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Metal-free photoredox-catalysed formal C–H/C–H coupling of arenes enabled by interrupted Pummerer activation

Nature Catalysis volume 3, pages 163–169 (2020)Cite this article

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Abstract

Aryl–aryl cross-coupling constitutes one of the most widely used procedures for the synthesis of high-value materials that range from pharmaceuticals to organic electronics and conducting polymers. The assembly of (hetero)biaryl scaffolds generally requires multiple steps; coupling partners must be functionalized before the key bond-forming event is considered. The development of selective C–H arylation processes in arenes—which sidestep the need for prefunctionalized partners—is thus crucial for streamlining the construction of these key architectures. Here we report an expedient, one-pot assembly of (hetero)biaryl motifs using photocatalysis and two non-prefunctionalized arene partners. The approach is underpinned by the functionalization of a C–H bond in an arene coupling partner using the interrupted Pummerer reaction. A unique pairing of the organic photoredox catalyst and the intermediate dibenzothiophenium salts enables highly selective reduction in the presence of sensitive functionalities. The utility of the metal-free, one-pot strategy is exemplified by the synthesis of a bioactive natural product and the modification of complex molecules of societal importance.

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Fig. 1: Strategies for arylation of arenes.
Fig. 2: A mechanistic proposal for a one-pot, metal-free, photoredox-catalysed C–H/C–H coupling of arenes, enabled by the interrupted Pummerer activation.
Fig. 3: Mechanistic investigations.
Fig. 4: Application of the one-pot, metal-free photoredox-catalysed, formal C–H/C–H coupling of arenes, enabled by interrupted Pummerer activation.

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Data availability

All data are available in the main text or Supplementary Information. Metrical parameters for the structures of 2, 60 and S12 (see Supplementary Information) are available free of charge from the Cambridge Crystallographic Data Centre (https://www.ccdc.cam.ac.uk/) under reference nos. 1922367, 1922368 and 1960231.

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Acknowledgements

We thank the EPSRC (Doctoral Prize Fellowship to M.H.A.; Established Career Fellowship to D.J.P.) and The University of Manchester (Lectureship to G.J.P.P.; Studentship to M.Š.) for their generous support. Additional thanks go to L. Natrajan and F. J. Hernandez for their assistance with the fluorescence quenching, electrochemical studies and quantum yield determination, as well as to D. Leonori for his advice on the design of the experiments.

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Authors and Affiliations

  1. Department of Chemistry, University of Manchester, Manchester, UK

    Miles H. Aukland, Mindaugas Šiaučiulis, Adam West, Gregory J. P. Perry & David J. Procter

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  2. Mindaugas Šiaučiulis
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Contributions

M.H.A. and D.J.P. conceived the study and co-wrote the manuscript. M.H.A. designed and performed experiments and M.Š., A.W. and G.J.P.P. performed experiments.

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Correspondence to David J. Procter.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–12, Tables 1–6 and references.

Compound 2

Crystallographic information for Compound 2.

Compound 60

Crystallographic information for Compound 60.

Compound S12

Crystallographic information for Compound S12.

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Aukland, M.H., Šiaučiulis, M., West, A. et al. Metal-free photoredox-catalysed formal C–H/C–H coupling of arenes enabled by interrupted Pummerer activation. Nat Catal 3, 163–169 (2020). https://doi.org/10.1038/s41929-019-0415-3

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