Synthesis of Functionalized 3‑Cyanoisoxazoles Using a Dianionic Reagent

A series of 5-acylated 3-cyanoisoxazoles were efficiently synthesized by the Michael addition of dianionic cyano-<i>aci</i>-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-<i>c</i>]­quinoline derivative.