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Cobalt-catalysed enantioselective C(sp3)–C(sp3) coupling

Nature Catalysis volume 4, pages 901–911 (2021)Cite this article

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Abstract

Enantioselective C(sp3)–C(sp3) coupling substantially impacts organic synthesis but remains challenging. Cobalt has played an important role in the development of homogeneous organometallic catalysis, but there are few examples of its use in asymmetric cross-coupling. Here we report a cobalt-catalysed enantioselective C(sp3)–C(sp3) coupling reaction, namely, alkene hydroalkylation, to access chiral fluoroalkanes. This reaction represents a catalyst-controlled enantioselective coupling mode in which a tailor-made auxiliary is unnecessary; via this reaction, an aliphatic C–F stereogenic centre can be introduced at the desired position in an alkyl chain.

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Fig. 1: Transition-metal-hydride-catalysed enantioselective C(sp3)–C(sp3) coupling and our strategy.
Fig. 2: Scope of alkyl halides in hydroalkylation.
Fig. 3: Scope of monofluoroalkenes in hydroalkylation.
Fig. 4: Preliminary mechanism studies.
Fig. 5: DFT calculations and proposed mechanism.
Fig. 6: Defluorinative hydroalkylation.

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Data availability

Data supporting the findings of this study are available within the article and Supplementary Information files. The experimental procedures, characterization of the compounds and DFT calculations are available in the Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2055682 (4aa), 2088231 (4fa), and 2088232 (4la). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data are available from the authors upon reasonable request.

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Acknowledgements

Financial support from the National Natural Science Foundation of China (grant numbers 21732006, 51821006 and 51961135104 for Y.F. and grant number 21927814 for X.L.) and the USTC Research Funds of the Double First-Class Initiative (grant number YD3530002002 for X.L.) is acknowledged. We thank L. Yu (HMFL) and C.L. Tian (USTC) for helpful discussions.

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Author notes

  1. These authors contributed equally: Y. Li, W. Nie, Z. Chang, J.-W. Wang.

Authors and Affiliations

  1. Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, Hefei, China

    Yan Li, Wan Nie, Zhe Chang, Jia-Wang Wang, Xi Lu & Yao Fu

  2. Institute of Energy, Hefei Comprehensive National Science Center, Hefei, China

    Yao Fu

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  1. Yan Li
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Contributions

X.L. and Y.F. directed the project and wrote the manuscript with input from all other authors. Y.F. directed and W.N. performed the DFT calculations. Under the guidance of X.L., Y.L. developed the methods, and Y.L. and J.-W.W. designed and performed the synthetic and mechanistic experiments with the help of Z.C. All the authors participated in the discussion and preparation of the manuscript.

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Correspondence to Xi Lu or Yao Fu.

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The authors declare no competing interests.

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Peer review information Nature Catalysis thanks Corinne Gosmini and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods, Figs. 1–37, Tables 1–8, discussion and references.

Supplementary Data 1

Crystallographic data of compound 4aa.

Supplementary Data 2

Crystallographic data of compound 4fa.

Supplementary Data 3

Crystallographic data of compound 4la.

Supplementary Data 4

DFT coordinates for optimized structures.

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Li, Y., Nie, W., Chang, Z. et al. Cobalt-catalysed enantioselective C(sp3)–C(sp3) coupling. Nat Catal 4, 901–911 (2021). https://doi.org/10.1038/s41929-021-00688-w

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