Synthesis of unsymmetrically disubstituted ethynes by the palladium/copper(I)-cocatalyzed sila-Sonogashira-Hagihara coupling reactions of alkynylsilanes with aryl iodides, bromides, and chlorides through a direct activation of a carbon-silicon bond

Article abstract of DOI:10.1016/j.tet.2012.03.093

In this paper, we explore the copper/palladium-cocatalyzed cross-coupling reactions of 1-aryl-2-trimethylsilylethynes with aryl iodides, bromides, and chlorides as coupling partners, to furnish unsymmetrically disubstituted ethynes in moderate to excellent yields. Various aryl iodides were subjected to reaction under the optimized conditions with 5 mol % of Pd(PPh₃) ₂ and 50 mol % of CuCl. The steric properties of the aryl iodide proved more influential to the outcome of the cross-coupling reaction than electronic factors. In addition, we succeeded in synthesizing unsymmetrical diarylethynes using two different aryl iodides in one-pot. Furthermore, under the same reaction conditions with 10 mol % of PdCl₂, 40 mol % of P(4-FC₆H₄)₃, and 50 mol % of CuCl as catalyst, we succeeded in synthesizing unsymmetrical diarylethynes from various aryl bromides. Finally, we explored reactions with aryl chlorides and duly discovered that unsymmetrical diarylethynes were obtainable in moderate to good yields when 10 mol % of Pd(OAc)₂, 10 mol % of (-)-DIOP, and 10 mol % of CuCl were used. These reactions proceed through a direct activation of a carbon-silicon bond in alkynylsilanes by CuCl to generate the corresponding alkynylcopper species via transmetalation from silicon to copper. Mechanistic investigations on the reaction of alkynylsilanes with aryl bromides confirmed that the trimethylsilyl bromide generated in situ retarded both transmetalation steps between CuCl and alkynylsilane, and between palladium(II) species formed by oxidative addition and alkynylcopper species.

Full text of DOI:10.1016/j.tet.2012.03.093

Tetrahedron 68 (2012) 4869e4881
Contents lists available at SciVerse ScienceDirect
Tetrahedron
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Synthesis of unsymmetrically disubstituted ethynes by the palladium/copper(I)-
cocatalyzed sila-SonogashiraeHagihara coupling reactions of alkynylsilanes
with aryl iodides, bromides, and chlorides through a direct activation of
a carbonesilicon bond
*
Yasushi Nishihara , Eiji Inoue, Shintaro Noyori, Daisuke Ogawa, Yoshiaki Okada, Masayuki Iwasaki,
Kentaro Takagi
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, we explore the copper/palladium-cocatalyzed cross-coupling reactions of 1-aryl-2-
trimethylsilylethynes with aryl iodides, bromides, and chlorides as coupling partners, to furnish un-
symmetrically disubstituted ethynes in moderate to excellent yields. Various aryl iodides were subjected
to reaction under the optimized conditions with 5 mol % of Pd(PPh3)2 and 50 mol % of CuCl. The steric
properties of the aryl iodide proved more influential to the outcome of the cross-coupling reaction than
electronic factors. In addition, we succeeded in synthesizing unsymmetrical diarylethynes using two
different aryl iodides in one-pot. Furthermore, under the same reaction conditions with 10 mol % of
PdCl2, 40 mol % of P(4-FC6H4)3, and 50 mol % of CuCl as catalyst, we succeeded in synthesizing un-
symmetrical diarylethynes from various aryl bromides. Finally, we explored reactions with aryl chlorides
and duly discovered that unsymmetrical diarylethynes were obtainable in moderate to good yields when
10 mol % of Pd(OAc)2, 10 mol % of (ꢀ)-DIOP, and 10 mol % of CuCl were used. These reactions proceed
through a direct activation of a carbonesilicon bond in alkynylsilanes by CuCl to generate the corre-
sponding alkynylcopper species via transmetalation from silicon to copper. Mechanistic investigations on
the reaction of alkynylsilanes with aryl bromides confirmed that the trimethylsilyl bromide generated in
situ retarded both transmetalation steps between CuCl and alkynylsilane, and between palladium(II)
species formed by oxidative addition and alkynylcopper species.
Received 18 February 2012
Received in revised form 22 March 2012
Accepted 24 March 2012
Available online 6 April 2012
Keywords:
CeSi bond activation
SonogashiraeHagihara coupling
Alkynylsilanes
Palladium
Copper
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
copper(I) co-catalyst systems, copper-free,10 palladium-free,11 sil-
ver-cocatalyzed,12 nickel-,13 iron-,14 silver-,15 rhodium-,16 and sa-
The unsymmetrical diarylethyne1 motif is common in pharma-
ceutical chemistry,2 natural products,3 and materials science.1e,4
Compounds incorporating this motif can be conveniently synthe-
sized by use of the SonogashiraeHagihara cross-coupling reaction
of terminal alkynes with aryl halides, or pseudo-halides, to con-
struct of C(sp2)eC(sp) bonds.5 This reaction employs a palladium
complex in conjunction with a copper(I) salt as a catalyst system
under basic conditions.1f,4f,6e8 The SonogashiraeHagihara reaction
has proven to be one of the most practical routes to unsymmetrical
diarylethynes, and, following on from the original protocol, various
modifications and improvements have been introduced to over-
come its identified limitations.9 Besides the original palladium/
marium-catalyzed11f protocols have all been developed.
A direct cross-coupling of alkynylsilanes without any activators,
if successful, under modified SonogashiraeHagihara coupling
conditions would provide an interesting and straightforward syn-
thetic method, especially as trimethylsilylated alkynes have pre-
viously been believed to be inert to the SonogashiraeHagihara
coupling. Accordingly, the trimethylsilyl group is often used as
a protective group in the SonogashiraeHagihara cross-coupling for
the introduction of appropriate peripheral functionalities decorat-
ing the alkyne. The silyl group can then, if desired, be removed to
furnish the target terminal alkyne,17 which after a second Sono-
gashiraeHagihara cross-coupling reaction can be converted to an
unsymmetrical diarylethyne. It follows that direct coupling of an
alkynylsilane via the CeSi bond activation would improve the ef-
ficiency of the overall process. This modification might also avoid
the decomposition of the highly reactive terminal alkynes,18 and
* Corresponding author. Fax: þ81 86 251 7855; e-mail addresses: ynishiha@
okayama-u.ac.jp, ynishiha@cc.okayama-u.ac.jp (Y. Nishihara).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.093

4870
Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
also formation of the alkyne homocoupling Glaser-type products,19
owing to the gradual generation of the alkynylcopper species when
only catalytic amount of a copper salt is required.20
2. Results and discussion
2.1. Cross-coupling reaction of alkynylsilanes with aryl
iodides
With these considerations in mind, we have developed a palla-
dium-catalyzed ‘sila’-SonogashiraeHagihara coupling of aryl tri-
flates with alkynylsilanes in the presence of a catalytic amount of
CuCl in DMF as solvent to yield unsymmetrical diarylethynes in
good to high yields.21,22 This reaction is the most straightforward
and powerful method for the formation of unsymmetrical diary-
lethynes via direct carbonesilicon bond activation without desily-
lation, compared to a typical SonogashiraeHagihara reaction. In
this reaction, transmetalation from silicon to copper has been
proposed when a copper(I) co-catalyst was used. Following our
studies, a copper-free version of this ‘sila’-SonogashiraeHagihara
reaction was achieved using a palladium/imidazolium salt sys-
tem.23 This process was applied to the copper-free sila-Sonoga-
shira-type cross-coupling of electron-poor aryl and heteroaryl
bromides or iodides, with 1-aryl-2-(trimethylsilyl)ethynes, to af-
ford the cross-coupled product in the presence of tetra-n-buty-
lammonium chloride under microwave irradiation.24 However, in
the aforementioned reactions, the yields of the desired products
from electron-rich aryl iodides were rather low and addition of
a base to activate the carbonesilicon bond was required.
In order to identify an appropriate palladium catalyst for the
sila-SonogashiraeHagihara cross-coupling reaction of 1-phenyl-2-
trimethylsilylethyne (1a, 0.3 mmol) with the electron-rich 4-
methoxyphenyl iodide (2a, 0.2 mmol) was used as a model re-
action. Stoichiometric quantities of CuCl (150 mol %) were used in
combination with 5 mol % of candidate palladium complexes at
80 ꢁC for 12 h in DMF (1 mL), the solvent of choice for homocou-
pling of alkynylsilanes26a and cross-coupling of alkynylsilanes with
aryl triflates.21,22 The results obtained are summarized in Table 1. By
using Pd(PPh3)4, the desired cross-coupled product, (4-
methoxyphenyl)(phenyl)ethyne (3a) was formed in 90% yield,
based on 2a. However, the reaction mixture contained 1,4-
diphenyl-1,3-butadiyne (4; 7% confirmed by GC and NMR, based
on 1a), presumably derived from homocoupling of 1a (entry 1). We
continued to explore other palladium catalysts for the reaction of
1a with 2a and determined that the catalyst employed had a con-
siderable influence on the yield of 3a obtained. Although
PdCl2(PPh3)2 alone delivered only a 19% yield of 3a, PdCl2(PPh3)2
combined with PPh3 (P/Pd¼2.0; 5 mol %) gave a 71% yield of 3a
(entry 2 vs 3). The basis for the high yield obtained with Pd(PPh3)4
or PdCl2(PPh3)2 with PPh3 may well be owing to stabilization of the
catalyst through coordination of excess PPh3 ligands. Among the
palladium catalysts examined in the coupling of 1a with 2a,
Pd(OAc)2 or Pd(dba)2 in the presence, or absence, of the added PPh3
Although numerous reports describe the coupling of trime-
thylsilylethyne with aryl halides under basic conditions,25 to the
best of our knowledge, there are no reports describing the synthesis
of unsymmetrical diarylethynes by Pd/Cu-cocatalyzed cross-cou-
pling of alkynylsilanes with aryl halides (iodides, bromides, and
chlorides) under neutral conditions. In continuation of our studies
Table 1
Cross-coupling of alkynylsilane 1a with aryl iodide 2a using various palladium catalystsa
Entry
Palladium catalyst
Yieldb (%)
3a
4
1
2
3
4
5
6
7
8
9
Pd(PPh3)4
90
71
19
<1
12
<1
10
8
7
11
6
<1
5
<1
2
PdCl2(PPh3)2/2PPh3
PdCl2(PPh3)2
PdCl2(NCPh)2
Pd(OAc)2/2PPh3
Pd(OAc)2
Pd(dba)2/2PPh3
Pd(dba)2
<1
10
PdCl2(dppf)c
46
a
Reaction conditions: 1a (0.3 mmol), 2a (0.2 mmol), Pd catalyst (5 mol %), and CuCl (0.3 mmol) in DMF (1 mL) at 80 ꢁC.
GC yields. Yields of 3a and 4 were based on 2a and 1a, respectively.
dppf¼1,10-bis(diphenylphosphino)ferrocene.
b
c
on a direct activation of a carbonesilicon bond in alkynylsilanes by
gave poor results (entries 5e8). PdCl2(dppf) bearing a bidentate
phosphine ligand gave 46% yield of 3a, albeit with contamination of
a relatively large amount of 4 as a by-product. In addition, other
transition metal complexes, such as Ni(cod)2 and RhCl(PPh3)3 did
not catalyze the reaction. With Pd(PPh3)4, increase of the 1a/2a
ratio to 2:1 attained the formation of 3a up to 96% yield.
a copper(I) salt,21,22,26 we herein describe the Pd-catalyzed ‘sila’-
Sonogashira-type cross-coupling reaction of alkynylsilanes with
aryl halides, which proceeds in the presence of a catalytic or sub-
stoichiometric amounts of CuCl under non-basic reaction condi-
tions, leading to various unsymmetrical diarylethynes.27

Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
4871
Table 2
Optimization of an amount of CuCl in the cross-coupling of 1a with 2a in the presence of Pd(PPh3)4 as a catalysta
Entry
X mol % of CuCl
Yieldb (%)
3a
4
1
2
3
4
5
200
150
100
50
90
96
99
94
<1
17
14
7
<1
0
10
a
Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), Pd(PPh3)4 (5 mol %) in DMF (1 mL) at 80 ꢁC.
GC yields. Yields of 3a and 4 were based on 2a and 1a, respectively.
b
With the optimized 2:1 ratio of 1a/2a for the cross-coupling
position with 1a proceeded to give the corresponding un-
symmetrical diarylethynes 3ae3g in good to excellent yields (en-
tries 1e7). However, a sterically hindered 2-substituted aryl iodides
2he2k partially retarded reaction of 1a and gave the lower yield of
the desired products 3he3k, respectively (entries 8e11). Reactions
of iodides 2l and 2m having heteroaromatic (e.g., 2-pyridyl and 2-
thienyl) substituted alkynes proved successful with the desired
cross-coupling products 3l and 3m being obtained in 69% and 68%
yields, respectively (entries 12 and 13).
reactions in hand, we next searched the amount of CuCl in the
reactions of 2a with 1a. The results are summarized in Table 2.
Although the use of an excess (>100 mol %) of CuCl afforded 3a in
over 90% yield, a significant amount of homocoupled product 4 was
also obtained (7e14%) (entries 1e3). We found a substoichiometric
amount (50 mol %) of CuCl to be optimal (entry 4), while use of
a catalytic amount (10 mol %) was found to retard the reaction
progress (entry 5).
Table 3
Sila-SonogashiraeHagihara cross-coupling reaction of alkynylsilanes 1 with aryl iodides 2a
Entry
Alkynylsilanes 1, R1¼
Iodides 2, R2¼
Time (h)
Products
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5e (1a)
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
4-MeOC6H4 (2a)
4-MeC6H4 (2b)
4-NCC6H4 (2c)
4-MeCOC6H4 (2d)
4-O2NC6H4 (2e)
4-ClC6H4 (2f)
4-EtO2CC6H4 (2g)
2-MeOC6H4 (2h)
2-MeC6H4 (2i)
2-MeCOC6H4 (2j)
2,4,6-Me3C6H2 (2k)
2-Pyridyl (2l)
2-Thienyl (2m)
2b
2c
2d
2a
C6H5 (2n)
2a
2a
2n
2a
2a
2n
2n
3
3
1
1
3
1
1
3
6
3
6
3
3
6
1
1
6
6
6
6
3
3
6
1
1
3a
3b
3c
3d
3e
3f
3g
3h
3i
84
75
89
90
92
92
93
49
66
77
36
69
68
73
78
89
71
88
83
59
77
47
75
48
49
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3j
3k
3l
1a
3m
3n
3o
3p
3o
3d
3p
3q
3r
3s
3t
4-MeOC6H4e (1b)
1b
1b
4-NCC6H4 (1c)
4-MeCOC6H4 (1d)
1d
4-O2NC6H4 (1e)
4-F3CC6H4 (1f)
2-Pyridyl (1g)
2-Thienyl (1h)
4-t-BuMe2SiOC6H4 (1i)
n-C6H13 (1j)
3u
3v
a
Conditions: 1 (2.0 mmol); 2 (1.0 mmol); CuCl (50 mol %); Pd(PPh3)4 (5 mol %); DMF (5 mL).
Isolated yields based on aryl iodides 2.
b
The generality of the cross-coupling reactions of a wide range of
In addition, reaction of alkynylsilanes 1be1h, which features
various aromatic and heteroaromatic groups also underwent suc-
cessful cross-coupling reaction and gave the corresponding un-
symmetrical diarylethynes 3ne3t in up to 89% yield (entries
14e23). The reaction was also applied to the cross-coupling
alkynylsilanes 1ae1j with aryl iodides 2ae2n was studied under
our optimized conditions, i.e., 50 mol % of CuCl and 5 mol % of
Pd(PPh3)4 and the results are summarized in Table 3. The reactions
of various aryl iodides 2 bearing the substituents in the para-

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Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
reaction of alkynylsilane 1i having
a
tert-butyldimethylsilyl
(TBDMS) group as a protecting group. In contrast to the palladium-
catalyzed cross-coupling reactions of alkynylsilanes (Hiyama cou-
pling) in the presence of a fluoride ion activator,28 which gives
desilylation, 1i smoothly coupled with 2n to give 3u wherein the
TBDMS group remained intact (entry 24). Alkyl-substituted alky-
nylsilane 1j also coupled with 2n to give 3v in 49% yield (entry 25).
It is of note that this reaction of aryl iodides 2 considerably
surpasses those of the corresponding aryl triflates as we reported
previously,22 probably owing to the much more reactive nature of
the CeI bond in 2. For instance, the reactions of 1c with 2a, 1d with
2n, and 1d with 2a furnished cross-coupled products 3o, 3d, and 3p
in 71%, 88%, and 83% yields, respectively, whereas the corre-
sponding reactions with aryl triflates delivered much lower yields
(27%, 30%, and 19%, respectively). Therefore, the use of aryl iodides
2 is superior to aryl triflates for the synthesis of 3.
The possibility that the in situ generated alkynylcopper species
could react with aryl iodides 2 via a direct oxidative addition
mechanism to form a copper(III) complex (a proposed intermediate
of StephenseCastro reaction),29 which, by reductive elimination,
expels the cross-coupled products 3 cannot be ruled out as very
recently we have observed Cu-catalyzed sila-Sonogashir-
aeHagihara couplings can occur without any addition of a palla-
dium catalyst.30
The direct transformation of a CeSi bond enables the double
arylation of bis(trimethylsilyl)ethyne (5) in place of acetylene. In-
deed, reaction of 5 with 2 M equiv of 4-methoxyphenyl (2a) and 4-
cyanophenyl iodides (2c) furnished the corresponding symmetrical
diarylethynes 6a and 6b in 19% and 72% yields, respectively (Eq. 1).
This new method for the synthesis of symmetrical diarylethynes
could prove highly useful since precise manipulation of gaseous
acetylene is experimentally difficult, although acetylene is gener-
ally used for the synthesis of symmetrical diarylethynes through
a typical SonogashiraeHagihara reaction.
Scheme 1. The one-pot sequential sila-SonogashiraeHagihara couplings of bis(-
trimethylsilyl)ethyne (5).
CuCl and 10 mol % of Pd(dba)2 as a palladium precursor, the re-
action of alkynylsilane 1a with aryl bromide 7a was investigated.
The results are summarized in Table 4. Since we have found the best
ratio of Pd/ligand to be 1:4 in the case of the cross-coupling re-
actions of alkynylsilanes 1 with aryl iodides 2 (vide supra), 40 mol %
of various ligands were added. When PPh3 was used, the cross-
coupled product 3b was obtained, alongside small amounts (3%)
of the undesired homocoupled product 4 (entry 1). Increasing the
amount of PPh3 added to the reaction resulted only in a lowering of
reaction yield (entries 2 and 3). Successful cross-coupling reaction
utilizing electron-deficient phosphine ligands such as P(4-
F3CC6H4)3 and P(4-ClC6H4)3 furnished 3b in 56% yield (entries 4
and 5). The best yield was achieved with P(4-FC6H4)3, although
a 40 mol % ligand loading was necessary (entry 6e8). An electron-
withdrawing bidentate ligand, (4-FC6H4)2P(CH2)4P(4-FC6H4)2, was
Additionally, the utility of the present sila-Sonogashir-
aeHagihara cross-coupling reaction via a direct activation of a car-
bonesilicon bond is demonstrated by a more challenging one-pot
synthesis of unsymmetrical diarylethynes 3, starting from 5. The
one-pot sila-SonogashiraeHagihara reactions of 5 with a sequential
addition of the first aryl iodide (R1eI) and the second aryl iodide
(R2eI) allowed us to synthesize unsymmetrical diarylethynes 3 as
shown in Scheme 1. Subsequent addition of two different aryl io-
dides resulted in three-component coupling of 5, R1-I, and R2-I to
give the corresponding products (R1eC^CeR2) 3o and 3w in 49%
and 93% GC yields, respectively.
found to be ineffective (entry 9). The reaction did not occur in the
absence of either the palladium catalyst or the copper catalyst.
We next examined the effect of a palladium source in the re-
action of 1a with 7a to afford the cross-coupled product 3b, as
shown in Table 5. As with cross-coupling reaction performed above
with various Pd(0) and Pd(II) species the desired product 3b was
contaminated with the homocoupled product 4. Among the cata-
lysts examined, PdCl2 was found to be the best catalyst affording
the cross-coupled product 3b in 70% yield, when 4 M equiv of P(4-
FC6H4)3 were used as an ancillary ligand.
The scope and limitations for the reactions of alkynylsilanes 1
with aryl bromides 7 were investigated under the optimized con-
ditions (i.e., 50 mol % of CuCl,10 mol % of PdCl2, and 40 mol % of P(4-
FC6H4)3). The results obtained are summarized in Table 6. Notable
here is that the correlation between substitution of the aryl bro-
mide 7 and their reactivity are considerably similar to that observed
for the aryl iodides 2, probably owing to the same trend in oxidative
addition of Pd(0) to the CeX bond of 2 (X¼I) and 7 (X¼Br). In
2.2. Cross-coupling reaction of alkynylsilanes with aryl
bromides
We progressed to employ 4-methylphenyl bromide (7a) as the
coupling partner, since aryl bromides are generally less expensive
than aryl iodides.31 With a substoichiometric amount (50 mol %) of

Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
4873
Table 4
Ligand effect of cross-coupling of alkynylsilane 1a with aryl bromide 7aa
Entry
Ligand
PPh3
X mol %
Yieldb (%)
3b
4
1
2
3
4
5
6
7
8
9
40
50
60
40
40
40
30
20
20
51
44
38
56
56
60
39
26
23
3
<1
<1
6
6
7
7
5
6
P(4-F3CC6H4)3
P(4-ClC6H4)3
P(4-FC6H4)3
c
a
Reaction conditions: 1a (0.3 mmol), 7a (0.2 mmol), Pd(dba)2 (10 mol %), and CuCl (0.1 mmol) in DMF (1 mL) at 100 ꢁC.
GC yields. Yields of 3b and 4 were based on 7a and 1a, respectively.
(4-FC6H4)2P(CH2)4P(4-FC6H4)2.
b
c
general, electron-rich aryl bromides such as 7a and 7b gave the
group cleanly coupled with aryl bromide 7n to afford 3u without
removal of a TBDMS group in 91% yield (entry 21). This cross-
coupling reaction was applicable to an alkyl-substituted alky-
nylsilane 1j, which gave 3v in 53% yield, upon coupling with an aryl
bromide 7n (entry 22).
desired products 3a and 3b in lower yields (entries 1 and 2). On the
other hand, aryl bromides with an electron-withdrawing sub-
stituent in the para-position, for example, 7ce7h were viable
coupling partners and gave the products 3ce3g, and 3r in excellent
yields (entries 3e8). The reaction of 1a with bulkier aryl bromides
7ie7k gave the corresponding cross-coupled products 3h, 3i, and
3k in 50%, 52%, and 38% yields, respectively (entry 9e11). 2-Pyridyl-
(7l) and 2-thienyl (7m) bromides were treated with 1a to afford 3l
and 3m, in 46% and 76% yields, respectively (entries 12 and 13). We
further studied the reaction of various alkynylsilanes 1be1d and
1fe1h with aryl bromides 7 to afford the corresponding cross-
coupled products 3 in moderate yields (entries 14e20). However,
a combination of electron-deficient alkynylsilanes and electron-
rich aryl bromides gave a lower yield of the cross-coupled prod-
ucts (entries 16 and 17). Therefore, the appropriate combination of
alkynylsilanes 1 and aryl bromides 7 is important for the formation
of 3 in high yield. Again, alkynylsilane 1i bearing a silyl protective
2.3. Cross-coupling reaction of alkynylsilanes with aryl
chlorides
We finally examined present sila-SonogashiraeHagihara cross-
coupling reaction using an aryl chloride as a coupling partner.
Aryl chlorides are less expensive and more easily available, but
generally more challenging substrates for coupling reactions
compared to the corresponding aryl bromides and iodides. Al-
though they have been believed to be inert due to a difficulty of an
insertion of palladium(0) to the CeCl bond of the aryl chloride,
recently, significant progress of the efficient palladium catalyst
Table 5
Cross-coupling of alkynylsilane 1a with aryl bromide 7a using various palladium catalystsa
a Pd precursor (10 mol %)
P(4-FC6H4)3 (40 mol %)
CuCl (50 mol %)
+
SiMe3
Ph
Me
Br
Me
Ph
DMF
100 ºC, 12 h
1a
(0.3 mmol)
7a
(0.2 mmol)
3b
Entry
Palladium catalyst
Yieldb (%)
3b
4
1
2
3
4
5
6
7
8
9
Pd(dba)2
Pd(OAc)2
PdCl2
PdCl2(NCPh)2
PdCl2(NCMe)2
Pd(OCOCF3)2
Pd(acac)2
Na2PdCl4
67
53
70
62
66
54
55
51
45
6
<1
4
4
3
2
<1
3
[PdCl(
p-allyl)]2
3
a
Reaction conditions: 1a (0.3 mmol), 7a (0.2 mmol), Pd catalyst (10 mol %), and CuCl (0.1 mmol) in DMF (1 mL) at 100 ꢁC.
GC yields. Yields of 3b and 4 were based on 7a and 1a, respectively.
b

4874
Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
Table 6
Sila-SonogashiraeHagihara cross-coupling reaction of alkynylsilanes 1 with aryl bromides 7a
PdCl2 (10 mol %)
P(4-FC6H4)3 (40 mol %)
CuCl (50 mol %)
R1
R2
R1
1a-1d, 1f-1j
SiMe3
Br R2
+
DMF
100 °C, 12 h
7a-7n
3
Entry
Alkynylsilanes 1, R1¼
Bromides 2, R2¼
Products
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5e (1a)
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
4-MeC6H4 (7a)
4-MeOC6H4 (7b)
4-NCC6H4 (7c)
4-MeCOC6H4 (7d)
4-O2NC6H4 (7e)
4-ClC6H4 (7f)
4-EtO2CC6H4 (7g)
4-F3CC6H4 (7h)
2-MeOC6H4 (7i)
2-MeC6H4 (7j)
2,4,6-Me3C6H2 (7k)
2-Pyridyl (7l)
2-Thienyl (7m)
7c
3b
3a
3c
3d
3e
3f
3g
3r
3h
3i
70
54
99
99
92
84
93
97
50
52
38
46
76
98
42
50
32
73
44
38
91
53
9
10
11
12
13
14
15
16
17
18
19
20
21
22
3k
3l
1a
3m
3o
3p
3o
3p
3r
4-MeOC6H4e (1b)
1b
7d
7b
7b
4-NCC6H4 (1c)
4-MeCOC6H4 (1d)
4-CF3C6H4 (1f)
2-Pyridyl (1g)
2-Thienyl (1h)
4-t-BuMe2SiOC6H4 (1i)
n-C6H13 (1j)
C6H5e (7n)
7n
7n
7n
7n
3l
3m
3u
3v
a
Conditions: 1 (0.3 mmol); 7 (0.2 mmol); CuCl (50 mol %); PdCl2 (10 mol %); P(4-FC6H4)3 (40 mol %); DMF (1 mL) at 100 ꢁC.
GC yields based on aryl bromides 7.
b
systems for SonogashiraeHagihara couplings of aryl chlorides has
bis(diphenylphosphino)butane) was used, indicating that an ap-
propriate bite angle is highly important to successful cross-
coupling reaction in this case (entries 9e13). We next explored
various bidentate phosphine ligands bearing cyclic moieties, in-
cluding dppf (1,10-bis(diphenylphosphino)ferrocene) (entries
14e19). Among the ligands examined, (ꢀ)-DIOP (2,2-dimethyl-1,3-
dioxolane-4,5-(diyl)bis(methylene)bis(diphenylphosphine)) was
found to be the best, with a 58% yield of 3d (entry 16). Again, this
indicated that a C4-tethered bidentate phosphine ligand could
improve the yield of 3d. As a palladium precursor, Pd(OAc)2 pro-
vided the best yield of the cross-coupled product in 62% yield in
combination with (ꢀ)-DIOP, which markedly surpasses the yield
previously obtained with PdCl2(dppb). However, other transition
metal catalyst systems, for example, Ni(cod)2/(ꢀ)-DIOP and
Pt(cod)2/dppb were completely ineffective. Increasing the
Pd(OAc)2/(ꢀ)-DIOP ratio had a significant effect on yield of 3d; 62%
yield (1:1) and 25% (1:2), respectively.
The reactions with other copper salts than CuCl were also ex-
plored, although lower yields of 3d were obtained with CuTC33
(18%), CuOAc (15%), Cu(OAc)2 (17%), and CuOt-Bu$KCl (20%) under
our optimized conditions. In all cases the reaction mixture con-
tained unreacted starting materials, but 1,4-diphenyl-1,3-
butadiyne (4) derived from homocoupling of 1a was not detect-
able by either GC or 1H NMR spectroscopy.
been made.8d,32
We have already reported that a catalytic amount of CuCl
(10 mol %) and PdCl2(dppb) (10 mol %) is the most effective catalyst
system in the cross-coupling reaction of trimethylsilylethyne 1a
with 4-acetylphenyl chloride (8a); this reaction gives rise to the
cross-coupled product 4-(phenylethynyl)phenylethanone (3d) in
47% yield.22 Accordingly, we first reexamined the ligand effect as
shown in Table 7. As a model reaction, we conducted the cross-
coupling reaction of 1a (0.48 mmol) with 8a (0.4 mmol) in the
presence of a catalytic amount of CuCl (10 mol %) and 10 mol % of
Pd(dba)2 (dba¼dibenzylideneacetone) in DMF at 120 ꢁC for 48 h.
The results of our studies are summarized in Table 7. Combination
of Pd(dba)2 with PPh3 (P/Pd¼2.0; 10 mol %) gave only 5% yield of
a cross-coupled product, 3d (entry 1). Other electron-deficient and
-rich monodentate phosphine ligands did not give the satisfactory
results (entries 2e5). In regard to the smooth oxidative addition
step, foregoing studies of the palladium-catalyzed cross-couplings
of aryl chlorides suggested that electron-rich phosphine ligands
may activate the less reactive carbonechlorine bond. Although
PCy3 and Pt-Bu3 are known to accelerate various cross-coupling
reactions using aryl chlorides, in this case they proved ineffective
(entries 6 and 7). In conjunction with these observations, we pos-
tulate that a mutual decelerating effect between the nucleophilic
phosphine ligands and the added CuCl as a phosphine scavenger in
the oxidative addition and transmetalation steps for the catalytic
cycle can impede reaction. Systematically, the series of bidentate
phosphine ligands Ph2P(CH2)nPPh2 (n¼1e5) was examined. The
reactions were carried out with the 1:1 molar ratio of Pd(dba)2 to
dppm (n¼1, 1,1-bis(diphenylphosphino)methane) resulting in the
formation of the cross-coupled product 3d in only 7% yield (entry
9). The reaction using other diphosphine ligands with increasing
numbers of the methylene spacer units revealed that up to a 43%
yield of 3d could be obtained when dppb (n¼4, 1,4-
An important observation was made for a catalyst derived from
Pd(OAc)2 and (ꢀ)-DIOP: the presence of CuCl has a deleterious ef-
fect on the desired cross-coupling reaction.34 More than 10 mol % of
CuCl was found to suppress the cross-coupling. Although the use of
10 mol % amounts of CuCl did not disturb the reaction progress and
produced 3d in 62% yield, the use of 30 mol % and 50 mol % of CuCl
afforded 3d in 13% and 8% yields, respectively. Thus 10 mol % of CuCl
appears optimal.
Reactions of a variety of aryl chlorides 8 under the optimized
conditions were conducted to the cross-coupling with 1. The results

Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
4875
Table 7
Ligand effect of cross-coupling of alkynylsilane 1a with aryl chloride 8aa
Entry
Ligand
Yieldb (%)
1
2
3
4
5
6
7
8
PPh3
5
29
3
35
10
13
18
<1
7
P(2-tolyl)3
P(4-tolyl)3
P(4-FC6H4)3
P(4-MeOC6H4)3
PCy3
Pt-Bu3
PMe3
9
Ph2P(CH2)PPh2
Ph2P(CH2)2PPh2
Ph2P(CH2)3PPh2
Ph2P(CH2)4PPh2
Ph2P(CH2)5PPh2
o-(PPh2)2C6H4
dppf
10
11
12
13
14
15
16
17
18
19
5
14
43
24
<1
28
58
22
31
28
(ꢀ)-DIOP
rac-BINAP
DPEphos
(S)-PHANEphos
a
Reaction conditions: 1a (0.48 mmol), 8a (0.4 mmol), Pd(dba)2 (10 mol %), and CuCl (0.04 mmol) in DMF (1 mL) at 120 ꢁC.
GC yields. Yield of 3d was based on 1a.
b
are shown in Table 8. Unfortunately, electronically rich aryl chlo-
rise to the formation of multiple products including disiloxane
derived from the starting material. Alkyl-substituted alkynylsilane
1j smoothly reacted with 8c afforded the desired product 3ee in
81% yield (entry 20).
rides, such as 4-methoxyphenyl chloride (8a) and 4-methylphenyl
chloride (8b), completely retarded reaction and gave no desired
product (entries 1 and 2). However, reactions of 1a with activated
aryl chlorides 8c and 8d at 120 ꢁC did take place and gave the
corresponding cross-coupled products 3c and 3d in moderate
yields (entries 3 and 4). However, the reactions of 1a with 4-
nitrophenyl chloride (8e) and 4-trifluoromethylphenyl chloride
(8f) gave the lower yields (10% and 34%, respectively) of 3e and 3f
(entries 5 and 6). Heteroaromatic chlorides such as the 2-pyridyl
and 2-thienyl systems gave contrasting results with cross-
coupling products 3l and 3m being obtained in 66% and <1%
yields, respectively (entries 7 and 8). With these results in hand,
aryl chlorides 8c, 8d, and 8g were subjected to reaction with vari-
ous alkynylsilanes 1, since it was evident that only activated aryl
chlorides underwent effective reaction. Alkynylsilane 1b bearing an
electron-donating methoxy group coupled smoothly with 8c, 8d,
and 8g to give the corresponding unsymmetrical diarylethynes 3o,
3p, and 3s in 90%, 50%, and 51% yields, respectively. Alkynylsilanes
1f and 1g having a CF3 group in the 3- or 4-position furnished the
moderate yields of cross-coupled products 3 (entries 13e16). An
advantage of the fluoride-free conditions is evident for the reaction
of TBDMS-protected alkynylsilane 1i with 8d when compared to
the reaction under typical Hiyama coupling conditions28,35 (entry
19). Under the conditions in the presence of CuCl, selective cross-
coupling occurred to generate 3dd in 50% yield. Under Hiyama
coupling conditions with TBAF as an activator, the reactions gave
2.4. Reaction mechanism
Concerning the mechanism, we proposed catalytic cycles of the
cross-coupling reaction using alkynyltrimethylsilanes 1 and aryl
halides 2, 7, and 8, as depicted in Scheme 2. On the basis of our
previous studies, in a first step, it seems reasonable to propose
transmetalation between CuCl and the alkynylsilanes 1 to generate
an alkynylcopper species 9.26e In the case of PdCl2 (for aryl bro-
mides) and Pd(OAc)2 (for aryl chlorides), the Pd(II) complexes
might be reduced by the formed alkynylcopper species 9 to the
unsaturated Pd(0) complexes, generating homocoupled conjugated
diyne 4 as a by-product. This process results in the requirement for
a slightly excess of alkynylsilanes 1 in the reaction. Oxidative ad-
dition of aryl halides to Pd(0) generates the arylpalladium(II) halide
10. Subsequently, alkynylcopper species 9 causes another trans-
metalation to palladium to produce an intermediate 11, whose re-
ductive elimination can then afford the unsymmetrical
diarylethynes 3, and regenerate the Pd(0) catalyst. It is noteworthy
that the reaction between 9 and 10 generates copper(I) halides,
which can serve as the reagent for transmetalation with alky-
nylsilanes 1 in the other catalytic cycles.

4876
Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
Table 8
Sila-SonogashiraeHagihara cross-coupling reaction of alkynylsilanes 1 with aryl chlorides 8aa
Entry
Alkynylsilanes 1, R1¼
Chlorides 8, R2¼
Time (h)
Products
Yieldb (%)
1
2
3
4
C6H5e (1a)
1a
1a
1a
4-MeOC6H4 (8a)
4-MeC6H4 (8b)
4-NCC6H4 (8c)
4-MeCOC6H4 (8d)
48
48
6
24
3
3a
3b
3c
3d
3e
<1
<1
51 (47)
62 (57)
(10)
5
1a
4-O2NC6H4 (8e)
6
1a
4-F3CC6H4 (8f)
6
3r
(34)
7
8
9
1a
1a
2-Pyridyl (8g)
2-Thienyl (8h)
3
3
12
12
3
3l
56 (60)
<1
3m
3o
3p
3s
3x
3y
4-MeOC6H4e (1b)
1b
1b
4-MeCOC6H4 (1d)
4-CF3C6H4 (1f)
3-CF3C6H4 (1k)
1k
8c
8d
8g
8g
8c
8c
8d
8g
8c
8d
8d
8c
8d
90 (71)
50 (34)
51 (45)
44 (36)
75 (54)
74 (63)
(48)
(65)
(38)
(37)
(50)
10
11
12
13
14
15
16
17
18
19
20
21
3
24
24
12
12
48
48
12
12
12
3z
3aa
3bb
3cc
3x
3dd
3ee
3ff
1k
2-Pyridyl (1g)
1g
4-t-BuMe2SiOC6H4 (1i)
n-C6H13 (1j)
81 (70)
(12)
1j
a
Conditions: 1 (1.2 mmol); 8 (1.0 mmol); CuCl (10 mol %); Pd(OAc)2 (10 mol %); (ꢀ)-DIOP (10 mol %); DMF (5 mL).
GC yields based on aryl iodides 8. Isolated yields were shown in parentheses.
b
X
R2
2, 7, 8
Ln
R2
X
Pd
10
CuX
SiMe3X
(X = I, Br, Cl)
2
R1
Cu
(X = I, Br, Cl)
9
Pd(0)
Pd(II)
R1
R1
R1
SiMe3
n Pd R2
L
R1
Cu
4
1
9
R1
R2
R1
11
3
Scheme 2. Plausible catalytic cycles of sila-SonogashiraeHagihara cross-coupling reactions of aryl halides (X¼I (2), Br (7), and Cl (8)) with alkynylsilanes 1 in Cu(I)/Pd(0) co-catalyst
system.
We have already reported that counter ions of a halogenated
copper(I) salt dramatically affected the sila-SonogashiraeHagihara
cross-couplings of alkynylsilanes 1. CuCl seems to play an impor-
tant role for generation of an alkynylcopper species 9 via cleavage
of the carbonesilicon bond owing to the high affinity of silicon and
the chloride anion. Thus, CuCl is the most effective among copper(I)
salts for transmetalation of alkynylsilanes 1, while CuBr and CuI are
less effective for the transmetalation from silicon to copper, even
though they were reportedly effective for coupling reactions using
organoboron36 and organotin37 reagents. These chemical proper-
ties of CuBr and CuI caused the excessive addition of CuCl as a co-
catalyst up to 50 mol % in the case of the cross-couplings using
aryl iodides and bromides. On the contrary, if the regenerated
copper catalyst is effective for the transmetalation of the alkynyl
group from silicon to copper, an initial addition of 10 mol % of CuCl
is enough for completion of the catalytic cycles in the case of re-
actions with aryl chlorides.
In regard to a different effect of a copper salt, another impor-
tant factor to be discussed is the formation of SiMe3X (X¼I, Br, Cl),
generated by transmetalation between alkynylsilanes 1 and CuCl
and/or the regenerated CuI and CuBr during the reaction. In order
to gain a mechanistic insight into the effect of SiMe3X, we in-
vestigated the reaction of an alkynylsilane 1a with an aryl bromide
5a in the presence or absence of SiMe3X as shown in Eq. 2. Un-
ambiguously, the reaction without an addition of SiMe3X gave the
cross-coupled product 3b in 70% yield, but the yields are de-
creased (X¼Cl; 58%, X¼Br; 12%) when an equimolar amount of
SiMe3X was added.

Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
4877
Since we additionally confirmed that the oxidative addition step
4. Experimental section
4.1. General
of 7a to Pd was not affected by the addition of SiMe3Br, we eluci-
dated transmetalation of 1a with CuBr in the presence or absence of
SiMe3X (X¼Cl and Br). As shown in Eq. 3, we found that trans-
metalation from silicon to copper was obviously retarded by ad-
dition of SiMe3X (X¼Cl and Br) and that the effect of SiMe3Br is
much more remarkable. Based on these comparisons, we postu-
lated the retardation process as follows: CuCl first coordinates to
a triple bond in alkynylsilanes 1, followed by the alkynyl group
transfer from silicon to copper to generate alkynylcopper species 9.
But, SiMe3Br would interact with alkynylsilanes 1 and inhibit the
approach of CuCl to a triple bond of alkynylsilanes, leading to the
suppression for the generation of alkynylcopper species 9. In cross-
couplings with aryl bromides, 50 mol % of CuCl was essential to
proceed the reaction, because the generated CuBr is not so effective
for transmetalation of alkynylsilanes 1 and the formed SiMe3Cl also
disturbs the transmetalation.
All the reactions were carried out under an Ar atmosphere using
standard Schlenk techniques. Glassware was dried in an oven
(150 ꢁC) and heated under reduced pressure before use. For thin
layer chromatography (TLC) analyses throughout this work, Merck
precoated TLC plates (silica gel 60 GF254, 0.25 mm) were used. Silica
gel column chromatography was carried out using Silica gel 60N
(spherical, neutral, 40e100 mm) from Kanto Chemicals Co., Ltd.
Copper(I) chloride, bromide, and iodide were purified by the liter-
ature method.38
4.2. Materials
The following alkynylsilanes were prepared by literature pro-
cedures:trimethyl(phenylethynyl)silane(1a),39 {(4-methoxyphenyl)
3. Conclusion
ethynyl}trimethylsilane (1b),39 {(4-cyanophenyl)ethynyl}trimethyl-
silane (1c),40 {(4-acetylphenyl)ethynyl}trimethylsilane (1d),41 {(4-
nitorophenyl)ethynyl}trimethylsilane (1e),41 trimethyl{(4-trifluoro-
methylphenyl)ethynyl}silane (1f),39 trimethyl(2-pyridylethynyl)si-
lane (1g),39 trimethyl(2-thienylethynyl)silane (1h),39 [{4-(1,1-dime-
thylethyl)dimethylsiloxyphenyl}ethynyl]trimethylsilane (1i),22 tri-
methyl(1-oct-1-ynyl)silane (1j),41 trimethyl(1-oct-1-ynyl)silane
In conclusion, we have successfully developed a preparative
synthetic method for the generation of unsymmetrical di-
substituted ethynes from the cross-coupling reactions of three
types of aryl halides with alkynylsilanes in the presence of palla-
dium/CuCl co-catalysts. Because the presented method is carried
out using the alkynes masked with the silicon moiety, side re-
actions leading to symmetrical conjugated diynes by the homo-
coupling of non-protected terminal alkynes by Glaser coupling, can
be avoided more successfully than the case for ‘traditional’ PdeCu-
catalyzed SonogashiraeHagihara cross-couplings. This reaction is
synthetically useful from a viewpoint of the straightforward car-
bonecarbon bond formation via a direct activation of carbon-
esilicon bond using a stable, nontoxic, and functional group
tolerant organosilicon compounds. Because these coupling re-
actions take place under neutral conditions, this catalytic system is
compatible with a wide range of sensitive functional groups and
should find synthetic application for the construction of not only
unsymmetrical diarylethynes, but also other novel molecules
bearing a carbonecarbon triple bond.
(1j),41
and
trimethyl{(3-trifluoromethylphenyl)ethynyl}silane
(1k).42
4.3. General procedure for synthesis of unsymmetrically
disubstituted ethynes with aryl iodides. Formation of
(4-methoxyphenyl)(phenyl)ethyne (3a)29a
To a solution of CuCl (50 mg, 0.5 mmol, 50 mol %), tetrakis(-
triphenylphosphine)palladium (58 mg, 0.05 mmol, 5 mol %), and 4-
iodoanisole (2a) (234 mg, 1 mmol) in DMF (5 mL) in a 20 mL of
Schlenk tube was added trimethyl(phenylethynyl)silane (1a)
(0.39 mL, 2 mmol). The reaction mixture was stirred for 3 h at 80 ꢁC,
quenched with 1.0 M HCl, and extracted with diethyl ether
(20 mLꢂ3). The combined ethereal layer was washed with brine

4878
Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
and dried over MgSO4. Filtration and evaporation afforded a dark
yellow oil. Column chromatography (silica gel, hexane/diethyl
ether¼9:1, Rf¼0.14) gave the title compound (197 mg, 0.84 mmol,
intensity)): 220 (Mþ, 100), 205 (80), 189 (14), 178 (10), 165 (9), 152
(4), 128 (8), 115 (7), 101 (9), 89 (6), 77 (6), 63 (3).
84% yield) as white solid. 1H NMR (300 MHz, CDCl3, rt):
d
3.83 (s,
4.3.11. (Phenyl)(2-pyridyl)ethyne (3l).43 1H NMR (300 MHz, CDCl3,
3H), 6.86e6.90 (m, 2H), 7.32e7.34 (m, 3H), 7.46e7.53 (m, 4H). MS
(EI, m/z (relative intensity)): 208 (Mþ, 100), 193 (50), 165 (41), 139
(10), 104 (6), 88 (5), 75 (2), 63 (4).
The following unsymmetrically disubstituted ethynes 3 are
synthesized according to the optimized reaction conditions de-
scribed above.
rt):
d
7.24 (td, J¼6.3, 1.2 Hz, 1H), 7.35e7.38 (m, 3H), 7.53 (dd, J¼8.2,
0.9 Hz, 1H), 7.59e7.61 (m, 2H), 7.68 (td, J¼7.5, 1.8 Hz, 1H), 8.62 (dd,
J¼5.7 Hz, 1H). MS (EI, m/z (relative intensity)): 179 (Mþ, 100), 167
(2), 151 (15), 126 (9), 100 (4), 89 (4), 76 (13), 63 (6).
4.3.12. (Phenyl)(2-thienyl)ethyne (3m).43 1H NMR (300 MHz, CDCl3,
rt):
d 7.00e7.03 (m, 1H), 7.27e7.36 (m, 5H), 7.50e7.54 (m, 2H). MS
4.3.1. (4-Methylphenyl)(phenyl)ethyne (3b).43 1H NMR (300 MHz,
(EI, m/z (relative intensity)): 184 (Mþ, 100), 152 (18), 139 (22), 126
CDCl3, rt):
d
2.37 (s, 3H), 7.16 (d, J¼8.4 Hz, 2H), 7.33e7.35 (m, 3H),
(6), 113 (5), 98 (3), 92 (6), 74 (4), 63 (4).
7.43 (d, J¼8.4 Hz, 2H), 7.51e7.54 (m, 2H). MS (EI, m/z (relative in-
tensity)): 192 (Mþ, 100), 176 (3), 165 (15), 152 (3), 139 (4), 126 (2),
115 (6), 96 (5), 82 (5), 74 (2), 63 (4).
4.3.13. (4-Methoxyphenyl)(4-methylphenyl)ethyne (3n).51 1H NMR
(300 MHz, CDCl3, rt):
d
2.36 (s, 3H), 3.83 (s, 3H), 6.87 (d, J¼8.4 Hz,
2H), 7.14 (d, J¼8.4 Hz, 2H), 7.39e7.47 (m, 4H). MS (EI, m/z (relative
intensity)): 222 (Mþ, 100), 207 (54), 178 (25), 152 (10), 111 (8), 89
(4), 76 (5), 63 (3).
4.3.2. (4-Cyanophenyl)(phenyl)ethyne (3c).44 1H NMR (300 MHz,
CDCl3, rt): d 7.39 (m, 3H), 7.53e7.56 (m, 2H), 7.59e7.63 (m, 4H). MS
(EI, m/z (relative intensity)): 203 (Mþ, 100), 176 (8), 164 (2), 151 (5),
124 (2), 101 (7), 88 (7), 75 (6), 63 (3).
4.3.14. (4-Cyanophenyl)(4-methoxyphenyl)ethyne (3o).46 1H NMR
(300 MHz, CDCl3, rt):
d
3.84 (s, 3H), 6.90 (d, J¼9.0 Hz, 2H), 7.48 (d,
4.3.3. 4-(Phenylethynyl)phenylethanone (3d).43 1H NMR (300 MHz,
CDCl3, rt): d 2.62 (s, 3H), 7.26e7.38 (m, 3H), 7.53e7.55 (m, 2H), 7.61
(d, J¼8.7 Hz, 2H), 7.94 (d, J¼8.4 Hz, 2H). MS (EI, m/z (relative in-
tensity)): 220 (Mþ, 70), 205 (100), 176 (54),165 (2),151 (20),126 (5),
103 (7), 88 (17), 75 (8), 63 (3).
J¼9.0 Hz, 2H), 7.58e7.61 (m, 4H). MS (EI, m/z (relative intensity)):
233 (Mþ, 100), 213 (40), 190 (47), 175 (2), 163 (13), 140 (5), 137 (4),
117 (3), 111 (2), 87 (4), 74 (3), 63 (4).
4.3.15. (4-Acetylphenyl)(4-methoxyphenyl)ethyne (3p).22 1H NMR
(300 MHz, CDCl3, rt):
d
2.61 (s, 3H), 3.84 (s, 3H), 6.89 (d, J¼9.0 Hz,
4.3.4. (4-Nitrophenyl)(phenyl)ethyne (3e).44 1H NMR (300 MHz,
2H), 7.49 (d, J¼9.0 Hz, 2H), 7.58 (d, J¼8.7 Hz, 2H), 7.93 (d, J¼8.7 Hz,
2H). MS (EI, m/z (relative intensity)): 250 (Mþ, 91), 235 (100), 207
(24),192 (14),176 (10),163 (40),137 (6),118 (8),103 (4), 88 (4), 75 (4).
CDCl3, rt):
d 7.39e7.41 (m, 3H), 7.55e7.57 (m, 2H), 7.66e7.68 (m,
2H), 8.22e8.24 (m, 2H). MS (EI, m/z (relative intensity)): 223 (Mþ,
100), 207 (3), 193 (45), 176 (73), 165 (37), 151 (32), 126 (4), 88 (8), 75
(13).
4.3.16. (4-Methoxyphenyl)(4-nitrophenyl)ethyne (3q).52 1H NMR
(300 MHz, CDCl3, rt):
d
3.85 (s, 3H), 6.91 (d, J¼8.4 Hz, 2H), 7.50 (d,
4.3.5. (4-Chlorophenyl)(phenyl)ethyne (3f).45 1H NMR (300 MHz,
J¼8.1 Hz, 2H), 7.63 (d, J¼8.1 Hz, 2H), 8.21 (d, J¼8.4 Hz, 2H). MS (EI,
m/z (relative intensity)): 253 (Mþ, 100), 223 (19), 207 (16), 192 (8),
176 (7), 163 (40), 152 (11), 137 (5), 113 (4), 87 (4), 75 (4), 63 (4).
CDCl3, rt):
d 7.32e7.36 (m, 5H), 7.45e7.47 (m, 2H), 7.51e7.53 (m,
2H). MS (EI, m/z (relative intensity)): 212 (Mþ, 100), 176 (34), 151
(11), 125 (2), 106 (7), 88 (8), 75 (6), 62 (2).
4.3.17. (Phenyl)(4-trifluoromethylphenyl)ethyne (3r).53 1H NMR
4.3.6. Ethyl 4-(phenylethynyl)benzoate (3g).46 1H NMR (300 MHz,
(300 MHz, CDCl3, rt): d 7.36e7.38 (m, 3H), 7.54e7.57 (m, 2H),
CDCl3, rt):
d
1.41 (t, J¼4.2 Hz, 3H), 4.39 (q, J¼4.2 Hz, 2H), 7.36e7.37
7.59e7.66 (m, 4H); 19F{1H} NMR (300 MHz, CDCl3, rt):
d
ꢀ62.83. MS
(m, 3H), 7.54e7.60 (m, 4H), 8.03 (dd, J¼4.2, 1.2 Hz, 2H). MS (EI, m/z
(relative intensity)): 250 (Mþ, 96), 222 (34), 205 (100), 176 (49), 151
(20), 126 (4), 102 (8), 88 (18), 75 (5), 63 (2).
(EI, m/z (relative intensity)): 246 (Mþ, 100), 227 (10), 207 (3), 196
(9), 176 (10), 150 (6), 123 (8), 98 (29), 85 (13), 75 (10), 63 (6).
4.3.18. (4-Methoxyphenyl)(2-pyridyl)ethyne
(300 MHz, CDCl3, rt):
(m,1H), 7.47e7.55 (m, 3H), 7.66 (td, J¼7.5,1.8 Hz,1H), 8.60 (dq, J¼4.8,
0.9 Hz, 1H). MS (EI, m/z (relative intensity)): 209 (Mþ, 100),194 (41),
166 (20), 140 (26), 113 (8), 105 (3), 87 (5), 75 (4), 63 (6).
(3s).43 1H
NMR
4.3.7. (2-Methoxyphenyl)(phenyl)ethyne (3h).47 1H NMR (300 MHz,
d
3.82 (s, 3H), 6.88 (d, J¼8.9 Hz, 2H), 7.18e7.22
CDCl3, rt):
d
3.92 (s, 3H), 6.90e6.96 (m, 2H), 7.29e7.36 (m, 4H),
7.49e7.57 (m, 3H). MS (EI, m/z (relative intensity)): 208 (Mþ, 100),
189 (6), 178 (22), 165 (37), 152 (4), 139 (11), 131 (33), 115 (9), 102 (3),
89 (8), 76 (7), 63 (5).
4.3.19. (4-Methoxyphenyl)(2-thienyl)ethyne
(3t).54 1H
NMR
4.3.8. (2-Methylphenyl)(phenyl)ethyne (3i).48 1H NMR (300 MHz,
(300 MHz, CDCl3, rt): 3.83 (s, 3H), 6.86e6.89 (m, 2H), 7.00e7.01
d
CDCl3, rt):
d
2.52 (s, 3H), 7.15e7.26 (m, 3H), 7.33e7.36 (m, 3H),
(m, 1H), 7.24e7.27 (m, 2H), 7.44e7.47 (m, 2H). MS (EI, m/z (relative
intensity)): 214 (Mþ, 100), 199 (68), 171 (23), 145 (5), 127 (21), 107
(6), 87 (5), 74 (3), 63 (4).
7.48e7.56 (m, 3H). MS (EI, m/z (relative intensity)): 192 (Mþ, 100),
191 (86), 165 (25), 152 (3), 139 (4), 115 (12), 95 (8), 82 (6), 63 (5).
4.3.9. 2-(Phenylethynyl)phenylethanone (3j).49 1H NMR (300 MHz,
4.3.20. {4-(1,1-Dimethylethyl)dimethylsiloxyphenyl}(phenyl)ethyne
CDCl3, rt):
d
2.80 (s, 3H), 7.36e7.38 (m, 3H), 7.42 (d, J¼7.5 Hz, 1H),
(3u).55 1H NMR (300 MHz, CDCl3, rt):
d 0.21 (s, 6H), 0.98 (s, 9H),
7.48 (t, J¼7.5 Hz, 1H), 7.54e7.57 (m, 2H), 7.64 (d, J¼7.8 Hz, 1H), 7.76
(d, J¼7.8 Hz, 1H). MS (EI, m/z (relative intensity)): 220 (Mþ, 77),
205 (100), 189 (5), 176 (51), 151 (19), 126 (4), 103 (4), 88 (17), 75 (6),
63 (3).
6.81 (dt, J¼6.6, 2.1 Hz, 2H), 7.30e7.35 (m, 3H), 7.41 (dt, J¼8.7, 2.1 Hz,
2H), 7.49e7.52 (m, 2H). MS (EI, m/z (relative intensity)): 308
(Mþ, 55), 251 (100), 235 (10), 221 (3), 208 (2), 191 (4), 165 (6), 151
(4), 126 (9), 111 (1), 89 (1), 73 (8).
4.3.10. (Phenyl)(2,4,6-trimethylphenyl)ethyne
(300 MHz, CDCl3, rt): 2.30 (s, 3H), 2.48 (s, 6H), 6.90 (s, 2H),
7.33e7.37 (m, 3H), 7.52e7.55 (m, 2H). MS (EI, m/z (relative
(3k).50 1H
NMR
4.3.21. 1-Oct-1-ynylbenzene (3v).43 1H NMR (300 MHz, CDCl3, rt):
d
d
0.91 (t, J¼6.9 Hz, 3H), 1.29e1.34 (m, 4H), 1.42e1.48 (m, 2H), 1.60
(quin, J¼8.1 Hz, 2H), 2.40 (t, J¼7.2 Hz, 2H), 7.26e7.28 (m, 3H),

Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
4879
7.37e7.41 (m, 2H). MS (EI, m/z (relative intensity)): 186 (Mþ, 25),157
(14), 143 (51), 129 (57), 115 (100), 102 (19), 91 (28), 77 (8), 63 (10).
100 ꢁC for 12 h and monitored by GC. GC yields of the corre-
sponding cross-coupled products 3 were determined using hep-
tylbenzene as an internal standard.
4.4. General procedure for synthesis of symmetrically
disubstituted ethynes by the reaction of bis(trimethylsilyl)-
ethyne with 2 equiv of aryl iodides. Di(4-cyanophenyl)ethyne
(6b)56
4.7. General procedure for synthesis of unsymmetrically
disubstituted ethynes with aryl chlorides. Formation of 4-
(phenylethynyl)phenylethanone (3d)43
To a solution of Pd(PPh3)4 (116 mg, 0.1 mmol), CuCl (99 mg,
1 mmol), and 4-iodobenzonitrile (2c) (458 mg, 2 mmol) in DMF
(8 mL) in a 20 mL of Schlenk tube was added bis(trimethylsilyl)
ethyne (5) (0.23 mL, 1 mmol) at rt. The reaction mixture was stirred
for 6 h at 80 ꢁC before quenching with 1 M HCl and extracted with
diethyl ether (20 mLꢂ3). The combined layers were washed with
brine and dried over MgSO4. Filtration and evaporation gave
a brown solid, which was purified by column chromatography
(silica gel, hexane/ethyl acetate¼9:1; Rf¼0.21) to give the titled
compound (164 mg, 0.72 mmol, 72% yield) as white solid. 1H NMR
To a solution of Pd(OAc)2 (45 mg, 0.2 mmol, 10 mol %) and
(ꢀ)-DIOP (100 mg, 0.2 mmol, 10 mol %) in DMF (5 mL) in a 20 mL of
Schlenk tube were added 4-chloroacetophenone (8d) (0.26 mL,
2 mmol) and trimethyl(phenylethynyl)silane (1a) (0.47 mL,
2.4 mmol), and CuCl (20 mg, 0.2 mmol, 10 mol %) at rt. The reaction
mixture was stirred for 24 h at 120 ꢁC, quenched with 1 M HCl, and
then extracted with diethyl ether (20 mLꢂ3). The combined ethe-
real layer was washed with brine, and dried over MgSO4. Filtration
and evaporation provided dark yellow solid. Column chromatog-
raphy (silica gel, hexane/diethyl ether¼8:2) gave 3d (251 mg,
1.14 mmol, 57% yield) as white solid.
(300 MHz, CDCl3, rt):
d 7.61e7.69 (m, 8H). MS (EI, m/z (relative in-
tensity)): 228 (Mþ, 100), 201 (10), 175 (5), 151 (5), 114 (5), 101 (3), 87
(5), 74 (5), 63 (2).
4.7.1. (4-Acetylphenyl)(2-pyridyl)ethyne (3x).43 1H NMR (300 MHz,
CDCl3, rt):
d
2.62 (s, 3H), 7.29 (td, J¼4.8, 1.2 Hz, 1H), 7.55 (dt, J¼7.8,
4.4.1. Di(4-methoxyphenyl)ethyne (6a).57 1H NMR (300 MHz, CDCl3,
1.1 Hz, 1H), 7.66e7.74 (m, 3H), 7.95 (dt, J¼8.4, 1.6 Hz, 2H), 8.64 (dt,
J¼3.9, 0.9 Hz, 1H). MS (EI, m/z (relative intensity)): 221 (Mþ, 59),
206 (100), 178 (37), 151 (24), 125 (9), 103 (14), 99 (13), 89 (18), 78
(26), 75 (31), 63 (12).
rt):
d
3.82 (s, 6H), 6.87 (d, J¼8.4 Hz, 4H), 7.45 (d, J¼8.4 Hz, 4H). MS (EI,
m/z (relative intensity)): 238 (Mþ, 100), 223 (69), 195 (19), 180 (9),
163 (5), 152 (21), 126 (5), 119 (9), 98 (2), 87 (2), 75 (2), 63 (2).
4.5. One-pot synthesis of unsymmetrically disubstituted
ethynes from bis(trimethylsilyl)ethyne. Formation of (4-
cyanophenyl)(4-methoxyphenyl)ethyne (3o)58
4.7.2. (4-Cyanophenyl)(4-trifluoromethylphenyl)ethyne
(3y). Isolated in 54% as white solid. Rf¼0.43 (hexane/diethyl
ether¼8:2); mp 119 ꢁC; FTIR (KBr, cmꢀ1): 2229 (m), 1611 (m), 1497
(w), 1322 (s), 1163 (s), 1120(s), 1063 (s), 834 (m), 554 (m); 1H NMR
To a solution of Pd(PPh3)4 (116 mg, 0.1 mmol, 10 mol %), CuCl
(99 mg, 1 mmol 100 mol %), and 4-iodobenzonitrile (2c) (458 mg,
2 mmol) in DMF (5 mL) in a 20 mL of Schlenk tube was added
bis(trimethylsilyl)ethyne (5) (0.91 mL, 4 mmol) at rt. The mixture
was stirred for 30 min at 80 ꢁC. Then, the unreacted 5 was evacu-
ated under reduced pressure. Again, Pd(PPh3)4 (57 mg, 0.05 mmol,
5 mol %), CuCl (50 mg, 0.5 mmol 50 mol %), and 4-iodoanisole (2a)
(234 mg, 1 mmol) in DMF (5 mL) were added to the reaction mix-
ture and the resulting mixture was stirred for 9 h at 80 ꢁC,
quenched with 1 M HCl, and then extracted with diethyl ether
(20 mLꢂ3). The combined ethereal layer was washed with brine,
and dried over MgSO4. Filtration and evaporation provided dark
brown solid. Column chromatography (silica gel, hexane/ethyl
acetate¼19:1; Rf¼0.15) gave the title compound (109 mg,
0.47 mmol, 47% yield) as white solid. GC yield was 49%. 1H NMR
(300 MHz, CDCl3, rt): d
7.61e7.68 (m, 8H); 13C{1H} NMR (75 MHz,
CDCl3, rt):
d
89.7, 91.9, 112.0, 118.3, 123.7 (q, 1JCeF¼270.7 Hz), 125.4
3
4
(q, JCeF¼3.8 Hz), 126.0 (q, JCeF¼1.3 Hz), 127.4, 130.6 (q,
2JCeF¼32.1 Hz), 132.0, 132.1, 132.2; 19F{1H} NMR (300 MHz, CDCl3,
rt):
d
ꢀ62.97. MS (EI, m/z (relative intensity)): 271 (Mþ, 100), 252
(10), 221 (8), 201 (5), 175 (4), 151 (2), 126 (2), 110 (12), 97 (4), 75 (4),
63 (2). Anal. Calcd for C16H8F3N: C, 70.85; H, 2.97; N, 5.16%. Found:
C, 70.88; H, 3.14; N, 5.17%.
4.7.3. (4-Cyanophenyl)(3-trifluoromethylphenyl)ethyne (3z).46 1H
NMR (300 MHz, CDCl3, rt):
d
7.51 (t, J¼7.8, 1H), 7.61e7.73 (m, 6H),
7.81 (s,1H); 19F{1H} NMR (300 MHz, CDCl3, rt):
d
ꢀ63.05. MS (EI, m/z
(relative intensity)): 271 (Mþ, 100), 252 (8), 221 (5), 201 (4), 175 (4),
169 (3), 151 (2), 135 (5), 126 (2), 110 (3), 99 (3), 87 (4), 75 (4), 63 (2).
(300 MHz, CDCl3, rt):
d
3.84 (s, 3H), 6.90 (d, J¼9.0 Hz, 2H), 7.48 (d,
4.7.4. (4-Acetylphenyl)(3-trifluoromethylphenyl)ethyne (3aa). Iso-
lated in 48% as white solid. Rf¼0.35 (hexane/diethyl ether¼7:3); mp
73 ꢁC; FTIR (KBr, cmꢀ1): 3057 (w), 2930 (w), 1689 (s), 1600 (s), 1346
(s), 1264 (s), 1116 (s), 900 (m), 802 (m), 693 (m); 1H NMR (300 MHz,
J¼9.0 Hz, 2H), 7.58e7.61 (m, 4H). MS (EI, m/z (relative intensity)):
233 (Mþ, 100), 213 (40), 190 (47), 175 (2), 163 (13), 140 (5), 137 (4),
117 (3), 111 (2), 87 (4), 74 (3), 63 (4).
CDCl3, rt):
d
2.63 (s, 3H), 7.50 (t, J¼7.2 Hz, 1H), 7.61e7.64 (m, 3H),
4.5.1. (4-Chlorophenyl)(4-cyanophenyl)ethyne (3w).58 1H NMR
7.72 (d, J¼7.5 Hz, 1H), 7.82 (br s, 1H), 7.95e7.98 (m, 2H); 13C{1H}
(300 MHz, CDCl3, rt):
d
7.36 (d, J¼8.4 Hz, 2H), 7.47 (d, J¼8.4 Hz, 2H),
NMR (75 MHz, CDCl3, rt): d 26.6, 89.9, 90.8, 123.6, 123.6 (q,
7.62 (quin, J¼8.0 Hz, 4H). MS (EI, m/z (relative intensity)): 237 (Mþ,
100), 201 (18), 175 (14), 151 (4), 125 (3), 118 (5), 101 (4), 87 (6), 75
(5), 63 (2).
1JCeF¼271 Hz), 125.3 (q, JCeF¼3.5 Hz), 127.4, 128.3, 128.5 (q,
3
3JCeF¼3.8 Hz), 129.0, 131.0 (q, JCeF¼31.9 Hz), 131.8, 134.7 (q,
2
4JCeF¼1.2 Hz), 136.5, 197.2; 19F{1H} NMR (300 MHz, CDCl3, rt):
d
ꢀ63.03. MS (EI, m/z (relative intensity)): 288 (Mþ, 51), 273 (100),
4.6. General procedure for synthesis of unsymmetrically
disubstituted ethynes with aryl bromides. Determination of
GC yield of cross-coupled products
245 (18), 225 (24), 176 (20), 136 (6), 122 (5), 111 (4), 99 (6), 87 (5), 75
(10), 63 (5). Anal. Calcd for C17H11F3O: C, 70.83; H, 3.85%. Found: C,
70.88; H, 3.98%.
To a solution of PdCl2 (4 mg, 0.02 mmol, 10 mol %), tri(4-
fluorophenyl)phosphine (25 mg, 0.08 mmol, 40 mol %), and CuCl
(10 mg, 0.1 mmol, 50 mol %) in dry DMF (1 mL) in a 20 mL of
Schlenk tube were added an aryl bromide (0.2 mmol) and an
alkynylsilane (0.3 mmol) at rt. The reaction mixture was heated at
4.7.5. (2-Pyridyl)(3-trifluoromethylphenyl)ethyne (3bb). Isolated in
65% as white solid. Rf¼0.15 (hexane/diethyl ether¼9:1); mp 38 ꢁC;
FTIR (KBr, cmꢀ1): 3045 (w), 2365 (w), 1580 (m), 1465 (m), 1339 (s),
1152 (s), 1114 (s), 897 (m), 813 (m), 775 (m); 1H NMR (300 MHz,
CDCl3, rt):
d
7.26e7.31 (m, 1H), 7.47e7.57 (m, 2H), 7.62 (d, J¼7.8 Hz,

4880
Y. Nishihara et al. / Tetrahedron 68 (2012) 4869e4881
2007, 46, 8223e8225; (e) Liu, J.; Lam, J. W. Y.; Tang, B. Z. Chem. Rev. 2009,
109, 5799e5867; (f) Heravi, M. M.; Sadjadi, S. Tetrahedron 2009, 65,
7761e7775.
1H), 7.72 (dt, J¼7.8, 1.7 Hz, 1H), 7.77 (d, J¼7.8 Hz, 1H), 7.87 (br s, 1H),
8.64 (dt, J¼4.8, 0.9 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3, rt):
d 87.9,
3
89.4, 123.0, 123.2, 123.5 (q, 1JCeF¼271 Hz), 125.5 (q, JCeF¼3.7 Hz),
127.3, 128.8 (q, 3JCeF¼3.8 Hz), 129.0, 130.9 (q, 2JCeF¼32.5 Hz), 135.0
(q, 4JCeF¼1.1 Hz), 136.6, 142.4, 149.7; 19F{1H} NMR (300 MHz, CDCl3,
2. (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120,
€
9722e9723; (b) Konigsberger, K.; Chen, G.-P.; Wu, R. R.; Girgis, M. J.; Prasad, K.;
Repic, O.; Blacklock, T. J. Org. Process Res. Dev. 2003, 7, 733e742; (c) Hartner, F.
W.; Hsiao, Y.; Eng, K. K.; Rivera, N. R.; Palucki, M.; Tan, L.; Yasuda, N.; Hughes, D.
L.; Weissman, S.; Zewge, D.; King, T.; Tschaen, D.; Volante, R. P. J. Org. Chem.
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2007, 48, 105e107; (e) Falcone, D.; Li, J.; Kale, A.; Jones, G. B. Bioorg. Med. Chem.
Lett. 2008, 18, 934e937; (f) Yu, S.; Haight, A.; Kotecki, B.; Wang, L.; Lukin, K.;
Hill, D. R. J. Org. Chem. 2009, 74, 9539e9542; (g) Berliner, M. A.; Cordi, E. M.;
Dunetz, J. R.; Price, K. E. Org. Process Res. Dev. 2010, 14, 180e187.
3. (a) Holmes, A. B.; Jennings-White, C. L. D.; Kendrick, D. A. J. Chem. Soc., Chem.
Commun. 1983, 415e417; (b) Nicolaou, K. C.; Zipkin, R. E.; Dolle, R. E.; Harris, B.
D. J. Am. Chem. Soc. 1984, 106, 3548e3551; (c) Crombie, L.; Hobbs, A. J. W.;
Horsham, M. A. Tetrahedron Lett. 1987, 28, 4875e4878; (d) Just, G.; O’Connor, B.
Tetrahedron Lett. 1988, 29, 753e756; (e) Holmes, A. B.; Tabor, A. B.; Baker, R. J.
Chem. Soc., Perkin Trans. 1 1991, 3307e3313; (f) Hoye, T. R.; Chanson, P. R. Tet-
rahedron Lett. 1993, 34, 5043e5046.
rt):
d
ꢀ63.05. MS (EI, m/z (relative intensity)): 247 (Mþ, 100), 226
(15), 219 (5), 208 (4),197 (6),178 (10),169 (5),151 (7),124 (3), 99 (4),
75 (6), 69 (2). Anal. Calcd for C14H8F3N: C, 68.02; H, 3.26; N, 5.67%.
Found: C, 68.05; H, 3.39; N, 5.64%.
4.7.6. (4-Cyanophenyl)(2-pyridyl)ethyne
(300 MHz, CDCl3, rt):
7.63e7.75 (m, 5H), 8.64 (dt, J¼5.7, 0.9 Hz, 1H). MS (EI, m/z (relative
intensity)): 204 (Mþ,100),177 (14),151 (13),124 (6),102 (9), 99 (11),
88 (14), 75 (25), 62 (9).
(3cc).59 1H
NMR
d
7.27e7.32 (m, 1H), 7.55 (dt, J¼7.8, 1.1 Hz,1H),
4. (a) Matsumi, N.; Naka, K.; Chujo, Y. J. Am. Chem. Soc. 1998, 120, 5112e5113; (b)
Martin, R. E.; Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350e1377; (c) In-
ouye, M.; Takahashi, K.; Nakazumi, H. J. Am. Chem. Soc. 1999, 121, 341e345; (d)
Erdogan, B.; Song, L.; Wilson, J. N.; Park, J. O.; Srinivasarao, M.; Bunz, U. H. F. J.
Am. Chem. Soc. 2004, 126, 3678e3679; (e) Yamaguchi, Y.; Ochi, T.; Wakamiya, T.;
Matsubara, Y.; Yoshida, Z. Org. Lett. 2006, 8, 717e720; (f) Yin, L.; Liebscher, J.
Chem. Rev. 2007, 107, 133e173.
4.7.7. (4-Acetylphenyl){4-(1,1-dimethylethyl)dimethylsiloxyphenyl}
ethyne (3dd). Isolated in 50% as white solid. Rf¼0.25 (hexane/ethyl
acetate¼9:1); mp 109 ꢁC; FTIR (KBr, cmꢀ1): 2930 (m), 2858 (m),
2217 (w), 1678 (s), 1595 (s), 1514 (m), 1496 (m), 1268 (s), 912 (s), 842
(s), 782 (m); 1H NMR (300 MHz, CDCl3, rt):
d 0.22 (s, 6H), 0.99 (s,
5. Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93, 259e263.
9H), 2.61 (s, 3H), 6.83 (d, J¼8.7 Hz, 2H), 7.43 (d, J¼8.7 Hz, 2H), 7.58
6. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467e4470;
(b) Tohda, Y.; Sonogashira, K.; Hagihara, N. Synthesis 1977, 777e778; (c) Mori,
A.; Shimada, T.; Kondo, T.; Sekiguchi, A. Synlett 2001, 649e650; (d) Mori, A.;
Mohamed Ahmed, M. S.; Sekiguchi, A.; Masui, K.; Koike, T. Chem. Lett. 2002,
756e757; (e) Mohamed Ahmed, M. S.; Mori, A. Tetrahedron 2004, 60,
9977e9982; (f) Mohamed Ahmed, M. S.; Sekiguchi, A.; Masui, K.; Mori, A. Bull.
Chem. Soc. Jpn. 2005, 78, 160e168.
7. For books on the SonogashiraeHagihara reaction: (a) Sonogashira, K. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 3; Chapter 2.4, pp 551e562; (b) Campbell, I. B. In Orga-
nocopper Reagents: A Practical Approach; Taylor, R. J. K., Ed.; Oxford University
Press: Oxford, 1994; pp 217e235; (c) Brandsma, L.; Vasilevsky, S. F.; Verk-
ruijsse, H. D. Application of Transition Metal Catalysts in Organic Synthesis;
Springer: Berlin, 1998, Chapter 10; (d) Sonogashira, K. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Wein-
heim, 1998; Chapter 5, pp 203e229; (e) Sonogashira, K. J. Organomet. Chem.
2002, 653, 46e49; (f) Sonogashira, K. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., de Meijere, A., Eds.; Wiley-In-
terscience: New York, NY, 2002; pp 493e529; (g) Sonogashira, K. In Metal-
Catalyzed Cross-Coupling Reactions; Diedrich, F., de Meijere, A., Eds.; Wiley-
VCH: Weinheim, 2004; Vol. 1, pp 319e394; (h) Viciu, M. S.; Nolan, S. P. In
Modern Arylation Methods; Ackermann, L., Ed.; Wiley-VCH: Weinheim, 2009;
pp 183e220.
(d, J¼8.7 Hz, 2H), 7.93 (d, J¼8.7 Hz, 2H); 13C{1H} NMR (75 MHz,
CDCl3, rt):
d
ꢀ4.4, 18.2, 25.6, 26.6, 87.6, 93.0, 115.3, 120.3, 128.2,
128.6, 131.5, 133.2, 135.9, 156.5, 197.3. MS (EI, m/z (relative in-
tensity)): 350 (Mþ, 52), 335 (2), 293 (100), 235 (8), 189 (5), 176 (7),
163 (3), 139 (8), 125 (5), 112 (4), 88 (2), 75 (15), 73 (21). Anal. Calcd
for C22H26O2Si: C, 75.38; H, 7.48%. Found: C, 75.22; H, 7.50%.
4.7.8. 4-(1-Oct-1-ynyl)benzonitrile (3ee).9a 1H NMR (300 MHz,
CDCl3, rt):
d
0.90 (t, J¼6.7 Hz, 3H), 1.29e1.47 (m, 6H), 1.61 (quin,
J¼7.8, 2H), 2.42 (t, J¼7.0 Hz, 2H), 7.45 (dd, J¼6.6, 1.8 Hz, 2H), 7.56
(dd, J¼6.3,1.5 Hz, 2H). MS (EI, m/z (relative intensity)): 211 (Mþ, 39),
182 (59), 168 (100), 154 (83), 140 (89), 127 (44), 116 (45), 95 (22), 82
(10), 69 (21), 67 (15), 63 (14).
4.7.9. 4-(1-Oct-1-ynyl)phenylethanone (3ff).22 1H NMR (300 MHz,
CDCl3, rt):
d
0.91 (t, J¼6.4 Hz, 3H), 1.29e1.34 (m, 4H), 1.45e1.48 (m,
2H), 1.58e1.64 (m, 2H), 2.43 (t, J¼7.0 Hz, 2H), 2.59 (s, 3H), 7.46 (dd,
J¼6.6, 1.5 Hz, 2H), 7.87 (dd, J¼6.6, 1.5 Hz, 2H). MS (EI, m/z (relative
intensity)): 228 (Mþ, 47), 213 (62), 119 (17), 185 (34), 171 (21), 157
(41), 143 (49), 129 (100), 114 (51), 101 (10), 95 (10), 88 (14), 77 (13),
63 (12).
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search on Priority Areas ‘Advanced Molecular Transformations of
Carbon Resources’ from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. Y.N. is grateful to Chisso Petro-
chemical Corporation for generous donation of trimethylsilylace-
tylene to prepare 1.
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Supplementary data
Experimental procedures, spectroscopic data, and copies of 1H
and 13C{1H} NMR spectra of new compounds 3y, 3aa, 3bb, and 3dd.
Supplementary data related to this article can be found in the
online version, at doi:10.1016/j.tet.2012.03.093.
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