March's Advanced Organic Chemistry

Conformation 133 4.A. Optical Activity and Chirality 133 4.B. Dependence of Rotation on Conditions of Measurement 135 4.C. What Kinds of Molecules Display Optical Activity? 136 4.D. The Fischer Projection 147 4.E. Absolute Configuration 148 4.E.i. The Cahn-Ingold-Prelog System 150 4.E.ii. Methods of Determining Configuration 152 4.F. The Cause of Optical Activity 156 4.G. Molecules with More Than One Stereogenic Center 157 4.H. Asymmetric Synthesis 161 4.I. Methods of Resolution 166 4.J. Optical Purity 173 4.K. Cis-Trans Isomerism 175 4.K.i. Cis-Trans Isomerism Resulting from Double Bonds 175 4.K.ii. Cis-Trans Isomerism of Monocyclic Compounds 179 4.K.iii. Cis-Trans Isomerism of Fused and Bridged Ring Systems 180 4.L. Out-In Isomerism 181 4.M. Enantiotopic and Diastereotopic Atoms, Groups, and Faces 183 4.N. Stereospecific and Stereoselective Syntheses 186 4.O. Conformational Analysis 187 4.O.i. Conformation in Open-Chain Systems 188 4.O.ii. Conformation in Six-Membered Rings 194 4.O.iii. Conformation in Six-Membered Rings Containing Heteroatoms 199 4.O.iv. Conformation in Other Rings 202 4.P. Molecular Mechanics 204 4.Q. Strain 206 4.Q.i. Strain in Small Rings 207 4.Q.ii. Strain in Other Rings 213 4.Q.iii. Unsaturated Rings 215 4.Q.iv. Strain Due to Unavoidable Crowding 218 5. Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes 223 5.A. Carbocations 224 5.A.i. Nomenclature 224 5.A.ii. Stability and Structure of Carbocations 224 5.A.iii. The Generation and Fate of Carbocations 234 5.B. Carbanions 237 5.B.i. Stability and Structure 237 5.B.ii. The Structure of Organometallic Compounds 244 5.B.iii. The Generation and Fate of Carbanions 249 5.C. Free Radicals 250 5.C.i. Stability and Structure 250 5.C.ii. The Generation and Fate of Free Radicals 261 5.C.iii. Radical Ions 265 5.D. Carbenes 266 5.D.i. Stability and Structure 266 5.D.ii. The Generation and Fate of Carbenes 269 5.D.iii. N-Heterocyclic Carbenes (NHCs) 274 5.E. Nitrenes 276 6. Mechanisms and Methods of Determining Them 279 6.A. Types of Mechanism 279 6.B. Types of Reaction 280 6.C. Thermodynamic Requirements for Reaction 283 6.D. Kinetic Requirements for Reaction 284 6.E. The Baldwin Rules for Ring Closure 288 6.F. Kinetic and Thermodynamic Control 290 6.G. The Hammond Postulate 291 6.H. Microscopic Reversibility 291 6.I. Marcus Theory 292 6.J. Methods of Determining Mechanisms 293 6.J.i. Identification of Products 293 6.J.ii. Determination of the Presence of an Intermediate 294 6.J.iii. The Study of Catalysis 295 6.J.iv. Isotopic Labeling 296 6.J.v. Stereochemical Evidence 296 6.J.vi. Kinetic Evidence 297 6.J.vii. Isotope Effects 304 6.K. Catalyst Development 308 7. Irradiation Processes and Techniques that Influence Reactions in Organic Chemistry 313 7.A. Photochemistry 314 7.A.i. Excited States and the Ground State 314 7.A.ii. Singlet and Triplet States: "Forbidden" Transitions 316 7.A.iii. Types of Excitation 317 7.A.iv. Nomenclature and Properties of Excited States 318 7.A.v. Photolytic Cleavage 319 7.A.vi. The Fate of the Excited Molecule: Physical Processes 320 7.A.vii. The Fate of the Excited Molecule: Chemical Processes 325 7.A.viii. The Determination of Photochemical Mechanisms 330 7.B. Sonochemistry 331 7.C. Microwave Chemistry 334 7.D. Flow Chemistry 336 7.E. Mechanochemistry 338 8. Acids and Bases 339 8.A. Brønsted Theory 339 8.A.i. Brønsted Acids 340 8.A.ii. Brønsted Bases 347 8.B. The Mechanism of Proton Transfer Reactions 350 8.C. Measurements of Solvent Acidity 352 8.D. Acid and Base Catalysis 355 8.E. Lewis Acids and Bases 357 8.E.i. Hard-Soft Acids-Bases 359 8.F. The Effects of Structure on the Strengths of Acids and Bases 361 8.G. The Effects of the Medium on Acid and Base Strength 370 9. Effects of Structure and Medium on Reactivity 375 9.A. Resonance and Field Effects 375 9.B. Steric Effects 377 9.C. Quantitative Treatments of the Effect of Structure on Reactivity 380 9.D. Effect of Medium on Reactivity and Rate 390 9.E. High Pressure 390 9.F. Water and Other Nonorganic Solvents 391 9.G. Ionic Liquid Solvents 393 9.H. Solventless Reactions 395 Part II Introduction 397 10. Aliphatic Substitution, Nucleophilic and Organometallic 403 10.A. Mechanisms 404 10.A.i. The SN2 Mechanism 404 10.A.ii. The SN1 Mechanism 410 10.A.iii. Ion Pairs in the SN1 Mechanism 414 10.A.iv. Mixed SN1 and SN2 Mechanisms 418 10.B. SET Mechanisms 420 10.C. The Neighboring-Group Mechanism 422 10.C.i. Neighboring-Group Participation by pi and sigma Bonds: Nonclassical Carbocations 425 10.D. The SNi Mechanism 440 10.E. Nucleophilic Substitution at an Allylic Carbon: Allylic Rearrangements 441 10.F. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 445 10.G. Reactivity 449 10.G.i. The Effect of Substrate Structure 449 10.G.ii. The Effect of the Attacking Nucleophile 457 10.G.iii. The Effect of the Leaving Group 464 10.G.iv. The Effect of the Reaction Medium 469 10.G.v. Phase-Transfer Catalysis 474 10.G.vi. Influencing Reactivity by External Means 477 10.G.vii. Ambident (Bidentant) Nucleophiles: Regioselectivity 478 10.G.viii. Ambident Substrates 481 10.H. Reactions 483 10.H.i. Oxygen Nucleophiles 483 10.H.ii. Sulfur Nucleophiles 506 10.H.iii. Nitrogen Nucleophiles 512 10.H.iv. Halogen Nucleophiles 534 10.H.v. Carbon Nucleophiles 545 11. Aromatic Substitution, Electrophilic 607 11.A. Mechanisms 607 11.A.i. The Arenium Ion Mechanism 608 11.A.ii. The SE1 Mechanism 613 11.B. Orientation and Reactivity 614 11.B.i. Orientation and Reactivity in Monosubstituted Benzene Rings 614 11.B.ii. The Ortho/Para Ratio 618 11.B.iii. Ipso Attack 620 11.B.iv. Orientation in Benzene Rings with More Than One Substituent 621 11.B.v. Orientation in Other Ring Systems 622 11.C. Quantitative Treatments of Reactivity in the Substrate 624 11.D. A Quantitative Treatment of Reactivity of the Electrophile: The Selectivity Relationship 626 11.E. The Effect of the Leaving Group 628 11.F. Reactions 629 11.F.i. Hydrogen as the Leaving Group in Simple Substitution Reactions 629 11.F.ii. Hydrogen as the Leaving Group in Rearrangement Reactions 675 11.F.iii. Other Leaving Groups 680 12. Aliphatic, Alkenyl, and Alkynyl Substitution: Electrophilic and Organometallic 687 12.A. Mechanisms 687 12.A.i. Bimolecular Mechanisms. SE2 and SEi 688 12.A.ii. The SE1 Mechanism 691 12.A.iii. Electrophilic Substitution Accompanied by Double-Bond Shifts 694 12.A.iv. Other Mechanisms 695 12.B. Reactivity 695 12.C. Reactions 697 12.C.i. Hydrogen as Leaving Group 697 12.C.ii. Metals as Leaving Groups 733 12.C.iii. Halogen as Leaving Group 746 12.C.iv. Carbon Leaving Groups 751 12.C.v. Electrophilic Substitution At Nitrogen 760 13. Aromatic Substitution: Nucleophilic and Organometallic 767 13.A. Mechanisms 768 13.A.i. The SNAr Mechanism 768 13.A.ii. The SN1 Mechanism 771 13.A.iii. The Benzyne Mechanism 772 13.A.iv. The SRN1 Mechanism 774 13.A.v. Other Mechanisms 776 13.B. Reactivity 776 13.B.i. The Effect of Substrate Structure 776 13.B.ii. The Effect of the Leaving Group 778 13.B.iii. The Effect of the Attacking Nucleophile 779 13.C. Reactions 779 13.C.i. All Leaving Groups Except Hydrogen and N2+ 779 13.C.ii. Hydrogen as Leaving Group 823 13.C.iii. Nitrogen as Leaving Group 824 13.C.iv. Rearrangements 834 14. Radical Reactions 839 14.A. Mechanisms 839 14.A.i. Radical Mechanisms in General 839 14.A.ii. Free-Radical Substitution Mechanisms 844 14.A.iii. Mechanisms at an Aromatic Substrate 845 14.A.iv. Neighboring-Group Assistance in Free-Radical Reactions 847 14.B. Reactivity 848 14.B.i. Reactivity for Aliphatic Substrates 848 14.B.ii. Reactivity at a Bridgehead 853 14.B.iii. Reactivity in Aromatic Substrates 854 14.B.iv. Reactivity in the Attacking Radical 855 14.B.v. The Effect of Solvent on Reactivity 856 14.C. Reactions 856 14.C.i. Hydrogen as Leaving Group 856 14.C.ii. Metals as Leaving Groups 880 14.C.iii. Halogen as Leaving Group 883 14.C.iv. Sulfur as Leaving Group 883 14.C.v. Carbon as Leaving Group 885 15. Addition to Carbon-Carbon Multiple Bonds 891 15.A. Mechanisms 892 15.A.i. Electrophilic Addition 892 15.A.ii. Nucleophilic Addition 895 15.A.iii. Free-Radical Addition 896 15.A.iv. Cyclic Mechanisms 898 15.A.v. Addition to Conjugated Systems 898 15.B. Orientation and Reactivity 899 15.B.i. Reactivity 899 15.B.ii. Orientation 902 15.B.iii. Stereochemical Orientation 904 15.B.iv. Addition to Cyclopropane Rings 906 15.C. Reactions 908 15.C.i. Isomerization of Double and Triple Bonds 908 15.C.ii. Reactions in Which Hydrogen Adds to One Side 910 15.C.iii. Reactions in Which Hydrogen Adds to Neither Side 992 15.C.iv. Cycloaddition Reactions 1027 16. Addition to Carbon-Heteroatom Multiple Bonds 1087 16.A. Mechanism and Reactivity 1087 16.A.i. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The Tetrahedral Mechanism 1089 16.B. Reactions 1094 16.B.i. Reactions in Which Hydrogen or a Metallic Ion Adds to the Heteroatom 1095 16.B.ii. Acyl Substitution Reactions 1218 16.B.iii. Reactions in Which Carbon Adds to the Heteroatom 1257 16.B.iv. Addition to Isocyanides 1264 16.B.v. Nucleophilic Substitution at a Sulfonyl Sulfur Atom 1266 17. Elimination Reactions 1273 17.A. Mechanisms and Orientation 1273 17.A.i. The E2 Mechanism 1274 17.A.ii. The E1 Mechanism 1280 17.A.iii. The E1cB Mechanism 1281 17.A.iv. The E1-E2-E1cB Spectrum 1286 17.A.v. The E2C Mechanism 1287 17.B. Regiochemistry of the Double Bond 1288 17.C. Stereochemistry of the Double Bond 1290 17.D. Reactivity 1291 17.D.i. Effect of Substrate Structure 1291 17.D.ii. Effect of the Attacking Base 1293 17.D.iii. Effect of the Leaving Group 1294 17.D.iv. Effect of the Medium 1294 17.E. Mechanisms and Orientation in Pyrolytic Eliminations 1295 17.E.i. Mechanisms 1295 17.E.ii. Orientation in Pyrolytic Eliminations 1298 17.E.iii. 1,4 Conjugate Eliminations 1298 17.F. Reactions 1299 17.F.i. Reactions in Which C C and C identical to C Bonds are Formed 1299 17.F.ii. Fragmentations 1321 17.F.iii. Reactions in Which C identical to N or C N Bonds are Formed 1325 17.F.iv. Reactions in Which C O Bonds are Formed 1328 17.F.v. Reactions in Which N N Bonds are Formed 1329 17.F.vi. Extrusion Reactions 1329 18. Rearrangements 1335 18.A. Mechanisms 1336 18.A.i. Nucleophilic Rearrangements 1336 18.A.ii. The Actual Nature of the Migration 1337 18.A.iii. Migratory Aptitudes 1340 18.A.iv. Memory Effects 1343 18.B. Longer Nucleophilic Rearrangements 1344 18.C. Free-Radical Rearrangements 1345 18.D. Carbene Rearrangements 1349 18.E. Electrophilic Rearrangements 1349 18.F. Reactions 1350 18.F.i. 1,2-Rearrangements 1350 18.F.ii. Non 1,2-Rearrangements 1389 19. Oxidations and Reductions 1439 19.A. Mechanisms 1440 19.B. Reactions 1442 19.B.i. Oxidations 1442 19.B.ii. Reductions 1510 Appendix A: The Literature of Organic Chemistry 1607 Appendix B: Classification of Reactions by Type of Compounds Synthesized 1645 Indexes Author Index 1669 Subject Index 1917