Pyrroles from azomethine ylides

In addition to cydocondensation reactions of the Paal-Knorr type, cycloaddition processes play a prominent role in the construction of pyrrole rings. Thus, 1,3-dipo-lar cycloadditions of azomethine ylides with alkene dipolarophiles are very important in the preparation of pyrroles. The group of de la Hoz has studied the micro-wave-induced thermal isomerization of imines, derived from a-aminoesters, to azomethine ylides (Scheme 6.185) [346]. In the presence of equimolar amounts of /i-nitrostyrenes, three isomeric pyrrolidines (nitroproline esters) were obtained under solvent-free conditions in 81-86% yield within 10-15 min at 110-120 °C through a [3+2] cycloaddition process. Interestingly, using classical heating in an oil bath (toluene reflux, 24 h), only two of the three isomers were observed. 

Dipolar cycloaddition is another route to benzopyrrolo[l,2-a]azepines by pyrrole ring formation. The azomethine ylide derived from imine 88 and difluorocarbene adds to DMAD to produce dimethyl 3-fluoro-9H-dibenzo[c,/]-pyrrolo[l,2-fl]azepine-l,2-dicarboxylate 89 in 20% yield (Equation (12)... 

Padwa et al. (75) found that the unsymmetrical miinchnone 137, which was generated from A-acetyl-7/-benzylglycine (136) and refluxing acetic anhydride, reacts with methyl propiolate to give an 8 1 mixture of pyrroles 138 and 139. The same product ratio is obtained from the reaction of methyl propiolate and the azomethine ylide derived from 7/-benzyl-A(-(a-cyanoethyl)-A(-[(trimethylsilyl)-methyl] amine. 

Fluoro-substituted dihydrofuro[3,2-r ]pyridinones are obtained from the thermolysis reaction of cyclopropa[3]-furo[2,3-f]pyrroles, 134, along with the loss of HF (Equation 67) <2005SL1006>. Compound 134 is generated from pyrroles via reaction with a carbene to give an azomethine ylide which undergoes an electrocyclization reaction. 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

The presence of an aroyl fragment in azomethine ylides obtained from opening of three-membered rings in the case of dipolarophiles with high LUMO (lowest unoccupied molecular orbital) energy or in the absence of an external dipolarophile can lead to the possibility of such unusual reactions as intramolecular 1,3-dipolar cycloaddition [80]. Examples of such reactions are the thermal isomerization of aroyl aziridines 63 into a pyrrole derivative 64 [81, 82] or into 2,5-diphenyloxazole 65 (in the presence of diphenyliodonium iodide) [83] (Scheme 1.16). 

When reacted with 1-aryl-3,3,3-trifluoropropynes, azomethine ylide 14, generated from the aziridine, provides pyrrolines in high yield, with no rcgioseleclivily. These cycloadducts can be converted into the corresponding pyrroles or pyrrolidines. ... 

A series of 3-pyrrolin-2-ones 6 has been s)mthesized from the readily available oxamates 7 and dimethyl acetylenedicarboxylate (DMAD) in the presence of PPhs <03SC2527>. Unexpectedly, the reaction of thioamides with DMAD involving a 1,3-dipolar cycloaddition of an intermediate azomethine ylide provided a new route to pyrroles <03TL4175>. 

From a synthetic viewpoint, iV-arylvinylamines are not appropriate as azomethine ylide precursors because the hydrogen shift from the intermediary ylides must be extremely accelerated by the rearomatization of the fused dihydro benzo moiety. Zaima and Mitsuhashi were the first to succeed with synthetic applications of the above photochemical generation method of cyclic azomethine ylides (83JHC1). The substrate employed in their work is bis(l-methoxycarbonylvinyl)amine. Irradiation of this divinylamine in carbon tetrachloride at 18°C in the presence of acetylenedicarboxylates produces excellent yields of 7-azabicyclo[2.2.1]hept-2-ene-l,2,3,4-tetracarboxylates 172, which correspond to the cycloadducts of the expected azomethine ylide intermediate 171. Heating the bicyclic cycloadducts 172 at 90-120°C induces a smooth cycloreversion eliminating a molecule of ethene to give pyrrole-2,3,4,5-tetracarboxylates in quantitative yields. The azomethine ylide 171 can be trapped also with olehnic dipolarophiles, such as maleates and fuma-rates, to furnish stereospecifically 7-azabicyclo [2.2.1] heptane-1,2,3,4-tetra-carboxylates 173 and 174, respectively (84JHC445). 

The N-unsubstituted azomethine ylides derived from the imines of a-amino nitriles are intramolecularly trapped by acetylenes to give pyrroles... 

Bashiardes et al. reported a study involving cydoaddition of O-allylic or O-propargylic salicylaldehydes 152 or 153 to a-amino esters 154 treated under different conditions toluene at reflux (A) conventional heating without solvent (B) or microwave irradiation under solvent-free conditions (C) (Scheme 11.38) [lOOj. The cydoaddition reaction involves polar 1,3-dipolar azomethine ylide intermediates 155 and 156. The best results were obtained in a one-pot procedure under micro-wave conditions providing pyrrolidines 157 or pyrroles 158 in excellent yields ranging from 70 to 98% at 130 °C for 5-30 min. 

Azomethine ylides can also be generated from a-cyano- or a-phenylthiomethylamines <85JOC4006, 86CB813). Silver fluoride promotes the elimination. The adducts from alkynes are 2,5-dihydropyrroles which can be oxidized to pyrroles by ddq (Scheme 82). 

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