Selective Photoredox Trifluoromethylation of Tryptophan‐Containing Peptides

Abstract

For application in drug discovery and biomedicine, it is crucial to develop new biocompatible methods to modify polypeptides. Herein, a visible‐light‐induced photoredox trifluoromethylation of tryptophan‐containing peptides is reported. Under a mild, biocompatible, and straightforward condition, this strategy could incorporate the trifluoromethyl group into tryptophan residue with excellent chemo‐ and site‐selectivity. The use of lower photocatalyst loading in 2 mol‐% and cheap CF3SO2Na salt represents a great catalytic activity and economic CF3 source. This direct trifluoromethylation strategy allows the ready study of fluorinated peptides exploiting 19F‐NMR. Additionally, the development of this protocol enables the study of biochemical systems and potentially modulates the function of biomolecules. Careful mechanistic studies (Stern‐Volmer fluorescence quenching, EPR, and radical inhibition/trapping experiments) indicate that the reaction would proceed with a radical–radical cross‐coupling procedure.