2850 J . Org. Chem., Vol. 61, No. 8, 1996
Shiraki et al.
added. The mixture was stirred for an additional 23 h, diluted
with EtOAc (1 L), and washed with saturated aqueous
NaHCO3 (1 L) and brine (1 L × 2). The organic layer was
dried and concentrated in vacuo. The residue was passed
through a short column of silica gel (EtOAc/hexane, 1:10) to
give 14 (14.8 g) as a colorless oil, which was used in the next
step. An analytical sample was obtained by repeated chro-
matography on silica gel: TLC, Rf 0.58 (EtOAc/hexane, 1:3);
(s, 1 H); HRMS calcd for C23H33O7 (M+ - CH2OCH3) m/ z
421.2224, found 421.2210.
(2R,3R,4S,5Z)-4-(Ben zyloxy)-3-(m et h oxym et h oxy)-4-
m eth yl-1,2-bis(p iva loyloxy)-5-d ecen e (23). The following
reaction was carried out under Ar. To a stirred solution of 20
(2.36 g, 5.1 mmol) in THF (60 mL) was added Ph3PdCH(CH2)3-
CH3 [1 M solution in THF, 15.0 mL, 15.0 mmol: this ylide
solution was prepared as follows; a mixture of 33.1 g (80.1
mmol) of CH3(CH2)4P+Ph3Br- and sodium amide (3.12 g, 80.0
mmol) in THF (80 mL) was heated under reflux for 4.5 h, the
solution was cooled to rt, and the supernatant solution was
used for the Wittig reaction]. The solution was stirred at rt
while 15.0 mL of the ylide solution was added after 10 min
and 20 min (total 30.0 mL). The solution was stirred for an
additional 30 min, quenched by adding a small amount of H2O,
diluted with EtOAc (300 mL), and washed with saturated
aqueous NH4Cl (150 mL) and saturated brine (150 mL × 2).
The organic layer was dried and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(EtOAc/hexane, 1:40) to give 23 (2.39 g, 91%) as a colorless
mp 78-80 °C; [R]19 +51.3° (c 1.40, CHCl3); IR (neat) 2990,
D
1740, 1480, 1460, 1400 cm-1; 1H NMR (270 MHz) δ 1.02, 1.17
(2 s, each 9 H), 1.31, 1.35 (2 s, each 3 H), 1.61 (s, 3 H), 4.09
(dd, J ) 6.2, 11.9 Hz, 1 H), 4.24 (d, J ) 8.6 Hz, 1 H), 4.37 (d,
J ) 3.7 Hz, 1 H), 4.47-4.59 (m, 3 H), 5.27 (ddd, J ) 2.6, 6.2,
8.6 Hz, 1 H), 5.71 (d, J ) 3.7 Hz, 1 H), 7.25-7.38 (m, 5 H).
Anal. Calcd for C27H40O8: C, 65.83; H, 8.19. Found: C, 65.83,
H, 8.15.
3-O-Ben zyl-3-C-m et h yl-5,6-d i-O-p iva loyl-r-D-a llofu r -
a n ose (15). A solution of 14 (14.8 g) in 60% aqueous CF3-
COOH (200 mL) was stirred for 6.5 h. The solution was
neutralized by addition of 10 M aqueous NaOH, diluted with
EtOAc (1 L), and washed with H2O (500 mL × 3). The organic
layer was dried and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (EtOAc/
hexane, 1:3) to give a 5:1 anomeric mixture 15 (12.1 g, 90%
from 5) as an inseparable colorless oil: TLC, Rf 0.15 (EtOAc/
hexane, 1:3); IR (neat) 3490, 2970, 1730, 1480 cm-1; 1H NMR
(270 MHz) δ 1.19 (s, 9 H × 2), 1.45 (s, 5/6 × 3 H), 1.51 (s, 1/6
× 3 H), 3.80 (d, J ) 2.2 Hz, 1/6 × 1 H), 3.82 (d, J ) 4.0 Hz, 5/6
× 1 H), 4.07-4.59 (m, 5 H), 5.08 (ddd, J ) 2.6, 5.9, 8.8 Hz, 5/6
× 1 H), 5.18-5.24 (m, 1/6 × 1 H), 5.22 (d, J ) 4.0 Hz, 5/6 × 1
H), 5.30 (d, J ) 2.2 Hz, 1/6 × 1 H), 7.26-7.40 (m, 5 H).
oil: TLC, Rf 0.61 (EtOAc/hexane, 1:5); [R]24 +16.0° (c 1.17,
D
CHCl3); IR (neat) 2950, 1730, 1480, 1460, 1400 cm-1; 1H NMR
(270 MHz) δ 0.82 (t, J ) 7.2 Hz, 3 H), 1.15, 1.19 (2 s, each 9
H), 1.29-1.32 (m, 4 H), 1.52 (s, 3 H), 2.21-2.24 (m, 2 H), 3.40
(s, 3 H), 3.79 (d, J ) 1.5 Hz, 1 H), 4.31 (dd, J ) 9.2, 12.3 Hz,
1 H), 4.45, 4.53 (ABq, J ) 12.3 Hz, each 1 H), 4.63 (dd, J )
2.2, 12.3 Hz, 1 H), 4.73, 4.80 (ABq, J ) 6.6 Hz, each 1 H), 5.27
(d, J ) 12.1 Hz, 1 H), 5.57-5.67 (m, 2 H), 7.29-7.32 (m, 5 H);
13C NMR (100 MHz) δ 13.9, 21.9, 22.5, 27.09, 27.14, 28.2, 31.9,
38.6, 38.7, 56.5, 64.5, 64.7, 72.6, 80.5, 83.9, 97.8, 126.91, 126.94,
128.1, 130.1, 135,4, 139.2, 177.2, 178.2; HRMS, calcd for
C30H47O7 (M+ - H) m/ z 519.3318, found 519.3292.
(2R,3R,4R)-2-(Ben zyloxy)-3-(m eth oxym eth oxy)-2-m eth -
yl-4,5-bis(p iva loyloxy)p en ta n a l (20). To a cold (0 °C)
stirred solution of 15 (2.92 g, 6.5 mmol) in MeOH (60 mL) was
added an aqueous solution (40 mL) of NaIO4 (5.52 g, 25.8
mmol). After stirring for 3 h, the solution was diluted with
saturated brine (200 mL) and extracted with CH2Cl2 (150 mL
× 3). The combined extracts were dried and concentrated in
vacuo to give crude 16 (3.25 g), which was used in the next
step without further purification, as a colorless oil: TLC, Rf
0.53 (EtOAc/hexane, 1:3); IR (neat) 2960, 1735, 1480, 1460,
(2R ,3R ,4S )-3-(Me t h o x y m e t h o x y )-4-m e t h y l-1,2-b is -
(p iva loyloxy)-4-d eca n ol (37). A solution of 23 (3.09 g, 5.9
mmol) in EtOH (60 mL) was hydrogenated in the presence of
10% Pd on charcoal (300 mg) under an atmosphere of H2 for 3
h. A 1 M aqueous HCl (1 mL) solution was then added to the
mixture. The hydrogenation was continued for 14 h, and an
additional 700 mg of the catalyst was added. The hydrogena-
tion was continued for an additional 3 h. The catalyst was
removed by filtration through a pad of Celite and washed well
with EtOH. The combined filtrate and washing were concen-
trated in vacuo. The residue was purified by column chroma-
tography on silica gel (EtOAc/hexane, 1:6) to give 37 (2.62 g,
>100%) as a colorless oil, which was used in the next step
without further purification: TLC, Rf 0.36 (EtOAc/hexane, 1:4);
1
1390, 1360 cm-1; H NMR (90 MHz) δ 1.14, 1.19 (2 s, each 9
H), 1.42 (s, 3 H), 4.05 (dd, J ) 5.0, 13.0 Hz, 1 H), 4.52 (dd, J
) 3.0, 13.0 Hz, 1 H), 4.64 (s, 2 H), 5.30-5.48 (m, 1 H), 5.68
(dd, J ) 1.0, 7.0 Hz, 1 H), 7.33 (s, 5 H), 8.17 (d, J ) 1.0 Hz, 1
H), 9.62 (s, 1 H).
[R]26 +2.7° (c 1.51, CHCl3); IR (neat) 3520, 2960, 1730, 1480,
D
1460, 1400 cm-1; H NMR (270 MHz) δ 0.89 (t, J ) 6.4 Hz, 3
1
A solution of crude 16 (3.25 g) in MeOH (60 mL) was stirred
in the presence of Et3N (2.7 mL, 19.4 mmol) for 1 h and
concentrated in vacuo to give crude 18 (3.00 g), which was used
in the next step without purification, as a colorless oil: TLC,
Rf 0.58 (EtOAc/hexane, 1:2); IR (neat) 3480, 2980, 1740, 1480,
1400, 1360 cm-1; 1H NMR (270 MHz) δ 1.16, 1.20 (2 s, each 9
H), 1.52 (s, 3 H), 2.94 (d, J ) 8.4 Hz, 1 H), 3.87 (t, J ) 8.4 Hz,
1 H), 4.36 (dd, J ) 3.7, 12.5 Hz, 1 H), 4.44 (dd, J ) 2.6, 12.5
Hz, 1 H), 4.63 (s, 2 H), 5.22 (ddd, J ) 2.6, 3.7, 8.4 Hz, 1H),
7.26-7.36 (m, 5 H), 9.63 (s, 1 H).
H), 1.17, 1.21 (2 s, each 9 H), 1.23 (s, 3 H), 1.11-1.62 (m, 10
H), 3.45 (s, 3 H), 3.55 (d, J ) 2.2 Hz, 1 H), 4.22 (dd, J ) 8.4,
12.5 Hz, 1 H), 4.60 (dd, J ) 2.2, 12.5 Hz, 1 H), 4.71, 4.83 (ABq,
J ) 6.4 Hz, each 1 H), 5.37 (dt, J ) 2.2, 8.4 Hz, 1 H); HRMS,
calcd for C23H43O6 (M+ - OH) m/ z 415.3056, found 415.3052.
(2R ,3R ,4S )-4-Me t h y l-1,2-b is (p iv a lo y lo x y )-3,4-d e c -
a n ed iol (38). A solution of 37 (2.62 g) in 6 M aqueous HCl
(100 mL) and THF (100 mL) was stirred for 6 h. The solution
was neutralized with 10 M aqueous NaOH and concentrated
in vacuo. The residue was partitioned between CH2Cl2 (200
mL) and saturated brine (200 mL), and the aqueous layer was
extracted with CH2Cl2 (200 mL × 2). The combined extracts
were dried and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (EtOAc/
hexane, 1:7) to give 38 (1.93 g, 82% from 23) as a colorless oil,
and 373 mg (14%) of 37 was recovered. 38: TLC, Rf 0.20
To a stirred solution of crude 18 (3.00 g) in CH2Cl2 (60 mL)
were added i-Pr2NEt (22.5 mL, 129.0 mmol) and methyl
chloromethyl ether (MOMCl) (4.9 mL, 64.5 mmol). The
solution was heated under reflux for 16 h, and i-Pr2NEt (9.0
mL) and MOMCl (2.5 mL) were added. After heating under
reflux for an additional 4 h, the solution was diluted with
EtOAc (250 mL) and washed with 0.2 M HCl solution (200
mL × 2), saturated aqueous NaHCO3 (200 mL), and saturated
brine (200 mL). The organic layer was dried and concentrated
in vacuo. The residue was purified by column chromatography
on silica gel (EtOAc/hexane, 1:10) to give 20 (2.36 g, 78% from
15) as a colorless oil, and 531 mg (19% from 15) of 18 was
recovered. 20: TLC, Rf 0.38 (EtOAc/hexane, 1:4); [R]26D -5.4°
(EtOAc/hexane, 1:5); [R]27 +5.1° (c 0.85, CHCl3); IR (neat)
D
3490, 2960, 2940, 1720, 1480, 1460, 1400 cm-1; 1H NMR (270
MHz) δ 0.89 (t, J ) 6.4 Hz, 3 H), 1.20, 1.22 (2 s, each 9 H),
1.23 (s, 3 H), 1.12-1.64 (m, 10 H), 3.57 (d, J ) 5.1 Hz, 1 H),
4.36 (dd, J ) 6.6, 12.5 Hz, 1 H), 4.55 (dd, J ) 2.8, 12.5 Hz, 1
H), 5.18 (ddd, J ) 2.8, 5.1, 6.6 Hz, 1 H); 13C NMR (100 MHz)
δ 14.1, 22.6, 23.2, 24.2, 27.06, 27.14, 29.9, 31.8, 37.2, 38.8, 63.1,
72.1, 73.9, 76.1, 177.5, 178.7; HRMS, calcd for C21H39O5 (M+
- OH) m/ z 371.2817, found 371.2795.
(c 1.27, CHCl3); IR (neat) 2970, 1740, 1480, 1400, 1370 cm-1
;
1H NMR (270 MHz) δ 1.17, 1.18 (2 s, each 9 H), 1.49 (s, 3 H),
3.37 (s, 3 H), 4.08 (d, J ) 4.9 Hz, 1 H), 4.19 (dd, J ) 6.8, 12.7
Hz, 1 H), 4.48, 4.65 (ABq, J ) 11.7 Hz, each 1H), 4.53 (dd, J
) 2.4, 12.7 Hz, 1 H), 4.63, 4.80 (ABq, J ) 6.6 Hz, each 1 H),
5.42 (ddd, J ) 2.4, 4.9, 6.8 Hz, 1 H), 7.24-7.35 (m, 5 H), 9.60
(2R,3R,4S)-3,4-(Isop r op ylid en ed ioxy)-4-m eth yl-1,2-bis-
(p iva loyloxy)d eca n e (39). To a cold (0 °C) stirred solution
of 38 (2.17 g, 5.6 mmol) in acetone (40 mL) was added