Abstract
Enantioselective dicarbofunctionalization of alkenes is a powerful strategy for constructing functionalized sp³-rich molecules, yet it remains challenging for unactivated substrates lacking directing groups. While asymmetric multicomponent reactions catalyzed by d¹⁰ transition metals have advanced for activated alkenes, enantioselective multicomponent cross-coupling of unactivated alkenes, particularly enabling remote functionalization to stereoselectively generate the nonadjacent stereocenters, is still underdeveloped. Herein, we report a palladium-catalyzed asymmetric migratory dicarbofunctionalization of directing-group-free, trisubstituted unactivated alkenes. This method forges remote stereogenic centers, enabling both 1,3-diarylation and 1,4-diarylation with high enantioselectivity and diastereoselectivity. Mechanistic studies indicate a chain-walking process involving irreversible Pd-H migration, rationalizing the observed regiocontrol.
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Data availability
All data to support the conclusions are available in the main text or the supplementary materials. The X-ray Crystallographic coordinates for structures reported in this study have been deposited at the Cambridge Crystallographic Data Center (CCDC) under deposition numbers CCDC 2474573 (4ae) and 2475482 (6a-D). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Data supporting the findings of this manuscript are also available from the corresponding author upon request.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (22371071, 22571081, 92356301, Y.C.), Science and Technology Commission of Shanghai Municipality (grant No.24DX1400200, Y.C.), the Program of Introducing Talents of Discipline to Universities (B16017, Y.C.), the China Postdoctoral Science Foundation (2024M750901, 2023TQ0118, Y.X.), Postdoctoral Fellowship Program of CPSF (GZB20230212, Y.X.), and the Fundamental Research Funds for the Central Universities. We thank the Analysis and Testing Center of East China University of Science and Technology for help with NMR and HRMS analysis.
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Y.C. conceived the projects. L.F., Y.X., H.G., and W.H. performed the experiments under the supervision of W.-H. Z., J.Q., and Y.C. Y.X. and Y.C. wrote the manuscript with the feedback of all other authors.
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Fan, L., Xi, Y., Gu, H. et al. Palladium-catalyzed asymmetric migratory diarylation of unactivated directing-group-free internal alkenes. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68006-7
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DOI: https://doi.org/10.1038/s41467-025-68006-7
