Side Reactions in Organic Synthesis (eBook)

F. Zaragoza Dörwald studied chemistry at the Georg-August University of Göttingen and Université 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, Måløv, 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


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

"...I enjoyed reading this book and will refer to it often to help understand problem reactions. Highly recommended..."
Organic Process Research & Development


"The text in this book is clear, and the diagrams are well presented. There are lots of references, with titles making it easier for the reader to access the value of a reference before they go to find it. The author has worked hard on this book and made a brave effort. Overall, though, it is one for research libraries, but does not merit a personal investment, in my opinion."
Journal of the American Chemical Society


"The book should be required reading for all who believe that making molecules is an easy task. If, after reading it, they still consider that our organic synthesis is a worked-out branch of science, they must go to the laboratory and try to do it themselves."
Miguel A. Sierra, Universidad Complutense, Madrid
Angewandte Chemie 2005-117/29 + International Edition 2005-44/29

http://www.organische-chemie.ch/index3.htm?http://www.organische-chemie.ch/Buch/3527310215.htm



"Wer mit der Annahme lebt, organische Synthesen gingen stets leicht von der Hand, sollte dieses Buch gelesen haben. Und wer selbst dann noch glaubt, die organische Chemie sei eine ausgereifte Wissenschaft, der möge sich ins Labor begeben und es selbst einmal versuchen."
Miguel A. Sierra, Universidad Complutense, Madrid
Angewandte Chemie 2005-117/29 + International Edition 2005-44/29