4350 J . Org. Chem., Vol. 67, No. 12, 2002
Zanoni et al.
ter t-Bu tyl[3-[2-(4-m eth oxyben zyloxy)-3,3a,4,6a-tetr ah y-
d r o-2H-cyclop en ta [b]fu r a n -4-yl]-1-p en tyla llyloxy]d im e-
th ylsila n e (16).
88.4 d, 73.2 d, 47.4 d, 42.1 d, 38.2 t, 35.5 t, 31.6 t, 25.7 3 × q,
24.7 t, 22.4 t, 18.1 s, 13.8 q, -4.3 q, -4.8 q; ESI-MS m/z 389
[M + Na+].
7-[2-[3-(ter t-Bu tyld im eth ylsila n yloxy)oct-1-en yl]-5-h y-
d r oxycyclop en t-3-en yl]h ep t-5-en oic Acid (19).
Crude hydroxysulfone 15 (287 mg, 0.4347 mmol) was dissolved
in dry MeOH (15 mL) under an argon atmosphere. To the
solution was added Na2HPO4 (1.5 g), and the slurry was cooled
to -40 °C; after 10 min of vigorous stirring, sodium amalgam
(2.36 g, 10% of Na) was slowly added portionwise in such a
way to keep the temperature below -40 °C. At the end of the
addition, the temperature was allowed to reach -20 °C, and
stirring was continued for an additional 1.5 h. The mixture
was warmed to rt and filtered through a filter paper. Evapora-
tion of volatiles in vacuo under 40 °C gave a residue that was
partitioned between DCM (50 mL) and an aqueous saturated
solution of NaHCO3. The two phases were separated, and the
aqueous layer was reextracted with DCM (3 × 15 mL). The
organic phases were combined, washed with brine, dried over
Na2SO4, and concentrated at reduced pressure to give a residue
that was purified by flash chromatography on silica gel (SiO2
10 g). Elution with hexanes-Et2O (94:6) gave adduct 16 as a
colorless oil (171 mg, 81%): IR (liquid film) 2930, 2856, 1612,
1514, 1464, 1249, 1033, 835, 775 cm-1. Major anomer: 1H
NMR (300 MHz, CDCl3) δ 0.02 (s, 3H), 0.03 (s, 3H), 0.88 (t, J
) 6.5 Hz, 3H), 0.90 (s, 9H), 1.2-1.4 (br m, 6H), 1.4-1.6 (br m,
2H), 1.64-1.96 (m, 2H), 3.24 (br quintuplet, J ) 8.6 Hz, 1H),
3.4-3.52 (m, 1H), 3.82 (s, 3H), 4.08 (m, 1H), 4.42 and 4.67
(AB system of benzylic CH2, J ) 11.8 Hz, 2H), 5.14-5.22 (m,
2H), 5.46-5.55 (m, 2H), 5.73 (br d, J ) 5.4 Hz, 1H), 5.86 (br
d, J ) 5.4 Hz, 1H), 6.84-7.35 (AA′BB′ system, J ,) 8.6 Hz,
4H); 13C NMR (75 MHz, CDCl3) δ 159.0 s, 135.3 d, 135.2 d,
131.3 d, 130.3 s, 129.4 d, 128.2 d, 113.7 d, 103.5 d, 88.3 d, 73.3
d, 68.1 t, 55.1 q, 47.6 d, 42.6 d, 38.4 t, 34.9 t, 31.7 t, 25.8 3xq,
24.8 t, 22.6 t, 18.2 s, 14.0 q, -4.3 q, -4.8 q; ESI-MS m/z 486
[M+]. Anal. Calcd for C29H46O4Si: C, 71.56; H, 9.53. Found:
C, 71.63; H, 9.55.
Solid phosphonium salt 17 (467 mg, 1.026 mmol, 4 equiv) was
suspended in dry THF (5 mL) in a two-neck round-bottom flask
under an argon atmosphere. To the suspension was added
freshly sublimed potassium tert-butoxide (236 mg, 2.051 mmol,
8 equiv) portionwise at rt. After being stirred for 20 min, the
solution became deeply orange and a THF solution (1.5 mL)
of lactol 18 (94 mg, 0.256 mmol) was added via cannula
dropwise at rt. Stirring was continued for an additional 2 h,
and the reaction was quenched by adding a saturated aqueous
solution of NH4Cl (15 mL) and acetic acid (0.127 mL, 1.05
equiv); Et2O (20 mL) was added to the mixture and the organic
layer was separated, whereas the aqueous phase was extracted
with an additional Et2O (3 × 20 mL). The organic phases were
combined, dried on MgSO4, filtered, and concentrated at
reduced pressure. The crude acid was purified on silica gel
(15 g) using hexanes-EtOAc (8:2) as eluent. The acid 19 (95
mg, 83%) was thus obtained as a pale yellow oil as a 1:1
mixture of epimers at C-15 hydroxyl group: IR (liquid film)
3300-2600 (OH and COOH), 2928, 2856, 1713, 1462, 1253,
1065, 836, 775 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.02-0.08
(4s, 6H overall), 0.88 (t, J ) 6.5 Hz, 3H), 0.9 (s, 9H), 1.28 (br
s, 6H), 1.38-1.56 (m, 2H), 1.72 (quintuplet, J ) 6.7 Hz, 2H),
2-2.2 (m, 4H), 2.24-2.36 (m, 1H), 2.36 (br t, J ) 6.7 Hz, 2H),
3.18 (m, 1H), 4.05 (br q, J ) 6.4 Hz, 1H), 4.52 (dd, J ) 5.3, 2.6
Hz, 1H), 5.32-5.48 (m, 3H), 5.48-5.64 (m, 1H), 5.96-6.08 (m,
2H); 13C NMR (75 MHz) δ 179.3 (COOH) s, 139.4 d, 135.5 d,
133.0 d, 131.4 d, 129.6 d, 129.2 d, 76.3 d, 73.5 d, 49.8 d,* 49.6
d,* 46.8 d, 38.42 t,§ 38.37 t,§ 33.4 t, 31.8 t, 26.6 t, 25.9 3 × q,
25.0 t, 24.5 t, 24.0 t, 22.6 t, 18.2 s, 14.0 q, -4.3 q, -4.8 q (*,§
doubled signals due to the presence of epimers); ESI-MS
(negative ions) m/z 485 [M + Cl-], 449 [M - H-]. Anal. Calcd
for C26H46O4Si: C, 69.28; H, 10.29. Found: C, 69.33; H, 10.31.
7-[2-[3-(ter t-Bu tyldim eth ylsilan yloxy)oct-1-en yl]-5-oxo-
cyclop en t-3-en yl]h ep t-5-en oic Acid (20).
4-[3-(ter t-Bu tyld im eth ylsila n yloxy)oct-1-en yl]-3,3a ,4,-
6a -tetr a h yd r o-2H-cyclop en ta [b]fu r a n -2-ol (18).
To a solution of allylic alcohol 19 (76 mg, 0.1686 mmol) in DCM
(4 mL) at rt was added solid Dess-Martin periodinane (100
mg, 0.236 mmol, 1.4 equiv) in one portion. After the homoge-
neous solution was stirred for 3 h, the reaction was quenched
by adding dry Et2O (15 mL) and the suspension was quickly
filtered on a short pad of Celite. The Celite layer was washed
with Et2O (3 × 30 mL), and the organic phases were combined
and concentrated at reduced pressure WITHOUT HEATING.
The residue was purified by flash chromatography on silica
gel (SiO2, 4.5); elution with hexanes-Et2O (6:4) gave the
desidered enone 20 as a colorless oil (70 mg, 93%): IR (liquid
film) 3200-2600 (COOH), 2930, 2857, 1712, 1586, 1462, 1251,
Protected lactol 16 (353 mg, 0.7252 mmol) was dissolved in
DCM (11 mL), and pH ) 7 phosphate buffer (1 mL) was added
at rt under vigorous stirring. To the suspension was added
freshly crystallized DDQ (247 mg, 1.088 mmol, 1.5 equiv). After
1.5 h of stirring, the mixture was filtered on a short pad of
Celite and washed with DCM (150 mL). The solution was dried
over MgSO4, filtered, and concentrated at reduced pressure
keeping the water bath below 35 °C. The residue was purified
by flash chromatography on silica gel (SiO2 27 g); elution with
DCM-EtOAc (96:4) gave the desidered lactol 18, mixture 5:1
of hemiacetals, as a colorless oil (161 mg, 61%), which was
immediately used in the following step: IR (liquid film) 3416,
2929, 2857, 1463, 1360, 1253, 1032, 836, 775 cm-1. Major
anomer: 1H NMR (300 MHz, CDCl3) δ 0.02 (s, 3H), 0.03 (s,
3H), 0.88 (t, J ) 6.5 Hz, 3H), 0.90 (s, 9H), 1.2-1.4 (br m, 6H),
1.4-1.6 (br m, 2H), 1.64-1.96 (m, 2H), 2.82 (br s, 1H, OH),
3.24 (br quintuplet, J ) 8.6 Hz, 1H), 3.4-3.52 (m, 1H), 4.04-
4.15 (m, 1H), 5.24 (d, J ) 7.4 Hz,1H), 5.46-5.55 (m, 2H), 5.72
(br d, J ) 5.4 Hz, 1H), 5.82 (br d, J ) 5.4 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 135.5 d, 135.3 d, 131.1 d, 128.0 d, 99.0 d,
1
1081, 973, 836, 776, cm-1; H NMR (300 MHz, CDCl3) δ 0.03
(s, 3H), 0.05 (s, 3H), 0.88 (t, J (H,H) ) 6.5 Hz, 3H), 0.9 (s, 9H),
1.28 (br s, 6H), 1.40-1.58 (m, 2H), 1.72 (quintuplet, J ) 7.4
Hz, 2H), 1.95-2.18 (m, 3H), 2.36 (br t, J ) 7.5 Hz, 2H), 2.42-
2.56 (m, 2H), 3.72 (br t, J ) 7.2 Hz, 1H), 4.08 (br q, J ) 6 Hz,
1H), 5.3-5.6 (m, 4H), 6.22 (dd, J ) 1.7, 5.6 Hz, 1H), 7.52 (dt,
1H, J ) 2.8, 5.6 Hz,1H); 13C NMR (75 MHz, CDCl3) δ 210.6 s,
210.5 s, 179.1 s, 179.0 s, 165.2 d, 165.1 d, 138.1 d, 138.0 d,
132.7 d, 132.7 d, 129.8 d, 129.8 d, 128.1 d, 128.1 d, 126.3 d,
126.3 d, 73.0 d, 72.9 d, 49.8 d, 47.6 d, 47.3 d, 38.3 t, 38.2 t,