Coupling reactions of alkynylsilanes mediated by a Cu(I) salt: Novel syntheses of conjugate diynes and disubstituted ethynes

Article abstract of DOI:10.1021/jo991686k

Reaction of 1-trimethylsilylalkyne with copper(I) chloride in a polar solvent, DMF, at 60 °C under an aerobic conditions smoothly undergoes homo- coupling to give the corresponding symmetrical 1,3-butadiynes in 70-99% yields. In addition, (arylethynyl)trimethylsilanes are found to couple with aryl triflates and chlorides in the presence of Cu(I)/Pd(0) (10 mol %/5 or 10 mol %) cocatalyst system to give the corresponding diarylethynes in 49-99% yields. The cross-coupling reaction is applied to a one-pot synthesis of the corresponding unsymmetrical diarylethynes from (trimethylsilyl)ethyne via sequential Sonogashira-Hagihara and the present cross-coupling reactions using two different aryl triflates. The reactions of (arylethynyl)trimethylsilanes with aryl(chloro)ethynes in the presence of 10 mol % of CuCl also yield the corresponding unsymmetrical 1,3-butadiynes in 43-97% yields.

Full text of DOI:10.1021/jo991686k

1
780
J . Org. Chem. 2000, 65, 1780-1787
Cou p lin g Rea ction s of Alk yn ylsila n es Med ia ted by a Cu (I) Sa lt:
Novel Syn th eses of Con ju ga te Diyn es a n d Disu bstitu ted Eth yn es
Yasushi Nishihara, Kazutaka Ikegashira, Kazunori Hirabayashi, J un-ichi Ando,
,
†
‡
Atsunori Mori,* and Tamejiro Hiyama
Research Laboratory of Resources Utilization, Tokyo Institute of Technology, 4259 Nagatsuta,
Yokohama 226-8503, J apan
Received October 27, 1999
Reaction of 1-trimethylsilylalkyne with copper(I) chloride in a polar solvent, DMF, at 60 °C under
an aerobic conditions smoothly undergoes homo-coupling to give the corresponding symmetrical
1
,3-butadiynes in 70-99% yields. In addition, (arylethynyl)trimethylsilanes are found to couple
with aryl triflates and chlorides in the presence of Cu(I)/Pd(0) (10 mol %/5 or 10 mol %) cocatalyst
system to give the corresponding diarylethynes in 49-99% yields. The cross-coupling reaction is
applied to a one-pot synthesis of the corresponding unsymmetrical diarylethynes from (trimeth-
ylsilyl)ethyne via sequential Sonogashira-Hagihara and the present cross-coupling reactions using
two different aryl triflates. The reactions of (arylethynyl)trimethylsilanes with aryl(chloro)ethynes
in the presence of 10 mol % of CuCl also yield the corresponding unsymmetrical 1,3-butadiynes in
4
3-97% yields.
In tr od u ction
Conjugated polyyne structures1 have received much
(NLO) materials.12 A variety of synthetic examples
including polymers13 and dendrimers have also been
14
15
documented. The Sonogashira-Hagihara coupling,
a
attention, since they are found in many natural prod-
ucts,2 particularly antifungal agents. Among a large
number of synthetic methods for conjugated diynes
cross-coupling reaction of terminal alkynes with aryl
halides in the presence of a base with a Cu(I)/Pd(0)
cocatalyst, is one of the most practical and widely used
synthetic routes to unsymmetrical diarylethynes.
3
4
developed, Hay’s coupling, a coupling reaction of termi-
nal alkynes by an oxidative dimerization, is recognized
to be particularly practical.5-7 In these reactions the
generation of alkynylcopper species by transmetalation
of an alkynyl group to copper is considered a key step.
Subsequent oxidative dimerization gives the correspond-
ing 1,3-butadiynes.8
On the other hand, trimethylsilylated alkynes are inert
to the Sonogashira-Hagihara coupling. The coupling
reaction of (trimethylsilyl)ethyne, for example, occurs at
the terminal alkyne while the silyl group remains intact.
In addition, the trimethylsilyl group is often employed
as a protective group for the preparation of a substrate
for the Sonogashira-Hagihara coupling, which is gener-
In addition to conjugate diynes, aryl- and alkenyl-
ethynes are also key structural moieties of a large
1
6
ally carried out after deprotection of the silyl group.
9
10
number of natural and unnatural products. In par-
ticular, unsymmetrical diarylethynes are often used in
the studies on liquid crystals11 and nonlinear optical
By contrast, the palladium-catalyzed coupling reactions
17
of alkynylsilanes proceed to give the coupling product,
although the addition of a fluoride ion as an activator to
†
Phone: +81-45-924-5231. Fax: +81-45-924-5224. Email: amori@
(10) (a) Ames, D. E.; Brohi, M. I. J . Chem. Soc., Perkin Trans. 1
1980, 1384. (b) Sakamoto, T.; Kondo, Y.; Yamanaka, H. Chem. Pharm.
Bull. 1985, 33, 626. (c) Tilley, J . W.; Zawoiski, S. J . Org. Chem. 1988,
53, 386. (d) Taylor, E. C.; Ray, P. S. J . Org. Chem. 1988, 53, 35. (e)
Chapdelaine, M. J .; Warwick, P. J .; Shaw, A. J . Org. Chem. 1989, 54,
1218.
(11) (a) Fouquey, C.; Lehn, J .-M.; Malth eˆ te, J . J . Chem. Soc., Chem.
Commun. 1987, 1424. (b) Chang, J . Y.; Baik, J . H.; Le, C. B.; Han, M.
J . J . Am. Chem. Soc. 1997, 119, 3197. (c) Kitamura, T.; Lee, C. H.;
Taniguchi, Y.; Fujiwara, Y.; Matsumoto, M.; Sano, Y. J . Am. Chem.
Soc. 1997, 119, 619.
res.titech.ac.jp.
‡
Present address: Department of Material Chemistry, Graduate
School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto
06-8501, J apan.
6
(
(
1) Schmidt, H.-W.; Guo, D. Makromol. Chem. 1988, 189, 2029.
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W.; Horsham, M. A. Tetrahedron Lett. 1987, 28, 4875. (c) Holmes, A.
B.; Tabor, A. B.; Baker, R. J . Chem. Soc., Perkin Trans. 1 1991, 3307.
(
d) Hoye, T. R.; Chanson, P. R. Tetrahedron Lett. 1993, 34, 5043.
(
(
3) St u¨ ts, A. Angew, Chem., Int. Ed. Engl. 1987, 26, 320.
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Chem. 1991, 95, 10643. (b) Kanis, D. R.; Ratner, M. A.; Marks, T. J .
Chem. Rev. 1994, 94, 195.
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5
61.
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(
Kendrick, D. A.; Holmes, A. B. Org. Synth. 1987, 65, 52. (c) Valent ´ı ,
E.; Peric a` s, M. A.; Serratosa, F. J . Am, Chem. Soc. 1990, 112, 7401.
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1975, 4467. (b) Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagi-
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5
23. (b) Liu, Q.; Burton, D. J . Tetrahedron Lett. 1997, 38, 4371.
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Puls, C.; Cooney, M. J .; Scott, L. T. Chem. Eur. J . 1995, 1, 124. (b)
Haley, M. M.; Bell, M. L.; Brand, S. C.; Kimball, D. B.; Pak, J . J .; Wan,
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(
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Lett. 1988, 29, 753.
1
0.1021/jo991686k CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/02/2000

Cu(I)-Mediated Coupling Reactions of Alkynylsilanes
J . Org. Chem., Vol. 65, No. 6, 2000 1781
Ta ble 1. Hom o-Cou p lin g Rea ction of Alk yn ylsila n es (1
a n d 2)
Ta ble 2. Su bstitu en t Effect on Alk yn ylsila n es 2a
a
entry
R
time, h
product
yield, %
Si
b
entry
time, h
yield of 4, %
1
2
3
4
5
C6H5- (1a )
6
12
12
12
3
3a
3b
3c
3d
4
>99
74
75
70
80
1
2
3
4
5
6
7
SiMe3
SiEt3
Si Pr3
SiPhMe2
Si(OMe)3
(2a )
(2b)
(2c)
(2d )
(2e)
(2f)
3
24
24
7.5
1
80
0
0
83
>99
92
89
4-MeO-C6H4- (1b)
4-MeCO-C6H4- (1c)
2-thienyl (1d )
n-C6H13 (2a )
i
a
Yields were determined by GC.
SiMe2OSiMe3
SiMe2(OH)
3
7.5
(2g)
form a pentacoordinate organosilicate is essential for the
reaction to occur. Thereby, the direct coupling of alkyn-
yltrimethylsilane without an additive activator, if suc-
cessful, under the modified condition of the Sonogashira-
Hagihara coupling would be a rather straightforward
synthesis and open a new area of organosilicon chemistry.
Herein we describe the following: (i) The homo-
coupling of 1-trimethylsilylalkyne in a polar solvent in
the presence of copper(I) chloride affords symmetrical
conjugate diynes. (ii) Unsymmetrical diarylethynes are
synthesized from the cross-coupling reaction of (aryleth-
ynyl)trimethylsilanes with aryl triflates or chlorides by
the use of a Cu(I)/Pd(0) cocatalyst. (iii) Unsymmetrical
conjugate diynes are obtained by the copper(I)-catalyzed
a
A mixture of 2 (0.2 mmol) and CuCl (0.2 mmol) in DMF (0.5
mL) was stirred at 60 °C. b GC yield based on alkynylsilanes 2.
(1-octynyl)silane (2a ) gave homo-coupled product 4, no
trace of 4 was obtained from triethyl- (2b) or triisopro-
pylsilane (2c) (entry 1 vs entries 2 and 3). On the other
hand, dimethylphenyl(1-octynyl)silane (2d ) afforded 4 in
83% yield (entry 4). Oxygen-substituted alkynylsilanes
such as trimethoxysilane (2e), pentamethyldisiloxane
(2f), and dimethylsilanol (2g) also underwent the homo-
coupling reactions to give 4 in good to excellent yields
(entries 5-7).
In these reactions, the alkynyl group presumably
migrates from silicon to copper without a nucleophilic
activator such as a fluoride ion. Thus, the process for the
generation of alkynylcopper species is postulated as
follows: CuCl first coordinates to a triple bond in
alkynylsilanes.20 The alkynyl group is successively trans-
ferred from silicon to copper to generate alkynylcopper
species, which then oxidatively dimerize to furnish sym-
metrical conjugate diynes. The reason no desired product
was obtained in cases of substrates 2b and 2c is that the
steric bulk of triethyl- and triisopropylsilyl groups in-
hibits the approach of CuCl to a triple bond leading to
transmetalation.
cross-coupling reaction of alkynylsilanes with aryl-
8
(
chloro)ethynes.1
Resu lts a n d Discu ssion
Hom o-Cou p lin g Rea ction of Alk yn ylsila n es: F or -
m a tion of Sym m etr ica l Con ju ga te Diyn es. In place
of a palladium catalyst for the fluoride ion-mediated
cross-coupling reaction, we examined the reaction of
1
-phenyl-2-trimethylsilylethyne (1a ) with iodobenzene
using a stoichiometric amount of CuCl, in the presence
of an equimolar amount of KF as an activator in DMF,
but found that homo-coupled product 1,4-diphenyl-1,3-
butadiyne (3a ) was quantitatively formed. During the
course of these studies, we found that KF did not
participate in the reaction when the reaction was per-
formed in the polar solvent DMF. In sharp contrast to
the earlier method for the preparation of symmetrical
Cr oss-Cou p lin g Rea ction of Alk yn ylsila n e: F or -
m a tion of Un sym m etr ica l Dia r yleth yn es. In the
above homo-coupling reactions of alkynyltrimethylsilane
, we suggested the formation of the alkynylcopper
species as an intermediate via transmetalation of the
1
21
alkynyl group from silicon to copper. Thus, the postu-
lated mechanism involving the transmetalation allowed
us to effect the cross-coupling reaction using alkynyltri-
methylsilanes. A planned catalytic cycle of the cross-
coupling reaction using alkynyltrimethylsilanes and a
coupling partner, aryl halides or triflate, is illustrated
in Scheme 1.
6
conjugate diynes, the reaction with alkynylsilanes is a
synthetically useful protocol in view of the straightfor-
1
9
ward carbon-carbon bond formation. The results for
the synthesis of symmetrical conjugate diynes such as
3
a -d (aromatic) and 4 (aliphatic) are shown in Table 1.
We examined substituent effects on silicon using (1-
First, an alkynyl group is transferred from the silicon
of alkynyltrimethylsilane 1 to copper to form alkynyl-
copper 5, while Pd(II) complex 9 is generated by oxidative
addition of the C-X bond of the aryl halides or triflate
octynyl)silanes 2a -2g with various substituents, and the
results are summarized in Table 2. Although trimethyl-
(
17) (a) Hatanaka, Y.; Hiyama, T. J . Org. Chem. 1988, 53, 918. (b)
Hatanaka, Y.; Matsui, K.; Hiyama, T. Tetrahedron Lett. 1989, 30, 2403.
c) Hiyama T. Metal-Catalyzed Cross-Coupling Reactions. In Organo-
6
-8 to the Pd(0) complex. The alkynyl group in 5
(
silicon Compounds in Cross-Coupling Reactions; Diederich F., Stang
P. J ., Eds.; Wiley-VCH: 1998; Chapter 10, pp 421-454. (d) Mowery,
M. E.; DeShong, P. J . Org. Chem. 1999, 64, 1684. (e) Denmark, S. E.;
Choi, J . Y. J . Am. Chem. Soc. 1999, 121, 5821.
(20) Recently, papers suggesting of transmetalation from silicon to
copper have appeared. See: (a) Kang, S.-K.; Kim, T.-H.; Pyun, S.-J . J .
Chem. Soc., Perkin Trans. 1 1997, 797. (b) Ito, H.; Arimoto, K.; Sensui,
H.-o.; Hosomi, A. Tetrahedron Lett. 1997, 38, 3977. (c) Pagenkopf, B.
L.; Kr u¨ ger, J .; Stojanovic, A.; Carreira, E. H. Angew. Chem., Int. Ed.
1998, 37, 3124. (d) Franz, A. K.; Woerpel, K. A. J . Am. Chem. Soc.
1999, 121, 949.
(
18) For preliminary commnications, see: (a) Ikegashira, K.; Nishi-
hara, Y.; Hirabayashi, K.; Mori, A.; Hiyama, T. Chem. Commun. 1997,
039. (b) Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama, T. Chem.
1
Lett. 1997, 1233. (c) Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama,
T. Tetrahedron Lett. 1998, 39, 4075.
(21) The use of a polar solvent, DMF, is essential to promote the
reaction. We consider that DMF would coordinate to an alkynylsilane
to form the pentacoordinate but tetravalent species, which may behave
as a pentavalent organosilicate that is formed by the addition of a
fluoride ion to the organosilane and is known to be highly active to
transmetalation.
(19) The use of triethylamine or pyridine barely effected the reaction
of 1a with a stoichiometric amount of CuCl to yield 3a in 9% and 1%,
respectively. No trace of 3a was obtained in acetonitrile, THF, or
toluene.

1
782 J . Org. Chem., Vol. 65, No. 6, 2000
Nishihara et al.
Sch em e 1. Ca ta lytic Cycle for th e Cou p lin g of Alk yn ylsila n es 1 w ith Ar yl Ha lid es or Tr ifla te 6-8 in a
Cu (I)/P d (0) System
Ta ble 3. Rea ction of Alk yn ylsila n e 1a w ith Ar yl Ha lid es
Ta ble 4. Cu /P d -Ca ta lyzed Cr oss-Cou p lin g Rea ction of
a
a
or Tr ifla te 6a -8a
Alk yn ylsila n es 1 w ith Ar yl Tr ifla tes 8
entry alkynylsilane 1, R1
)
triflate 8, R2
)
11 yield, %
b
1
2
3
4
5
6
7
8
9
0
C
6
H
5
- (1a )
4-MeCO-C
6
H
4
- (8a ) 11a
11b >99 (65)
11c 64 (50)
11d >99 (51)
97 (89)
4-MeO-C
6
H
4
- (1b)
8a
1b
1b
1b
1b
C
6
H
5
- (8b)
4-NC-C
2,4-F -C
Pd(PPh3)4, CuCl, time, yield of yield of
H
4
- (8c)
- (8d )
- (8e)
b
b
6
entry
X
mol %
mol %
h
11a , % 3a , %
2
6
H
3
11e
11f
11g
11h
11i
11g
11j
11k
82 (79)
49 (40)
95
60 (43)
79 (52)
98 (65)
82 (71)
87 (65)
1
2
3
4
5
6
7
8
Br (6a )
I (7a )
OTf (8a )
5
5
5
5
1
5
0
5
120
120
120
10
2
5
10
0
12
12
12
12
24
12
12
12
27
84
41
97
97
93
0
20
7
40
0
0
0
2-MeO-C
6
H
4
4-MeCO-C
2-thienyl (1d )
1d
4-NC-C
4- BuMe
n-C
6
H
4
- (1c)
8c
8a
8c
8a
1
6
H
2
4
- (1e)
SiO-C
13- (2a )
t
c
11
2
6
H
4
- (1f) 8c
1
6
H
8a
0
0
0
a
Conditions: 1 (1.2 mmol); 8 (1.0 mmol); CuCl (10 mol %);
b
a
Pd(PPh3)4 (5 mol %); DMF (5 mL) unless otherwise noted. GC
yield based on alkynylsilanes 1 and isolated yields were shown in
parentheses.
Reaction conditions: 1a (1.2 mmol); 6a -8a (1.0 mmol); DMF
5 mL) unless otherwise noted. b GC yield based on 1a . c Pd-
(
(
PPh3)2Cl2 was used as a catalyst.
with 1 mol % of Pd(PPh
with longer reaction times (entry 5). A palladium(II)
complex, Pd(PPh Cl , was also an effective precatalyst,
generating a Pd(0) species for the reaction (entry 6). The
reaction did not occur in the absence of either the
palladium catalyst or the copper catalyst (entries 7 and
3 4
) and 2 mol % of CuCl albeit
successively migrates from copper to palladium to gener-
ate 10 whose reductive elimination furnishes the desired
cross-coupled product 11, regenerating CuX (X ) halide
or triflate) as a catalyst. If the regenerated copper
catalyst is effective for the transmetalation of the alkynyl
group from silicon to copper, an initial addition of a
catalytic amount of CuCl is enough for completion of the
catalytic cycles.
3
)
2
2
8
).
The generality of the reaction of alkynylsilanes 1a -1f
and 2a with aryl triflates 8a -8e was studied under the
On the basis of our plan, we first optimized the
palladium-catalyzed cross-coupling reaction of 1a with
optimum conditions, i.e., 10 mol % of CuCl and 5 mol %
3 4
of Pd(PPh ) . The results are summarized in Table 4.
4
-acetylphenyl bromide (6a ), iodide (7a ), or triflate (8a )
Notable is that this reaction is considerably affected by
substituents of aryl triflates 8, probably owing to the
efficiency of oxidative addition of Pd(0) to the C-O bond
of 8. In general, triflates with an electron-withdrawing
substituent, for example, 8a (entries 1, 8, 10, and 13) and
in the presence of a stoichiometric or catalytic amount
of CuCl and a palladium(0) catalyst. The results are listed
in Table 3.
Combination of a stoichiometric amount of CuCl and
6
a mediated the coupling with 1a to furnish cross-coupled
8
c (entries 4, 7, 9, and 12), were viable and gave the
product 11a in 27% yield and homo-coupled product 3a
derived from 1a in 20% yield (entry 1). In place of 6a the
use of 7a provided 11a in 84% yield, although an
equimolar amount of CuCl was required (entry 2). This
is probably because regenerated CuI is less effective in
the transmetalation.
Accordingly, we employed triflate 8a as the coupling
partner. However, with a stoichiometric amount of CuCl,
undesired homo-coupled product 3a was obtained in 40%
yield (entry 3). A successful cross-coupling reaction
utilized 5 mol % of palladium(0) complex and 10 mol %
of copper(I) chloride and furnished 11a in 97% yield
cross-coupled products 11 in high to excellent yields. On
the other hand, electron-rich triflates such as 2-methoxy-
phenyl trifluoromethanesulfonate (8e) and 4-methoxy-
phenyl trifluoromethanesulfonate (8f) gave 11 in low
yields.22 Therefore, the appropriate combination of alkyn-
ylsilane 1 and triflate 8 is important for the formation
of 11 in high yield. The reaction of 1b with 8d smoothly
gave the corresponding cross-coupled product 11e in 82%
(22) For instance, the appropriate choice of 1 and 8 furnished cross-
coupling products 11a , 11b, and 11d in 97, >99, and >99% yields,
respectively, whereas the unfavored combination (1c with 8b, 1c with
8f, and 1e with 8f) decreased the yields (30, 19, and 27%, respectively).
(entry 4). The cross-coupling reaction was also achieved

Cu(I)-Mediated Coupling Reactions of Alkynylsilanes
J . Org. Chem., Vol. 65, No. 6, 2000 1783
yield (entry 5),23 whereas the reaction of 1b with 8e with
an o-OMe group resulted in the formation of 11f in lower
yield (entry 6). (2-Thienylethynyl)trimethylsilane (1d )
was treated with 8a and 8c to afford 11h and 11i, in 60
and 79% yields, respectively (entries 8 and 9). Since the
present protocol allows the cross-coupling reaction with-
out a fluoride ion, alkynylsilane 1f bearing a silyl
protective group cleanly coupled with aryl triflate 8c to
afford 11j without removal of a TBDMS group (entry 11).
The coupling reaction of trimethyl(1-octynyl)silane (2a )
with aryl triflate 8a smoothly proceeded to afford 11k in
flate 8a , a comparable yield of 11a was obtained with
an aryl nonaflate. This suggests that the coproduced
copper(I) nonaflate is also effective for catalyzing the
cross-coupling reactions. However, mesylate and tosylate
were shown to be ineffective.
Because CuCl is found to be highly effective in mediat-
ing transmetalation of an alkynyl group from silicon to
copper, an aryl chloride could be employed as the
substrate, based on the catalytic cycles of the cross-
coupling reactions of alkynylsilanes with aryl halides
shown in Scheme 1. Thus, we next examined a cross-
coupling reaction using an aryl chloride as a coupling
partner. Although aryl chlorides are inexpensive and
easily available compared with aryl bromides and iodides,
they have been rarely used for the Pd-catalyzed cross-
coupling reaction because of inertness to an insertion of
palladium(0) to the C-Cl bond of the aryl chloride.
Recently, with electron-rich phosphines as a ligand, a
number of Pd-catalyzed cross-coupling reactions with aryl
chlorides including Mizoroki-Heck reaction have been
reported.24
8
7% yield (entry 12).
This cross-coupling reaction was applicable to alkenyl
triflate 8g which gave 11l and 11m in >99 and 86%
yields, respectively, upon coupling with alkynylsilanes
1
b and 1e as shown in eq 1. We further studied the
We examined a palladium catalyst for the cross-
coupling of alkynylsilane 1b and 4-acetylphenyl chloride
(
15a ) in DMF at 120 °C for 12 h. The use of a palladium
i
complex with two monodentate phosphines, PCy
PPh , or PPhEt , gave a trace of cross-coupled product
1b. We next employed a bidentate phosphine ligand
3 3
, P Pr ,
3
2
1
2
5
such as dppf, dppe, dppp, or dppb and found that, in
particular, PdCl (dppb) proved to be most effective and
2
furnished 11b in 56% yield as shown in eq 4.
reaction of 1a with polycyclic and heterocyclic triflates
8
h -8k to observe the formation of corresponding cross-
coupled products 11n -11q in moderate yields (eq 2).
2
Accordingly, we optimized the amount of PdCl (dppb)
and CuCl and found that 86% yield of 11b was attained
when 10 mol % of each catalyst was employed. Reactions
of a variety of aryl chlorides 15 under the optimum
conditions were conducted. The results are shown in
Table 5. Aryl chlorides 15 are more affected by a
substituent at the para-position of an aromatic ring than
are aryl triflates. Alkynylsilane 1b bearing an electron-
donating methoxy group coupled smoothly with 15a
bearing an electron-withdrawing acetyl group to give 11b
in 86% yield. Both alkynylsilane 1e having an electron-
withdrawing group (entry 1 vs 3) and aryl chloride 15c
having an electron-donating group (entry 3 vs 6) tend to
lower the yields of cross-coupled products 11.
We examined the effect of a leaving group in the
reaction of 1a with 4-acetylphenyl p-nonafluorobutane-
sulfonate (12, nonaflate, Nf), p-toluenesulfonate (13,
tosylate, Ts), or methanesulfonate (14, mesylate, Ms) to
afford the cross-coupled product 11a (eq 3). As with a
The protocol disclosed herein allows us to use bis-
(trimethylsilyl)ethyne (16) as an alternative to ethyne.
Indeed, the reaction of 16 (1 mol amount) with 4-cyano-
(
24) (a) Mitchell, M. B.; Wallbank, P. J . Tetrahedron Lett. 1991, 32,
2
1
273. (b) Portnoy, M.; Ben-David, Y.; Milstein, D. Organometallics
993, 12, 4734. (c) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047.
(
d) Niecke, E.; Becker, P.; Nieger, M.; Stalke, D.; Schoeeller, W. W.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1849. (e) Gouda, K.-i.;
Hagiwara, E.; Hatanaka, Y.; Hiyama, T. J . Org. Chem. 1996, 61, 7232.
(
f) Shen, W. Tetrahedron Lett. 1997, 38, 5575. (g) Reddy, N. P.; Tanaka,
M. Tetrahedon Lett. 1997, 38, 4807. (h) Littke, A. F.; Fu, G. C. J . Org.
Chem. 1999, 64, 10. (i) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed.
1
999, 38, 2411. (j) Zhang, C.; Huang, J .; Trudell, M. L.; Nolan, S. P. J .
similar cross-coupling reaction performed with aryl tri-
Org. Chem. 1999, 64, 3804.
(
25) dppf ) 1,1′-bis(diphenylphosphino)ferrocene, dppe ) 1,2-bis-
(
23) On the contrary, a triflate bearing an acetyl group at the ortho-
(diphenylphosphino)ethane, dppp ) 1,3-bis(diphenylphosphino)pro-
pane, and dppb ) 1,4-bis(diphenylphosphino)butane.
position gave a trace amount of the cross-coupled product.

1
784 J . Org. Chem., Vol. 65, No. 6, 2000
Nishihara et al.
Sch em e 2. On e-P ot Sequ en tia l
Ta ble 5. Cr oss-Cou p lin g Rea ction of Alk yn ylsila n es 1
a
w ith Ar yl Ch lor id es 15
Son oga sh ir a -Ha gih a r a a n d Cu Cl/P d (0)-Ca ta lyzed
Cou p lin g of (Tr im eth ylsilyl)eth yn e (18)
entry alkynylsilane 1, R ) aryl chloride 15, R2
1
)
11 yield, %
b
1
2
3
4
5
6
4-MeO-C
6
H
4
- (1b)
- (1e)
- (1c)
4-MeCO-C
15a
15a
6
H
4
- (15a )
11b
11a
11g
11c
11a
11d
86
47
42
43
3
6 5
C H
- (1a )
4-NC-C
6
H
4
1b
6 5
C H - (15b)
4-MeCO-C
1e
6
H
4
15b
4-MeO-C
6
H
4
- (15c)
0
a
Conditions: 1 (1.0 mmol); 15 (1.2 mmol); CuCl (10 mol %);
b
PdCl2(dppb) (10 mol %); DMF (5 mL). GC yield based on
alkynylsilanes 1.
phenyl triflate (8c, 2 mol amounts) under the conditions
described in eq 5 furnished 1,2-bis(4-cyanophenyl)ethyne
ined the synthesis of unsymmetrical conjugate diynes 20
using alkynylsilanes 1 and aryl(chloro)ethynes 19. To
synthesize unsymmetrical 1,4-disubstituted 1,3-buta-
diynes, the Cadiot-Chodkiewicz coupling is often em-
(17) in 86% yield. This method for the synthesis of
1
ployed, i.e., a copper(I)-catalyzed reaction of R CtCH
2
with R CtCX (X ) Br, I) in the presence of diethylamine
as base.28 However, the Cadiot-Chodkiewicz reaction is
not applicable to aryl(chloro)ethynes as these substrates
often fail to give unsymmetrical conjugate diynes under
2
9
the standard conditions (a copper(I)/palladium cocata-
lyst system)30 probably owing to the lower reactivity of
1
-chloroalkynes than 1-bromo- and 1-iodoalkynes. We
symmetrical diarylethynes is useful because precise
control of the amount of ethyne is considerably difficult
in laboratory experiments although ethyne is usually
used for the synthesis of symmetrical diarylethynes
through the Sonogashira-Hagihara coupling.
first examined the catalyst and substrate ratio for the
reaction of [(4-methoxyphenyl)ethynyl]trimethylsilane
(1b) with 1-chloro-2-phenylethyne (19d ) as shown in eq
6
. In the presence of a catalytic amount of CuCl (10 mol
The utility of the cross-coupling reaction with alkyn-
ylsilanes is demonstrated by a one-pot synthesis of
unsymmetrical diarylethynes 11. Unsymmetrical diaryl-
ethynes have usually been prepared via the following
reaction pathways: (i) a coupling reaction of aryl halides
with (1-trimethylsilyl)ethyne (Sonogashira-Hagihara
coupling), (ii) a desilylation to convert the resulting
(arylethynyl)trimethylsilane into the terminal alkyne,
and (iii) a second cross-coupling reaction with another
3 2 2
%) and Pd(PPh ) Cl (10 mol %), which is the most
aryl triflate. In contrast, a sequence of the Sonogashira-
effective catalyst system in the cross-coupling reaction
of alkynylsilanes with aryl triflates, the reaction with a
1:1.1 molar ratio of 19d to 1b at 80 °C for 24 h resulted
in the formation of cross-coupled product 20c in 35% yield
along with a homo-coupled product derived from 19d , 1,4-
diphenyl-1,3-butadiyne (3a , 21% yield). The reaction
using only CuCl improved the yield of 20c to 80%. The
use of 1.5 molar amounts of 19d to 1b afforded 20c in
90% yield, although the homo-coupled product 3a was
detected in 29% yield as a byproduct. The use of pal-
1
Hagihara reaction of 1-trimethylsilylethyne (18) with R -
3 4
OTf using a Pd(PPh ) catalyst and triethylamine as a
base,26 without isolation of the formed compound, fol-
lowed by the present coupling reaction using another
2
triflate, R OTf, allows the preparation of unsymmetrical
diarylalkynes in one pot as shown in Scheme 2. As a
result, three-component coupling of (trimethylsilyl)-
1
2
ethyne, R OTf, and R OTf is readily attained to give
1
2
R CtCR 11d , 11g, and 11r in fairly good yields.
Compound 11r serves as an important skeleton found
in liquid crystals and NLO materials.12,27
3 2 2
ladium catalyst Pd(PPh ) Cl alone was futile. The reac-
tion proceeded in a manner similar to the Cadiot-
Chodkiewicz coupling reaction, in which the oxidative
addition of 1-haloalkyne to an alkynylcopper species or
σ-bond metathesis mechanism is proposed.
Cu (I)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Alk -
yn ylsila n es w ith Ar yl(ch lor o)eth yn es: F or m a tion
of Un sym m etr ica l Con ju ga te Diyn es. We next exam-
Various alkynylsilanes 1 and 1-chloroalkynes 19 were
coupled in the presence of 10 mol % of CuCl. The results
are summarized in Table 6. The reaction of 1-phenyl-2-
(
26) The palladium-catalyzed cross-coupling reaction of aryl triflates
with terminal alkynes to give the corresponding Sonogahshira coupling
products without CuI has been reported. See: Chen, Q.-Y.; Yang, Z.-
Y. Tetrahedron Lett. 1986, 27, 1171.
(
27) (a) Stiegman, A. E.; Miskowski, V. M.; Perry, J . W.; Coulter,
(28) (a) Cadiot, P.; Chodkiewicz, W. C. R. Hebd. Seance Acad. Sci.
1955, 241, 1055. (b) Chodkiewicz, W. Ann. Chim. Paris 1957, 2, 819.
(29) Philippe, J . L.; Chodkiewicz, W.; Cadiot, P. Tetrahedron Lett.
1970, 1795.
(30) Alami, M.; Ferri, F. Tetrahedron Lett. 1996, 37, 2763 and
references therein.
D. R. J . Am. Chem. Soc. 1987, 109, 5884. (b) Graham, E. M.;
Miskowski, V. M.; Perry, J . W.; Coulter, D. R.; Stiegman, A. E.;
Schaefer, W. P.; Marsh, R. E. J . Am. Chem. Soc. 1989, 111, 8771. (c)
Stiegman, A. E.; Graham, E.; Perry, K. J .; Khundkar, L. R.; Cheng,
L.-T.; Perry, J . W. J . Am. Chem. Soc. 1991, 113, 7658.

Cu(I)-Mediated Coupling Reactions of Alkynylsilanes
J . Org. Chem., Vol. 65, No. 6, 2000 1785
and benzophenone prior to use. Pd(PPh Cl was prepared
Ta ble 6. Cu (I)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of
Alk yn ylsila n es 1 w ith 1-Ch lor oa lk yn es 19a
3
)
2
2
32
according to the literature. Copper(I) chloride, bromide, and
iodide were purified by the literature method.33
The following alkynylsilanes were prepared by literature
procedures:34 1-phenyl-2-trimethylsilylethyne (1a ), [(4-meth-
35
1
5b
oxyphenyl)ethynyl]trimethylsilane (1b), 1-{4-[(trimethylsilyl)-
1
5b
ethynyl]phenyl}ethanone (1c), (2-thienylethynyl)trimethyl-
36
37
39
alkynylsilane 1,
1-chloroalkyne
yield,b
%
silane (1d ), 4-[(trimethylsilyl)ethynyl]benzonitrile (1e),
1
2
38
entry
R
)
19, R
)
product
trimethyl(1-octynyl)silane (2a), triethyl(1-octynyl)silane (2b),
and dimethylphenyl(1-octynyl)silane (2d ).40
1
2
3
4
C
1a
1a
6
H
5
- (1a )
4-MeCO-C
6
H
4
- (19a ) 20a
62 (56)
85 (53)
43
4-Cl-C
4-MeO-C
19a
6
H
4
6
- (19b)
H - (19c) 20c
4
20b
Spectroscopic data and physical properties of new alkynyl-
silanes 1 and 2 are listed below.
4-MeO-C
1b
1b
4-MeCO-C
1c
1c
6
H
4
- (1b)
20d
20e
20c
20f
20d
20a
20g
20h
97 (52)
95 (54)
90 (65)
60 (42)
60
69
93 (61)
62 (32)
[(4-ter t-Bu t yld im et h ylsiloxyp h en yl)et h yn yl]t r im et h -
ylsila n e (1f): isolated in 99% yield as a colorless liquid; IR
c
5
19b
6
7
8
9
0
1
C
6
H
5
- (19d )
-1 1
(
neat) 2959, 2932, 2897, 2860, 2159, 1262, 841 cm ; H NMR
200 MHz, CDCl ) δ 0.19 (s, 6 H), 0.25 (s, 9 H), 0.98 (s, 9 H),
.76 (d, J ) 9.0 Hz, 2 H), 7.36 (d, J ) 9.0 Hz, 2 H); C NMR
50.3 MHz, CDCl ) δ -4.44, 0.06, 18.21, 25.63, 92.56, 105.23,
115.96, 120.08, 133.44, 156.12; HRMS calcd for C17
6
H
4
- (1c)
19b
19c
19d
(
6
3
1
3
(
3
1
1
4-NC-C
4- BuMe
6
H
4
- (1e)
19a
t
H28OSi
2
2
SiO-C
6
H
4
- (1f) 19b
+
3
04.1679, found M , 304.1681.
Tr iisop r op yl(1-octyn yl)sila n e (2c): isolated in 74% yield
as a colorless oil; bp 140 °C/0.6 Torr; IR (neat) 2959, 2942,
a
Typical procedure: 1 (1.0 mol) and 19 (1.5 mol) were used in
b
DMF (5 mL) for 48 h otherwise noted. GC yield based on 1 and
isolated yields are given in parentheses. Reaction time was 96
c
-1 1
2
3
867, 2172, 1464, 1383, 883 cm ; H NMR (300 MHz, CDCl )
h.
δ 0.91 (t, J ) 7.0 Hz, 3 H), 0.99-1.56 (m, 29 H), 2.24 (t, J )
trimethylsilylethyne (1a ) with electron-deficient 1-chloro-
alkynes (19a or 19b) gave coupled products 20a and 20b
in 62 and 85% yields, respectively (entries 1 and 2). The
reaction of 1a and 19c furnished 20c in only 43% yield
entry 3), whereas the opposite substituent combination
of substrates (1b and 19d ) gave 20c in 90% yield (entry
). Electron-rich alkynylsilane 1b produced unsym-
metrical 1,3-butadiynes 20 in higher yields (entries 4-6)
than electron-deficient alkynylsilane 1c (entries 7-9).
Thus, successful formation of the desired cross-coupled
products requires not only an appropriate choice of a
substituent on the aromatic ring but also an appropriate
combination of starting materials.
7.0 Hz, 2 H); 13C NMR (75 MHz, CDCl ) δ 11.37, 14.01, 18.63,
3
19.85, 22.63, 28.42, 28.87, 31.35, 79.92, 109.28; HRMS calcd
+
for C17
H
34Si 266.2428, found M , 266.2427.
Gen er a l P r oced u r e for Hom o-Cou p lin g R ea ct ion of
Alkyn ylsilan es: For m ation of 1,4-Diph en yl-1,3-bu tadiyn e
(
(
3a ).41 To a DMF (0.5 mL) solution of CuCl (57 mg, 0.58 mmol)
placed in a reaction tube equipped with a magnetic stirring
bar was added 1a (100 mg, 0.58 mmol). The reaction mixture
was stirred for 3 h at 60 °C and quenched with 1 M
hydrochloric acid. The aqueous layer was separated and
extracted with 20 mL of diethyl ether. The combined ethereal
6
2 4
layer was washed with brine and dried over Na SO . Bulb-to-
bulb distillation (200-210 °C/3 Torr) gave 1a in 86% yield as
a colorless solid (GC yield; >99%). The following symmetrical
conjugate diynes were prepared by literature procedures: 1,4-
4
2
di(4-methoxyphenyl)-1,3-butadiyne (3b), 1,4-di(4-acetylphe-
Con clu sion
43
44
nyl)-1,3-butadiyne (3c), and 7,9-hexadecadiyne (4).
,4-Di(2-th ien yl)-1,3-bu ta d iyn e (3d ): isolated in 20%
yield as a light sensitive pale yellow solid; GC yield was 70%;
1
We have developed a convenient synthesis of conju-
gated diynes through the homo-coupling of alkynyltri-
methylsilanes using copper(I) salt in DMF under aerobic
conditions. The reaction proceeds on the basis of trans-
metalation of the alkynyl group from silicon to copper
followed by oxidative dimerization leading to the diyne.
The successful transmetalation allowed us to effect the
cross-coupling of alkynylsilanes with aryl- or alkenyl
triflates using a Cu(I)/Pd(0) cocatalyst system. An alter-
native route to Cadiot-Chodkiewicz coupling leading to
the synthesis of unsymmetrical conjugate diynes starting
with aryl(chloro)ethynes and (arylethynyl)silanes was
explored. These coupling reactions are synthetically
useful since a readily available trimethylsilyl group is
employed as substrate in contrast to the coupling of aryl
or alkenyl silicon compounds that generally require
-1
1
mp 92-93 °C; IR (neat) 3106, 2141, 1408, 714 cm ; H NMR
200 MHz, CDCl ) δ 7.00 (dd, J ) 5.1, 3.7 Hz, 2 H), 7.32 (dd,
J ) 5.1, 1.2 Hz, 2 H), 7.34 (dd, J ) 3.7, 1.2 Hz, 2 H); C NMR
(50.3 MHz, CDCl ) δ 76.63, 77.77, 121.95, 127.20, 128.90,
34.39. Anal. Calcd for C12 : C, 67.25; H, 2.28. Found: C,
7.12; H, 2.69.
Gen er a l P r oced u r e for Syn th esis of Ar yl Tr ifla tes 8.
(
3
1
3
3
1
6
6 2
H S
To a solution of a phenol in pyridine was added triflic
anhydride (1.2 molar amounts) dropwise at 0 °C. After being
warmed to room temperature and stirred for 1 h, the mixture
was extracted with diethyl ether. The organic layer was
separated, and the aqueous layer was extracted with diethyl
(32) Chatt, J .; Mann, F. G. J . Chem. Soc. 1939, 1622.
(33) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: Oxford, 1988; p 322.
(
34) Campbell, I. B. The Sonogashira Cu-Pd-catalyzed alkyne
heteroatom substituent(s) on the silicon for a smooth
coupling reaction. In Organocopper Reagents A Practical Approach;
Taylor, R. J . K.. Ed.; Oxford University Press: Oxford, 1994; pp 217-
35.
reaction.1
7c,31
Because these coupling reactions take place
2
under neutral conditions, a wide variety of synthetic
applications for the construction of novel molecules
bearing a carbon-carbon triple bond would be possible.
(35) Benkeser, R. A.; Hickner, R. A. J . Am. Chem. Soc. 1958, 80,
5298.
(36) Genet, J . P.; Balart, E.; Savinac, M. Synlett 1992, 715.
37) Soderquist, J . A.; Rane, A. M.; Matos, K.; Ramos, J . Tetrahedron
(
Lett. 1995, 36, 6847.
(
(
38) Ashby, E. C.; Noding, S. A. J . Org. Chem. 1980, 45, 1035.
39) Uchida, K.; Utimoto, K.; Nozaki, H. J . Org. Chem. 1976, 41,
Exp er im en ta l Section
DMF, triethylamine, pyridine, and acetonitrile were distilled
2215.
(
40) Hayami, H.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1984,
from CaH
2
and stored over MS-4A under an argon atmosphere.
2
5, 4433.
Tetrahydrofuran (THF) and toluene were distilled from sodium
(
(
41) Liu, Q.; Burton, D. J . Tetrahedron Lett. 1997, 38, 4371.
42) Galamb, V.; Gopal, M.; Alper, H. Organometallics 1983, 2, 801.
(
31) Homo-coupling of aryl- and alkenylsilanes in the presence of a
(43) Akiyama, T.; Amino, M.; Saitou, T.; Utsunomiya, K.; Seki, K.;
Ikoma, Y.; Kajitani, M.; Sugiyama, T.; Shimizu, K.; Sugimori, A. Bull.
Chem. Soc. J pn. 1998, 71, 2351.
copper salt will be described in due course: Nishihara, Y.; Ikegashira,
K.; Toriyama, F.; Mori, A.; Hiyama, T. Bull. Chem. Soc. J pn., in press.

1
786 J . Org. Chem., Vol. 65, No. 6, 2000
Nishihara et al.
ether. The combined organic layers were washed with two
portions of water, 3 M hydrochloric acid, and brine and dried
Hz, 2 H), 7.67 (d, J ) 8.2 Hz, 2 H), 7.86 (d, J ) 8.6 Hz, 2 H);
1
3
C NMR (50.3 MHz, CDCl ) δ 21.60, 26.48, 122.36, 128.33,
3
over MgSO
4
. Filtration and concentration, followed by removal
129.84, 129.94, 131.98, 135.58, 145.71, 152.86, 196.54; HRMS
+
of the solvent under reduced pressure, gave analytically pure
triflates 8a -8f and 8i-8m in yields ranging from 58% to 95%.
Cyclic enol triflate 8g was prepared from 4-tert-butylcyclo-
14 4
calcd or C15H O S 290.0612, found M , 290.0612.
Gen er a l P r oced u r e for Syn th esis of Un sym m etr ica l
Disu bstitu ted Eth yn es: F or m a tion of 1-[4-(P h en yleth -
4
7
54
hexanone with LDA, followed by addition of PhN(SO
2
CF
3
) ,
yn yl)p h en yl]eth a n on e (11a ). To a solution of CuCl (10 mg,
and 1-naphthyl trifluoromethanesulfonate (8h ) was purchased
from Aldrich Chemical Co., Inc. and used without further
purification. Aryl triflates 8a -8f and 8i-8m were prepared
0.1 mmol, 2 mol %) and tetrakis(triphenylphosphine)palladium
(58 mg, 0.05 mmol, 1 mol %) in DMF (25 mL) were added
1-phenyl-2-trimethylsilylethyne (1a ) (984 µL, 6.0 mmol) and
4-acetylphenyl trifluoromethanesulfonate (8a ) (945 µL, 5.0
mmol) at room temperature. The reaction mixture was stirred
for 24 h at 80 °C, quenched with 3 M HCl, and extracted with
diethyl ether (25 mL × 2). The combined ethereal layer was
washed with aqueous NaHCO3 and brine and dried over
4
5,46
according to the previously described procedures:
4-acetyl-
4
5
phenyl trifluoromethanesulfonate (8a ), phenyl trifluoro-
4
8,49
methanesulfonate (8b),
4-cyanophenyl trifluoromethane-
4
9
sulfonate (8c), 2-methoxyphenyl trifluoromethanesulfonate
8e), 4-methoxyphenyl trifluoromethanesulfonate (8f), 4-(1,1-
4
9
46
(
dimethylethyl)-1-cyclohexen-1-yl trifluoromethanesulfonate
MgSO . Filtration and evaporation afforded a brown oil.
4
5
0
51
(
8g), 2-naphthyl trifluoromethanesulfonate (8i), 2-pyridyl
Column chromatography (silica gel, hexane-diethyl ether )
5
2
trifluoromethanesulfonate (8j), 2-quinolyl trifluoromethane-
sulfonate (8k ), 4-acetylphenyl methanesulfonate (14).
1:1, R ) 0.56) gave a brown powder. Bulb-to-bulb distillation
f
4
6
53
(200-210 °C/5 Torr) gave 11a (979 mg, 89% yield) as colorless
Spectroscopic data and physical properties of triflates (8d ,
l, and 8m ), nonaflate 12, and tosylate 13 are listed below.
solid. The GC yield was 97%.
8
The following unsymmetrical disubstituted ethynes were
2
,4-Diflu or op h en yl t r iflu or om et h a n esu lfon a t e (8d ):
prepared by literature procedures: 1-{4-[(4-methoxyphenyl)-
isolated in 88% yield as a colorless liquid; IR (neat) 3132, 3097,
55
ethynyl]phenyl}ethanone (11b), 1-methoxy-4-(phenylethyn-
3
075, 1624, 1608, 1509, 1306, 745, 688 cm-1; H NMR (300
MHz, CDCl
) δ 6.92-7.07 (m, 2 H), 7.30-7.38 (m, 1 H); 13
NMR (75 MHz, CDCl ) δ 106.02 (dd, J C-F ) 27, 22 Hz), 112.08
dd, J C-F ) 23, 4 Hz), 118.72 (q, J C-F ) 318 Hz), 124.43 (d,
C-F ) 10 Hz), 133.25 (dd, J C-F ) 14, 5 Hz), 154.07 (dd, J C-F
254, 13 Hz), 161.61 (dd, J C-F ) 251, 10 Hz);HRMS calcd for
1
56
yl)benzene (11c), 4-[(4-methoxyphenyl)ethynyl]benzonitrile
C
57
58
3
(
11d), 1-[4-(2-thienylethynyl)phenyl]ethanone (11h ), 1-(phen-
59
3
ylethynyl)naphthalene (11n ), 2-(phenylethynyl)naphthalene
(
J
)
C
59
60
(
11o), 2-(phenylethynyl)pyridine (11p ), 2-(phenylethynyl)-
61
quinoline (11q).
2
,4-Diflu or o-1-[(4-m e t h oxyp h e n yl)e t h yn yl]b e n ze n e
+
7
H
3
F
5
O
3
S 261.9723, found M , 261.9746.
-P en tylp h en yl tr iflu or om eth a n esu lfon a te (8l): iso-
lated in 92% yield as a colorless liquid; bp 165 °C/5 Torr; IR
(
11e): isolated in 79% yield as colorless solid; GC yield was
4
8
8
6
2%; mp 65-66 °C; IR (KBr) 2844, 2150, 1615, 1510, 1248,
1
-1
18 cm ; H NMR (300 MHz, CDCl ) δ 3.83 (s, 3 H), 6.83-
13
3
-
1 1
(
neat) 2961, 2934, 2861, 1501, 1142, 845 cm ; H NMR (300
MHz, CDCl ) δ 0.89 (t, J ) 7.0 Hz, 3 H), 1.27-1.39 (m, 4 H),
.60 (quintet, J ) 7.8 Hz, 2 H), 2.60 (t, J ) 7.5 Hz, 2 H), 7.15,
3
.91 (m, 4 H), 7.44-7.51 (m, 3 H); C NMR (75 MHz, CDCl )
3
δ 55.29, 80.33, 94.15, 104.19 (dd, J C-F ) 26, 25 Hz), 108.53
d, J C-F ) 20 Hz), 111.46 (dd, J C-F ) 22, 4 Hz), 113.99, 114.76,
33.10, 134.00 (dd, J C-F ) 10, 3 Hz), 159.86, 162.38 (dd, J C-F
250, 11 Hz), 162.75 (dd, J C-F ) 252, 12 Hz); HRMS calcd
1
(
(
1
1
3
d, J ) 9.0 Hz, 2 H), 7.22 (d, J ) 9.0 Hz, 2 H); C NMR (75
MHz, CDCl ) δ 13.85, 22.45, 30.96, 31.38, 35.24, 118.80 (q, J C-F
319 Hz), 120.94, 129.98, 143.49, 147.67; HRMS calcd for
S 296.0693, found M , 296.0686.
,4-Diflu or op h en yl tr iflu or om eth a n esu lfon a te (8m ):
isolated in 64% yield as a colorless liquid; IR (neat) 3098, 1626,
3
)
)
C
+
for C15
-[(2-Meth oxyp h en yl)eth yn yl]m eth oxyben zen e (11f):
isolated in 40% yield as a yellow liquid; GC yield was 49%; IR
10 2
H F O 244.0700, found M , 244.0703.
+
12
H
15
F
3
O
3
4
3
-1
1
(
KBr) 2838, 2216, 1607, 1489, 834 cm ; H NMR (300 MHz,
CDCl ) δ 3.82 (s, 3 H), 3.91 (s, 3 H), 6.85-6.96 (m, 4 H), 7.26-
.32 (m, 1 H), 7.47-7.53 (m, 3 H); C NMR (75 MHz, CDCl
δ 55.26, 55.81, 84.26, 93.39, 110.59, 112.68, 113.82, 115.64,
20.44, 129.39, 133.07, 133.40, 159.44, 159.69; HRMS calcd
-
1 1
1
3
294, 781 cm ; H NMR (300 MHz, CDCl ) δ 7.05-7.11 (m, 1
13
3
H), 7.15-7.23 (m, 1 H), 7.27-7.32 (m, 1 H); C NMR (75 MHz,
CDCl ) δ 111.89 (d, J C-F ) 21 Hz), 117.85 (dd, J C-F ) 7, 4
Hz), 118.20 (d, J C-F ) 20 Hz), 118.68 (q, J C-F ) 319 Hz), 144.40
dd, J ) 7, 4 Hz), 150.05 (dd, J C-F ) 249, 13 Hz), 150.26 (dd,
C-F ) 253, 14 Hz); HRMS calcd for C S 261.9723,
13
7
3
)
3
1
(
J
+
for C16
-{4-[(4-Cya n op h en yl)eth yn yl]p h en yl}eth a n on e (11g):
isolated in 65% yield as colorless solid; GC yield was 98%; mp
14 2
H O 238.0994, found M , 238.0993.
7 3 5 3
H F O
1
+
found M , 261.9711.
-Acetylp h en yl n on a flu or obu ta n esu lfon a te (12): iso-
lated in 71% yield as white solid; mp 41-42 °C; IR (KBr) 1694,
4
-1
1
28-129 °C; IR (KBr) 3080, 3050, 2226, 1688, 1603, 828 cm ;
1
H NMR (200 MHz, CDCl ) δ 2.63 (s, 3 H), 7.60-7.66 (m, 6
H), 7.94-8.00 (m, 2 H); C NMR (50.3 MHz, CDCl
9
1
8
3
-
1 1
1
266 cm ; H NMR (300 MHz, CDCl
J ) 9.0 Hz, 2 H), 8.05 (d, J ) 9.0 Hz, 2 H); C NMR (75 MHz,
CDCl ) δ 26.46, 105-120 (m), 121.54, 130.50, 136.81, 152.66,
95.98; F NMR (188 MHz, CDCl
m), -109.13 (m), -81.10 (t, J F-F ) 10 Hz); HRMS calcd for
3
) δ 2.63 (s, 3 H), 7.38 (d,
1
3
3
) δ 26.55,
13
2.58, 111.98, 118.26, 126.88, 128.27, 128.47, 131.85, 132.04,
32.13, 133.83, 136.81, 197.05. Anal. Calcd for C17
3.25; H, 4.52; N: 5.71. Found: C, 83.63; H, 4.57; N, 5.49.
3
H
11NO: C,
1
9
1
(
C
3
) δ -126.32 (m), -121.35
+
4-(2-Th ien yleth yn yl)ben zon itr ile (11i): isolated in 52%
12
H
7
F
9
O
4
S 417.9920, found M , 417.9926.
-Acetylp h en yl (4-tolu en esu lfon a te) (13): isolated in
1% yield as white solid; mp 74-75 °C; IR (KBr) 3062, 3048,
yield as colorless solid; GC yield was 79%; mp 134-135 °C;
4
-1 1
IR (KBr) 3100, 2228, 2203, 1603, 839 cm ; H NMR (200 MHz,
CDCl
7
2
3
919, 1682, 1269 cm-1; H NMR (200 MHz, CDCl
1
3
) δ 6.45-6.60 (m, 2 H), 7.26-7.42 (m, 2 H), 7.48-7.70
13
3
) δ 2.41 (s,
(
1
3
m, 3 H); C NMR (50.3 MHz, CDCl ) δ 87.13, 91.43, 111.54,
H), 2.53 (s, 3 H), 7.05 (d, J ) 8.6 Hz, 2 H), 7.29 (d, J ) 8.2
18.46, 122.13, 127.34, 127.89, 128.53, 131.74, 132.05, 133.01.
(
44) Hubert, A. J . J . Chem. Soc. 1965, 6669.
(45) Subramanian, L. R.; Hanack, M.; Chang, L. W. K.; Imhoff, M.
(54) Stephens, R. D.; Castro, C. E. J . Org. Chem. 1963, 28, 3313.
(55) Kiryu, T.; Ebisawa, M. Patent, J P 07188095 Heisei; Chem.
A.; Schleyer, P. R.; Kurtz, W.; Stang, P. J .; Dueber, T. E. J . Org. Chem.
1
976, 41, 4099.
46) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987, 109,
478.
Abstr. 1995, 123, 301658w.
(56) Larrock, R. C.; Doty, M. J .; Cacchi, S. J . J . Org. Chem. 1993,
58, 4579.
(
5
(
(
(
47) McMurry, J . E.; Scott, W. J . Tetrahedron Lett. 1980, 21, 4313.
48) Stang, P. J .; Anderson, A. G. J . Org. Chem. 1976, 41, 781.
49) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J . Org.
(57) Bresse, M. Patent, FR 2243023 750404; Chem. Abstr. 1975, 83,
171287s.
(58) Zimmer, O.; Vollenberg, W.; Seipp, U.; Englberger, S.; Strohm-
ann, W.; Haurand, M.; Bosman, B. J .; Schneider, J . Patent, EP 91-
111487 910710; Chem. Abstr. 1992, 117, 26103v.
(59) Rausch, M. D.; Tokas, E. F.; Mintz, E. A.; Clearfield, A.;
Mangion, M.; Bernal, I. J . Organomet. Chem. 1979, 172, 109.
(60) Agawa, T.; Miller, S. I. J . Am. Chem. Soc. 1961, 83, 449.
(61) Yamanaka, H.; Shiraiwa, M.; Edo, K.; Sakamoto, T. Chem.
Pharm. Bull. 1979, 27, 270.
Chem. 1992, 57, 1481.
(50) Scott, W. J .; Stille, J . K. J . Am. Chem. Soc. 1986, 108, 3033.
(51) McMurry, J . E.; Mohanraj, S. Tetrahedron Lett. 1983, 24, 2723.
(52) Keumi, T.; Saga, H.; Taniguchi, R.; Kitajima, H. Chem. Lett.
1
977, 1099.
53) Perces, V.; Bae, J .-Y.; Zhao, M.; Hill, D. H. J . Org. Chem. 1995,
0, 176.
(
6

Cu(I)-Mediated Coupling Reactions of Alkynylsilanes
J . Org. Chem., Vol. 65, No. 6, 2000 1787
Anal. Calcd for C13
C, 74.95; H, 3.57; N, 6.73.
-{[4-t er t -B u t y l(d im e t h y ls ilo x y )p h e n y l]e t h y n y l}-
H
7
N: C, 74.61; H, 3.37; N: 6.69. Found:
4-cyanophenyl trifluoromethanesulfonate (8c) and CuCl (10
mg, 0.1 mmol 10 mol %) were added to the reaction mixture
at 60 °C, and the resulting mixture was stirred for 12 h at 80
°C and the GC yield was calculated using an authentic sample
of 11g to be 94%. 1,2-Difluoro-4-[(4-pentylphenyl)ethynyl]-
4
ben zon itr ile (11j): isolated in 71% yield as colorless solid;
GC yield was 82%; mp 77-78 °C; IR (KBr) 2959, 2930, 2889,
-
1
1
63
2
861, 2230, 2211, 1597, 1512, 1287, 839 cm ; H NMR (200
benzene (11r ) was reported in the literature.
MHz, CDCl
3
) δ 0.22 (s, 6 H), 0.98 (s, 9 H), 6.83 (d, J ) 8.8 Hz,
Gen er a l P r oced u r e for Syn th esis of 1-Ch lor oa lk yn es
19a -19d ). To a solution of a terminal alkyne (1.0 mmol) in
THF (2.0 mL) was added butyllithium (1.1 mmol, 1.59 M
hexane solution) dropwise at -78 °C. The reaction mixture
was stirred for 30 h at -78 °C and then treated with
N-chlorosuccinimide (1.3 mmol) at -78 °C. The reaction
mixture was warmed to room temperature under stirring for
h, quenched with H O, and extracted with diethyl ether. The
2
organic layer was separated, and the aqueous layer was
extracted with diethyl ether. The combined ethereal layers
4
were washed with brine and dried over MgSO . Filtration and
concentration in vacuo, followed by purification with column
2
H), 7.42 (d, J ) 8.8 Hz, 2 H), 7.56 (d, J ) 8.8 Hz, 2 H), 7.62
(
1
3
(d, J ) 8.8 Hz, 2 H); C NMR (50.3 MHz, CDCl
3
) δ 4.41, 18.22,
2
1
3
5.61, 86.82, 94.12, 111.06, 114.90, 118.61, 120.37, 128.64,
31.85, 132.00, 133.33, 156.75; HRMS calcd for C21
33.1549, found M , 333.1555.
H
23ONSi
+
1
-{4-[1-(Octyn yl)p h en yl]}eth a n on e (11k ): isolated in
6
5% yield as a pale yellow oil; GC yield was 87%; bp 190-200
1
-
1 1
°
C/5 Torr; IR (neat) 2226, 1686, 1601, 841 cm ; H NMR (200
MHz, CDCl ) δ 0.91 (t, J ) 6.5 Hz, 3 H), 1.28-1.66 (m, 8 H),
.43 (t, J ) 7.0 Hz, 2 H), 2.58 (s, 3 H), 7.46 (d, J ) 8.0 Hz, 2
3
2
1
3
H), 7.87 (d, J ) 8.0 Hz, 2 H); C NMR (50.3 MHz, CDCl
1
1
3
) δ
3.63, 19.12, 22.18, 25.90, 28.19, 28.24, 30.96, 79.80, 93.87,
27.69, 128.72, 131.16, 135.25, 196.32. Anal. Calcd for
20O: C, 84.16; H, 8.83. Found: C, 83.93; H, 8.87.
-{[4-(1,1-Dim eth yleth yl)-1-cycloh exen -1-yl]eth yn yl}-
chromatography, gave 19a -19d .
The following 1-chloroalkynes were prepared by literature
C
16
H
64
65
procedures: 1-chloro-2-(4-chlorophenyl)ethyne (19b), 1-chloro-
4
65
2
(
-(4-methoxyphenyl)ethyne (19c), 1-chloro-2-phenylethyne,
m eth oxyben zen e (11l): isolated in 90% yield as a colorless
solid; GC yield was >99%; mp 85-86 °C; IR (KBr) 2953, 2874,
64,66
19d ).
1
-Ch lor o-2-(4-a cetylp h en yl)eth yn e (19a ): isolated in
2
841, 1509, 830 cm-1; 1H NMR (200 MHz, CDCl
3
) δ 0.88 (s, 9
-
1
3
0% yield as a yellow liquid; IR (neat) 2222, 1690, 1603 cm
;
H), 1.10-1.38 (m, 2 H), 1.77-2.00 (m, 2 H), 2.08-2.40 (m, 3
H), 3.80 (s, 3 H), 6.25 (brs, 1 H), 6.82 (d, J ) 8.8 Hz, 2 H), 7.36
1
H NMR (200 MHz, CDCl
3
) δ 2.57 (s, 3 H), 7.50 (d, J ) 8.5
Hz, 2 H), 7.88 (d, J ) 8.5 Hz, 2 H); 13C NMR (50.3 MHz, CDCl
)
1
3
3
(
2
1
d, J ) 8.8 Hz, 2 H); C NMR (50.3 MHz, CDCl ) δ 23.87,
3
δ 26.51, 68.68, 71.53, 126.89, 128.17, 132.06, 136.50, 197.08;
7.14, 27.50, 30.86, 32.21, 43.30, 55.26, 86.89, 89.62, 113.91,
15.99, 120.70, 132.87, 134.79, 159.28. Anal. Calcd for
24O: C, 85.03; H, 9.01. Found: C, 84.72; H, 8.97.
-{[4-(1,1-Dim eth yleth yl)-1-cycloh exen -1-yl]eth yn yl}-
+
HRMS calcd for C10
7
H ClO 178.0185, found M , 178.0185.
Gen er a l P r oced u r e for Syn th esis of Un sym m etr ica l
Con ju ga te Diyn es: F or m a tion of 1-(4-Meth oxyp h en yl)-
-p h en yl-1,3-bu ta d iyn e (20c). To a solution of CuCl (2.4 mg,
19
C H
4
4
0
ben zon itr ile (11m ): isolated in 44% yield as colorless solid;
GC yield was 86%; mp 138-140 °C; IR (KBr) 2926, 2885, 2224,
.02 mmol, 10 mol %) in DMF (1.5 mL) were added 1-chloro-
209, 1601, 1501, 839 cm- ; H NMR (200 MHz, CDCl
1
1
2-phenylethyne (19d ) (50 mg, 0.37 mmol) and [(4-methoxy-
phenyl)ethynyl]trimethylsilane (1b) (50 µL, 0.24 mmol) at
room temperature. The reaction mixture was stirred for 48 h
at 120 °C, quenched with 3 M HCl, and then extracted with
diethyl ether (25 mL × 2). The combined ethereal layer was
2
3
) δ 0.89
(
s, 9 H), 1.09-1.39 (m, 2 H), 1.78-2.03 (m, 2 H), 2.12-2.34
(
)
m, 3 H), 6.26 (brs, 1 H), 7.47 (d, J ) 8.6 Hz, 2 H), 7.58 (d, J
1
3
3
8.6 Hz, 2 H); C NMR (50.3 MHz, CDCl ) δ 23.71, 27.10,
7.65, 30.46, 32.19, 43.15, 85.63, 95.67, 110.85, 118.64, 120.03,
28.86, 131.86, 131.92, 137.57. Anal. Calcd for C19 21N: C,
2
1
8
3
washed with aqueous NaHCO and brine and dried over
H
4
MgSO . Filtration and evaporation provided brown oily sub-
6.65; H, 8.04; N: 5.32. Found: C, 86.86; H, 7.89; N, 5.25.
stances. Column chromatography (silica gel, hexane:dichlo-
romethane ) 10:1) gave 20c (36 mg, 65% yield) as a colorless
solid. The GC yield was 90%; mp 96-97 °C; IR (KBr) 3076,
Rea ction of Alk yn ylsila n e (1b) w ith Ar yl Ch lor id e
(
15a ) Lea d in g to 11b. To a solution of CuCl (2.3 mg, 0.020
mmol, 10 mol %) and PdCl (dppb) (14 mg, 0.020 mmol, 10 mol
) in DMF (2.0 mL) were added [(4-methoxyphenyl)ethynyl]-
2
-
1
1
3
056, 3035, 2216, 1599, 1506, 828 cm ; H NMR (200 MHz,
CDCl ) δ 3.83 (s, 3 H), 6.86 (d, J ) 9.0 Hz, 2 H), 7.30-7.58 (m,
H); 13C NMR (50.3 MHz, CDCl
) δ 55.32, 72.73, 74.17, 81.01,
1.81, 113.71, 114.17, 122.02, 128.40, 129.01, 132.42, 134.12,
%
3
trimethylsilane (1b) (52 mg, 0.25 mmol) and 4-acetylphenyl
chloride (15a ) (30 µL, 0.23 mmol) at room temperature. The
reaction mixture was stirred for 48 h at 120 °C, and the GC
yield was calculated using an authentic sample of 11b to be
7
8
1
3
+
60.38; HRMS calcd for C17H12O 232.0888, found M , 232.0896.
8
6%.
,2-Bis(4-cya n op h en yl)eth yn e (17).62 To a solution of
CuCl (9 mg, 0.1 mmol, 20 mol %) and Pd(PPh (51 mg, 0.05
1
Ack n ow led gm en t. This work was partially sup-
ported by a Grant-in-aid for Scientific Research (A)
Grant 07405042) and a grant from the Scientific
Research in Priority Area of Inter-element Linkage
Grant 09239102), both from the Ministry of Education,
3 4
)
mmol 10 mol %) in DMF (4 mL) were added 4-cyanophenyl
(
trifluoromethanesulfonate (8c) (167 µL, 1.0 mmol) and bis-
(trimethylsilyl)ethyne (16) (100 µL, 0.44 mmol) at room
(
temperature. The reaction mixture was stirred for 12 h at 80
C before being quenched with 3 M HCl and extracted with
dichloromethane (25 mL × 2). The combined layers were
washed with aqueous NaHCO and brine and dried over
MgSO . Filtration and evaporation gave a brown oil, which
was purified by column chromatography (silica gel, hexane:
Science, Sports, and Culture, J apan.
°
3
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for 2e-2f, 20a , 20b, and 20d -20h and 1H and C NMR
spectra of compounds 1f, 2c, 2e-2g, 8d , 8l, 8m , 11e, 11f, 11j,
12, 13, 19a , and 20a -20h . This material is available free of
charge via the Internet at http://pubs.acs.org.
13
4
dichloromethane ) 1:1; R ) 0.25). The residue was bulb-to-
f
bulb distilled (200-210 °C/5 Torr) to give 17 (81.4 mg, 40%
yield) as colorless solid. The GC yield was 86%.
J O991686K
On e-P ot Syn th esis of 11g fr om (Tr im eth ylsilyl)eth yn e.
To a solution of Pd(PPh
3 4
) (122 mg, 0.1 mmol, 10 mol %) in
DMF (4 mL) and Et N (1 mL) were added 4-acetylphenyl
3
(63) Hsu, C. S.; Tsay, K. T.; Chang, A. C.; Wang, S. R.; Wu, S. T.
trifluoromethanesulfonate (8a ) (200 µL, 1.05 mmol) and (1-
trimethylsilyl)ethyne (18) (150 µL, 1.06 mmol) at room tem-
perature. The mixture was stirred for 6 h at 60 °C. Then,
Liq. Cryst. 1995, 19, 409.
(64) Beltrame, P. L.; Cattania, M. G.; Simonetta, M. J . Chem. Soc.,
Perkin Trans. 2 1973, 63.
(
(
65) Villieras, J .; Perriot, P.; Normant, J . F. Synthesis 1975, 458.
66) Nelson, D. J .; Blue, C. D.; Brown, H. C. J . Am. Chem. Soc. 1982,
(62) Cassar, L. J . Organomet. Chem. 1975, 93, 253.
104, 4913.