Pyridine <i>N</i> -Oxide Mediators for Electrochemical Benzylic C(sp ³ )–H Oxygenation

The electrooxidation of ubiquitous benzylic C(sp3)–H bonds offers a sustainable pathway to synthesize value-added carbonyl compounds. However, the lack of a versatile electrocatalytic system to accommodate the structural diversity of compounds containing benzylic C–H bonds hinders the practical implementation of electrochemical benzylic C–H oxidation technology. Herein, we designed and evaluated a library of electrochemical hydrogen atom transfer (HAT) mediators, derived from pyridine N-oxides, for the selective oxygenation of benzylic C(sp3)–H bonds. The O–H bond dissociation energy and oxidation potential of pyridine N-oxides can be fine-tuned by modifying the electronic properties of substituent groups on the pyridine ring, thus offering a facile way to adjust HAT characteristics to suit the target benzylic C–H bonds. A predictive neural network model was constructed based on experimental high-throughput screening data to map the quantitative structure-activity relationship (QSAR) for catalyst–substrate pairs. In addition, the practicality of the developed electrocatalytic system was demonstrated with a good substrate scope and scalability to achieve gram-scale synthesis using a flow electrochemical reactor.