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Double alkyl–alkyl bond construction across alkenes enabled by nickel electron-shuttle catalysis

Nature Catalysis volume 6, pages 847–857 (2023)Cite this article

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Abstract

Selective construction of two distinct alkyl–alkyl bonds across the C=C bond of simple unactivated olefins is a persistent challenge in organic synthesis. Transition metal-catalysed alkene-dicarbofunctionalization reactions proceeding via classic organometallic elementary reaction mechanism (oxidative addition/transmetalation/reductive elimination) suffered from non-bond forming side reactivities of alkyl–metal intermediates (facile β-hydride elimination) and thus strongly limited the substrate scope of olefins and coupling reagents. Here we demonstrate that the problem of alkyl–metal side reactivities can be overcome with an electron-shuttle catalysis approach, wherein the metal catalyst acts as an electron shuttle to induce and quench the radical intermediates and facilitate the alkyl–alkyl bond formation via radical-unsaturated bond addition. This strategy was applied to a modular alkylative aminomethylation of olefins with two distinct alkyl–alkyl bonds generated through nickel electron-shuttle catalysis. Mechanistic studies supported the formation of carbon-centred radical species and the involvement of radical addition processes.

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Fig. 1: Metal-catalysed dicarbofunctionalization of alkenes.
Fig. 2: Olefin scope.
Fig. 3: Alkyl bromide scope.
Fig. 4: Four-component reaction.
Fig. 5: Synthetic applications.
Fig. 6: Mechanistic investigation.
Fig. 7: Mechanistic investigation.

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Data availability

All data supporting the findings of this study are available within the article and its Supplementary Information files, or from the corresponding author upon reasonable request. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2216659 (36), 2216660 (150), 2216661 (Ni-I) and 2269279 (trans-45-deriv). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

Financial support for this project was provided by National Natural Science Foundation of China (21925111), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB0450301) and National Key R&D Program of China (2021YFA1501003) (H.H.). We thank F. G. Deng for proofreading.

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Author notes

  1. These authors contributed equally: Changqing Rao, Tianze Zhang.

Authors and Affiliations

  1. Hefei National Research Center for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, P. R. China

    Changqing Rao, Tianze Zhang, Hongchi Liu & Hanmin Huang

  2. Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, Huaibei Normal University, Huaibei, P. R. China

    Hanmin Huang

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Contributions

H.H. conceived the concept and directed the project. C.R., T.Z. and H.L. developed the reaction. T.Z. and H.H. wrote the manuscript. All authors contributed to the analysis and interpretation of the results.

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Correspondence to Hanmin Huang.

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Nature Catalysis thanks Xin-Hua Duan and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods, Tables 1–11 and Figs. 1–21.

Supplementary Data 1

Crystallographic data for compound 36.

Supplementary Data 2

Crystallographic data for compound 150.

Supplementary Data 3

Crystallographic data for compound Ni-I.

Supplementary Data 4

Crystallographic data for compound trans-45-deriv.

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Rao, C., Zhang, T., Liu, H. et al. Double alkyl–alkyl bond construction across alkenes enabled by nickel electron-shuttle catalysis. Nat Catal 6, 847–857 (2023). https://doi.org/10.1038/s41929-023-01015-1

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