Primary nitro compounds: progress in the synthesis of isoxazoles by condensation with aldehydes or activated ketones

Among the known strategies directed towards the synthesis of isoxazole derivatives, the reactions of aldehydes with primary nitro compounds deserve a comprehensive treatment, including the historical development as well as the more recent applications. The reactions of aldehydes with primary nitro compounds in a 1 : 2 molar ratio have been shown to lead to isoxazoline-N-oxides or isoxazole derivatives, via β-dinitro derivatives. Several modifications of the process allowed the formation of products bearing substituents at various positions of the heterocyclic ring with control of regioselectivity. Ketones are reported to react with primary nitro compounds, only if activated (β-diketones, α-nitroketones, or strained ketones), to give isoxazole derivatives. Symmetric 2,4-dinitroglutarates formed from aromatic aldehydes and nitroacetate undergo ring closure to form isoxazole derivatives or, according to reaction conditions, 5-hydroxy-6-oxo-4-aryl-6H-1,2-oxazine-3-carboxylates ("oxazinones"), by loss of alcohol instead of water. Isoxazole-4-carbaldehydes are obtained by the reaction of 3-oxetanone with primary nitro compounds.