Electrochemical synthesis in chemical biology is a milder, biocompatible, and environmentally friendly process for constructing novel types of bioconjugated systems. Herein, we report on the development of an indirect electrochemical strategy that allows a trifluoromethyl group to be incorporated into a tryptophan residue. This protocol allowed fluorinated peptides to be produced, thus allowing their characterization by 19F‐NMR. Interestingly, the trifluoromethylation of tryptophan did not appear under conditions of direct electrolysis; instead, as we introduced ferrocene as a mediator to allow indirect electrosynthesis, the desired product could be obtained in 67% isolated yield. Furthermore, various oligopeptides are successfully coupled to the Trp residue selectively. Mechanistic studies involving CV and DFT calculations indicated that the transformation proceeds through the homo‐cleavage of CF3SO2Na via ferrocene‐mediated indirect electrolysis. Subsequently, the addition of a CF3 radical allowed the labelled Trp to be incorporated into the corresponding products. This electrochemical protocol provides a new toolkit for the trifluoromethylation of peptides that contain tryptophan.

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