Synthesis of the Sex Pheromone of the Hair Crab
1535
=
29.8 mmol) in dry THF (100 ml) was added dropwise
to a blue solution of lithium (3.01 g, 447 mmol) in
ethylamine (88 g) while stirring at „70 C for 1 h.
HaHb), 3.81 (1H, dd,
J
10.2, 4.1 Hz, 1-HaHb), 4.24
= =
6.4, 5.9 Hz, 3-H), 4.63 (1H, d, J
(1H, dd-like,
J
=
9
6.8 Hz, N–H), 5.21 (1H, dd,
J
15.8, 6.4 Hz, 4-H),
5.60 (1H, dt-like, J 15.8, 6.1 Hz, 5-H), 7.27 (2H, d,
8.2 Hz, -Ar), 7.74 (2H, d, 8.2 Hz, -Ar).
Anal. Found: C, 64.07; H, 10.49; N, 1.93 . Calcd.
for C34H65NO4SSi2: C, 63.79; H, 10.23; N, 2.19
=
The mixture was then stirred overnight while being
allowed to warm to room temperature, before being
quenched with NH4Cl (ca. 48 g, 894 mmol). After
removing the ethylamine by evaporation, the mixture
was diluted with water and extracted with diethyl
ether. The extract was successively washed with water
and brine, dried with Na2SO4, and concentrated un-
der reduced pressure to give the reduction product
(8.14 g, quant.) as a brown waxy solid. This reduc-
tion product was used for the next reaction without
puriˆcation.
J
=
m
J
=
o
z
z.
(2S,3S,4R,5S)-1,3-bis-tert-Butyldimethylsilyloxy-
4,5-epoxy-2-p-toluenesulfonylaminopentadecane
(
16). A solution of dimethyldioxirane in acetone
(prepared from 250 g of Oxone}, 120 g of NaHCO3,
200 ml of H2O and 160 ml of acetone) was added to
15 (200 mg, 0.31 mmol) at 0
ture was stirred at 0 C for 4 d, before being concen-
trated under reduced pressure. The residue was chro-
matographed on silica gel to give later-eluted
epoxide 16 (139 mg, 68
) as a colorless oil, nD24
9C, and the reaction mix-
To a stirred mixture of the reduction product
(8.14 g, 31.6 mmol) in dry CH2Cl2 (100 ml) were
added 2.6-lutidine (2,6-dimethylpyridine; 18.4 ml,
9
b
-
160 mmol) and TBSOTf (29 ml, 128 mmol) at 0
9
C.
z
25
After having been stirred at room temperature for
1 h, the resulting solution was quenched with
methanol. It was then poured into water and extract-
ed with diethyl ether. The extract was successively
washed with water, saturated aq. NaHCO3 and brine,
dried with MgSO4, and concentrated under reduced
1.4827. [
a
]
„20.2 (c 1.05, CHCl3). IR nmax (ˆlm)
D
cm„1: 3290 (w, N–H), 1600 (w, Ar), 1335 (m, SO2),
1255 (m, Si-Me), 1165 (s, SO2), 1095 (m, Si–O).
NMR
d
H (500 MHz, CDCl3): „0.05, 0.02, 0.04, 0.05
-Bu), 0.85
6.9 Hz, 15-H3),
14-H2), 1.52–1.61 (2H, m,
(total 12H, each s, Si-Me), 0.82 (9H, s,
t
=
t-Bu), 0.88 (3H, t, J
(9H, s,
1.26–1.43 (16H, br.s, 7
6-H2), 2.41 (3H, s, Ar-Me), 2.66 (1H, dd,
Hz, 4-H), 2.78 (1H, m, 5-H), 3.27 (1H, ddt,
5.2, 4.9 Hz, 2-H), 3.55 (1H, dd, 10.4, 4.9 Hz, 1-
10.4, 4.9 Hz, 1-HaHb), 3.77
5.2 Hz, 3-H), 4.76 (1H, d, 6.7 Hz,
pressure. The residue was chromatographed on silica
¿
24
=
5.2, 2.2
gel to give 14 (10.4 g, 85
z
) as a pale yellow oil, nD
J
24
=
6.7,
1.4542. [
a
]
„1.48 (
c
1.01, CHCl3). IR nmax (ˆlm)
H (500 MHz, CDCl3):
J
D
cm„1: 1255 (m, Si-Me). NMR
d
J
=
=
J
0.01, 0.04 (6H, each s, Si-Me), 0.06 (6H, s, Si-Me),
HaHb), 3.71 (1H, dd,
(1H, t,
N–H), 7.27 (2H, d,
8.1 Hz, -Ar). Anal. Found: C, 62.06; H, 9.79; N,
1.87 . Calcd. for C34H65NO5SSi2: C, 62.24; H, 9.99;
N, 2.13
The earlier-eluted
tained as an oil (36 mg, 17
0.86–0.90 (21H, m,
t
-Bu, 15-H3), 1.22–1.32 (16H, m,
J
=
J
=
= =
8.1 Hz, m-Ar), 7.75 (2H, J
7
¿
14-H2), 1.34–1.41 (2H, m, N-H2), 2.04 (2H, dd,
J
=
=
6.7, 4.9 Hz,
J
13.6, 6.7 Hz, 6-H2), 2.78 (1H, dt,
J
o
2-H), 3.55 (1H, dd,
J
=
9.8, 6.7 Hz, 1-HaHb), 3.70
z
=
=
(1H, dd,
ϑ
9.8, 4.9 Hz, 1-HaHb), 4.04 (1H, t,
15.4, 6.7 Hz,
15.4, 6.7 Hz, 5-H). Anal
Found: C, 66.47; H, 12.28; N, 2.79 . Calcd. for
C27H59NO2Si2: C, 66.74; H, 12.24; N, 2.88
J
z.
6.7 Hz, 3-H), 5.38 (1H, dd-like,
J
=
a
-epoxy isomer was also ob-
).
=
4-H), 5.70 (1H, dt,
J
.
z
z
z
.
(2S,3S,4R)-1,3-bis-tert-Butyldimethylsilyloxy-2-p-
toluenesulfonylamino-4-pentadecanol
(17). To a
(2S,3R,4E)-1,3-bis-tert-Butyldimethylsilyloxy-2-p-
toluenesulfonylamino-4-pentadecene (15). To an ice-
cooled solution of 14 (9.78 g, 20.1 mmol) in dry pyri-
dine (90 ml), TsCl (5.76 g, 30.2 mmol) was added,
and the mixture was stirred for 24 h at room tempera-
ture. The reaction mixture was then poured into dil.
aq. HCl and extracted with diethyl ether. The extract
was successively washed with saturated aq. CuSO4,
water, saturated aq. NaHCO3 and brine, dried with
MgSO4, and concentrated under reduced pressure.
The residue was chromatographed on silica gel to
stirred and cooled solution of 16 (1.63 g, 2.48 mmol)
in dry toluene (20 ml), a solution of diisobutylalumi-
num hydride (1.01
was added dropwise at „78
ture was warmed gradually to 0
M
in toluene; 8.8 ml, 8.9 mmol)
C under Ar. This mix-
C while stirring for
9
9
3 h, quenched with saturated aq. Rochelle's salt and
then diethyl ether was added. The resulting slurry
was stirred at room temperature until two clear layers
had formed. These layers were separated, and the a-
queous layer was extracted with diethyl ether. The ex-
tract was successively washed with water and brine,
dried with Na2SO4, and concentrated under reduced
pressure. The residue was chromatographed on silica
give 15 (11.6 g, 90
z
) as a colorless oil, n2D4 1.4834.
[
a
]2D6 „2.43 (
c
1.04, CHCl3). IR n
max (ˆlm) cm„1: 3290
(m, N–H), 1600 (w, Ar), 1335 (m, SO2), 1255 (m, Si-
Me), 1165 (s, SO2). NMR dH (90 MHz, CDCl3):
„0.05 (6H, s, Si-Me), „0.01, 0.00 (6H, each s, Si-
gel to give 17 (1.37 g, 84
z
) as a colorless oil, nD25
25
1.4841. [
a
]
„1.51 (c 1.03, CHCl3). IR nmax (ˆlm)
D
cm„1: 3540 (m, O-H), 3320 (m, N–H), 1600 (m, Ar),
1335 (s, SO2), 1255 (s, Si-Me), 1160 (s, SO2). NMR
dH (500 MHz, CDCl3): „0.05, „0.02, 0.09, 0.11
Me), 0.76–0.98 (21H, m,
14-H2), 1.96 (2H, m, 6-H2), 2.41 (3H, s, Ar-Me),
3.15 (1H, m, 2-H), 3.45 (1H, dd, 10.2, 6.1 Hz, 1-
t-Bu, 15-H3), 1.26 (16H, m,
7
¿
J
=
(total 12H, each s, Si-Me), 0.82 (9H, s, t-Bu), 0.88