Synthesis of 3,4,5-Trisubstituted Isoxazoles from Morita-Baylis-Hillman Acetates by an NaNO 2 /I 2 -Mediated Domino Reaction

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.