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C–C bond activation enabled by dyotropic rearrangement of Pd(iv) species

Nature Chemistry volume 13, pages 671–676 (2021)Cite this article

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Abstract

The weak carbon–metal bond combined with the kinetic inertness of the carbon–carbon bond renders metal-catalysed C–C bond activation to be highly challenging. Most of the reported C–C bond activation methodologies involve strain-releasing cleavage of small rings to compensate for unfavourable kinetic and thermodynamic penalties associated with C–C bond cleavage. Here we report that the 1,2-positional interchange of vicinal C–C and C–Pd(iv) bonds (dyotropic rearrangement) can be realized in a stereospecific manner under mild conditions, giving access to quaternary carbon–palladium bonds. An enantioselective synthesis of medicinally relevant fluorinated cyclopentanes, featuring this rearrangement as a key step, has been developed. We anticipate that implementing a Pd-based dyotropic rearrangement in reaction design could provide a new tool in the development of Pd-catalysed transformations.

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Fig. 1: Dyotropic rearrangement involving metals.
Fig. 2: Side products and mechanistic implication.
Fig. 3: Structure characterization of key reaction intermediates.

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Data availability

Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 1979593 (2a), CCDC 1978762 (2d), CCDC 1978761 (6s), CCDC 2024253 (7b). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. The data supporting the findings of this study are available within the article and its Supplementary Information files.

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Acknowledgements

We thank F.-T. Farzaneh and R. Scopelliti for the X-ray structural analysis of compounds 2a, 2d, 6s and 7b. Financial support from EPFL (Switzerland) and the Swiss National Science Foundation (SNSF 200021-178816/1) is gratefully acknowledged. J.C. thanks the China Scholarship Council for a Visiting Scholar Fellowship.

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Author notes

  1. These authors contributed equally: Jian Cao, Hua Wu.

Authors and Affiliations

  1. Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Jian Cao, Hua Wu, Qian Wang & Jieping Zhu

  2. Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou, P. R. China

    Jian Cao

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Contributions

J.C., H.W., Q.W. and J.Z. conceived the work, designed the experiments and analysed the data. J.C. and H.W. optimized the reaction conditions and performed the experiments. J.C., H.W., Q.W. and J.Z. co-wrote the paper.

Corresponding author

Correspondence to Jieping Zhu.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Chemistry thanks the anonymous reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

General information, Supplementary Tables S1–S3, Figs. S1 and S2, synthesis and characterization data, procedural details, X-ray crystallographic data, references, NMR spectra, supercritical fluid chromatography chromatograms.

Supplementary Data 1

Crystallographic data for compound 2a. CCDC reference 1979593.

Supplementary Data 2

Crystallographic data for compound 2d. CCDC reference 1978762.

Supplementary Data 3

Crystallographic data for compound 6s. CCDC reference 1978761.

Supplementary Data 4

Crystallographic data for compound 7b. CCDC reference 2024253.

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Cao, J., Wu, H., Wang, Q. et al. C–C bond activation enabled by dyotropic rearrangement of Pd(iv) species. Nat. Chem. 13, 671–676 (2021). https://doi.org/10.1038/s41557-021-00698-y

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