5-alkoxy-2-methyloxazoles

The primary adducts (156) and (157) of oxazoles with alkenes and alkynes, respectively, are usually too unstable to be isolated. An exception is compound (158), obtained from 5-ethoxy-4-methyloxazole and 4,7-dihydro-l,3-dioxepin, which has been separated into its endo and exo components. If the dienophile is unsymmetrical the cycloaddition can take place in two senses. This is usually the case in the reactions of oxazoles with monosubstituted alkynes with alkenes on the other hand, regioselectivity is observed. Attempts to rationalize the orientation of the major adducts by the use of various MO indices, such as 7r-electron densities or localization energies and by Frontier MO theory (80KGS1255) have not been uniformly successful. A general rule for the reactions of alkyl- and alkoxy-substituted oxazoles is that in the adducts the more electronegative substituent R4 of the dienophile occupies the position shown in formula (156). The primary adducts undergo a spontaneous decomposition, whose outcome depends on the nature of the groups R and on whether alkenes or alkynes have been employed. 

Pathways C and D are less well documented, mainly because oxazoles lacking a 5-alkoxy substituent show reduced reactivity towards the usual dienophiles. An example of reaction C is the formation of 3-hydroxy-2-methylpyridine from 4-methyloxazole and acrylonitrile (equation 13). Dehydrogenation (path D) is rare but proceeds in the presence of a hydride acceptor. Thus 4-methyloxazole reacts with ethyl acrylate in the presence of hydrogen peroxide to give ethyl 3-hydroxy-2-methylpyridine-5-carboxylate in 27% yield (equation 14). 

Reaction of a 5-alkoxy-4-methyloxazole with nitroethylene in benzene at -4°, followed by acid hydrolysis, leads to the 3-nitropyrrole 3 (57%).2 1-Nitropropene similarly gave 2-acetyl-4-methyl-3-nitropyrrole (4).3 The initial Diels-Alder adduct under acidic conditions is transformed as in Scheme 2. 

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