Electrochemical Benzylic C–H Carboxylation

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.