Copper-Catalyzed Stereoselective Hydroarylation of 3-Aryl-2-propynenitriles with Arylboronic Acids

The selective synthesis of 3,3-diarylacrylonitriles has been achieved by copper-catalyzed hydroarylation of 3-aryl-2-propynenitriles with arylboronic acids. The starting cyanoalkynes were efficiently prepared from the appropriate aromatic aldehydes and diethyl cyanomethylphosphonate in two steps. The hydroarylation of the obtained cyanoalkyne substrates proceeded in methanol at ambient temperature to produce 3,3-diarylacrylonitriles in good to high yields with excellent syn selectivity. The present method was successfully applied to the regiospecific synthesis of both stereoisomers of CC-5079, which was recently reported as a potent anticancer drug.