Development of a highly α-regioselective metal-mediated allylation reaction in aqueous media: New mechanistic proposal for the origin of α-homoallylic alcohols

Abstract

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 by a 2-oxonia[3,3]-sigmatropic rearrangement to furnish the α-adduct. The α-adduct can also be synthesized via the formation of an oxonium ion intermediate between the γ-adduct and the unreacted aldehyde. The proposed mechanisms were further supported by experimental findings from the addition of InBr3 to γ-adduct under similar conditions.