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Home , Organogermanium compound, Organomercury, Organonickel, Organopalladium

COMPREHENSIVE ORGANIC TRANSFORMATIONS

A Guide to Functional Group Preparations Second Edition

By Richard C. Larock

WILEY-VCH New York • Chichester • Weinheim • Brisbane • Singapore • Toronto CONTENTS

LITERATURE ABBREVIATIONS xxxv CHEMICAL ABBREVIATIONS xli

ALKANES AND ARENES 1 GENERAL REFERENCES 3

1.REDUCTION 5 1. Cyclic Alkanes 5 2. Arenes 6 3. 7 3.1. Catalytic Hydrogenation 7 3.2. Diimide Reduction (HN = NH) 12 3.3. Hydroboration-Protonolysis 12 3.4. Metal Hydrides 12 3.5. Miscellaneous Reagents 13 3.6. Conjugate Reduction 13 3.7. Reductive Dimerization 28 4. 28 4.1. Catalytic Hydrogenation 28 4.2. Hydroalumination-Protonolysis 28 4.3. Miscellaneous Reagents 28 5. Organic Halides 29 5.1. Low-Valent Metals 29 5.2. Metal Hydrides 30 5.3. Miscellaneous Reagents 34 6. and Derivatives 39 7. Nitro Compounds 41 8. Ethers 42 9. Alcohols and Phenols 44 9.1. Direct Reduction 44 9.2. Via Phosphorus Compounds 46 9.3. Via Sulfonates 47 9.4. Via Other Derivatives 49 10. Sulfur Compounds 53

xv XVI Contents

11. Selenium Compounds 60 12. Aldehydes and Ketones 61 12.1 Direct Reduction 61 12.2. Via Hydrazones 64 12.3. Via and Sulfur Derivatives 65 12.4. Via Selenium Derivatives 65 12.5. Decarbonylation 65 12.6. Ketone Cleavage 67 12.7. Reductive Coupling 67 13. Acetals 68 14. Carboxylic Acids 68 15. Acid Halides 70 16. Esters and Lactones 70 17. Nitriles 75 18. Isonitriles 76

2. COUPLING REACTIONS 77 1. Symmetrical or Intramolecular Coupling 77 2. Unsymmetrical Coupling 88 2.1. Organolithium Reagents 88 2.2. Organosodium or-Potassium Compounds 100 2.3. Grignard Reagents 101 2.4. Organoboron Reagents 104 2.5. Organoaluminum Reagents 106 2.6. Organothallium Reagents 107 2.7. Reagents 108 2.8. Organogermanium Reagents 109 2.9. Organotin Reagents 109 2.10. Reagents 111 2.11. Sulfur Reagents 111 2.12. Selenium Reagents 112 2.13. Tellurium Reagents 113 2.14. Phosphorus Reagents 113 2.15. Organotitanium and- Reagents 113 2.16. Organozirconium Reagents 114 2.17. Vanadium Reagents 114 2.18. Organochromium Reagents 115 2.19. Organomanganese Reagents 116 2.20. Organoiron Reagents 116 2.21. Reagents 116 2.22. Reagents 117 2.23. Organocopper Reagents 118 2.24. Organosilver Reagents 122 2.25. Organozinc Reagents 122 2.26. Reagents 124 2.27. Miscellaneous Reagents 125

3. FRIEDEL-CRAFTS AND RELATED ALKYLATION REACTIONS 129 4. RING-FORMING REACTIONS 135 1. Three-Membered Rings 135 2. Four-Membered Rings 161 Contents XVII

3. Five-Membered Rings 168 4. Six-Membered Rings 174 5. Various Ring Sizes 175 6. Carbocationic Cyclization 185 7. Polycyclics 185

5. AROMATIZATION 187 1. Dehydrogenation 187 2. Elimination 191 3. Reductive Elimination 193 4. Rearrangement 195 5. Cyclization and Annulation 196 6. Diels-Alder and Related Reactions 207

ALKENES 215 GENERAL REFERENCES 217

1. ISOMERIZATION OF ALKENES 219 1. Inversion 219 2. Simple Rearrangement 220 2.1. Thermal 220 2.2. Photochemical 220 2.3. Cation Radical 221 2.4. Base-Promoted 222 2.5. Acid-Catalyzed 223 2.6. Sulfur Dioxide 223 2.7. Ene Reaction-Reduction 223 2.8. lodine 223 2.9. Transition Metal-Catalyzed 223 2.10. Organoboranes 226 2.11. Trimethylsilyl Chloride 226 2.12. Addition-Elimination 227 3. Functional Group Rearrangement 227 4. Reductive Transposition 229 5. Oxidative Transposition 231 6. Metal and Heteroatom Displacement 234 7. Ene Reaction 236 8. Alkylative Transposition 236

2. ELIMINATION 251 1. Dehydrogenation 251 2. Dehydrohalogenation of Halides 256 3. 1,1-Dihalides 258 4. 1,2-Dihalides 259 5. 1,3-Dihalides 263 6. jS-Halo Ethers 263 7. Halohydrins 266 8. 0-Halo Esters 267 9. jß-Halo Sulfonates 268 10. Amines 268 11. ß-Halo Amines 269 XVIII Contents

12. Oxides (Cope Elimination) 269 13. Quaternary Ammonium Salts 269 14. A/-Alkyl-A/,A/-disulfonimides 270 15. A/-Nitrosocarboxamides 270 16. Nitro Compounds 270 17. Diazo Compounds 271 18. /?-Substituted Azides 272 19. Ethers 272 20. ß-Substituted Ethers 277 21. Sulfides 278 22. a-Halosulfides 279 23. ß-Halosulfides 279 24. ß-Hydroxysulfides 279 25. Sulfoxides 280 26. ß-Hydroxysulfoxides 281 27. Sulfones 281 28. a-Halosulfones (Ramberg-Bäcklund Reaction) 283 29. ß-Hydroxysulfones 283 30. ß-Acyloxysulfones 284 31. Other ß-Substituted Sulfones 285 32. Disulfones 286 33. Sulfonyl Halides 286 34. ß-Oxyselenides 286 35. Selenoxides 287 36. Tellurides 290 37. Organosilanes 290 38. ß-Halosilanes 290 39. jß-Oxysilanes and -Stannanes 291 40. ß-Aminosilanes 291 41. Dehydration of Alcohols 291 42. Sulfonate Esters 294 43. Sulfates 295 44. Phosphates and Thiophosphates 295 45. Xanthates 296 46. Thiocarbonates 296 47. Carbamates 297 48. A/-Methyl-4-alkoxypyridinium lodides 297 49. 1,2-Diols and Derivatives 297 49.1. Stereospecific Cis Elimination 297 49.2. Nonstereospecific or Unknown Stereochemistry 298 50. 1,2-Disulfonates 300 51. 1,3-Diols 300 52. Acetals 300 53. Dithioacetals 300 54. Aldehydes and Ketones 301 54.1. Direct Elimination 301 54.2. Arenesulfonylhydrazone Eliminations 301 54.3. Enone Conversions 303 54.4. Reduction of Carbonyl Derivatives 304 54.5. Dimerization of Aldehydes and Ketones 305 54.6. Miscellaneous Reactions 308 55. Lactols 309 Contents XIX

56. Carboxylic Acids 309 57. Acid Halides 311 58. Acid Anhydrides 312 59. Esters and Lactones 312 60. Thioesters 314 61. Amides and Lactams 314 62. Imides 315 63. Nitriles 315 64. Miscellaneous Reactions 315

3. ALKYLIDENATION OF CARBONYL AND RELATED COMPOUNDS 317 4. WITTIG AND RELATED REACTIONS 327 1. Wittig Reaction 327 1.1. General 327 1.2. Intramolecular Wittig 328 1.3. Mechanism 328 1.4. Miscellaneous Reactions 328 2. ß-Oxido Ylids 332 3. Ylid Anions 332 4. Phosphonates 332 4.1. General 332 4.2. Intramolecular 333 4.3. Miscellaneous Reactions 333 5. Phosphonamidates [(R2N)(R0)P0CHÜR] 334 6. Phosphonic Acid bis Amides [(R2N)2POCHLiR] 334 7. Phosphinothioic Amides [PhPS(NR2)CHLiR] 334 8. Phosphine Oxides 335 9. Arsenic Ylids 335 10. Sulfur Reagents 336 11. Selenium Reagents 336 12. Tellurium Reagents 337 13. Boron Reagents 337 14. Peterson Reaction (Oxysilane Elimination) and Related Reactions 337 15. Isonitriles 341 16. Miscellaneous Reactions 341

5. METAL-PROMOTED COUPLING REACTIONS 351 1. Reagents 351 2. Grignard Reagents 359 3. Boron Reagents 362 4. Aluminum Reagents 364 5. Indium Reagents 364 6. Thallium Reagents 365 7. Reagents 365 8. Reagents 373 9. Reagents 373 10. Sulfur Reagents 378 11. Selenium Reagents 379 12. Tellurium Reagents 379 13. Titanium Reagents 379 14. Zirconium Reagents 379 XX Contents

15. Molybdenum Reagents 380 16. Manganese Reagents 380 17. Iron Reagents 380 18. Ruthenium Reagents 381 19. Cobalt Reagents 381 20. Reagents 382 21. Reagents 386 22. Copper Reagents 392 23. Silver Reagents 399 24. Zinc Reagents 399 25. Reagents 400 26. 401

6. ARENE, AND DIENE ADDITION REACTIONS 403 1. Hydrogen Addition 403 2. Alkylation and Functionalization 410 2.1. Thermal or Lewis Acid-Promoted 410 2.2. Photochemical 413 2.3. Free Radical 413 2.4. Michael Additions 418 2.5. Organolithium Compounds 419 2.6. Organomagnesium Compounds 420 2.7. Organocalcium Compounds 421 2.8. Organoboron Compounds 421 2.9. Organoaluminum Compounds 427 2.10. Organosilicon Compounds 432 2.11. Organotin Compounds 434 2.12. Organsulfur and-selenium Compounds 437 2.13. Organotellurium Compounds 438 2.14. Organotitanium Compounds 438 2.15. Organozirconium Compounds 440 2.16. Organotantalum Compounds 443 2.17. Organochromium and -tungsten Compounds 444 2.18. Organomanganese Compounds 444 2.19. Organoiron Compounds 445 2.20. Organoruthenium Compounds 445 2.21. Organoosmium Compounds 446 2.22. Organocobalt Compounds 446 2.23. Organorhodium Compounds 446 2.24. Organoiridium Compounds 447 2.25. Organonickel Compounds 447 2.26. Organopalladium Compounds 448 2.27. Organopalladium and -platinum Compounds 452 2.28. Organocopper Compounds 452 2.29. Organosilver Compounds 460 2.30. Organozinc Compounds 460 2.31. Organomercury Compounds 461 2.32. Miscellaneous Reagents 461

7. DIENES AND POLYENES 463 1. Rearrangement 463 2. Elimination Reactions 466 Contents XXI

3. Organometallic Approaches 475 3.1. Organolithium and-sodium Compounds 475 3.2. Organomagnesium Compounds 476 3.3. Organobarium Compounds 479 3.4. Organoboron Compounds 479 3.5. Organoaluminum Compounds 482 3.6. Organoindium Compounds 484 3.7. Organosilicon Compounds 484 3.8. Organotin Compounds 487 3.9. Sulfur Reagents 490 3.10. Tellurium Reagents 491 3.11. Phosphorus Reagents 492 3.12. Organotitanium Compounds 493 3.13. Organozirconium Compounds 494 3.14. Organoniobium Compounds 496 3.15. Organochromium Compounds 496 3.16. Organoiron Compounds 497 3.17. Organoruthenium Compounds 498 3.18. Organocobalt Compounds 499 3.19. Organorhodium Compounds 499 3.20. Organonickel Compounds 499 3.21. Organopalladium Compounds 501 3.22. Organocopper Compounds 506 3.23. Organosilver Compounds 513 3.24. Organozinc Compounds 514 3.25. Organomercury Compounds 515 4. Arene Conversions 516 5. Cyclization 518 6. Miscellaneous Reactions 522

8. DIELS-ALDER REACTIONS 523 1. General Reviews 523 2. 523 3. Exo/Endo Selectivity 524 4. Asymmetrie Diels-Alder Reaction 524 4.1. Reviews 524 4.2. Regulär Diels-Alder Reaction 525 4.3. Inverse Electron-Demand Diels-Alder Reaction 527 4.4. Hetero Diels-Alder Reaction 527 5. Mechanism 528 6. Use of High Pressure 528 7. Microwave Irradiation 528 8. Ultracentifugation 528 9. Use of Ultrasound 528 10. 528 11. Solvent Effects 530 12. Retro-Diels-Alder Reaction 530 13. Intramolecular Diels-Alder Reaction 530 14. Inverse Electron-Demand Diels-Alder Reaction 532 15. Radical Cation Diels-Alder Reaction 532 16. lonic Diels-Alder Reaction 532 17. Use of Heterodienophiles 533 XXII Contents

18. Use of Heteroatom-Containing Dienes 533 19. Use of substituted 1,3-Dienes 534 19.1. Heteroatom-substituted 1,3-Dienes 534 19.2. -Substituted 1,3-Dienes 535 20. o-Quinodimethanes and Heterocyclic Analogues 536 21. 537 22. Some Other Dienophiles 537 23. Dienophile Equivalents 541 24. Transition Metal as Dienophiles 544

9. CYCLIZATION, ANNULATION AND RELATED REACTIONS 545 1. Three-Membered Rings 545 2. Four-Membered Rings 546 3. Five-Membered Rings 547 4. Six-Membered Rings 556 5. Seven-Membered Rings 558 6. Eight-Membered Rings 559 7. Nine-Membered Rings 559 8. Various-Membered Rings 559

10. MISCELLANEOUS REACTIONS 561 ALKYNES 563 GENERAL REFERENCES 565

1. ISOMERIZATION 567

2. ELIMINATION REACTIONS 569

3. WITTIG AND RELATED APPROACHES 581

4. ALKYLATION, ALKENYLATION AND ARYLATION OF ALKYNES AND ALLENES 585 1. Organolithium, -sodium and -magnesium Compounds 585 2. Organoboron Compounds 589 3. Organoaluminum Compounds 590 4. Organothallium Compounds 591 5. Organosilicon Compounds 591 6. Organotin Compounds 592 7. Organozirconium Compounds 594 8. Organocobalt Compounds 594 9. Organonickel Compounds 596 10. Organopalladium Compounds 596 11. Organocopper Compounds 599 12. Organozinc Compounds 604 13. Organomercury Compounds 604 14. Organosamarium Compounds 604 15. Miscellaneous Reactions 605 HALIDES 607 GENERAL REFERENCES 609

1. HALOGENATION OF HYDROCARBONS 611 1. Aliphatic Halogenation 611 2. Allylic Halogenation 614 Contents XXIII

3. Benzylic Halogenation 615 2. AROMATIC HALOGENATION 619

3. HALOGENATION OF ALKENES 629 1. Halogen Addition 629 2. Hydrohalogenation 633 2.1. Markovnikov Addition 633 2.2. Anti-Markovnikov Addition 635 2.3. Unknown Regiochemistry 636 2.4. Isomerization-Addition 636 3. Hydrogen Substitution 636 4. Halofunctionalization 638 5. Haloalkylation 647 6. Miscellaneous Reactions 653

4. HALOGENATION OF ALKYNES 655

5. INTERCONVERSION OF HALIDES 667 1. Aliphatic Halides 667 2. Vinylic Halides 671 3. Aromatic Halides 671 4. Homologation of Halides 672 5. Rearrangement of Halides 674

6. HALOGENATION OF NITROGEN COMPOUNDS 677 7. HALOGENATION OF ETHERS 685

8. HALOGENATION OF ALCOHOLS 689 1. Direct Methods 689 2. Via Sulfonates 697 3. Via Haloformates 700 4. Other Approaches 701 5. Diols 701

9. HALOGENATION OF PHENOLS 703

10. HALOGENATION OF SULFUR AND SELENIUM COMPOUNDS 705

11. HALOGENATION OF CARBONYL AND RELATED COMPOUNDS 709 1. Aldehydes and Ketones 709 2. Acetals 727 3. Lactols 730 4. Carboxylic Acids 730 5. Acid Halides 731 6. Esters and Lactones 732 7. Amides 736 8. Imides and Related Compounds 739 9. Nitriles 739

12. HALODECARBOXYLATION AND DECARBONYLATION OF ACIDS AND DERIVATIVES 741

13. HALOGENATION OF ORGANOMETALLICS 745 XXIV Contents

AMINES 753 GENERAL REFERENCES 755

1. FROM ALKANES 757

2. FROM ARENES 759

3. FROM ALKENES, DIENES AND ALKYNES 761

4. FROM ALKYL AND ARYL HALIDES OR SULFONATES 779

5. FROM OTHER AMINES AND DERIVATIVES 785 1. Reduction 785 2. Alkylation on Nitrogen 789 3. Alkylation on Carbon 792 4. Ring Opening 802 5. Dealkylation 807 6. Rearrangement 810

6. FROMAZIDES 815

7. FROM NITRO COMPOUNDS 821

8. HETEROATOM AND METAL DISPLACEMENT 829

9. FROM ETHERS, ALCOHOLS AND DERIVATIVES 831

10. FROM ALDEHYDES, KETONES AND DERIVATIVES 835 1. Transamination 835 2. Reductive Amination 835 3. Alkylative Amination 847 4. Mannich and Related Reactions 863 5. a-Amination 865 6. Miscellaneous Reactions 866

11. FROM CARBOXYLIC ACIDS AND DERIVATIVES 867 1. Molecular Rearrangements 867 1.1. Hoff man 867 1.2. Curtius 868 1.3. Lossen 869 1.4. Schmidt 869 1.5. Miscellaneous 869 2. Reduction of Amides and Imides 869 3. Reductive Alkylation 872 4. Substitution 874

12. FROM NITRILES 875

13. FROM ISONITRILES 879 Contents xxv

ETHERS 881 GENERAL REFERENCES 883

1. FROM OTHER ETHERS 885

2. ALKYLATION OF ALCOHOLS AND PHENOLS 889

3. ALKANE, ARENE, ALKENE AND ALKYNE ADDITIONS AND SUBSTITUTIONS 911 1. Alkane Substitution 911 2. Arene Addition and Substitution 911 3. Alkene Substitution 912 4. Alkene Addition 912 5. Epoxidation of Alkenes 915 6. Diene Addition 927 7. Alkyne Addition 928

4. ACETAL, CARBONYL AND ORTHO ESTER CONVERSIONS 931 1. Acetals 931 2. Aldehydes and Ketones 942 3. Lactols 951 4. Carboxylic Acids 953 5. Esters and Lactones 953 6. Peresters 956 7. Ortho Esters and Related Compounds 956

5. MISCELLANEOUS REACTIONS 957

ALCOHOLS AND PHENOLS 959 GENERAL REFERENCES 961

1. RESOLUTION 963

2. ALCOHOL TRANSPOSITION 965

3. SUBSTITUTION 969 1. Hydrogen Substitution 969 2. Halide and Sulfonate Substitution 970 3. Cyclic Sulfite, Sulfate and Thiocarbonate Substitution 972 4. Nitrogen Substitution 973 5. Acetate Substitution 974

4. OXIDATION 975 1. Alkanes 975 2. Arenes 977 3. Alkenes 978 4. Dienes 980 5. Alkynes 981 6. Alcohols 981 7. Carbonyl Compounds 981 8. Organometallics 987 XXVI Contents

5. ALKENE, DIENE AND ALKYNE ADDITIONS 991 1. Alkenes 991 2. Dienes 1003 3. Alkynes 1003

6. ORGANOBORANES 1005 1. Hydroboration-Oxidation 1005 1.1. Asymmetrie Hydroboration 1008 2. and Related Reactions 1009 3. Other Reactions 1010

7. ETHER CLEAVAGE 1013 1. Cleavage of Acyclic Ethers 1013 2. Reduction of Cyclic Ethers 1019 3. Nucleophilic Opening of Cyclic Ethers 1027 4. Alkylation of Cyclic Ethers 1045 4.1. Epoxides 1045 4.2. Oxetanes 1061 4.3. Larger Rings 1061 4.4. Various Rings 1063 5. Rearrangement 1063 6. Acetal Cleavage 1067

8. REDUCTION 1073 1. Peroxides 1073 2. Aldehydes and Ketones 1075 2.1. Hydrogenation 1075 2.2. Reduction by Metals 1076 2.3. Metal Hydride Reduction 1077 2.4. Miscellaneous Reagents 1087 2.5. Reduction of Aldehydes in Preference to Ketones 1089 2.6. Reduction of Ketones in Preference to Aldehydes 1090 2.7. Selective Reduction Between Aldehydes 1091 2.8. Reduction of Conjugated Aldehydes in Preference to Nonconjugated Aldehydes 1091 2.9. Reduction of Conjugated Aldehydes in Preference to Enones 1091 2.10. Selective Reduction Between Ketones 1091 2.11. Reduction of Enones in Preference to Aldehydes 1091 2.12. Reduction of Enones in Preference to Ketones 1092 2.13. Reduction of Ketones in Preference to Enones 1092 2.14. Reduction of Enals and Enones to Allylic Alcohols 1092 2.15. Reduction of Enals and Enones to Saturated Alcohols 1096 2.16. Asymmetrie Reduction of Aldehydes and Ketones 1097 2.17. Pinacol Reaction 1111 3. Carboxylic Acids and Derivatives 1114

9. ALKYLATION OF CARBONYL COMPOUNDS 1125 1. Addition to 1125 2. Addition to Aldehydes and Ketones 1125 2.1. Organometallic Additions 1125 2.2. Miscellaneous Additions 1176 Contents XXVII

3. Alkylation of a-Haloketones 1188 4. Addition to Hemiacetals 1189 5. Addition to Carboxylic Acids and Derivatives 1190

10. MISCELLANEOUS REACTIONS 1195

ALDEHYDES AND KETONES 1197 GENERAL REFERENCES 1199

1. CARBONYL TRANSPOSITION 1201

2. OXI DATION 1205 1. Alkanes 1205 2. Alkenes 1207 3. Enamines 1215 4. Alkenylphosphonates 1216 5. Dienes and Polyenes 1216 6. Alkynes 1217 7. Halides, Nitrates and Sulfonates 1222 8. Amines 1225 9. Nitro Compounds 1227 10. Diazo Compounds 1229 11. Azides 1229 12. Phosphorus Ylids 1229 13. Ethers 1230 14. Sulfides 1233 15. Sulfoxides 1233 16. Sulfones 1234 17. Phenols 1234 18. Alcohols 1234 19. Allylic Alcohols 1249 20. Homoallylic Alcohols 1250 21. Propargylic Alcohols 1250 22. Diols and Derivatives 1250 23. Halohydrins 1256 24. a-Hydroxyketones 1256 25. Hydroxyacids and Derivatives 1256 26. Aldehydes 1257 27. Ketones 1257 28. Acetals 1258 29. Carboxylic Acids 1258 30. Esters 1259 31. Amides 1259 32. Nitriles 1260 33. Furans 1260 34. Organometallics 1261

3. REDUCTION OF PHENOLS, CARBOXYLIC ACIDS AND DERIVATIVES, AND NITRILES 1263 1. Phenols 1263 2. Acylsilanes 1263 XXVIII Contents

3. Carboxylic Acids 1263 4. Acid Halides 1265 5. Anhydrides 1266 6. Esters 1267 7. Thioesters 1268 8. Selenoesters 1268 9. Lactones 1268 10. Amides and Imides 1269 11. Nitriles 1271 12. 4,5-Dihydrooxazoles 1273 4. REARRANGEMENTS 1275 1. Isomerization 1275 2. Epoxides 1277 3. Vinylic Ethers 1280 4. Pinacol and Related Rearrangements 1281 5. Ring Rearrangement 1283 6. Ring Opening 1284 7. Ring Contraction 1285 8. Ring Expansion 1287 9. Electrocyclic Rearrangements 1302 9.1. 1,3-Claisen 1302 9.2. 3,3-Claisen 1302 9.3. Amino-Claisen 1303 9.4. Oxy-Claisen 1304 9.5. Thio-Claisen 1304 9.6. Claisen-Cope 1304 9.7. Cope-Claisen 1305 9.8. 2,3-Wittig-Oxy-Cope 1305 9.9. 1,3-Oxy-Cope 1305 9.10. 3,3-Oxy-Cope 1306 9.11. Oxy-Cope-Claisen 1307 9.12. Oxy-Cope-Cope 1307 9.13. Mannich-Aza-Cope 1308 9.14. Carroll 1308 9.15. Nazarov 1308 9.16. Electrocyclization 1309 9.17. 2,3-Sigmatropic Rearrangements 1309 9.18. Fries Rearrangement 1310 10. Miscellaneous Rearrangements 1311 5. CONDENSATION REACTIONS 1313 1. Acetoacetic Ester 1313 2. Acyloin 1313 3. Benzoin and Related Reactions 1315 4. Dieckmann and Related Reactions 1316 5. Mannich 1317 6. Michael 1317 7. Thorpe-Ziegler 1317 8. Aldol and Related Reactions 1317 8.1. Metal Enolates 1318 8.2. Related Reactions 1325 9. Other Condensation Reactions 1327 Contents XXIX

6. CYCLIZATION AND ANNULATION REACTIONS 1329 1. Cyclization 1329 2. Spiroannulation 1337 3. One-Carbon Annulation 1338 4. Two-Carbon Annulation 1338 5. Three-Carbon Annulation 1345 6. Four-Carbon Annulation 1356 6.1. Robinson and Related Annulations 1356 6.2. Reversed Robinson Annulation 1358 6.3. Other Four-Carbon Annulations 1358 7. Four-and Five-Carbon Annulation 1362 8. Five-and Six-Carbon Annulation 1362 9. Six-Carbon Annulation 1362

7. CARBONYLATION AND RELATED REACTIONS 1363 1. Alkanes 1363 2. Free Radicals 1363 3. Organolithium Compounds 1364 4. Organoboron Compounds 1365 5. Organosilicon Compounds 1367 6. Organotin Compounds 1367 7. Organotitanium Compounds 1368 8. Organozirconium Compounds 1368 9. Organomolybdenum Compounds 1369 10. Organotungsten Compounds 1369 11. Organomanganese Compounds 1369 12. Organoiron Compounds 1370 13. Organoruthenium Compounds 1370 14. Organocobalt Compounds 1371 15. Organorhodium Compounds 1372 16. Organonickel Compounds 1373 17. Organopalladium Compounds 1374 18. Compounds 1377 19. Organocopper Compounds 1377 20. Organomercury Compounds 1378 21. Organosamarium Compounds 1378 22. Hydroformylation, Hydroacylation and Related Reactions 1378

8. ELECTROPHILIC ACYLATION 1381 1. Synthesis of Aldehydes 1381 2. Synthesis of Ketones 1383 2.1. From Carbonyl Cation Equivalents 1383 2.2. From Acylium Salts 1384 2.3. From Aldehydes 1384 2.4. From Acylsilanes 1386 2.5. From Carboxylic Acids 1386 2.6. From Acid Halides 1389 2.7. From Acid Anhydrides 1400 2.8. From Esters and Lactones 1403 2.9. From Thioesters 1411 2.10. From Selenoesters 1411 XXX Contents

2.11. From Ortho Esters 1412 2.12. From Ketenes 1412 2.13. From Amides 1412 2.14. From Thioamides 1418 2.15. From Imides 1418 2.16. From Acid Nitriles 1419 2.17. From Nitriles 1420 2.18. From Isocyanide Dichlorides 1422 3. Friedel-Crafts and Related Reactions 1422

9. NUCLEOPHILIC ACYLATION 1435 1. Cyanohydrin Derivatives 1435 2. Isonitriles 1438 3. Iron Carbonyl Reagents 1439 4. Allylic Amides 1440 5. Allylic Ethers and Carbamates 1440 6. Vinylic Ethers 1441 7. Other Metallated Ethers 1445 8. Amino Acetals 1446 9. Miscellaneous Nucleophilic Acylation Reactions 1447

10. SULFUR, SELENIUM AND TELLURIUM REAGENTS 1451 1. Sulfur Acetals 1451 2. a-Thiosulfoxides 1455 3. a-Substituted Sulfones 1456 4. Thiocarbamates 1456 5. Thioesters 1457 6. Vinylic and Allylic Sulfides and Selenides 1457 7. Miscellaneous Reactions 1458

11.HETEROCYCLES 1461 1. Pyrylium Salts 1461 2. 1,3-Dioxanes 1461 3. 5,6-Dihydro-4H-1,3-oxazines 1462 4. 4,5-Dihydrooxazoles 1463 5. 4,5-Dihydroisoxazoles 1463 6. 4,5-Dihydro-1 H-imidazoles 1464 7. Benzotriazoles 1464 8. 4,5-Dihydrothiazoles 1464 9. Thiazoles 1465 10. Benzothiazoles 1465 11. 1,3-Oxathiolane-3,3-dioxides 1465 12. 1,3-Benzooxathiolium Salts 1465

12. CARBONYL HOMOLOGATION 1467

13. ALKYLATION AND ACYLATION OF ALDEHYDES, KETONES AND THEIR DERIVATIVES 1475 1. Free Radical Alkylation 1475 2. Direct Enol or Enolate Alkylation and Acylation 1476 3. Enol Ethers 1483 Contents XXXI

4. Enol Esters 1484 4.1. Synthesis of Enol Esters 1484 4.2. Applications 1485 5. Enol Alanes 1487 6. Enol Boranes 1488 7. Enol Silanes 1488 7.1. Preparation 1488 7.2. Reactions 1494 8. Enol Stannanes and Related Compounds 1506 9. Enol Phosphorus Compounds 1507 10. Enol Triflates 1507 11. Enamines 1507 12. Nitroalkenes 1511 13. 1513 14. Hydrazones 1516 15. Oxime Ethers 1519 16. Oximes 1519 17. Blocking Groups 1520 18. Alkylation and Acylation of Carbonyl Dianions 1520 19. Alkylation and Acylation of /J-Ketoaldehydes 1521 20. Alkylation and Acylation of ß-Diketones 1522 21. Alkylation and Acylation of ß-Polyketones 1528 22. Synthesis of ß-Keto Acids, Esters, Amides, Imides and Nitriles and 1528 23. Alkylation of Enones 1546

14. ALKYLATION OF a- AND ß-SUBSTITUTED CARBONYL COMPOUNDS 1559 1. Alkylation of Cyclopropyl Ketones 1559 2. Reduction and Alkylation of a-Substituted Ketones 1560 3. Substitutive Alkylation of a-Halocarbonyl Compounds 1562 3.1. Free Radical Reactions 1562 3.2. Electrophilic Substitution 1562 3.3. Organolithium and -magnesium Compounds 1562 3.4. Organoboron Compounds 1563 3.5. Tin Reagents 1563 3.6. Organocopper Compounds 1564 4. Substitutive Alkylation of ß-Halocarbonyl Compounds 1564 5. Substitutive Alkylation of a-Diazocarbonyl Compounds 1565 6. Decarboxylation-Allylation of /?-Keto Acids and Esters 1566

15. 1,4-ADDITION TO a,ß-UNSATURATED CARBONYL COMPOUNDS AND DERIVATIVES 1567 1. Free Radical and Related Addition Reactions 1567 2. Michael and Michael-like Addition Reactions 1571 3. Organoboron Compounds 1588 4. Organoaluminum -gallium and -thallium Compounds 1589 5. Organosilicon Compounds 1591 6. Organogermanium Compounds 1593 7. Organotin Compounds 1593 8. Organolead Compounds 1594 XXXII Contents

9. Organostibine Compounds 1594 10. Titanium Reagents 1594 11. Organozirconium Compounds 1595 12. Organomanganese Compounds 1595 13. Organoiron Compounds 1595 14. Organocobalt Compounds 1596 15. Organorhodium Compounds 1596 16. Organonickel Compounds 1596 17. Organopalladium Compounds 1598 18. Organocopper Compounds 1599 19. Organosilver Compounds 1613 20. Organozinc Compounds 1614 21. Organomercury Compounds 1615 22. Other Reagents 1616

16. MISCELLANEOUS REACTIONS 1617

NITRILES, CARBOXYLIC ACIDS AND DERIVATIVES 1621 GENERAL REFERENCES 1623

1. OXIDATION, SUBSTITUTION AND ADDITION 1625 1. Alkanes 1625 2. Arenes 1627 3. Alkenes 1628 4. Dienes 1634 5. Alkynes 1636 6. Alkyl Halides 1639 7. Amines 1640 8. Imines 1641 9. Nitro Compounds 1641 10. Nitrothioalkenes 1641 11. Ethers 1641 12. Sulfides 1646 13. Alcohols 1646 14. Diols 1650 15. Aminoalcohols 1652 16. Phenols 1653 17. Aldehydes and Derivatives 1653 18. Ketones 1661 19. Hemiacetals and Lactols 1670 20. Acetals 1670 21. Carboxylic Acids 1672 22. Esters 1673 23. Amides 1674 24. Nitriles 1675

2. REDUCTION 1677

3. CARBONYLATION, CARBOXYLATION AND RELATED REACTIONS 1681 1. Carboxylic Acids 1681 2. Acid Halides 1690 Contents

3. Esters 1690 4. Lactones 1700 5. Acid Anhydrides 1700 6. Amides 1700 7. Lactams 1704 8. Imides 1704 9. Nitriles 1705

4. CARBONYL HOMOLOGATION AND DEGRADATION 1711 1. Homologation 1711 2. Degradation 1716

5. ALKYLATION, ACYLATION AND SUBSTITUTION OF NITRILES, CARBOXYLIC ACIDS AND DERIVATIVES 1717 1. Carboxylic Acids 1717 2. Esters 1724 3. Anhydrides 1777 4. Amides and Carbamates 1778 5. Imides and Related Derivatives 1792 6. Nitriles 1801

6. CONJUGATE ADDITION TO a,jS-UNSATURATED NITRILES, CARBOXYLIC ACIDS AND DERIVATIVES 1809

7. REARRANGEMENTS 1843 1. Willgerodt and Related Reactions 1843 2. Baeyer-Villager 1845 3. Beckmann and Related Reactions 1845 4. Schmidt 1846 5. Curtius 1847 6. Oxaziridine—> Amide 1847 7. Favorski and Related Reactions 1847 8. BenzilicAcid 1849 9. Arndt-Eistert and Wolff 1850 10. Cope 1851 11. Aza-Cope 1851 12. Claisen 1851 13. Aza-Claisen and Related Rearrangements 1855 14. Allylic Selenides 1857 15. Imidate Esters 1857 16. 2,3-Sigmatropic Rearrangement 1858 17. Ene Reaction-Oxidation 1859 18. Ring Opening 1859 19. Ring Expansion 1859 20. Decarboxylation-Allylation 1860 21. Other Reactions 1860

8. LACTONE AND LACTAM FORMATION 1861 XXXIV Contents

9. INTERCONVERSION OF NITRILES, CARBOXYLIC ACIDS AND DERIVATIVES 1929 1. Carboxylic Acids to Acid Halides 1929 2. Carboxylic Acids to Acid Anhydrides 1930 3. Carboxylic Acids to Esters 1932 4. Carboxylic Acids to Amides 1941 5. Carboxylic Acids to Imides 1949 6. Carboxylic Acid to Nitriles 1949 7. Acid Halides to Other Acid Halides 1950 8. Acid Halides to Acid Anhydrides 1951 9. Acid Halides to Esters 1952 10. Acid Halides to Amides 1953 11. Acid Halides to Imides 1954 12. Acid Halides to Nitriles 1955 13. Acid Anhydrides to Acid Halides 1955 14. Acid Anhydrides to Esters 1955 15. Acid Anhydrides to Amides 1957 16. Acid Anhydrides to Imides 1958 17. Esters to Carboxylic Acids 1959 18. Esters to Acid Halides 1968 19. Esters to Acid Anhydrides 1968 20. Esters to Other Esters 1969 21. Esters to Amides 1973 22. Esters to Nitriles 1976 23. Amides to Carboxylic Acids 1976 24. Amides to Esters 1977 25. Amides to Other Amides 1978 26. Amides to Imides 1982 27. Amides to Nitriles 1983 28. Imides to Esters or Lactones 1985 29. Imides to Amides 1985 30. Imides to Other Imides 1986 31. Nitriles to Carboxylic Acids 1986 32. Nitriles to Esters 1987 33. Nitriles to Amides 1988 34. Other Interconversions 1990

10. MISCELLANEOUS REACTIONS 1995

TRANSFORMATION INDEX 1997