Enantiopure‐Grafted Metal–Organic Framework for the Separation of the Enantiomers of Baclofen

Chiral separation via adsorption is a rapid, energy-efficient method for obtaining enantiopure compounds, essential in pharmaceuticals and fine chemicals. Homochiral metal-organic frameworks (HMOFs) have emerged as promising adsorbents due to their tunable chirality and porosity. Herein, a sustainable (water-based), activation-free post-synthetic modification strategy for grafting enantiopure agents onto MOF-808 via aqueous anion exchange to construct HMOFs is reported. Using naturally occurring L-malic acid (MA), labile acetates on the Zr₆ nodes of MOF-808 are fully substituted under mild conditions without the need for thermal activation of the as-synthesized MOF, yielding robust chiral frameworks. The MA-grafted HMOF demonstrates efficient enantioselective adsorption of R-baclofen, a clinically relevant drug, from racemic baclofen solution, achieving enantiomeric excesses of up to 91.0%. This work highlights a practical, scalable, and environmentally benign approach to constructing chiral porous materials under green conditions and provides insight into optimizing chiral site density for enhanced enantiomeric resolution.