Most syntheses in the chemical research laboratory fail and usually require several attempts before proceeding satisfactorily. Failed syntheses are not only discouraging and frustrating, but also cost a lot of time and money. Many failures may, however, be avoided by understanding the structure-reactivity relationship of organic compounds. This textbook highlights the competing processes and limitations of the most important reactions used in organic synthesis. By allowing chemists to quickly recognize potential problems this book will help to improve their efficiency and success-rate. A must for every graduate student but also for every chemist in industry and academia. Contents: 1 Organic Synthesis: General Remarks 2 Stereoelectronic Effects and Reactivity 3 The Stability of Organic Compounds 4 Aliphatic Nucleophilic Substitutions: Problematic Electrophiles 5 The Alkylation of Carbanions 6 The Alkylation of Heteroatoms 7 The Acylation of Heteroatoms 8 Palladium-Catalyzed C-C Bond Formation 9 Cyclizations 10 Monofunctionalization of Symmetric Difunctional Substrates

F. Zaragoza Dorwald studied chemistry at the Georg-August University of Gottingen and Universite Louis Pasteur, Strasbourg, where he obtained his Ph.D. in 1990 on the synthesis of natural products under the guidance of M. Franck-Neumann and M. Miesch. He spent each one postdoctoral year in the groups of A. Pfaltz (University of Basel) and A.P. Marchand (University of North Texas), and worked then on the synthesis of unnatural amino acids at the Technical University of Dresden. Since 1995 he has a position as medicinal chemist at Novo Nordisk A/S, M?l?v, Denmark. His main interests are the development of parallel and solid-phase syntheses for lead identification and optimization.

ORGANIC SYNTHESIS: GENERAL REMARKS Introduction Synthesis Design Hard and Soft Acids and Bases The Curtin-Hammett Principle STEREOELECTRONIC EFFECTS AND REACTIVITY Hyperconjugation with sigma Bonds Hyperconjugation with Lone Electron Pairs Hyperconjugation and Reactivity Conclusion THE STABILITY OF ORGANIC COMPOUNDS Introduction Strained Bonds Incompatible Functional Groups Conjugation and Hyperconjugation of Incompatible Functional Groups Stability towards Oxygen Detonations ALIPHATIC NUCLEOPHILIC SUBSTITUTIONS: PROBLEMATIC ELECTROPHILES Mechanisms of Nucleophilic Substitution Structure of the Leaving Group Structure of the Electrophile THE ALKYLATION OF CARBANIONS Introduction The Kinetics of Deprotonations Regioselectivity of Deprotonations and Alkylations The Stability of Carbanions THE ALKYLATION OF HETEROATOMS Alkylation of Fluoride Alkylation of Aliphatic Amines Alkylation of Anilines Alkylation of Alcohols Alkylation of Phenols Alkylation of Amides Alkylation of Carbamates and Ureas Alkylation of Amidines and Guanidines Alkylation of Carboxylates THE ACYLATION OF HETEROATOMS Problematic Carboxylic Acids Problematic Amines Problematic Alcohols PALLADIUM-CATALYZED C-C BOND FORMATION Introduction Chemical Properties of Organopalladium Compounds Mechanisms of Pd-Catalyzed C--C Bond Formation Homocoupling and Reduction of the Organyl Halide Homocoupling and Oxidation of the Carbon Nucleophile Transfer of Aryl Groups from the Phosphine Ligand Ipso- vs Cine-Substitution at Vinylboron and -tin Derivatives Allylic Arylation and Hydrogenation as Side Reactions of the Heck Reaction Protodemetalation of the Carbon Nucleophile Sterically Hindered Substrates Cyclometalation Chelate Formation CYCLIZATION Introduction Baldwin's Cyclization Rules Structural Features of the Chain Ring Size Heterocycles MONOFUNCTIONALIZATION OF SYMMETRIC DIFUNCTIONAL SUBSTRATES Introduction Monofunctionalization of Dicarboxylic Acids Monofunctionalization of Diols Monofunctionalization of Diamines Monoalkylation of C,H-Acidic Compounds Monoderivatization of Dihalides