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Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution

Abstract

Dynamic kinetic resolutions (DKRs) allow for the conversion of both enantiomers of starting material into a single enantiomer of product, hence avoiding the 50% yield limit observed in traditional kinetic resolutions. Transition-metal-catalysed variants have become an important and useful method in asymmetric synthesis. Here we report an asymmetric hydrogenation of allylic alcohols using an Ir–N,P-ligand complex via DKR. In contrast to the many DKRs involving carbonyl reduction, this methodology allows for DKR during alkene reduction. Mechanistic studies support the hypothesis that racemization of the substrate is achieved by cleavage and reforming of the oxygen–carbon bond. Under the cooperative dynamic kinetic asymmetric hydrogenation, a broad range of chiral alcohols containing two stereogenic centres were produced with excellent diastereoselectivities (up to 95:5) and enantioselectivities (up to 99%).

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Fig. 1: DKR using catalysts and enzymes.
Fig. 2

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Acknowledgements

The Swedish Research Council (VR) and Stiftelsen Olle Engkvist Byggmästare supported this work. J.L. thanks the Guangzhou Elite Scholarship Council for the PhD fellowship and Thishana Singh, School of Chemistry and Physics, University of Kwazulu-Natal, South Africa for proofreading and editing the manuscript.

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P.G.A. conceived and designed the experiments. J.L., S.K., J.Y. and J.-Q.L. performed experiments and prepared the Supplementary Information. P.G.A. and J.L. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Pher G. Andersson.

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Supplementary Methods, Supplementary Figures 1–60, Supplementary References

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Liu, J., Krajangsri, S., Yang, J. et al. Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution. Nat Catal 1, 438–443 (2018). https://doi.org/10.1038/s41929-018-0070-0

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