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Organocatalytic nitrogen transfer to unactivated olefins via transient oxaziridines

Nature Catalysis volume 3, pages 386–392 (2020)Cite this article

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Abstract

Organocatalytic nitrogen transfer to C=C bonds provides straightforward access to aziridines under mild conditions with low financial and environmental impacts; however, previous methods were typically limited to conjugated C=C bonds (that is, activated olefins), whereas aziridination of isolated C=C bonds (that is, unactivated olefins) remains underexplored. Here we demonstrate a strategy for nitrogen transfer to unactivated olefins by utilizing electron-deficient ketones as catalysts. An oxaziridine intermediate, generated in situ from the ketone catalyst and a nitrogen source, transfers nitrogen to unactivated C=C bonds preferentially over activated C=C bonds. This ‘unusual’ chemoselectivity, as well as the enantioselectivity realized through the use of a chiral ketone catalyst, cannot be achieved by previously developed methods that are based on either organocatalysts or metal catalysts. Moreover, mechanistic studies through modified mass spectrometry allow capture and further investigation of the transient oxaziridine intermediate, establishing its essential role in this nitrogen transfer process.

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Fig. 1: Catalytic heteroatom transfer to C=C bonds.
Fig. 2: Organocatalytic nitrogen transfer to unactivated olefins.
Fig. 3: Additional substrates and comparisons between organocatalysts and rhodium catalysts.
Fig. 4: Mass spectrometric studies of the reaction mechanism.
Fig. 5: Computational studies of the reaction mechanism.

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Data availability

The data supporting the findings of this study are available within the article and its Supplementary Information. Additional data are available from the corresponding authors on reasonable request.

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Acknowledgements

L.K. acknowledges financial support from Rice University, the National Institutes of Health (R01 grant no. GM-114609-04), the National Science Foundation (CAREER:SusChEM grant no. CHE-1546097) and the Robert A. Welch Foundation (grant no. C-1764). X.Z. is grateful for financial support from the Shenzhen STIC (grant no. JCYJ20170412150343516) and the Shenzhen San-Ming Project (grant no. SZSM201809085). D.H.E. thanks BYU and the Fulton Supercomputing Lab.

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Authors and Affiliations

  1. Department of Chemistry, Rice University, BioScience Research Collaborative, Houston, TX, USA

    Qing-Qing Cheng, Zhe Zhou, Juha H. Siitonen & László Kürti

  2. Lab of Computational Chemistry and Drug Design, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China

    Heming Jiang & Xinhao Zhang

  3. Shenzhen Bay Laboratory, Shenzhen, China

    Heming Jiang & Xinhao Zhang

  4. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA

    Daniel H. Ess

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Contributions

Q.-Q.C. and L.K. conceived this work and designed the synthetic studies; Q.-Q.C. conducted the synthetic studies with assistance from Z.Z.; X.Z. and D.H.E. designed the mechanistic studies; H.J. and D.H.E. conducted the mechanistic studies with assistance from Q.-Q.C. and J.H.S.; Q.-Q.C. and L.K. prepared the manuscript with input from all other authors.

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Correspondence to László Kürti.

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Supplementary Information

Supplementary Notes 1–3, Tables 1–4, methods, Figs. 1–7 and references.

Supplementary Data 1

Cartesian coordinates and energies for calculated structures.

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Cheng, QQ., Zhou, Z., Jiang, H. et al. Organocatalytic nitrogen transfer to unactivated olefins via transient oxaziridines. Nat Catal 3, 386–392 (2020). https://doi.org/10.1038/s41929-020-0430-4

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