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Light-induced Pd catalyst enables C(sp2)–C(sp2) cross-electrophile coupling bypassing the demand for transmetalation

Nature Catalysis volume 7, pages 285–294 (2024)Cite this article

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A preprint version of the article is available at ChemRxiv.

Abstract

Transition metal-catalysed cross-coupling is a versatile tool for the construction of (hetero)biaryl scaffolds. However, the cross-electrophile coupling using abundant (hetero)aryl halides and pseudohalides is still in its infancy. In particular, a robust and general method for the cross-electrophile coupling would allow unparalleled entry into the vast collection of commercially available, structurally diverse (hetero)aryl halides and pseudohalides as coupling partners. Here we demonstrate a ligand-controlled visible light-driven mono-metallic cross-electrophile coupling platform in which the synergistic operation of a dual palladium catalytic cycle differentiates the electrophiles based on the bond dissociation enthalpy. This method is mild and selective and displays efficacy towards a wide range of functional groups and challenging heteroaryls. The power of the transformation has been revealed through the synthesis of (hetero)biaryl cores of various pharmaceuticals and diversification of peptides. Bypassing the traditional transmetalation step, this technology enables a general strategy for the cross-electrophile coupling of (hetero)aryl halides and pseudohalides.

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Fig. 1: C(sp2)–C(sp2) XEC via visible light-driven Pd catalysis.
Fig. 2: Proposed mechanistic hypothesis and evaluation of reaction parameters.
Fig. 3: The scope of XEC of (hetero)aryl iodides with (hetero)aryl bromides.
Fig. 4: The scope of XEC of (hetero)aryl iodides with (hetero)aryl bromides.
Fig. 5: The scope of XEC of (hetero)aryl triflate with (hetero)aryl halides.

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Data availability

All data relating to materials and methods, experimental procedures, mechanistic studies, characterization data and NMR spectra are available in Supplementary Information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2220229 (L80), 2220165 (complex E) and 2286772 (complex F). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

The financial support received from the Science and Engineering Research Board (CRG/2022/004197) is gratefully acknowledged. The authors are thankful for the financial support from Bristol Myers Squibb. Financial support received from the University Grants Commission–India (fellowship to S.M.), Prime Minister’s Research Fellows – India (Ministry of Human Resource Development) (fellowship to P.G. and S.G.) and Indian Institute of Technology Bombay (fellowship to S.R., D.R. and V.S.) are gratefully acknowledged. G.K.L. acknowledges support from the J.C. Bose fellowship.

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Authors and Affiliations

  1. Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, India

    Sudip Maiti, Pintu Ghosh, Dineshkumar Raja, Sudev Ghosh, Sagnik Chatterjee, Velayudham Sankar, Sayan Roy, Goutam Kumar Lahiri & Debabrata Maiti

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Contributions

S.M. and D.M. conceived the concept. All authors designed, performed and analysed the experiments. D.M. supervised the experimental work. S.M. and D.M. prepared the paper.

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Correspondence to Debabrata Maiti.

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Competing interests

A patent application (application number 202321010040) has been filed by the Indian Institute of Technology Bombay based on the work described in this paper. The authors declare no other competing financial interests.

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Nature Catalysis thanks Krishnamoorthy Muralirajan, Da-Gang Yu 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 Methods, Tables 1–19, Figs. 1–9 and references.

Supplementary Data 1

CheckCIF data of all crystals reported in the article.

Supplementary Data 2

Crystallographic data for L80; CCDC reference 2220229.

Supplementary Data 3

Crystallographic data for complex E; CCDC reference 2220165.

Supplementary Data 4

Crystallographic data for complex F; CCDC reference 2286772.

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Maiti, S., Ghosh, P., Raja, D. et al. Light-induced Pd catalyst enables C(sp2)–C(sp2) cross-electrophile coupling bypassing the demand for transmetalation. Nat Catal 7, 285–294 (2024). https://doi.org/10.1038/s41929-024-01109-4

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