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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

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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.