A Recyclable Thermoresponsive Catalyst for Highly Asymmetric Henry Reactions in Water

The synthesis of enantiomerically pure chiral β-nitroalcohols is a crucial objective in asymmetric catalysis. In order to efficiently obtain such chiral products, we developed a series of thermoresponsive, oxazoline–copper catalysts (CuII-PNxFeyOz) via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. These catalysts can self-assemble in water into single-chain nanoparticles (SCNPs) with biomimetic behavior, in which intramolecular hydrophobic and metal-coordination interactions generate a confined hydrophobic cavity. Comprehensive characterization by FT-IR, TEM, DLS, CD, CA, and ICP analysis confirmed the nanostructure and composition. When applied to the aqueous-phase asymmetric Henry reaction between nitromethane and 4-nitrobenzaldehyde, the optimal catalyst (2.0 mol%) achieved a quantitative yield (96%) with excellent enantioselectivity (up to 99%) within 12 h. Furthermore, the thermosensitive poly(N-isopropylacrylamide, NIPAAm) block enabled facile catalyst recovery through temperature-induced precipitation above its lower critical solution temperature (LCST). This work presents an efficient and recyclable biomimetic catalytic system, offering a novel strategy for designing sustainable chiral catalysts for green organic synthesis.