5
28 J . Org. Chem., Vol. 66, No. 2, 2001
Wang et al.
being stirred at 0 °C for 15 h, the reaction mixture was
quenched with saturated aqueous NH Cl, extracted with CH
Cl , washed with water and brine, dried (Na SO ), and
concentrated to give 20a as a yellow syrup which was used
for the next step without further purification.
J ) 14.8, 7.5, 0.9 Hz, 1H), 1.70 (dd, J ) 14.8, 8.8 Hz, 1H),
1.51 (s, 3H), 1.50 (s, 6H), 1.36 (s, 3H).
Ketone 9a was prepared in a way similar to that of ketone
8, using DMSO (0.117 g, 1.5 mmol), oxalyl chloride (0.072 mL,
0.75 mmol), 23a (0.16 g, 0.5 mmol), triethylamine (0.34 mL,
4
2
-
2
2
4
2
.45 mmol), and CH
2 2
Cl (total 2.0 mL). Ketone 9a was obtained
To a solution of the above crude 20a in pyridine (50 mL) at
as a colorless syrup (0.15 g, 98%) after flash chromatography
0
°C was added POCl
temperature for 3 h, the reaction mixture was diluted with
ether and quenched with saturated aqueous NH Cl at 0 °C.
The aqueous layers were extracted with ether (4 × 30 mL),
SO ), filtered,
3
(2.5 mL). After being stirred at room
2
5
(
Cl
hexanes-ethyl acetate, 5:1 to 2:1): [R]
D
) -42.9 (c 0.49, CH
2
-
-
1 1
2
); IR (NaCl) 1741 cm ; H NMR δ 4.73 (d, J ) 6.9 Hz, 1H),
4
4
.64 (d, J ) 7.3 Hz, 1H), 4.62 (d, J ) 6.9 Hz, 1H), 4.57 (ddd,
J ) 7.3, 4.2, 1.2 Hz, 1H), 4.34 (d, J ) 9.0 Hz, 1H), 3.80 (ddd,
J ) 6.0, 4.2, 3.3 Hz, 1H), 3.78 (d, J ) 9.0 Hz, 1H), 3.34 (s, 3H),
2
washed with water (3 × 50 mL), dried (Na
2
4
concentrated, and purified by flash chromatography (hexanes-
.44 (dd, J ) 15.2, 3.3 Hz, 1H), 2.29 (ddd, J ) 15.2, 6.0, 1.2
ether, 2:1) to give 21a as a colorless syrup (3.7 g, 54% from
2
5
-1
1
Hz, 1H), 1.50 (s, 3H), 1.43 (s, 3H), 1.40 (s, 3H), 1.33 (s, 3H);
1
9a ): [R]
D
) -34.4 (c 0.57, CHCl
3
); IR (NaCl) 1719 cm ; H
1
3
C NMR δ 203.7, 111.6, 111.4, 95.0, 82.2, 79.9, 77.5, 72.3, 70.8,
5.8, 37.3, 26.7, 26.5, 26.1, 24.7. Anal. Calcd for C15
6.95; H, 7.65. Found: C, 56.74; H, 7.49.
NMR δ 6.89 (dt, J ) 3.6, 1.5 Hz, 1H), 4.73 (s, 2H), 4.73 (m,
5
5
24 7
H O : C,
1
1
2
H), 4.20 (dd, J ) 6.9, 6.0 Hz, 1H), 3.94 (td, J ) 6.9, 4.2 Hz,
H), 3.76 (s, 3H), 3.38 (s, 3H), 2.73 (dm, J ) 17.1 Hz, 1H),
.35 (ddt, J ) 17.1, 6.9, 1.5 Hz, 1H), 1.41 (s, 3H), 1.39 (s, 3H);
C NMR δ 166.9, 134.6, 130.0, 109.8, 95.8, 75.9, 73.2, 72.4,
5.7, 52.3, 28.1, 27.1, 26.1
To a solution of 21a (2.3 g, 8.5 mmol) in dry THF (10 mL)
was added dropwise a solution of DIBAL-H (1.0 M in hexane,
8.0 mL, 18.0 mmol) over 20 min at -15 °C. Upon stirring at
°C for 1 h, the reaction mixture was quenched with the
P r ep a r a tion of Keton e 9b. Enoate 21b was prepared from
19b9d in a way similar to that of 21a : colorless syrup (57%
1
3
2
5
yield); [R]
D
) -47.8 (c 0.41, CHCl
3
); IR (NaCl) 1722, 1654
5
-
1 1
cm ; H NMR δ 6.91 (ddd, J ) 3.3, 1.8, 1.2 Hz, 1H), 4.74 (s,
2
6
4
1
1
2
H), 4.73 (m, 1H), 4.20 (dd, J ) 6.6, 6.0 Hz, 1H), 3.97 (td, J )
.6, 4.5 Hz, 1H), 3.77 (s, 3H), 3.39 (s, 3H), 2.73 (ddt, J ) 17.7,
.5, 1.2 Hz, 1H), 2.35 (ddt, J ) 17.7, 6.6, 1.8 Hz, 1H), 1.70-
.50 (m, 8H), 1.40 (m, 2H); 13C NMR δ 166.9, 134.9, 129.9,
10.4, 95.8, 75.5, 73.2, 72.0, 55.7, 52.3, 38.0, 35.6, 27.2, 25.2,
4.2, 23.9.
1
0
4
saturated aqueous NH Cl, filtered, and washed with ether. The
filtrate was concentrated to give the allylic alcohol as a
colorless syrup (2.2 g, 100%) which was used directly for the
next step.
To a solution of the above allylic alcohol (2.2 g, 8.5 mmol),
NMO (1.76 g, 15.0 mmol), pyridine (4.2 mL, 27.0 mmol), water
Triol 22b was prepared from 21b in a way similar to that
of triol 22a : white crystals (71% yield); mp 104.0-105.5 °C
25
(
recrystallized from hexanes-ether); [R]
D
) +25.3 (c 0.28,
-1
1
CHCl
3
); IR (NaCl) 3420 cm ; H NMR δ 4.76 (d, J ) 6.6 Hz,
(
(
0.85 mL, 24.0 mmol) in t-BuOH (16 mL) was added OsO
0.015 g) under N with stirring. Upon refluxing for 6 h, the
4
1
4
3
1
H), 4.72 (d, J ) 6.6 Hz, 1H), 4.29 (dd, J ) 4.8, 1.8 Hz, 1H),
2
.26 (d, J ) 4.8 Hz, 1H), 4.04 (td, J ) 6.3, 4.8 Hz, 1H), 3.71-
.64 (m, 1H), 3.67 (d, J ) 11.1 Hz, 1H), 3.54 (d, J ) 11.1 Hz,
H), 3.41 (s, 3H), 1.95 (dd, J ) 14.8, 4.8 Hz, 1H), 1.89 (dd, J
reaction mixture was cooled, quenched with saturated aqueous
Na (5 mL), and concentrated. The resulting residue was
filtered through a short silica gel plug, and washed with ethyl
acetate and CH Cl -EtOH (2:1). The filtrate was concentrated,
2
2 3
S O
) 14.8, 6.3 Hz, 1H), 1.75-1.50 (m, 8 H), 1.45-1.30 (m, 2H);
2
2
13
C NMR δ 110.4, 95.8, 77.9, 73.7, 73.6, 73.2, 69.3, 68.2, 56.0,
7.9, 35.1, 33.4, 25.2, 24.2, 23.8. Anal. Calcd for C15
6.59; H, 8.23. Found: C, 56.61; H, 8.03.
and the residue was purified by flash chromatography (ethyl
3
5
26 7
H O : C,
acetate-hexane, 2:1 to 1:0 v/v) to give triol 22a as a light
2
5
yellow syrup (1.4 g, 77%): [R]
D
3
) +25.7 (c 0.35, CHCl ); IR
Ketalization of 22b (1.2 g, 3.77 mmol) in a way similar to
-
1 1
(
NaCl) 3439 cm ; H NMR δ 4.74 (d, J ) 6.7 Hz, 1H), 4.70 (d,
J ) 6.7 Hz, 1H), 4.32-4.23 (m, 2H), 3.94 (dt, J ) 7.5, 4.8 Hz,
that of 22a led to the formation of a mixture of 23b and 24b
in a ratio of 3.5:1. The mixture was separated by flash
chromatography (hexanes-ethyl acetate, 5:1 to 1:1 v/v) to give
1
1
1
1
7
H), 3.77 (m, 2H), 3.68 (dd, J ) 6.3, 5.4 Hz, 1H), 3.61 (dd, J )
1.2, 4.2 Hz, 1H), 3.55 (dd, J ) 11.2, 6.0 Hz, 1H), 3.38 (s, 3H),
.98 (dd, J ) 14.7, 4.8 Hz, 1H), 1.80 (dd, J ) 14.7, 7.5 Hz,
H), 1.49 (s, 3H), 1.36 (s, 3H); 13C NMR δ 109.6, 95.8, 78.2,
7.5, 73.6, 73.3, 73.1, 67.9, 55.8, 34.0, 27.9, 25.6.
2
3b as a white crystal (1.05 g, 77%) and 24b as a colorless
25
syrup (0.25 g, 19%). 23b: mp 106-108 °C; [R]
0
D
) -38.8 (c
-1
1
.41, CHCl ); IR (NaCl) 3484 cm ; H NMR δ 4.78 (d, J ) 6.9
3
Hz, 1H), 4.71 (d, J ) 6.9 Hz, 1H), 4.32 (dd, J ) 5.7, 3.0 Hz,
1H), 4.26 (d, J ) 8.9 Hz, 1H), 4.09 (dd, J ) 7.8, 5.7 Hz, 1H),
3.92 (br d, J ) 3.0 Hz, 1H), 3.83 (d, J ) 8.9 Hz, 1H), 3.55 (ddd,
J ) 12.6, 7.8, 4.5 Hz, 1H), 3.40 (s, 3H), 2.61 (br s, 1H, OH),
2.07 (t, J ) 12.6 Hz, 1H), 1.78 (ddd, J ) 12.6, 4.5, 0.9 Hz, 1H),
1.70-1.30 (m, 10 H), 1.46 (s, 3H), 1.40 (s, 3H); C NMR δ
109.8, 109.4, 95.2, 81.9, 77.6, 77.1, 74.5, 71.5, 70.5, 55.6, 38.3,
35.2, 34.2, 27.8, 26.5, 25.2, 24.2, 23.9. Anal. Calcd for
To a solution of triol 22a (0.42 g, 1.5 mmol) in 2,2-
dimethoxypropane (5 mL) was added a solution of catalytic
amount of SnCl in 1,2-dimethoxyethane (0.2 mL) at -10 °C
2
with stirring. After stirring at -10 °C for 12 h, the reaction
mixture was slowly warmed to 0 °C and stirred at this
temperature for another 2 h. The reaction mixture was then
quenched with triethylamine (0.2 mL) and diluted with water
and ether. The aqueous solution was extracted with ether. The
combined organic layers were washed with water and brine,
1
3
18 30 7
C H O : C, 60.32; H, 8.44. Found: C, 60.65; H, 8.32. 24b:
-
1 1
IR (NaCl) 3486 cm ; H NMR δ 4.81 (d, J ) 6.9 Hz, 1H), 4.71
(d, J ) 6.9 Hz, 1H), 4.40-4.30 (m, 2H), 3.90-3.80 (m, 2H),
3.77 (d, J ) 11.7 Hz, 1H), 3.57 (d, J ) 11.7 Hz, 1H), 3.40 (s,
3H), 3.22 (br s, 1H, OH), 1.84 (ddd, J ) 14.7, 7.2, 1.8 Hz, 1H),
1.75-1.25 (m, 11H), 1.50 (s, 6H).
2 4
dried (Na SO ), filtered, and concentrated to give a yellow
syrup (a mixture of 23a and 24a in a ratio of 3.2:1 as judged
1
by H NMR). The mixture was separated by flash chromatog-
raphy (hexanes-ethyl acetate, 5:1 to 1:1 v/v) to afford 23a as
a colorless oil (0.29 g, 62%) and 24a as a colorless oil (0.09 g,
Alcohol 23b (1.10 g, 3.08 mmol) was oxidized in a way
2
5
-1
1
9%). 23a : [R]
D
) -51.1 (c 0.19, CHCl
3
); IR (NaCl) 3485 cm
;
similar to that of 23a to afford ketone 9b as a colorless syrup
(1.05 g, 97%): [R]
1
25
H NMR δ 4.77 (d, J ) 6.6 Hz, 1H), 4.70 (dd, J ) 6.6, 0.6 Hz,
D
2 2
) -38.8 (c 0.76, CH Cl ); IR (NaCl) 1742
-
1 1
1
H), 4.33 (dd, J ) 6.0, 3.1 Hz, 1H), 4.22 (d, J ) 9.0 Hz, 1H),
.11 (dd, J ) 7.8, 6.0 Hz, 1H), 3.88 (dd, J ) 3.1, 2.4 Hz, 1H),
.84 (d, J ) 9.0 Hz, 1H), 3.57 (ddd, J ) 12.3, 7.8, 4.5 Hz, 1H),
.39 (s, 3H), 2.62 (d, J ) 2.4 Hz, 1H, OH), 2.06 (dd, J ) 12.9,
2.3 Hz, 1H), 1.82 (ddd, J ) 12.9, 4.5, 0.6 Hz, 1H), 1.48 (s,
H), 1.45 (s, 3H), 1.40 (s, 3H), 1.35 (s, 3H); 13C NMR δ 109.5,
09.2, 95.3, 81.9, 78.0, 77.5, 74.2, 71.5, 70.6, 55.6, 34.5, 28.1,
cm ; H NMR δ 4.77 (d, J ) 6.9 Hz, 1H), 4.66 (d, J ) 6.9 Hz,
1H), 4.63 (d, J ) 7.2 Hz, 1H), 4.59 (ddd, J ) 7.2, 3.9, 1.5 Hz,
1H), 4.38 (d, J ) 9.0 Hz, 1H), 3.86 (ddd, J ) 6.0, 3.9, 3.0 Hz,
1H), 3.83 (d, J ) 9.0 Hz, 1H), 3.37 (s, 3H), 2.49 (dd, J ) 15.0,
3.0 Hz, 1H), 2.32 (ddd, J ) 15.0, 6.0, 1.5 Hz, 1H), 1.80-1.20
4
3
3
1
3
1
2
13
(m, 10H), 1.47 (s, 3H), 1.43 (s, 3H); C NMR δ 204.0, 112.3,
111.6, 94.9, 82.2, 79.6, 77.2, 72.7, 70.8, 55.8, 37.3, 36.4, 34.1,
7.7, 26.6, 25.9. Anal. Calcd for C15
H
26
O
7
: C, 56.59; H, 8.23.
26.7, 26.1, 25.2, 24.1, 23.6. Anal. Calcd for C18
H, 7.92. Found: C, 60.39; H, 7.76.
P r ep a r a tion of Keton e 10. To a solution of enoate 14a
(0.954 g, 4.5 mmol) in dry THF (10 mL) was added dropwise
methylmagnesium bromide (3 M in ether, 4.5 mL, 13.5 mmol)
28 7
H O : C, 60.66;
1
Found: C, 56.50; H,7.99. 24a : H NMR δ 4.78 (d, J ) 6.9 Hz,
1
6
H), 4.69 (d, J ) 6.9 Hz, 1H), 4.41-4.32 (m, 2H), 3.85 (d, J )
.6 Hz, 1H), 3.80 (m, 1H), 3.78 (d, J ) 12.0 Hz, 1H), 3.57 (d,
J ) 12.0 Hz, 1H), 3.40 (s, 3H), 3.21 (br s, 1H, OH), 1.86 (ddd,