Copper‐Catalyzed One‐Pot Synthesis of 3‐(N‐Heteroarenyl)acrylonitriles through Radical Conjugated Addition of β‐Nitrostyrene to Methylazaarenes

A simple procedure for the copper‐catalyzed synthesis of 3‐(N‐heteroaryl)acrylonitriles was developed. Using a combination of Lewis and Brønsted acids, this one‐pot procedure undergoes via a radical conjugated addition and dehydration processes, without isolation of any intermediate, affording the acrylonitriles. This diastereoselective approach allowed the synthesis of a broad scope of quinazoline derivatives (22 examples) with moderate to good yields and good functional‐group tolerance and could be extended to other N‐heterocyles such as quinolines and isoquinolines. Based on control experiments, a mechanistic proposal for this new transformation is also presented. A one‐pot synthesis of new acrylonitriles using a combination of Lewis and Brønsted acid catalysts was developed. Under the optimized conditions, 22 quinazoline, quinoline, and isoquinoline derivatives were prepared containing electron‐donating or electron‐withdrawing groups. A mechanistic pathway was proposed via a radical conjugated addition of β‐nitrostyrenes to methylazaarenes followed by dehydration processes.