Synthetic Stitching with Silicon: Geminal Alkylation−Hydroxylation of Alkynyl Carbonyl Compounds

A new strategy for the synthesis of beta-carbonyl-substituted tertiary alcohols from alpha,beta-alkynyl ketones and esters has been demonstrated. A silicon tether is used to internally deliver an alkyl group, which, combined with a C-Si to C-O transformation, can regio- and diastereoselectively "stitch" together geminal C-C and C-O bonds at the beta-position of an electron-withdrawing group. Regioselective alkyne hydrosilylation by a trans addition process provides clean access to trisubstituted vinylsilanes. Subsequent one-pot fluoride-induced C-C bond formation and oxidation of the resulting tertiary silane, a type of silane not normally reactive to such conditions, affords the desired products. The utility of neighboring ketone and carboxylate groups in promoting the oxidation of these highly hindered tertiary alcohols, an observation that may affect synthetic design of routes depending on such oxidations, is demonstrated. Good diastereoselection (>10:1) is observed for substrates bearing gamma-alkoxy stereocenters.