Unveiling the Correlation between the Alkyl ChainLength of Amphiphiles in Chiral Supramolecular Nanocatalysts and Enantioselectivity

The correlation between the molecular structure of chiral amphiphiles and the enantioselectivity exhibited by their corresponding chiral supramolecular assemblies is a critical factor in enabling asymmetric catalysis. Herein, the self-assembly of l/d-phenylglycine-based amphiphiles (l/d-PhgC_<i>n</i>, <i>n</i> = 8, 12, 15, 16, 17, 18, and 20) with varying alkyl chain lengths into chiral supramolecular catalysts via Cu(II) coordination is reported, and their enantioselectivity in catalyzing the asymmetric Diels–Alder reaction is systematically investigated. Among the series, the l-PhgC₁₇-based supramolecular catalyst achieves exceptional enantioselectivity (96% <i>ee</i>), whereas analogs with shorter (<i>n</i> < 16) or longer (<i>n</i> > 18) alkyl chains display diminished selectivity or even racemic outcomes. Both experimental and computational analyses reveal that alkyl chain length governs the hierarchical organization of supramolecular nanostructures, which directly modulates the efficiency of chirality transfer between the aza-chalcone and the nanocatalysts. This structural regulation mechanism ultimately determines the enantioselectivity in the asymmetric Diels–Alder reaction. By establishing a clear structure–function relationship between the alkyl chain length of the amphiphiles and enantioselectivity in the supramolecular nanocatalyst systems, this work advances the rational engineering supramolecular chiral catalysts for high-performance enantioselective transformations.