Electrochemical Desilylative Fluorination Enables Access to N-Monofluoromethyl Amides and Peptides.

N-Fluoroalkyl amides have emerged as highly attractive targets because N-fluoromethylation can modulate conformation, stability, lipophilicity, and molecular recognition. However, despite the rapidly advancing chemistry of N-CF3 and N-CF2H amides, access to the corresponding N-monofluoromethyl (N-CH2F) amides remains significantly underdeveloped. Existing approaches are often constrained by the use of silver-based fluorinating reagents, unstable intermediates, and limited compatibility with peptide substrates. In this study, we report an electrochemical strategy for the synthesis of N-monofluoromethyl amides using fluoride as the fluorine source. Employing N-CH2TMS amides as readily accessible precursors, the target framework is efficiently constructed through electrochemical oxidative activation. The transformation proceeds under mild conditions and exhibits broad compatibility with amino acid-derived amides and peptide substrates of varying chain lengths.