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

• Published in: Journal of organic chemistry 2017-07, Vol.82 (14), p.7583-7594
• Main Authors: Funt, Liya D, Tomashenko, Olesya A, Mosiagin, Ivan P, Novikov, Mikhail S, Khlebnikov, Alexander F
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b01341

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 NH2-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.