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Photoinduced nickel-catalysed enantioconvergent sp3–sp3 coupling of unactivated olefins and aziridines

Nature Catalysis volume 8, pages 348–356 (2025)Cite this article

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Abstract

Catalytic sp3–sp3 bond-forming reactions have been the subject of considerable interest in both academic and pharmaceutical laboratories. This is largely due to the observation that a higher content of sp3-hybridized carbons has recently been shown to improve several molecular attributes that contribute to clinical success. Although the ready availability of unactivated olefins and aziridines makes them ideal precursors to forge enantioenriched sp3–sp3 architectures with added-value amine functions, an enantioconvergent catalytic scenario of these counterparts has not yet been realized. Here we describe a nickel-catalysed blueprint that enables the enantioselective construction of amine-containing sp3–sp3 architectures via photoinduced enantioconvergent coupling of racemic aziridines with alkylzirconium reagents generated in situ from unactivated terminal and even internal olefins. The broad applicability of this protocol is illustrated in a series of late-stage diversification of advanced synthetic intermediates.

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Fig. 1: Metal-catalysed enantioselective sp3–sp3 cross-coupling reactions.
Fig. 2: Optimization of the reaction conditions.
Fig. 3: Photoinduced enantioconvergent sp3–sp3 coupling of unactivated olefins with aziridines.
Fig. 4: Late-stage functionalization and synthetic applications.
Fig. 5: Control experiments.

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Data availability

Experimental procedures and characterization data for the synthesized compounds are included in the Supplementary Information. Crystallographic data are available from the Cambridge Crystallographic Data Centre with the following codes: 3w (CCDC 2360556) and 3ah (CCDC 2360555). Other data are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank ICIQ and FEDER/MCI PID2021-123801NB-I00 and MCI/AIE (Secero Ochoa Excellence Accreditation 2002-2023 CEX2019-000925-S) for financial support. L.Z. thanks the Deutsche Forschungsgemeinschaft (DFG) for a postdoctoral fellowship and H.W. and W.-J.Y. thank the China Scholarship Council (CSC) for a predoctoral fellowship. We also thank the ICIQ X-ray diffraction, NMR and mass spectrometry units.

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Authors and Affiliations

  1. Institute of Chemical Research of Catalonia, The Barcelona Institute of Science and Technology, Tarragona, Spain

    Liangliang Zhang, Hao Wang, Tomás G. Santiago, Wen-Jun Yue & Ruben Martin

  2. Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, Tarragona, Spain

    Hao Wang, Wen-Jun Yue & Ruben Martin

  3. ICREA, Barcelona, Spain

    Ruben Martin

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  1. Liangliang Zhang
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Contributions

L.Z. and R.M. conceived the project. L.Z. designed and performed experiments and analysed the data unless otherwise stated. R.M. supervised the project. H.W. performed parts of the late-stage functionalization experiments. T.G.S. performed a series of mechanistic experiments. W.-J.Y. performed parts of the synthetic application experiments. H.W., T.G.S. and W.-J.Y. contributed equally. L.Z. and R.M. wrote the paper. All authors participated in the discussion and preparation of the paper.

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Correspondence to Ruben Martin.

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Nature Catalysis thanks Haohua Huo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Figs. 1–13, discussion and Tables 1–17.

Supplementary Tables 1–17

Supplementary Tables 1–17.

Supplementary Data 1

Crystallographic Information File (CIF) of compound 3w.

Supplementary Data 2

Crystallographic Information File (CIF) of compound 3ah.

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Zhang, L., Wang, H., Santiago, T.G. et al. Photoinduced nickel-catalysed enantioconvergent sp3–sp3 coupling of unactivated olefins and aziridines. Nat Catal 8, 348–356 (2025). https://doi.org/10.1038/s41929-025-01319-4

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