Shell cross-linked micelles (SCMs) containing acid sites in the shell and base sites in the core are prepared from amphiphilic poly(2-oxazoline) triblock copolymers. The materials are utilized as two-chamber nanoreactors for a prototypical acid− base bifunctional tandem deacetalization−nitroaldol reaction. The acid and base sites are localized in different regions of the micelle, allowing the two steps in the reaction sequence to largely proceed in separate compartments, akin to the compartmentalization that occurs in biological systems.

Cooperative catalysts combining weak acids and basic amines have been utilized to effectively catalyze aldol and related coupling reactions under mild conditions. Most cooperative chemical catalysts for the aldol reaction have been based on silica‐supported amines. In this work, an alternate approach is demonstrated whereby cooperative amine/acid interactions are tailored through the implementation of polymeric supports. By using linear poly(styrene) supports, this work demonstrates that the design and spacing of monomer units plays an essential role in the cooperativity of the acid–base sites in the aldol condensation. The monomer sequence of each polymer catalyst dramatically affects the catalytic activity, with a random copolymer displaying optimal cooperativity between the acid and base, and block copolymers drastically reducing catalyst activity. Trends established in the silica‐supported systems, such as use of stronger acid monomers demonstrating reduced activity, are verified and extended to these polymer‐supported systems. Overall, this first generation polymer‐supported system is not as efficient as the optimal silica‐supported catalysts developed over the last decade, with the polymers studied here being poorly soluble, leading to inefficient use of the amine sites.