Diastereo- and Enantioselective Catalytic Radical Oxysulfonylation of Alkenes in beta,gamma-Unsaturated Ketoximes

The asymmetric radical-initiated difunctionalization of internal alkenes, which creates two vicinal stereocenters, has been a significant synthetic challenge despite the tremendous progress achieved for terminal alkenes. This is attributable to the common stepwise mechanism that involves an initial free radical addition to the alkene in a nonstereoselective fashion. We report here the first asymmetric radical 1,2-oxysulfonylation of both terminal and internal aryl alkenes in beta,gamma-unsaturated ketoximes in the presence of copper(I)cinchona alkaloid-based sulfonamide catalyst The experimental and computational mechanistic studies collectively support a Cu-II-Cu-I mechanism featuring fast, reversible addition of sulfonyl radicals to alkenes and subsequent rate- and stereo-determining C-O bond formation, namely, a scenario under Curtin-Hammett kinetic control. The method provides a robust platform for collective synthesis of a diverse array of valuable chiral sulfonyl-containing building blocks.