Safe Cyano(nitro)methylating Reagent

4-Nitro-5(2H)-isoxazolone pyridinium salt (1), which has been developed by Nishiwaki et al., undergoes a ring opening reaction quantitatively under mild conditions upon treatment with a base and is converted to cyano-aci-nitroacetate 2, which works as a synthetic equivalent of nitroacetonitrile (NAN).¹⁾ 2 has high solubility in organic solvents whether polar or non-polar. Hence, it is useful as an easy-to-handle cyano(nitro)methylating reagent for synthesis of versatile polyfunctionalized compounds. For example, bifunctional pyridine 4, which possesses vicinally substituted nitro group and amino group, is formed when the Michael adduct 3, which is obtained by adding a vinyl ketone to generated 2, reacts with amines.²⁾ Furthermore, the syntheses of polyfunctionalized heterocyclic compounds such as isoxazolines, isoxazoles, dihydropyridines, and naphthyridines by using 2 have been reported, ^2-4) so that 1 is expected to be applied as a safe synthetic equivalent of NAN in the future.