Site-selective sequential coupling reactions controlled by "electrochemical Reaction Site Switching": A straightforward approach to 1,4-bis(diaryl)buta-1,3-diynes

Article abstract of DOI:10.1039/c2ob26567b

Site-selective sequential coupling reactions directed toward bis(diaryl)butadiynes are described. The reaction site could be controlled completely by the on/off application of electricity. The electro-oxidative homo-coupling of terminal alkynes (electricity ON) and the subsequent Suzuki-Miyaura coupling (electricity OFF) afforded bis(diaryl)butadiynes in high yields. The obtained 1,4-bis(diaryl)butadiynes could be converted to a 2,5-bis(diaryl)thiophene derivative, which exhibited blue fluorescence. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2ob26567b

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
PAPER
Site-selective sequential coupling reactions controlled
by “Electrochemical Reaction Site Switching”:
a straightforward approach to 1,4-bis(diaryl)buta-
1,3-diynes†
Cite this: Org. Biomol. Chem., 2012, 10,
9562
Koichi Mitsudo,*a Natsuyo Kamimoto,a Hiroki Murakami,a Hiroki Mandai,a
Atsushi Wakamiya,b Yasujiro Muratab and Seiji Suga*a
Site-selective sequential coupling reactions directed toward bis(diaryl)butadiynes are described. The reac-
tion site could be controlled completely by the on/off application of electricity. The electro-oxidative
homo-coupling of terminal alkynes (electricity ON) and the subsequent Suzuki–Miyaura coupling (electri-
city OFF) afforded bis(diaryl)butadiynes in high yields. The obtained 1,4-bis(diaryl)butadiynes could be
converted to a 2,5-bis(diaryl)thiophene derivative, which exhibited blue fluorescence.
Received 8th August 2012,
Accepted 22nd October 2012
DOI: 10.1039/c2ob26567b
www.rsc.org/obc
Oxidative homo-coupling
Introduction
π-Conjugated compounds have received considerable attention
because they are known to be key building blocks for pharma-
ceuticals and candidates for electrochemical and optical
materials.1 One of the most straightforward and powerful ways
to construct π-skeletons is through transition-metal catalysed
cross-coupling reactions using aryl halides or triflates and
organometallic species such as in Suzuki–Miyaura coupling
(eqn (1)).2 Alternatively, transition metal-catalysed oxidative
homo-coupling reactions of aryl metal species (e.g., aryl
boronic acids and esters)3 or terminal alkynes4 have also been
shown to be convenient methods for building symmetrical
π-structures (eqn (2)).
ð2Þ
In these oxidative homo-coupling reactions, a stoichio-
metric amount of an oxidant is usually required. One way to
overcome this drawback is to use electro-oxidation instead of a
stoichiometric oxidant.5,6 The electrochemical method is advan-
tageous, not only because it does not require excess oxidant,
but also because the system can be switched between oxidative
and neutral conditions by the on/off application of electricity.
We considered that this feature could make it possible to realize
a site selective coupling reaction controlled by the on/off appli-
cation of electricity. For instance, under neutral conditions
(electricity OFF), the treatment of a haloaryl metal species with
Pd0 usually causes cleavage of the C–X bond through oxidative
addition (Scheme 1, a). In contrast, under electro-oxidative con-
ditions (electricity ON), Pd0 would be oxidized to PdII, which
undergoes cleavage of the C–M bond of the haloaryl metal
species via transmetallation to give a haloaryl palladium inter-
mediate, leading to dihalodiarene (Scheme 1, b). This means
that the reaction site of the haloaryl metal species could be con-
trolled by the on/off application of electricity, and we call this
strategy “Electrochemical Reaction Site Switching”.
Typical cross-coupling
ð1Þ
aGraduate School of Natural Science and Technology, Okayama University, 3-1-1
Tsuhsima-naka, Kita-ku, Okayama 700-8530, Japanmitsudo@cc.okayama-u.ac.jp,
suga@cc.okayama-u.ac.jp; Fax: +81 86 251 8081; Tel: +81 86 251 8081
bInstitute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
E-mail: wakamiya@scl.kyoto-u.ac.jp, yasujiro@scl.kyoto-u.ac.jp;
We expected that the ability to control the reaction site by
“Electrochemical Reaction Site Switching” could make it possi-
ble to build up a π-conjugated structure in a one-sequence
Fax: +81 774 38 3178; Tel: +81 774 38 3172
†Electronic supplementary information (ESI) available. CCDC 868776. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c2ob26567b
process. For instance,
a
sequential coupling reaction
9562 | Org. Biomol. Chem., 2012, 10, 9562–9569
This journal is © The Royal Society of Chemistry 2012

Organic & Biomolecular Chemistry
Paper
View Article Online
characteristics.9 The sequential reactions consist of two coup-
ling reactions (Scheme 2). The first step is a Pd/Cu-catalysed
electrochemical homo-coupling of p-bromophenylacetylene to
give bis(p-bromophenyl)butadiyne (1st step: electricity ON),
and the second step is a sequential Suzuki–Miyaura coupling
reaction to build up 1,4-bis(diaryl)butadiynes (2nd step: elec-
tricity OFF).
Results and discussion
Optimization of the first step
To realize the sequential reaction, we started by seeking to
identify the optimal conditions for the first step. In this step,
oxidative homo-coupling of the terminal alkynes should
proceed selectively without affecting the bromo group
(Table 1). In the presence of a catalytic amount of Pd(OAc)2
(5 mol%) and TEMPO (15 mol%), the electro-oxidation of
p-bromophenylacetylene (1) was carried out, but only a trace
amount of diyne (2) was obtained (4%, entry 1). Further tuning
of the reaction conditions revealed that the addition of a cata-
lytic amount of copper salt was essential for the reaction. With
CuCl, the yield increased to 32% (entry 2). The addition of
CuBr gave a similar result (entry 3). CuI was found to be an
effective catalyst for the reaction, and the yield of 2 increased
drastically to 73%. Without Pd(OAc)2, the yield decreased to
20% (entry 4). These results suggest that both Pd and Cu play
a key role in the reactions. CuCN and Cu(OAc)2 were not suit-
able for the reaction (entries 5 and 6). Next, tuning of the
mediators was conducted (entries 7–10). Among the several
mediators examined thus far, p-benzoquinone (pbq) gave the
best results and homo-coupling product 2 was obtained in
Scheme 1 Electrochemical Reaction Site Switching for the construction of
π-conjugated compounds.
consisting of the homo-coupling of a haloaryl metal species
(1st step: electricity ON) and a subsequent cross-coupling reac-
tion with another aryl metal species under neutral conditions
(2nd step: electricity OFF) affords π-conjugated compounds
that contain four π-units (Scheme 1, c). Therefore, “Electroche-
mical Reaction Site Switching” should offer a straightforward
approach to π-conjugated compounds. This idea prompted us
to design a novel integrated sequential reaction7,8 that con-
sisted of an oxidative homo-coupling reaction and a typical
coupling reaction.
As the first example of the construction of π-conjugated
compounds by a sequential coupling reaction controlled by
Electrochemical Reaction Site Switching, we chose π-conju-
gated compounds that include a diyne moiety as a target; they
are of interest due to their unique optical and electrochemical
Table 1 Pd/Cu-Catalysed electro-oxidative homo-coupling of terminal alkyne 1
with several Cu sources and mediatorsa
Entry
Cu source
Mediator
Yield (%)
1
2
None
CuCl
CuBr
CuI
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
AZADO
pbq
4
32
3
40
4
73 (20)b
7
5
CuCN
Cu(OAc)2
CuI
6
23
7
40
8
CuI
87
9
CuI
(4-Br-C6H4)3N
None
27
10
CuI
25
a Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (5 mol%), Cu source
(20 mol%), mediator (15 mol%), Et3N (2.0 equiv.), 0.1 M NaClO4
in CH3CN–H2O (7 : 1), 30 °C, 10 mA, 2 F mol−1 (2 h 40 min). Yields
were determined by 1H NMR. b Without Pd(OAc)2.
Scheme 2 Electrochemical Reaction Site Switching for the synthesis of 1,4-bis-
(diaryl)butadiynes.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 9562–9569 | 9563

Paper
Organic & Biomolecular Chemistry
View Article Online
Table 2 Effects of reaction temperature and currency on the Pd/Cu-catalysed
electro-oxidative homo-coupling of 1a
Entry
Temperature (°C)
Current (mA)
Yield (%)
1
2
3
4
5
6
7
0
10
10
10
5
10
20
10
33
55
89
86
87
53
67
10
20
30
30
30
40
Fig. 1 A plausible mechanism of electro-oxidative Pd-catalysed homo-coupling
of terminal alkyne.
a Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (5 mol%), CuI
(20 mol%), pbq (15 mol%), Et3N (2.0 equiv.), 0.1 M NaClO4 in
CH3CN–H2O (7 : 1),
2 F h 40 min). Yields were
mol−1 (2
determined by 1H NMR.
87% yield (entry 8). To the best of our knowledge, this is the
first report of transition metal-catalysed electrochemical oxi-
dative homo-coupling of terminal alkynes.
A plausible mechanism for the Pd-catalysed electro-oxi-
dative homo-coupling of an arylacetylene is shown in Fig. 1.
First, transmetallation with PdII and copper acetylide, gener-
ated in situ, would give (arylethynyl)palladium species, and the
second transmetallation would then give bis(arylethynyl)palla-
dium species. Subsequent reductive elimination would afford
diaryldiyne and Pd0 species. Pd0 would be oxidized by pbq to
PdII species. The reduced benzoquinone would be oxidized on
the anode to regenerate pbq. The reaction consists of two
cycles: a catalytic cycle of palladium (Pd cycle), and an electro-
chemical mediator cycle of pbq (e cycle). For the reaction to
proceed efficiently, the efficiencies of the two cycles should be
synchronized. The efficiency of the Pd cycle can be adjusted
via the reaction temperature and that of the e cycle can be pri-
marily controlled by the applied current. Optimization of these
two factors is illustrated in Table 2. First, the effect of tempera-
ture was investigated with 10 mA of current (entries 1–3, 5,
and 7). The homo-coupling reaction proceeded even at 0 °C,
and coupling product 2 was obtained in 33% yield (entry 1).
With an increase in the reaction temperature to 20–30 °C, 1
was consumed completely, and the yield of 2 increased to as
much as 87–89% (entries 3 and 5). At a higher temperature
(40 °C), the yield of 2 decreased to 67% (entry 7). Under these
conditions, the Pd cycle might become faster than the e cycle,
which would make the reaction less effective. The current
value was optimized at 30 °C (entries 4–6). Similar amounts of
2 were obtained with 5 or 10 mA of current, but the reaction
with 20 mA of current gave a lower yield of 2, probably because
20 mA of current was excess to synchronize with the Pd cycle at
30 °C and oxidation of other compounds would occur.
Table 3 Effects of electrolyte on the Pd/Cu-catalysed electro-oxidative homo-
coupling of 1a
Entry
Electrolyte
Yield (%)
1
2
3
4
5
6
7
LiClO4
NaClO4
KClO4
RbClO4
CsClO4
Et4NClO4
Bu4NClO4
70
87
93
95
84
80
66
a Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (5 mol%), CuI
(20 mol%), pbq (15 mol%), Et3N (2.0 equiv.), 0.1 M electrolyte in
CH3CN–H2O (7 : 1),
2 F h 40 min). Yields were
mol−1 (2
determined by 1H NMR.
and 2 was obtained in 93% and 95% yields, respectively
(entries 3 and 4). With CsClO4, the yield of 2 was similar to
that with NaClO4 (84%, entry 2). Tetraalkylammonium salts
such as Et4NClO4 and Bu4NClO4 can also be used for the reac-
tion (entries 6 and 7). Among the electrolytes thus far exam-
ined, KClO4 and RbClO4 were the most suitable electrolytes for
the reaction. Because KClO4 was much cheaper than RbClO4,
we hereafter used KClO4 as an electrolyte.
We next optimized the supporting electrolyte on the Pd/Cu-
catalysed electro-oxidative homo-coupling of 1 (Table 3). With
LiClO4, the yield of 2 decreased to 70% (entry 1). In contrast,
the use of KClO4 and RbClO4 was efficient for the reaction,
With the optimized conditions for the first step in hand, we
next carried out the sequential reactions, including the electro-
oxidative homo-coupling of 1 and subsequent Suzuki–Miyaura
coupling with several arylboronic acids on the basis of the
9564 | Org. Biomol. Chem., 2012, 10, 9562–9569
This journal is © The Royal Society of Chemistry 2012

Organic & Biomolecular Chemistry
Paper
View Article Online
Table 4 Synthesis of bis(diaryl)butadiynes by sequential coupling reactions controlled by Electrochemical Reaction Site Switchinga
a Reaction conditions ON: 1 (0.5 mmol), Pd(OAc)2 (5 mol%), CuI (20 mol%), pbq (15 mol%), Et3N (2.0 equiv.), KClO4 (0.1 M), CH3CN–
H2O (7 : 1), 30 °C, 10 mA, 2 F mol−1 (2 h 40 min). OFF: additionally added were arylboronic acid (0.75 mmol), P(t-Bu)3·HBF4 (10 mol%),
Cs2CO3 (3.0 mmol), DME (5 mL), and refluxed for 24 h. Isolated yield. b NaClO4 was used instead of KClO4.
Electrochemical Reaction Site Switching strategy (Table 4). phenylacetylene (1, 0.5 mmol), the electricity was turned off
After the electro-oxidative homo-coupling of p-bromo- and to the resulting mixture were added p-tolylboronic acid
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 9562–9569 | 9565

Paper
Organic & Biomolecular Chemistry
View Article Online
Table 5 Conversion of bis(diaryl)butadiyne 3 to bis(diaryl)thiophene 4a
Fig. 2 ORTEP drawing of 3g (50% probability ellipsoids; hydrogen atoms and
disorder atoms omitted for clarity).
Entry
3
4
Yieldb (%)
(1.5 mol amt to 1), P(t-Bu)3·HBF4 (10 mol%), Cs2CO3 (6 mol
amt to 1), and DME, then refluxed to give 1,4-bis(p-tolylphe-
nyl)butadiyne 3a in 95% yield. When the reaction was carried
out with 1.0 mmol of 1, the yield of 3a slightly decreased to
87%. In a similar manner, i-Pr- or t-Bu-substituted 1,4-bis-
(diaryl)butadiyne 3b and 3c were obtained in 79 and 86%
yields, respectively. Phenol and aniline skeletons can also be
introduced (3d and 3e). Arylboronic acids bearing electron-
withdrawing functional groups could also be used in the reac-
tions. 1,4-Bis-(diaryl)butadiynes with fluoro (3f), acetyl (3g),
and cyano (3h) groups at the p-position can be synthesized by
the sequential coupling reactions in respective yields of 68%,
65%, and 47%. The synthesis of aryl-substituted diynes with
much greater π-conjugation was achieved by the use of
2-naphthylboronic acid or 2-phenylethenylboronic acid to
afford 3i and 3j in 72% and 70% yields, respectively.
The results of X-ray single-crystal analysis of 3g are pres-
ented in Fig. 2.10 Two conformers were incorporated within
the crystal cell. The torsion angles of their benzene rings on
the diynes were 7.9° and 71.2°, respectively. The angles were
different from that of 1,4-bis(4-diphenyl)butadiyne (63.7°)
reported by Housecroft and co-workers.11 This result indicates
that the crystal structure and packing structure of 1,4-bis-
(diaryl)butadiynes were significantly affected by the substitu-
ents on the aryl groups.
1
2
3
4
5
3b (Ar = p-i-Pr-C6H4)
3c (Ar = p-t-Bu-C6H4)
3d (Ar = p-MeO-C6H4)
3e (Ar = p-Me2N-C6H4)
3i (Ar = 2-Np)
4b
4c
4d
4e
4i
55
69
42
78
26
a Reaction conditions: 3 (0.05 mmol), Na2S·9H2O (5 equiv.) in
DMF 150 °C, 24 h. b Isolated yield.
Conclusions
In conclusion, we have developed a sequential coupling reac-
tion that includes the Pd/Cu-catalysed electro-oxidative homo-
coupling of p-bromophenylacetylene and subsequent Suzuki–
Miyaura coupling to give 1,4-bis(diaryl)butadiynes. The reac-
tion site could be controlled by electrochemical reaction site
switching. The 1,4-bis(diaryl)butadiynes were readily converted
to 2,5-bis(diaryl)thiophenes. The scope of the reaction system
is under investigation in our laboratory.
Experimental
General
Nuclear magnetic resonance (NMR) spectra were recorded on a
Varian 600 System (1H 600 MHz, 13C 150 MHz), a Varian 400-
MR (1H 400 MHz, 13C 100 MHz), and a Varian GEMINI 2000
(1H 300 MHz, 13C 75 MHz) spectrometer. Chemical shifts for
1H NMR are expressed in parts per million (ppm) relative to
residual CHCl3 in CDCl3 (δ 7.26 ppm). Chemical shifts for 13C
NMR are expressed in ppm relative to CDCl3. IR spectra were
recorded on a JASCO FT/IR-4100 spectrophotometer. Elemen-
tal analysis was obtained with a Perkin-Elmer PE 2400 Series II
CHNS/O analyzer. The electrochemical reactions were carried
out with two platinum electrodes (1.0 × 1.5 cm2) in a cylindri-
cal beaker-like divided cell (1.5 cm diameter, 8 cm height,
14 mL volume) separated by a glass filter, which was pur-
chased from Techno-Sigma (K-3). Analytic thin layer chromato-
graphy (TLC) was performed on Merck, pre-coated plate silica
gel 60 F254 (0.25 mm thickness). Column chromatography was
performed on KANTO CHEMICAL silica gel 60N (40–50 μm).
All materials were obtained from commercial suppliers and
used without further purification. All reactions were performed
under argon.
Transformation of bisdiaryldiynes to bis(diaryl)thiophenes
1,4-Bis(diaryl)butadiynes could be readily transformed to 2,5-
bis(diaryl)thiophenes, which have been known as active
materials for field effect transistors,12 in one step by treatment
with Na2S (Table 5). For instance, the reaction of 3b with
Na2S·9H2O led to cycloaddition to afford 4b in moderate yield
with complete consumption of 3b. The treatment of 3c–3e and
3i under similar conditions afforded the corresponding 2,5-
bis(diaryl)thiophenes 4 in moderate yields (entries 2–5).
Among the thus obtained bis(diaryl)thiophenes, 4c exhibited
strong blue luminescence. To clarify its optical characteristics,
the measurement of UV/vis absorption and fluorescence
spectra was carried out. 4c shows UV/vis absorption over a
wide range (292–416 nm) with an absorption maximum (λabs
)
at 357 nm (log ε = 4.73). In the fluorescence spectra, the
longest emission maxima (λem) of 4c were 479 nm as a solid
and 432 nm in CH2Cl2 solution (1.0 × 10−6 M) with moderate
fluorescence quantum yields (ΦFL = 0.46 as a solid and 0.45 in
CH2Cl2).
Electrochemical reaction
PD/CU-CATALYZED ELECTRO-OXIDATIVE HOMO-COUPLING OF P-BROMOPHE-
NYLACETYLENE (TABLE 1, ENTRY 8). In the anodic chamber was
9566 | Org. Biomol. Chem., 2012, 10, 9562–9569
This journal is © The Royal Society of Chemistry 2012

Organic & Biomolecular Chemistry
Paper
View Article Online
placed a solution of 4-bromophenylacetylene (1) (90.0 mg, 4H), 7.53 (d, J = 8.4 Hz, 4H), 7.57 (d, J = 8.4 Hz, 4H), 7.59 (d, J =
0.497 mmol), Pd(OAc)2 (5.8 mg, 0.026 mmol), CuI (19.3 mg, 8.4 Hz, 4H); 13C NMR (150 MHz, CDCl3) δ 24.1, 34.0, 72.0,
0.101 mmol), p-benzoquinone (pbq) (8.2 mg, 0.076 mmol) and 82.0, 120.4, 127.0, 127.1, 127.2, 133.1, 133.7, 142.0, 148.9; IR
Et3N (140 μL, 1.00 mmol) in a 0.1 M NaClO4 solution of (KBr) 2956, 2924, 2150, 1488, 821 cm−1; HRMS (EI) m/z calcd
CH3CN–H2O (7 : 1, 5 mL). In the cathodic chamber was placed for C34H30 [M+]: 438.2348, found: 438.2349; mp: 248.5–
a 0.1 M NaClO4 solution of CH3CN–H2O (7 : 1, 5 mL). Under an 249.0 °C.
argon atmosphere, a constant current (10 mA, 2 F mol−1) was
1,4-BIS(4′-TERT-BUTYL-4-BIPHENYL)BUTA-1,3-DIYNE (3C). 86% yield
supplied at 30 °C with magnetic stirring.13 To the resulting from 1; colorless solid; 1H NMR (600 MHz, CDCl3) δ 1.37 (s,
mixture was added MeOH (15 mL). The precipitate was filtered 18H), 7.48 (d, J = 8.4 Hz, 4H), 7.55 (d, J = 8.4 Hz, 4H), 7.57 (d, J
and the residue was washed with MeOH (50 mL) to afford a = 8.4 Hz, 4H), 7.60 (d, J = 8.4 Hz, 4H); 13C NMR (150 MHz,
brown solid. The yield of 1,4-bis(4-bromo-phenyl)buta-1,3- CDCl3) δ 31.5, 34.8, 74.7, 82.0, 120.5, 126.0, 126.8, 127.1, 133.1,
diyne (2) was determined by 1H NMR analysis using 1,1,2,2- 137.3, 141.9, 151.2; IR (KBr) 3025, 2927, 2360, 1491, 822 cm−1
;
tetrachloroethane as an internal standard (87%). Purification by HRMS (EI) m/z calcd for C36H34 [M+]: 466.2661, found:
recrystallization from CHCl3 afforded 1,4-bis(4-bromophenyl)- 466.2672; mp: >300 °C.
buta-1,3-diyne (2) as brown needle crystals (46.0 mg, 51%).
1,4-BIS(4′-METHOXY-4-BIPHENYL)BUTA-1,3-DIYNE (3D). 65% yield
1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 8.4 Hz, 4H), 7.48 (d, from 1; colorless solid; 1H NMR (400 MHz, CDCl3) δ 3.86 (s,
J = 8.4 Hz, 4H); 13C NMR (150 MHz, CDCl3) δ 74.8, 81.0, 120.6, 6H), 6.99 (d, J = 8.8 Hz, 4H), 7.52–7.59 (m, 12H); 13C NMR
123.9, 131.8, 133.8; IR (KBr) 3077, 2367, 1898, 1480, 1067, (150 MHz, CDCl3) δ 55.5, 74.6, 82.0, 114.5, 120.1, 126.7, 128.3,
816 cm−1
.
132.7, 133.1, 141.7, 159.8; IR (KBr) 2836, 2140, 1577, 1489,
1248, 823 cm−1; HRMS (EI) m/z calcd for C30H22O2 [M+]:
414.1620, found: 414.1610; mp: 250.5–251.5 °C.
Sequential coupling reactions controlled by Electrochemical
Reaction Site Switching
1,4-BIS(4′-N,N-DIMETHYL-4-BIPHENYL)BUTA-1,3-DIYNE
(3E). 76%
TYPICAL PROCEDURE FOR SYNTHESIS OF 1,4-BIS(DIARYL)DIYNE (3) yield from 1; brown solid; 1H NMR (600 MHz, CDCl3) δ 3.01 (s,
(TABLE 3, ENTRY 1). The electro-oxidation was carried out in an 12H), 6.80 (d, J = 9.0 Hz, 4H), 7.52 (d, J = 9.0 Hz, 4H), 7.53–7.57
H-type divided cell (glass filter) equipped with two platinum (m, 8H); 13C NMR (150 MHz, CDCl3) δ 40.6, 112.8, 126.1,
electrodes (1.0 × 1.5 cm2). In the anodic chamber was placed a 112.8, 126.1, 127.8, 133.0; IR (KBr) 2889, 2133, 1594, 1492,
solution of 4-bromophenylacetylene (90.5 mg, 0.500 mmol), 1356, 811 cm−1; HRMS (EI) m/z calcd for C32H28N2 [M+]:
Pd(OAc)2 (5.5 mg, 0.024 mmol), CuI (18.7 mg, 0.098 mmol), p- 440.2252, found: 440.2242; mp: >300 °C.
benzoquinone (pbq) (8.0 mg, 0.075 mmol) and Et3N (140 μL,
1,4-BIS(4′-FLUORO-4-BIPHENYL)BUTA-1,3-DIYNE (3F). 68% yield from
1.00 mmol) in a 0.1 M KClO4 solution of CH3CN–H2O (7 : 1, 1; colorless solid; 1H NMR (600 MHz, CDCl3) δ 7.15 (dd, J =
5 mL). In the cathodic chamber was placed a 0.1 M KClO4 8.4 Hz, JH–F = 8.4 Hz, 4H), 7.53 (d, J = 8.4 Hz, 4H), 7.56 (dd, J =
solution of CH3CN–H2O (7 : 1, 5 mL). Under an argon atmos- 8.4 Hz, JH–F = 5.6 Hz, 4H), 7.60 (d, J = 8.4 Hz, 4H); 13C NMR
phere, a constant current (10 mA, 2 F mol−1) was supplied at (150 MHz, CDCl3) δ 74.8, 81.9, 116.0 (d, JC–F = 21.3 Hz), 120.8,
30 °C with magnetic stirring. The resulting mixture in the 127.1, 128.8 (d, JC–F = 8.1 Hz), 133.2, 136.4 (d, JC–F = 3.3 Hz),
anodic chamber was poured into a 30 mL Schlenk flask. To 141.1, 162.9 (d, JC–F = 246.0 Hz); IR (KBr) 3040, 2330, 1235,
the mixture were added DME (5 mL), Cs2CO3 (976.1 mg, 1155, 822 cm−1; HRMS (EI) m/z calcd for C28H16F2 [M+]:
3.00 mmol), P(t-Bu3)·HBF4 (14.5 mg, 0.050 mmol), and p-tolyl- 390.1220, found: 390.1213; mp: 231.5–232.3 °C.
boronic acid (101.8 mg, 0.749 mmol), and then the mixture
1,4-BIS(4′-ACETYL-4-BIPHENYL)BUTA-1,3-DIYNE (3G). 65% yield from
was refluxed for 24 h. After cooling to room temperature, the 1; colorless solid; 1H NMR (400 MHz, CDCl3) δ 2.65 (s, 6H),
resulting mixture was concentrated under reduced pressure 7.62 (d, J = 8.8 Hz, 4H), 7.65 (d, J = 8.8 Hz, 4H), 7.70 (d, J =
and filtered. The filter cake was washed with MeOH (50 mL), 8.0 Hz, 4H), 8.05 (d, J = 8.0 Hz, 4H); 13C NMR (150 MHz,
H2O (20 mL) and EtOAc (3 × 20 mL). The crude mixture was CDCl3) δ 26.7, 75.1, 81.8, 121.6, 127.2, 127.3, 129.0, 133.1,
purified by column chromatography on silica gel (CH2Cl2) to 136.3, 140.6, 144.5, 197.6; IR (KBr) 3650, 3033, 2349, 1681,
afford 1,4-bis(4′-methyl-4-biphenyl)buta-1,3-diyne (3a) in 95% 1603, 1268, 817 cm−1; HRMS (FAB) m/z calcd for C32H23O2
yield as a colorless solid.
[MH+]: 439.1653, found: 439.1686; mp: 262.0–264.0 °C.
1,4-BIS(4′-METHYL-4-BIPHENYL)BUTA-1,3-DIYNE (3A). 95% yield from
1,4-BIS(4′-CYANO-4-BIPHENYL)BUTA-1,3-DIYNE (3H). 47% yield from
1; colorless solid; 1H NMR (600 MHz, CDCl3) δ 2.40 (s, 6H), 1; colorless solid; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J =
7.26 (d, J = 8.4 Hz, 4H), 7.49 (d, J = 8.4 Hz, 4H), 7.56 (d, J = 8.4 Hz, 4H), 7.65 (d, J = 8.4 Hz, 4H), 7.69 (d, J = 8.4 Hz, 4H),
9.0 Hz, 4H), 7.59 (d, J = 9.0 Hz, 4H); 13C NMR (150 MHz, 7.75 (d, J = 8.4 Hz, 4H); 13C NMR (150 MHz, CDCl3) δ 75.5,
CDCl3) δ 21.3, 74.7, 82.0, 120.4, 127.0, 129.8, 133.0, 137.3, 81.8, 111.7, 118.9, 122.2, 127.4, 127.8, 132.9, 133.4, 140.0,
137.9, 142.0; IR (KBr) 3029, 2361, 1491, 850, 812 cm−1; HRMS 144.6; IR (KBr) 3053, 2227, 2137, 1604, 1487, 820 cm−1; HRMS
(EI) m/z calcd for C30H22 [M+]: 382.1722, found: 382.1715; mp: (EI) m/z calcd for C30H16N2 [M+]: 404.1313, found: 404.1309;
258.0–259.5 °C.
mp: 268.5–269.0 °C.
1,4-BIS(4′-ISOPROPYL-4-BIPHENYL)BUTA-1,3-DIYNE (3B). 79% yield
from 1; colorless solid; H NMR (600 MHz, CDCl3) δ 1.29 (d, J from 1; purified by silica gel column chromatography (hexane–
= 8.4 Hz, 12H), 2.96 (sept, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, EtOAc = 10 : 1); colorless solid; 1H NMR (600 MHz, CDCl3)
1,4-BIS[4-(2-NAPHTHYL)-PHENYL]BUTA-1,3-DIYNE (3I). 72% yield
1
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 9562–9569 | 9567

Paper
Organic & Biomolecular Chemistry
View Article Online
δ 7.49–7.54 (m, 4H), 7.67 (d, J = 8.4 Hz, 4H), 7.73 (d, J = 8.4 Hz,
4H), 7.75 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.91 (d, J =
Acknowledgements
7.2 Hz, 2H), 7.94 (d, J = 8.4 Hz, 2H), 8.06 (s, 2H); 13C NMR This work was supported by The Grants-in-Aid for Scientific
(150 MHz, CDCl3) δ 74.9, 82.1, 120.8, 125.3, 126.2, 126.5, Research on Innovative Areas “Organic Synthesis based on
126.6, 127.5, 127.8, 128.5, 128.8, 133.0, 133.2, 133.8, 137.5, Reaction Integration” (No. 2105) from MEXT, Japan, by the
142.0; IR (KBr) 3050, 2147, 1596, 1495, 835 cm−1; HRMS (EI) Grant-in-Aid for Young Scientists (B) from JSPS, Japan, and by
m/z calcd for C36H22 [M+]: 454.1722, found: 454.1715; mp: the Collaborative Research Program of Institute for Chemical
240.7–241.5 °C.
Research, Kyoto University (grant # 2011-16). We are grateful to
1,4-BIS(4′-(E)-STYRYLPHENYL)BUTA-1,3-DIYNE (3J). 70% yield from the SC-NMR Laboratory of Okayama University for the NMR
1; colorless solid; 1H NMR (600 MHz, CDCl3) δ 7.09 (d, J = measurement. We also thank Prof. Fumitoshi Kakiuchi for a
16.2 Hz, 2H), 7.15 (d, J = 16.2 Hz, 2H), 7.29 (t, J = 7.2 Hz, 2H), fruitful discussion.
7.38 (t, J = 7.2 Hz, 4H), 7.49 (d, J = 8.4 Hz, 4H), 7.52 (d, J =
8.4 Hz, 8H); 13C NMR (150 MHz, CDCl3) δ 75.1, 82.5, 120.8,
126.6, 126.8, 127.9, 128.2, 128.9, 130.4, 133.0, 137.0, 138.4; IR
Notes and references
(KBr) 3024, 2361, 1494, 972, 822 cm−1; HRMS (EI) m/z calcd for
C32H22 [M+]: 406.1722, found: 406.1728; mp: 278.6–279.5 °C.
1 (a) C. Wang, H. Dong, W. Hu, Y. Liu and D. Zhu, Chem.
Rev., 2012, 112, 2208–2267; (b) F. Zhang, D. Wu, Y. Xu and
X. Feng, J. Mater. Chem., 2011, 21, 17590–17590; (c) J. Wu,
W. Pisula and K. Müllen, Chem. Rev., 2007, 107, 718–747;
(d) S. Sergeyev, W. Pisula and Y. H. Geerts, Chem. Soc. Rev.,
2007, 36, 1902–1929.
Conversion to 2,5-bis(diaryl)thiophenes
TYPICAL PROCEDURE FOR SYNTHESIS OF BIS(DIARYL)THIOPHENE (TABLE 4,
ENTRY 2). Into a flame-dried Schlenk flask was placed a mixture
of 1,4-bis(4′-tert-butyl-4-biphenyl)buta-1,3-diyne (3c) (23.1 mg,
0.050 mmol) and Na2S·9H2O (63.1 mg, 0.263 mmol) in dry
DMF (1 mL) and heated at 150 °C under an argon atmosphere
for 24 h. After being allowed to cool to room temperature, Et2O
(3 mL) was added to the resulting mixture, and the precipitate
was washed with Et2O (10 mL), H2O (10 mL), and CH2Cl2
(10 mL) to afford 4c as a yellow solid (17.1 mg, 69%).
2 J. Tsuji, Palladium Reagents and Catalysts, John Wiley &
Sons, Chichester, 2004.
3 For recent examples, see: (a) R. N. Dhital, A. Murugadoss
and H. Sakurai, Chem.–Asian J., 2012, 7, 55–59;
(b) K. M. Parida, S. Singha, P. C. Sahoo and S. Sahu, J. Mol.
Catal. A: Chem., 2011, 342–343, 11–17; (c) B. Kaboudin,
Y. Abedi and T. Yokomatsu, Eur. J. Org. Chem., 2011, 6656–
6662; (d) G. Cheng and M. Luo, Eur. J. Org. Chem., 2011,
2519–2523; (e) N. Kirai and Y. Yamamoto, Eur. J. Org.
Chem., 2009, 1864–1867; (f) T. Vogler and A. Studer, Adv.
Synth. Catal., 2008, 350, 1963–1967; (g) C. Amatore,
C. Cammoun and A. Jutand, Eur. J. Org. Chem., 2008, 4567–
4570; (h) Y. Yamamoto, Synlett, 2007, 1913–1916;
(i) Y. Yamamoto, R. Suzuki, K. Hattori and H. Nishiyama,
Synlett, 2006, 1027–1030; ( j) C. Adamo, C. Amatore,
I. Ciofini, A. Jutand and H. Lakmini, J. Am. Chem. Soc.,
2006, 128, 6829–6836.
4 (a) S. Zhang, X. Liu and T. Wang, Adv. Synth. Catal., 2011,
353, 1463–1466; (b) K. Yin, C.-J. Li, J. Li and X.-S. Jia, Appl.
Organomet. Chem., 2011, 25, 16–20; (c) K. Yin, C. Li, J. Li
and X. Jia, Green Chem., 2011, 13, 591–593; (d) T.-M. Wu,
S.-H. Huang and F.-Y. Tsai, Appl. Organomet. Chem., 2011,
25, 395–399; (e) R. Schmidt, R. Thorwirth, T. Szuppa,
A. Stolle, B. Ondruschka and H. Hopf, Chem.–Eur. J., 2011,
17, 8129–8138; (f) S. Perrone, F. Bona and L. Troisi, Tetrahe-
dron, 2011, 67, 7386–7391; (g) J. Park, E. Park, A. Kim,
S.-A. Park, Y. Lee, K.-W. Chi, Y. H. Jung and I. S. Kim,
J. Org. Chem., 2011, 76, 2214–2219.
2,5-BIS(4′-ISOPROPYL-4-BIPHENYL)THIOPHENE (4B). 55% yield from
3b; yellow solid; 1H NMR (600 MHz, CDCl3) δ 1.30 (d, J =
6.6 Hz, 12H), 2.97 (sept, J = 6.6 Hz, 2H), 7.33 (d, J = 8.4 Hz,
4H), 7.35 (s, 2H), 7.57 (d, J = 8.4 Hz, 4H), 7.62 (d, J = 8.4 Hz,
4H), 7.70 (d, J = 8.4 Hz, 4H); 13C NMR (150 MHz, CDCl3)
δ 24.0, 33.8, 124.0, 125.9, 126.8, 126.9, 127.4, 133.0, 138.0,
140.2, 143.3, 148.2; IR (KBr) 2960, 2362, 2340, 1559, 823 cm−1
;
HRMS (EI) m/z calcd for C34H32S [M+]: 472.2225, found:
472.2215; mp: >300 °C.
2,5-BIS(4′-TERT-BUTYL-4-BIPHENYL)THIOPHENE (4C). 69% yield from
3c; yellow solid; 1H NMR (600 MHz, CDCl3) δ 1.34 (s, 18H),
7.35 (s, 2H), 7.49 (d, J = 8.4 Hz, 4H), 7.58 (d, J = 8.4 Hz, 4H),
7.63 (d, J = 8.4 Hz, 4H), 7.71 (d, J = 8.4 Hz, 4H); 13C NMR
(150 MHz, CDCl3) δ 31.5, 34.7, 124.2, 126.0, 126.1, 126.7,
127.6, 133.2, 137.7, 140.2, 143.4, 150.7; IR (KBr) 3080, 2957,
1909, 1491, 822 cm−1; HRMS (EI) m/z calcd for C36H36S [M+]:
500.2538, found: 500.2533; mp: >300 °C.
2,5-BIS(4′-METHOXY-4-BIPHENYL)THIOPHENE (4D). 42% yield from
3d; yellow solid; IR (KBr) 2363, 2340, 1653, 1258, 798 cm−1
;
HRMS (EI) m/z calcd for C34H30O2S [M+]: 448.1497, found:
448.1495; mp: >300 °C.14
2,5-BIS(4′-N,N-DIMETHYL-4-BIPHENYL)THIOPHENE (4E). 78% yield
from 3e; yellow solid; IR (KBr) 2796, 2361, 1494, 813,
795 cm−1; HRMS (EI) m/z calcd for C32H30N2S [M+]: 474.2130,
found: 474.2116; mp: >300 °C.14
2,5-BIS[4-(2-NAPHTHYL)-PHENYL]THIOPHENE (4I). 26% yield from 3i;
yellow solid; IR (KBr) 3058, 2360, 1559, 817, 799 cm−1; HRMS
(EI) m/z calcd for C36H24S [M+]: 488.1599, found: 488.1589;
mp: >300 °C.14
5 For reviews on electro-oxidation, see: (a) J. Yoshida,
K. Kataoka and R. Horcajada, Chem. Rev., 2008, 2265–2299;
(b) J. B. Sperry and D. L. Wright, Chem. Soc. Rev., 2006, 35,
605–621; (c) J. Yoshida and S. Suga, Chem.–Eur. J., 2002, 8,
2651–2658; (d) H. Lund, J. Electrochem. Soc., 2002, 149,
S21–S33; (e) K. D. Moeller, Tetrahedron, 2000, 56,
9527–9554.
9568 | Org. Biomol. Chem., 2012, 10, 9562–9569
This journal is © The Royal Society of Chemistry 2012

Organic & Biomolecular Chemistry
Paper
View Article Online
6 (a) K. Mitsudo, T. Shiraga, J. Mizukawa, S. Suga and
H. Tanaka, Chem. Commun., 2010, 46, 9256–9258;
(b) K. Mitsudo, T. Shiraga, D. Kagen, D. Shi, J. Y. Becker
and H. Tanaka, Tetrahedron, 2009, 65, 8384–8388;
(c) F. Kakiuchi, T. Kochi, H. Mutsutani, N. Kobayashi,
S. Urano, M. Sato, S. Nishiyama and T. Tanabe, J. Am.
Chem. Soc., 2009, 131, 11310–11311; (d) K. Mitsudo,
T. Shiraga and H. Tanaka, Tetrahedron Lett., 2008, 49, 6593–
Int. Ed., 2012, 51, DOI: 10.1002/anie.201204251, Early
View.
8 Quite recently, a sequential reaction using the electroche-
mical method was reported by Kakiuchi’s group, see:
H. Aiso, T. Kochi, H. Mutsutani, T. Tanabe, S. Nishiyama
and F. Kakiuchi, J. Org. Chem., 2012, 77, 7718–7724.
9 For a review, see: P. Siemsen, R. C. Livingston and
F. Diederich, Angew. Chem., Int. Ed., 2000, 39, 2632–2657.
6595; (e) C. Amatore, C. Cammoun and A. Jutand, 10 CCDC-868776 contains the supplementary crystallographic
Eur. J. Org. Chem., 2008, 4567–4570; (f) K. Mitsudo, data for this paper.
T. Kaide, E. Nakamoto, K. Yoshida and H. Tanaka, J. Am. 11 E. C. Constable, D. Gusmeroli, C. E. Housecroft,
Chem. Soc., 2007, 129, 2246–2247; (g) C. Amatore,
C. Cammoun and A. Jutand, Adv. Synth. Catal., 2007, 349,
292–296.
7 (a) J. Yoshida, K. Saito, T. Nokami and A. Nagaki, Synlett,
2011, 1189–1194; (b) S. Suga, D. Yamada and J. Yoshida,
Chem. Lett., 2010, 39, 404–406; (c) A. J. Bard,
M. Neuburger and S. Schaffner, Acta Crystallogr., Sect. C:
Cryst. Struct. Commun., 2006, 62, o505–o509.
12 (a) M. Mushrush, A. Facchetti, M. Lefenfeld, H. E. Katz and
T. J. Marks, J. Am. Chem. Soc., 2003, 125, 9414–9423;
(b) S. Hotta, H. Kimura, S. A. Lee and T. Tamaki, J. Hetero-
cycl. Chem., 2000, 37, 281–286.
Integrated Chemical Systems: A Chemical Approach to Nano- 13 Terminal voltage was 11–16 V.
technology, Wiley, New York, 1994; (d) B. M. Trost, 14 1H and 13C NMR could not be measured due to their poor
D. A. Thaisrivongs and M. M. Hansmann, Angew. Chem.,
solubility.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 9562–9569 | 9569