lactams 430
2.2.4.15.2 Cyclization of Pyrroles onto N-Acyliminium Ions 432
2.2.4.15.3 Acyl-Pictet--Spengler Reaction 433
2.2.4.15.4 Protio-Pictet--Spengler Reaction 435
2.2.4.16 Biginelli Reaction 436
2.2.4.16.1 Biginelli Reaction of (Thio)ureas with Benzaldehydes and Ethyl Acetoacetate 436
2.2.4.17 Petasis Reaction 438
2.2.4.17.1 Petasis-Type 2-Vinylation of Quinolines 438
2.2.4.18 Transfer Hydrogenation 440
2.2.4.18.1 Transfer Hydrogenation of Nitroalkenes 440
2.2.4.18.2 Transfer Hydrogenation of ß-Nitroacrylates 441
2.2.4.19 Reduction of Ketones 442
2.2.4.20 a-Amination 443
2.2.4.20.1 a-Amination of a-Cyano Ketones 443
2.2.4.20.2 a-Amination of Aldehydes 445
2.2.4.21 a-Alkylation of Aldehydes 447
2.2.4.22 a-Chlorination of Aldehydes 449
2.2.4.23 Cationic Polycyclization 450
2.2.4.23.1 Cationic Polycyclizations of Lactam Derivatives 450
2.2.4.24 Addition to Oxocarbenium Ions 452
2.2.4.24.1 Addition to Oxocarbenium Ions: Synthesis of 3,4-Dihydro-1H-2-benzopyran Derivatives 452
2.2.5 Hydrogen-Bonding Catalysts Other than Ureas and Thioureas 460
2.2.5.1 Nonionic Hydrogen-Bonding Catalysts 460
2.2.5.1.1 Diols 460
2.2.5.1.1.1 Hetero-Diels--Alder Reactions 460
2.2.5.1.1.2 Diels--Alder Reactions 462
2.2.5.1.1.3 Mukaiyama Aldol Reactions 463
2.2.5.2 Ionic Hydrogen-Bonding Catalysts 466
2.2.5.2.1 Guanidinium and Amidinium Salts 466
2.2.5.2.1.1 Diels--Alder Reactions 466
2.2.5.2.1.2 Aza-Henry Reactions 467
2.2.5.2.1.3 Phospha-Mannich Reactions 469
2.2.5.2.1.4 Michael Additions 470
2.2.5.2.1.5 Claisen Rearrangements 471
2.2.5.2.2 Aminophosphonium Salts 473
2.2.5.2.2.1 Henry Reactions 473
2.2.5.2.2.2 Hydrophosphonylation Reactions 474
2.2.5.2.2.3 Mannich-Type Reactions 475
2.2.5.2.2.4 Michael Additions 476
2.2.5.2.2.5 Hetero-Michael Additions 477
2.2.5.2.2.6 Protonation Reactions 478
2.2.5.2.3 Pyridinium and Quinolinium Salts 479
2.2.5.2.3.1 Mannich-Type Reactions 479
2.2.5.2.3.2 Michael Additions 480
2.2.6 Bifunctional (Thio)urea and BINOL Catalysts 484
2.2.6.1 Bifunctional Amino (Thio)ureas 484
2.2.6.1.1 Michael Addition with Nitroalkenes and Alkenyl Sulfones 484
2.2.6.1.1.1 Addition of Active Methylene Compounds 484
2.2.6.1.1.2 Addition of Ketones and Aldehydes 492
2.2.6.1.1.3 Addition of Heteroatomic Compounds 496
2.2.6.1.2 Michael Addition to a,ß-Unsaturated Ketones and Carboxylic Acid Derivatives 498
2.2.6.1.2.1 Addition of Active Methylene Compounds to a,ß-Unsaturated Ketones 498
2.2.6.1.2.2 Addition of Carbon and Heteroatom Nucleophiles to a,ß-Unsaturated Imides and Esters 499
2.2.6.1.3 1,2-Nucleophilic Additions with Aldehydes and Ketones 504
2.2.6.1.3.1 Addition of Carbon Nucleophiles to Aldehydes 504
2.2.6.1.3.2 Addition of Trimethylsilyl Cyanide and Hydride to Ketones 508
2.2.6.1.3.3 Addition of Alcohols to Lactones 511
2.2.6.1.4 1,2-Nucleophilic Additions with Imines 512
2.2.6.1.4.1 Addition of Active Methylene Compounds 512
2.2.6.1.4.2 Addition of Ketones 515
2.2.6.1.4.3 Addition of 1,1-Dicyanoalkenes 516
2.2.6.1.5 Amination Reaction with Azodicarboxylates 518
2.2.6.1.5.1 Addition of ß-Oxo Esters 518
2.2.6.1.6 Other Amino Thiourea Catalyzed Reactions 519
2.2.6.1.6.1 Asymmetric Nazarov Cyclization 519
2.2.6.1.6.2 Asymmetric a-Alkylation of Aldehydes 520
2.2.6.1.6.3 Asymmetric Iodolactonization of Alkenoic Acids 522
2.2.6.2 Bifunctional Hydroxy (Thio)ureas 524
2.2.6.2.1 Michael Addition with Electron-Deficient Alkenes 524
2.2.6.2.1.1 Friedel--Crafts-Type Alkylation of Indoles with Nitroalkenes 524
2.2.6.2.1.2 Michael Addition of Formaldehyde N,N-Dialkylhydrazones to ß,.-Unsaturated a-Oxo Esters 526
2.2.6.2.1.3 Michael Addition of Alkenylboronic Acids to .-Hydroxy Enones 527
2.2.6.2.2 1,2-Nucleophilic Addition with Imines and Quinolines 529
2.2.6.2.2.1 Aza-Henry Reaction 529
2.2.6.2.2.2 Petasis-Type Reaction of Quinolines with Alkenylboronic Acids 530
2.2.6.3 Other Bifunctional (Thio)ureas 532
2.2.6.3.1 Sulfinamide Ureas 532
2.2.6.3.1.1 Allylation of Acylhydrazones 532
2.2.6.3.2 Phosphino Thioureas 534
2.2.6.3.2.1 [3 + 2] Cycloaddition of an Imine and an Allene 534
2.2.6.3.2.2 Aza-Morita--Baylis--Hillman Reaction with Imines 536
2.2.6.3.2.3 Ring Opening of Aziridines 538
2.2.6.4 Bifunctional BINOLs 540
2.2.6.4.1 BINOL-Pyridine Catalysts 540
2.2.6.4.1.1 Aza-Morita--Baylis--Hillman Reaction with Imines 540
2.3 Additional Topics 546
2.3.1 Phase-Transfer Catalysis: Natural-Product-Derived PTC 546
2.3.1.1 Cinchona-Derived Phase-Transfer Catalysts 548
2.3.1.1.1 Alkylation Reactions 548
2.3.1.1.1.1 a-Alkylation of a Glycine Schiff Base 548
2.3.1.1.1.2 a,a-Dialkylation of a Glycine Schiff Base 567
2.3.1.1.1.3 a-Alkylation of 4,5-Dihydrooxazole- and 4,5-Dihydrothiazole-4-carboxylates 570
2.3.1.1.1.4 a-Alkylation of a-Alkoxycarbonyl Compounds 572
2.3.1.1.1.5 a-Alkylation of ß-Oxo Esters 573
2.3.1.1.2 Michael Additions 576
2.3.1.1.3 Aldol Reactions 580
2.3.1.1.4 Mannich Reaction 582
2.3.1.1.5 Epoxidation Reactions 583
2.3.1.1.5.1 Epoxidation with Hydrogen Peroxide 584
2.3.1.1.5.2 Epoxidation with Potassium Hypochlorite 585
2.3.1.1.6 Asymmetric Darzens Reactions 586
2.3.1.1.7 Aziridination Reactions 588
2.3.1.1.8 Hydroxylation Reactions 589
2.3.1.1.8.1 a-Hydroxylation 589
2.3.1.1.8.2 a-Dihydroxylation 589
2.3.1.1.9 a-Fluorination Reactions 590
2.3.1.2 Tartrate-Derived Phase-Transfer Catalysts 591
2.3.2 Phase-Transfer Catalysis: Non-Natural-Product-Derived PTC 598
2.3.2.1 Asymmetric Alkylation 598
2.3.2.1.1 Asymmetric Benzylation of a Glycine Derivative for the Synthesis of a Phenylalanine Derivative 598
2.3.2.1.1.1 Asymmetric Alkylation of Glycine Derivatives for the Synthesis of a-Alkyl-a-amino Acids 602
2.3.2.1.1.2 Asymmetric Alkylation of a Glycine Derivative Using Recyclable Catalysts 602
2.3.2.1.1.3 Synthesis of Biologically Active Compounds via the Asymmetric Alkylation of a Glycine Derivative 604
2.3.2.1.2 Asymmetric Double Alkylation of a Glycine Derivative for the Synthesis of a,a-Dialkyl-a-amino Acids 605
2.3.2.1.2.1 Asymmetric Alkylation of a-Alkyl-a-amino Acid Derivatives for the Synthesis of a,a-Dialkyl-a-amino Acids 605
2.3.2.1.2.2 Asymmetric Alkylation of an Azlactone for the Synthesis of an a,a-Dialkyl-a-amino Acid 606
2.3.2.1.2.3 Asymmetric Synthesis of a-Alkylated Serines 607
2.3.2.1.2.4 Asymmetric Synthesis of a-Alkylated Cysteines 607
2.3.2.1.2.5 Asymmetric Synthesis of Cyclic a-Alkyl Amino Acids 608
2.3.2.1.3 N-Terminal Alkylation of Dipeptides 608
2.3.2.1.3.1 N-Terminal Alkylation of Tri- and Tetrapeptides 610
2.3.2.1.3.2 Alkylation of the Peptide Backbone of a C-Terminal Azlactone 610
2.3.2.1.4 Asymmetric Alkylation of a Glycine Amide Schiff Base 611
2.3.2.1.4.1 Diastereo- and Enantioselective Alkylation of a Glycine Amide Schiff Base through Kinetic Resolution of ß-Branched Racemic Alkyl Halides 612
2.3.2.1.4.2 Asymmetric Alkylation of a Protected Glycine Weinreb Amide 612
2.3.2.1.5 Asymmetric Alkylation of ß-Keto Esters 614
2.3.2.1.5.1 Asymmetric Alkylation of a 3-Oxoproline Derivative 614
2.3.2.1.5.2 Asymmetric Alkylation of a-(Benzoyloxy)-ß-keto Esters 615
2.3.2.1.5.3 Asymmetric Alkylation of a ß-Amino-ß-oxo Ester 616
2.3.2.1.6 Asymmetric Alkylation of a-Cyanocarboxylates 616
2.3.2.1.7 Asymmetric Alkylation of a-Alkynyl Esters 617
2.3.2.1.7.1 Alkene Isomerization/a-Alkylation of an a-Alkynylcrotonate as a Route to a 1,4-Enyne 618
2.3.2.1.7.2 Asymmetric Alkylation of 5-[(Triphenylsilyl)ethynyl]-1,3-dioxolan-4-one 618
2.3.2.1.8 Asymmetric Alkylation of Diaryloxazolidine-2,4-diones 619
2.3.2.2 Asymmetric Michael Additions 621
2.3.2.2.1 Asymmetric Michael Addition of Glycine Derivatives 621
2.3.2.2.1.1 Asymmetric Michael Addition of an Alanine Derivative 622
2.3.2.2.1.2 Asymmetric Michael Addition of tert-Butyl 2-(1-Naphthyl)-4,5-dihydrooxazole-4-carboxylate to Ethyl Acrylate 623
2.3.2.2.1.3 Asymmetric Synthesis of (+)-Monomorine 623
2.3.2.2.2 Asymmetric Michael Addition of ß-Keto Esters 624
2.3.2.2.2.1 Asymmetric Michael Addition of ß-Keto Esters to Acetylenic Ketones 625
2.3.2.2.3 Asymmetric Michael Addition of Diethyl Malonate to Chalcone Derivatives 626
2.3.2.2.4 Asymmetric Michael Addition of Nitroalkanes to Alkylidenemalonates 627
2.3.2.2.4.1 Asymmetric Michael Addition of Nitroalkanes to Cyclic a,ß-Unsaturated Ketones 628
2.3.2.2.4.2 Asymmetric Michael Addition of 2-Nitropropane to Chalcone 628
2.3.2.2.5 Asymmetric Michael Addition of Cyanoacetates to Acetylenic Esters 629
2.3.2.2.5.1 Asymmetric Michael Addition of Cyanoacetates to Acetylenic Ketones 630
2.3.2.2.6 Asymmetric Michael Addition of 3-Aryloxindoles to Methyl Vinyl Ketone 631
2.3.2.2.6.1 Asymmetric Michael Addition of 3-Aryloxindoles to Nitroalkenes 632
2.3.2.3 Asymmetric Aldol Reactions 633
2.3.2.3.1 Asymmetric Aldol Reaction of a Glycine Derivative 633
2.3.2.4 Asymmetric Mannich Reactions 634
2.3.2.4.1 Asymmetric Mannich Reaction of a Glycine Derivative 634
2.3.2.4.2 Asymmetric Mannich Reaction of a 3-Phenyloxindole 635
2.3.2.5 Asymmetric Strecker Reactions 635
2.3.2.5.1 Asymmetric Strecker Reaction of Aldimines 635
2.3.2.5.1.1 Asymmetric Strecker Reaction of N-Arylsulfonylated Imines Generated In Situ 636
2.3.2.6 Asymmetric Amination 637
2.3.2.6.1 Asymmetric Amination of ß-Keto Esters 637
2.3.2.7 Asymmetric Fluorination 639
2.3.2.7.1 Asymmetric Fluorination of ß-Keto Esters 639
2.3.2.8 Asymmetric Epoxidation 641
2.3.2.8.1 Asymmetric Epoxidation of a,ß-Unsaturated Ketones 641
2.3.2.9 Asymmetric Neber Rearrangement 642
2.3.2.9.1 Asymmetric Neber Rearrangement of Ketoxime Sulfonates 642
2.3.2.10 Asymmetric Darzens Reactions 643
2.3.2.10.1 Asymmetric Darzens Reaction of Haloamides 643
2.3.3 Computational and Theoretical Studies 648
2.3.3.1 Methodology and Computational Approaches 648
2.3.3.2 Enamine Catalysis 649
2.3.3.2.1 Intramolecular Aldol Reactions 649
2.3.3.2.2 Intermolecular Aldol Reactions 651
2.3.3.2.3 Mannich Reactions 655
2.3.3.2.4 Michael Additions 656
2.3.3.2.5 a-Functionalization of Carbonyl Compounds 658
2.3.3.2.6 .-Functionalization of a,ß-Unsaturated Aldehydes 659
2.3.3.2.7 Organo-SOMO Catalysis 659
2.3.3.3 Iminium Catalysis 660
2.3.3.3.1 Imidazolidinone-Catalyzed Reactions 660
2.3.3.3.2 Iminium Catalysis by Diarylprolinol Silyl Ethers 661
2.3.3.4 Catalysis via Other Types of Lewis Base Activation 662
2.3.3.4.1 Acyl-Transfer Reactions 662
2.3.3.4.2 Carbene-Catalyzed Reactions 663
2.3.3.4.3 Morita--Baylis--Hillman Reactions 664
2.3.3.5 Hydrogen-Bond Catalysis 665
2.3.3.5.1 Thioureas as Hydrogen-Bond Donors 665
2.3.3.5.2 TADDOL-Catalyzed Diels--Alder Reactions 666
2.3.3.5.3 Cationic Hydrogen-Bond Donor Catalysts 667
2.3.3.6 Organocatalysis by Brønsted Bases 668
2.3.3.6.1 Bifunctional Catalysis by Chiral Amines 668
2.3.3.6.2 Guanidines as Bifunctional Organocatalysts 671
2.3.3.7 Organocatalysis by Chiral Brønsted Acids 672
2.3.3.7.1 Asymmetric Addition to Imines 672
2.3.3.7.2 Asymmetric Imine Reduction 675
2.3.3.7.3 Asymmetric Addition to Carbonyls 675
2.3.4 Mechanism in Organocatalysis 680
2.3.4.1 Experimental Methods for Mechanistic Studies in Organocatalysis 680
2.3.4.1.1 Substrate and Product Studies 681
2.3.4.1.2 Catalyst Studies 682
2.3.4.1.2.1 Structure--Performance Relationships 682
2.3.4.1.3 Catalytic Intermediate Studies 684
2.3.4.1.3.1 By NMR Spectroscopy 684
2.3.4.1.3.2 By Mass Spectrometry 686
2.3.4.1.3.3 By X-ray Crystallography 687
2.3.4.1.4 Kinetic Studies 688
2.3.4.1.4.1 Obtaining Kinetic Data 688
2.3.4.1.4.2 Standard Evaluation of Kinetic Data 689
2.3.4.1.4.3 Reaction Progress Kinetic Analysis 690
2.3.4.1.4.4 Kinetic Isotope Effects 692
2.3.4.1.4.5 Hammett Studies 693
2.3.4.1.5 Other Methods 694
2.3.4.1.5.1 Nonlinear Effects in Asymmetric Catalysis 694
2.3.4.1.5.2 Solvent and Water Effects 696
2.3.4.1.5.3 Stereochemical Considerations 696
2.3.4.2 Selected Case Studies 696
2.3.4.2.1 Enamine Catalysis 696
2.3.4.2.1.1 Substrate and Product Studies 697
2.3.4.2.1.2 Catalyst Studies 698
2.3.4.2.1.3 Enamine Formation 701
2.3.4.2.1.4 Enamine Structure 703
2.3.4.2.1.5 Reaction with the Electrophile 704
2.3.4.2.1.6 Kinetic Studies 706
2.3.4.2.1.7 Nonlinear Effects 707
2.3.4.2.2 Iminium Catalysis 707
2.3.4.2.2.1 Catalyst Studies 708
2.3.4.2.2.2 Iminium Formation and Structure 710
2.3.4.2.2.3 Reaction with the Nucleophile 711
2.3.4.2.2.4 Nonlinear Effects 714
2.3.4.2.2.5 Water and Solvent Effects 714
2.3.5 Supported Organocatalysts 720
2.3.5.1 Polymer-Supported Cinchona Alkaloid Amine Catalysts 720
2.3.5.2 Polymer-Supported Proline-Derived Organocatalysts 724
2.3.5.2.1 Cross-Linked Methacrylic Polymer Beads Containing Proline 725
2.3.5.3 Supported Prolinamide Catalysts 726
2.3.5.4 Polymer-Supported Chiral Pyrrolidine Catalysts 729
2.3.5.5 Polymer-Supported Peptides and Poly(amino acids) 729
2.3.5.6 Supported Chiral Quaternary Ammonium Salts 730
2.3.5.6.1 Benzylation of N-(Diphenylmethylene)glycine tert-Butyl Ester Using Polymer-Supported Cinchona Alkaloid Quaternary Ammonium Salts 731
2.3.5.6.2 Benzylation of N-(Diphenylmethylene)glycine tert-Butyl Ester Using Main Chain Chiral Cinchona Alkaloid Quaternary Ammonium Salt Polymers 733
2.3.5.6.3 Epoxidation of Chalcones Using Polymer-Supported Cinchona Alkaloid Quaternary Ammonium Salts 736
2.3.5.7 Supported MacMillan Catalysts 737
2.3.5.8 Supported Chiral Phosphoramides 739
2.3.5.9 Polymer-Supported Chiral Acidic Organocatalysts 739
2.3.6 Organocatalysis Combined with Metal Catalysis or Biocatalysis 744
2.3.6.1 Combination of Phase-Transfer Catalysts with Transition-Metal Complexes 745
2.3.6.2 Combination of Amine Catalysis with Transition-Metal Catalysis 746
2.3.6.2.1 Enamines with p-Allylpalladium Electrophiles 747
2.3.6.2.2 Enamine Catalysis with p-Acid Catalysis 750
2.3.6.2.3 Enamine Catalysis with Photoredox Catalysis 754
2.3.6.2.4 Enamine Catalysis with Rhodium-Catalyzed Hydroformylation 757
2.3.6.2.5 Cinchona Alkaloid Derived Catalysts with p-Acids 758
2.3.6.3 Combination of Brønsted Acids with Transition-Metal Complexes 760
2.3.6.3.1 Cooperative Catalysis of Brønsted Acids with Transition-Metal Complexes 760
2.3.6.3.2 Relay Catalysis of Brønsted Acids with Transition-Metal Complexes 768
2.3.6.4 Combination of Nucleophilic Catalysts with Lewis Acids 777
2.3.6.4.1 Cinchona Alkaloid Derivatives with Lewis Acids 777
2.3.6.4.2 N-Heterocyclic Carbenes with Lewis Acids 781
2.3.6.5 Combination of Organocatalysis with Enzyme Catalysis 783
2.3.7 Peptide Catalysis 788
2.3.7.1 Peptide-Catalyzed Oxidation Reactions 788
2.3.7.1.1 Epoxidation Reactions 788
2.3.7.1.1.1 Juliá--Colonna Epoxidation 788
2.3.7.1.1.2 Other Epoxidations 796
2.3.7.1.2 a-Aminoxylation of Aldehydes 799
2.3.7.1.3 Oxidation of Indoles 800
2.3.7.2 Peptide-Catalyzed Acylation, Phosphorylation, and Sulfonylation 801
2.3.7.2.1 Kinetic Resolution of Alcohols by Acylation 801
2.3.7.2.1.1 Kinetic Resolution of Secondary Alcohols 801
2.3.7.2.1.2 Kinetic Resolution of Tertiary Alcohols 804
2.3.7.2.2 Kinetic Resolution of Thioformamides 805
2.3.7.2.3 Desymmetrization of Prochiral Substrates 807
2.3.7.2.3.1 Remote Desymmetrization of Prochiral Diols by Acylation and Site-Selective Catalysis 807
2.3.7.2.3.2 Desymmetrization of myo-Inositol Derivatives by Phosphorylation 808
2.3.7.2.3.3 Desymmetrization of meso-Diols by Sulfonylation 809
2.3.7.2.4 Multicatalyst Systems for Acylation Followed by Oxidation 811
2.3.7.3 Peptide-Catalyzed C--C Bond-Forming Reactions 812
2.3.7.3.1 Hydrocyanation of Aldehydes 812
2.3.7.3.2 Aldol Reactions 814
2.3.7.3.2.1 Acetone and Cyclic Ketones as Aldol Donors 814
2.3.7.3.2.2 Hydroxyacetone as the Aldol Donor 817
2.3.7.3.3 Conjugate Addition Reactions 818
2.3.7.3.3.1 Conjugate Addition Reactions with Iminium Activation 818
2.3.7.3.3.2 Conjugate Addition Reactions with Enamine Activation 819
2.3.7.3.4 Morita--Baylis--Hillman Reactions 823
2.3.7.3.5 Reactions of Acyl Anion Equivalents 824
2.3.7.3.6 Enantioselective Protonation of Lithium Enolates 826
2.3.7.3.7 Atroposelective Bromination of Biaryl Compounds 828
2.3.8 Organocatalytic Cascade Reactions 834
2.3.8.1 Secondary Amine Catalyzed Cascade Reactions 834
2.3.8.1.1 Enamine Activation 834
2.3.8.1.1.1 Asymmetric Synthesis of Tetrahydro-1,2-oxazine-6-carbaldehydes by a Domino Aminoxylation/Aza-Michael Reaction 834
2.3.8.1.2 Iminium Activation 836
2.3.8.1.2.1 Asymmetric Synthesis of Pyrroloindolines and Furanoindolines by a Domino Michael/Cyclization Reaction 836
2.3.8.1.2.2 Asymmetric Synthesis of 6-Carboxycyclohex-2-en-1-ones by Domino Michael/Wittig or Michael/Knoevenagel Reactions 839
2.3.8.1.3 Activation of Singly Occupied Molecular Orbitals 842
2.3.8.1.3.1 Asymmetric Synthesis of Steroidal Frameworks 842
2.3.8.1.3.2 Asymmetric Synthesis of Cyclohexanecarbaldehydes by a Domino Alkene Addition/Friedel--Crafts Reaction 846
2.3.8.1.4 Iminium--Enamine Activation 848
2.3.8.1.4.1 Asymmetric Synthesis of Cyclopent-1-enecarbaldehydes by a Domino Michael/Aldol Reaction 848
2.3.8.1.4.2 Asymmetric Synthesis of Cyclopentanecarbaldehydes by Domino Double Michael Reaction 849
2.3.8.1.4.3 Asymmetric Synthesis of 2,3-Dihydro-1H-indene-2-carbaldehydes by a Reductive Michael Reaction 851
2.3.8.1.4.4 Asymmetric Synthesis of 2H-1-Benzopyran-3-carbaldehydes by Domino Michael/Aldol Reaction 853
2.3.8.1.4.5 Asymmetric Synthesis of 2H-1-Benzothiopyran-3-carbaldehydes by a Domino Michael/Aldol Reaction 854
2.3.8.1.4.6 Asymmetric Synthesis of 1,2-Dihydroquinoline-3-carbaldehydes by a Domino Michael/Aldol Reaction 856
2.3.8.1.5 Iminium--Allenamine Activation 857
2.3.8.1.5.1 Asymmetric Synthesis of 4H-1-Benzopyran-3-carbaldehydes by a Domino Double Michael Reaction 857
2.3.8.1.6 Enamine--Iminium--Enamine Activation 859
2.3.8.1.6.1 Asymmetric Synthesis of Tetrasubstituted Cyclohexenecarbaldehydes by a Domino Michael/Michael/Aldol Reaction 859
2.3.8.1.6.2 Asymmetric Synthesis of Six-Membered Spirocyclic Oxindoles by a Domino Michael/Michael/Aldol Reaction 860
2.3.8.1.7 Iminium--Enamine--Iminium--Enamine Activation 863
2.3.8.1.7.1 Asymmetric Synthesis of Tetrahydro-6H-dibenzo[b,d]pyrans by a Domino Oxa-Michael/Michael/Michael/Aldol Reaction 863
2.3.8.1.7.2 Asymmetric Synthesis of Polycyclic Spirooxindole Frameworks by a Domino Michael/Michael/Michael/Aldol Reaction 864
2.3.8.2 Primary Amine Catalyzed Cascade Reactions 866
2.3.8.2.1 Enamine--Iminium Activation: Asymmetric Synthesis of Spirocyclic Oxindolic Cyclohexanones by a Domino Double Michael Reaction 867
2.3.8.2.2 Iminium--Enamine Activation: Asymmetric Synthesis of Octahydronaphthalen-2(1H)-ones by a Domino Double Michael Reaction 870
2.3.8.3 Tertiary Amine Catalyzed Cascade Reactions 871
2.3.8.3.1 Cascade Reactions Catalyzed by Cinchona Alkaloids by Covalent Catalysis: Asymmetric Synthesis of Bicyclo[4.1.0]alkane Frameworks by a Nitrogen Ylide Catalyzed Intramolecular Cyclopropanation 872
2.3.8.3.2 Cascade Reactions Catalyzed by Cinchona Alkaloids by Noncovalent Catalysis: Asymmetric Synthesis of Dihydropyrroles 874
2.3.8.4 Brønsted Acid Catalyzed Cascade Reactions 876
2.3.8.4.1 Phosphoric Acid Catalyzed Cascade Reactions 876
2.3.8.4.1.1 Asymmetric Synthesis of 9-(Indol-3-yl)fluorene Derivatives by a Domino Double Friedel--Crafts Reaction 876
2.3.8.4.1.2 Asymmetric Synthesis of Tetrahydro-ß-carboline Derivatives 880
2.3.8.4.1.3 Asymmetric Synthesis of 3-Substituted Cyclohexylamines 882
2.3.8.4.2 Thiourea-Catalyzed Cascade Reactions: Asymmetric Synthesis of Substituted Benzothiopyran-4-ols by a Domino Michael/Aldol Reaction 885
2.3.8.5 N-Heterocyclic Carbene Catalyzed Cascade Reactions 886
2.3.8.5.1 Homoenolate Activation: Asymmetric Synthesis of Bicyclic ß-Lactams by a Domino Benzoin/Oxy-Cope/Mannich Reaction 886
2.3.9 Industrial Applications 894
2.3.9.1 Historical Background 894
2.3.9.2 Kinetic Resolution and Desymmetrization 895
2.3.9.2.1 Kinetic Resolution of Urethane-Protected a-Amino Acid N-Carboxyanhydrides 895
2.3.9.2.2 Asymmetric Synthesis of a Methyl (S)-4-(4-Fluorophenyl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate by Desymmetrization 897
2.3.9.3 Asymmetric Phase-Transfer-Catalyzed Alkylations 899
2.3.9.3.1 Synthesis of an Enantioenriched a-Amino Acid by Phase-Transfer-Catalyzed Alkylation with a Cinchona Alkaloid 899
2.3.9.3.2 Novel Asymmetric Phase-Transfer Catalysts for Practical Synthesis of Unnatural Amino Acids 902
2.3.9.4 Asymmetric Aldol Reactions, Mannich Reactions, and Michael Additions 906
2.3.9.4.1 Practical Asymmetric Synthesis of a Key Building Block for an HIV Protease Inhibitor by the Proline-Catalyzed Direct Cross-Aldol Reaction 906
2.3.9.4.2 Asymmetric Synthesis of a Key Building Block for Maraviroc by a Proline-Catalyzed Mannich Reaction of Acetaldehyde 908
2.3.9.4.3 Asymmetric Synthesis of a Pharmaceutical Intermediate by Michael Addition of a Dialkyl Malonate 909
2.3.9.4.4 Efficient Synthesis of ( )-Oseltamivir by an Organocatalyzed Michael Reaction of an Aldehyde and a Nitroalkene 911
2.3.9.5 Organocatalyzed Asymmetric Epoxidations 913
2.3.9.5.1 Practical Procedure for the Large-Scale Preparation of Methyl (2R,3S)-3-(4-Methoxyphenyl)oxirane-2-carboxylate, a Key Intermediate for Diltiazem 913
2.3.9.5.2 Approach to a Chiral Lactone: Application of the Shi Epoxidation 914
2.3.9.6 Diastereoselective and Enantioselective Aza-Henry Reaction 915
2.3.9.7 Enantioselective Organocatalytic Amine Conjugate Addition 916
2.3.9.8 Enantioselective Friedel--Crafts Reaction 919
2.3.9.9 Asymmetric Hydrocyanation and Strecker Reactions 920
2.3.9.10 Future Prospects 921
2.4 Future Perspectives 924
2.4.1 Future Perspectives for Lewis Base and Acid Catalysts 924
2.4.2 Future Perspectives for Brønsted Base and Acid Catalysts, and Additional Topics 925
Keyword Index 928
Author Index 990
Abbreviations 1016
List of All Volumes 1022