Ruthenium-Catalyzed C-H Alkenylation of Flavones with Alkenes: Chemoselective Synthesis and Mechanistic Insights from DFT Studies.

A strategy for the selective C-H alkenylation of flavones is described. By using the carbonyl group of the flavone core as an intrinsic directing group, a series of 5-alkenylated derivatives were synthesized via coupling with alkenes, including acrylates, styrene, methyl vinyl ketone, and phenyl vinyl sulfone, affording the desired products in good to excellent yields (up to 92%). Notably, when a carbamate substituent was present at C7, the reaction proceeded with complete chemoselectivity, exclusively yielding C-5 alkenylated products. Although carbamate groups are widely recognized as efficient directing groups in alkenylation reactions, they proved to be ineffective within the flavone scaffold. Density functional theory (DFT) calculations were performed to rationalize the observed chemoselectivity and to provide mechanistic insight into the C-H activation process. The preference for C5 alkenylation arises from the lower energy profiles of the corresponding transition states and intermediates, whereas C8 functionalization is disfavored due to a greater tendency toward protodemetalation over migratory insertion.