N, N-Dimethylformamide-stabilized palladium nanoclusters as a catalyst for Larock indole synthesis

Article abstract of DOI:10.1039/c8ra01410h

We show that N,N-dimethylformamide-stabilized Pd nanoclusters (NCs) have high catalytic activity in the reaction of substituted 2-iodoanilines with alkynes to give 2,3-disubstituted indoles. This indole synthesis does not require phosphine ligands and proceeds with low Pd catalyst loadings. The Pd NCs were separated from the mixture after the reaction, and recycled at least three times. Transmission electron microscopy images showed that the Pd particle size before the reaction was 1.5-2.5 nm. The particle size after the reaction was 2-3 nm. X-ray photoelectron spectroscopy showed that the binding energy of the Pd NCs before the reaction was 335.0 eV.

Full text of DOI:10.1039/c8ra01410h

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N,N-Dimethylformamide-stabilized palladium
nanoclusters as a catalyst for Larock indole
Cite this: RSC Adv., 2018, 8, 11324
synthesis†
a
Kaito Onishi,a Kei Oikawa,a Hiroki Yano,a Takeyuki Suzukib and Yasushi Obora
*
We show that N,N-dimethylformamide-stabilized Pd nanoclusters (NCs) have high catalytic activity in the
reaction of substituted 2-iodoanilines with alkynes to give 2,3-disubstituted indoles. This indole synthesis
does not require phosphine ligands and proceeds with low Pd catalyst loadings. The Pd NCs were
separated from the mixture after the reaction, and recycled at least three times. Transmission electron
microscopy images showed that the Pd particle size before the reaction was 1.5–2.5 nm. The particle
size after the reaction was 2–3 nm. X-ray photoelectron spectroscopy showed that the binding energy
of the Pd NCs before the reaction was 335.0 eV.
Received 14th February 2018
Accepted 16th March 2018
DOI: 10.1039/c8ra01410h
rsc.li/rsc-advances
catalyst loading is highly desirable. Transition-metal nano-
clusters (NCs) have attracted attention for use in industrial,
chemical, and medical research.16
Introduction
Indoles are important building blocks in many areas of organic
synthesis.1 Indole moieties are common in bioactive
substances,2 optically responsive materials,3 electronic mate-
rials,4 and uorescent polymer sensors.5 Many methods for the
synthesis of indole derivatives have been developed.6–16 Fischer
and co-workers reported that the reactions of aryl hydrazines
with ketones gave 2,3-disubstituted indoles.7 Buchwald
prepared 2,3-disubstituted indoles from hydrazines and aryl
halides and ketones using a Pd catalyst.8 Bischler reported
a reaction of aniline with a-haloketones.9 Fukuyama reported
radical cyclization of 2-alkenylthioanilides using Sn radicals.10
An Ir-catalyzed oxidative cyclization of amino alcohols has been
reported.11 Transition metals coordinated with NHC-ligands
can catalyze C–H activation of substituted anilines.12 Recently,
easily available 2-haloanilines were used to prepare substituted
indoles. The reaction of 2-iodoanilines with vinyl sulfones
yielded 3-substituted indoles under Pd catalysis.13 In 1991,
Larock reported an efficient and powerful method for obtaining
2,3-disubstituted indoles, with a Pd complex as the catalyst.14 Li
and co-workers reported the synthesis of mono-substituted
indoles, catalyzed by Pd nanoparticles in metal–organic
framework cages.15
We previously reported the preparation of N,N-dime-
thylformamide (DMF)-stabilized transition-metal nanoparticles
via reduction with DMF.17 The obtained metal NCs showed high
catalytic activity in Suzuki–Miyaura cross-coupling, Mizoroki–
Heck coupling,16 Migita–Kosugi–Stille coupling,18 and Ullmann
coupling reactions.19 The DMF-stabilized metal nanoparticles
gave high turnover numbers and could be recovered aer the
reactions.16–19 Furthermore, the DMF-stabilized Pd NCs were
relatively long-lived at high temperatures compared with typical
heterogeneous catalysts. Our work has focused on reducing
catalyst loadings or reactions by using transition-metal NCs as
catalysts.
In this paper, we report the synthesis of 2,3-disubstituted
indoles from 2-iodoanilines and internal alkynes, catalyzed by
DMF-stabilized Pd NCs. This reaction proceeded under ligand-
free conditions at low catalyst loadings. The Pd NCs were recy-
cled at least three times.
Results and discussion
Pd NCs were prepared via reduction with DMF.18 The Pd NCs
were examined using transmission electron microscopy (TEM).
The TEM image and particle size distribution indicated that the
Pd NC particle size was 1.5–2.5 nm (Fig. 1).
Fourier-transfer infrared (FT-IR) spectra of the DMF mole-
cules and DMF-protected Pd NCs were obtained. The Pd NCs
gave an absorption peak at around 1680 cmꢀ1. This peak
corresponds to the n(C]O) vibration of DMF molecules and was
shied relative to that for pure DMF. This indicates that the
DMF molecules interacted with the Pd NCs (Fig. S1†).20,21
Transition metals or ligands were used in these reac-
tions.8,10–15 From an industrial point of view, reducing the
aDepartment of Chemistry and Materials Engineering, Faculty of Chemistry, Materials
and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. E-mail: obora@
kansai-u.ac.jp; Fax: +81-6-6339-4026; Tel: +81-6-6368-0876
bComprehensive Analysis Center, The Institute of Scientic and Industrial Research
(ISIR), Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0057, Japan
† Electronic supplementary information (ESI) available: Characterization and
spectra. See DOI: 10.1039/c8ra01410h
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Table 1 Pd NC-catalyzed synthesis of 2,3-diphenylindole (3a) from 2-
iodoaniline (1a) and diphenylacetylene (2a)a
Entry Solvent
Additive
Base
X
Yieldb (%)
1
2
3
4
5
6
7
8
DMF
DMF/H2O (1 : 1)
NMP/H2O (1 : 1)
NaCl
NaCl
NaCl
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
96 (88)
Trace
28
Trace
Trace
Trace
69
51
24
87
Trace
Fig. 1 (a) TEM image of DMF-stabilized Pd nanoclusters (scale bar ¼ 5
nm) and (b) nanoparticle size distribution.
MeOH/H2O (1 : 1) NaCl
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
LiCl
The electron states of the DMF-protected Pd NCs were
determined using X-ray photoelectron spectroscopy (XPS). The
binding energy (BE) 335.0 eV of Pd 3d5/2 for the Pd NCs, namely
335.0, indicated the presence of zero-valent Pd in the Pd NCs.
The BE of Pd 3d5/2 for the Pd NCs was ꢀ3.2 eV lower than that
of Pd 3d5/2 in PdCl2 (338.2 eV) (Fig. 2).22
The results are shown in Table 1. The reaction of 2-iodoa-
niline (1a, 0.5 mmol) with diphenylacetylene (2a, 0.5 mmol) in
the presence of Pd NCs (3.0 ꢁ 10ꢀ1 mol%; prepared as previ-
ously reported18), K2CO3 (1.5 mmol), and NaCl (1.5 mmol) in
DMF at 135 ꢂC for 48 h under Ar was used as a model reaction;
2,3-diphenylindole (3a) was obtained. The use of the low cata-
lyst loading (3.0 ꢁ 10ꢀ1 mol%) achieved the high catalytic
activity, which demonstrate the superiority to the turnover
number (TON) for the formation of 3a was 3.2 ꢁ 102 (mol)/Pd
NCs (mol), which show the advantage of this Pd NCs in
comparison with other known catalytic system.8,11,13–15
We optimized the conditions for Pd-NC-catalyzed Larock
indole synthesis; the results are shown in Table 1. We examined
the effects of the solvent. DMF was the most effective solvent
and 3a was obtained in 88% isolated yield (entry 1). Next, we
examined mixed solvents, namely DMF/H2O (1 : 1) (entry 2), N-
methylpyrrolidone (NMP)/H2O (1 : 1) (entry 3), and MeOH/H2O
(1 : 1) (entry 4). When DMF/H2O (1 : 1) was used, a trace amount
of 3a was obtained (entry 2). When NMP/H2O (1 : 1) was used, 3a
was obtained in 28% yield (entry 3). When MeOH/H2O was
used, a trace amount of 3a was obtained (entry 4).
n-Bu4NCl K2CO3
None
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
K2CO3
KOAc
Cs2CO3
9
10
11
12
13c
14d
15e
Na2CO3 0.3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.03
None n.d.
1.0
0.3
0.3
47
88
Trace
a
Conditions: 1a (0.5 mmol), 2a (0.5 mmol), Pd NCs (3.0 ꢁ 10ꢀ1 mol%),
solvent (2 mL), additive (1.5 mmol), base (1.5 mmol), 135 ꢂC, 48 h. b GC
yields based on limiting reagent used. The number in parentheses
c
shows the isolated yield. PdCl2 (1.0 mol%) was used instead of Pd
NCs. d K2CO3 (0.25 mmol). e Hg (5 equiv.) was used.
used as additives in the Larock indole synthesis.14 In the present
method, NaCl was the best additive (entries 5 and 6). Without
NaCl, product 3a was obtained in 69% yield (entry 7). The
addition of salts such as NaCl enhanced the catalytic activity by
the formation of a chloride-ligated zerovalent palladium species
as was reported (as catalytically active species) in the palladium-
complex catalyzed Larock indole synthesis.14b
Next, various bases were tested. When KOAc was used, 3a
was obtained in 51% yield (entry 8). Cs2CO3 gave 3a in 24% yield
(entry 9). When Na2CO3 was used, 3a was obtained in 87% yield
(entry 10).
When the amount of Pd NCs was reduced to 3.0 ꢁ
10ꢀ2 mol%, a trace amount of 3a was obtained (entry 11).
Next, the effects of the Pd NCs were examined. The product
3a was not observed in the absence of Pd NCs (entry 12).
When PdCl2 (1.0 mol%; the precursor used to prepare the
DMF-stabilized Pd NCs) was used, the reaction was ineffective
and the product yield was low (entry 13). The catalytic activity
was therefore derived from the Pd NCs, not from PdCl2.
When K2CO3 (0.25 mmol) was used, 3a was obtained in 88%
yield (entry 14). The conditions in Table 1, entry 14 were used in
recycling experiments. The Pd NC particle size aer the reaction
was determined.
Next, we examined the effect of using LiCl and n-Bu4NCl
instead of NaCl as additives. LiCl and n-Bu4NCl are traditionally
The stability of the Pd NCs was further investigated by con-
ducted poisoning tests with Hg (5 equiv.) under the conditions
in Table 1, entry 1. The conversions of 1a and 2a were 38% and
26%, respectively, and product 3a was obtained in trace
amounts. These results indicate that the catalytic activity of the
Pd NCs was decreased by forming an amalgam with Hg.
Fig. 2 XPS spectra of Pd NCs.
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Table 2 Pd NC-catalyzed 2,3-disubstituted indole synthesis of various
halo anilines 1 and internal alkynes 2a
A TEM image was used to determine the effects of DMF
molecules on the Pd NCs aer the reaction performed under the
conditions in Table 1, entry 14.
The TEM image showed the presence of Pd in the sample;
this was conrmed using inductively coupled plasma atomic
emission spectroscopy (ICP-AES).
The sample for ICP-AES was obtained as follows. The DMF in
the mixture aer the reaction under the conditions in Table 1,
entry 1 was removed by evaporation, and the sample was
redissolved in CH2Cl2. Next, K2CO3 and NaCl were removed
from the sample solution by ltration with a membrane lter,
using CH2Cl2. Finally, CH2Cl2 was removed by evaporation and
the sample was redissolved in MeOH. This sample was analyzed
using ICP-AES to determine the concentrations of Pd, Na, and K.
The concentrations of Pd and Na were 3.4 and 2.7 ppm,
respectively. The concentration of K was below the detection
limit. The ICP-AES data charts and standard curve are shown in
Fig. S2–S4.† These results indicated that Pd was the main
component in the sample. The sample prepared by the same
method was analyzed by TEM. The results show aggregation of
some of the Pd NCs (Fig. S5†).
Entry
1
Aryl halide
Alkyne
Product
Yieldb (%)
77
2
3
71
80
We used TEM images (Fig. 3a and S6†) to investigate the Pd
NC particle size aer the reaction performed under the condi-
tions in Table 1, entry 14. The Pd NC particle size distribution
was 2–3 nm, i.e., the particles were slightly larger aer the
reaction. However, inhibition of Ostwald ripening21,23 during
the catalytic reaction led to the nanoparticles retaining their
original size, <3 nm.
4
5
66
88 (4 : 1)
Dynamic light scattering (DLS) measurements showed that
the Pd NCs had an average particle diameter of 2.3 nm,
(Fig. S8†).
The substrate scope was examined by performing reactions
between haloanilines 1 and internal alkynes 2 under the
conditions in Table 1, entry 1. The results are shown in Table 2.
The reaction of 2-iodoaniline (1a) with 2,3-diphenylacetylene
(2a) gave 2,3-diphenylindole (3a) in excellent yield. A compar-
ison of entries 1 and 2 shows how the electronic effects of the
substituents in haloaniline 1 affect the reaction. The reactions
of haloanilines bearing electron-donating groups, e.g., 4-Me
(1b) and 5-Me (1c), with diphenylacetylene (2a), gave the cor-
responding indoles 3b and 3c in moderate and excellent yields,
respectively (entries 1 and 2). However, when the substituents
were electron-withdrawing groups such as 4-CF3 and 5-Cl, the
reaction became sluggish.
6
7
95
49
8
30 (2 : 1)
a
Conditions: same as in Table 1, entry 1. b Isolated yields.
Various aliphatic and aromatic alkynes were good substrates
for the reactions of alkynes 2 with 2-iodoaniline (1a). 3-Hexyne
(2b) and 5-decyne (2c) reacted with 2-iodoaniline (1a) to give the
corresponding 2,3-disubstituted indoles 3d and 3e in good
yields (entries 3 and 4). The reaction of the asymmetric alkyne 1-
phenyl-1-butyne (2d) gave the corresponding products 3f and 3f0
in 88% yield as a mixture of regioisomers (3f : 3f0 ¼ 4 : 1; entry
5). When terminal alkynes such as ethynylbenzene were used in
Fig. 3 (a) TEM image of Pd NCs after reaction under conditions in
Table 1, entry 14 (scale bar ¼ 5 nm) and (b) nanoparticle size
distribution.
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the reaction, the corresponding products were not obtained; the
related Sonogashira coupling reaction also did not proceed with
the Pd NCs. An alkyne bearing a trimethylsilyl group, namely 1-
phenyl-2-(trimethylsilyl)acetylene, was used to examine the
effects of steric hindrance; the desired product was not ob-
tained. This lack of reactivity is assumed to be the result of
steric hindrance.
The secondary amine N-methyl-2-iodoaniline (1d) reacted
with diphenylacetylene (2a) to give the corresponding indole 3g
in 95% yield (entry 6).
We also used easily accessible 2-bromoaniline (1e) instead of
2-iodoaniline, and obtained 3a in good yield (entry 7). When the
asymmetric alkyne 1-phenyl-1-butyne (2d) was used, the corre-
sponding products 3f and 3f0 were obtained in 30% yield; the
regioisomer ratio 3f : 3f0 was 2 : 1 (entry 8).
Fig. 5 Multiple catalyst recycling. Conditions: as given in Table 1, entry
14.
Next, we examined the recyclability of the catalyst. The
In contrast, the PdCl2 catalyst could not be recycled. Only
reaction was performed using substrates of 1a and 2a. In the 11% yield of the product 3a was obtained in the rst cycle when
rst cycle, the desired product 3a was obtained in 88% yield, PdCl2 was used instead of Pd NCs under the reaction conditions
under the conditions in Table 1, entry 14 (step 1 to step 2 in in Table 1, entry 14.
Fig. 4). Next, the Pd NCs were separated from 3a using a mixed
solvent (hexane : ethyl acetate ¼ 77 : 23, 5 mL ꢁ seven times;
Conclusions
upper phase); the Pd NCs remained in the DMF solvent (bottom
phase) (step 3). The hexane : ethyl acetate ratio was important We have developed a useful catalytic system for the Larock
for achieving complete separation of the Pd NCs from 3a. In the indole synthesis, using DMF-protected Pd clusters, which can
next step, the DMF solution containing the Pd NCs was ltered be easily prepared by simply heating the Pd NCs in DMF. This
through a cotton plug to remove K2CO3 and NaCl from the DMF catalytic system does not require external ligands and the
solution. The DMF was removed under vacuum and the residue reaction was achieved at low catalyst loadings.
was redissolved in DMF (2 mL); these Pd NCs in DMF were used
An advantage of this catalytic system is that the catalyst can
for the next catalytic reaction (step 4). In the second cycle, be recycled at least three times without considerable loss of
product 3a was obtained in 80% yield (Fig. 5). Re-addition of catalytic activity. The catalyst can be easily recovered by simple
NaCl and K2CO3 is necessary for achieving high catalytic activity extraction with hexane–ethyl acetate/DMF (the Pd NCs move
in the recycling experiments. At this time, large amount of into the DMF phase). The recycled Pd NCs maintain high
insoluble solid material was formed during the course of catalytic activity and the recovered catalyst does not need pre-
multiple recycling experiments, which resulted in substantially activation for the next catalytic cycle.
decreasing the catalytic activity. Therefore, the resulting solid
was removed by ltration in prior to the next catalytic recycling synthesis. The amount of Pd NC catalyst used can be kept low by
process.
multiple recycling. The present ligandless DMF–Pd NC-
This process provides a green method for the Larock indole
We performed ICP analysis and the concentration of Pd in catalyzed process could be extended to a wide range of
the hexane/ethyl acetate phase was 6.2 ppm (Table S2, organic transformations. This will be investigated in future
Fig. S10†). The catalyst metal leaching resulted in decreasing of work by our group.
the yield of 3a during the multiple recycling steps.
Experimental section
1. General
GLC analysis was performed with a ame ionization detector
1
using a 0.22 ꢁ 25 m capillary column (BP-5). H and 13C NMR
spectra were recorded at 400 and 100 MHz, respectively, in
CDCl3 with Me4Si as the internal standard. The products were
characterized by 1H NMR and 13C NMR spectroscopies. All
reagents were commercially available and used without further
purication. The DMF-protected Pd NCs were prepared
Fig.
4 Photographs of catalyst-recycling procedure in indole
synthesis under reaction conditions in Table 1, entry 14. Step 1: reac- according to the reported method.18 TEM images were obtained
tion mixture containing 1a, 2a, Pd NCs, K2CO3, and NaCl before the
reaction. Step 2: mixture containing 3a after reaction (after first cycle).
Step 3: hexane : ethyl acetate (77 : 23) mixed solvent was added (upper
phase: mixed solvent containing 3a, bottom phase: DMF containing Pd
with a JEOL JEM-ARM200F instrument at an accelerating
voltage of 200 kV. X-ray photoelectron spectroscopy (XPS)
spectrum was used JPS-9010MC with the Al Ka radiation. The
measured spectra were calibrated by a C 1s electron peak (284.0
eV). ICP-AES was analyzed by a Shimadzu ICPS-8100.
NCs). Step 4: reaction mixture for next run, containing 1a, 2a, Pd NCs,
K2CO3, and NaCl.
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Compounds 3a,24 3b,25 3c,26 3d,27 3e,28 3f,29 3f0,29 and 3g (ref. 1H NMR (CDCl3, 400 MHz) d 1.19–1.34 (m, 3H), 2.77 (q, J ¼ 8 Hz,
30) are known compounds and have been reported previously. 2H), 7.10–7.64 (m, 9H), 7.84 (br, 1H); 13C NMR (CDCl3, 100
MHz) d 15.6 (CH3), 17.7 (CH2), 110.8 (CH), 113.7 (C), 115.3 (C),
119.1 (CH), 119.4 (CH), 119.95 (C), 122.1 (CH), 127.4 (CH), 127.8
2. Typical procedure for Pd NC-catalyzed indole synthesis of
1a with 2a (Table 1, entry 1)
(CH), 128.7 (CH), 128.9 (CH), 129.5 (CH), 133.2 (C), 133.6 (C).
3g (ref. 30). Blown solid, mp ¼ 138–139 ꢂC (Lit.28 137–139 ꢂC),
A mixture of 2-iodoaniline (1a, 109 mg, 0.5 mmol), diphenyla- 1H NMR (CDCl3, 400 MHz) d 3.63 (s, 3H), 7.13–7.78 (m, 13H),
cetylene (2a, 89 mg, 0.5 mmol), K2CO3 (207 mg, 1.5 mmol), NaCl 7.80 (br, 1H); 13C NMR (CDCl3, 100 MHz) d 30.87 (CH3), 109.55
(88 mg, 1.5 mmol), Pd NCs in DMF (1.5 mL, 1 mM) as the (CH), 115.08 (C), 119.58 (CH), 120.16 (CH), 122.15 (CH), 125.47
catalyst, in DMF (0.5 mL) as the solvent was stirred at 135 ꢂC for (CH), 126.95 (C), 127.98 (CH), 128.14 (2CH), 128.35 (2CH),
48 h in an Ar atmosphere. To ensure reproducibility of the 129.83 (2CH), 131.11 (2CH), 131.87 (C), 135.19 (C), 137.30 (C),
reaction, K2CO3 and NaCl were ground with an agate pestle and 137.67 (C).
mortar before addition to the mixture. The product conversions
and yields were estimated by GC from peak areas, based on an
internal standard (n-nonane); product 3a was obtained in
3. Preparation of TEM sample
quantitative yield. The reaction mixture was extracted with Aer the reaction under the conditions shown in Table 1, entry
water and ethyl acetate to separate the products from the Pd 14, DMF was removed from the reaction mixture by evaporation.
NCs and salts. Product 3a was isolated by column chromatog- Next, the Pd NCs were redissolved in CH2Cl2. The solution was
raphy [silica gel (230–400 mesh), n-hexane and ethyl acetate as ltered with a membrane lter (20 nm) to remove K2CO3 and
eluent] in 88% yield (119 mg).
NaCl. CH2Cl2 was removed by evaporation and the Pd NCs were
3a (ref. 24 and 31). White solid, mp ¼ 115–116 ꢂC (Lit.30 114– redissolved in MeOH.
1
ꢂ
116 C), H NMR (CDCl3, 400 MHz) d 7.13–7.45 (m, 13H), 7.68
(d, J ¼ 4 Hz, 1H), 8.19 (br, 1H); 13C NMR (CDCl3, 100 MHz)
4. Preparation of IR sample
d 110.9 (CH), 115.0 (C), 119.7 (CH), 120.4 (CH), 122.7 (CH), 126.2
(CH), 127.7 (CH), 128.2 (CH), 128.5 (2CH), 128.7 (CH), 128.8
(2CH), 130.2 (2CH), 132.7 (C), 134.1 (C), 135 (2C), 135.9 (C).
(a) Pd NCs (before the reaction): Pd NCs (0.3 mol%) were
aged in DMF (2 mL) with 1a (0.5 mmol), 2a (0.5 mmol), K2CO3
3b (ref. 25 and 32). Beige solid, mp ¼ 143–147 ꢂC (Lit.31 151– (1.5 mmol), and NaCl (1.5 mmol) for 0.5 h. Next, the solution
152 ꢂC), 1H NMR (CDCl3, 400 MHz) d 2.31 (s, 3H), 6.92–7.34 (m, was ltered to remove K2CO3 and NaCl and DMF was removed
13H), 7.85 (br, 1H); 13C NMR (CDCl3, 100 MHz) d 21.52 (CH3), by evaporation under vacuum.
110.56 (C), 114.55 (C), 119.17 (CH), 124.23 (CH), 126.10 (CH),
(b) Pd NCs (aer the reaction): aer the reaction under the
127.51 (CH), 128.06 (CH), 128.47 (CH), 128.58 (2CH), 128.93 conditions given in Table 1, entry 1, the reaction mixture was
(2CH), 129.66 (CH), 130.00 (C), 130.15 (2CH), 132.72 (C), 134.15 extracted with a mixed solvent [hexane : ethyl acetate (77 : 23)],
(2C), 135.20 (C).
(5 mL ꢁ seven times) to remove product 3a, and DMF was
3c (ref. 26 and 33). Beige solid, mp ¼ 102–106 ꢂC (Lit.32 70–80 removed by evaporation under vacuum.
ꢂC), 1H NMR (CDCl3, 400 MHz) d 2.45 (s, 3H), 6.95–7.56 (m,
13H), 8.01 (br, 1H); 13C NMR (CDCl3, 100 MHz) d 21.52 (CH3),
5. Recycling experiment
110.55 (CH), 114.56 (C), 119.16 (CH), 124.23 (CH), 126.10 (CH),
127.50 (CH), 128.06 (2CH), 128.46 (2CH), 128.58 (2CH), 128.80 2-Iodoaniline (1a, 109 mg, 0.5 mmol), diphenylacetylene (2a,
(C), 128.94 (C), 129.66 (2CH), 130.16 (C), 132.76 (C), 134.16 (C), 89 mg, 0.5 mmol), K2CO3 (35 mg, 0.25 mmol), and NaCl (88 mg,
135.21 (C).
1.5 mmol) were placed in a pressure container and Pd NCs in
3d (ref. 27). Yellow oil, 1H NMR (CDCl3, 400 MHz) d 1.19–1.23 DMF (1 mM, 1.5 mL) as the catalyst and DMF (0.5 mL) were
(m, 6H), 2.64–2.72 (m, 4H), 7.04–7.20 (m, 3H), 7.51–7.53 (m, added. The reaction mixture was stirred at 135 ꢂC for 48 h under
2H); 13C NMR (CDCl3, 100 MHz) d 14.5 (CH3), 15.8 (CH3), 17.3 Ar. The reaction was performed under the conditions in Table 1,
(CH2), 19.3 (CH2), 110.3 (CH), 113.0 (C), 118.2 (CH), 118.9 (CH), entry 14 and then the Pd NCs were separated from 3a using
120.8 (CH), 128.4 (C), 135.2 (C), 136.1 (C).
a mixed solvent (hexane : ethyl acetate ¼ 77 : 23, 5 mL ꢁ seven
3e (ref. 28). Pale-yellow oil, 1H NMR (CDCl3, 400 MHz) d 0.91– times; upper phase containing 3a); the Pd NCs remained in the
0.96 (m, 6H), 1.36–1.40 (m, 4H), 1.41–1.64 (m, 4H), 2.66–2.72 DMF solvent (bottom phase). The conversion of the substrate
(m, 4H), 7.04–7.11 (m, 2H), 7.22–7.26 (m, 1H), 7.51 (d, J ¼ and yield of the product were calculated from their GC peak
8.0 Hz, 1H), 7.65 (br, 1H); 13C NMR (CDCl3, 100 MHz) d 13.9 areas, based on an internal standard (n-nonane). In the next
(CH3), 14.1 (CH3), 22.5 (CH2), 22.8 (CH2), 23.9 (CH2), 25.8 (CH2), step, the DMF solution containing the Pd NCs was ltered
32.1 (CH2), 33.3 (CH2), 110.2 (CH), 112.2 (C), 118.3 (CH), 118.8 through a cotton plug to remove K2CO3 and NaCl from the DMF
(CH), 120.7 (CH), 128.8 (C), 135.2 (C), 135.3 (C).
solution. The DMF was removed under vacuum and the residue
3f, 3f0 (ref. 29). Yellow oil; 3f: 1H NMR (CDCl3, 400 MHz) was redissolved in DMF (2 mL); these Pd NCs in DMF were used
d 1.19–1.34 (m, 3H), 2.88 (q, J ¼ 8 Hz, 2H), 7.10–7.64 (m, 9H), for the next catalytic reaction under the reaction conditions
7.84 (br, 1H); 13C NMR (CDCl3, 100 MHz) d 14.3 (CH3), 19.5 given in Table 1, entry 14, by adding 2-iodoaniline (1a, 109 mg,
(CH2), 110.4 (CH), 118.8 (CH), 119.85 (CH), 121.5 (CH), 125.8 0.5 mmol), diphenylacetylene (2a, 89 mg, 0.5 mmol), K2CO3
(CH), 128.5 (CH), 135.1 (C), 135.4 (C), 135.9 (2C), 137.2 (C); 3f0: (35 mg, 0.25 mmol), and NaCl (88 mg, 1.5 mmol).
11328 | RSC Adv., 2018, 8, 11324–11329
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15 H. Li, Z. Zhu, F. Zhang, S. Xie, H. Li, P. Li and X. Zhou, ACS
Catal., 2011, 1, 1604–1612.
Conflicts of interest
16 M. Hyotanishi, Y. Isomura, H. Yamamoto, H. Kawasaki and
Y. Obora, Chem. Commun., 2011, 47, 5750–5752.
17 (a) H. Kawasaki, H. Yamamoto, H. Fujimori, R. Arakawa,
M. Inada and Y. Iwasaki, Chem. Commun., 2010, 46, 3759–
3761; (b) H. Kawasaki, H. Yamamoto, H. Fujimori,
R. Arakawa, Y. Iwasaki and M. Inada, Langmuir, 2010, 26,
5926–5933; (c) M. Chiba, M. N. Thanh, Y. Hasegawa,
Y. Obora, H. Kawasaki and T. Yonezawa, J. Mater. Chem. C,
2015, 3, 514–520.
There are no conicts to declare.
Acknowledgements
This work was performed under the Research Program of
“Dynamic Alliance for Open Innovation Bridging Human,
Environment and Materials” in “Network Joint Research Center
for Materials and Devices”. We thank the members of the
Comprehensive Analysis Center, SANKEN (ISIR), Osaka
University for TEM, XPS, and ICP-AES analysis.
18 H. Yano, Y. Nakajima and Y. Obora, J. Organomet. Chem.,
2013, 745–746, 258–261.
19 Y. Isomura, T. Narushima, H. Kawasaki, T. Yonezawa and
Y. Obora, Chem. Commun., 2012, 48, 3784–3786.
20 K. Oikawa, S. Itoh, H. Yano, H. Kawasaki and Y. Obora,
Chem. Commun., 2017, 53, 1080–1083.
21 H. Oka, K. Kitai, T. Suzuki and Y. Obora, RSC Adv., 2017, 7,
22869–22874.
22 Y. Sun, Y. Guo, X. Meng, W. Xiaohua, Y. Guo, Y. Wang,
X. Liu, Z. Zhang and Q. Lu, Catal. Lett., 2005, 100, 213–217.
23 R. Narayanan and M. A. El-Sayed, J. Am. Chem. Soc., 2003,
125, 8340–8347.
24 L. Ackermann, R. Sandmann, A. Villar and L. T. Kaspar,
Tetrahedron, 2008, 64, 769–777.
25 X. Cui, J. Li, Y. Fu, L. Liu and Q. Guo, Tetrahedron Lett., 2008,
49, 3458–3462.
26 G. Baccolini and E. Marotta, Tetrahedron, 1985, 41, 4615–
4620.
27 S. Banerjee, E. Barnea and A. L. Odom, Organometallics,
2008, 27, 1005–1014.
28 L. Jiao and T. Bach, J. Am. Chem. Soc., 2011, 133, 12990–
12993.
Notes and references
1 For reviews, see: D. F. Taber and P. K. Tirunahari,
Tetrahedron, 2011, 67, 7195–7210.
2 M. Zhang, Q. Chen and G. Yang, Eur. J. Med. Chem., 2015, 89,
421–441.
3 G. Chang, L. Yang, S. Liu, X. Luo, R. Lin and L. Zhang, RSC
Adv., 2014, 4, 30630–30637.
4 G. Nie, X. Han, J. Hou and S. Zhang, Electroanal. Chem., 2007,
604, 125–132.
5 Q. Wang, L. Xiong, F. Zhu, L. Yang and G. Chang, Polym. Int.,
2016, 65, 841–844.
6 For reviews, see: M. Inman and C. J. Moody, Chem. Sci., 2013,
4, 29–41.
7 E. Fischer and F. Jourdan, Eur. J. Inorg. Chem., 1883, 16,
2241–2245.
8 S. Wagaw, B. H. Yang and S. L. Buchwald, J. Am. Chem. Soc.,
1998, 120, 6621–6622.
9 A. Bischler, Eur. J. Inorg. Chem., 1892, 25, 2860–2879.
10 H. Tokuyama, T. Yamashita, M. T. Reding, Y. Kaburagi and
T. Fukuyama, J. Am. Chem. Soc., 1999, 121, 3791–3792.
11 K. Fujita, K. Yamamoto and R. Yamaguchi, Org. Lett., 2002, 4,
2691–2694.
29 Y. Tan and J. F. Hartwig, J. Am. Chem. Soc., 2010, 132, 3676–
3677.
30 M. Miyasaka, A. Fukushima, T. Satoh, K. Hirano and
M. Miura, Chem.–Eur. J., 2009, 15, 3674–3677.
31 F. Zhou, X. Han and X. Lu, Tetrahedron Lett., 2011, 52, 4681–
4685.
12 For reviews, see: T. Guo, F. Huang, L. Yu and Z. Yu,
Tetrahedron Lett., 2015, 56, 296–302.
´
´
13 D. Sole, F. Perez-Janer, E. Zulaica, J. F. Guastavino and
32 N. Batail, V. Dufaud and L. Djakovitch, Tetrahedron Lett.,
2011, 52, 1916–1918.
´
I. Fernandez, ACS Catal., 2016, 6, 1691–1700.
14 (a) R. C. Larock and E. K. Yum, J. Am. Chem. Soc., 1991, 113,
6689–6690; (b) R. C. Larock, E. K. Yum and M. D. Refvik, J.
Org. Chem., 1998, 63, 7652–7662.
33 D. W. Ockenden and K. Schoeld, J. Chem. Soc., 1957, 3175–
3180.
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