A recyclable copper catalyst with mPEG-supported chiral Schiff base ligands for the asymmetric Henry reaction and drug synthesis.

The asymmetric Henry reaction represents a powerful method for constructing chiral β-nitro alcohols; however, most existing catalytic systems suffer from poor recyclability, which limits their sustainable application. To address this challenge, based on the concept of green organocatalysis, this study is dedicated to developing a novel recyclable chiral catalytic system. A dual-core design strategy was adopted: (i) methoxy polyethylene glycol, which exhibits good biocompatibility, was selected as an environmentally friendly carrier; (ii) readily available L-tert-leucine was used as the precursor of the chiral catalytic center. A novel methoxy polyethylene glycol-supported chiral Schiff base ligand, L12, was successfully prepared. This ligand, in cooperation with copper acetate, facilitated the construction of a rationally designed catalytic system that exhibits remarkable activity for asymmetric Henry reactions. The system enables the efficient synthesis of various chiral β-nitro alcohols with considerable stereoselectivity. Notably, the catalytic system demonstrates satisfactory recyclability, further enhancing its practical value. Based on these performance advantages, the system shows significant application potential in the synthesis of chiral drug molecules and active intermediates. Overall, this work not only provides an efficient and recyclable protocol for the green synthesis of chiral β-nitro alcohols, but also offers a promising route for the sustainable preparation of key intermediates in chiral drug synthesis, highlighting its potential for industrial application.