David Ager1574446649, 9781574446647
The handbook first elaborates upon starting materials obtained from a “chiral pool,” which can be derived from natural products. Then it explains methods and reactions that can introduce or influence stereogenic centers, particularly asymmetric hydrogenations, oxidations, pericyclic reactions, and enzymatic methods. While hydrogenations have been the most widely employed approach for the large-scale synthesis of several commercial compounds, the search for the ideal catalyst has consistently led researchers to enzymes present in biological systems. Several chapters concentrate on understanding how to manipulate enzymes for catalyzing new reactions for taking new substrates. Other significant topics include chiral auxiliaries, chromatographic techniques, enantiomers-specific reactions, and resolution.
This second edition updates all its chapters, illustrating the speed of development in this field, and features new chapters that highlight successful approaches in an industrial setting. The Handbook of Chiral Chemicals, Second Edition is a guide to advances in the field that result in more efficient and cost-effective synthesis of chiral chemicals.
Table of contents :
Handbook of Chiral Chemicals, Second Edition……Page 2
Contents……Page 4
Preface……Page 7
The Editor……Page 9
Contributors……Page 10
Table of Contents……Page 0
CONTENTS……Page 13
1.3 CHIRAL REAGENTS……Page 14
1.4.2 BIOLOGICAL CATALYSTS……Page 16
1.6 RESOLUTION……Page 17
1.7.1.2 Chemically Catalyzed Oxidations……Page 18
1.7.1.7 Substitution Reactions (SN2)……Page 19
REFERENCES……Page 20
2.1.1 UNNATURAL AMINO ACID SYNTHESIS……Page 22
2.2 CHOICE OF APPROACH……Page 23
2.3 SMALL-SCALE APPROACHES……Page 24
2.3.2 CHIRAL AUXILIARIES……Page 25
2.3.2.1 Vancomycin……Page 27
2.3.3 RESOLUTIONS……Page 29
2.5 LARGE-SCALE METHODS……Page 31
2.5.1.1 Asymmetric Hydrogenations……Page 32
2.5.1.2 Chiral Pool Approaches……Page 33
2.5.2.2 Decarboxylases……Page 34
2.5.2.3.2 Amidases……Page 35
2.6 beta-AMINO ACIDS……Page 36
REFERENCES……Page 38
3.1 INTRODUCTION……Page 42
3.2 BACTERIAL PRODUCTION OF L-PHENYLALANINE……Page 43
3.2.2 DEREGULATION OF DAHP SYNTHASE……Page 45
3.2.3 DEREGULATION OF CHORISMATE MUTASE AND PREPHENATE DEHYDRATASE……Page 46
3.2.4 PRECURSOR SUPPLY……Page 47
3.3.2 ENGINEERING THE PATHWAYS OF L-LYSINE AND L-THREONINE BIOSYNTHESIS……Page 48
3.4.1 ADAPTATION OF THE L-CYSTEINE PATHWAY TO PRODUCE UNNATURAL AMINO ACIDS……Page 50
3.6 NOVEL AMINOTRANSFERASE PATHWAYS……Page 51
3.7 SUMMARY……Page 52
REFERENCES……Page 54
4.1 INTRODUCTION……Page 57
4.2.1 SUCROSE……Page 58
4.2.1.2.1 Chemical Approaches……Page 59
4.2.1.2.2 Enzymatic Approaches……Page 60
4.3.1 D-GLUCONIC ACID……Page 61
4.3.4 D-ERYTHROSE……Page 62
4.4.1 S-SOLKETAL……Page 63
4.4.2 R-SOLKETAL……Page 64
4.5.4 3-HYDROXYBUTYRIC ACID……Page 65
4.6 SUMMARY……Page 66
REFERENCES……Page 67
5.1 INTRODUCTION……Page 69
5.3.1 alpha-PINENE……Page 70
5.3.2.1 Other Monoterpenes Derived from Pinenes……Page 71
5.3.3 LIMONENE……Page 72
5.3.4 MENTHONES……Page 73
5.3.6 CARVONES……Page 74
5.3.8 CAMPHOR……Page 75
5.4.1.1 Alkylations……Page 76
5.4.1.2 Aldol Reaction……Page 77
5.4.3 MONOTERPENES AS CHIRONS……Page 78
5.4.3.1 Robinson Annelation……Page 79
5.4.3.3 Cinmethylin……Page 81
REFERENCES……Page 82
6.1 INTRODUCTION……Page 85
6.2.1 NAPROXEN……Page 86
6.2.2 IBUPROFEN……Page 90
6.2.3 D-PROLINE……Page 92
6.2.4 HYDROLYTIC KINETIC RESOLUTION OF EPOXIDES……Page 93
6.3 ENZYMATIC RESOLUTIONS……Page 94
6.3.1 alpha,alpha-DISUBSTITUTED alpha-AMINO ACIDS……Page 95
6.3.2 PREPARATION OF D-AMINO ACIDS USING HYDANTOINASE……Page 100
REFERENCES……Page 102
7.1 INTRODUCTION……Page 106
7.2 RESOLUTION BY DIASTEREOISOMERIC SALT FORMATION……Page 107
7.3 AUTOMATED SCREENING OF RESOLVING AGENTS……Page 109
7.4 DUTCH RESOLUTION……Page 111
7.4.1 NEW FAMILIES OF RESOLVING AGENTS……Page 116
7.4.2 RECIPROCAL AND REVERSE DUTCH RESOLUTION……Page 117
7.5 CRYSTALLIZATION-INDUCED ASYMMETRIC TRANSFORMATION……Page 119
REFERENCES AND NOTES……Page 124
8.2 CHIRAL DISCRIMINATION OF 2-ARYLALKANOIC ACIDS……Page 126
8.3 ENANTIOSELECTIVE ACETYLATION OF RACEMIC SECONDARY ALKYL AMINES……Page 127
8.4 KINETIC RESOLUTION OF SECONDARY ARYL ALCOHOLS……Page 129
8.5.1 TRANS-6-NITRO-1-AMINO-2-INDANOL……Page 130
REFERENCES……Page 131
9.1 INTRODUCTION……Page 132
9.2.1 SHARPLESS EPOXIDATION……Page 134
9.2.1.2 Reactions of 2,3-Epoxy Alcohols……Page 135
9.2.1.3 Commercial Applications……Page 136
9.2.2.1 Resolutions……Page 138
9.2.3 OTHER CHEMICAL METHODS……Page 141
9.3 ASYMMETRIC DIHYDROXYLATION……Page 142
9.3.1 REACTIONS OF DIOLS……Page 144
9.4 AMINOHYDROXYLATION……Page 146
9.5 HALOHYDROXYLATIONS……Page 147
9.8.1.1 alpha-Oxidations……Page 148
9.8.2 SILYL COMPOUNDS……Page 149
REFERENCES……Page 150
10.1 INTRODUCTION……Page 156
10.2.1 SYNTHESIS OF FRUCTOSE-DERIVED KETONE……Page 157
10.2.2 THE PH EFFECT ON EPOXIDATION……Page 158
10.2.3 SUBSTRATE SCOPE……Page 159
10.2.4 HYDROGEN PEROXIDE AS PRIMARY OXIDANT……Page 161
10.2.5 TRANSITION STATE MODEL……Page 162
10.2.6 STRUCTURAL EFFECT OF KETONES ON CATALYSIS……Page 163
10.3 KETONE CATALYSTS FOR CIS- AND TERMINAL OLEFINS……Page 164
10.4 SYNTHETIC APPLICATIONS……Page 168
REFERENCES……Page 170
11.1 INTRODUCTION……Page 173
11.2.1 L-ISOXAZOLYLALANINE……Page 174
11.2.3 beta-HYDROXY-gamma-AMINO ACIDS……Page 175
11.3.1 DRIMANES……Page 176
11.3.2 IMMUNOSUPPRESSANTS……Page 177
11.3.4 TACHYKININ ANTAGONISTS……Page 178
11.3.5 ANTIINFLAMMATORY DRUGS……Page 179
11.3.6 PROSTAGLANDIN ENDOPEROXIDES……Page 180
11.3.7 EPOXYCHOLESTEROL……Page 181
11.3.8 PRAVASTATIN……Page 182
11.4.1 ARTEMISININ……Page 183
11.4.2 YINGZHAOSU A ANALOGUES……Page 184
11.5 ANTIBIOTICS……Page 185
11.5.2 ACETOMYCIN……Page 186
11.5.3 SULFENIC ACID DERIVATIVES……Page 187
11.5.5 beta-LACTAM ANTIBIOTICS……Page 188
11.5.7 TRANS-CONFIGURATED beta-LACTAMS……Page 189
REFERENCES……Page 190
CONTENTS……Page 193
12.1 INTRODUCTION……Page 194
12.2.1 DIPAMP……Page 197
12.2.2 BINAP……Page 199
12.2.2.1 Menthol……Page 200
12.2.2.2 Carbapenem Intermediates……Page 201
12.2.2.4 Nonsteroidal Antiinflammatory Drugs……Page 202
12.2.2.5 Levofloxacin……Page 203
12.2.2.6 Latest and Potential Ru(BINAP) Technologies……Page 204
12.2.4 FERROCENYLPHOSPHINES……Page 205
12.2.4.3 Dextromethorphan……Page 208
12.2.6.1 3,4-Bisphosphinopyrrolines (DeguPHOS)……Page 209
12.2.6.2 4-Phosphino-2-(phosphinomethyl)pyrrolidines (PPM and BPPM)……Page 210
12.2.7 BIS(PHOSPHOLANES) (DUPHOS)……Page 211
12.2.8 TANGPHOS……Page 212
12.2.9 MALPHOS AND CATASIUM FAMILY……Page 213
12.3.1.1 BisP* and MiniPHOS……Page 214
12.3.1.2 Trichickenfootphos……Page 215
12.3.2.1.1 MeO-BIPHEP……Page 217
12.3.2.1.3 Cl-MeO-Biphemp……Page 219
12.3.2.1.4 SegPhos……Page 221
12.3.2.1.5 TunePhos Family……Page 222
12.3.2.1.6 Synphos and Difluorphos……Page 225
12.3.2.1.7 P-Phos Ligands……Page 226
12.3.2.1.8 4,4-Bis(diphenylphosphino)-2,2′,5,5′-tetramethyl-3,3′-dithiophene……Page 227
12.3.2.2.1 PhanePhos……Page 228
12.3.3.1 BoPhoz……Page 230
12.3.3.2 Miscellaneous Ferrocenylphosphines……Page 232
12.3.4 RUTHENIUM/BISPHOSPHINES/DIAMINE CATALYSTS……Page 234
12.4.1 NI/R,R-TARTARIC ACID/NABR……Page 237
12.4.2 CINCHONA-MODIFIED PLATINUM……Page 238
12.5 ASYMMETRIC HYDROGEN TRANSFER……Page 239
12.5.1.2 (S)-4-Fluorophenylethanol……Page 240
12.5.1.3 (R)-3,5-Bistrifluoromethylphenylethanol……Page 241
12.5.2.1 (R)-1-Methylnaphthylamine……Page 242
12.6 HYDROFORMYLATION……Page 243
12.8 ASYMMETRIC CYCLOPROPANATIONS……Page 246
12.9 SUMMARY……Page 247
REFERENCES……Page 249
13.1 INTRODUCTION……Page 256
13.2 PHOSPHOLANE LIGANDS……Page 257
13.3 PHOSPHETANE LIGANDS……Page 259
13.4.1 AMINO ACID DERIVATIVES……Page 260
13.4.2 AMINES AND AMINO ALCOHOLS……Page 264
13.4.3 HYDRAZINES……Page 265
13.4.4 ALCOHOLS……Page 266
13.4.5 CARBOXYLIC ACIDS……Page 267
13.4.9 CYCLOPENTANES……Page 269
13.5 OTHER APPLICATIONS OF PHOSPHOLANE LIGANDS……Page 270
13.6 SUMMARY……Page 272
REFERENCES AND NOTES……Page 273
14.1 INTRODUCTION……Page 276
14.2 MONODENTATE PHOSPHONITES……Page 277
14.3 MONODENTATE PHOSPHITES……Page 279
14.4 MONODENTATE PHOSPHORAMIDITES……Page 284
13.5 SUMMARY……Page 291
REFERENCES AND NOTES……Page 292
15.1 INTRODUCTION……Page 294
15.2 CATALYTIC TEST RESULTS……Page 295
15.3 LIGANDS WITH PHOSPHINE SUBSTITUENTS BOUND TO BOTH CYCLOPENTADIENE RINGS……Page 296
15.3.1 BPPFOH AND RELATED LIGANDS……Page 297
15.3.1.1 Industrial Applications……Page 298
15.3.3 MISCELLANEOUS DIPHOSPHINES……Page 299
15.4.1 JOSIPHOS FAMILY……Page 301
15.4.2 TANIAPHOS……Page 303
15.4.3 BOPHOZ……Page 304
15.5.1 WALPHOS FAMILY……Page 305
15.5.2 TRAP (TRANS-CHELATING) LIGANDS……Page 306
15.6.1 HYDROGENATION OF SUBSTITUTED OLEFINS……Page 307
15.6.2 HYDROGENATION OF C=O AND C=N FUNCTIONS……Page 308
REFERENCES……Page 309
16.1 INTRODUCTION……Page 311
16.3 THE CATALYTIC APPROACH……Page 312
16.3.2 CATALYST PREPARATION……Page 313
16.3.3 REDUCING AGENT……Page 315
16.3.5 VERSATILITY OF THE REACTION……Page 316
16.4 THE INDUSTRIAL APPLICATION IN THE SYNTHESIS OF PHARMACEUTICALS……Page 318
REFERENCES……Page 321
17.1 INTRODUCTION……Page 324
17.2.1 TRANSFER HYDROGENATION……Page 326
17.1.2 BORANE REDUCTIONS……Page 327
17.3.1 TRIMETHYLSILYLCYANIDE ADDITIONS……Page 330
17.4 CONJUGATE ADDITIONS……Page 331
17.5.1 DIELS-ALDER REACTIONS……Page 333
17.5.2 HETERO DIELS-ALDER REACTIONS……Page 335
17.5.3 HETERO-ENE REACTIONS……Page 338
17.6 AZIDE ADDITIONS……Page 339
17.7.1 CATALYTIC ASYMMETRIC CYCLOPROPANATIONS……Page 340
17.7.3 ALLYLIC ALKYLATIONS……Page 341
17.8 RELATED AMINO ALCOHOLS AND THEIR APPLICATIONS IN ASYMMETRIC SYNTHESIS……Page 342
17.8.1 CIS-N-SULFONYL-2-AMINO-1-INDANOL……Page 343
17.8.2 CIS-2-AMINO-3,3-DIMETHYL-1-INDANOL……Page 344
17.8.3 CIS-1-AMINO-2-HYDROXY-1,2,3,4-TETRAHYDRONAPHTHALENE……Page 345
REFERENCES……Page 347
18.1 INTRODUCTION……Page 349
18.2 alpha-KETO ACID DERIVATIVES……Page 350
18.3 alpha,gamma-DIKETO ESTERS……Page 351
18.4 TRIFLUOROMETHYL KETONES……Page 353
18.5 alpha-KETO ACETALS……Page 354
18.6 alpha-KETO ETHERS……Page 355
18.8.2 MODIFIERS……Page 357
18.9 SUMMARY AND OUTLOOK……Page 358
REFERENCES AND NOTES……Page 359
19.1 INTRODUCTION……Page 362
19.2.1 OXIDOREDUCTASES (E.C. 1.X.X.X)……Page 363
19.2.1.1.1 Reductions of 2-Oxo Acids……Page 364
19.2.1.2.1 Yeast Reductions……Page 366
19.2.1.2.2 Bacterial and Fungal Reductions……Page 370
19.2.2 TRANSFERASES (E.C. 2.X.X.X)……Page 372
19.2.2.1 Aminotransferases……Page 373
19.2.3 HYDROLASES (E.C. 3.X.X.X)……Page 375
19.2.3.1 Esterases and Lipases……Page 376
19.2.3.1.1 Prochiral and meso-Substrates……Page 377
19.2.3.1.2 Dynamic Kinetic Resolution……Page 379
19.2.3.2 Proteases……Page 380
19.2.4 LYASES (E.C. 4.X.X.X)……Page 382
19.2.4.1 Aldolases……Page 384
19.2.4.2 Decarboxylases……Page 385
19.2.4.3 Hydroxynitrile Lyases……Page 386
19.2.5 ISOMERASES (E.C. 5.X.X.X)……Page 387
19.3.1 AROMATIC AMINO ACID PATHWAY……Page 388
19.3.2 POLY-beta-HYDROXYALKANOATES……Page 389
19.3.3 POLYKETIDES AND NONRIBOSOMAL PEPTIDES……Page 390
19.4 SCREENING FOR BIOCATALYSTS……Page 393
19.5 SUMMARY……Page 395
REFERENCES……Page 396
20.1 INTRODUCTION……Page 407
20.2.1 DISCOVERY……Page 408
20.2.2.2 Multiple Gene Methods……Page 409
20.3 NITRILASES……Page 410
20.4 CEPHALOSPORIN C AMIDASE……Page 413
20.5 ALDOLASES……Page 414
20.6 EPOXIDE HYDROLASES……Page 416
REFERENCES……Page 418
21.1 INTRODUCTION……Page 420
21.3.1.1 Kinetic Considerations……Page 421
21.3.2 ONE-POT SYNTHESIS AND ONE-POT PROCESSING……Page 422
21.3.2.1 Biocatalyst Environment: Types of Chemistry……Page 423
21.4.1 CHEMISTRY IN AQUEOUS ENVIRONMENTS……Page 424
21.4.2 CHEMISTRY IN ORGANIC ENVIRONMENTS……Page 426
21.5 SUMMARY AND FUTURE TRENDS……Page 427
REFERENCES……Page 428
22.2 SN2 REACTIONS……Page 430
22.3 EPOXIDE OPENINGS……Page 433
22.5 IODOLACTONIZATIONS……Page 434
22.6 ALLYLIC SUBSTITUTIONS……Page 435
22.7 SUMMARY……Page 439
REFERENCES……Page 440
23.1.1 GENERAL CHIRAL AUXILIARY REVIEW……Page 444
23.2 CHIRAL AUXILIARY STRUCTURES IN PHARMACEUTICALS……Page 445
23.3.1 EZETIMIBE……Page 447
23.3.3 ZAMBON NAPROXEN PROCESS……Page 448
23.3.4 PARKE-DAVIS ROUTE TO CI-1008……Page 449
23.4 POTENTIAL APPLICATIONS OF CHIRAL AUXILIARIES……Page 450
REFERENCES……Page 456
24.1 INTRODUCTION……Page 458
24.2 CIS-1-AMINO-2-INDANOL IN BIOLOGICAL TARGETS……Page 459
24.3 PRACTICAL SYNTHESIS OF ENANTIOPURE CIS-1-AMINO-2-INDANOL……Page 464
24.3.1 ASYMMETRIC EPOXIDATION OF INDENE……Page 465
24.3.2 RITTER-TYPE PROCESS FOR CIS-1-AMINO-2-INDANOL SYNTHESIS……Page 466
24.4.1 ALDOL CONDENSATION……Page 467
24.4.2 ALKYLATION AND HOMOALDOL REACTIONS……Page 469
24.4.3 CONJUGATE ADDITION……Page 472
24.4.4 DIELS-ALDER REACTION……Page 473
24.4.5 ASYMMETRIC ADDITIONS TO alpha-KETOESTERS AND alpha-KETOAMIDES……Page 475
24.4.6 ASYMMETRIC REARRANGEMENTS……Page 477
24.4.8 PRACTICAL SYNTHESIS OF ENANTIOPURE SULFINAMIDES AND SULFOXIDES……Page 478
24.5.1 CIS-2-AMINO-3,3-DIMETHYL-1-INDANOL……Page 480
24.5.2 CIS-1-AMINO-2-HYDROXY-1,2,3,4-TETRAHYDRONAPHTHALENE……Page 483
REFERENCES AND NOTES……Page 484
25.1 INTRODUCTION……Page 488
25.2 ENANTIOPURE alpha-AMINO ACIDS PREPARED BY MEANS OF DIASTEREOSELECTIVE STRECKER REACTIONS……Page 490
25.3 DIASTEREOSELECTIVE ALLYLATION REACTIONS……Page 492
25.3.1 SYNTHESIS OF ENANTIOPURE 1-AMINOBUTANES FROM PGA-HOMOALLYLAMINES……Page 494
25.3.2 SYNTHESIS OF ENANTIOPURE HOMOALLYLAMINES VIA NONREDUCTIVE REMOVAL OF (R)-PGA……Page 495
25.4 DIASTEREOSELECTIVE HYDROGENATIONS OF (R)-PGA-IMINES……Page 496
25.5 SUMMARY……Page 500
REFERENCES AND NOTES……Page 501
26.1 INTRODUCTION……Page 503
26.2.1 REGIOCHEMISTRY AND STEREOCHEMISTRY……Page 504
26.2.2.1 Chiral Lewis Acids……Page 505
26.2.3 CHIRAL DIENOPHILES……Page 507
26.2.4 CHIRAL DIENES……Page 510
26.2.8 INTRAMOLECULAR DIELS-ALDER REACTIONS……Page 511
26.2.9 HETERO DIELS-ALDER REACTIONS……Page 512
26.3 CLAISEN-TYPE REARRANGEMENTS……Page 513
26.3.3 ESTER ENOLATE CLAISEN REARRANGEMENT……Page 514
26.4 THE ENE REACTION……Page 515
26.5 DIPOLAR CYCLOADDITIONS……Page 516
26.6.2 EVANS REARRANGEMENT……Page 517
26.8 SUMMARY……Page 519
REFERENCES……Page 520
27.1 INTRODUCTION……Page 530
27.2 STOICHIOMETRIC FREE-RADICAL REDUCTIONS……Page 531
27.2.2 EXAMPLES RELEVANT TO THE FINE CHEMICAL INDUSTRY……Page 533
27.3 STRATEGIES FOR THE AVOIDANCE OF TIN WASTE……Page 534
27.3.2 REDUCTIONS CATALYTIC IN TIN……Page 535
27.4 SUMMARY……Page 536
REFERENCES……Page 537
28.2 REACTION TYPES……Page 538
28.3 MECHANISM……Page 540
28.4 RING CLOSING METATHESIS……Page 541
28.5 CROSS METATHESIS……Page 548
28.6 CHIRAL METATHESIS……Page 550
28.8 RUTHENIUM REMOVAL……Page 554
REFERENCES……Page 555
29.2.1 2-CHLOROPROPIONIC ACID……Page 558
29.2.2 ANATOXIN a……Page 559
29.2.3 CHROMATOGRAPHY……Page 560
29.3.1 A KEY LEUKOTRIENE INTERMEDIATE……Page 561
29.4.2 THE METHADONE STORY……Page 562
29.4.2.1 Early Methods for Producing Chiral Methadones……Page 563
29.4.2.2 Lipase-Catalyzed Resolution of (R,S)–Dimethylaminopropan-2-ol……Page 564
29.4.2.3 Levo-alpha-Acetylmethadol……Page 565
29.4.3 ENZYMATIC GENERATION AND IN SITU SCREENING OF DYNAMIC COMBINATORIAL LIBRARIES……Page 566
REFERENCES AND NOTES……Page 569
30.2 CHOICES OF SYNTHETIC APPROACH……Page 571
30.2.1 COREY LACTONE APPROACH TO PROSTAGLANDINS……Page 572
30.2.2 NEWTON-ROBERTS (TRICYCLOHEPTANONE) ROUTES TO PROSTAGLANDINS……Page 573
30.2.3 CYCLOPENTENONE-INTERMEDIATE ROUTES TO PROSTAGLANDINS……Page 574
30.3 CHOICE OF ROUTE FOR TRAVOPROST SYNTHESIS……Page 576
30.4 COMMERCIAL SYNTHESIS OF TRAVOPROST……Page 577
30.5 PROCESS-RELATED IMPURITIES……Page 581
REFERENCES……Page 584
31.1 INTRODUCTION……Page 586
31.2 PHARMACEUTICALS……Page 587
31.2.1 LIPITOR……Page 588
31.2.2 SIMVASTATIN……Page 591
31.2.5 PAROXETINE……Page 592
31.2.6 SERTRALINE……Page 594
31.2.7 SERETIDE……Page 595
31.2.9 AUGMENTIN……Page 597
31.2.10 VALSARTAN……Page 598
31.3.2.1 Chemical Synthesis……Page 599
31.3.2.2 Enzymatic Synthesis……Page 601
31.4.1 METOLACHLOR……Page 602
31.4.2 PHENOXYPROPIONIC ACID HERBICIDES……Page 603
31.5 SUMMARY……Page 604
REFERENCES……Page 605
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