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Synlett 2013; 24(7): 843-846
DOI: 10.1055/s-0032-1318488
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© Georg Thieme Verlag Stuttgart · New York

2-Ethynylpyridine-Promoted Rapid Copper(I) Chloride Catalyzed Azide–Alkyne Cycloaddition Reaction in Water

Hidekatsu Hiroki
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga Bunkyo-ku, Tokyo 112-8551, Japan   Fax: +81(3)38171895   Email: orgsynth@kc.chuo-u.ac.jp
,
Kenichi Ogata
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga Bunkyo-ku, Tokyo 112-8551, Japan   Fax: +81(3)38171895   Email: orgsynth@kc.chuo-u.ac.jp
,
Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga Bunkyo-ku, Tokyo 112-8551, Japan   Fax: +81(3)38171895   Email: orgsynth@kc.chuo-u.ac.jp
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Further Information

Publication History

Received: 28 January 2013

Accepted after revision: 28 February 2013

Publication Date:
18 March 2013 (online)

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Abstract

The copper(I) chloride catalyzed reaction of azides with alkynes in water at room temperature was promoted by the addition of a catalytic amount of 2-ethynylpyridine, affording the corresponding 1,4-disubstituted 1,2,3-triazoles in good yields after a specific reaction time. The catalytic system could be successfully applied to electron-rich, electron-poor, and sterically crowded substrates. A study of the additive effect of pyridine derivatives revealed that alkynyl and 2-pyridyl groups were essential for activating the copper catalyst.

Key words

cycloaddition - azides - alkynes - copper - heterocycles

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 4 We obtained the X-ray crystal structure of pyta–CuI complex (see Supporting Information).
  • 5 Hohloch et al. demonstrated that the CuI complex with 5 catalyzed the reaction of phenylacetylene with benzylazide under neat conditions, but gave less than 20% yield after 100 min reaction. See: Hohloch S, C.-Y Su, Sarkar B. Eur. J. Inorg. Chem. 2011; 3067
  • 6 An equimolar mixture of CuCl and 1 in MeOH (or H2O) at r.t. overnight afforded a precipitate, which had a strong absorption at 1947 cm–1 in the IR spectrum attributed to the presence of a Cu acetylide complex. It has been reported that polymeric Cu acetylide complexes catalyze the CuAAC reaction ‘on water’ under microwave irradiation. See: Buckley BR, Dann SE, Heaney H, Stubbs EC. Eur. J. Org. Chem. 2011; 770
  • 7 Yoshida and Hosoya reported that the more sterically hindered azide occasionally reacts with a specified alkyne preferentially. See: Yoshida S, Shiraishi A, Kanno K, Matsushita T, Johmoto K, Uekusa H, Hosoya T. Sci. Rep. 2011; 1: 82
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      • Compound 19 has previously been prepared by NHC–Cu complexes:
    • 8a Nakamura T, Terashima T, Ogara K, Fukuzawa S.-i. Org. Lett. 2011; 13: 620
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    • 8b Huang J, Hong J.-T, Hong SH. Eur. J. Org. Chem. 2012; 6630
  • 9 General Procedure for 2-Ethynylpyridine-Promoted Cu(I)-Catalyzed Azide–Alkyne 1,3-Dipolar Cycloaddition In a vial containing a magnetic stirrer bar was added CuCl (2.98 mg, 0.03 mmol), H2O (3 mL), 2-ethynylpyridine (3.0 μL, 0.03 mmol) followed by an alkyne (1.0 mmol) and an azide (1.05 mmol) were loaded. The vial was closed with a screw cap, and the reaction mixture was stirred at specified temperature for the time specified in Table 3. The resulting solution was quenched with NH3 solution, extracted with EtOAc, washed with brine, dried over MgSO4, filtered, and finally the solvent was removed under reduced pressure. GC–MS analysis revealed the presence of the corresponding 1,2,3-triazole. The crude product was purified by PTLC or short silica gel column (hexane–EtOAc as eluent)