Oxidative C(sp3)–H bond functionalization is a powerful tool in organic synthesis, but the stoichiometric oxidants required for bond formation raise environmental concerns. Electrochemical synthesis is typically carried out under environmentally benign conditions and hence is increasingly used in organic reactions. Recent advances revealed that electrochemical oxidative cross-coupling reactions employing either free radicals or carbocations can be conducted in the absence of external oxidants. In this Review, we outline the electrochemical oxidative C(sp3)–H cross-coupling to C(sp3)–C(X) (X = N, O, S, P, F, I and Br) bonds with hydrogen evolution under external oxidant-free conditions. Two commonly used electrochemical methods, namely direct and indirect oxidation electrolysis, are discussed for C(sp3)–H activation. The outline of electrochemical oxidative C(sp3)–H cross-coupling is organized based on the reactive intermediates (C(sp3)–M, a C(sp3) radical or a C(sp3) cation). Electrochemical asymmetric C(sp3)–H cross-coupling and late-stage functionalization of C(sp3)–H bonds in complex molecules are included to demonstrate the utility. Future perspectives for the development of electrochemical C(sp3)–H bond functionalization are proposed.
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This work was supported by the National Key R&D Program of China (no. 2022YFA1505100 and 2021YFA1500100), National Natural Science Foundation of China (22031008) and Science Foundation of Wuhan (2020010601012192). This research work was funded by the Institution Fund Projects under grant IFPRP 263-135-1442. Also, we gratefully acknowledge technical and financial support from the Ministry of Education and Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia
The authors declare no competing interests.
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Yang, Z., Shi, W., Alhumade, H. et al. Electrochemical oxidative C(sp3)–H cross-coupling with hydrogen evolution. Nat. Synth 2, 217–230 (2023). https://doi.org/10.1038/s44160-022-00221-2