Asymmetric Radical Sulfinylation via Stereoablative Sulfinyl Radical Generation

Abstract

Stereogenic sulfur functional groups constitute an important class of chiral motifs with broad utility in medicinal chemistry, asymmetric synthesis, and catalysis, yet catalytic strategies for their enantioselective construction from simple and abundant precursors remain limited. We report herein a previously unexplored enantioconvergent decarboxylative sulfinylation of carboxylic acids enabled by a merger of acridine photocatalysis and cobalt-catalyzed asymmetric carbon–sulfur bond formation. This catalytic platform leverages stable N-sulfinylphthalimides as sulfinyl group transfer reagents and proceeds through a stereoablative S–N bond cleavage process that generates a sulfinyl radical under mild conditions. The method provides efficient access to chiral sulfoxides with high enantioselectivity. Mechanistic studies revealed that acridinyl radical-mediated PCET activation of the sulfinamide reagent, followed by selective cobalt-catalyzed sulfinyl radical trapping and coupling of the resulting sulfinyl-cobalt intermediate with an alkyl radical collectively underpin the observed stereocontrol and efficiency. Together, these findings establish a mechanistically distinct blueprint for asymmetric radical sulfoxide synthesis and open new avenues for catalytic strategies that leverage stereoablative radical processes to access sulfur-centered stereogenic motifs.