Pillararene-Catalyzed Kemp Elimination: High Efficiency through Orthogonal Self-Sorting Binding and Ion Modulation

Enhancing the efficiency and versatility of supramolecular catalysis remains a central research goal. Water-soluble pillar[6]arenes (H1), per-substituted with quaternary ammonium groups, catalyze the aqueous-phase Kemp elimination of 1,2-benzisoxazole (R1), achieving <i>k</i>_cat/<i>k</i>_uncat ratio up to 1.5 × 10⁵ at pH 8, surpassing previously reported macrocycles for the reaction and rivaling the remarkable rate enhancements (up to 2 × 10⁵-fold) of coordination cages. Orthogonal self-sorting binding enables R1 to anchor in the hydrophobic cavity while OH^- enriches at the positively charged portals, facilitating substrate preorganization and enrichment. Ions, including OH^-, selectively weaken the binding of the anionic product while strengthening substrate R1 association, mitigating product inhibition and boosting turnover. Robust catalysis at pH 6-7 and recyclability provide a sustainable, enzyme-mimetic catalytic strategy.