Synthesis of Pyrrolotriazoloisoquinoline Frameworks by Intramolecular Cu-Mediated or Free Radical Arylation of Triazoles

Abstract

The cyclization of (2-bromophenyl)pyrrolyl-1,2,4-triazoles via copper-mediated intramolecular direct C-arylation of 1,2,4-triazoles was first accomplished under triazole-NHC control to give unknown fused heterocyclic skeletons, pyrrolo[3,2-c][1,2,4]triazolo[5,1-a] or [3,4-a]isoquinolines. The primary products underwent a triazole ring opening under the basic arylation conditions, providing N-(1H-pyrrolo[3,2-c]isoquinolin-5-yl)cyanamides. The formation of the cyanamides from isomeric pyrrolo[3,2-c][1,2,4]triazolo[3,4-a]isoquinolines involves, besides the triazole ring opening, the unusual migration of the cyano group. Cyanamides can be easily reduced to 1H-pyrrolo[3,2-c]isoquinolin-5-amines, the first NH-substituted derivatives of 1H-pyrrolo[3,2-c]isoquinoline. An insight into the mechanism of the triazole ring cleavage was achieved by performing a DFT study at the B3LYP/6-31G+(d,p) level. Free radical cyclization of (2-bromophenyl)pyrrolyl-1,2,4-triazoles with TTMSS/AIBN under neutral conditions allows obtaining pyrrolo[3,2-c][1,2,4]triazolo[5,1-a] and [3,4-a]isoquinolines, as well two more new heterocyclic systems, pyrrolo[3,4-c][1,2,4]triazolo[5,1-a] and [3,4-a]isoquinolines, in good yields without triazole ring cleavage. The developed cyclizations provide a concise, atom-economical route to novel fluorescent fused polyheterocycles containing pyrrole and 1,2,4-triazole moieties.

Metalated Ir(III) Complexes Based on the Luminescent Diimine Ligands: Synthesis and Photophysical Study

“…Unsubstituted 3-phenyl-2-(pyridin-2-yl)­pyrido­[2,1- a ]­pyrrolo­[3,2- c ]­isoquinoline ( N ∧ N-A ) was synthesized from 1-(2-(2-bromophenyl)-4-phenyl-5-(pyridin-2-yl)-1 H -pyrrol-3-yl)­pyridin-1-ium bromide through four-step procedure including as a key stage Pd­(II)-catalyzed direct intramolecular arylation (Scheme , left). Trifluoromethyl-substituted ( N ∧ N-B ) and methoxy-substituted ( N ∧ N-C ) ligands were prepared by a modified procedure, which gave pyrido­[2,1- a ]­pyrrolo­[3,2- c ]­isoquinolines directly from 1-(2-(2-bromophenyl)-4-phenyl-5-(pyridin-2-yl)-1 H -pyrrol-3-yl)­pyridin-1-ium bromides under free radical conditions employing AIBN/TTMSS system (Scheme right).…”

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

“…241 Similar studies was reported by Khlebnikov et al starting from (2bromophenyl)pyrrolyl-1,2,4-triazoliums, affording the corresponding cyclized products in moderate yields. 242 An interesting intramolecular radical addition of an aryl radical generated from aryl iodides 333a−333b onto an aryl azide was shown to proceed in the presence of TTMSS, affording spirodienones 334a−334b after hydrolysis of the resulting iminium salts. 243 This approach affords 5-and 6-membered ring spirodienones with satisfying overall yields.…”

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).…”