Synthesis of 3-Nitroisoxazoles via Copper Acetate-Mediated Reaction of Benzaldehydes with Nitromethane

A copper acetate-mediated reaction of benzaldehydes with nitromethane to synthesis of 3-nitroisoxazoles is reported. A variety of nitro-aryl-disubstituted isoxazole derivatives can be prepared in moderate to good yields with benign functional group tolerance. This protocol is successfully applied in gram-scale reaction. Preliminary mechanistic studies reveal that the aldehyde provided one carbon atom for the isoxazole ring, and nitromethane provided two carbon atoms and one nitrogen atom for the isoxazole ring. In this protocol, the C-O-N unit in the final isoxazole ring is formed from the rearrangement of nitromethane.