Efficient Synthesis of Trifluoromethyl Amines through a Formal Umpolung Strategy from the Bench‐Stable Precursor (Me ₄N)SCF ₃

Abstract

Reported herein is the one‐pot synthesis of trifluoromethylated amines at room temperature using the bench‐stable (Me ₄N)SCF ₃ reagent and AgF. The method is rapid, operationally simple and highly selective. It proceeds via a formal umpolung reaction of the SCF ₃ with the amine, giving quantitative formation of thiocarbamoyl fluoride intermediates within minutes that can readily be transformed to N‐CF ₃. The mildness and high functional group tolerance render the method highly attractive for the late‐stage introduction of trifluoromethyl groups on amines, as demonstrated herein for a range of pharmaceutically relevant drug molecules.