南开大学仇友爱研究小组开发出电化学C-H羧基化。这一研究成果于2025年4月9日发表在国际顶尖学术期刊《美国化学会杂志》上。

在此，该研究团队报告了他们通过卤化物促进的线性配对电解来克服这一障碍的努力，以产生各种各样的苯基羧酸。值得注意的是，该工艺不含过渡金属和碱性，使其对环境无害，成本效益高。

此外，它适合在温和的反应条件下构建广泛的伯、仲、叔苯基羧酸，具有广泛的底物范围和良好的官能团耐受性。

此外，他们的方案可以直接合成一些药物分子，包括氟比洛芬、布洛芬和萘普生，并促进了复杂化合物的后期修饰，展示了在合成化学中的实际应用，并强调了其推进苯基羧酸及相关化合物合成的潜力。

研究人员表示，苯基C-H直接羧化是一种高原子经济、高效、便捷的合成有价值的苯基羧酸的途径，在许多药物和生物活性分子中具有重要意义。然而，苯碳氢键和二氧化碳的固有惰性对进一步的转化提出了很大的挑战。

附：英文原文

Title: Electrochemical Benzylic C–H Carboxylation

Author: Weimei Zeng, Chengyi Peng, Youai Qiu

Issue&Volume: April 9, 2025

Abstract: Direct benzylic C–H carboxylation stands as a high atom economy, efficient, and convenient route for the synthesis of valuable benzylic carboxylic acids, which are of great significance in many pharmaceuticals and bioactive molecules. However, the inherent inertness of both benzylic C–H bonds and carbon dioxide presents a great challenge for further transformations. Herein, we report our efforts to overcome this obstacle via halide-promoted linear paired electrolysis to generate various benzylic carboxylic acids. Remarkably, this process is transition-metal- and base-free, making it environmentally benign and cost-effective. Besides, it is suitable for constructing a wide range of primary, secondary, and tertiary  benzylic carboxylic acids under mild reaction conditions, demonstrating broad substrate scopes and good functional group tolerance. Furthermore, our protocol enables the direct synthesis of some drug molecules, including Flurbiprofen, Ibuprofen, and Naproxen, and facilitates the late-stage modification of complex compounds, showcasing the practical application in synthetic chemistry and underscores its potential to advance the synthesis of benzylic carboxylic acids and related compounds.

DOI: 10.1021/jacs.5c00259

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c00259