Chiral Amine Synthesis: Methods, Developments and Applications

Chiral Amine Synthesis......Page 2
Foreword......Page 10
Contents......Page 12
Preface......Page 20
List of Contributors......Page 26
1.1 Introduction......Page 30
1.2.2 N-Sulfinyl Imines......Page 32
1.2.3 N-Sulfonyl Imines......Page 33
1.2.4 N-Phosphinoyl Imines......Page 34
1.3 Chiral Auxiliary-Based Approaches......Page 35
1.3.1 Imines Derived from Chiral Aldehydes......Page 36
1.3.2 Imines Bearing a Chiral Protecting/Activating Group......Page 38
1.4 Catalytic Asymmetric Nucleophilic Addition to Achiral Imines......Page 44
1.4.1.1 Copper-Catalyzed Dialkylzinc Additions......Page 45
1.4.1.3 Early Transition Metal (Zr, Hf)-Catalyzed Dialkylzinc Additions......Page 49
1.4.1.4 Rhodium-Catalyzed Dialkylzinc Addition Reactions......Page 52
1.4.2 Catalytic Asymmetric Allylation of Imines......Page 53
1.4.3 Catalytic Asymmetric Addition of sp2 Hybridized Carbanions......Page 58
1.4.3.1 Catalytic Asymmetric Vinylation......Page 60
1.4.3.2.1 Amino Alcohol-Catalyzed Addition of Organozinc Reagents......Page 61
1.4.3.2.2 Rhodium Phosphine-Catalyzed Arylation of Imines......Page 63
1.4.3.2.3 Rhodium Diene-Catalyzed Arylation of Imines......Page 67
1.4.4 Catalytic Asymmetric Addition of sp Hybridized Carbanions......Page 68
1.5 Conclusion......Page 71
References......Page 73
2.1 Background and Introduction......Page 80
2.2.1 Design of Chiral N-Acylhydrazones......Page 81
2.2.2 Preparation of Chiral N-Acylhydrazones......Page 83
2.2.3 Tin-Mediated Addition of Secondary and Tertiary Radicals......Page 84
2.2.4 Tin-Free Radical Addition......Page 87
2.2.5 Manganese-Mediated Radical Addition......Page 88
2.2.6.1 Hybrid Radical–Ionic Annulation......Page 89
2.2.6.2 Precursors Containing Hydroxyl or Protected Hydroxyl Groups......Page 91
2.2.6.3 Ester-Containing N-Acylhydrazones......Page 93
2.2.6.4 Additions to Ketone Hydrazones......Page 94
2.3 Asymmetric Catalysis of Radical Addition......Page 96
2.4 Closing Remarks......Page 97
References......Page 98
3.1 Introduction......Page 104
3.2.1.1 Mannich Reaction......Page 105
3.2.1.2 Nucleophilic Addition of Diazoacetates to Aldimine......Page 110
3.2.1.3 Vinylogous Mannich Reaction......Page 112
3.2.1.4 Aza-Petasis–Ferrier Rearrangement......Page 113
3.2.2.1 Strecker Reaction......Page 114
3.2.2.2 Aza-Henry Reaction......Page 115
3.2.3.1 Friedel–Crafts Reaction via Activation of Aldimines......Page 116
3.2.3.2 Friedel–Crafts Reaction via Activation of Electron-Rich Alkenes......Page 120
3.2.3.3 Pictet–Spengler Reaction......Page 122
3.2.4.1 Hetero-Diels–Alder Reaction of Aldimines with Siloxydienes......Page 123
3.2.4.2 Direct Cycloaddition Reaction of Aldimines with Cyclohexenone......Page 124
3.2.4.3 Inverse Electron-Demand Aza-Diels–Alder Reaction (Povarov Reaction)......Page 125
3.2.4.4 1,3-Dipolar Cycloaddition Reaction......Page 126
3.2.5.2 Cascade Transformations Based on Tandem Aza–Ene-Type Reaction......Page 128
3.2.5.3 Two-Carbon Homologation of Hemiaminal Ethers......Page 129
3.2.5.4 Homocoupling Reaction of Enecarbamates......Page 131
3.2.6.2 Aldol-Type Reaction of Azlactones with Vinyl Ethers......Page 133
3.2.6.3 Cooperative Catalysis by Metal Complexes and Chiral Phosphoric Acids......Page 135
3.3 Carbon–Hydrogen Bond Forming Reactions......Page 137
3.3.1 Transfer Hydrogenation of Acyclic and Cyclic Imines......Page 138
3.3.2 Cascade Transfer Hydrogenation of Quinoline and Pyridine Derivatives......Page 142
3.3.3 Application of Transfer Hydrogenation to Cascade Reaction......Page 145
3.4.1 Hydrophosphonylation (Kabachnik–Fields Reaction)......Page 146
3.4.2 Formation of (Hemi)Aminals......Page 148
3.4.3 Nucleophilic Ring Opening of Aziridines and Related Reactions......Page 150
3.5 Conclusion......Page 152
References......Page 154
4.1 Introduction......Page 160
4.2 Formamides as Lewis-Basic Organocatalysts in Hydrosilylation of Imines......Page 161
4.3 Other Amides as Organocatalysts in Hydrosilylation of Imines......Page 170
4.4 Sulfinamides as Organocatalysts in Hydrosilylation of Imines......Page 172
4.5 Supported Organocatalysts in Hydrosilylation of Imines......Page 173
4.6 Mechanistic Considerations......Page 176
4.7 Synthetic Applications......Page 178
4.8 Conclusions......Page 180
4.9.1 Catalytic Hydrosilylation of Simple Imines [12c,h]......Page 181
4.9.2 Catalytic Hydrosilylation of Enamines [12g]......Page 182
References......Page 183
5.1 Introduction......Page 186
5.2 Vinylogous Mukaiyama–Mannich Reactions of Silyl Dienolates......Page 188
5.3 Direct Vinylogous Mannich Reactions of Unmodified Substrates......Page 199
5.4 Miscellaneous......Page 203
5.5 Conclusion......Page 204
References......Page 205
6.2.1 Direct Asymmetric Hydrogenation of Alkyl- and Aryl-Substituted Imines......Page 208
6.2.1.1 Development......Page 209
6.2.1.2 Pressure in the Asymmetric Hydrogenation of Alkyl- and Aryl-Substituted Imines......Page 212
6.2.1.3 Reducing the Environmental Impact of the Reaction......Page 214
6.2.2.1 Quinolines and Isoquinolines......Page 219
6.2.2.1.1 Quinolines – A Representative Synthesis......Page 224
6.2.2.1.2 Isoquinolines – A Representative Synthesis......Page 225
6.2.2.2 Quinoxalines......Page 226
6.2.2.3 Pyridines......Page 227
6.2.3 Direct Asymmetric Hydrogenation of .Activated. Imines......Page 231
6.2.4 Asymmetric Transfer Hydrogenation of Imines......Page 233
6.2.4.1 Reducing the Environmental Impact of the Reaction......Page 236
6.3.1 Hydrogenation and Transfer Hydrogenation of N,N-Disubstituted Iminiums......Page 240
6.3.2 Hydrogenation and Transfer Hydrogenation of Enamines......Page 242
6.4 Conclusion......Page 245
References......Page 247
7.1 Introduction......Page 254
7.2 Transition Metal-Mediated Homogeneous Reductive Amination......Page 255
7.3 Enantioselective Organocatalytic Reductive Amination......Page 260
7.4.1 Stereoselective Reductive Amination with Chiral Ketones......Page 263
7.4.2 The Phenylethylamine Auxiliary and Stereoselective Reductive Amination......Page 266
7.4.3 The tert-Butylsulfinamide Auxiliary and Stereoselective Reductive Amination......Page 269
7.5 Conclusions......Page 272
References......Page 273
8.1 Introduction......Page 276
8.2.1 Chiral Monodentate Phosphoramidite Ligands......Page 278
8.2.2 Chiral Monodentate Phosphite Ligands......Page 286
8.2.3 Other Chiral Monodentate Phosphorus Ligands......Page 291
8.2.4 Mixed Chiral Monodentate Phosphorus Ligands......Page 292
8.3 Asymmetric Hydrogenation of N,N-Dialkyl Enamines......Page 293
8.4 Conclusion and Outlook......Page 298
References......Page 299
9.1 Introduction......Page 302
9.2.1 Synthesis of Enamides......Page 303
9.2.2.1 Chiral Phospholane Ligands for Rh-Catalyzed Asymmetric Hydrogenation......Page 305
9.2.2.2 Chiral 1,4-Diphosphine Ligands for Rh-Catalyzed Asymmetric Hydrogenation......Page 307
9.2.2.3 Bisaminophosphine Ligands for Rh-Catalyzed Asymmetric Hydrogenation......Page 312
9.2.2.4 Unsymmetrical Hybrid Phosphorus-Containing Ligands for Rh-Catalyzed Asymmetric Hydrogenation......Page 313
9.2.3 Catalytic Asymmetric Hydrogenation of Cyclic Enamides......Page 318
9.3 Conclusions......Page 325
References......Page 326
10.1.1 Ir- and Ru-Catalyzed Asymmetric Hydrogenation of Quinolines......Page 328
10.1.2 Organocatalyzed Asymmetric Transfer Hydrogenation of Quinolines......Page 347
10.2 Asymmetric Hydrogenation of Isoquinolines......Page 349
10.3 Asymmetric Hydrogenation of Indoles......Page 351
10.4 Asymmetric Hydrogenation of Pyrroles......Page 356
10.6 Asymmetric Hydrogenation of Pyridine Derivatives......Page 358
10.7 Summary and Outlook......Page 365
References......Page 366
11.1 Introduction: Synthesis of Amines via Hydroamination......Page 370
11.2.1 Intermolecular Hydroamination of Simple Alkenes......Page 371
11.2.2.1 Rare Earth Metal-Based Catalysts......Page 375
11.2.2.2 Alkali Metal-Based Catalysts......Page 382
11.2.2.3 Group 4 Metal-Based Catalysts......Page 385
11.2.2.4 Organocatalytic Asymmetric Hydroamination......Page 387
11.3.1 Intermolecular Hydroaminations......Page 389
11.3.2 Intramolecular Reactions......Page 390
11.4.1 Hydroaminations Using Achiral Catalysts......Page 392
11.4.2 Kinetic Resolution of Chiral Aminoalkenes......Page 395
11.5 Synthesis of Chiral Amines via Tandem Hydroamination/Hydrosilylation......Page 397
11.7 Experimental Section......Page 398
References......Page 401
12.1 Introduction......Page 406
12.2 Background......Page 407
12.3.1 Intramolecular C- H Amination......Page 408
12.3.2 Intermolecular C- H Amination......Page 411
12.4 Substrate-Controlled Chiral Amine Synthesis via C- H Amination......Page 413
12.5.1 Enantioselective C- H Amination with Rhodium(II) Catalysts......Page 415
12.5.2 Enantioselective C H Amination with Ruthenium(II) Catalysts......Page 419
12.6 Conclusion......Page 421
References......Page 423
13.1 Introduction......Page 426
13.2 Recent Mechanistic Insights......Page 427
13.4 Chiral Auxiliary-Induced Diastereoselective Aza-MBH Reaction......Page 429
13.5.1 Cinchona-Derived Bifunctional Catalysts......Page 430
13.5.2 Chiral Binol-Derived Bifunctional Amine Catalysts......Page 437
13.5.3 Chiral Acid/Achiral Amine......Page 439
13.6 Chiral Phosphine Catalysts......Page 440
13.7 Chiral Bifunctional N-Heterocyclic Carbenes......Page 447
13.9 Aza-MBH-Type Reaction to Obtain Chiral Amines......Page 448
13.10 Strategies for the Removal of Protecting Groups......Page 451
13.11.2 Typical Procedures for b-ICD-Catalyzed Aza-MBH Reaction of MVK with N-(p-Ethylbenzenesulfonyl) Benzaldimine [16]......Page 452
13.11.6 Typical Procedures for Trifunctional Phosphine 27-Catalyzed Aza-MBH Reaction of N-Tosylimines with MVK [36]......Page 453
13.11.9.1 Reduction of the Aza-MBH Reaction Product with LiAlH4......Page 454
13.12 Summary and Outlook......Page 455
References......Page 457
14.1 Introduction......Page 460
14.2.1 Hydrolytic Enzymes......Page 461
14.2.2 Transaminases......Page 470
14.2.3 Amine Oxidases......Page 472
14.3.1 DKR Using Hydrolytic Enzymes and Racemization Catalysts......Page 473
14.3.2 Deracemization Reactions Using Amine Oxidases......Page 477
14.4 Asymmetric Synthesis of Amines Using Transaminases......Page 479
14.5 Conclusions and Future Perspectives......Page 484
References......Page 486
Appendix: Solution......Page 490
Index......Page 508