1748
Y. MASUDA et al.
= =
7.2 Hz, 1-H3), 1.10 (3H, d, J
7.1 Hz, 4-CH3), 1.46–1.65 (4H, m, 5-, 8-H2),
1.79–1.87 (1H, m, 6-H), 2.06 (3H, s, OAc), 2.40 (1H,
brine, dried with MgSO4, and concentrated under
reduced pressure. The residue was chromatographed
1.04 (3H, t,
J
on silica gel to give 14 (647 mg, 87
z
) as a colorless
21
oil, n2D1 1.4586. [
a
]
11.8 (
c
1.00, CHCl3). IR nmax
dq,
J
17.8, 7.2 Hz, 2-Ha), 2.52 (1H, dq,
J
-
=
=
17.8,
D
(ˆlm) cm-1: 3335 (s, O–H). NMR dH (500 MHz,
7.2 Hz, 2-Hb), 2.66 (1H, ddq, J
=
9.2, 7.1, 4.6 Hz,
=
=
7.8, 4.9 Hz, 7-H). NMR dC
CDCl3): 0.91 (3H, d,
J
6.8 Hz, 4-CH3), 0.96 (3H, t,
4-H), 4.67 (1H, dt,
J
=
=
6.7 Hz, 2-CH3),
J
7.4 Hz, 7-H3), 0.97 (3H, d,
J
(100 MHz, CDCl3): 7.7, 10.0, 15.8, 18.1, 21.1, 23.3,
0.93–0.99 (1H, m, 3-Ha), 1.32–1.45 (1H, m, 3-Hb),
1.49–1.59 (2H, m, 6-H2), 1.60–1.67 (1H, m, 4-H),
34.0, 34.1, 35.4, 43.8, 78.9, 171.0, 215.0. Anal.
Found: C, 68.21; H, 10.41
C, 68.38; H, 10.59
z. Calcd. for C13 H24O3:
1.67–1.76 (1H, m, 2-H), 3.34 (1H, ddd,
J
=
8.9, 5.5,
10.7, 6.1 Hz, 1-Ha),
10.7, 4.9 Hz, 1-Hb). Anal. Found:
C, 67.24; H, 12.53 . Calcd. for C9H20O2: C, 67.45;
H, 12.58
z
.
=
J
3.4 Hz, 5-H), 3.45 (1H, dd,
=
3.53 (1H, dd,
J
(3R,5S,6R)-6-Acetoxy-3,5-dimethyl-2-octanone
z
(4
). To a stirred solution of 15 (100 mg, 0.64 mmol)
z.
in dry Et2O (10 ml) was added a solution of
MeMgBr in THF (0.93
M
, 0.72 ml, 0.67 mmol) at
C. The mixture was stirred for 0.5 h at room
temperature, quenched by adding sat. NH4Cl aq. at
C, and extracted with diethyl ether. The extract
-
(2R,4S,5R)-2,4-Dimethyl-5-heptanolide (15). To a
stirred solution of 14 (448 mg, 2.80 mmol) in CH2Cl2
(6 ml) were added NMO (1.31 g, 11.2 mmol) and
TPAP (74.6 mg, 0.212 mmol) at room temperature.
The mixture was stirred for 12 h at room tempera-
ture, ˆltered through silica gel, and the silica gel layer
was washed with CH2Cl2. The combined ˆltrate and
washings were concentrated under reduced pressure.
The residue was chromatographed on silica gel to
78
9
0
9
was successively washed with water and brine, dried
with Na2SO4, and concentrated under reduced pres-
sure, before pyridine (5 ml) and Ac2O (1 ml) were
added to residual 2 at 0
stirred for 48 h at room temperature, quenched by
adding water at 0 C, and extracted with diethyl
9C. The reaction mixture was
9
give 15 (344 mg, 79
z
) as a colorless solid, mp 32–
ether. The extract was successively washed with
water, sat. CuSO4 aq., sat. NaHCO3 aq. and brine,
dried with Na2SO4, and concentrated under reduced
pressure. The residue was chromatographed on silica
20
+
33
9
C. [
a
]
32.6 (
c
1.10, CHCl3). IR nmax (ˆlm)
D
cm- : 1730 (s, C O). NMR dH (400 MHz, CDCl3):
1
=
0.97 (3H, d,
Hz, 5-CH2C
J
=
6.8 Hz, 4-CH3), 1.00 (3H, t,
J
=
7.3
=
H
3), 1.28 (3H, d,
J
7.1 Hz, 3-CH3),
gel to give 4 (97 mg, 2 steps, 70z) as a pale yellow
20
1.30–1.40 (1H, m, 4-H), 1.50–1.62 (1H, m, 5-
aCH3), 1.74–1.85 (2H, m, 3-Ha, 5-C bCH3),
13.2, 6.3, 3.2 Hz, 3-Hb), 2.49 (1H,
7.1, 6.8, 6.3 Hz, 2-H), 3.90 (1H, ddd,
10.0, 7.1, 2.9 Hz, 5-H). Anal. Found: C, 69.20; H,
10.56 . Calcd. for C9H16O2: C, 69.19; H, 10.32
oil, n2D1 1.4365. [
a
]
D
+
=
20.4 (
c
1.00, CHCl3). IR nmax
(ˆlm) cm- : 1735 (s, C O), 1720 (s, C O), 1245 (s,
1
=
C
H
H
=
1.90 (1H, ddd,
ddq,
J
C–OAc). NMR
7.8 Hz, 8-H3), 0.87 (3H, d,
1.05–1.13 (1H, m, 4-Ha), 1.12 (3H, d,
d
H (400 MHz, CDCl3): 0.86 (3H, t,
J
J
=
J
=
=
J
=
7.1 Hz, 5-CH3),
=
J
6.8 Hz,
z
z
.
3-CH3), 1.48–1.68 (3H, m, 4-Hb, 7-H2), 1.77–1.84
(1H, m, 5-H), 2.07 (3H, s, OAc), 2.13 (3H, s, 1-H3),
=
9.2, 6.8, 4.9 Hz, 3-H), 4.68 (1H,
(4R,6S,7R)-7-Acetoxy-4,6-dimethyl-3-nonanone
2.63 (1H, ddq,
J
(
3
). To a stirred solution of 15 (100 mg, 0.64 mmol)
dt, J 7.8, 4.9 Hz, 6-H). NMR dC (100 MHz,
=
in dry Et2O (10 ml) was added a solution of
CDCl3): 9.9, 15.7, 17.7, 21.1, 23.3, 27.8, 33.9, 35.3,
EtMgBr in THF (0.89
M
, 0.76 ml, 0.67 mmol) at
C. The mixture was stirred for 0.5 h at room
temperature, quenched by adding sat. NH4Cl aq. at
C, and extracted with diethyl ether. The extract
44.9, 78.8, 171.1, 212.6. Anal. Found: C, 67.46; H,
-
78
9
z z
10.50 . Calcd. for C12H22O3: C, 67.26; H, 10.35 .
0
9
(2R,4S,5S)-1-tert-Butyldimethylsilyloxy-5-hydrox-
y-2,4-dimethylheptane (11 ). Lipase PS-D (Amano
was successively washed with water and brine, dried
with Na2SO4, and concentrated under reduced pres-
sure, before pyridine (5 ml) and Ac2O (1 ml) were
?
Enzyme, Inc.; 96 mg) was suspended in a solution of
11 (1.84 g, 6.70 mmol) in vinyl acetate (18.5 ml), and
the mixture was stirred at room temperature for 2
days. Additional lipase PS-D (90 mg) was then added
to the reaction mixture. After stirring for 9 days, the
mixture was ˆltered through Celite, and the Celite
layer was washed with diethyl ether. The combined
ˆltrate and washings were concentrated under
reduced pressure. The residue was chromatographed
added to residual 1 at 0
for 48 h at room temperature, quenched by adding
water at 0 C, and extracted with diethyl ether. The
9C. The mixture was stirred
9
extract was successively washed with water, sat.
CuSO4 aq., sat. NaHCO3 aq. and brine, dried with
Na2SO4, and concentrated under reduced pressure.
The residue was chromatographed on silica gel to
give 3 (95 mg, 2 steps, 65
z
) as a pale yellow oil, nD21
on silica gel to give 11
?
(1.19 g, 64
z
) as a colorless
20
24
D
+
+
7.62 (
1.4355. [
a
]
12.1 (
c
1.05, CHCl3). IR nmax (ˆlm)
oil, n2D4 1.4438. [
a
]
c 1.45, CHCl3). IR nmax
D
cm- : 1735 (s, C O), 1720 (s, C O), 1245 (s,
(ˆlm) cm-1: 3385 (br.m, O–H), 1090 (s, Si–O). NMR
1
=
=
C–OAc). NMR dH (400 MHz, CDCl3): 0.857 (3H, t,
dH (400 MHz, CDCl3): 0.03 (6H, s, Si–CH3), 0.85
J
=
7.6 Hz, 9-H3), 0.86 (3H, d,
J
=
7.1 Hz, 6-CH3),
(3H, d, J 6.8 Hz, 4-CH3), 0.88 (3H, d, J 6.6 Hz,
= =