SYSTEMATIC ORGANIC CHEMISTRY: MODERN METHODS OF PREPARATION AND ESTIMATION

By PAUL RAMIREZ

I Conformational Analysis 1 A Acyclic sp3–sp3 Systems 1 B Cyclohexane and Substituted Cyclohexanes, A Values (DG°) 2 C Cyclohexene 7 D Decalins 7 E 1,3-Dioxanes 8 F Acyclic sp3–sp2 Systems 8 G Anomeric Effect 13 H Strain 15 I pKa of Common Organic Acids 16 II Kinetics and Thermodynamics of Organic Reactions 17 A Free Energy Relationships 17 B Transition State Theory 18 C Intramolecular Versus Intermolecular Reactions 18 D Kinetic and Thermodynamic Control 20 E Hammond Postulate 21 F Principle of Microscopic Reversibility 22 III Reaction Mechanisms and Conformational Effects on Reactivity 23 A Ester Hydrolysis 23 B Alcohol Oxidations 25 C SN2 Reactions 25 D Elimination Reactions 26 E Epoxidation by Intramolecular Closure of Halohydrins 29 F Epoxide Openings (SN2) 29 G Electrophilic Additions to Olefins 30 H Rearrangement Reactions 31 I Pericyclic Reactions 33 J Subtle Conformational and Stereoelectronic Effects on Reactivity and Reaction 36 Regioselectivity K Methods for the Synthesis of Optically Active Materials 39 IV Oxidation Reactions 41 A Epoxidation Reactions 41 B Additional Methods for Epoxidation of Olefins 51 C Catalytic Asymmetric Epoxidation 56 D Stoichiometric Asymmetric Epoxidation 66 E Baeyer–Villiger and Related Reactions 67 F Beckmann Rearrangement and Related Reactions 70 G Olefin Osmylation (Dihydroxylation) 75 H Asymmetric Dihydroxylation 81 I Sharpless Catalytic Asymmetric Aminohydroxylation 84 J Ozonolysis 87 V Oxidation of Alcohols 87 A Chromium-based Oxidation Reagents 87 B Manganese-based Oxidation Reagents 90 C Other Oxidation Reagents 91 D Swern Oxidation and Related Oxidation Reactions 93 VI Reductions Reactions 95 A Conformational Effects of Carbonyl Groups on Reactivity 95 B Reactions of Carbonyl Groups 96 C Reversible Reduction Reactions: Stereochemistry 96 D Irreversible Reduction Reactions: Stereochemistry of Hydride Reduction Reactions 97 and Other Nucleophilic Additions to Carbonyl Compounds E Aluminum Hydride Reducing Agents 113 F Borohydride Reducing Agents 114 G Hydride Reductions of Functional Groups 116 H Characteristics of Hydride Reducing Agents 120 I Asymmetric Carbonyl Reductions 127 J Catalytic Hydrogenation 130 K Dissolving Metal Reductions 131 L Other Reduction Methods 137 VII Hydroboration–Oxidation 139 A Mechanism 139 B Regioselectivity 140 C Diastereoselectivity 140 D Metal-catalyzed Hydroboration 143 E Directed Hydroboration 144 F Asymmetric Hydroboration 144 VIII Enolate Chemistry 147 A Acidic Methylene Compounds 147 B Enolate Structure 155 C Enolate Alkylations 156 D Enolate Generation 159 E Alkylation Reactions: Stereochemistry 168 F Asymmetric Alkylations 175 G Aldol Addition (Condensation) 179 H Aldol Equivalents 197 I Enolate-imine Addition Reactions 199 J Claisen Condensation 199 K Dieckmann Condensation 201 L Enolate Dianions 203 M Metalloimines, Enamines and Related Enolate Equivalents 203 N Alkylation of Extended Enolates 206 IX Metalation Reactions 207 A Directed Metalation 207 B Organolithium Compounds by Metal–Halogen Exchnage 210 C Organolithium Compounds by Metal–Metal Exchange (Transmetalation) 211 D Organolithium Compounds from the Shapiro Reaction 211 X Key Ring Forming Reactions 213 A Diels–Alder Reaction 213 B Robinson Annulation 273 C Birch Reduction 289 D Dieckmann Condensation 289 E Intramolecular Nucleophilic Alkylation 289 F Intramolecular Aldol Condensation 290 G Intramolecular Michael Reaction 291 H Cation–Olefin Cyclizations 291 I Free Radical Cyclizations 300 J Anionic Cyclizations 318 K 1,3-Dipolar Cycloadditions 319 L [1,3]-Sigmatropic Rearrangements 324 M Electrocyclic Reactions 326 N Nazarov Cyclization 327 O Divinylcyclopropane Rearrangement 329 P Carbene Cycloaddition to Alkenes 330 Q [2 + 3] Cycloadditions for 5-Membered Ring Formation 335 R Cyclopropenone Ketal Cycloaddition Reactions 338 S [2 + 2] Cycloadditions 342 T Arene–Olefin Photoadditions 345 U Intramolecular Ene Reaction 346 V Oxy–Ene Reaction: Conia Reaction 348 W Cyclopentenone Annulation Methodology 349 X Pauson–Khand Reaction 352 Y Carbonylation Cyclizations 354 Z Olefin Ring Closing Metathesis 355 XI Olefin Synthesis 359 A Wittig Reaction 359 B Wadsworth–Horner–Emmons Reaction 365 C Peterson Olefination 367 D Tebbe Reaction and Related Titanium-stabilized Methylenations 370 E Other Methods for Terminal Methylene Formation 371 F Olefin Inversion Reactions 372 G [3,3]-Sigmatropic Rearrangements: Claisen and Cope Rearrangements 374 H [2,3]-Sigmatropic Rearrangements 378 I Olefin Synthesis Illustrated with Juvenile Hormone 381 XII Conjugate Additions: Organocuprate 1,4-Additions 395 XIII Synthetic Analysis and Design 427 A Classifications 428 B Retrosynthetic Analysis 431 C Strategic Bond Analysis 440 D Total Synthesis Exemplified with Longifolene 443 XIV Combinatorial Chemistry 461