Uncatalyzed conjugate addition of organozinc halides to enones in DME: a combined experimental/computational study on the role of the solvent and the reaction mechanism

Abstract

Both aryl and alkylzinc halides prepared by direct insertion of zinc into organic halides in the presence of LiCl underwent the conjugate addition reaction to nonenolizable unsaturated ketones in excellent yield, provided that DME was used instead of THF as the solvent. Diffusion NMR measurements highlighted that the species undergo considerable aggregation under the experimental conditions used in the synthetic procedure, but no substantial differences have been found between the two solvents. Density functional theory calculations, prompted by the experimental aggregation study, revealed an unexpected reaction mechanism, where the coordinating capabilities of DME stabilize a transition state involving two organozinc moieties, lowering the activation energy of the reaction with respect to that seen for THF, enough to explain the fast and quantitative reactions observed experimentally and the different behaviors of the two solvents.