Radical Fluorosulfonylmethylation:\nA Photocatalytic\nand Facile Access to PMSF and Related Derivatives

Phenylmethylsulfonyl fluoride (PMSF) and its analogues\nhave been\nused for decades as an enzyme inhibitor. Herein, we describe the successful\ndevelopment of a radical fluorosulfonylmethylation reaction under\nphotoredox catalysis, allowing for direct access to PMSF derivatives\nfrom arenes and heteroarenes via C–H functionalization. This\nmethod greatly expands the library of accessible PMSF-type molecules\nand thus benefits the related study in chemical biology and drug discovery.\nBy combination with the SuFEx click reaction, these PMSF products\ncan be readily converted to sulfonates and sulfonamides, which could\novercome the low efficiency in the direct functionalization of arenes\nwith the corresponding radicals. In addition, an extension of radical\nfluorosulfonylmethylation to the functionalization of olefins via\naddition, cyclization, and migration reactions is also demonstrated,\nproviding a facile synthesis of various alkyl sulfonyl fluorides.