Electrochemically Chemoselective N-C(O) Bond Activation for Amide Esterification

The activation of the N-C(O) bond in amides posed a significant challenge in organic synthesis due to resonance stability. Herein, we present an electrochemical method for the direct esterification of primary amides with O-based nucleophiles facilitated by TBAB. This sustainable protocol operates under mild, open-to-air conditions, exhibits excellent functional group tolerance, and is effective for the late-stage modification of complex molecules. Mechanistic studies indicate that the process involves the in situ formation of N-bromobenzamide, followed by a hydrogen-bond-assisted nucleophilic attack to achieve the transformation. This strategy provides a practical and scalable alternative for amide activation and esterification.