Repetitive two-step method for o,o,p- and o,p-oligophenylene synthesis through Pd-catalyzed cross-coupling of hydroxyterphenylboronic acid

Article abstract of DOI:10.3390/molecules181215207

A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy group has been developed for the synthesis of oligophenylenes. This method readily afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray crystallography was employed to obtain the structure of the o,p-oligophenylene 9-mer.

Full text of DOI:10.3390/molecules181215207

Molecules 2013, 18, 15207-15219; doi:10.3390/molecules181215207
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene
Synthesis through Pd-Catalyzed Cross-Coupling of
Hydroxyterphenylboronic Acid
Miyuki Yamaguchi, Takeshi Kimura, Naomi Shinohara and Kei Manabe *
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
Shizuoka 422-8526, Japan; E-Mails: yamaguchim@u-shizuoka-ken.ac.jp (M.Y.);
t.kimura@ki-chem.co.jp (T.K.); m08060@u-shizuoka-ken.ac.jp (N.S.)
* Author to whom correspondence should be addressed; E-Mail: manabe@u-shizuoka-ken.ac.jp;
Tel.: +81-54-264-5754; Fax: +81-54-264-5586.
Received: 16 October 2013; in revised form: 22 November 2013 / Accepted: 27 November 2013 /
Published: 10 December 2013
Abstract: A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura
coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy
group has been developed for the synthesis of oligophenylenes. This method readily
afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray crystallography
was employed to obtain the structure of the o,p-oligophenylene 9-mer.
Keywords: palladium; Suzuki-Miyaura coupling; oligoarene; nonaflate
1. Introduction
Oligophenylenes, which are composed of benzene rings connected through single bonds, have
attracted considerable attention as an important class of oligomers [1–5]. Oligophenylenes are widely
used architectures in electronic devices [6] and are employed as self-assembling [7–9], biologically
active [10], and catalytic molecules [11,12]. In addition, oligophenylenes can be used as building
blocks for the synthesis of well-defined graphite subunits [13]. The conformational and electronic
properties of oligophenylenes have also been subjects of intensive research [14–18]. Owing to such
widespread interest, it is crucial to develope synthetic methods that can produce oligophenylenes with
the desired chain length and connectivity pattern. Although one-step syntheses of long polyphenylenes
have been reported [2], the resulting compounds are obtained as mixtures of varying chain lengths

Molecules 2013, 18
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rather than a single species. In order to synthesize oligophenylenes with structural homogeneity,
stepwise synthetic methods are necessary. However, while several synthetic protocols for the
preparation of such molecules have been reported [11,19], the development of efficient methods still
remains a challenging task.
We previously developed a method for oligophenylene synthesis via repetitive Suzuki-Miyaura
coupling [20,21] of hydroxyphenylboronic acids with sebsequent triflation of the hydroxy group
(Scheme 1a) [22,23]. While this repetitive two-step method realizes the facile synthesis of a variety of
oligophenylenes with a specific chain length and different functional groups, it was only able to
introduce one benzene unit in a single Suzuki-Miyaura coupling step. Based on this two-step protocol,
Hartley et al. developed an improved method in which two benzene units could be introduced in a
single step [15]. However, the development of more efficient methods for synthesizing longer
oligophenylenes is still needed. Herein, we describe a new version of the repetitive two-step method,
which utilizes hydroxyterphenylboronic acid 1 and enables the introduction of three benzene units in
one step (Scheme 1b). By employing this method, oligophenylenes with two different types of
connectivity pattern, o,o,p- and o,p-oligophenylenes, were successfully synthesized in a small
number of steps.
Scheme 1. Repetitive two-step method for oligophenylene synthesis. (a) Our previous
method; (b) Method based on the use of hydroxyterphenylboronic acid. Tf = –SO2CF3,
Nf = –SO2C4F9.
OH
(a)
(HO)2B
repetition
OH
OTf
OTf
Pd cat.
OTf
Suzuki–Miyaura
coupling
n
triflation
(b)
OH
(HO)2B
ONf
1
repetition
ONf
OH
ONf
Pd cat.
n
Suzuki–Miyaura
coupling
nonaflation
2. Results and Discussion
The key boronic acid, hydroxyterphenylboronic acid 1, was easily prepared according to the route
shown in Scheme 2. Compound 2 [24] was treated with BuLi in Et2O at −78 °C, and then THF was
added. This sequential use of the two solvents (Et2O and THF) ensured satisfactory conversion to the
dilithiated compound, without the formation of a significant amount of the byproduct protonated at the
lithiated carbon [25]. This was possible because the Li–Br exchange occurred only after the addition of
THF [26]. The dilithiated compound was then boronated to give 1 in good yield (72%).

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Scheme 2. Preparation of hydroxyterphenylboronic acid 1.
Boronic acid 1 was first applied to the synthesis of o,o,p-oligophenylenes, composed of benzene
rings connected in the order of ortho, ortho, and then para. These were envisioned to make up a new
structural motif of folding oligophenylenes [27]. While o,o,p-oligophenylenes could be synthesized
using our previous reported method [27] involving the C–H arylation of bipheny-2-ols as the key step,
the present method using 1 would be more efficient for synthesis of longer oligomers.
Thus, we started with compound 3 (Scheme 3), with dodecanoyl groups introduced in order to
increase the solubility of the oligomers in organic solvents. While the triflyl group (Tf, –SO2CF3) was
used to activate hydroxy groups in the previous work (Scheme 1a), we decided to use the nonaflyl
group (Nf, –SO2C4F9) [27,28], as this is more stable against O–SO2 bond cleavage [29,30] and can be
prepared with NfF, which is usually less expensive than the commonly used triflating agent, Tf2O.
Scheme 3. Synthesis of o,o,p-oligophenylenes.
COC11H23
COC11H23
1 (3 equiv)
Pd(OAc)2 (10 mol%)
SPhos (12 mol%)
KF (7.5 equiv)
1 (3 equiv)
Pd(OAc)2 (10 mol%)
SPhos (12 mol%)
KF (7.5 equiv)
X
X
X
X
THF/H2O (4/1), 70 ºC
78%
THF/H2O (4/1), 50 ºC
72%
Suzuki–Miyaura coupling
Suzuki–Miyaura coupling
COC11H23
COC11H23
NfF (4 equiv)
Et3N (8 equiv)
CH3CN, rt
92%
NfF (4 equiv)
Et3N (8 equiv)
CH3CN, rt
82%
5: X = OH
3: X = OH
4: X = ONf
nonaflation
6
: X = ONf
nonaflation
COC11H23
1 (3 equiv)
Pd(OAc)2 (10 mol%)
SPhos (12 mol%)
KF (7.5 equiv)
X
X
THF/H2O (4/1), 70 ºC
43%
Suzuki–Miyaura coupling
COC11H23
NfF (4 equiv)
Et3N (8 equiv)
CH3CN, rt
46%
7: X = OH
8: X = ONf
nonaflation
COC11H23
OH
OH
9
COC11H23

Molecules 2013, 18
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Nonaflation of 3 gave bisnonaflate 4, which was then subjected to Suzuki-Miyaura coupling with 1
in the presence of a Pd/SPhos catalyst [31]. Double Suzuki-Miyaura coupling introduced two terphenyl
units to give 5 in good yield (72%). Repetition of the nonaflation/Suzuki-Miyaura-coupling sequence
twice afforded symmetric o,o,p-oligophenylene 9. It should be emphasized that only six steps were
required to synthesize 21-mer oligophenylene 9 from 3. Although these o,o,p-oligophenylenes showed
1
complicated H- and 13C-NMR spectra because of the existence of rotamers, even at 100 °C,
high-resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC)
analysis verified the identities and the purities of the oligomers.
We next turned our attention to combining the previous and present strategies (Scheme 1a,b) to
facilitate synthesis of another type of oligophenylenes. o,p-Oligophenylenes, which are used as
precursors in bottom-up synthesis of graphene nanoribbons [32], were selected as the model target [33]
in order to demonstrate the feasibility of the combined strategy.
The synthesis commenced using 1,4-dibromobenzene, which was subjected to Suzuki-Miyaura
coupling with 1 (Scheme 4). Although the reaction was slow at rt, raising the temperature to 70 °C
resulted in a good yield of 7-mer 10 (72%). After nonaflation, Suzuki-Miyaura-coupling with
4-hydroxyphenylboronic acid was conducted, affording 9-mer 12. While nonaflation of 12 in CH3CN
resulted in a low yield due to the low solubility of 12 in this particular solvent, use of a mixed solvent
(CH3CN/CH2Cl2) improved the yield to 77%. For the final Suzuki-Miyaura-coupling step, it was
necessary to change the reaction conditions, as the low solubility of 13 in THF/H2O hampered the
reaction under the previous employed conditions. Finally, we found that the use of K3PO4·nH2O in
toluene gave 15-mer 14 in a modest yield (43%). In contrast to the o,o,p-oligophenylenes, rotamers
were not observed in the NMR spectra of the o,p-oligophenylenes at room temperature. The synthesis
shown in Scheme 4 clearly demonstrates that o,p-oligophenylenes with a specific chain length can be
easily synthesized through this strategy.
Scheme 4. Synthesis of o,p-oligophenylenes.

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Crystals of 9-mer 12 suitable for X-ray analysis were obtained by recrystallization from CH3CN,
with the resulting structure shown in Figure 1 [34]. This is the first X-ray structure of
o,p-oligophenylenes that has been obtained. The 9-mer can be seen adopt an S-shaped,
centrosymmetric conformation in which the inversion center is located at the central benzene ring.
Both of the hydroxy groups were observed to form hydrogen bonds with CH3CN molecules.
Figure 1. ORTEP representation (50% ellipsoid probability) of the X-ray structure of
12·2CH3CN. Only one CH3CN molecule is shown. Left, front view; Right, side view.
3. Experimental Section
3.1. General
All reactions were performed under argon atmosphere. Reactions were monitored by TLC on Merck
(Tokyo, Japan) silica gel 60 F254 plates visualized by UV lump at 254 nm. Column chromatography
was performed on Merck (Tokyo, Japan) silica gel 60 and preparative TLC was performed on Merck
(Tokyo, Japan) silica gel 60 F254 0.5 mm plates. NMR spectra were measured on a JEOL (Akishima,
Japan) AL-400 NMR spectrometer (400 MHz for 1H spectra and 100 MHz for 13C spectra) and a JEOL
1
Akishima, Japan) ECA-500 NMR spectrometer (500 MHz for H spectra and 125 MHz for 13C
1
spectra). For H NMR, tetramethylsilane (TMS) (δ = 0) in CDCl3 served as an internal standard. For
13C NMR, CDCl3 (δ = 77.0) served as an internal standard. Infrared spectra were measured on a
SHIMADZU (Kyoto, Japan) IR Prestige-21 spectrometer (ATR). High-resolution mass spectra
(HRMS) were measured on a JEOL (Akishima, Japan) JMS-T100TD time-of-flight mass spectrometer
(DART), Bruker (Billerica, MA, USA) micrOTOF mass spectrometer (ESI), or Bruker (Billerica, MA,
USA) Ultraflex TOF/TOF mass spectrometer (MALDI). Melting points were measured using MPA
100 OptiMelt (Stanford Research Systems, Sunnyvale, CA, USA) and uncorrected. X-ray analysis was
made on a Rigaku (Tokyo, Japan) AFC7R diffractometer using graphite monochromated Mo-Kα
radiation and a rotating anode generator.
Anhydrous solvents (except for acetonitrile) were purchased from Kanto Chemical (Tokyo, Japan)
and used without further purification. Acetonitrile was purchased from Wako Pure Chemical Industries

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(Osaka, Japan) and distilled from CaH2 under argon. All other chemicals were purchased from Wako
Pure Chemical Industries, Kanto Chemical, Tokyo Chemical Industry (Tokyo, Japan), and Aldrich
(Milwaukee, US) and used without further purification.
HPLC charts of 5-9 and 1H- and 13C-NMR spectra of 1, 3-14 are shown in Supplementary Materials.
3.2. 2''-Hydroxy-[1,1':4',1''-terphenyl]-2-yl) Boronic Acid (1)
n-BuLi (1.59 M in hexane, 12.6 mL, 20.0 mmol) was added over the course of 3 min to a solution
of 2 (3.25 g, 10.0 mmol) in Et2O (20.0 mL) at −78 °C under Ar. After 10 min, THF (20.0 mL) was
added. After a further 10 min, triisopropyl borate (2.7 mL, 12.0 mmol) was added over the course of
5 min, and the mixture was warmed to room temperature and stirred for 3 h. Aqueous HCl (1 M,
50 mL) was added. The THF was then removed in vacuo. The mixture was subsequently extracted
with Et2O, and the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo.
The residue was purified by recrystallization (EtOAc/hexane/H2O = 10:4:1) to give 1 (2.12 g, 72%) as
1
a white solid. mp. 126.6–129.6 °C; IR (ATR) (cm−1) 3500, 1473, 1332, 752; H-NMR (500 MHz,
acetone-d6 with one drop of D2O): δ 6.93 (1H, t, J = 7.2 Hz), 7.03 (1H, d, J = 8.0 Hz), 7.18 (1H, t, J =
8.0 Hz), 7.31–7.37 (2H, m), 7.41–7.44 (2H, m), 7.50 (2H, d, J = 8.0 Hz), 7.65 (3H, m);
13C-NMR (125 MHz, acetone-d6 with one drop of D2O): δ 116.8, 120.6, 126.8, 129.3, 128.5, 128.9,
129.2, 129.6, 129.8, 131.1, 133.8, 136.3, 138.2, 142.3, 145.9, 155.0; Anal. calcd for C18H15BO3: C,
74.52; H, 5.21, found: C, 74.53; H, 5.27.
3.3. 3-mer (OH) (3)
[1,1':4',1''-Terphenyl]-2,2''-diol [35] (78.7 mg, 0.300 mmol) and n-dodecanoyl chloride (136 mg,
0.622 mmol) were dissolved in TfOH [36] (0.6 mL) at rt, and the mixture was stirred for 1 h at the
same temperature. After the reaction was complete, H2O (5.0 mL) was added. The mixture was then
extracted with CH2Cl2, and the organic layer was washed with saturated NaHCO3 and brine, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by recrystallization from methanol to
give 3 (160 mg, 85%) as a white solid. mp. 119.4–121.5 °C; IR (ATR) (cm−1) 3331, 1467, 1278, 1193,
1
844, 667; H-NMR (400 MHz, CDCl3): δ 0.87 (6H, t, J = 6.8 Hz), 1.26 (32H, bs), 1.74 (4H, quint,
J = 6.8 Hz), 2.94 (4H, t, J = 7.2 Hz), 6.56 (2H, s), 7.06 (2H, d, J = 8.4 Hz), 7.62 (4H, s), 7.92 (2H, dd,
13
J = 8.8, 2.0 Hz), 7.96 (2H, d, J = 2.0 Hz); C-NMR (100 MHz, CDCl3): δ 14.0, 22.6, 24.8, 29.3,
29.45, 29.49, 29.58, 29.6, 31.9, 38.4, 116.2, 127.9, 129.8, 130.0, 130.4, 131.2, 136.4, 157.5, 200.2 (one
carbon overlapped.); HRMS (ESI): m/z calcd for C42H57O4 ([M − H]−) 625.4262; found: 625.4275.
3.4. 3-mer (ONf) (4)
Perfluorobutanesulfonyl fluoride (0.182 mL, 1.02 mmol) was added over 1 min to a solution of 21
(0.160 g, 0.255 mmol) and Et3N (0.28 mL, 2.04 mmol) in MeCN (0.85 mL) at 0 °C, and the mixture
was stirred for 1 min at the same temperature. The reaction mixture was warmed to room temperature
and then stirred for a further 4 h. After the reaction was complete, aqueous HCl (1 M, 5.0 mL) was
added. The mixture was extracted with CH2Cl2, and the organic layer was washed with H2O and brine,
dried over Na2SO4, and concentrated in vacuo. The residue was purified using silica gel

Molecules 2013, 18
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chromatography (hexane/CH2Cl2 = 4:1) to give 4 (0.250 g, 82%) as a yellow oil. IR (ATR) (cm−1)
1
1695, 1427, 1236, 887; H-NMR (400 MHz, CDCl3): δ 0.86–0.90 (6H, m), 1.28–1.38 (32H, brs),
1.76–1.79 (4H, m), 2.98–3.02 (4H, m), 7.52–7.70 (6H, m), 8.06 (2H, dd, J = 2.0, 8.8 Hz), 8.13 (2H, d,
13
J = 2.0 Hz); C-NMR (125 MHz, CDCl3): δ 14.1, 22.7, 24.1, 29.26, 29.32, 29.45, 29.48, 29.6, 31.9,
38.8, 122.4, 129.1, 129.7, 131.9, 135.2, 135.5, 137.0, 149.6, 198.6 (one carbon signal overlapped).
Nonaflyl carbons were not observed because of the low signal intensities; HRMS (dart): m/z calcd for
C50H57F18O6S2 ([M + H]+) 1191.3202; found: 1191.3194.
3.5. 9-mer (OH) (5)
Nonaflate 4 (1.23 g, 1.04 mmol), 1 (0.699 g, 2.41 mmol), KF (0.451 g, 7.76 mmol), Pd(OAc)2
(23.2 mg, 0.104 mmol), and SPhos (51.0 mg, 0.124 mmol) were placed in a sealable tube, which was
then evacuated and backfilled with Ar. A mixture of THF/H2O (4:1, 1.0 mL) was then added. The tube
was sealed, and the mixture was stirred at 50 °C for 17 h. After the reaction was complete, H2O
(5.0 mL) was added. The mixture was extracted with CH2Cl2, and the organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified using silica gel
chromatography (hexane/CH2Cl2 = 1:2) to give 5 (0.807 g, 72%) as a white solid. mp. 130.1–134.3 °C;
1
IR (ATR) (cm−1) 3516, 1685, 1450, 1267, 827, 746; H-NMR (400 MHz, CDCl3): δ 0.86 (6H, t,
J = 6.8 Hz), 1.24 (32H, brs), 1.70–1.77 (4H, m), 2.95–3.00 (4H, m), 6.02 (0.5H, s), 6.31 (4.5H, s), 6.53
(3H, d, J = 8.0 Hz), 6.57 (1H, s), 6.73 (1H, d, J = 7.6 Hz), 6.87–6.97 (4H, m), 7.08–7.39 (16.5H, m),
7.52 (1.5H, d, J = 7.6 Hz), 7.85 (2.5H, s), 7.96 (1.5H, d, J = 8.0 Hz) (mixture of rotamers); 13C-NMR
(125 MHz, CDCl3): δ 14.1, 22.7, 24.3, 29.31, 29.36, 29.48, 29.5, 29.6, 31.9, 38.7, 115.8, 116.0, 120.7,
120.8, 126.9, 127.0, 127.5, 127.58, 127.6, 127.7, 128.16, 128.2, 128.3, 128.5, 128.9, 129.0, 129.5,
129.7, 129.86, 129.97, 130.0, 130.1, 131.4, 131.5, 132.2, 134.9, 135.1, 135.4, 136.1, 136.2, 138.3,
138.6, 138.8, 139.0, 139.5, 139.9, 140.0, 140.1, 140.8, 140.9, 152.4, 152.6, 200.7 (mixture of
rotamers); HRMS (ESI): m/z calcd for C78H81O4 ([M − H]−) 1081.6140; found: 1081.6102.
3.6. 9-mer (ONf) (6)
Perfluorobutanesulfonyl fluoride (0.70 mL, 3.86 mmol) was added over 1 min to a solution of 5
(1.05 g, 0.965 mmol) and Et3N (1.10 mL, 7.72 mmol) in MeCN (3.2 mL) at room temperature, and the
mixture was stirred for 2 h at the same temperature. After the reaction was complete, aqueous HCl
(1 M, 5.0 mL) was added. The mixture was extracted with CH2Cl2, and the organic layer was washed
with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified using
silica gel chromatography (hexane/CH2Cl2 = 3:1) to give 6 (1.46 g, 92%) as a colorless oil. IR (ATR)
(cm−1) 1685, 1236, 1142, 835, 765; 1H-NMR (500 MHz, CDCl3): δ 0.87 (6H, t, J = 7.5 Hz), 1.25–1.32
(32H, m), 1.68–1.73 (4H, m), 2.92–2.98 (4H, m), 6.44 (2.6H, s), 6.648 (2.6H, d, J = 8.5 Hz), 6.649
(1.4H, s), 6.80 (1.4H, d, J = 8.5 Hz), 7.09 (2.6H, d, J = 8.5 Hz), 7.12 (1.4H, d, J = 8.0 Hz), 7.29–7.51
(18H, m), 7.70 (1.3H, s), 7.83 (0.7H, s), 7.86 (0.7H, d, J = 8.0 Hz), 7.95 (1.3H, dd, J = 8.0, 1.5 Hz)
(mixture of rotamers); 13C-NMR (100 MHz, CDCl3): δ 14.1, 22.8, 24.3, 24.4, 29.4, 29.60, 29.63, 29.7,
32.0, 38.6, 121.9, 126.6, 127.5, 128.1, 128.2, 128.56, 128.63, 128.7, 128.88, 128.9, 129.0, 129.7,
129.9, 130.1, 130.2, 130.3, 131.2, 131.5, 131.9, 132.1, 133.9, 135.7, 136.2, 136.3, 138.9, 139.2, 139.5,
140.35, 140.43, 140.8, 140.9, 141.2, 141.4, 141.47, 144.54, 147.3, 200.2, 200.3 (mixture of rotamers)

Molecules 2013, 18
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(Nonaflyl carbons were not observed because of the low signal intensities) HRMS (MALDI,
α-cyano-4-hydroxycinnamic acid as the matrix): m/z calcd for C86H80F18O6S2 ([M + H]+) 1646.5007;
found: 1647.5108.
3.7. 15-mer (OH) (7)
Nonaflate 6 (0.972 g, 0.590 mmol), 1 (0.514 g, 1.77 mmol), KF (0.257 g, 4.43 mmol), Pd(OAc)2
(13.2 mg, 0.0590 mmol), and SPhos (29.1 mg, 0.0708 mmol) were placed in a flask, which was then
evacuated and backfilled with Ar. A mixture of THF/H2O (4:1, 0.59 mL) was then added. The tube
was sealed, and the mixture was stirred at 70 °C for 17 h. After the reaction was complete, H2O
(5.0 mL) was added. The mixture was extracted with CH2Cl2, and the organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified using silica gel
chromatography (hexane/EtOAc = 10:1) to give 7 (0.711 g, 78%) as a yellow solid. mp. 109.5–115.0 °C;
1
IR (ATR) (cm−1) 3529, 1678, 1467, 1269, 829, 748; H-NMR (500 MHz, CDCl3): δ 0.87 (6H, m),
1.24 (32H, brs), 1.71 (4H, brs), 2.95 (4H, brs), 5.50–6.70 (18H, m), 6.92–7.97 (42H, m) (mixture of
13
rotamers); C-NMR (100 MHz, CDCl3): δ 14.1, 22.7, 24.2, 24.29, 29.31, 29.35, 29.38, 29.48, 29.51,
29.6, 31.9, 38.7, 115.7, 115.8, 120.5, 120.6, 120.7, 126.9, 127.3, 127.5, 127.7, 127.9, 128.0, 128.3,
128.4, 128.6, 128.7, 128.9, 129.0, 129.6, 129.8, 129.9, 131.4, 131.6, 134.8, 136.0, 138.26, 138.30,
138.4, 138.5, 138.9, 139.0, 139.7, 140.0, 140.1, 140.2, 140.3, 140.8, 141.6, 152.7, 152.8, 200.4
(mixture of rotamers); HRMS (ESI): m/z calcd for C114H105O4 ([M − H]−) 1537.8018; found: 1537.8010.
3.8. 15-mer (ONf) (8)
Perfluorobutanesulfonyl fluoride (0.11 mL, 0.604 mmol) was added over 1 min to a solution of 7
(0.233 g, 0.151 mmol) and Et3N (0.17 mL, 1.21 mmol) in MeCN (0.5 mL) at room temperature, and
the mixture was stirred for 2 h at the same temperature. After the reaction was complete, aqueous HCl
(1 M, 10.0 mL) was added. The mixture was extracted with CH2Cl2, and the organic layer was washed
with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified using
silica gel chromatography (hexane/CH2Cl2 = 4:1) to give 8 (0.146 g, 46%) as a colorless oil. IR (ATR)
1
(cm−1) 1685, 1423, 1236, 889, 732; H-NMR (400 MHz, CDCl3): δ 0.85–0.88 (6H, m), 1.25 (32H,
brs), 1.71 (4H, brs), 2.95 (4H, brs), 5.65–6.71 (18H, m), 6.91–7.95 (42H, m) (mixture of rotamers);
13C-NMR (100 MHz, CDCl3): δ 14.1, 22.7, 24.2, 24.3, 29.3, 29.4, 29.5, 29.6, 31.9, 38.6, 118.5, 121.9,
126.4, 126.8, 127.1, 127.4, 127.9, 128.2, 128.5, 128.6, 128.75, 128.83, 128.9, 129.1, 129.4, 129.8,
129.9, 130.0, 130.2, 130.7, 131.3, 131.7, 131.8, 132.1, 133.4, 133.5, 135.5, 135.6, 136.1, 138.5, 138.6,
139.1, 139.3, 139.6, 140.1, 140.3, 141.0, 141.1, 141.6, 144.9, 145.2, 147.0, 199.7, 200.2 (mixture of
rotamers) (Nonaflyl carbons were not observed because of the low signal intensities); HRMS
(MALDI, α-cyano-4-hydroxycinnamic acid as a matrix): m/z calcd for C122H105F18O6S2 ([M + H]+)
2103.6958; found: 2103.7120.
3.9. 21-mer (OH) (9)
Nonaflate 8 (0.186 g, 0.088 mmol), 1 (76.9 mg, 0.264 mmol), KF (38.3 mg, 0.660 mmol),
Pd(OAc)2 (2.0 mg, 0.00880 mmol), and SPhos (4.3 mg, 0.0106 mmol) were placed in a flask, which

Molecules 2013, 18
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was then evacuated and backfilled with Ar. A mixture of THF/H2O (4:1, 0.09 mL) was then added.
The tube was sealed, and the mixture was stirred at 70 °C for 17 h. After the reaction was complete,
H2O (5.0 mL) was added. The mixture was extracted with CH2Cl2, and the organic layer was washed
with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified using silica gel
chromatography (hexane/CH2Cl2 = 1:2) to give 9 (76.3 mg, 43%) as a white solid. mp. 135.3–138.9 °C;
1
IR (ATR) (cm−1) 3537, 1678, 1467, 748; H-NMR (500 MHz, CDCl3): δ 0.85–0.86 (6H, m), 1.24
(32H, bs), 1.49–1.72 (4H, m), 2.73–2.91 (4H, m), 5.35–5.60 (2H, m), 6.04–6.67 (23H, m), 6.83–8.00
13
(59H, m) (mixture of rotamers); C-NMR (100 MHz, CDCl3): δ 14.1, 22.7, 23.9, 24.2, 29.28, 29.33,
29.5, 29.6, 29.7, 31.9, 38.4, 38.6, 115.7, 120.7, 126.4, 126.8, 126.9, 127.1, 127.3, 127.4, 127.5, 127.6,
127.7, 127.96, 128.04, 128.2, 128.5, 128.6, 128.9, 129.0, 129.7, 130.0, 130.3, 130.7, 131.1, 131.3,
131.4, 134.4, 135.9, 138.37, 138.45, 138.6, 138.8, 138.9, 139.1, 139.3, 139.6, 139.8, 139.9, 140.0,
140.1, 140.2, 140.4, 140.9, 141.0, 141.4, 144.9, 152.5, 152.6, 151.7, 199.5, 200.1 (mixture of
rotamers); HRMS (ESI): m/z calcd for C150H129O4 ([M − H]−) 1993.9896; found: 1993.9873.
3.10. 7-mer (OH) (10)
4-Dibromobenzene (236.5 mg, 1.00 mmol), 1 (725.6 mg, 2.50 mmol), KF (437.2 mg, 7.53 mmol),
Pd(OAc)2 (22.7 mg, 0.101 mmol), and SPhos (49.7 mg, 0.121 mmol) were placed in a sealable tube,
which was then evacuated and backfilled with Ar. A mixture of THF/H2O (4:1, 1.0 mL) was then
added. The tube was sealed, and the mixture was stirred at 70 °C for 21 h. After the reaction was
complete, H2O (10.0 mL) was added. The mixture was extracted with EtOAc, and the organic layer
was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by
recrystallization (toluene) to give 10 (412.4 mg, 72%) as a white solid. mp. 255.6–257.5 °C; IR (ATR)
1
(cm−1) 3003, 1711, 1358, 1221, 750; H-NMR (400 MHz, CDCl3) δ: 5.14 (2H, s), 6.93 (2H, d,
J = 7.8 Hz), 6.95 (2H, d, J = 7.8 Hz), 7.07 (4H, s), 7.20–7.23 (2H, m), 7.26 (4H, d, J = 8.3 Hz), 7.33
13
(4H, d, J = 8.3 Hz), 7.41–7.46 (10H, m); C-NMR (125 MHz, CDCl3) δ: 115.9, 121.0, 127.7, 127.8,
128.5, 129.2, 129.6, 130.3, 130.6, 130.8, 130.8, 135.3, 139.8, 139.9, 140.3, 141.2, 152.5; HRMS (ESI):
m/z calcd for C42H29O2 ([M − H]−) 565.2173; found: 565.2170.
3.11. 7-mer (ONf) (11)
Perfluorobutanesulfonyl fluoride (1.65 mL, 9.40 mmol) was added over 1 min to a solution of 10
(1.31 g, 2.31 mmol) and Et3N (2.6 mL, 18.7 mmol) in MeCN (7.9 mL) at room temperature, and the
mixture was stirred for 2 h at the same temperature. After the reaction was complete, aqueous HCl
(1 M, 20.0 mL) was added. The mixture was extracted with EtOAc, and the organic layer was washed
with H2O and brine, dried over MgSO4, and concentrated in vacuo. MeOH was then added to the
residue. After stirring, filtration gave 11 (1.65 g, 63%) as a white solid. mp. 198.5–199.8 °C; IR (ATR)
1
(cm−1) 1429, 1202, 1140; H-NMR (400 MHz, CDCl3) δ: 7.03 (4H, s), 7.24 (4H, d, J = 8.3 Hz), 7.31
13
(4H, d, J = 8.3 Hz), 7.35–7.45 (16H, m); C-NMR (125 MHz, CDCl3) δ: 121.9, 127.4, 127.7, 128.6,
128.9, 129.7, 130.2, 130.5, 130.7, 132.0, 133.9, 135.9, 139.4, 139.9, 140.5, 141.9, 147.3; HRMS (ESI):
m/z calcd for C50H28F18NaO6S2 ([M + Na]+) 1153.0932; found: 1153.0875.

Molecules 2013, 18
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3.12. 9-mer (OH) (12)
Nonaflate 11 (564 mg, 0.499 mmol), 4-hydroxyphenylboronic acid (173.6 mg, 1.26 mmol), KF
(219.3 mg, 3.78 mmol), Pd(OAc)2 (11.8 mg, 0.0526 mmol), and SPhos (25.1 mg, 0.0611 mmol) were
placed in a sealable tube, which was then evacuated and backfilled with Ar. A mixture of THF/H2O
(4:1, 1.0 mL) was then added. The tube was sealed, and the mixture was stirred at 70 °C for 23 h. H2O
(10.0 mL) was added. The mixture was extracted with EtOAc, and the organic layer was washed with
brine, dried over MgSO4, and concentrated in vacuo. The residue was purified using silica gel
chromatography (hexane/EtOAc = 4:1 to 2:1) to give 12 (222.2 mg, 62%) as a white solid.
1
mp. 244.1–246.5 °C; IR (ATR) (cm−1) 3003, 1709, 1358, 1219, 1092, 903; H-NMR (400 MHz,
CDCl3) δ: 3.82 (2H, s), 6.39 (4H, d, J = 8.8 Hz), 6.85 (4H, d, J = 8.8 Hz), 6.87 (4H, d, J = 8.3 Hz),
13
6.93 (4H, d, J = 8.3 Hz), 6.93 (4H, s), 7.32–7.52 (16H, m); C-NMR (125 MHz, CDCl3) δ: 114.9,
127.2, 127.4, 127.6, 127.7, 129.2, 129.6, 129.7, 130.4, 130.5, 130.6, 130.6, 131.0, 139.2, 139.4, 140.1,
140.3, 140.4, 140.5, 140.5, 154.1; HRMS (ESI): m/z calcd for C54H37O2 ([M − H]−) 717.2799; found:
717.2770.
3.13. 9-mer (ONf) (13)
Perfluorobutanesulfonyl fluoride (0.21 mL, 1.20 mmol) was added over 1 min to a solution of 12
(216.4 mg, 0.301 mmol) and Et3N (0.33 mL, 2.37 mmol) in MeCN/CH2Cl2 (1:1, 1.0 mL) at room
temperature, and the mixture was stirred for 22 h at the same temperature. After the reaction was
complete, aqueous HCl (1 M, 5.0 mL) was added. The mixture was extracted with EtOAc, and the
organic layer was washed with H2O and brine, dried over MgSO4, and concentrated in vacuo. MeOH
was then added to the residue. After stirring, filtration gave 13 (298.4 mg, 77%) as a white solid. mp.
204.4–205.8 °C; IR (ATR) (cm−1) 1713, 1429, 1358, 1221, 1138, 845; 1H-NMR (400 MHz, CDCl3) δ:
6.89 (4H, d, J = 8.3 Hz), 6.94 (4H, d, J = 8.3 Hz), 6.95 (4H, s), 7.01 (4H, d, J = 8.8 Hz), 7.10 (4H, d,
13
J = 8.8 Hz), 7.33–7.43 (16H, m); C-NMR (125 MHz, CDCl3) δ: 120.8, 127.7, 127.7, 128.3, 129.3,
129.5, 129.7, 130.4, 130.5, 130.5, 130.6, 131.6, 138.6, 139.1, 139.8, 139.9, 140.1, 140.2, 140.4, 142.1,
148.6; HRMS (ESI): m/z calcd for C62H36ClF18O6S2 ([M + Cl]−) 1317.1360; found: 1317.1356.
3.14. 15-mer (OH) (14)
Nonaflate 13 (320.5 mg, 0.250 mmol), 1 (218.6 mg, 0.753 mmol), K3PO4·nH2O (502.2 mg),
Pd(OAc)2 (5.6 mg, 0.0249 mmol), and SPhos (20.5 mg, 0.0499 mmol) were placed in a sealable tube,
which was then evacuated and backfilled with Ar. Toluene (2.0 mL) was then added. The tube was
sealed, and the mixture was stirred at 120 °C for 24 h. After the reaction was complete, H2O (10.0 mL)
was added. The mixture was extracted with EtOAc and CHCl3, and the organic layer was washed with
brine, dried over MgSO4, and concentrated in vacuo. The residue was purified using silica gel
chromatography (hexane/CH2Cl2 = 1:1 to 1:2) to give 14 (126.3 mg, 43%) as a white solid.
1
mp. 280.2–282.0 °C; IR (ATR) (cm−1) 3003, 1709, 1358, 1219, 1092, 903; H-NMR (400 MHz,
CDCl3) δ: 5.03 (2H, s), 6.88 (2H, d, J = 8.3 Hz), 6.90 (4H, s), 6.91 (8H, s), 6.94 (8H, s), 7.11 (2H, dd,
13
J = 7.8, 2.0 Hz), 7.16–7.19 (6H, m), 7.21–7.24 (4H, m), 7.27–7.41 (26H, m); C-NMR (125 MHz,
CDCl3) δ: 115.9, 120.9, 127.5, 127.5, 127.6, 127.8, 128.5, 129.1, 129.4, 129.5, 129.6, 130.3, 130.5,

Molecules 2013, 18
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130.6, 130.7, 130.8, 135.2, 139.6, 139.7, 139.8, 139.9, 140.2, 140.3, 140.4, 141.1, 152.5, 153.2;
HRMS (ESI): m/z calcd for C90H61O2 ([M − H]−) 1173.4677; found: 1173.4636.
4. Conclusions
In conclusion, a repetitive two-step method for oligophenylene synthesis using hydroxyterphenylboronic
acid 1 has been developed. By employing this method, o,o,p-oligophenylenes with precise chain
lengths were readily synthesized. Furthermore, the combined use of 1 and 4-hydroxyphenylboronic
acid efficiently gave o,p-oligophenylenes. The X-ray structure of 9-mer 12 was also determined. The
synthetic strategy presented here is applicable to oligophenylenes with various connectivity
patterns. By introducing a substituent on the benzene rings of the boronic acids, it would be also
possible to synthesize oligophenylenes with substituents at a desired position. The present work not
only contributes to the progress of oligophenylene chemistry, but also extends the applicability of
Pd-catalyzed cross coupling.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/18/12/15207/s1.
Conflicts of Interest
The authors declare no conflict of interest.
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© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).