A new, efficient, and inexpensive copper(II)/salicylic acid complex catalyzed Sonogashira-type cross-coupling of haloarenes and iodoheteroarenes with terminal alkynes

Article abstract of DOI:10.1016/j.tet.2010.07.072

A new, efficient, and inexpensive CuCl₂/salicylic acid catalytic system has been developed to catalyze Sonogashira-type cross-coupling of haloarenes and iodoheteroarenes with terminal alkynes under mild reaction conditions to afford the corresponding coupling products in 18-95% yields. The role of salicylic acid might act as a bidentate O,O-donor ligand to activate the catalytic reactivity of copper chloride in coupling reactions was also briefly discussed.

Full text of DOI:10.1016/j.tet.2010.07.072

Tetrahedron 66 (2010) 7755e7761
Contents lists available at ScienceDirect
Tetrahedron
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A new, efficient, and inexpensive copper(II)/salicylic acid complex catalyzed
Sonogashira-type cross-coupling of haloarenes and iodoheteroarenes with
terminal alkynes
Horung-Jyh Chen, Zhe-Yi Lin, Meng-Yuan Li, Ruei-Jheng Lian, Qing-Wen Xue, Jui-Lun Chung,
*
Shu-Chih Chen, Yao-Jung Chen
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, efficient, and inexpensive CuCl2/salicylic acid catalytic system has been developed to catalyze
Sonogashira-type cross-coupling of haloarenes and iodoheteroarenes with terminal alkynes under mild
reaction conditions to afford the corresponding coupling products in 18e95% yields. The role of salicylic
acid might act as a bidentate O,O-donor ligand to activate the catalytic reactivity of copper chloride in
coupling reactions was also briefly discussed.
Received 23 March 2010
Received in revised form 20 July 2010
Accepted 26 July 2010
Available online 6 August 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Salicylic acid
Sonogashira-type cross-coupling reaction
Copper chloride
Haloarenes
Terminal alkynes
1. Introduction
important role in the reaction. For examples, recent studies have
shown that a copper catalyst associated with a P-donor ligand [such
Alkynes are useful building blocks in organic synthesis and
a basic functional group in many natural products and bioactive
compounds.1 The Sonogashira reaction (palladium complexes in
the presence of an amine and a catalytic amount of CuI catalyzed
coupling of terminal alkynes with aryl and alkenyl halides) has
been known as one of the most powerful and straightforward
methods for the construction of C(sp)eC(sp2) bonds in organic
synthesis.2 This method has been widely used for the synthesis of
natural products,3 biologically active molecules,4 and some in-
teresting and useful materials.5 However, the palladium complexes
commonly used are considerably expensive and air-sensitive, es-
pecially the involvement of a tedious multistep procedure toward
the synthesis of various phosphine ligands. These drawbacks have
limited their application for large scale reactions.6
as PPh38a], a N- or N,N-donor ligand [such as 1,10-phenan-
throline,8d,e N,N-dimethylglycine,8c ethylenediamine,8d DABCO,8f
1,10-binaphthyl-2,20-diamine (BINAM)8g], an O,O-donor ligand
[such as rac-BINOL8h and
b
-diketone8i], and a N,O-donor ligand
[such as 8-hydroxyquinoline8j] are effective catalysts in the
Sonogashira reaction. Copper nanoparticles with no Pd, ligand, and
co-catalyst also have been demonstrated to catalyze the cross-
coupling of alkynes and aryl halides to give the corresponding
disubstituted alkynes in good yields.9 It is believed that the Cu-
catalyzed coupling occurs through a CuI/CuIII mechanistic pathway,
as postulated by Miura and co-workers.8a Although significant
contributions have been made in these methods, they still have
some drawbacks, such as the high cost of ligands, in some cases
high reaction temperatures (ꢀ140 ꢁC), and/or poor substrate gen-
erality. Hence, to find other efficient, more economic, and readily
available ligands for copper-catalyzed Sonogashira type coupling
reaction with broad variety of the substrates is still desirable.
In recent reports, metal carboxylates have been extensively
studied not only due to their interesting electro-conductive, optical,
and magnetic properties,10 but also because the carboxylic group
can bind to metal ion in various modes, such as monodentate,
bidentate, and bridging.11 From the coordination chemistry point of
view, salicylic acid is a versatile ligand for chelating metal ion, since
Recently, much attention has been attracted to the use of copper
complexes as the catalysts for the Sonogashira-type cross-coupling
of aryl halides with terminal alkynes,7,8 because copper salts are
more economic and the system is relatively simple and mild. No-
tably, the ligand associated with copper has been found to play an
* Corresponding author. Fax: þ886 4 22862547; e-mail address: yjchen@drag-
on.nchu.edu.tw (Y.-J. Chen).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.072

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H.-J. Chen et al. / Tetrahedron 66 (2010) 7755e7761
it can offer two hard and strongly basic O-donor centers either from
both of carboxylic and hydroxyl group or only from the carboxylic
group as a bidentate chelator. Particularly, Cu(II) complexes of
salicylic acid are of interest from both structural and biological view
points. For example, dinuclear Cu(II) salicylates are biologically
interesting owing to their anti-inflammatory activity.12 It has been
reported that Cu(dps)2 [dps¼3,5-diisopropylsalicylate] and other
Cu(II) salicylates can show superoxide dismutase activity,13 which
may be used in the photodynamic therapy.14 Moreover, Cu(dps)2
also has been suggested to be an active ingredient in a sunscreen
composition.15 Surprisingly, although Cu(II) complexes of salicylic
acid have been demonstrated as an effectively bioactive species, no
further reports dealing with these complexes in metal-catalyzed
cross-coupling reactions have been presented up to date. To the
best of our knowledge, only two related studies have been reported.
One is from Buchwald’s group, which is an efficient Cu(I)-catalyzed
amination of aryl bromides with primary alkylamines by using
diethylsalicylamide as the ligand.16a The other one is from Fu’s
group, which also demonstrated an efficient Cu(I)-catalyzed
N-arylations of aliphatic amines by using rac-BINOL as the ligand,
but no cross-coupling reaction product was obtained in their study
while using salicylic acid as the ligand.16b In general, the catalyst of
Cu(I) species always plays an important role in the copper-cata-
lyzed cross-coupling reactions. Nevertheless, it must be noted that
the reaction is catalyzed by Cu(I) species that are either added di-
rectly as cuprous salts, or generated by the reduction of Cu(II) salts,
or by the in situ oxidation of copper metal to give Cu(I) species.
Rothenberg and co-workers have reported that there is no need for
a reducing agent as in the case of Cu(II) except reactions being
relatively slow and requiring a significant amount of catalyst.17 It is
interesting to note that the two speculated and concomitant
mechanisms usually used to interpret experimental results have
been proposed.18 In general, Cu(0) and Cu(I) starting materials and
Cu(I), Cu(II), and Cu(III) intermediates can be involved in these
coupling processes. In view of this, we are prompted to examine
salicylic acid as an efficient and versatile ligand in a variety of Cu
(II)-catalyzed cross-coupling reactions. This report will disclose our
results in the CuCl2/salicylic acid mixture catalyzed cross-coupling
reactions for arylealkyne bond formations by using this new
protocol.
found to be the most effective although K3PO4, K2CO3, and t-BuOK
were also effective. Interestingly, the ratio of CuCl2 and salicylic
acid/ligand used in this study is only equal to 1:1 while the 1:2 ratio
is usually used in most of other copper-catalyzed cross-coupling
reactions by using other bidentate ligands. Notably, this probably
indicates that this bidentate O,O-donor ligand might be more ef-
fective in stabilizing or solublizing the copper complex.
Table 1
CuCl2/salicylic acid-catalyzed Sonogashira-type cross-coupling reaction of 4-io-
doanisole with phenylacetylenea
I
CuCl2,/ salicylic acid
+
OCH3
base, solvent
OCH3
130 oC
1
2
3
Entry
CuCl2:ligand
Base
Solvent
Yieldb
Product 3
1
2
3
4
5
6
7
8
5:5
Cs2CO3
DMF
DMF
DMF
DMF
DMF
DMF
PhCH3
CH3CN
DMSO
Dioxane
MeOH
DMF
12
38
60
57
88
34
6
37
60
24
10
78
56
40
10:10
10:20
20:10
20:20
20:0
20:20
20:20
20:20
20:20
20:20
20:20
20:20
20:20
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K3PO4
9
10
11
12
13
14
K2CO3
t-BuOK
DMF
DMF
a
Reaction conditions: 4-iodoanisole (1.0 mmol), CuCl2 (5, 10, or 20 mol %), sali-
cylic acid(0, 5, 10, or 20 mol %), phenylacetylene (1.2 mmol), and base (2.0 mmol) in
solvent (2 mL) at 130 ꢁC for 36 h.
b
Only isolated yield of cross-coupling product was reported, not including
homocoupling product of phenylacetylene.
On the basis of the optimized reaction conditions obtained, we
initiated our investigation into the scope of CuCl2/salicylic acid
catalyzed Sonogashira-type coupling reactions and the results are
summarized in Table 2. By using this new protocol, the coupling
reaction of various functionalized aryl and heteroaryl iodides with
various substituted terminal alkynes can give the corresponding
arylated or heteroarylated alkynes in good to excellent yields. It has
been found that iodobenzene containing electron-withdrawing
groups, such as acetyl, cyano, nitro, and ester group (Table 2, entries
2e7) reacted with phenylacetylene to afford arylated alkynes in
very high isolated yields, while it containing electro-donating
groups, such as methoxy, amino, and methyl group often gave
lower yields even with a longer reaction time (Table 2, entries
8e13). Interestingly, no significant steric effects were observed in
this study, because highly sterically hindered ortho-substituted
iodobenzene also provided good yields with phenylacetylene and
n-butyl acetylene (Table 2, entries 9e11, 14, 16, and 18). Substituted
phenylacetylenes also reacted with aryl iodides and/or heteroaryl
iodide to give corresponding arylated products in good to very good
isolated yields even in 24 h (Table 2, entries 21e25). Under our
optimized reaction conditions, it has been found that iodohetero-
arenes can readily react with terminal alkynes in 24 h to afford the
corresponding C-arylated alkynes (Table 2, entries 25e27), but aryl
bromides reacted less effectively with terminal alkynes to provide
the expected cross coupling products in 24 h or even in extending
reaction time to 36 h (Table 2, entries 28e30). As a practical pro-
cedure, two scale-up reactions were also testified and the results
came out as expected good yields while the longer reaction time
(72 h) was needed (Table 2, entries 4 and 8).
2. Results and discussion
As a model study, we first chose to study the effect of salicylic
acid as a bidentate O,O-donor ligand on the efficiency of the CuCl2-
catalyzed cross-coupling reaction of phenylacetylene with iodo-
anisole and the results are summarized in Table 1. When the reaction
was performed with 20 mol % of CuI and 20 mol % of salicylic acid
ligand in the presence of Cs2CO3 as a base in DMF at 130 ꢁC for 36 h,
the expected cross-coupling product of 1-methoxy-4-(phenyl-
ethynyl)benzene 3 was afforded in 88% yield with homocoupling
reaction product of phenylacetylene in 6% yield (Table 1, entry 5).
For a blank test (Table 1, entry 6), a significantly lower 34% yield of
the cross-coupling product 3 was obtained with 27% isolated yield
of homocoupling product while the same reaction condition was
carried out in the absence of the salicylic acid ligand. The result
indicates that this bidentate O,O-donor ligand must play an
important role on accelerating the rate of the Cu(II)-catalyzed
cross-coupling reaction. For further optimization of the reaction
conditions, the decreasing yields of the coupling product were
observed by decreasing the added amounts of CuCl2 (20, 10, and
5 mol %) and/or salicylic acid/ligand (20, 10, and 5 mol %) (Table 1,
entries 1e4). To evaluate the effect of the solvent (Table 1, entries 5,
7e11), results showed that both of DMSO and DMF are effective, but
DMF is the best choice. For comparison on the efficiency of the base
in this coupling reaction (Table 1, entries 5, 12, 13), Cs2CO3 was

H.-J. Chen et al. / Tetrahedron 66 (2010) 7755e7761
Table 2 (continued )
7757
Table 2
CuCl2/salicylic acid-catalyzed Sonogashira-type cross-coupling reaction of various
Entry
Aryl hailides
Alkynes
Products
Yieldb
aryl halides with terminal alkynesa
H3CO
H3CO
CuCl2 (20 mol%)
salicylic acid (20 mol%)
Ar'
R
Ar
Ar
Ar'
R
22
92
84
75
73
I
ArX
or
or
+
Cs2CO3, DMF
130 oC
4
Ar = aryl,
23
24
25
COOH
I
H3CO
or heteroaryl
5
6
OH
salicylic acid
X = I, Br
OCH3
H3CO
H3CO
O2N
I
O2N
S
Entry
1
Aryl hailides
Alkynes
Products
Yieldb
89
Ph
Ph
Ph
Ph
I
Ph
S
I
OCH3
2
3
4
87
95
H3COC
I
Ph
Ph
Ph
COCH3
CN
OCH3
Ph
N
Ph
26
27
92
88
I
NC
I
N
91
I
Ph
Ph
Ph
O2N
I
NO2
86d
N
N
CN
I
NC
28
29
30
Ph
Ph
Ph
Br
5
6
88
81
Ph
Ph
Ph
18c
50
H3CO
O2N
Br
Br
Ph
Ph
OCH3
NO2
NO2
O2N
30
Ph
I
a
Reaction conditions: aryl halides and/or heteroaryl iodides (1.0 mmol), CuCl2
(20 mol %), salicylic acid (20 mol %), terminal alkynes (1.2 mmol), and Cs2CO3
(2.0 mmol) in DMF (2 mL) at 130 ꢁC for 24 h.
O
O
O
O
7
8
9
84
Ph
I
Ph
Ph
Ph
b
Isolated yield.
36 h.
88c
82d
c
H3CO
I
Ph
OCH3
d
Scale-up reaction conditions: aryl iodides (10.0 mmol), CuCl2 (20 mol %), sali-
cylic acid (20 mol %), terminal alkynes (12.0 mmol), and Cs2CO3 (20.0 mmol) in DMF
(20 mL) at 130 ꢁC for 72 h.
OCH3
I
H3CO
H2N
80c
76c
Ph
NH2
I
Based on the results as shown above, the bidentate O,O-donor
ligand of salicylic acid must play an important role on accelerating
the rate of the Cu(II)-catalyzed cross-coupling reaction. For further
understanding how salicylic acid activated the catalytic reactivity of
copper chloride in these coupling reactions, the direct isolation of
the CuCl2/salicylic acid complex from the reaction mixture has been
tried but was failed.
10
Ph
Ph
Ph
Ph
11
12
87c
87c
Ph
Ph
I
I
Although the exact structure of the CuCl2/salicylic acid complex
in these coupling reactions is still unknown, some correlated
studies have been reported. For example, Chen and co-workers
recently have reported a novel neutral mixed-valence Cu(I)Cu(II)Cu
13
14
85c
90
Ph
Ph
I
Ph
Br
Br
I
Ph
(I) linear trinuclear copper metallomacrocycle [(PPh3)2Cu]2[m-o-
OC6H4COO]2Cu, which was synthesized by treatment of KOH so-
lution of the salicylic acid with the aqueous solution of CuSO4
resulted in the formation of polynuclear copper complex, and then
followed by the reaction of this complex with PPh3 in acetonitrile.19
Interestingly, this linear trinuclear copper compound consists of
two Cu(I) ions and one Cu(II) ion which are bridged by two salic-
ylate (2ꢂ) ligands, and the external copper(I) atoms are coordinated
by four terminal PPh3. On the other hand, a variety of Cu(II)/salic-
ylate complexes also have been prepared and characterized. Some
of the results indicate that both of the carboxylic group and the
phenolate oxygen of salicylate ligands participate in the co-
ordination to Cu(II).20 Notably, it also has been known that the
unusual pKa values of the carboxylic group and phenol of salicylic
acid are 3.00 and 12.38, respectively.21 In the stronger basicity of
hydroxide reaction solution, both of carboxylic group and phenol of
salicylic acid could be deprotonated completely, but may not be for
the case in the weaker basicity of carbonate reaction solution. On
the basis of above discussion, although the exact structure of the
CuCl2/salicylic acid complex in these coupling reactions is still
15
16
C4H9
C4H9
76c
82c
I
C4H9
H3CO
OCH3
I
C4H9
H3CO
17
18
C4H9
C4H9
85c
80c
H3CO
I
C4H9
I
C4H9
C4H9
19
20
C4H9
C4H9
72c
83c
I
I
C4H9
21
70
I
Ph
OCH3
OCH3

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H.-J. Chen et al. / Tetrahedron 66 (2010) 7755e7761
unconfirmed, it is probable to expect that salicylic acid might act as
a bidentate O,O-donor ligand to activate the catalytic reactivity of
copper chloride in this study.
After the septum of tube was exchanged with a Teflon screw-cap,
the reaction mixture was heated at 130 ꢁC for the time as in-
dicated, and then allowed to cool to room temperature. The re-
action mixture was directly passed through Celite. After rinsed
with further 50 mL of ethyl acetate, the combined filtrate was
evaporated by vacuum to yield the crude product. Column chro-
matography of the residue on silica gel (hexane/EtOAc) afforded
the desired product.
Obviously, some advantages of this new protocol have been
observed. For example, salicylic acid, an inexpensive and com-
mercially available bidentate ligand, has not been used effectively
in the copper-catalyzed cross-coupling reactions up to date. On the
other hand, CuCl2 is less costive and more stable than CuI without
increasing the amount of catalyst used in the course of the
reaction. Notably, it has also been known that cuprous salt as
a catalyst generally performs more effectively than cupric salt in
accelerating the rate of cross-coupling reactions, but we have
successfully demonstrated that this new CuCl2/salicylic acid cata-
lytic system also performs effectively in the Sonogashira-type
coupling reaction.
4.3. Typical procedure for CuCl2/salicylic acid-catalyzed
Sonogashira-type cross-coupling reaction of 4-iodoanisole
with phenylacetylene (Table 1)
Typical procedure: Cs2CO3 (652 mg, 2.0 mmol), CuCl2 (27.4 mg,
0.2 mmol, 20 mol %), and salicylic acid (27.6 mg, 0.2 mmol,
20 mol %) were added to a screw-capped test tube with a septum.
The tube was evacuated with heating and back-filled with ni-
trogen three times. DMF (2 mL), 4-iodoanisole (234 mg,
1.0 mmol), and phenylacetylene (0.13 mL, 1.2 mmol) were added
by syringe at room temperature. After the septum of tube was
exchanged with a Teflon screw-cap, the reaction mixture was
heated at 130 ꢁC for 36 h, and then allowed to cool to room
temperature. The reaction mixture was directly passed through
Celite. After rinsed with further 50 mL of ethyl acetate, the
combined filtrate was evaporated by vacuum to yield the crude
product. The residue was purified by column chromatography on
silica gel using ethyl acetate/hexane as eluent to give 1-methoxy-
4-(phenylethynyl)benzene 3 (183 mg, 88%) (Table 1, entry 5).
3. Conclusion
In summary, we have successfully developed a new, efficient,
inexpensive, and experimentally simple CuCl2/salicylic acid cata-
lytic system to catalyze Sonogashira-type cross-coupling of hal-
oarenes and iodoheteroarenes with terminal alkynes under mild
reaction conditions. Using this new protocol, aryl iodides contain-
ing both electron-withdrawing groups and electron-donating
groups react effectively with terminal alkynes to provide the cor-
responding arylated alkynes in high yields, as well as in the case of
heteroaryl iodides. Further applications in the synthesis of bio-
active molecules by using our new protocol are undergoing the
investigation.
4. Experimental section
4.1. General
4.4. Spectroscopic and analytical data
4.4.1. 1-Methoxy-4-(phenylethynyl)benzene (3)22. White solid: mp
82 ꢁC (lit.22 79e81 ꢁC); 1H NMR (400 MHz, CDCl3)
d 3.83 (3H, s),
Dimethylformamide (DMF), dimethylsulfoxide (DMSO), and
toluene were freshly distilled over calcium hydride prior to use. All
reagents were purchased from Aldrich and other commercial
sources, and used without further purification. All reactions were
performed in oven-dried glassware under reaction conditions de-
scribed below. The reactions were monitored by TLC on silica gel 60
F254 (Merck, 0.15e0.20 mm), and reaction mixtures were purified
by column chromatography using silica gel 60 (Merck,
0.063e0.200 mm). NMR spectra were recorded on a Varian Mer-
cury-400 spectrometer, operating at 400 MHz and 100 MHz for 1H
and 13C, respectively. Proton and carbon spectra were performed by
using CDCl3 as solvent and tetramethylsilane (TMS) as the internal
6.86 (2H, d, J¼8.8 Hz), 7.30e7.37 (3H, m), 7.46e7.52 (4H, m); 13C
NMR (100 MHz, CDCl3)
d 55.2, 88.0, 89.4, 113.9, 115.3, 123.6, 127.9,
128.3, 131.4, 133.0, 159.6; EIMS m/z (rel int%): 209 (7), 208 (100,
[Mþ]), 193 (40), 165 (42), 139 (8); IR nmax (cmꢂ1) (KBr): 3039, 2956,
2931, 2859, 2227, 1606, 1508, 1463, 1245.
4.4.2. 1,2-Diphenylethyne (Table 2, entries 1 and 28)23. Colorless oil:
1H NMR (400 MHz, CDCl3)
d 7.42e7.45 (6H, m), 7.65e7.67 (4H, m);
d 89.3, 123.2, 128.2, 128.3, 131.5; EIMS
13C NMR (100 MHz, CDCl3)
m/z (rel int%): 178 (100, [Mþ]); HRMS calcd for C14H10: 178.0785,
found: 178.0788; IR nmax (cmꢂ1) (neat): 3019, 2278, 1642, 1571.
standard. Chemical shifts are given on the
d
scale (ppm). Coupling
4.4.3. 1-(4-(Phenylethynyl)phenyl)ethanone (Table 2, entry 2)24. Yellow
solid: mp 95e96 ꢁC (lit.24 95e96 ꢁC); 1H NMR (400 MHz, CDCl3)
constants (J) are given in hertz. Multiplicities are indicated as fol-
lows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), or
br (broadened). All coupling constants are expressed in hertz. Mass
spectra and high-resolution mass spectra were obtained with
a JEOL JMS-SX/SX 102A GC/MS/MS spectrometer. Data are reported
as m/z (relative intensity). Infrared spectra were recorded on
Hitachi 270-30 or Bruker FTIR (EQUINOX55) spectrophotometer.
Melting points were determined on a Fargo melting point appara-
tus (MP-2D) and are uncorrected.
d
2.62 (3H, s), 7.37e7.39 (3H, m), 7.54e7.57 (2H, m), 7.62 (2H, d,
J¼8.4 Hz), 7.95 (2H, d, J¼8.4 Hz); 13C NMR (100 MHz, CDCl3)
d 26.4,
88.5, 92.6, 122.5, 128.0, 128.1, 128.3, 128.7, 131.6, 131.7, 136.1, 197.1;
EIMS m/z (rel int%): 220 (80, [Mþ]), 205 (100), 176 (41), 151 (16), 117
(16); IR nmax (cmꢂ1) (KBr): 3078, 2920, 2218, 1679, 1602, 1442, 1403.
4.4.4. 4-(Phenylethynyl)benzonitrile (Table 2, entry 3)25. White
solid: mp 109 ꢁC (lit.25 106e108 ꢁC); 1H NMR (400 MHz, CDCl3)
d
7.36e7.40 (3H, m), 7.53e7.57 (2H, m), 7.58e7.65 (4H, m); 13C NMR
4.2. General procedure for CuCl2/salicylic acid-catalyzed
Sonogashira-type cross-coupling reaction of various aryl
halides with terminal alkynes
(100 MHz, CDCl3) d 87.7, 93.7, 111.5, 118.5, 122.2, 128.2, 128.5, 129.1,
131.7, 132.0, 132.1; EIMS m/z (rel int%): 203 (100, [Mþ]), 176 (6), 151
(4); HRMS calcd for C15H9N: 203.0738, found: 203.0741; IR nmax
(cmꢂ1) (KBr): 3085, 3021, 2985, 2227, 2216, 1604, 1443.
Cs2CO3 (2.0 mmol), CuCl2 (0.2 mmol), and salicylic acid
(0.2 mmol) were added to a screw-capped test tube with a septum.
The tube was evacuated with heating and back-filled with nitrogen
three times. DMF (2 mL), aryl halides (1.0 mmol), and terminal
alkynes (1.2 mmol) were added by syringe at room temperature.
4.4.5. 1-Nitro-4-(phenylethynyl)benzene (Table 2, entries
4 and
30)24. Yellow solid: mp 118e119 ꢁC (lit.24 119 ꢁC); 1H NMR
(400 MHz, CDCl3) d 7.38e7.42 (3H, m), 7.54e7.58 (2H, m), 7.67 (2H,
d, J¼7.6 Hz), 8.23 (2H, d, J¼8.4 Hz); 13C NMR (100 MHz, CDCl3)

H.-J. Chen et al. / Tetrahedron 66 (2010) 7755e7761
7759
d
87.5, 94.7, 122.1, 123.6, 128.5, 129.3, 130.2, 131.8, 132.2, 147.0; EIMS
EIMS m/z (rel int%): 192 (100, [Mþ]), 189 (19), 165 (12); IR nmax
m/z (rel int%): 223 (100, [Mþ]), 193 (16), 176 (51), 165 (17), 151 (19);
HRMS calcd for C14H9NO2: 223.0635, found: 223.0637; IR nmax
(cmꢂ1) (KBr): 3081, 2217, 1650, 1513.
(cmꢂ1) (neat): 3060, 2206, 1643.
4.4.14. 1-Methyl-4-(phenylethynyl)benzene
(Table
2,
entry
13)25. White solid: mp 72e73 ꢁC (lit.25 70e71 ꢁC); 1H NMR
4.4.6. 2-(Phenylethynyl)benzonitrile (Table 2, entry 5)26. Yellow oil:
(400 MHz, CDCl3)
d
2.35 (3H, s), 7.14 (2H, d, J¼8.0 Hz), 7.31e7.34
1H NMR (400 MHz, CDCl3)
d
7.36e7.43 (4H, m), 7.56 (1H, t,
(3H, m), 7.42 (2H, d, J¼8.0 Hz), 7.50e7.54 (2H, m); 13C NMR
J¼8.0 Hz), 7.61e7.64 (3H, m), 7.67 (1H, d, J¼8.4 Hz); 13C NMR
(100 MHz, CDCl3) d 21.5, 88.7, 89.5, 120.2, 123.5, 128.0, 128.3, 129.1,
(100 MHz, CDCl3):
d
85.6, 96.0, 115.3, 117.5, 122.0, 127.2, 128.2, 128.4,
131.4, 131.5,138.4; EIMS m/z (rel int%): 192 (100, [Mþ]),189 (15),165
(10); IR nmax (cmꢂ1) (KBr): 3052, 2963, 2216, 1510, 1441.
129.2, 131.9, 132.1, 132.3, 132.6; EIMS m/z (rel int%): 203 (100, [Mþ]),
202 (28), 191 (17), 176(15); HRMS calcd for C15H9N: 203.0741,
found: 203.0747; IR nmax (cmꢂ1) (neat): 3145, 3053, 2987, 2917,
2227, 2165, 1596, 1443.
4.4.15. 1-Bromo-2-(2-phenylethynyl)benzene
14)32. Colorless oil: 1H NMR (400 MHz, CDCl3)
m), 7.14e7.19 (1H, m), 7.26e7.31 (3H, m), 7.47e7.57 (4H, m); 13C
NMR (100 MHz, CDCl3) 88.0, 93.9, 122.7, 125.2, 125.5, 126.9,
(Table
2,
entry
d
7.03e7.10 (1H,
4.4.7. 1-Nitro-3-(phenylethynyl)benzene (Table 2, entry 6)27. Yellow
d
oil: 1H NMR (400 MHz, CDCl3)
d
7.26e7.41 (3H, m), 7.50e7.58 (3H,
128.3, 128.5, 129.2, 131.5, 132.3, 133.0; EIMS m/z (rel int%): 256
(100, [Mþ]), 202 (51), 176 (74), 151 (28), 88 (25); HRMS calcd for
C14H9Br: 255.9900, found: 255.9894; IR nmax (cmꢂ1) (neat): 3059,
2150, 1598, 1464, 842, 752.
m), 7.81 (1H, d, J¼7.6 Hz), 8.16 (1H, d, J¼8.4 Hz), 8.37 (1H, s); 13C
NMR (100 MHz, CDCl3)
d 87.1, 92.2, 122.4, 123.1, 123.7, 125.4, 126.6,
128.7, 129.3, 129.5, 129.6, 132.0, 137.4, 148.4; EIMS m/z (rel int%):
223 (100, [Mþ]), 176 (58), 151 (23); IR nmax (cmꢂ1) (neat): 3038,
2218, 1623, 1538.
4.4.16. 1-Phenylhex-1-yne (Table 2, entry 15)33. Colorless oil: 1H
NMR (400 MHz, CDCl3)
d
0.95 (3H, t, J¼7.2 Hz), 1.47e1.62 (4H, m),
4.4.8. Ethyl 4-(phenylethynyl)benzoate (Table 2, entry 7)28. Yellow
solid: mp 79e80 ꢁC (lit.28 83e84 ꢁC); 1H NMR (400 MHz, CDCl3)
2.41 (2H, t, J¼7.2 Hz), 7.24e7.28 (3H, m), 7.39e7.41 (2H, m); 13C
NMR (100 MHz, CDCl3) d 13.7,19.1, 22.0, 30.8, 80.5, 90.4, 124.1, 127.4,
d
1.40 (3H, t, J¼7.2 Hz), 4.39 (2H, q, J¼7.6 Hz), 7.37 (3H, t,
128.1, 131.5; EIMS m/z (rel int%): 158 (32, [Mþ]), 143 (52), 129 (66),
115 (100), 91 (18); HRMS calcd for C12H14: 158.1092, found:
158.1094; IR nmax (cmꢂ1) (neat): 3033, 2958, 2232, 1668, 1598.
J¼2.8 Hz), 7.54 (4H, m), 8.03 (2H, d, J¼6.8 Hz); 13C NMR (100 MHz,
CDCl3)
d 14.2, 61.0, 88.6, 92.2, 122.6, 127.8, 128.3, 128.6, 129.4,
129.7, 131.4, 131.6, 165.9; EIMS m/z (rel int%): 250 (91, [Mþ]), 205
(100), 176 (47), 151 (17); HRMS calcd for C17H14O2: 250.0995,
found: 250.0996; IR nmax (cmꢂ1) (KBr): 3059, 2982, 2219, 1710,
1606, 1442, 1278.
4.4.17. 1-(1-Hexynyl)-2-methoxybenzene
(Table
2,
entry
16)34. Yellow oil: 1H NMR (400 MHz, CDCl3)
d
0.94 (3H, t,
J¼14.6 Hz), 1.45e1.65 (4H, m), 2.47 (2H, t, J¼7.2 Hz), 3.87 (3H, s),
6.83e6.89 (2H, m), 7.23 (1H, d, J¼8.2 Hz), 7.37 (1H, d, J¼7.2 Hz); 13C
4.4.9. 1-Methoxy-4-(phenylethynyl)benzene (3) (Table 2, entries 8,
21, and 29). The data are same as compound 3 and have been
shown in Section 4.4.1.
NMR (100 MHz, CDCl3) d 13.6, 19.5, 22.0, 30.9, 55.8, 77.0, 94.6, 110.6,
113.3,120.3, 128.8, 133.6, 159.8; EIMS m/z (rel int%): 188 (100, [Mþ]),
173 (55), 159 (38), 144 (28), 131 (51), 115 (54), 102 (16), 91 (46); IR
nmax (cmꢂ1) (neat): 2957, 2932, 2871, 2232, 1777, 1648, 1462.
4.4.10. 1-Methoxy-2-(phenylethynyl)benzene
(Table
3.92 (3H, s), 6.90e6.96
2,
entry
9)29. Yellow oil: 1H NMR (400 MHz, CDCl3)
d
4.4.18. 1-(1-Hexynyl)-4-methoxybenzene
(Table
0.94 (3H, t, J¼7.2 Hz),
2,
entry
(2H, m), 7.28e7.36 (4H, m), 7.50 (1H, dd, J¼6.0, 2.4 Hz), 7.55e7.57 (2H,
17)35. Yellow oil: 1H NMR (400 MHz, CDCl3)
d
m); 13C NMR (100 MHz, CDCl3)
d
55.7, 85.7, 93.3, 110.6, 112.4, 120.4,
1.44e1.62 (4H, m), 2.88 (2H, t, J¼6.8 Hz), 3.80 (3H, s), 6.80 (2H, d,
123.5, 128.0, 128.2, 129.7, 131.6, 133.4, 159.8; EIMS m/z (rel int%): 207
(58), 208 (100, [Mþ]), 165 (36), 139 (11); IR nmax (cmꢂ1) (neat): 3075,
2956, 2931, 2859, 2216, 1594, 1492, 1463, 1261.
J¼8.7 Hz), 7.33 (2H, d, J¼8.7 Hz); 13C NMR (100 MHz, CDCl3)
d 13.6,
19.0, 22.0, 30.9, 55.2, 80.2, 88.7, 113.7, 116.2, 132.8, 158.9; EIMS m/z
(rel int%): 188 (80, [Mþ]), 173 (59), 159 (43), 145 (100), 129 (19), 115
(23), 102 (36), 91 (16); IR nmax (cmꢂ1) (neat): 3040, 2957, 2932,
2871, 2231, 1643, 1607, 1463.
4.4.11. 2-(Phenylethynyl)aniline (Table 2, entry 10)30. Yellow solid:
mp 91e94 ꢁC (lit.30 93e94 ꢁC); 1H NMR (400 MHz, CDCl3)
d
4.28
(2H, br s), 6.70e6.74 (2H, m), 7.14 (1H, t, J¼7.6 Hz), 7.33e7.38 (4H,
m), 7.52e7.54 (2H, m); 13C NMR (100 MHz, CDCl3)
86.2, 95.0,
4.4.19. 1-(2-Methylphenyl)hex-1-yne (Table 2, entry 18)36. Colorless
d
oil: 1H NMR (400 MHz, CDCl3)
d
0.94 (3H, t, J¼7.2 Hz), 1.46e1.61
108.2, 114.6, 118.3, 123.6, 128.5, 128.7, 130.0, 131.7, 132.4, 148.1; EIMS
m/z (rel int%): 193 (100, [Mþ]), 165 (28), 90 (10); HRMS calcd for
C14H11N: 193.0908, found: 193.0900; IR nmax (cmꢂ1) (KBr): 3457,
3369, 3059, 2921, 2207, 1569, 1453.
(4H, m), 2.44 (3H, s), 2.42 (2H, t, J¼6.8 Hz), 7.06e7.09 (1H, m),
7.10e7.19 (2H, m), 7.35 (1H, d, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3)
d
13.6, 19.2, 20.7, 22.0, 31.0, 79.4, 94.3, 123.8, 125.4, 127.4, 129.2,
131.7, 139.8; EIMS m/z (rel int%): 172 (44, [Mþ]), 157 (34), 143 (58),
129 (100), 115 (37), 91(13); IR nmax (cmꢂ1) (neat): 3063, 2927, 2231,
1643, 1486.
4.4.12. 1-Methyl-2-(phenylethynyl)benzene
11)8g,29. Colorless oil: 1H NMR (400 MHz, CDCl3)
7.15e7.26 (3H, m), 7.30e7.39 (3H, m), 7.49e7.55 (3H, m); 13C NMR
(Table
2,
entry
d
2.52 (3H, s)
4.4.20. 1-(3-Methylphenyl)hex-1-yne (Table 2, entry 19)37. Colorless
(100 MHz, CDCl3)
d
20.7, 88.3, 93.3, 123.0, 123.5, 125.6, 128.1, 128.2,
oil: 1H NMR (400 MHz, CDCl3)
d
0.94 (3H, t, J¼7.2 Hz), 1.47e1.64
(4H, m), 2.30 (3H, s), 2.40 (2H, t, J¼6.8 Hz), 7.07e7.10 (1H, m),
7.16e7.26 (2H, m); 13C NMR (100 MHz, CDCl3)
13.6,19.0, 21.2, 22.0,
128.3, 129.4, 131.4, 131.8, 140.1; EIMS m/z (rel int%): 192 (100, [Mþ]),
189 (37), 165 (24), 139 (4), 115 (11); IR nmax (cmꢂ1) (neat): 2972,
2215, 1642, 1493.
d
30.8, 80.6, 89.9, 123.9, 128.0, 128.3, 128.5, 132.1, 137.7; EIMS m/z (rel
int%): 172 (41, [Mþ]), 157 (50), 143 (61), 129 (100), 115 (42), 105 (21),
91 (27); IR nmax (cmꢂ1) (neat): 3038, 2958, 2228, 1648, 1580.
4.4.13. 1-Methyl-3-(phenylethynyl)-benzene
12)31. Colorless oil: 1H NMR (400 MHz, CDCl3)
(1H, d, J¼8.0 Hz), 7.22 (1H, t, J¼12.0 Hz), 7.34e7.42 (5H, m),
7.51e7.60 (2H, m); 13C NMR (100 MHz, CDCl3)
21.2, 89.0, 89.6,
123.0, 123.3, 128.1, 128.2, 128.3, 128.6, 129.1, 131.6, 132.1, 137.9;
(Table
2,
entry
d
2.25 (3H, s), 7.12
4.4.21. 1-(4-Methylphenyl)hex-1-yne (Table 2, entry 20)38. Colorless
d
oil: 1H NMR (400 MHz, CDCl3)
(4H, m), 2.32 (3H, s), 2.38 (2H, t, J¼6.8 Hz), 7.07 (2H, d, J¼8.4 Hz),
d
0.94 (3H, t, J¼7.2 Hz), 1.44e1.60

7760
H.-J. Chen et al. / Tetrahedron 66 (2010) 7755e7761
7.27 (2H, d, J¼8.4 Hz); 13C NMR (100 MHz, CDCl3)
d
13.7, 19.1, 21.4,
Supplementary data
22.0, 30.9, 80.5, 89.5, 121.0, 128.9, 131.4, 137.3; EIMS m/z (rel int%):
172 (32, [Mþ]), 157 (53), 143 (46), 129 (100), 115 (30), 91(17); IR nmax
(cmꢂ1) (neat): 3028, 2958, 2230, 1649, 1509.
1
Copies of H and 13C NMR spectra of all compounds in Tables 1
and
2 and some experimental details. Supplementary data
associated with this article can be found in the online version at
doi:10.1016/j.tet.2010.07.072.
4.4.22. 2-[(4-Methylphenyl)-ethynyl]anisole
(Table
2,
entry
22)8g. Colorless oil: 1H NMR (400 MHz, CDCl3)
d
2.36 (3H, s), 3.92
(3H, s), 6.93 (2H, dd, J¼7.6, 7.6 Hz), 7.14 (2H, d, J¼8.0 Hz), 7.30 (1H, t,
References and notes
J¼8.0 Hz), 7.44e7.50 (3H, m); 13C NMR (100 MHz, CDCl3)
d 21.4,
55.7, 85.0, 93.5, 110.5, 112.5, 120.4, 128.9, 129.5, 131.4, 133.4, 138.1,
159.7; EIMS m/z (rel int%): 222 (100, [Mþ]), 207 (27), 178 (46), 131
(26), 89 (12); HRMS calcd for C16H14O: 222.1039, found: 222.1042;
IR nmax (cmꢂ1) (neat): 3029, 2959, 2917, 2834, 2250.
1. (a) Viehe, H. G. Chemistry of Acetylene; Marcel Dekker: New York, NY, 1969;
p 597; (b) Bohlmann, F.; Burkhart, F. T.; Zero, C. Naturally Occurring Acetylenes;
Academic: New York, NY, 1973; (c) Trahanovsky, W. S. Oxidation in Organic
Chemistry; Academic: New York, NY, 1973; Vol. 5-B; (d) Hansen, L.; Boll, P. M.
Phytochemistry 1986, 25, 285; (e) Kim, Y. S.; Jin, S. H.; Kim, S. L.; Hahn, D. R. Arch.
Pharm. Res. 1989, 12, 207; (f) Matsunaga, H.; Katano, M.; Yamamoto, H.; Fujito,
H.; Mori, M.; Tukata, K. Chem. Pharm. Bull. 1990, 38, 3480; (g) Hudlicky, M.
Oxidation in Organic Chemistry; ACS Monograph 186; American Chemical Soci-
ety: Washington, DC, 1990; p 58; (h) Sonogashira, K. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, UK, 1991; Vol. 3;
p 551; (i) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079.
2. (a) Sonogashira, K. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 3, Chapter 2; (b) Sonogashira, K. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998; Chapter 5; (c) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D.
Application of Transition Metal Catalysts in Organic Synthesis; Springer: Berlin,
1998; Chapter 10; (d) Sonogashira, K. In Handbook of Organopalladium Chemistry
for Organic Synthesis; Negishi, E.-i., Meijere, A., Eds.; Wiley-VCH: New York, NY,
2002; (e) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2,
1729; (f) Erdelyi, M.; Gogoll, A. J. Org. Chem. 2001, 66, 4165; (g) Miyaura, N.; Suzuki,
A. Chem. Rev. 1995, 95, 2457; (h) Negishi, E. Handbook of Organopalladium
Chemistry forOrganic Synthesis; Wiley-Interscience: New York, NY, 2002; (i) Yong,
B. S.; Nolan, S. P. Chemtracts: Org. Chem. 2003, 205; (j) de Meijere, A.; Diederich, F.
Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004.
3. (a) Paterson, I.; Davies, R. D. M.; Marquez, R. Angew. Chem., Int. Ed. 2001, 40,
603; (b) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. 1991, 30, 1387.
4. (a) Cosford, N. D. P.; Tehrani, L.; Roppe, J.; Schweiger, E.; Smith, N. D.; Anderson,
J.; Bristow, L.; Brodkin, J.; Jiang, X.; McDonald, I.; Rao, S.; Washburn, M.; Varney,
M. A. J. Med. Chem. 2003, 46, 204; (b) Kort, M.; Correa, V.; Valentijin, A. R. P. M.;
Marel, G. A.; Potter, B. V. L.; Taylor, C. W.; Boom, J. H. J. Med. Chem. 2000, 43,
3295.
4.4.23. 1-(2-(4-Methoxyphenyl)ethynyl)-4-methylbenzene (Table 2,
entry 23)39. White solid: mp 118e121 ꢁC (lit.39 125e126 ꢁC); 1H
NMR (400 MHz, CDCl3)
d 2.36 (3H, s), 3.83(3H, s), 6.87 (2H, d,
J¼8.0 Hz), 7.14 (2H, d, J¼8.0 Hz), 7.40 (2H, d, J¼8.0 Hz), 7.46 (2H, d,
J¼8.0 Hz); 13C NMR (100 MHz, CDCl3)
d 21.5, 55.3, 88.2, 88.6, 114.0,
115.6, 120.5, 129.1, 131.3, 133.0, 138.0, 159.5; EIMS m/z (rel int%): 222
(100, [Mþ]), 207 (65), 178 (23); IR nmax (cmꢂ1) (KBr): 2967, 2817,
2190, 1643, 1510, 1452, 1246.
4.4.24. 2-[(4-Nitrophenyl)ethynyl]anisole
(Table
2,
entry
24)40. Yellow oil: 1H NMR (400 MHz, CDCl3)
d
3.93 (3H, s),
6.92e6.99 (2H, m), 7.34 (1H, t, J¼8.4 Hz), 7.50 (1H, d, J¼8.0 Hz),
7.67 (2H, d, J¼8.8 Hz), 8.19 (2H, d, J¼8.8 Hz); 13C NMR (100 MHz,
CDCl3)
d 56.0, 91.4, 91.5, 110.8, 111.3, 120.6, 123.5, 130.6, 130.8,
132.2, 133.7, 147.0, 160.2; EIMS m/z (rel int%): 253 (100, [Mþ]), 206
(30), 178 (32), 163 (31), 131 (26); IR nmax (cmꢂ1) (neat): 3104,
3071, 2965, 2837, 2183, 1591, 1511, 1460, 1380.
4.4.25. 2-(4-Methoxyphenyl)ethynylthiophene (Table 2, entry
25)41. White solid: mp 53e54 ꢁC (lit.41 53e54 ꢁC); 1H NMR
5. (a) Nalwa, H. S.; Miyata, S. Nonlinear Optics of Organic Molecules and Polymers;
CRC: Boca Raton, FL, 1997; (b) Wegner, G.; Müllen, K. Electronic Materials the
Oligomer Approach; Wiley-VCH: Weinheim, 1998; (c) Li, J.; Ambroise, A.; Yang,
S. I.; Diers, J. R.; Seth, J.; Wack, C. R.; Bocian, D. F.; Holten, D.; Lindsey, J. S. J. Am.
Chem. Soc. 1999, 121, 8927; (d) Onitsuka, K.; Fujimoto, M.; Ohshiro, N.; Taka-
hashi, S. Angew. Chem., Int. Ed. 1999, 38, 689; (e) Brunsveld, L.; Meijer, E. W.;
Prince, R. B.; Moore, J. S. J. Am. Chem. Soc. 2001, 123, 7978; (f) Wong, K.-T.; Hsu,
C. C. Org. Lett. 2001, 3, 173; (g) Mongin, O.; Porres, L.; Moreaux, L.; Merta, J.;
(400 MHz, CDCl3)
d
3.80 (3H, s), 6.86 (2H, d, J¼8.8 Hz), 6.98 (1H,
t, J¼4.8 Hz), 7.24e7.26 (2H, m), 7.45 (2H, d, J¼9.2 Hz); 13C NMR
(100 MHz, CDCl3)
d 55.2, 81.2, 93.0, 114.0, 115.0, 123.7, 126.8,
127.0, 132.4, 132.9, 159.7; EIMS m/z (rel int%): 214 (100, [Mþ]),
199 (85), 171 (37), 127 (15); HRMS calcd for C13H10OS: 214.0444,
found: 214.0435; IR nmax (cmꢂ1) (KBr): 3206, 2910, 2205, 1604,
1463.
€
Blanchard-Desce, M. Org. Lett. 2002, 4, 719; (h) Hoger, S.; Rosselli, S.;
Ramminger, A.-D.; Enkelmann, V. Org. Lett. 2002, 4, 4269.
6. For reviews, see: (a) Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-Coupling
Reactions; Wiley-VCH: Weinheim, Germany, 1998; (b) Miyaura, N. Cross-Cou-
pling Reaction; Springer: Berlin, 2002; (c) de Meijere, A.; Diederich, F. Metal-
Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, Germany, 2004; (d)
Doucei, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834; (e) Chinchilla, R.;
Nájera, C. Chem. Rev. 2007, 107, 874.
7. For special reviews on copper-catalyzed cross-couplings, see: (a) Siemsen, P.;
Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632; (b) Hassan,
J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359; (c)
Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400; (d) Beletskaya, I.
P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337.
8. For papers on the Sonogashira cross-coupling reaction catalyzed by a catalytic
amount of copper, see: (a) Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura,
M. J. Org. Chem.1993, 58, 4716; (b) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D.
Org. Lett. 2001, 3, 4315; (c) Ma, D,; Liu, F. Chem. Commun. 2004,1934; (d) Wang, Y.
F.; Deng, W.; Liu, L.; Guo, Q. X. Chin. Chem. Lett. 2005, 16, 1197; (e) Saejueng, P.;
Bates, C. G.; Venkataraman, D. Synthesis 2005,1706; (f) Li, J.-H.; Li, J.-L.; Wang, D.-
P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org. Chem. 2007, 72, 2053; (g)
Thakur, K. G.; Jaseer, E. A.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50, 2865;
(h) Mao, J.; Guo, J.; Ji, S. J. Mol. Catal. A 2008, 284, 85; (i) Monnier, F.; Turtaut, F.;
Duroure, L.; Taillefer, M. Org. Lett. 2008, 10, 3203; (j) Wu, M.; Mao, J.; Guo, J.; Ji, S.
Eur. J. Org. Chem. 2008, 4050.
9. Thathagar, M. B.; Beckers, J.; Rothenberg, G. Green Chem. 2004, 6, 215.
10. (a) Lehn, J. M. Supramolecular Chemistry, Concepts and Perspectives; VCH:
Weinheim, 1995; (b) Eddaoudi, M.; Moler, D. B.; Li, H.; Chen, B.; Reineke, T. M.;
O’Keeffe, M.; Yaghi, O. M. Acc. Chem. Res. 2001, 34, 319; (c) Maury, O.; Bozec, H.
L. Acc. Chem. Res. 2005, 38, 691; (d) Deacon, G. B.; Phillips, R. J. Coord. Chem. Rev.
1980, 33, 227.
4.4.26. 2-(Phenylethynyl)pyridine (Table 2, entry 26)42. Yellow oil:
1H NMR (400 MHz, CDCl3)
d
7.09e7.13 (1H, m), 7.22e7.28(3H, m),
7.42 (1H, d, J¼7.6 Hz) 7.55e7.57 (3H, m), 8.52 (1H, d, J¼5.2 Hz);
13C NMR (100 MHz, CDCl3)
88.5, 89.0, 122.0, 122.6, 126.9, 128.2,
d
128.8, 131.8, 135.9, 143.2, 149.8; EIMS m/z (rel int%): 179 (100,
[Mþ]), 178 (32), 151 (11), 126 (9); HRMS calcd for C13H9N:
179.0739, found: 179.0743; IR nmax (cmꢂ1) (neat): 3079, 2222,
1633, 1491, 989.
4.4.27. 3-(Phenylethynyl)pyridine (Table 2, entry 27)29. Yellow oil:
1H NMR (400 MHz, CDCl3)
d 7.26e7.30 (1H, m), 7.36e7.38 (3H, m),
7.54e7.56 (2H, m), 7.80 (1H, td, J¼8.0, 2.4 Hz), 8.55 (1H, dd,
J¼6.4 Hz), 8.77 (1H, s); 13C NMR (100 MHz, CDCl3)
d 85.8, 92.5,
120.3, 122.4, 122.9, 128.3, 128.7, 131.6, 138.3, 148.4, 152.1; EIMS m/z
(rel int%): 179 (100, [Mþ]), 151 (11), 126 (14); HRMS calcd for
C13H9N: 179.0742, found: 179.0749; IR nmax (cmꢂ1) (neat): 3056,
2220, 1491, 1410.
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We are grateful to the National Science Council of the Republic
of China and the National Chung-Hsing University for financial
support.

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