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Dearomative dihydroxylation with arenophiles

Nature Chemistry volume 8, pages 922–928 (2016)Cite this article

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A Corrigendum to this article was published on 21 October 2016

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Abstract

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N–N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

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Figure 1: Current strategies in dearomative functionalization of arenes, which include this work.
Figure 2: Mechanistic considerations and necessary criteria for arenophile reactivity.
Figure 3: Synthetic applications of dearomative dihydroxylation.

Change history

  • 22 September 2016

    In the version of this Article originally published, in the Figure 2 caption, the HOMO–LUMO gap of the arene, rather than the arenophile, was described as the first requirement for arenophile reactivity. Furthermore, in the caption for Table 3, an oversight resulted in the inclusion of p-TsNH2 as the additive, however, the additive used in this reaction was citric acid (0.5 equiv.); and 2.0 equivalents of NMO were used. This has been corrected in the online versions of this Article.

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Acknowledgements

The authors acknowledge the University of Illinois for generous support of this work. E.H.S. is a Springborn Graduate Fellow and J.P. is a Fellow of the German Research Foundation (DFG). We thank S. E. Denmark and P. J. Hergenrother (University of Illinois) for critical proofreading of this manuscript. We dedicate this article to K. C. Nicolaou on the occasion of his 70th birthday.

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Author notes

  1. Emma H. Southgate and Jola Pospech: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, 61801, Illinois, USA

    Emma H. Southgate, Jola Pospech, Junkai Fu, Daniel R. Holycross & David Sarlah

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Contributions

E.H.S., J.P., J.F. and D.R.H. conducted the experiments, analysed the data and prepared the Supplementary Information. E.H.S., J.P. and D.S. conceived and designed the project, analysed the data and wrote the manuscript.

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Correspondence to David Sarlah.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 8141 kb)

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Crystallographic data for compound 5a (CIF 966 kb)

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Structure factors file for compound 5a (FCF 108 kb)

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Crystallographic data for compound 8a (CIF 989 kb)

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Structure factors file for compound 8a (FCF 242 kb)

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Crystallographic data for compound Ac-9a (CIF 597 kb)

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Structure factors file for compound Ac-9a (FCF 53 kb)

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Southgate, E., Pospech, J., Fu, J. et al. Dearomative dihydroxylation with arenophiles. Nature Chem 8, 922–928 (2016). https://doi.org/10.1038/nchem.2594

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