Oxazoles cycloadditions, forming furans

The bicyclic intermediate arising from Diels-Alder reaction of oxazoles with alkynes extrudes nitriles (comprised of the nitrogen atom and C4 of the oxazole) to form furans as the ultimate product of the cycloaddition. The same regioselectivity seen in alkene Diels-Alder reactions is noted here. 

Oxazole cycloadditions have been reported with alkyne dienophiles (tandem Diels-Alder addition and retro Diels-Alder loss of a nitrile leads on to furans), benzyne (the primary adduct can be isolated), and with typical alkene dienophiles. The primary adducts from addition of singlet oxygen rearrange, by a mechanism which is not definitely established, to form triamides, themselves useful synthetic intermediates. The only example of this sort of process with an imidazole is an intramolecular example, the product in this case being a pyr-role. ... 

Since perfluoroalkyl-substituted olefins and alkynes possess low-lying frontier orbitals, [4 + 2] cycloaddition reactions to oxazoles and thiazoles without strongly electron-donating substituents are unfavorable. On the other hand, five-membered heteroaromatic compounds possessing an electron-rich diene substructure, like furans, thiophenes, and pyrroles, should be able to add perfluoroalkyl-substituted olefins as well as alkynes in a normal Diels-Alder process. A reaction sequence consisting of a Diels-Alder reaction with perfluoroalkyl-substituted alkynes as dienophile, and a subsequent retro-Diels-Alder process of the cycloadduct initially formed, represents a preparatively valuable method for regioselective introduction of perfluoroalkyl groups into five-membered heteroaromatic systems. 

Diethylacetylene reacted with 4-phenyloxazole 55 in an autoclave for 3 days at 250°C to afford a 70% yield of 3,4-diethylfuran 124 (Fig. 3.35). This furan was then converted into the interesting tetraoxaporphyrin 125 in two steps. The novel diimidazole copper ligand 127 is formed in 84% yield by the cycloaddition of 4-phenyloxazole with the acetylenic diimidazole 126 at 185°C for 18 h (Fig. 3.36). An application of the oxazole-alkyne Diels-Alder reaction in natural product synthesis is exemplified by the construction of the maleic anhydride portion of the... 

A domino sequence comprising a cycloaddition and subsequent cycloreversion step can often find a more general application in organic synthesis, especially in the formation of aromatic compounds such as furans or pyrroles. Oxazole moieties as electron-deficient dienes often serve as the crucial reactive centers which cycloadd to a triple bond and eliminate a nitrile upon cycloreversion. If the first step is intramolecular, the impelling enthalpy preserved in the stability of the formed CN function is additionally accompanied by a positive entropy when the nitrile, sometimes volatile, leaves the substrate. In an older example from 1984 [10], Jacobi and coworkers devised a scheme for the preparation of a highly substituted furan on their synthetic way to paniculide A. An intramolecular Diels-Alder reaction was followed by the critical extrusion of volatile acetonitrile, furnishing the bicycle 8 in 94% yield (Scheme 6.2). 

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