Methylene-Bridged Chiral BINOL Macrocycle for Molecular Recognition in Water

Abstract Efficient synthesis of chiral macrocycles with strong aqueous recognition remains challenging. Here we report C[2]B[4]N, an eight-naphthalene macrocycle requiring only two enantiopure BINOL units, with the remaining junctions formed by methylene bridges. Friedel–Crafts macrocyclization afforded the protected ring in 52% yield on a gram scale. Its water-soluble derivative binds diverse guests with association constants up to 4.9 × 108 M–1 and differentiates enantiomers by up to 4.7-fold, providing an accessible platform for aqueous chiral recognition.