Asymmetric Synthetic Methodology (New Directions in Organic & Biological Chemistry)

This comprehensive text presents a critical discussion of the scopes and limitations of various organic synthetic methodologies that are available for performing asymmetric transformations. In addition to purely chemical methods, the book covers applications of new enzymes and other biological systems that are increasingly useful in asymmetric methodology. Cover......Page 1 Title Page......Page 2 Copyright Page......Page 3 The Authors......Page 4 Preface......Page 5 Table of Contents......Page 7 List of Figures......Page 14 List of Tables......Page 17 Chapter 1: Introduction......Page 20 1.1.3. Nomenclature Conventions......Page 21 1.1.4. Optical Purity......Page 23 1.2. Why Asymmetric Synthesis?......Page 24 1.3.1. Transition States......Page 26 1.3.2.1. Chiral Substrates......Page 27 1.3.2.3. Self Regeneration of Stereocenters......Page 31 1.3.2.4. Chiral Reagents......Page 33 1.3.2.7. The Introduction of Asymmetry......Page 34 1.4. Resolution......Page 35 1.4.1. Kinetic Resolution......Page 36 1.5. A Question of Scale......Page 37 1.7. References......Page 38 2.1.1. Anh-Felkin Addition......Page 42 2.1.2. Chelation Controlled Addition......Page 44 2.1.3. Dipolar Addition......Page 48 2.1.4. Prelog's Rule......Page 49 2.2. Houk' s Rule......Page 50 2.3. Allylic Strain......Page 53 2.4. Baldwin's Rules......Page 54 2.5. Pericyclic Transition States......Page 57 2.5.2. Stereochemical Consequences......Page 58 2.6. Summary......Page 59 2.7. References......Page 60 3.1. Inversions at a Single Carbon Center......Page 64 3.1.2. The Mitsunobu Reaction......Page 68 3.2. Chiral Organometallic Reagents......Page 69 3.3. Other Reactions......Page 70 3.5. References......Page 71 4.1.1. Additions of Organometallic Species to Carbonyl Compounds......Page 74 4.1.2. Alkylating Agents......Page 75 4.1.3. Homologation Procedures......Page 77 4.1.4. Reactions of Vinyl Anions......Page 79 4.1.5. Use of "Extended" Organometallic Reagents......Page 80 4.1.5.1. Allylboranes......Page 87 4.1.5.2. Other "Neutral" Allylic Nucleophiles......Page 90 4.1.5.3. Allyl Anions......Page 91 4.2. Acetal Reactions......Page 93 4.3. Other Electrophiles......Page 95 4.4. Other Reactions......Page 97 4.5.1.2. Addition to Cyclic Carbonyl Compounds......Page 98 4.5.4.1. Borohydrides......Page 100 4.5.5. Boron Reagents......Page 101 4.5.6. Other Reducing Agents......Page 102 4.6. Summary......Page 103 4.7. References......Page 104 5.1. Enol Ethers and Enolate Formation......Page 116 5.2.1. Alkylation Reactions......Page 118 5.2.2. α-Hydroxylation of Carbonyl Compounds......Page 122 5.2.3. Reactions of Enol Ethers With Other Electrophiles......Page 126 5.3. Use of Nitrogen Derivatives......Page 127 5.4. Asymmetric Deprotonations and Protonations......Page 129 5.4.1. Asymmetric Deprotonations......Page 30 5.4.2. Asymmetric Protonations......Page 130 5.5. Summary......Page 132 5.6. References......Page 133 6.1.1. Alkylations of Glycolates and Glyoxylates......Page 142 6.1.2.2. α-Amino Carbonyl Compounds......Page 143 6.2.1. 1,2-Dicarbonyl Compounds......Page 146 6.2.2.1. α-Hydroxy Carbonyl Compounds......Page 148 6.2.2.3. Other α-Functionalized Carbonyl Compounds......Page 150 6.3.1. 1,3-Dicarbonyl Alkylations......Page 152 6.3.2.2. Other β-Functionalized Carbonyl Compounds......Page 154 6.4.1. 1,3-Dicarbonyl Reductions......Page 155 6.4.2.1. Reductions of 13-Hydroxy and Amino Carbonyl Compounds......Page 157 6.5. Other Systems......Page 158 6.5.1. Reactions of Anhydrides and Related Systems......Page 159 6.7. References......Page 160 7.1. The Aldol Reaction: Methods of Control......Page 168 7.2. The Aldol Reaction: The Role of Enolate Geometry and Metal Counterion......Page 178 7.2.1. Boron Enolates......Page 181 7.2.2. Lithium Enolates......Page 184 7.2.4. Silyl Enol Ethers......Page 186 7.2.5. Tin Compounds......Page 189 7.2.7. Zinc Enolates and the Reformatsky Reaction......Page 190 7.3. The Formose Reaction......Page 193 7.5. References......Page 194 8.1.1.1. Simple Alkenes......Page 204 8.1.1.3. Heteroatom Substituted Alkenes......Page 205 8.1.2.1.1. The Wittig Reaction......Page 206 8.1.2.1.3. The Julia Reaction......Page 208 8.1.2.1.6. Alternate Routes......Page 209 8.1.2.2. Conjugated Alkenes......Page 210 8.1.3.1. Simple Alkenes......Page 212 8.1.4. Eliminations......Page 213 8.1.5. Inversion......Page 214 8.2.1.1. Addition of Acids......Page 215 8.2.1.3. Oxymercuration......Page 216 8.2.2.3. Hydroboration......Page 217 8.3. Summary......Page 218 8.4. References......Page 219 9.1. Hydrogenations......Page 228 9.1.1. Functionalized Alkenes......Page 229 9.1.2. Allylic Substrates......Page 233 9.2.1. Isomerizations......Page 235 9.2.2. Hydrosilylations......Page 236 9.2.4. Hydrocarboxylations and Hydroesterifications......Page 238 9.3.1. Hydroborations of Allyl Systems......Page 239 9.4.1. Reactions of Functionalized Silanes......Page 240 9.4.2. Propargylic Substrates......Page 242 9.5.1.1. Carbon Nucleophiles......Page 243 9.5.1.2. Conjugate Reductions......Page 248 9.5.1.3. Other Nucleophiles......Page 249 9.5.2. Other Systems......Page 250 9.6. Allyl Alkylations......Page 251 9.7. Other Reactions......Page 254 9.8. Summary......Page 255 9.9. References......Page 256 10.1.1. Peroxy Acid Epoxidation......Page 268 10.1.3. Metal Catalyzed Epoxidations......Page 269 10.1.4. Other Epoxidation Methods......Page 270 10.2. Reactions of Epoxides......Page 273 10.3.2. Osmium Reagents......Page 275 10.4. Formation and Reactions of Cyclic Sulfates......Page 278 10.5. Preparation and Reactions of Aziridines......Page 280 10.7. References......Page 281 11.1.1.1. With Vanadium......Page 288 11.1.1.3. Tungsten......Page 290 11.1.2. Sharpless Epoxidation......Page 291 11.1.2.1. Kinetic Resolution With The Sharpless Epoxidation Procedure......Page 294 11.1.3. Peroxy Acid Oxidations of AllyI Alcohols......Page 295 11.1.4. Other Methods to 2,3-Epoxy Alcohols......Page 298 11.2. Reactions of 2,3-Epoxy Alcohols and Related Systems......Page 299 11.2.1. Oxygen Nucleophiles......Page 302 11.2.3. Sulfur Nucleophiles......Page 303 11.2.4. Reactions Involving Cyclic Intermediates......Page 304 11.2.5. Organometallic Reagents......Page 306 11.2.8. Reactions of Modified 2,3-Epoxy Alcohols......Page 307 11.3.1.2. Reactions......Page 311 11.3.2.1. Epoxidation......Page 312 11.3.3.1. Epoxidation......Page 313 11.3.5.2. Reactions......Page 314 11.3.6. Other Systems......Page 315 11.4.1. Osmylation......Page 316 11.5. Other Systems......Page 318 11.7. References......Page 319 12.1.1. Regio- and Stereochemistry......Page 328 12.1.2. Chiral Dienophiles......Page 329 12.1.3. Lewis Acids......Page 334 12.1.3.1. Chiral Lewis Acids......Page 335 12.1.5. Cooperative Blocking Groups......Page 339 12.1.10. Intramolecular Diels-Alder Reactions......Page 340 12.1.12. Inverse Electron Demand Diels-Alder Reactions......Page 342 12.1.13. Reactions of Dienes with Carbonyl Compounds......Page 343 12.1.13.1. Related Cycloaddition Reactions......Page 344 12.2.1. Cope Rearrangement......Page 345 12.2.2. Claisen Rearrangement......Page 346 12.2.3. Ester Enolate Claisen Rearrangement......Page 348 12.3. Ene Reaction......Page 352 12.4. Dipolar Cycloadditions......Page 355 12.5.1. Wittig Rearrangement......Page 361 12.5.2. Evans Rearrangement......Page 365 12.6. Photochemical Reactions......Page 366 12.7. Other Reactions......Page 368 12.9. References......Page 369 13.1.1. Cyclopropanations......Page 386 13.1.2. Cyclizations......Page 387 13.2.1. Electrophilic Cyclizations......Page 388 13.2.2. Preparations of Butyrolactones......Page 391 13.2.3. Preparation of Valerolactones and Related Systems......Page 395 13.3.1. Reactions of Butyrolactones......Page 397 13.3.3. Reactions of Other Oxygen Systems......Page 399 13.3.3.1. Larger Ring Systems......Page 400 13.5. Summary......Page 401 13.6. References......Page 402 Chapter 14: Biochemical Methods......Page 410 14.1. Esters and Related Compounds......Page 411 14.2. Reductions......Page 421 14.3. Other Reactions......Page 427 14.3.1. Aldol Reactions......Page 433 14.6. References......Page 435 Index......Page 444 This book evolved out of two reviews, courses on ""asymmetric synthetic methodology"" in both academic and industrial settings, and personal needs to implement asymmetric synthesis in an industrial chemistry environment.