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Z. Novak et al. / Tetrahedron 59 (2003) 7509–7513
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1.85 mmol) was dissolved in a mixture of THF (11 mL) and
water (1.3 mL) at 08C and TBAF (2.17 mmol, 2.17 mL, 1 M
in THF) was added to the solution. The reaction mixture was
left to warm up to 258C. After the starting material
disappeared (1 h by GC) water (13 mL) was added to the
mixture and half of the volume of the solvent was removed
under reduced pressure. The remaining solution was
extracted with diethylether, the combined organic phases
were dried over MgSO4 and the solvent was removed in
vacuum. The crude product was purified by silica gel
column chromatography to afford 7 (353 mg, 1.62 mmol) as
yellow oil. Yield: 88%. 1H NMR (CDCl3; 250 MHz): d 7.50
(d, 1H, J¼8.2 Hz), 6.88–7.00 (m, 2H), 3.24 (s, 1H), 2.31 (s,
3H), 2.26 (s, 3H); 13C NMR (CDCl3, 62.5 MHz): d 168.4,
168.3, 152.5, 151.2, 133.8, 119.1, 116.1, 113.7, 82.0, 77.8,
20.9, 20.7; MS (EI, 70 eV) m/z (% relative intensity, ion):
218(5, [Mþ]), 217(12), 176(39), 134(100), 105(15), 78(31).
IR (KBr) nmax: 3279, 2926, 1769, 1610, 1493, 1369, 1191,
1144, 1099, 1013 cm21; Anal. calcd for C12H10O4: C,
66.05; H, 4.62. Found: C, 65.85; H, 4.78.
under reduced pressure to give a brown solid. The crude
product was purified by silica gel column chromatography
to afford 10 (784 mg, 3.35 mmol) as a white solid. Yield:
67%; mp: 145–1488C; 1H NMR (CDCl3; 250 MHz): d 6.80
(s, 1H), 6.48 (s, 1H), 5.92 (s, 2H), 3.81 (s, 3H), 2.27 (br, 1H),
1.61 (s, 6H); 13C NMR (CDCl3, 62.5 MHz): d 156.6, 148.8,
140.9, 112.1, 103.6, 101.5, 96.7, 94.8, 78.4, 65.7, 56.8, 31.5;
MS (EI, 70 eV) m/z (% relative intensity, ion): 235(71,
[Mþ1þ]), 234(90, [Mþ]), 220(48), 219(55), 218(54),
216(59), 203(92), 201(52), 177(62), 176(95), 175(71),
161(100), 147(64), 115(52). IR (KBr) nmax: 3293, 2991,
2222, 1617, 1502, 1485, 1466, 1247, 1199, 1163, 1089,
1034, 931 cm21; Anal. calcd for C13H14O4: C, 66.66%; H,
6.02%. Found: C, 66.80%; H, 5.91%.
3.2.5. 1-Ethynyl-2-methoxy-4,5-methylenedioxybenzene
(11). KOH (1.88 g, 33.5 mmol) was added to the solution of
10 (784 mg, 3.35 mmol) in toluene (60 mL) and the reaction
mixture was placed into an oil bath preheated at 1108C and
stirred vigorously. The reaction was followed by TLC. The
deprotection started after 15–20 min and was complete in
5–10 min. In certain runs it was necessary to add more
KOH (in 200 mg portions) to the hot mixture to complete
the hydrolysis. The resulting suspension was cooled to room
temperature, the KOH was filtered off and the toluene was
evaporated. The brown crude product was recrystallized
from cyclohexane to afford 11 (495 mg, 2.81 mmol) as a
yellow solid. Yield: 84%; mp: 69–728C; 1H NMR (CDCl3;
250 MHz): d 6.87 (s, 1H), 6.50 (s, 1H), 5.94 (s, 2H), 3.84 (s,
3H), 3.23 (s, 1H); 13C NMR (CDCl3, 62.5 MHz): d 157.5,
149.3, 140.8, 112.5, 102.6, 101.6, 94.4, 80.2, 79.8, 56.7; MS
(EI, 70 eV) m/z (% relative intensity, ion): 176(100, [Mþ]),
3.2.3. 1-Bromo-2-methoxy-4,5-methylenedioxybenzene
(9).22 Sesamol (7.29 g, 52.8 mmol) was dissolved in glacial
acetic acid (16 mL), cooled to 08C and a solution of bromine
(6.64 g, 2.13 mL, 41.5 mmol) in glacial acid (9 mL) was
added to it dropwise. The reaction mixture was poured onto
ice and the separated greenish solid was filtered, and dried
over P2O5 in vacuum resulting in bromosesamol (7.2 g,
33.0 mmol). Yield: 66%; mp: 87–888C (lit.: 888C). 1H
NMR (d6-DMSO; 250 MHz): d 9.8 (br, 1H), 7.04 (s, 1H),
6.58 (s, 1H), 5.95 (s, 2H); 13C NMR (d6-DMSO, 62.5 MHz):
d 148.7, 147.2, 140.5, 111.6, 101.4, 98.30, 98.25; MS (EI,
70 eV) m/z (% relative intensity, ion): 218(80), 216(85,
[Mþ]), 187(14), 160(54), 158(57), 132(37), 130(39),
109(76), 108(100), 95(91).
161(74), 133(15), 103(28), 75(56), 53(61). IR (KBr) nmax
:
3303, 2981, 2918, 2107, 1622, 1503, 1482, 1420, 1360,
1269, 1192, 1149, 1077, 1034, 1002, 926, 749 cm21; Anal.
calcd for C10H8O3: C, 68.18; H, 4.58. Found: C, 67.97; H,
4.74.
To a solution of bromosesamol (7.20 g, 33 mmol) in
dioxane (34 mL) was added KOH (6.72 g, 120 mmol) and
dimethyl sulfate (3.20 mL, 34 mmol). The reaction mixture
was stirred at 658C for 10 h and was left standing at room
temperature overnight. Then it was poured onto ice and the
white crystals were filtered, washed with water and dried
over P2O5 in vacuum to give 9 (6.94 g, 30 mmol). Yield:
91%; mp: 75–778C; 1H NMR (CDCl3; 250 MHz): d 6.99 (s,
1H), 6.56 (s, 1H), 5.94 (s, 2H), 3.82 (s, 3H); 13C NMR
(CDCl3, 62.5 MHz): d 151.1, 147.7, 141.8, 112.6, 101.7,
101.3, 95.8, 57.1; MS (EI, 70 eV) m/z (% relative intensity,
ion): 232(81), 230(90, [Mþ]), 217(89), 215(96), 187(39),
65(39), 53(100).
3.2.6. 6-(20-(200,400-Diacetoxyphenyl)ethynyl)-1-methoxy-
3,4-methylenedioxybenzene (12a). A 10 mL dry Schlenk
flask was purged with argon and charged with 3e (219 mg,
0.80 mmol), 11 (237 mg, 1.35 mmol), Pd(OAc)2 (9 mg,
0.04 mmol, 5%), CuI (1.52 mg, 0.008 mmol, 1%), P(tBu)3-
HBF4 (12 mg, 0.04 mmol, 5%), and diisopropylamine
(1 mL). The reaction mixture was stirred under argon at
508C for 1.5 h, than it was cooled to 258C, diluted with
ether, filtered through a Celite pad and concentrated under
reduced pressure. The crude product was purified by silica
gel column chromatography to afford 12 (73 mg, 0.2 mmol)
as white solid. Yield: 26%; mp: 153–1548C; 1H NMR
(CDCl3; 250 MHz): d 7.53 (d, 1H, J¼8.5 Hz), 6.95–7.02
(m, 2H), 6.87 (s, 1H), 6.52 (s, 1H), 5.95 (s, 2H), 3.84 (s, 3H),
2.36 (s, 3H), 2.29 (s, 3H); 13C NMR (CDCl3, 62.5 MHz): d
168.7, 168.5, 156.8, 151.6, 150.5, 149.2, 141.0, 133.0,
119.1, 116.0, 115.5, 111.9, 103.7, 101.6, 94.7, 91.1, 86.3,
56.6, 21.1, 20.8; MS (EI, 70 eV) m/z (% relative intensity,
ion): 368(82, [Mþ]), 326(100), 295(31), 285(35), 270(57),
241(92), 69(75). IR (KBr) nmax: 2971, 1761, 1614, 1502,
1486, 1424, 1369, 1196, 1033 cm21; Anal. calcd for
C20H16O7: C, 65.22; H, 4.38. Found: C, 65.37; H, 4.49.
3.2.4. 1-(30-Hydroxy-30-methyl-butyn-10-yl)-2-methoxy-
4,5-methylenedioxybenzene (10). A dry Schlenk flask
was charged with 9 (1.16 g, 5 mmol), PdCl2(PPh3)2
(176 mg, 0.25 mmol, 5%), CuI (50 mg, 0.25 mmol, 5%)
and diisopropylamine (15 mL), followed by the addition of
2-methyl-3-butyn-2-ol (2.9 mL, 2.52 g, 30 mmol, 6 equiv.).
The reaction mixture was stirred under argon in 808C oil
bath for 24 h. After this time (75% conversion) PdCl2(PPh3)2
(44 mg, 0.063 mmol, 1.25%), CuI (10 mg, 0.05 mmol, 1%)
and alkyne (0.60 mL, 1.25 equiv.) were added and the
reaction was continued for another 24 h, when it was
complete. The precipitate (diisopropyl-ammonium bromide)
was removed by filtration and the solvent was evaporated
3.2.7. Cicerfuran (1).7 A dry Schlenk flask was charged
with 3e (200 mg, 0.73 mmol), 11 (193.4 mg, 1.09 mmol),