Copper-Catalyzed Chemoselective (Amino)fluorosulfonylation of Hydrocarbons via Intramolecular Fluorine-atom Transfer

Sulfonyl fluorides have found increasing applications as functional molecules in chemistry and biology. We herein report copper-catalyzed atom-economical access to two categories of sulfonyl fluorides through a radical relay strategy in the presence of a SO2 surrogate. The aliphatic C(sp3)–H bond in N-fluoro-N-alkyl sulfonamides reacted via a 1,5-hydrogen atom transfer (HAT) process, affording alkanesulfonyl fluorides with a proximal amino group. On the other hand, utilizing substrates containing a proper C=C double bond resulted in intramolecular olefin aminofluorosulfonylation, allowing synthesis of fluorosulfonyl-functionalized pyrrolidines and piperidines via atom-transfer radical addition (ATRA). Both reaction systems proceeded under mild conditions requiring no additional fluorine source. Experimental and computational studies suggest that the S-F coupling is likely achieved through an intramolecular radical rebound pathway. By taking advantage of SuFEx chemistry and multifunctionality of the products, the method is applicable to late-stage modification of bioactive compounds, drug ligation chemistry and organic synthesis.