Nanocatalyst- CuFe₂O₄/Kaolin- promoted facile synthesis of 2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) derivatives

Nanocatalyst-catalyzed transformations in organic synthesis have recently attracted growing interest within the scientific community. Indeed, these catalytic nanomaterials offer the possibility of performing regio- and stereoselective conversions under mild operating conditions, while limiting the formation of undesirable by-products, which represents a major asset for the development of cleaner and more efficient processes. In this context, a simple, efficient, and eco-friendly synthetic method has been developed for the preparation of a series of 2,2'-arylmethylene dicyclohexane-1,3-dione derivatives, which are molecules of pharmacological interest. The reaction proceeds via a Knoevenagel–Michael cascade sequence involving various substituted aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione (dimedone), in the presence of CuFe₂O₄ supported on kaolin as a nanocatalyst. The operating conditions are remarkably mild: the reaction is carried out at room temperature and requires only a few minutes to reach complete conversion. This heterogeneous catalytic system offers the advantage of being readily recoverable by simple magnetic separation and can be reused over several cycles without significant loss of activity. Compared to conventional synthetic routes, which often rely on homogeneous catalysts, toxic organic solvents, and harsh conditions, our protocol provides major benefits, including a simplified work-up procedure (simple filtration and recrystallization), good to excellent yields (80–95%), excellent functional group compatibility, and a low environmental impact, thus fully aligning with the principles of sustainable chemistry.