Abstract

α-Halo ketones play a significant role in organic synthesis because of their ready availability and the diversity of their chemical reactions, which reflect the various functionalities in the molecule, viz., a reactive halogencarbon bond, acidic hydrogen atoms, and a carbonyl moiety. An important reaction of halo ketones is removal of the halogen atom(s) by low-valent transition metals and related reducing agents to generate reactive species that are capable of undergoing carboncarbon bond-forming reactions. The cyclocoupling reactions of α,α′-dihalo or more highly halogenated ketones across 1,3-dienic or olefinic substrates to give seven- or five-membered ketones, respectively, are especially noteworthy from the synthetic viewpoint.

The direct preparation of odd-membered carbocycles has remained a persistent problem, and until recently only a few methods of synthesis were available. The existing methods for obtaining seven-membered carbocycles have been limited to expansion of six-membered rings and certain cyclization reactions. The construction of five-membered carbocyclic systems has generally been accomplished only by intramolecular condensation of open-chain dicarbonyl compounds or dicarboxylic acid derivatives, ring contraction of six-membered cyclic ketones, or ring expansion of four-membered cyclic ketones. These methods, however, are not always useful because of the limited availability of the starting materials in certain reactions. In principle the most direct method for construction of seven-membered carbocycles is the cyclo-condensation between three-carbon and four-carbon units, viz., 1,3-dienes, for preparation of five-membered carbocycles, the combination of three-carbon and two-carbon units, viz., olefinic substances, or one-carbon and four-carbon units, respectively, can be considered. However, these reactions are not achieved easily because of the difficulty of generating reactive three-carbon and one-carbon units that are capable of undergoing cycloaddition across the unsaturated substrates. Reactions of low-valent metals and α,α′-dihalo or more highly halogenated ketones generate such bifunctional three-carbon species that can enter into both types of cycloaddition reactions. Moreover, these reactive species also undergo [3 + 2] cycloadditions across certain unsaturated bonds containing heteroatoms, thereby giving rise to five-membered heterocycles. Thus these [3 + 4] and [3 + 2] annulations have allowed easy access to a wide range of organic frameworks that are of theoretical or practical importance. The scope and limitations of these cyclocoupling reactions and their synthetic applications are the main concern of this chapter, which briefly describes other examples of dehalogenation of α-mono- and α,α′-polyhalo ketones using low-valent transition metals and related reducing agents. Also described are the mechanistic aspects of the reductions and several representative experimental procedures.