Elsevier

Tetrahedron Letters

Volume 55, Issue 50, 10 December 2014, Pages 6787-6790
Tetrahedron Letters

Scandium(III) triflate mediated intramolecular ring expansion of aziridines: a direct access to 4-aryltetrahydroisoquinolines

https://doi.org/10.1016/j.tetlet.2014.10.047Get rights and content

Abstract

A novel, high yielding facile synthesis of 4-substituted tetrahydroisoquinolines has been developed by employing scandium(III) triflate mediated intramolecular ring expansion of aziridines. The meta-substituted electron-donating group on the benzene ring facilitates trapping of an in situ generated benzyl carbenium ion cation leading to the formation of tetrahydroisoquinolines.

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Acknowledgments

We sincerely appreciate the financial support from Albany Molecular Research Inc. The authors also thank Dr. Chen Zhen Zia for his support and Dr. Isherwood Matthew for useful discussions during the preparation of this manuscript.

References and notes (15)

  • R.N. Brogden et al.

    Drugs

    (1979)
  • A.D. Cox et al.

    Chem. Rev.

    (1995)
  • S. Wang et al.

    Org. Lett.

    (2013)
  • J.D. Scott et al.

    Chem. Rev.

    (2002)
    H. He et al.

    Tetrahedron Lett.

    (2000)
    E.J. Corey et al.

    J. Am. Chem. Soc.

    (1996)
    A. Endo et al.

    J. Am. Chem. Soc.

    (2002)
    B. Herberich et al.

    Tetrahedron Lett.

    (2001)
    (f) Liu, S.; Molino, B. F.; Nacro, K. Patent. WO2010132437A1, 2010; Chem. Abstr. 2010, 153,...
  • P.A. Dandridge et al.

    J. Med. Chem.

    (1984)
    J. Guillon et al.

    Pharm. Sci.

    (1997)
There are more references available in the full text version of this article.

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