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

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.

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

References

For reviews see:

<A NAME="RG30005ST-1A">1a</A> Fan W.-Q. Katritzky AR. In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Katritzky AR. Rees CW. Scriven CWV. Elsevier; Oxford: 1996.  p.1-126  

<A NAME="RG30005ST-1B">1b</A> Dehne H. In Methoden der organischen Chemie (Houben-Weyl)   Vol. E8d:  Schaumann E. Thieme; Stuttgart: 1994.  p.305-405  

<A NAME="RG30005ST-1C">1c</A> Abu-Orabi ST. Alfah MAI. Jibril Mari’I FM. Ali AA.-S. J. Heterocycl. Chem.  1989,  26:  1461 

<A NAME="RG30005ST-2">2</A> 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 

<A NAME="RG30005ST-3">3</A> 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 

<A NAME="RG30005ST-4">4</A> 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 

<A NAME="RG30005ST-5A">5a</A> Huisgen R. Szeimies G. Mobius L. Chem. Ber.  1967,  100:  2494 

<A NAME="RG30005ST-5B">5b</A> 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  

<A NAME="RG30005ST-6A">6a</A> Tornøe CW. Christensen C. Meldal M. J. Org. Chem.  2002,  67:  3057 

<A NAME="RG30005ST-6B">6b</A> 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:

<A NAME="RG30005ST-7A">7a</A> Holzer W. Ruso K. J. Heterocycl. Chem.  1992,  29:  1203 

<A NAME="RG30005ST-7B">7b</A> Ohta S. Kawasaki I. Uemura T. Yamashita M. Yoshioka T. Yamaguchi S. Chem. Pharm. Bull.  1997,  45:  1140 

<A NAME="RG30005ST-7C">7c</A> Uhlmann P. Felding J. Vedsø P. Begtrup M. J. Org. Chem.  1997,  9177 

<A NAME="RG30005ST-7D">7d</A> Felding J. Uhlmann P. Kristensen J. Vedsø P. Begtrup M. Synthesis  1998,  1181 

<A NAME="RG30005ST-7E">7e</A> Krasiñski A. Fokin VV. Sharpless KB. Org. Lett.  2004,  6:  1237 

<A NAME="RG30005ST-8">8</A> Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis  2005,  1314 

<A NAME="RG30005ST-9">9</A> Leroy J. Synth. Commun.  1992,  576 

<A NAME="RG30005ST-10">10</A>

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.

<A NAME="RG30005ST-11">11</A>

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.

<A NAME="RG30005ST-12">12</A> Wu Y.-M. Deng J. Li Y. Chen Q.-Y. Synthesis  2005,  1314 

<A NAME="RG30005ST-13">13</A> Kuijpers BHM. Groothuys S. Keereweer AR. Quaedflieg PJLM. Blaauw RH. van Delft FL. Rutjes FPJT. Org. Lett.  2004,  6:  3123