Copper-catalyzed three-component synthesis of pyrrole-substituted 1,2-dihydroisoquinolines

Abstract

A general approach to the synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines was achieved with pyrrole and various electron withdrawing groups as substituents. CuAAC reaction on enynes yielded the resulting 1,2,3-triazole which spontaneously decomposed to the corresponding ketenimine. Nucleophilic attack by pyrrole and subsequent intramolecular Aza-Michael cyclization generated 1,2-dihydroisoquinolines in moderate to good yields. The optimized conditions allow for a range of substituents with excellent reproducibility.

Graphical Abstract

Keywords:

• 1,2-dihydroisoquinoline
• ketenimine
• CuAAC
• pyrrole

Acknowledgments

We thank the School of Chemical Sciences Mass Spectrometry Center at the University of Illinois for mass spectra data.

Disclosure statement

In accordance with Taylor & Francis policy and my ethical obligation as a researcher, I am reporting that there are no competing interests (legal, professional, financial, commercial or otherwise) affecting the research reported in the enclosed manuscript. No potential conflict of interest was reported by the author(s).

Additional information

Funding

Financial support of this research by the College of the Holy Cross and the Weiss Summer Research Fellowship Program is gratefully acknowledged.