A catalytic fluoride-rebound mechanism for C(sp3)-CF3 bond formation

Abstract

The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(sp³)-CF₃ reductive elimination from Au(III) that accesses these compounds by a distinct mechanism proceeding via fluoride abstraction, migratory insertion, and C-F reductive elimination to achieve a net C-C bond construction. The parent bis(trifluoromethyl)Au(III) complexes tolerate a surprising breadth of synthetic protocols, enabling the synthesis of complex organic derivatives without cleavage of the Au-C bond. This feature, combined with the "fluoride-rebound" mechanism, was translated into a protocol for the synthesis of ¹⁸F-radiolabeled aliphatic CF₃-containing compounds, enabling the preparation of potential tracers for use in positron emission tomography.