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

作者：Xinxin Zhao, Jian Wang, Huaisong Hu, Zhihui Wang, Longyu Cheng, Yexu Wang, Z. H. Qu, Ting Li, Ming Chen · 发表于：Organic Letters · 年份：2025 · DOI：10.1021/acs.orglett.5c01878 · 被引用次数：4 · 研究领域：Advanced Synthetic Organic Chemistry、Asymmetric Synthesis and Catalysis、Asymmetric Hydrogenation and Catalysis

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.