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The emergence of Pd-mediated reversible oxidative addition in cross coupling, carbohalogenation and carbonylation reactions

Nature Catalysis volume 2, pages 843–851 (2019)Cite this article

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Abstract

Exploiting the reversibility of chemical processes is a long-standing tactic of organic chemists, and permeates most areas of the discipline. The notion that oxidative addition of Pd(0) to Ar–X bonds can be considered an irreversible process has been challenged, periodically, over the last 30 years. Recent examples of methodologies that harness the reversibility of oxidative addition reactions in catalytic processes have enabled access to challenging carbocyclic and heterocyclic scaffolds. This Perspective seeks to describe the development of these processes from the early proof-of-principle findings, and highlight key challenges that remain in this avenue of research. In particular, we draw attention to significant deficiencies that remain in the choice of suitable ligands and additives for these transformations. We conclude by describing how the concept of reversible oxidative addition has recently been exploited in the development of novel carbonylation reactions.

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Fig. 1: Applications of reductive elimination of ArPd(II)X to give Ar–X and Pd(0) discussed in this perspective.
Fig. 2: Development of reductive elimination of Ar–X from ArXPd(II)L2.
Fig. 3: Cyclization reactions involving reversible oxidative addition.
Fig. 4: Intramolecular carbohalogenation facilitated by reductive elimination and reversible oxidative addition.
Fig. 5: Reversible oxidative addition in carbonylation/decarbonylation sequences.

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Acknowledgements

P. Byrne is thanked for useful discussion, and N. Kayambu is acknowledged for his assistance in the preliminary literature search.

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Authors and Affiliations

  1. School of Chemistry, University College Cork, Cork, Ireland

    David J. Jones & Gerard P. McGlacken

  2. School of Pharmacy, University College Cork, Cork, Ireland

    David J. Jones

  3. Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland

    David J. Jones & Gerard P. McGlacken

  4. Davenport Laboratories, Department of Chemistry, University of Toronto, Toronto, Canada

    Mark Lautens

  5. Synthesis and Solid State Pharmaceutical Centre, Cork, Ireland

    Gerard P. McGlacken

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Jones, D.J., Lautens, M. & McGlacken, G.P. The emergence of Pd-mediated reversible oxidative addition in cross coupling, carbohalogenation and carbonylation reactions. Nat Catal 2, 843–851 (2019). https://doi.org/10.1038/s41929-019-0361-0

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