The unique features of uniform and adjustable cavities, abundant chiral active sites, and high enantioselectivity make chiral metal‐organic frameworks popular as an emerging candidate for enantioselective separation. However, the wide particle size distribution and irregular shape of as‐synthesized metal–organic frameworks result in low column efficiency, undesired chromatographic peak shape, and high column backpressure of such metal–organic frameworks packed columns. Herein, we report the fabrication of chiral core‐shell microspheres [Cu2(d‐Cam)2(4,4′‐bpy)]n@SiO2 composite for high‐performance liquid chromatography enantioseparation to overcome the above‐mentioned problems. The [Cu2(d‐Cam)2(4,4′‐bpy)]n@SiO2 packed column gave high‐resolution separation of racemates under low column backpressure (10‐22 bar), indicating its synergistic effect of the good column packing property of the SiO2 microspheres and the chiral recognition ability of [Cu2(d‐Cam)2(4,4′‐bpy)]n crystals. Thirteen kinds of chiral compounds including alcohols, amines, ketones, epoxides, and organic bases were well separated with good peak shapes and high column efficiency (18200 plates/m for 1‐(9‐anthryl)‐2,2,2‐trifluoroethanol) on the [Cu2(d‐Cam)2(4,4′‐bpy)]n@SiO2 packed column. Among them, seven pairs of enantiomers achieved baseline separation and the resolution value for 1‐(9‐anthryl)‐2,2,2‐trifluoroethanol reached 11.22. Some effects such as column temperature, and analytes mass on the enantioseparations have been investigated. In addition, the [Cu2(d‐Cam)2(4,4′‐bpy)]n@SiO2 packed column exhibited good stability and repeatability for the separation of chiral compounds. The relative standard deviations for five replicate separations of 1‐phenylethanol were less than 1.0, 1.5, 3.0, and 2.0% for the retention time, peak area, number of theoretical plates, and resolution, respectively. The research results demonstrated the development of chiral metal–organic frameworks core‐shell microspheres composite provide a promising platform for their practical application in chiral separation fields.

Chiral metal-organic frameworks have shown great potential in enantioselective separation and asymmetric catalysis due to their diverse and adjustable structures with abundant chiral recognition sites. Herein, a new chiral post-synthetic modification was used for preparing an achiral@chiral metal-organic frameworks core-shell composite [Cu 3 (Btc) 2 ]@[Cu 2 ((+)-Cam) 2 Dabco] by a superficial chiral etching method. The [Cu 3 (Btc) 2 ]@[Cu 2 ((+)-Cam) 2 Dabco] composite was utilized as a novel chiral stationary phase for HPLC enantioseparation. Various racemates were separated on the [Cu 3 (Btc) 2 ]@[Cu 2 ((+)-Cam) 2 Dabco]-packed column (column A). It exhibited good chiral resolving ability toward many different kinds of racemates, especially chiral drugs. Among them, the highest resolution value for 1,2-diphenyl-1,2-ethanediol reaches 2.70. The relative standard deviations of retention time and peak area for repeated separation of 1,2-diphenyl-1,2-ethanol were 0.45% and 0.81%, respectively. Compared with the resolution ability of [Cu 2 ((+)-Cam) 2 Dabco]-packed column (column B), column A shows higher column efficiency and better separation performance than those of column B. The results indicated that the [Cu 3 (Btc) 2 ]@[Cu 2 ((+)-Cam) 2 Dabco] as a stationary phase can greatly improve the column efficiency and chiral resolution ability of chiral metal-organic frameworks, which demonstrated that the superficial chiral etching as an economic and efficient strategy opens up a new way for the application of metal-organic frameworks.