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