C-H arylation of 3-substituted thiophene with regioselective deprotonation by tmpMgCl·LiCl and transition metal catalyzed cross coupling

Article abstract of DOI:10.3987/COM-12-S(N)6

The reaction of 3-hexylthiophene with Knochel-Hauser base (TMPMgCl·LiCl) induced the metalation at the 5-position of the thiophene ring selectively. Following addition of several aryl halides in the presence of a nickel or palladium catalyst afforded regi

Full text of DOI:10.3987/COM-12-S(N)6

HETEROCYCLES, Vol. 86, No. 1, 2012, pp. -. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 18th March, 2012, Accepted, 26th April, 2012, Published online, 8th May, 2012
DOI: 10.3987/COM-12-S(N)6
C-H ARYLATION OF 3-SUBSTITUTED THIOPHENE WITH
REGIOSELECTIVE DEPROTONATION BY TMPMgCl·LiCl AND
TRANSITION METAL CATALYZED CROSS COUPLING‡
Shota Tanaka, Shunsuke Tamba, Atsushi Sugie, and Atsunori Mori*
Department of Chemical Science and Engineering, Kobe University, 1-1
Rokkodai, Nada, Kobe 657-8501, Japan
E-mail: amori@kobe-u.ac.jp
‡This paper is dedicated to Professor Ei-ichi Negishi on celebration of his 77th
birthday.
Abstract – The reaction of 3-hexylthiophene with Knochel-Hauser base
(TMPMgCl·LiCl) induced the metalation at the 5-position of the thiophene ring
selectively. Following addition of several aryl halides in the presence of a nickel
or palladium catalyst afforded regioselectively arylated thiophene in good to
excellent yields.
INTRODUCTION
CH functionalization of heteroaromatic compounds recently attracts much attention1,2 since a variety of
organic compounds bearing heteroaromatic moiety in the structure are found in a wide range of advanced
organic materials3 as well as biologically active molecules.4 Therefore, development of a practical
synthetic strategy for such molecules is an important issue in organic synthesis. We have been engaged in
the development of synthetic methodologies to afford functionalized heteroaromotics via transition metal
catalyzed CH functionalization.5 Several functionalization reactions, which take place at a carbon atom
of an electron-deficient6 and enriched7 CH bond have been achieved. Accordingly, the selective
functionalization based on the electronic characteristics of the CH bond of heteroaromatic compounds
becomes indeed plausible. By contrast, selection of an electronically similar CH bond based on
stereochemical differentiation has not been extensively studied so far and thus controlled
functionalization of such CH bond is intriguing. We have recently found the reaction of
3-hexylthiophene in the presence of Knochel-Hauser base TMPMgCl·LiCl8 (TMP
=

2,2,6,6-tetramethylpiperidine) induces the metalation at room temperature for 3 h at the 5-position
selectively. And we have shown novel synthetic methodology leading to head-to-tail-type oligothiophene
with regioselective metalation of 3-substituted thiophene and nickel-catalyzed cross coupling of
halothiophenes9 (Scheme 1). We envisaged that such a regioselective metalating system of 3-substituted
thiophenes is also effective not only for the coupling to form thiophene‒thiophene bond but also for the
reaction with various aryl halides. Herein, we describe regiocontrolled CH arylation of several
3-substituted thiophene derivatives that occurs at the less hindered position selectively with
TMPMgCl·LiCl.
nHex
nHex
nHex
nHex

MgCl LiCl
N
nHex
Br
S

LiCl ClMg
H
S
S
S
rt, 3 h
S
Ni cat
(ref 9)
Scheme 1. Regioselective metalation of 3-hexylthiophene with TMPMgCl·LiCl and following coupling
with a bromothiophene
RESULTS AND DISCUSSION
We first studied the reaction of 3-hexylthiophene (1a) that possessed two possible CH bonds at the
2- and 5- positions with aryl halides under several conditions. The reaction with tBuOLi as a base10 in the
presence of 4-methyl-1-bromobenzene (2a) and 2.0 mol% of a palladium catalyst resulted to afford a
mixture of 5-Aryl (27%), 2-Aryl (9%) and 2,5-diaryl (20%) suggesting that uncontrollable metalation
occurred at both 2- and 5-positions. The use of a catalytic amount of PdCl2(PPh3)2 (2.0 mol%) and
AgNO3/KF7c resulted in giving a mixture of 5-Aryl (21%), 2-Aryl (8%) and 2,5-diarylated product
(24%). The similar trend was observed in the arylation with K2CO3/tBuCOONa.4d By contrast, the perfect
selectivity was achieved when TMPMgClLiCl was employed as a base, to afford 5-arylated product in
91% yield. The use of diisopropyl amide (iPr2NMgCl·LiCl) instead of TMPMgCl·LiCl decreased the
selectivity and the reactivity. These results are summarized in Table 1.
The arylation reaction with several 3-substituted thiophenes is then examined to study the selectivity of
the CH bond as summarized in Table 2. The reaction of 4-methoxy-1-bromobenzene (2b) with
3-methylthiophene (1b), and 3-fluoroalkylated thiophene 1c, 3-arylated thiophene 1d also occurred

Table 1. Regiochemistry of the reaction of 3-hexylthiophene with CH couplinga
nHex
additive
Pd cat.
H
H
+
R
X
S
1a
2
nHex
nHex
nHex
+
R
R
+
R
R
S
S
S
2-Aryl
5-Aryl
2,5-Aryl
Yield/%b
Additive
Entry
1c
Aryl halide
Pd cat. (2.0 mol%)
tBuOLi
Pd(PtBu3)2
5-Aryl
2-Aryl
2,5-Aryl
Me
Br
27
9
8
20
(2a)
AgNO3/KF
2d
21
13
91
28
24
42
0
EtO2C
I
PdCl2(PPh3)2
K2CO3/tBuCOONa
Pd(OAc)2/2PCy3
TMPMgClLiCl
PEPPSI-IPr
3e
2a
2a
2a
29
0
4
iPr2NMgClLiCl
5
2
0
PEPPSI-IPr
a The reaction was carried out with 1a (0.50 mmol) and aryl halide (0.6 mmol) according to literature
procedure. b The ratio of 5-Aryl/2-Aryl was determined by 1H NMR analysis. c In 1.0 mL of DMF at 100
ºC for 20 h. d In 1.0 mL of DMSO at 100 ºC for 23 h. e In 1.6 mL of DMA at 100 ºC for 20 h.
regioselectively at the 5-position. By contrast, the reaction of 3-methoxythiophene (1f) resulted to afford
2-arylated product predominantly probably due to the directing effect of the methoxy group in the
reaction of magnesium amide.11 Less selective metalation was found to occur with an alkynyl
group-substituted thiophene 1e. Although the metalation reaction of 3-bromothiophene (1g) and
N,N-diethyl-3-thiophenecarboxamide (1h) with TMPMgCl·LiCl proceeded smoothly in non-selective
(40:60) and 2-selective (0/100) manners, respectively, following coupling with aryl halide in the presence
of a palladium catalyst resulted in no arylation.

Table 2. Regiochemical preference of 3-substituted thiophenes in the reaction with TMPMgCl·LiCla
R'
Br
R
R
R
catalyst (2.0 mol%)
rt
TMPMgCl·LiCl
rt, 3 h
R'
+
R'
S
S
S
2-Aryl
5-Aryl
Yield/%b
(5-Aryl/2-Aryl)c
R
R'
Catalyst
Time/h
nHex (1a)
Me (1b)
Me
OMe
OMe
Me
PEPPSI-IPr
PEPPSI-IPr
PEPPSI-IPr
NiCl2(dppf)
PEPPSI-IPr
PEPPSI-IPr
PEPPSI-IPr
PEPPSI-IPr
20
2
91 (>99/1) (3aa)
87 (>99/1) (3bb)
64 (>99/1) (3cb)
56 (>99/1) (3da)
62 (65/35)
46 (3/97)d (3fb)
0 (40/60)f
n
-(CH2)3 C4F9 (1c)
20
21
20
21
16
24
-4-(OMe)C6H4 (1d)
-CCnHex (1e)
-OMe (1f)
OMe
OMe
OMee
OMe
-Br (1g)
-CONEt2 (1h)
0 (0/100)f
a Unless noted, the reaction was carried out with thiophene (0.5 mmol), TMPMgClLiCl (0.6 mmol), aryl
bromide (0.6 mmol) and catalyst (0.01 mmol) in 2.0 mL of THF. b Isolated yield. c Unless otherwise
1
specified, the ratio of 5-Aryl/2-Aryl was determined by H NMR analysis. d The ratio of 5-Aryl/2-Aryl
e
was determined by GC analysis.
The reaction was performed with 0.50 mmol of 1-iodo-4-
f
methoxybenzene. In the parenthesis, the metalation ratio, which was confirmed by formylation with
DMF, was given.
Our further concern is the scope of the regioselective CH arylation of 3-hexylthiophene (1a) with
several aryl bromides. Results are summarized in Table 3. The reaction of 1a with
4-methyl-1-bromobenzene (2a) was found to take place at room temperature to afford 3aa in excellent
yield when a palladium catalyst with NHC ligand PEPPSI-IPr12 was employed. On the other hand, the use
of a palladium catalyst with bulky phosphine ligand Pd(PtBu3)2 resulted in poor yield (20%). The reaction
with 2.0 mol% of nickel catalyst of bidentate diphosphine NiCl2(dppf) at room temperature for 20 h
proceeded smoothly to give 3aa in 81% yield. The reaction with NiCl2(dppe) also gave 3aa in a
reasonable yield (63%), whereas other nickel catalyst, NiCl2(PCy3)2 and NiCl2(dppb) was found to be
ineffective. The use of Ni(cod)2/2SIPr, which showed excellent performance in the reaction of 1a with
2-bromo-3-hexylthiophene,8 resulted in poor yield (7%). Various aryl bromides bearing an

electron-withdrawing or donating substituent (2b-2e) reacted with 1a to afford the coupling products in
good to excellent yields. Although the reaction with ethyl 4-bromobenzoate (2f) proceeded, the yield was
slightly inferior (35%).
Table 3. Regioselective CH coupling reaction of 3-hexylthiophene (2a) with aryl bromidesa
nHex
nHex
Aryl-Br
catalyst (2.0 mol%)
TMPMgCl·LiCl
rt, 3 h
Aryl
rt
S
S
1a
Aryl bromide
Catalyst
Time/h Yield/%b
Me
Br
PEPPSI-IPr
20
91 (3aa)
(2a)
Pd(PtBu3)2
NiCl2(dppf)
NiCl2(dppe)
NiCl2(dppb)
NiCl2(PCy3)2
Ni(cod)2/2SIPr
20
20
20
20
20
20
20c
81
63
9
0
7
77d (3ab)
82 (3ac)
85 (3ad)
88d, e (3ae)
35 (3af)
MeO
Br
NiCl2(dppf)
NiCl2(dppf)
PEPPSI-IPr
PEPPSI-IPr
PEPPSI-IPr
25
20
20
5
(2b)
(2c)
(2d)
Br
F
F3C
Br
Br
Br
(2e)
(2f)
EtO2C
20
a
Unless otherwise specified, the reaction was carried out with 0.5 mmol of 1a, 0.6 mmol of
b
c
TMPMgCl·LiCl and 0.6 mmol of aryl bromides in THF.
Isolated yield. 1a: 0.55 mmol,
TMPMgCl·LiCl: 0.50 mmol, 2a: 0.6 mmol. d The reaction was carried out with 0.5 mmol of aryl bromide.
e Accompanied by 3ae, 2,5-diarylated product was also obtained in 5% yield.

It is also remarkable that the reaction with aryl chlorides proceeded under similar conditions. The reaction
of 1a with 4-methyl-1-chlorobenzene (4a) took place at room temperature for 20 h with NiCl2(dppf) to
afford 3aa in 82% yield. As shown in Table 4, several aryl chlorides such as 4b, 4c and 4e reacted
smoothly with 1a to afford the corresponding coupling products in good to excellent yields. The reaction
of 1a with 2-chlorobenzothiazole (4g) in the presence of PEPPSI-IPr proceeded to give 3ag in 83%.
Table 4. Regioselective CH coupling reaction of 3-hexylthiophene (1a) with aryl chloridesa
nHex
nHex
Aryl-Cl 4
catalyst (2.0 mol%)
TMPMgCl·LiCl
rt, 3 h
Aryl
rt
S
S
1a
Aryl chloride
Catalyst
Time/h
Yield/%
Me
Cl
NiCl2(dppf)
20
20
25
5
82 (3aa)
(4a)
(4b)
NiCl2(dppf)
NiCl2(dppf)
PEPPSI-IPr
90 (3ab)
92b (3ac)
92b, c (3ae)
Cl
(4c)
F3C
Cl
(4e)
N
S
Cl
PEPPSI-IPr
31
83 (3ag)
(4g)
a
Unless noted, the reaction was performed with 1a (0.5 mmol), TMPMgCl·LiCl (0.6 mmol), aryl
chloride (0.60 mmol) and a catalyst (2.0 mol %) in 2.0 mL of THF. b The reaction was carried out with 0.5
mmol of aryl chloride. c Accompanied by 3ae, 2,5-diarylated product was also obtained in 7% yield.
By employing the selective 5-arylation method of thiophene it is possible to undergo concise synthesis of
differently-substituted 2,5-diarylthiophene derivatives as illustrated in Scheme 2. The reaction at the
t
sterically-hindered position was found to be operative when BuOLi was used as an additive in the
presence of a palladium catalyst, Pd(PtBu3)2.10a The reaction of 3aa with 4-methoxy-1-bromobenzene
(2b) also afforded the corresponding 2,5-diarylated thiophene 3aab in 70% yield. When AgNO3/KF was
employed as additives,7c the reaction of 3aa with ethyl 4-iodobenzoate in the presence of 2.0 mol% of
PdCl2(PPh3)2 also proceeded at the 2-position to afford 3aaf in 45% yield.

nHex
nHex
H
additive
Pd cat.
+
X
Me
R
R
Me
S
S
t
t
3aab
(70%)
3aa
BuOLi, Pd(P Bu3)2 (R=OMe, X=Br):
AgNO3/KF, PdCl2(PPh3)2, (R=CO2Et, X=I): 3aaf (45%)
Scheme 2. Concise synthesis of differently-substituted 2,5-diarylthiophene
CONCLUSION
In summary, we have shown that regioselective CH arylation of 3-substituted thiophene derivatives is
achieved with TMPMgCl·LiCl, in which selective reaction takes place at the less hindered CH bond.
Accordingly, it was revealed that the regiocontrolled CH functionalization with TMPMgCl·LiCl is not
only effective for the formation of thiophene‒thiophene bond but also for the arylation reaction of
3-substituted thiophene with aryl bromides and chlorides. Since the reaction proceeds under mild
conditions, the method is potentially practical for syntheses of regioselectively arylated thiophenes.
EXPERIMENTAL
1
General. All the reactions were carried out under nitrogen atmosphere. H NMR (300 MHz) and 13C
NMR (75 MHz) spectra were measured on Varian Gemini 300 as a CDCl3 solution unless noted. The
1
13
chemical shifts were expressed in ppm with CHCl3 (7.26 ppm for H) or CDCl3 (77.0 ppm for C) as
internal standards. IR spectra were recorded on Bruker Alpha with an ATR attachment (Ge). High
resolution mass spectra (HRMS) were measured by JEOL JMS-T100LP AccuTOF LC-Plus (ESI) with a
JEOL MS-5414DART attachment or JEOL JMS-700 MStation (EI) at the Graduate School of Material
Science, Nara Institute of Science and Technology. For thin layer chromatoraphy (TLC) analyses
throughout this work, Merck precoated TLC plates (silica gel 60 F254) were used. Purification by HPLC
with preparative SEC column (JAI-GEL-2H) was performed by JAI LC-9201. Gas chromatography
analyses were carried out with SHIMADZU GCMS-QP2010 Plus. TMPMgCl·LiCl was prepared by
following the literature procedure13 and stored in the freezer as 1.0 M THF solution. Nickel catalysts,
NiCl2(dppe), NiCl2(dppp), NiCl2(dppb), NiCl2(dppf), and NiCl2(PCy3)2 were prepared according to the
literature procedures.14 Other chemicals were purchased and used without further purification.
General procedure for the reaction of 3-hexylthiophene (1a) with aryl bromide in the presence of
Knochel-Hauser base: To 25 mL Schlenk tube equipped with a magnetic stirring bar was added
TMPMgCl·LiCl (0.60 mmol, 1.0 M in THF) at room temperature. To the resulting mixture
3-hexylthiophene (1a, 0.099 mL, 0.50 mmol) was added and stirring was continued for 3 h. Then, THF

(1.4 mL), 4-methyl-1-bromobenzene (0.074 mL, 0.60 mmol) and PEPPSI-IPr (6.79 mg, 0.01 mmol) were
added successively. The mixture was stirred at room temperature for 20 h and quenched by hydrochloric
acid (1.0 M, 1.0 mL). The solution was poured into the mixture of Et2O/water and two phases were
separated. The aqueous phase was extracted with Et2O twice and the combined organic phase was dried
over anhydrous sodium sulfate. Removal of the solvent left a crude oil, which was purified by
chromatography on silica gel using hexanes as an eluent to afford 117.2 mg of
1
5-(4-methyphenyl)-3-hexylthiophene (3aa, colorless oil, 91%): H NMR δ 0.90 (t, J = 6.6 Hz, 3H),
1.23-1.44 (m, 6H), 1.58-1.73 (m, 2H), 2.36 (s, 3H), 2.61 (t, J = 7.7 Hz, 2H) , 6.83 (d, J = 1.3 Hz, 1H),
7.11 (d, J = 1.3 Hz, 1H), 7.17 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H); 13C NMR δ 14.1, 21.1, 22.6,
29.0, 30.4, 30.6, 31.7, 118.9, 124.0, 125.6 (×2), 129.4 (×2), 131.9, 137.1, 144.1, 144.2; IR (ATR) 2955,
2926, 2856, 1511, 1465, 1458, 812, 729, 649, 639 cm-1; HRMS (EI+) Calcd for C17H22S [M]+: 258.1442;
found: m/z 258.1439.
1
5-(4-Methoxyphenyl)-3-methylthiophene (3bb, colorless solid, 87%): H NMR δ 2.28 (s, 3H), 3.83 (s,
3H), 6.80 (s, 1H), 6.91 (d, J = 8.8 Hz, 2H), 7.02 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H); 13C NMR δ 15.8, 55.3,
114.2 (×2), 119.1, 124.5, 127.0 (×2), 127.5, 138.5, 144.0, 159.1; IR (ATR) 3004, 2960, 2934, 2836, 1606,
1510, 1289, 1248, 1184, 1031, 826, 810, 746, 734, 707 cm-1; HRMS (EI+) Calcd for C12H12OS [M]+:
204.0609; found: m/z 204.0609.
5-(4-Methoxyphenyl)-3-(4,4,5,5,6,6,7,7,7-nonafluoroheptan-1-yl)thiophene (3cb, colorless oil, 64%):
1H NMR δ 1.89-2.06 (m, 2H), 2.07-2.23 (m, 2H), 2.72 (t, J = 7.3 Hz, 2H), 3.84 (s, 3H), 6.84 (d, J = 1.1
Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 1.1 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H); 13C NMR δ 20.9 (t,
J
C-F = 3.7 Hz), 29.7, 30.2 (t, JC-F = 22 Hz), 55.2, 114.2 (×2), 119.2, 122.8, 127.0 (×2), 127.2, 141.7, 144.7,
159.2; IR (ATR) 1513, 1357, 1295, 1274, 1253, 1216, 1181, 1170, 1132, 1091, 1031, 1009, 878, 867, 851,
824, 741, 723, 709, 649, 604 cm-1; HRMS (DART-ESI+) Calcd for C18H16F9OS [M+H]+: 451.0778;
found: m/z 451.0781.
3-(4-Methoxyphenyl)-5-(4-methylphenyl)thiophene (3da): 56% yield. 1H NMR δ 2.38 (s, 3H), 3.85 (s,
3H), 6.95 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 1.4 Hz, 1H), 7.50 (d, J = 1.4 Hz, 1H),
7.54 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H); 13C NMR δ 21.2, 55.3, 114.2 (×2), 117.9, 121.8, 125.7
(×2), 127.4 (×2), 128.8, 129.6 (×2), 131.6, 137.5, 142.7, 145.0, 158.9; IR (ATR) 1500, 1295, 1254, 1183,
1029, 830, 812, 751 cm-1; HRMS (EI+) Calcd for C18H16OS [M]+: 280.0922; found: m/z 280.0922.
3-Methoxy-2-(4-methoxyphenyl)thiophene (3fb, brown oil, 51 mg, 45%). 1H NMR δ 3.83 (s, 3H), 3.90

(s, 3H), 6.92 (d, J = 5.5 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 5.5 Hz, 1H), 7.66 (d, J = 8.8 Hz,
13
2H); C NMR δ 55.3, 58.7, 114.0 (×2), 117.5, 121.1, 126.1, 126.7, 128.2 (×2), 152.8, 158.2; IR (ATR)
2956, 2936, 2847, 2836, 1609, 1549, 1510, 1462, 1378, 1291, 1266, 1246, 1180, 1098, 1070, 1035, 926,
830, 795, 707, 643 cm-1; HRMS (EI+) Calcd for C12H12O2S [M]+: 220.0558; found: m/z 220.0561.
The reaction of 3-(1-octyn-1-yl)thiophene (1e) with aryl bromide in the presence of Knochel-Hauser
base: The reaction was carried out in a similar manner to that of 1a with aryl bromide in the presence of
Knochel-Hauser base with 3-(1-octyn-1-yl)thiophene (1e, 96.2 mg, 0.50 mmol), TMPMgCl·LiCl (0.60
mmol, 1.0 M in THF), 4-bromoanisole (2b, 0.075 mL, 0.60 mmol) and PEPPSI-IPr (6.79 mg, 0.01 mmol)
at room temperature for 21 h to afford the mixture of 2-arylated and 5-arylated products. The ratio of
2-Ar/5-Ar was determined to be 35:65 by 1H NMR analysis.
1
5-(4-Methoxyphenyl)-3-hexylthiophene (3ab): H NMR δ 0.90 (t, J = 6.6 Hz, 3H), 1.24-1.43 (m, 6H),
1.57-1.71 (m, 2H), 1.86-2.20 (4H, m), 2.60 (t, J = 7.7 Hz, 2H), 3.83 (s, 3H), 6.80 (d, J = 1.1 Hz, 1H), 6.90
(d, J = 8.8 Hz, 2H), 7.04 (d, J = 1.4 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H); 13C NMR δ 14.1, 22.6, 29.0, 30.4,
30.6, 31.7, 55.3, 114.2 (×2), 118.4, 123.5, 127.0 (×2), 127.6, 143.8, 144.2, 159.0; IR (ATR) 2956, 2926,
2851, 1608, 1511, 1296, 1255, 1181, 1032, 824, 712, 649 cm-1; HRMS (EI+) Calcd for C17H22OS [M]+:
274.1391; found: m/z 274.1389.
5-Phenyl-3-hexylthiophene (3ac): 1H NMR δ 0.79 (t, J = 6.9 Hz, 3H), 1.19-1.46 (m, 6H), 1.57-1.72 (m,
2H), 1.86-2.20 (4H, m), 2.61 (t, J = 7.7 Hz, 2H), 2.85 (t, J = 7.5 Hz, 2H), 6.86 (d, J = 1.1 Hz, 1H), 7.15 (d,
J = 1.4 Hz, 1H), 7.26 (ddd, J = 8.0, 6.6, 1.4 Hz, 1H), 7.36 (td, J = 6.6, 1.4 Hz, 1H), 7.59 (dd, J = 8.0, 1.4
13
Hz, 1H); C NMR δ 14.1, 22.6, 29.0, 30.4, 30.6, 31.7, 119.4, 124.5, 125.7 (×2), 127.2, 128.8 (×2),
134.7, 143.9, 144.2; IR (ATR) 2955, 2926, 2854, 1496, 1453, 837, 758, 715, 690 cm-1; HRMS (EI+)
Calcd for C16H20S [M]+: 244.1286; found: m/z 244.1283.
1
5-(4-Fluorophenyl)-3-hexylthiophene (3ad): H NMR δ 0.93 (t, J = 6.6 Hz, 3H), 1.23-1.49 (m, 6H),
1.59-1.75 (m, 2H), 2.63 (t, J = 7.7 Hz, 2H), 6.87 (d, J = 1.1 Hz, 1H), 7.07 (dd, J = 8.8 Hz, JH-F = 8.8 Hz,
2H), 7.10 (s, 1H), 7.56 (dd, J = 8.8 Hz, JH-F = 5.2 Hz, 2H); 13C NMR δ 14.1, 22.6, 29.0, 30.4, 30.6, 31.7,
115.7 (×2, d, JC-F = 21.8 Hz), 119.4, 127.2 (×2, d, JC-F = 8.0 Hz), 130.9 (d, JC-F = 3.4 Hz), 142.8, 144.3,
162.2 (d, JC-F = 247 Hz); IR (ATR) 2955, 2927, 2856, 1509, 1465, 1232, 1159, 1095, 826, 810, 734 cm-1;
HRMS (EI+) Calcd for C16H19FS [M]+: 262.1191; found: m/z 262.1193.

5-(4-Trifluoromethylphenyl)-3-hexylthiophene (3ae): 1H NMR δ 0.90 (t, J = 6.9 Hz, 3H), 1.21-1.45 (m,
6H), 1.58-1.72 (m, 2H), 2.62 (t, J = 7.6 Hz, 2H), 6.95 (d, J = 1.1 Hz, 1H), 7.23 (d, J = 1.1 Hz, 1H), 7.60
(d, J = 8.5 Hz, 2H), 7.68 (d, J = 8.5 Hz, 2H); 13C NMR δ 14.1, 22.6, 29.0, 30.4, 30.6, 31.7, 120.9, 125.7,
125.8, 129.0 (q, JC-F = 33 Hz), 129.4, 138.0, 142.1, 144.6; IR (ATR) 2956, 2927, 2857, 1615, 1324, 1166,
1124, 1068, 1017, 831 cm-1; HRMS (EI+) Calcd for C17H19F3S [M]+: 312.1160; found: m/z 312.1160.
1
Ethyl 4-(3-hexylthiophen-2-yl)benzoate (3af): H NMR δ 0.90 (t, J = 6.6 Hz, 3H), 1.41 (t, J = 7.1 Hz,
3H), 1.24-1.38 (m, 6H), 1.54-1.71 (m, 2H), 2.62 (t, J = 7.7 Hz, 2H), 4.39 (q, J = 7.1 Hz, 2H), 6.94 (s, 1H),
7.26 (s, 1H), 7.64 (d, J = 8.5 Hz, 2H), 8.03 (d, J = 8.5 Hz, 2H); 13C NMR δ 14.0, 14.3, 22.5, 28.9, 30.4,
30.5, 31.6, 60.9, 120.9, 125.2 (×2), 125.8, 128.9, 130.1 (×2), 138.8, 142.6, 144.6, 166.3; IR (ATR)
2953, 2925, 2856, 1707, 1606, 1274, 1181, 1107, 770, 695 cm-1; HRMS (DART-ESI+) Calcd for
C19H25O2S [M+H]+: 317.1575; found: m/z 317.1575.
5-(Benzothiazole-2-yl)-3-hexylthiophene (3ag): 1H NMR δ 0.90 (t, J = 6.7 Hz, 3H), 1.20-1.47 (m, 6H),
1.59-1.77 (m, 2H), 2.64 (t, J = 7.7 Hz, 2H), 7.10 (d, J = 1.3 Hz, 1H), 7.32-7.40 (m, 1H), 7.43-7.50 (m,
1H), 7.50 (d, J = 1.3 Hz, 1H), 7.81-7.89 (m, 1H), 7.98-8.05 (m, 1H); 13C NMR δ 14.0, 22.5, 28.9, 30.28,
30.33, 31.6, 121.3, 122.8, 124.1, 125.0, 126.3, 129.7, 134.6, 136.7, 144.3, 153.7, 161.6; IR (ATR) 2956,
2923, 2856, 1502, 1466, 1456, 1437, 1429, 1312, 1256, 1217, 1192, 1131, 1016, 901, 865, 832, 823, 793,
754, 727, 705, 672 cm-1; HRMS (DART-ESI+) Calcd for C17H20NS2 [M+H]+: 302.1037; found: m/z
302.1038.
2-(4-Methoxyphenyl)-5-(4-methylphenyl)-3-hexylthiophene (3aab)10a: The reaction was carried out in
a manner described previously with 5-(4-methyphenyl)-3-hexylthiophene (3aa, 129.2 mg, 0.50 mmol),
4-methoxy-l-bromobenzene (0.075 mL, 0.60 mmol), LiOtBu (1.5 mmol) in 1.0 mL of DMF at 100 ºC for
1
20 h to afford 128.5 mg of 3aab as a colorless oil (70%). H NMR δ 0.87 (t, J = 6.7 Hz, 3H), 1.17-1.41
(m, 6H), 1.56-1.73 (m, 2H), 2.36 (s, 3H), 2.62 (t, J = 7.8 Hz, 2H), 3.85 (s, 3H), 6.95 (d, J = 8.8 Hz, 2H),
7.14 (s, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H); 13C NMR δ 14.1,
21.1, 22.6, 28.8, 29.2, 30.9, 31.6, 55.2, 113.9 (×2), 125.0, 125.4 (×2), 127.2, 129.5 (×2), 130.4 (×2),
131.8, 136.7, 137.0, 139.0, 141.6, 158.9; IR (ATR) 2955, 2927, 2857, 1608, 1504, 1462, 1441, 1289,
1248, 1177, 1037, 1111, 908, 830, 812, 793, 757, 735, 669, 622 cm-1; HRMS (ESI+) Calcd for C24H29OS
[M+H]+: 365.1939; found: m/z 365.1939.
2-(4-Ethoxycarbonylphenyl)-5-(4-methylphenyl)-3-hexylthiophene (3aaf)7c: The reaction was carried

out in a manner described previously with 5-(4-methyphenyl)-3-hexylthiophene (3aa, 129.2 mg, 0.50
mmol), 4-iodobenzoate (0.100 mL, 0.60 mmol), AgNO3 (212.5 mg, 1.25 mmol), KF (72.6 mg, 1.25
mmol) in 3.0 mL of DMSO at 100 ºC for 27 h to afford 3aaf as a colorless oil (45%). 1H NMR δ 0.86 (t, J
= 6.7 Hz, 3H), 1.15-1.37 (m, 6H), 1.41 (t, J = 7.1 Hz, 3H), 1.59-1.73 (m, 2H), 2.37 (s, 3H), 2.68 (t, J =
7.9 Hz, 2H), 3.85 (q, J = 7.1 Hz, 2H), 7.18 (s, 1H), 7.19 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 7.53
13
(d, J = 8.3 Hz, 2H), 8.09 (d, J = 8.3 Hz, 2H); C NMR δ 14.0, 14.4, 21.2, 22.6, 29.1, 29.2, 30.9, 31.6,
61.0, 125.49, 125.52 (×2), 128.8 (×2), 128.9, 129.6 (×2), 129.8 (×2), 131.4, 135.5, 137.5, 139.4,
140.7, 143.4, 166.4; IR (ATR) 2954, 2925, 2856, 1716, 1605, 1503, 1457, 1405, 1366, 1308, 1271, 1178,
1104, 1021, 854, 812, 771, 721, 701 cm-1; HRMS (DART-ESI+) Calcd for C24H31O2S [M+H]+:
407.2045; found: m/z 407.2040.
ACKNOWLEDGEMENTS
This work was partially supported by KAKENHI (21655051) for Challenging Exploratory Research by
Japan Society for the Promotion of Science (JSPS). The authors thank Nara Insititute of Science and
Technology for measurements of high-resolution mass spectra.
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