K. Matsuda et al.
FULL PAPERS
extracted with CH2Cl2, and the organic layer was washed with brine,
dried over MgSO4, and evaporated. The crude product was dissolved in
EtOH (40 mL), and then pyridinium-p-toluene sulfonate (PPTS, 310 mg,
1.25 mmol) was added. The solution was stirred for 6 h at room tempera-
ture. The solution was evaporated to remove EtOH, and the product was
extracted with CH2Cl2, and the organic layer was washed with brine,
dried over MgSO4, and evaporated to yield 12 (1.8 g, 10.1 mmol, 80.8%)
as a yellow oil. 1H NMR (CDCl3, TMS, 400 MHz): d=1.13 (d, J=6 Hz,
3H, Me), 2.82 (brs, 1H, OH), 3.23–3.31 (m, 1H), 3.39 (s, 3H, Me), 3.47–
3.76 (m, 9H), 3.92–4.03 ppm (m, 1H); MS (FAB HRMS): m/z (%) calcd
for C8H19O4: 179.1283 [M+H]+; found: 179.1285.
7.41 ppm (d, J=9 Hz, 2H, Ar); MS (FAB HRMS): m/z (%) calcd for
C18H23BrO4S: 414.0500 [M]+; found: 414.0509.
1,2-Bis-[5-(4-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-2-methyl-
thiophene-3-yl]-perfluorocyclopentene (5a): An nBuLi solution in
hexane (1.6m, 3.15 mL, 5.04 mmol) was slowly added to a solution of
compound 18 (2.0 g, 4.8 mmol) in dry THF (20 mL) at À788C under an
argon atmosphere. The solution was stirred for 15 min at À788C. After
addition of a solution of perfluorocyclopentene (1.3 mL, 9.6 mmol) in dry
THF (25 mL) at À908C, the reaction mixture was further stirred for 2 h.
The reaction was quenched by the addition of water. The reaction prod-
uct was extracted with ethyl acetate (ꢁ3), and the organic layer was
washed with brine (ꢁ2), dried over MgSO4, filtrated, and evaporated.
The crude product was purified by silica gel column chromatography
(ethyl acetate/acetone=1:1) to yield 5a (1.0 g, 1.2 mmol, 24.5%) as a
blue oil. 1H NMR (CDCl3, TMS, 400 MHz): d=1.94 (s, 6H, Me), 3.38 (s,
6H, Me), 3.53–4.18 (m, 24H), 6.93 (d, J=9 Hz, 4H, Ar), 7.16 (s, 2H),
7.45 ppm (d, J=9 Hz, 4H, Ar); MS (FAB HRMS): m/z (%) calcd for
C41H46F6O8S2: 844.2538 [M]+; found: 844.2540.
(S)-toluene-4-sulfonic acid 2-[2-(2-methoxy-ethoxy)-ethoxy]-1-methyl-
ethyl ester (13):
A solution of (S)-1-[2-(2-methoxy-ethoxy)-ethoxy]-
propan-2-ol (12) (1.10 g, 6.17 mmol) in THF (1.0 mL) was added to a so-
lution of sodium hydroxide (320 mg, 8.02 mol) in water (0.5 mL) at 08C.
Then a solution of p-tosyl chloride (1.24 g, 6.48 mmol) in THF (2.0 mL)
was slowly dropped into the solution. After warming to room tempera-
ture, the mixture was stirred for 17 h. The reaction mixture was acidified
by 6m H2SO4. The reaction product was extracted with CH2Cl2, and the
organic layer was washed with brine, dried over MgSO4, and evaporated.
The crude product was purified by silica gel column chromatography
(hexane/ethyl acetate=1:1) to yield 13 (1.22 g, 3.68 mmol, 59.6%) as a
(R)-3-Bromo-5-[4-(2-{2-[2-methoxy-ethoxy]-ethoxy}-1-methyl-ethoxy)-
phenyl]-2-methyl-thiophene (19): An nBuLi solution in hexane (1.6m,
4.83 mL, 7.73 mmol) was slowly added to a solution of 2,4-dibromo-5-
methylthiophene (17) (1.88 g, 7.36 mmol) in dry THF (50 mL) at À788C
under an argon atmosphere. The solution was stirred for 10 min at
À788C. After the addition of boric acid tri-n-butyl ester (2.94 mL,
11.0 mmol), the reaction mixture was further stirred for 1.5 h. The reac-
tion was quenched by the addition of water. (R)-1-Iodo-4-{2-[2-(2-me-
thoxy-ethoxy)-ethoxy]-1-methyl-ethoxy}-benzene (16) (1.4 g, 3.7 mmol),
1
colorless oil. H NMR (CDCl3, TMS, 400 MHz): d=1.28 (d, J=7 Hz, 3H,
Me), 3.38 (s, 3H, Me), 3.42–3.65 (m, 10H), 4.65–4.79 (m, 1H), 7.33 (d,
J=8 Hz, 2H, Ar), 7.81 ppm (d, J=8 Hz, 2H, Ar); MS (FAB HRMS):
m/z (%) calcd for C15H25O6S: 333.1383 [M+H]+; found: 333.1383.
1-Iodo-4-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-benzene (15): Tolu-
ene-4-sulfonic acid 2-[2-(2-methoxy-ethoxy)-ethoxy]-ethyl ester (TsOTig)
(5.0 g, 0.016 mol) and p-iodophenol (14) (3.96 g, 0.018 mol) were added
to a solution of K2CO3 (22.1 g, 0.16 mol) in DMF (225 mL). The solution
was stirred overnight (20 h) at 708C. After cooling, the mixture was
poured into aqueous HCl (pH 2, 225 mL) and extracted with CH2Cl2
(ꢁ3), and the organic layer was washed with brine (ꢁ2), dried over
MgSO4, and the solvent was evaporated in vacuo to yield 15 (5.8 g,
0.0158 mol, 98.8%) as a brown oil. 1H NMR (CDCl3, TMS, 400 MHz):
d=3.38 (s, 3H, Me), 3.52–4.11 (m, 12H)), 6.69 (d, J=9 Hz, 2H, Ar),
7.54 ppm (d, J=9 Hz, 2H, Ar); MS (FAB HRMS): m/z (%) calcd for
C13H19IO4: 366.0328 [M]+; found: 366.0320.
PdACHTUNGTRNEU(GN PPh3)4 (430 mg, 0.37 mmol), and aqueous Na2CO3 (20 w%, 40 mL)
were added to the solution. The solution was refluxed overnight (20 h).
The reaction product was extracted with ether (ꢁ3), and the organic
layer was washed with brine (ꢁ2), dried over MgSO4, filtered, and
evaporated. The crude product was purified by silica gel column chroma-
tography (hexane/ethyl acetate=1:1) to yield 19 (1.2 g, 2.79 mmol,
75.8%) as a pale yellow oil. 1H NMR (CDCl3, TMS, 400 MHz): d=1.32
(d, J=6 Hz, 3H, Me), 2.42 (s, 3H, Me), 3.38 (s, 3H, Me), 3.51–3.76 (m,
10H), 4.52–4.65 (m, 1H), 6.92 (d, J=8 Hz, 2H, Ar), 6.98 (s, 1H),
7.40 ppm (d, J=9 Hz, 2H, Ar); MS (FAB HRMS): m/z (%) calcd for
C19H25BrO4S: 428.0657 [M]+; found: 428.0660.
(R)-1-Iodo-4-{2-[2-(2-methoxy-ethoxy)-ethoxy]-1-methyl-ethoxy}-ben-
zene (16): (S)-toluene-4-sulfonic acid 2-[2-(2-methoxy-ethoxy)-ethoxy]-1-
methyl-ethyl ester (13) (1.22 g, 3.67 mmol) and p-iodophenol 14 (870 mg,
4.04 mmol) were added to a solution of K2CO3 (5.07 g, 36.7 mmol) in
DMF (60 mL). The solution was stirred overnight (12 h) at 708C. After
cooling, the mixture was poured into aqueous HCl (pH 2, 60 mL) and ex-
tracted with CH2Cl2 (ꢁ3), and the organic layer was washed with brine
(ꢁ2) and dried over MgSO4. The solvent was evaporated in vacuo to
yield 16 (1.43 g, 3.76 mmol, quant.) as a reddish brown oil. 1H NMR
(CDCl3, TMS, 400 MHz): d=1.29 (d, J=6 Hz, 3H, Me), 3.38 (s, 3H,
Me), 3.51–3.75 (m, 10H), 4.45–4.58 (m, 1H), 6.71 (d, J=9 Hz, 2H, Ar),
7.51 ppm (d, J=8 Hz, 2H, Ar); MS (FAB HRMS): m/z (%) calcd for
C14H21IO4: 380.0485 [M]+; found: 380.0487.
ACHTUNGTNER(NUNG R,R)-1,2-Bis-[5-(4-{2-[2-(2-methoxy-ethoxy)-ethoxy]-1-methyl-ethoxy}-
phenyl)-2-methyl-thiophene-3-yl]-perfluorocyclopentene (6a): An nBuLi
solution in hexane (1.6m, 1.76 mL, 2.81 mmol) was slowly added to a so-
lution of (R)-3-bromo-5-[4-(2-{2-[2-methoxy-ethoxy]-ethoxy}-1-methyl-
ethoxy)-phenyl]-2-methyl-thiophene (19) (1.15 g, 2.68 mmol) in dry THF
(10 mL) at À788C under an argon atmosphere. The solution was stirred
for 5 min at À788C. After the addition of a solution of perfluorocyclo-
pentene (0.56 mL, 4.02 mmol) in dry THF (15 mL), the reaction mixture
was further stirred for 2 h at that temperature. The reaction was
quenched by the addition of water. The reaction product was extracted
with ether (ꢁ3), and the organic layer was washed with brine (ꢁ3), dried
over MgSO4, filtered, and evaporated. The crude product was purified by
silica gel column chromatography (hexane/ethyl acetate=1:1) to yield 6a
(500 mg, 0.57 mmol, 42.(%) as a green oil. 1H NMR (CDCl3, TMS,
400 MHz): d=1.32 (d, J=6 Hz, 6H, Me), 1.94 (s, 6H, Me), 3.37 (s, 6H,
Me), 3.52–3.79 (m, 20H), 4.53–4.67 (m, 2H), 6.94 (d, J=8 Hz, 4H, Ar),
7.15 (s, 2H), 7.44 ppm (d, J=8 Hz, 4H, Ar); MS (FAB HRMS): m/z (%)
calcd for C43H50F6O8S2: 872.2851 [M]+; found: 872.2853.
3-Bromo-(5-{4-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-phenyl)-2-methyl-
thiophene (18): An nBuLi solution in hexane (1.6m, 18.4 mL,
0.029 mmol) was slowly added to a solution of 2,4-dibromo-5-methylthio-
phene (17) (7.17 g, 0.028 mol) in dry THF (200 mL) at À788C under an
argon atmosphere. The solution was stirred for 15 min at À788C. After
addition of boric acid tri-n-butyl ester (11.4 mL, 0.043 mmol), the reac-
tion mixture was further stirred for 1 h. The reaction was quenched by
the addition of water. 1-Iodo-4-{2-[2-(2-methoxy-ethoxy)-ethoxy]-
3-Bromo-5-(4-methoxymethoxy-phenyl)-2-methyl-thiophene (20): An
nBuLi solution in hexane (1.6m, 23.6 mL, 37.7 mmol) was slowly added
to a solution of 2,4-dibromo-5-methylthiophene (17) (9.2 g, 35.9 mmol) in
dry THF (150 mL) at À788C under an argon atmosphere. The solution
was stirred for 5 min at À788C. After addition of boric acid tri-n-butyl
ester (14.4 mL, 53.9 mmol), the reaction mixture was further stirred for
1.5 h. The reaction was quenched by the addition of water. 1-Iodo-4-me-
ethoxy}-benzene (15) (5.0 g, 0.0137 mol), PdACHTNURTGNEUNG(PPh3)4 (1.0 g, 0.865 mmol),
and aqueous NaCO3 (20 w%, 150 mL) were added to the solution. The
solution was refluxed overnight (20 h). The reaction product was extract-
ed with ethyl acetate (ꢁ3), and the organic layer was washed with brine
(ꢁ2), dried over MgSO4, filtrated, and evaporated. The crude product
was purified by silica gel column chromatography (hexane/ethyl ace-
tate=1:1) to yield 18 (4.8 g, 0.0116 mol, 84.7%) as a pale yellow solid.
1H NMR (CDCl3, TMS, 400 MHz): d=2.40 (s, 3H, Me), 3.38 (s, 3H,
Me), 3.53–4.18 (m, 12H), 6.91 (d, J=9 Hz, 2H, Ar), 6.98 (s, 1H),
thoxymethoxybenzene (9.5 g, 35.9 mmol), PdACHTNURTGNEUNG(PPh3)4 (1.3 g, 1.12 mmol)
and aqueous NaCO3 (20 w%, 150 mL) were added to the solution. The
solution was refluxed overnight (20 h). The reaction product was extract-
ed with ethyl acetate (ꢁ3), and the organic layer was washed with brine
(ꢁ2), dried over MgSO4, filtrated, and evaporated. The crude product
64
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Chem. Asian J. 2009, 4, 58 – 66