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 a-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 alpha-adduct in high selectivities. To account for the origin of the alpha-homoallylic alcohol, the reaction mechanism was carefully studied using H-1 NMR, a crossover experiment, and the inversion stereochemical studies of 22beta gamma-adduct homoallylic sterol to the 22alpha alpha-adduct homoallylic sterol. From the results of mechanism studies, it is possible that two mechanism pathways coexisted in the metal-mediated alpha-regioselective allylation. The metal salts formed from the metal-mediated allylation can catalyze the gamma-adduct to undergo a bond cleavage to generate the parent aldehyde in situ followed by a concerted rearrangement, perhaps a retroene reaction followed by a 2-oxonia[3,3]-sigmatropic rearrangement to furnish the alpha-adduct. The alpha-adduct can also be synthesized via the formation of an oxonium ion intermediate between the gamma-adduct and the unreacted aldehyde. The proposed mechanisms were further supported by experimental findings from the addition of InBr3 to gamma-adduct under similar conditions.