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Photocatalytic carbyne reactivity of phosphorus ylides for three-component formal cycloaddition reactions

Nature Synthesis (2024)Cite this article

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Abstract

Selective reactions between more than two molecules are governed by appropriate combinations of polar functionalities. This restriction can be ameliorated by photoredox umpolung reactivity, which enables the functionalization of unreactive bonds of chemical reagents while leaving their inherent reactive functional groups intact, paving the way for otherwise difficult multicomponent reactions. Here we report that the photocatalytic single-electron oxidation of phosphorus ylides underpins their sequential assembly with electron-rich olefins and α,β-unsaturated carbonyl compounds to form functionalized six-membered carbocycles. This three-component formal cycloaddition, featuring consecutive C–H functionalization and Wittig reaction of phosphorus ylides, offers a carbyne-like transformation that involves the conversion of inert C–H and C=P bonds into C–C and C=C bonds, respectively, as a powerful tool for the rapid construction of versatile synthetic building blocks from readily available substrates.

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Fig. 1: Transformation of carbynes and carbyne equivalents.
Fig. 2: Proposed mechanism for the three-component formal cycloaddition.
Fig. 3: Scope of the substrates.
Fig. 4: Gibbs free energy profile of the radical additions of the phosphorus ylide to t-butyl vinyl ether and acrolein.
Fig. 5: Four-component coupling reaction.

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Data availability

The experimental procedures, characterization (including the spectra of the new compounds) and details of the theoretical studies are available in the Supplementary Information. Crystallographic data for the structure reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition number CCDC 2287406 (2q). A copy of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

This work was financially supported by JSPS KAKENHI grants JP23H04901 (T.O.), JP23H04907 (Green Catalysis Science, T.O.), JP23H00296 (T.O.), JP22K21346 (T.O.) and JP21H01930 (K.O.); and JST FOREST grant JPMJFR221L (K.O.). R.S. acknowledges a JSPS Research Fellowship for Young Scientists. F.D. acknowledges the Studienstiftung des Deutschen Volkes and M. van Gemmeren.

Author information

Author notes

  1. Kohsuke Ohmatsu

    Present address: Department of Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan

  2. These authors contributed equally: Taiga Ando, Fritz Deufel.

Authors and Affiliations

  1. Institute of Transformative Bio-Molecules (WPI-ITbM), and Department of Molecular and Macromolecular Chemistry, Graduate School of Engineering, Nagoya University, Nagoya, Japan

    Ryuhei Suzuki, Taiga Ando, Fritz Deufel, Kohsuke Ohmatsu & Takashi Ooi

  2. Otto-Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Kiel, Germany

    Fritz Deufel

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Contributions

K.O. and T.O. prepared the manuscript. R.S., T.A. and F.D. performed the experiments. F.D. conducted theoretical calculations. All authors contributed to study design, data analysis and manuscript editing.

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Correspondence to Kohsuke Ohmatsu or Takashi Ooi.

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Peer review information

Nature Synthesis thanks Xuewei Liu, Boris Maryasin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Thomas West, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–20, Discussion, Tables 1–9, experimental and computational details and characterization data.

Supplementary Data 1

Crystallographic data for 2q, CCDC 2287406.

Supplementary Data 2

Cartesian coordinates of calculated compounds.

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Suzuki, R., Ando, T., Deufel, F. et al. Photocatalytic carbyne reactivity of phosphorus ylides for three-component formal cycloaddition reactions. Nat. Synth (2024). https://doi.org/10.1038/s44160-024-00612-7

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