Oxazoles heterodienophiles

TABLE 3.4. INTERMOLECULAR OXAZOLE-HETERODIENOPHILE DIELS-ALDER REACTIONS... 

Intermolecular oxazole-heterodienophile reactions are summarized in Table 3.4, p. 461. 

Diels-Alder reactions of oxazoles afford useful syntheses of pyridines (Scheme 53) (74AHC( 17)99). A study of the effect of substituents on the Diels-Alder reactivity of oxazoles has indicated that rates decrease with the following substituents alkoxy > alkyl > acyl >> phenyl. The failure of 2- and 5-phenyl-substituted oxazoles to react with heterodienophiles is probably due to steric crowding. In certain cases, bicyclic adducts of type (359) have been isolated and even studied by an X-ray method (87BCJ432) they can also decompose to yield furans (Scheme 54). With benzyne, generated at 0°C from 1-aminobenzotriazole and lead tetraacetate under dilute conditions, oxazoles form cycloadducts (e.g. 360) in essentially quantitative yield (90JOC929). They can be handled at room temperature and are decomposed at elevated temperatures to isobenzofuran. 

There have been reports on the reaction of oxazoles with heterodienophiles, including N=N, C=N, C=0, and types, to give new heterocycles <89X3535, 88JOO 663>. In most cases, the products may be envisioned to arise from ring opening and rearrangement of Diels-Alder adducts followed by reclosure, but so far no proof of this mechanism has appeared. A reaction of 5-ethoxy-... 

Hassner and Fischer " also studied the intramolecular bis-heteroannulation of oxazoles tethered to a variety of heterodienophiles. The azo-compounds 258 n = 3 ), prepared in situ via (diacetoxyiodo)benzene oxidation of the corresponding hydrazide in refluxing benzene, gave a 40% yield of 259 (n = 1-2) (Fig. 3.76). 

Several heterodienes and heterodienophiles are used in hetero-Diels-Alder reactions in the synthesis of heterocyclic compounds. For example, aza-butadiene 81 and 81a and oxazoles 82 and 83 are used as heterodienes for synthesis of heterocycles. 

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