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

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.