Volume 2020, Issue 29 p. 4563-4570
Full Paper

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

Natália M. Moreira

Natália M. Moreira

Centre of Excellence for Research in Sustainable Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil

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Lorena S. R. Martelli

Lorena S. R. Martelli

Centre of Excellence for Research in Sustainable Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil

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Kiyara I. R. de Julio

Kiyara I. R. de Julio

Centre of Excellence for Research in Sustainable Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil

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Prof. Julio Zukerman-Schpector

Prof. Julio Zukerman-Schpector

Chemistry Department, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil

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Prof. Till Opatz

Prof. Till Opatz

Department of Chemistry, Johannes Gutenberg-University, 55128 Mainz, Germany

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Prof. Arlene G. Corrêa

Corresponding Author

Prof. Arlene G. Corrêa

Centre of Excellence for Research in Sustainable Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil

Centre of Excellence for Research in Sustainable Chemistry, Federal University of São Carlos, 13565-905, São Carlos, SP, Brazil

E-mail: [email protected]

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First published: 20 May 2020
Citations: 5

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.