9142 J . Org. Chem., Vol. 63, No. 24, 1998
Notes
subjected to flash chromatography (silica, 19:1 hexane/ethyl
acetate elution), and concentration of the appropriate fractions
afforded the title compound 20 (453 mg, 89%) (Rf ) 0.6) as a
Anhydrous potassium carbonate (41 mg, 0.30 mmol) was
added to a magnetically stirred solution of 3-methoxy-4-(triiso-
propylsiloxy)phenyl formate (48 mg, 0.15 mmol) in methanol (1
mL). The resulting solution was left to stir at room temperature
for 2 h and then treated with water (3 mL) and extracted with
CH2Cl2 (3 × 5 mL). The combined organic phases were then
dried (MgSO4), filtered, and concentrated under reduced pres-
sure to give a viscous, yellow oil, which was subjected to flash
chromatography (silica, 9:1 hexane/ethyl acetate elution). Con-
centration of the appropriate fractions afforded 3-methoxy-4-
(triisopropylsiloxy)phenol (40 mg, 91%) (Rf ) 0.5, silica, 4:1
hexane/ethyl acetate elution) as a clear, colorless oil: IR (neat,
1
clear, colorless oil: IR (neat, NaCl, cm-1) 1692, 1584; H NMR
(300 MHz) δ 10.41 (s, 1H), 7.38 (dd, J ) 7.7 and 1.7 Hz, 1H),
7.12 (m, 2H), 4.57 (septet, J ) 6.0 Hz, 1H), 3.98 (s, 3H), 1.39 (d,
J ) 6.0 Hz, 6H); 13C NMR (75 MHz) δ 190.2, 153.7, 150.1, 129.9,
123.8, 121.4, 119.2, 71.3, 61.9, 21.9; MS (70 eV) m/z 194 (25,
M
+•), 152 [100, (M - C3H6)+•], 134 [68, (M - CO - C3H6)+•];
HRMS calcd for C11H14O3 194.0943, found 194.0940.
d. Wan g Resin /3-Hydr oxy-4-m eth oxyben zaldeh yde Con -
ju ga te (22). The procedure described by Hamper et al.20 for
the attachment of 4-hydroxybenzaldehyde to Wang resin was
followed. Thus, Wang resin (642 mg of 200-400 mesh material,
0.73 mmol/g loading, Calbiochem-Novabiochem) was washed
with CH2Cl2 (1 × 10 mL) and THF (1 × 10 mL). The dried resin
was then treated with THF (12 mL), 3-hydroxy-4-methoxyben-
zaldehyde (23, isovanillin) (500 mg, 3.8 mmol), and triphen-
ylphosphine (447 mg, 1.7 mmol), and the resulting mixture was
stirred at room temperature for 5 min. Diethyl azodicarboxylate
(298 µL, 1.9 mmol) was then added dropwise, and the resulting
mixture was stirred overnight at room temperature. The
reaction solvents were then removed, and the resin was washed
successively with THF, DMF, methanol, CH2Cl2, and diethyl
ether (2 × 5 mL of each). The filtered resin was dried under
reduced pressure to give conjugate 22 (652 mg). This material
had ca. 10% w/w attached 3-hydroxy-4-methoxybenzaldehyde as
determined by trifluoroacetic acid (TFA) cleavage (see below).
1
NaCl, cm-1) 3562, 1610; H NMR (300 MHz) δ 6.75 (d, J ) 8.6
Hz, 1H), 6.46 (d, J ) 2.7 Hz, 1H), 6.38 (dd, J ) 8.6 and 2.7 Hz,
1H), 5.22 (s, 1H), 3.85 (s, 3H), 1.23 (m, 3H), 1.07 (m, 18H); MS
(70 eV) m/z 296 (19, M+•), 253 [73, (M - C3H6)+•], 238 [100, (M
- C3H6 - H3C•)+]; HRMS calcd for C16H28O3Si 296.1808, found
296.1802.
A magnetically stirred solution of 3-methoxy-4-(triisopropyl-
siloxy)phenol (280 mg, 0.94 mmol) and potassium carbonate (456
mg, 3.3 mmol) in DMF (6 mL) was treated in one portion with
2-bromopropane (348 µL, 2.8 mmol). The resulting mixture was
heated at 100 °C for 24 h and then cooled to room temperature,
diluted with water (10 mL), and extracted with diethyl ether (3
× 20 mL). The combined organic phases were washed with
water (2 × 5 mL), dried (MgSO4), filtered, and concentrated
under reduced pressure to give an orange oil. This material was
subjected to flash chromatography (silica, 49:1 hexane/ethyl
acetate elution), and two major fractions were obtained.
Concentration of the fraction containing the more mobile
component afforded the title compound 29 (60 mg, 34% at 56%
conversion) (Rf ) 0.7, silica, 4:1 hexane/ethyl acetate elution)
as a clear, colorless oil: 1H NMR (300 MHz) δ 6.75 (d, J ) 8.7
Hz, 1H), 6.47 (d, J ) 2.7 Hz, 1H), 6.37 (dd, J ) 8.7 and 2.7 Hz,
1H), 4.36 (septet, J ) 6.2 Hz, 1H), 3.80 (s, 3H), 1.31 (d, J ) 6.2
Hz, 6H), 1.25 (m, 3H), 1.10 (d, J ) 6.8 Hz, 18H); 13C NMR (75
MHz) δ 151.3, 150.9, 141.2, 118.0, 110.6, 105.0, 72.3, 55.7, 22.1,
17.8, 12.5; MS (70 eV) m/z 338 (76, M+•), 296 [47, (M - C3H6)+•],
253 [100, (M - C3H6 - C3H7•)+]; HRMS calcd for C19H34O3Si
338.2277, found 338.2283.
e. 3-Meth oxy-4-isop r op oxyp h en yla cetylen e (26). n-Bu-
tyllithium (51 mL of a 1.6 M solution in hexane, 82 mmol) was
added dropwise to a magnetically stirred solution of â,â-dibromo-
4-isopropoxy-3-methoxystyrene2 (14.4 g, 41 mmol) in THF (250
mL) maintained under a nitrogen atmosphere at -78 °C (dry
ice/acetone bath). The resulting dark-red solution was stirred
at -78 °C for a further 0.33 h and then allowed to warm to room
temperature. After an additional 1.5 h, the reaction mixture
was quenched with ammonium chloride (150 mL of a saturated
aqueous solution) and the THF was removed under a stream of
nitrogen. The residue was extracted with diethyl ether (1 × 150
mL), and the separated organic phase was dried (MgSO4),
filtered, and concentrated under reduced pressure to give a light-
yellow oil. This material was subjected to flash chromatography
(silica, 2:1 then 1:1 hexane/CH2Cl2 elution), and concentration
of the appropriate fractions then gave compound 26 (6.6 g, 85%)
(Rf ) 0.4, 1:1 hexane/CH2Cl2) as a clear, amber oil: IR (neat,
Concentration of the fraction containing the less mobile
component afforded starting material (123 mg, 44% recovery)
(Rf ) 0.5, silica, 4:1 hexane/ethyl acetate elution), which was
identical, in all respects, with an authentic sample.
Gen er a lized P r oced u r e for th e AlCl3-P r om oted Clea v-
a ge of Isop r op yl Ar yl Eth er s. A solution of the substrate (1
mmol) in CH2Cl2 (2.45 mL/mmol of substrate) was treated in
one portion with AlCl3 (1.15-1.3 mmol/isopropoxy group), and
the resulting mixture was stirred at room temperature for the
specified time (see below). Saturated aqueous ammonium
chloride (5 mL/mmol of substrate) was added to the reaction
mixture, which was then extracted with CH2Cl2 (3 × 25 mL/
mmol of substrate). The CH2Cl2 extracts were washed with
water (2 × 50 mL/mmol of substrate), dried (MgSO4), filtered,
and concentrated under reduced pressure. The resulting crude
products were purified according to the procedures described
below.
a . La m ella r in K (5). Subjection of lamellarin K trisisopro-
pyl ether (4) to the reaction conditions defined in the generalized
procedure afforded a solid on workup. This material was
subjected to flash chromatography (silica, 20:1, 10:1, then 5:1
CH2Cl2/methanol elution), and concentration of the appropriate
fractions then gave lamellarin K (5) (96%) (Rf ) 0.6, 10:1 CH2-
Cl2/methanol elution) as white needles, mp 230-232 °C (lit.2 mp
230-232 °C), which was identical, in all respects, to authentic
material.
b. La m ella r in T (7). Subjection of lamellarin T bisisopropyl
ether (6) to the reaction conditions defined in the generalized
procedure afforded a solid on workup. This material was
subjected to flash chromatography (silica, 99:1, 95:5, then 9:1
CH2Cl2/methanol elution), and concentration of the appropriate
fractions then gave lamellarin T (7) (89%) (Rf ) 0.2, 20:1 CH2-
Cl2/methanol elution) as white needles, mp 283-284 °C (lit.3 mp
214-218 °C), which was identical, in all respects, to authentic
material.
1
KBr, cm-1) 3286, 2105, 1598; H NMR (300 MHz) δ 7.04 (dd, J
) 8.2 and 1.5 Hz, 1H), 6.98 (d, J ) 1.5 Hz, 1H), 6.78 (d, J ) 8.2
Hz, 1H), 4.51 (septet, J ) 6.0 Hz, 1H), 3.81 (s, 3H), 3.01 (s, 1H),
1.33 (d, J ) 6.0 Hz, 6H); 13C NMR (75 MHz) δ 149.6, 148.1, 125.1,
115.2, 114.6, 114.1, 83.7, 75.6, 71.1, 55.7, 21.8; MS (70 eV) m/z
190 (28, M+•), 148 [100, (M - C3H6)+•], 133 [90, (M - C3H6
-
H3C•)+]; HRMS calcd for C12H14O2 190.0994, found 190.0990.
f. 3-Meth oxy-4-(tr iisopr opylsiloxy)ph en ylisopr opyl Eth er
(29). Triisopropylsilyl chloride (90 µL, 0.52 mmol) was added
to a magnetically stirred solution of 2-methoxy-1,4-benzenediol-
4-formate (13)21 (56 mg, 0.33 mmol) and imidazole (46 mg, 0.67
mmol) in DMF (1 mL). The resulting mixture was stirred at
room temperature for 16 h then quenched with water (2 mL)
and extracted with CH2Cl2 (1 × 20 mL). The separated organic
phase was washed with water (5 × 20 mL) and then dried
(MgSO4), filtered, and concentrated under reduced pressure. The
resulting light-yellow oil was subjected to flash chromatography
(silica, 19:1 hexane/ethyl acetate elution) and afforded, after
concentration of the appropriate fractions, 3-methoxy-4-(triiso-
propylsiloxy)phenyl formate (79 mg, 73%) (Rf ) 0.5, 4:1 hexane/
ethyl acetate elution) as a clear, colorless oil: IR (neat, NaCl,
1
cm-1) 1744, 1601; H NMR (300 MHz) δ 8.27 (s, 1H), 6.84 (d, J
) 8.6 Hz, 1H), 6.63 (d, J ) 2.7 Hz, 1H), 6.57 (dd, J ) 8.6 and
2.7 Hz, 1H), 3.78 (s, 3H), 1.23 (m, 3H); 1.05 (m, 18H); MS (70
eV) m/z 324 (9, M+•), 281 [100, (M - CO - CH3•)+]; HRMS calcd
for C17H28O4Si 324.1757, found 324.1757.
(20) Hamper, B. C.; Dukesherer, D. R.; South, M. S. Tetrahedron
Lett. 1996, 37, 3671.
(21) Guzman, J . A.; Mendoza, V.; Garcia, E.; Garibay, C. F.; Olivares,
L. Z.; Maldonado, L. A. Synth. Commun. 1995, 25, 2121.
c. 6-Hyd r oxy-2-(3′-h yd r oxy-4′-m eth oxyp h en yl)-5-m eth -
oxy-3-(3′,4′,5′-tr im eth oxyp h en yl)ben zo[b]fu r a n (9). Subjec-