Ruthenium-Catalyzed Oxidative Coupling/Cyclization of Isoquinolones with Alkynes through C-H/N-H Activation: Mechanism Study and Synthesis of Dibenzo[a,g]quinolizin-8-one Derivatives

The mechanism of [{RuCl2-(p-cymene)}(2)]-catalyzed oxidative annulations of isoquinolones with alkynes was investigated in detail. The first step is an acetate-assisted C-H bond activation process to form cyclometalated compounds. Subsequent mono-alkyne insertion of the Ru-C bonds of the cyclometalated compounds then takes place. Finally, oxidative coupling of the C-N bond of the insertion compounds occurs to afford Ru-0 sandwich complexes that undergo oxidation to regenerate the catalytically active Ru-II complex with the copper oxidant and release the desired dibenzo[a,g]quinolizin-8-one derivatives. All of the relevant intermediates were fully characterized and determined by single crystal X-ray diffraction analysis. The [{RuCl2(p-cymene)}(2)]-catalyzed C-H bond functionalization of isoquinolones with alkynes to synthesize dibenzo[a,g]quinolizin-8-one derivatives through C-H/N-H activation was also demonstrated.