Cohalogenation in Organic Synthesis

The usefulness of the intermolecular cohalogenation in organic synthesis is reviewed. After a short background of this almost centenarian reaction we develop some mechanistic considerations in order to explain briefly the exceptional regio-, chemo- and stereoselectivity of this simple process, which allows the facile preparation of various bifunctional derivatives. Cohalogenation with oxygen and nitrogen containing nucleophiles such as water, hydrogen peroxide, carboxylic acid derivatives, alcohols, ethers, nitriles, amines and pseudohalogens are presented successively in wide detail and we focus on the different applications of the cohalogenated compounds. The synthetic potential of such mixed halogenations is illustrated by the numerous examples in which these reactions have provided powerful simplification in the functionalization and in the synthesis of natural and medicinal products. 1. Introduction 2. The Cohalogenation Reaction 2.1 Background 2.2 General Mechanistic Considerations 3. Cohalogenation with Oxygen Containing Nucleophiles 3.1 With Protic Solvents (a) Water (b) Hydrogen Peroxide (c) Carboxylic Acid Derivatives (d) Alcohols 3.2 With Aprotic Solvents 4. Cohalogenation with Nitrogen Containing Nucleophiles 4.1 Nitrogen as External Nucleophile (a) Nitriles (b) Amine Derivatives 4.2 Pseudohalogens 5. Conclusion