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

Abstract

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 1H‐NMR spectroscopy and 2D 1H‐1H nuclear overhauser enhancement spectroscopy.

Amino alcohol‐derived chiral stationary phases

“…45,46,[106][107][108][109][110][111][112][113][114][115] Such symmetric molecules have been developed as CSPs and used in the chiral separation. [116][117][118][119][120][121][122] Recently, our laboratory has developed amino alcohol-based symmetric CSPs and examined their chiral separation performance. [123][124][125] The synthesized symmetric CSPs were Pirkle-type, which has a π-acidic or π-basic group, and a non-Pirkle-type.…”

“…Symmetric chiral molecules have been widely used as chiral catalysts in the field of asymmetric organic synthesis and for the preparation of chiral discriminating reagents 45,46,106–115 . Such symmetric molecules have been developed as CSPs and used in the chiral separation 116–122 . Recently, our laboratory has developed amino alcohol‐based symmetric CSPs and examined their chiral separation performance 123–125 .…”