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) ( PPEGMA ) and hydrophobic poly(methyl methacrylate) ( PMMA ) macro-chain transfer agents. Boc group expulsion from the block copolymers produced double hydrophilic PPEGMA- b -P(Pro-Ala-HEMA) ( 1b ) and amphiphilic PMMA- b -P(Pro-Ala-HEMA) ( 1c ) polymers. The solution behaviors of the polymers were studied by various physical techniques, which showed the formation of self-assembled aggregates of 1c in water and N , N -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 1c 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).