Isoxazoles side-chain reactions

The nucleophilic substitution reactions are still more limited in scope owing to the instability of the isoxazole ring toward nucleophilic reagents. Homolytic reactions appear to be unknown though some of the reactions being studied are possibly of this type. Besides those reactions which are characteristic of the reactivity of the isoxazole nucleus itself, we shall consider in this section some substitution reactions in the side chain organomagnesium synthesis in the isoxazole series, condensation reactions of the methyl groups of methyl-isoxazoles, and finally some miscellaneous reactions. 

Reactions involving the introduction and substitution of functional groups in the side chain of isoxazole derivatives are of synthetic value and have been used to synthesize various substituted isoxazoles. 

Many of the reactions of functional groups attached to an isoxazole ring are unexceptional. This section is therefore confined to an account of two topics the first, rearrangements involving three-atom side chains, is of intrinsic interest, and the second, reactions proceeding via deprotonation at an a-carbon atom, is very useful in synthesis. 

Direct interaction of a nitro substituent with electron-rich and electron-poor side-chains in ort o-substituted nitroaromatic and nitro-heteroaromatic compounds is a well-documented and fruitful source of novel heterocycliza-tion reactions. In this context, efficient solution-phase pyrolytic transformations of 4-nitro-l//-imidazol-5-ylethano-ates 356 and 3-nitropyridinyl- and 5-nitropyrimidinyl-ethanoates 358 gave 3,4-fused isoxazoles 357 and 359, plausibly through ketene intermediates (Scheme 87) <2002ARK80>. 

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