Rh-Catalyzed Oxidative Coupling between Primary and Secondary Benzamides and Alkynes: Synthesis of Polycyclic Amides

A methodology for the high yield and facile synthesis of isoquinolones from benzamides and alkynes via the oxidative ortho C-H activation of benzamides has been developed. Ag(2)CO(3) proved to be an optimal oxidant when MeCN was used as a solvent, and [RhCp*Cl(2)](2) was utilized as an efficient catalyst. Both N-alkyl and N-aryl secondary benzamides can be applied as effective substrates. Furthermore, primary benzamides react with two alkyne units, leading to tricyclic products via double C-H activation and oxidative coupling. The reactivity of the structurally related 1-hydroxyisoquinoline was also demonstrated, where both N- and O-containing rhodacyclic intermediates can be generated, leading to the construction of different O- or N-containing heterocycles.