Enhanced Selectivity in 4-Quinolone Formation: A Dual-Base System for Palladium-Catalyzed Carbonylative Cyclization...

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Traditional palladium-catalyzed carbonylative quinolone synthesis using gaseous carbon monoxide (CO) faces safety and pressure control issues.
• Developing safer and more efficient synthetic routes for 4-quinolone compounds is crucial for pharmaceutical research.

Purpose of the Study:

• To establish a streamlined, non-gaseous method for synthesizing 4-quinolone compounds.
• To introduce a tunable carbon monoxide (CO)-releasing system for palladium-catalyzed reactions.
• To investigate a novel CO transfer mechanism for homogeneous carbonylative cyclization.

Main Methods:

• Utilized iron pentacarbonyl (Fe(CO)5) as a liquid CO source, activated by a dual-base system (piperazine and triethylamine).
• Performed palladium-catalyzed carbonylative C-C coupling followed by intramolecular cyclization.
• Employed a three-component condensation of Fe(CO)5, 2-iodoaniline, and terminal alkynes.
• Conducted operando mechanistic studies to elucidate the CO transfer pathway.

Main Results:

• Successfully synthesized 22 diverse 4-quinolone compounds with excellent yields.
• Demonstrated precise control over reaction selectivity.
• Identified a novel CO transfer mechanism enabling homogeneous carbonylative cyclization.

Conclusions:

• The developed non-gaseous method offers a safer and more controllable alternative to traditional gaseous CO methods.
• This approach has significant implications for the efficient synthesis of pharmaceutical and bioactive compounds.
• The novel CO transfer mechanism provides new insights into carbonylative cyclization reactions.