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-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.