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

Citations Over TimeTop 10% of 2003 papers

Abstract

This paper described a general method to obtain alpha-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 (1)H NMR, a crossover experiment, and the inversion stereochemical studies of 22 beta gamma-adduct homoallylic sterol to the 22 alpha 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 InBr(3) to gamma-adduct under similar conditions.

Related Papers

• → Recent Advances in the Regioselective Synthesis of Pyrazoles(2011)73 cited
• → Perfectly Regioselective and Sequential Protection of Glucopyranosides(2010)53 cited
• → Remote substituent effects on regioselectivity in the Pauson–Khand reaction of 2-substituted norbornenes(2001)19 cited
• → N-CHLORO-2,3,4,4,5,6-HEXACHLOROCYCLOHEXA- 2,5-DIENYLIDENEAMINE AS A MILD AND HIGHLY REGIOSELECTIVE CHLORINATING REAGENT(2002)5 cited
• → β-Aminoenones in the regioselective synthesis of 1,3,5-trialkylpyrazoles. The influence of the substituents in the mechanism and the regioselectivity of the reaction(1998)12 cited