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Catalytic enantioselective tandem B–H insertion and [3,3]-sigmatropic rearrangement

Nature Synthesis (2026) Cite this article

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Abstract

[3,3]-Sigmatropic rearrangements are powerful transformations in synthetic chemistry, enabling atom-economical construction of complex architectures through stereospecific molecular skeleton reorganization. Despite their widespread utility, achieving asymmetric catalysis of [3,3]-sigmatropic rearrangements remains a substantial challenge due to the difficulty in controlling the stereochemistry and the limited availability of catalytic systems compatible with diverse substrates. Here we report a catalytic enantioselective boron-incorporating [3,3]-sigmatropic rearrangement enabling the synthesis of δ-amino acid derivatives with two adjacent stereocentres (up to 99% enantiomeric excess). This strategy combines transition-metal-catalysed carbene B–H insertion with [3,3]-sigmatropic rearrangement into a one-pot cascade sequence through a borane-traceless design.

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Fig. 1: Representative [3,3]-sigmatropic rearrangements and new reaction proposal.
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Fig. 2: Substrate scope of imine-boranes.
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Fig. 3: Substrate scope of vinyldiazoacetates.
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Fig. 4: Extension of the reaction concept.
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Fig. 5: Synthetic applications.
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Fig. 6: Mechanistic investigations.
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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information. The X-ray crystallographic coordinates for structure 45 reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number 2382269. These data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.

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Acknowledgements

We acknowledge the financial support from the National Natural Science Foundation of China (grant nos. 22571141, 21971103 to M.-H.X., 22101119 to W.X.), Guangdong Science and Technology Department (grant no. 2019CX01Y251 to M.-H.X.), Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis (grant no. ZDSYS20190902093215877 to M.-H.X.) and Guangdong Provincial Key Laboratory of Catalysis (grant no. 2020B121201002 to M.-H.X.).

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Authors and Affiliations

  1. Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, PR China

    Weici Xu  (许维词), Peilin Tian  (田沛霖), Liangfu Li  (李良富) & Ming-Hua Xu  (徐明华)

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  1. Weici Xu  (许维词)
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  2. Peilin Tian  (田沛霖)
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Contributions

W.X. conceived of the project, conducted most of the experiments (including designing, optimizing and studying the scope and mechanism of the synthetic method) and wrote the initial draft. P.T. participated in preparing diazo substrates and the substrate scope study. L.L. participated in preparing diazo and imine-borane substrates. M.-H.X. conceived of and supervised the project, and wrote the final paper.

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Correspondence to Ming-Hua Xu  (徐明华).

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Nature Synthesis thanks Xiaoming Feng, Armen Zakarian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information (download PDF )

Experimental details, Sections 1–11 and Figs. 1–8.

Supplementary Data 1

X-ray crystallographic data for compound 45, CCDC 2382269.

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Xu, W., Tian, P., Li, L. et al. Catalytic enantioselective tandem B–H insertion and [3,3]-sigmatropic rearrangement. Nat. Synth (2026). https://doi.org/10.1038/s44160-026-01064-x

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