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

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 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.

Recent Advances in Developing Radical Methods for the Synthesis of Aliphatic Sulfonyl Fluorides

“…While the above examples for the construction of FSO 2 group via the electrophilic fluorination of alkyl sulfonyl radicals/ anions or the nucleophilic attack of the alkyl sulfonyl cations or their surrogates by fluoride anion, a recent excellent strategy for the efficient construction of FSO 2 group via Cu-mediated radical fluorine atom transfer (FAT) to alkyl sulfonyl radical has been developed by the groups of Zhang and Cao, [51] Li and Wang, [52] respectively. Both groups noticed that the use of copper catalysis enables to promote the nitrogen radicaldirected site-selective Csp 3 -H fluorosulfonylation (Scheme 34).…”