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Base-free nickel-catalysed decarbonylative Suzuki–Miyaura coupling of acid fluorides

Nature volume 563, pages 100–104 (2018)Cite this article

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Abstract

The Suzuki–Miyaura cross-coupling of organoboron nucleophiles with aryl halide electrophiles is one of the most widely used carbon–carbon bond-forming reactions in organic and medicinal chemistry1,2. A key challenge associated with these transformations is that they generally require the addition of an exogenous base, the role of which is to enable transmetallation between the organoboron nucleophile and the metal catalyst3. This requirement limits the substrate scope of the reaction because the added base promotes competitive decomposition of many organoboron substrates3,4,5. As such, considerable research has focused on strategies for mitigating base-mediated side reactions6,7,8,9,10,11,12. Previous efforts have primarily focused either on designing strategically masked organoboron reagents (to slow base-mediated decomposition)6,7,8 or on developing highly active palladium precatalysts (to accelerate cross-coupling relative to base-mediated decomposition pathways)10,11,12. An attractive alternative approach involves identifying combinations of catalyst and electrophile that enable Suzuki–Miyaura-type reactions to proceed without an exogenous base12,13,14. Here we use this approach to develop a nickel-catalysed coupling of aryl boronic acids with acid fluorides15,16,17, which are formed in situ from readily available carboxylic acids18,19,20,21,22. This combination of catalyst and electrophile enables a mechanistic manifold in which a ‘transmetallation-active’ aryl nickel fluoride intermediate is generated directly in the catalytic cycle13,16. As such, this transformation does not require an exogenous base and is applicable to a wide range of base-sensitive boronic acids and biologically active carboxylic acids.

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Fig. 1: Suzuki–Miyaura reaction and mechanistic design for the direct generation of transmetallation-active [Ar–M–X*] intermediates.
Fig. 2: Discovery of transmetallation-active nickel fluoride intermediates generated from decarbonylation enables Suzuki–Miyaura reaction of carboxylic acids and aryl boronic acids.
Fig. 3: Scope of the nickel-catalysed decarbonylative Suzuki–Miyaura reaction with various carboxylic acids.
Fig. 4: Scope of the nickel-catalysed decarbonylative Suzuki–Miyaura coupling with various organoboron reagents.

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Data availability

The main data supporting the findings of this study are available within the article and its Supplementary Information. Additional data are available from the corresponding author upon request. Metrical parameters for the structures of complexes 2b and 3 (see Supplementary Information) are available free of charge from the Cambridge Crystallographic Data Centre (https://www.ccdc.cam.ac.uk/) under reference numbers CCDC 1837039 and CCDC 1837038, respectively.

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Acknowledgements

We acknowledge financial support from National Institutes of Health NIGMS (GM073836) and the Danish National Research Foundation (Carbon Dioxide Activation Center; CADIAC). We acknowledge J. Kampf for X-ray crystallographic analyses of 2b and 3.

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Authors and Affiliations

  1. Department of Chemistry, University of Michigan, Ann Arbor, MI, USA

    Christian A. Malapit, James R. Bour, Conor E. Brigham & Melanie S. Sanford

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Contributions

C.A.M., J.R.B. and C.E.B. developed the stoichiometric reactions. C.A.M. discovered and developed the catalytic reactions. C.A.M., J.R.B. and M.S.S. conceived and designed the investigations. M.S.S. directed and supported the research. C.A.M., J.R.B. and M.S.S. wrote and revised the manuscript.

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Correspondence to Melanie S. Sanford.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

This file contains supplementary information for methods and characterization data; which includes supplementary figures S1-S9 and supplementary tables S1-S5.

Supplementary Data

This file contains SI Complex 2b.

Supplementary Data

This file contains SI Complex 3.

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Malapit, C.A., Bour, J.R., Brigham, C.E. et al. Base-free nickel-catalysed decarbonylative Suzuki–Miyaura coupling of acid fluorides. Nature 563, 100–104 (2018). https://doi.org/10.1038/s41586-018-0628-7

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