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Synlett 2005(20): 3059-3062  
DOI: 10.1055/s-2005-921919
LETTER
© Georg Thieme Verlag Stuttgart · New York

Copper(I)-Mediated Synthesis of Trisubstituted 1,2,3-Triazoles

Brian H. M. Kuijpersa, Guido C. T. Dijkmansa, Stan Groothuysa, Peter J. L. M. Quaedfliegb, Richard H. Blaauwc, Floris L. van Delfta, Floris P. J. T. Rutjes*a
a Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
Fax: +31(24)3653393; e-Mail: F.Rutjes@science.ru.nl;
b DSM Research, Life Sciences-Advanced Synthesis, Catalysis and Development, P.O. Box 18, 6160 MD Geleen, The Netherlands
c Chiralix B.V., Toernooiveld 100, 6525 EC Nijmegen, The Netherlands
Further Information

Publication History

Received 15 September 2005
Publication Date:
28 November 2005 (online)

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Abstract

A copper-catalysed coupling of bromo-alkynes and ­organic azides is described. This coupling results in the formation of bromo-containing trisubstituted 1,2,3-triazole derivatives in high yield and a regioselective manner.

Key words

1,4,5-trisubstituted-1,2,3-triazole - click reaction - [3+2] dipolar cycloaddition - Cu-catalysis - glycopeptide

    References

  • For reviews see:
  • 1a Fan W.-Q. Katritzky AR. In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Katritzky AR. Rees CW. Scriven CWV. Elsevier; Oxford: 1996.  p.1-126  
    CrossrefSearch in Google Scholar
  • 1b Dehne H. In Methoden der organischen Chemie (Houben-Weyl)   Vol. E8d:  Schaumann E. Thieme; Stuttgart: 1994.  p.305-405  
    CrossrefSearch in Google Scholar
  • 1c Abu-Orabi ST. Alfah MAI. Jibril Mari’I FM. Ali AA.-S. J. Heterocycl. Chem.  1989,  26:  1461 
    CrossrefSearch in Google Scholar
  • 2 Alvarez R. Velazquez S. San-Felix A. Aquaro S. Clercq ED. Perno CF. Karlesson A. Balzarini J. Camarasa MJ. J. Med. Chem.  1994,  37:  4185 
    CrossrefPubMedSearch in Google Scholar
  • 3 Genin MJ. Allwine DA. Anderson DJ. Barbachyn MR. Emmert DE. Garmon SA. Graber DR. Grega KC. Hester JB. Hutchinson DK. Morris J. Reischer RJ. Ford CW. Zurenco GE. Hamel JC. Schaadt RD. Stapert D. Yagi BH. J. Med. Chem.  2000,  43:  953 
    CrossrefSearch in Google Scholar
  • 4 Brockunier LL. Parmee ER. Ok HO. Candelore MR. Cascieri MA. Colwell LF. Deng L. Feeney WP. Forest MJ. Hom GJ. MacIntyre DE. Tota L. Wyvratt MJ. Fisher MH. Weber AE. Bioorg. Med. Chem. Lett.  2000,  10:  2111 
    CrossrefSearch in Google Scholar
  • 5a Huisgen R. Szeimies G. Mobius L. Chem. Ber.  1967,  100:  2494 
    CrossrefSearch in Google Scholar
  • 5b For a recent review on synthesis of 1,2,3-triazoles, see: Tome AC. In Science of Synthesis   Vol. 13:  Thieme; Stuttgart: 2004.  p.415-601  
    CrossrefSearch in Google Scholar
  • 6a Tornøe CW. Christensen C. Meldal M. J. Org. Chem.  2002,  67:  3057 
    Search in Google Scholar
  • 6b Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 
    Search in Google Scholar
  • For a selection of recent entries into trisubstituted triazole synthesis, see:
  • 7a Holzer W. Ruso K. J. Heterocycl. Chem.  1992,  29:  1203 
    CrossrefSearch in Google Scholar
  • 7b Ohta S. Kawasaki I. Uemura T. Yamashita M. Yoshioka T. Yamaguchi S. Chem. Pharm. Bull.  1997,  45:  1140 
    CrossrefSearch in Google Scholar
  • 7c Uhlmann P. Felding J. Vedsø P. Begtrup M. J. Org. Chem.  1997,  9177 
    Crossref
  • 7d Felding J. Uhlmann P. Kristensen J. Vedsø P. Begtrup M. Synthesis  1998,  1181 
    Crossref
  • 7e Krasiñski A. Fokin VV. Sharpless KB. Org. Lett.  2004,  6:  1237 
    CrossrefSearch in Google Scholar
  • 8 Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis  2005,  1314 
    Thieme Connect
  • 9 Leroy J. Synth. Commun.  1992,  576 
  • 12 Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis  2005,  1314 
    Thieme Connect
  • 13 Kuijpers BHM. Groothuys S. Keereweer AR. Quaedflieg PJLM. Blaauw RH. van Delft FL. Rutjes FPJT. Org. Lett.  2004,  6:  3123 
    CrossrefSearch in Google Scholar
10

The regiochemistry was determined via reduction to the 5-hydrogen-1,2,3-triazole, using i-PrMgCl and subsequent quenching with MeOH, followed by comparison to the known 1,4-disubstituted triazole.

11

Heating of the reaction mixture to temperatures higher than 50 °C led to the formation of small amounts of the 1,5-regioisomer, which was probably formed via a thermal [3+2] cycloaddition.