New organometallic Schiff-base copper complexes as efficient "click" reaction precatalysts

Article abstract of DOI:10.1039/c5nj02681d

A new ferrocenyl-containing unsymmetrical Cu^II-Schiff-base complex, 2, and its covalently poly(methyl) (methacrylate) (PMMA)-grafted counterpart 3 were synthesized and characterized using elemental analysis, electrospray ionisation (ESI) mass s

Full text of DOI:10.1039/c5nj02681d

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New Journal of Chemistry
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DOI: 10.1039/C5NJ02681D
New organometallic Schiff-base copper complexes
as efficient “click” reaction precatalysts
Xiang Liu,a Néstor Novoa,b Carolina Manzur*,b
David Carrillo*b and Jean-René Hamon*a
a
b
UMR 6226 «Institut des Sciences Chimiques de Rennes», CNRS-Université de Rennes 1, Campus
de Beaulieu, 35042 Rennes Cedex, France. E-mail: jean-rene.hamon@univ-rennes1.fr
Laboratorio de Química Inorgánica, Instituto de Química, Pontificia Universidad Católica de
Valparaíso, Avenida Universidad 330, Valparaíso, Chile. E-mails: cmanzur@ucv.cl;
david.carrillo@ucv.cl
Abstract
A new ferrocenyl-containing unsymmetrical CuII-Schiff-base complex, 2 and its
covalently poly(methyl) (methacrylate) (PMMA)-grafted counterpart 3 were synthesized and
characterized by elemental analysis, electrospray ionisation (ESI) mass spectrometry for 2,
and FT-IR spectroscopy. The new complex 3 was employed as precatalyst in the copper-
catalyzed [3+2] cycloaddition of organic azides to alkynes (CuAAC, “click reaction). The
active CuI species generated from only 0.2 mol% of CuII precatalyst 2 and sodium ascorbate
displayed high activity at room temperature in ethanol for 24 hours allowing the synthesis of a
wide variety of 1,4-disubstituted 1,2,3-triazoles in high isolated yields. The PMMA-supported
catalyst 3 is also efficient and has been reused at least three times in these “click” reactions
without any lost of activity or copper leaching.
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DOI: 10.1039/C5NJ02681D
Introduction
1,2,3-Triazoles, one of the most vital type of N-containing heterocyclic compounds,
are of continuing interest, not only as biological active drugs1 but also as functional
materials.2 In addition, interest for these compounds is mainly due to their use in numerous
fields of organic semiconductors,3 dyes,4 dehydroannulenes,5 and electroluminescent
material.6 During the last decades, many methodologies for the preparation of 1,2,3-triazoles
have been developed. Among them, the concept of a “click” reaction was designed by
Sharpless and co-workers in 2001.7 One year later, the research groups of Sharpless8 and of
Meldal9 independently reported the efficient copper-catalyzed azide-alkyne cycloaddition
(CuAAC) that has been proven to be the archetypal click reaction.10 The popularity of the
CuAAC reaction is mainly due to its 100% atom economy, mild reaction conditions, wide
substrate scope and exclusive regioselectivity in the formation of the 1,4-disubstituted 1,2,3-
triazoles. CuAAC has found widespread applications in organic10and material syntheses,11 as
for instance, preparation of ferrocene-containing polymers12 and redox-active metallocene-
containing dendrimers.13
Schiff base ligands have attracted considerable attention due to their facile synthesis,
diversity in structural topology and their ability to produce stable complexes with a large
number of transition metal ions.14 Such types of ligands can also stabilize metal ions in
various oxidation states and, therefore, play a crucial role in controlling the conversions of
organic reactions catalyzed by their transition metal complexes. Schiff base metal complexes
present effective applications in various fields of scientific research such as magnetism,15
catalysis16 and functional molecular-based materials.17,18 Among them, unsymmetrical
tetradentate N2O2 salen-type Schiff base complexes19 are easily obtained by the 1:1:1 stepwise
condensation of -diketone, salicylaldehyde and a primary alkyl- or aryldiamine in the
presence of a metal salt.20 Using this methodology, our groups have synthesized and fully
characterized a lot of robust neutral heterobimetallic unsymmetrical salen-type complexes of
nickel(II) and copper(II), and thoroughly investigated their electrochemical, linear and second
order nonlinear optical properties.21,22 Side-chain metallopolymers containing an
unsymmetrical ferrocenyl substituted Schiff base complex of Ni(II) linked to a
polymethylmethacrylate (PMMA) matrix were also prepared.23
To the best of our knowledge, there are no examples of the use of such CuII
tetradentate Schiff base complexes as catalysts or catalyst precursors for the CuAAC reaction.
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Polydentate nitrogen donor ligands are commonly used to enhance the rate of the CuAAC
DOI: 10.1039/C5NJ02681D
reactions24 and catalysts based on the tren architecture were shown to behave as highly
efficient and reusable catalysts.25 As part of our current studies on the application of
tetradentate N2O2 Schiff base metal complexes, herein, we report: (i) the synthesis and
characterization of a new ferrocenyl-containing substituted copper(II) unsymmetrical Schiff
base complex 2 and of its polymeric counterpart 3 obtained by a covalent grafting of the
heterobimetallic complex 2 onto a PMMA matrix upon trans-esterification; (ii) their use,
efficiency, scope and recyclability as catalysts for the synthesis of 1,4-disubstituted 1,2,3-
triazoles via “click” reactions of organic azides and alkynes.
Results and discussion
Synthesis and characterization of the catalysts 2 and 3
The paramagnetic heterobimetallic FeII-CuII unsymmetrical Schiff base complex 2 was
prepared by a one-pot template procedure reacting the metalloligand 1, and equimolar
amounts of 2,5-dihydroxobenzaldehyde and copper(II) acetate monohydrate in refluxing
ethanol for 8 hours (Scheme 1). The ferrocenyl group was introduced because (i) its
functionalization and branching to the Schiff-base is easy and convenient, (ii) its color
provides easy trace of the catalyst, and (iii) it involves specific bulk that differ from simple
organic fragments and allows to study this bulk effect on catalytic results. Compound 2 was
isolated in a reasonable yield of 60% as an air and moisture insensitive, thermally stable dark
red powder, exhibiting a rather good solubility in common polar organic solvents, but it is
insoluble in diethylether and hydrocarbons. The metallopolymer 3 was synthetized under
basic conditions by a trans-esterification reaction between the in situ deprotonated form of the
heterobimetallic Schiff base complex 2 with a polymethylmetacrylate matrix in refluxing THF
overnight (Scheme 1). The PMMA-supported catalyst 3 was obtained as a dark brown
amorphous solid upon slow evaporation of a THF solution at room temperature (rt).
Compound 3 shows good solubility in dichloromethane and THF, but is insoluble in ethanol
and other common solvents. Both compounds 2 and 3 were characterized by FT-IR
spectroscopy and the bulk composition of 2 was firmly established by elemental analysis and
confirmed by the molecular peak in the ESI mass spectrum (see the experimental section).
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Scheme 1 Synthesis of the heterobimetallic complex 2 and of its PMMA-supported derivative 3a
a The PMMA-supported derivative 3 is a mixture resulting from random ordering of the monomer units and
bulk effect of the inorganometallic group in the polymer. The monomer ordering that is represented in the
drawing of 3 is a simplification.
The solid-state FT-IR spectrum of 2 (Fig. S1)† presents a set of medium- to strong-
intensity bands in the range 1603-1512 cm-1 due to the C-C/C-N/C-O stretching vibrations of
the organic Schiff base skeleton. The shift by about 30 cm-1 of these absorptions and the
disappearance of the enamine N-H vibration observed at 3203 cm-1 in the spectrum of the
starting metalloligand26 clearly indicate that coordination of the CuII metal ion takes place
through the imine nitrogen and carbonyl oxygen atoms. On the other hand, the solid-state FT-
IR spectrum of the metallopolymer 3 (Fig. S1)† is superimposable to that of its PMMA-
supported Ni(II) counterpart,23 exhibiting the characteristic band of the ester carbonyl group
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(1732 cm ) and the vibrational pattern of the organic Schiff base skeleton in the DrOanI: g10e.101369/3C65N-J02681D
1566 cm-1. In addition, the disappearance of the (O-H) vibration at 1447 cm-1 in the spectrum
of 3 bears testimony of the successful trans-esterification reactions.
Catalysis
Both catalysts 2 and 3 were used in the [3+2] cycloaddition of organic azides to
alkynes in CuAAC click reactions. All the reactions were performed on a 0.50 mmol scale
relative to alkyne and azide reagents in 2 mL of solvent at rt during 24 h under N2 in the
presence of sodium ascorbate as reducing agent (eq. 1). This means that the CuII-Schiff base
1
complex is reduced to CuI by sodium ascorbate as shown by H NMR by the shift of the
imine proton (see Fig. S2)†, and as anticipated from the previously well-known reduction of
CuSO4 to CuI by sodium ascorbate.8
First, the reaction conditions were optimized for the synthesis of 4 using
ethynylbenzene and (azidomethyl)benzene as model substrates, with the heterobimetallic
Fe(II)-Cu(II) Shiff base complex 2 as catalyst (Table 1). The first attempt performed in
ethanol with 5 mol% loading of catalyst afforded the desired 1-benzyl-4-phenyl-1H-1,2,3-
triazole product 4a in almost quantitative yield (Table 1, entry 1). Such a result is not
surprising with respect to the amount of catalyst used.8-10 Thus, we investigated the reaction at
different loading of complex 2, and found that the isolated yield of the 1,2,3-triazole 4a
slightly decreased from 98.2 to 92.0% when the loading of catalyst is reduced from 5 to 0.2
mol% (Table 1, entry 1-5). Further decreasing of the catalyst loading to 0.1 mol% caused a
dramatic drop of the yield to 45.2%, however (Table 1, entry 6). Based on these results, it
appeared that the best yield to catalyst compromise is provided in entry 5 (Table 1) and we,
therefore, chose to run the click reactions with 0.2 mol% loading of catalyst.
Next, with this 0.2 mol% loading of catalyst 2, the reactions were carried out in
different solvents including water, tetrahydrofuran (THF), dimethylformamide (DMF) and
dimethylsulfoxide (DMSO) (Table 1, entry 7-10). Under these reaction conditions, the 1,2,3-
triazole 4a is formed in lower yields, ranging from 12.2% in water to 83.3% in THF. Thus,
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among the solvents tested, ethanol was found to be the best one (Table 1, entry 5). The very
DOI: 10.1039/C5NJ02681D
low conversion observed in water is presumably due to the lack of solubility of the organic
reagents and catalyst in this medium. On the other hand, the organic substrates are soluble in
ethanol. The reaction is heterogeneous as the precatalyst and catalyst are not soluble in
ethanol without copper leaching.
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Table 1 Optimization of the click reaction conditionsa using complex 2 as catalyst, and
ethynylbenzene and benzylazide as reagents.
Entry
Catalyst (%)
Sodium
Solvent
Yield (%)b
ascorbate (%)
1
2
3
4
5
6
7
8
9
10
5
2
1
0.5
0.2
0.1
0.2
0.2
0.2
0.2
50
20
10
5
2
1
2
2
2
2
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
THFc
H2O
98.2
97.8
95.2
94.9
92.0
45.2
83.3
12.2
67.3
70.1
DMSOd
DMFe
aReaction conditions: 0.50 mmol of alkyne and azide reagents in 2 mL of solvent, 25
°C, 24 h, N2. bIsolated yield of 1-benzyl-4-phenyl-1H-1,2,3-triazole (4a).
cTetrahydrofuran. dDimethylsulfoxide. eDimethylformamide.
The scope extension of the protocol to other azides and alkynes was also investigated
under the previously optimized reaction conditions. As shown in Table 2, various organic
azides and alkynes were well suited for the “click” reaction with the CuII Schiff base complex
2 as catalyst. For example, in the presence of ethynylbenzene, either the electron withdrawing
substituted azides or electron donating substituted azides including PhCH2N3,3-MeC6H4N3,
PhN3, 4-BrC6H4CH2N3, and 4-CNC6H4CH2N3 undergo facile conversion into corresponding
1,4,disubstituted 1,2,3-triazole derivatives 4a-e in good to excellent yields (Table 2, entries 1-
5 ). Similar high isolated yields (87.5 to 93.6%) of 1,4-disubstituted 1,2,3-triazoles 4f-h are
obtained when (azidomethyl)benzene is reacted with variously electronically substituted R1-
C≡CH alkynes (R1 = 4-anisyl, 4-bromophenyl or 2-pyridyl ; Table 2, entry 6-8). In addition,
C6H5N3, 4-BrC6H4CH2N3, 4-CNC6H4CH2N3, 4-BrC6H4N3, and 4-MeOC6H4N3, are also
suitable for the cycloaddition reactions with 2-ethynylpyridine affording the corresponding
1,2,3-triazole products 4i-m in very good yields (Table 2, entries 9-13). Even though no
strong trend can be traced from Table 2, one can, however, note that the lowest yields are
obtained when the azide reagent bears the strong 4-CN electron withdrawing substituent
(entries 5 and 11).
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Table 2 Substrate scope of alkynes and azides in the click [3 + 2] cycloaddition reDaOcIt:i1o0n.10s39/C5NJ02681D
catalyzed by complex 2.a
Entry
R1-C≡CH
C6H5
R2-N3
C6H5CH2
3-MeC6H4CH2
C6H5
4-BrC6H4CH2
4-CNC6H4CH2
Product
4a
4b
4c
4d
Yield (%)b
92.0
88.7
88.5
93.4
82.5
1
2
3
4
5
C6H5
C6H5
C6H5
C6H5
4e
6
7
8
9
4-MeOC6H4 C6H5CH2
87.5
93.6
91.3
90.4
92.5
83.5
90.4
88.4
4f
4-BrC6H4
2-NC5H4
2-NC5H4
2-NC5H4
2-NC5H4
2-NC5H4
2-NC5H4
C6H5CH2
C6H5CH2
C6H5
4-BrC6H4CH2
4-CNC6H4CH2
4-BrC6H4
4g
4h
4i
4j
4k
4l
10
11
12
13
4-MeOC6H4
4m
aReaction conditions: alkyne (0.50 mmol), azide (0.50 mmol), complex 2 (0.2 mol%),
sodium ascorbate (2 mol%), EtOH (2 mL), rt, 24 h, N2. bIsolated yield.
The next step was the recycling study of the catalytic material anchored onto the
PMMA matrix. Recycling investigations were carried out using catalyst at 2 mol% in the click
[3 + 2] cycloaddition reaction between the (azidomethyl)benzene and three different alkynes
(Table 3). The supported precatalyst 3 was recovered by filtration and reused three times in
the same reaction. Na ascorbate was added again for each recycling, because the CuI catalyst
is air sensitive and oxidized by air to CuII. No leached copper was detected in solution by
TEM (nanoparticles, Fig. S3)† and 1H NMR spectroscopy (CuII) after catalysis (Figs. S4-S6)†.
We know that the presence of CuI in solution containing triazole significantly shifts the
triazole proton from 7.6 downfield to 8 ppm,27 and this was shown again by adding CuSO4
and sodium ascorbate to a solution of 4. The absence of CuII in the solution resulting from the
click reaction catalyzed by 3 was shown by the absence of shift of the triazole proton in the
1H NMR spectrum of this solution to which sodium ascorbate was added. This shows the
stability of the catalyst 3 under the reaction condition and the heterogeneous mechanism of
the reaction, the precatalyst 3 being insoluble in EtOH. Under the above conditions, catalyst 3
afforded the expected 1-benzyl-4-phenyl-1H-1,2,3-triazole 4a in 95.2-95.0% yield in three
cycles in the reaction involving the model substrate (Table 3, entry 1). The reusability test was
extended to two other alkynes, namely, 4-ethynylanisole and 4-bromophenylacetylene,
providing the desired 1,4-disubstituted 1,2,3-triazoles 4f and 4g in 88.3% and 94.2-93.4%
yields, respectively, in three cycles (Table 3, entries 2 and 3). These results clearly indicate
that the highly active PMMA-supported heterobimetallic unsymmetrical Schiff base complex
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3 can be reused at least three times without significant loss of its catalytic activityDaOnI:d10w.10i3t9h/oC5uNtJ02681D
copper ion leaching.
Table 3 Reusability tests of the PMMA-supported catalyst 3 in the click [3 + 2] cycloaddition
reactionsa
Entry R1-C≡CH
R2-N3
Product
Run 1
yield (%)b
95.2
Run 2
yield (%)b
95.0
Run 3
yield (%)b
95.0
1
2
3
C6H5
4-MeOC6H4
4-BrC6H4
C6H5CH2
C6H5CH2
C6H5CH2
4a
4f
88.4
88.3
88.3
94.2
93.8
93.4
4g
aReaction conditions: alkyne (0.50 mmol), azide (0.50 mmol), catalyst 3 (2 mol%), sodium ascorbate (20
mol%) , EtOH (2 mL), rt, 24 h, N2. bIsolated yield.
Conclusion
In summary, a new heterobimetallic Cu(II) complex of ferrocene-based unsymmetrical
tetradentate Schiff base ligand has been synthesized, characterized, and its efficient catalytic
performances have been investigated in the [3 + 2] cycloaddition of organic azides to alkynes.
The procedure is general, convenient, simple to carry out, eco-friendly, with a broad scope
and atom economy, leading to the regioselective formation of a wide variety of 1,4-
disubstituted 1,2,3-triazoles in high isolated yields. The PMMA-supported catalyst was
obtained by trans-esterification of the novel copper(II) complex of unsymmetrical dianionic
quadridentate organometallic salen-type Schiff base ligand 2 with the polymer matrix. The
heterobimetallic Schiff base complex 2 and its PMMA-anchored derivative 3 were
characterized by elemental analysis and solid-state infrared spectroscopy. The
heterobimetallic Schiff base complex 2 exhibits a good catalytic activity with a 0.2 mol% of
loading with various organic alkynes and azides under ambient conditions in ethanol. The
ferrocenyl group appears fully compatible to the catalytic activity of both precatalysts. The
catalytic results favorably compare with literature data27 using here a practical catalyst in very
low loading. The CuII precatalysts 2 and 3 are not active unless sodium ascorbate is added,
which fully parallels the finding by the Sharpless group with CuSO4.8 Recycling the catalyst
supported on PMMA matrix 3 was also investigated. The experiments involving
(azidomethyl)benzene and three different alkynes gave the corresponding 1,2,3-triazoles in
excellent yields after three cycles without copper leaching from the precatalyst 3 to solution.
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This does, therefore, demonstrate that this material shows good recyclability withDoOuI:t10a.n10y39l/oC5sNsJ02681D
in activity, opening new potential applications for copper(II) Schiff base compounds in
catalysis.
Experimental
General methods
All manipulations were performed under a dinitrogen or argon atmosphere using
standard Schlenk techniques. All the solvents and reagents needed were purchased from
commercial sources and used without further purification. The organometallic tridentate
metalloligand 1 was synthesized according to the procedures described in the literature.26
PMMA beads (average MW 35000) were purchased from ACROS Organics. Column
chromatography was carried out on silica gel. Solid-state FT-IR spectra were recorded on a
Perkin-Elmer, Model Spectrum One or a Bruker IFS28 FT-IR spectrophotometer, with KBr
1
13
disks in the 4000 to 400 cm-1 range. The H and C NMR spectra were recorded in CDCl3
solutions at 298 K with either a Bruker AC 300 or a Bruker AVIII 400 spectrometer. All
NMR spectra are reported in parts per million (ppm, ) relative to tetramethylsilane (Me4Si),
with the residual solvent proton resonance and carbon resonances used as internal standards.
Coupling constants (J) are reported in Hertz (Hz), and integrations are reported as number of
protons. Microanalyses were conducted on a Thermo-FINNIGAN Flash EA 1112 CHNS/O
analyzer by the Microanalytical Service of the CRMPO at the University of Rennes 1
(France).
Synthesis of the heterobimetallic Schiff base complex 2
To a Schlenk tube containing a stirred solution of the metalloligand 1 (400 mg, 1.11
mmol) in ethanol (30 mL) was added a solution of 2,5-dihydroxobenzaldehyde (153.3 mg,
1.11 mmol) in ethanol (10 mL). The resulting solution was stirred for 15 min at rt. A solution
of copper(II) acetate monohydrate (334 mg, 1.67 mmol) in ethanol (10 mL) was then added,
and the resulting solution was refluxed for 8 h. The mixture was allowed to cool to r. t.
evaporation of the solution to half of its volume under vacuum gave a dark red precipitate.
The solid material was filtered off, washed with cold methanol (5 x 10 mL) and diethyl ether
(5 x 10 mL), and dried in vacuo for 1 h to afford 364 mg (0.67 mmol, 60 % yield) of a dark
red powder. Found: C, 59.43; H, 3.75; N, 5.35. C27H22N2O3FeCu requires C, 59.85; H, 4.09;
N, 5.17%. ESI MS (m/z), calcd for C27H22N2O3Na56Fe63Cu: 564.0168, found: 564.0167 (0
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ppm) [M Na] . FT-IR (KBr pellet, cm ): 3436(w) (O-H), 3096(w) (C-H aryl), 2965–
2925(w) (C-H alkyl), 1603(m)-1512(s) (C…O), (C…N), (C…C), 1447(m) (O-H).
Synthesis of the PMMA-supported Schiff base complex 3
A Schlenk tube was charged with a magnetic stir bar, complex 2 (101 mg, 0.186
mmol), potassium tert-butoxide (31mg, 0.279 mmol) and 1.5 mL of THF. After 15 min of
stirring a dark purple precipitate was formed, the reaction mixture was vigorously stirred for 5
h. Then, 93 mg of PMMA (complex 2 / monomeric unit PMMA = 1/5) was slowly added.
After 10 min of stirring, 2 mL of THF were added, and vigorous stirring was continued for 30
min while the resulting solution was refluxed overnight. The mixture was cooled to r. t. and
evaporation of the solution to half of its volume under reduced pressure gave a precipitate that
was filtered off, washed with cold THF (3 x 3 mL), diethyl ether (2 x 3 mL), and dried in
vacuo for 2 h. The solid material was dissolved in THF at 35°C, filtered off and the filtrate
allowed to slowly evaporate to afford 180 mg of a dark brown amorphous solid. Elemental
analysis: C, 38.53; H, 2.97; N, 2.88%. The compared elemental analyses of 2 and 3 gives
6.53% Cu in complex 3, i.e. a ratio complex 2: PMMA = 1: 4.3 in complex 3. FT-IR (KBr
pellet, cm-1): 3443(w) (O-H), 3012 (w) (C-H aryl), 2966-2929 (w) (C-H alkyl), 1732(s)
(CO2), 1636-1566 (m) (C…O), (C…N), (C…C).
General procedure for the synthesis of the 1,2,3-triazoles 4a-m catalyzed by 2
The alkyne (0.50 mmol), the azide (0.50 mmol), the heterobimetallic Schiff base
catalyst 2 (0.2 mol%), sodium ascorbate (2 mol%) and ethanol (2 mL) were placed in a round
bottom flask equipped with a magnetic stirrer. The resulting mixture was stirred for 24 h at rt
under dinitrogen atmosphere. Then, water (2 mL) was added to the reaction mixture that was
extracted with ethyl acetate (3 × 10 mL). The combined organic phases were washed with
brine (2 × 5 mL), dried over anhydrous MgSO4 and concentrated in vacuo. The residue was
subjected to flash column chromatography with hexanes/ethyl acetate (5/1) as eluent, to
provide, upon evaporation of the solvents and vacuum drying, the desired 1,4-disubstituted
1,2,3-triazoles 4a-m as white solids. Reagents and yields are given in Table 2, whereas NMR
data and spectrum of the 13 triazole derivatives are provided in the ESI.†
Recyclability of the PMMA-supported catalyst 3
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The PMMA-anchored precatalyst 3 (10.5 mg, 2 mol%) and sodium ascorbate (20 DmOoI: l1%0.1)03w9/Ce5rNeJ02681D
added in a Schlenk flask. The system was purged three times with N2 and alkyne (0.50 mmol),
azide (0.50 mmol) and 2 mL of degassed ethanol were successively added by syringe. The
resulting mixture was stirred for 24 h at RT under N2. Then, the mixture was diluted with
diethyl ether and filtered through a filter paper. Water (20 mL) was added to the filtrate, and
then extracted three times with ethyl acetate (3×10 mL). The combined organic phases were
washed with brine (2×5 mL), dried over anhydrous MgSO4, filtered, and the organic solution
was concentrated in vacuo. The residue was purified by silica gel flash chromatography with
hexane/EtOAc (5/1) as eluent to obtain the desired product 4a as a white solid (95.2% yield).
The collected solid containing 3 was washed with water, ethanol and dichloromethane then
transferred into a round bottom flask and dried by a N2 flux. Sodium ascorbate (20 mol%)
was introduced, and the system was purged three times with N2 before adding the alkyne
(0.50 mmol), azide (0.50 mmol) and 2 mL of degassed ethanol like previously. This process
was repeated three times without correction of the amounts of reactants compared to the mass
loss of catalyst at each cycle. The reagents, products, and yields of the various runs are
provided in Table 3.
Acknowledgements
This research has been performed as part of the Chilean-French International
Associated Laboratory for “Inorganic Functional Materials’’ (LIAMIF-CNRS N°836).
Financial support from the China Scholarship Council (CSC) from the People’s Republic of
China (XL), and the Fondo Nacional de Desarrollo Científico y Tecnológico [FONDECYT
(Chile), grants no. 10903010 and 1130105 (D.C. and C.M.)], the Vicerrectoría de
Investigación y Estudios Avanzados, Pontificia Universidad Católica de Valparaíso, Chile
(D.C. and C.M.), the CNRS and the Université de Rennes 1 is gratefully acknowledged. N.N.
thanks the CONICYT (Chile) and BECAS-CHILE for support of a graduate and Joint
Supervision Scholarship (PUCV / UR1).
Notes and References
†
Electronic supplementary information (ESI) available: Solid-state FT-IR spectra of the
1
catalysts (Fig. S1), Fig. S2-S6, spectral data and H and 13C NMR spectra of compounds
4a-m (Figs. S7-S25).
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1
(a) R. Manetsch, A. Krasiski, Z. Radi, J. Raushel, P. Taylor, K. B. Sharpless and
DOI: 10.1039/C5NJ02681D
H.C.Kolb, J. Am. Chem. Soc., 2004, 126, 12809; (b) M. Whiting, J. Muldoon, Y. C. Lin,
S. M. Silverman, W. Lindstrom, A. J. Olson, H. C. Kolb, M. G. Finn, K. B. Sharpless, J.
H. Elder and V. V. Fokin, Angew. Chem., Int. Ed., 2006, 45, 1435; (c) J. Wang, G. Sui,
V. P. Mocharla, R. J. Lin, M. E. Phelps, H. C. Kolb and H.-R. Tseng, Angew. Chem.,
Int. Ed., 2006, 45, 5276; (d) G. C. Tron, T. Pirali, R. A. Billington, P. L Canonico, G.
Sorba and A. A. Genazzani, Med. Res. Rev., 2008, 28, 278; (e) Y. M. A. Yamada, A.
Ohno, T. Sato and Y. Uozumi, Chem. Eur. J., 2015, 21, 17269, (f) N. Singh, C. R.
Chim., 2015, 18, 1257.
2
(a) H. Nandivada, X. W. Jiang and J. Lahann, Adv. Mater., 2007, 19, 2197; (b) C. F.
Ye, G. L. Gard, R. W. Winter, R. G. Syvret, B. Twamleyand and J. M. Shreeve, Org.
Lett., 2007, 9, 3841; (c) P. Wu, A. K. Feldman, A. K. Nugent, C. J. Hawker, A. Scheel,
B. Voit, J. Pyun, J. M. J. Fréchet, K. B. Sharpless and V. V. Fokin, Angew. Chem., Int.
Ed., 2004, 43, 3928; (d) V. Aucagne, K. D. Hanni, D. A. Leigh, P. J. Lusby and D. B.
Walker, J. Am. Chem. Soc., 2006, 128, 2186; (e) D. Astruc, R. Ciganda, C. Deraedt, S.
Gatard, L. Liang, N. Li, C. Ornelas, A. Rapakousiou, J. Ruiz, D. Wang, Y. Wang and P.
Zhao, Synlett, 2015, 26, 1437; (f) D. Huang, P. Zhao and D. Astruc, Coord. Chem. Rev.,
2014, 272, 145; (g) F. Alonso, Y. Moglie and G. Radivoy, Acc. Chem. Res., 2015, 48,
2516.
3
4
(a) D. T. Mowry, Chem. Rev., 1948, 42, 189; (b) G. P. Ellis and T. M. Romney-
Alexandar, Chem. Rev., 1987, 87, 779; (c) R. G. R. Bacon and H. A. O. Hill, J. Chem.
Soc., 1964, 1097; (d) T. Sandmeyer, Ber. Dtsch, Chem. Ges., 1884, 17, 2650; (e) C. F.
Koelsch and A. G. Whitney, J. Org. Chem., 1941, 6, 795.
(a) K. Mori, K. Yamaguchi, T. Mizugaki, K. Ebitani and K. Kaneda, Chem. Commun.,
2001, 461; (b) K. Yamaguchi and N. Mizuno, Angew. Chem. Int. Ed., 2003, 42, 1480;
(c) M. Kotani, T. Koike, K. Yamaguchi and N. Mizuno, Green Chem., 2006, 8, 735; (d)
F. Li, J. Chen, Q. Zhang and Y. Wang, Green Chem., 2008, 10, 553; (e) Y. Zhang, K.
Xu, X. Chen, T. Hu, Y. Yu, J. Zhang and J. Hung, Catal. Commun., 2010, 11, 951.
(a) M. L. Mihailovic, A. Stojiljikovic and V. Andrewjevic, Tetrahedron Lett., 1965, 6,
461; (b) T. Kajimoto, H. Takahashi and J. Tsuji, J. Org. Chem., 1976, 41, 1389; (c) W.
P. Griffith, B. Reddy, A. G. F. Shoair, M. Suriaatmaja, A. J. P. White and D. J.
Williams, J. Chem. Soc., Dalton Trans., 1998, 2819.
5
6
(a) P. Capdevielle, A. Lavigne, D. Sparfel, J. Baranne-Lafont, K. C. Ngyuen and M.
Maumy, Tetrahedron Lett. 1990, 31, 3305; (b) R. Tang, S. E. Diamond, N. Neary and F.
13

New Journal of Chemistry
Page 14 of 17
View Article Online
Marks, J. Chem. Soc., 1978, 562; (c) F. Porta, C. Crotti and S. Cennini, J. DMOIo: 1l0..1C03a9t/Ca5lN.,J02681D
1989, 50, 333; (d) A. Bailey and B. R. James, J. Chem. Soc., Chem. Commun., 1996,
2343; (e) Y. Maeda, T. Nishimura and S. Uemura, Bull. Chem. Soc. Jpn., 2003, 76,
2399.
7
8
H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed., 2001, 40, 2004.
V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem. Int. Ed.,
2002, 41, 2596.
9
C. W. Tornoe, C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057.
10 L. Liang and D. Astruc, Coord. Chem. Rev., 2011, 255, 2933 and references cited
therein.
11 Y. Shi, R. W. Graff, X. Cao, X. Wang and H. Gao, Angew. Chem. Int. Ed., 2015, 54,
7631.
12 (a) For a recent review, see: B. Yao, J. Zhi Sun, A. Qin and B. Z. Tang, J. Inorg.
Organomet. Polym. Mater., 2015, 25, 37 and references cited therein; (b) C. Deraedt, A.
Rapakousiou, Y. Wang, L. Salmon, M. Bousquet and D. Astruc, Angew. Chem., Int.
Ed., 2014, 53, 8445.
13 D. Astruc, L. Liang, A. Rapakousiou and J. Ruiz, Acc. Chem. Res., 2012, 45, 630.
14 Recent review articles: (a) M. Rezaeivala and H. Keypour, Coord. Chem. Rev., 2014,
280, 203; (b) P. A. Vigato, V. Peruzzo and S. Tamburini, Coord. Chem. Rev., 2012,
256, 953; (c) C. J. Whiteoak, G. Salassa and A. W. Kleij, Chem. Soc. Rev., 2012, 41,
622.
15 D. Venegas-Yazigi, D. Aravena, E. Spodine, E. Ruiz and S. Alvarez, Coord. Chem.
Rev., 2010, 254, 2086.
16 See for example: (a) A. Decortes, A. M. Castilla and A. W. Kleij, Angew. Chem. Int.
Ed., 2010, 49, 9822; (b) D. J. Darensbourg, Chem. Rev., 2007, 107, 2388; (c) K.
Matsumoto, B. Saito and T. Katsuki, Chem. Commun., 2007, 3619; (d) C. Baleizo and
H. Garcia, Chem. Rev., 2006, 106, 3987; (e) E. M. McGiarrigle and D. G. Gilheany,
Chem. Rev., 2005, 105, 1563; (f) P. G. Cozzi, Chem. Soc. Rev., 2004, 33, 410; (g) E. N.
Jacobsen, Acc. Chem. Res., 2000, 33, 421; (h) L. Canali and D. C. Sherrington, Chem.
Soc. Rev., 1999, 28, 85.
17 (a) C.- M. Che, C.-C. Kwok, S.-W. Lai, A. F. Rausch, W. J. Finkenzeller, N. Zhu and
H. Yersin, Chem. Eur. J., 2010, 16, 233; (b) T. Akitsu and T. Itoh, Polyhedron, 2010,
29, 477; (c) S. Yang, H. Kou, H. Wang, K. Cheng and J. Wang, New J. Chem., 2010,
34, 313; (d) T. M. Ross, S. M. Neville, D. S. Innes, D. R. Turner, B. Moubaraki and K.
14

Page 15 of 17
New Journal of Chemistry
View Article Online
S. Murray, Dalton Trans., 2010, 39, 149; (e) B. Weber, Coord. Chem. Rev., 2009, 253,
DOI: 10.1039/C5NJ02681D
2432; (f) S. J. Wezenberg and A. W. Kleij, Angew. Chem. Int. Ed., 2008, 47, 2354.
18 (a) S. Righetto and S. Di Bella, Dalton Trans., 2014, 43, 2168; (b) I. P. Oliveri, G.
Malandrino and S. Di Bella, Dalton Trans., 2014, 43, 10208; (c) I. P. Oliveri, G.
Malandrino and S. Di Bella, Inorg. Chem., 2014, 53, 9771.
19 Traditionally, the term salen refers to ligands prepared via the condensation of
salicylaldehyde and ethylenediamine, but has come to include dianionic N2O2 ligands
with varying carbonyl-containing substituents and diamine backbones.
20 (a) R. Hernandez-Molina and A. Mederos, in Comprehensive Coordination Chemistry
II, Eds. J. A. McCleverty and T. J. Meyer, Elsevier Pergamon, Oxford, 2004, vol. 1, pp.
411-458; (b) S. Chattopadhyay, M. Sinha and S. Chaudhuri, Inorg. Chim. Acta, 2006,
359, 1367; (c) J.-P. Costes, Polyhedron, 1987, 6, 2169.
21 (a) M. Fuentealba, J.-R. Hamon, D. Carrillo and C. Manzur, New J. Chem., 2007, 31,
1815; (b) A. Trujillo, S. Sinbandhit, L. Toupet, D. Carrillo, C. Manzur and J.-R.
Hamon, J. Inorg. Organomet. Polym. Mater., 2008, 18, 81; (c) A. Trujillo, M.
Fuentealba, D. Carrillo, C. Manzur and J.-R. Hamon, J. Organomet. Chem., 2009, 694,
1435; (d) A. Trujillo, F. Justaud, L. Toupet, O. Cador, D. Carrillo, C. Manzur and J.-R.
Hamon, New J. Chem., 2011, 35, 2027.
22 (a) A. Trujillo, M. Fuentealba, D. Carrillo, C. Manzur, I. Ledoux-Rak, J.-R. Hamon and
J.-Y. Saillard, Inorg. Chem., 2010, 49, 2750; (b) S. Celedón, V. Dorcet, T. Roisnel, A.
Singh, I. Ledoux-Rak, J.-R. Hamon, D. Carrillo and C. Manzur, Eur. J. Inorg. Chem.,
2014, 4984; (c) J. Cisterna, V. Dorcet, C. Manzur, I. Ledoux-Rak, J.-R. Hamon and D.
Carrillo, Inorg. Chim. Acta, 2015, 430, 82.
23 N. Novoa, J. P. Soto, R. Henríquez, C. Manzur, D. Carrillo and J.-R. Hamon, J. Inorg.
Organomet. Polym. Mater., 2013, 23, 1247.
24 M. Meldal, C. W. Tornoe, Chem. Rev., 2008, 108, 2952.
25 (a) L. Liang, J. Ruiz and D. Astruc, Adv. Syn. Catal., 2011, 353, 3434; (b) N. Candelon,
D. Lastécouères, A. K. Diallo, J. Ruiz, D. Astruc and J.-M. Vincent, Chem. Commun.,
2008, 741.
26 M. Fuentealba, A. Trujillo, J.-R. Hamon, D. Carrillo and C. Manzur, J. Mol. Struct.
2008, 881, 76.
27 C. Deraedt, N. Pinaud and D. Astruc, J. Am. Chem. Soc., 2014, 136, 12092.
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DOI: 10.1039/C5NJ02681D
Table of contents entry
New organometallic Schiff-base copper complexes
as efficient “click” reaction precatalysts
Xiang Liu, Néstor Novoa, Carolina Manzur, David Carrillo and Jean-René Hamon
In the presence of sodium ascorbate, the recyclable CuAAC precatalysts displayed
high activity allowing the synthesis of a wide variety of 1,4-disubstituted 1,2,3-triazoles in
high isolated yields.