Abstract
The tunable enantioselective functionalization of alkene feedstocks represents a highly desirable yet predominantly unresolved tactic for generating high-value scaffolds. Herein, we report a tunable enantioselective electrolytic system for dehydrogenative allylation, dehydrogenative alkenylation, and hydroalkylation reactions with identical substrates to afford structurally diverse products. This success hinges on the rational design of the stereoselective coupling of an electrogenerated nickel-bound α-carbonyl radical species that can trap unactivated alkenes and engage in various subsequent radical termination processes to enable the intermolecular functionalization of unactivated alkenes. The mild reaction conditions and sustainable electrocatalytic radical platform guarantee excellent functional group tolerance and substrate compatibility with unactivated alkenes (63 examples, up to 98% e.e.), and the process evolves H₂ without the need for external chemical oxidants. The utility of this enantioselective electrolytic strategy is demonstrated by its application in the stereoselective formal synthesis of (S)-SYK inhibitor, signifying substantial progress in synthetic methods.
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Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2430133 (3t) and CCDC 2430132 (4l). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data supporting the findings of this study, including experimental procedures and compound characterization, NMR, and HPLC are available within the Article and its Supplementary Information or from the corresponding authors. The authors declare that all other data supporting the findings of this study are available within this Article and its Supplementary Information. Source Data are provided with this paper. NMR data in a Mnova file format and HPLC traces are available at Zenodo at https://zenodo.org/records/17364427, under the Creative Commons Attribution 4.0 International license. Source data are provided with this paper.
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Acknowledgements
The authors thank the supercomputing center of USTC for providing computational resources and the Instruments Center for Physical Science of USTC. The authors acknowledge financial support from the National Key R&D Program of China (2023YFA1506700, C.G.), the National Natural Science Foundation of China (grant no. 21971227, 22222113, C.G.), CAS Project for Young Scientists in Basic Research (YSBR-054, C.G.), the Fundamental Research Funds for the Central Universities (WK9990000090, WK9990000111, C.G.), and the Fundamental Research Funds for the Central Universities (WK9990000133, C.G.). The project was supported by the Open Research Fund of the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, China Postdoctoral Science Foundation (grant no.2023M743373, 2024T170881, L.P.), and the Postdoctoral Fellowship Program of CPSF (GZB20230708, L.P.).
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C.G. conceived the project. T.X. performed the experiments and analyzed the data. M.L., J.Z., and L.P. synthesized the substrates and ligands. All authors discussed the results and prepared the manuscript.
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Xie, T., Liu, M., Zhang, J. et al. Tunable enantioselective electrocatalytic functionalization of unactivated alkenes. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68123-3
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DOI: https://doi.org/10.1038/s41467-025-68123-3
