5 -Oxazolones with dipolarophiles

Phosphites and 2,2-bis(trifluoromethyl)-5(2//)-oxazolone 71 react with elimination of carbon dioxide to give 2-aza-4-phospha-l,l-bis(trifluoromethyl)-l,3-butadiene 72 that can be used as a synthon for the previously unknown hydrogen-substituted nitrile ylide 72a in [3 + 2]-cycloaddition reactions. Examples of cycloadditions of 72a with dipolarophiles to give heterocyclic compounds 12t-ll are shown in Scheme 7.18. 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

Although in most cyclization reactions the 5(4//)-oxazolones react as 1,3-dipolar reactants (azo-methine ylides) through the mesoionic tautomers, they serve as dipolarophiles with nitrile imines <92H(34)315>. The nitrile imines, generated by the thermal decomposition of tetrazoles (82), add across the 2,3 double bond to generate triazoles (83) after further reaction (Scheme 26). Since the 5(4//)-oxazolones with a hydrogen at position 4 are in equilibrium with the 5(2//)-oxazolones under the reaction conditions, the addition of the nitrile imine also occurs across the 3,4-double bond of these compounds to afford an isomeric triazole (84). Pyrazines (85), which are products of the thermal decomposition of 5(4 0 Oxazolones <76HCA2149>, as well as diarylethylenes (86), are also formed. 

Acetyl-2(3//)-oxazolone 84 serves as a good 1,3-dipolarophile in the [3+2] cycloaddition to A-alkyl-a-phenylnitrones 239, giving a mixture of the four possible isomers 240-243, but with the predominant formation of the exo-syn adduct 240 (Fig. 5.59). Diastereoselective cycloadditions proceed when mixtures of optically active 3-(2-exo-alkoxy-l-apocamphanecarbonyl)-2(3/7)-oxazolones and A-benzyl- and A-ferf-butyl-a-phenylnitrones are heated at 110 °C ... 

The thermolysis of 4-(alkylthio or arylthio)-5(277)-oxazolones 57 in the presence of dipolarophiles with activated double bonds leads to hve-membered cycloadducts. 

TABLE 7.27. SUBSTITUTED PYRROLES VIA CYCLOADDITION OF DIPOLAROPHILES WITH MUNCHNONES PREPARED FROM SATURATED 5(4/ )-OXAZOLONES... 

During the last two decades, the importance of the dipolarophilic nature of unsaturated 5(4/l/)-oxazolones has been widely recognized and studied with a variety of 1,3-dipoles. Among the systems studied, diazoalkanes, particularly diazomethane, are the most frequently used and have opened the way for the synthesis of aminocyclopropanecarboxyhc acid derivatives. 

Cycloadditions were found to be first-order reactions with respect to both 1,3-dipole and dipolarophile, in all cases so far investigated. There are some limits to kinetic studies of these reactions, as many 1,3-dipoles are very reactive substances. While aryl azides, diazoalkanes, some classes of azomethine imines (for instance sydnones), and some classes of azomethine oxides (nitrones) are stable and isolable, azomethine ylides are usually unstable, an exception being represented by a mesoionic oxazolone that has been used for kinetic investigations benzonitrile oxide has a very limited stability, although some substituted derivatives are stable for long periods nitrile imines are not commonly isolable because of their strong tendency to dimerise. 1,3-Dipoles of... 

The 1,3-dipolar cycloaddition of acetylenes and alkenes with oxazolones is widely used for the construction of the pyrrole ring. The presence of a CFs-group in the 1,3-dipolar component opens a pathway to 2-CF3-pyrroles, while the application of trifluoromethylated dipolarophiles provides 3-CF3-pyiroles. For example, the dimethyl pyrroledicarboxylate 120 was synthesized in 78 % yield by the reaction of the CFs-containing oxazolone 118, prepared from proline 117 and trifluoroacetic anhydride (TFAA), with dimethyl acetylene dicarboxylate (DMAD) [53]. 

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