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A gold-catalysed enantioselective Cope rearrangement of achiral 1,5-dienes

Nature Chemistry volume 4, pages 405–409 (2012)Cite this article

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Abstract

Since the discovery of the Cope rearrangement in the 1940s, no asymmetric variant of the rearrangement of achiral 1,5-dienes has emerged, despite the successes that have been achieved with its heteroatom variants (Claisen, aza-Cope, and so on). This article reports the first example of an enantioselective Cope reaction that starts from an achiral diene. The new gold(I) catalyst derived from double Cl−-abstraction of ((S)-3,5-xylyl-PHANEPHOS(AuCl)2), has been developed for the sigmatropic rearrangement of alkenyl-methylenecyclopropanes. The reaction proceeds at low temperature and the synthetically useful vinylcyclopropane products are obtained in high yield and enantioselectivity. Density functional theory calculations predict that: (1) the reaction proceeds via a cyclic carbenium ion intermediate, (2) the relief of strain in the methylenecyclopropane moiety provides the thermodynamic driving force for the rearrangement and (3) metal complexation of the transition-state structure lowers the rearrangement barriers.

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Figure 1: Transition-metal catalysed Cope rearrangements.
Figure 2: Computational investigation of the rearrangement pathway.

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Acknowledgements

The University of North Carolina group acknowledges the National Institute of General Medicine (GM-60578), D.W. acknowledges the Fulbright Foreign Student Program, D.J.T. acknowledges support from the ACS-PRF program (49119-ND4) and the National Science Foundation's Partnership for Advanced Computational Infrastructure (CHE-030089, Pittsburgh Supercomputer Center) and O.G. acknowledges R.M. Hussing, and M. and L. Defenbaugh for support.

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Authors and Affiliations

  1. Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-3290, North Carolina, USA

    Ryan J. Felix, Dieter Weber & Michel R. Gagné

  2. Department of Chemistry, University of California at Davis, Davis, 95616, California, USA

    Osvaldo Gutierrez & Dean J. Tantillo

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  1. Ryan J. Felix
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Contributions

R.J.F., D.W. and M.R.G. conceived and designed the experiments. R.J.F. performed the experiments and analysed the data. R.J.F., D.J.T. and M.R.G. co-wrote the paper. O.G. and D.J.T. performed the DFT calculations. All authors discussed the results and commented on the manuscript.

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Correspondence to Dean J. Tantillo or Michel R. Gagné.

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Crystallographic data for compound 4. (CIF 24 kb)

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Felix, R., Weber, D., Gutierrez, O. et al. A gold-catalysed enantioselective Cope rearrangement of achiral 1,5-dienes. Nature Chem 4, 405–409 (2012). https://doi.org/10.1038/nchem.1327

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