Oxazoles with acetylenic esters

A variety of substituents—including alkyl, alkenyl, cyano, acetyl, and alkoxy— is tolerated at the 2 and 5 positions of the oxazole ring for these cycloadditions. Acetylenic dienophiles with alkyl, trialkylsilyl, phenyl, ester, ketone, and acetal substituents, as well as terminal alkynes, are precedented. Ab initio calculations predict a slightly higher activation energy for the cycloaddition of oxazole with acetylene compared to the oxazole-ethylene reaction. ... 

Huisgen s group488 have described a new synthesis of pyrroles (26) from oxazol-5-ones (azlactones) (25) with DMAD and MP. The pyrrole derivatives formed in situ from 2,4-dimethyl- and 4-benzyl-2-methyloxazolone with DMAD underwent nucleophilic addition to a second mole of the acetylenic ester to give the Michael adducts 27 and 28... 

The Diels-Alder reaction of oxazoles with alkynes has become a preferred method for the synthesis of substituted furans with diverse applications. A large number of early examples of this reaction have been tabulated. Activated dienophiles such as acetylenic ketones and esters can be used, although unactivated alkyl, aryl, and silyl alkynes have been used as well. In particular, the reaction of 4-phenyloxazole with substituted acetylenes is frequently used for preparing 3,4-disubstimted furans. Cycloadducts derived from 4-phenyloxazole typically decompose under milder conditions than 4-alkyloxazoles, allowing the synthesis of a wider range of functionalized furans. Several examples are shown below. 

The reverse reactions of Diels-Alder reactions for thermal dissociations of cycloadducts in to dienes and dienophiles at higher temperatures or in the presence of Lewis acid or base are known as the retro-Diels-Alder (rDA) reactions. These reactions in most cases proceed in a concerted process. These reactions are often used for separation of diene or dienophile from their mixture with other compounds. Proper selection of conditions of these reactions provides new dienes and dienophiles, which are important synthons for synthesis of several bioactive natural products and organic molecules of complex structures. For example, the D-A adduct of 4-phenyl oxazole 110 with methyl acetylene dicarboxylate, on retro-D-A reaction gives new compounds, benzonitrile, and furan 3,4-dicarboxylic acid methyl ester 111 [65]. 

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