Multicomponent Reaction of Aliphatic Organozinc Reagents, Acrylates and Acyl chlorides: Synthesis of α-Substituted β-Ketoesters

An uncatalyzed three-component reaction employing aliphatic organozinc reagents for the preparation of & alpha;-substituted & beta;-ketoesters is described. This modular procedure, which relies on a formal conjugate addition/crossed-Claisen domino reaction between an organozinc, an acrylate and an acyl chloride, allows the straightforward synthesis of the reaction products under mild conditions. The three-component coupling can also be conducted from alkyl iodides, in an even more simple procedure. Experimental findings account for a probable polar concerted mechanism involving at least two organozinc compounds at the stage of the transition state.