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

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. Effective preparation of enantiopure cis‐ and trans‐2‐(2‐aminocyclohexyl)phenols, novel 1,4‐aminoalkylphenols, as well as their performance as chiral organocatalyst are presented.