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

Abstract

An 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 SN Ar reactions and hydrogenolysis allows access to useful products.