Semiconductor-gold nanocomposite catalysts for the efficient three-component coupling of aldehyde, amine and alkyne in water

Article abstract of DOI:10.1002/adsc.200900518

An efficient heterogeneous lead sulfide-gold catalyst has been successfully developed for the synthesis of propargylic amines via a three-component coupling reaction of aldehyde, amine and alkyne in water. The process is simple and applicable to a diverse range of aromatic and aliphatic alde hydes, amines and alkynes. Furthermore, the catalyst is stable to air and water, and can be easily recovered and reused.

Full text of DOI:10.1002/adsc.200900518

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DOI: 10.1002/adsc.200900518
Semiconductor-Gold Nanocomposite Catalysts for the Efficient
Three-Component Coupling of Aldehyde, Amine and Alkyne in
Water
Leng Leng Chng,a Jun Yang,a Yifeng Wei,a and Jackie Y. Yinga,*
a
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669
Fax : (+65)-6478-9020; e-mail: jyying@ibn.a-star.edu.sg
Received: July 27, 2009; Revised: October 5, 2009; Published online: November 18, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900518.
Abstract: An efficient heterogeneous lead sulfide- hydes, amines and alkynes. Furthermore, the catalyst
gold catalyst has been successfully developed for the is stable to air and water, and can be easily recov-
synthesis of propargylic amines via a three-compo- ered and reused.
nent coupling reaction of aldehyde, amine and
alkyne in water. The process is simple and applicable Keywords: alkynes; gold; heterogeneous catalysis;
to a diverse range of aromatic and aliphatic alde- multicomponent reactions; nanocomposite catalysts
Introduction
ed in a separate step, and used in stoichiometric
amounts. Furthermore, these reagents were moisture-
Supported transition metal nanoparticles have attract- sensitive and incompatible with sensitive substrates. A
ed much attention in recent years due to their inter- more attractive and atom-efficient strategy to propar-
esting structure and high catalytic activities.[1] These gylic amine synthesis is through a one-pot, three-com-
heterogeneous catalysts offer the advantage of ease of ponent coupling reaction of aldehyde, amine and
À
separation from the media after completion of the re- alkyne via a C H activation catalyzed by a transition
action. They could be recovered and reused multiple metal. Catalytic multicomponent reactions are highly
times, making them attractive for applications in atom-efficient processes that would enable the imple-
green and sustainable chemistry. Nanoparticles of mentation of several transformations in a single ma-
many transition metals (e.g., Fe,[1b,2] Ru,[1b,3] Rh,[1b,3a,4] nipulation. These reactions also produce less side
Pd,[1b,5] Pt,[1b,6] Cu,[1b,7] Ag[1b,8] and Au[1b,9]) have been products as compared to classical stepwise methodol-
prepared and investigated in various catalytic reac- ogies. A number of homogeneous systems such as
tions. Au nanoparticles, in particular, have received iron salts,[16] copper salts[17a] and their complexes,[17b]
widespread attention as catalysts over the past silver salts,[18] gold salts[19a,b] and their complexes,[19c,d]
decade. Au was originally considered to be chemically iridium complexes,[20] Hg2Cl2,[21] and a Cu/Ru[22] bi-
inert and hence a poor catalyst. However, upon re- metallic system have been reported for the prepara-
duction of the particle size to the nanometer length tion of propargylic amines via this three-component
scale and upon dispersion on a suitable support, Au coupling protocol. Although these catalysts were
could become a highly active catalyst in many reac- highly effective, the homogeneous systems could not
tions including hydrogenation,[10] oxidation,[11] hydroa- be recovered for reuse.
mination[12] and coupling reactions.[13]
Heterogeneous catalysts, on the other hand, would
Propargylic amines are useful and versatile precur- be able to overcome this recyclability issue. Heteroge-
sors for the synthesis of various nitrogen-containing neous systems such as silica-immobilized and
biologically active compounds, such as natural prod- hydroxyACTHNUTRGNEUNG
apatite-supported Cu(I) complexes,[17b,c,23]
ucts and therapeutic drug molecules.[14] These com- CuO nanoparticles,[24] Ag(I) salts in ionic liquids,[25]
pounds could be synthesized by classical methods in- unsupported[13a] and supported gold nanoparticles on
volving the nucleophilic addition of an alkynyl-Li or CeO2 and ZrO2,[13b] and layered double hydroxide[13d]
Mg reagent to an imine or other similar C=N electro- have been reported to display high activities for the
philes.[15] The alkynyl-Li or Mg reagents were generat- three-component coupling reaction of aldehyde,
Adv. Synth. Catal. 2009, 351, 2887 – 2896
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amine and alkyne. In these reports, some of the heter-
All three semiconductor-Au nanocomposites
ogeneous catalysts have been recovered and reused showed an improved yield of the propargylamine
for a number of cycles with nearly consistent activity. product (Table 1, entries 3, 6 and 9) when a higher
Our group has recently developed new synthetic catalyst loading (0.5 mol% Au instead of 0.3 mol%
methodologies for the preparation of various transi- Au) and a longer reaction time (12 h instead of 6 h)
tion metal nanoparticles.[26] In this paper, we report were used. The PbS-Au nanocomposite was again the
our results on the efficient three-component coupling most active catalyst, producing the desired product in
reaction of aldehyde, amine and alkyne catalyzed by 85% isolated yield. Comparable yields of 86–87%
semiconductor-gold nanocomposites in water.
were obtained when even higher PbS-Au catalyst
loadings (0.8–1.0 mol% Au) were used (Table 1, en-
tries 10 and 11).
Results and Discussion
The differences in the catalytic activities of the
CdS-Au, CdSe-Au and PbS-Au nanocomposites could
Three different types of quantum dots (QDs) were not be due to the size of the Au nanoparticles as their
prepared as hybrids with Au nanoparticles via solu- diameters were similar (1–2 nm). The CdS-Au, CdSe-
tion methods. Figure 1 shows the transmission elec- Au and PbS-Au nanocomposites have different Au
tron microscopy (TEM) images of the CdS, CdSe and contents (25.4, 20.5 and 17.1 wt%, respectively). To
PbS QDs and their nanocomposites with Au. Since investigate the possibility of the Au content affecting
Au has a strong imaging contrast, it was easily identi- the catalytic activities of the nanocomposites, two ad-
fied in the semiconductor-Au nanocomposites. Au was ditional samples of the PbS-Au nanocomposites with
deposited at multiple sites on each QD. Energy dis- a lower and higher Au content of 10.0 and 45.0 wt%
persive X-ray (EDX) analysis (Supporting Informa- were synthesized. The Au nanoparticles on these two
tion, Figure S1) further confirmed that the heteroge- PbS-Au nanocomposites were similar in size (Sup-
neous structure was composed of the semiconductor porting Information, Figure S2). Both catalysts gave
and Au components. The Au loading on the QDs comparable yields of the propargylic amine product
ranged from 17.1 to 25.4 wt%, and the Au nanoparti- (Table 1, entries 12 and 13). Hence, the different Au
cles were 1–2 nm in diameter (Figure 1).
The three semiconductor-Au nanocomposites were not affect the catalytic activities of these materials.
tested for their catalytic activities in the three-compo- The surface chemistry of Au nanoparticles on the
contents in the semiconductor-Au nanocomposites did
nent coupling reaction of the model substrates benzal- three QDs was subjected to X-ray photoelectron
dehyde, piperidine and phenylacetylene in water at spectroscopy (XPS) analysis. As shown in Figure 2,
1008C (Table 1, entries 1–11). These initial screening for PbS-Au nanocomposite (with 17.1 wt% Au), the
experiments showed that with a catalyst loading of Au 4 f XPS spectra could be deconvoluted into two
0.3 mol% Au and a reaction time of 6 h at 1008C in pairs of doublets. The more intense doublet (at 84.1
air, PbS-Au nanocomposite provided the highest ac- and 87.8 eV) was attributed to Au(0). The second and
tivity, giving the desired propargylic amine product in weaker doublet (at 84.7 and 88.4 eV) could be as-
76% isolated yield (Table 1, entry 7). The CdS-Au signed to Au(I).[27,28] The PbS-Au nanocomposites
and CdSe-Au nanocomposites gave lower isolated with Au contents of 10.0 and 45.0 wt% also showed
yields of 43% and 53%, respectively (Table 1, en- similar XPS spectra with two pairs of doublets (Sup-
tries 1 and 4). Recycling of the catalysts was investi- porting Information, Figure S3). On the other hand,
gated by recovering the three semiconductor-Au the Au 4f XPS spectra of CdS-Au and CdSe-Au ex-
nanocomposites via centrifugation of the reaction hibited mainly one set of doublets associated with
mixture after the addition of a non-polar solvent (i.e., Au(0).
hexane), followed by three more hexane washes. The
In the three-component coupling reaction of alde-
aqueous layer containing the recovered catalyst was hyde, amine and alkyne catalyzed by gold salts, it was
then used in the subsequent run without further addi- proposed that a Au(I) species was the active catalys-
tion of the solvent (i.e., water). As shown in Table 1 t.[19a,b] For heterogeneous Au/CeO2 and Au/ZrO2 cata-
(entries 2, 5 and 8), the catalytic activities of the three lysts, AuACTHNUTRGNE(UNG III) was considered to be the most active
semiconductor-Au nanocomposites decreased upon catalytic species [as compared to Au(I) and
recycling. Note that the Au content in these nanocom- Au(0)].[13b] In our studies, although the exact nature
posite catalysts was quite high (17.1–25.4 wt%), and of the active Au species in the coupling reaction re-
since these experiments were performed on a 1 mmol mained unknown, the improved catalytic activity of
scale, the catalyst loading (0.3 mol% Au) for each ex- the PbS-Au nanocomposite as compared to the CdS-
periment was small (2.3–3.5 mg). Hence, some of the Au and CdSe-Au nanocomposites could nevertheless
materials might be lost in handling during the catalyst be attributed to the presence of the oxidized Au(I)
recovery process, leading to a decrease in the isolated species in the former. Au(0) species would be expect-
yield of the propargylic amine product.
ed to be less active than Au(I) as evidenced by the re-
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Figure 1. TEM images of (a) CdS, (b) CdSe and (c) PbS QDs, and (d) CdS-Au, (e) CdSe-Au and (f) PbS-Au nanocomposites.
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Table 1. Three-component coupling of benzaldehyde, piperidine and phenylacetylene catalyzed by semiconductor-Au nano-
composites.[a]
Entry
Catalyst
Au content [wt%]
Au [mol%]
Time [h]
Yield [%][b]
TON[c]
TOF[d]
1
CdS-Au
CdS-Au
CdS-Au
CdSe-Au
CdSe-Au
CdSe-Au
PbS-Au
PbS-Au
PbS-Au
PbS-Au
PbS-Au
PbS-Au
PbS-Au
25.4
25.4
25.4
20.5
20.5
20.5
17.1
17.1
17.1
17.1
17.1
10.0
45.0
0.3
0.3
0.5
0.3
0.3
0.5
0.3
0.3
0.5
0.8
1.0
0.5
0.5
6
6
12
6
6
12
6
6
12
12
12
12
12
43
33
77
53
29
62
76
61
85
87
86
87
87
143
110
154
177
97
124
253
203
170
109
86
24
18
13
30
16
10
42
34
14
9
2[e]
3
4
5[f]
6
7
8[g]
9
10
11
12
13
7
15
15
174
174
[a]
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol) and phenylacetylene (1.3 mmol), H2O (HPLC
grade, 1.0 mL), 1008C, 1000 rpm, under air.
Isolated and unoptimized yield based on benzaldehyde.
Number of moles of product per mole of catalyst.
Number of moles of product per mole of catalyst per hour.
The recycled CdS-Au catalyst from entry 1 was used in this experiment.
The recycled CdSe-Au catalyst from entry 4 was used in this experiment.
The recycled PbS-Au catalyst from entry 7 was used in this experiment.
[b]
[c]
[d]
[e]
[f]
[g]
duced activities of CdS-Au and CdSe-Au as compared supported by numerous examples of the activation of
to PbS-Au. The validity of this hypothesis was further alkynes by cationic gold species in the literature.[29]
The PbS-Au nanocomposite powder was not very
easy to handle due to its sticky nature from the use of
oleylamine surfactants in its synthesis. To facilitate its
handling and recycling, PbS-Au was supported on
carbon. Two samples of PbS-Au/C catalysts, both with
a low Au content of 4.4 wt% were prepared; they
were non-sticky black solids. One of the samples was
subjected to an acetic acid reflux (1208C for 3 h) to
remove the oleylamine surfactants from the Au sur-
face. There was no aggregation of the nanocomposite
particles in both samples as confirmed by their TEM
images (Figure 3).
The two PbS-Au/C catalysts were tested in the
model three-component coupling reaction of benzal-
dehyde, piperidine and phenylacetylene (Table 2, en-
tries 1 and 2). At a catalyst loading of 0.5 mol% Au in
the solvent water at 1008C, the two samples gave
comparable results after 12 h in air (85–88% isolated
yield). There were no significant differences between
the two PbS-Au/C samples, although the sample sub-
jected to an acetic acid reflux appeared to stick less
to the walls of the glass vial. The effect of solvent on
the standard three-component coupling reaction was
Figure 2. Au 4 f XPS spectra of (a) CdS-Au, (b) CdSe-Au
and (c) PbS-Au. Approximately 34% of Au in PbS-Au nano-
composite is in the Au(I) oxidation state.
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Figure 3. TEM images of PbS-Au/C powders (a) before and (b) after reflux in acetic acid at 1208C for 3 h.
Table 2. Three-component coupling of benzaldehyde, piperidine and phenylacetylene catalyzed by PbS-Au/C.[a]
Entry
Catalyst
Solvent[b]
Temperature [8C]
Yield [%][c]
TON[d]
TOF[e]
1
2
3
4
5
PbS-Au/C[f]
PbS-Au/C[g]
PbS-Au/C[g]
PbS-Au/C[g]
PbS-Au/C[g]
Water
Water
Acetonitrile
1,4-Dioxane
Methanol
100
100
100
100
80
85
88
8
10
26
170
176
16
20
52
14
15
1
2
4
[a]
Reaction conditions: PbS-Au/C catalyst (0.5 mol% Au), benzaldehyde (1.0 mmol), piperidine (1.2 mmol) and phenylacety-
lene (1.3 mmol), solvent (1.0 mL), 80–1008C, 12 h.
Reaction mixture was heated under air for the solvent water (1000 rpm), and under argon for the solvents acetonitrile,
1,4-dioxane and methanol (500 rpm).
Isolated and unoptimized yield based on benzaldehyde.
Number of moles of product per mole of catalyst.
Number of moles of product per mole of catalyst per hour.
This PbS-Au/C sample (with 17.1 wt% Au content in PbS-Au and 4.4 wt% Au content in PbS-Au/C) was not subjected to
an acetic acid reflux.
This PbS-Au/C sample (with 17.1 wt% Au content in PbS-Au and 4.4 wt% Au content in PbS-Au/C) was subjected to an
acetic acid reflux to remove the oleylamine surfactants.
[b]
[c]
[d]
[e]
[f]
[g]
further investigated using the sample subjected to an aqueous layer after centrifugation and separation
acetic acid reflux. As shown in Table 2 (entries 2–5), from the organic layer containing the product and the
water was found to be the best solvent for this reac- hexane washes. The recovered PbS-Au/C catalyst in
tion. The use of other polar solvents, for example, the aqueous layer was then used in the subsequent
acetonitrile, 1,4-dioxane and methanol, led to a signif- run without the addition of more water. This catalyst
icant decrease in the yield of the propargylamine could be recycled and reused three times (Table 3, up
product (8–26% isolated yields). The PbS-Au/C cata- to run #4) without a significant reduction in catalytic
lyst could be recovered and reused easily when the re- activity. The catalytic activity decreased by 1%, 10%
action was performed in water. For the recyclability and 18% after the first, second and third consecutive
study (Table 3), the catalyst was recovered in the cycles, respectively. The slight decrease in the isolated
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Table 3. Recycling of PbS-Au/C catalyst for the three-com-
ponent coupling reaction of benzaldehyde, piperidine and
phenylacetylene.[a]
tolerated in this coupling reaction as shown by the
equivalent yields (95%) attained when the methyl
group was at either the ortho or para position of the
benzaldehyde (Table 4, entries 3 and 4). However,
when the aryl aldehyde became too bulky (with two
methyl substituents at the ortho positions), there was
no coupling reaction (Table 4, entry 5). Benzalde-
hydes with electron-withdrawing substituents, such as
chloro or bromo at the para position, also coupled
smoothly with piperidine and phenylacetylene to give
Run #
1
2
3
4
5
Yield [%][b]
TON[c]
88
176
15
87
174
15
79
158
13
72
144
12
23
46
4
TOF[d]
[a]
Reaction conditions: PbS-Au/C catalyst (0.5 mol% Au),
benzaldehyde (1.0 mmol), piperidine (1.2 mmol) and
phenylacetylene (1.3 mmol), H2O (HPLC grade, 1.0 mL), their respective propargylic amine products in good
1008C, 12 h, 1000 rpm. This PbS-Au/C sample (with
17.1 wt% Au content in PbS-Au and 4.4 wt% Au content
in PbS-Au/C) was subjected to an acetic acid reflux prior
to catalytic studies. For the recycling experiments (runs
#2–5), the aqueous layer containing the recovered cata-
lyst was used in the subsequent run without the addition
of more water.
Isolated and unoptimized yield based on benzaldehyde.
Number of moles of product per mole of catalyst.
Number of moles of product per mole of catalyst per
hour.
yields (88–89%, Table 4, entries 7 and 8). However,
with stronger electron-withdrawing groups such as 4-
cyanobenzaldehyde and pentafluorobenzaldehyde
(Table 4, entries 9 and 10), no coupling reaction oc-
curred. Aliphatic aldehydes such as cyclohexanecar-
boxaldehyde (Table 4, entry 15) also showed high re-
activity with a good yield of 84%. However, with va-
[b]
[c]
[d]
leraldehyde,
octylaldehyde
and
pivalaldehyde
(Table 4, entries 11, 12 and 16), moderate to low
yields of 40%, 36% and 8% were achieved, respec-
tively. In the case of pivalaldehyde, the low yield
could be due to the lower boiling point of the alde-
hyde substrate (74–768C). As the coupling reaction
yield of the product was probably due to some loss of was performed at 1008C, most of the pivalaldehyde
the nanocomposite catalysts during the recovery pro- substrate could exist in the vapor phase, thus, there
cess.
would be less of the substrate for reaction. For valer-
The PbS-Au nanocomposite system offered certain aldehyde and octylaldehyde, the low yields could be
advantages over other reported heterogeneous gold attributed to the formation of an unwanted side-prod-
catalysts such as unsupported gold nanoparticles[13a] uct. These two aldehydes contained an a-hydrogen,
and supported gold nanoparticles on CeO2 and and in the presence of a catalytic amount of acid
ZrO2,[13b] and layered double hydroxide.[13d] Compared (present in the PbS-Au/C that was subjected to an
to the unsupported gold nanoparticles (TONꢀ10) acetic acid reflux), the aldol condensation could
and supported gold nanoparticles on layered double occur, resulting in the formation of the a,b-unsaturat-
hydroxide (TONꢀ33), the catalytic activity of the ed carbonyl side-product after a dehydration step.
PbS-Au nanocomposite (TONꢀ253) was higher. Al- This was further confirmed with two more coupling
though the supported gold nanoparticles on CeO2 and reactions with the octylaldehyde substrate. Using a
ZrO2 displayed higher catalytic activities (TONꢀ PbS-Au/C catalyst that was not subjected to an acetic
788), these catalysts showed a greater decrease in acid reflux (Table 4, entry 13), a higher isolated yield
their activity upon recycling (a decrease of 13%, 22% of 49% was achieved. In this case, although the cata-
and 25% after the first, second and third successive lyst was not subjected to an acetic acid reflux, the
cycles, respectively). Furthermore, the synthetic route carbon support contained some carboxylic acid func-
for the semiconductor-Au nanocomposites was simple tional groups that could act as a catalyst in the aldol
and flexible, and could be easily extended to the fab- condensation side reaction. When the coupling reac-
rication of other types of semiconductor-Au nanocom- tion was performed with a PbS-Au catalyst that was
posites. Thus, the catalytic activity of these nanocom- not supported on carbon (Table 4, entry 14), the yield
posites could be further modified by varying the improved to 79%, and very little of the unwanted
structure and composition of the nanocomposites.
a,b-unsaturated carbonyl by-product was detected in
To investigate the scope and generality of the the gas chromatography-mass spectrometry (GC-MS)
three-component coupling reaction with the PbS-Au/ analysis of the reaction mixture.
C catalyst, a variety of different aldehydes, amines
Heterocyclic aldehydes (Table 4, entries 17–22) gen-
and alkynes were examined (see Table 4). The alde- erally did not participate in the three-component cou-
hydes selected for this investigation included aliphatic pling reaction catalyzed by PbS-Au nanocomposite.
as well as aromatic compounds with different func- With the exception of 3-thiophenecarboxaldehyde
tional groups. Aryl aldehydes with electron-donating (Table 4, entry 22), which gave an isolated yield of
groups (Table 4, entries 2–4 and 6) gave good to ex- 68%, the heterocyclic aldehydes (2-pyridyl, 2-furfuryl,
cellent yields of 70–95%. Some steric hindrance was 3-furfuryl and 2-thiophenyl) displayed either no reac-
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Table 4. Coupling of aldehyde, amine and alkyne by PbS-Au/C in water.[a]
Entry
R1
R2R3NH
R4
Time [h]
Yield [%][b]
TON[c]
TOF[d]
1
2
3
4
5
6
7
8
Ph
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
12
12
12.5
12.5
12.5
12
13
12
12
12
88
91
95
95
0
70
88
89
0
176
182
190
190
0
140
176
178
0
15
15
15
15
0
12
14
15
0
1-Naphthyl
4-MeC6H4
2-MeC6H4
2,6-Me2C6H3
4-MeOC6H4
4-ClC6H4
4-BrC6H4
4-NCC6H4
C6F5
9
Piperidine
Piperidine
Ph
Ph
10
11
12
13[e]
14[f]
15[e]
16
17
18
19[e]
20[e]
21[f]
22[e]
23
24
25[e]
26[f]
27
28
29
30
31
32
33
34
35
36
37
0
0
0
Butyl
Heptyl
Heptyl
Heptyl
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Morpholine
R2 =R3 =PhCH2
R2 =R3 =PhCH2
R2 =R3 =PhCH2
R2 =R3 =Allyl
cis-2,6-Dimethylpiperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Piperidine
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
12
40
36
49
79
84
8
0
0
0
1
80
72
98
158
168
16
0
0
0
2
16
136
124
56
52
64
7
6
8
13
13
1
0
0
0
<1
1
11
10
4
4
5
10
0
12
14
14
14
8
2
2
14
0
12.5
12.5
12.5
12.5
12.5
12
Cyclohexyl
A
2-Pyridyl
2-Furfuryl
3- Furfuryl
2-Thiophenyl
2-Thiophenyl
3-Thiophenyl
12
12.5
12.5
12.5
12.5
13
12.5
12.5
12.5
12.5
12.5
12.5
13
12.5
12.5
13
12.5
12
8
68
62
28
26
32
63
0
77
90
90
86
50
10
13
92
0
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
126
0
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
Cyclohexyl
(CH3)3C
Butyl
3-Thiophenyl
2-Pyridyl
154
180
180
172
100
20
26
184
0
13
12
[a]
Reaction conditions: PbS-Au/C catalyst (0.5 mol% Au), aldehyde (1.0 mmol), amine (1.2 mmol) and alkyne (1.3 mmol),
H2O (HPLC grade, 1.0 mL), 1008C, 1000 rpm, unless otherwise specified. The PbS-Au/C sample (with 17.1 wt% Au con-
tent in PbS-Au and 4.4 wt% Au content in PbS-Au/C) was subjected to an acetic acid reflux prior to catalytic studies.
Isolated and unoptimized yield based on aldehyde.
Number of moles of product per mole of catalyst.
Number of moles of product per mole of catalyst per hour.
PbS-Au/C catalyst (0.5 mol% Au) was used. This PbS-Au/C sample (with 17.1 wt% Au content in PbS-Au and 4.4 wt%
Au content in PbS-Au/C) was not subjected to an acetic acid reflux prior to catalytic studies.
PbS-Au catalyst (0.5 mol% Au) was used. This PbS-Au sample (with 17.1 wt% Au content in PbS-Au) was not supported
on C.
[b]
[c]
[d]
[e]
[f]
tivity or very low yields of 1–8% (Table 4, entries 17– (Table 4, entries 23–28). With morpholine and diallyl-
21). amine (Table 4, entries 23 and 27), moderate yields of
Different types of secondary amines (cyclic and 62% and 63% were attained, respectively. Dibenzyl-
acyclic) were also studied with the PbS-Au catalyst amine, on the other hand, gave lower yields of 26–
AHCTUNGTRENNUNG
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Conclusions
In conclusion, we have successfully developed an effi-
cient heterogeneous PbS-Au catalyst for the synthesis
of propargylic amines via a three-component coupling
reaction of aldehyde, amine and alkyne in water. The
process is simple and applicable to a diverse range of
aromatic and aliphatic aldehydes, amines and alkynes.
Furthermore, the catalyst is stable to air and water,
and can be easily recovered and reused.
Experimental Section
Synthesis of QDs
Scheme 1. Tentative mechanism for the PbS-Au catalyzed
three-component coupling of aldehyde, amine and alkyne in
water.
CdS QDs were synthesized according to a published
method.[30] In a three-neck flask equipped with a condenser
and a magnetic stirring bar, 91.5 mg of CdCl2 and 20 mL of
oleylamine were heated to 908C with concurrent degassing
with nitrogen for 30 min. In another flask, 16 mg of elemen-
tal sulfur and 2 mL of oleylamine were heated to 908C with
concurrent degassing with nitrogen for 30 min. The sulfur
precursor solution was injected rapidly into the three-neck
flask containing the cadmium precursor at 1608C. The solu-
tion was left at the growth temperature of 1608C for 1 h,
and then cooled down to room temperature. The CdS nano-
crystals were purified by precipitation with ethanol, centri-
fuging, and re-dispersing in 20 mL of toluene.
32% (Table 4, entries 24–26). No coupling reaction
occurred with a sterically hindered cyclic secondary
amine, such as cis-2,6-dimethylpiperidine (Table 4,
entry 28).
A variety of different alkyl- and arylalkynes were
also tested (Table 4, entries 29–37) with the PbS-Au
nanocomposite. In general, the arylalkynes gave
better yields than the alkylalkynes. Arylalkynes with
electron-withdrawing substituents (F, Cl, Br) dis-
played higher reactivities with good yields of 86–90%
(Table 4, entries 30–32), while the electron-donating
substituents led to a slightly lower yield of 77% for 4-
methoxyphenylacetylene (Table 4, entry 29). For the
aliphatic alkynes (Table 4, entries 33–35), the reactivi-
ties correlated to the boiling points of the substrates.
A higher boiling substrate (130–1328C for cyclohexyl-
CdSe QDs were prepared by a previously reported solu-
tion method.[31] In a typical synthesis of the CdSe cores,
65 mg of CdO, 400 mg of octadecylphosphonic acid
(ODPA), and 25 mL of trioctylamine (TOA) were first
placed in a four-neck round-bottom flask under an argon
flow, and stirred at 3008C until CdO was completely dis-
solved. Se powder (200 mg) was dissolved in 2.5 mL of trioc-
tylphosphine (TOP). The TOPSe solution was then injected
into the Cd solution with rapid stirring, and kept at 3008C
for 2 min, followed by cooling down to room temperature.
25 mL of chloroform and 50 mL of methanol were added to
precipitate the CdSe nanocrystals. The product was then
washed twice with copious methanol, and re-dispersed in
20 mL of toluene.
ACHTUNGTRENNUNGacetylene) would result in a higher yield of the de-
sired propargylamine product (50% isolated yield)
(Table 4, entry 33). Alkyne substrates with lower boil-
ing points (33–358C for 3,3-dimethyl-1-butyne and
71–728C for 1-hexyne) gave lower yields of the cou-
pled products (10–13%) (Table 4, entries 34 and 35).
Heterocyclic alkyne, such as 3-ethynylthiophene, pro-
duced an excellent yield of 92% (Table 4, entry 36).
However, for 2-ethynylpyridine (Table 4, entry 37), no
coupling reaction was observed.
Synthesis of PbS QDs was achieved using an established
solution method with some modification.[32] In brief, 190 mg
of PbACTHNUTRGNE(NUG OAc)2, 20 mL of oleylamine, and 2 mL of oleic acid
were placed in a two-neck round-bottom flask, and the mix-
ture was heated to 1608C under an argon flow until all the
solids were completely dissolved. S powder (16 mg) was dis-
solved in 2 mL of oleylamine. The S solution in oleylamine
was then injected into the Pb(II) solution with rapid stirring,
and kept at 1608C for 5 min, followed by cooling down to
room temperature. 10 mL of toluene and 60 mL of methanol
were added to precipitate the PbS nanocrystals. The product
was then washed twice with copious methanol, and re-dis-
persed in 20 mL of toluene.
A tentative mechanism for the three-component
coupling reaction catalyzed by PbS-Au nanocompo-
sites was proposed (Scheme 1). The reaction mecha-
nism of the PbS-Au catalyst could proceed via the ac-
À
tivation of the Csp H bond of the terminal alkyne by
the PbS-Au nanocomposite. The alkynyl-Au inter-
mediate generated would then react with the immoni-
um ion generated in situ from the aldehyde and sec-
ondary amine to produce the corresponding propar-
gylic amine product, and regenerate the active PbS-
Au species for further reactions.
Transfer of AuACTHNUTRGNE(UNG III) into Toluene
The transfer of Au
ACHTUNGTRENN(UNG III) from water to toluene was accom-
plished using a common method developed by Brust et al.[33]
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Semiconductor-Gold Nanocomposite Catalysts for the Efficient Three-Component Coupling
FULL PAPERS
30 mL of 20 mM of aqueous HAuCl4 solution were mixed
with 60 mL of 50 mM of toluene solution of tetraoctylam-
monium bromide. The mixture was stirred for 1 min, and
settled for phase separation. The toluene layer containing
the AuACHTUNGTRENNUNG(III) species (10 mM) was separated, and used in the
synthesis of the semiconductor-Au nanocomposites.
Ho, W.-Y. Yu, C.-M. Che, Angew. Chem. 2004, 116,
3365; Angew. Chem. Int. Ed. 2004, 43, 3303; d) A.
Gual, M. R. Axet, K. Philippot, B. Chaudret, A. Deni-
court-Nowicki, A. Roucoux, S. Castillon, C. Claver,
Chem. Commun. 2008, 2759.
[4] a) J. A. Cabello, J. M. Campelo, A. Garcia, D. Luna,
J. M. Marinas, J. Mol. Catal. 1993, 78, 249; b) T.
Harada, S. Ikeda, Y. H. Ng, T. Sakata, H. Mori, T. Tori-
moto, M. Matsumura, Adv. Funct. Mater. 2008, 18,
2190; c) I. Nakamula, Y. Yamanoi, T. Yonezawa, T.
Imaoka, K. Yamamoto, H. Nishihara, Chem. Commun.
2008, 5716.
Synthesis of Semiconductor-Au Nanocomposites
The preparation of semiconductor-Au nanocomposites fol-
lowed a method established for the synthesis of PbS-Au
nanocomposites with slight modification.[34] Briefly, 12.5 mL
of AuACHTUNGTRENNUNG(III) in toluene were mixed with the QD organosol
[5] a) L. Djakovitch, K. Kçhler, J. G. de Vries, in: Nano-
particles and Catalysis, (Ed.: D. Astruc), Wiley, 2008,
Chap. 10, p 303; b) N. Erathodiyil, S. Ooi, A. M.
Seayad, Y. Han, S. S. Lee, J. Y. Ying, Chem. Eur. J.
2008, 14, 3118; c) K. Sawai, R. Tatumi, T. Nakahodo,
H. Fujihara, Angew. Chem. 2008, 120, 7023; Angew.
Chem. Int. Ed. 2008, 47, 6917; d) J. Durand, E. Teuma,
M. Gꢅmez, Eur. J. Inorg. Chem. 2008, 3577; e) C. P.
Mehnert, J. Y. Ying, Chem. Commun. 1997, 2215;
f) C. P. Mehnert, D. W. Weaver, J. Y. Ying, J. Am.
Chem. Soc. 1998, 120, 12289.
[6] a) M. Takasaki, Y. Motoyama, K. Higashi, S.-H. Yoon,
I. Mochida, H. Nagashima, Org. Lett. 2008, 10, 1601;
b) J. Chen, B. Lim, E. P. Lee, Y. Xia, Nano Today 2009,
4, 81; c) H. Song, R. M. Rioux, J. D. Hoefelmeyer, R.
Komor, K. Niesz, M. Grass, P. Yang, G. A. Somorjai, J.
Am. Chem. Soc. 2006, 128, 3027; d) J. M. Campelo,
A. F. Lee, R. Luque, D. Luna, J. M. Marinas, A. A.
Romero, Chem. Eur. J. 2008, 14, 5988; e) J. N. Kuhn, W.
Huang, C.-K. Tsung, Y. Zhang, G. A. Somorjai, J. Am.
Chem. Soc. 2008, 130, 14026.
[7] a) M. L. Kantum, V. S. Jaya, M. J. Lakshmi, B. R.
Reddy, B. M. Choudary, S. K. Bhargava, Catal.
Commun. 2007, 8, 1963; b) H. Sharghi, R. Kahlifeh,
M. M. Doroodmand, Adv. Synth. Catal. 2009, 351, 207;
c) T. Mitsudome, Y. Mikami, K. Ebata, T. Mizugaki, K.
Jitsukawa, K. Kaneda, Chem. Commun. 2008, 4804;
d) J. Zhang, Z. Zhang, Y. Wang, X. Zheng, Z. Wang,
Eur. J. Org. Chem. 2008, 5112; e) S. Bhadra, A. Saha,
B. C. Ranu, Green Chem. 2008, 10, 1224.
[8] a) J. M. Campelo, T. D. Conesa, M. J. Gracia, M. J.
Juardo, R. Luque, J. M. Marinas, A. A. Romero, Green
Chem. 2008, 10, 853; b) T. Mitsudome, S. Arita, H.
Mori, T. Mizugaki, K. Jitsukawa, K. Kaneda, Angew.
Chem. 2008, 120, 8056; Angew. Chem. Int. Ed. 2008, 47,
7938; c) P. Christopher, S. Linic, J. Am. Chem. Soc.
2008, 130, 11264.
prepared above, followed by the addition of 2.5 mL of dode-
cylamine. The mixture was aged for 2 h under stirring at
room temperature. 60 mL of methanol were added to pre-
cipitate the hybrid materials. The products were then
washed twice with copious methanol, and dried under
vacuum at room temperature.
Three-Component Coupling Reactions
General procedure for the three-component coupling reac-
tion of aldehyde, amine and alkyne (Table 4, entries 1–37):
A mixture of the PbS-Au nanocomposite catalyst (0.5 mol%
Au), aldehyde (1.0 mmol), amine (1.2 mmol), alkyne
(1.3 mmol) and water (HPLC grade, 1.0 mL) was heated at
1008C (1000 rpm) in a closed 8 mL glass vial under air for
12–13 h. The reaction mixture was cooled to room tempera-
ture, and 3 mL of hexane were added. The mixture was cen-
trifuged at 5000 rpm for 5 min. The upper organic layer con-
taining the product was separated, and the lower aqueous
layer containing the catalyst was washed with hexane (3ꢁ
3 mL). The solvent was removed from the combined organic
layers by rotary evaporation, followed by purification by
column chromatography (silica gel, dichloromethane to 9/1
dichloromethane/ethyl acetate, unless noted otherwise).
Acknowledgements
This work is funded by the Institute of Bioengineering and
Nanotechnology (Biomedical Research Council, Agency for
Science, Technology and Research, Singapore).
References
[1] a) D. Astruc, in: Nanoparticles and Catalysis, (Ed.: D.
Astruc), Wiley, 2008, Chap. 1, p 1; b) J. M. Campelo, D.
Luna, R. Luque, J. M. Marinas, A. A. Romero, Chem-
SusChem 2009, 2, 18.
[9] a) A. Corma, H. Garcia, in: Nanoparticles and Cataly-
sis, (Ed.: D. Astruc), Wiley, 2008, Chap. 12, p 389;
b) C. D. Pina, E. Falletta, M. Rossi, in: Nanoparticles
and Catalysis, (Ed.: D. Astruc), Wiley, 2008, Chap. 13,
p 427; c) A. Corma, H. Garcia, Chem. Soc. Rev. 2008,
37, 2096; d) M. Chen, D. W. Goodman, Chem. Soc.
Rev. 2008, 37, 1860; e) C. D. Pina, E. Falletta, L. Prati,
M. Rossi, Chem. Soc. Rev. 2008, 37, 2077; f) M. Haruta,
Gold Bull. 2004, 37, 27; g) J. C. Fierro-Gonzalez, B. C.
Gates, Chem. Soc. Rev. 2008, 37, 2127.
[2] a) C. Gonzꢂlez-Arellano, J. M. Campelo, D. J. Macquar-
rie, J. M. Marinas, A. A. Romero, R. Luque, Chem-
ACHTUNGTRENNUNGSusChem 2008, 1, 746; b) Y. Zhang, S. N. Riduan, J. Y.
Ying, Chem. Eur. J. 2009, 15, 1077.
[3] a) A. Roucoux, A. Nowicki, K. Philippot, in: Nanopar-
ticles and Catalysis, (Ed.: D. Astruc), Wiley, 2008,
Chap. 11, p 349; b) F. Shi, M. K. Tse, S. Zhou, M.-M.
Pohl, J. Radnik, S. Hꢃbner, K. Jꢄhnisch, A. Brꢃckner,
M. Beller, J. Am. Chem. Soc. 2009, 131, 1775; c) C.-M.
[10] a) A. Corma, P. Serna, Science 2006, 313, 332; b) P.
Claus, Appl. Catal. A: Gen. 2005, 291, 222.
Adv. Synth. Catal. 2009, 351, 2887 – 2896
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2895

Leng Leng Chng et al.
FULL PAPERS
[11] a) G. J. Hutchings, Chem. Commun. 2008, 1148;
b) M. D. Hughes, Y.-J. Xu, P. Jenkins, P. McMorn, P.
Landon, D. I. Enache, A. F. Carley, G. A. Attard, G. J.
Hutchings, F. King, E. H. Stitt, P. Johnston, K. Griffin,
C. J. Kiely, Nature 2005, 437, 1132; c) P. Lignier, F.
Morfin, S. Mangematin, L. Massin, J.-L. Rousset, V.
Caps, Chem. Commun. 2007, 186; d) F.-Z. Su, Y.-M.
Liu, L.-C. Wang, Y. Cao, H.-Y. He, K.-N. Fan, Angew.
Chem. 2008, 120, 340; Angew. Chem. Int. Ed. 2008, 47,
334.
[19] a) C. Wei, C.-J. Li, J. Am. Chem. Soc. 2003, 125, 9584;
b) B. Huang, X. Yao, C.-J. Li, Adv. Synth. Catal. 2006,
348, 1528; c) V. K.-Y. Lo, Y. Liu, M.-K. Wong, C.-M.
Che, Org. Lett. 2006, 8, 1529; d) V. K.-Y. Lo, K. K.-Y.
Kung, M.-K. Wong, C.-M. Che, J. Organomet. Chem.
2009, 694, 583.
[20] C. Fischer, E. M. Carreira, Org. Lett. 2001, 3, 4319.
[21] P.-H. Li, L. Wang, Chin. J. Chem. 2005, 23, 1076.
[22] C.-J. Li, C. Wei, Chem. Commun. 2002, 268.
[23] a) B. M. Choudary, C. Sridhar, M. L. Kantam, B. Sreed-
har, Tetrahedron Lett. 2004, 45, 7319; b) M. Wang, P.
Li, L. Wang, Eur. J. Org. Chem. 2008, 2255; c) P. Li, L.
Wang, Tetrahedron 2007, 63, 5455.
[12] A. Corma, P. Concepciꢅn, I. Domꢆnguez, V. Fornes,
M. J. Sabater, J. Catal. 2007, 251, 39.
[13] a) M. Kidwai, V. Bansal, A. Kumar, S. Mozumdar,
Green Chem. 2007, 9, 742; b) X. Zhang, A. Corma,
Angew. Chem. 2008, 120, 4430; Angew. Chem. Int. Ed.
2008, 47, 4358; c) N. G. Willis, J. Guzman, Appl. Catal.
A: Gen. 2008, 339, 68; d) M. L. Kantam, B. V. Prakash,
C. R. V. Reddy, B. Sreedhar, Synlett 2005, 2329; e) J.
Han, Y. Liu, R. Guo, J. Am. Chem. Soc. 2009, 131,
2060.
[14] a) T. Naota, H. Takaya, S.-I. Murahashi, Chem. Rev.
1998, 98, 2599; b) N. Miyachi, F. Kanada, M. Shibasaki,
J. Org. Chem. 1989, 54, 3511; c) M. A. Huffman, N.
Yasuda, A. E. Decamp, E. J. J. Grabowski, J. Org.
Chem. 1995, 60, 1590; d) M. Miura, M. Enna, K.
Okuro, M. Nomura, J. Org. Chem. 1995, 60, 4999;
e) J. J. Fleming, J. Du Bois, J. Am. Chem. Soc. 2006,
128, 3926.
[15] L. Zani, C. Bolm, Chem. Commun. 2006, 4263.
[16] P. Li, Y. Zhang, L. Wang, Chem. Eur. J. 2009, 15, 2045.
[17] a) L. Shi, Y.-Q. Tu, M. Wang, F.-M. Zhang, C.-A. Fan,
Org. Lett. 2004, 6, 1001; b) N. Gommermann, P. Kno-
chel, Chem. Eur. J. 2006, 12, 4380.
[18] a) C. Wei, Z. Li, C.-J. Li, Org. Lett. 2003, 5, 4473; b) X.
Yao, C.-J. Li, Org. Lett. 2005, 7, 4395; c) K. M. Reddy,
N. S. Babu, I. Suryanarayana, P. S. S. Prasad, N. Lin-
gaiah, Tetrahedron Lett. 2006, 47, 7563; d) Y. Zhang,
A. M. Santos, E. Herdtweck, J. Mink, F. E. Kꢃhn, New
J. Chem. 2005, 29, 366.
[24] M. L. Kantam, S. Laha, J. Yadav, S. Bhargava, Tetrahe-
dron Lett. 2008, 49, 3083.
[25] Z. Li, C. Wei, L. Chen, R. S. Varma, C.-J. Li, Tetrahe-
dron Lett. 2004, 45, 2443.
[26] J. Yang, J. Y. Ying, Nature Mater. 2009, 8, 683.
[27] J. Zeng, J. Yang, J. Y. Lee, W. Zhou, J. Phys. Chem. B
2006, 110, 24606.
[28] C. D. Wagner, A. V. Naumkin, A. Kraut-Vass, J. W. Al-
lison, C. J. Powell, J. R. Rumble, Jr., NIST Standard
Reference Database 20, Version 3.2 (Web Version).
[29] a) Z. Li, C. Brouwer, C. He, Chem. Rev. 2008, 108,
3239; b) A. Arcadi, Chem. Rev. 2008, 108, 3266; c) J. H.
Teles, S. Brode, M. Chabanas, Angew. Chem. 1998, 110,
1475; Angew. Chem. Int. Ed. 1998, 37, 1415; d) Y.
Fukuda, K. Utimoto, J. Org. Chem. 1991, 56, 3729.
[30] J. H. Warner, R. D. Tilley, Adv. Mater. 2005, 17, 2997.
[31] S. Jun, E. Jang, J. E. Lim, Nanotechnology 2006, 17,
3892.
[32] J. Joo, H. B. Na, T. Yu, J. H. Yu, Y. W. Kim, F. Wu, J. Z.
Zhang, T. Hyeon, J. Am. Chem. Soc. 2003, 125, 11100.
[33] M. Brust, M. Walker, D. Bethell, D. J. Schiffrin, R.
Whyman, J. Chem. Soc. Chem. Commun. 1994, 801.
[34] J. Yang, L. Levina, E. H. Sargent, S. O. Kelley, J. Mater.
Chem. 2006, 16, 4025.
2896
asc.wiley-vch.de
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2887 – 2896