2-ARYL-6,8-Dibromoquinolinones as synthons for the synthesis of Polysubstituted 4-ARYL-6-Oxopyrrolo [3,2,1-ij] Quinolines

Abstract

The known 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones 122 were dehydrogenated using thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to afford the 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136. Palladium-catalyzed Sonogashira cross-coupling of the 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones with terminal alkynes in the presence of PdCl2(PPh3)2-CuI (as homogeneous catalyst source) and 10% Pd/C-PPh3-CuI (as heterogeneous catalyst source) catalyst mixture and NEt3 as a base and co-solvent in ethanol under reflux afforded the corresponding 6,8-dialkynyl-2-aryl-2,3-dihydroquinolin-4(1H)-ones 138 and 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones 137, respectively. PdCl2-catalyzed electrophilic cyclization of the 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones in acetonitrile under reflux afforded the 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 or the 2-aryl-6-bromo-8-(4-hydroxybutanoyl)-2,3-dihydroquinolin-4(1H)-ones 140 from the 4-phenylethynyl-substituted or 4-alkylethynyl-substituted precursors, respectively. The 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136 wturn, subjected to similar homogeneous and heterogeneous palladium catalyst sources using NEt3 as a base in DMF-water mixture under reflux and K2CO3 as a base in dioxane under reflux afforded 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 143 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142, respectively. The monoalkynylated 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142 were subsequently transformed using palladium-catalyzed Suzuki-Miyaura cross-coupling with arylboronic acids in the presence of PdCl2(PPh3)2-PCy3 catalyst mixture and K2CO3 as a base in dioxane-water mixture to afford the corresponding novel 8-substituted 2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 141 and 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 144, respectively. All the new compounds were characterized using a combination of 1H NMR, 13C NMR, IR, mass spectroscopic techniques and X-ray crystallography.