Formal γ-C(sp³)–H Activation of Ketones via Microwave-Promoted and Iminyl-Radical-Mediated 1,5-Hydrogen Atom Transfer

Abstract

Microwave irradiation of O-phenyloximes triggers N–O homolysis and 1,5-hydrogen atom transfer (HAT), resulting in formal γ-C–H functionalization of ketones after trapping of the radical intermediate and in situ imine hydrolysis. The Lewis acid InCl3·H2O facilitated HAT, enabling functionalization of benzylic and nonbenzylic secondary carbon atoms. Functionalization of primary carbons was feasible but afforded low yields, requiring ClCH2CO2H instead of InCl3·H2O as an additive. C–O and C–C bond formation could both be accomplished by this method.