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 a copper-catalyzed
atom-economical access to two categories of sulfonyl fluorides through
a radical relay strategy in the presence of an 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 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.