Methyl fluorosulfonyldifluoroacetate (MFSDA): An Underutilised Reagent for Trifluoromethylation

Abstract

The introduction of fluorine groups to pharmaceutical compounds can have a dramatic effect on the lipophilicity and metabolic stability of the molecule in vivo. Around 20 % of drugs contain at least one fluorine atom. The trifluoromethyl group is known to have beneficial effects and can dramatically affect the biological activity when substituted for a methyl group, for example. In any case, the direct and late-stage introduction of a trifluoromethyl group is a powerful transformation in the tool box of the medicinal chemist. The use of methyl fluorosulfonyldifluoroacetate (MFSDA) as a relatively inexpensive reagent for trifluoromethylation was first reported in 1989; however, in our opinion it has been somewhat underutilised. Herein, a comprehensive review of trifluoromethylation using MFSDA is reported, which we hope will further expose readers to this useful reagent.

Keywords: fluorine; methyl fluorosulfonyldifluoroacetate; trifluoromethylation.