posted on 2019-11-07, 18:05authored byAnna V. Serebryannikova, Ekaterina E. Galenko, Mikhail S. Novikov, Alexander F. Khlebnikov
The first synthesis
of isoxazole-4-carboxylic acid derivatives
by domino isoxazole-isoxazole isomerization is reported. Fe(II)-catalyzed
isomerization of 4-acyl-5-methoxy-/5-aminoisoxazoles (dioxane, 105
°C) leads to the formation of isoxazole-4-carboxylic esters and
amides in good yields. 4-Formyl-5-methoxyisoxazoles give methyl oxazole-4-carboxylates
under the same reaction conditions. Fe(II)-catalyzed isomerization
of 4-acyl-5-methoxyisoxazoles under milder conditions (MeCN, 50 °C)
allows the preparation of transient 2-acyl-2-(methoxycarbonyl)-2H-azirines. The azirines isomerize quantitatively either
into isoxazoles under catalytic conditions (dioxane, 105 °C)
or into oxazoles under noncatalytic thermolysis (o-dichlorobenzene, 170 °C). The mechanism of the isomerization
and dependence of the reaction routes on substituents at starting
isoxazole core and reaction conditions are discussed on the basis
of DFT calculations.