Abstract
Precision in site-selective functionalization of molecules bearing multiple potentially reactive positions is a longstanding challenge in organic synthesis. Although migratory difunctionalization offers a powerful strategy for programmed functional group installation along carbon chains, its implementation with multisubstituted alkenes has been impeded by the increased complexity of site-selectivity. Here we report a head–tail carboboration of multisubstituted alkenes with exceptional site-selectivity, enabled by ligand steric exclusion in a nickel-catalysed chain-walking system. This catalytic system enables selective migratory transformations of tertiary alkyl–metal intermediates across a range of thermodynamically and kinetically accessible reaction site combinations. The importance of this study is evident in not only its capacity to efficiently couple structurally diverse carbon electrophiles with complex substrates, including natural terpenes, but also its contribution to streamlining the synthesis of natural products and materials.
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Data availability
The data supporting the findings of this study are available in the article and its Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2376317 (52), CCDC 2376318 (54-1) and CCDC 2313837 (56-1). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
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Acknowledgements
National Natural Science Foundation of China (grant nos. 22122107 to G.Y. and 22401220 to Yangyang Li), Guangdong Basic and Applied Basic Research Foundation (grant no. 2024A1515011689 to G.Y.), Fundamental Research Funds for the Central Universities (grant no. 413100070 to Yangyang Li) and Scientific Research Innovation Capability Support Project for Young Faculty (ZYGXQNJSKYCXNLZCXM-H17 to G.Y.) are acknowledged for financial support. We thank J. Min from Wuhan University for providing the intermediate compounds essential for synthesizing organic solar cells. We also thank the Core Facility of Wuhan University for their assistance with X-ray crystallographic analysis. Additionally, the numerical calculations for this research were conducted on the supercomputing system at the Supercomputing Center of Wuhan University.
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G.Y. designed the project and directed the work. W.K., H.W., D.W. and P.L. conducted the experiments and data analysis. B.G. and Yuqiang Li performed all density functional theory calculations. G.Y., W.K., D.W. and Yangyang Li wrote the paper.
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Kong, W., Wu, D., Wei, H. et al. Head–tail carboboration of multisubstituted alkenes enabled by chain recognition. Nat. Chem. (2025). https://doi.org/10.1038/s41557-025-01903-y
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DOI: https://doi.org/10.1038/s41557-025-01903-y
