LETTER
Azide–Alkyne Cycloaddition Reaction in Water
845
Table 3 Scope of the Reaction of Azides with Alkynesa
References and Notes
R2
CuCl/1
(3 mol %)
(1) For reviews on the CuAAC reaction, see: (a) Korb, H. C.;
Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001,
40, 2004. (b) Bock, V. D.; Hiemstra, H.; Maarseveen, J. H.
Eur. J. Org. Chem. 2006, 1, 51. (c) Meldal, M.; Tornøe, C.
W. Chem. Rev. 2008, 108, 2952. (d) Hein, J. E.; Fokin, V. V.
Chem. Soc. Rev. 2010, 39, 1302. (e) Kappe, C. O.; Eycken,
E. V. Chem. Soc. Rev. 2010, 39, 1280. (f) Liang, L.; Astruc,
D. Coord. Chem. Rev. 2011, 255, 2933. (g) Struthers, H.;
Mindt, T. L.; Schibli, R. Dalton Trans. 2010, 39, 675. For
recent selected works on CuAAC reaction, see:
(h) Özçubukçu, S.; Ozkai, E.; Jimeno, C.; Pericàs, M. A.
Org. Lett. 2009, 11, 4680. (i) Ozkal, E.; Özçubukçu, S.;
Jimeno, C.; Pericàs, M. A. Catal. Sci. Technol. 2012, 2, 195.
(j) Nakamura, T.; Terashima, T.; Ogata, K.; Fukuzawa, S.-i.
Org. Lett. 2011, 13, 620. (k) Yamada, Y. M. A.; Sarkar, S.
M.; Uozumi, Y. J. Am. Chem. Soc. 2012, 134, 9285. (l) Shin,
J.-A.; Lim, Y.-G.; Lee, K.-H. J. Org. Chem. 2012, 77, 4117.
(m) Berg, R.; Straub, J.; Schreiner, E.; Mader, S.; Rominger,
F.; Straub, B.-F. Adv. Synth. Catal. 2012, 354, 3445.
(2) (a) Click Chemistry for Biotechnology and Materials
Science; Lahnn, J., Ed.; John Wiley and Sons: Chichester,
2009. For reviews, see: (b) Gil, M. V.; Arévalo, M. J. López
Ó. Synthesis 2007, 1589. (c) Binder, W. H.; Sachsenhofer,
R. Macromol. Rapid. Commun. 2008, 29, 952. (d) Aragão-
Leoneti, V.; Campo, V. L.; Gomes, A. S.; Field, R. A.;
Carvalho, I. Tetrahedron 2010, 66, 9475. (e) Muller, T.;
Bräse, S. Angew. Chem. Int. Ed. 2011, 50, 11844.
(3) For examples of pyta–metal complexes, see: (a) Obata, M.;
Kitamura, A.; Mori, A.; Kameyama, C.; Czaplewska, J. A.;
Tanaka, R.; Kinoshita, I.; Kusumoto, T.; Hashimoto, H.;
Harada, M.; Mikata, Y.; Funabiki, T.; Yano, S. Dalton
Trans. 2008, 3292. (b) Fletcher, J. T.; Bumgarner, B. J.;
Engels, N. D.; Skoglung, D. A. Organometallics 2008, 27,
5430. (c) Schweinfurth, D.; Pattacini, R.; Strobel, S.; Sarkar,
B. Dalton Trans. 2009, 9291. (d) Felici, M.; Contrera-
Carballda, P.; Vida, Y.; Smits, J. M. M.; Nolte, R. J. M.;
Cola, L. D.; Williams, R. M.; Feiters, M. C. Chem. Eur. J.
2009, 15, 13124. (e) Uranker, D.; Pinter, B.; Pevec, A.; De
Proft, F.; Turel, I.; Košmrlj, J. Inorg. Chem. 2010, 49, 4820.
(f) Fleischel, O.; Wu, N.; Petitjean, A. Chem. Commun.
2010, 46, 8454. (g) Happ, B.; Escudero, D.; Hager, M. D.;
Friebe, C.; Winter, A.; Görls, H.; Altuntas, E.; Gonzáles, L.;
Schubert, U. S. J. Org. Chem. 2010, 75, 4025. (h) Crowley,
J. D.; Bandeen, P. H.; Honton, L. R. Polyhedron 2010, 29,
70. (i) Kilpin, K. J.; Crowley, J. D. Polyhedron 2010, 29,
3111. (j) Schweinfurth, D.; Strobel, S.; Sarkar, B. Inorg.
Chim. Acta 2011, 374, 253. (k) Stengel, I.; Mishra, A.;
Pootrakulchote, N.; Moon, S.-J.; Zakeerruddin, S. M.;
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(l) Zhang, G.; Wang, Y.; Wen, X.; Ding, C.; Li, Y. Chem.
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41, 12984.
N
N
R2N3
+
R1
R1
H2O, r.t.
N
Entry
R1
Ph
R2
Time (h) Yield (%)b
1
2
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
0.5
0.1
0.5
0.25
1
5, 96c
6, 97
4-MeC6H4
2-MeC6H4
2-MeOC6H4
4-CF3C6H4
2-FC6H4
n-C4H9
c-C3H5
CH2OH
CO2Me
2-pyridyl
2-pyridyl
Ph
3
7, 89
4
8, 93
5
9, 93
6
0.1
1
10, 94
11, 91
12, 89
13, 83
14, 91
3, 45c
3, 86
7
8
1
9
1.5
3
10
11
12
13
14
15
16
17d
18e
19e
1
3
n-C8H17
5.5
15, 81
16, 94
17, 93
18, 89
18, 93
18, 91
19, 64
Ph
Ph
10
5.5
60
Ph
Mes
Mes
Mes
Mes
Dipp
Mes
Mes
7
1
Mes
Dipp
17
a Reaction conditions: Alkyne (1.0 mmol), azide (1.05 mmol), CuCl
(0.03 mmol), 1 (0.03 mmol), H2O (3.0 mL), r.t.
b Isolated yield.
c GC yield.
d The reaction was carried out at 50 °C.
e The reaction was carried out at 100 °C.
In conclusion, this report highlights the use of a combina-
tion of 2-ethynylpyridine and CuCl as an effective catalyst
for the CuAAC reaction in water and demonstrates its tol-
erance of various functional groups, including sterically
crowded substituents on the alkynes or azides; 1,4-dipp-
1,2,3-triazole can easily be prepared by using this catalyst
without employing active but expensive NHC–Cu com-
plexes.9
(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:
Acknowledgement
This work was financially supported by a Chuo University Grant for
Special Research.
Supporting Information for this article is available online at
m
iotSrat
ungIifoop
r
t
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 843–846