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  • Review Article
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Quinone methides and indole imine methides as intermediates in enantioselective catalysis

Nature Synthesis volume 1, pages 426–438 (2022)Cite this article

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Abstract

As a consequence of their propensity towards aromatization, quinone methides (QMs) and indole imine methides (IIMs) are versatile intermediates in organic synthesis. Although QMs and IIMs have been known for many decades, their application in catalytic asymmetric synthesis, and particularly in organocatalysis, has been achieved only recently. Catalysts for the asymmetric transformations of QMs and IIMs include chiral Brønsted acids, Lewis acids and bases, as well as transition metal complexes. Although the sole activation of either the electrophile or the nucleophile is a viable approach for asymmetric control, dual activation of both reaction partners, particularly by a bifunctional catalyst, has proved to be highly effective in these reactions. In this Review, we discuss advances in this field with a focus on reaction pathways and activation modes, aiming to promote a systematic understanding of the chemistry of QMs and IIMs in asymmetric synthesis.

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Fig. 1: Resonance forms of representative QMs and IIMs and topological isomers and analogues of these structures.
Fig. 2: Asymmetric reactions of o-QMs involving transition metal and Lewis acid activation.
Fig. 3: Activation of o-QMs by Brønsted acids.
Fig. 4: Enantioselective reactions of o-QMs involving Lewis or Brønsted base activation.
Fig. 5: Asymmetric addition to p-QMs by means of nucleophile activation.
Fig. 6: Asymmetric transformations through primary activation of p-QMs.
Fig. 7: Asymmetric additions and annulations of IIMs.

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Acknowledgements

Financial support was provided by the National Natural Science Foundation of China (91956114 and 22071210), the Research Grants Council of Hong Kong (16303420 and 16309321) and the Innovation and Technology Commission (ITC-CNERC14SC01).

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Authors and Affiliations

  1. Department of Chemistry and the Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR, China

    Xingguang Li, Zhiyang Li & Jianwei Sun

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  1. Xingguang Li
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X.L., Z.L. and J.S. wrote the manuscript.

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Correspondence to Jianwei Sun.

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Li, X., Li, Z. & Sun, J. Quinone methides and indole imine methides as intermediates in enantioselective catalysis. Nat. Synth 1, 426–438 (2022). https://doi.org/10.1038/s44160-022-00072-x

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