3.4.5- trisubstituted-2 -oxazolones

The photocycloaddition of 3-acetyl-2(3//)-oxazolone 84 with 9,10-phenanthrene-quinone 244 gives the spirooxetane 245 regioselectively as a major cycloadduct. Irradiation of 3,4,5-trisubstituted-2(37/)-oxazolones 247 in the presence of 244 results in the predominant formation of dioxane derivatives 248. When duroquinone 249 is irradiated in the presence of the 3,4,5-trisubstituted-2(37/)-oxazolone 247a,... 

TABLE 7.17. SYNTHESIS OF SATURATED 2,4,4-TRISUBSTITUTED 5(4H)-OXAZOLONES VIA ALKYLATION OF SATURATED 5(4H)-OXAZOLONES AT C-4... 

The direct condensation of unsaturated oxazolones with tryptamine in hydrochloric acid is an important and interesting case that deserves special attention. The reaction occurs via in situ hydrolysis of the oxazolone to a keto acid followed by a Pictet-Spengler-like reaction with tryptamine. This protocol affords a tetrahydro-p-carboline wherein the oxazolone is the synthetic equivalent of an arylacetalde-hyde. The reaction has been extended to substituted tryptamines 500 thus, allowing access to 1,3,4-trisubstituted tetrahydro-p-carbolines 501 as shown in Scheme 7.159. Some of these compounds have shown promising central nervous system activity. 

The phenyl group of trisubstituted 4-benzylidene-5(4//)-oxazolones is nearly planar whereas the styryl moieties in (Z)-2-phenyl-4-(a-phenylethylidene)-5(4//)-oxazolone and fZ)-2-methyl-4-(a-phenylethylidene)-5(4//)-oxazolone show significant deviations from planarity. ... 

The primary site of electrophilic attack on 5(4//)-oxazolones is at position C-4. The oxazolones are activated by deprotonation. For example, a variety of 2,4-disubstituted-5(4.H)-oxazolones (80) react with l-fluoro-2,4-dinitrobenzene and sodium carbonate to give 2,4,4-trisubstituted products <88CB67>. When the products are refluxed in methanol containing a catalytic amount of p-toluene-sulfonic acid, they rearrange to 1-hydroxyindazoles (81) (Scheme 24). Apparently, under certain conditions the site of electrophilic attack may be diverted to the 2 position <93TL3907>. Methylene chloride solutions of a, -unsaturated aldehydes, ketones, and esters containing a catalytic amount... 

Equilibration of the Z-E isomers also occurs in acetonitrile.25 With 2-acetoxyphenylmethylene oxazolones, isomerization to the E isomer was observed.63 Isomerizations to benzamidocoumarin derivatives under photochemical conditions have also been reported 64,65 While the 2-oxazolin-5-ones are thermally stable, the introduction of a 4-acyl or aroyl group, a potential site for further reaction, markedly decreases the stability. Thus, when 2,4-dialkyl-4-aroyl-2-oxazolin-5-ones are heated to 180°, decarboxylation occurs readily with the formation of trisubstituted oxazoles in yields of 71-95%66 [Eq. (13)). 

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