Design and Applications of an Efficient Amphiphilic "click" CuI Catalyst in Water

Article abstract of DOI:10.1021/acscatal.6b01389

The copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) using the conventional Sharpless-Fokin catalyst that consists of CuSO₄ + Na ascorbate, the most well-known and used "click" reaction, is considerably accelerated by the addition of a tr

Full text of DOI:10.1021/acscatal.6b01389

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Article
Design and applications of an efficient
amphiphilic “click” CuI catalyst in water
Changlong Wang, Dong Wang, Shilin Yu, Thomas Cornilleau, Jaime Ruiz, Lionel Salmon, and Didier Astruc
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01389 • Publication Date (Web): 24 Jun 2016
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Design and applications of an efficient amphiphilic “click” CuI
catalyst in water
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Changlong Wang,a Dong Wang,a Shilin Yu,a Thomas Cornilleau,a Jaime Ruiz,a Lionel
Salmon,b and Didier Astruca*
a ISM, UMR CNRS Nº 5255, Univ. Bordeaux, 33405 Talence, France
Laboratoire de Chimie de Coordination, UPR CNRS N。8241, 31077 Toulouse,
b
France
Abstract:
The copper(I)ꢀcatalyzed azide alkyne cycloaddition (CuAAC) using the conventional
SharplessꢀFokin catalyst that consists of CuSO4 + Na ascorbate, the most wellꢀknown
and used “click” reaction, is considerably accelerated by the addition of a
tris(triazolyl)ꢀpolyethylene glycol (trisꢀtrzꢀPEG) amphiphilic ligand in water under
ambient conditions. Only partsꢀperꢀmillion CuI were necessary to reach quantitative
yields with TON up to 86000 and TOF 3600 h–1. The ligand was fully recycled, and
the catalyst reused at least 6 times without decomposition. Largeꢀscale syntheses were
also successfully achieved with 93 % yield. The catalyst was applied to the efficient
synthesis of various useful functional products with medicinal, catalytic, targeting,
and labeling properties.
Keywords: click reaction, CuAAC, trisꢀtrzꢀPEG, CuI, partꢀperꢀmillion, catalyst,
triazole
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Introduction:
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The concept of “click chemistry” proposed by Kolb, Finn and Sharpless in 20011 has
undoubtedly revolutionized molecular engineering science. Following the seminal and
independent report by the SharplessꢀFokin2 and Meldal3 groups in 2002 of
copper(I)ꢀcatalyzed azideꢀalkyne cycloaddition (CuAAC) selectively yielding
1,4ꢀdisubstituted 1,2,3ꢀtriazoles, CuAAC has been applied to an enormous range of
new syntheses and applications to macromolecules and nanomaterial science.4ꢀ7 For
such CuAAC reactions, the catalytic active CuI species was usually generated from
the cheap and easy available mixture of CuSO4 and sodium ascorbate (NaAsc),
known as the SharplessꢀFokin catalyst. The CuAAC reaction rate is low if the catalyst
is not present in high concentration and in the presence of activating ligand, however.
For practical reaction processes, in most of the cases the SharplessꢀFokin catalyst is
used in relatively large quantities in order to avoid the formation of the 1,5ꢀisomer8a
and to keep an acceptable reaction rate.8b,c The problem then remains to remove the
copper ions, which limits this “click” chemistry in electronics and biomedicine.9 To
overcome these difficulties, some ligands have been shown to considerably accelerate
the reactions and reduce the catalyst amounts. Among them, nitrogenꢀbased ligands
such as polytriazoles10,11 and tris(2ꢀaminoethyl)amine derivatives (tren),12ꢀ14 have
been found to be excellent, reducing the amount of CuI catalyst to the order of 1% or
less. Recently it was reported that a recyclable dendritic nanoreactor containing
intradendritic triazoles9 and the poly(NꢀisopropylacrylamideꢀcoꢀNꢀvinylimidazole)
polymer15 promoted CuAAC reactions in water and in tꢀBuOH/H2O, respectively,
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down to the remarkable partsꢀperꢀmillion level of CuI catalyst under the conditions of
in situ Cu2+ reduction using NaAsc. With such low amounts of catalysts and
exceptional efficiencies, CuAAC reactions in aqueous solution under mild reaction
conditions effectively contributed to the pursuit of “green chemistry” with potential
industrial applications. Nevertheless, only very few useful examples of synthetic
applications under such conditions are known. In addition, in the case of the
dendrimer,9 such efficiency is associated with the complicated and timeꢀconsuming
synthetic procedure of the catalyst. In this context we now address the utilization of
an amphiphilic tripodal ligand, tris(triazolyl)ꢀpolyethylene glycol (trisꢀtrzꢀPEG)16 for
which the synthesis is simple, “green” and biocompatible. It catalytic efficiency is
similar to that of the dendrimer,9 promoting the use of the conventional
SharplessꢀFokin catalyst to the high efficiency of partsꢀperꢀmillion CuI in water for
various organic syntheses of medicinal, catalytic, targeting, and labeling interests.
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Results and Discussion
The preparation of the new “click” catalyst involves addition of CuSO4·5H2O under
nitrogen to an aqueous solution containing the amphiphilic trisꢀtrzꢀPEG ligand, then
in situ reduction of the preꢀcatalyst PEGꢀtrisꢀtrzꢀCu2+ to the PEGꢀtrisꢀtrzꢀCuI catalyst
by dropwise addition of NaAsc (Scheme 1 and SI).
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Scheme 1. Synthesis of the PEGꢀtrisꢀtrzꢀCuI “click” catalyst.
1
The synthetic procedure has been monitored by UVꢀvis. (Figure 1) and H NMR
spectroscopy (SI). In UVꢀvis spectroscopy, an aqueous solution of CuSO4·5H2O has
an absorption in the range of 700ꢀ800 nm (Figure 1, insert), which is attributed to the
Cu2+ dꢀd transition.17 Upon coordination of Cu2+ to the triazole rings this absorption
disappears. After further reduction by NaAsc (10 equiv. per mol CuSO4), the
PEGꢀtrisꢀtrzꢀCuI complex exhibits a moderately intense band in the range between
300 and 400 nm (main absorption at 370 nm, Figure 1) which is assigned to a
metalꢀtoꢀligand chargeꢀtransfer (MLCT) transition.18 These phenomena are also
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confirmed by H NMR spectroscopy using D2O as the solvent (Figure S1). After
addition of Cu2+, the NMR signal of the triazole proton of the trisꢀtrzꢀPEG ligand
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vanishes due to the paramagnetism of the Cu2+ species, suggesting complexation.9
When NaAsc is added, the NMR signal of the triazole proton of the trisꢀtrzꢀPEG
ligand reappears, but it is shifted to 8.19 ppm compared to the initial proton signal at
8.04 ppm (Figure S1), indicating that the triazole rings are coordinated to CuI.9, 19
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Figure 1. Synthetic process for the PEGꢀtrisꢀtrzꢀCuI catalyst monitored by UVꢀvis.
spectroscopy.
The efficiency of this new CuAAC catalyst was then tested using the standard “click”
reaction between benzyl azide and phenylacetylene with various amounts of catalyst
in neat water as the solvent (Equation 1 and Table 1). When this reactions was
performed in the presence of 2000, 200 and 100 ppm PEGꢀtrisꢀtrzꢀCuI catalyst
respectively in water at 35℃ or 30℃, the crude reaction yields after 20 h were
quantitative, and the desired 1,2,3ꢀtriazole was obtained in 97% yields (entries 1ꢀ3).
Decrease of the catalyst amount to 50 ppm also resulted in quantitative conversion
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and 95 % of isolated yield at 35
℃
(entry 4). Although the catalyst amount has been
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successfully decreased to 20 or 10 ppm (entries 5 and 6) without quantitative
conversions, excellent yields are obtained, leading to TONs up to 86000 and TOF up
to 3600 hꢀ1. When the catalyst was reduced to 4 ppm (entry 7), the yield decreased but
resulted in TON and TOF values that were still higher than those obtained with 20
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ppm. The best conditions for this CuAAC catalytic system are at 50 ppm and 35
℃
for 20 h leading to full conversions, high isolated yields. A large scale reaction under
these conditions was also successfully conducted, and a similar isolated yield (93%)
being obtained (entry 4). Moreover, recycling the catalyst was also successful,
because the amphiphilic trisꢀtrzꢀPEG ligand is insoluble in cold diethyl ether,
allowing complete extraction of the “click” products from the aqueous solution while
keeping the catalyst in the water phase. In this way, the catalyst was recycled at least
six times without change of ligand structure during the CuAAC reactions (Figure S2).
However, a little decrease of the yields was observed (Table S2), which was due to the
unavoidable lost of copper ions that were stoichiometrically trapped inside the
product through interaction with the trz group (before being extracted with an
ammonia solution).20
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Table 1. CuAAC reactions between benzyl azide and phenylacetylene using various
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amounts of PEGꢀtrisꢀtrzꢀCuI catalyst.a
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Entry
Temperature CuI (ppm) Time (h)
Conversionb/yieldc TON
(%)
TOF (hꢀ1)
(℃)
1d
2d
3d
4e,f
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2000
200
100
50
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100/97
100/97
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100/95
95/90
90/86
37/30
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485
24.25
242.5
485
4850
9700
19000
45000
86000
75000
ꢀꢀ
950
20
2250
3600
3125
ꢀꢀ
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10
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8
0
a Reaction conditions: 0.1 mmol benzyl azide, 0.105 mmol phenylacetylene and 1 mL water. b 1
H
c
d
e
NMR conversion. Isolated yield. Similar yields were also obtained at 30℃. Similar yield
(93 %) was also obtained when large amounts of benzyl azide (10 mmol) and phenylacetylene
(10.5 mmol) were used in 10 mL H2O. f The catalyst was recycled 6 times under these conditions.
It was then of interest to investigate the underlying reason(s) for such an efficiency in
the CuAAC reactions in water using such low amounts of PEGꢀtrisꢀtrzꢀCuI catalyst.
To this end, CuI stabilized by PEG 2000 (B), monotrzꢀPEG (1 equiv. and 3 equiv. for
C and D, respectively) and trisꢀtrzꢀPEG (E) were compared with the original neat CuI
(CuSO4 + NaAsc, A) catalyst for the CuAAC of benzyl azide and phenylacetylene in
water under identical conditions. First, the original CuI and PEGꢀstabilized CuI
species were compared, because the trisꢀtrzꢀPEG has a PEG tail. The waterꢀsoluble
and ecoꢀfriendly PEG is used extensively as a solvent or coꢀsolvent in water for a
variety of purposes due to the phaseꢀtransfer catalytic nature that is efficient in
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organic synthesis.21 Previously, it was shown that “click” synthesis of
1,4ꢀdisubstituted 1,2,3ꢀtriazoles proceeded in good yields using CuSO4 + NaAsc in
PEG 400/water under mild conditions for a short time, due to very efficient activation
by PEG 400.22ꢀ25 However this effect is not observed in the present study, because
similar yields were obtained when compared between A and B under different
catalysts loading. It appears that the concentration of PEG played a key role in the
previous studies (PEG 400/water = 1:1, v:v).22ꢀ25 Here the present PEG concentration
is too low to provide such an effect, and therefore the PEG ligand does not lead to a
good yield. When the monofunctional 1,2,3ꢀtriazole terminated with PEG 2000
(PEGꢀmonoꢀtrzꢀCuI, 1 equiv., C),26 was introduced the yields increased, especially
that under low catalyst amounts (i.e. 26.5% vs. 5% at 100 ppm). This confirmed that
the nitrogen based ligand served as a rate accelerator in this CuI catalysis resulting in
increased yields.4ꢀ7 When a stoichiometric amount of monoꢀtrzꢀPEG vs. Cu2+ was
used in the synthetic procedure (3 equiv., D), the yields also greatly enhanced
compared to those of the reactions catalyzed by A under various catalysts loading (i.e.
66.7% vs. 5% at 100 ppm; 34.0% vs 0% at 50 ppm). Surprisingly, quantitative
conversions with excellent isolated yields were generally obtained at 2000, 200, 100,
and 50 ppm using the PEGꢀtrisꢀtrzꢀCuI catalyst (E) under the present conditions. It
thus appears that a strong chelation effect is becoming more and more important as
the concentration decreases.4ꢀ7,10,11 In the cases of Cu2+ in neat water and Cu2+ in water
in the presence of PEG and 1 equiv. monoꢀtrzꢀPEG, when NaAsc was added, the color
of the aqueous solution turned very fast from colorless to light yellow. This was not
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the case for Cu2+ in water in the presence of the ligands that are in stoichiometric ratio
of trz to Cu2+ (3 equiv. of monoꢀtrzꢀPEG and 1 equiv. of trisꢀtrzꢀPEG). In these cases
half an hour or more was required to change from colorless to light yellow. The
differences of Cu2+ reduction rates are seemingly due to the increased electron density
brought about on Cu2+ upon complexation by all trz ligands making reduction of Cu2+
thermodynamically and subsequently kinetically more difficult. Altogether, as
depicted in Figure 2, the high efficiency of these click reactions catalyzed by very low
amounts of PEGꢀtrisꢀtrzꢀCuI catalysts benefit from (i) the chelation effect, (ii) the
amphiphilicity of the trisꢀtrzꢀPEG ligand containing a trisꢀtriazole tripod that increases
the electron density on the metal center, and (iii) a PEG chain allowing homogeneous
click reactions in water.
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Figure 2. Comparison studies between CuI, PEGꢀCuI, PEGꢀmonoꢀtrzꢀCuI, and
PEGꢀtrisꢀtrzꢀCuI catalysts in the CuAAC reaction between benzyl azide and
phenylacetylene.
Encouraged by the success of the initial efforts, the scope of applicability of this very
low level catalyst of PEGꢀtrisꢀtrzꢀCuI catalyst was explored with CuAAC reactions
between various alkynes and organic azides in water (Table 2). As the inspection of
Table 2 reveals, excellent yields were generally obtained in the CuAAC of a wide
variety of alkynes with organic azides. In addition, in most of the studied cases,
purifications of the products by silica chromatography were not necessary, because
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most of the clicked products are waterꢀinsoluble solids, and the excess alkyne was
removed by simple solvent washing and eventually by recycling. Thus these “click”
products were obtained by a simple extractionꢀwashingꢀfiltration process, revealing
the advantages of this low level of PEGꢀtrisꢀtrzꢀCuI catalyst for CuAAC reactions in
neat water.
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Table 2. Substrate scope of CuAAC reactions between various azides and alkynes
using the PEGꢀtrisꢀtrzꢀCuI catalyst.a
N
R2
N
PEG-tristrz-CuI
N3
N
+
(2)
R2
35 oC, 20 h, H2O, N2
R1
R1
Entry
9
Azide
Alkyne
CuI
Conversionb Yieldc
(ppm)
20
(%)
95
(%)
90
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90
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93
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100
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100
91
50(20)
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100(72)
100
95(66)
93
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a Reaction conditions: 0.1 mmol azide, 0.105 mmol alkyne and 1 mL water.
b 1H NMR conversion. c Isolated yield.
As shown in Scheme 2, the catalyst PEGꢀtrisꢀtrzꢀCuI was also successfully used to
prepare functional materials, namely clickꢀtriazoleꢀfunctionalized
1ꢀethynylcyclohexanol (1, Equation 3), 6ꢀmonodeoxyꢀ6ꢀmonoazidoꢀβꢀCD (2,
Equation 4), ꢀbis (ferrocenylꢀ1,2,3ꢀtriazolylmethyl) benzene (3, Equation 5),
p
clickꢀtriazole functionalized 7ꢀ(propargyloxy)coumarin (4, Equation 6), two kinds of
9ꢀtriazolyl dendrimers, (5 and 6, Equation 7), clickꢀtriazole functionalized moxestrol
(7, Equation 8), and 3′ꢀdeoxyꢀ3ꢀazidothymidine (8, Equation 9).
First, 1ꢀethynylcyclohexanol was chosen, because it has a simple structure, and it is
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known as an active metabolite of the old central nervous system depressant drug
ethinamate. The click reaction with benzyl azide in excellent isolated yield (93%) was
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achieved using only 200 ppm at 35
℃ for 20 h (Scheme 2, Equation 3).
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Cyclodextrin (CD) has been largely dominated by its unique ability to form inclusion
complexes with guests fitting in their hydrophobic activity,27ꢀ28 and its
functionalizations have been a powerful means to improve its applications towards
drug delivery, sensing or enzyme mimicking, pharmaceuticals and biomedicine, and
also as catalysts of aqueous phase metalꢀcatalyzed organic reactions.29ꢀ36 Previously, it
has been shown by Ding’s group that a waterꢀsoluble palladium complex based on 2
exhibited extremely high TONs and TOFs for Suzuki–Miyaura cross coupling
reactions in neat water. This was mainly attributed to the βꢀCDꢀfragmentꢀenhanced
water solubility of the catalyst and accommodated the substrate through a recognition
process, although the SharplessꢀFokin catalyst was used in high amount (10 mol%).37
Now with the promotion of the amphiphilic trisꢀtrzꢀPEG ligand, only 300 ppm of the
SharplessꢀFokin catalyst efficiently catalyzed the “click” reaction with 2 in 85%
isolated yield (Scheme 2, Equation 4). Furthermore, hostꢀguest molecular interactions
between βꢀCD and ferrocene derivatives38 for nanoparticles catalyst in aqueous
solution are also known, and recently this hostꢀguest system was utilized in AuNP
assembly for photothermal therapy.39 Now the click synthesis of one of this hostꢀguest
system precursor,
p
ꢀbis (ferrocenylꢀ1,2,3ꢀtriazolylmethyl) benzene 3, was achieved
for 24 hours with 83% isolated yield
using only 100 ppm per branch at 35
℃
(Scheme 2, Equation 5). It is expected that this material will be useful to complex
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βꢀCD in a hostꢀguest assembly to stabilize metal nanoparticles for catalysis in
aqueous solvents38 and develop smart nanocarriers for intracellular diagnosis and
therapy.
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Clickꢀtriazole functionalized 7ꢀ(propargyloxy)coumarin, 4, was also tested in the
CuAAC “click” reaction with PEGꢀtrisꢀtrzꢀCuI in water (Scheme 2, Equation 6).
Coumarin derivatives are often used for their antioedematous properties, and their
flavor properties have rendered this family famous in perfume industry. Moreover
coumarins are also known as fluorescence dyes. With 300 ppm PEGꢀtrisꢀtrzꢀCuI
catalyst, this “click” product was isolated in 89% yield.
The CuAAC click reaction is a superb synthetic tool that has also been usefully and
successfully applied to the synthesis of “click” dendrimers.7, 40 Following our original
report of the first click synthesis of metallodendrimers.19,41 iterative click
constructions of metallodendrimers terminated by redox ferrocenyl groups and
pyridyltriazole ligands were achieved.42 Subsequently the use of these
trzꢀmetallodendrimers in redox sensing20 and catalysis of carbon−carbon cross
coupling reactions42ꢀ43 attracted increasing attention. However, the constructions of
multiple and pure 1,4ꢀregioisomer of 1,2,3ꢀtriazoleꢀterminated click dendrimers are
rather difficult, unless specific CuI catalysts are designed or/and used with high
catalyst loading in organic solvents at relative high temperature. Also click
dendrimers tend to trap organic solvents and other impurities such as Cu ions that are
more or less difficult to remove. The present study using the PEGꢀtrisꢀtrzꢀCuI catalyst
allows click synthesis of 9ꢀferrocenyltriazole dendrimer 5 and 9ꢀpyridyltriazole
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dendrimer 6 in excellent yields with 100 ppm Cu per azido branch of catalyst under
ambient conditions in water (Scheme 2, Equation 7). Moreover the purification of the
dendrimers was achieved by straightforward solid/liquid phase separation. After the
reaction, dendrimers 5 and 6 are separated from water as light yellow waxy solid
sticking the wall of glass vessel and magnetic stirring bar by simply removing the
liquid water phase and washing with pentane.
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Fe
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Fe
N
N
Fe
N
N
N
N
N
Si
N
N
Si
N
Fe
N
N
N
Si
Si
Fe
Si
N
N
N
Si
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N
Si
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N
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N
Si
Fe
N3
Fe
Si
Fe
N3
N
N
N
Si
N
Si
N
5
N3
Fe
Fe
N3
Si
Isolated yield : 93%
PEG-tristrz-CuI
(100 ppm per branch)
H2O, 40 oC, 24 h, Ar
Si
"Click"
(7)
Si
N3
N
N
N
Si
N
N
N
N
N
N
N
N3
Si
N3
N
Si
Si
Si
N
N
N
Si
N3
N
N
Si
Si
N
N
N3
Si
N
N
N
Si
N
N
N
Si
N
N
N
N
Si
N
N
Si
N
N
6
N
N
Isolated yield : 90%
N
N
N
Scheme 2. Application of the PEGꢀtrisꢀtrzꢀCuI catalyst to the synthesis of functional
materials.
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Moxestrol is known as a synthetic steroidal estrogen for the treatment
of menopausal symptoms, and it is one of the most potent estrogens known. The
natural alkyne of moxestrol has afforded easy functional ability for various medicinal
applications. Herein we use the easy accessible “click” mean to functionalize this
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useful material, with 500 ppm PEGꢀtrisꢀtrzꢀCuI in only water at 35
℃ for 48 h with
100% conversion and 93% isolated yield to the desired product 7 (Scheme 2,
Equation 8). Another key important natural product, 3′ꢀdeoxyꢀ3ꢀazidothymidine (AZT,
zidovudine), a nucleosideꢀanalog reverse transcriptase inhibitor, was the first
approved antiviral product for the treatment of human immunodeficiency virus (HIV).
The 3′ꢀazido group of AZT has afforded its potential application to HIV RT binding,43
and its “click” functionalization has shown to be a convenient tool for the synthesis of
novel nucleoside inhibitors with low to submicromolar potencies against HIVꢀ1,44ꢀ45
novel fluorescent markers and cytostatic agents.46ꢀ47 Moreover “click”
functionalization of AZT that formed nucleosideꢀbased bioconjugates has also
recently been employed as a biological CO tracer.48 Herein, we quote an example of
these useful AZTꢀderived 1,2,3ꢀtriazoles by synthesizing 8 using 500 ppm of
PEGꢀtrisꢀtrzꢀCuI in only water at 45
℃ for 48 h with 100% conversion and 89%
isolated yield (Scheme 2 Equation 9). To the best of our knowledge, the AZTꢀderived
1,2,3ꢀtriazoles have never been synthesized using such a low amount of CuI catalysts
under ambient condition in water. This successful attempt not only opens the way to
efficiently synthesize clean AZTꢀderived 1,2,3ꢀtriazoles for drug design (especially
for anti HIV), but also contributes to the developments of new class of potential
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biological tracers/labeling for various applications.
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Conclusion
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The family of nitrogen based ligands that accelerate the CuAAC reactions has been
extended here with the utilization of the amphiphilic trisꢀtrzꢀPEG ligand. This
recyclable ligand has now been shown to promote the conventional SharplessꢀFokin
catalyst as a highly efficient CuI “click” catalyst in water for various organic
syntheses. Comparative catalytic studies indicate that the trisꢀtrzꢀPEG ligand is more
efficient than the monoꢀtrzꢀPEG ligand, and reduction of CuII to CuI is considerably
slower with the former ligand than with later. These trends confirm the favorable
effect of the chelation in trisꢀtrzꢀPEG concerning the catalytic properties. This study
should contribute to the more effective synthesis of clicked compounds that are useful
in current organic reactions and in various fields with the use of the copper catalyst in
minute quantities down to industrially tolerable amounts.
Experimental Section
Synthesis of the CuI-L catalysts: Generally, in a dried Schlenk flask, 1 mL of
degassed aqueous solution of ligand (L) and CuSO4·5H2O (0.8 mg, 3.20 × 10ꢀ6 mol)
solubilized in 1 mL of degassed water were successively added. 12 mL of degassed
water were added into the Schlenk flask, and the solution was stirred at r.t. for 30 min
under N2. Sodium ascorbate (NaAsc, 10 equiv. per Cu2+) solubilized in 2 mL of
degassed water was added dropwise to the solution of Cu2+-L. After stirring for
another 30 min under N2, the CuI-L solution was ready for use. The details of the
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synthesis of these catalysts are described in the Supporting Information.
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General procedure for the CuAAC reactions: A glass vessel equipped with a
magnetic stir bar was charged with 0.1 mmol of organic azide and 0.105 mmol of
alkyne under a nitrogen atmosphere. Catalytic amounts of catalyst were added into the
vessel under N2, and degassed water was added in order to obtain 1 mL as the total
volume of water. The reaction mixture was stirred during 20 h at 35 °C under N2.
After the reaction, the mixture was filtered and then extracted using CH2Cl2 (3×10
mL). The organic layer was dried over Na2SO4 and filtered, and the solvent was
removed in vacuo to give the corresponding 1,2,3ꢀtriazoles. The product was then
purified by silica chromatography when necessary.
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ASSOCIATED CONTENT
Supporting Information: General data, syntheses and characterizations of the catalysts,
detailed experimental procedures for CuAAC reactions and their recycling, and
spectra for all compounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
didier.astruc@uꢀbordeaux.fr
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
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Financial support from the China Scholarship Council (CSC) of the People’s Republic
of China (grant to C.W.), the Universities of Bordeaux, Toulouse 3, the LCC
(Toulouse), and the Centre National de la Recherche Scientifique (CNRS) is
gratefully acknowledged.
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