Copper-Catalyzed Synthesis of Difluoromethylated/C-4- and C-5-Functionalized Polycyclic Coumarin Derivatives.

A facile and novel synthetic method for the synthesis of functionalized polycyclic coumarins at the C-4 and C-5 positions is proposed for the first time, which employs copper-catalyzed addition reactions of undiscovered alkenes with difluoromethyl radicals to construct polycyclic coumarins. This strategy is characterized by high regioselectivity, easy availability of raw materials, and simple operation. Additionally, such undiscovered coumarin alkenes can be reacted with a variety of difluoromethyl precursors to obtain a wide range of valuable C-4 and C-5 position functionalized/difluoromethylated polycyclic coumarins. More importantly, some of the products showed significant inhibition of proliferation in vitro against melanoma B16-F10 and lung cancer A549 cell lines with optimal IC50 values of 8.57 and 16.04 μM, respectively.