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Iron-catalysed regioselective hydrogenation of terminal epoxides to alcohols under mild conditions

Nature Catalysis volume 2, pages 523–528 (2019)Cite this article

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Abstract

The reduction of epoxides has been recognized as an important method for the synthesis of alcohols using stoichiometric amounts of metal hydride reducing agents. However, homogeneous catalysis-enabled hydrogenation processes with molecular hydrogen remain scarce. Here, we present a general methodology for the synthesis of primary alcohols in high yields, selectively and under mild conditions, from aliphatic and aromatic epoxides. Crucial for the hydrogenation of terminal epoxides is the presence of an Fe(BF4)2.6H2O/tetraphos catalyst system. Compared to existing methods, which make use of noble metals, the presented protocol shows broad substrate scope and good functional group tolerance. The generality of this is showcased by transformation of various natural products, including steroids, terpenoids, sesquiterpenoids and drug derivatives, which give the desired alcohols in moderate to excellent yields. Mechanistic studies confirm the distinct feature of the catalyst system, which is active for Meinwald rearrangement of epoxides as well as for carbonyl hydrogenations.

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Fig. 1: Synthesis of primary alcohols from olefins.
Fig. 2: Hydrogenation of terminal epoxides to alcohols.
Fig. 3: Iron-catalysed hydrogenation of terminal epoxides.
Fig. 4: Iron-catalysed hydrogenation of epoxides derived from natural products and drug derivatives.
Fig. 5: Mechanistic findings.
Fig. 6: Mechanistic studies.

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Data availability

CCDC 1895726 (S7), 1895727 (S9), 1895728 (S10), 1895729 (9a) and 1895730 (10′) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Further data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the analytic department (LIKAT) for their support, and the State of Mecklenburg-Western Pomerania, the Federal State of Germany (BMBF) and the EU (grant 670986) for financial support. The authors also thank W. Baumann (LIKAT) for helpful discussions regarding NMR analyses and D. Leonard (LIKAT) for assistance with manuscript preparation.

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Authors and Affiliations

  1. Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Rostock, Germany

    Weiping Liu, Wu Li, Anke Spannenberg & Matthias Beller

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  4. Kathrin Junge
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Contributions

M.B. and W. Liu. conceived and designed the experiments. W. Liu and W. Li performed the experiments and analysed the data. A.S. performed X-ray crystal structure analyses. K.J. participated in the discussions and supported the project. M.B. and W. Liu co-wrote the paper.

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Correspondence to Matthias Beller.

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Supplementary information

Supplementary Information

Supplementary methods, Supplementary Tables 1-6, Supplementary references

compound S7

Crystallographic Data for compound S7

compound S9

Crystallographic Data for compound S9

compound S10

Crystallographic Data for compound S10

compound 9a

Crystallographic Data for compound 9a

compound 10’

Crystallographic Data for compound 10’

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Liu, W., Li, W., Spannenberg, A. et al. Iron-catalysed regioselective hydrogenation of terminal epoxides to alcohols under mild conditions. Nat Catal 2, 523–528 (2019). https://doi.org/10.1038/s41929-019-0286-7

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