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Development of a practical non-noble metal catalyst for hydrogenation of N-heteroarenes

Nature Catalysis volume 3, pages 135–142 (2020)Cite this article

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Abstract

Due to their availability, price and biological relevance, the use of catalysts based on 3d transition metals is of substantial importance for the synthesis of industrial chemicals, but also for organic synthesis in general. Hence in recent years, especially in homogeneous catalysis, the use of such Earth-abundant, biocompatible metals has become a major area of interest. However, to achieve reactivity comparable to that of noble-metal catalysts, generally sophisticated ligands—typically expensive phosphorus derivatives—have to be used. Here, we report the chemoselective reduction of quinolines and related N-heterocycles by molecular hydrogen, using a simple Mn(i) complex [Mn(CO)5Br]. Under very mild reaction conditions this catalytic system is able to reduce a wide range of quinolines, affording high yields of the corresponding tetrahydroquinolines, a scaffold present in many bioactive compounds, including marketed pharmaceuticals. Mechanistic studies reveal the formation of the active catalyst and also show the important role of a concomitantly formed Mn(ii) species and HBr for the hydrogenation of the heterocyclic substrates.

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Fig. 1: Mn complexes.
Fig. 2: Development of quinoline hydrogenation catalysts.
Fig. 3: Screening of catalysts for the hydrogenation of quinoline 1a.
Fig. 4: Scope of substrates.
Fig. 5: Chemoselective hydrogenation of quinolines and other N-heterocycle hydrogenations.
Fig. 6: Mechanistic investigations.
Fig. 7: Proposed mechanism.

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Data availability

CCDC 1922866 (Mn-2), 1922867 (Mn-3), 1941549 (Mn-4) and 1941550 (2u) (Supplementary Fig. 1) 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

We thank the analytical department (LIKAT) for their support, and the State of Mecklenburg–Western Pomerania and the Federal State of Germany (BMBF) for financial support. V.P. thanks the Ermenegildo Zegna Founder’s Scholarship for financial support and F. Balzamo for the graphical abstract. We also thank J. Rabeah (LIKAT) and R. Grauke (LIKAT) for the electron paramagnetic resonance spectra reported in the Supporting Information, W. Baumann for the variable temperature NMR spectra measured under in situ hydrogen flow, D. Formenti for the fruitful discussion and D. K. Leonard (LIKAT) for the assistance in manuscript preparation.

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Authors and Affiliations

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

    Veronica Papa, Yixuan Cao, Anke Spannenberg, Kathrin Junge & Matthias Beller

  2. Université de Rennes 1, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France

    Yixuan Cao

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Contributions

M.B. and V.P. conceived and designed the experiments. V.P. and Y.C. 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 V.P. co-wrote the paper.

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Correspondence to Matthias Beller.

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Supplementary information

Supplementary information

Supplementary methods, Tables 1–2, Figures 1–8, references

Compound Mn-2

Crystallographic data for compound Mn-2

Compound Mn-3

Crystallographic data for compound Mn-3

Compound Mn-4

Crystallographic data for compound Mn-4

Compound 2u

Crystallographic data for compound 2u

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Papa, V., Cao, Y., Spannenberg, A. et al. Development of a practical non-noble metal catalyst for hydrogenation of N-heteroarenes. Nat Catal 3, 135–142 (2020). https://doi.org/10.1038/s41929-019-0404-6

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