Pyrroles 5 -oxazolones

The reaction of 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

Alkyl(aryl)-2-(trifluoromethyl)-5(277)-oxazolones have been used as intermediates to prepare 2-(trifluoromethyl)pyrroles interesting compounds frequently used as insecticides and acaricides. The oxazolones react with electron-dehcient unsaturated compounds in the presence of a base. Reaction of 5(277)-oxazolones, usually with a substituted aryl ring at C-4, with a wide variety of alkynes and alkenes has given rise to numerous 2-(trifluoromethyl)pyrroles 56. For example,... 

TABLE 7.10. 2-(TRIFLUOROMETHYL)PYRROLES FROM REACTION OF 5(2/7)-OXAZOLONES WITH ELECTRON-DEFICIENT UNSATURATED COMPOUNDS... 

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. 

Munchnones 298 obtained in situ by N-alkylation of 5(4/f)-oxazolones undergo 1,3-dipolar cycloaddition with dimethyl acetylenedicarboxylate to give Al-alkylpyr-roles 299. 1,3-Dipolar cycloaddition of munchnones with triphenylvinylphos-phonium bromides affords tri- and tetrasubstituted pyrroles 300. In this case, the interaction of the phosphonium group with the carbonyl group leads to high levels of regioselectivity (Scheme 7.99 Table 7.27, Fig. 7.29). ... 

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

Finally, reaction of 2,4-diphenyl-5(4//)-oxazolone 322 with 4-phenyl-A -tosyl-1-azabuta-1,3-diene was found to be highly dependent on the experimental conditions. At room temperature the sole product was 323 that arises from alkylation of 322 by addition at the imine carbon. However, heating 322 and 4-phenyl-A-tosyl-1-azabuta-1,3-diene gave rise to several products including a 2-pyridone 324, 2,3,6-triphenylpyridine 325, and the pentasubstituted pyrroles 326 and 327. The authors postulated two different reaction mechanisms. Here, both a 1,3-dipolar cycloaddition of the oxazolone and a nucleophilic addition of the oxazolone are possible and that may account for the formation of 324—327. The marked differences in reactivity of 4-phenyl-A-tosyl-l-azabuta-l,3-diene relative to A-alkyl- or A-aryl-1-aza-1,3-dienes was attributed to the powerful electron-withdrawing nature of the tosyl group (Scheme 7.107). ... 

Dipolar cycloaddition of 4-arylmethyleneisoxazol-5-ones 794 and 2-methyl-4-phenyl-5(4//)-oxazolone 795 leads to pyrrole-3-carboxyhc acids that have been isolated as hydroxamates 796. The authors carried out this cycloaddition-nitrile oxide addition as a one-pot reaction (Scheme 7.243). ... 

A synthesis of the marine antibiotic from Pseudomonas bromoutilis has been achieved by 1,3-dipolar cycloaddition of the oxazolone (388) with diethyl acetylenedicarboxylate (73CI(L)275). Hydrolysis and decarboxylation gave the pyrrole (390), identical with a sample prepared previously by other workers, and converted by them to pentabromopseudilin (391 Scheme 85) (66JA4509). 

Some cycloadditions to azirines have been reviewed by Anderson and Hassner.27 Schmid et al. 28 photolyzed the arylazirine 1 in benzene in the presence of 2 equivalents of DM AD and obtained 40% of the pyrrole 3, a compound prepared previously by Huisgen et al.29 30 from oxazolones and sydnones with DMAD. Padwa and his co-workers have investigated the scope of these photoinduced cycloadditions to arylazirines. Irradiation of 1 in pentane for 3 hours in the presence of DMAD gave 95% of (3)31 the azomethine ylid 2 was postulated as an intermediate. 

Padwa and Hamilton examined other aziridines where the nitrogen was unsubstituted.43 44 cis-1,2-Diphenylaziridine (21) on refluxing with DMAD in benzene gave 85% of the adduct 22 DEAD was also used. tranj-2-Benzoyl-3-phenylaziridine (23) gave the pyrrole 24 with DMAD the latter was also synthesized from 4-benzyl-2-phenyl-5-oxazolone (26), via 25, which was oxidized with selenium dioxide to 24. 

Huisgen and co-workers486,490 have described a useful synthesis of N-substituted pyrroles (41) from mesoionic oxazolones (39) via the intermediates 40, which were not isolated. A variety of acetylenic esters (phenylpropiolic, propiolic, tetrolic, and DMAD) were used. The kinetics of these reactions have been studied.491 The addition of carbon... 

Oxazole chemistry, advances in, 17, 99 Oxazolone chemistry new developments in, 21, 175 recent advances in, 4, 75 Oxidation of monocyclic pyrroles, 15, 67 Oxidative transformations of heteroaromatic iminium salts, 41, 275 3-Oxo-2,3-dihydrobenz[d]isothiazole 1,1-dioxide (saccharin) and derivatives, IS, 233... 

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