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

Abstract

Abstract An efficient NaNO 2 /I 2 ‐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 NaNO 2 to the MBH acetate furnishes the allylnitro intermediate which undergoes I 2 ‐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 S N Ar reactions and hydrogenolysis allows access to useful products.