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Palladium-catalysed asymmetric anti-Michael-type addition of α,β-unsaturated carboxylic acids with carboranes

Nature Catalysis (2026)Cite this article

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Abstract

The catalytic asymmetric Michael addition of α,β-unsaturated carbonyl compounds is one of the most valuable methods for constructing the β-carbon chirality centre because of its atom economy and efficiency. However, the catalytic asymmetric reverse α-addition of a nucleophile to an α,β-unsaturated carbonyl compound is much less common. Here we realize a palladium-catalysed asymmetric α-carboranylation of α,β-unsaturated carboxylic acids via an inverse electron-demand nucleophilic addition. The reaction features good B(9)-site selectivity of o/m-carboranes, precise α-regioselectivity towards α,β-unsaturated carboxylic acids, wide functional group tolerance and excellent enantioselectivities. A detailed reaction mechanism is proposed based on experimental and computational results that elucidates the origin of the enantioselectivity and α-selectivity. This finding has a guiding significance for the catalytic asymmetric anti-Michael-type addition of α,β-unsaturated carbonyl compounds and provides a different avenue for synthesizing α-chiral carboxylic acids.

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Fig. 1: Applications of carboranes and catalytic asymmetric Michael and anti-Michael addition.
Fig. 2: Screening of ligands.
Fig. 3: Scope of α,β-unsaturated carboxylic acids.
Fig. 4: Scope of carboranes.
Fig. 5: Synthetic applications.
Fig. 6: Mechanistic studies.
Fig. 7: DFT calculations.
Fig. 8: Proposed mechanism.

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Data availability

Crystallographic data for compounds 1, 36, (S)-48, (R)-48, 66 and 72 have been deposited at the Cambridge Crystallographic Data Centre under deposition numbers CCDC 2380830-2380835. Additional optimization, experimental procedures, characterization of compounds and all other data supporting the findings are available in the Supplementary Information and from the corresponding author upon request.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (grant nos. 22271256 to Y.-N.M.; U23A2078 and 22171246 to X.C.; 22473100 to D.W.), Natural Science Foundation of Henan Province (grant nos. 232301420046 and 232300421088 to Y.-N.M.) and the Key Project of the Joint Fund for Science and Technology Research and Development in Henan Province (grant no. 232301420008 to D.W.).

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Author notes

  1. These authors contributed equally: Chao Lei, Wen Lu, Tingting Shen.

Authors and Affiliations

  1. College of Chemistry, Zhengzhou University, Zhengzhou, China

    Chao Lei, Wen Lu, Tingting Shen, Meng Huang, Yan-Xuan Wu, Donghui Wei, Yan-Na Ma & Xuenian Chen

  2. School of Chemistry and Chemical Engineering, Henan Key Laboratory of Boron Chemistry and Advanced Materials, Henan Normal University, Xinxiang, China

    Xuenian Chen

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Contributions

Y.-N.M. and X.C. conceived and designed the study. D.W. directed the DFT calculations and mechanism analysis. C.L. and W.L. conducted most experiments on the asymmetric reactions. T.S. conducted the DFT calculations. Y.-X.W. conducted the experiments on the synthesis of ligands. M.H. conducted the experiments on the synthesis of substrates. Y.-N.M. and X.C. prepared the manuscript. C.L. prepared the Supplementary Information.

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Correspondence to Donghui Wei, Yan-Na Ma or Xuenian Chen.

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Supplementary Information

Supplementary Figs. 1–49, Tables 1–19 and Spectra of NMR and HPLC.

Supplementary Data

CIF files of compounds 1, 36, (S)-48, 66, 72 and (R)-48.

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Lei, C., Lu, W., Shen, T. et al. Palladium-catalysed asymmetric anti-Michael-type addition of α,β-unsaturated carboxylic acids with carboranes. Nat Catal (2026). https://doi.org/10.1038/s41929-026-01480-4

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