Synthesis of N-Substituted 4-Quinolones via Palladium-Catalyzed Enantioselective C-N Coupling and Base-Promoted Reactions

A highly efficient palladium-catalyzed asymmetric synthesis of N-substituted 4-quinolones was developed via C-N coupling reaction. Various chiral quinolones were readily obtained with desirable enantioselectivity (up to 95% ee) and excellent yield (up to 99%), enabled by a simple system of palladium acetate and chiral ferrocene bisphosphine as auxiliary ligand. The corresponding racemic derivatives can also be synthesized by a transition metal-free strategy of potassium hydroxide in DMSO. The influence of temperature on the configurational stability of these C-N axially chiral compounds was also investigated. The efficient functionalization at 3-position further expands the application range of this synthetic technique.