Iron-catalysed substrate-directed Suzuki biaryl cross-coupling

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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Fig. 1: Suzuki biaryl cross-coupling reactions.
Fig. 2: Single-crystal X-ray structures.
Fig. 3: The influence on the reaction of the type and position of the aryl halide and the nature of the amide.
Fig. 4: Mechanistic investigations.
Fig. 5: Tentative and simplified catalytic cycle.
Fig. 6: Probing pyrrole π-coordination and possible radical formation.

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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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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.

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Correspondence to Robin B. Bedford.

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Supporting Information

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

Compound 1a

Crystallographic data for compound 1a

Compound 5a

Crystallographic data for compound 5a

Compound 5b

Crystallographic data for compound 5b

Compound 8

Crystallographic data for compound 8

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O’Brien, H.M., Manzotti, M., Abrams, R.D. et al. Iron-catalysed substrate-directed Suzuki biaryl cross-coupling. Nat Catal 1, 429–437 (2018). https://doi.org/10.1038/s41929-018-0081-x

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