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. Alkenes 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. Alkynes 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. Amines 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 Oxygen 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. Organosilicon Reagents 108 2.8. Organogermanium Reagents 109 2.9. Organotin Reagents 109 2.10. Lead 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-zinc 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. Organonickel Reagents 116 2.22. Organopalladium Reagents 117 2.23. Organocopper Reagents 118 2.24. Organosilver Reagents 122 2.25. Organozinc Reagents 122 2.26. Organomercury 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. Alkene 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 Alkyl 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. Amine 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. Alkali Metal Reagents 351 2. Grignard Reagents 359 3. Boron Reagents 362 4. Aluminum Reagents 364 5. Indium Reagents 364 6. Thallium Reagents 365 7. Silicon Reagents 365 8. Germanium Reagents 373 9. Tin 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. Nickel Reagents 382 21. Palladium Reagents 386 22. Copper Reagents 392 23. Silver Reagents 399 24. Zinc Reagents 399 25. Mercury Reagents 400 26. Olefin Metathesis 401 6. ARENE, ALKYNE 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. Regioselectivity 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. Catalysis 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.