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stirred suspension of magnesium turnings (0.3 g, 12.3 mmol) in dry
diethyl ether (10 mL). After 2 h at reflux, the mixture was cooled to
room temperature, dropped into a stirred solution of 2-bromo-3-
methoxythiophene (1.5 g, 7.7 mmol) and NiCl2(dppp) (0.424 g, 0.77
mmol) in dry diethyl ether (30 mL), and refluxed for 10 h. After an
overnight stirring at room temperature, the reaction mixture was
quenched with ice and an aqueous solution of HCl (2M) and extracted
with diethyl ether/H2O. The organic layer was dried over Na2SO4, and
the solvent was removed under reduced pressure. The product was
purified using silica gel flash chromatography with petroleum benzine/
DCM 9:1 to give the desired product as a yellow liquid in 88% yield.
1H NMR (400 MHz; CDCl3, 25 °C, TMS): δ 7.217 (dd, 3J(H3′,H4′) =
3.6 Hz, 3J(H3′,H5′) = 1 Hz, 1H; H3′ thiophene), 7.182 (dd, 3J(H5′,H4′)
= 5.0 Hz, 3J(H5′,H3′) = 1 Hz, 1H; H5′ thiophene), 7.045 (d, 3J(H,H) =
5.6 Hz, 1H; H5 thiophene), 6.992 (dd, 3J(H43′,H3′) = 3.6 Hz,
3J(H4′,H5′) = 5.3 Hz, 1H; H4′ thiophene), 6.85 (d, J(H,H) = 5.6 Hz,
5,5′-Bis-(3,5-di-tert-butyl-4-hydroxy)phenyl-3,3′-dipentoxy-2,2′-bi-
thiophene (13): 5,5′-Dibromo-3,3′-dipentoxy-2,2′-bithiophene (0.200
g, 0.403 mmol), Pd(PPh3)4 (0.046 g, 0.04 mmol), tris[3,5-di-tert-butyl-
4-(trimethylsilyloxy)phenyl]boroxine (0.348 g, 0.403 mmol),
NaHCO3 solution (5 mL, 5 mmol). Flash chromatography using
petroleum benzine/ethyl acetate 95:5 afforded 13 as a light green solid
in 33% yield. 1H NMR (400 MHz; DMSO, 25 °C, TMS): δ 7.354 (s,
4H; −H phenyl), 7.267 (s, 2H; −OH), 7.106 (s, 2H; H4,H4′
thiophene), 4.202 (t, J(H,H) = 6.32 Hz, 4H; −OCH2), 1.822 (m,
4H; −CH2−), 1.604 (m, 4H; −CH2−), 1.429 (s, 36H; -tert-butyl),
3
1.398 (m, 4H; −CH2−), 0.929 ppm (t, J(H,H) = 7.411 Hz; −CH3).
(d) 5,5′-Bis-(3,5-di-iso-propyl-4-hydroxy)phenyl-3,3′-dipentoxy-
2,2′-bithiophene (14): 5,5′-Dibromo-3,3′-dipentoxy-2,2′-bithiophene
(0.318 g, 0.64 mmol), Pd(PPh3)4 (0.500 g, 0.64 mmol), tris[3,5-di-iso-
propyl)-4-(trimethylsilyloxy)phenyl]boroxine (0.750 g, 0.06 mmol),
NaHCO3 solution (6 mL, 5.76 mmol). Flash chromatography using
petroleum benzine/ethyl acetate 9:1 afforded 14 as a light green solid
in 43% yield. 1H NMR (400 MHz; DMSO, 25 °C, TMS): δ 8.282 (s,
2H; −OH), 7.325 (s, 2H; H4,H4′ thiophene), 7.247 (s, 4H; −H
1H; H4 thiophene), 3.993 ppm (s, 3H; −OCH3).
General Procedure for the Preparation of 5,5′-Dibromo-3,3′-
R1,R2-2,2′-bithiophene. To a solution of 3,3′-R1,R2-2,2′-bithiophene
(1 equiv) in dry DMF was added dropwise N-bromosuccinimide (2
equiv) in dry DMF, in the absence of light. After 1 h, the reaction
mixture was extracted with DCM and washed with water. The organic
layer was dried over Na2SO4, and the solvent was removed under
reduced pressure. The product was purified using flash chromatog-
raphy (silica gel). (a) 5,5′-Dibromo-3-methoxy-2,2′-bithiophene
(6): 3-Methoxy-2,2′-bithiophene (1 g, 5 mmol) in DMF (10 mL),
N-bromosuccinimide (1.78 g, 10 mmol) in DMF (10 mL). Flash
chromatography in petroleum benzine/DCM 9:1 afforded the desired
3
phenyl), 4.212 (t, J(H,H) = 5.883 Hz, 4H; −OCH2), 3.327 (m, 4H;
−CH iso-propyl), 1.827 (m, 4H; −CH2−), 1.627 (m, 4H; −CH2−),
3
1.447 (m, 4H; −CH2−), 1.210 (d, J(H,H) = 6.986 Hz, 24H; −CH3
iso-propyl), 0.950 ppm (t, 3J(H,H) = 7.354 Hz, 6H; −CH3). (e) 5,5′-
Bis-(3,5-dimethyl-4-hydroxy)phenyl-3,3′-dipentoxy-2,2′-bithio-
phene (15): 5,5′-Dibromo-3,3′-dipentoxy-2,2′-bithiophene (0.320 g,
0.645 mmol), Pd(PPh3)4 (0.750 g, 0.065 mmol), 4-hydroxy-3,5-
dimethylphenyl boronic acid pinacol ester (0.400 g, 1.613 mmol),
NaHCO3 solution (6 mL, 5.8 mmol). Flash chromatography using
petroleum benzine/ethyl acetate 2:1 afforded 15 as a light green solid
in 60% yield. 1H NMR (400 MHz; DMSO, 25 °C, TMS): δ 7.254 (s,
2H; H4,H4′ thiophene), 7.199 (s, 4H; −H phenyl), 4.176 (t, 3J(H,H) =
5.883 Hz, 4H; −OCH2), 2.195 (s, 12H; −CH3 phenyl), 1.812 (m, 4H;
−CH2−), 1.573 (m, 4H; −CH2−), 1.433 (m, 4H; −CH2−), 0.959
1
product as a light green solid in 74% yield. H NMR (400 MHz;
CDCl3, 25 °C, TMS): δ 6.915 (d, 3J(H,H) = 3.6 Hz, 1H; H3′
3
thiophene), 6.85 (s, 1H; H4 thiophene), 6.81 (d, J(H,H) = 3.6 Hz,
1H; H4′ thiophene), 3.993 ppm (s, 3H; −OCH3). (b) 5,5′-Dibromo-
3,3′-dipentoxy-2,2′-bithiophene (7): 3,3′-Dipentoxy-2,2′-bithio-
phene26 (1.5 g, 4.44 mmol) in DMF (20 mL), N-bromosuccinimide
(1.74 g, 9.76 mmol) in DMF (10 mL). Flash chromatography using
petroleum benzine/DCM 3:1 afforded the desired product as a yellow
solid in 72% yield. 1H NMR (400 MHz; CDCl3, 25 °C, TMS): δ 6.811
(s, 2H; H4,H4′ thiophene), 4.039 (t, 3J(H,H) = 6.539 Hz, 4H;
−OCH2−), 1.836 (m, 4H; −CH2−), 1.481 (m, 4H; −CH2−), 1.409
3
ppm (t, J(H,H) = 7.383 Hz, 6H; −CH3 pentoxy). (f) 5,5′-Bis-(4-
hydroxy)phenyl-3,3′-dipentoxy-2,2′-bithiophene (16): 5,5′-Dibro-
mo-3,3′-dipentoxy-2,2′-bithiophene (1 g, 2.016 mmol), Pd(PPh3)4
(0.233 g, 0.2 mmol), 4-hydroxyphenylboronic acid (0.8346 g, 6.048
mmol), NaHCO3 solution (18 mL, 18.145 mmol). Flash chromatog-
raphy using petroleum benzine/ethyl acetate 2:1 afforded 16 as a
3
1
(m, 4H; −CH2−), 0.948 ppm (t, J(H,H) = 7.193 Hz, 6H; −CH3).
green powder in 66% yield. H NMR (400 MHz; DMSO, 25 °C,
TMS): δ 7.447 (d, 3J(H,H) = 8.719 Hz, 4H; H2,H6 phenyl), 7.278 (s,
2H, H4,H4′ thiophene), 6.8 (d, 3J(H,H) = 8.719 Hz, 4H; H3,H5
General Procedure for the Preparation of 5,5′-Bis(3,5-dialkyl-4-
hydroxy)phenyl-3,3′-R1,R2-2,2′-bithiophene. To a solution of 5,5′-
dibromo-3,3′-R1,R2-2,2′-bithiophene (1 equiv) and Pd(PPh3)4 (0.1
equiv) in previously degassed DME (2:1 with respect to water) were
rapidly added boronic acid (2.5 equiv) or boroxine (1 equiv) and
aqueous base solution (9 eq, 1 M). The resulting mixture was refluxed
overnight. Next, it was allowed to cool to room temperature, poured
into water, and extracted with diethyl ether or DCM. The organic layer
was dried over Na2SO4, and, after solvent removal, the raw product
was purified using flash chromatography (silica gel). (a) 5,5′-Bis-(3,5-
di-tert-butyl-4hydroxy)phenyl-2,2′-bithiophene (11): 5,5′-Dibromo-
2,2′-bithiophene (0.413 g, 1.276 mmol), Pd(PPh3)4 (0.147 g, 0.1276
mmol), tris[3,5-di-tert-butyl-4-(trimethylsilyloxy)phenyl]boroxine
(1.165 g, 1.276 mmol), Na2CO3 solution (11.5 mL, 11.484 mmol).
Flash chromatography with petroleum benzine/DCM 9:1 afforded the
3
phenyl), 4.173 (t, J(H,H) = 6.321 Hz, 4H; −OCH2), 1.812 (m, 4H;
−CH2−), 1.533 (m, 4H; −CH2−), 1.412 (m, 4H; −CH2−), 0.930
3
ppm (t, J(H,H) = 7.411 Hz, 6H; −CH3).
General Procedure for the Preparation of 5,5′-Bis-(3,5-R3,R3-4-
oxo-2,5-cyclohexadiene-1-ylidene)-3,3′-R1,R2-2,2′-dihydroxy Bithio-
phene. To a solution of 5,5′-bis-(3,5-R3,R3-4-hydroxy)phenyl-3,3′-
R1,R2-2,2′-bithiophene (1 equiv) in DCM were added K3Fe(CN)6 (10
equiv) and an aqueous solution of KOH (100 equiv, 0.3 M). The
resulting mixture was stirred until the starting material completely
reacted (∼3 h). The reaction mixture was extracted with DCM and
washed with water. Solvent removal afforded the desired product in
quantitative yield. (a) 5,5′-Bis-(3,5-di-tert-butyl-4-oxo-2,5-cyclohex-
adiene-1-ylidene)-2,2′-dihydroxy Bithiophene (QBT-tbu-HH):
5,5′-Bis-(3,5-di-tert-butyl-4-hydroxy)phenyl-2,2′-bithiophene (0.641 g,
1.115 mmol, 75 mL), K3Fe(CN)6 (3.67 g, 11.15 mmol), aqueous
KOH solution (6.25 g, 111.5 mmol, 150 mL). The product was
isolated as a green solid. 1H NMR (400 MHz; CDCl3, 25 °C, TMS): δ
1
desired product as a yellow solid in 87% yield. H NMR (400 MHz;
CDCl3, 25 °C, TMS): δ 7.414 (s, 4H; H2,H6 phenyl), 7.123 (d,
3J(H,H) = 3.8 Hz, 2H; H3,H3′ thiophene), 7.086 (d, 3J(H,H) = 3.8 Hz,
2H; H4,H4′ thiophene), 5.278 (s, 2H; −OH), 1.491 ppm (s, 36H; tert-
butyl). (b) 5,5′-Bis-(3,5-di-tert-butyl-4-hydroxy)phenyl-3-methoxy-
2,2′-bithiophene (12): 5,5′-Dibromo-3-methoxy-2,2′-bithiophene
(0.530 g, 1.5 mmol), Pd(PPh3)4 (0.170 g, 0.15 mmol), tris[3,5-di-
tert-butyl-4-(trimethylsilyloxy)phenyl]boroxine (0.9 g, 1.0 mmol),
Na2CO3 solution (13.5 mL, 13.5 mmol). Flash chromatography
using petroleum benzine/DCM 9:1 afforded the desired product as a
yellow solid in 75% yield. 1H NMR (400 MHz; CDCl3, 25 °C, TMS):
δ 7.418 (s, 2H; −H phenyl), 7.384 (s, 2H; −H phenyl), 7.175 (d,
3
7.530 (s, 2H; H thiophene), 7.415 (d, J(H,H) = 5 Hz, 4H; H2,H6
phenyl), 7.246 (s, 2H; H thiophene), 1.369 ppm (s, 36 H; -tert-butyl).
HRMS (ESI): m/z calcd for C36H44O2S2+H+, 573 [M + H+]; found,
573.3 (M+). FT-IR (KBr, cm−1): 1575, 1484, 1452, 1359, 1323, 1026,
989. (b) 5,5′-Bis-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadiene-1-yli-
dene)-3-methoxy-2,2′-dihydroxy Bithiophene (QBT-tbu-HO): 5,5′-
Bis-(3,5-di-tert-butyl-4-hydroxy)phenyl-3-methoxy-2,2′-bithiophene
(0.250 g, 0.44 mmol), DCM (75 mL), K3Fe(CN)6 (1.7 g, 5 mmol),
aqueous KOH solution (2.8 g, 50 mmol, 150 mL). The product is
isolated as an iridescent green/red solid. 1H NMR (400 MHz; CDCl3,
25 °C, TMS): δ 7.407 (d, 2H; H phenyl), 7.329 (s, 2H; H phenyl),
3
3J(H,H) = 3.8 Hz, 1H; H3′ thiophene), 7.074 (d, J(H,H) = 3.8 Hz,
1H; H4′ thiophene), δ 6.984 (s, 1H; H4 thiophene), 5.227 (s, 2H;
−OH), 4.016 (s, 3H; −OCH3), 1.429 ppm (s, 36H; tert-butyl). (c)
19072
dx.doi.org/10.1021/ja3072385 | J. Am. Chem. Soc. 2012, 134, 19070−19083