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The aromatic ene reaction

Nature Chemistry volume 6, pages 34–40 (2014)Cite this article

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Abstract

The ene reaction is a pericyclic process in which an alkene with an allylic hydrogen atom (the ene donor) reacts with a second unsaturated species (the enophile) to form a new product with a transposed π-bond. The aromatic ene reaction, in which the alkene component is embedded in an aromatic ring, has only been reported in a few (four) instances and has proceeded in low yield (≤6%). Here, we show efficient aromatic ene reactions in which a thermally generated aryne intermediate engages a pendant m-alkylarene substituent to produce a dearomatized isotoluene, itself another versatile but rare reactive intermediate. Our experiments were guided by computational studies that revealed structural features conducive to the aromatic ene process. We proceeded to identify a cascade comprising three reactions: (1) hexadehydro-Diels–Alder (for aryne generation), (2) intramolecular aromatic ene and (3) bimolecular Alder ene. The power of this cascade is evident from the structural complexity of the final products, the considerable scope, and the overall efficiency of these multistage, reagent- and by-product-free, single-pot transformations.

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Figure 1: Structural delineation and previous example of an aromatic ene reaction.
Figure 2: Arynes as enophiles reacting with various types of ene donor.
Figure 3: Competition between aromatic ene and aromatic Diels–Alder pathways.
Figure 4: Studies giving insight into the importance of reaction conditions and the mechanism of the HDDA//aromatic ene reactions.

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Acknowledgements

D.N. was partially supported by a University of Minnesota Graduate School Doctoral Dissertation Fellowship. Financial support was provided by the National Institutes of Health (CA76497 and GM65597).

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  1. Department of Chemistry, University of Minnesota, Minneapolis, 55455, Minnesota, USA

    Dawen Niu & Thomas R. Hoye

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  1. Dawen Niu
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  2. Thomas R. Hoye
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D.N and T.R.H. designed the experiments, analysed the data and wrote the manuscript.

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Correspondence to Thomas R. Hoye.

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The authors declare no competing financial interests.

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Crystallographic data for compound 42i (CIF 22 kb)

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Niu, D., Hoye, T. The aromatic ene reaction. Nature Chem 6, 34–40 (2014). https://doi.org/10.1038/nchem.1797

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