Enantiopure cis- and trans-2-(2-Aminocyclohexyl)phenols: Effective Preparation, Solid-State Characterization, and Application in Asymmetric Organocatalysis


TEZEREN M. A. , YESIL T. A. , Zorlu Y., TİLKİ T. , ERTURK E.

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol.2018, no.48, pp.7017-7032, 2018 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 2018 Issue: 48
  • Publication Date: 2018
  • Doi Number: 10.1002/ejoc.201801445
  • Title of Journal : EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
  • Page Numbers: pp.7017-7032

Abstract

Effective synthesis of cis- and trans-2-(2-methoxyphenyl)cyclohexylamine as well as their multigram-scale optical resolution by diastereomeric salt formation with dibenzoyl tartaric acid have been described. Assignment of absolute configurations to the enantiomers has been made by X-ray crystallography. Starting from the resolved precursor, diverse aminoalkylphenols (AAPs) having primary, secondary, and tertiary amine group as well as a quaternary ammonium phenol have been prepared as potential bifunctional organocatalysts based on the cyclohexane backbone. We furthermore report herein that AAPs carrying a primary amine and a phenolic hydroxyl group can catalyze the direct aldol reaction with high activity and setereoselectivity, and thus up to 97 % yield, 90:10 syn/anti diastereomeric ratio, and 80 % enantiomeric excess can be achieved.