Three-Component Coupling of 2-Iodoanilines, Isocyanides, and Carbon Dioxide under Palladium Catalysis

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Abstract

The formation of quinazoline-2,4(1H,3H)-diones via a three-component coupling of ortho-iodoanilines, isocyanides, and CO2 under palladium catalysis was investigated. It was established that the use of the coordinatively unsaturated phosphine complex [PdCl(μ-Cl)(PPh3)2] in DMF at 80°C and atmospheric pressure of CO2 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 S. aureus MRSA ATCC 33591.

About the authors

T. K Nguyen

Saint Petersburg University

St. Petersburg, Russia

S. A Katkova

Saint Petersburg University

St. Petersburg, Russia

L. A Kraeva

Pasteur Research Institute of Epidemiology and Microbiology

St. Petersburg, Russia

N. V Rostovsky

Saint Petersburg University

St. Petersburg, Russia

M. A Kinzhalov

Saint Petersburg University

Email: m.kinzhalov@spbu.ru
St. Petersburg, Russia

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