• • Cascade Sonogashira-Hagihara coupling and Friedel-Crafts alkylation yields a 400-fold increase in specific surface area, enabling interconnected porous networks that boost mass transport and overcome the selectivity-permeability trade-off.
• • Size-matching effect: matched molecular dimensions achieve 97% enantioselectivity, while mismatch drops selectivity to 9%, as demonstrated across four chiral molecules, underscoring the critical role of pore architecture.
• • Naproxen flux reaches 37 mmol m−2 h−1, surpassing literature values, indicating superior permeability for scalable pharmaceutical enantioseparation.
• • First membrane-based separation of Raceanisodamine achieves 89% selectivity for the 6S, 2′S and 6R, 2′R-isomer after cascade enrichment, expanding the applicability to complex chiral drugs.