Knoevenagel condensation of aromatic aldehydes with active methylene compounds catalyzed by lipoprotein lipase

• A green and efficient enzymatic method for Knoevenagel condensation was developed.
• Products were obtained in good to excellent yields in short reaction times.
• Only Z-isomers were obtained under our reaction conditions.

A screening of using different lipases to catalyze the Knoevenagel reaction was realized, and lipase lipoprotein (LPL) from Aspergillus niger showed the best catalytic performance. The reaction conditions including solvent, enzyme loading, and temperature were screened to improve the reaction efficiency. Various kinds of substrates were investigated, and almost all the target products were obtained in good to excellent yields (76–98%) with Z configuration exclusively. This procedure provides a novel, green and efficient method for the Knoevenagel condensation of aromatic aldehydes with active methylene compounds.