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Cu-catalysed enantioselective radical heteroatomic S–O cross-coupling

Nature Chemistry volume 15, pages 395–404 (2023)Cite this article

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Abstract

The transition-metal-catalysed cross-coupling reaction has established itself as one of the most reliable and practical synthetic tools for the efficient construction of carbon–carbon/heteroatom (p-block elements other than carbon) bonds in both racemic and enantioselective manners. In contrast, development of the corresponding heteroatom–heteroatom cross-couplings has so far remained elusive, probably due to the under-investigated and often challenging heteroatom–heteroatom reductive elimination. Here we demonstrate the use of single-electron reductive elimination as a strategy for developing enantioselective S–O coupling under Cu catalysis, based on both experimental and theoretical results. The reaction manifests its synthetic potential by the ready preparation of challenging chiral alcohols featuring congested stereocentres, the expedient valorization of the biomass-derived feedstock glycerol, and the remarkable catalytic 4,6-desymmetrization of inositol. These results demonstrate the potential of enantioselective radical heteroatomic cross-coupling as a general chiral heteroatom–heteroatom formation strategy.

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Fig. 1: Challenges and development of transition-metal-catalysed enantioselective heteroatom–heteroatom cross-coupling.
Fig. 2: Substrate scope and synthetic applications.
Fig. 3: Desymmetrization of polyols from natural resources.
Fig. 4: Experimental mechanistic studies.
Fig. 5: Computational studies.

Data availability

The data that support the findings of this study are available within the paper 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 2102449 (L*4), 2102446 (16), 2102451 (45), 2102448 (59), 2102450 (69) and 2102452 (72). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We appreciate the help of W. Jiang and his colleagues from SUSTech for enantiopurity characterization, and the assistance of SUSTech Core Research Facilities. Financial support from the National Key R&D Program of China (nos. 2021YFF0701604 and 2021YFF0701704, X.-Y.L.), the National Natural Science Foundation of China (nos. 22025103, 92256301, and 21831002, X.-Y.L.; 22001111, Y.-F.C.; 22001109 and 22271133, Q.-S.G.; 21873081 and 22122109, X.H.), the Guangdong Innovative Program (no. 2019BT02Y335, X.-Y.L.), Guangdong Provincial Key Laboratory of Catalysis (no. 2020B121201002, X.-Y.L.), Shenzhen Science and Technology Program (nos. KQTD20210811090112004, X.-Y.L. and Q.-S.G.; JCYJ20200109141001789, X.-Y.L.), the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study (no. SN-ZJU-SIAS-006, X.H.), Beijing National Laboratory for Molecular Sciences (no. BNLMS202102, X.H.), CAS Youth Interdisciplinary Team (no. JCTD-2021-11, X.H.), Fundamental Research Funds for the Central Universities (nos. 226-2022-00140 and 226-2022-00224, X.H.), the Center of Chemistry for Frontier Technologies and Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province (no. PSFM2021-01, X.H.) and the State Key Laboratory of Clean Energy Utilization (no. ZJUCEU2020007, X.H.) is gratefully acknowledged.

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Author notes

  1. These authors contributed equally: Yong-Feng Cheng, Zhang-Long Yu, Yu Tian, Ji-Ren Liu.

Authors and Affiliations

  1. Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, China

    Yong-Feng Cheng, Zhang-Long Yu, Yu Tian, Han-Tao Wen, Na-Chuan Jiang, Jun-Qian Bian, Dan-Tong Xu & Xin-Yuan Liu

  2. Center of Chemistry for Frontier Technologies, Department of Chemistry, State Key Laboratory of Clean Energy Utilization, Zhejiang University, Hangzhou, China

    Ji-Ren Liu, Guo-Xiong Xu & Xin Hong

  3. Beijing National Laboratory for Molecular Sciences, Beijing, China

    Ji-Ren Liu, Guo-Xiong Xu & Xin Hong

  4. Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, Hangzhou, China

    Ji-Ren Liu, Guo-Xiong Xu & Xin Hong

  5. Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China

    Zhong-Liang Li & Qiang-Shuai Gu

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Contributions

Y.-F.C., Z.-L.Y. and Y.T. designed the experiments and analysed the data. Y.-F.C., Z.-L.Y., Y.T., H.-T.W., N.-C.J., J.-Q.B., D.-T.X. and Z.-L.L. performed the experiments. X.H. designed the DFT calculations. J.-R.L. and G.-X.X. performed the DFT calculations. All authors participated in writing the manuscript. Q.-S.G. and X.-Y.L. conceived of and supervised the project.

Corresponding authors

Correspondence to Qiang-Shuai Gu, Xin Hong or Xin-Yuan Liu.

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The authors declare no competing interests.

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Peer review information

Nature Chemistry thanks Hye-Young Jang, Allan Watson and Yanying Zhao for their contribution to the peer review of this work.

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Supplementary Information

Supplementary Information

Supplementary Figs. 1–46, Tables 1–20, experimental procedures, synthetic procedures, characterization data, density functional theory (DFT) calculations and mechanistic discussion.

Supplementary Data 1

Crystallographic data for compound 16; CCDC reference 2102446.

Supplementary Data 2

Crystallographic data for compound 45; CCDC reference 2102451.

Supplementary Data 3

Crystallographic data for compound 59; CCDC reference 2102448.

Supplementary Data 4

Crystallographic data for compound 69; CCDC reference 2102450.

Supplementary Data 5

Crystallographic data for compound 72; CCDC reference 2102452.

Supplementary Data 6

Crystallographic data for compound L*4; CCDC reference 2102449.

Supplementary Data 7

Tables of energies and coordinates in XYZ format.

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Cheng, YF., Yu, ZL., Tian, Y. et al. Cu-catalysed enantioselective radical heteroatomic S–O cross-coupling. Nat. Chem. 15, 395–404 (2023). https://doi.org/10.1038/s41557-022-01102-z

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