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Exploiting attractive non-covalent interactions for the enantioselective catalysis of reactions involving radical intermediates

Nature Chemistry volume 12, pages 990–1004 (2020)Cite this article

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A Publisher Correction to this article was published on 18 November 2020

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Abstract

The past decade has seen unprecedented growth in the development of new chemical methods that proceed by mechanisms involving radical intermediates. This new attention has served to highlight a long-standing challenge in the field of radical chemistry — that of controlling absolute stereochemistry. This Review will examine developments using a strategy that offers enormous potential, in which attractive non-covalent interactions between a chiral catalyst and the substrate are leveraged to exert enantiocontrol. In a simplistic sense, such an approach mimics the modes of activation and control in enzyme catalysis and the realization that this can be achieved in the context of small-molecule catalysts has had sizable impact on the field of asymmetric catalysis in recent years. This strategy is now starting to quickly gather pace as a powerful approach for control of enantioselectivity in radical reactions and we hope that this focused survey of progress so far will inspire future developments in the area.

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Fig. 1: A selection of enantioselective radical reactions to date, enabled by primarily covalent modes of catalysis.
Fig. 2: Summary of commonly used modes in non-covalent enantioselective catalysis.
Fig. 3: Design approach and selected applications of chiral hydrogen bonding templates and photosensitizers.
Fig. 4: Cationic hydrogen bond donors in asymmetric photoredox-mediated processes.
Fig. 5: Chiral phosphoric acids as enantioselective catalysts in radical-based reactions.
Fig. 6: Recent advances in asymmetric radical processes using chiral phosphate catalysts.
Fig. 7: Non-covalent interactions in asymmetric radical-based organometallic reactions.
Fig. 8: Examples demonstrating the use of biocatalysis to control enantioselectivity in non-natural radical reactions.

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Change history

  • 18 November 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

R.S.J.P. is grateful to GlaxoSmithKline and the EPSRC for a CASE PhD studentship. We are grateful to the Leverhulme Trust for a research grant (RPG-2018-081), which provided funding for A.C.C. R.J.P. is grateful to the Royal Society for a University Research Fellowship and the ERC for a starting grant (StG 757381, NonCovRegioSiteCat).

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  1. Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

    Rupert S. J. Proctor, Avene C. Colgan & Robert J. Phipps

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R.S.J.P and R.J.P. conceived and planned the article and R.S.J.P., A.C.C. and R.J.P. wrote the manuscript.

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Proctor, R.S.J., Colgan, A.C. & Phipps, R.J. Exploiting attractive non-covalent interactions for the enantioselective catalysis of reactions involving radical intermediates. Nat. Chem. 12, 990–1004 (2020). https://doi.org/10.1038/s41557-020-00561-6

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