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Reactivity of oximes for diverse methodologies and synthetic applications

Nature Synthesis volume 1, pages 24–36 (2022)Cite this article

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Abstract

Oximes are valuable synthetic building blocks with reactivity modes that enable their use in diverse methodologies, from cycloadditions to bioconjugation. Their reactivity towards photocatalysis and transition metals makes them ideal starting materials for N-containing heterocycles, amino alcohols and amines. Developments in oxime reactivity since 2016 have enabled transformations such as the addition of iminyl radicals to alkenes to generate functionalized imines, and [2 + 2]-cycloadditions to access azetidines. The unique properties imparted by the oxime N–O bond have also been used to integrate dynamic chemistries into materials. In this Review, we discuss the innovative use of this powerful functional group, with a focus on N–O bond fragmentation and cycloadditions, along with applications including dynamic materials, energetic materials and biocatalytic oxime reductions. We conclude by highlighting methodologies based on oxime starting materials, along with the challenges of using oximes for diverse applications, and offer insight into future directions in these areas.

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Fig. 1: Overview of oxime scaffolds.
Fig. 2: General mechanisms for N–O bond fragmentation.
Fig. 3: Generation of iminyl radicals via transition metal catalysis.
Fig. 4: Photomediated N–O bond fragmentation transformations.
Fig. 5: Photomediated cycloaddition reactions of oximes.
Fig. 6: Nitrone and amide synthesis via oximes.
Fig. 7: Oxime that contain polymers and chiral reductions of oximes.
Fig. 8: New and future directions for the development of oxime reactivity.

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Acknowledgements

We thank the Alfred P. Sloan Foundation, the David and Lucile Packard Foundation, the Camille and Henry Dreyfus Foundation, the National Science Foundation (NSF CHE-1654223) and NIH (R01-GM141340) for funding. K.A.R. and E.R.W. thank the National Science Foundation for predoctoral fellowships.

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  1. These authors contributed equally: K. A. Rykaczewski; E. R. Wearing.

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  1. Department of Chemistry, William Henry Dow Laboratory, University of Michigan, Ann Arbor, MI, USA

    K. A. Rykaczewski, E. R. Wearing, D. E. Blackmun & C. S. Schindler

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K.A.R., E.R.W. and C.S.S. created the initial outline for the review. All further drafts and the final manuscript were written through contributions by all the authors. All the authors gave approval to the final version of the manuscript.

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Rykaczewski, K.A., Wearing, E.R., Blackmun, D.E. et al. Reactivity of oximes for diverse methodologies and synthetic applications. Nat Synth 1, 24–36 (2022). https://doi.org/10.1038/s44160-021-00007-y

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  • DOI: https://doi.org/10.1038/s44160-021-00007-y

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