转自：康龙化成

Electrochemical Benzylic C−H Carboxylation

Weimei Zeng, Chengyi Peng, and Youai Qiu*

State Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, College of Chemistry, Nankai University, Tianjin 300071, China;

—J. Am. Chem. Soc. 2025, 10.1021/jacs.5c00259

Recommended by Chunlei Lu_ MC2

KEY WORDS:Benzylic C−H Carboxylation, Electro chemistry (反应类型), C(sp3) - C(sp2)(成键类型), Carbon dioxide, Benzyl compounds (原料), benzylic carboxylic acids (产物) ,nBu4NClO4, NaI (其他)

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.

Synthetic approaches to benzylic carboxylic acids

Scope of benzylic C−H bonds (selected)

Proposed mechanism

In conclusion, Prof. Youai Qiu et al achieved electrochemical benzylic C−H carboxylation withCO2, overcoming the inherent inertness of both reactants. This process with high atom-utilization offers a wide substrate scope, which could allow effective construction of primary, secondary, and tertiary benzylic carboxylic acids. Besides, it is compatible with several sensitive functional groups, such as halides, alkenes, and ketones. It is worth noting that the strategy could be applied to the direct synthesis of drugs and late-stage modification of biorelevant compounds under mild conditions. In the absence of sacrificial anodes/reagents, transition metals, or strong bases, the protocol offers more opportunities for further applications in a cleaner and more sustainable manner. Detailed mechanistic exploration reveals the proposed mechanism promoted by halide atom to realize the linear paired electrolysis. 

（转自：康龙化成）