Carbonylative Transformations Using a DMAP-Based Pd-Catalyst through Ex Situ CO Generation

A phosphine-free, efficient protocol for aminocarbonylation and carbonylative Suzuki-Miyaura coupling has been developed using a novel palladium complex, [Pd^II(DMAP)₂(OAc)₂]. The complex was successfully synthesized using a stoichiometric reaction between Pd^II(OAc)₂ and DMAP in acetone at room temperature and characterized using single-crystal X-ray analysis. Only 5 mol % catalyst loading was sufficient for effective carbonylative transformations. "Chloroform-COware" chemistry was utilized for safe and facile insertion of the carbonyl unit using chloroform as an inexpensive CO source in a two-chamber setup. Various value-added pharmaceutically relevant compounds such as CX-516, CX-546, and farampator were synthesized using the technique. Furthermore, the commercially designed COware was engineered to COware-RB setup for sequential one-pot synthesis of indenoisoquinolines (topoisomerase I inhibitors).