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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Article number1871
Pages1-16
Number of pages16
JournalMolecules
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 2017

Fingerprint

Azepines
hydroboration
Hydroxylation
Regioselectivity
enzyme inhibitors
oxidation
Epitopes
synthesis
activity (biology)
rhodium
chemical properties
hydrogenation
Molecular recognition
Oxidation
Rhodium
Hydrogenation
Enzyme Inhibitors
catalysts
Scaffolds
Chemical properties

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

Cite this

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title = "Synthesis of substituted oxo-azepines by regio - and diastereoselective hydroxylation",
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.",
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Synthesis of substituted oxo-azepines by regio - and diastereoselective hydroxylation. / Spedding, Harold; Karuso, Peter; Liu, Fei.

In: Molecules, Vol. 22, No. 11, 1871, 11.2017, p. 1-16.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Spedding, Harold

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