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Nickel-catalysed Suzuki–Miyaura coupling of amides

Nature Chemistry volume 8, pages 75–79 (2016)Cite this article

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Abstract

The Suzuki–Miyaura coupling has become one of the most important and prevalent methods for the construction of C–C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon–heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki–Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C–N bond after N-tert-butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C–C bonds through cleavage of the C–N bond using non-precious metal catalysis.

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Figure 1: Development of Ni-catalysed coupling of amides with carbon nucleophiles.
Figure 2: Several applications of the Suzuki–Miyaura coupling of amides were carried out to assess the synthetic utility of the methodology.

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Change history

  • 09 December 2015

    In the version of this Article originally published online, the footnotes in Table 2 were incorrectly defined. The asterisk (*) should have indicated that yields were the average of two isolation experiments. Yields marked by the double dagger (ǂ) should have been defined as those determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an internal standard. These errors have been corrected in all versions of the Article.

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Acknowledgements

The authors are grateful to Boehringer Ingelheim, DuPont, Bristol-Myers Squibb, the Camille and Henry Dreyfus Foundation, the A. P. Sloan Foundation, the S. T. Li Foundation and the University of California, Los Angeles. S. Anthony (UCLA) is acknowledged for experimental assistance. We are grateful to the National Science Foundation (NSF) (N.A.W. and E.L.B., No. DGE-1144087) and the Foote Family (N.A.W.) for fellowship support. These studies were also supported by shared instrumentation grants from the NSF (No. CHE-1048804) and the National Center for Research Resources (No. S10RR025631).

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  1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 90095, California, USA

    Nicholas A. Weires, Emma L. Baker & Neil K. Garg

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  1. Nicholas A. Weires
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Contributions

N.A.W. and E.L.B. designed and performed the experiments and analysed the experimental data. N.K.G. directed the investigations and prepared the manuscript with contributions from all the authors; all the authors contributed to discussions.

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Correspondence to Neil K. Garg.

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The authors declare no competing financial interests.

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Weires, N., Baker, E. & Garg, N. Nickel-catalysed Suzuki–Miyaura coupling of amides. Nature Chem 8, 75–79 (2016). https://doi.org/10.1038/nchem.2388

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