Asymmetric Aldol Reactions Catalyzed by Polymeric Self-Assembly with Side-Chain Dipeptide Pendants.

To explore the role of proline amide moieties in polymer-supported organocatalysts, side-chain l-proline-l-alanine (Pro-Ala) dipeptide-containing block copolymers were synthesized, and their catalytic potential for the aldol reaction was explored. The dipeptide monomer (Boc-Pro-Ala-HEMA) was polymerized to prepare block copolymers in the presence of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) () and hydrophobic poly(methyl methacrylate) () macro-chain transfer agents. Boc group expulsion from the block copolymers produced double hydrophilic () and amphiphilic () polymers. The solution behaviors of the polymers were studied by various physical techniques, which showed the formation of self-assembled aggregates of in water and ,-dimethylformamide (DMF)/water solvent mixtures. These polymers are used as organocatalysts during the aldol reaction of cyclohexanone and 4-nitrobenzaldehyde in different solvent polarities, catalyst loadings, temperatures, and reaction times. This work emphasizes superior catalytic activity of at lower catalyst loadings (5%) while maintaining high conversion (95%) and enantioselectivity (94%) across multiple recycling cycles in DMF/water at a 3:1 ratio (v/v).