title: Development of a highly alpha-regioselective metal-mediated allylation reaction in aqueous media: new mechanistic proposal for the origin of alpha-homoallylic alcohols.
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.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543.
authors.forename: Kui-Thong
authors.initials: KT
authors.lastname: Tan
authors.forename: Shu-Sin
authors.initials: SS
authors.lastname: Chng
authors.forename: Hin-Soon
authors.initials: HS
authors.lastname: Cheng
authors.forename: Teck-Peng
authors.initials: TP
authors.lastname: Loh
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006842:Hydrocarbons, Brominated / Q000737:chemistry; D007204:Indium / Q000737:chemistry*; D020005:Propanols / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000498:Allyl Compounds; D006842:Hydrocarbons, Brominated; D020005:Propanols; D012996:Solutions; D007204:Indium; D014867:Water; C006463:allyl alcohol