LETTER
Synthesis of 1-Substituted 1,2,3-Triazoles
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which was due to higher steric hindrance. In the case of
aliphatic azide (n-octanyl azide) the reaction worked well
to give the triazole in 97% yield (entry 16, Table 2).
In summary, CuI and Et3N in DMSO proved to be an ef-
fective and convenient catalytic system for ‘click chemis-
try’ with acetylene gas. The reaction produced a series of
1-substituted-1,2,3-triazoles in moderate to excellent
yields from both aliphatic and aromatic azides.
(6) (a) Fletcher, J. T.; Walz, S. E.; Keeney, M. E. Tetrahedron
Lett. 2008, 49, 7030. (b) Song, R.-J.; Deng, C.-L.; Xie,
Y.-X.; Li, J.-H. Tetrahedron Lett. 2007, 48, 7845.
(c) Taillefer, M.; Xia, N.; Ouali, A. Angew. Chem. Int. Ed.
2007, 46, 934. (d) Cristau, H. J.; Cellier, P. P.; Spindler,
J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607.
(e) Taillefer, M.; Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.
FR 2833947, 2001. (f) Taillefer, M.; Cristau, H.-J.; Cellier,
P. P.; Spindler, J.-F. WO 0353225, 2001; Pr. Nb. Fr 2001
16547. (g) Taillefer, M.; Cristau, H.-J.; Cellier, P. P.;
Spindler, J.-F.; Ouali, A. FR 2840303, 2002. (h) Taillefer,
M.; Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Ouali, A.
WO 03101966, 2002; Pr. Nb. Fr 200206717.
Supporting Information for this article is available online at
Acknowledgment
The authors thank the NSF-20621091 and the ‘Hundred Scientist’
from the Chinese Academy of Sciences for the financial support of
this work. Thank Dr. Ze-Yi Yan of Lanzhou University for his help
in preparation of manuscript.
References and Notes
(7) (a) Fan, H.; Xu, G.; Chen, Y.; Jiang, Z.; Zhang, S.; Yang, Y.;
Ji, R. Eur. J. Med. Chem. 2007, 42, 1137. (b) Kauer, J. C.;
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Y.-M. Tetrahedron 2005, 61, 9331. (b) Zhao, Y.-B.; Yan,
Z.-Y.; Liang, Y.-M. Tetrahedron Lett. 2006, 47, 1545.
(c) Yan, Z.-Y.; Niu, Y.-N.; Wei, H.-L.; Wu, L.-Y.; Zhao,
Y.-B.; Liang, Y.-M. Tetrahedron: Asymmetry 2006, 17,
3288. (d) Wu, L.-Y.; Yan, Z.-Y.; Xie, Y.-X.; Niu, Y.-N.;
Liang, Y.-M. Tetrahedron: Asymmetry 2007, 18, 2086.
(e) Niu, Y.-N.; Yan, Z.-Y.; Li, G.-Q.; Wei, H.-L.; Gao,
G.-L.; Wu, L.-Y.; Liang, Y.-M. Tetrahedron: Asymmetry
2008, 19, 912.
(9) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467.
(10) The present reaction exhibited strong solvent effect, which is
greatly different from the typical ‘click chemistry’. The
discrepancy was presumed to cause by the acetylene gas. In
the reactions, abundant reddish-brown precipitate was
formed.
(1) Reviews on 1,2,3-triazoles, see: (a) Fan, W.-Q.; Katritzky,
A. R. In Comprehensive Heterocyclic Chemistry II, Vol. 4;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Elsevier: Oxford, UK, 1996, 1–126. (b) Dehne, H. In
Methoden der Organischen Chemie (Houben-Weyl), Vol.
E8d; Schumann, E., Ed.; Thieme: Stuttgart, 1994, 305.
(2) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem.
Int. Ed. 2001, 40, 2004. (b) Rostovtsev, V. V.; Green, L. G.;
Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002,
41, 2596. (c) Tornøe, C. W.; Christensen, C.; Meldal, M.
J. Org. Chem. 2002, 67, 3057.
(3) For recent reviews, see: (a) Bock, V. D.; Hiemstra, H.; van
Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51.
(b) Fournier, D.; Hoogenboom, R.; Schubert, U. S. Chem.
Soc. Rev. 2007, 36, 1369. (c) Moses, J. E.; Moorhouse, A.
D. Chem. Soc. Rev. 2007, 36, 1249. (d) Wu, P.; Fokin, V. V.
Aldrichimica Acta 2007, 40, 7. (e) Tron, G. C.; Pirali, T.;
Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani,
A. A. Med. Res. Rev. 2008, 28, 278. (f) Gil, M. V.; Arévalo,
M. J.; López, Synthesis 2007, 1589. (g) Meldal, M.;
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(11) Acetonitrile and DMSO–H2O both gave excellent results in
the template reaction. But when other azides used, the yields
decreased significantly. In MeCN, 2b and 2c were obtained,
respectively, in 52% and 63% after 24 h. In DMSO–H2O
(4:1), 4-methylphenyl azide was tried, but the yield was only
poor 40%. Therefore, we chose DMSO as typical solvent in
subsequent experiments. The reason of the discrepancy is
unknown.
(4) For examples, see: (a) Whiting, M.; Muldoon, J.; Lin, Y.-C.;
Silverman, S. M.; Lindstrom, W.; Olson, A. J.; Kolb, H. C.;
Finn, M. G.; Sharpless, K. B.; Elder, J. H.; Fokin, V. V.
Angew. Chem. Int. Ed. 2006, 45, 1435. (b) Kolb, H. C.;
Sharpless, K. B. Drug Discov. Today 2003, 8, 1128. (c) Ye,
C. F.; Gard, G. L.; Winter, R. W.; Syvret, R. G.; Twamley,
B.; Shreeve, J. M. Org. Lett. 2007, 9, 3841. (d) Angelos, S.;
Yang, Y. W.; Patel, K.; Stoddart, J. F.; Zink, J. I. Angew.
Chem. Int. Ed. 2008, 47, 2222. (e) Fazio, F.; Bryan, M. C.;
Blixt, O.; Paulson, J. C.; Wong, C.-H. J. Am. Chem. Soc.
2002, 124, 14397. (f) Lutz, J.-F. Angew. Chem. Int. Ed.
2007, 46, 1018.
(12) Typical Procedure for Compound 2.
To a 5 mL flask with Et3N (0.4 mmol), azides 1 (1.0 mmol),
and solvent (1.5 mL), CuI (0.1 mmol) was added into the
mixture under N2 atmosphere. The flask was purged with
acetylene for several times. Then the mixture was stirred
under a balloon pressure of acetylene at r.t. After the
designed time, the mixture was diluted with 25 mL EtOAc,
and washed by 10 mL H2O for four times then by brine. The
organic phase dried over anhyd Na2SO4. After removal of
the solvent under reduced pressure, the residue was purified
on SiO2 with PE–EtOAc (4:1 to 1:2). Caution: Azides are
potentially explosive compounds and should be handled
with great care.
Synlett 2009, No. 9, 1453–1456 © Thieme Stuttgart · New York