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

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.