Résumé
We report the structural optimization of ATC-based foldamer catalysts for the enantioselective nitro-Michael addition of ketones to nitro-olefins. Building on our previous work with heteroaromatic γ-peptides, we investigated the influence of the spatial arrangement and flexibility around the catalytic site. A series of modified sequences were designed to finetune transition state preorganization while revisiting the contribution of an intramolecular proton donor function in ATC catalysts. These modifications led to enhanced catalytic performance, with faster reaction rates and improved enantioselectivities under optimized conditions.