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 Zr 6 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.