Introduction of ethynylene and thienylene spacers into 2,5-diarylthiazole and 2,5-diarylthiophene

Article abstract of DOI:10.1016/j.tet.2006.07.097

Syntheses of 2,5-diarylthiazole and 2,5-diarylthiophene derivatives bearing ethynylene and thienylene spacers are performed. With the methods for coupling reactions of terminal alkynes and at the CH bond of heteroaromatic compounds, which we have develope

Full text of DOI:10.1016/j.tet.2006.07.097

Tetrahedron 62 (2006) 9548–9553
Introduction of ethynylene and thienylene spacers into
2,5-diarylthiazole and 2,5-diarylthiophene
*
Kei Kobayashi, Mohamed S. Mohamed Ahmed and Atsunori Mori
Chemical Resources Laboratory, Tokyo Institute of Technology, R1-4 4259 Nagatsuta, Yokohama 226-8503, Japan
Received 7 July 2006; revised 27 July 2006; accepted 28 July 2006
Available online 21 August 2006
Abstract—Syntheses of 2,5-diarylthiazole and 2,5-diarylthiophene derivatives bearing ethynylene and thienylene spacers are performed.
With the methods for coupling reactions of terminal alkynes and at the CH bond of heteroaromatic compounds, which we have developed,
five kinds of thiazole and thiophene derivatives 3–7 are prepared. Spectroscopic characteristics of 3–7 are also measured.
Ó 2006 Elsevier Ltd. All rights reserved.
N
1. Introduction
R2
R1
R2
R1
S
S
We have recently shown syntheses and properties of 2,5-di-
arylthiazoles 1 and 2,5-diarylthiophenes 2. These molecules
bearing donor–acceptor-type substituents showed intense
photoluminescent properties and liquid crystalline character-
istics based on the difference of the heteroaromatic ring
structure.1 Preparations of 1 and 2 were carried out by utiliz-
ing palladium-catalyzed C–H substitution reactions of
5-membered heteroaromatic compounds with various aryl
halides, which we developed recently.1–3 Introduction of
conjugative spacer molecules into thiazole and thiophene
derivatives is of considerable interest in the studies on the
relationship of the structure and physical properties.4 We
envisaged that synthetic strategies utilizing transition
metal-catalyzed coupling reactions show great advantage in
the facile preparation of such compounds.5 In particular,
Sonogashira coupling is a powerful tool for the introduction
of carbon–carbon triple bond.6,7 Hence, the reaction using
aqueous ammonia or 2-ethanolamine as an additive, which
we have recently shown, play a significant role for the effi-
cient synthesis of such derivatives.8 Herein, we report synthe-
sis of the derivatives of 1 and 2 bearing ethynylene spacers.
Synthesis of 2,5-diarylthiophene bearing thienylene spacer
is also described. Effect of the introduction of such spacers
to spectroscopic characteristics is studied.9
2
1
2. Results and discussion
2.1. Syntheses of 2,5-diarylthiazole 3 and 2,5-diaryl-
thiophenes 4–7 bearing ethynylene and thienylene
spacers
We have designed several 2,5-diarylated thiazole and thio-
phene derivatives bearing ethynylene and thienylene spacers
3–7 as summarized in Chart 1. Preparation of these com-
pounds were carried out as shown in Schemes 1–5.
Introduction of the arylethynyl group into the 2-position of a
thiazole ring was performed by utilizing the coupling reac-
tion of terminal alkynes, which we developed recently.7
The reaction of the terminal alkyne 8 with 2-bromothiazole
in the presence of a palladium catalyst/CuI (3 mol %/
2 mol %) using 2-ethanolamine as an activator afforded
2-arylethynylthiazole 9 in 77% yield after stirring at 60 ꢀC
for 5 h. Arylation of 9 at the 5-position was carried out
with the palladium-catalyzed C–H substitution reaction
using silver(I) fluoride as an activator.1 Treatment of 9 with
ethyl 4-iodobenzoate (10) in the presence of PdCl2(PPh3)2
(3 mol %) and AgF (2 equiv) furnished the 2,5-diarylthiazole
derivative bearing ethynylene spacer at the 2-position of
thiazole 3 in 46% yield as shown in Scheme 1.
Keywords: Sonogashira coupling; 2-Ethanolamine; Palladium catalyst; CH
arylation.
* Corresponding author at present address: Department of Chemical
Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe
657-8501, Japan. Tel./fax: +81 788036181; e-mail: amori@kobe-u.ac.jp
Scheme 2 shows synthesis of the thiophene derivative bear-
ing the spacer. The arylethynyl group was introduced in
a similar manner as in the case of the thiazole 9 with
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.097

K. Kobayashi et al. / Tetrahedron 62 (2006) 9548–9553
9549
O
C
O
C
N
EtO
OMe
OMe
EtO
EtO
EtO
S
S
3
6
O
C
O
C
EtO
OMe
OMe
OMe
S
S
S
4
7
O
C
S
5
Chart 1.
PdCl2(PPh3)2 (3 mol%)
CuI (2 mol%)
N
N
Br
+
OMe
OMe
2-ethanolamine (2 eq)
THF
S
S
9 (77%)
8
O
C
EtO
I
10
O
C
N
PdCl2(PPh3)2 (3 mol%)
AgF, DMSO
EtO
OMe
S
3 (46%)
Scheme 1.
PdCl2(PPh3)2 (3 mol%)
CuI (2 mol%)
PdCl2(PPh3)2 (3 mol%)
CuI (2 mol%)
8
Br
S
+
OMe
8
Br
I +
OMe
Br
2-ethanolamine (2 eq)
THF
S
aq NH3 (2 eq), rt
THF
S
S
11 (92%)
16 (48%)
15
10
O
C
PdCl2(PPh3)2 (3 mol%)
AgF, DMSO
OMe
EtO
S
14
PdCl2(PPh3)2 (3 mol%)
CuI (2 mol%)
4 (68%)
O
C
EtO
OMe
Scheme 2.
2-ethanolamine (2 eq)
THF
S
6 (88%)
PdCl2(PPh3)2 (5 mol%)
AgNO3/KF, DMSO
+
OMe
Br
Br
OMe
I
Scheme 4.
S
S
12
13 (60%)
2-bromothiophene to afford 2-(arylethynyl)thiophene 11 in
92% yield.8c Following introduction of the aryl group bear-
ing an electron-withdrawing substituent with 8 was also per-
formed similarly to the manner of the thiazole case1 to afford
4 in 68% yield.
O
C
EtO
14
PdCl2(PPh3)2 (3 mol%)
CuI (2 mol%)
O
C
EtO
OMe
S
Synthesis of the thiophene derivative bearing ethynylene
spacer between the electron-deficient aryl group and thio-
phene was performed as shown in Scheme 3. As we reported
that CHcouplingoccurred inthereactionofbromothiophenes
2-ethanolamine (2 eq)
THF
5 (82%)
Scheme 3.

9550
K. Kobayashi et al. / Tetrahedron 62 (2006) 9548–9553
PdCl2(PPh3)2 (10 mol%)
CuI (20 mol%)
+
SnBu3
Br
OMe
OMe
CsF, 60 °C
THF
S
S
S
S
18 (82%)
17
10
O
C
PdCl2(PPh3)2 (3 mol%)
AgNO3/KF, DMSO
EtO
OMe
S
S
7 (33%)
Scheme 5.
with the bromo group intact even in the presence of a palla-
dium catalyst,2c synthesis of the 5-aryl-2-bromothiophene
was performed by utilizing the CH coupling reaction with
aryl iodide. Treatment of 2-bromothiophene with 1-iodo-
4-methoxybenzene 12 in the presence of PdCl2(PPh3)2
(5 mol %) and KF/AgNO3 as an activator furnished 2-aryl-
5-bromothiophene 13 in 60% yield. The reaction of the ethyl
4-ethynylbenzoate 14 with 13 in the presence of a palladium
catalyst/CuIusing2-ethanolamine asanactivator8c afforded5
in 82% yield.
2.2. Properties of thiazole and thiophene derivatives
bearing ethynylene spacers
Measurements of UV–vis absorption and photoluminescent
spectra were carried out and the results were summarized
in Table 1. The lmax value of thiazole 3 was slightly red-
shifted compared with 1 by the introduction of ethynylene
group at the 2-position compared with the corresponding
2,5-diarylthiazole, while the lmax value of 4 was observed
at the slightly smaller wavelength than that of 2.1 Properties
of 5, which possessed ethynylene spacer into the opposite
position, were also found to show similar values. The lmax
value of thiophene 6, which possessed two ethynylene
groups at the 2- and 5-positions was observed at 364 nm,
which red-shifted ca. 5–10 nm. On the other hand, the lmax
value of the corresponding bithiophene derivative was ob-
served at 395 nm suggesting that the introduction of the
thiophene ring showed more remarkable than ethynylene.
Concerning photoluminescent spectra of thiophene and
thiazole derivatives, quantum yields were found to decrease
by the introduction of spacers compared with the correspond-
ing 2,5-diarylthiazole 1 (F¼0.24) and 2,5-diarylthiophene 2
(F¼0.79).1
Preparation of the 2,5-diarylthiophene derivative bearing
ethynyl groups at the both positions was carried out as shown
in Scheme 4. The reaction of 2-iodo-5-bromothiophene 15
with a terminal alkyne using Sonogashira coupling with
aqueous ammonia at room temperature8a selectively took
place at the carbon–iodine bond to afford 16 in 48% yield.
Introduction of the second arylethynyl group was performed
with the Sonogashira coupling reaction of 16 with 14 in the
presence of aqueous 2-ethanolamine at 60 ꢀC to afford 6 in
88% yield.8c
Bithiophene 7 was also synthesized as shown in Scheme 5.
Palladium-catalyzed cross-coupling of bromothiophene 17
with thienyl(tributyl)tin was effected to afford 18.10 CH sub-
stitution reaction of 18 with aryl iodide 10 in the presence of
AgNO3/KF afforded 7.2c
Table 1. Spectroscopic characteristics of 2,5-diarylthiazole and 2,5-thio-
phenes bearing ethynylene and thienylene spacersa
Compound UV–vis absorption spectrum Photoluminescent spectrum
For the coupling reactions of a (hetero)aryl bromide with ter-
minal alkynes, for which higher reaction temperature was
necessary to proceed, the method using 2-ethanolamine as
an additive8c was found to be highly effective, while the re-
action with aryl iodide at room temperature was carried out
with aqueous ammonia.8a The reaction with ammonia at
room temperature was found to proceed selectively at the
carbon–iodine bond of 2-bromo-5-iodo-thiophene 15.
lmax, nm
3
Em
F
3
4
5
6
354
350
358
364
395
347
357
26 500
24 013
29 875
69 565
31 655
26 800
32 200
429
438
445
437
485
424
441
0.20
0.40
0.11
0.03
0.10
0.24
0.79
7
1b
2b
a
See Section 4. Em: wavelength maximum of the photoluminescent
spectrum. F: quantum yield of the photoluminescence.
Data from Ref. 1 (R1¼OMe, R2¼COOEt).
CH arylation reactions of thiazole and thiophene derivatives
were shown to proceed with AgF1 or AgNO3/KF.2c Both pro-
tocols were similarly effective for the reaction with aryl ha-
lides. Introduction of aryl group by the reaction at the CH
bonds of heteroaromatic groups proceeds with a palladium
or palladium/copper catalyst system in the presence of an
activator. As shown in Scheme 2, the method was found to
be effective for the substrate bearing a carbon–carbon triple
bond.
b
3. Conclusion
In summary, several thiazole and thiophene derivatives,
which possessed ethynylene and thiophene spacers were
synthesized and UV–vis absorption and photoluminescent
properties were examined. These thiazole and thiophene

K. Kobayashi et al. / Tetrahedron 62 (2006) 9548–9553
9551
derivatives, which had not been synthesized previously, were
prepared in a facile manner by employing coupling method-
ologies at the CH bond of heteroaromatic compounds and
coupling of terminal alkynes using 2-ethanolamine as an ac-
tivator that underwent the reaction smoothly and efficiently.
Although remarkable spectroscopic characteristics were not
observed in these thiazole and thiophene derivatives bearing
a spacer molecule, the synthesis demonstrated that coupling
methodologies with a transition metal catalyst were highly
effective for the synthesis of compounds bearing heteroaro-
matic and/or alkyne moieties.
added to the mixture and the Schlenk tube was heated at
80 ꢀC for 24 h. After cooling to room temperature, the result-
ing suspension was filtered and the residue was washed with
dichloromethane repeatedly. The filtrate was washed with
water and the aqueous layer was extracted with chloroform.
The combined organic layers were dried over anhydrous
sodium sulfate and concentrated under reduced pressure to
leave a crude solid, which was purified by chromatography
on silica gel to afford 83.4 mg of 3 as a yellow solid (46%):
1H NMR (300 MHz, CDCl3) d 1.41 (t, J¼7.2 Hz, 3H), 3.84
(s, 3H), 4.39 (q, J¼7.2 Hz, 2H), 6.90 (d, J¼8.7 Hz, 2H),
7.55 (d, J¼8.7 Hz, 2H), 7.62 (d, J¼8.4 Hz, 2H), 8.07 (d,
J¼8.4 Hz, 2H), 8.08 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 14.28, 55.32, 61.14, 81.50, 95.67, 113.18, 114.21,
126.41, 130.25, 130.41, 133.62, 133.66, 134.97, 140.11,
141.04, 160.70, 165.86; IR (KBr) 2978, 2924, 2581, 2548,
2207, 1703, 1605, 1516, 1275, 1254, 1190, 1106, 1026,
841, 772, 695 cmꢂ1. HRMS (EIMS) m/z calcd for
C19H22OS; 363.0929, found; 363.0903.
4. Experimental
4.1. General
DMSO was distilled from CaH2 and stored over MS 4A
under an argon atmosphere. THF (anhydrous grade) was
purchased from Kanto Chemicals Co. Ltd and used without
further purification. 1H (300 MHz) and 13C (75 MHz) NMR
spectra were measured on Varian Mercury 300 NMR spec-
trometer. Infrared spectra were measured with Shimadzu
FTIR-8000A. High-resolution mass spectra (EI) were ob-
tained by JEOL MStation. Elemental analyses were carried
out at Elemental Analysis Center of Chemical Resources
Laboratory, Tokyo Institute of Technology using Yanako
MT2 CHN CORDER. UV–vis spectra were measured as a
1ꢁ10ꢂ5 M chloroform solution with JASCO Ubest V-550.
Photoluminescent spectra were measured as a 1ꢁ10ꢂ6 M
chloroform solution with JASCO FP-6300. Quantum yields
(F) were estimated with an aqueous solution of quinine
sulfate (F¼0.59) as a reference.
4.1.3. 2-(4-Methoxyphenylethynyl)thiophene (11). To
a 25-mL of Schlenk tube equipped with a magnetic stirring
bar were added PdCl2(PPh3)3 (10.5 mg, 0.015 mmol), CuI
(1.7 mg, 0.010 mmol), 2-bromothiophene (0.048 mL,
0.5 mmol), 4-(methoxyphenyl)acetylene (8, 79.2 mg,
0.6 mmol), and 3 mL of THF under an argon atmosphere.
Then, 2 mL of 2-ethanolamine aqueous solution (0.5 M,
1.0 mmol) was added to the mixture and the Schlenk tube
was heated at 60 ꢀC for 5 h. After cooling to room tempera-
ture, the solution was washed with water and the aqueous
layer was extracted with chloroform. The combined organic
layers were dried over anhydrous sodium sulfate and concen-
trated under reduced pressure to leave a crude oil, which was
purified by chromatography on silica gel to afford 98.6 mg of
1
4.1.1. 2-(4-Methoxyphenylethynyl)thiazole (9). To a
25-mL of Schlenk tube equipped with a magnetic stirring
bar were added PdCl2(PPh3)3 (10.5 mg, 0.015 mmol), CuI
(1.7 mg, 0.010 mmol), 2-bromothiazole (82.0 mg, 0.5 mmol),
4-(methoxyphenyl)acetylene (8, 79.2 mg, 0.6 mmol), and
3 mL of THF under an argon atmosphere. Then, 2 mL of
aqueous 2-ethanolamine solution (0.5 M, 1.0 mmol) was
added to the mixture and the Schlenk tube was heated at
60 ꢀC for 5 h. After cooling to room temperature, the solution
was washed with water and the aqueous layer was extracted
with chloroform. The combined organic layers were dried
over anhydrous sodium sulfate and concentrated under re-
duced pressure to leave a crude oil, which was purified by
chromatography on silica gel to afford 82.9 mg of 9 as a
colorless oil (77%): 1H NMR (300 MHz, CDCl3) d 3.84 (s,
3H), 6.90 (d, J¼9.0 Hz, 2H), 7.35 (d, J¼3.3 Hz, 1H), 7.54
(d, J¼9.0 Hz, 2H), 7.84 (d, J¼3.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 55.28, 81.24, 94.26, 113.33, 114.14,
120.27, 133.51, 143.38, 149.17, 160.53; IR (KBr) 2837,
2206, 1605, 1514, 1294, 1252, 1175, 1091, 1055,
831 cmꢂ1. HRMS (EIMS) m/z calcd for C12H9NOS;
215.0405, found; 215.0404.
11 as a colorless oil (92%): H NMR (300 MHz, CDCl3)
d 3.83 (s, 3H), 6.87 (d, J¼9.0 Hz, 2H), 7.00 (dd, J¼2.7 Hz,
1H), 7.25 (m, 2H), 7.45 (d, J¼9.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 55.09, 81.22, 93.01, 113.93, 114.81,
123.57, 126.73, 126.96, 131.34, 132.80, 159.63; IR (KBr)
3102, 3073, 2963, 2842, 1603, 1524, 1501, 1460, 1289,
1246, 1186, 1175, 1109, 1021, 853, 700 cmꢂ1. HRMS
(EIMS) m/z calcd for C13H10OS; 214.0452, found; 214.0427.
4.1.4. 5-(4-Ethoxycarbonylphenyl)-2-(4-methoxyphenyl-
ethynyl)thiophene (4). To a 25-mL of Schlenk tube equip-
ped with a magnetic stirring bar were added PdCl2(PPh3)3
(17.5 mg, 0.025 mmol), ethyl 4-iodobenzoate (10,
0.100 mL, 0.6 mmol), 11 (107.0 mg, 0.5 mmol), and 3 mL
of DMSO under an argon atmosphere. AgF (64 mg,
0.5 mmol) was added to the mixture and the Schlenk tube
was heated at 100 ꢀC for 5 h. After cooling to room temper-
ature, the resulting suspension was filtered and the residue
was washed with dichloromethane repeatedly. The filtrate
was washed with water and the aqueous layer was extracted
with chloroform. The combined organic layers were dried
over anhydrous sodium sulfate and concentrated under re-
duced pressure to leave a crude solid, which was purified
by chromatography on silica gel to afford 123.1 mg of 4 as
4.1.2. 5-(4-Ethoxycarbonylphenyl)-2-(4-methoxyphenyl-
ethynyl)thiazole (3). To a 25-mL of Schlenk tube equipped
with a magnetic stirring bar were added PdCl2(PPh3)3
(10.5 mg, 0.015 mmol), ethyl 4-iodobenzoate (10, 0.101 mL,
0.6 mmol), 9 (107.6 mg, 0.5 mmol), and 3 mL of DMSO
under an argon atmosphere. AgF (64 mg, 0.5 mmol) was
1
a yellow solid (68%): H NMR (300 MHz, CDCl3) d 1.41
(t, J¼8.4 Hz, 3H), 3.84 (s, 3H), 4.39 (q, J¼8.4 Hz, 2H),
6.89 (d, J¼8.7 Hz, 2H), 7.23 (d, J¼3.6 Hz, 1H), 7.31 (d,
J¼3.6 Hz, 1H), 7.47 (d, J¼8.7 Hz, 2H), 7.64 (d, J¼8.4 Hz,
2H), 8.05 (d, J¼8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)

9552
K. Kobayashi et al. / Tetrahedron 62 (2006) 9548–9553
d 14.33, 55.31, 61.02, 81.27, 94.65, 114.10, 114.77, 124.39,
125.36, 129.46, 130.28, 132.63, 132.97, 137.87, 143.78,
159.92, 166.14; IR (KBr) 2988, 2940, 2842, 1713, 1603,
1514, 1291, 1275, 1248, 1186, 1109, 1028, 851, 837, 808,
768 cmꢂ1. HRMS (EIMS) m/z calcd for C22H18O3S;
363.0929, found; 363.0903.
Then, 2 mL of 2-ethanolamine aqueous solution (0.5 M,
1.0 mmol) was added to the mixture and the Schlenk tube
was heated at 60 ꢀC for 5 h. After cooling to room tempera-
ture, the solution was washed with water and the aqueous
layer was extracted with chloroform. The combined organic
layers were dried over anhydrous sodium sulfate and concen-
trated under reduced pressure to leave a crude oil, which was
purified by chromatography on silica gel to afford 70.4 mg of
6 as a yellow solid (88%): 1H NMR (300 MHz, CDCl3) d 1.41
(t, J¼7.2 Hz, 3H), 3.84 (s, 3H), 4.39 (q, J¼7.2 Hz, 2H), 6.89
(d, J¼8.7 Hz, 2H), 7.13 (d, J¼3.9 Hz, 1H), 7.19 (d,
J¼3.9 Hz, 1H), 7.46 (d, J¼8.7 Hz, 2H), 7.57 (d, J¼8.4 Hz,
2H), 8.03 (d, J¼8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 14.25, 55.22, 61.11, 80.85, 85.22, 93.13, 94.58, 114.03,
114.40, 123.28, 125.86, 127.10, 129.43, 131.15, 131.34,
132.25, 132.34, 132.44, 132.99, 159.93, 165.88; IR (KBr)
2979, 2842, 2197, 1715, 1605, 1528, 1512, 1308, 1287,
1281, 1173, 1107, 1028, 831, 768 cmꢂ1. HRMS (EIMS)
m/z calcd for C24H18O3S; 386.0977, found; 386.0988.
Synthesis of 2-bromo-5-(4-methoxyphenyl)thiophene (13)
was carried out in a similar manner to that we described pre-
viously. Spectroscopic characteristics and physical proper-
ties of 132c were identical with those of the authentic sample.
4.1.5. 2-(4-Ethoxycarbonylphenylethynyl)-5-(4-methoxy-
phenyl)thiophene (5). To a 25-mL of Schlenk tube equip-
ped with a magnetic stirring bar were added PdCl2(PPh3)3
(10.5 mg, 0.015 mmol), CuI (1.7 mg, 0.010 mmol), 13
(134.6 mg, 0.5 mmol), 4-(ethoxycarbonylphenyl)acetylene
(14, 104.5 mg, 0.6 mmol), and 3 mL of THF under an argon
atmosphere. Then, 2 mL of 2-ethanolamine aqueous solution
(0.5 M, 1.0 mmol) was added to the mixture and the Schlenk
tube was heated at 60 ꢀC for 5 h. After cooling to room tem-
perature, the solution was washed with water and the aqueous
layer was extracted with chloroform. The combined organic
layers were dried over anhydrous sodium sulfate and concen-
trated under reduced pressure to leave a crude oil, which was
purified by chromatography on silica gel to afford 147.2 mg
of 5 (82%): 1H NMR (300 MHz, CDCl3) d 1.40 (t, J¼7.2 Hz,
3H), 3.84 (s, 3H), 4.39 (q, J¼7.2 Hz, 2H), 6.93 (d, J¼9.0 Hz,
2H), 7.11 (d, J¼3.9 Hz, 1H), 7.26 (d, J¼3.9 Hz, 1H), 7.53 (d,
J¼9.0 Hz, 2H), 7.55 (d, J¼9.0 Hz, 2H), 8.03 (d, J¼9.0 Hz,
2H); 13C NMR (75 MHz, CDCl3) d 14.26, 55.29, 61.07,
86.05, 92.90, 114.36, 120.59, 122.08, 126.37, 127.15,
127.55, 129.44, 131.01, 132.35, 133.70, 146.70, 159.68,
165.96; IR (KBr) 2965, 2936, 2840, 1723, 1605, 1514,
4.1.8. 2-(4-Methoxyphenyl)-5,50-bithiophene (18).2c To
a 25-mL of Schlenk tube equipped with a magnetic stirring
bar were added 17 (0.135 g, 0.5 mmol), PdCl2(PPh3)2
(35 mg, 0.05 mmol), CuI (0.019 g, 0.10 mmol), and DMF
(3 mL) under an argon atmosphere. To the mixture was
added tributyl(2-thienyl)stannane (0.190 mL, 0.6 mmol)
dropwise. CsF (0.151 g, 1.0 mmol) was then added in one
portion. The resulting mixture was heated at 60 ꢀC and stir-
ring was continued for 8 h. After cooling to room tempera-
ture, the mixture was poured into 20 mL of water. The
aqueous was extracted with chloroform twice (20 mLꢁ2)
and the combined organic layers were dried over anhydrous
magnesium sulfate. The solvent was removed under reduced
pressure to leave a crude oil, which was purified by column
chromatography on silica gel using hexanes–ethyl acetate
(5:1) as an eluent to afford 0.111 g of 5-(4-methoxy-
phenyl)-2,20-bithiophene (18) in 82% yield: 1H NMR
(CDCl3) d 3.48 (s, 3H), 6.91 (d, J¼9.0 Hz, 2H), 7.02 (dd,
J¼4.8, 3.6 Hz, 1H), 7.12 (AB, 2H), 7.17–7.22 (m, 2H),
7.53 (d, J¼9.0 Hz, 2H); 13C NMR (CDCl3) d 57.70,
114.35, 122.64, 123.37, 124.11, 124.56, 126.92, 127.80,
135.69, 137.58, 143.14, 147.96, 159.31; IR (KBr) 3070,
2960, 2910, 2845, 1605, 1497, 1289, 1246, 1183, 1032, 797.
1497, 1306, 1291, 1252, 1181, 1105, 1028, 801, 764 cmꢂ1
.
Anal. Calcd for C22H18O3S: C, 72.90; H, 5.01; S, 8.85.
Found: C, 72.72; H, 4.85; S, 8.70.
4.1.6. 2-Bromo-5-(4-methoxyphenylethynyl)thiophene
(16). To a 25-mL of Schlenk tube equipped with a
magnetic stirring bar were added PdCl2(PPh3)3 (10.5 mg,
0.015 mmol), CuI (1.7 mg, 0.010 mmol), 2-bromo-5-
iodothiophene (15, 173.4 mg, 0.6 mmol), 8 (66.1 mg,
0.5 mmol), and 3 mL of THF under an argon atmosphere.
Then, 2 mL of aqueous ammonia (0.5 M, 1.0 mmol) was
added to the mixture and stirred at room temperature for
5 h. The solution was washed with water and the aqueous
layer was extracted with chloroform. The combined organic
layers were dried over anhydrous sodium sulfate and concen-
trated under reduced pressure to leave a crude oil, which was
purified by chromatography on silica gel to afford 70.4 mg of
16. The product 16, whose yield was estimated to be 48% by
1H NMR analysis, contained a trace amount of impurity,
which was hardly eliminated by column chromatography
on silica gel. Thus, the mixture was conducted to the follow-
ing reaction without further purification.
4.1.9. 2-(4-Ethoxycarbonylphenyl)-20-(4-methoxy-
phenyl)-5,50-bithiophene (7). To a 25-mL of Schlenk tube
equipped with a magnetic stirring bar were added
PdCl2(PPh3)3 (17.5 mg, 0.025 mmol), 10 (0.100 mL,
0.6 mmol), 18 (136.2 mg, 0.5 mmol), potassium fluoride
(72.6 mg, 1.25 mmol), and 5 mL of DMSO under an argon
atmosphere. The mixture was heated in an oil bath at
100 ꢀC for 8 h, during which period AgNO3 (168.9 mg,
1.0 mmol) was added in 4 portions with a 2 h interval. After
cooling to room temperature, the resulting suspension was
filtered and the residue was washed with dichloromethane
repeatedly. The filtrate was washed with water and the aque-
ous layer was extracted with chloroform. The combined or-
ganic layers were dried over anhydrous sodium sulfate and
concentrated under reduced pressure to leave a crude solid,
which was purified by chromatography on silica gel to afford
4.1.7. 5-(4-Ethoxycarbonylphenylethynyl)-2-(4-methoxy-
phenylethynyl)thiophene (6). To a 25-mL of Schlenk
tube equipped with a magnetic stirring bar were added
PdCl2(PPh3)3 (10.5 mg, 0.015 mmol), CuI (1.7 mg,
0.010 mmol), 16 (146.6 mg, 0.5 mmol), 12 (104.5 mg,
0.6 mmol), and 3 mL of THF under an argon atmosphere.
1
40.9 mg of 7 as a yellow solid (33%): H NMR (CDCl3)
d 1.41 (t, J¼7.2 Hz, 3H), 3.85 (s, 3H), 4.39 (q, J¼7.2 Hz,
2H), 6.93 (d, J¼8.7 Hz, 2H), 7.13 (d, J¼3.9 Hz, 1H), 7.18

K. Kobayashi et al. / Tetrahedron 62 (2006) 9548–9553
9553
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(d, J¼3.3 Hz, 2H), 7.35 (d, J¼3.6 Hz, 1H), 7.54 (d,
J¼8.7 Hz, 2H), 7.65 (d, J¼8.7 Hz, 2H), 8.05 (d, J¼8.7 Hz,
2H); IR (KBr) 2910, 2890, 1709, 1605, 1283, 1184, 1111,
1030, 830, 795, 770. HRMS (EIMS) m/z calcd for
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Acknowledgements
This work was partially supported by the Grant-in-Aid for
Scientific Research (No. 16550092) by Ministry of Educa-
tion, Sports, Culture, Science, and Technology, Japan.
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