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Article

Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid

by
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
*
Author to whom correspondence should be addressed.
Molecules 2013, 18(12), 15207-15219; https://doi.org/10.3390/molecules181215207
Submission received: 16 October 2013 / Revised: 22 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
(This article belongs to the Special Issue Palladium Catalysts)
Browse Figures
Versions Notes

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.

Graphical Abstract

1. Introduction

Oligophenylenes, which are composed of benzene rings connected through single bonds, have attracted considerable attention as an important class of oligomers [1,2,3,4,5]. Oligophenylenes are widely used architectures in electronic devices [6] and are employed as self-assembling [7,8,9], 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 [14,15,16,17,18]. 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 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.
Molecules 18 15207 g002 550
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.
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.
Molecules 18 15207 g002

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%).
Molecules 18 15207 g003 550
Scheme 2. Preparation of hydroxyterphenylboronic acid 1.
Scheme 2. Preparation of hydroxyterphenylboronic acid 1.
Molecules 18 15207 g003
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.
Molecules 18 15207 g004 550
Scheme 3. Synthesis of o,o,p-oligophenylenes.
Scheme 3. Synthesis of o,o,p-oligophenylenes.
Molecules 18 15207 g004
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 complicated 1H- 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.
Molecules 18 15207 g005 550
Scheme 4. Synthesis of o,p-oligophenylenes.
Scheme 4. Synthesis of o,p-oligophenylenes.
Molecules 18 15207 g005
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.
Molecules 18 15207 g001 550
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.
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.
Molecules 18 15207 g001

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 Akishima, Japan) ECA-500 NMR spectrometer (500 MHz for 1H spectra and 125 MHz for 13C spectra). For 1H 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 (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 a white solid. mp. 126.6–129.6 °C; IR (ATR) (cm−1) 3500, 1473, 1332, 752; 1H-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, 844, 667; 1H-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, J = 8.8, 2.0 Hz), 7.96 (2H, d, J = 2.0 Hz); 13C-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 chromatography (hexane/CH2Cl2 = 4:1) to give 4 (0.250 g, 82%) as a yellow oil. IR (ATR) (cm−1) 1695, 1427, 1236, 887; 1H-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, J = 2.0 Hz); 13C-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; IR (ATR) (cm−1) 3516, 1685, 1450, 1267, 827, 746; 1H-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) (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; IR (ATR) (cm−1) 3529, 1678, 1467, 1269, 829, 748; 1H-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 rotamers); 13C-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) (cm−1) 1685, 1423, 1236, 889, 732; 1H-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 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; IR (ATR) (cm−1) 3537, 1678, 1467, 748; 1H-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 (59H, m) (mixture of rotamers); 13C-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) (cm−1) 3003, 1711, 1358, 1221, 750; 1H-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 (4H, d, J = 8.3 Hz), 7.41–7.46 (10H, m); 13C-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) (cm−1) 1429, 1202, 1140; 1H-NMR (400 MHz, CDCl3) δ: 7.03 (4H, s), 7.24 (4H, d, J = 8.3 Hz), 7.31 (4H, d, J = 8.3 Hz), 7.35–7.45 (16H, m); 13C-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.

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. mp. 244.1–246.5 °C; IR (ATR) (cm−1) 3003, 1709, 1358, 1219, 1092, 903; 1H-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), 6.93 (4H, d, J = 8.3 Hz), 6.93 (4H, s), 7.32–7.52 (16H, m); 13C-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, J = 8.8 Hz), 7.33–7.43 (16H, m); 13C-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. mp. 280.2–282.0 °C; IR (ATR) (cm−1) 3003, 1709, 1358, 1219, 1092, 903; 1H-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, J = 7.8, 2.0 Hz), 7.16–7.19 (6H, m), 7.21–7.24 (4H, m), 7.27–7.41 (26H, m); 13C-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, 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: https://www.mdpi.com/1420-3049/18/12/15207/s1.

Conflicts of Interest

The authors declare no conflict of interest.

References and Notes

  1. Tour, J.M. Conjugated macromolecules of precise length and constitution. Organic synthesis for the construction of nanoarchitectures. Chem. Rev. 1996, 96, 537–554. [Google Scholar] [CrossRef]
  2. Berresheim, A.J.; Müller, M.; Müllen, K. Polyphenylene nanostructures. Chem. Rev. 1999, 99, 1747–1786. [Google Scholar] [CrossRef]
  3. Grimsdale, A.C.; Müllen, K. The chemistry of organic nanomaterials. Angew. Chem. Int. Ed. 2005, 44, 5592–5629. [Google Scholar] [CrossRef]
  4. Hoeben, F.J.M.; Jonkheijm, P.; Meijer, E.W.; Schenning, A.P.H.J. About supramolecular assemblies of π-conjugated systems. Chem. Rev. 2005, 105, 1491–1546. [Google Scholar] [CrossRef]
  5. Tsubaki, K. Synthesis and properties of the chiral oligonaphthalenes. Org. Biomol. Chem. 2007, 5, 2179–2188. [Google Scholar] [CrossRef]
  6. Li, C.; Liu, M.; Pschirer, N.G.; Baumgarten, M.; Müllen, K. Polyphenylene-based materials for organic photovoltaics. Chem. Rev. 2010, 110, 6817–6855. [Google Scholar] [CrossRef]
  7. Sakai, N.; Mareda, J.; Matile, S. Rigid-rod molecules in biomembrane models: From hydrogen-bonded chains to synthetic multifunctional pores. Acc. Chem. Res. 2005, 38, 79–87. [Google Scholar] [CrossRef]
  8. Goto, H.; Katagiri, H.; Furusho, Y.; Yashima, E. Oligoresorcinols fold into double helices in water. J. Am. Chem. Soc. 2006, 128, 7176–7178. [Google Scholar] [CrossRef]
  9. Miwa, K.; Furusho, Y.; Yashima, E. Ion-triggered spring-like motion of a double helicate accompanied by anisotropic twisting. Nat. Chem. 2010, 2, 444–449. [Google Scholar] [CrossRef]
  10. Ernst, J.T.; Kutzki, O.; Debnath, A.K.; Jiang, S.; Lu, H.; Hamilton, A.D. Design of a protein surface antagonist based on α-helix mimicry: Inhibition of gp41 assembly and viral fusion. Angew. Chem. Int. Ed. 2002, 41, 278–281. [Google Scholar] [CrossRef]
  11. Manabe, K.; Ishikawa, S. Oligoarenes as molecular backbones of catalysts: Synthesis and applications. Chem. Commun. 2008, 3829–3838. [Google Scholar] [CrossRef]
  12. Ishikawa, S.; Manabe, K. Synthesis of hydroxylated oligoarene-type phosphines by a repetitive two-step method. Tetrahedron 2010, 66, 297–303. [Google Scholar] [CrossRef]
  13. Müller, M.; Kübel, C.; Morgenroth, F.; Iyer, V.S.; Müllen, K. Oligophenylenes as building blocks for well-defined graphite subunits. Carbon 1998, 36, 827–831. [Google Scholar] [CrossRef]
  14. Blake, A.J.; Cooke, P.A.; Doyle, K.J.; Gair, S.; Simpkins, N.S. Poly-orthophenylenes: Synthesis by suzuki coupling and solid state helical structures. Tetrahedron Lett. 1998, 39, 9093–9096. [Google Scholar]
  15. He, J.; Crase, J.L.; Wadumethrige, S.H.; Thakur, K.; Dai, L.; Zou, S.; Rathore, R.; Hartley, C.S. ortho-Phenylenes: Unusual conjugated oligomers with a surprisingly long effective conjugation length. J. Am. Chem. Soc. 2010, 132, 13848–13857. [Google Scholar] [CrossRef]
  16. Mathew, S.M.; Engle, J.T.; Ziegler, C.J.; Hartley, C.S. The role of arene-arene interactions in the folding of ortho-phenylenes. J. Am. Chem. Soc. 2013, 135, 6714–6722. [Google Scholar] [CrossRef]
  17. Ohta, E.; Sato, H.; Ando, S.; Kosaka, A.; Fukushima, T.; Hashizume, D.; Yamasaki, M.; Hasegawa, K.; Muraoka, A.; Ushiyama, H.; Yamashita, K.; Aida, T. Redox-responsive molecular helices with highly condensed-clouds. Nat. Chem. 2011, 3, 68–73. [Google Scholar] [CrossRef]
  18. Diebold, C.; Weekes, D.M.; Torres Navarrete, M.; Mobian, P.; Kyritsakas, N.; Henry, M. Synthetic approaches to zigzag-shaped oligophenylene strands laterally decorated with hydroxy functions. Eur. J. Org. Chem. 2010, 6949–6956. [Google Scholar]
  19. For a review: Wang, C.; Glorius, F. Controlled iterative cross-coupling: On the way to the automation of organic synthesis. Angew. Chem. Int. Ed. 2009, 48, 5240–5244. [Google Scholar] [CrossRef]
  20. For a review: Schlüter, A.D.; Bo, Z. Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons Ltd.: New York, NY, USA, 2002; pp. 825–861. [Google Scholar]
  21. Suzuki, A. Cross-coupling reactions of organoboranes: An easy way to construct C–C bonds. Angew. Chem. Int. Ed. 2011, 50, 6723–6737. [Google Scholar]
  22. Ishikawa, S.; Manabe, K. Repetitive two-step method for oligoarene synthesis through rapid cross-coupling of hydroxyphenylboronic acids and anhydrides. Chem. Lett. 2006, 35, 164–165. [Google Scholar] [CrossRef]
  23. Ishikawa, S.; Manabe, K. Synthetic method for multifunctionalized oligoarenes using pinacol esters of hydroxyphenylboronic acids. Chem. Commun. 2006, 2589–2591. [Google Scholar] [CrossRef]
  24. Ishikawa, S.; Manabe, K. Ortho-selective cross coupling of dibromophenols and dibromoanilines with grignard reagents in the presence of palladium catalysts bearing hydroxylated oligoarene-type phosphine. Chem. Lett. 2007, 36, 1304–1305. [Google Scholar] [CrossRef]
  25. Beak, P.; Musick, T.J.; Chen, C.W. Does formal intramolecular transfer of an acidic deuterium to a site of halogen-lithium exchange show that lithium-halogen exchange is faster than loss of the acidic deuterium? Evidence in favor of an alternative mechanism. J. Am. Chem. Soc. 1988, 110, 3538–3542. [Google Scholar] [CrossRef]
  26. Shimizu, H.; Manabe, K. Negishi coupling strategy of a repetitive two-step method for oligoarene synthesis. Tetrahedron Lett. 2006, 47, 5927–5931. [Google Scholar] [CrossRef]
  27. Manabe, K.; Kimura, T. Repetitive synthetic method for o,o,p-oligophenylenes using C−H arylation. Org. Lett. 2013, 15, 374–377. [Google Scholar] [CrossRef]
  28. Högermeier, J.; Reissig, H.-U. Nine times fluoride can be good for your syntheses. Not just cheaper: Nonafluorobutanesulfonates as intermediates for transition metal-catalyzed reactions. Adv. Synth. Catal. 2009, 251, 2747–2763. [Google Scholar] [CrossRef]
  29. Han, X.; Stoltz, B.M.; Corey, E.J. Cuprous chloride accelerated stille reactions. general and effective coupling system for sterically congested substrates and for enantioselective synthesis. J. Am. Chem. Soc. 1999, 121, 7600–7605. [Google Scholar] [CrossRef]
  30. Ikawa, T.; Nishiyama, T.; Nosaki, T.; Takagi, A.; Akai, S. A domino process for benzyne preparation: Dual activation of o-(trimethylsilyl)phenols by nonafluorobutanesulfonyl fluoride. Org. Lett. 2011, 13, 1730–1733. [Google Scholar] [CrossRef]
  31. Barder, T.E.; Walker, S.D.; Martinelli, J.R.; Buchwald, S.L. Catalysts for Suzuki-Miyaura coupling processes: Scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 2005, 127, 4685–4696. [Google Scholar] [CrossRef]
  32. Dossel, L.; Gherghel, L.; Feng, X.; Müllen, K. Graphene nanoribbons by chemists: Nanometer-sized, soluble, and defect-free. Angew. Chem. Int. Ed. 2011, 50, 2540–2543. [Google Scholar] [CrossRef]
  33. An example regarding compounds containing o,p-oligophenylene skeleton: Arslan, H.; Saathoff, J.D.; Bunck, D.N.; Clancy, P.; Dichtel, W.R. Highly efficient benzannulation of poly(phenylene ethynylene)s. Angew. Chem. Int. Ed. 2012, 51, 12051–12054. [Google Scholar] [CrossRef]
  34. CCDC 972877 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via. (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-Mail: [email protected]). Available online: http://www.ccdc.cam.ac.uk/conts/retrieving.html.
  35. Shukla, R.; Lindeman, S.V.; Rathore, R. Terphenyl crowns: A new family of receptors containing ethereal canopies that direct potassium cation onto benzenoid platforms for cation-π Interactions. Chem. Commun. 2009, 5600–5602. [Google Scholar] [CrossRef]
  36. Murashige, R.; Hayashi, Y.; Ohmori, S.; Torii, A.; Aizu, Y.; Muto, Y.; Murai, Y.; Oda, Y.; Hashimoto, M. Comparisons of O-acylation and Friedel-Crafts acylation of phenols and acyl chlorides and fries rearrangement of phenyl esters in trifluoromethanesulfonic acid: Effective synthesis of optically active homotyrosines. Tetrahedron 2011, 67, 641–649. [Google Scholar] [CrossRef]
  • Sample Availability: Samples of the compounds are available from the authors.

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MDPI and ACS Style

Yamaguchi, M.; Kimura, T.; Shinohara, N.; Manabe, K. Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid. Molecules 2013, 18, 15207-15219. https://doi.org/10.3390/molecules181215207

AMA Style

Yamaguchi M, Kimura T, Shinohara N, Manabe K. Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid. Molecules. 2013; 18(12):15207-15219. https://doi.org/10.3390/molecules181215207

Chicago/Turabian Style

Yamaguchi, Miyuki, Takeshi Kimura, Naomi Shinohara, and Kei Manabe. 2013. "Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid" Molecules 18, no. 12: 15207-15219. https://doi.org/10.3390/molecules181215207

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