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Catalytic acyloin-type heterocoupling of thioesters via a putative cobalt siloxycarbene

Nature Chemistry (2026)Cite this article

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Abstract

α-Oxy-metallocarbenes exemplify Fischer carbenes and find use in the synthesis of diverse materials. Most, however, arise from the addition of reactive organometallics to toxic metal carbonyls. Here we report a method to access α-siloxycarbenes from thioesters via the reductive silylation of cobalt acyls. The reaction results in carbonyl dimerization with high hetero- and stereo-selectivity to yield unsymmetrical tetrasubstituted disiloxyalkenes, while avoiding competitive decarbonylation. These products can be further elaborated to new functionalized fragments, heterocycles and challenging enolsilanes. Several different reactivity patterns combined with mechanistic interrogation converge on α-oxycarbenes as fleeting catalytic intermediates, indicating a way to generate and exploit these reactive species under mild conditions. This method provides a general platform to harness carbene reactivity from carboxylates via metal acyls and enables a range of diverse reactivities.

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Fig. 1: Background.
Fig. 2: Optimization and trends for thioester homo- and hetero-dimerization.
Fig. 3: Mechanistic studies and hypothesis.
Fig. 4: Substrate scope.
Fig. 5: Product derivatization and other applications of a cobalt complex in XEC.

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Data availability

Crystallographic data for compound 2d are available from the Cambridge Crystallographic Data Center under reference number CCDC 2448630. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures. All other data to support the conclusions are available in the main text or Supplementary Information, including experimental procedures, copies of NMR spectra and X-ray structure reports.

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Acknowledgements

Financial support from the National Science Foundation (NSF CAT CHE 2400341) is gratefully acknowledged. We thank Q. N. Wong, J. Lee and B. Orzolek for analysis and glovebox provision, L. Pasternack and G. J. Kroon for assistance with NMR spectroscopy and M. Gembicky, S. Yang, J. Bailey and the entire UCSD Crystallography Facility for X-ray crystallographic analysis. We thank M. A. Smith and J. J. Rojas for manuscript review and D. G. Blackmond for helpful mechanistic discussions.

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Author notes

  1. These authors contributed equally: Lingran Kong, Kevin Zong.

Authors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA

    Lingran Kong, Kevin Zong, Jiaxu Guo & Ryan Shenvi

  2. Skaggs Graduate School of Chemical and Biological Sciences, La Jolla, CA, USA

    Kevin Zong

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Contributions

L.K., K.Z. and R.S. conceived the concept. L.K., K.Z. and J.G. designed, conducted and analysed the experiments. L.K., K.Z. and R.S. wrote the paper, L.K. and K.Z. compiled the Supplementary Information and R.S. provided editorial feedback and oversight.

Corresponding author

Correspondence to Ryan Shenvi.

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Supplementary Figs. 1–30, procedures, discussion, references, X-ray crystallography data and NMR spectra.

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Kong, L., Zong, K., Guo, J. et al. Catalytic acyloin-type heterocoupling of thioesters via a putative cobalt siloxycarbene. Nat. Chem. (2026). https://doi.org/10.1038/s41557-025-02036-y

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