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Photoelectrochemical asymmetric catalysis enables site- and enantioselective cyanation of benzylic C–H bonds

Nature Catalysis volume 5, pages 943–951 (2022)Cite this article

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Abstract

The enantioselective functionalization of ubiquitous C(sp3)–H bonds is ideally suited for the construction of three-dimensional chiral structures. However, organic molecules often contain multiple C(sp3)–H bonds with a similar energy and steric environment, rendering the simultaneous control of site-, chemo- and stereoselectivity extremely challenging. Here we show the merger of molecular photoelectrochemistry with asymmetric catalysis for the highly site- and enantioselective cyanation of benzylic C(sp3)–H bonds. This example of photoelectrochemical asymmetric catalysis requires no chemical oxidant and exhibits an exceptional level of site selectivity and functional group tolerance, enabling not only the efficient conversion of feedstock chemicals but also the late-stage functionalization of complex bioactive molecules and natural products, including ones with multiple benzylic sites.

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Fig. 1: Asymmetric functionalization of benzylic C(sp3)–H bonds.
Fig. 2: Mechanistic design and reaction development.
Fig. 3: Functional-group tolerance of the photoelectrocatalytic reaction and late-stage functionalization.
Fig. 4: Substrate scope of the alkylarene and product transformations.
Fig. 5: Mechanistic studies.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information, or from the authors on reasonable request. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre under deposition number CCDC 2093942 (9). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We acknowledge the financial support of this research by the National Natural Science Foundation of China, nos 22121001 (H.-C.X.), 21971213 (H.-C.X.), 22225101 (H.-C.X.) and 22173083 (J.S.), and the Fundamental Research Funds for the Central Universities. J.S. thanks the Henan Province Supercomputing Centre.

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  1. State Key Laboratory of Physical Chemistry of Solid Surfaces and College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China

    Chen-Yan Cai, Xiao-Li Lai, Yu Wang, Hui-Hui Hu, Ye Yang, Cheng Wang & Hai-Chao Xu

  2. Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, China

    Jinshuai Song

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Contributions

C.-Y.C. and X.-L.L contributed equally. C.-Y.C., X.-L.L. and H.-C.X. conceived the project. C.-Y.C. and X.-L.L. performed the experiments and analysed the data. Y.W., H.-H.H., C.W., Y.Y. and J.S. contributed to the mechanistic studies. H.-C.X. directed the project and wrote the manuscript.

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Correspondence to Hai-Chao Xu.

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Supplementary Figs. 1–16, Tables 1–5 and Methods.

Supplementary Data 1

The .cif file for crystallographic data (compound 9).

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The .fcf file for structure factors of crystallographic data (compound 9).

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Cai, CY., Lai, XL., Wang, Y. et al. Photoelectrochemical asymmetric catalysis enables site- and enantioselective cyanation of benzylic C–H bonds. Nat Catal 5, 943–951 (2022). https://doi.org/10.1038/s41929-022-00855-7

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