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

Abstract 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.