Synthesis of 2,3-Diarylbenzo[b]thiophenes via Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling
FULL PAPERS
Hydrolysis of Methyl 3-Phenylbenzo[b]thiophene-2-
carboxylate (3a)
Preparation of 2,6-Bis(butoxycarbonyl)-3,7-
dichlorobenzo[1,2-b;4,5-b’]dithiophene (10)
In a 100-mL flask were added methyl 3-phenylbenzo[b]thio-
phene-2-carboxylate (3a) (2.0 mmol, 536 mg), potassium hy-
droxide (12 mmol, 673 mg), water (4.0 mL), and ethanol
(8.0 mL). The mixture was heated at 808C (bath tempera-
ture) for 8 h under N2. After cooling and acidification with
aqueous HCl (2.0M), a white precipitate was collected,
washed with water, and dried under vacuum to afford car-
boxylic acid 4a;[20] yield: quantitative; mp 188–1918C;
1H NMR (400 MHz, DMSO-d6): d=7.38–7.56 (m, 8H), 8.08
(d, J=8.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d=
122.9, 124.6, 125.2, 127.3, 127.9, 128.0, 129.69, 129.72, 134.3,
139.4, 139.8, 142.3, 163.3; HR-MS: m/z=254.0399 (M+),
calcd. for C15H10O2S: 254.0402.
In a 100-mL two-necked flask were added 3,7-dichloroben-
zo[1,2-b;4,5-b’]dithiophene-2,6-dicarbonyl
dichloride[12c]
(5.0 mmol, 1.9 g), n-butanol (20 mmol, 1.8 mL), pyridine
(20 mmol, 1.6 mL), and chlorobenzene (10 mL). The result-
ing mixture was stirred under N2 (balloon) at 1008C (bath
temperature) for 6 h. After cooling, the reaction mixture
was filtered through a filter paper with diethyl ether as an
eluent followed by evaporation of the solvent. The resulting
solid was washed with water, and dried under vacuum. The
diester 10 (yield: 1.9 g, 4.2 mmol, 83%) was isolated by re-
crystallization from toluene/hexane; mp 128–1298C;
1H NMR (400 MHz, CDCl3): d=1.01 (t, J=7.3 Hz, 6H),
1.48–1.57 (m, 4H), 1.76–1.84 (m, 4H), 4.40 (t, J=6.6 Hz,
4H), 7.96 (s, 2H); 13C NMR (100 MHz, CDCl3): d=13.9,
19.5, 30.8, 66.1, 121.4, 126.5, 128.4, 133.1, 137.3, 161.0; HR-
MS: m/z=458.0172 (M+), calcd. for C20H20Cl2O4S2:
458.0180.
Palladium-Catalyzed Decarboxylative Arylation of 3-
Phenylbenzo[b]thiophene-2-carboxylic Acid (4a) with
Bromobenzene (5a) (Table 2, entry 10)
In a 20-mL two-necked flask were added 3-phenylbenzo[b]-
thiophene-2-carboxylic acid (4a) (0.50 mmol, 127 mg), bro-
Acknowledgements
mobenzene
(0.050 mmol, 11 mg), P(biphenyl-2-yl)ACHTUNGTRENNNUG
(5a)
(1.5 mmol,
235 mg),
(t-Bu)2 (0.10 mmol,
PdACTHNGURETNNU(G OAc)2
This work was partly supported by Grants-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan. M. M. acknowledges JSPS for financial support.
30 mg), Cs2CO3 (1.0 mmol, 325 mg), 1-methylnaphthalene
(ca. 50 mg) as internal standard, and DMAc (2.5 mL). The
resulting mixture was stirred under N2 (balloon) at 1608C
(bath temperature) for 48 h. Analysis of the mixture by GC
confirmed the formation of compound 6aa (yield: 140 mg,
98%). After cooling, the reaction mixture was poured into
diluted aqueous HCl, extracted with diethyl ether, and dried
over Na2SO4. The product 6aa[21] (yield: 135 mg, 0.47 mmol,
94%) was isolated by column chromatography on silica gel
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1
using hexane as eluent; mp 115–1178C; H NMR (400 MHz,
CDCl3): d=7.22–7.27 (m, 3H), 7.30–7.42 (m, 9H), 7.58–7.61
(m, 1H), 7.85–7.90 (m, 1H); 13C NMR (100 MHz, CDCl3):
d=122.1, 123.4, 124.4, 124.5, 127.4, 127.7, 128.3, 128.6, 129.6,
130.4, 133.2, 134.2, 135.5, 138.8, 139.5, 140.9; HR-MS: m/z=
286.0811 (M+), calcd. for C20H14S: 286.0816.
Reaction of 3-Chlorobenzo[b]thiophene-2-
carbACHTUNGTRENNUNGoxylate (1a) with 3,4-Dimethoxybenzenethiol (7)
In a 100-mL two-necked flask were added 3-chlorobenzo[b]-
thiophene-2-carboxylate (1a) (3.0 mmol, 680 mg), 3,4-dime-
thoxybenzenethiol (7) (3.6 mmol, 612 mg), K2CO3
(6.0 mmol, 829 mg), and DMF (20 mL). The resulting mix-
ture was stirred under N2 (balloon) at 808C (bath tempera-
ture) for 6 h. After cooling, the reaction mixture was poured
into diluted aqueous HCl, extracted with diethyl ether, and
dried over Na2SO4. The product 8 (yield: 623 mg, 1.8 mmol,
60%) was isolated by column chromatography on silica gel
using hexane-ethyl acetate as eluent (90:10, v/v); mp 111–
1
1138C; H NMR (400 MHz, CDCl3): d=3.74 (s, 3H), 3.82
(s, 3H), 3.95 (s, 3H), 6.72 (d, J=8.4 Hz, 1H), 6.83–6.90 (m,
2H), 7.29–7.33 (m, 1H), 7.42–7.46 (m, 1H), 7.78–7.84 (m,
2H); 13C NMR (100 MHz, CDCl3): d=52.5, 55.87, 55.92,
111.6, 113.3, 122.6, 122.7, 125.0, 125.5, 126.6, 127.4, 132.7,
132.9, 139.8, 139.9, 148.3, 149.2, 162.4; HR-MS: m/z=
360.0488 (M+), calcd. for C18H16O4S2: 360.0490.
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Adv. Synth. Catal. 2009, 351, 2683 – 2688
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2687