Synthesis of substituted oxo-azepines by regio - and diastereoselective hydroxylation

Harold Spedding, Peter Karuso, Fei Liu*

*Corresponding author for this work

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    Abstract

    Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity.

    Original languageEnglish
    Article number1871
    Pages (from-to)1-16
    Number of pages16
    JournalMolecules
    Volume22
    Issue number11
    DOIs
    Publication statusPublished - Nov 2017

    Bibliographical note

    Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Azepines
    • DFT
    • Diastereoselectivity
    • Hydroboration
    • Oxo-Azepines

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