Synthesis of Functionalized 3-Cyanoisoxazoles Using a Dianionic Reagent

5 years ago

Synthesis of Functionalized 3-Cyanoisoxazoles Using a Dianionic Reagent

Nagatoshi Nishiwaki, Kento Iwai, Haruyasu Asahara

A series of 5-acylated 3-cyanoisoxazoles were efficiently synthesized by the Michael addition of dianionic cyano-aci-nitroacetate to α-chloro-α,β-unsaturated ketones followed by intramolecular nucleophilic substitution of the nitronate ion intermediate. In this process, the dianionic reagent serves as the safe synthetic equivalent of the explosive nitroacetonitrile. The 3-cyano group is sufficiently reactive toward ethanolysis and 1,3-dipolar cycloaddition with an azide to afford ethyl ester and tetrazole, respectively. A pyridine ring between the 5-acyl and the 4-aryl group was also constructed. This led to the formation of the isoxazolo[5,4-c]quinoline derivative.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00811

DOI: 10.1021/acs.joc.7b00811