Adaptive Cinchona Alkaloid-Derived Organoboron Crystalline Sponges Enable Enantioseparation of Weakly Interacting Molecules

The enantioseparation of small, weakly interacting organic molecules remains a fundamental challenge, as they lack the functional groups required for efficient chiral recognition. Consequently, their enantiopure forms are typically accessed via asymmetric synthesis rather than resolution. Herein, we demonstrate that adaptive supramolecular crystalline sponges assembled from air- and moisture-stable cinchona alkaloid-derived organoboron complexes enable efficient enantiodiscrimination of small ethers, lactones, and cyclic ketones through guest inclusion within porous crystalline frameworks. Structural analysis reveals that enantioselectivity arises from adaptive confinement within homochiral cavities, where subtle framework rearrangements and modulation of cavity volume amplify cooperative weak host-guest interactions. Systematic tuning of the molecular building blocks affords crystalline sponges capable of resolving challenging substrates such as the biobased green solvent 2-methyltetrahydrofuran, γ-valerolactone, and methylcyclohexanone isomers with enantiomeric excesses of up to 76%. These findings establish adaptive confinement in supramolecular crystalline sponges as a general mechanism for chiral discrimination in the solid state and provide a conceptual framework for enantioseparation beyond conventional crystallization-based approaches.