Efficient protocol for the SO2F2-mediated deoxyfluorination of aliphatic alcohols

Abstract

Alkyl fluorides are prevalent in both the pharmaceutical and agrochemical industries. As such, there has been significant interest over the past 40 years in the development of new synthetic methods to access these important fluorinated motifs. Herein we report the sulfuryl fluoride-mediated deoxyfluorination of alcohols using room temperature reaction conditions in only an hour. A wide range of primary aliphatic alcohols were efficiently converted to the corresponding fluoride in 46-70% isolated yields. Secondary alcohols were also effectively deoxyfluorinated in 50–92% yields. Chiral secondary alcohols were cleanly converted to the corresponding alkyl fluoride with only a minor deterioration of the enantioenrichment. A steroid derivative also underwent deoxyfluorination in 50% yield and 5.9:1 dr, with the major product resulting from net inversion of the stereocenter.