Preparation of Novel Chiral Stationary Phases Based on the Chiral Porous Organic Cage by Thiol-ene Click Chemistry for Enantioseparation in HPLC

Porous organic cages (POCs) are an emerging class of porous materials that have aroused considerable research interest because of their unique characteristics, including good solubility and a well-defined intrinsic cavity. However, there have so far beenno reports of chiral POCs as chiral stationary phases (CSPs) forenantioseparation by high-performance liquid chromatography(HPLC). Herein, we report the first immobilization of a chiralPOC, NC1-R, on thiol-functionalized silica using a mild thiol-eneclick reaction to prepare novel CSPs for HPLC. Two CSPs (CSP-1and CSP-2) with different spacers have been prepared. CSP-1, witha cationic imidazolium spacer, exhibited excellent enantioselectivity for the resolution of various racemates. Twenty-three and 12racemic compounds or chiral drugs were well enantioseparated on the CSP-1-packed column under normal-phase and reversed-phase conditions, respectively, including alcohols, diols, esters, ethers, ketones, epoxides, organic acids, and amines. In contrast,chiral resolution using CSP-2 (without a cationic imidazolium spacer)-packed column B was inferior to that of column A,demonstrating the important role of the cationic imidazolium spacer for chiral separation. The chiral separation capability of columnA was also compared with that of two most popular commercial chiral columns, Chiralpak AD-H and Chiralcel OD-H, whichexhibits good chiral recognition complementarity with the two commercial chiral columns. In addition,five positional isomersdinitrobenzene, nitroaniline, chloroaniline, bromoaniline, and iodoaniline were also well separated on column A. The effects of temperature, mobile phase composition, and injected analyte mass for separation on column A were investigated. Column A also showed good stability and reproducibility after repeated injections. This work demonstrates that chiral POCs are promising chiral materials for HPLC enantioseparation

Automated summary

This study demonstrates the first immobilization of a chiral porous organic cage on thiol-functionalized silica to prepare novel chiral stationary phases for high-performance liquid chromatography. The prepared CSPs exhibited excellent enantioselectivity for the resolution of various racemates. The importance of the cationic imidazolium spacer for chiral separation was also demonstrated. The chiral POCs showed good chiral recognition complementarity with the two most popular commercial chiral columns.