Click chemistry in CuI-zeolites: The Huisgen [3 + 2]-cycloaddition

Article abstract of DOI:10.1021/ol0631152

(Chemical Equation Presented) Cu^I-exchanged solids based on zeolite materials were investigated for the first time as catalysts in organic synthesis. The catalytic potential of these materials was evaluated in the Huisgen [3 + 2]-cycloaddition.

Full text of DOI:10.1021/ol0631152

ORGANIC
LETTERS
I
2007
Vol. 9, No. 5
Click Chemistry in Cu -zeolites: The
8
83-886
Huisgen [3
+
2]-Cycloaddition
†
†
†,‡
Stefan Chassaing, Mayilvasagam Kumarraja, Abdelkarim Sani Souna Sido,
,
‡
,†
Patrick Pale,* and Jean Sommer*
Laboratoire de Physicochimie des Hydrocarbures, assosi e´ au CNRS, and Laboratoire
de Synth e` se et R e´ actiVit e´ Organique, associ e´ au CNRS, Institut de Chimie, UniVersit e´
L. Pasteur, 4 rue B. Pascal, 67000 Strasbourg, France
sommer@chimie.u-strasbg.fr; ppale@chimie.u-strasbg.fr
Received December 24, 2006
ABSTRACT
I
Cu -exchanged solids based on zeolite materials were investigated for the first time as catalysts in organic synthesis. The catalytic potential
I
I
of these materials was evaluated in the Huisgen [3
+ 2]-cycloaddition. Five Cu -exchanged zeolites were examined and Cu -USY proved to be
a novel and efficient heterogeneous ligand-free catalyst for this “click chemistry”-type transformation.
7
The development of synthetic tools able to connect highly
functionalized fragments still constitutes an exciting chal-
lenge for organic chemists. The so-called “click chemistry”
establishing heteroatom linkages between unsaturated build-
ing blocks is probably the most effective way to connect
of Cu turnings. More flexible, supported, and reusable
catalysts would clearly improve the scope of this click
8
reaction.
Involved in zeolite and other solid acid-catalyzed chem-
istry, we were aware of the possibility of modifying such
catalysts. Because Cu -modified zeolites have been recently
described and characterized, we thus wondered if such
9
1
I
2
I
molecules. Among them, the Cu -catalyzed version of the
3
10
Huisgen [3 + 2]-cycloaddition between a terminal alkyne
I
1
and an azide 2 is to date the most practical and useful
heterogeneous Cu species would catalyze the Huisgen
“
1
click” reaction, regioselectively affording 1,4-disubstituted
reaction and give rise to click chemistry. We show here that
Cu -zeolites are indeed an effective ligand-free catalyst for
the Huisgen [3 + 2]-cycloaddition (Scheme 1).
,2,3-triazoles 3 (Scheme 1).4
,5
I
I
In this reaction, the active Cu catalytic species are directly
I
2a,6
formed from Cu salts in the presence of ligands
prepared in situ by reduction of Cu salts or by oxidation
or
II
2b
Scheme 1
†
Laboratoire de Physicochimie des Hydrocarbures.
Laboratoire de Synth e` se et R e´ activit e´ Organique.
‡
(1) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004-2021. (b) Kolb, H. C.; Sharpless, K. B. Drug DiscoVery
Today 2003, 8, 1128-1137.
I
(
2) For pioneering reports on a Cu -catalyzed variant, see: (a) Tornøe,
C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057-3064.
(
b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2002, 41, 2596-2599. For a recent review, see: (c) Bock,
V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51-
6
2
8.
(
3) (a) Huisgen, R.; Szeimis, G.; Moebius, L. Chem. Ber. 1967, 100,
a
b
Classical catalytic system (L ) ligand). Investigated catalytic
system.
494-2507. (b) Huisgen, R. In 1,3-Dipolar Cycloadditional Chemistry;
Padwa, A., Ed.; Wiley: New York, 1984; pp 1-176. (c) Huisgen, R. Pure
Appl. Chem. 1989, 61, 613-628.
1
0.1021/ol0631152 CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/08/2007

Because zeolites are solids mainly characterized by their
topologies (cage or channel-type), pore size (typically 6-8
Å), and acidity (correlated to the Si/Al ratio), we prepared a
series of catalysts derived from five representative zeolites,
Table 1. Screening of Catalysts for the Cycloaddition of
Phenylacetylene 1a to Benzyl Azide 2aa
1
1
e.g., H-USY, H-Y, H-MOR, H-ZSM5, and H-â, by
subjecting them to CuCl treatment.12 It is noteworthy that
I
the incorporation as well as the stabilization of Cu ions in
zeolite frameworks have been largely demonstrated in
previous reports.10
The classical cycloaddition of phenylacetylene 1a with
benzyl azide 2a was used to explore the efficiency of these
Cu -modified zeolites (Tables 1 and 2).
Without any catalyst, this reaction did not take place in
toluene at room temperature (Table 1, entry 1), but led to a
entry
catalyst
temp (°C)
time (h)
yield (%)b,c
I
d
1
2
3
4
5
6
7
8
9
none
none
CuCl
rt
110
rt
rt
110
rt
110
rt
110
rt
110
rt
110
rt
96
48
48
15
5
15
5
15
5
15
5
15
5
<5
70
70
e
f
I
Cu -USY
83
87
68
75
69
79
63
79
47
1:1 mixture of regioisomers after a prolonged reaction time
I
Cu -USY
at reflux (Table 1, entry 2). With CuCl alone as the catalyst,
the reaction was still very slow but yielded a single
I
Cu -Y
I
Cu -Y
I
Cu -MOR
I
(4) For recent applications (a) in organic synthesis, see: Bodine, K. D.;
Cu -MOR
Gin, D. Y.; Gin, M. S. J. Am. Chem. Soc. 2004, 126, 1638-1639. Ryu,
E.-H.; Zhao, Y. Org. Lett. 2005, 7, 1035-1037. Dichtel, W. R.; Miljanic,
O. S.; Spruell, J. M.; Health, J. R.; Stoddart, J. F. J. Am. Chem. Soc. 2006,
I
1
1
1
0
1
2
Cu -ZSM5
I
Cu -ZSM5
I
Cu -â
1
28, 10388-10390. Aucagne, V.; Leigh, D. A. Org. Lett. 2006, 8, 4505-
I
4
507. (b) In combinatorial chemistry, see: L o¨ ber, S.; Rodriguez-Loaiza,
13
Cu -â
73
-d
P.; Gmeiner, P. Org. Lett. 2003, 5, 1753-1755. Rodriguez-Loaiza, P.; L o¨ ber,
S.; H u¨ bner, H.; Gmeiner, P. J. Comb. Chem. 2006, 8, 252-261. (c) In
bioconjugation, see: Cavalli, S.; Tipton, A. R.; Ovarhand, M.; Kros, A.
Chem. Commun. 2006, 3193-3195. Brennan, J. L.; Hatzakis, N. S.;
Tshikhudo, T. R.; Dirvianskyte, N.; Razumas, V.; Patkar, S.; Vind, J.;
Svendsen, A.; Nolte, R. J. M.; Rowan, A. E.; Brust, M. Bioconjugate Chem.
14
H-USY
15
a
Reagents and reaction conditions: 1a (1.2 equiv), 2a (1.0 equiv),
solution concentration (1 M), 10 mol % of catalyst,13 toluene. Yields of
b
isolated pure product 3a after complete conversion unless otherwise stated
c
(see Supporting Information). Only the 1,4-adduct was formed and isolated
unless otherwise noted. dMainly recovery of the starting materials. 1:1
e
2
006, 17, 1373-1375. (d) In materials and surface science, see: Lummer-
f
storfer, T.; Hoffmann, H. J. Phys. Chem. B 2004, 108, 3963-3966. Parrish,
mixture of regioisomers. Incomplete conversion.
B.; Breitenkamp, R. B.; Emrick, T. J. Am. Chem. Soc. 2005, 127, 7404-
7
410. Such, G. K.; Quinn, J. F.; Quinn, A.; Tjipto, E.; Caruso, F. J. Am.
Chem. Soc. 2006, 128, 9318-9319.
5) Triazoles exhibit interesting properties. (a) In liquid crystals, see:
Gallardo, H.; Ely, F.; Bortoluzzi, A. J.; Conte, G. Liq. Cryst. 2005, 32,
67-671. (b) In multipolar chromophores, see: Parent, M.; Mongin, O.;
(
regioisomer (Table 1, entry 3). In sharp contrast, the modified
I
I
I
I
I
zeolites Cu -USY, Cu -Y, Cu -MOR, Cu -ZSM5, and Cu -â
gave the expected adduct even at room temperature as a
single regioisomer (Table 1, entries 4-13). Good to high
6
Kamada, K.; Katan, C.; Blanchard-Desce, M. Chem. Commun. 2005, 2029-
2
3
031. (c) As â-turn mimics, see: Oh, K.; Guan, Z. Chem. Commun. 2006,
069-3071.
yields were obtained in refluxing toluene (entries 5, 7, 9,
(
6) (a) Lewis, W. G.; Magallon, F. G.; Fokin, V. V.; Finn, M. G. J. Am.
Chem. Soc. 2004, 126, 9152-9153. (b) Diez-Gonzalez, S.; Correa, A.;
I
1
(
1, and 13) and even at room temperature, except for Cu -â
Cavallo, L.; Nolan, S. P. Chem.-Eur. J. 2006, 12, 7558-7564.
I
entry 12 vs 4, 6, 8, and 10). Cu -USY clearly appeared as
(7) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman,
L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210-216.
I
(
8) A polymer-supported catalyst, involving a Cu -nitrogen ligand
combination, has recently been reported. See: (a) Girard, C.; O¨ nen, E.;
Aufort, M.; Beauvi e` re, S.; Samson, E.; Herscovici, J. Org. Lett. 2006, 8,
Table 2. Optimization of the Solventa
1
689-1692. For copper catalysts avoiding the use of an additive ligand or
reducing agent, see: (b) Pachon, L. D.; van Maarseveen, J. H.; Rothenberg,
G. AdV. Synth. Catal. 2005, 347, 811-815. (c) Molteni, G.; Bianchi, C. L.;
Marinoni, G.; Santod, N.; Ponti, A. New J. Chem. 2006, 30, 1137-1139.
(9) For recent examples, see: (a) Koltunov, K. Y.; Walspurger, S.;
Sommer, J. Chem. Commun. 2004, 1754-1755. (b) Haouas, M.;
Walspurger, S.; Taulelle, F.; Sommer, J. J. Am. Chem. Soc. 2004, 126,
5
99-606. (c) Koltunov, K. Y.; Walspurger, S.; Sommer, J. Tetrahedron
Lett. 2005, 46, 8391-8394. (d) Walspurger, S.; Sun, Y.; Sani Souna Sido,
A.; Sommer, J. J. Phys. Chem. B 2006, 110, 18368-18373. (e) Koltunov,
K. Y.; Walspurger, S.; Sommer, J. J. Mol. Catal. A 2006, 245, 231-234.
entry
solvent
yield (%)b,c
(10) (a) Lamberti, C.; Turnes Palomino, G.; Bordiga, S.; Berlier, G.;
1
2
3
4
5
6
PhCH3
PhH
CH2Cl2
THF
CH3CN
CH3OH
83
64
82
62
61
61
D’Acapito, F.; Zecchina, A. Angew. Chem., Int. Ed. 2000, 39, 2138-2141.
(
b) Turnes Palomino, G.; Bordiga, S.; Zecchina, A.; Marra, G. L.; Lamberti,
C. J. Phys. Chem. B 2000, 104, 8641-8651. (c) Bolis, V.; Meda, L.;
D’Acapito, F.; Turnes Palomino, G.; Bordiga, S. J. Chem. Phys. 2000, 113,
d
d
9
248-9261. (d) Lamberti, C.; Bordiga, S.; Bonino, F.; Prestipino, C.;
d
Berlier, G.; Capello, L.; D’Acapito, F.; Llabr e´ s i Xamena, F. X.; Zecchina,
A. Phys. Chem. Chem. Phys. 2003, 5, 4502-4509. (e) Prestipino, C.;
Capello, L.; D’Acapito, F.; Lamberti, C. Phys. Chem. Chem. Phys. 2005,
d,e
a
7
, 1743-1746. For a recent review, see: (f) Berthomieu, D.; Delahay, G.
Reagents and reaction conditions: 1a (1.2 equiv), 2a (1.0 equiv),
solution concentration (1 M), 10 mol % of catalyst, 15 h, rt. Yields of
isolated pure product 3a. Only the 1,4-adduct was formed and isolated
unless otherwise noted. Unidentified byproducts were formed. Incomplete
conversion even after 48 h.
13
b
Catal. ReV. 2006, 48, 269-313.
c
(
11) Characteristics of H-zeolites are given in Supporting Information.
12) For the preparation of Cu -zeolites, we adopted the solid-state
I
d
e
(
exchange procedure reported in: Li, Z.; Xie, K.; Slade, R. C. T. Appl. Catal.
A: Gen. 2001, 209, 107-115.
884
Org. Lett., Vol. 9, No. 5, 2007

the best system (entries 4 and 5 vs 6-13). Furthermore, an
experiment performed on native H-USY did not yield any
expected adduct 3a, highlighting the key role of copper
loaded in the zeolite (entry 14 vs 4).
Table 3. Scope of the Catalytic Systema
I
These data thus show that the Cu catalytic activity is
significantly enhanced in the presence of modified zeolites.
After selection of the most efficient catalyst, we screened
different solvents to adjust the reaction conditions (Table
2). Among the solvents examined, toluene and benzene were
the only ones where reactions proceeded without detectable
formation of byproducts. Toluene proved to be the best
solvent, being more effective than benzene (Table 2, entry
1
vs 2). In dichloromethane, the yield was very similar to
the one in toluene (entry 3), but the reaction was however
less clean. More polar solvents such as tetrahydrofuran,
acetonitrile, and methanol led to lower yields and to the
formation of undesirable byproducts (entries 4-6). In the
case of toluene and benzene, purity of the crude adduct was
1
more than 95% as judged by H NMR (see Supporting
Information). With other solvents, chromatography purifica-
tion was required to obtain pure 3a (entries 3-6). We also
examined the recycling of the catalyst. It is noteworthy that,
under the optimized reaction conditions (i.e., Cu-USY
catalyst in toluene), the catalyst was reused three times
without dramatic yield loss.
To explore the scope of this reaction, simple alkynes
bearing different functional groups 1b-g were submitted to
I
various azides 2b-d in the presence of Cu -USY as catalyst
(Table 3, entries 1-10).
Simple nonfunctionalized alkynes such as 1b reacted with
benzyl azide 2a very efficiently, giving the expected adduct
3e as a single regioisomer in excellent yield (Table 3, entry
5). Hydroxy-substituted alkynes such as 1c and 1d also gave
the expected adducts 3f,g as a single regioisomer in good to
high yields (Table 3, entries 6 and 7).
Electronic effects are known to influence cycloaddi-
tions.1
4,15
Although the mechanism of the Cu -catalyzed
Huisgen reaction is probably different from a classical [3 +
I
16
2
]-cycloaddition, we nevertheless investigated on one hand
a
Reagents and reaction conditions: 1 (1.2 equiv), 2 (1.0 equiv), solution
the reaction of terminal alkynes substituted by either an
electron-donating or -withdrawing group (entries 1 and
I
13
b
concentration (1 M), 10 mol % of Cu -USY, toluene, 15 h, rt. Yields of
isolated pure product 3. Only the 1,4-adduct was formed and isolated unless
otherwise noted. Mainly recovery of the starting materials. Unidentified
byproducts were formed.
c
d
e
5-10) and on the other hand the reaction of phenyl azides
bearing or not an electron-donating or -withdrawing group
at the para position (entries 2-4).
1
,4-diphenyl-1,2,3-triazole 3b in good yield after chroma-
With benzyl azide 2a, no significant difference was
observed with acetylenes substituted with an alkyl, a phenyl,
or an electron-withdrawing group (entries 1, 5, and 10). With
phenylacetylene 1a, phenyl azide itself 2b gave the expected
tography (entry 2). Its para-methoxy analogue 2c reacted
similarly (entry 3). However, the corresponding para-
nitrophenyl azide 2d did not react under the same conditions
and only traces of the expected adduct could be detected,
revealing a deleterious effect of electron-withdrawing sub-
stitutents on the reaction (entry 4).
Acetylenes conjugated with either an amide or an ester
group such as 1f and 1g reacted without any problem with
benzyl azide. The corresponding triazoles 3i and 3j were
obtained in high yields (entries 9 and 10). However,
I
(
13) Concerning Cu -zeolite, 10 mol % of catalyst corresponds to 10
I
mol % of Cu species based on the theoretical number of native acidic sites
of the corresponding H-zeolite. For a recent method of determination of
Br o¨ nsted acid sites on zeolites, see: Louis, B.; Walspurger, S.; Sommer, J.
Catal. Lett. 2004, 93, 81-84.
(
14) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: Chichester, 1976; p 86.
15) For some reviews, see: (a) L’abb e´ , G. Chem. ReV. 1969, 69, 345-
(
1
-phenylpropynone 1e seemed to decompose under the
3
63. (b) Herndon, W. C. Chem. ReV. 1972, 72, 157-179. (c) Houk, K. N.
Acc. Chem. Res. 1975, 8, 361-369. (d) Gothelf, K. V.; Jorgensen, K. A.
reaction conditions, even at room temperature, and byprod-
ucts were formed. The yield of triazole 3h was therefore
lower (entry 8).
Chem. ReV. 1998, 98, 863-909.
(
16) Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Angew. Chem., Int.
Ed. 2005, 44, 2210-2215.
Org. Lett., Vol. 9, No. 5, 2007
885

In conclusion, we have reported for the first time an
original use of Cu -modified zeolites as catalysts in organic
Acknowledgment. The authors thank the CNRS and the
French Ministry of Research as well as the Loker Hydro-
carbon Institute, University of Southern California, Los
Angeles, for financial support.
I
synthesis. With such catalysts, we have developed a simple
and efficient method for the [3 + 2]-cycloaddition of terminal
alkynes with azides. Moreover, a single regioisomer, the 1,4-
diphenyl-1,2,3-triazole, was formed. These results thus
broaden the scope of this so-called click chemistry.
Further work is now underway to expand the use of
modified zeolites as catalysts in organic synthesis and to
better understand the role of the zeolite core in these
reactions.
Supporting Information Available: General procedure
and 13C NMR spectra of known compounds are provided.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL0631152
886
Org. Lett., Vol. 9, No. 5, 2007