Cu0NPs@CMC: an efficient recoverable nanocatalyst for decarboxylative A3 and A3 couplings under neat condition

Article abstract of DOI:10.1007/s11164-019-03795-3

Abstract: Copper nanoparticles assembled on carboxymethylcellulose (Cu⁰NPs@CMC) were successfully synthesized and well characterized by FT-IR, SEM, EDS, TEM, XPS, and ICP-AES. The new prepared nanocatalyst was applied effectively as a heterogen

Full text of DOI:10.1007/s11164-019-03795-3

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03795-3
Cu0NPs@CMC: an efcient recoverable nanocatalyst
for decarboxylative A3 and A3 couplings under neat
condition
Xiaoping Liu1 · Xiaobin Tan1 · Yuemin Zhou1 · Yiqun Li1,2 · Zhubao Zhang1
Received: 11 December 2018 / Accepted: 2 March 2019
© Springer Nature B.V. 2019
Abstract
Copper nanoparticles assembled on carboxymethylcellulose (Cu0NPs@CMC) were
successfully synthesized and well characterized by FT-IR, SEM, EDS, TEM, XPS,
and ICP-AES. The new prepared nanocatalyst was applied efectively as a hetero-
geneous catalyst for the synthesis of propargylamines via decarboxylatived A3 and
classic A3 reaction under solvent-free condition. A broad spectrum of diversely pol-
ysubstituted propargylamines could be obtained in moderate to excellent yields. The
present method showed several merits such as easy work-up, short reaction time,
additive-free characteristic, solvent-free condition, functional group tolerance, usage
of recyclable green and sustainable nanocatalyst.
Graphical abstract
Keywords Carboxymethylcellulose · Copper nanoparticles · Decarboxylative A3
reaction · A3 reaction · Solvent-free condition
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-03795-3) contains supplementary material, which is available to authorized users.
*
Zhubao Zhang
drubao@163.com
Extended author information available on the last page of the article
Vol.:(0123456789)
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X. Liu et al.
Introduction
Propargylamines are one of the most widely used versatile synthetic building
blocks for the construction of various biologically active, nitrogen-containing
heterocyclic compounds and a key intermediate for the synthesis of complicated
natural products and value-added chemicals [1–4]. They are also structural frag-
ments presenting in natural products and potential therapeutic drug molecules
[5–7]. Because of their unique biological and pharmaceutical properties, great
efort has been made to synthesize these compounds. Conventionally, propargy-
lamines are synthesized by nucleophilic addition of lithium acetylides, Grignard
reagents, and organozinc reagents to imines or their derivatives [8–10]. However,
in most cases, these methods often require stoichiometric amounts of organo-
metallic reagents under hash reaction conditions. An efcient alternative cou-
pling of an aldehyde, an alkyne, and an amine (referred as A3 coupling) in the
presence of homogeneous or heterogeneous transition metal catalysts has been
developed [11–13]. These catalysts include homogeneous transition metal salts
and complexes such as AgI [14–16], AuI [17] and AuIII [18, 19], FeIII [20, 21],
ZnII [22–24], and RuIII/CuI bimetallic system [25], as well as heterogeneous cata-
lysts such as Fe3O4@SiO2 [26], Ag(I)-functionalized MOF [27], Ag(I)-exchanged
K10 montmorillonite clay [28], AuNPs-Fe3O4-rGO [29], and core–shell Au@
MOF-5 [30]. Recently, many A3 coupling reactions have been focused on using
copper as a catalyst because copper is an abundant material and copper catalyst
precursors are highly reactive, cheap, and easily available. Along this line, difer-
ent homogeneous copper catalysts [31–35] and heterogeneous catalysts immobi-
lized on diferent carriers [36–39] have been reported for A3 coupling reactions.
Recently, great attention has been focused on the catalytic performance of transi-
tion metal NPs due to their high surface area-to-volume ratio. These nanocata-
lysts are considered to bridge the gap between homogeneous and heterogeneous
catalysis. Thus, a number of CuNP catalysts have been employed for A3 cou-
pling to synthesize propargylamine and is also well documented in the literature
[40–44]. With the growing environmental concern, solvent-free organic synthesis
has recently gained momentum from academia and industry. Therefore, rational
design of solvent-free reactions is an important aim in the current research for the
synthesis of propargylamines. Few reports using Cu catalysts have been reported
for the synthesis of propargylamines under solvent-free conditions [40].
Similarly, decarboxylative A3-coupling is a practical transformation, wherein
alkynyl carboxylicacids act as a stable surrogate to traditional organometallic
reagents formed in situ decarboxylation. Eforts employing homogeneous cata-
lysts such as CuI [45–47], CuBr [48, 49], CuCl2/CuI [50], CuI/Cu(OTf)2 [51],
and heterogeneous catalysts including CuO/Fe2O3NPs [52], Cu(II)–hydromagne-
−
site [53], and silica-embedded CuO nanospheres(Cu@SiO2 NS) [54] have been
successfully done in decarboxylative A3 coupling reactions. Among the decar-
boxylative coupling reactions, copper-catalyzed methods are well studied and
provide an attractive approach for the fabrication of propargylamines. Although
homogeneous catalysts have many advantages including high reactivity, excellent
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
selectivity, and good yields, some drawbacks like tedious separation and reusabil-
ity are encountered. In order to achieve recyclability of the catalysts, heterogene-
ous catalysts, especially supported nanocatalysts, have attracted much more atten-
tions recently. However, Cu0NPs catalyzed decarboxylative strategies are rarely
used in the decarboxylative A3 coupling reaction. Therefore, seeking new highly
active and stable heterogeneous nanocatalyst is still demanded.
In recent years, using ecofriendly and biodegradable materials as supports for sta-
bilization of metal nanoparticles has attracted great attention. Because of its wide-
spread natural abundance and environmentally benign sustainable resource, sodium
carboxymethylcellulose (Na@CMC) has become a green renewable alternative of
currently used synthetic templates for metal nanoparticle synthesis. It is one of the
most important cellulose derivatives with complete biodegradability, low cost and
renewability, and can be regenerated from CO2 and H2O via photosynthesisin the
chlorophyll-containing cells. Na@CMC bearing carboxylic groups (–COO−Na+)
and hydroxyl groups (–OH) on its cellulosic framework possess the potential to act
as an excellent metallic cation exchange agent and ligand, which makes it a power-
ful support to immobilize metal nanoparticles via the interaction of ionic bonds and
coordinated bonds between the counter metal cation species and polymer support
[55]. More recently, we reported green ion exchange approach for the one-step prep-
aration of Pd0NPs@CMC [56], CuII-CMC@Fe3O4 [57], assembled Pd0@Ce(OH)4/
CMC [58], Pd0@CMC/Fe3O4 [59], and CMC-CeIV [60] to construct C–C bond and
heterocycles. To the best of our knowledge there is no report on the decarboxyla-
tive A3 and A3 couplings using Cu0NPs@CMC nanocatalyst. With this background
and in continuation of our interest towards green and sustainable nanocatalysis, we
herein report the catalytic potential of Cu0NPs@CMC for decarboxylative A3 and
A3 couplings under solvent-free conditions for the frst time (Scheme 1).
Scheme 1 Overview of Cu0NPs@CMC-catalyzed decarboxylative A3 (A and B) and classical A3 cou-
pling (C)
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X. Liu et al.
Experimental
Chemicals and characterization
Fourier transform infrared spectra (FT-IR) were recorded on a Nicolet 6700
FT-IR spectrometer using KBr disc. 1H and 13C NMR spectra were recorded on a
1
Bruker-300 Avance (300 MHz) instrument. The chemical shifts of H NMR and
13C NMR are reported in ppm relative to TMS (0.00 ppm) and CD3Cl (77.0 ppm),
respectively. Scanning electron microscopy (SEM) with energy-dispersive X-ray
(EDX) were performed with a Zeiss Merlin instrument. Transmission electron
microscopy (TEM) was conducted with a JEM 2100F instrument. Transmission
electron micrography (TEM) images were taken with a Philips Tecnai instrument.
X-ray photoelectron spectroscopy (XPS) was performed on a Kratos Axis Ultra
DLD spectrometer using Al X‐ray source. The elemental copper content of the
catalyst was determined by inductively coupled plasma-atomic emission spec-
trometry (ICP-AES) using Perkin Elmer Optima 2000 DV instrument. Thin-layer
chromatography (TLC) analysis was performed on silica gel G/GF 254 plates.
The products were purifed by preparative TLC.
All solvents and chemicals were obtained from commercial sources and were
used without prior purifcation.
Preparation of the hybrid Cu0NPs@CMC nanocatalyst
The general procedure used for the preparation of the hybrid CuII@CMC was
described by our group previously [38]. The hydrazine hydrate solution (80%,
12 mL) was added by drops into the CuII@CMC (3 g) suspension for 15 min with
vigorous stirring at room temperature. A black solid formed, which visually indi-
cates the formation of Cu0NPs@CMC. Then the mixture was allowed to further
react for 12 h. After that, the solid was fltered, washed several times with deion-
ized water, successively with acetone, and fnally dried under vacuum resulting
Cu0NPs@CMC nanocatalyst. The Cu content was determined to be 2.34 mmol/g
by ICP-AES.
General procedure for the decarboxylative A3 coupling from 3‑phenylpropiolic
acid
Aryl adehyde 1 (1 mmol), secondary amine 2 (1.5 mmol) and 3-phenylpropiolic
acid 3 (1.5 mmol) were added into a 10-mL glass tube. The reaction vessel was
sealed with a Tefon septum and stirred in preheated oil bath for 12 h at 120 °C.
Upon completion of the reaction, the resulting reaction mixture was loaded on a
preparative TLC and eluted with EtOAc/heptanes (1/6, v/v) to aford the desired
product 6.
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
General procedure for A3 coupling and decarboxylative A3 coupling
of 2‑oxo‑2‑phenylacetic
The experimental procedures were followed according to that mentioned above.
A3 coupling: aryl aldehyde (1 mmol), amine (1.2 mmol), and alkyne (1.5 mmol)
for 5 h at 100 °C.
Decarboxylative A3 coupling: 2-oxo-2-phenylacetic acid (1 mmol), amine
(1.2 mmol), and phenylacetlene (1.5 mmol) for 15 h at 110 °C.
Results and discussion
Preparation and characterization of Cu0NPs@CMC
The Cu0NPs@CMC nanocatalyst consisting of Cu0NPs and CMC matrix was pre-
pared in two simple steps. In the frst step, the CuII@CMC was prepared via metath-
esis of Na@CMC with CuSO4 following our previous work based on the property
of Na@CMC being capable of exchanging with CuII [38]. In the second step, the
as-prepared CuII@CMC was treated with hydrazine hydrate solution thoroughly for
12 h to aford the corresponding Cu0NPs based catalyst in which Cu0NPs assembled
and nucleated on the CMC supports. The schematic illustration of the formation of
the CuII@CMC and Cu0NPs@CMC are shown in Scheme 2.
Then, the as-prepared Cu0NPs@CMC nanocatalyst was well characterized by
FT-IR, SEM, EDX, TEM, and XPS techniques. The analytical data of the prepared
copper nanoparticles were in good agreement with those reported.
Scheme 2 The procedure for the preparation of CuII@CMC and Cu0NPs@CMC
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X. Liu et al.
Figure 1 shows the FT-IR spectra for Na@CMC (curve a), CuII@CMC (curve
b), and Cu0NPs@CMC (curve c). In curve (a), a strong and broad absorption band
at 3428 cm−1 is related to the –OH group stretching vibrations. The characteristic
peaks at 1602 cm−1 and 1423 cm−1 are assigned to the carboxylate (–COO−Na+)
asymmetric and symmetric stretching vibration. The band at 1059 cm−1 is assigned
to the –CH2–O–CH2– ether bonds stretches. These absorb peaks are shifted to
3439 cm−1, 1626 cm−1, 1419 cm−1, 1062 cm−1 (curve b) and 3433 cm−1, 1595 cm−1,
1418 cm−1, 1061 cm−1 (curve c) correspondingly. These shifts imply coordina-
tion between Cu2+, Cu0 with –COO−, –OH, and –CH2–O–CH2– groups. Notably,
the wavenumber separation Δ between the asymmetric ν (–COO−) and symmet-
ric ν (–COO−) stretches can be used to identify the type of the interactions. Char-
acteristically, the Δ value lies on the scope of 200–320 cm−1 for monodentate,
140–190 cm−1 for bidentate bridging, and <110 cm−1 for chelating bidentate [56,
61, 62]. As can be seen from curve (b) and curve (c), the Δ values of 207 cm−1
and 177 cm−1 were observed, and thus, it is clear that the mode of the carboxylate
binding in CuII@CMC and Cu0NPs@CMC are correlated to monodentate chelating
and bidentate chelating mode correspondingly. Evidently, CMC can interact with
Cu2+, Cu0 via the –COO−, –OH, and –CH2–O–CH2– functional groups, the pos-
sible chemical structure of CuII@CMC and Cu0NPs@CMC may be suggested and
depicted in Scheme 2.
The morphology of the freshly prepared Cu0NPs@CMC was characterized by SEM.
SEM images in Fig. 2 are presented at diferent magnifcations. The SEM images
(Fig. 2a, b) clearly show that all these Cu0NPs@CMC catalysts have similar micropar-
ticles microstructures in varying sizes and shapes have rough surface, which facilitates
the better mass transfer and enlarges its contact area and thus increases catalytic activ-
ity. The TEM images of the Cu0NPs@CMC catalyst (Fig. 2c, d) shows the presence of
Fig. 1 FT-IR spectra of Na@CMC (a), CuII@CMC (b), and Cu0NPs@CMC (c)
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Fig. 2 SEM images of Cu0NPs@CMC (the bar scale is 100 μm and 20 μm at a and b) and TEM images
of Cu0NPs@CMC (the bar scale is 50 nm and 20 nm at c and d)
extremely uniform CuNPs with an average size of 2–10 nm, well dispersed throughout
the polymer matrix, and almost no aggregation of CuNPs is found.
The existence of metallic elements in the catalyst was also confrmed by energy-
dispersive X-ray spectroscopy (EDS) coupled with the SEM, which showed the metal-
lic elements Cu, and non-metallic elements C and O in Fig. 3. Obviously, the presence
of these elements confrmed that Cu is successfully immobilized on the CMC matrix.
We studied the oxidation state of the Cu of the hybrid using X-ray photoelectron
spectroscopy (XPS). As shown in Fig. 4, two intense doublet peaks corresponding
to Cu 2p1/2 and Cu 2p3/2 at 935.02, 955.00 eV related to CuII (Fig. 4a), and peaks at
932.61, 952.65 eV, which is typically attributed to Cu0 (Fig. 4b), respectively [63, 64].
Cu0NPs@CMC as a heterogeneous catalyst for one‑pot three‑component
decarboxylative couplings
To evaluate the optimized condition, a model reaction of 4-methylbenzaldehyde 1a,
morpholine 2a, and phenylpropiolic acid 3 was explored using catalytic amount of
the prepared Cu0NPs@CMC catalyst in various media at specifc temperature. The
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X. Liu et al.
Fig. 3 EDS data for the fresh catalyst
Fig. 4 Cu 2p XPS spectra of CuII@CMC (a) and Cu0NPs@CMC (b)
results are summarized in Table 1. At the beginning, it is important to understand
the role of Cu0 NPs in the reaction. The most likely possibility is that CuI and CuII
salts, as well as supported CuII and Cu0 are truly active species to catalyze the reac-
tion. To prove this assumption, diferent copper salts such as CuSO4, Cu(OAc)2,
CuCl, as well as supported CuII@CMC, Cu0NPs@CMC, and even Na@CMC were
investigated in the model reactions in toluene (Table 1, Entries 1–6). Among them,
Cu0NPs@CMC gave the highest yield of 54% (Table 1, entry 6). When the reactions
were performed in the presence of Na@CMC in toluene, a trace amount of product
was formed (Table 1, entry 4). These results confrmed the catalytic role of the cop-
per nanoparticles in the reaction. Subsequently, a variety of solvents were screened,
a 54% yield of the desired product 6a was observed in toluene using Cu0NPs@CMC
as catalyst (Table 1, entry 6). THF, CH3CN, DMSO, EtOH, and H2O provide lower
yields (Table 1, entries 7–11). Remarkably, the highest yield of 6a was obtained
when the reaction was carried out in neat condition (Table 1, entry 13). Then, we
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Table 1 Screening of the optimal parameters
Entry
Catalyst (mol%)
Solvent
Temp (°C)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
CuSO4 (20)
Cu(OAC)2 (20)
CuCl (20)
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
THF
CH3CN
DMSO
EtOH
H2O
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
100
100
100
100
100
100
100
100
100
100
100
100
100
100
110
120
120
120
120
120
120
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
15
12
9
31
40
47
Trace
21
54
21
22
27
30
Trace
42
53
60
63
77
53
78
Na@CMC (7.5)
CuII@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
CuII@CMC (7.5)
9
10
11
12
13
14b
15b
16b
17b
18b
19b
20b
21b
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (7.5)
Cu0NPs@CMC (5)
Cu0NPs@CMC (10)
Cu0NPs@CMC(7.5)
Cu0NPs@CMC(7.5)
Cu0NPs@CMC (7.5)
78
85
77
Neat
Neat
Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), 3a (1.2 mmol), solvent (2 ml), reaction was monitored
by TLC
aDetermined by 1H NMR analysis using CH2Br2 as the internal standard
bThe molar number of 1a, 2a, and 3a is 1 mmol, 1.5 mmol, and 1.5 mmol
explored the efect of the molar ratio of the substrates on the model reaction. To
our delight, the product yield increased from 53 to 60% by changing the substrates
molar ratio of 1a, 2a, and 3 from 1/1.2/1.2 to 1/1.5/1.5 (Table 1, entries 13 and 14).
Next, the efect of reaction temperature and time were examined on the model reac-
tion. As shown from Table 1, increasing the reaction temperature to 110 °C and
120 °C, the product yields increased from 63 to 77%, respectively (Table 1, entries
15 and 16). At the same temperature, the best suitable time was found to be 12 h.
Finally, the efect of amount of catalyst ranging from 5 to 10 mol% of Cu on the
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X. Liu et al.
Table 2 Cu0NPs@CMC-catalyzed decarboxylative A3 coupling of phenylpropiolic acid, aldehydes, and
amines
Entry
R1CHO
R2R3NH
Product
Yielda
(%)
1
2
6
1
85
6a
2
3
81
82
6b
6c
6d
4
8
86
80
6e
9
75
6f
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Table 2 (continued)
Entry
R1CHO
R2R3NH
Product
Yielda
(%)
1
2
6
9
84
80
6g
6h
6i
10
11
12
81
83
6j
6k
6l
13
12
84
81
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X. Liu et al.
Table 2 (continued)
Entry
R1CHO
R2R3NH
Product
Yielda
(%)
1
2
6
13
75
6m
6n
14
15
72
80
6o
6p
16
17
90
85
6q
18
trace
trace
6r
19
6s
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Table 2 (continued)
Reaction conditions: 1 (1 mmol), 2 (1.5 mmol), 3 (1.5 mmol), 7.5 mol% Cu0NPs@CMC, 120 °C, 12 h
under neat conditions
aIsolated yield
model was tested. Lowering the amount of the Cu to 5 mol% still allowed the reac-
tion to proceed smoothly, decreasing the desired product 6a in 53% yield respec-
tively (Table 1, entry 17). However, a further increase of the catalyst to 10 mol%
resulted in no improvement in yield at all (Table 1, entry 18).
With the optimized reaction conditions in hand, the scope of this decarboxylative
coupling reaction of various aryl aldehydes 1, amine 2, and phenylpropiolic acid 3
was explored, and the results are summarized in Table 2. In most cases, a range of
aromatic aldehydes bearing electron-withdrawing group or electron-donating sub-
stituent aforded the corresponding products in moderate to excellent yields. These
substituents have not apparent impact on the product yields. We next looked to
expand the scope of aldehydes, and were delighted to fnd that aliphatic aldehydes
could perform well. It is notable that the primary amines give no desired products.
Encouraged by these results of this decarboxylative coupling of aryl aldehyde,
secondary amine, and phenylpropiolic acid, we envisaged this catalyst is also prac-
tical in traditional A3 couplings under the similar optimal condition. Therefore,
we further deployed the Cu0NPs@CMC catalyst in A3 coupling of aryl aldehyde
1, secondary amines 2, and phenylacetylene 4a. The results listed in Table 3. As
expected, all substrates aford the desired product in 77–92%. Generally, the tradi-
tional A3 reaction is commonly catalyzed by CuI catalysts, the results demonstrated
that Cu0NPs@CMC nanocatalyst is also an efcient catalyst for this transformation.
The decarboxylative coupling of glyoxylic acid has been widely used as a valu-
able synthetic strategy for the synthesis of various molecules with a high density of
functional groups. To achieve a more universal approach for the synthesis of pro-
pargylamines, we further expanded our method to a variety of decarboxylative A3
coupling reactions of glyoxylic acid 5, phenylactylenes 4, and secondary amines 2
using Cu0NPs@CMC catalyst under similar conditions. The results listed in Table 4.
Surprisingly, the Cu0NPs@CMC catalyst was also efective as using glyoxylic acid
as an aldehyde source, which represents an elegant alternative for A3 coupling.
Reusability of the catalyst
Recyclability of heterogeneous catalysts is important factor from the economical and
sustainable chemistry stand points. Along this line we have studied recyclability of the
catalyst for the model reaction of 4-methylbenzaldehyde 1a, morpholine 2a, and phenyl-
propiolic acid 3 under optimized reaction conditions. After completion of the reaction,
the Cu0NPs@CMC catalyst was recovered by simple fltration and reused in subsequent
run. The results shown in Fig. 5 indicate that the Cu0NPs@CMC catalyst can be used for
four consecutive cycles successfully with small drops in catalytic activity. The drop of
catalytic activity seemed to be the loss of catalyst during the fltration process.
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X. Liu et al.
Table 3 The traditional A3 couplings catalyzed by Cu0NPs@CMC nanocatalyst
R1CHO
R2R3NH
Product
Yield a
(%)
Entry
1
2
6
88
1
6a
2
3
80
86
6b
6c
4
5
78
77
6e
6f
6
89
6g
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Table 3 (continued)
R1CHO
R2R3NH
Product
Yield a
(%)
Entry
1
2
6
7
8
9
84
92
90
6i
6j
6l
10
11
trace
85
6d
6p
Reaction conditions: 1 (1 mmol), 2 (1.2 mmol), 4a (1.5 mmol), 7.5 mol% Cu0NPs@CMC, 100 °C, 5 h
under neat conditions
aIsolated yield
A comparison of the efciency and catalytic activity of the Cu0NPs@CMC cata-
lyst with several previous documented methods is presented in Table 5. It turned
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X. Liu et al.
Table 4 Cu0NPs@CMC-catalyzed decarboxylative A3 coupling of glyoxylic acid, phenylactylenes and
amines
Entry
R2R3NH
phenylactylene
Product
Yield a
(%)
2
4
6
1
53
60
6e
6v
2
3
55
61
6w
6x
4
5
trace
70
6y
6z
6
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Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
Table 4 (continued)
Entry
R2R3NH
phenylactylene
Product
Yield a
(%)
2
4
6
7
72
65
6aa'
8
6ab'
Reaction conditions: Reaction conditions: 5 (1 mmol), 2 (1.2 mmol),4 (1.5 mmol), 7.5 mol% Cu0NPs@
CMC, 110 °C, 15 h under neat conditions
aIsolated yield
Fig. 5 Recyclability of Cu0NPs@CMC catalyst for the synthesis of 6a
out that Cu0NPs@CMC catalyst gave comparable results than the other catalysts in
terms of yield. In addition to this, stability, non-toxicity, and ease of separation and
recycling are some obvious benefts with respect to the other methods.
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X. Liu et al.
Table 5 A comparison on the efciency of Cu0NPs@CMC with other reported methods in the synthesis
of propargylamine via decarboxylative A3 coupling
Entry
Catalyst (mol%)
Solvent
Temp (°C)
Yielda (%)
Ref
1
2
3
4
Cu0NPs@CMC (7.5)
CuI (10)
CuO/Fe2O3 (5)
Neat
CH3CN
Neat
100
70
110
80
92
92
83
This work
[47]
[52]
Chit@CuI(0.04)
Neat
140
[39]
Conclusion
In conclusion, we have successfully developed a novel Cu0NPs@CMC nanocatalyst
for the decarboxylative three-component coupling of an aryl aldehyde, a secondary
amine, and a phenylpropiolic acid, providing an efcient approach for the synthesis
of polysubstituted propargylamines. Interestingly, the catalyst was also applicable to
traditional A3 couplings as well as the decarboxylative three-component coupling of
a glyoxylic acid, an amine, and an alkyne. Our method employs commercially avail-
able reagents and has signifcant advantages over the most reported copper decar-
boxylative A3 couplings and A3 couplings which usually require the use of nitrogen
or phosphorus ligands, strong bases, and toxic solvents, in that it proceeds in neat
under mild reaction conditions and displays a broad substrate scope and high yields.
Therefore, this novel and efcient nanocatalyst can be regarded as a welcomed addi-
tional method for the existing catalysts generally applied to decarboxylative A3 and
traditional A3 coupling reactions.
Acknowledgements We are grateful to the National Science Foundation of China (No. 21372099) and
the Key Laboratory of Functional Molecular Engineering of Guangdong Province (2016kf06) for fnan-
cial support.
References
1. V.A. Peshkov, O.P. Pereshivko, A.A. Nechaev, A.A. Peshkov, E.V. Van der Eycken, Chem. Soc. Rev.
47, 3861 (2018)
2. K. Lauder, A. Toscani, N. Scalacci, D. Castagnolo, Chem. Rev. 117, 14091 (2017)
3. E. Vessally, L. Edjlali, A. Hosseinian, A. Bekhradnia, M.D. Esrafli, RSC Adv. 6, 49730 (2016)
4. C.E. Meyet, C.H. Larsen, J. Org. Chem. 79, 9835 (2014)
5. S. Arshadi, E. Vessally, L. Edjlali, R. Hosseinzadeh-Khanmiri, E. Ghorbani-Kalhor, Beilstein J.
Org. Chem. 13, 625 (2017)
6. B.A. Orit, T. Amit, M.B. Youdim, O. Weinreb, J. Neural Transm. 123, 125 (2016)
7. F.T. Zindo, J. Joubert, S.F. Malan, Future Med. Chem. 7, 609 (2015)
1 3

Cu0NPs@CMC: an efcient recoverable nanocatalyst for…
8. K.B. Aubrecht, M.D. Winemiller, D.B. Collum, J. Am. Chem. Soc. 122, 11084 (2000)
9. T. Murai, Y. Mutoh, Y. Ohta, M. Murakami, J. Am. Chem. Soc. 126, 5968 (2004)
10. L. Zani, C. Bolm, Chem. Commun. 41, 4263 (2006)
11. V.A. Peshkov, O.P. Pereshivko, E.V. Van der Eycken, Chem. Soc. Rev. 41, 3790 (2012)
12. W.J. Yoo, L. Zhao, C.J. Li, Aldrich. Acta 44, 43 (2011)
13. T.K. Saha, R. Das, ChemistrySelect 3, 12206 (2018)
14. A. Beillard, T.X. Metro, X. Bantreil, J. Martinez, F. Lamaty, Eur. J. Org. Chem. 31, 4642 (2017)
15. O. Prakash, H. Joshi, U. Kumar, A.K. Sharma, A.K. Singh, Dalton Trans. 44, 1962 (2015)
16. M.T. Chen, B. Landers, O. Navarro, Org. Biomol. Chem. 10, 2206 (2012)
17. C. Wei, C.J. Li, J. Am. Chem. Soc. 125, 9584 (2003)
18. G.A. Price, A.K. Brisdon, K.R. Flower, R.G. Pritchard, P. Quayle, Tetrahedron Lett. 55, 151 (2014)
19. V.K. Lo, Y. Liu, M.K. Wong, C.M. Che, Org. Lett. 8, 1529 (2006)
20. P. Li, Y. Zhang, L. Wang, Chem. Eur. J. 15, 2045 (2009)
21. W.W. Chen, R.V. Nguyen, C.J. Li, Tetrahedron Lett. 50, 2895 (2009)
22. S. Layek, B. Agrahari, S. Kumari, Anuradha, D.D. Pathak, Catal. Lett. 148, 2675 (2018)
23. M. Periasamy, P.O. Reddy, A. Edukondalu, M. Dalai, L.M. Alakonda, B. Udaykumar, Eur. J. Org.
Chem. 27, 6067 (2014)
24. E. Ramu, R. Varala, N. Sreelatha, S.R. Adapa, Tetrahedron Lett. 48, 7184 (2007)
25. E.R. Bonfeld, C.J. Li, Org. Biomol. Chem. 5, 435 (2007)
26. A. Maleki, Helv. Chim. Acta 97, 587 (2014)
27. M. Jeganathan, A. Dhakshinamoorthy, K. Pitchumani, ACS Sustain. Chem. Eng. 2, 781 (2014)
28. N. Hussain, M.R. Das, New J. Chem. 41, 12756 (2017)
29. L. He, Y. Liu, J. Liu, Y. Xiong, J. Zheng, Y. Liu, Z. Tang, Angew. Chem. Int. Ed. 52, 3741 (2013)
30. K.S. Sindhu, G. Anilkumar, RSC Adv. 4, 27867 (2014)
31. A. Grirrane, E. Alvarez, H. Garcia, A. Corma, Angew. Chem. Int. Ed. 53, 7253 (2014)
32. V.S. Kashid, M.S. Balakrishna, Catal. Commun. 103, 78 (2018)
33. Q. Zhang, J.X. Chen, W.X. Gao, J.C. Ding, H.Y. Wu, Appl. Organomet. Chem. 24, 809 (2010)
34. J.R. Cammarata, R. Rivera, F. Fuentes, Y. Otero, E. Ocando-Mavárez, A. Arce, J.M. Garcia, Tetra-
hedron Lett. 58, 4078 (2017)
35. Y. Ju, C.J. Li, R.S. Varma, QSAR Comb. Sci. 23, 891 (2004)
36. N. Bahri-Laleh, S. Sadjadi, Res. Chem. Intermed. 44, 6351 (2018)
37. J. Safaei-Ghomi, S.H. Nazemzadeh, H. Shahbazi-Alavi, Res. Chem. Intermed. 43, 7375 (2017)
38. X. Liu, B. Lin, Z. Zhang, H. Lei, Y. Li, RSC Adv. 6, 94399 (2016)
39. P. Kaur, B. Kumar, V. Kumar, R. Kumar, Tetrahedron Lett. 59, 1986 (2018)
40. M.J. Albaladejo, F. Alonso, Y. Moglie, M. Yus, Eur. J. Org. Chem. 16, 3093 (2012)
41. S. Frindy, A. El Kadib, M. Lahcini, A. Primo, H. García, Catal. Sci. Technol. 6, 4306 (2016)
42. M. Gholinejad, F. Saadati, S. Shaybanizadeh, B. Pullithadathil, RSC Adv. 6, 4983 (2016)
43. V.G. Ramu, A. Bordoloi, T.C. Nagaiah, W. Schuhmann, M. Muhler, C. Cabrele, Appl. Catal. A
431–432, 88 (2012)
44. M. Kidwai, V. Bansal, N.K. Mishra, A. Kumar, S. Mozumdar, Synlett 2007, 1581 (2007)
45. D.S. Ermolat’ev, H. Feng, G. Song, E.V. Van der Eycken, Eur. J. Org. Chem. 24, 5346 (2014)
46. J. Choi, J. Lim, F.M. Irudayanathan, H. Kim, J. Park, S.B. Yu, Y. Jang, G.C.E. Raja, K.C. Nam, J.
Kim, S. Lee, Asian J. Org. Chem. 5, 770 (2016)
47. J. Lim, K. Park, A. Byeun, S. Lee, Tetrahedron Lett. 55, 4875 (2014)
48. H. Feng, D.S. Ermolat’ev, G. Song, E.V. Van der Eycken, Org. Lett. 14, 1942 (2012)
49. H. Feng, D.S. Ermolat’ev, G. Song, E.V. Van der Eycken, J. Org. Chem. 76, 7608 (2011)
50. P. Zhao, H. Feng, H. Pan, Z. Sun, M. Tong, Org. Chem. Front. 4, 37 (2017)
51. T. Palani, K. Park, M.R. Kumar, H.M. Jung, S. Lee, Eur. J. Org. Chem. 26, 5038 (2012)
52. U. Gulati, U.C. Rajesh, D.S. Rawat, Tetrahedron Lett. 57, 4468 (2016)
53. U.C. Rajesh, U. Gulati, D.S. Rawat, ACS Sustain. Chem. Eng. 4, 3409 (2016)
54. U. Gulati, U.C. Rajesh, N. Bunekar, D.S. Rawat, ACS Sustain. Chem. Eng. 5, 4672 (2017)
55. M.N. Nadagouda, R.S. Varma, Biomacromol 8, 2762 (2007)
56. J. Xiao, Z. Lu, Y. Li, Ind. Eng. Chem. Res. 54, 790 (2015)
57. Z. Zhang, P. Song, J. Zhou, Y. Chen, B. Lin, Y. Li, Ind. Eng. Chem. Res. 55, 12301 (2016)
58. B. Lin, X. Liu, Z. Zhang, Y. Chen, X. Liao, Y. Li, J. Colloid Interf. Sci. 497, 134 (2017)
59. Z. Zhang, Y. Zhang, X. Liu, B. Shen, T. Zhang, Y. Li, Appl. Organomet. Chem. 31, e3912 (2017)
60. Y. Chen, T. Zhang, D. Wang, J. Zhou, Y. Zhang, Y. Li, J. Chem. Sci. 129, 421 (2017)
1 3

X. Liu et al.
61. F. He, D. Zhao, J. Liu, C.B. Roberts, Ind. Eng. Chem. Res. 46, 29 (2007)
62. J. Liu, F. He, E. Durham, D. Zhao, C.B. Roberts, Langmuir 24, 328 (2008)
63. K. Wang, L. Yang, W. Zhao, L. Cao, Z. Sun, F. Zhang, Green Chem. 19, 1949 (2017)
64. K.R. Reddy, N.S. Kumar, B. Sreedhar, M.L. Kantam, J. Mol. Catal. A Chem. 252, 136 (2006)
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Afliations
Xiaoping Liu1 · Xiaobin Tan1 · Yuemin Zhou1 · Yiqun Li1,2 · Zhubao Zhang1
1
Department of Chemistry, Jinan University, Guangzhou 510632, People’s Republic of China
2
Key Lab of Functional Molecular Engineering of Guangdong Province, South China University
of Technology, Guangzhou 510640, People’s Republic of China
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