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Hydroacylation of α,β-unsaturated esters via aerobic C–H activation

Nature Chemistry volume 2, pages 592596 (2010) | Download Citation

Abstract

The development of methods for carbon–carbon bond formation under benign conditions is an ongoing challenge for the synthetic chemist. In recent years there has been considerable interest in using selective C–H activation as a direct route for generating reactive intermediates. In this article, we describe the use of aldehyde auto-oxidation as a simple, clean and effective method for C–H activation, resulting in the generation of an acyl radical. This acyl radical can be used for carbon–carbon bond formation and herein we describe the application of this method for the hydroacylation of α,β-unsaturated esters without the requirement of additional catalysts or reagents. This methodology generates unsymmetrical ketones, which have been shown to have broad use in organic synthesis.

  • Compound C4H8O

    Butanal

  • Compound C4H8O

    2-Methylpropanal

  • Compound C5H10O

    3-Methylbutanal

  • Compound C6H12O

    Hexanal

  • Compound C7H12O

    Cyclohexanecarbaldehyde

  • Compound C8H16O

    2-Ethylhexanal

  • Compound C10H20O

    Decanal

  • Compound C6H8O4

    Dimethyl (2Z)-but-2-enedioate

  • Compound C10H16O5

    Dimethyl 2-butanoylbutanedioate

  • Compound C10H16O5

    Dimethyl 2-(2-methylpropanoyl)butanedioate

  • Compound C11H18O5

    Dimethyl 2-(3-methylbutanoyl)butanedioate

  • Compound C12H20O5

    Dimethyl 2-hexanoylbutanedioate

  • Compound C13H20O5

    Dimethyl 2-(cyclohexylcarbonyl)butanedioate

  • Compound C14H24O5

    Dimethyl 2-(2-ethylhexanoyl)butanedioate

  • Compound C16H28O5

    Dimethyl 2-decanoylbutanedioate

  • Compound C6H8O4

    Dimethyl (2E)-but-2-enedioate

  • Compound C13H24O4

    Dimethyl 2-(heptan-3-yl)butanedioate

  • Compound C9H14O4

    Diethyl ethylidenepropanedioate

  • Compound C10H16O4

    Diethyl propan-2-ylidenepropanedioate

  • Compound C10H16O5

    Diethyl (ethoxymethylidene)propanedioate

  • Compound C13H22O5

    Diethyl (3-oxohexan-2-yl)propanedioate

  • Compound C14H24O5

    Diethyl (5-methyl-3-oxohexan-2-yl)propanedioate

  • Compound C15H26O5

    Diethyl (3-oxooctan-2-yl)propanedioate

  • Compound C16H26O5

    Diethyl (1-cyclohexyl-1-oxopropan-2-yl)propanedioate

  • Compound C17H30O5

    Diethyl (4-ethyl-3-oxooctan-2-yl)propanedioate

  • Compound C19H34O5

    Diethyl (3-oxotridecan-2-yl)propanedioate

  • Compound C14H24O6

    Diethyl (1-ethoxy-2-oxopentyl)propanedioate

  • Compound C15H26O6

    Diethyl (1-ethoxy-4-methyl-2-oxopentyl)propanedioate

  • Compound C16H28O6

    Diethyl (1-ethoxy-2-oxoheptyl)propanedioate

  • Compound C17H28O6

    Diethyl (2-cyclohexyl-1-ethoxy-2-oxoethyl)propanedioate

  • Compound C18H32O6

    Diethyl (3-ethyl-1-ethoxy-2-oxoheptyl)propanedioate

  • Compound C20H36O6

    Diethyl (1-ethoxy-2-oxoundecyl)propanedioate

  • Compound C6H10O2

    Ethyl (2E)-but-2-enoate

  • Compound C10H18O3

    Ethyl 3-methyl-4-oxoheptanoate

  • Compound C13H22O7

    Diethyl 5-hydroxy-4-methyl-5-propyl-1,2-dioxolane-3,3-dicarboxylate

  • Compound C15H26O4

    Diethyl (1-cyclohexylethyl)propanedioate

  • Compound C16H30O4

    Diethyl (3-ethylheptan-2-yl)propanedioate

  • Compound C12H20O5

    Diethyl 2-butanoylbutanedioate

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Acknowledgements

We thank A.G. Davies and K.U. Ingold for helpful discussions. We gratefully acknowledge EPSRC, BBSRC, MRC, GSK, UCL and CEM UK for support of our program. We also thank the EPSRC Mass Spectrometry Service for provision of mass spectra.

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Affiliations

  1. Department of Chemistry, University College London, London WC1H 0AJ

    • Vijay Chudasama
    • , Richard J. Fitzmaurice
    •  & Stephen Caddick

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Contributions

S.C., R.J.F. and V.C. conceived the experiments. V.C. performed the laboratory experiments and analysed the data. V.C., R.J.F. and S.C. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stephen Caddick.

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DOI

https://doi.org/10.1038/nchem.685

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