Synthesis Of4-Arylcoumarins By Palladium-Catalyzed Oxidative Heck Reaction

4-Arylcoumarins (neoflavones) belong to the family members of flavonoids. They are widely distributed in natural products, microbial and other bioactive molecules as important pharmaceutical intermediates. Research has shown that they exhibit several significant biological activities such as antitumor, antimalarial, anti-HIV, antidiabetic, antibacterial, anti-oxidative, anti-inflammatory, antiallergic, antivirus. antiprotozoal and cytotoxic. In recent years, researches of4-arylcoumarins and derivatives attracted widespread attentions due to their unique nature.Nowadays, many procedures have been published in the literature for the synthesis of4-arylcoumarins. Most known methods for synthesizing4-arylcoumarins can be divided into two groups:those in which the benzopyran-2-one ring is closed (Pechmann, Perkin, Ponndorf and other reactions) and those based on arylation of coumarins activated at the4-position. However, these routes suffer from poor atom-economic, stoichiometric amounts of mineral or Lewis acids, toxic reagents and poor yields. The problem that how to synthesize4-arylcoumarins via direct arylation of4-unsubstituted coumarins still be unsolved.In this paper, we synthesized4-arylcoumarins using inexpensive4-unsubstituted coumarins and arylboronic acids as raw marterials. We determined using10mol%Pd(OAc)2as the catalyst,15mol%5-nitro-1,10-phenanthroline (phen-NO2) as the ligand, dioxygen as the oxidant, DMF as solvent,0.3mmol coumarins with0.9mmol arylboronic acids at80℃for24h as the optimal reaction conditions after screening the reaction parameters such as catalysts, ligands, solvents, temperature and oxidant. And twenty-three4-arylcoumarins were synthesized, the isolated yield is up to97%. Besides the reaction system can also be applied to synthesis of2-arylchromone. In addition, we also carried out the palladium-catalyzed Michael addition reaction of coumarins with arylboronic acids.In this paper, we have developed a convenient efficient atom-economic protocol for the synthesis of4-arylcoumarins via palladium-catalyzed oxidative Heck coupling reaction of coumarins with arylboronic acids.