Synthesis of 2,3-Diaryl-4 Methoxyquinolines via Palladium- catalyzed cross coupling reactions

Abstract

The main objective of this investigation was to study palladium-catalyzed coupling of 2-aryl-4-chloro-3-iodoquinolines with phenyl boronic acid in order to assess the regioselectivity of carbon-carbon bond formation at either C3 or C4. The 2-aryl-4- chloro-3-iodoquinolines were subjected to Pd(PPh3)4-catalyzed coupling reaction with phenyl boronic acid in DMF in the presence of 2M sodium carbonate (aq) to afford 2,3-diaryl-4-chloroquinolines. Reaction of 2,3-diaryl-4-chloroquinolines with sodium methoxide in MeOH-DMF mixture under reflux afforded the corresponding 2,3-diaryl-4-methoxyquinoline. An alternative route to the latter involving palladiumcatalyzed cross-coupling reaction of 2-aryl-3-iodo-4-methoxyquinolines derived from the reaction of 2-aryl-4-chloro-3-iodoquinolines with sodium methoxide in refluxing methanol-THF mixture was also investigated. The 2,3-diaryl-4-methoxyquinolines were subjected to further studies of chemical transformation with boron tribromide to afford the corresponding 2,3-diarylquinolin-4(1H)-ones. All new compounds were characterized using a combination of NMR (1H and 13C), IR and mass spectroscopic techniques as well as elemental analysis.