Synthesis of ardisinol II

Article abstract of DOI:10.1055/s-1998-2193

The first and also a concise synthesis of ardisinol II by two routes in excellent yields are described.

Full text of DOI:10.1055/s-1998-2193

SYNTHESIS
November 1998
1619
Synthesis of Ardisinol II
Wei Yan Sun,*¶ Qin Zong, Rue Lin Gu, Bai Chuan Pan*
Shanghai Institute of Metaria Medica, Shanghai 200031, China
Fax +86(21)62164681
Received 9 February 1998; revised 13 April 1998
Abstract: The first and also a concise synthesis of ardisinol II by
two routes in excellent yields are described.
Synthesis of the side chain part was achieved by the trans-
formations presented in Scheme 2 from commercially
available, 7-bromoheptan-1-ol (7). Protection5 of 7 with
ethyl vinyl ether in the presence of a catalytic amount of
TsOH in anhydrous CH2Cl2 provided the ethoxy ethyl
(EE) ether 8 in 95% yield, which was converted succes-
sively into the aldehyde 9 by Kornblum oxidation with
DMSO/NaHCO3 in 50% yield.8
Key words: resorcinol derivatives, Wittig reaction, Würtz coup-
ling, antitubercular agent, ardisinol II
Ardisinol II is the active principle isolated from Ardisia
japonic (Hornsted) Blume (Myrsinaceae),1 the Chinese
medicinal herb, which has been used for treatment of lung
tuberculosis and asthma in folk medicine.2 The compound
inhibits the growth of Mycobacterium tuberculosis in vit-
ro. In tests with 201 patients, the compound was 81.5%
effective.3 Its structure was elucidated as (Z)-5-(8'-tridece-
nyl)resorcinol (1).1 Due to its safety and effectivity, fur-
ther studies aimed at development of these new amor-
phous resorcinol derivatives as antitubercular agents were
carried out in China, Japan, UK and USA.4 In this paper
we describe the first and also a concise synthesis of ardis-
inol II (1) by two different routes in high overall yields.
This second approach for convergent synthesis of ardisi-
nol II via Würtz-type cross-coupling established an effi-
cient strategy for construction of the amorphous resorci-
nol derivatives and other structurally related substances
such as cadol4 in excellent yield.
Scheme 2
The coupling (Scheme 3) of the phosphonium salt 6 with
the aldehyde 9 was carried out by the Wittig reaction to
form the olefin 109 in 43% yield. Catalytic hydro-
genation10 of the olefin 10 with palladium-charcoal in eth-
anol and deprotection of the EE group of compound 10
under the hydrogenation conditions gave the hydrogena-
tion and deprotection product 11 in 77% yield. This was
converted into the aldehyde 12 in 80% yield by treatment
with pyridinium chlorochromate (PCC) in anhydrous
CH2Cl2.11 Conversion of 12 to the cis-enriched olefin 13
(Z/E, 85:15, AgNO3/SiO2 column, hexane/Et2O, 20:1)12
was achieved by the Wittig reaction at –70°C in 70%
yield. Finally, deprotection5 of the silyl ether 13 with tet-
rabutylammonium fluoride afforded the final product 1 in
99% yield.
Commercially available, methyl 3,5-dihydroxybenzoate
(2) was protected5 with tert-butyldimethylsilyl chloride in
the presence of triethylamine in anhydrous THF to give
the bis(silyl) ether 3 in 100% yield (Scheme 1). Reduction
of 3 with LiAlH4 in anhydrous diethyl ether afforded the
corresponding alcohol 4 in almost 100% yield. The alco-
hol 4 was converted efficiently into the benzyl chloride 56
under triphenylphosphine and carbon tetrachloride
conditions6 in 87% yield. The benzyl chloride 5 reacted
with triphenylphosphine to generate the phosphonium
chloride7 6 in 85% yield.
Scheme 3
A second project focused on exploring a facile route to
provide a large amount of the target compound which was
assayed for pharmacological activity. The conceived ap-
proach to ardisinol II (1) has been centered around the key
step, coupling between the aromatic part 5 and the side
Scheme 1

SYNTHESIS
Papers
1620
chain part such as (Z)-1-iodododec-7-ene (14) via Würtz- In summary, the first total synthesis of ardisinol II (1) was
type cross-coupling reaction in good yield of 90% realized in 14% overall yield in the first route via 9 steps
(Scheme 4). The organolithium reagent generated in situ through conventional Wittig strategy. In the second con-
from iodide 14 reacted preferentially with benzyl chloride vergent approach the excellent yield of 64% via 5 steps
5, which is more reactive than 14 as an alkyl halide, and has been attained by utilizing Würtz-type cross-coupling
that a high yield of coupling product 13 was attained. Al- as the key reaction. All the spectra were identical to the
though the Würtz-type cross-coupling reaction is normal- natural product. All the new compounds were character-
ly of less synthetic value in total synthesis of natural prod- ized by spectroscopic measurements.
ucts due to dimerization, in this case the desired cross-
coupling reaction takes precedence over dimerization
probably through the organolithium as an intermediate,
according to the model study shown below (Scheme 5).
Melting points are uncorrected. 1H NMR spectra were obtained on a
JEOL PS-100 or a Bruker AM 400 NMR spectrometer. IR spectra
were recorded on a Perkin-Elmer 599B Spectrometer. Mass spectra
were recorded on a Varian MAT-711 Spectrometer. All air-sensitive
reactions were run under argon atmosphere, and anhydrous reagents
were added through using oven-dried syringes.
Methyl 3,5-Bis(tert-butyldimethylsilyloxy)benzoate (3):
To a solution of tert -butyldimethylsilyl chloride (4.97 g, 33 mmol) in
THF (15 mL) was added a solution of 2 (2.52 g, 15 mmol) and Et3N
Scheme 4
(6.7 mL, 45 mmol) in THF (20 mL) at r.t. The mixture was stirred
overnight, diluted with THF, then filtered and extracted with Et2O.
The organic extract was dried (Na2SO4) and concentrated. The resi-
due was chromatographed (hexane/Et2O, 20:1) to give 3 as an oil
(6.0 g, ≈100%).
1H NMR (100 MHz, CCl4): δ = 6.96 (s, 2 H, ArH), 6.34 (s, 1 H, ArH),
3.80 (s, 3 H, CO2CH3), 0.96 [s, 18 H, 2 SiC(CH3)3], 0.16 [s, 12 H, 2
Si(CH3)2].
Scheme 5
IR (film): ν = 2950, 2930, 2860, 1730, 1590, 1450, 1340, 1170, 930,
830, 770 cm–1.
Synthesis of the side chain part was achieved by the trans-
formations presented in Scheme 6 from oct-7-yn-1-ol
MS: m/z = 396 (M+), 339.
Anal. Calcd. for C20H36O4Si2: C, 60.56; H, 9.15. Found: C, 60.43; H,
(17). Thus, 17 was treated with LiNH2 in liq. NH3 to form
the corresponding lithium alkynide in the presence of
Fe(NO3)3 as a catalyst,13 and then reacted with BuBr to
afford dodec-7-yn-1-ol (18)13 in 88% yield. The semihy-
drogenation of 18 was carried out in pyridine by using
10% palladium on barium sulfate as a catalyst to yield
only the cis-isomer of dodec-7-en-1-ol (19)14 (GC analy-
sis) in 95% yield. The (Z)-dodec-7-en-1-ol (19) was con-
verted into the corresponding tosylate 20 by treatment
with TsCl and Et3N in CH2Cl2 in 94% yield. Furthermore,
the tosylate 20 was reacted with NaI in acetone at reflux
to give (Z)-1-iodododec-7-ene (14) in 91% yield (Scheme
6). After Würtz-type cross-coupling between the aromatic
part 5 and the side chain part of 14, the corresponding silyl
ether 13 was obtained as described before (Scheme 4).
9.04.
3,5-Bis(tert-butyldimethylsilyloxy)benzyl Alcohol (4):
To a solution of LiAlH4 (0.7 g, 18.4 mmol) in Et2O (50 mL) was
added silyl ether 3 in Et2O (50 mL) at r.t. The mixture was stirred for
2 h and quenched with H2O. The organic layer was washed with brine,
dried (Na2SO4) and concentrated. The residue was chromatographed
(hexane/Et2O, 3:1) to give the alcohol 4 as an oil (5.58 g, ≈100%).
1H NMR (100 MHz, CCl4): δ = 6.28 (s, 2 H, ArH), 6.06 (s, 1 H, ArH),
4.20 (s, 2 H, ArCH2), 1.56 (br, 1 H, OH), 0.94 [s, 18 H, 2 SiC(CH3)3],
0.12 [s, 12 H, 2 Si(CH3)2].
IR (film): ν = 3340 (br), 2950, 2930, 2860, 1590, 1450, 1330, 1165,
930, 830, 770 cm–1.
MS: m/z = 368 (M+), 311, 293.
Anal. Calcd. for C19H36O3Si2: C, 61.90; H, 9.84. Found: C, 61.88; H,
9.76
3,5-Bis(tert-butyldimethylsilyloxy)benzyl Chloride (5):
A mixture of 4 (110 mg, 0.3 mmol), PPh3 (170 mg, 0.64 mmol) and
CCl4 (excess) was heated in a sealed tube at 110°C for 2 h. The mix-
ture was evaporated and chromatographed (hexane/Et2O, 20:1) to
give chloride 5 as an oil (100 mg, 87%).
1H NMR (100 MHz, CCl4): δ = 6.26 (s, 2 H, ArH), 6.00 (s, 1 H, ArH),
4.26 (s, 2 H, ArCH2), 0.88 [s, 18 H, 2 SiC(CH3)3], 0.08 8s, 12 H, 2
Si(CH3)2].
IR (film): ν = 2950, 2930, 2860, 1590, 1450, 1340, 1260, 1170, 1060,
930, 830, 770 cm–1.
MS: m/z = 387 (M++1), 386 (M+), 330, 329, 287.
Anal. Calcd. for C19H35ClO2Si2: C, 58.95; H, 9.11. Found: C, 58.77
H, 9.08
Scheme 6
3,5-Bis(tert-butyldimethylsilyloxy)benzyltriphenylphosphonium

SYNTHESIS
November 1998
1621
Chloride (6):
3.50 (t, 2 H, J = 7 Hz, CH2OH), 2.40 (t, 2 H, J = 7.5 Hz, ArCH2), 1.16–
1.60 (m, 13 H), 1.00 [s, 18 H, SiC(CH3)3], 0.16 [s, 12 H, Si(CH3)2].
IR (film): ν = 3350 (br), 2950, 2930, 2860, 1590, 1470, 1250, 1160,
1020, 830, 770 cm–1.
A mixture of 5 (90 mg, 0.23 mmol) and PPh3 (65 mg, 0.25 mmol) was
heated to melting state and then to 100°C for 5 h. The mixture was
cooled to r.t. and washed with Et2O (5 mL) to give salt 6 (130 mg,
86%); mp 229–233°C.
MS: m/z = 409, 352, 311, 239.
1H NMR (100 MHz, TFA): δ = 7.51 [m, 15 H, P(C6H5)3], 6.48 (s, 1
H, ArH), 6.18 (s, 2 H, ArH), 4.36 (s, 1 H, ArCHPPh3Cl), 4.22 (s, 1 H,
ArCHPPh3Cl), 0.8 [s, 18 H, 2 SiC(CH3)3], 0.0 [s, 12 H, 2 Si(CH3)2].
IR (film): ν = 3400 (br), 3100, 2950, 2930, 2860, 2760, 1590, 1470,
1460, 1450, 1440, 1335, 1250, 1160, 1025, 830, 770 cm–1.
MS: m/z = 613, 612, 555.
Anal. Calcd. for C26H50O3Si2: C, 66.89; H, 10.80. Found: C, 66.73;
H, 10.58
8-(3,5-Bis(tert-butyldimethylsilyloxy)phenyl)octan-1-al (12):
To a mixture of PCC (57 mg, 0.28 mmol) in CH2Cl2 (1 mL) was add-
ed 11 (80 mg, 0.17 mmol) in CH2Cl2 (1 mL) at r.t. The mixture was
stirred for 2 h, then diluted with a solution of hexane/Et2O (2:1) and
filtered through a silica gel column, and concentrated. The residue
was chromatographed (hexane/Et2O, 4:1) to give the aldehyde 12 as
an oil (70 mg, 80%).
Anal. Calcd. for C37H50ClO2PSi2: C, 68.43; H, 7.76. Found: C, 68.50
H, 7.81
7-(1-Ethoxyethoxy)heptanal (9):
To a solution of 7 (100 mg, 0.55 mmol) and TsOH (10 mg) in CH2Cl2
(2 mL) was added ethyl vinyl ether (42 mg, 0.58 mmol) at 0°C. The
mixture was stirred for 10 min, diluted with Et2O (20 mL) and then
washed with 5% aq NaHCO3 solution to pH 8. The organic layer was
dried (Na2SO4) and concentrated. The residue was chromatographed
(hexane/Et2O, 20:1) to give 1-bromo-7-(ethoxyethyl)heptane (8) as
an oil (140 mg, 95%).
1H NMR (100 MHz, CCl4): δ = 9.60 (s, 1 H, CHO), 6.06 (s, 2 H,
ArH), 5.92 (s, 1 H, ArH), 2.34 (m, 4 H), 1.20–1.60 (m, 10 H), 0.92 [s,
18 H, SiC(CH3)3], 0.12 [s, 12 H, Si(CH3)2].
IR (film): ν = 2950, 2930, 2860, 1730, 1590, 1470, 1250, 1165, 830,
770 cm–1.
MS: m/z = 464 (M+), 449, 435, 407, 379, 365, 351.
Anal. Calcd. for C26H48O3Si2: C, 67.18; H, 10.41. Found: C, 67.03;
H, 10.40
1H NMR (100 MHz, CCl4): δ = 4.48 (q, 1 H, J = 6 Hz, OCH), 3.25
(m, 6 H, BrCH2, OCH2, OCH2), 1.72 (m, 2 H), 1.38 (m, 6 H), 1.02–
1.20 (m, 8 H).
(Z)-5-(8'-Tridecenyl)resorcinol Disilyl Ether (13):
To a solution of C5H11P+Ph3Br– (80 mg, 0.19 mmol) in THF (1 mL)
was added BuLi (0.14 mL, 1.39 M, 0.19 mmol) at –20°C. The mix-
ture was stirred for 2 h and then cooled to –70°C. To this solution was
added aldehyde 12 (70 mg, 0.15 mmol) in THF (1 mL) at –70°C. The
mixture was stirred at –70°C for 2 h and diluted with Et2O. The Et2O
layer was washed with H2O and brine. The organic layer was dried
(Na2SO4) and concentrated. The residue was chromatographed on
AgNO3/SiO2 (hexane/Et2O, 20:1) to give Z-13 (47 mg, 60%) and E-
13 (8 mg, 10%).
A solution of 8 (267 mg, 1 mmol) and NaHCO3 (100 mg, 1 mmol) in
DMSO (5 mL) was heated at 120°C for 3 h. To this mixture was add-
ed NaI (15 mg) and ether (10 mL) at r.t. The mixture was washed with
a solution of hexane/Et2O (1:1, 30mL). The organic layer was dried
(Na2SO4) and concentrated. The residue was chromatographed (hex-
ane/Et2O, 2:1) to give aldehyde 9 as an oil (100 mg, 50%).
1H NMR (100 MHz, CCl4): δ = 9.64 (s, 1 H, CHO), 4.50 (q, 1 H, J =
6 Hz, OCH), 3.10–3.54 (m, 4 H, 2 OCH2), 2.30 (t, 2 H, J = 7 Hz,
CH2CHO), 1.36 (m, 6 H), 1.02–1.18 (m, 8 H).
IR (film): ν = 2950, 1720, 1250, 1025 cm–1.
1H NMR (100 MHz, CCl4): δ = 6.00 (2 H, s, ArH), 5.84 (1 H, s, ArH),
5.21 (2 H, t, J = 5 Hz, CH=CH), 2.26 (2 H, t, J = 7.5 Hz, ArCH2), 1.80
(4 H, m, CH2C=CCH2), 1.10–1.17 [17 H, m, (CH2)7, CH3] 0.80 [18
H, s, SiC(CH3)3], 0.00 [12 H, s, Si(CH3)2].
MS: m/z = 202 (M+), 173, 156, 109.
Anal. Calcd. for C11H22O3: C, 65.31; H, 10.96. Found: C, 65.12 H,
10.79
IR (film): ν = 2960, 2930, 2860, 1590, 1475, 1465,1450, 1260, 1250,
1-[3,5-Bis(tert-butyldimethylsilyloxy)phenyl]-8-(1-ethoxy-
ethoxy)oct-1-ene (10):
1165, 835, 770 cm–1.
MS: m/z = 518 (M+), 461, 447, 433,419, 405, 391, 377.
Anal. Calcd. for C31H58O2Si2: C, 71.75; H, 11.26. Found: C, 71.89;
H, 11.40
To a suspension of 6 (2.5 g, 4.47 mmol) in THF (8 mL) was added
BuLi (3.4 mL, 1.39 M, 4.73 mmol) at r.t. The mixture was stirred for
75 min and then cooled to –70°C. To this solution was added alde-
hyde 9 (880 mg, 4.36 mmol) in THF (3 mL) at that temperature and
then the mixture was stirred overnight at r.t. The solution was diluted
with Et2O (200 mL), washed with H2O, brine, dried (Na2SO4) and
evaporated. The residue was chromatographed (hexane/Et2O, 12.5:1)
to give the olefin triether 10 as an oil (1 g, 43%).
(Z)-5-(8'-Tridecenyl)resorcinol (1):
To a solution of 13 (130 mg, 0.25 mmol) in THF (1 mL) was added
Bu4NF (250 mg, 0.79 mmol) in THF (1 mL) at r.t. The mixture was
stirred for 0.5 h and concentrated. The residue was chromatographed
(benzene/EtOAc, 15:1) to give 1 as an oil (73 mg, ≈100%).
1H NMR (100 MHz, CCl4): δ = 6.08 (br, 1 H, OH), 6.08 (s, 2 H, ArH),
6.00 (s, 1 H, ArH), 5.21 (t, 2 H, J = 5 Hz, CH=CH) 2.06 (t, 2 H,
ArCH2), 1.90 (m, 4 H, CH2C=CCH2), 1.20 [m, 14 H, (CH2)7] 0.82 (t,
3 H, J = 7 Hz, CH3).
1H NMR (100 MHz, CCl4): δ = 6.00–6.20 (m, 5 H, ArH, CH=CH),
4.48 (q, 1 H, J = 6 Hz, OCH), 3.20–3.40 (m, 4 H, 2 OCH2), 2.10 (m,
2 H), 1.00–1.40 (m, 14 H) 0.94 [s, 18 H, 2 SiC(CH3)3], 0.12 [s, 12 H,
Si(CH3)2].
IR (film): ν = 2950, 2930, 2860, 1590, 1470, 1250, 1060, 1030, 830,
770 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.23 (d, 2 H, J = 2 Hz, ArH), 6.16
(s, 1 H, ArH), 5.68 (br, 1 H, OH), 5.35 (m, 2 H, J = 5, 10Hz, CH=CH),
2.44 (t, 2 H, J = 7.5 Hz, ArCH2), 1.98(m, 4 H, CH2C=CCH2), 1.30 (m,
14 H, (CH2)7], 0.88 (t, 3 H, J = 7 Hz, CH3).
MS: m/z = 537 (M++1), 536 (M+), 522, 507, 490, 464, 448, 443, 407,
389, 377, 366, 352.
Anal. Calcd. for C30H56O4Si2: C, 67.11; H, 10.51. Found: C, 67.12;
H, 10.60
IR (film): ν = 3350 (br), 2950, 2930, 2860, 1630, 1600, 1470, 1340,
1305, 1260, 1155, 1000, 840, 790, 700 cm–1.
UV (MeOH): λmax = 208, 275, 280 nm.
8-(3,5-Bis(tert-butyldimethylsilyloxy)phenyl)octan-1-ol (11)
A solution of 10 (60 mg, 0.11 mmol) and Pd/C (70 mg, 5%) in EtOH
(2 mL) was hydrogenated for 16 h under 1 atm at r.t. The mixture was
filtered and the filtrate concentrated. The residue was chromato-
graphed (hexane/Et2O, 2:1) to give the disilyl ether alcohol 11 as an
oil (40 mg, 77%).
MS: m/z = 290 (M+), 247, 233, 208, 205, 194, 191, 177, 163, 149, 137,
124 (100), 111.
Anal. Calcd. for C19H30O2: C, 78.57; H, 10.41. Found: C, 78.50; H,
10.41
Dodec-7-yn-1-ol (18):
1H NMR (100 MHz, CCl4): δ = 6.12 (s, 2 H, ArH), 6.00 (s, 1 H, ArH),
To a solution of Fe(NO3)3 (200 mg, 0.83 mmol) in liquid NH3

SYNTHESIS
Papers
1622
(250 mL) was added lithium (1.8 g, 260 mmol) at –78°C. The mixture
was stirred for 1 h and warmed to –50°C. To this solution was added
oct-7-yn-1-ol (17;12 g, 95 mmol) at –50°C. After 2 h, BuBr (16 mL,
150 mmol) in THF (50 mL) was added. The mixture was stirred for
2 h at –50°C, then stirred overnight at r.t. The mixture was diluted
with benzene (300 mL) and H2O (50 mL). The organic layers were
separated and washed with aq 0.5 N HCl and H2O. The aqueous layer
was extracted with benzene and the combined organic layers were
dried (Na2SO4) and concentrated. The residue was chromatographed
(hexane/Et2O, 2:1) to give 18 as an oil (15.14 g, 88%).
MS: m/z = 294 (M+), 167, 125, 111, 97.
Anal. Calcd. for C12H23I: C, 48.99; H, 7.88. Found: C, 48.80; H, 7.71
Cross-Coupling Between 3,5-bis(tert-butyldimethylsilyloxy)ben-
zyl Chloride (5) and (Z)-1-Iodododec-7-ene (14):
To a solution of 5 (100 mg, 0.25 mmol) and (Z)-1-iodododec-7-ene
(14; 90 mg, 0.30 mmol) in THF (1.5 mL) was added fresh lithium
(5 mg, 0.71 mmol). The mixture was refluxed for 3 h until metallic
lithium was consumed. The mixture was diluted with Et2O (50 mL),
washed with H2O (20 mL) and brine (20 mL). The organic layer was
dried (Na2SO4) and concentrated. The residue was chromatographed
(hexane/Et2O, 10:1) to give the silyl-protected ardisinol II (13)
(120 mg, 90%). Its spectral data were identical with the previous sam-
ple reported above.
1H NMR (100 MHz, CCl4): δ = 3.48 (t, 2 H, J = 7 Hz, CH2OH), 2.04
(m, 4 H), 1.36 (m, 12 H), 0.86 (t, 3 H, J = 7 Hz, CH3).
IR (film): ν = 3330, 2940, 2840, 2260, 1440, 1070, 720 cm–1.
MS: m/z = 181 (M+–1), 165, 123, 109, 95, 81, 69, 67.
Anal. Calcd. for C12H22O: C, 79.06; H, 12.16. Found: C, 79.21; H,
12.39
¶ New address: CaoYang Lu 1107/6/506, Shanghai 200062, P.R. China.
(Z)-Dodec-7-en-1-ol (19):
A mixture of 18 (2 g, 11 mmol), pyridine (50 mL) and Pd/BaSO4
catalyst (200 mg, 10%) was hydrogenated for 3 h. The mixture was
filtered and concentrated. The residue was chramatographed (hexane/
Et2O, 1:1) to give 19 as an oil (1.92 g, 95%).
(1) Hu, Y.; Chen, W.-S.; Huang, B.-H.; Lin, L.-Z. Acta Chimica
Sinica 1981, 153; Chem. Abstr. 1981, 95, 39119.
(2) Huang, B.-H.; Chen, W.-S.; Hu, Y.; Qin, C.-B.; Zhang, W.-J.
Yaoxue Xuebao 1981, 27; Chem. Abstr. 1981, 95, 175623.
(3) Huang, B.-H.; Chen, W.-S.; Hu, Y. Yaoxue Xuebao 1980, 39;
Chem. Abstr. 1980, 95, 138449.
(4) (a) Ogawa, H.; Natori, S. Phytochemistry 1968, 773.
(b) Ogawa, H.; Natori, S. Chem. Pharm. Bull. 1968, 1709
(c) Tyman, J. H. P. J. Chem. Soc. Perkin I 1973, 1639.
(d) Occolowitz, J.L. Anal. Chem. 1964, 2177
1H NMR (100 MHz, CCl4): δ = 5.20 (t, 2 H, J = 5 Hz, CH=CH), 3.44
(t, 2 H, J = 7 Hz, CH2OH), 2.70 (br, 1 H, OH), 1.94 (m, 4 H), 1.30
(m, 12 H), 0.86 (t, 3 H, J = 7 Hz, CH3).
IR (film): ν = 3330, 1665, 1470, 1060, 700 cm–1.
MS: m/z = 184 (M+), 167, 166, 125, 111, 97, 83, 71, 69.
Anal. Calcd. for C12H24O: C, 78.20; H, 13.12. Found: C, 78.09; H,
13.00
(e) Madrigal, R.V.; Beencar, G. F.; Plattner, R. D.; Smith, Jr., C.
R. Lipids 1977, 402.
(5) Greene, T. W. Protective Groups in Organic Synthesis; Wiley-
Interscience: New York, 1981
(6) Slagle, J. D.; Huang, T.-S.; Franzus, B. J. Org. Chem. 1981,
3526.
(7) Johnson, A. W. Ylid Chemisty; Academic Press: New York,
1966
(Z)-1-Iodododec-7-ene (14):
To a solution of 19 (1 g, 5.4 mmol) and Et3N (1.7 mL, 12.2 mmol) in
CH2Cl2 (10 mL) was added TsCl (1.74 g, 9.1 mmol) in CH2Cl2 (10
mL) at –20°C. The mixture was stirred overnight, and quenched with
aq satd NaHCO3 solution (10 mL) and extracted with Et2O (3 × 20
mL). The extract was dried (Na2SO4) and concentrated and the resi-
due chromatographed (hexane/Et2O, 4:1) to give the tosylate 20
(1.75 g, 94%).
1H NMR (100 MHz, CDCl3): δ = 7.80 (d, 2 H, ArH), 7.30 (d, 2 H,
ArH), 5.30 (t, 2 H, J =5Hz, CH=CH), 3.98 (t, 2 H, CH2OTs), 2.40 (s,
3 H), 1.90 (m, 4 H), 1.60 (m, 2 H), 1.26 (m, 10 H), 0.82 (t, 3 H, CH3).
A solution of 20 (1.75 g, 5.1 mmol), NaI (2 g, 13 mmol) and acetone
(25 mL) was refluxed for 2 h and concentrated. The mixture was di-
luted with Et2O and washed with aq 0.23 N Na2S2O3 solution and the
aqueous layer was extracted with Et2O. The combined layers were
dried (Na2SO4) and concentrated. The residure was chromatographed
(hexane) to give 14 as an oil (1.39 g, 91%).
(8) Kornblum, N.; Jones, W. J.; Anderson, G. J. J. Am. Chem. Soc.
1959, 4113.
(9) Murphy, P. J.; Brennan, J. Chem. Soc. Rev. 1988, 1.
(10) Nishimura, S.; Takagi, U. Catalytic Hydrogenation. Applica-
tion to Organic Synthesis; Tokyo Kagaku Dojin: Tokyo, 1987
(11) Piancatelli, G.; Scettri, A.; D'Auria, M. Synthesis 1982, 245.
(12) Zhang, H.; Pan, B.; Tao, Z.; Qin, Q. Acta Chimica Sinica, 1989,
896.
(13) Brandsma, L. Preparative Acetylenic Chemistry. 2nd ed., Else-
vier: Amsterdam, 1988, and earlier references given in these
sources.
1H NMR (100 MHz, CCl4): δ = 5.18 (t, 2 H, J = 5 Hz, CH=CH), 3.0
(t, 2 H, J = 7 Hz, CH2I), 1.10–1.20 (m, 16 H), 0.80 (t, 3 H, J = 7 Hz,
CH3).
(14) Johnson, F.; Paul, K. G.; Favara, D. J. Org. Chem. 1982, 4254.
IR (film): ν = 2950, 2930, 2865, 1630, 1470, 1340, 1305, 1155, 1000,
840, 700 cm–1.