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Exploiting the Divergent Reactivity of α-Isocyanoacetate: Multicomponent Synthesis of 5-Alkoxyoxazoles and Related Heterocycles

Authors

  • Dr. Claudia Lalli,

    1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
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  • Marinus J. Bouma,

    1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
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  • Dr. Damien Bonne ,

    1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
    2. Aix-Marseille Université, Institut des Sciences Moléculaires de Marseille iSm2 CNRS UMR 6263, Centre Saint Jérôme service 531-13397 Marseille Cedex 20 (France)
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  • Dr. Géraldine Masson,

    Corresponding author
    1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
    • Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
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  • Dr. Jieping Zhu

    Corresponding author
    1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
    • Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex (France), Fax: (+33) 1-6907-7247
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Abstract

A novel multicomponent synthesis of 5-alkoxyoxazoles, based on a new reactivity profile of α-isocyanoacetates, is described. Thus, simply heating a solution of amine, aldehyde, and α-(EWG-phenyl)-α-isocyanoacetate or α-(4-pyridyl)-α-isocyanoacetate (EWG=electron-withdrawing group) in toluene provided 5-alkoxyoxazoles in good to excellent yields. Reaction of the 5-alkoxyoxazoles with various α,β-unsaturated acyl chlorides led to the formation of epoxytetrahydropyrrolo[3,4-b]pyridin-5-ones by a domino N-acylation/Diels–Alder cycloaddition sequence. Subsequent fragmentation under basic conditions provided 6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-ones. A four-component synthesis of the pyridin-5-one compounds, without isolation of the 5-alkoxyoxazole, was subsequently developed.

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