Regioreversed Carbosulfenylation of Fluoroalkenes via Nickel-Mediated Radical Sorting.

Abstract

Carbosulfenylation of olefins represents an important class of reactions for the synthesis of structurally diverse organosulfur compounds. Previous studies typically yield 1,2-regioselectivity. In the context of diversity-oriented synthesis, accessing the regioreversed products is desirable, significantly broadening the scope of these reactions. In this study, we report a nickel-catalyzed 2,1-carbosulfenylation of trifluoromethyl- and gem-difluoroalkenes, using free thiols and benzyl bromides as sulfur and carbon sources, respectively. The unusual regioselectivity observed is enabled by a 'radical sorting' mechanism. The Ni catalyst activates benzyl bromide to generate a benzylic radical that undergoes HAT with the thiol to form a sulfur-centered radical. The sulfur radical subsequently adds to the fluoroalkenes, resulting in an α-fluoroalkyl C-radical. This radical undergoes SH2 with a Ni-CH2Ar to form a C(sp3)-C(sp3) bond and quaternary center, ultimately producing valuable fluoroalkyl thioethers. Isotopic labeling experiments corroborate a hydrogen atom transfer (HAT) event within the working mechanism.