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 kcat/kuncat 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.