Palladium-catalyzed cross-coupling reaction of aryl trimethoxysilanes with terminal alkynes

Article abstract of DOI:10.1016/j.tetlet.2008.11.049

A palladium-catalyzed cross-coupling reaction of aryl trimethoxysilanes with terminal alkynes was described. Thus, di-substituted alkynes were prepared in moderate to good yields. The electron-deficient terminal alkynes also worked well in the procedure.

Full text of DOI:10.1016/j.tetlet.2008.11.049

Tetrahedron Letters 50 (2009) 530–532
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Tetrahedron Letters
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Palladium-catalyzed cross-coupling reaction of aryl
trimethoxysilanes with terminal alkynes
Zhishi Ye, Miaochang Liu, Baoda Lin, Huayue Wu, Jinchang Ding, Jiang Cheng *
College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed cross-coupling reaction of aryl trimethoxysilanes with terminal alkynes was
described. Thus, di-substituted alkynes were prepared in moderate to good yields. The electron-deficient
terminal alkynes also worked well in the procedure.
Received 24 August 2008
Revised 11 November 2008
Accepted 14 November 2008
Available online 19 November 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Alkynes are a recurring functional group in a wide range of nat-
ural products and other bioactive compounds, as well as versatile
intermediates in synthesis.1 Since its introduction in 1975, the
Sonogashira reaction is one of the most straightforward methods
for the preparation of aforementioned compounds.2 Although an
impressive variety of modifications have been reported for this
the most effective among the tested bases, and the yield of 3aa was
sharply increased to 87% (Table 1, entry 11). Other bases, such as
KOAc and KHCO
not as effectively as NaHCO
11). Remarkably, switching the solvent to CH
yield (Table 1, entry 14). Several palladium sources were also
examined, PdCl (dppf) turned out to be better than other ones.
Under our optimized reaction conditions (3.0 mol % of
PdCl (dppf), 3 equiv of AgF and 3 equiv of NaHCO in CH CN), we
3
, also accelerated the cross-coupling process but
(Table 1, entries 9 and 10 vs entry
CN led to a superior
3
3
3
reaction, some drawbacks still remained. For example, alkynes
2
substituted with electron-withdrawing groups have indeed been
generally poor nucleophiles in the Sonogashira alkynylation. And
excess alkynes were required due to the oxidative dimerization
reaction of alkynes in Sonogashira reaction. In 2003, Zou et al.
reported a new procedure for constructing arylalkynes through
cross-coupling of terminal alkynes with arylboronic acids cata-
2
3
3
examined the scope of this transformation. The results are
summarized in Table 2. The aryl trimethoxysilane substrates
Table 1
4
Effects of Pd sources, solvents, bases, and F sources on the palladium-catalyzed cross-
coupling reaction of phenyl trimethoxysilane with phenyl acetylene
lyzed by a palladium–silver system under mild conditions. Very
recently, Wu and co-workers described the cross-coupling reaction
of arylboronic reagents with terminal alkynes catalyzed by cyclo-
Pd,F source
PhSi(OMe)3
+
Ph
Ph
Ph
5
palladated ferrocenylimine/silver(I) oxide at room temperature.
base, solvent
Compared with the organoborons, organosilane reagents especially
1a
2a
3
aa
6
aryl triethoxysilanes are of lowercost and are easily purified by
Entry
Pd source
Solvent
F source
Base
Yielda (%)
distillation or chromatography.7 However, to the best of our
knowledge, employing organosilanes in this transformation was
scarcely reported or studied before.8 Herein, we wish to report a
mild palladium-catalyzed cross-coupling reaction of aryl trimeth-
oxysilanes with terminal alkynes, providing the aryl alkynes in
moderate to good yields.
1
2
3
4
5
6
7
8
9
PdCl
PdCl
PdCl
2
2
2
(dppf)
(dppf)
(dppf)
CH
CH
CH
2
2
2
Cl
Cl
Cl
2
2
2
KF
AgF
AgF
CuF2
TBAFÁ3H
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
K
K
K
K CO
2
K
2
2
2
CO
CO
CO
3
3
3
3
3
<5
62
59
<5
<5
<5
31
<5
35
85
87
20
42
93
34
84
84
2
PdCl (dppf)
2
CH Cl2
2
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
2
2
2
2
2
2
2
2
2
2
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
(dppf)
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
2
O
2
CO
Na
2
CO
3
AcOK
Initial studies were conducted using phenyl trimethoxysilane
t
BuOK
(
1a) and phenyl acetylene (2a) in CH
2
Cl
2
as a model reaction under
(dppf), 3 equiv of
K
3
PO
4
Á3H
3
2
O
air with the combination of 3.0 mol % of PdCl
2
10
KHCO
1
1
1
1
1
2
3
4
NaHCO
NaHCO
NaHCO
NaHCO
NaHCO3
NaHCO
NaHCO
3
3
3
3
various fluoride sources, and bases. The results suggested that
the fluoride sources had dramatic effects on the yields of the
cross-coupling reaction. Among the fluoride sources screened, only
Toluene
THF
CH
3
CN
AgF and AgF
2
showed good catalytic activity (Table 1, entries 2 and
was
15
16
PdCl (dppf)
DMF
2
3
). The bases were also crucial in this transformation. NaHCO
3
PdCl
Pd(OAc)
2
CH
CH
3
CN
CN
3
17
2
3
3
a
3
PhSi(OMe) (59 mg, 0.3 mmol), phenyl acetylene (20 mg, 0.2 mmol), palladium
*
Corresponding author. Tel./fax: +86 577 88156826.
E-mail address: jiangcheng@wzu.edu.cn (J. Cheng).
source (3 mol %), indicated base (0.6 mmol), and fluoride source (0.6 mmol) in dry
solvent (3 mL), rt, 3 h. Isolated yield.
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.11.049

Z. Ye et al. / Tetrahedron Letters 50 (2009) 530–532
531
Table 2
Table 3
Cross-coupling reaction of aryl trimethoxysilane with phenyl acetylene
Cross-coupling reaction of phenyl trimethoxysilane with alkynes
Pd, AgF
Pd, AgF
ArSi(OMe)3
+
Ph
Ph
Ar
PhSi(OMe)3
+
R
Ph
R
NaHCO
3
, CH
3
CN
NaHCO , CH CN
1
2a
3
1a
2
3
3
3
Entry
Ar
Product
Yielda (%)
93
Entry
R
Product
Yielda (%)
Ph
Ph
1
2
3
4
5
6
7
8
Ph 1a
Ph
COOEt
6b
7
3
aa
1
2
COOEt 2b
Bn 2c
3
ab
Ph
4-tolyl
4-Tolyl 1b
90
93
93
99
94
88
64
Ph
Bn
51b
3
ba
3
ac
Ph
Ph
Ph
Ph
Ph
Ph
2-tolyl
Ph
Ph
Ph
Ph
CH OH
2
2-Tolyl 1c
3
4
5
6
CH
2
OH 2d
45
59
38
50
3
ca
3
ad
2-anisolyl
4-anisolyl
CH N(Et)
2
2-Anisolyl 1d
4-Anisolyl 1e
3,5-Xylenyl 1f
2
CH
2 2
N(Et) 2e
3
da
3
ae
CH(OEt)2
2
CH(OEt) 2f
3
ea
3
af
HO
3,5-xylenyl
HO
3
fa
2
g
3ag
naphthenyl
Naphthenyl 1g
a
PhSi(OMe)
3
(59 mg, 0.3 mmol), aryl acetylene (0.2 mmol), PdCl
2
(dppf) (4.4 mg,
CN
3
ga
3
mol %), NaHCO
3
(50 mg, 0.6 mmol), and AgF (76 mg, 0.6 mmol) in dry CH
3
(
3 mL), rt, 3 h. Isolated yield.
Dry CH Cl (3 mL). Isolated yield.
2 2
2-naphthenyl
b
2-Naphthenyl 1h
3
ha
a
ArSi(OMe)
4.4 mg, 3 mol %), NaHCO
CH CN (3 mL), rt, 3 h. Isolated yield.
3
(0.3 mmol), phenyl acetylene (20 mg, 0.2 mmol), PdCl
2
(dppf)
In conclusion, we have successfully developed a new method of
(
3
(50 mg, 0.6 mmol), and AgF (76 mg, 0.6 mmol) in dry
palladium-catalyzed cross-coupling reaction of aryl trimethoxysil-
anes with terminal alkynes. The procedure possessed a broad
scope, including electron-poor alkynes, for which the traditional
3
worked well under the reaction conditions. Electron-donating as
well as electron-neutral aryl trimethoxysilanes coupled efficiently
with phenylacetylene, and good yields were obtained (Table 2, en-
tries 1–6). The dimerization of terminal alkynes, which is a serious
side-reaction in the Sonogashira reaction, was inhibited in the pro-
cedure. And nearly quantitative yield of 3ea was produced based
on the phenyl acetylene used. The method is also tolerant of
ortho-substitution in aryl trimethoxysilanes, and the hindrance
had little effect on the reaction (Table 2, entries 3 and 4). When
naphthalen-1-yl trimethoxysilane (1f) and naphthalen-2-yl tri-
methoxysilane (1h) were employed as the substrates, 3ga and
ArSi(OMe)3
1
AgF
-
[
ArSiF(OMe)3]
4
R
transmetallation
2
3
ha were obtained in 88% and 64% yields, respectively (Table 2,
ArPd2+
5
Pd2+
entries 7 and 8).
AgF
Ag
In the next stage, we explored the reaction of a variety of al-
kynes with PhSi(OMe)
the electron-deficient ethyl propiolate (2b) also gave good yields
Table 3, entry 1), whereas the traditional Sonogashira reaction
does not work well for electron-deficient alkynes. As such, this rep-
resents a simple and practical complemental method for the Sono-
gashira reaction. However, for hydroxy containing alkynes (2d and
3
, as shown in Table 3. It is notable that
R
(
transmetallation
Ag+
2
g) and aliphatic alkyne (2c), lower yields were obtained (Table 3,
R
PdAr
Pd(0)
6
entries 3, 5, and 2).
Based upon the experimental results and the mechanism of pre-
5
vious reports, a plausible mechanism is outlined (Scheme 1). The
catalytic cycle may contain four steps: (1) transmetallation of pal-
À
Ar
R
ladium(II) with [ArSiF(OMe)
3
]
gives the palladium(II) species 5;
3
(
2) palladium(II) intermediate 5 then encounters the second trans-
metallation with alkynylsilver(I) to afford palladium (II) species 6;
3) intermediate 6 reductively eliminates to form the desired prod-
(
Acknowledgments
uct 3 and produces palladium (0); (4) the palladium (0) species is
oxidized by the silver(I) species, and palladium(II) is regenerated.
Scheme 1. Plausible mechanism.

5
32
Z. Ye et al. / Tetrahedron Letters 50 (2009) 530–532
Sonogashira reaction did not work well. Efforts to apply the cata-
lytic system in other cross-coupling transformations are underway
in our laboratory.
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Acknowledgment
We thank the National Natural Science Foundation of China
(
No. 20504023) for financial support.
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Supplementary data
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9. General procedure: Under air, a reaction tube was charged with terminal alkynes
(0.2 mmol), aryl trimethoxysilane (0.3 mmol), PdCl (dppf) (4.4 mg, 3 mol %),
NaHCO (50 mg, 0.6 mmol), AgF (76 mg, 0.6 mmol), and dry CH CN or dry
CH Cl (3 mL). The mixture was stirred at room temperature. The mixture was
2
.
.
2
3
3
2
2
3
For recent reviews, see: (a) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979;
concentrated in vacuo, and the residue was purified by flash column
chromatography on a silica gel to give the desired product.
(
b) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874. For recent examples, see: