Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO₂ for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes

A novel CCOF core–shell composite material (S)-DTP-COF@SiO₂ was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO₂ was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO₂ (CC-MP CCTF@SiO₂ and MDI-β-CD-modified COF@SiO₂)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO₂ column, and MDI-β-CD-modified COF@SiO₂ column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO₂-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core–shell composite (S)-DTP-COF@SiO₂ exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.