Mild and Selective Trifluoromethylation of Peptides at Tryptophane Residues by a Water-Soluble Copper Complex with Redox-Active Ligands.

Selective chemical modifications of biomolecules are in high demand for the development and implementation of chemical biology strategies. Methods involving radicals have emerged as powerful options yet potentially generate side reactivities when involving harsh reaction conditions. We report the development of a mild catalytic method for the selective functionalization of tryptophane residues in peptides with a trifluoromethyl group using a water-soluble copper complex with redox-active ligands. This method displays both inter- and intramolecular selectivity for tryptophane residues and its synthetic relevance is demonstrated by the selective conversion of a 13-residue peptidic sequence and an endomorphine analogue in good yields.