Ultrasound-generated cyclodextrin–amino acid inclusion complex with NH3+-mediated chalcone activation: metal-free catalysis surpassing nanoparticles

Abstract

Efficient cycloaddition of chalcones remains challenging due to extensive π-delocalization and steric shielding of the α,β-unsaturated carbonyl unit, which limit classical Lewis-acid activation strategies. Here, we report a metal-free supramolecular organocatalytic platform that enables selective chalcone activation through noncovalent Lewis-acidic interactions. The catalyst comprises NH₃⁺-bearing amino acids embedded within cyclodextrin inclusion complexes, assembled via ultrasound energy. Mechanistically, directional N–H⋯O hydrogen bonding and localized electrostatic polarization activate the chalcone carbonyl, while cyclodextrin-mediated confinement enforces productive orientation and transition-state stabilization. This compact activation mode overcomes steric constraints imposed by bulky aromatic substituents, delivering cycloaddition reactions with enhanced activity providing the yields up to 97% under mild conditions in ethanol. The system outperforms conventional metal nanoparticle-based catalysts, preserves substrate integrity, and exhibits broad functional-group tolerance. This work establishes a generalizable, sustainable paradigm for chalcone cycloaddition catalysis by synergistically integrating organocatalytic Lewis acidity with supramolecular confinement.