Synthesis of (
R
)- and (
S
)- Muscone
1391
・
=
5.7 Hz,
25.0 mmol) in THF (12.5 ml) was added BH3 THF
5.7 Hz, 10.5 Hz, 1 H, 1-Ha), 3.86 (dd,
J
(1.0 in THF; 25.0 ml, 25.0 mmol) at „15 C, and
M
9
10.5 Hz, 1 H, 1-Hb), 4.95 (m, 2 H, 5-H2), 5.62 (m,
=
the reaction mixture was stirred overnight at room
temperature. The reaction was quenched by adding
1 H, 4-H), 7.33 (d,
J
8.4 Hz, 2 H, Ar-H), 7.77 (d,
8.4 Hz, 2 H, Ar-H). Anal. Found: C, 61.48; H,
=
J
water at 0
9
C, and the aqueous phase was treated with
7.23
7.13
z
z
. Calcd. for C13H18O3S (254.35): C, 61.39; H,
.
potassium carbonate to separate from the THF
phase. The aqueous phase was extracted with ether
and concentrated in vacuo. The resulting residue was
(R)-3-Methylhex-5-enenitrile (7). To a stirred solu-
chromatographed on silica gel (hexane ethyl acetate,
tion of 6 (3.6 g, 14.3 mmol) in DMSO (50.0 ml) was
W
8:1) to give 3.7 g (85
z
) of 3. The analytical sample
added NaCN (839 mg, 17.1 mmol), and the reaction
was further puriˆed by distillation; bp 58
9
C at 2
mixture was stirred overnight at 40 C. The reaction
9
Torr, n2D4 1.4295, [
a
]
c
2.07, MeOH). IR
was quenched by adding water at 09C, and then the
22
=
=
+10.9 (
D
=
(ˆlm)
n
maxcm„1: 3450 (s, O-H), 1725 (s, C O), 1160
aqueous phase was extracted with pentane and con-
(s, C-O), 1H-NMR (300 MHz, CDCl3)
d
: 0.94 (d,
J
centrated in vacuo. The residue was puriˆed by distil-
=
6.9 Hz, 3 H, 3-CH3), 1.43 [s, 9 H, C(CH3)3], 1.79 (s,
lation, bp 77
9
C at 50 Torr, to give 1.0 g (65
z
) of 7,
20
D
n2D5 1.4280, [
a
]
c
2.18, MeOH). IR (ˆlm)
=
=
„16.6 (
1 H, OH), 2.11 (m, 1 H, 3-H), 2.17 (m, 1 H, 2-Ha),
=
=
2.33 (m, 1 H, 2-Hb), 3.44 (dd,
J
6.6 Hz, 10.8 Hz,
5.1 Hz, 10.8 Hz, 1 H, 4-Hb).
n
maxcm„1: 2240 (m, C
ø
N), 1640 (m, C C), 1000 (s),
1 H, 4-Ha), 3.55 (dd,
J
920 (s). 1H-NMR (300 MHz, CDCl3)
d
: 1.08 (d,
6.6 Hz, 3 H, 3-CH3), 1.94 (m, 1 H, 3-H), 2.11 (t,
7.2 Hz, 2 H, 4-H2), 2.22 (dd, 6.6 Hz, 16.5 Hz,
5.7 Hz, 16.5 Hz, 1 H, 2-Hb),
5.08 (m, 2 H, 6-H2), 5.70 (m, 1 H, 5-H). Anal.
Found: C, 77.14; H, 10.40; N, 12.42 . Calcd. for
C7H11N (109.17): C, 77.01; H, 10.16; N, 12.83
=
=
=
Anal. Found: C, 61.71; H, 10.41
C9H18O3 (174.24): C, 62.04; H, 10.41
z
z
. Calcd for
.
J
J
J
=
=
J
1 H, 2-Ha), 2.33 (dd,
(R)-2-Methylpent-4-enyl p-toluenesulfonate
To a stirred solution of 3 (3.0 g, 17.2 mmol) in pyri-
dine (6.0 ml) and CH2Cl2 (4.0 ml) was added -tol-
uenesulfonyl chloride (3.9 g, 20.5 mmol) at 0 C.
After stirring overnight at 0 C, the reaction mixture
(6).
z
p
z.
9
9
(R)-4-Methylheptadeca-1,16-dien-6-one (
stirred solution of 11-iodoundec-1-ene (436 mg,
1.56 mmol) in ether (4.0 ml) was added -BuLi
(1.62 in pentane; 1.92 ml, 3.11 mmol) at „50 C.
8). To a
was quenched with water and extracted with ether.
Evaporation of the solvent provided 4 which was
subjected directly to the next reaction without further
puriˆcation.
t
M
9
A solution of nitrile 7 (100 mg, 0.92 mmol) in ether
(1.0 ml) was then added at this temperature. The
reaction mixture was quenched by adding 3 N HCl.
After stirring overnight at room temperature, the
aqueous phase was extracted with ethyl acetate and
concentrated in vacuo. The resulting residue was
To a stirred solution of 4 (200 mg, 0.61 mmol) in
CH2Cl2 (10.0 ml) was added DIBAL (0.90
M
in
hexane; 1.01 ml, 0.91 mmol) at „78
9
C over 30 min.
The reaction mixture was then quenched at once with
a saturated Rochelle salt (potassium sodium tartrate)
solution. After stirring at room temperature for 2 h,
the aqueous phase was extracted with CH2Cl2 and
concentrated in vacuo to give aldehyde 5 which was
subjected directly to the next reaction without further
puriˆcation.
chromatographed on silica gel (hexane ethyl acetate,
W
24
30:1) to give 140 mg (58
+3.3 ( 1.14, MeOH). IR (ˆlm)
) of 8, n2D5 1.4550, [
= =
z a]
D
c
n
maxcm„1: 1710 (s, C
1
=
=
O), 1640 (m, C C), 1000 (s), 910 (s). H-NMR
(300 MHz, CDCl3)
d: 0.88 (d, J 6.3 Hz, 3 H,
=
To a slurry of methyl(triphenyl)phosphonium
bromide (426 mg, 1.19 mmol) in DME (8.0 ml)
4-CH3), 1.25–1.35 (m, 12 H), 1.53–1.55 (m, 2 H,
8-H2), 1.94–2.21 (m, 6 H, 3-, 15-H2, 4-H and 5-Ha),
2.32–2.42 (m, 3 H, 5-Hb and 7-H2), 4.89–5.01 (m, 4
H, 1-, 17-H2), 5.68–5.80 (m, 2 H, 2-, 16-H). Anal.
was added NaHMDS (0.60
M
in toluene; 1.89 ml,
1.14 mmol) at room temperature, and the resulting
yellow solution was stirred for 30 min. To the alde-
hyde 5 (145 mg, 0.57 mmol) in DME (8.0 ml) was
added this Wittig reagent at room temperature, and
the reaction mixture was stirred for 30 min. The reac-
tion mixture was quenched with water and extracted
with ether. Evaporation of the solvent and puriˆca-
tion of the product by silica gel column chro-
Found: C, 81.83; H, 12.20
z
. Calcd. for C18H32O
(264.45): C, 81.75; H, 12.20
z
.
(R)-3-Methylcyclopentadec-5-enone
(
9
). To
a
stirred solution of 8 (34.7 mg, 0.131 mmol) in dry
degassed CH2Cl2 (25.0 ml) was added a solution of
Grubbs' reagent (5.0 mg, 0.006 mmol) predissolved
in CH2Cl2 (6.0 ml). The resulting purple-colored so-
matography (hexane ethyl acetate, 8:1) gave 98.5 mg
W
28
(66
z
) of 6, n2D5
=
n
1.5050, [
a
]
=
„2.1 (
c
0.39,
lution was heated overnight at 45
9
C and then concen-
D
=
MeOH). IR (ˆlm)
maxcm„1: 1640 (m, C C), 1600
trated in vacuo. The resulting residue was chro-
=
=
d
×
matographed on silica gel (hexane ether, 20:1 2) to
(m, aromatic), 1360 (s, S O), 1180 (s, S O), 980
W
1
(s), 820 (s). H-NMR (300 MHz, CDCl3)
: 0.87 (d,
6.3 Hz, 3 H, 2-CH3), 1.88 (m, 2 H, 3-H2), 2.07
(m, 1 H, 2-H), 2.43 (s, 3 H, Ar-CH3), 3.80 (dd,
give 16.4 mg (53
z
) of 9. IR (ˆlm)
n
maxcm„1: 1710 (s,
O), 970 (s). H-NMR (300 MHz, CDCl3) : 0.91
, 5 )-9] and 0.98 [(3 , 5 )-9] (d, 6.6 Hz,
1
=
=
J
C
d
J
=
[(3
R
Z
R
E
J
=