CuI/PPh3/PEG-Water: An efficient catalytic system for cross-coupling reaction of aryl iodides and alkynes

Article abstract of DOI:10.1080/00397911.2010.517363

An efficient protocol for the copper-catalyzed Sonogashira coupling of aryl iodides with terminal acetylenes in water-polyethylene glycol has been established. Both electron-rich and electron-deficient aryl iodides were arylalkynated under microwave heating or reflux in oil bath to afford good to excellent yields. Copyright

Full text of DOI:10.1080/00397911.2010.517363

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CuI/PPh3/PEG–Water: An Efficient
Catalytic System for Cross-Coupling
Reaction of Aryl Iodides and Alkynes
Gong Chen a , Jianwei Xie a , Jiang Weng a , Xinhai Zhu a , Zhanchao
Zheng a , Jiwen Cai a & Yiqian Wan a
a School of Chemistry and Chemical Engineering, Sun Yat-Sen
University , Guangzhou , China
Published online: 27 Jul 2011.
To cite this article: Gong Chen , Jianwei Xie , Jiang Weng , Xinhai Zhu , Zhanchao Zheng ,
Jiwen Cai & Yiqian Wan (2011) CuI/PPh3/PEG–Water: An Efficient Catalytic System for Cross-
Coupling Reaction of Aryl Iodides and Alkynes, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:21, 3123-3133, DOI:
10.1080/00397911.2010.517363
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517363
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Synthetic Communications1, 41: 3123–3133, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517363
CuI/PPh3/PEG–WATER: AN EFFICIENT CATALYTIC
SYSTEM FOR CROSS-COUPLING REACTION OF ARYL
IODIDES AND ALKYNES
Gong Chen, Jianwei Xie, Jiang Weng, Xinhai Zhu, Zhanchao
Zheng, Jiwen Cai, and Yiqian Wan
School of Chemistry and Chemical Engineering, Sun Yat-Sen University,
Guangzhou, China
GRAPHICAL ABSTRACT
Abstract An efficient protocol for the copper-catalyzed Sonogashira coupling of aryl iodides
with terminal acetylenes in water–polyethylene glycol has been established. Both electron-
rich and electron-deficient aryl iodides were arylalkynated under microwave heating or
reflux in oil bath to afford good to excellent yields.
Keywords Alkynation; aqueous chemistry; copper; coupling; microwave-assisted chemistry
INTRODUCTION
Because of the presence of the aryl alkynes motifs in naturally occurring
compounds and synthetic materials, as well as the extensive application of aryl
alkynes both in industry and academic laboratories, pursuing an efficient and versa-
tile strategy for construction of molecules containing aryl alkynes is of great interest.
During past decades, the Sonogashira-type reaction has proved to be one of the most
efficient and straightforward methods for the construction of carbon (sp2)–carbon
(sp) bonds.[1] Typical procedures for the Sonogashira coupling utilize a catalytic
palladium catalyst combined with CuI as a cocatalyst and a large amount of amine
as base or cosolvent[2] Dramatic modifications have been made to achieve economic
and environmentally friendly reactions, including the use of other cheaper metals
such as copper[3] and nickel[4] in place of palladium catalyst, a copper-free version,[5]
microwave irradiation technology,[3g–i,6] ionic liquid,[7] aqueous solvent,[8] and so on.
In recent years, significant efforts have been dedicated to develop economical
and mild coupling reactions carried out in aqueous media or pure water, because
Received July 21, 2009.
Address correspondence to Jianwei Xie and Yiqian Wan, School of Chemistry and Chemical
Engineering, Sun Yat-Sen University, Guangzhou 510275, China. E-mail: xiejwei@mail.sysu.edu.cn;
ceswyq@mail.sysu.edu.cn
3123

3124
G. CHEN ET AL.
these efforts would conquer one of the complications of the Sonogashira coupling:
the reaction needs degassed solvents and has to be carried out under an inert atmos-
phere. Moreover, water is the most safe (water is nontoxic and nonflammable) and
economical solvent.[9] The use of water as solvent in transition-metal-catalyzed
coupling reactions makes the workup procedure easy. Compared to the extensive
investigation of the palladium-catalyzed Sonogashira reaction in water,[8] the
copper-catalyzed cross-coupling reaction between aryl halides and terminal alkynes
remains less well studied.[3i]
Our previous experiment has demonstrated that the copper-catalyzed coupling
reaction of aryl iodides and terminal acetylenes can be conducted in water with excel-
lent yields in the presence of 1 equivalent of tetrabutylammonium bromide (TBAB)
as the phase-transfer catalyst.[3i] Compared to TBAB or other toxic phase-transfer
catalyst, polyethylene glycol (PEG) is known to be a nontoxic, recyclable, thermally
stable, and inexpensive medium for phase-transfer catalyst.[10] Recently, Lamaty and
coworkers described microwave-assisted copper-catalyzed alkynation of aryl iodides
in various pure PEGs solvent. It was performed at relatively hash condition (at
150–220 ꢀC for 1–2.5 h under microwave irradiation) with moderate yields, and the
addition of PPh3 gave no significant improvement in yield.[3h] Another microwave-
assisted procedure using water–PEG as solvent also was conducted at high reaction
temperature (175 ꢀC) with limited substrate scope.[6a] The harsh reaction conditions
make these methods difficult to apply in industry. Therefore, the development of a
highly efficient procedure for the copper-catalyzed Sonogashira reaction is still an
important topic in organic synthesis both in laboratories and in industry.
RESULTS AND DISCUSSION
As a result of our ongoing investigation on microwave-assisted coupling reac-
tions in aqueous media, [3i,11] we describe our results of using a copper-catalyzed Sono-
gashira reaction in aqueous PEGs. It is notable that the reactions performed well both
under microwave irradiation (120 ꢀC, 20–50 min) or with conventional thermal heat-
ing (reflux in 120 ꢀC oil bath, 24 h), producing good to excellent yields (Scheme 1).
Initially, the coupling reaction between 4-iodotoluene and phenyl acetylene
under microwave irradiation was employed as a model reaction to optimize the reac-
tion in water with PEG600 and a series of organic cosolvents. As summarized in
Table 1, dimethylformamide (DMF) and acetone showed beneficial effects on the
reaction, while ethanol retarded the reaction. The best result was obtained using
PEG600 as a cosolvent, resulting in 91% yield. When the ratio of water=PEG was
3:1, the yield increased to 96% (Table 1, entry 11).
Encouraged by these results, we explored further the effect of the chain length
of PEGs on the reaction efficiency under the same reaction conditions. PEG1000 and
Scheme 1. Cross-coupling reaction of aryl iodides with alkynes in PEG-water.

CuI/PPh3/PEG–WATER FOR SONOGASHIRA COUPLING
3125
Table 1. Optimization of the reaction conditions
Entry
Catalysta
Baseb
Solventc
Yieldd (%)
1
2
CuI
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
H2O
EtOH=H2O (1:1)
DMF=H2O (1:1)
52
42
86
64
91
83
74
41
47
96
77
92
91
45
78
76
79
24
29
0
3
CuI
CuI
4
Acetone=H2O (1:1)
PEG600=H2O (1:1)
PEG600=H2O (1:1)
PEG600=H2O (1:1)
PEG600=H2O (1:1)
PEG600=H2O (1:1)
PEG600=H2O (1:3)
PEG300=H2O(1:3)
PEG1000=H2O (1:3)
PEG2000=H2O (1:3)
PEG4000=H2O (1:3)
PEG600=H2O (1:3)
PEG600=H2O (1:3)
PEG600=H2O (1:3)
PEG600=H2O (1:3)
PEG600=H2O (1:3)
PEG600=H2O (1:3)
5
CuI
6
Cu(OAc)2
CuO
Cu(NO3)2
Cu2O
CuI
7
8
9
10
11
12
13
14
15
16
17
18
19
20
CuI
CuI
CuI
CuI
CuI
CuI
K3PO4
Cs2CO3
CsF
CuI
CuI
CuI
CuI
Et3N
–
a2 Equiv. PPh3 was used as ligand based on copper source.
b2 Equiv. base was used based on 4-iodotoluene.
c2 g in total, weight ratio.
dIsolated yields.
PEG2000 showed slightly less efficiency than PEG600. Substituting PEG600 with
PEG4000 led to dramatic decrease of yield from 96% to 45%. PEG300 was also less
efficient than PEG600. PEGs not only acted as cosolvent but also as a phase-transfer
catalyst (PTC), similar to crown ethers at the same reaction conditions, and the
phase catalytic activity was influenced by the PEG molecular weight, chain end
effects, and so on.[10f] Hence, we further investigated the conditions to optimize
the base and copper catalyst sources (Table 1). CuI, as expected, was remarkably
effective in the test conditions, whereas Cu(OAc)2 and CuO give moderate yields
(83% and 74%, respectively). It should be noted that K2CO3, a readily available weak
base, gave the best result among the tested bases, including KOH, K2CO3, K3PO4,
Cs2CO3, CsF, and Et3N.
The coupling reactions of various aryl iodides and alkynes were performed
under microwave irradiation to investigate the scope and limitation of the optimum
conditions. As summarized in Table 2, both electron-rich and electron-deficient aryl
iodides can be coupled with aryl alkynes smoothly at 120 ꢀC in a short reaction time.
Even the hindered o-iodotoluene could provide good yield (90%) with only a bit
longer reaction time of 30 min. The reaction between aryl iodides and hept-1-yne

3126
G. CHEN ET AL.
Table 2. Cross-coupling reaction of aryl iodides with alkynes under microwave irradiationa
Entry
1
Product
Time (min)
20
Yieldb (%)
96
2
3
4
30
30
20
88
69
92
5
30
90
6
7
20
20
97
94
8
9
20
20
50
50
93
88
87
91
10
11
12
50
86
73
13
14
50
50
81
(Continued )

CuI/PPh3/PEG–WATER FOR SONOGASHIRA COUPLING
3127
Table 2. Continued
Entry
15
Product
Time (min)
50
Yieldb (%)
82
aReaction conditions: 0.5 mmol aryl iodide, 1.2 mmol phenyl acetylene, or 1.5 mmol hept-1-yne,
0.05 mmol CuI, 0.1 mmol PPh3, 0.5 g PEG600, 1 mmol K2CO3 in 1.5 g water, 120 ꢀC, under microwave
irradiation.
bIsolated yield.
need more time (50 min) to consume the starting materials completely, and the
amount of hept-1-yne should be increased to 1.5 equivalents compared with aryl
iodides (Table 2, entries 10–15).
It was well documented that most of the palladium catalyst system in PEG
could be readily recycled. To check the reusability of this CuI=PPh3=PEG–H2O
system, the coupling reaction of 4-iodotoluene and phenyl acetylene was carried
out as a model reaction. After the initial experiment, the reaction mixture was
extracted with diethyl ether. The resulting mixture was used in the next run. The
second run of this reaction gave a little decrease in isolated yield (88%) with
Table 3. Cross-coupling reaction of aryl iodides with phenyl acetylene under
conventional thermal heating conditionsa
Entry
1
Product
Yield (%)b
89
91c
2
3
4
5
83
87
89
84
aReaction conditions: 0.5 mmol aryl iodide, 1.2 mmol phenyl acetylene,
0.05 mmol CuI, 0.1 mmol PPh3, 0.5 g PEG600, 1 mmol K2CO3 in 1.5 g water,
reflux in oil bath under balloon nitrogen gas protection for 24 h.
bIsolated yield.
cLarge-scale reaction condition: 20 mmol 4-iodotoluene, 24 mmol phenyl
acetylene, 2 mmol CuI, 4 mmol PPh3, 20 g PEG600, 10 mmol K2CO3 in 60 g
water, reflux in oil bath under balloon nitrogen gas protection for 24 h.

3128
G. CHEN ET AL.
prolongation of the reaction time to 30 min (Table 2, entry 2). The isolated yield
decreased dramatically to 69% in the third run (Table 2, entry 3).
Although a shorter reaction time is beneficial for library generation, and was
easily accomplished under microwave irradiation, the conventional thermal heating
is still a favorable option in large-scale synthesis both in industry and in academic
laboratories. Moreover, the conventional thermal heating devices are much less
expensive than a professional microwave synthesizer. Hence, we conducted the
reactions in an oil bath and also carried out the model reaction on a relative large
scale by taking 20 mmol of 4-iodotoluene and 24 mmol of phenylacetylene. As sum-
marized in Table 3, the coupling reactions proceeded equally successfully under
reflux in the CuI=PPh3=PEG–H2O system with the reaction time increasing from
minutes to hours, and the large-scale reaction proceeded without any difficulty to
give excellent yields of the corresponding product under the present conditions.
CONCLUSIONS
In summary, an efficient CuI=PPh3=PEG–H2O system has been developed for
the coupling reaction of aryl iodides and alkynes. It works well either under micro-
wave irradiation or conventional thermal heating. This offers a practical alternative
to the more general Sonogashira-type reaction procedure for both high-throughput
pharmaceutical research in laboratories and large scale synthesis in industry.
EXPERIMENTAL
Microwave-assisted coupling reactions were carried out in the CEM Discover
microwave in glass vessels (capacity 10 mL) sealed with a septum with a stirring option.
Column chromatography was performed with silica gel (200–300 mesh) purchased
from Qingdao Haiyang Chemical Co. Ltd. Thin-layer chromatography (TLC) was
carried out with Merck silica- gel GF254 plates. All products were characterized by
1
electron impact–mess spectrometry (EI-MS) and H NMR data, which were com-
1
pared to the literature. H NMR spectra were recorded at room temperature on a
Varian Mercury-Plus 300 instrument with solvent as reference. Mass spectra were
recorded on a Thermo Trace DSQ EI-mass spectrometer.
General Procedure for the Coupling Reaction of Aryl Iodides and
Terminal Acetylenes Under Microwave Irradiation
A 10 mL glass tube was charged with CuI (10 mg, 0.05 mmol), PPh3 (26 mg,
0.1 mmol), and H2O (1.5 g). The mixture was stirred for 15 min at room temperature.
PEG600 (0.5 g), aryl iodide (0.5 mmol), phenylacetylene (62 mg, 1.2 mmol), and
K2CO3 (138 mg, 1 mmol) were added to this solution. The vessel was sealed with a
septum and placed into the microwave cavity. The temperature of the mixture was
ramped from r t to 120 ꢀC under microwave irradiation, and it took 40–60 s. Once
120 ꢀC was reached, the reaction mixture was held at this temperature for 20 min.
After allowing the mixture to cool to room temperature, the reaction mixture was
extracted with EtOAc (3 ꢁ 15 mL), and the combined organic layer was dried over
Na2SO4. The solvent was removed under vacuum, and the residue was purified by
chromatography on silica gel to give the target product.

CuI/PPh3/PEG–WATER FOR SONOGASHIRA COUPLING
3129
General Procedure for the Coupling Reaction of Aryl Iodides and
Phenyl Acetylenes Under Reflux Conditions
CuI (10 mg, 0.05 mmol), PPh3 (26 mg, 0.1 mmol), and H2O (1.5 g) were added
to a 10 mL flask. The mixture was stirred for 15 min at room temperature. PEG600
(0.5 g), aryl iodide (0.5 mmol), phenylacetylene (62 mg, 1.2 mmol) and K2CO3
(138 mg, 1 mmol), were added to this solution. The resulting mixture was stirred in
oil bath preheated to 120 ꢀC (0.5 g PEG600 in 1.5 g water, bp: 101 ꢀC) under
balloon nitrogen gas protection for 24 hr. The reaction mixture was then extracted
with EtOAc (3 ꢁ 15 mL), and the combined organic layer was dried over Na2SO4.
The solvent was removed under vacuum, and the residue was purified by chromato-
graphy on silica gel to give the target product.
Spectral Data for All Products
4-(Phenylethynyl)toluene (1)[8e]
.
1H NMR (300 MHz, CDCl3): d ¼ 2.40
(s, 3H), 7.17 (d, J ¼ 8.1 Hz, 2H), 7.33–7.39 (m, 3H), 7.46 (d, J ¼ 8.1 Hz, 2H),
7.52–7.56 (m, 2H). EI-MS (m=z) ¼ 192 [M]þ.
4-(Phenylethynyl)anisole (2)[12]. H NMR (300 MHz, CDCl3): d ¼ 3.84 (s,
1
3H), 6.87–6.90 (m, 2H), 7.26–7.35 (m, 3H), 7.47–7.54 (m, 4H). EI-MS (m=z) ¼ 208 [M]þ.
2-(Phenylethynyl)toluene (3)[3j]. H NMR (300 MHz, CDCl3): d ¼ 2.42 (s,
1
3H), 7.12–7.20 (m, 3H), 7.20–7.26 (m, 3H), 7.37–7.44 (m, 3H). EI-MS (m=z) ¼ 192 [M]þ.
4-(Phenylethynyl)nitrobenzene (4)[8e] 1H NMR (300 MHz, CDCl3):
.
d ¼ 7.39–7.41 (m, 3H), 7.55–7.57 (m, 2H), 7.67 (d, J ¼ 8.4 Hz, 2H), 8.22 (d,
J ¼ 8.4 Hz, 3H). EI-MS (m=z) ¼ 223 [M]þ.
4-(Phenylethynyl)benzonitrile (5)[8e]
.
1H NMR (300 MHz, CDCl3): d ¼
7.37–7.39 (m, 3H), 7.53–7.56 (m, 2H), 7.59–7.63 (m, 4H). EI-MS (m=z) ¼ 203 [M]þ.
4-(Phenylethynyl)acetophenone (6)[8e] 1H NMR (300 MHz, CDCl3):
.
d ¼ 2.63 (s, 3H), 7.36–7.38 (m, 3H), 7.54–7.57 (m, 2H), 7.61 (d, J ¼ 8.4 Hz, 2H),
7.94 (d, J ¼ 8.1 Hz, 2H). EI-MS (m=z) ¼ 220 [M]þ.
Diphenylacetylene (7)[12]
.
1H NMR (300 MHz, CDCl3): d ¼ 7.35–7.40 (m,
6H), 7.54–7.57 (m, 4H). EI-MS (m=z) ¼ 178 [M]þ.
1-(1-Heptynyl)-4-methylbenzene (8)[13] 1H NMR (300 MHz, CDCl3):
.
d ¼ 0.96 (t, J ¼ 7.1 Hz, 3H), 1.35–1.51 (m, 4H), 1.59–1.66 (m, 2H), 2.36 (s, 3H),
2.42 (t, J ¼ 7.1 Hz, 2H), 7.10 (d, J ¼ 7.9 Hz, 2H), 7.31 (d, J ¼ 8.0 Hz, 2H). EI-MS
(m=z) ¼ 186 [M]þ.
1-(1-Heptynyl)-4-methoxybenzene (9)[12] 1H NMR (300 MHz, CDCl3):
.
d ¼ 0.94 (t, J ¼ 7.0 Hz, 3H), 1.36–1.45 (m, 4H), 1.57–1.64 (m, 2H), 2.38 (t, J ¼ 7.1 Hz,
2H), 3.81 (s, 3H), 6.80-6.83 (m, 2H), 7.32–7.35 (m, 2H). EI-MS (m=z) ¼ 202 [M]þ.
1-(1-Heptynyl)-2-methylbenzene (10)[12] 1H NMR (300 MHz, CDCl3):
.
d ¼ 0.95 (t, J ¼ 7.2 Hz, 3H), 1.35–1.53 (m, 4H), 1.60–1.67 (m, 2H), 2.43 (s, 3H),
2.47 (t, J ¼ 6.9 Hz, 2H), 7.08–7.14 (m, 1H), 7.16-7.18 (m, 2H), 7.35–7.38 (m, 1H).
EI-MS (m=z) ¼ 186 [M]þ.

3130
G. CHEN ET AL.
1-(1-Heptynyl)-4-nitrobenzene (11)[13] 1H NMR (300 MHz, CDCl3):
.
d ¼ 0.94 (t, J ¼ 6.9 Hz, 3H), 1.37–1.48 (m, 4H), 1.62–1.67 (m, 2H), 2.45 (t, J ¼ 7.2 Hz,
2H), 7.49–7.52 (m, 2H), 8.13-8.16 (m, 2H). EI-MS (m=z) ¼ 217 [M]þ.
1-(4-(Hept-1-ynyl)phenyl)ethanone (12)[3j] 1H NMR (300 MHz, CDCl3):
.
d ¼ 0.94 (t, J ¼ 7.2 Hz, 3H), 1.36–1.48 (m, 4H), 1.59–1.68 (m, 2H), 2.44 (t, J ¼ 7.2 Hz,
2H), 2.59 (s, 3H), 7.55 (d, J ¼ 8.4 Hz, 2H), 7.87 (d, J ¼ 8.1 Hz, 2H). EI-MS
(m=z) ¼ 214 [M]þ.
1-Phenyl-1-heptyne (13)[12]
.
1H NMR (300 MHz, CDCl3): d ¼ 0.94 (t,
J ¼ 7.2 Hz, 3H), 1.37–1.49 (m, 4H), 1.58–1.66 (m, 2H), 2.42 (t, J ¼ 7.1 Hz, 2H),
7.26–7.30 (m, 3H), 7.38–7.42 (m, 2H). EI-MS (m=z) ¼ 172 [M]þ.
ACKNOWLEDGMENTS
We acknowledge the National High Technology Research and Development
Program of China (863 Program), No. 2006AA09Z446, and the Foundation of
Sun Yat-Sen University for financial support of this work. We also thank CEM
Corporation for providing the Discover microwave.
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Sonogashira-type coupling of aryl halides and 1-aryl-2-(trimethylsilyl)acetylenes. Tetra-
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reaction catalyzed by palladium on carbon at low catalyst loading and by exposure to air.
Synlett 2005, 619–622; (d) Li, J. H.; Zhang, X. D.; Xie, Y. X. Efficient and copper-free
Pd(OAc)2=DABCO-catalyzed Sonogashira cross-coupling reaction. Synthesis 2005,
804–808; (e) Gholap, A. R.; Venkatesan, K.; Pasricha, R.; Daniel, T.; Lahoti, R. J.;
Srinivasan, K. V. Copper- and ligand-free Sonogashira reaction catalyzed by Pd(0)
nanoparticles at ambient conditions under ultrasound irradiation. J. Org. Chem. 2005,
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shira coupling 5-endo–dig cyclization. Tetrahedron 2006, 62, 5109–5115; (h) Li, P.;
Wang, L. An amine-, copper-, and phosphine-free Sonogashira coupling reaction catalyzed
by immobilization of palladium in organic–inorganic hybrid materials. Adv. Synth. Catal.
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using a Pd=MgLa mixed oxide. Tetrahedron Lett. 2006, 47, 3023–3026; (j) Consorti, C. S.;
Flores, F. R.; Rominger, F.; Dupont, J. A simple and efficient copper-free catalytic system
based on a palladacycle for the arylation of alkynes. Adv. Synth. Catal. 2006, 348, 133–141;
(k) Liang, Y.; Xie, Y. X.; Li, J. H. Modified palladium-catalyzed Sonogashira cross-
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2006, 71, 379–381; (l) Ruiz, J.; Cutillas, N.; Lopez, F.; Lopez, G.; Bautista, D. A
copper- and amine-free Sonogashira reaction of aryl halides catalyzed by 1,3,5-triaza-7-
phosphaadamantane palladium systems. Organometallics 2006, 25, 5768–5773; (m) Kuang,
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Sonogashira-type couplings. Org. Lett. 2003, 5, 3919–3922; (b) Appukkuttan, P.; Dehaen,
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7. (a) Fukuyama, T.; Shinmen, M.; Nishitani, S.; Sato, M.; Ryu, I. A copper-free
Sonogashira coupling reaction in ionic liquids and its application to a microflow system
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Recyclable Sonogashira coupling reactions in an ionic liquid, effected in the absence of

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both a copper salt and a phosphine. Chem. Commun. 2004, 1306–1307; (c) de Lima, P. G.;
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8. For recent papers on palladium-catalyzed Sonogashira reactions in aqueous media, see
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(Sonogashira reaction) in water. Tetrahedron Lett. 2004, 45, 8733–8736 and references
therein; (b) Wolf, C.; Lerebours, R. Palladium-phosphinous acid-catalyzed Sonogashira
cross-coupling reactions in water. Org. Biomol. Chem. 2004, 2, 2161–2164; (c) Djakovitch,
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copper-free Pd-zeolites. Tetrahedron Lett. 2004, 45, 1367–1370 (d) Genin, E.; Amengual,
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soluble m-TPPTC ligand: Steric and electronic features–Recent developments in Pd- and
Rh-catalyzed C-C bond formations. Adv. Synth. Catal. 2004, 346, 1733–1741; (e) Liang,
B.; Dai, M.; Chen, J.; Yang, Z. Copper-free Sonogashira coupling reaction with PdCl2
in water under aerobic conditions. J. Org. Chem. 2005, 70, 391–393; (f) Batchu, V. R.;
Subramanian, V.; Parasuraman, K.; Swamy, N. K.; Kumar, S.; Pal, M. Pd=C-mediated
coupling of aryl halides with terminal alkynes in water. Tetrahedron 2005, 61, 9869–
9877; (g) Li, J. H.; Hu, X. C.; Liang, Y.; Xie, Y. X. PEG-400 promoted Pd(OAc)2=
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and solutions of polyethylene glycol as green reaction media. Green. Chem. 2005, 7, 64–82.

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11. (a) Zhu, X.; Ma, Y.; Su, L.; Song, H.; Chen, G.; Liang, D.; Wan, Y. Bis
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