Copper(I)-zeolites as new heterogeneous and green catalysts for organic synthesis

Article abstract of DOI:10.1055/s-0029-1218733

We have evaluated the potential of Cu^I-doped zeolites as heterogeneous catalysts for organic synthesis. Such catalysts proved to be easy to prepare, handle, recover, and recycle. They could be applied to different synthetic applications, such as [3+2] cycloadditions of alkynes with either azides or azomethine imines and the homocoupling of alkynes. These interesting characteristics make them highly attractive as catalysts for organic chemists, especially with regard to aspects of 'green chemistry'. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218733

FEATURE ARTICLE
1557
Copper(I)-Zeolites as New Heterogeneous and Green Catalysts for Organic
Synthesis
pt fan Chassaing, Aurélien Alix, Thirupathi Boningari, Karim Sani Souna Sido, Murielle Keller,b
d
a
b
a,b
T
S
he Zeo-Clic
k
t
Conce
e
b,c
c
b
a
Philippe Kuhn, Benoit Louis, Jean Sommer, Patrick Pale*
a
Laboratoire de Synthèse et Réactivité Organiques, Institut de Chimie de Strasbourg, Université de Strasbourg,
rue Blaise Pascal, 67000 Strasbourg, France
4
Fax +33(3)68851517; E-mail: ppale@chimie.u-strasbg.fr; E-mail: ppale@unistra.fr
Laboratoire de Physicochimie des Hydrocarbures, Institut de Chimie de Strasbourg, Université de Strasbourg,
b
c
d
4
rue Blaise Pascal, 67000 Strasbourg, France
Laboratoire des Matériaux, Surfaces et Procédés pour la Catalyse (UMR 7515 du CNRS),
5 rue Becquerel, 67087 Strasbourg Cedex 2, France
Laboratoire de Synthèse et Physicochimie de Molécules d’Intérêt Biologique (UMR 5068 du CNRS), Université Paul Sabatier,
18 route de Narbonne, 31062 Toulouse Cedex 9, France
2
1
Received 23 December 2009; revised 18 January 2010
I
rently exploring the potential of Cu -doped zeolites in
I
Abstract: We have evaluated the potential of Cu -doped zeolites as
organic synthesis. We reported here an update of our re-
sults in this new area, showing that such catalysts are able
heterogeneous catalysts for organic synthesis. Such catalysts
proved to be easy to prepare, handle, recover, and recycle. They
could be applied to different synthetic applications, such as [3+2] to promote efficiently different cycloaddition and cou-
cycloadditions of alkynes with either azides or azomethine imines pling reactions. Such easy and efficient ways to perform
and the homocoupling of alkynes. These interesting characteristics
reactions led us to coin the term ‘zeo-click’ for such pro-
make them highly attractive as catalysts for organic chemists, espe-
cesses (Figure 1) by analogy to the Sharpless ‘click’
cially with regard to aspects of ‘green chemistry’.
chemistry principles.4
1
2
3
3
3
3
3
4
Introduction
I
Synthesis and Structures of Cu -Doped Zeolites
I
Cu -Zeolites as Catalysts in Organic Synthesis
.1
.2
.3
.4
Cycloadditions: ‘Click in Zeo’
Cascade Reactions: Substitution and Cycloaddition
Cycloadditions: Mechanistic Investigations
Homocoupling of Alkynes
Conclusion
Key words: zeolite, copper, catalysis, green chemistry
1
Introduction
Increasing environmental concerns within the past decade1
have led to the emergence of so-called ‘green chemistry’.
Within this ‘green chemistry’ context, we are looking for
new classes of heterogeneous catalysts that are easy-to-
handle and recyclable, but they can replace environmen-
tally unfriendly reagents and/or solvents, and, at the same
time, they can carry out the desired organic reactions with
higher yield and better selectivity, while minimizing ener-
gy and waste.
Figure 1 The zeo-click concept
Our interest in liquid or solid superacid-mediated organic
2
transformations recently led us to envisage exploiting the
I
2
Synthesis and Structure of Cu -Doped Zeo-
lites
catalytic and discrimination properties of zeolites while
combining this with the catalytic properties of selected
metallic ions. Due to the large number of organic reac-
3
The ion-exchange properties of zeolites are well known
and have been extensively exploited, inter alia, in water
treatments. For stability and solubility reasons, zeolites
containing copper(II) could be easily prepared through
tions promoted by copper salts or complexes, we are cur-
5
SYNTHESIS 2010, No. 9, pp 1557–1567
x
x
.
x
x
.2
0
1
0
Advanced online publication: 12.04.2010
DOI: 10.1055/s-0029-1218733; Art ID: Z27909SS
Georg Thieme Verlag Stuttgart · New York
II
such exchange. Cu -Zeolites are thus common and have
©

1
558
S. Chassaing et al.
FEATURE ARTICLE
been used for depollution processes such as NO
[Equation 1 (a)]. These acidic zeolites were then mixed
x
6
7
reduction and ammoniac oxidation. They have also been with dry solid copper(I) chloride and the corresponding
utilized to improve the production of cyanamide from mixtures were heated under nitrogen flow at 350 °C or
8
9
urea, to convert syngas into methanol, and for the carbo- higher for 7–65 hours [Equation 1 (b)].
1
0
nylation of methanol to dimethyl carbonate. In contrast,
zeolites containing copper(I) are scarce, probably due to
the sensitivity of such species to redox processes and to
550 °C
H4N Zeolite
H
Zeolite + NH3
(a)
5
h
I
the low solubility of Cu(I) salts in water. Cu -Zeolites
3
50–650 °C
7–65 h
CuI Zeolite + HCl (b)
H
Zeolite
+
CuCl
have been obtained by ion-exchange from aqueous solu-
tions of copper(II) acetate, copper nitrate, or copper(II)
tetraamine nitrate with subsequent reduction under carbon
I
Equation 1 Preparation of Cu -doped zeolites
1
1
monoxide or hydrogen at high temperatures. A type of
zeolite, the ferrierite, has been directly obtained by in situ
Although the temperature was below the melting point of
copper(I) chloride (430 °C), copper(I) chloride was clear-
ly able to sublimate at such temperatures and the nitrogen
flow allowed it to diffuse within the zeolite, whatever its
+
formation of a copper(I) complex [Cu(NH ) ] during the
3
2
2
1
sol-gel preparation of the ferrierite itself. Alternatively,
Cu -zeolites could be obtained by interactions of H-zeo-
lites with gaseous copper(I) chloride. Surprisingly, the
so-formed Cu -zeolites have always been studied in redox
I
+
1
3
structure and internal shape. During this process, Cu ions
I
exchanged with the zeolite protons. HCl was indeed de-
tected at the exhaust with each zeolite investigated. Sev-
II
processes for depollution, in comparison with Cu -zeo-
+
eral physical techniques confirmed that Cu ions migrated
lites. No other application has so far been reported.
within the zeolite crystalline framework, replacing zeolite
I
On this basis, we prepared Cu -doped zeolites from five
protons at such relatively high temperatures. Interesting-
representative zeolites, H-USY, H-Y, H-MOR, H-ZSM5,
and H-b. They were prepared by heating the commercially
available ammonium zeolites under nitrogen flow
+
ly, the Cu loading could be tuned by varying the temper-
ature and the contact time, from 80% at 350 °C to almost
1
00% at 650 °C.14
Biographical Sketches
Stefan Chassaing was born synthesis. Following his Quideau at the European In-
in 1975 in Haguenau, doctoral studies, he re- stitute of Chemistry and Bi-
France. He studied physics mained for a further year at ology where he worked on
and chemistry at the Louis the Louis Pasteur University ellagitannin chemistry and
Pasteur University in Stras- as a postdoctoral research oxidative dearomatization
bourg where, after also associate in the group of of phenols. In 2008, he
teaching in a secondary Prof. Jean Sommer, where joined the group of Dr.
school for two years, he ob- he contributed to the devel- Michel Baltas at the Paul
tained his Ph.D. in 2006 un- opment of zeolite-based cat- Sabatier University in Tou-
der the supervision of Prof. alysts for organic synthesis. louse as assistant professor.
Raymond Brouillard; his re- In 2007, he moved to Bor- His current research inter-
search focused on methods deaux, France, for a second ests focus on the synthesis
and their development and postdoctoral stay in the and biological activity of
application to flavonoid group of Prof. Stéphane natural products and ana-
logues.
Patrick Pale studied at the Ardenne as a CNRS fellow. University L. Pasteur in
University of Champagne- Working on rearrangements Strasbourg. Subsequently,
Ardenne, France, where he and reaction mechanisms he was awarded Professor at
obtained his Ph.D. in 1982 with the late Prof. J. the ‘Institut Universitaire de
under the direction of Profs. Chuche, he obtained a ‘Doc- France’ from 1996 to 2001.
J. P. Pete and J. Muzart. Af- torat d’Etat’ in 1988, and His scientific interests in-
ter an industrial stay in a then a research associate po- clude total synthesis of bio-
pharmaceutical company, sition at Harvard University active
compounds,
he joined the group of Prof. in the group of Prof. G. organometallic chemistry,
L. Ghosez at Louvain-La- Whitesides in 1988–1990. asymmetric synthesis, car-
Neuve in Belgium for post- He returned to the Universi- bohydrate chemistry, and
doctoral work on the devel- ty of Champagne-Ardenne, enzymatic chemistry, and
opment of azadienes. In and took up his present posi- more recently chemistry in
1984, he returned to the tion in 1995 as Professor of nanoreactors such as zeo-
University of Champagne- Organic Chemistry at the lites.
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

FEATURE ARTICLE
The Zeo-Click Concept
1559
After this doping process, the zeolite structures were
mostly preserved, as revealed by X-ray powder diffrac-
tion. However, depending on the duration of vaporization
and the temperature, de-alumination occurred, leading to
the formation of extra-framework aluminum species, in-
R1
N
N
N
N
N
N
N
N
N
N
N
N
heat
R2
(a)
(b)
R2
R1
R1
R2
R1
1
5
ducing higher Lewis acidity of the modified zeolites.
I
N
N
Cu -L cat.
N
N
I
R2
Cu -Zeolites prepared at 350 °C exhibited fewer structural
modifications, while those prepared at 650 °C were more
affected. Crystallinity decreased under severe exchange
conditions, from 86% for zeolites prepared at 350 °C to
R2
r.t.
R1
R3
R3
R3
R4
R2
N
R4
R2
N
R4
R2
N
N
6
5% for zeolite prepared at 650 °C for 15 hours, and even
N
heat
(c)
lower for prolonged calcination times. Moreover, the
H/Cu exchange varied upon the calcination temperature
R1
R1
R1
I
R3
and time. Cu -USY prepared at 350 °C still contained
R3
I
R4
2
0% protons, while none remained in Cu -USY prepared
R2
N
R2
N
R4
I
1
5
N
Cu -L cat.
N
at 650 °C.
(
d)
R1
r.t.
R1
I
Scheme 1 [3+2] Cycloadditions catalyzed by copper compared to
the original version. (a) Huisgen cycloaddition, (b) Meldal–Sharpless
version, (c) Dorn cycloaddition, (d) Fu version.
3
Organic Synthesis with Cu -Doped Zeolites
I
These so-formed Cu -doped zeolites were then investigat-
ed as new catalysts for specific problems in organic syn-
thesis. To better comply with the principles of ‘green
chemistry’, we applied such catalysts to reactions that
are, in essence, economic in steps and atoms, such as cy-
cloadditions and coupling reactions (Figure 1).
duction of copper(II) salts or by oxidation of copper
turnings.
1
a
In contrast, several studies showed that the zeolite frame-
work could behave like a ligand towards various inserted
2
2
metal ions. Therefore, and although copper zeolites have
usually been used in redox reactions, we reasoned that im-
mobilizing copper(I) ions into zeolites would stabilize
them, the zeolite framework acting as a ligand. Doping as
such zeolites would provide a stable, supported, and reus-
able copper(I) catalyst. Moreover, with such catalysts,
discrimination could also be expected depending on the
I
3
.1
Cu -Zeolite-Catalyzed Cycloadditions
It is well known that cycloadditions can be catalyzed by
Brønsted or, more conveniently, by Lewis acids. In paral-
lel with the acceleration of the reaction, such catalysis
usually reinforced regioselectivity, as amply demonstrat-
ed for [4+2] cycloadditions. More recently, [3+2] cy-
cloadditions have also been reinvestigated with catalysis
in mind; a typical example is the Huisgen reaction. In this
reaction, alkynes and azides were heated together, yield-
ing a mixture of regioisomeric disubstituted 1,2,3-tria-
I
1
6
zeolite pore size and shape. We, thus, investigated Cu -ze-
olites as catalysts for the Huisgen and Dorn cycloaddition
(
Scheme 2).
N
N
(a)
1
7
N
N
zoles [Scheme 1 (a)].
Meldal and Sharpless
R2
R1
R2
N
N
independently found that copper(I) can catalyze the cy-
cloaddition between alkynes and azides at room tempera-
ture regioselectively yielding 1,4-disubstituted 1,2,3-
triazoles [Scheme 1 (b)]. This concomitant discovery
led to a revival of the Huisgen cycloaddition and initiated
a vast number of applications of this reaction.1
I
Cu -Zeo
R4
R1
?
R3
N
R5
N
1
8
N
(b)
R3
N
R5
R1
R4
9
I
Scheme 2 Cu -Zeolites as potential cycloaddition catalysts
The lesser-known Dorn reaction allowed the preparation
of pyrazolines from alkynes and azomethine imines.
However, harsh conditions were usually required and this
I
I
Among the Cu -doped zeolites examined, Cu -USY
proved to be the best for both reactions, giving the highest
yields at room as well as at higher temperatures. USY
contains a pore network made of adjacent large cages ap-
proximately 7.4 Å in diameter, the largest of the zeolite
[
3+2] cycloaddition led to mixtures of regioisomers in
2
0
variable proportions and yields [Scheme 1 (c)]. In anal-
ogy with the Huisgen reaction, Fu recently developed a
copper(I)-catalyzed version of the Dorn reaction. Copper
catalysis improved the reaction and dramatically en-
I
series investigated. With such large cages, Cu -USY was
2
1
able to readily accommodate the two cycloaddition part-
ners within its cages and promote the reaction.
hanced its regioselectivity [Scheme 1 (d)].
Due to their inherent instability and their poor solubility,
copper(I) salts must be used in the presence of ligands in
these reactions. In the Meldal and Sharpless version, ac-
tive catalytic species could also be in situ generated by re-
I
The Cu -USY-catalyzed Huisgen reaction could be per-
formed at room temperature in any organic solvent, but
the highest yields were achieved in toluene. Running the
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

1
560
S. Chassaing et al.
FEATURE ARTICLE
R2
reaction at higher temperatures increased the reaction rate
from overnight to a few hours with a slight increase in the
R1 = alkyl, aryl, alcohol,
tertiary amine, ketone,
ester, amide
R2 = alkyl, aryl, alcohol
N
H
R2
N
N
2
3
yields. A single regioisomer, the 1,4-disubstituted 1,2,3-
triazole, was always formed regardless of the zeolite and
N
H
R1
N
N
2
3
solvent used (Scheme 3).
I
Cu -USY
catalyzed
version
Ph
N
N
I
Ph
N
N
N
Cu -Zeolite
toluene, r.t.
R1
R1 = only EWG
(i.e., ketone, ester,
electron-deficient aryl
groups)
N
H
Ph
O
Ph
N
R1
I
I
I
I
I
N
Cu -USY Cu -Y Cu -ZSM5
Cu -MOR Cu -β
H-USY
0%
O
R4
R2 = alkyl, aryl
R2
N
R2
R3
yield
87%
75%
79%
79%
73%
3
4
R , R = H, alkyl
N
I
Scheme 3 Efficiency of the Cu -zeolite-catalyzed Huisgen cycload-
R3 R4
dition between benzyl azide and phenylacetylene
I
Scheme 5 Scope and limitations of the Cu -USY-catalyzed Huisgen
I
In contrast, The Cu -USY-catalyzed Dorn reaction could and Dorn cycloadditions versions (EWG = electron-withdrawing
groups)
only be performed in dichloromethane at room tempera-
ture, but the reaction was slow and the yields were mod-
R1
N
erate (40–58% yield in 24–48 h). However, at 60 °C,
toluene was again the best solvent, giving very high yields
R1
X
N
N
Na N3
R2
N
N N
R2 Cu -L cat.
I
R1
2
4
I
in a rapid reaction (4 h, Scheme 4). In this Cu -USY-cat-
alyzed cycloaddition, a single regioisomer was again al- Scheme 6 One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
from in situ generated azides
ways obtained.
was tempting to perform this step in the presence of termi-
Ph
I
nal alkynes and Cu -USY as a catalyst in order to set up a
N
I
Cu -Zeolite
N
N
I
Cu -zeolite-catalyzed cascade reaction (Scheme 6).
Ph
COOEt
COOEt
N
toluene, 60 °C
O
Benzyl bromide was, thus, placed under various condi-
tions in the presence of sodium azide, phenylacetylene,
and 10% of Cu -USY. Using the optimized conditions dis-
O
I
I
I
I
I
I
Cu -USY Cu -Y Cu -ZSM5
95% 95% 80%
Cu -MOR Cu -β
H-USY
0%
cussed above, no transformation could be detected
yield
89%
69%
(
Table 1, entries 1, 2). Sodium azide was not readily solu-
I
Scheme 4 Efficiency of the Cu -zeolite-catalyzed Dorn cycloaddi-
tion between (Z)-1-benzylidene-5,5-dimethyl-3-oxopyrazolidin-1-
ium-2-ide and ethyl propiolate
ble in such an apolar solvent. Adding a polar co-solvent
did not help (entries 3, 4), but performing the reaction in
more polar N,N-dimethylformamide led to the expected
one-pot reaction; at room temperature, the expected tria-
zole was directly obtained in a good overall yield (entry 5)
while at higher temperatures in N,N-dimethylformamide
the reaction was faster, giving a slightly better overall
yield (entry 6). Interestingly, the same one-pot reaction
I
These Cu -modified zeolites acted as true catalysts, since
2
5
only 5–10 mol% was used. Moreover, these catalysts
could be easily recovered and recycled several times with-
out any significant change in yield and conversion.2
I
3,24
With Cu -USY as the catalyst (Scheme 5), the scope of also took place in the highly polar solvent water and with
these Cu -zeolite-catalyzed cycloadditions was explored. better efficiency since reaction times were decreased and
I
For the Huisgen reaction, it proved as broad as the now overall yields increased (entries 7, 8). Again, high temper-
classical Meldal–Sharpless version; for the latter, only ter- atures accelerated the reaction rate (entry 8 vs 7). Even
I
minal alkynes reacted. In our Cu -USY-catalyzed version, more interesting, the triazole adduct precipitated out of
only compounds having either free amino or acid group the reaction mixture in water, facilitating its recovery as
2
3
I
did not react. The scope of the Dorn reaction proved also well as the recovery of the Cu -zeolite catalyst.
very similar to the one of the initial or Fu versions. Only
Interestingly, even chlorides could be engaged in such
terminal alkynes carrying sufficiently strong electron-
cascade reaction, but for solubility reasons, a mixture of
withdrawing group reacted.
solvent had to be used [Scheme 7 (a)]. Moreover, this one-
pot process could be extended to aliphatic iodides or bro-
mides, provided that the appropriate mixture of solvents
was used, again for solubility reasons [Scheme 7 (b) and
I
3
.2
Cu -Zeolite-Catalyzed Cascade: Substitution
and Cycloaddition
(
c)].
To go further along ‘green chemistry’ principles, we
looked for a one-pot zeolite-catalyzed formation of tria-
zoles. Since organic azides are usually prepared from the
corresponding bromides by nucleophilic substitution, it
I
This one-pot Cu -USY-catalyzed substitution–cycloaddi-
tion cascade seemed general and various aryl- or alkyl-
substituted acetylene derivatives reacted under such con-
ditions (Table 2). With arylacetylenes, this one-pot reac-
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

FEATURE ARTICLE
The Zeo-Click Concept
1561
Table 1 Reaction Condition Optimization of One-Pot Synthesis of
Table 2 One-Pot Cascade Synthesis of 1,4-Disubstituted 1,2,3-Tri-
azoles from In Situ Generated Azides
1
-Benzyl-4-phenyl-1,2,3-triazole from In Situ Generated Azides
Ph
N
N
Na N3
N
N
Na N3
Ph
Br
+
Ph
N
R
I
Ph
Br
+
R
I
N
Cu -USY
Cu -USY cat.
H2O, 90 °C
Ph
Ph
N
Entry
Solvent
Temp (°C) Time (h) Yield (%)
Entry Alkyne
Product
Time Yield
1
2
3
4
5
6
7
8
toluene
toluene
20
110
20
15
15
15-72
15
15
8
0
(
h)
(%)
trace
0
N
N
N
N
Ph
Ph
1
2
90
toluene–THF
toluene–THF
DMF
Ph
Ph
80
trace
71
N
20
2
2
89
4
4
-MeC6H4
DMF
100
20
78
6
4-MeC H4
N
H O
9
90
2
N
N
Ph
3
4
2
4
98
75
-F3CC6H4
H O
100
2
90
2
4
-F3CC6H4
N
N
Ph
N
N
Na N3
N
N
N
N
Ph
Ph
Ph
Cl
Ph
(a)
(b)
n-Hex
I
Cu -USY
Ph
n-Hex
H2O–EtOH
6
2%
8
0 °C
OH
N
N
N
N
5
6
8
72
Na N3
Ph
4
Br
Ph
I
Cu -USY
4
H2O–toluene, 90 °C
HO
70%
HO
N
3
–
12
trace
N
Na N3
Ph (c)
O
I
Ph
N
I
Cu -USY
H2O–dioxane
64%
350 °C (Table 3, entries 1 and 2), while only modest
yields were obtained with zeolites prepared at 650 °C (en-
tries 4 and 5). Interestingly, the reaction could be sped up
if performed under microwave irradiation, but only with
90 °C
Scheme 7 One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles
from aliphatic bromides or iodides or benzyl chloride
I
Cu -USY prepared at 350 °C. Microwave proved deleteri-
I
tion in water proved to be more effective than the zeo- ous when using Cu -USY obtained at 650 °C as catalyst
click reaction in toluene at room temperature.
2
3,24
Elec- (entry 5 vs 6).
tronic effects had a stronger influence than in our previous
zeo-click version. An electron-donating group on the phe-
nyl moiety of phenylacetylene decreased the yield but not
significantly (entry 2 vs 1), while a strong electron-with-
drawing group increased the yield (entry 3 vs 2 vs 1). In
contrast, alkylacetylenes were less reactive in this one-pot
reaction in water compared to the zeo-click reaction in tol-
Table 3 Cycloaddition between Phenylacetylene and Benzyl Azide
in Toluene, Catalyzed by Differently Prepared Cu -USY, under Vari-
ous Conditions
I
Ph
N
N
Ph
N
Ph
N3
I
Cu -Zeolite
Ph
2
3,24
As expect- Entry Catalysta
uene at room temperature (entries 4 and 5).
Temp (°C)
20
Time (h) Yield (%)
ed, the same limitations were observed under the one-pot
water conditions as under the room temperature toluene
conditions and no cycloaddition occurred with acetylenic
derivatives containing free acid or amine groups (entry 6).
I
1
2
3
4
5
Cu -USY-350
15
5
83
87
89
37
45
16
I
Cu -USY-350
110
I
Cu -USY-350
110 (MW)
20
0.5
I
I
Cu -USY-650
15
5
3
.3
Cu -Zeolite-Catalyzed Cycloadditions:
Mechanistic Investigations
I
Cu -USY-650
110
The method by which the zeolite was prepared proved to
be critical in the cycloaddition reactions examined. Under
the conditions mentioned above, starting from benzyl
azide and phenylacetylene, high yields of 1-benzyl-4-phe-
nyl-1,2,3-triazole were achieved with zeolites prepared at
I
6
Cu -USY-650
110 (MW)
0.5
a
I
I
I
Cu -USY-350: Cu -USY heated to 350 °C during preparation; Cu -
I
USY-650: Cu -USY heated to 650 °C during preparation.
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

1
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S. Chassaing et al.
FEATURE ARTICLE
These results reflected the structural differences observed cially for the Dorn reaction, while internal protons seemed
I
for Cu -zeolites prepared at various temperatures. As important for reaction efficiency.
mentioned in Section 2, zeolites obtained at 350 °C did
To try to understand this discrepancy and shed some light
on the mechanism of these Cu -USY-catalyzed reactions,
not exhibit morphological changes. Whatever the calcina-
I
I
tion temperature and duration, Cu -USY exhibited powder
reactions were performed with labeled materials. As men-
tioned above, Cu-zeolites prepared at 350 °C were the
most active, but around 20% of the protons of the original
zeolite remained. Control experiments revealed one role
that these protons could play. Indeed, 1-deutero-2-phenyl-
XRD patterns very similar to those of native USY. How-
I
ever, Cu -USY prepared at 350 °C still contained 20%
I
acid sites/protons, while none remained in Cu -USY pre-
1
5
pared at 650 °C. The presence of protons could, thus,
play a role in the Huisgen or Dorn cycloadditions.
I
acetylene lost some deuterium when submitted to Cu -
26
For an in-depth view, reactions were performed in the USY prepared at 350 °C, but none in the presence of
I
I
presence of protic solvents. In methanol, the Cu -USY- Cu -USY prepared at 650 °C or H-USY. Moreover, the
catalyzed Huisgen reaction proceeded at room tempera- exchange rate depended on reaction conditions
ture, but was slower and less clean than the same per- (Scheme 8). These results showed that the remaining
formed in toluene (Table 4, entry 1). Surprisingly, zeolitic protons were able to exchange acetylenic protons
excellent results were obtained in water (entries 2 and 3). in the presence of copper, suggesting the in situ formation
High yields of triazole were achieved, whatever the reac- of a p-complex. Exchange processes via a p-complex
tion temperature (entry 2 vs 3). As before, zeolite pre- have already been reported for silver ions, although in so-
pared at 650°C gave less effective results (entries 4–6). lution.27
I
Surprisingly, Cu -ZSM5, which gave the second best re-
sults in toluene (Scheme 3), proved to be a poor catalyst
in water (entry 7), as well as in a mixture of solvent con-
taining water (entry 8).
I
Cu -H-USY-350
Ph
D
Ph
D
Ph
H
toluene, 20 °C, 15 h
toluene, 60 °C, 4 h
9
9
5%
70:30
80:20
(a)
(b)
2%
I
Table 4 Cycloaddition between Phenylacetylene and Benzyl Azide
in Toluene, Catalyzed by Differently Prepared Cu -Zeolites in Vari-
ous Protic Solvents
Scheme 8 D/H-Exchange induced by Cu -USY on 1-deutero-2-phe-
nylacetylene
I
I
Entry Catalyst
Solvent
MeOH
Temp Time Yield
To avoid such exchange, Cu -USY was prepared at 350 °C
28
(
°C)
(h) (%)
from deuterated USY, so that the remaining acidic sites
only were deuterated. With this zeolite, the Huisgen reac-
tion was performed starting with 1-deutero-2-phenylacet-
ylene and benzyl azide, while the Dorn reaction was
applied to ethyl 3-deuteropropiolate (Scheme 9). In the
former, all of the deuterium label was recovered in the ad-
duct [Scheme 9 (a)], while in the latter, deuterium was al-
most completely lost [Scheme 9 (b)].
I
1
2
3
4
5
6
7
Cu -USY-350
20
15
9
61
90
90
42
35
41
23
42
I
Cu -USY-350
H O
20
2
I
Cu -USY-350
H O
100
20
2
2
I
Cu -USY-650
MeOH
15
15
5
I
Cu -USY-650
H O
20
2
I
N
Cu -USY-650
H O
100
20
2
Ph
CuI-D-USY-350
N3
N
N
Ph
(a)
Ph
D
I
Cu -ZSM5-350
H O
15
15
2
D
Ph
I
8
a
Cu -ZSM5-350
H O–CH Cl (75:25) 20
2 2 2
1
00% D, 80%
I
I
I
I
Cu -USY-350 or Cu -ZSM5-350: Cu -USY or Cu -ZSM5 heated to
N
I
I
3
50 °C during preparation; Cu -USY-650: Cu -USY heated to 650 °C
Ph
N
Ph
during preparation.
O
N
COOEt
b)
EtOOC
D
I
Cu -D-USY-350
N
(
I
For the Cu -USY-catalyzed Dorn reaction, this slowing
O
H
effect of protic solvents was more dramatic. In methanol,
the reaction, even performed at 60 °C, required 72 hours
to give 20% of the cycloadduct, while in toluene only 4
hours was sufficient to give an almost quantitative yield
9
% D, 80%
I
Scheme 9 Cu -Zeolite-catalyzed Huisgen and Dorn cycloadditions
with deuterated alkynes and zeolite
(
Scheme 4). Surprisingly, the second regioisomer could
These results revealed that acetylide was produced during
the Dorn reaction while none was formed in the Huisgen
reaction. Therefore, the intermediate p-complex evolved
differently in each reaction. In the Huisgen reaction, the p-
complex probably became a new p-complex after coordi-
nation of the azide, and further bond reorganization led to
the 1,4-disubstituted triazole (Scheme 10, top). In the
be detected in protic solvents.
I
Hence, the Cu -USY-catalyzed Huisgen and Dorn cy-
cloadditions could be performed in protic solvents, in-
cluding water, but with variable results. External proton
sources seemed mostly deleterious to the reaction, espe-
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

FEATURE ARTICLE
The Zeo-Click Concept
1563
Dorn reaction, the p-complex rearranged to a copper
acetylide, the anionic part of the 1,3-dipole possibly act-
ing as a base. Coordination of the dipole, again through its
anionic part, led to a cuprate complex, which upon further
bond reorganization gave the corresponding bicyclic
pyrazolines (Scheme 10, bottom).
(a) Glaser
Ph
CuCl
O2
Ph
Cu
Ph
Ph
NH4OH
MeOH
NH OH
4
isolated
R
EtOH
(b) Eglington & Galbraith
Cu(OAc) xs
2
R
R
pyridine, MeOH
These possible mechanisms allowed understanding of the
effects of protic solvents. In the Huisgen reaction, external
protons could possibly interfere through solvation of the
azide as well as by changing the solubility of the organic
reagents. In contrast, external protons in the Dorn reaction
might prevent the p-complex deprotonation step, possibly
due to the 1,3-dipole, as well as further coordination to
copper, dramatically reducing the reaction rate.
(
(
c) Hay
R
O2
R
R
CuCl-TMEDA cat.
d) Pd-Cu catalyzed verson
I2 (0.5 equiv)
PdCl2(PPh3)2-CuI cat.
i-Pr2NH
R
R
R
I
(
e) Cu -Zeolite catalyzed version
D
R1
R2
?
D
R
R
R
R2
N
I
Cu -Zeolite
R1
N
N
N
2
N
R N3
CuI
zeo
N
Scheme 11 Known alkyne homocoupling conditions promoted
either by stoichiometric or catalytic amounts of copper (a–c) or by
catalytic amount of palladium and copper (d), and proposal for a
D
R1
B
R1
I
Cu -zeolite-catalyzed version (e)
Cu
R1
zeo
R1
CuI
zeo
I
air Cu -Zeolite
R2
R2
Ph
Ph
BD
Ph
H
DMF, 110 °C
O
N
CuI
N
N
I
I
I
I
I
N
O
Cu -USY Cu -Y Cu -ZSM5 Cu -MOR Cu -β
H-USY
0%
N
N
zeo
O
yield
R2
97%
84%
12%
5%
19%
Scheme 12 Cu-Zeolite-catalyzed dimerization of terminal alkynes
I
Scheme 10 Proposed mechanisms for Cu -zeolite-catalyzed cy-
cloadditions explaining observed results using deuterated terminal al-
kynes
I
As for the preceding cycloadditions, Cu -USY was the
I
most effective catalyst among the Cu -zeolites examined.
I
I
Nevertheless, Cu -Y was fairly efficient. Surprisingly, the
3
.4
Cu -Zeolite-Catalyzed Coupling Reactions
I
other Cu -zeolites were not as active as catalysts for this
Homocoupling of terminal alkynes is one of the oldest reaction (Scheme 12).
methods known for C–C bond formation, and one of the
oldest involving a metal, in this case copper. The so-ob-
tained 1,3-diynes are an important motif found in natural
products exhibiting interesting biological properties, as
well as in manmade compounds, such as oligo- and poly-
mers, organic conductors, and conjugated connectors
or synthetic receptors in molecular recognition. Numer-
ous methods have, thus, been developed and are still being
developed to increase the efficiency and selectivity of
alkyne homocoupling, especially under catalytic condi-
tions [Scheme 11 (a–d)]. Surprisingly, few supported or
heterogeneous versions of such homocoupling reactions
Such strong differences could be ascribed to the rigid
shape of diynes and to the possible transition state of such
a dimerization. Although still unknown, proposals have
been made, involving dinuclear copper(II) alkyne–acetyl-
2
9
3
0
34e
ide complexes. As demonstrated in the preceding sec-
3
1
32
I
tion, Cu -zeolites obviously formed intermediate p-
3
3
complexes in the presence of alkynes. Under oxygen, such
complexes could reorganize to copper(II) acetylides and if
two copper ions are present in the same zeolite pore, they
can produce dinuclear copper(II) alkyne–acetylide com-
plexes, suggested as intermediates in the homocoupling of
terminal alkynes (Scheme 13). Therefore, only zeolites
carrying the largest pores can accommodate such large
complex intermediates. Moreover, the more copper load-
3
4
3
5
I
have been described. It was thus tempting to apply Cu -
zeolites as a catalyst to this coupling [Scheme 11 (e)].
Phenylacetylene was used as the starting material to sur- ed into the zeolite, increasing the probability of having
I
+
vey the catalysts and conditions for this Cu -zeolite-cata- more than one Cu ion in the pore, the more efficient the
lyzed homocoupling reaction. Solvent screening revealed catalyst should be. This is exactly what was observed.
that only the highly polar N,N-dimethylformamide led to
This mechanistic proposal was also supported by a size ef-
the expected diyne product and the highest yield was
fect observed by coupling alkynes of increasing sizes. Ex-
achieved at high temperatures. As expected, dimerization
cellent yields were achieved for the formation of 1,3-
only occurred under oxygen, but an air atmosphere was
diynes 12 to 15 Å long, indicating an optimal length for
3
6
sufficient (Scheme 12).
the coupling (Figure 2). Interestingly, this size optimum
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

1
564
S. Chassaing et al.
FEATURE ARTICLE
air
Ph
Ph
Ph
Si
O
Si
O
DMF, 110 °C
O
Al
Al
O
O
I
Cu -USY-350
97% (a)
52%
(b)
CuII
O
O
Cu+
O2
R
I
Cu -USY-650
R
Si
Si
I
R
CuII
Scheme 14 Effect of Cu -USY preparation on the efficiency of the
phenylacetylene homocoupling reaction
O
Cu+
O
Al
Al
O
Si
O
Si
O
I
at 350 °C was the most effective compared to Cu -USY
prepared at 650 °C (Scheme 14).
Under these conditions, a wide range of terminal alkynes
could be dimerized, including aryl-, alkyl-, and silylacet-
ylenes [Scheme 15 (a–c)]. Even propargyl glycosides
could be dimerized under these conditions without any
isomerization [Scheme 15 (d)]. Moreover, this method
Si
O
Al
O
CuI
O
R
R
Si
38
O
CuI
gave the highest yields compared to known routes. The
corresponding glycosylated hexa-2,4-diyne-1,6-diols are
important compounds since they mimic the multivalent
interactions between carbohydrates and proteins responsi-
ble for most of recognition and communication processes
within cells, between cells, and between cells and viruses
or bacteria. Such compounds could, thus, be applied to
immunology, as drugs, or as synthetic vaccines.3
Al
O
Si
O
I
Scheme 13 Proposed mechanism for the Cu -zeolite-catalyzed
homocoupling reaction
9
F3C
CF3
91%
(a)
9
0%
(b)
(c)
i-Pr3Si
Sii-Pr3
88%
OPG
R2
R3
R4
O
87–88%
(d)
PGO
O
R1
O
R1
OPG
R
I
O
Figure 2 Effect observed on the yield (%) for the Cu -USY-cata-
4
lyzed homocoupling reaction of 1,3-diynes of various sizes (Å)
R2
R3
PGO
perfectly fitted with the USY supercage size (13 Å), sug-
gesting adequate accommodation of the dinuclear cop-
per(II) alkyne–acetylide intermediate within the cage.
Such an optimal supramolecular arrangement has led zeo-
lites to be regarded as inorganic enzyme analogues, the
I
Scheme 15 Diynes obtained by Cu -USY-catalyzed homocoupling
of aryl-, alkyl-, and silylacetylene derivatives and of propargyl glyco-
sides
Capitalizing on reactivity differences of some alkynes and
on the size effect mentioned above, we looked for selec-
3
7
so-called zeozymes.
It is also worth noting that X-ray (XPS) experiments per- tivity in the formation of nonsymmetrical diynes. The
I
formed on Cu -USY before, during, and after its use as ‘small’ (triisopropylsilyl)acetylene and pent-1-yne were
I
catalyst in the homocoupling of phenylacetylene con- submitted to the Cu -USY-catalyzed homocoupling con-
firmed that the oxidation state of the loaded copper varied ditions and the best fit, the heterodiyne 1-(triisopropylsi-
from +I before use to +II during use (binding energy of Cu lyl)hepta-1,3-diyne was, indeed, formed as the major
2
p : 932.8, 933.3, and 933.1 eV, respectively, as com- product [Scheme 16 (a)]. As expected from the size limit
3
/2
pared to Cu O and CuO; 932.8 and 933.3–934.4 eV, re- observed (Figure 2), the combination of (triisopropylsi-
2
spectively). Interestingly, this study revealed that during lyl)acetylene with (4-trifluorophenyl)acetylene led to the
the catalytic run only approximately 40% of the loaded heterodiyne, but with lower selectivity [Scheme 16 (b)].
copper ions were oxidized and that around 20% remained
oxidized after use.
Toward the same selectivity goal in alkyne coupling, a
1
4
zeo-click variant of the Cadiot–Chodkewicz reaction40
I
As in the preceding cycloadditions, the way the Cu -zeo- was examined. Various 1-bromoalk-1-ynes were submit-
I
I
lites were prepared was again critical. Cu -USY prepared ted to different terminal alkynes in the presence of Cu -
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

FEATURE ARTICLE
The Zeo-Click Concept
1565
n-Pr
i-Pr3Si
i-Pr3Si
n-Pr
60%
i-Pr3Si
(a)
(b)
I
Cu -USY
Sii-Pr3
40%
4
-F3CC6H4
i-Pr3Si
i-Pr3Si
C6H4(4-CF3) 45%
Sii-Pr3
55%
i-Pr3Si
I
Cu -USY
I
Scheme 16 Nonsymmetrical Cu -USY-catalyzed coupling of various terminal alkynes
USY in different solvents (Table 5). Whatever the solvent Merck) using UV light and p-anisaldehyde for visualization. Col-
umn chromatographies were performed on silica gel 60 (0.040–
and the nature of the substituent, almost no reaction took
1
13
0
.063 mm, Merck). H and C NMR spectra were recorded on a
place and at best, less than 10% of the 1,3-diyne derived
from the terminal alkyne engaged in the reaction was ob-
tained (entries 1–9). Similar results were observed starting
from the corresponding 1-iodoalk-1-ynes. Under these
Bruker Avance 300 spectrometer at 300 and 75 MHz, respectively.
Chemical shifts d and coupling constants J are given in ppm and Hz,
respectively. Chemical shifts are reported relative to residual sol-
1
vent as an internal standard (chloroform-d : 7.26 ppm for H and
conditions, the halogenated alkynes could not be recov- 77.0 ppm for C).
1
1
3
ered, suggesting their reaction with copper(I) ions loaded
into USY, but without further evolution.
I
Cu -USY; Typical Procedure
Commercial NH USY was loaded in an oven and heated at 550 °C
4
for 4 h giving H-USY. H-USY (1 g) and CuCl (475 mg, 1.1 equiv)
were mixed using a mortar and charged in a closed reactor. The
Table 5 Cadiot–Chodkewicz-Type Heterocoupling Attempts via
the Reaction between 1-Bromoalkynes and Terminal Alkynes
mixture of powders was heated at 350 °C under N flow, quantita-
2
I
a
tively yielding Cu -USY. The same procedure was applied to other
Entry Bromoalkyne
Alkyne
Conditions Yield
zeolites.
(
%)
I
1
2
3
4
5
toluene
CH Cl
THF
MeCN
DMF
0b
Cu -Zeolite-Catalyzed [3+2] Cycloaddition of Azides and Ter-
c
trace
minal Alkynes; General Procedure
To a suspension of Cu -USY (50 mg, 0.1 equiv) in toluene (1.5 mL)
was added the azide (1.3 mmol, 1.0 equiv) and then the terminal
alkyne (1.6 mmol, 1.2 equiv). The mixture was stirred at r.t. over-
night (15 h) and then it was taken up in CH Cl (15 mL). The solid
catalyst was removed by filtration over Nylon membranes (0.20
mm) and washed with CH Cl . Solvent evaporation provided the re-
sulting triazole, usually of sufficient purity (from NMR spectra).
2
2
tracec
tracec
98
I
Ph
Br
4-MeC6H4
tracec
2
2
6
7
8
DMF
DMF
DMF
4
-MeOC6H4
-F3CC6H4
9c
2
2
4
0b
0b
n-Hex
I
Cu -Zeolite-Catalyzed Cascade from Halides, Sodium Azide,
9
n-Hex
Br
6 4
4-F CC H
DMF
and Terminal Alkynes; General Procedure
To a suspension of Cu -USY (20 mg, 0.1 equiv) in solvent (3 mL)
(see Table 1) was added successively NaN (1.1 mmol, 1.1 equiv),
the halide (1.0 mmol, 1 equiv), and then the terminal alkyne (1.0
mmol, 1 equiv). For reactions performed in H O, the mixture was
filtered, then extracted with EtOAc (3 × 5 mL). The combined or-
ganic layers were then dried (anhyd MgSO ), filtered, and concen-
3
I
a
I
Cu -USY (0.3 to 1 equiv), r.t. to reflux; concomitant and sequential
3
additions were examined.
b
The starting terminal alkyne was recovered.
2
c
The homocoupling product derived from the terminal alkyne was de-
tected or isolated.
4
trated under vacuum, providing the resulting triazole, usually of
sufficient purity (from NMR spectra).
4
Conclusion
23,26
1
-Benzyl-4-phenyl-1,2,3-triazole
I
From BnBr: To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O
2
Copper(I)-modified zeolites were, for the first time, used (3 mL) was added NaN (71.5 mg), BnBr (171 mg), and then phe-
3
as catalysts in organic synthesis. They proved to be very nylacetylene (102 mg). The mixture was heated at 90 °C for 2 h,
then cooled, filtered, and extracted as mentioned above, leading to
the expected triazole (212 mg, 90%).
efficient catalysts for various cycloadditions as well as for
the homocoupling of terminal alkynes.
I
From BnCl: To a suspension of Cu -USY (20 mg, 0.1 equiv) in
Easy to prepare, handle, recover, and recycle, such hete-
rogeneous catalysts offer, thus, an interesting alternative
to more conventional homogeneous catalysts in organic
H O–EtOH (1:1, 3 mL) was added NaN (71.5 mg), BnCl (126 mg),
2
3
and then phenylethyne (102 mg). The mixture was heated at 78 °C
for 5 h, then cooled, filtered, and extracted as mentioned above,
synthesis. Moreover, they exhibit typical characteristics leading to the expected triazole (146 mg, 62%).
of ‘green chemistry’ towards synthetic applications.
2
3,26
1
-Benzyl-4-tolyl-1,2,3-triazole
I
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O (3 mL) was
2
All starting materials were commercial and were used as received.
The zeolites used were those that had been prepared at 350 °C, ex-
cept in the few cases where the role of this preparation temperature
was being examined. The reactions were monitored by thin-layer
added NaN (71.5 mg), BnBr (171 mg) and then (4-methylphe-
3
nyl)acetylene (116 mg). The mixture was heated at 80 °C for 2 h,
then cooled, filtered, and extracted as mentioned above, leading to
the expected triazole (222 mg, 89%).
chromatography carried out on silica plates (silica gel 60 F254
,
Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York

1
566
S. Chassaing et al.
FEATURE ARTICLE
I
1
-Benzyl-4-[4-(trifluoromethyl)phenyl]-1,2,3-triazole
Cu -Zeolite-Catalyzed Homocoupling of Terminal Alkynes;
General Procedure
I
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O (3 mL) was
added NaN (71.5 mg), BnBr (171 mg) and then [4-(trifluorometh-
2
I
To a suspension of Cu -USY (70 mg, 0.3 equiv) in DMF (3 mL) was
3
yl)phenyl]acetylene (170 mg). The mixture was heated at 90 °C for
added the terminal alkyne (1 mmol, 1.0 equiv). The mixture was
stirred at 110 °C vigorously overnight (15 h) and then it was taken
up in CH Cl (25 mL) and filtered over Nylon membranes (0.20
2
h, then cooled, filtered, and extracted as mentioned above, leading
to the expected triazole (296 mg, 98%).
2
2
1
mm). After washing with 0.1 M HCl (3 × 25 mL), the organic layer
H NMR (300 MHz, CDCl ): d = 7.93–7.90 (m, 2 H), 7.74 (s, 1 H),
3
was dried (MgSO ) and filtered. Solvent evaporation provided the
4
7
1
.66–7.63 (m, 2 H), 7.43–7.31 (m, 5 H), 5.59 (s, 2 H).
resulting diyne, usually with >95% purity (from NMR).
3
C NMR (75 MHz, CDCl ): d = 147.1, 136.9, 135.0, 134.2 (q,
3
2J = 31 Hz), 129.3, 129.0, 128.0, 127.1 (q, J = 268 Hz), 125.7,
1
C-F
C-F
1
25.8, 120.2, 54.4.
Acknowledgment
4
1
The authors thank the CNRS and the French Ministry of Research,
as well as the ANRS and the Loker Institute, USA, for financial sup-
ports. T.B., who is on leave from the Indian Institute of Chemical
Technology, Hyderabad 500607, Andhra Pradesh, India, also thanks
the French Embassy in India for a ‘sandwich’ fellowship.
1
-Benzyl-4-hexyl-1,2,3-triazole
I
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O (3 mL) was
added NaN (71.5 mg), BnBr (171 mg), and then oct-1-yne (110
mg). The mixture was heated at 90 °C for 4 h, then cooled, filtered,
and extracted as mentioned above, leading to the expected triazole
2
3
(
160 mg, 66%).
References
1
-Benzyl-4-(1-hydroxyhexyl)-1,2,3-triazole
I
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O (3 mL) was
(1) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory
and Practice; Oxford University Press: Oxford, 1998.
(b) Green Chemistry: Frontiers in Benign Chemical
Synthesis and Processes; Anastas, P.; Williamson, T. C.,
Eds.; Oxford University Press: Oxford, 1998. (c) Green
Chemistry: Challenging Perspectives; Tundo, P.; Anastas,
P. T., Eds.; Oxford University Press: Oxford, 1999.
2
added NaN (71.5 mg), BnBr (171 mg) and then 3-hydroxyoct-1-
yne (126 mg). The mixture was heated at 90 °C for 8 h, then cooled,
filtered and extracted as mentioned above, leading to the expected
triazole (186 mg, 72%).
3
1
H NMR (300 MHz, CDCl ): d = 7.40 (s, 1 H), 7.24–7.16 (m, 3 H),
3
7
.13–7.09 (m, 2 H), 5.31 (s, 2 H), 4.75 (t, J = 6.6 Hz, 1 H), 4.45 (br
(
d) Clark, J. H. Green Chem. 1999, 1, 1.
2) For recent examples with liquid superacids, see:
a) Vasilyev, A.; Walspurger, S.; Haouas, M.; Pale, P.;
Sommer, J.; Rudenko, A. P. Org. Biomol. Chem. 2004, 2,
483. (b) Vasilyev, A.; Walspurger, S.; Sommer, J.; Pale, P.
s, 1 H, OH), 1.76–1.66 (m, 2 H), 1.38–1.15 (m, 6 H), 0.80–0.73 (m,
H).
(
3
(
1
3
C NMR (75 MHz, CDCl ): d = 152.4, 134.8, 128.9, 128.5, 127.9,
3
1
20.9, 66.6, 53.7, 37.3, 31.6, 25.1, 22.5, 14.0.
3
Tetrahedron 2005, 61, 3559. (c) Vasilyev, A.; Walspurger,
S.; Chassaing, S.; Pale, P.; Sommer, J. Eur. J. Org. Chem.
2007, 5740. For recent examples with solid superacids (i.e.,
zeolites), see: (d) Sani Souna Sido, A.; Chassaing, S.;
Kumarraja, M.; Pale, P.; Sommer, J. Tetrahedron Lett. 2007,
4
2
1
-Ethyl-4-phenyl-1,2,3-triazole
I
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O–toluene
1:1, 3 mL) was added NaN (71.5 mg), 1-bromoethane (108 mg),
and then phenylacetylene (102 mg). The mixture was heated at 90
C for 12 h, then cooled, filtered, and extracted as mentioned above,
leading to the expected triazole (121 mg, 70%).
2
(
3
°
48, 5911. (e) Sani Souna Sido, A.; Chassaing, S.; Pale, P.;
Sommer, J. Appl. Catal., A 2008, 336, 101. (f) Chassaing,
S.; Kumarraja, M.; Pale, P.; Sommer, J. Org. Lett. 2007, 9,
1
-Propyl-4-phenyl-1,2,3-triazole
To a suspension of Cu -USY (20 mg, 0.1 equiv) in H O–dioxane
1:1, 3 mL) was added NaN (71.5 mg), 1-iodopropane (170 mg),
and then phenylacetylene (102 mg). The mixture was heated at 90
C for 15 h, then cooled, filtered, and extracted as mentioned above,
3889.
I
2
(3) (a) Evano, G.; Blanchard, N.; Tourni, M. Chem. Rev. 2008,
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(
3
°
leading to the expected triazole (120 mg, 64%).
1
H NMR (300 MHz, CDCl ): d = 7.84–7.82 (m, 2 H), 7.71 (s, 1 H),
.47–7.30 (m, 3 H), 4.37 (t, J = 7.2 Hz, 2 H), 1.98 (sextuplet, J = 7.2
Hz, 2 H), 0.99 (t, J = 7.2 Hz, 3 H).
3
7
(
b) Larsen, S. C. In Environmental Catalysis; Grassian, V.
1
3
C NMR (75 MHz, CDCl ): d = 149.6, 130.7, 129.0, 128.9, 128.1,
3
K., Ed.; CRC Press: Boca Raton, 2005, 269.
1
25.7, 52.1, 23.8, 11.1.
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I
Cu -Zeolite-Catalyzed [3+2] Cycloaddition of Azomethine
Imines and Terminal Alkynes; General Procedure
To a suspension of Cu -USY (7 mg, 0.05 equiv) in toluene (2 mL)
was added pyrazolidin-3-one ylide (0.4 mmol, 1.0 equiv) and then
the terminal alkyne (0.48 mmol, 1.2 equiv). The mixture was heated
to 60 ° for 4 h, then cooled to r.t. The catalyst was then removed by
filtration over Nylon membranes (0.20 mm) and washed with
CH Cl . Solvent evaporation provided the resulting adduct usually
I
2004,108,264, 2004.
(
(
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2
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of sufficient purity (from NMR spectra). Column chromatography
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(
(
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FEATURE ARTICLE
The Zeo-Click Concept
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Synthesis 2010, No. 9, 1557–1567 © Thieme Stuttgart · New York