Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction

JF Hooper; NC James; E Bozkurt; V Aviyente; JM White; MC Holland; R Gilmour; AB Holmes; KN Houk

Journal article

Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction

JF Hooper, NC James, E Bozkurt, V Aviyente, JM White, MC Holland, R Gilmour, AB Holmes, KN Houk

Journal of Organic Chemistry | Published : 2015

DOI: 10.1021/acs.joc.5b02037

Abstract

The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9-membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins.

University of Melbourne Researchers

Jonathan White Author

Andrew Holmes Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank the Australian government for an Australian Postgraduate Award (JFH) and the Australian Research Council for the award of a Discovery Project (DP0451189). We are grateful to the Gates Millennium Scholarship Program (NCJ), the National Institute of General Medical Sciences, and the National Institutes of Health (GM 36700 K.N.H.) for support of this work. Computations were performed using the Extreme Science and Engineering Discovery Environment (XSEDE) resources supported by the NSF (OCI-1053575) and the UCLA Institute for Digital Research and Education (IDRE)Hoffman2 cluster. We thank the German Academic Exchange Service (DAAD) for generous financial support (postdoctoral fellowship to M.C.H.). We thank Dr. Jonathan Burton for his interest in this work. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre under CCDC Nos. 1047892-1047894.