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Enantioselective C–C cross-coupling of unactivated alkenes

Nature Catalysis volume 6, pages 1087–1097 (2023)Cite this article

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Abstract

Metal-catalysed cross-coupling has played a central role in modern chemical synthesis for decades. Unactivated alkenes, including light olefins, are manufactured on enormous scale in the petroleum industry and represent ideal starting materials for the preparation of pharmaceuticals, agrochemicals and materials. However, enantioselective cross-coupling of unactivated alkenes remains a challenging and long-standing goal. Here we report a highly enantio- and regioselective three-component cross-coupling of unactivated alkenes with aryl (or alkenyl) triflates and organometallics (or reductant) to construct diverse C sp3 stereocentres by nickel catalysis. Specifically, selective carbonickelation and in situ trapping with nucleophiles enable efficient hydrofunctionalization and dicarbofunctionalization of unactivated alkenes in a directing group-free manner. Nickel catalysts bearing bulky C2-symmetric chiral N-heterocyclic carbene ligands were crucial for attaining high reactivity and selectivity. This strategy offers a general, modular and divergent platform for rapidly upgrading feedstock alkenes to various value-added molecules and is expected to inspire the development of other challenging enantioselective alkene cross-couplings.

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Fig. 1: The importance of enantioselective olefin cross-coupling reactions.
Fig. 2: Substrate scope of hydrocarbofunctionalization reactions.
Fig. 3: Substrate scope of dicarbofunctionalization reactions.
Fig. 4: Synthetic applications and light alkene cross-couplings.
Fig. 5: Mechanistic studies.

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Data availability

All data supporting the findings of this study are available within the article and its Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number 2223535 (7d). 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 was provided by the National Key R&D Program of China (2022YFA1503702 and 2021YFF0701600), the National Natural Science Foundation of China (22325110, 92256303, 22171280 and 21821002), the Program of Shanghai Academic Research Leader (22XD1424900), the CAS Youth Interdisciplinary Team (JCTD-2021-11), the Ningbo Natural Science Foundation (2022J017, S.-L.S.) and the Ministry of Education of Singapore Academic Research Fund Tier 2: A-8000034-00-00 (M.J.K.).

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Author notes

  1. These authors contributed equally: Zi-Chao Wang, Xiaohua Luo, Jia-Wen Zhang, Chen-Fei Liu.

Authors and Affiliations

  1. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Zi-Chao Wang, Jia-Wen Zhang & Shi-Liang Shi

  2. Department of Chemistry, National University of Singapore, Singapore, Republic of Singapore

    Xiaohua Luo, Chen-Fei Liu & Ming Joo Koh

  3. Joint School of National University of Singapore and Tianjin University, Fuzhou, China

    Xiaohua Luo

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Contributions

Z.-C.W., X.L., J.-W.Z. and C.-F.L. developed the catalytic method and conducted mechanistic studies. S.-L.S. and M.J.K. conceived the project and directed the investigations. S.-L.S. and Z.-C.W. wrote the paper with input from the other authors.

Corresponding authors

Correspondence to Ming Joo Koh or Shi-Liang Shi.

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Nature Catalysis thanks Naoto Chatani and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Information

Supplementary Tables 1–7, Methods, NMR spectra, HPLC traces and References.

Supplementary Data 1

Cif file of crystal structure for compound 7d.

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Wang, ZC., Luo, X., Zhang, JW. et al. Enantioselective C–C cross-coupling of unactivated alkenes. Nat Catal 6, 1087–1097 (2023). https://doi.org/10.1038/s41929-023-01037-9

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