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Photoelectrochemical asymmetric dehydrogenative [2 + 2] cycloaddition between C–C single and double bonds via the activation of two C(sp3)–H bonds

Nature Catalysis volume 6, pages 1186–1193 (2023)Cite this article

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Abstract

The efficient generation of high structural complexity, which correlates with the number of stereocentres, is an important objective in organic synthesis. Ideally, from a perspective of economy and sustainability, the conversion should include the direct functionalization of unactivated C(sp3)–H bonds. Here we introduce a methodology that enables the generation of complex cyclobutanes with up to four consecutive stereocentres, including all-carbon quaternary stereocentres, from a direct reaction of C–C single bonds with C=C double bonds. The asymmetric photoelectrocatalysis combines photocatalysis, electrochemical redox catalysis and asymmetric catalysis. It avoids the use of chemical oxidants, exhibits excellent enantioselectivity and diastereoselectivity, reveals high functional group compatibility, and also succeeds in the simultaneous conversion of two C(sp3)–H bonds into consecutive carbon stereocentres. This work demonstrates the power of combining electrochemistry with photochemistry and asymmetric catalysis to generate complex structures in an economic and sustainable fashion.

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Fig. 1: [2π + 2π] and [2π + 2σ] photocycloadditions, and this work.
Fig. 2: Scope of ketones and alkenes.
Fig. 3: Synthetic applications of the photoelectrochemical asymmetric dehydrogenative [2 + 2] cycloaddition.
Fig. 4: Mechanistic studies.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information, or from the authors on reasonable request. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre under deposition number CCDC 2258577 (11) and CCDC 2258578 (28). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We are grateful for funding from the Deutsche Forschungsgemeinschaft (ME 1805/17-1 for E.M.) and to X. Huang for his early related explorations. P.X. is grateful for a postdoctoral fellowship from the Alexander von Humboldt Foundation.

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Authors and Affiliations

  1. Fachbereich Chemie, Philipps-Universität Marburg, Marburg, Germany

    Peng Xiong, Sergei I. Ivlev & Eric Meggers

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  1. Peng Xiong
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Contributions

E.M. and P.X. wrote the manuscript. E.M. and P.X. conceived of the project and devised the synthetic experiments. P.X. performed the synthetic experiments and analysed the data. S.I. collected the crystallographic data and solved and refined the X-ray crystal structures.

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Correspondence to Eric Meggers.

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Nature Catalysis thanks Qingquan Lu, Maurizio Benaglia 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. 1–68, Tables 1–5, experimental procedures and characterization data, HPLC and NMR spectra.

Supplementary Data 1

CIF file of the crystal structure of compound 11.

Supplementary Data 2

CIF file of the crystal structure of compound 28.

Supplementary Data 3

Checkcif file of the crystal structure of compound 11.

Supplementary Data 4

Checkcif file of the crystal structure of compound 28.

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Xiong, P., Ivlev, S.I. & Meggers, E. Photoelectrochemical asymmetric dehydrogenative [2 + 2] cycloaddition between C–C single and double bonds via the activation of two C(sp3)–H bonds. Nat Catal 6, 1186–1193 (2023). https://doi.org/10.1038/s41929-023-01050-y

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