780
D. Oguro, H. Watanabe / Tetrahedron 67 (2011) 777e781
combined organic layer was washed with aqueous sodium bisulfate
solution, aqueous sodium carbonate solution and brine, dried over
anhydrous magnesium sulfate, and concentrated in vacuo. The res-
idue was chromatographed on silica gel (200 g). Elution with n-
hexane/ethyl acetate (30/1e10/1) gave (ꢀ)-3a (2.94 g, 50%) and
(ꢀ)-3b (0.84 g, 14%) both as colorless oils. Compound (ꢀ)-3a: IR
170.23; GCeMS: 194 (1, [Mꢁ1]þ), 137 (8), 108 (100), 91 (4), 79 (36),
53 (5), 41 (6), 29 (4); HRMS (ESI) calcd for C12H18NaO2 (MþNa)þ:
217.1205, found 217.1222.
4.1.4. (1R
*
,10S )-1-(20-Bromocyclohex-20-enyl)pentyl 2-chloroacetate
*
[(ꢀ)-4a]. To a stirred solution of (ꢀ)-3a (10.0 g, 40.5 mmol), pyri-
dine (5.8 g, 73.0 mmol) and DMAP (0.1 g, 0.8 mmol) in ether
(100 mL) was added chloroacetyl chloride (6.9 g, 60.8 mmol) at 2e8
ꢂC over 20 min. After stirred at room temperature for 1 h, to the
mixture was added water (100 mL) at 0 ꢂC and stirred for several
min. The aqueous layer, which was separated from the mixture was
extracted with ether. The combined organic layer was washed with
aqueous copper sulfate solution, water, aqueous sodium bi-
carbonate solution and brine, dried over anhydrous magnesium
sulfate, and concentrated in vacuo. The residue was chromato-
graphed on silica gel (300 g). Elution with n-hexane/ethyl acetate
(60/1e40/1) gave (ꢀ)-4a (12.3 g, 94%) as a colorless oil. IR (film):
(film) 3464, 2932, 2859, 1640, 1456, 1329, 1066, 975, 887, 709 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
1.70e1.85 (m, 3H), 2.04e2.08 (m, 2H), 2.38 (m, 1H), 4.20 (m, 1H),
6.32 (m, 1H); 13C NMR (100 MHz, CDCl3)
: 14.05, 20.77, 22.74, 23.29,
d: 0.92 (t, J¼7.1 Hz, 3H),1.26e1.60 (m, 8H),
d
27.78, 28.63, 33.22, 47.14, 71.74, 126.15, 133.96; GCeMS: 246
([Mꢁ1]þ), 160 (30), 87 (13), 81 (100), 69 (70), 57 (13), 51 (4), 41 (30),
29 (8); HRMS (FAB) calcd for C11H20BrO (MþH)þ: 247.0698, found
247.0722. Compound (ꢀ)-3b: IR (film) 3357, 2859, 1638, 1450, 1325,
1072, 1019, 970, 718 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d: 0.91 (t,
J¼7.1 Hz, 3H), 1.28e1.59 (m, 8H), 1.67e1.75 (m, 2H), 1.87 (m, 1H),
2.03e2.08 (m, 2H), 2.65 (m, 1H), 4.11 (br, 1H), 6.18 (dt, J¼1.8, 4.1 Hz,
1H); 13C NMR (100 MHz, CDCl3)
d
: 14.09, 20.21, 22.63, 24.71, 27.84,
2955, 2870, 1738, 1643, 1456, 1411, 1286, 1183, 973, 734 cmꢁ1
NMR (400 MHz, CDCl3)
;
1H
28.82, 31.83, 47.67, 73.93, 124.33, 132.27; GCeMS: 246 ([Mꢁ1]þ), 160
(28), 87 (15), 81 (100), 69 (76), 57 (14), 51 (5), 41 (31), 29 (7); HRMS
(FAB) calcd for C11H20BrO (MþH)þ: 247.0698, found 247.0679.
d
: 0.90 (t, J¼6.9 Hz, 3H), 1.20e1.40 (m, 4H),
1.50e1.65 (m, 2H), 1.70e1.90 (m, 4H), 2.05 (m, 2H), 2.53 (m, 1H),
4.02 (s, 2H), 5.48 (dt, J¼2.5, 7.1 Hz, 1H), 6.21 (dt, J¼4.1, 1.5 Hz, 1H);
13C NMR (100 MHz, CDCl3)
d: 13.90, 19.95, 22.49, 24.30, 27.44, 27.76,
4.1.2. (3R
hol [(ꢀ)-3a, 247 mg, 1.0 mmol] in ether (13 mL) was added
pentane solution of tert-butyllithium (1.48 M, 3.4 mL,
*
,3aR
*
)-Sedanolide [(ꢀ)-1a]. To a solution of bromoalco-
31.14, 40.97, 44.75, 76.32, 123.71, 133.07, 166.50; HRMS (ESI) calcd
for C13H20BrClNaO2 (MþNa)þ: 345.0233, found 345.0225.
a
5.0 mmol) at ꢁ78 ꢂC over 15 min. After being stirred at the same
temperature for 5 min, CO2 gas was bubbled into the reaction
mixture at the same temperature for 0.5 h. Then to the mixture at
ꢁ78 ꢂC was dropped methanol (0.5 mL) and the mixture was
allowed to warm to room temperature. The reaction mixture was
diluted with n-hexane and extracted with aqueous sodium car-
bonate solution. The combined aqueous layer was washed with
n-hexane and acidified by the addition of 3 N HCl at 0 ꢂC. To the
acidic solution was saturated with NaCl and the resulting mix-
ture was extracted with ethyl acetate. The extract was dried over
anhydrous magnesium sulfate and concentrated in vacuo to give
a crude hydroxy acid (286 mg). After a solution of crude hydroxy
acid (286 mg) and catalytic amount of TsOH in toluene (13 mL)
was stirred at room temperature for 12 h, the reaction mixture
was washed with saturated aqueous sodium bicarbonate solu-
tion and brine, dried over anhydrous magnesium sulfate, and
concentrated in vacuo. The residue was chromatographed on
silica gel (7 g). Elution with n-hexane/ethyl acetate (30/1e10/1)
gave (ꢀ)-1a (157 mg, 81%) as a colorless oil. For analysis further
distillation with using Kugelrohr gave (ꢀ)-1a as a colorless oil. IR
(film): 2936, 2865, 1758, 1683, 1454, 1332, 1225, 1185, 1028, 943,
4.1.5. (1R,10S)-1-(20-Bromocyclohex-20-enyl)pentan-1-ol
[(ꢁ)-3a]
and (1S,10R)-1- (20-bromocyclohex-20-enyl)pentan-1-ol [(þ)-3a]. A
mixture of (ꢀ)-4a (10.0 g, 30.9 mmol), Lipase OF (3.0 g) and a 0.1 M
phosphate buffer solution (pH 7.0, 200 mL) was stirred at room
temperature for 25 h. After filtration through CeliteÒ, filtrate was
extracted with ether and the extract was washed with aqueous
sodium bicarbonate solution and brine, dried over magnesium
sulfate, and concentrated in vacuo. The residue was chromato-
graphed on silica gel (300 g). Elution with n-hexane/ethyl acetate
(60/1e15/1) gave alcohol (ꢁ)-3a (5.88 g, 46%) as a product and
chloroacetate (ꢁ)-4a (3.07 g, 52%) as a residual substrate. In the
same manner described for the synthesis of (ꢀ)-4a, alcohol (ꢁ)-3a
(3.35 g, 13.6 mmol) afforded chloroacetate (þ)-4a (4.3 g, 97%) as
20
a colorless oil. [
a]
þ38.6 (c1.60, CHCl3); HRMS (ESI) calcd for
D
C13H20BrClNaO2 (MþNa)þ: 345.0233, found 345.0233. The chlor-
oacetate (þ)-4a (4.17 g, 12.9 mmol) was similarly hydrolyzed with
Lipase OF under the condition mentioned above excluding the re-
action time (24 h) to give alcohol (ꢁ)-3a (2.8 g, 87%, 99.8% ee) as
20
a colorless oil. [
a]
ꢁ23.9 (c1.25, CHCl3); HRMS (FAB) calcd for
D
C11H20BrO (MþH)þ: 247.0698, found 247.0739. On the other hand
chloroacetate (ꢁ)-4a (5.04 g, 15.6 mmol), which was obtained as
a residual substrate on the first enzymatic hydrolysis, was hydro-
lyzed again with Lipase OF similarly under the condition mentioned
752, 702 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
: 0.88 (t, J¼7.1Hz, 3H),
1.24e1.60 (m, 8H), 1.87e1.97 (m, 2H), 2.14e2.38 (m, 2H),
3.00e3.10 (m, 1H), 4.63 (dt, J¼2.8, 9.2 Hz, 1H), 6.82 (dd, J¼7.1,
above excluding the reaction time (60 h) to give residual chlor-
20
3.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
: 13.90, 21.14, 22.45,
oacetate (ꢁ)-4a (2.8 g, 81%) as a colorless oil. [
a]
ꢁ40.8 (c 1.19,
D
22.54, 25.12, 27.51, 31.49, 39.69, 81.84, 129.57, 136.18, 170.18;
GCeMS: 194 (1, [Mꢁ1]þ), 137 (8), 108 (100), 91 (4), 79 (36), 53 (5),
41 (6), 29 (4); HRMS (ESI) calcd for C12H18NaO2 (MþNa)þ:
217.1205, found 217.1222.
CHCl3); HRMS (ESI) calcd for C13H20BrClNaO2 (MþNa)þ: 345.0233,
found 345.0216. A mixture of (ꢁ)-4a (2.59 g, 8.0 mmol) and po-
tassium carbonate (0.13 g, 0.9 mmol), and MeOH (75 mL) was
stirred at room temperature for 3 h. After being neutralized with
acetic acid, the reaction mixture was concentrated in vacuo. The
residue was chromatographed on silica gel (80 g). Elution with n-
hexane/ethyl acetate (60/1e15/1) gave alcohol (þ)-3a (1.96 g, 99%,
4.1.3. (3S
*
,3aR
*
)-Sedanolide [(ꢀ)-1b]. In the same manner de-
scribed for the synthesis of (ꢀ)-1a, (ꢀ)-3b (247 mg, 1.0 mmol)
afforded sedanolide (ꢀ)-1b (136 mg, 70%) as a colorless oil. For
analysis further distillation with using Kugelrohr gave (ꢀ)-1b as
colorless crystals. Mp 34.5e35.0ꢂC; IR (film): 2933, 2861, 1763,
99.8% ee) as a colorless oil. [
a
]
20 þ24.6 (c 1.04, CHCl3); HRMS (FAB)
D
calcd for C11H20BrO (MþH)þ: 247.0698, found 247.0679.
1683, 1455, 1422, 1327, 1249, 1226, 1183, 1025, 930, 726 cmꢁ1
;
1H
4.1.6. (S)-1-(20-Bromocyclohex-20-enyl)pentan-1-one
[(þ)-5]. To
NMR (400 MHz, CDCl3)
d
: 0.91 (t, J¼7.3 Hz, 3H), 1.16 (m, 1H),
a stirred mixture of pyridinium chlorochromate (2.16 g, 10.0 mmol),
CeliteÒ (3.24 g), and dichloromethane (80 mL) was added alcohol
(ꢁ)-3a (1.24 g, 5.0 mmol) at room temperature for 5 min. After
being stirred at room temperature for overnight, the mixture was
decantated and filtered through silica gel pad and eluted with ether
1.30e1.60 (m, 5H),1.70e1.82 (m, 2H),1.94 (m,1H), 2.06 (m,1H), 2.19
(m, 1H), 2.35 (m, 1H), 2.49 (m, 1H), 3.96 (ddd, J¼8.9, 7.3, 5.3 Hz, 1H),
6.77 (dd, J¼6.9, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d: 13.88,
20.75, 22.51, 24.98, 25.36, 27.51, 34.31, 43.06, 85.32, 131.14, 135.18,