Synthesis of Aza-Fused Isoquinolines through Domino Cross-Aldol Condensation and Palladium-Catalyzed Intramolecular Direct Arylation

A straightforward method has been developed for the synthesis of aroyl-substituted imidazo-/benzimidazo-fused isoquinolines. The cascade reaction proceeds via a cross-aldol condensation of 2-(1H-imidazol-1-yl/benzimidazolyl-1-yl)-1-arylethanones and 2-bromobenzaldehyde followed by palladium-catalyzed intramolecular C-H functionalization. This approach offers a simple and efficient alternative one-pot protocol for the assembly of imidazo/benzimidazo[2,1-a]isoquinolines in moderate to good yields.