A highly efficient and atom-economical method for the C–H trifluoromethylation of (hetero)arenes and complex biomolecules has been developed using a substoichiometric amount of the stable tetrakis(trifluoromethyl)cuprate(iii) salt. Upon violet-light irradiation in the presence of an oxidant, all four CF3 groups are sequentially converted into trifluoromethyl radicals, enabling high-yielding transformations under mild conditions. The protocol exhibits excellent functional group tolerance and is applicable to the late-stage trifluoromethylation of pharmaceuticals, amino acids, and nucleosides. Mechanistic studies support a photoinitiated radical pathway and reveal the full utilization of the Cu(iii) species. The results presented advance the use of copper-mediated strategies for the sustainable incorporation of fluorine into complex molecules.
