Preface ..................................................... XV
List of Contributors ...................................... XVII
List of Abbreviations ...................................... XXI
1 Asymmetric Organocatalysis: A New Stream in Organic
Synthesis .................................................... 1
Peter I. Dalko
1.1 Introduction ............................................ 1
1.2 Historical Background ................................... 2
1.3 Catalysts ............................................... 6
1.3.1 Privileged Catalysts ............................. 9
1.3.1.1 Proline ................................. 9
1.3.1.2 Cinchona Alkaloids ..................... 10
1.3.1.3 TADDOLs and Derivatives ................ 11
1.3.1.4 Binaphthol Derivatives ................. 11
1.4 Reaction Types ......................................... 12
1.4.1 Covalent Catalysis .............................. 12
1.4.2 Non-Covalent Organocatalysis .................... 12
1.5 How This Book is Organized ............................. 13
References and Notes ................................... 13
2 Enamine Catalysis ........................................... 19
2.1 Aldol and Mannich-Type Reactions ....................... 19
Fujie Tanaka and Carlos F. Barbas, III
2.1.1 Introduction .................................... 19
2.1.2 Aldol Reactions ................................. 20
2.1.2.1 Aldol Reactions of Alkyl Ketone
Donors ................................. 20
2.1.2.2 Aldol Reactions of α-Oxyketone
Donors ................................. 23
2.1.2.3 Aldol Reactions of Aldehyde Donors ..... 25
2.1.2.4 Aldol Reactions with Ketone
Acceptors .............................. 30
2.1.2.5 Intramolecular Aldol Reactions ......... 31
2.1.2.6 Mechanism and Transition States of
Aldol Reactions and Effects of Water
on Aldol Reactions ..................... 31
2.1.2.7 Catalyst Recycling ..................... 38
2.1.2.8 Catalyst Development Strategies ........ 38
2.1.3 Mannich Reactions ............................... 38
2.1.3.1 Mannich-Type Reactions of Aldehyde
Donors with Glyoxylate Imines .......... 38
2.1.3.2 Mannich-Туре Reactions of Aldehyde
Donors with Other Preformed Imines ..... 45
2.1.3.3 Three-Component Mannich Reactions
using Aldehyde Donors .................. 45
2.1.3.4 Mannich-Туре Reactions of Ketone
Donors ................................. 47
References ............................................. 51
2.2 α-Heteroatom Functionalization ......................... 56
Mauro Marigo and Karl Anker Jørgensen
2.2.1 Introduction .................................... 56
2.2.2 Direct α-Amination of Aldehydes and Ketones ..... 59
2.2.3 Direct α-Amination of α-Cyanoacetates and
β-Dicarbonyl Compounds .......................... 64
2.2.4 Direct α-Oxygenation Reactions of Aldehydes
and Ketones ..................................... 64
2.2.5 Direct α-Oxygenation Reactions of
β-Ketoesters .................................... 67
2.2.6 Direct α-Halogenation Reactions of Aldehydes
and Ketones ..................................... 68
2.2.6.1 Direct α-Fluorination of Aldehydes ..... 68
2.2.6.2 Direct α-Fluorination of
β-Ketoesters ........................... 69
2.2.6.3 Direct α-Chlorination of Aldehydes
and Ketones ............................ 69
2.2.6.4 Direct α-Chlorination of
β-Ketoesters ........................... 72
2.2.6.5 Direct α-Bromination of Aldehydes
and Ketones ............................ 72
2.2.7 Direct α-Sulfenylation of Aldehydes ............. 73
2.2.8 Direct α-Sulfenylation of Lactones, Lactams,
and β-Diketones ................................. 74
2.2.9 Direct α-Selenation of Aldehydes and Ketones .... 74
References ............................................. 75
2.3 Direct Conjugate Additions via Enamine Activation ...... 77
Cyril Bressy and Peter I. Dalko
2.3.1 Introduction .................................... 77
2.3.2 Factors Determining the Stereoselectivity of
the Organocatalytic Conjugate Additions ......... 77
2.3.3 Addition of Ketones to Nitroolefms and
Alkylidene Malonates ............................ 79
2.3.3.1 Proline ................................ 79
2.3.3.2 Pyrrolidine Amines and Pyrrolidine
Amine Salts as Catalysts for Michael-
Type Addition of Ketones to Activated
Olefins ................................ 79
2.3.3.3 Chiral Primary Amines .................. 82
2.3.3.4 Amine/Thiourea Catalysts ............... 82
2.3.4 Addition of Aldehydes to Nitroolefins and
Alkylidene Malonates ............................ 84
2.3.4.1 Aminopyrrolidine Catalysts ............. 84
2.3.4.2 Addition of Aldehydes and Ketones to
Enones ................................. 87
2.4 Conclusions ............................................ 92
References ............................................. 93
3 Iminium Catalysis ........................................... 95
Gerald Lélais and David W.С. MacMillan
3.1 Introduction ........................................... 95
3.2 The Catalysis Concept of Iminium Activation ............ 95
3.3 Development of the "First-Generation" Imidazolidinone
Catalysts .............................................. 96
3.4 Development of the "Second-Generation"
Imidazolidinone Catalysts .............................. 98
3.5 Cyloaddition Reactions ................................. 98
3.5.1 Diels-Alder Reactions ........................... 98
3.5.2 [3+2]-Cycloadditions ........................... 102
3.5.3 Cyclopropanations .............................. 103
3.5.4 Epoxidations ................................... 104
3.5.5 [4+3]-Cycloadditions ........................... 105
3.6 1,4-Addition Reactions ................................ 106
3.6.1 Friedel-Crafts Alkylations ..................... 106
3.6.2 Mukaiyama-Michael Reactions .................... 108
3.6.3 Michael Reactions of αβ-Unsaturated Ketones .... 108
3.7 Transfer Hydrogenation ................................ 110
3.8 Organocatalytic Cascade Reactions ..................... 111
3.8.1 Cascade Addition-Cyclization Reactions ......... 111
3.8.2 Cascade Catalysis: Merging Iminium and
Enamine Activations ............................ 113
3.9 Conclusions ........................................... 115
References ............................................ 116
4 Ammonium Ions as Chiral Templates .......................... 121
Takashi Ooi and Keiji Maruoka
4.1 Introduction .......................................... 121
4.2 Homogeneous Catalysis with Chiral Quaternary
Ammonium Fluorides .................................... 121
4.2.1 Aldol and Nitroaldol Reactions (Preparation
of Chiral Quaternary Ammonium Fluorides) ....... 121
4.2.2 Trifluoromethylation ........................... 124
4.2.3 Hydrosilylation ................................ 124
4.3 Homogeneous Catalysis with Chiral Quaternary
Ammonium Bifluorides .................................. 125
4.3.1 Aldol and Nitroaldol Reactions ................. 125
4.3.2 Michael Reaction ............................... 127
4.4 Homogeneous Catalysis with Chiral Quaternary
Ammonium Phenoxides ................................... 129
4.5 Heterogeneous Catalysis: Chiral Phase-Transfer
Catalysis ............................................. 129
4.5.1 Pioneering Study ............................... 129
4.5.2 Monoalkylation of Glycinate Schiff Base:
Asymmetric Synthesis α-Amino Acids ............. 130
4.5.3 Dialkylation of Schiff Bases Derived from
α-Alkyl-α-Amino Acids .......................... 138
4.5.4 Michael Reaction of Glycinate Benzophenone
Schiff Bases ................................... 141
4.5.5 Aldol and Mannich Reactions .................... 142
4.6 Conclusions ........................................... 147
References ............................................ 147
5 Organocatalytic Enantioselective Morita-Baylis-Hillman
(MBH) Reactions ............................................ 151
Candice Menozzi and Peter I. Dalko
5.1 Addition of Ketones and Aldehydes to Activated
Olefins ............................................... 151
5.1.1 Reaction Mechanism ............................. 154
5.1.2 Diastereoselectivity ........................... 156
5.1.3 Chiral Amine Catalysts ......................... 157
5.1.3.1 Chiral (Thio)Urea/Amine Catalysts
Systems ............................... 167
5.1.4 Chiral Phosphine-Catalyzed MBH Reactions ....... 169
5.1.4.1 Phosphine/Binaphthol-Derived
Catalysts ............................. 172
5.2 Asymmetric Aza-MBH Reactions .......................... 174
5.2.1 Reaction Mechanism ............................. 175
5.2.2 Chiral Amine Catalysts ......................... 175
5.2.2.1 Cinchona-Derived Catalysts ............ 175
5.2.2.2 Non-Natural Tertiary Amine/Phenol
Catalysts ............................. 178
5.2.2.3 Chiral Acid/Achiral Amine ............. 179
5.2.3 Phosphine-Mediated Aza-MBH Reactions ........... 180
5.3 Conclusions ........................................... 183
References and Notes .................................. 184
6 Asymmetric Proton Catalysis ................................ 189
Jeff D. McGilvra, Vijaya Bhasker Gondi, and
Viresh H. Rawal
6.1 Introduction .......................................... 189
6.2 Conjugate Addition Reactions .......................... 193
6.2.1 Conjugate Addition Reactions of
α,β-Unsaturated Carbonyl Substrates ............ 193
6.2.2 Conjugate Addition Reactions of Nitroolefms .... 197
6.2.3 Conjugate Addition Reactions of Vinyl
Sulfones ....................................... 206
6.3 Hydrocyanation Reactions .............................. 207
6.3.1 Hydrocyanation Reactions of Aldehydes .......... 207
6.3.2 The Strecker Reaction .......................... 209
6.3.3 Hydrocyanation Reactions of Ketones ............ 214
6.4 Mannich Reactions ..................................... 215
6.5 Aza-Henry Reactions of Aldimines ...................... 220
6.6 Acyl Pictet-Spengler Reactions of Iminium Ions ........ 222
6.7 Aza-Friedel-Crafts Reactions of Aldimines ............. 224
6.8 Hydrophosphonylation Reactions of Aldimines ........... 225
6.9 Direct Alkylation Reactions of α-Diazoesters .......... 227
6.10 Imine Amidation Reactions ............................. 228
6.11 Transfer Hydrogenation Reactions of Imines ............ 229
6.12 Morita-Baylis-Hillman Reactions ....................... 231
6.13 Cycloaddition Reactions ............................... 234
6.13.1 Hetero Diels-Alder (HDA) Reactions ............ 235
6.13.2 Diels-Alder (DA) Reactions .................... 241
6.14 Aldol and Related Reactions ........................... 244
6.15 Conclusion and Prospects .............................. 248
6.16 Addendum .............................................. 249
References ............................................ 250
7 Chiral Lewis Bases as Catalysts ............................ 255
Pavel Kočovsky and Andrei V. Malkou
7.1 Introduction .......................................... 255
7.2 Allylation Reactions .................................. 256
7.2.1 Catalytic Allylation of Aldehydes .............. 256
7.2.2 Stoichiometric Allylation of Aldehydes and
Ketones ........................................ 264
7.2.3 Allylation of Imines ........................... 264
7.3 Propargylation, Allenylation, and Addition of
Acetylenes ............................................ 265
7.3.1 Addition to Aldehydes .......................... 265
7.3.2 Addition to Imines ............................. 266
7.4 Aldol-Type Reactions .................................. 267
7.5 Hydrocyanation and Isonitrile Addition ................ 273
7.5.1 Cyanation of Aldehydes ......................... 273
7.5.2 Cyanation of Imines (Strecker Reaction) ........ 274
7.6 Reduction of Imines ................................... 275
7.7 Epoxide Opening ....................................... 278
7.8 Conclusions and Outlook ............................... 281
References ............................................ 281
8 Asymmetric Acyl Transfer Reactions ......................... 287
Alan С. Spivey and Paul McDaid
8.1 Introduction .......................................... 287
8.2 Type I Acyl Transfer Processes ........................ 290
8.2.1 Type I Acylative KR of Racemic Alcohols and
Amines ......................................... 291
8.2.1.1 Aryl Alkyl sec-Alcohols ............... 291
8.2.1.2 Allylic sec-Alcohols .................. 299
8.2.1.3 Propargylic sec-Alcohols .............. 302
8.2.1.4 1,2-Amino Alcohols and Mono-
Protected 1,2-Diols ................... 302
8.2.1.5 α-Chiral Primary Amines ............... 306
8.2.2 Type I Acylative ASD of Achiral/meso-Diols ..... 307
8.2.3 Type I Asymmetric Acyl Addition to
π-Nucleophiles: Steglich and Related
Rearrangements and Additions to Silyl Ketene
Acetals/Imines ................................. 309
8.3 Type II Acyl Transfer Processes ....................... 311
8.3.1 Type II Alcoholative ASD of Achiral/meso-
Cyclic Anhydrides .............................. 312
8.3.2 Type II Alcoholative KR of Racemic
Anhydrides, Azlactones, N-Carboxyanhydrides,
Dioxolanediones and N-Acyloxazolodin-
ethiones ....................................... 316
8.3.3 Type II Asymmetric Alcohol, Phenol, Enol, and
Amine Addition to Ketenes ...................... 321
8.4 Concluding Remarks .................................... 324
References ............................................ 324
9 Nucleophilic N-Heterocyclic Carbenes in Asymmetric
Organocatalysis ............................................ 331
Dieter Enders, Tim Balensiefer, Oliver Niemeier, and
Mathias Christmann
9.1 The Benzoin Condensation .............................. 331
9.2 The Stetter Reaction .................................. 338
9.3 Further Applications .................................. 344
9.3.1 a3 to d3 Umpolung .............................. 344
9.3.2 Transesterifications and Polymerizations ....... 349
References ............................................ 353
10 Ylide-Based Reactions ...................................... 357
Eoghan M. McGarrigle and Varinder K. Aggarwal
10.1 Introduction .......................................... 357
10.2 Epoxidation ........................................... 357
10.2.1 Sulfur Ylide-Catalyzed Epoxidation ............. 358
10.2.1.1 Catalysis via Sulfide Alkylation/
Deprotonation ........................ 359
10.2.1.2 Conditions and Results for
Alkylation/Deprotonation Cycle ....... 359
10.2.1.3 Catalysis via Ylide Formation from
a Carbene Source ..................... 360
10.2.1.4 Carbenes from In Situ Diazo
Compound Generation .................. 361
10.2.1.5 Scope of Carbene-Based
Methodologies ........................ 362
10.2.1.6 Catalytic Cycle Using the Simmons-
Smith Reagent ........................ 364
10.2.1.7 Synthesis of Glycidic Amides ......... 364
10.2.1.8 Optimum Sulfide in Carbene-Based
Cycle ................................ 364
10.2.1.9 Diastereoselectivity in S-Ylide
Epoxidations ......................... 365
10.2.1.10 Enantioselectivity in S-Ylide
Epoxidations ......................... 366
10.2.1.11 Applications of S-Ylide Epoxidation
in Synthesis ......................... 367
10.2.2 Te-Ylide-Catalyzed Epoxidation ................. 369
10.2.3 Se-Ylide-Catalyzed Epoxidation ................. 369
10.2.4 Summary of Ylide-Mediated Epoxidation .......... 370
10.3 Asymmetric Aziridination .............................. 370
10.3.1 Sulfur Ylide-Catalyzed Aziridination ........... 370
10.3.1.1 Ylide Regeneration via Carbenes ....... 370
10.3.1.2 Scope and Limitations of the
Carbene-Based Cycle ................... 371
10.3.1.3 Catalysis via Sulfonium Salt
Formation and Deprotonation ........... 373
10.3.1.4 Selectivity in S-Ylide
Aziridinations ........................ 374
10.3.1.5 Use of S-Ylide Aziridinations in
Synthesis ............................. 375
10.3.1.6 Summary of Ylide-Catalyzed
Aziridination ......................... 376
10.4 Asymmetric Cyclopropanation ........................... 377
10.4.1 S-Ylide-Mediated Cyclopropanation .............. 377
10.4.1.1 Catalytic Cycle Based on Carbene
Generation of Ylide ................... 377
10.4.1.2 Catalysis via In Situ Generation of
Diazo Compounds ....................... 378
10.4.1.3 Control of Selectivity Using
Carbene-Derived Ylides ................ 379
10.4.1.4 Catalytic Cycle Based on Sulfide
Alkylation and Sulfonium Salt
Deprotonation ......................... 379
10.4.1.5 Scope and Limitations of the
Alkylation/Deprotonation Method ....... 380
10.4.1.6 Control of Selectivity in the
Alkylation/Deprotonation Method ....... 381
10.4.1.7 Use of S-Ylide-Catalyzed
Cyclopropanations in Synthesis ........ 381
10.4.2 Tellurium Ylide-Mediated Cyclopropanation ...... 382
10.4.3 Nitrogen Ylide-Mediated Cyclopropanation ....... 382
10.4.3.1 Development of a Catalytic Method ..... 382
10.4.3.2 Enantioselective Cyclopropanation ..... 383
10.4.3.3 Mechanism of N-Ylide-Catalyzed
Cyclopropanation ...................... 385
10.4.4 Summary of Ylide-Catalyzed Cyclopropanation .... 385
10.5 Summary of Ylide-Catalyzed Asymmetric Reactions ....... 386
References ............................................ 386
11 Organocatalytic Enantioselective Reduction of Olefins,
Ketones, and Imines ........................................ 391
Henri B. Kagan
11.1 Introduction .......................................... 391
11.2 The General Concept ................................... 391
11.3 Asymmetric Organocatalytic Reduction of Olefins ....... 393
11.4 Reduction of Ketones or Ketimines ..................... 397
11.4.1 Hantzsch Ester/Chiral Bransted Acids ........... 397
11.4.2 Silanes/Phase-Transfer Catalysts ............... 398
11.4.3 Silanes/Formamide Catalysts .................... 399
11.5 Conclusions ........................................... 401
References ............................................ 401
12 Oxidation Reactions ........................................ 403
Alan Armstrong
12.1 Epoxidation of Alkenes ................................ 403
12.1.1 Ketone-Mediated Epoxidation .................... 404
12.1.2 Iminium Salt-Catalyzed Epoxidation ............. 410
12.1.3 Amine-Catalyzed Epoxidation .................... 412
12.2 Epoxidation of Enoates, Enones, and Enals ............. 413
12.2.1 Epoxidation of Enoates ......................... 413
12.2.2 Epoxidation of Enones .......................... 414
12.2.2.1 Phase-Transfer Catalysis .............. 414
12.2.2.2 Polyleucine-Mediated Epoxidation ...... 416
12.2.3 Epoxidation of Enals ........................... 417
12.3 Asymmetric Baeyer-Villiger Reaction ................... 418
12.4 Oxidation of Thioethers ............................... 419
12.5 Resolution of Alcohols by Oxidation ................... 420
12.6 Conclusions ........................................... 421
References ................................................. 421
13 Shape-and Site-Selective Asymmetric Reactions .............. 425
Nicolas Bogliotti and Peter I. Dalko
13.1 I ntroduction ......................................... 425
13.2 Acylation Reactions with Oligopeptide-Based
Catalysts ............................................. 426
13.2.1 Regioselective Acetylation of Glucose
Derivatives .................................... 426
13.2.2 Regioselective Phosphorylation ................. 427
13.3 Sequence-Specific RNA-Cleaving Agents ................. 428
13.3.1 RNA Hydrolysis by DNA-DETA Adduct .............. 429
13.3.2 RNA Hydrolysis by PNA-DETA Adduct .............. 430
13.3.3 Methyl Phosphonate Oligonucleotides as
RNA-Cleaving Agents ............................ 431
13.4 Chiral Cavitands: Calixarenes and Cyclodextrins ....... 432
13.4.1 Calixarenes .................................... 433
13.4.1.1 Specific Esterification of
N-Acetyl-L-Amino Acids ................ 433
13.4.2 Cyclodextrins .................................. 434
13.4.2.1 Aryl Glycoside Hydrolysis ............. 435
13.4.2.2 Phosphate Hydrolysis .................. 435
13.4.2.3 Transamination Reactions .............. 437
13.4.2.4 Amidation Reactions ................... 437
13.4.2.5 Epoxidation of Alkenes ................ 438
13.5 Molecular Imprinting .................................. 442
13.5.1 Enantioselective Ester Hydrolysis .............. 443
13.6 Conclusion ............................................ 446
References ............................................ 446
14 Appendix I: Reaction Procedures ............................ 451
14.1 Aldol Reactions ...................................... 451
14.2 Mannich Reaction ..................................... 457
14.3 Pictet-Spengler Reaction ............................. 459
14.4 Nitroaldol (Henry) Reaction .......................... 460
14.5 Hydrocyanation and Cyanosilylation Reactions ......... 461
14.6 Alkylation of α-Diazoesters .......................... 464
14.7 Heteroatom Addition to Imines ........................ 464
14.8 α-Heteroatom Functionalization ....................... 466
14.9 1,4-Additions ........................................ 468
14.10 Morita-Baylis-Hillman (MBH) Reactions ................ 476
14.11 Cyclopropanation ..................................... 478
14.12 Aziridination ........................................ 480
14.13 Epoxide Formation .................................... 481
14.14 Epoxide Opening ...................................... 488
14.15 Nucleophilic Substitution Reactions .................. 488
14.16 Allylation Reactions ................................. 490
14.17 Acylation ............................................ 491
14.18 [4+2] Cycloadditions ................................. 500
14.19 [3+2]-Cycloadditions ................................. 503
14.20 Acyloin and Benzoin Condensations .................... 504
14.21 Reduction of Ketones and Imines ...................... 505
14.22 Hydrogenation of Olefins ............................. 506
14.23 Multicomponent Domino Reactions ...................... 508
References ........................................... 510
15 Appendix II: Catalysts ..................................... 513
Subject Index ........................................ 531
|
