The formation of quinazoline-2,4(1,3)-diones via a three-component coupling of ortho-iodoanilines, isocyanides, and CO under palladium catalysis was investigated. It was established that the use of the coordinatively unsaturated phosphine complex PdCl(μ-Cl)(PPh) in DMF at 80°C and atmospheric pressure of CO leads to a quantitative yield of the target product within 3 h. The reaction parameters, including solvent choice, temperature conditions, and reagent ratios, were optimized. Key intermediates were identified by ESI-HRMS, indicating a molecular mechanism involving a dynamic equilibrium between monomeric and dimeric forms of palladium complexes. The reaction demonstrated broad substrate scope, including sterically hindered isocyanides. Biological screening revealed that several of the synthesized quinazolinidones exhibit moderate antibacterial activity against methicillin-resistant MRSA ATCC 33591.
T.K. Nguyen (Wed,) studied this question.