Cyclopalladated ferrocenylimines: efficient catalysts for homocoupling and Sonogashira reaction of terminal alkynes

Article abstract of DOI:10.1016/j.tet.2006.12.064

A novel pathway for homocoupling of terminal alkynes has been described using cyclopalladated ferrocenylimine 1 or 2/CuI as catalyst in the air. This catalytic system could tolerate several functional groups. The palladacycle 2 in the presence of n-Bu₄NBr as an additive could be applied to Sonogashira cross-coupling reaction of aryl iodides, aryl bromides, and some activated aryl chlorides with terminal alkynes under amine- and copper-free conditions, mostly to give moderate to excellent yields.

Full text of DOI:10.1016/j.tet.2006.12.064

Tetrahedron 63 (2007) 1963–1969
Cyclopalladated ferrocenylimines: efficient catalysts for
homocoupling and Sonogashira reaction of terminal alkynes
a,b
Fan Yang, Xiuling Cui, Ya-nan Li, Jinli Zhang, Ge-rui Ren and Yangjie Wu
a,b
a,b
a,b
a,b
a,b,*
a
Chemistry Department, The Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province,
Zhengzhou University, Zhengzhou 450052, PR China
The Key and Open Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, PR China
b
Received 10 October 2006; revised 20 December 2006; accepted 21 December 2006
Available online 27 December 2006
Abstract—A novel pathway for homocoupling of terminal alkynes has been described using cyclopalladated ferrocenylimine 1 or 2/CuI as
catalyst in the air. This catalytic system could tolerate several functional groups. The palladacycle 2 in the presence of n-Bu NBr as an additive
4
could be applied to Sonogashira cross-coupling reaction of aryl iodides, aryl bromides, and some activated aryl chlorides with terminal
alkynes under amine- and copper-free conditions, mostly to give moderate to excellent yields.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
Only oxime-derived palladacycles catalyzed homocoupling
1
2
of terminal alkynes were reported recently. This coupling
reaction was effective for both aromatic and aliphatic
alkynes. However, for alkynes with hydroxyl group, the
expected product was obtained in low yield (25%). The
catalytic systems for Sonogashira reaction catalyzed by
Alkynes are important skeleton in some natural products,
pharmaceuticals, biologically active molecules, and non-
linear optical materials. Of the various approaches to
synthesize symmetrical diynes and substituted alkynes,
palladium-catalyzed homocoupling and Sonogashira cross-
coupling of terminal alkynes are two of the most efficient
1
,2
1
2,13
palladacycles had also been reported.
For example,
oxime-derived palladacycles are quite effective for aryl
iodides and bromides with phenylacetylene or other
alkynes. Very recently, Dupont and co-workers have also
3
–10
routes.
A number of catalytic systems has been devel-
6
–9
12
oped. For the successful palladium-catalyzed homocou-
pling of terminal alkynes, an oxidant is necessary besides
phosphine ligands, CuI and the additive such as TBAB as de-
scribed in detail by Fairlamb and co-workers. To satisfy the
environmental concerns, O is an evidently more attractive
alternative to the reported oxidants. So palladium-catalyzed
homocoupling of terminal alkynes performed in the air is ex-
tremely significant. Palladium-catalyzed Sonogashira reac-
tion is typically catalyzed by palladium complexes in the
presence of a copper salt as cocatalyst and an amine as
base. CuI is generally employed as the cocatalyst, which
can result in Cu(_) acetylides in situ and induce the homo-
coupling. Therefore Sonogashira reaction catalyzed by
described a new type of palladacycles. The substrates could
1
3
be iodoarenes and activated bromoarenes. However, both
of the two catalytic systems are limited to aryl iodides and
bromides. So a new system for the Sonogashira cross-
coupling reaction of a wide range of aryl halides using
palladacycle as the catalyst should be developed.
7
2
Here we would like to report cyclopalladated ferrocenyl-
imine 1 or 2 in the presence of CuI as an efficient, mild, and
air stable catalytic system for the synthesis of diynes via
dimerization of terminal alkynes bearing several functional
8
1
0
groups, and palladacycle 2 as the catalyst with n-Bu NBr
4
palladium complexes without amines and copper salts has
attracted more and more attentions recently.
in Sonogashira cross-coupling reaction of ArX (X¼I, Br,
9
and Cl) with terminal alkynes under amine- and copper-
free conditions.
1
4
On the other hand, cyclopalladated complexes emerging as
a new family of palladium catalysts have been widely used
in carbon–carbon and carbon–heteroatom bond formation.
CH3
N
CH3
1
1
C
C
CH3
N
CH3
Fe
Fe
Pd
Pd Cl
Keywords: Cyclopalladated ferrocenylimine; Homocoupling; Sonogashira
reaction; Terminal alkynes.
PPh3
2
Cl
*
Corresponding author. Tel./fax: +86 371 67766667; e-mail: wyj@zzu.
edu.cn
1
2
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.064

1964
F. Yang et al. / Tetrahedron 63 (2007) 1963–1969
Table 2. Palladium-catalyzed homocoupling of alkynes
a
2
. Results and discussion
Pd-Cat CuI
Base
R
R
R
2.1. Palladium-catalyzed homocoupling of terminal
alkynes
3
4
Entry
Alkyne
Cat Cat
t (h)
Product
The results for the screening of the reaction conditions to
promote the catalytic homocoupling of phenylacetylene are
shown in Table 1. It showed that DMF was the best solvent
(mol %)
b
No. Yield (%)
n-C
H
(
3b)
1
2
1
1
17 4b 94
28 4b 95
1
2
5
11
(
entries 1–5), palladacycle 2 was more active than catalyst 1
entries 6 and 7). Even with 0.1 mol % of 2, the expected
(
product was formed in 95% yield within 10 h (entry 8). If
3b
3c
3
(3c)
1
1
30 4c 70
the loading of catalyst 2 was reduced to 0.01 mol %, only
5
N
5% yield was obtained after 24 h (entry 9). In the absence
of the palladacycle, the reaction proceeded slowly (24 h)
with low yield (20%, entry 10) and only moderate yield
4
5
2
1
1
1
25 4c 75
20 4d 50
CH
(CH
)
C
3d
3d
CH (3d)
CH (3e)
3
2
4
6
7
2
2
1
0.1
20 4d 88
40 4d 87
(
57%) was obtained without CuI (entry 11).
a
8
9
CH (CH ) C
1
2
1
1
20 4e 61
21 4e 82
Table 1. Palladium-catalyzed homocoupling of phenylacetylene
3
2 7
Pd-Cat CuI
3e
Ph
Ph
Ph
Base
3
a
4a
1
0
HO
(3f)
2
2
1
1
40 4f 42
26 4f 92
ꢀ
b
Entry Solvent Cat Cat (mol %) t (h) T ( C) Yield (%)
c
c
11
12
3f
1
2
3
4
5
6
7
8
9
1
1
DMSO
1
1
1
1
1
1
2
2
2
—
2
0.5
1
1
0.5
0.5
1
4
6
29
45
45
7
50
50
rt
rt
rt
40
40
40
40
40
40
20
36
25
79
95
85
96
95
55
20
57
OH
CH
CH
CH
3
3
3
CN
CN
CN
(3g)
2
2
1
1
44 4g 61
31 4g 89
1
1
3
3g
DMF
DMF
DMF
DMF
DMF
DMF
DMF
O
4
5
(3h)
2
2
1
1
18 4h 52
1
2
O
0.1
0.01
0
10
24
24
24
c
1
3h
8
4h 71
c
0
1
a
Reaction conditions: 3 (1 mmol), palladacycle, CuI (2.5 mol %), KOAc
ꢀ
d
1
(1.5 equiv), and DMF (2.5 mL) at 40 C in the air.
Isolated yields.
b
c
a
Reaction conditions: 3a (1 mmol), palladacycle, CuI (2.5 mol %), KOAc
1.5 equiv), and solvent (2.5 mL) in the air.
Isolated yields.
Without palladacycle.
In the absence of CuI.
Reaction conditions: 3 (1 mmol), palladacycle, CuI (2.5 mol %), i-Pr
ꢀ
2
EtN
(
b
c
d
(1.2 equiv), and THF (2.5 mL) at 40 C in the air.
However, homocoupling product (4a) increased with de-
creased loading of the catalyst (entries 7–10).
Under these optimized conditions, we examined the sub-
strate scope. As shown in Table 2, this catalytic system could
be used for homocoupling of various terminal alkynes. For
the aromatic or heterocyclic aromatic alkynes, both 1 and
Under the optimized reaction conditions, we first investi-
gated the reactions of aryl iodides bearing electron-donating
a
Table 3. Sonogashira cross-coupling of PhI (5a) with phenylacetylene (3a)
2
gave almost similar results (entries 1–4). While for
Pd-cat
Ph I + Ph
3a
Ph
Ph + Ph
Ph
aliphatic alkynes, the catalytic activity of 2 was higher
than that of 1 (entries 5–9). For hydroxyl (3f and g) or ester
5
a
6aa
4a
(3h) containing alkynes (entries 10, 12, and 14), only lower
yields (42%, 61%, 52%, respectively) were obtained. It is
b
Entry Base/solvent
Additive
t (h) Cat
Yield
(mol %) (%) 6aa
6aa/4a
notable that when the base and solvent were i-Pr EtN and
2
1
2
3
4
5
6
7
8
9
1
KOAc/DMF
KOAc/DMA
i-Pr EtN/THF
n-Bu
4
NBr
NBr
3
1.5
11
1
1
2
3
8
1
1
1
1
1
1
1
34
41
8
28
64
63
90
88
77
57
1/1
3/1
30/1
1.5/1
4/1
THF (entries 11, 13, and 15), moderate to good yields
(
c
—
—
d
c
92%, 89%, 71%, respectively) were obtained.
2
Cs
2
CO
3
/DMA n-Bu
4
KOAc/DMA
KOAc/DMA
KOAc/DMA
KOAc/DMA
KOAc/DMA
KOAc/DMA
CuI
2.2. Palladium-catalyzed Sonogashira cross-coupling
reaction of aryl halides with terminal alkynes
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
4
4
4
4
4
NBr
NBr
NBr
NBr 24
NBr 48
31/1
—
e
e
e
f
f
0.1
0.01
0.001
—
Initially, palladacycle-catalyzed Sonogashira reaction of PhI
(5a) with phenylacetylene (3a) was investigated to survey
the optimal conditions. As shown in Table 3, with 1 mol %
10/1
7/1
e
0
a
Reaction conditions: PhI (0.5 mmol), phenylacetylene (0.6 mmol), base
(0.75 mmol), n-Bu NBr (0.75 mmol) or CuI (3 mol %), palladacycle 2,
of palladacycle 2 the best result was obtained using KOAc
as base, n-Bu NBr as an additive in DMA under nitrogen at-
4
ꢀ
and solvent (2.5 mL) at 80 C.
Isolated yields.
No additives or CuI.
i-Pr EtN (2 equiv).
2
Reactions under nitrogen atmosphere.
No detectable butadiyne.
4
b
c
d
e
f
mosphere (entry 7). The catalytic activity was also examined
(
entries 7–10). The catalyst loadings could be decreased
from 1 mol % to 0.01 mol %, and moderate yield (77%)
could be obtained after prolonging to 24 h (entry 9).

F. Yang et al. / Tetrahedron 63 (2007) 1963–1969
1965
groups (5b–e) with various terminal alkynes. As shown in
Table 4, Sonogashira reaction proceeded smoothly and
moderate to excellent yields were obtained (entries 1–4).
The reaction of p-iodoanisole with phenylacetylene gave
only 56% yield with 0.01 mol % of palladacycle 2 (entry
The electron-poor, electron-neutral, and electron-rich aryl
bromides as substrates were investigated (entries 10–23).
The moderate to high yields were obtained for electron-
poor aryl bromides (5f–h) (entries 10–15). It is notable that
good to excellent yields were obtained for heteroaryl bro-
mides (5i–l) (entries 16–19). However, for electron-neutral
and electron-rich aryl bromides (5m–p), relatively lower to
moderate yields were observed (entries 20–23).
5
). The reaction of electron-rich p-iodoanisole with aro-
matic alkynes, aliphatic alkynes, and alkynes with hydroxyl
group also gave moderate yields (entries 6–9).
a
Table 4. Sonogashira cross-coupling of ArX with terminal alkynes
Pd-Cat KOAc N2
Ar
X
+
R
Ar
R
n-Bu NBr DMA
4
5
3
6
Entry
ArX
R
t (h)
Product
b
Yield (%)
No.
1
2
Ph
Ph
(3a)
(3a)
5.5
5.5
6ba
>99
I
(5c)
6ca
6da
75
74
CH O
3
3
4
Ph
(3a)
5.5
I(5d)
CH O
3
I(5e)
Ph
Ph
(3a)
(3a)
(3b)
11
24
24
21
23
24
6
6ea
6ea
6eb
6ed
6ee
6ef
83
56
68
74
80
61
91
c
5
CH
CH
CH
CH
CH
3
3
3
3
O
O
O
O
O
I(5e)
I(5e)
I(5e)
I(5e)
I(5e)
6
7
8
9
CH
3
(CH
2
)
3
CH
2
1-Hextyne (3d)
1-Decyne (3e)
(3f)
3
HO
10
O N
Br (5f)
Br (5f)
Br (5f)
Br (5f)
Br (5g)
Ph
(3a)
6fa
2
d
O N
Ph
(3a)
2
11
10
24
6fa
6fb
93
90
12
O N
CH (CH ) CH
2
(3b)
2
3
2 3
13
14
15
O N
1-Decyne (3e)
24
10
24
6fe
63
93
77
2
(3a)
(3a)
(3a)
6ga
6ha
CN
Ph
Ph
Ph
H COC
Br (5h)
3
Br (5i)
Br (5j)
1
1
1
6
7
8
20
20
20
6ia
6ja
6ka
99
96
83
N
Ph
Ph
(3a)
(3a)
N
(5k)
S
Br
(
continued)

1966
F. Yang et al. / Tetrahedron 63 (2007) 1963–1969
Table 4. (continued)
Entry
ArX
R
t (h)
Product
b
Yield (%)
No.
Br
5l)
19
Ph
(3a)
22
6la
85
(
S
2
0
1
Br (5m)
Ph
Ph
(3a)
(3a)
6.5
6aa
6ea
60
42
2
CH O
Br (5n)
20
22
3
2
2
2
3
Cl
Br (5o)
Ph
Ph
(3a)
(3a)
6ma
6na
63
85
Br
22.5
(
5p)
e
e
2
2
2
4
Cl (5q)
Ph
(3a)
(3a)
24
24
6ia
6fa
87
50
N
5
O
2
N
Cl (5r)
Ph
Ph
e
e
Cl (5s)
(
3a)
24
30
6ja
29
33
6
N
2
7
H COC
Cl (5t)
6ha
3
Ph
(3a)
a
Reaction conditions: ArX (0.5 mmol), alkyne (0.6 mmol), KOAc (0.75 mmol), n-Bu
ꢀ
4
NBr (0.75 mmol), palladacycle 2 (1 mol %), and DMA (2.5 mL) under
nitrogen at 80 C.
Isolated yields.
b
c
d
e
Palladacycle 2 (0.01 mol %).
Palladacycle 2 (0.1 mol %).
ꢀ
At 110 C.
We also studied the coupling reaction of electron-poor aryl
chlorides at higher temperature and observed that the substi-
tuted groups had a notable effect on the yields. For example,
good (87%) and moderate (50%) yields were obtained for
TMS as an internal standard. Melting points were measured
using a WC-1 microscopic apparatus and are uncorrected.
GC analysis was performed on Agilent 4890D gas chromato-
graph. High-resolution mass spectra were measured on a
Waters Q-Tof MicroÔ spectrometer. Compound 3h was syn-
2
-chloropyridine (5q) and p-chloronitrobenzene (5r), re-
1
5
spectively (entries 24 and 25). While cross-coupling reaction
of 3-chloropyridine (5s) and p-chloroacetophenone (5t) gave
products in low yields (entries 26 and 27).
thesized according to the literature. The other chemicals
were reagent grade and used without further purification.
All of the products 4 and 6 except 4h were known and the
purified products were identified by comparison of melting
1
13
3. Conclusion
points, H NMR or C NMR spectra with the literatures.
In summary, the cyclopalladated ferrocenylimine 1 or 2 in
the presence of CuI is efficient catalyst for the homocoupling
reactions of terminal alkynes to synthesize 1,3-diynes in the
air. Several functional groups can be tolerated in this reac-
tion. The cyclopalladated ferrocenylimine 2 as the catalyst
4.2. Typical experimental procedure for the
homocoupling of alkynes
A mixture of alkyne 3 (1 mmol), palladacycle, CuI
(2.5 mol %), base, and solvent (2.5 mL) was stirred under
air in preheated oil bath followed by TLC or GC. After the re-
action was finished, 10 mL water was added. The mixture
wasextractedwithethylacetate.Thecombinedorganicphases
were washed with water, dried over anhydrous Na SO , and
filtered. The solvent was removed on a rotary evaporator.
The residue was purified by column chromatography using
hexane or hexane/ethyl acetate as an eluent to afford pure 4.
with n-Bu NBr can be applied to Sonogashira cross-cou-
4
pling reaction of aryl halides with various terminal alkynes
under amine- and copper-free conditions. The aryl halides
can be extended to some activated aryl chlorides. Further
studies on these two reactions are undergoing in our group.
2
4
4. Experimental
6
h
4
.1. General methods
4.2.1. 1,4-Diphenyl buta-1,3-diyne (4a). White solid, mp
ꢀ ꢀ
6–88 C (lit. 88 C); H NMR (400 MHz, CDCl ) d: 7.54–
3
7.52 (m, 4H), 7.38–7.34 (m, 6H); C NMR (100 MHz,
CDCl ) d: 132.5, 129.2, 128.5, 121.8, 81.5, 73.9.
1
8
1
13
13
H NMR and C NMR spectra were recorded on a Bruker
DPX-400 spectrometer with CDCl3 as the solvent and
3

F. Yang et al. / Tetrahedron 63 (2007) 1963–1969
6a
1967
1
9d
4
White solid, mp 85–86 C (lit. 86 C);
.2.2. 1,4-Bis(p-pentylphenyl)buta-1,3-diyne (4b).
ꢀ
4.3.1. Diphenylacetylene (6aa). White solid, mp 58–
ꢀ
1
ꢀ ꢀ
61 C (lit. 60–62 C); H NMR (400 MHz, CDCl ) d:
3
1
H
NMR
1
3
(
400 MHz, CDCl ) d: 7.43 (d, J¼8.00 Hz, 4H), 7.14 (d,
7.62–7.52 (m, 4H), 7.42–7.28 (m, 6H);
(100 MHz, CDCl ) d: 132.0, 128.7, 128.6, 123.7, 89.7.
C NMR
3
J¼8.00 Hz, 4H), 2.60 (t, J¼7.80 Hz, 4H), 1.65–1.50 (m,
3
1
3
4
NMR (100 MHz, CDCl ) d: 144.9, 132.8, 129.0, 119.4,
H), 1.36–1.25 (m, 8H), 0.89 (t, J¼6.80 Hz, 6H);
C
1
7
4.3.2. (p-Tolyl)phenylacetylene (6ba). White solid, mp
3
ꢀ ꢀ
71–72 C (lit. 72–73 C); H NMR (400 MHz, CDCl ) d:
3
1
8
2.0, 73.9, 36.4, 31.8, 31.3, 22.9, 14.4.
7
.54–7.49 (d, J¼8.08 Hz, 2H), 7.42 (d, J¼8.08 Hz, 2H),
1
6b
4
.2.3. 1,4-Bis(3-pyridyl)buta-1,3-diyne (4c).
ꢀ
White
solid, mp 144–146 C (lit. 145–146 C); H NMR
7.34–7.32 (m, 3H), 7.14 (d, J¼8.00 Hz, 2H), 2.36 (s, 3H);
ꢀ
1
13
C NMR (100 MHz, CDCl ) d: 138.4, 131.6, 131.5,
3
(
400 MHz, CDCl ) d: 8.79 (s, 2H), 8.62 (d, J¼4.00 Hz,
129.1, 128.3, 128.0, 123.5, 120.2, 89.6, 88.7, 21.5.
3
2
H), 7.86 (d, J¼8.00 Hz, 2H), 7.34 (t, J¼4.80 Hz, 2H);
1
3
18
1
C NMR (100 MHz, CDCl ) d: 152.7, 149.0, 139.9,
3
4.3.3. (3-Tolylphenyl)acetylene (6ca). Colorless oil; H
NMR (400 MHz, CDCl ) d: 7.55–7.50 (m, 2H), 7.40–7.29
1
23.3, 119.1, 79.1.
3
1
3
(m, 5H), 7.27–7.10 (m, 2H), 2.36 (s, 3H); C NMR
(100 MHz, CDCl ) d: 138.0, 132.2, 131.6, 129.2, 128.7,
128.3, 128.2, 128.1, 123.3, 123.0, 89.5, 89.0, 21.3.
6
h
1
4
.2.4. Tetradeca-6,8-diyne (4d). Colorless oil; H NMR
3
(
(
400 MHz, CDCl ) d: 2.25 (t, J¼7.20 Hz, 4H), 1.54–1.48
3
1
3
m, 4H), 1.39–1.28 (m, 8H), 0.89 (t, J¼7.20 Hz, 6H);
C
1
8
NMR (100 MHz, CDCl ) d: 77.5, 65.1, 31.0, 28.0, 22.1,
3
4.3.4. (3-Methoxyphenyl)phenylacetylene (6da). Color-
less oil; H NMR (400 MHz, CDCl ) d: 7.56–7.49 (m,
1
1
9.1, 13.9.
3
2H), 7.42–7.30 (m, 3H), 7.30–7.21 (m, 1H), 7.18–7.10 (m,
1H), 7.08–7.01 (m, 1H), 6.95–6.85 (m, 1H), 3.83 (s, 3H);
C NMR (100 MHz, CDCl ) d: 159.3, 131.6, 129.4, 128.4,
3
6
h
1
4
(
(
.2.5. Eicosa-9,11-diyne (4e). Colorless oil; H NMR
1
3
400 MHz, CDCl ) d: 2.24 (t, J¼7.50 Hz, 4H), 1.57–1.50
3
m, 4H), 1.41–1.35 (m, 4H), 1.34–1.20 (m, 16H), 0.88 (t,
128.3, 124.2, 124.1, 123.1, 116.2, 115.0, 89.3, 89.2, 55.3.
1
3
J¼6.60 Hz, 6H); C NMR (100 MHz, CDCl ) d: 77.6,
3
9d
6
5.2, 31.8, 29.2, 29.1, 28.9, 28.3, 22.7, 19.2, 14.1.
4.3.5. (p-Methoxyphenyl)phenylacetylene (6ea). White
solid, mp 59–60 C (lit. 57–61 C); H NMR (400 MHz,
ꢀ
ꢀ
CDCl ) d: 7.53–7.50 (m, 2H), 7.50–7.45 (m, 2H), 7.37–
1
1
2
4.2.6. 2,7-Dimethyl octa-3,5-diyne-2,7-diol (4f). White
needles, mp 131 C (lit. 131–133 C); H NMR (400 MHz,
C NMR
3
ꢀ
CDCl ) d: 1.89 (s, 2H), 1.54 (s, 12H);
ꢀ
1
7.30 (m, 3H), 6.89–6.86 (d, J¼8.80 Hz, 2H), 3.83 (s, 3H);
1
3
13
C NMR (100 MHz, CDCl ) d: 159.6, 133.1, 131.5,
3
3
(
100 MHz, CDCl ) d: 84.0, 66.3, 65.6, 31.0.
3
128.3, 128.0, 123.6, 115.4, 114.0, 89.4, 88.1, 55.3.
6
h
4
.2.7. 1,4-Bis(1-hydroxycyclohexyl)buta-1,3-diyne (4g).
ꢀ
4.3.6. 1-Hexyl-4-[(4-methoxyphenyl)ethynyl]benzene
(6eb). Colorless oil; H NMR (400 MHz, CDCl ) d:
ꢀ
1
19
1
White solid, mp 175 C (lit. 173–175 C); H NMR
400 MHz, CDCl ) d: 1.95–1.91 (m, 4H), 1.82 (s, 2H),
3
(
7.50–7.35 (m, 4H), 7.13 (d, J¼8.00 Hz, 2H), 6.90–6.80
13
3
1
4
3
.71 (t, J¼8.00 Hz, 4H), 1.63–1.53 (m, 8H), 1.26–1.20 (m,
(m, 2H), 2.60 (t, J¼7.90 Hz, 2H), 1.63–1.58 (m, 2H),
1
3
H); C NMR (100 MHz, CDCl ) d: 83.0, 69.2, 68.3,
3
1.35–1.25 (m, 4H), 0.89 (t, J¼6.50 Hz, 3H); C NMR
9.7, 25.0, 23.1.
(100 MHz, CDCl ) d: 159.5, 143.1, 133.0, 131.3, 128.4,
3
120.7, 115.6, 114.0, 88.7, 88.2, 55.3, 35.9, 31.4, 30.9,
22.5, 14.0.
4.2.8. Methacrylic acid-2,7-dimethyl octa-3,5-diyne-2,7-
diyl ester (4h). Yellow oil; H NMR (400 MHz, CDCl ) d:
1
3
20
6
.06 (s, 2H, CH ]), 5.55 (m, 2H, CH ]), 1.92 (d,
2
4.3.7. 1-(Hept-1-ynyl)-4-methoxy benzene (6ed). Color-
less oil; H NMR (400 MHz, CDCl ) d: 7.32 (d, J¼7.40 Hz,
2
1
J¼0.80 Hz, 6H, C]C–CH ), 1.70 (s, 12H, C(CH ) –
3
3 2
3
1
3
C^C); C NMR (100 MHz, CDCl ) d: 165.5, 136.7,
3
2H), 6.81 (d, J¼7.40 Hz, 2H), 3.81 (s, 3H), 2.38 (t,
J¼7.11 Hz, 2H), 1.62–1.55 (m, 2H), 1.45–1.25 (m, 4H),
1
2
9
25.6, 80.3, 71.9, 68.5, 28.7, 18.2; IR (film): 3023, 2991,
153, 1724, 1466, 1382, 1326, 1231, 1176, 1120, 1008,
39, 857, 811, 729; HRMS (positive ESI) calcd for
1
3
0.92 (t, J¼7.20 Hz, 3H); C NMR (100 MHz, CDCl ) d:
3
159.0, 132.9, 116.3, 113.8, 88.8, 80.2, 55.2, 31.2, 28.6,
22.3, 19.4, 14.0.
+
C H O [M+Na] : 325.1416, found: 325.1404.
18 22 4
9
d
4.3. Typical experimental procedure for Sonogashira
reaction of ArX with terminal alkynes
4.3.8. 1-(Dec-1-ynyl)-4-methoxy benzene (6ee). Color-
less oil; H NMR (400 MHz, CDCl ) d: 7.32 (d,
1
3
J¼8.80 Hz, 2H), 6.80 (d, J¼8.80 Hz, 2H), 3.80 (s, 3H),
2.38 (t, J¼7.50 Hz, 3H), 1.61–1.55 (m, 2H), 1.46–1.41 (m,
2H), 1.40–1.25 (m, 12H), 0.88 (t, J¼6.80 Hz, 3H);
Under nitrogen atmosphere, a mixture of ArX (0.5 mmol),
alkyne (0.6 mmol), palladacycle 2, n-Bu NBr (0.75 mmol),
4
1
3
KOAc (0.75 mmol), and DMA (2.5 mL) was stirred at 80
ꢀ
C NMR (100 MHz, CDCl ) d: 159.0, 132.8, 116.3, 113.8,
3
or 110 C in an oil bath followed by TLC or GC. After the
88.8, 80.2, 55.2, 31.8, 29.2, 29.1, 28.9, 28.8, 22.7, 19.4, 14.1.
reaction was finished, 10 mL water was added, and the mix-
ture was extracted with ethyl acetate. The combined organic
phases were washed with water, dried over anhydrous
Na SO , and filtered. The solvent was removed under re-
duced pressure. The residue was purified by column chroma-
tography using hexane or hexane/ethyl acetate as an eluent
to afford pure 6.
4.3.9. 4-(4-Methoxyphenyl)-2-methyl-3-butyn-2-ol
(6ef). Colorless oil; H NMR (400 MHz, CDCl ) d:
2
0
1
3
7.34 (d, J¼8.80 Hz, 2H), 6.82 (d, J¼8.80 Hz, 2H), 3.80 (s,
2
4
1
3
3H), 2.08 (s, 1H), 1.61 (s, 6H); C NMR (100 MHz,
CDCl ) d: 159.5, 133.0, 114.8, 113.9, 92.4, 82.0, 65.6,
55.3, 31.6.
3

1
968
F. Yang et al. / Tetrahedron 63 (2007) 1963–1969
13
9
d
4
.3.10. 1-Nitro-4-(phenylethynyl)benzene (6fa). Yellow
ꢀ
C NMR (100 MHz, CDCl ) d: 131.5, 129.9, 128.6,
3
ꢀ
1
solid, mp 119–120 C (lit. 118–120 C); H NMR
400 MHz, CDCl ) d: 8.22 (d, J¼8.80 Hz, 2H), 7.66 (d,
128.4, 128.2, 125.4, 123.2, 122.3, 88.8, 84.5.
(
3
2
7
J¼8.80 Hz, 2H), 7.60–7.54 (m, 2H), 7.41–7.38 (m, 3H);
4.3.19. (p-Chlorophenyl)phenylacetylene (6ma). Yellow
oil; H NMR (400 MHz, CDCl ) d: 7.56–7.48 (m, 2H), 7.48–
1
3
1
C NMR (100 MHz, CDCl ) d: 147.0, 132.3, 131.9,
3
3
1
30.3, 129.3, 128.6, 123.7, 122.1, 94.7, 87.6.
7.42 (m, 2H), 7.37–7.32 (m, 4H), 7.32–7.29 (m, 1H);
C NMR (100 MHz, CDCl ) d: 134.7, 133.2, 132.0,
129.1, 128.9, 128.8, 123.3, 122.2, 90.7, 88.6.
1
3
3
4
.3.11. 1-Hexyl-4-[(4-nitrophenyl)ethynyl]benzene
ꢀ
2
1
ꢀ
1
(
6fb). Yellow solid, mp 66–68 C (lit. 70–71 C);
H
2
8
NMR (400 MHz, CDCl ) d: 8.21 (d, J¼8.80 Hz, 2H), 7.65
4.3.20. (1-Phenylethynyl)naphthalene (6na). Yellow oil;
H NMR (400 MHz, CDCl ) d: 8.47–8.42 (m, 1H), 7.90–
3
1
(
d, J¼8.80 Hz, 2H), 7.47 (d, J¼8.00 Hz, 2H), 7.20 (d,
3
1
3
J¼8.00 Hz, 2H), 2.63 (t, J¼7.80 Hz, 2H), 1.65–1.55 (m,
7.59 (m, 3H), 7.68–7.26 (m, 8H); C NMR (100 MHz,
CDCl ) d: 133.4, 133.3, 131.8, 130.5, 128.9, 128.6, 128.5,
128.4, 126.8, 126.5, 126.3, 125.4, 123.5, 121.0, 94.5, 87.7.
2
H), 1.36–1.29 (m, 4H), 0.89 (t, J¼7.20 Hz, 3H);
3
1
3
C NMR (100 MHz, CDCl ) d: 146.8, 144.7, 132.2,
3
1
3
31.8, 130.6, 128.7, 123.7, 119.2, 95.2, 87.1, 36.0, 31.4,
0.9, 22.5, 14.0.
Acknowledgements
9
d
4
.3.12. 1-(Dec-1-ynyl)-4-nitrobenzene (6fe). Colorless
1
oil; H NMR (400 MHz, CDCl ) d: 8.15 (d, J¼8.80 Hz,
We are grateful to the National Natural Science Foundation
of China (No. 20472074) and the Innovation Fund for
Outstanding Scholar of Henan Province (No. 0621001100)
for the financial support of this research.
3
2
1
0
1
2
H), 7.51 (d, J¼8.80 Hz, 2H), 2.44 (t, J¼7.20 Hz, 2H),
.66–1.58 (m, 2H), 1.49–1.41 (m, 2H), 1.32–1.25 (m, 8H),
.89 (t, J¼7.20 Hz, 3H); C NMR (100 MHz, CDCl ) d:
1
3
3
46.6, 132.2, 131.3, 123.5, 96.9, 79.3, 31.9, 29.2, 29.1,
9.0, 28.4, 22.7, 19.6, 14.1.
References and notes
22
4
solid, mp 107–109 C (lit. 108.5–109.5 C); H NMR
.3.13. (4-Cyanophenyl)phenylacetylene (6ga). White
ꢀ
ꢀ
1
1. Bohlmann, F.; Burkhart, F. T.; Zero, C. Naturally Occurring
Acetylenes; Academic: London and New York, NY, 1973.
2. Hunstman, V. D. The Chemistry of the Carbon–Carbon Triple
Bond; Patai, S., Ed.; Wiley-Interscience: London, 1978;
pp 553–620.
(
400 MHz, CDCl ) d: 7.65–7.60 (m, 4H), 7.59–7.53 (m,
3
H), 7.40–7.35 (m, 3H); C NMR (100 MHz, CDCl ) d:
3
1
3
2
1
1
32.1, 132.1, 131.8, 129.1, 128.5, 128.3, 122.2, 118.5,
11.5, 93.8, 87.7.
3
. (a) Paterson, I.; Davies, R. D.; Marquez, R. Angew. Chem., Int.
Ed. 2001, 40, 603; (b) Sonogashira, K. J. Organomet. Chem.
2002, 653, 46; (c) Negishi, E.; Anastasia, L. Chem. Rev.
2003, 103, 1979; (d) Nicolaou, K. C.; Bulger, P. G.; Sarlah,
D. Angew. Chem., Int. Ed. 2005, 44, 4442.
2
3
4
solid, mp 95–96 C (lit. 94–96 C); H NMR (400 MHz,
.3.14. (4-Acetylphenyl)phenylacetylene (6ha). White
ꢀ
ꢀ
1
CDCl ) d: 7.94 (d, J¼8.41 Hz, 2H), 7.61 (d, J¼8.41 Hz,
3
2
3
1
2
H), 7.57–7.55 (m, 2H), 7.38–7.36 (m, 3H), 2.62 (s,
H);
1
3
C NMR (100 MHz, CDCl ) d: 197.3, 136.2,
3
4. For representative reviews on palladium-catalyzed homocou-
pling reactions of alkynes, see: (a) Siemsen, P.; Livingston,
R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632;
31.8, 131.7, 128.9, 128.5, 128.3, 128.2, 122.7, 92.7, 88.6,
6.6.
(
b) Negishi, E.; Alimardanov, A. Handbook of Organo-
2
4
1
4
.3.15. (2-Phenylethynyl)pyridine (6ia). Yellow oil; H
palladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley-Interscience: New York, NY, 2002; Vol. 1, p 989.
NMR (400 MHz, CDCl ) d: 8.63 (d, J¼4.48 Hz, 1H), 7.70
3
(
td, J¼7.91, 1.44 Hz, 1H), 7.65–7.58 (m, 2H), 7.54 (d,
5. For representative reviews on palladium-catalyzed Sonogashira
reactions of alkynes, see: (a) Sonogashira, K. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
New York, NY, 1991; Vol. 3, pp 521–549; (b) Rossi, R.;
Carpita, A.; Bellina, F. Org. Prep. Proced. Int. 1995, 27, 129;
(c) Tsuji, J. Palladium Reagents and Catalysts; Wiley:
Chichester, UK, 1995; pp 168–171; (d) Nicolaou, K. C.;
Sorensen, E. J. Classics in Total Synthesis; VCH: Weinheim,
Germany, 1996; pp 582–586; (e) Brandsma, L.; Vasilevsky,
S. F.; Verkruijsse, H. D. Application of Transition Metal
Catalysts in Organic Synthesis; Springer: Berlin, 1998; pp
J¼7.80 Hz, 1H), 7.41–7.33 (m, 3H), 7.26–7.20 (m, 1H);
1
3
C NMR (100 MHz, CDCl ) d: 150.0, 143.4, 136.3,
3
1
32.1, 129.0, 128.4, 127.2, 122.8, 122.2, 89.4, 88.5.
2
0
4
mp 48–49 C (lit. 50–51 C); H NMR (400 MHz, CDCl )
.3.16. (3-Phenylethynyl)pyridine (6ja). Yellow solid,
ꢀ
ꢀ
1
3
d: 8.78 (s, 1H), 8.56 (s, 1H), 7.83 (d, J¼7.88 Hz, 1H),
7
.60–7.49 (m, 2H), 7.45–7.35 (m, 3H), 7.35–7.27 (m, 1H);
C NMR (100 MHz, CDCl ) d: 152.0, 148.3, 138.7,
31.7, 128.9, 128.5, 123.2, 122.5, 120.7, 92.9, 85.8.
1
3
3
1
1
79–225; (f) Sonogashira, K. Metal-Catalyzed Cross-
2
5
4
.3.17. (2-Phenylethynyl)thiophene (6ka). Yellow oil;
H NMR (400 MHz, CDCl ) d: 7.60–7.48 (m, 2H), 7.40–
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, Germany, 1998; pp 203–229.
1
3
7
.30 (m, 3H), 7.30–6.90 (m, 2H), 7.02 (d, J¼4.00 Hz, 1H);
6. For palladium-catalyzed homocoupling of alkynes, see: (a)
Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467; (b) Vlassa, M.; Ciocan-Tarta, I.; Margineanu,
F.; Oprean, I. Tetrahedron 1996, 52, 1337; (c) Li, J.; Mau,
A. W.-H.; Strauss, C. R. Chem. Commun. 1997, 1275; (d) Li,
J.; Jiang, H. Chem. Commun. 1999, 2369; (e) Chao, D. H.; Lee,
J. H.; Kim, B. H. J. Org. Chem. 1999, 66, 8480; (f) Lei, A.;
1
3
C NMR (100 MHz, CDCl ) d: 131.9, 131.4, 128.4,
3
1
28.4, 127.2, 127.1, 123.3, 123.0, 93.0, 82.6.
2
6
4
.3.18. (3-Phenylethynyl)thiophene (6la). Yellow oil;
H NMR (400 MHz, CDCl ) d: 7.58–7.46 (m, 3H), 7.39–
1
3
7
.31 (m, 3H), 7.31–7.27 (m, 1H), 7.22–7.15 (m, 1H);

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. Batsanov, A. S.; Collings, J. C.; Fairlamb, I. J. S.; Holland, J. P.;
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. For recent papers on palladium-catalyzed Sonogashira reaction
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4
6
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1
0. (a) Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422; (b) Hay,
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