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Catalytic access to carbocation intermediates via nitrenoid transfer leading to allylic lactams

Nature Catalysis volume 4, pages 79–88 (2021)Cite this article

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Abstract

Carbocation intermediacy is postulated in numerous organic transformations and provides the foundation for retrosynthetic logics in chemical synthesis. Although a number of catalytic approaches are designed to generate transient carbocations under mild conditions, there is room for improvement in the context of selectivity control and synthetic utility. Here we present an approach that enables catalytic access to carbocation intermediates via metal-nitrenoid transfer into alkenes, which subsequently allows a regiocontrolled elimination reaction. Customized catalysts are capable of bypassing competing pathways of the reactive intermediates to furnish valuable allylic lactams with excellent regioselectivity. Mechanistic investigations suggest that the ligand plays a critical role as an internal base in the selectivity-determining proton transfer process. This protocol is broadly applicable for preparing both five- and the more challenging four-membered allylamides. The virtue of this platform is further demonstrated by achieving the enantioselective construction of γ-lactams.

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Fig. 1: Carbocation intermediacy.
Fig. 2: General applicability.
Fig. 3: Further advances in Ir-catalysed cyclization.
Fig. 4: DFT calculations for the proposed mechanism.
Fig. 5: Experimental support for the proposed carbocation intermediacy.

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Data availability

The X-ray crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition nos. 1999590–1999595. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif. All other data are available from the authors upon reasonable request.

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Acknowledgements

This research was supported by the Institute for Basic Science (IBS-R010-D1) in Korea. The authors thank S. Seo (Institute for Basic Science) for helpful discussions and critical reading.

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Authors and Affiliations

  1. Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, Republic of Korea

    Seung Youn Hong, Dongwook Kim & Sukbok Chang

  2. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    Seung Youn Hong, Dongwook Kim & Sukbok Chang

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Contributions

S.Y.H. and S.C. conceived and designed the project and wrote the manuscript. S.Y.H. carried out the experiments and DFT calculations. D.K. performed the X-ray crystallographic analysis. S.C. organized the research. All the authors analysed the data, discussed the results and commented on the manuscript.

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Correspondence to Sukbok Chang.

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The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Forrest Michael and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–21 and Tables 1–9.

Supplementary Data 1

Cartesian coordinates of DFT-optimized structures.

Supplementary Data 2

Crystallographic Data for compound 40 (CCDC 1999590).

Supplementary Data 3

Crystallographic Data of compound 36 (CCDC 1999591).

Supplementary Data 4

Crystallographic Data of compound 19 (CCDC 1999592).

Supplementary Data 5

Crystallographic Data of compound Ir11 (CCDC 1999593).

Supplementary Data 6

Crystallographic Data of compound 6-OAc (CCDC 1999594).

Supplementary Data 7

Crystallographic Data of compound 29 (CCDC 1999595).

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Hong, S.Y., Kim, D. & Chang, S. Catalytic access to carbocation intermediates via nitrenoid transfer leading to allylic lactams. Nat Catal 4, 79–88 (2021). https://doi.org/10.1038/s41929-020-00558-x

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