Multicomponent Synthesis of Oxazoles and Furopyrrolones

Significance

A three-component synthesis of 5-methoxyoxazoles from aldehydes, amines and methyl α-isocyanoacetates is reported. The nitro group in the α-isocyanophenylacetate is essential for the transformation; otherwise, an imidazole product is formed (R. V. A. Orru and co-workers Org. Lett. 2003, 5, 3759). The reaction is proposed to proceed by formation of nitrilium intermediate B from the reaction of the iminium species A with the enolate C, which, upon cyclization, leads to the oxazole product. Interestingly, a fourth component may be incorporated by treatment of the unisolated isoxazole with 3-arylprop-2-ynoyl chlorides to construct furopyrrolones via acylation followed by an intramolecular Diels-­Alder and retro-Diels-Alder sequence.