The utilization of stimuli-responsive hydrogels as bifunctional catalysts for an aqueous sequential natural transformation to arrange chiral natural molecules is just not solely environmentally pleasant but additionally enhances the artificial limitations of mutually contradictory multistep reactions. Nonetheless, discovering an answer to the incompatible conflicts arising from sophisticated multicomponent cross-interactions in sequential transformations presents a big problem. To handle this situation, we’ve got developed a core-shell-structured hydrogel as a site-isolated bifunctional catalyst. This catalyst encompasses a thermoresponsive poly(N-isopropylmethacrylamide) as a switching operate by way of a reversible transition between its hydrogel and resolution phases that completely matches a temperature-tuned base-catalyzed Aldol condensation/oxa-Michael addition at 70 °C and the ruthenium-catalyzed dynamic kinetic decision uneven switch hydrogenation (DKR-ATH) course of at 40 °C. As we envision, by way of the harmonization of the conflicting sequential reactions, this Aldol condensation/oxa-Michael addition/DKR-ATH cascade course of might be achieved by transitioning from incompatibility to compatibility, enabling direct entry to chiral chromanols with 1.3-position twin stereocenters from commercially accessible orth–hydroxyl arylketones and aldehydes. Mechanistic investigations, which contain monitoring the cascade response and analyzing the deuterium-labeling experiments, reveal a domino-like Aldol condensation/oxa-Michael addition/DKR-ATH sequential route comprising an preliminary Aldol condensation/oxa-Michael addition adopted by the following DKR-ATH course of.