Synthesis of chiral cyclohexanol derived benzylamines and their applications in enantiodiscrimination of optically active analytes by NMR spectroscopy

Abstract

Cyclohexanol derived benzyl amines are synthesized and evaluated as chiral solvating agents (CSAs) for chiral discrimination of optically active analytes by NMR analysis. A pair of diastereomeric CSAs is prepared and investigated for various acidic analytes, showing an interesting match–mismatch effect. A series of divergent analytes, derivatives of mandelic acid, α-aryloxypropionic acids, α,β-disubstituted carboxylic acids, binaphthylphosphoric acids, α-hydroxy phosphonates and α-cyclic phosphoric acids are analyzed. Based on these results, a working model is proposed to explain the mode of molecular recognition. Possible interactions may involve anisotropic effects, π–π interactions and hydrogen bond formation in the process of recognition. The stability of diastereomeric structures and binding affinities were evaluated by DFT calculations.