DBU⋅HI3-catalyzed oxidative cyclization: An efficient route to flavones and azaflavones

Abstract

Abstract An efficient and operationally simple protocol has been developed for the synthesis of biologically significant flavones and 2-arylquinolin-4-ones (azaflavones). The methodology utilizes a bench-stable organocatalyst, DBU⋅HI3, to drive the oxidative cyclization of substituted 2’-hydroxychalcones and 2’-aminochalcones. Optimization studies revealed that a 15 mol % catalyst loading in DMSO at 110 °C selectively promotes rapid dehydrogenative cyclization within 1-2.5 h, suppressing side products like flavanones. Conversely, protic or nonpolar solvents resulted in poor conversions or incomplete aromatization. This metal-free strategy tolerates a broad range of substrates, including electron-donating, electron-withdrawing, and selected heteroaryl groups, delivering the target frameworks in exceptional isolated yields (up to 94% for flavones and 91% for azaflavones). The synthesized products were structurally confirmed by spectroscopic analysis, and the efficient metal-free protocol provides a practical alternative to conventional transition-metal-based oxidative systems. Graphical AbstractChemical reaction scheme showing transformation of acyclic ketone to cyclic ketone involving DBU·HI3 in DMSO at 110 °C.The figure illustrates a chemical reaction pathway for synthesizing flavones and azaflavones. On the left, an acyclic precursor with heteroatom 'X' (O, NH) is depicted, featuring two benzene rings connected by a central carbon. The arrow indicates transformation into a cyclic product on the right. Above, reagents DBU·HI3 and conditions in DMSO at 110 °C are specified. Below, it notes the formation of 15 flavones and 12 azaflavones, detailing the successful reaction outcomes.