Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO2/I2‐Mediated Domino Reaction

Abstract

AbstractAn efficient NaNO2/I2‐mediated one‐pot transformation of Morita–Baylis–Hillman (MBH) acetates into alkyl 3‐nitro‐5‐(aryl/alkyl)isoxazole‐4‐carboxylates is described. In a cascade event, initial Michael addition of NaNO2 to the MBH acetate furnishes the allylnitro intermediate which undergoes I2‐catalyzed oxidative α‐CH nitration of the nitromethyl subunit followed by [3+2] cycloaddition to afford the title compounds. Structural elaborations of these highly substituted isoxazoles by SNAr reactions and hydrogenolysis allows access to useful products.