Preparation of a Homochiral Porous Organic Cage RCC2-S-Bonded Silica as a Stationary Phase for High-Performance Liquid Chromatography Enantioseparation.

In this work, a reduced homochiral porous organic cage (RCC2-S)-based chiral stationary phase (CSP), RCC2-S@SiO2-SH, was prepared by bonding RCC2-S on thiolated silica (SiO2-SH) via a thiol-ene click reaction. The CSP (RCC2-S@SiO2-SH) showed excellent enantioseparation in both normal-phase HPLC (NP-HPLC) and reversed-phase HPLC (RP-HPLC) modes, effectively separating various chiral compounds, including alcohols, esters, ketones, amines, imidazoles, epoxides, and organic acids. As a result, 12 racemates were enantioseparated under NP-HPLC, and 17 racemates were enantioseparated under RP-HPLC. The CSP also exhibited good complementarity in chiral separation with commercial Chiralpak AD-H, Chiralcel OD-H, and the previously reported chiral POC CC19-R columns, successfully separating some racemates that remained unresolved or poorly resolved on these three columns. Additionally, the fabricated RCC2-S@SiO2-SH packed column demonstrated good reproducibility and stability. The relative standard deviations (RSDs) of retention time and resolution value were less than 0.5% and 1.5%, respectively, after the column had been subjected to hundreds of injections. This work indicates that chiral porous organic cages have great potential for the separation of enantiomers in HPLC.