New sulfuryl fluoride-derived alkylating reagents for the 1,1-dihydrofluoroalkylation of thiols

Abstract

Herein, we report a new method for the one-pot synthesis of 1,1-dihydrofluoroalkyl sulfides by bubbling sulfuryl fluoride (SO₂F₂) through a solution of the corresponding alcohol and thiol. The reaction proceeds through a new class of bis(1,1-dihydrofluoroalkyl) sulfate reagents, to afford the desired 1,1-dihydrofluoroalkyl sulfides in 55–90% isolated yields. The bis(1,1-dihydrofluoroalkyl) sulfates are highly chemoselective for thiol alkylation, and are unreactive with competing, unprotected nucleophiles, including amines, alcohols, and carboxylic acids.