Abstract

Although the replacement of ubiquitous palladium catalysts with more sustainable iron-based analogues continues apace, the simple biaryl Suzuki cross-coupling reaction remains stubbornly elusive. It appears that the main issue hampering the reaction is activation of the aryl halide C–X bond. Here we show that a simple N-pyrrole amide and related directing groups on the aryl halide substrates facilitate this process by transient π-coordination to the iron centre. This allows iron-catalysed Suzuki biaryl cross-coupling to proceed, under mild conditions, with alkyllithium-activated aryl pinacol boronic esters.

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Acknowledgements

We thank the EPSRC for funding (Grant no. EP/K012258/1), for the provision of a studentship through the EPSRC Centre for Doctoral Training in Catalysis (M.M.) and for a part-studentship (H.M.O’B.). We thank AstraZeneca for CASE top-up funding (H.M.O’B.) and A. Stark and N. Fey for informative and useful discussions.

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  1. School of Chemistry, University of Bristol, Bristol, UK

    • Harry M. O’Brien
    • , Mattia Manzotti
    • , Roman D. Abrams
    • , David Elorriaga
    • , Hazel A. Sparkes
    • , Sean A. Davis
    •  & Robin B. Bedford

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Contributions

H.M.O’B., M.M., R.D.A., R.B.B., D.E., H.A.S. and S.A.D. performed and analysed the experiments. H.M.O’B., R.D.A. and R.B.B. designed the optimization experiments. H.M.O’B., M.M. and R.B.B. designed experiments to study the effect of varying the halide and directing groups. H.M.O’B. and R.B.B. designed experiments to explore the scope of the reaction. H.M.O’B., M.M. and R.B.B. designed experiments to probe the mechanism. R.B.B. designed the computational experiments. H.M.O’B., M.M. and R.B.B. prepared this manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Robin B. Bedford.

Supplementary information

  1. Supporting Information

    Supplementary Methods, Supplementary Figures 1–16, Supplementary Tables 1–3, Supplementary References

  2. Compound 1a

    Crystallographic data for compound 1a

  3. Compound 5a

    Crystallographic data for compound 5a

  4. Compound 5b

    Crystallographic data for compound 5b

  5. Compound 8

    Crystallographic data for compound 8

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https://doi.org/10.1038/s41929-018-0081-x

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