Development of a Highly α-Regioselective Metal-Mediated Allylation Reaction in Aqueous Media: New Mechanistic Proposal for the Origin of α-Homoallylic Alcohols

This paper described a general method to obtain α-adduct homoallylic alcohols using indium, zinc, and tin in water. A new mechanism was proposed to account for the formation of these synthetically difficult-to-obtain molecules. Generally, this method can be performed with a wide range of aldehydes and allylic halides with just 6 equiv of water added, giving the α-adduct in high selectivities. To account for the origin of the α-homoallylic alcohol, the reaction mechanism was carefully studied using 1H NMR, a crossover experiment, and the inversion stereochemical studies of 22β γ-adduct homoallylic sterol to the 22α α-adduct homoallylic sterol. From the results of mechanism studies, it is possible that two mechanism pathways coexisted in the metal-mediated α-regioselective allylation. The metal salts formed from the metal-mediated allylation can catalyze the γ-adduct to undergo a bond cleavage to generate the parent aldehyde in situ followed by a concerted rearrangement, perhaps a retroene reaction followed...