Palladium-Catalyzed Oxidative Cyclocarbonylation of Isoquinolones with CO via C-H/N-H Bond Cleavage: Easy Access to Isoindolo[2,1-b]isoquinoline-5,7-dione Derivatives

An efficient and practical synthesis of isoindolo[2,1-b]isoquinoline-5,7-diones through Pd-catalyzed C-H activation/carbonylative annulation of isoquinolones with CO (1atm) is presented. Deuterium-labeling experiments revealed that the aryl C(sp(2))-H bond activation might be the rate-determining step. More interestingly, the title compounds could also be prepared directly from the cascade reaction of N-methoxy benzamides and internal alkynes, as the precursors of isoquinolones, under an atmospheric pressure of carbon monoxide through a Rh/Pd relay catalysis in a user-friendly manner.