近日，常州工学院孔宪强团队实现了通过Criegee-Kolbe自由基接力的非活化醇的电化学去羟甲基化功能化。相关论文于2025年12月11日发表在《美国化学会志》上。

醇类的直接脱羟甲基官能化为分子多样化提供了一个简洁高效的平台，但其发展仍不充分。

研究组开发了一种在温和、无金属条件下运行的电化学平台，利用氢原子转移（HAT）/O₂–Criegee串联反应，将多种醇类（如脂肪醇、苄醇和烯丙醇）转化为缩短一个碳的烷基自由基。该方法实现了脱羟甲基的硝化、氟磺酰化、叠氮化和膦酰化反应，并展现出广泛的官能团耐受性及克级规模的实用性。将阳极自由基生成过程与阴极镍催化循环相结合，进一步实现了C(sp²)–C(sp³)偶联，包括使用乙醇作为甲基源对芳基卤化物进行一步甲基化。

机理实验（对照研究及电子顺磁共振/高分辨率质谱/循环伏安法）支持了以下反应序列：HAT、O₂捕获、Criegee组装、Baeyer–Villiger氧合、阳极脱羧以及自由基捕获，并表明反应遵循介质先导的阳极门控机制。该平台拓展了直接从简单醇类构建C–N、C–SO₂F、C–P及C–C键的途径，为惰性C–C键的选择性编辑及生物相关分子的后期多样化提供了一种通用策略。

附：英文原文

Title: Electrochemical Dehydroxymethylative Functionalization of Unactivated Alcohols via Criegee–Kolbe Radical Relay

Author: Yiyi Chen, Yi Xu, Shuangquan Zhang, Xiaohui Chen, Fangqun Gan, Xianliang Tan, Kun Feng, Xiao Xiao, Zhong Yan Cao, Ming Chen, Xianqiang Kong

Issue&Volume: December 11, 2025

Abstract: Direct dehydroxymethylative functionalization of alcohols offers a streamlined platform for molecular diversification but remains underdeveloped. An electrochemical platform operating under mild, metal-free conditions leverages a hydrogen atom transfer (HAT)/O2–Criegee relay to convert various alcohols (such as aliphatic, benzylic, and allylic alcohols) into one-carbon-shortened radicals, enabling dehydroxymethylative nitration, fluorosulfonylation, azidation, and phosphinoylation with broad functional-group tolerance and gram-scale practicality. Pairing the anodic radical generation with a cathodic Ni cycle further delivers C(sp2)–C(sp3) coupling, including the one-step methylation of aryl halides using ethanol as a feedstock methyl source. Mechanistic experiments (control studies and electron paramagnetic resonance/high-resolution mass spectrometry/cyclic voltammetry) support a sequence of HAT, O2 trapping, Criegee assembly, Baeyer–Villiger oxygenation, anodic decarboxylation, and radical interception and indicate mediator-first anodic gating. The platform expands access to C–N, C–SO2F, C–P, and C–C bonds directly from simple alcohols, providing a general strategy for selective editing of inert C–C bonds and late-stage diversification of biorelevant molecules.

DOI: 10.1021/jacs.5c18031

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c18031