Simple Access to Isoxazole-Containing Heterocyclic Hybrids: Isoxazole/Oxazole and Isoxazole/Pyridine

Abstract

The synthesis of substituted isoxazole–oxazole hybrids by the noncatalytic reaction of methyl 2-diazo-2-(alkyl/aryl/hetarylisoxazol-5-yl)acetates with alkyl and aryl cyanides has been reported. According to DFT calculations, the reaction proceeds through the intermediate formation of a nitrile ylide and its subsequent cyclization at the carbonyl oxygen. The reaction of acrylonitrile with methyl 2-diazo-2-(isoxazol-5-yl)acetate proceeds quite differently and leads to a mixture of the cis and trans isomers of cyclopropanes, which, according to DFT calculations, are formed by the cycloaddition of a diazo-derived carbene to the C=C bond of acrylonitrile. The hetero-Diels–Alder reaction of the 5-alkoxyoxazole moiety of isoxazole–oxazole hybrids makes it possible to obtain isoxazole–pyridine hybrids, albeit in low yield.