(6S,7S,9R,10R)-6,9-Epoxynonadec-18-ene-7,10-diol Synthesis
J . Org. Chem., Vol. 63, No. 5, 1998 1417
4H), 5.31-5.26 (m, 2H), 4.17-4.09 (m, 4H), 3.72-3.68 (m, 2H),
3.64-3.60 (m, 2H), 2.14 (s, 6H) ppm; 13C NMR (75 MHz,
CDCl3) δ 170.13, 152.94, 115.78, 70.78, 67.54, 30.37, 20.91
ppm.
required compound 13 (295 mg, 79% yield) as white crystals:
mp 69-72 °C; [R]D -6.79 (c 0.66, CHCl3); IR (neat) 1596, 1509,
1
1358, 1239, 1187 cm-1; H NMR (300 MHz, CDCl3) 7.80 (d, J
) 8.4 Hz, 4H), 7.31 (d, J ) 8.4 Hz, 4H), 6.61 (s, 4H), 5.51-
5.46 (m, 2H), 5.25-5.15 (m, 2H), 4.74-4.71 (m, 2H), 3.95 (dd,
J ) 5.28, 3.98 Hz, 4H), 2.51-2.44 (m, 10H), 1.90 (dt, J ) 6.6,
6.6 Hz, 4H), 1.33-1.19 (m, 12H), 0.87 (t, J ) 6.7 Hz, 6H) ppm;
13C NMR (75 MHz, CDCl3) 152.72, 144.57, 135.76, 134.18,
129.66, 127.98, 122.70, 115.45, 80.27, 68.67, 34.88, 32.52,
31.39, 28.87, 22.51, 21.63, 14.04 ppm; EIMS (m/z) 726 (M+,
0.4), 418 (8.5), 246 (7.9), 199 (15), 172 (52), 107 (42), 91 (100).
1,4-Bis((2S ,4S ,5S )-2-(t osyloxy)-4,5-d ih yd r oxyd e c-1-
yloxy)ben zen e (14). To a stirred solution of AD-mix-R [K2-
CO3 (248 mg, 1.8 mmol), K3Fe(CN)6 (592 mg, 1.8 mmol),
NaHCO3 (151 mg, 1.8 mmol), K2OsO2(OH)4 (225 mg), and
(DHQ)2PHAL (23 mg, 0.03 mmol)] in 50% aqueous t-BuOH (6
mL) was added E-olefin 13 (217.8 mg, 0.3 mmol). The
resulting mixture was stirred for 24 h at rt. Sodium sulfite
(0.9 g) was added. The mixture was stirred for 3 h and
extracted with ethyl acetate. The combined extracts were
washed with aqueous HCl and brine and dried over Na2SO4.
Evaporation of the solvent gave a residue (14) without
purification.
1,4-Bis((2S)-2,3-ep oxy-1-p r op oxy) ben zen e (5). K2CO3
(8.28 g, 60 mmol) was added to a stirred solution of the bromide
acetate (9.4 g) in methanol (30 mL). The mixture was stirred
at room temperature for 2 days and filtered. After evaporation
of the filtrate, the residue was dissolved in ethyl acetate (200
mL) and water (20 mL), washed with water and brine, and
dried over Mg2SO4. The solvent was evaporation and the crude
product was recrystallized from hexanes-ethyl acetate to give
4.0 g of compound 5 in 90% yield: mp 69-71 °C; [R]D +9.14 (c
1
0.7, CHCl3); IR (neat) 3073, 1590, 1464 cm-1; H NMR (300
MHz, CDCl3) δ 6.86 (s, 4H), 4.17 (dd, J ) 8.4, 2.4 Hz, 2H),
3.90 (dd, J ) 8.4, 4.2 Hz, 2H), 3.35-3.33 (m, 2H), 2.90 (dd, J
) 3.6, 3.0 Hz, 2H), 2.75 (dd, J ) 3.6, 2.1 Hz, 2H) ppm; 13C
NMR (75 MHz, CDCl3) δ 153.06, 115.64, 69.43, 50.25, 44.76
ppm; EIMS (m/z) 222 (M+, 100), 205 (3.0), 192 (9.2), 179 (15);
HRMS calcd for C12H14O4 222.0892, found 222.0900.
1,4-Bis((2S)-2-h yd r oxy-4-d ecyn -1-yloxy)ben zen e (11).
A solution of heptyne (3.89 g, 40.5 mmol) in tetrahydrofuran
(100 mL) at -78 °C was treated with n-butyllithium (2.5 M in
hexane, 16.2 mL), and the resultant mixture was stirred for
15 min. Diepoxide 5 (3 g, 13.5 mmol) and boron trifluoride
etherate (5 mL) were successively added dropwise. After an
additional 2 h at -78 °C, the cold bath was removed.
Saturated aqueous NaHCO3 (50 mL) was then added. The
aqueous layer was extracted with ethyl acetate (3 × 50 mL),
and the combined organic layers were dried over Na2SO4,
filtered, and concentrated. Flash chromatography (petroleum
ether/ethyl acetate ) 10/1) furnished the alcohol 11 (4.2 g, 75%
yield) as a white solid: mp 56-59 °C; [R]D +272.6 (c 0.08,
CHCl3); IR (neat) 3368, 2240, 1508, 1458 cm-1; 1H NMR (300
MHz, CDCl3) δ 6.86 (s, 4H), 4.13-4.08 (m, 2H), 4.05 (dd, J )
9.2, 3.9 Hz, 2H), 3.93 (dd, J ) 9.2, 6.4 Hz, 2H), 2.57-2.52 (m,
6H), 2.19-2.13 (m, 4H), 1.51-1.44 (m, 4H), 1.37-1.26 (m, 8H),
0.89 (t, J ) 7.1 Hz, 6H) ppm; 13C NMR (75 MHz, CDCl3)
153.12, 115.64, 83.50, 75.04, 71.44, 68.86, 31.11, 28.63, 23.98,
22.21, 18.73, 13.98 ppm; EIMS (m/z) 414 (M+, 57), 304 (2.9),
263 (3.9), 262 (20), 219 (0.6), 152 (11), 110 (100); HRMS calcd
for C26H38O4 414.2770, found 414.2805.
1,4-Bis((2R,4S,5S)-2,5-epoxy-4-h ydr oxydec-1-yloxy)ben -
zen e (15). To a solution of crude product 14 (250 mg) in
MeOH (10 mL) was added K2CO3 (250 mg). After 24 h of
stirring at rt, most of the MeOH was evaporated under reduced
pressure. The residue was dissolved in water and extracted
with ethyl acetate. The combined organic layers were washed
with brine, dried over Na2SO4, and concentrated to give 15
without purification.
1,4-Bis((2R,4S,5S)-2,5-ep oxy-4-((ter t-b u t yld im et h ylsi-
lyl)oxy)d ec-1-yloxy)ben zen e (16). To a stirred solution of
15 in dry THF (10 mL) was added tert-butyldimethylsilyl
chloride (151 mg, 1 mmol) at rt. The mixture was stirred for
24 h at the same temperature, and water (5 mL) was added.
The organic layer was separated, and the aqueous layer was
extracted with ethyl acetate (3 × 10 mL). The combined
organic layers were washed with brine, dried (Na2SO4), and
concentrated under reduced pressure. The residue was puri-
fied by flash chromatography (petroleum ether/ethyl acetate
) 20/1) to afford 16 (180 mg, 90% yield for three steps) as a
colorless oil: [R]D +21.08 (c 0.3, CHCl3); IR (neat) 1508, 1470,
1,4-Bis((E)-(2S)-2-h ydr oxy-4-decen -1-yloxy)ben zen e (12).
THF (5 mL) and diglyme (50 mL) were added to a flask with
LiAlH4 (2 g). The solution was heated until THF was distilled
out, and then the solution was allowed to cool to rt. A solution
of alkyne 11 (2.1 g, 5.1 mmol) in diglyme (5 mL) was then
added. The reaction mixture was refluxed for 24 h. The oil
bath was replaced with a salt-ice bath. Water was slowly
added dropwise until the solid turned gray. After filtration,
the solid was washed with ethyl acetate and the combined
organic layers were washed with water and brine, dried over
Na2SO4, and concentrated under reduced pressure. The crude
product was purified by flash chromatography (petroleum
ether/ethyl acetate ) 3/1) to afford 12 (2.02 g, 95% yield) as a
white solid: mp 70-75 °C; [R]D +13.5 (c 1.02, CHCl3); IR (neat)
1
1255 cm-1; H NMR (300 MHz, CDCl3): δ 6.83 (s, 4H), 4.51
(ddd, J ) 12.5, 7.8, 4.7 Hz, 2H), 4.28 (dt, J ) 2.9, 2.9 Hz, 2H),
3.91 (d, J ) 4.8, 4H), 3.85 (dt, J ) 6.9, 3.1 Hz, 2H), 2.01-1.98
(m, 4H), 1.61 (m, 4H), 1.31-1.26 (m, 12H), 0.91-0.86 (m, 24H),
0.10-0.04 (m, 12H) ppm; 13C NMR (75 MHz, CDCl3) 153.44,
115.58, 83.83, 75.47, 73.22, 71.41, 38.61, 32.24, 29.49, 26.08,
25.85, 22.76, 18.15, 14.17 ppm; EIMS (m/z) 678 (M+, 15), 319
(6.8), 285 (33), 263 (13), 227 (35), 187 (42), 171 (51), 149 (32),
113 (39); HRMS calcd for C38H70O6Si2 678.4711, found 678.4683.
(2R ,4S ,5S )-2,5-E p o x y -4-((t er t -b u t y ld im e t h y ls ily l)-
oxy)d eca n -1-ol (17). To a stirred solution of 16 (100 mg, 0.2
mmol) in 2:1 CH3CN-H2O (9 mL) was added CAN (345 mg,
0.63 mmol) at 0 °C. The mixture was stirred for an additional
1 h at 0 °C. The product was extracted with ethyl acetate (3
× 10 mL). The combined organic layers were washed with
water, an aqueous sodium bisulfite solution, and brine and
dried over Na2SO4. After evaporation of the solvent, the crude
product was purified by flash chromatography (petroleum
ether/ethyl acetate ) 10/1) to afford 17 (61 mg, 68% yield) as
a colorless oil. The ratio of diastereomers was 94:6 (deter-
mined by GC-MS (column: OV-1, 30 m × 0.2 mm)): IR (neat)
1
3416, 1601, 1454 cm-1; H NMR (300 MHz, CDCl3) δ 6.84 (s,
4H), 5.58 (dt, J ) 15.3, 6.4 Hz, 2H), 5.45 (dt, J ) 15.3, 6.8 Hz,
2H), 4.00 (m, 2H), 3.93 (dd, J ) 9.3, 3.4 Hz, 2H), 3.82 (dd, J )
9.3, 7.1 Hz, 2H), 2.35-2.29 (m, 4H), 2.09-1.99 (m, 4H), 1.20-
1.40 (m, 14H), 0.88 (t, J ) 7.0 Hz, 6H) ppm; 13C NMR (75 MHz,
CDCl3) 153.20, 134.90, 124.82, 115.65, 72.27, 69.82, 36.80,
32.68, 31.47, 29.14, 22.60, 14.14 ppm; EIMS (m/z) 418 (M+,
43), 313 (1.4), 264 (14), 199 (1.7), 165 (2.4), 151 (13), 135 (7.9),
110 (100); HRMS calcd for C26H42O4 418.3083, found 418.3075.
1,4-Bis((E-(2S)-2-(t osyloxy)-4-d ecen -1-yloxy)b en zen e
(13). Sodium hydride (48 mg, 2 mmol) was added to the
solution of 12 (215 mg, 0.51 mmol) in 10 mL of THF at 0 °C.
After the solution was stirred for 1 h, N-TsIm (334 mg, 1.53
mmol) was added. After an additional 24 h at 0 °C, saturated
NH4Cl (10 mL) was added and the reaction mixture was
extracted with ethyl acetate (3 × 20 mL). The organic phases
were washed with brine, dried (Na2SO4), and evaporated.
Purification of the crude product by flash chromatography
(petroleum ether/ethyl acetate ) 20/1 to 5/1) yielded the
3426, 1464, 1285, 1191 cm-1 1H NMR (300 MHz, CDCl3) δ
;
4.28-4.23 (m, 2H), 3.79-3.69 (m, 1H), 3.72 (dd, J ) 11.7, 3.0,
1H), 3.48 (m, 1H), 2.30 (br, 1H), 1.90-1.84 (m, 2H), 1.55 (m,
2H), 1.30-1.22 (m, 6H), 0.87 (m, 12H), 0.07 (s, 3H), 0.06 (s,
3H) ppm; EIMS (m/z) 303 (M+ + 1, 7.00), 301 (M+ - 1, 1.7),
285 (51), 267 (6.9), 245 (48), 227 (65), 187 (39), 171 (100);
HRMS calcd for C16H33O3Si 301.2199, found 301.2182.
(2R ,4S ,5S )-2,5-E p o x y -4-((t er t -b u t y ld im e t h y ls ily l)-
oxy)d eca n -1-a l (18). A solution of the oxalyl chloride (26 mg,
0.2 mmol) in dichloromethane (5 mL) was stirred and cooled
to -60 °C. Dimethyl sulfoxide (33 mg, 0.425 mmol) in