Copper-Catalyzed Chemoselective (Amino)fluorosulfonylation of Hydrocarbons via Intramolecular Fluorine-Atom Transfer
Shuting Qu, Xiao‐Xi Li, Xiao‐Xi Li, Xingwei Li, Xingwei Li, Lin Wang
Abstract
Sulfonyl fluorides have found increasing applications as functional molecules in chemistry and biology. We herein report a copper-catalyzed atom-economical access to two categories of sulfonyl fluorides through a radical relay strategy in the presence of an SO 2 surrogate. The aliphatic C(sp 3 )–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 the 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 S–F coupling is likely achieved through an intramolecular radical-rebound pathway. By taking advantage of the SuFEx chemistry and multifunctionality of the products, the method is applicable to the late-stage modification of bioactive compounds, drug ligation chemistry, and organic synthesis.