Design and application of l-isoleucine-derived helical polyisocyanide catalyst for asymmetric aldol and oxa-Michael–aldol cascade reactions

Abstract

This study designed and synthesized a chiral helical polyisocyanide-supported catalyst, poly-1_m, derived from natural L-isoleucine. Through alkyne-Pd(II)-initiated polymerization of isocyanide-functionalized L-isoleucine monomers, a heterogeneous catalytic system with a rigid helical backbone and steric hindrance effects was successfully constructed. Systematic optimization revealed saturated brine as the optimal solvent for asymmetric aldol reactions, achieving 67.9% enantiomeric excess (ee) for cyclohexanone/4-nitrobenzaldehyde (76% yield, 6 days) and an exceptional 99.8% ee for cyclopentanone/4-nitrobenzaldehyde (80% yield). The catalyst retained >98% ee over three recycling cycles without significant degradation. Furthermore, in the oxa-Michael–aldol cascade reaction, poly-1₂₀₀ achieved 81.8% ee in tetrahydrofuran with p-toluenesulfonic acid as a additive. This work provides a novel strategy for designing green and recyclable chiral catalysts while expanding the application potential of natural amino acids in asymmetric catalysis.