Comparison of Substituting Ability of Nitronate versus Enolate for Direct Substitution of a Nitro Group

Abstract

α-Nitrocinnamate underwent the conjugate addition of an active methylene compound such as nitroacetate, 1,3-dicarbonyl compound, or α-nitroketone, and the following ring closure afforded functionalized heterocyclic frameworks. The reaction of cinnamate with nitroacetate occurs via nucleophilic substitution of a nitro group by the O-attack of the nitronate, which results in isoxazoline N-oxide. This protocol was applicable to 1,3-dicarbonyl compounds to afford dihydrofuran derivatives, including those derived from direct substitution of a nitro group caused by O-attack of enolate. It was found the reactivity was lowered by an electron-withdrawing group on the carbonyl moiety. When α-nitroketone was employed as a substrate, three kinds of products were possibly formed; of these, only isoxazoline N-oxide was identified. This result indicates that the substituting ability of nitronate is higher than that of enolate for the direct SN2 substitution of a nitro group.

A Walk through Recent Nitro Chemistry Advances

“…A carbon–carbon double bond is formed upon the elimination of a HNO 2 from nitroalkane, which was energetically studied by Ballini et al [ 12 , 31 ]. The combination of roles as an activator and as a leaving group enables the synthesis of polyfunctionalized compounds [ 32 , 33 ]. Furthermore, nitrobenzenes can be used as substrates for the transition-metal catalyzed cross-coupling, in which the nitro group is substituted with various nucleophiles [ 34 ].…”

Unusual Reactivities of ortho-Hydroxy-β-nitrostyrene

“…In addition, chemical conversion of the nitro group, such as reduction followed by diazotization and Sandmeyer reactions, facilitates the approach to versatile compounds from a nitro compound [ 10 , 11 ]. Furthermore, the leaving ability of a nitro group also plays an important role in organic synthesis [ 12 , 13 , 14 , 15 ]. Despite numerous reports, the chemistry of β-nitrostyrene is still a hot topic and is energetically studied.…”

The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study

“…Cyclic nitronates (1,2-oxazine- N -oxides 1 and isoxazoline- N -oxides 2 ) are useful intermediates in the synthesis of complex nitrogen containing scaffolds due to their versatile reactivity as 1,3-dipoles and accessibility from nitroalkenes ( Scheme 1 a) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Denmark’s group extensively exploited the inter- and intramolecular (3 + 2)-cycloaddition reactions with six-membered cyclic nitronates 1 to construct various bi- and polycyclic nitroso acetal frameworks 3 , which were then converted into fused pyrrolidine derivatives by an intramolecular reductive amination ( Scheme 1 b) [ 1 , 11 ].…”