Metal/organo relay catalysis in a one-pot synthesis of methyl 4-aminopyrrole-2-carboxylates from 5-methoxyisoxazoles and pyridinium ylides

Abstract

Methyl 4-aminopyrrole-2-carboxylates were synthesized in one-pot mode by the relay catalytic cascade reaction of 5-methoxyisoxazoles with pyridinium ylides by the use of a FeCl2/Et3N binary catalytic system leading to 1-(5-methoxycarbonyl-1H-pyrrol-3-yl)pyridinium salts followed by hydrazinolysis. The approach permits the introduction of a substituent at the pyrrole nitrogen via a nucleophilic reaction of the pyrrolylpyridinium ylide derived from the salt. Catalytic reduction of the ylides gives methyl 4-piperidinopyrrole-2-carboxylates.

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

“…Based on our experience of using isoxazoles in the synthesis of heterocyclic compounds [14][15][16][17][18], we hypothesized that isoxazoles 1 can undergo reductive ring opening under the action of Mo(CO) 6 /H 2 O/MeCN [14,[19][20][21][22][23] to enamines 3, which can be cyclized on acyl R 3 C(O) group to form pyridones 2 (Scheme 2, route a). The alternative cyclization scenario, which may involve the ester group of enamine 3 and lead to the formation of pyridone 5 (route b), is less likely due to the lower electrophilicity of the ester carbon compared to the acyl carbon.…”

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

“…It is important that the reaction of iodide 1m with 2-pyridyl substituent gave a good yield of the product 3m, which could be used for the preparation of bidentate ligand for metal complexes. Reaction of salts 1 with electron-donating para-substituents (Me, MeO, Me 2 N) in the pyridine ring (1n-p,s) and aryl substituents (1q,r) afforded the corresponding compounds 3 in 51-82% yield (Table 2, entries [14][15][16][17][18][19].…”

“…Fused polyheteroarenes, containing a pyrrole moiety, are widely present in natural products and pharmacologically important agents and have a significant importance in the development of new materials useful for bioimaging applications and chemosensor systems [3][4][5][6][7][8][9][10][11][12][13]. Pyrroles with vicinal o-bromophenyl and heteroaryl substituents, which are readily accessible via reactions of the corresponding 2H-azirines and phenacylcycloiminium ylides [14][15][16][17][18][19], are excellent precursors for various fused aza-heteroaromatics via metal-catalyzed arylation [17][18][19]. We have recently successfully applied this approach to synthesize the new luminescent heterocyclic system pyrido [2,1a]pyrrolo [3,2-c]isoquinoline A [17], which turned out to be useful for bioimaging [13] and as a ligand for the preparation of luminescent metal complexes, Au(I) [20], Ir(III) [21] and Eu(III) [22] (Scheme 1).…”

Recent Advancements in Pyrrole Synthesis

“…Literature survey on pyrrole synthesis between 2014 and 2019 also revealed interesting strategies in which different classes of heterocycles have been effectively employed as starting materials. [126][127][128][129][130][131][132][133][134][135] Some examples discussed in this section include münchnones, isoxazoles, carbohydrates, hydroxyprolines, and pyrrolines. It is interesting to note that these heterocyclic motifs readily produce pyrroles that are densely substituted.…”