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Split cross-coupling via Rh-catalysed activation of unstrained aryl–aryl bonds

Nature Catalysis volume 7, pages 432–440 (2024)Cite this article

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Abstract

Constructive functionalization of unstrained aryl–aryl bonds has been a fundamental challenge in organic synthesis due to the inertness of these bonds. Here we report a split cross-coupling strategy that allows twofold arylation with diverse aryl iodides through cleaving unstrained aryl–aryl bonds of common 2,2′-biphenols. The reaction is catalysed by a rhodium complex and promoted by a removable phosphinite directing group and an organic reductant such as tetrakis(dimethylamino)ethylene. The combined experimental and computational mechanistic studies reveal a turnover-limiting reductive elimination step that can be accelerated by a Lewis acid co-catalyst. The utility of this coupling method has been illustrated in the modular and simplified syntheses of unsymmetrical 2,6-diarylated phenols and skeletal insertion of phenylene units.

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Fig. 1: From activation of unstrained aryl–aryl bonds to SXC.
Fig. 2: Substrate scope for the SXC reaction.
Fig. 3: Mechanistic studies.
Fig. 4: Synthesis of unsymmetrical 2,6-diarylated phenols.
Fig. 5: Phenylene insertion into 2,2′-biphenols via a cut-and-sew transformation.

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Data availability

All data are available in the main text or Supplementary Information. Additional data are available from the corresponding authors upon request. Metrical parameters for the structure of 1i are available free of charge from the Cambridge Crystallographic Data Centre (https://www.ccdc.cam.ac.uk/) under reference number CCDC 2240576.

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Acknowledgements

Financial supports from NIGMS (2R01GM109054) and the University of Chicago are acknowledged. Umicore AG & Co. KG is thanked for a generous donation of Rh salts. We are grateful for the support of the Research Computing Center at the University of Chicago for the calculation performed in this work. R. Zhang from the University of Chicago is thanked for checking the experimental procedures.

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Authors and Affiliations

  1. Department of Chemistry, University of Chicago, Chicago, IL, USA

    Congjun Yu, Zining Zhang & Guangbin Dong

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  1. Congjun Yu
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  3. Guangbin Dong
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Contributions

C.Y. discovered the reaction. C.Y. and G.D. conceived the idea. C.Y. conducted the experimental investigation. Z.Z. conducted the DFT calculation. C.Y., Z.Z. and G.D. wrote the manuscript. G.D. directed the research.

Corresponding author

Correspondence to Guangbin Dong.

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Supplementary information

Supplementary Information

Supplementary methods, discussion, note, references, Figs. 1–14 and Tables 1–4.

Supplementary Data

.cif file of the X-ray structure of 1i.

Supplementary Data

Structure factors for the X-ray structure of 1i.

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Yu, C., Zhang, Z. & Dong, G. Split cross-coupling via Rh-catalysed activation of unstrained aryl–aryl bonds. Nat Catal 7, 432–440 (2024). https://doi.org/10.1038/s41929-024-01120-9

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