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.
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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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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.
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Chudasama, V., Fitzmaurice, R. & Caddick, S. Hydroacylation of α,β-unsaturated esters via aerobic C–H activation. Nature Chem 2, 592–596 (2010). https://doi.org/10.1038/nchem.685
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DOI: https://doi.org/10.1038/nchem.685
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