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Formation of thioesters by dehydrogenative coupling of thiols and alcohols with H2 evolution

Nature Catalysis volume 3, pages 887–892 (2020)Cite this article

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Abstract

Thioesters play important roles in chemistry and biology, but their synthesis generally exhibits a poor atom economy and generates copious waste. We report here the dehydrogenative coupling of alcohols and thiols to yield thioesters and evolve H2. This waste-free reaction is catalysed by an acridine-based ruthenium pincer complex in hexamethyldisiloxane as the optimal solvent without any additives. Various thioesters were formed in good-to-excellent yields using equivalent amounts of alcohols and thiols in excellent selectivity with hydrogen gas as the only by-product. A plausible mechanism, which involves an outer-sphere dehydrogenation process in which the thiol not only serves as a reactant, but also as an assisting ligand, is proposed based on mechanistic studies and the isolation of intermediates. This system provides a facile, efficient and waste-free synthesis of thioesters.

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Fig. 1: Synthesis of thioesters.
Fig. 2: Mechanistic studies and control experiments.
Fig. 3: Proposed mechanism.

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Data availability

Synthetic procedures, NMR spectra and characterization data for all the new compounds and computational details are available within this article and its Supplementary Information. The X-ray crystallographic coordinates for structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition numbers CCDC 1971793 and 1981726. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. Any further relevant data are available from the authors upon reasonable request.

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Acknowledgements

This research was supported by the European Research Council (ERC AdG 692775). We thank S. Semenov for his help during the project. M.R. acknowledges the Zuckerman STEM Leadership Program for a research fellowship. D.M. is the Israel Matz Professorial Chair of Organic Chemistry.

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Authors and Affiliations

  1. Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel

    Jie Luo, Michael Rauch, Yehoshoa Ben-David & David Milstein

  2. Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel

    Liat Avram, Yael Diskin-Posner & Guy Shmul

Authors
  1. Jie Luo
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  5. Guy Shmul
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  6. Yehoshoa Ben-David
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  7. David Milstein
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Contributions

D.M. conceived and directed the project. J.L. and D.M. designed the experiments. J.L. performed and analysed the experiments. M.R. performed the computational studies. L.A., Y.D.-P. and G.S. provided helpful discussions towards NMR spectroscopy, X-ray structure determination and high-resolution mass spectrometry of the Ru complexes, respectively. Y.B.-D. prepared the ligands. J.L. and D.M. prepared the manuscript.

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Correspondence to David Milstein.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary Notes 1–4, Methods, Tables 1–4 and Figs. 1–64.

Supplementary Data 1

Crystallographic Data of compounds Ru-7 and Ru-8.

Supplementary Data 2

Computational Data (DFT Calculation Coordinates).

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Luo, J., Rauch, M., Avram, L. et al. Formation of thioesters by dehydrogenative coupling of thiols and alcohols with H2 evolution. Nat Catal 3, 887–892 (2020). https://doi.org/10.1038/s41929-020-00514-9

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