A novel C₂ symmetric chiral stationary phase with N-[(4-Methylphenyl)sulfonyl]-l-leucine as chiral side chains

In this study, a series of chiral stationary phases based on N-[(4-methylphenyl)sulfonyl]-l-leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N-[(4-methylphenyl)sulfonyl]-l-leucine showed much better enantioselectivities than that based on N-(4-methylbenzoyl)-l-leucine amide. The construction of C₂ symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C₂ symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C₂ symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π-π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans-N,N'-(1,2-diphenyl-1,2-ethanediyl)bis-acetamide, which had an excellent separation factor on the C₂ symmetric chiral stationary phase, was investigated by ¹ H-NMR spectroscopy and 2D ¹ H-¹ H nuclear overhauser enhancement spectroscopy.