Copper‐Catalyzed Carbonylative Cyclization of CO2: A Promising Approach for Synthesis of Flavone

Abstract

Abstract Flavones are an important class of building blocks for numerous biologically active molecules, pharmaceuticals, and natural products. Reductive carbonylation of CO2 is a powerful method to provide high‐value heterocycles quickly. However, examples of transition metal‐catalyzed carbonylation to produce flavones using CO2 are quite scarce, and the related copper‐catalyzed carbonylative cyclization of CO2 is not reported. Here, a general procedure is developed for the copper‐catalyzed carbonylative C(sp3)‐H bond synthesis of flavone using CO2 as the C1 source. Additionally, 13C‐labeled flavones are successfully synthesized using [13C]‐CO2, demonstrating significant inhibitor activity against MCF‐7 cells in antitumor assays. Mechanistic investigations suggest that the phenolic group accelerates CO2 mass transfer by promoting nucleophilic addition to DBU‐CO2 complexes, followed by selective intramolecular carbonylative cyclization.

Keywords

• Carbon dioxide utilization
• Carbonylation
• CO2 mass transfer
• Copper catalyst
• Flavone