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Electrophotocatalytic oxygenation of multiple adjacent C–H bonds

Nature volume 614, pages 275–280 (2023)Cite this article

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Abstract

Oxygen-containing functional groups are nearly ubiquitous in complex small molecules. The installation of multiple C–O bonds by the concurrent oxygenation of contiguous C–H bonds in a selective fashion would be highly desirable but has largely been the purview of biosynthesis. Multiple, concurrent C–H bond oxygenation reactions by synthetic means presents a challenge1,2,3,4,5,6, particularly because of the risk of overoxidation. Here we report the selective oxygenation of two or three contiguous C–H bonds by dehydrogenation and oxygenation, enabling the conversion of simple alkylarenes or trifluoroacetamides to their corresponding di- or triacetoxylates. The method achieves such transformations by the repeated operation of a potent oxidative catalyst, but under conditions that are sufficiently selective to avoid destructive overoxidation. These reactions are achieved using electrophotocatalysis7, a process that harnesses the energy of both light and electricity to promote chemical reactions. Notably, the judicious choice of acid allows for the selective synthesis of either di- or trioxygenated products.

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Fig. 1: Oxygenation of multiple C–H bonds.
Fig. 2: Substrate scope of electrophotocatalytic vicinal C–H dioxygenation.
Fig. 3: Electrophotocatalytic vicinal C–H trioxygenation.
Fig. 4: Vicinal C–H di- and trioxygenation of trifluoroacetamides and synthetic applications of electrophotocatalytic multiple adjacent C–H oxygenations.

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The data supporting the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

Funding for this work was provided by the National Institutes of Health (no. R35GM127135 to T.H.L.) and the National Natural Science Foundation of China (no. 22171046 to K.-Y.Y.). We thank X.-X. Li, X. He, Y. Yu and Z. Shi from Fuzhou University for their help with X-ray single-crystal analysis. We also thank S. Liao and Q. Song from Fuzhou University for their help with gas chromatography–mass spectrometry analysis. We thank I. Keresztes (Cornell University), J. Cheng and C. Xu (both from Fuzhou University) for their help with two-dimensional nuclear magnetic resonance analysis.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA

    Tao Shen & Tristan H. Lambert

  2. Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Tao Shen

  3. Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou, Fujian, China

    Tao Shen, Yi-Lun Li & Ke-Yin Ye

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Contributions

T.H.L. conceived of and directed the project and prepared the manuscript. T.H.L., T.S. and K.-Y.Y. designed experiments. T.S. and Y.-L.L. performed experiments. Y.-L.L. synthesized key substrates. T.S. performed all reactions and collected and analysed data.

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Correspondence to Ke-Yin Ye or Tristan H. Lambert.

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Supplementary Information

Analytical methods, experimental tips, mechanistic data, challenging substrates, compound characterization, nuclear magnetic resonance spectra and X-ray data analysis.

cif File for product 84 X-ray.

cif File for product 79 X-ray.

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Shen, T., Li, YL., Ye, KY. et al. Electrophotocatalytic oxygenation of multiple adjacent C–H bonds. Nature 614, 275–280 (2023). https://doi.org/10.1038/s41586-022-05608-x

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