4038
F.E. ZIEGLER et al.
(90 MHz), a Varian EM-360 spectrometer (60 MHz), or a Bruker
HX-270 spectrometer (270 MHz) using TMS as an internal stan-
dard. '3C NMR spectra were recorded on a Jeol FX-90 spec-
trometer (22.5 MHz) or a Bruker HX-270 spectrometer (67 MHz)
using CDCI3 as internal standard. Chemical shifts are reported in
ppm (6) downfield from TMS. Mass spectra were recorded on a
Hewlett-Packard 5985 gas chromatograph/mass spectrometer.
Electron impact mass spectra (ELMS) were obtained at 70eV,
and chemical ionization mass spectra (CIMS) utilized methane as
the ionizing gas. UV spectra were obtained on a Bausch and
Lomb spectronic 200 UV. Gas chromatographic (GC) analyses
were performed on a Perkin-Elmer 3920 instrument equipped
with a flame ionization detector.
s, IH); CIMS, m/e (relative intensity) 315 (P+ 1, 9.3), 297 (P-OH,
14.8), 281 (P-CH~-H20, 48.9).
(E)-1-1odo-4-acetoxy-l-pentene (2b).Compound6wasprepared
in 34% yield (crude) from 4-pentyn-2-ol (Farchan) bythe method
of Zweifel.17 ~H NMR (CC14) (90 MHz) 1.16 (d, 3H, J=7Hz),
2.00-2.27 (m, 2H), 3.60-4.00(m, IH), 6.05 (d, IH,J= 15Hz),6.49
(m, IH).
A soln of crude (E)-6 (5.81g, 0.027moi), pyridine (19.6g,
0.25tool) and Ac20 (21.6g, 0.21 mol) was stirred for I0hr at25*.
The mixture was diluted with water(50 mL) and ether (50mL).
The organic layer was separated and the aqueous layer was
extracted with ether(3x50mL). The combined organic layers
were washed successively with sat NaHCO3 aq (4x25 mL) and
brine (25mL). Evaporation of the dried (MgSO4) organic layer
under reducedpressure gave ayellowoil which was chromato-
graphed on silica gel. Elution with hexanes-EtOAc (50:I) gave
E-2b (4.74g; 69%) as a pale yellow oil: IR (neat) 3053 and
1737cm-~; IH NMR (CDCI3)(270 MHz) 1.30(d, 3H,J=5.4Hz),
2.10 (s, 3H), 2.33-2.40 (m, 2H), 4.87-4.99 (m, IH), 6.12 (dt, IH,
J= 14.5Hz, 1.5Hz), 6.43(dt, IH, J--- 14.7Hz, 7.3Hz); ~3C NMR
(CDCI3, 22.5 MHz) 19.1, 20.9,41.7, 68.5, 77.4, 140.9, 169.6; CIMS
m/e (relative intensity) 255 (P+I, 48.4), 195 (P+ I-CH3CO2H,
100.0), 194 (P-CH~CO2H, 26.6). Analysis by gas chromatography
(5% Carbowax 20 M) indicated > 95% purity.
Column chromatography was performed by the method of
Still)'~
Methyl 9-hydroxyundec-IO-ynoate. THF (120 mL) was cooled
to - 70* and acetylene gas (735 mL; 0.033 tool) was added slowly
via a gas-tight syringe)~ The mixture was treated with a 2.9M
soln of n-BuLi (9.8 mL; 0.028 tool) in hexane. After the clear soln
had been stirred for 30rain at -70*, 8~3 (4.76g, 0.026mol) in
30mL THF was slowly added. The mixture was stirred for
15 rain at -70°, warmed to 0., and diluted with water (10mL).
The mixture was concentrated in vacuo and diluted with ether
(100 mL). The organic layer was washed with water (2 x 50 mL)
and the combined aqueous extracts were washed with ether
(100mL). Evaporation of the dried MgSO4 organic extracts
5'-lodepent-4'-en-2'-yl
enoate (10). A soln of 9-t-butyldimethylsilyoxyundec-10-enoic
acid (4.15g, 0.014retool), (3.22g, 0.015tool), DCC (3.12g,
9-t-butyldimethylsilyloxyundec-lO-
6
afforded methyl 9-hydroxyundec-10-ynoate (4.76g; 87%) as
a
0.015 moll and 4-dimethylaminopyridine (0.189 g, 0.0015 tool) in
4oraL ether was stirred for 38 hr at 25*)s The mixture was
filtered and concentration of the filtrate/n vacuo gave a crude oil
which was chromatographed on silica gel. Elution with hexanes-
EtOAc (50: I) afforded 10 (5.35g; 76%) as a clear, colorless oil:
IR (neat 3075, 3056, and 1737cm-t; ~H NMR (CCI4) (90 MHz)
0.88 is, 9H), 1.15-1.78 (m, 15H), 2.08-2.38 (m, 4H), 3.92-4.15 (m,
IH), 4.75-5.20 (m, 3H), 5.52-5.95 (m, IH), 6.07 (d, IH, J = 15 Hz),
6.28-6.97 (m, IH).
pale yellow oil: IR (CCh) 3620 and 1735cm-~; IH NMR (CCh)
(90MHz) 1.20-1.97 (m, 12H), 2.13-2.40 (m, 3H), 3.63 (s, 3H),
4.13--4.40 (m, IH). (Found: C, 68.11; H, 9.71. Calc. for CI2H~O3:
C, 67.89; H, 9.50).
Methyl 9-hydroxyundec-lO-enoate.
A
soln of methyl 9-
hydroxyundec-10-ynoate (4.94 g, 0.023 tool) and pyridine (0.7 mL)
in 200 mL EtOH was stirred under H2 at 25° in the presence of
Pd/BaSO4 (0.51 g). The reaction was monitored by gas chroma-
tography (6 ft 5% Carbowax 20 M column) for the disappearance
of starting material. The mixture was filtered through Celite and
concentrated in vacuo to afford 4.49 g of methyl-9-hydroxyun-
dec-10-enoate as an oil: IR (neat) 3456, 3078, and 1740 cm-~; ~H
NMR (CC14) (90 MHz) 1.18-1.88 (m, 12H), 2.05-2.42 (m, 3H), 3.62
(s, 3H), 3.82-4.15 (m, IH), 4.92-5.32 (m, 2H), 5.60--6.02 (m, IH);
CIMS, m/e (relative intensity) 215 (P+ I, 2.1), 197 (P-OH, 58.7),
165 (P-HzO-CH30, 100).
5'-lodopent-4'-en-2'-yl
9-undec-lO-enoate
(II).
Dry
Bu4N+F-(3.48g,13.3retool,preparedbyheatingBt~N+F-.3H20at
80*underhigh vacuumovernight) was treated witha THF (5 mL)
soln of I0(721 rag, 1.42retool). Themixturewasstirred for71 hr
at25°,concentratedin vacuo, anddiluted withether (30mL). The
ether soln was washed withwater(30mL), dried (MgSO4), and
evaporated to afford 565 mg of a clear oil consisting of the
hydroxy ester: ~H NMR (CC14) (90MHz) 1.13-1.73 (m, 15H)
2.10-2.37 (m, 4H), 2.83 (br. s, IH), 3.83--4.10 (m, IH), 4.67-5.27
(m, 3H), 5.57-5.90 (m, IH), 6.05(d, IH, J= 15Hz), and 6.23-6.63
(m, IH).
Methyl-9-t-butyldimethylsilyloxyundec-lO-enoate (9). A soln of
methyl-9-hydroxyundec-10.-enoate
(4.49g, 0.021tool),
4-
dimethylaminopyridine (0.85 g, 0.007 tool), Et;N(2.56 g, 0.025 tool)
and t-butyldimethysilylchloride (3.51g, 0.023mol) in 4oraL
CHzCI2 was stirred for 37 hr at 25°)6 The mixture was concen-
trated in vacuo and diluted with ether (50 mL). The organic soln
was washed successively with brine (50 mL) and water (50 mL).
Evaporation of the dried (MgSO4) organic extract gave a crude
mixture which was chromatographed on silica gel. Elution with
hexanes-EtOAc (25:1) afforded 4.77 g (63% from the alkynyi al-
cohol) of 9 as a pale yellow oil: IR (neat) 3078 and 1743 cm-~; ~H
NMR (CC14) (90MHz) 0.03 (s, 6H), 0.88 (s, 9H), 1.17-1.73 (m,
12H), 2.10-2.33 (m, 2H), 3.57 is, 3H), 3.90--4.13 (m, IH), 4.83--5.17
(m, 2H), 5.52-5.93 (m, IH); (Found: C, 65.91; H, 11.06. Calc. for
CisH~sO3Si: C, 65.80; H, 11.04).
A mixture of the crudealcohol and active MnO2 (2.97g) in
CH2CI2 (70 mL) was stirred for 4.5 hr at 25°. The suspension was
filtered and concentrated/n vacuo to give a crude mixture which
was chromatographed on silica gel. Elution with hexanes-EtOAc
(10: I) afforded 383 mg (69% from 10) of 11 as
oil: IR (neat) 3053, 1730, 1699, and 1680cm-m; ~H NMR
(270 MHz), CDCI3) 1.21 (d, 3H, J 6.6 Hz), 1.27-1.36 (m, 6H),
a clear colorless
=
1.53-1.69 (m, 4H), 2.24-2.32 (m, 4H), 2.58 (t, 2H, J = 7.0 Hz),
4.91-4.98 (m, IH), 5.81 (dd, I H, J = 9.9 Hz, 1.5 Hz), 6.11 (td, IH,
J = 14.3 Hz, 1.5 Hz), 6.17-6.37 (m, 2H), 6.41-6.52 (m, IH); 13C
NMR (CDCI3) (22.5 MHz) 19.4, 23.8, 24.9, 29.0, 34.5, 39.5, 42.0,
68.6, 77.5, 127.7, 141.5, 173.0, 200.7; CIMS m/e (relative intensity)
393 (P+ I, 11.2), 199 (p-Csl~l, 11.8), 181 (P--CsHaOI, 100).
E,E-16-Methyl-oxacyclohexadeca-l l,13-diene-2,10-dione (12).
9-t-Butyidimethylsilyloxyundec-IO-enoic
acid.
A
soln of 9
A
stirred MeCN (4mL) soln of PdCI2(MeCNh (82mg,
(5.39g, 0.016tool) and LiOH-H20 (3.45g, 0.082tool) in 220 mL
DME: H20 (2.5:I)was stirred at25°for 3days. The mixture was
concentrated under reduced pressure and diluted with HzO
(I00mL). The aqueous soln was washed with ether(2x25mL),
acidified with 10% NaHzPO~ aq. and extracted with ether (4x
50mL). The combined organicextracts were washed with brine
(50mL), dried (MgSO4), and concentrated to afford 9-t-butyl-
dimethylsilyloxyunedec-10-enoic acid(3.99g;84%)asayellowoil:
IR (neat) 3647-2281 (br), 3077, and 1710cm-~; ~H NMR (CC14)
(90MHz) 0.88 (s, 9H), 1.17-1.83 (m, 12H), 2.17-2.43 (m, 2H),
3.90-4.17 (m, II-I), 4.87-5.20 (m,2H),5.53-5.97 (m, IH), 11.13 (br.
0.32 retool), Et3N (262 rag, 2.60 retool) and formic acid (42 rag,
0.91 retool) at 25° was treated dropwise (syringe pump) with a
MeCN (8 mL) soln of 11 (118 rag, 0.30 mmol) over a period of
9.75 hr. The mixture was stirred for an additional 1.5 hr at 25°,
filtered through Florisil, and concentrated/n vacuo to give a deep
red oil which was chromatographed on silica gel. Elution with
hexanes--EtOAc (10:1 and 5:1) afforded 44 mg (55%) of 12 as a
white crystalline solid: m.p. 76.0-77.0*; UV (EtOH) Am~ =
274nm (e=8500); IR (neat) 3030, 1727, 1688, 1658, and
1640cm-~; ~H NMR (CDCI;) (270MHz) 1.12-1.37 (m, 6H), 1.28