Engineering Thiol–Ene Click Chemistry for the Fabrication of Novel Structurally Well-Defined Multifunctional Cyclodextrin Separation Materials for Enhanced Enantioseparation

Abstract

The preparation of two novel multifunctional cyclodextrin (CD) separation materials and their ultimate enantioseparation performances in high performance liquid chromatography are reported. A mild thiol-ene click reaction was used to anchor 1-allylimidazolium-per(p-methyl)phenylcarbamoylated-β-CD and 1-allylimidazolium-per(p-chloride)phenylcarbamoylated-β-CD onto thiol-modified porous silica giving structurally well-defined stable cationic multifunctional CD chiral stationary phases (CSP1 and CSP2 respectively). These covalently bonded CD phases have typical interaction modes such as H-bonding, π-π effect, electrostatic and dipole-dipole interactions as well as steric effects which result in superior chiral resolution for a variety of chiral compounds in different separation modes. In a reverse-phase mode, both CSPs exhibited excellent separation abilities for isoxazolines, flavonoids, β-blockers, and some other neutral and basic racemates. In a polar-organic mode, isoxazolines and flavonoids were well resolved. CSP1 with an electron-rich phenyl substitution on the CD rims gave a better resolution for isoxazolines whereas CSP2 with an electron-deficient phenyl substitution on the CD rims gave better resolution for flavonoids. Among isoxazolines, 4ClPh-OPr gained a high selectivity and resolution up to 18.6 and 38.7, respectively, which is an amazing result for CD enantioseparation materials.