Advanced Organic Chemistry: Part B: Reaction and Synthesis (Advanced Organic Chemistry / Part B: Reactions and Synthesis)

Since its original appearance in 1977, Advanced Organic Chemistry has maintained its place as the premier textbook in the field, offering broad coverage of the structure, reactivity and synthesis of organic compounds. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples of data and reactions that illustrate and document the generalizations. While the text assumes completion of an introductory course in organic chemistry, it reviews the fundamental concepts for each topic that is discussed. The two-part fifth edition has been substantially revised and reorganized for greater clarity. Among the changes: Updated material reflecting advances in the field since 2001’s Fourth Edition, especially in computational chemistry; A companion Web site provides digital models for study of structure, reaction and selectivity; Solutions to the exercises provided to instructors online. The control of reactivity to achieve specific syntheses is one of the overarching goals of organic chemistry. Part B describes the most general and useful synthetic reactions, organized on the basis of reaction type. Together with Part A: Structure and Mechanisms, the two volumes are intended to provide the advanced undergraduate or beginning graduate student in chemistry with a sufficient foundation to comprehend and use the research literature in organic chemistry. Preface 5 Acknowledgment and Personal Statement 8 Introduction 10 Table of Contents 21 1. Alkylation of Enolates and Other Carbon Nucleophiles 29 Introduction 29 1.1. Generation and Properties of Enolates and Other Stabilized Carbanions 30 1.1.1. Generation of Enolates by Deprotonation 30 1.1.2. Regioselectivity and Stereoselectivity in Enolate Formation from Ketones and Esters 33 1.1.3. Other Means of Generating Enolates 42 1.1.4. Solvent Effects on Enolate Structure and Reactivity 45 1.2. Alkylation of Enolates 49 1.2.1. Alkylation of Highly Stabilized Enolates 49 1.2.2. Alkylation of Ketone Enolates 52 1.2.3. Alkylation of Aldehydes, Esters, Carboxylic Acids, Amides, and Nitriles 59 1.2.4. Generation and Alkylation of Dianions 64 1.2.5. Intramolecular Alkylation of Enolates 64 1.2.6. Control of Enatioselectivity in Alkylation Reactions 69 1.3. The Nitrogen Analogs of Enols and Enolates: Enamines and Imine Anions 74 General References 83 Problems 84 2. Reactions of Carbon Nucleophiles with Carbonyl Compounds 91 Introduction 91 2.1. Aldol Addition and Condensation Reactions 92 2.1.1. The General Mechanism 92 2.1.2. Control of Regio- and Stereoselectivity of Aldol Reactions of Aldehydes and Ketones 93 2.1.2.1. Aldol Reactions of Lithium Enolates 95 2.1.2.2. Aldol Reactions of Boron Enolates 99 2.1.2.3. Aldol Reactions of Titanium, Tin, and Zirconium Enolates 101 2.1.2.4. Summary of the Relationship between Diastereoselectivity and the Transition Structure 106 2.1.3. Aldol Addition Reactions of Enolates of Esters and Other Carbonyl Derivatives 106 2.1.4. The Mukaiyama Aldol Reaction 110 2.1.5. Control of Facial Selectivity in Aldol and Mukaiyama Aldol Reactions 114 2.1.5.1. Stereochemical Control by the Aldehyde 117 2.1.5.2. Stereochemical Control by the Enolate or Enolate Equivalent 129 2.1.5.3. Complementary/Competitive Control: Double Stereodifferentiation 136 2.1.5.4. Stereochemical Control Through Chiral Auxiliaries 142 2.1.5.5. Stereochemical Control Through Reaction Conditions 147 2.1.5.6. Enantioselective Catalysis of the Aldol Addition Reaction 153 2.1.5.7. Summary of Facial Stereoselectivity in Aldol and Mukaiyama Reactions 161 2.1.6. Intramolecular Aldol Reactions and the Robinson Annulation 162 2.2. Addition Reactions of Imines and Iminium Ions 167 2.2.1. The Mannich Reaction 168 2.2.2. Additions to N-Acyl Iminium Ions 173 2.2.3. Amine-Catalyzed Condensation Reactions 175 2.3. Acylation of Carbon Nucleophiles 176 2.3.1. Claisen and Dieckmann Condensation Reactions 177 2.3.2. Acylation of Enolates and Other Carbon Nucleophiles 178 2.4. Olefination Reactions of Stabilized Carbon Nucelophiles 185 2.4.1. The Wittig and Related Reactions of Phosphorus-Stabilized Carbon Nucleophiles 185 2.4.1.1. Olefination Reactions Involving Phosphonium Ylides 186 2.4.1.2. Olefination Reactions Involving Phosphonate Anions 192 2.4.2. Reactions of alpha-Trimethylsilylcarbanions with Carbonyl Compounds 199 2.4.3. The Julia Olefination Reaction 202 2.5. Reactions Proceeding by Addition-Cyclization 205 2.5.1. Sulfur Ylides and Related Nucleophiles 205 2.5.2. Nucleophilic Addition-Cyclization of alpha-Haloesters 210 2.6. Conjugate Addition by Carbon Nucleophiles 211 2.6.1. Conjugate Addition of Enolates 211 2.6.2. Conjugate Addition with Tandem Alkylation 217 2.6.3. Conjugate Addition by Enolate Equivalents 218 2.6.4. Control of Facial Selectivity in Conjugate Addition Reactions 221 2.6.5. Conjugate Addition of Organometallic Reagents 225 2.6.6. Conjugate Addition of Cyanide Ion 226 General References 228 Problems 228 3. Fuctional Group Interconversion by Substitution, Including Protection and Deprotection 243 Introduction 243 3.1. Conversion of Alcohols to Alkylating Agents 244 3.1.1. Sulfonate Esters 244 3.1.2. Halides 245 3.2. Introduction of Functional Groups by Nucleophilic Substitution at Saturated Carbon 251 3.2.1. General Solvent Effects 252 3.2.2. Nitriles 253 3.2.3. Oxygen Nucleophiles 254 3.2.4. Nitrogen Nucleophiles 257 3.2.5. Sulfur Nucleophiles 261 3.2.6. Phosphorus Nucleophiles 261 3.2.7. Summary of Nucleophilic Substitution at Saturated Carbon 262 3.3. Cleavage of Carbon-Oxygen Bonds in Ethers and Esters 266 3.4. Interconversion of Carboxylic Acid Derivatives 270 3.4.1. Acylation of Alcohols 271 3.4.2. Fischer Esterification 280 3.4.3. Preparation of Amides 280 3.5. Installation and Removal of Protective Groups 286 3.5.1. Hydroxy-Protecting Groups 286 3.5.1.1. Acetals as Protective Groups 286 3.5.1.2. Ethers as Protective Groups 290 3.5.1.3. Silyl Ethers as Protective Groups 292 3.5.1.4. Esters as Protective Groups 293 3.5.1.5. Protective Groups for Diols 294 3.5.2. Amino-Protecting Groups 295 3.5.3. Carbonyl-Protecting Groups 300 3.5.4. Carboxylic Acid-Protecting Groups 303 Problems 305 4. Electrophilic Additions to Carbon-Carbon Multiple Bonds 317 Introduction 317 4.1. Electrophilic Addition to Alkenes 318 4.1.1. Addition of Hydrogen Halides 318 4.1.2. Hydration and Other Acid-Catalyzed Additions of Oxygen Nucleophiles 321 4.1.3. Oxymercuration-Reduction 322 4.1.4. Addition of Halogens to Alkenes 326 4.1.5. Addition of Other Electrophilic Reagents 333 4.1.6. Addition Reactions with Electrophilic Sulfur and Selenium Reagents 335 4.2. Electrophilic Cyclization 338 4.2.1. Halocyclization 339 4.2.2. Sulfenylcyclization and Selenenylcyclization 348 4.2.3. Cyclization by Mercuric Ion 352 4.3. Electrophilic Substitution (alpha) to Carbonyl Groups 356 4.3.1. Halogenation (alpha) to Carbonyl Groups 356 4.3.2. Sulfenylation and Selenenylation (alpha) to Carbonyl Groups 359 4.4. Additions to Alkenes and Alkynes 361 4.5. Addition at Double Bonds via Organoborane Intermediates 365 4.5.1. Hydroboration 365 4.5.2. Reactions of Organoboranes 372 4.5.3. Enantioselective Hydroboration 375 4.5.4. Hydroboration of Alkynes 380 4.6. Hydroalumination, Carboalumination, Hydrozirconation, and Related Reactions 381 General References 386 Problems 386 5. Reduction of Carbon-Carbon Multiple Bonds, Carbonyl Groups, and Other Functional Groups 394 Introduction 394 5.1. Addition of Hydrogen at Carbon-Carbon Multiple Bonds 395 5.1.1. Hydrogenation Using Heterogeneous Catalysts 395 5.1.2. Hydrogenation Using Homogeneous Catalysts 401 5.1.3. Enantioselective Hydrogenation 403 5.1.4. Partial Reduction of Alkynes 414 5.1.5. Hydrogen Transfer from Diimide 415 5.2. Catalytic Hydrogenation of Carbonyl and Other Functional Groups 417 5.3. Group III Hydride-Donor Reagents 423 5.3.1. Comparative Reactivity of Common Hydride Donor Reagents 423 5.3.1.1. Partial Reduction of Carboxylic Acid Derivatives 428 5.3.1.2. Reduction of Imines and Amides to Amines 430 5.3.1.3. Reduction of alpha,beta-Unsaturated Carbonyl Compounds 433 5.3.2. Stereoselectivity of Hydride Reduction 434 5.3.2.1. Cyclic Ketones 434 5.3.2.2. Acyclic Ketones 437 5.3.2.3. Chelation Control 438 5.3.3. Enatioselective Reduction of Carbonyl Compounds 442 5.3.3.1. Reduction with Chiral Boranes 442 5.3.3.2. Catalytic Enantioselective Reduction of Ketones 443 5.3.4. Reduction of Other Functional Groups by Hydride Donors 449 5.4. Group IV Hydride Donors 452 5.4.1. Reactions Invovling Silicon Hydrides 452 5.4.2. Hydride Transfer from Carbon 456 5.5. Reduction Reactions Involving Hydrogen Atom Donors 458 5.6. Dissolving-Metal Reductions 461 5.6.1. Addition of Hydrogen 462 5.6.1.1. Reduction of Ketones and Enones 462 5.6.1.2. Dissolving-Metal Reduction of Aromatic Compounds and Alkynes 463 5.6.2. Reductive Removal of Functional Groups 466 5.6.3. Reductive Coupling of Carbonyl Compounds 471 5.7. Reductive Deoxygenation of Carbonyl Groups 479 5.7.1. Reductive Deoxygenation of Carbonyl Groups to Methylene 479 5.7.2. Reduction of Carbonyl Compounds to Alkenes 481 5.8. Reductive Elimination and Fragmentation 484 Problems 489 6. Concerted Cycloadditions, Unimolecular Rearrangments, and Thermal Eliminations 499 Introduction 499 6.1. Diels-Adler Reactions 500 6.1.1. The Diels-Adler Reaction: General Features 500 6.1.2. Substituent Effects on the Diels-Adler Reaction 501 6.1.3. Lewis Acid Catalysts of the Diels-Adler Reaction 507 6.1.4. The Scope and Synthetic Applications of the Diels-Adler Reaction 513 6.1.4.1. Examples of Dienes and Dienophiles 513 6.1.4.2. Synthetic Applications of the Diels-Adler Reaction 520 6.1.5. Diastereoselective Diels-Adler Reactions Using Chiral Auxilaries 525 6.1.6. Enantioselective Catalysts for Diels-Adler Reactions 531 6.1.7. Intramolecular Diels-Adler Reactions 544 6.2. 1,3-Dipolar Cycloaddition Reactions 552 6.2.1. Regioselectivity and Stereochemistry 554 6.2.2. Synthetic Applications of Dipolar Cycloadditions 557 6.2.3. Catalysts of 1,3-Dipolar Cycloaddition Reactions 561 6.3. [2+2] Cycloadditions and Related Reactions Leading to Cyclobutanes 564 6.3.1. Cycloaddition Reactions of Ketenes and Alkenes 565 6.3.2. Photochemical Cycloaddition Reactions 570 6.3.2.1. Photocycloaddition of Alkenes and Dienes 570 6.3.2.2. Photocycloaddition Reactions of Enones 571 6.3.2.3. Photocycloaddition Reactions of Carbonyl Compounds and Alkenes 574 6.4. [3,3]-Sigmatropic Rearrangements 578 6.4.1. Cope Rearrangements 578 6.4.2. Claisen and Modified Claisen Rearrangements 586 6.4.2.1. Claisen Rearrangement of Allyl Vinyl Ethers 587 6.4.2.2. Orthoester Claisen Rearrangements 590 6.4.2.3. Rearrangements of Silyl Ketene Acetals and Ester Enolates 593 6.4.2.4. Claisen Rearrangements of Ketene Aminals and Imidates 602 6.5. [2,3]-Sigmatropic Rearrangements 607 6.5.1. Rearrangement of Allylic Sulfoxides, Selenoxides, and Amine Oxides 607 6.5.2. Rearrangement of Allylic Sulfonium and Ammonium Ylides 609 6.5.3. Anionic Wittig and Aza-Wittig Rearrangements 613 6.6. Unimolecular Thermal Elimination Reactions 616 6.6.1. Chelation Elimination 617 6.6.2. Decomposition of Cyclic Azo Compounds 619 6.6.3. Beta-Eliminations Involving Cyclic Transition Structures 622 Problems 630 7. Organometallic Compounds of Group I and II Metals 644 Introduction 644 7.1. Preparation and Properties of Organomagnesium and Organolithium Reagents 645 7.1.1. Preparation and Properties of Organomagnesium Reagents 645 7.1.2. Preparation and Properties of Organolithium Compounds 649 7.1.2.1. Preparation Using Metallic Lithium 649 7.1.2.2. Preparation by Lithiation 652 7.1.2.3. Preparation by Halogen-Metal Exchange 657 7.1.2.4. Preparation by Metal-Metal Exchange 658 7.2. Reactions of Organomagnesium and Organolithium Compounds 659 7.2.1. Reactions with Alkylating Agents 659 7.2.2. Reactions with Carbonyl Compounds 662 7.2.2.1. Reaction sof Grignard Reagents 662 7.2.2.2. Reactions of Organolithium Compounds 669 7.2.2.3. Stereoselectivity of Addition to Ketones 673 7.3. Organometallic Compounds of Group IIB and IIIB Metals 675 7.3.1. Organozinc Compounds 675 7.3.1.1. Preparation of Organozinc Compounds 675 7.3.1.2. Reactions of Organozinc Compounds 677 7.3.1.3. Related Reactions Involving Organozinc Compounds 684 7.3.2. Organocadmium Compounds 686 7.3.3. Organomercury Compounds 687 7.3.4. Organoindium Reagents 688 7.4. Organolanthanide Reagents 689 General References 691 Problems 692 8. Reactions Invovling Transition Metals 699 Introduction 699 8.1. Organocopper Intermediates 699 8.1.1. Preparation and Structure of Organocopper Reagents 699 8.1.2. Reactions Involving Organocopper Reagents and Intermediates 704 8.1.2.1. SN1 and SN2' Reactions with Halides and Sulfonates 704 8.1.2.2. Opening of Epoxides 709 8.1.2.3. Conjugate Addition Reactions 710 8.1.2.4. Copper-Catalyzed Reactions 714 8.1.2.5. Mixed Organocopper-Zinc Reagents 718 8.1.2.6. Carbometallation with Mixed Organocopper Compounds 719 8.1.2.7. Mechanistic Interpretation of the Reactivity of Organocopper Compounds 721 8.1.2.8. Enantioselective Reactions of Organocopper Reagents 726 8.1.2.9. Aryl-Aryl Coupling Using Organocopper Reagents 727 8.1.2.10. Summary of Synthetic Reactions of Organocopper Reagents and Intermediates 729 8.2. Reactions Involving Organopalladium Intermediates 730 8.2.1. Palladium-Catalyzed Nucleophilic Addition and Substitution 733 8.2.1.1. The Wacker Reaction and Related Oxidations 733 8.2.1.2. Nucleophilic Substitution of pi-Allyl Palladium Complexes 736 8.2.2. The Heck Reaction 739 8.2.3. Palladium-Catalyzed Cross Coupling 747 8.2.3.1. Coupling with Organometallic Reagents 748 8.2.3.2. Palladium-Catalyzed Arylation of Enolates 752 8.2.3.3. Coupling with Stannanes 755 8.2.3.4. Coupling with Organoboron Reagents 763 8.2.4. Carbonylation Reactions 772 8.2.4.1. Hydrocarbonylation 773 8.2.4.2. Solvocarbonylation 774 8.3. Reactions Involving Other Transition Metals 778 8.3.1. Organonickel Compounds 778 8.3.2. Reactions Involving Rhodium and Cobalt 783 8.4. The Olefin Methathesis Reaction 785 8.5. Organometallic Compounds with pi-Bonding 791 General References 795 Problems 795 9. Carbon-Carbon Bond-Forming Reactions of Compounds of Boron, Silicon, and Tin 807 Introduction 807 9.1. Organoboron Compounds 808 9.1.1. Synthesis of Organoboranes 808 9.1.2. Carbonylation and Other One-Carbon Homologation Reactions 810 9.1.3. Homologation via alpha-Haloenolates 816 9.1.4. Stereoselective Alkene Synthesis 817 9.1.5. Nucleophilic Addition of Allylic Groups from Boron Compounds 821 9.2. Organosilicon Compounds 833 9.2.1. Synthesis of Organosilanes 833 9.2.2. General Features of Carbon-Carbon Bond-Forming Reactions of Organosilicon Compounds 838 9.2.3. Addition Reactions with Aldehydes and Ketones 839 9.2.4. Reactions with Iminium Ions 849 9.2.5. Acylation Reactions 850 9.2.6. Conjugate Addition Reactions 854 9.3. Organotin Compounds 857 9.3.1. Synthesis of Organostannanes 857 9.3.2. Carbon-Carbon Bond-Forming Reactions 860 9.3.2.1. Reactions of Allylic Trialkylstannanes 860 9.3.2.2. Reactions of Allylic Halostannanes 862 9.3.2.3. Reactions Involving Transmetallation 865 9.3.2.4. gamma-Oxygen-Substituted Stannanes 866 9.3.2.5. Enantioselective Addition Reactions of Allylic Stannanes 867 9.3.2.6. Allenyl Stannanes 874 9.4. Summary of Stereoselectivity Patterns 875 General References 876 Problems 877 10. Reactions Involving Carbocations, Carbenes, and Radicals as Reactive Intermediates 885 Introduction 885 10.1. Reactions and Rearrangement Involving Carbocation Intermediates 886 10.1.1. Carbon-Carbon Bond Formation Involving Carbocations 886 10.1.1.1. Intermolecular Alkylation by Carbocations 886 10.1.1.2. Polyene Cyclization 888 10.1.1.3. Ene and Carbonyl-Ene Reactions 893 10.1.1.4. Reactions with Acylium Ions 905 10.1.2. Rearrangement of Carbocations 907 10.1.2.1. Pinacol Rearrangement 907 10.1.2.2. Pinacol Rearrangement in Tandem with the Carbonyl-Ene Reaction 910 10.1.2.3. Rearrangements Involving Diazonium Ions 914 10.1.3. Related Rearrangements 916 10.1.3.1. The Favorskii Rearrangement 916 10.1.3.2. The Ramburg-Backlund Reaction 919 10.1.4. Fragmentation Reactions 921 10.2. Reactions Involving Carbenes and Related Intermediates 927 10.2.1. Reactivity of Carbenes 929 10.2.2. Generation of Carbenes 933 10.2.2.1. Carbenes from Diazo Compounds 933 10.2.2.2. Carbenes from Sulfonylhydrazones 937 10.2.2.3. Carbenes from Diazirines 937 10.2.2.4. Carbenes from Halides by alpha-Elimination 938 10.2.2.5. Carbenes from Organomercury Compounds 939 10.2.3. Addition Reactions 940 10.2.3.1. Cyclopropanation with Halomethylzinc Reagents 940 10.2.3.2. Metal-Catalyzed Cyclopropanation 945 10.2.3.3. Other Cyclopropanation Methods 951 10.2.3.4. Examples of Cyclopropanations 951 10.2.3.5. Enantioselective Cyclopropanation 955 10.2.4. Insertion Reactions 958 10.2.5. Generation and Reactions of Ylides by Carbenoid Decomposition 962 10.2.6. Rearrangement Reactions 964 10.2.7. Related Reactions 965 10.2.8. Nitrenes and Related Intermediates 968 10.2.9. Rearrangements to Electron-Deficient Nitrogen 971 10.3. Reactions Involving Free Radical Intermediates 980 10.3.1. Sources of Radical Intermediates 981 10.3.2. Addition Reactions of Radicals with Substituted Alkenes 983 10.3.3. Cyclization of Free Radical Intermediates 991 10.3.4. Additions to C-N Double Bonds 997 10.3.5. Tandem Radical Cyclizations and Alkylations 1003 10.3.6. Fragmentation and Rearrangement Reactions 1008 10.3.7. Intramolecular Functionalization by Radical Reactions 1013 Problems 1016 11. Aromatic Substitution Reactions 1027 Introduction 1027 11.1. Electrophilic Aromatic Substitution 1028 11.1.1. Nitration 1028 11.1.2. Halogenation 1032 11.1.3. Friedel-Crafts Alkylation 1038 11.1.4. Friedel-Crafts Acylation 1041 11.1.5. Related Alkylation and Acylation Reactions 1047 11.1.6. Electrophilic Metallation 1050 11.2. Nucleophilic Aromatic Substitution 1051 11.2.1. Aryl Diazonium Ions as Synthetic Intermediates 1051 11.2.1.1. Reductive Dediazonization 1053 11.2.1.2. Phenols from Diazonium Ion Intermediates 1054 11.2.1.3. Aryl Halides from Diazonium Ion Intermediates 1054 11.2.1.4. Introduction of Other Nucleophiles Using Diazonium Ion Intermediates 1056 11.2.1.5. Meerwein Arylation Reactions 1059 11.2.2. Substitution by the Addition-Elimination Mechanism 1059 11.2.3. Substitution by the Elimination-Addition Mechanism 1063 11.3. Transition Metal-Catalyzed Aromatic Substitution Reactions 1066 11.3.1. Copper-Catalyzed Reactions 1066 11.3.2. Palladium-Catalyzed Reactions 1069 11.4. Aromatic Substitution Reactions Involving Radical Intermediates 1076 11.4.1. Aromatic Radical Substitution 1076 11.4.2. Substitution by the SRN1 Mechanism 1077 Problems 1080 12. Oxidations 1087 Introduction 1087 12.1. Oxidation of Alcohols to Aldehydes, Ketones, or Carboxylic Acids 1087 12.1.1. Transition Metal Oxidants 1087 12.1.2. Other Oxidants 1094 12.1.2.1. Oxidations Based Dimethyl Sulfoxide 1094 12.1.2.2. Oxidation by the Dess-Martin Reagent 1096 12.1.2.3. Oxidations Using Oxoammonium Ions 1098 12.2. Addition of Oxygen at Carbon-Carbon Double Bonds 1098 12.2.1. Transition Metal Oxidants 1098 12.2.1.1. Dihydroxylation of Alkenes 1098 12.2.1.2. Transition Metal-Catalyzed Epoxidation of Alkenes 1105 12.2.2. Epoxides from Alkenes and Peroxidic Reagents 1115 12.2.2.1. Epoxidation by Peroxy Acids and Related Reagents 1115 12.2.2.2. Epoxidation by Dioxirane Derivatives 1121 12.2.3. Subsequent Transformations of Epoxides 1128 12.2.3.1. Nucleophilic and Solvolytic Ring Opening 1128 12.2.3.2. Reductive Ring Opening 1133 12.2.3.3. Rearrangement of Epoxides to Carbonyl Compounds 1135 12.2.3.4. Base-Catalyzed Ring Opening of Epoxides 1138 12.3. Allylic Oxidation 1140 12.3.1. Transition Metal Oxidants 1140 12.3.2. Reaction of Alkenes with Singlet Oxygen 1141 12.3.3. Other Oxidants 1148 12.4. Oxidative Cleavage of Carbon-Carbon Double Bonds 1150 12.4.1. Transition Metal Oxidants 1150 12.4.2. Ozonolysis 1153 12.5. Oxidation of Ketones and Aldehydes 1155 12.5.1. Transition Metal Oxidants 1155 12.5.2. Oxidation of Ketones and Aldehydes by Oxygen and Peroxidic Compounds 1158 12.5.2.1. Baeyer-Villiger Oxidation of Ketones 1158 12.5.2.2. Oxidation of Enolates and Enolate Equivalents 1162 12.5.3. Oxidation with Other Reagents 1167 12.6. Selective Oxidation Cleavages at Functional Groups 1168 12.6.1. Cleavage of Glycols 1168 12.6.2. Oxidative Decarboxylation 1169 12.7. Oxidations at Unfunctionalized Carbon 1172 Problems 1175 13. Multistep Syntheses 1187 Introduction 1187 13.1. Synthetic Analysis and Planning 1188 13.1.1. Retrosynthetic Analysis 1188 13.1.2. Synthetic Equivalent Groups 1190 13.1.3. Control of Stereochemistry 1195 13.2. Illustrative Syntheses 1197 13.2.1. Juvabione 1198 13.2.2. Longifolene 1210 13.2.3. Prelog-Djerassi Lactone 1220 13.2.4. Baccatin III and Taxol 1234 13.2.5. Epothilone A 1244 13.2.6. Discodermolide 1255 13.3. Solid Phase Synthesis 1269 13.3.1. Solid Phase Polypeptide Synthesis 1269 13.3.2. Solid Phase Synthesis of Oligonucleotides 1274 13.4. Combinatorial Synthesis 1276 General References 1283 Problems 1284 References for Problems 1295 Chapter 1 1295 Chapter 2 1296 Chapter 3 1299 Chapter 4 1301 Chapter 5 1302 Chapter 6 1304 Chapter 7 1307 Chapter 8 1308 Chapter 9 1310 Chapter 10 1311 Chapter 11 1313 Chapter 12 1314 Chapter 13 1316 Index 1320 Since its original appearance in 1977, Advanced Organic Chemistry has maintained its place as the premier textbook in the field, offering broad coverage of the structure, reactivity and synthesis of organic compounds. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples of data and reactions that illustrate and document the generalizations. While the text assumes completion of an introductory course in organic chemistry, it reviews the fundamental concepts for each topic that is discussed. The two-part fifth edition has been substantially revised and reorganized for greater clarity. Part A begins with the fundamental concepts of structure and stereochemistry, and the thermodynamic and kinetic aspects of reactivity. Major reaction types covered include nucleophilic substitution, addition reactions, carbanion and carbonyl chemistry, aromatic substitution, pericyclic reactions, radical reactions, and photochemistry. Among the changes: Coverage of the importance of computational chemistry in modern organic chemistry, including applications to many specific reactions. Expanded coverage of stereoselectivity and enantioselectivity, including discussion of several examples of enantioselective reagents and catalysts Chapter 10, Concerted Pericyclic Reactions, has been reorganized and now begins with cycloaddition reactions. The treatment of photochemical reactions has been extensively updated to reflect both experimental and computational studies of the transient intermediates involved in photochemical reactions. A companion Web site provides digital models for study of structure, reaction and selectivity. Here students can view and manipulate computational models of reaction paths. These sites also provide exercises based on detailed study of the computational models. Several chapters in Part A conclude with Topics - short excursions into specific topics such as more detailed analysis of polar substituent effects, efforts to formulate substituent effects in terms of density functional theory, or the role of carbocations in petroleum refining Solutions to the chapter problems are provided to instructors online Advanced Organic Chemistry Part A provides a close look at the structural concepts and mechanistic patterns that are fundamental to organic chemistry. It relates those mechanistic patterns, including relative reactivity and stereochemistry, to underlying structural factors. Understanding these concepts and relationships will allow students to recognize the cohesive patterns of reactivity in organic chemistry. Part A: Structure and Mechanism and Part B: Reaction and Synthesis - taken together - are intended to provide the advanced undergraduate or beginning graduate student in chemistry with a foundation to comprehend and use the research literature in organic chemistry Since its original appearance in 1977, "Advanced Organic Chemistry" has maintained its place as the premier textbook in the field, offering broad coverage of the structure, reactivity and synthesis of organic compounds. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples of data and reactions that illustrate and document the generalizations. While the text assumes completion of an introductory course in organic chemistry, it reviews the fundamental concepts for each topic that is discussed. The two-part fifth edition has been substantially revised and reorganized for greater clarity. Among the changes: updated material reflecting advances in the field since 2001's Fourth Edition, especially in computational chemistry. A companion Web site provides digital models for study of structure, reaction and selectivity. Solutions to the exercises are provided to instructors online. The material in Part A is organized on the basis of fundamental structural topics such as structure, stereochemistry, conformation and aromaticity and basic mechanistic types, including nucleophilic substitution, addition reactions, carbonyl chemistry, aromatic substitution and free radical reactions. Together with Part B: Reaction and Synthesis, the two volumes are intended to provide the advanced undergraduate or beginning graduate student in chemistry with a sufficient foundation to comprehend and use the research literature in organic chemistry The two-part, fifth edition of Advanced Organic Chemistry has been substantially revised and reorganized for greater clarity. The material has been updated to reflect advances in the field since the previous edition, especially in computational chemistry. Part A covers fundamental structural topics and basic mechanistic types. It can stand-alone; together, with Part B: Reaction and Synthesis, the two volumes provide a comprehensive foundation for the study in organic chemistry. Companion websites provide digital models for study of structure, reaction and selectivity for students and exercise solutions for instructors.

The two-part, fifth edition of Advanced Organic Chemistry has been substantially revised and reorganized for greater clarity. The material has been updated to reflect advances in the field since the previous edition, especially in computational chemistry. Part B describes the most general and useful synthetic reactions, organized on the basis of reaction type. It can stand-alone; together, with Part A: Structure and Mechanisms, the two volumes provide a comprehensive foundation for the study in organic chemistry. Companion websites provide digital models for students and exercise solutions for instructors.