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Enantioselective hydrogenation of dialkyl ketones

Nature Catalysis volume 3, pages 621–627 (2020)Cite this article

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An Author Correction to this article was published on 04 August 2020

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Abstract

Chiral catalyst development is a key to asymmetric catalysis research. The enantioselectivity of a chiral catalyst relies on its ability to distinguish the prochiral centres or faces of substrates, which is difficult when the two groups attached to the centre or face are spatially and electronically similar. For example, dialkyl ketones are difficult to reduce enantioselectively. Here we report a protocol for the highly enantioselective hydrogenation of dialkyl ketones catalysed by a rationally designed chiral spiro iridium complex. The tridentate spiro structure and the bulky phosphino groups of the chiral ligand imparted a remarkable stability and enantioselectivity to the catalyst. The protocol is highly efficient for generating chiral aliphatic alcohols, and has potential for a wide application in pharmaceuticals and fine chemicals.

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Fig. 1: Catalytic asymmetric hydrogenation of dialkylketones.
Fig. 2: Preparations of SpiroPNP ligands and Ir–SpiroPNP catalyst.
Fig. 3: Asymmetric hydrogenation of dialkylketones catalysed by (R)-Cat1.
Fig. 4: Asymmetric hydrogenation of aliphatic cyclic ketones catalysed by (R)-Cat1.
Fig. 5: DFT calculations.

Data availability

Data relating to the materials and methods, optimization studies, experimental procedures, DFT calculations, HPLC spectra, GC spectra and NMR spectra are available in the Supplementary Information. Crystallographic data for catalyst (R)-Cat1 is available free of charge from the CCDC under reference number 1913872. All other data are available from the authors upon reasonable request.

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Acknowledgements

We thank the National Natural Science Foundation of China (nos 21790332, 21532003 and 9195600) and the ‘111’ project (B06005) of the Ministry of Education of China for financial support. We thank H. Song of the State Key Laboratory of Elemento-Organic Chemistry for the measurement and analysis of the single-crystal structure of (R)-Cat1.

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Authors and Affiliations

  1. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China

    Feng-Hua Zhang, Fa-Jian Zhang, Mao-Lin Li, Jian-Hua Xie & Qi-Lin Zhou

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Contributions

Q.-L.Z. conceived this work; F.-H.Z., J.-H.X. and Q.-L.Z. designed the experiments and analysed the data; F.-H.Z., F.-J.Z. and M.-L.L. conducted the experiments; F.-H.Z. and Q.-L.Z. wrote the manuscript.

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Correspondence to Qi-Lin Zhou.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1 and 2, Tables 1–4 and references.

Supplementary Data 1

The Cartesian coordinates (Å) for the transition state in DFT calculations.

Supplementary Data 2

Crystallographic data for Cat1.

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Zhang, FH., Zhang, FJ., Li, ML. et al. Enantioselective hydrogenation of dialkyl ketones. Nat Catal 3, 621–627 (2020). https://doi.org/10.1038/s41929-020-0474-5

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