Tailored Catalysts Based on Polymers of Intrinsic Microporosity for Asymmetric Aza-Henry Reaction of Pyrazolinone Ketimines in Batch and Flow

Abstract

We report the design and application of heterogeneous organocatalysts based on polymers of intrinsic microporosity (PIMs) for the asymmetric aza-Henry reaction of N-Boc-protected pyrazolinone ketimines with nitromethane. Two copolymers (PIM-10 and PIM-20) incorporating a flexible isatin-derived monomer were synthesized and postfunctionalized with a quinine-derived thiourea. The resulting materials, PIM-10-TU and PIM-20-TU, exhibited high thermal stability, tailored porosity, and effective enantioselective catalytic performance in batch- and continuous-flow conditions. PIM-10-TU showed superior activity and recyclability, achieving full conversion in 2–4 h and affording β-nitroamine derivatives in up to 87% yield and 85:15 er. Flow experiments enabled gram-scale synthesis with short residence times and a sustained efficiency. The synthetic utility of the chiral aminopyrazolones was demonstrated via derivatization to ureas and thioureas without erosion of the enantiopurity. This study highlights the potential of PIM-supported organocatalysts as robust and recyclable platforms for asymmetric synthesis under sustainable conditions.