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

Brian H. M. Kuijpers; Guido C. T. Dijkmans; Stan Groothuys; Peter J. L. M. Quaedflieg; Richard H. Blaauw; Floris L. van Delft; Floris P. J. T. Rutjes

doi:10.1055/s-2005-921919

LETTER

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

Brian H. M. Kuijpers^a, Guido C. T. Dijkmans^a, Stan Groothuys^a, Peter J. L. M. Quaedflieg^b, Richard H. Blaauw^c, Floris L. van Delft^a, 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

Abstract

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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

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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

1b Dehne H. In Methoden der organischen Chemie (Houben-Weyl) Vol. E8d: Schaumann E. Thieme; Stuttgart: 1994. p.305-405

1c Abu-Orabi ST. Alfah MAI. Jibril Mari’I FM. Ali AA.-S. J. Heterocycl. Chem. 1989, 26: 1461

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

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

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

5a Huisgen R. Szeimies G. Mobius L. Chem. Ber. 1967, 100: 2494

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

6a Tornøe CW. Christensen C. Meldal M. J. Org. Chem. 2002, 67: 3057

6b Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596

For a selection of recent entries into trisubstituted triazole synthesis, see:

7a Holzer W. Ruso K. J. Heterocycl. Chem. 1992, 29: 1203

7b Ohta S. Kawasaki I. Uemura T. Yamashita M. Yoshioka T. Yamaguchi S. Chem. Pharm. Bull. 1997, 45: 1140

7c Uhlmann P. Felding J. Vedsø P. Begtrup M. J. Org. Chem. 1997, 9177

7d Felding J. Uhlmann P. Kristensen J. Vedsø P. Begtrup M. Synthesis 1998, 1181

7e Krasiñski A. Fokin VV. Sharpless KB. Org. Lett. 2004, 6: 1237

8 Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis 2005, 1314

9 Leroy J. Synth. Commun. 1992, 576

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.

12 Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis 2005, 1314

13 Kuijpers BHM. Groothuys S. Keereweer AR. Quaedflieg PJLM. Blaauw RH. van Delft FL. Rutjes FPJT. Org. Lett. 2004, 6: 3123