Conformational regulation of substituted azepanes through mono-, di-, and trifluorination

Alpesh Ramanlal Patel, Luke Hunter, Mohan M. Bhadbhade, Fei Liu*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Substituted azepanes have flexible ring structures and this conformational diversity is important for their bioactivity. We have shown that a single fluorine atom, when installed diastereoselectively on a model azepane ring, can bias its ring to one major conformation. Here the conformational effects of mono-, di-, and trifluorination, as well as hydroxylation, on substituted azepanes have been investigated by 1H NMR spectroscopy and computational modeling in chloroform. Fluorine substitution was found to be more effective than hydroxyl group substitution in reducing conformational disorder; however, multiple fluorinations may not lead to additive conformational control and can result in complex conformational outcomes. Seven-membered nitrogen heterocycles have flexible ring structures and this conformational diversity is important for their bioactivity. Here the conformational effects of fluorination, as well as hydroxylation, on an azepane model system are investigated by 1H NMR spectroscopy and computational modeling.

Original languageEnglish
Pages (from-to)2584-2593
Number of pages10
JournalEuropean Journal of Organic Chemistry
Volume2014
Issue number12
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Conformation analysis
  • Density functional calculations
  • Fluorine
  • Medium-ring compounds
  • Nucleophilic substitution

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