Practical synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene: The major pheromone of the saltmarsh caterpillar moth Estigmene acrea

Article abstract of DOI:10.1002/bkcs.10240

An efficient synthesis of (3Z,6Z)-cis-9,10-epoxy-3,6-henicosadiene (1), the major component of sex pheromone of saltmarsh caterpillar moth Estigmene acrea (Drury), was accomplished from commercially available pentadec-3-yn-1-ol and bromoundecane. Chiralit

Full text of DOI:10.1002/bkcs.10240

Article
DOI: 10.1002/bkcs.10240
BULLETIN OF THE
D. Kumar et al.
KOREAN CHEMICAL SOCIETY
Practical Synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene: The
Major Pheromone of the Saltmarsh Caterpillar moth Estigmene acrea
Deepak Kumar,† Sridhar Chirumarry,† B. V. D. Vijaykumar,† S. J. Harshavardhan,† Kiwan Jang,‡
Dong-Ha Lee,§ and Dong-Soo Shin†,
*
†Department of Chemistry, Changwon National University, Changwon 641-773, South Korea.
*E-mail: dsshin@changwon.ac.kr
‡Department of Physics, Changwon National University, Changwon 641-773, South Korea
§KIP, Hanbat National University, Daejeon 305-719, South Korea
Received November 25, 2014, Accepted January 10, 2015, Published online March 17, 2015
An efficient synthesis of (3Z,6Z)-cis-9,10-epoxy-3,6-henicosadiene (1), the major component of sex phero-
mone of saltmarsh caterpillar moth Estigmene acrea (Drury), was accomplished from commercially available
pentadec-3-yn-1-ol and bromoundecane. Chirality was introduced by employing Sharpless asymmetric dihy-
droxylation on cis-olefin intermediate in the synthesis of 1, for the first time. The other key reactions include
metal-dissolving coupling, Lindlar's catalyst-assisted partial hydrogenation, one-pot, three-step epoxidation
from vicinal diol, and Wittig olefination. The overall yield of 1 was 24.7% in eight steps. The efficiency
and simplicity of this synthesis allow the potential use of pheromone 1 in pest management programs.
Keywords: Sex pheromone, Sharpless dihydroxylation, Asymmetric synthesis, Estigmene acrea,
Wittig olefination
Introduction
synthetic chemists to focus on various practical and efficient
preparation methods.
Pheromones play an important role in studying the social
response among the members of same species with opposite
sex, and thus are used in traps/lures to control pests.
(9S,10R)-9,10-Epoxy-(3Z,6Z)-henicosadiene (1) is one of
themajorpheromonecomponentsofmanyLepidopteran pests
such as fall webworm moth or American white moth Hyphan-
tria cunea (Drury), saltmarsh caterpillar moth Estigmene
acrea (Drury), and Bihar hairy caterpillar moth Diacrisia
oblique (Arctiidae).1,2 These moths are widespread in USA,
Canada, and South Asian countries such as China, Japan,
and India. The larva of these pests attacks crops, oil-seed
plants, fruit, and ornamental trees. The other pheromone
components identified in these pests include (9S,10R)-9,10-
epoxy-(3Z,6Z)-henicosatriene (2), (9S,10R)-9,10-epoxy-
(3Z,6Z)-icosatriene (3), (9Z,12Z)-9,12-octadecadienal (4),
and (9Z,12Z,15Z)-9,12,15-octadecatrienal (5) (Figure 1).
According to field tests, an appropriate proportions of these
pheromones 1–5 of female H. cunea and D. oblique attracted
males.2b,3 Senda et al. reported that a blend of 1, 2, and 5 was
good enough to attract H. cunea in the field, which was then
commercialized.4 On the other hand, the optically active com-
ponents 1, 2, and 3 are also found to be biologically active anti-
feedants and self-defensive substances against rice blast dis-
ease.5 A considerable amount of research work on these insect
pheromones has been performed and reported for almost three
decades. Though pesticides are used to control pests all the
time, organic cultivation in food industry is again demanding
pheromone usage for healthy victuals, thereby enthusing
However, the stereochemical purity of synthetic phero-
mones also plays a vital role on their activities.6 Hill and Roe-
lofs suggested the absolute configuration for 1 as (9S,10R), the
active pheromone component among three isolated from
E. acrea.1a The first highly efficient asymmetric synthesis
of 1 and its enantiomer was reported by utilizing Sharpless
asymmetric epoxidation as the key step, which was an
improved version of theirpreliminary communication.7b Most
of the known syntheses of 1 employed the same asymmetric
epoxidation, while a few followed kinetic resolution to
achieve the required chirality.2b,7 All these approaches are
inefficient and furnished 1 in only 7–12% overall yields until
a recent report by Du et al. with 31% overall yield.7h The lim-
itation of this method is that the unstable epoxide will interfere
with further homologation so it is difficult to synthesize the
Figure 1. Pheromone components of H. cunea (Drury).
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Practical synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene
KOREAN CHEMICAL SOCIETY
compound 1 on a large scale. Thus, it is still a target for che-
mists to achieve such pheromone components by using new
and practical synthetic strategies that ensure optical purity
and good overall yields.
Our previous work toward the total synthesis of various
pheramones8 encouraged us to take up a different approach
to synthesize 1; also it is a part of our research on the synthesis
of biologically and pharmacologically9 important chemical
entities. Here we report a practical synthesis of the sex phero-
mone 1 in eight steps by utilizing Sharpless asymmetric
dihydroxylation as the key step.
it was filtered through Celite and washed with ethyl acetate
(2 × 150 mL). The combined organic layer was dried over
anhydrous Na2SO4. The crude compound was purified by
flash column chromatography to get the pure alkene com-
pound 10 (7.52 g, 94%) as a light yellowish oil. IR (neat) νmax
3327, 2955, 2918, 2850, 1629, 1471, 1372, 1048, 885 cm−1;
1H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H),
1.22–1.35 (m, 18H), 1.95–2.12 (m, 2H), 2.23–2.37 (m, 2H),
3.59–3.67 (m, 2H), 5.32–5.44 (m, 1H), 5.50–5.61 (m, 1H)
ppm; 13C NMR (100 MHz, CDCl3): δ 125.6, 124.9, 62.3,
31.9, 30.8, 29.7, 29.7, 29.6, 29.6, 29.5, 29.5, 29.3, 27.9,
22.7, 14.2 ppm; GC-MS (m/z): 226 [M]+; Anal. calcd for
C15H30O: C, 79.58; H, 13.36. Found: C, 79.27; H, 13.07.
Experimental
(3S,4R)-Pentadecane-1,3,4-triol (11).
Into a round-
t
All glassware was dried thoroughly in a hot oven and streamed
with nitrogen before use. Solvents were dried and purified by
conventionalmethods priorto use. All thechemicals werepur-
chased from Sigma-Aldrich (St. Louis, MO, USA). IR mea-
surements were performed on an FTIR-6300 spectrometer
bottomed flask was added BuOH (85 mL) and H2O (85
mL), AD-mix-β (43 g), and methane sulfonamide (2.99 g,
31.4 mmol, 1.0 equiv). The mixture was stirred at room tem-
perature (RT) until the solution became clear, and then the
reaction mixture was cooled to 0 ꢁC. To this cooled solution
was added compound 10 (6.68 g, 31.4 mmol, 1.0 equiv) and
stirred at 0 ꢁC for 2 days. The reaction was quenched with sat-
urated sodium sulfite solution and extracted with ethyl acetate.
The organic layer was dried over Na2SO4 and concentrated.
On silica gel column chromatography with 1:9 (methanol/
ethyl acetate) gave pure diol 11 (7.88 g, 96%, 86.5% ee
[checked by chiral HPLC, Chiral Pak AD-H, 250 × 4.6 × 5
m, 0.01 MNH4OAc inwater:ACN (1:9), 1mL/min withmono
p-nitro benzoate derivative of 12]) as a white solid.
M.p. 79–81 ꢁC. ½αꢂD25 = +6:9 (c 1.0, methanol); IR (KBr) νmax
3313, 3270, 3214, 2917, 2850, 1632, 1467, 1314, 1143, 1062,
884, 778, 688 cm−1; 1H NMR (400 MHz, CDCl3): δ 0.90 (t, J
= 6.8 Hz, 3H), 1.24–1.38 (m, 18H), 1.49–1.88 (m, 4H),
3.29–3.33 (m, 2H), 3.36–3.42 (m, 1H), 3.51–3.61 (m, 1H),
3.65–3.78 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ
76.0, 73.3, 60.4, 36.0, 33.7, 33.1, 30.9, 30.8, 30.5, 27.0,
23.7, 14.2 ppm; GC-MS (m/z): 260 [M]+; Anal. calcd for
C15H32O3: C, 69.18; H, 12.39. Found: C, 69.39; H, 12.00.
1
(JASCO, Tokyo, Japan). H NMR (at 400 MHz) and 13C
NMR (at 100 MHz) spectroscopic data were recorded on an
Avance 400 MHz spectrometer (Bruker, Rheinstetten, Ger-
many). Gas chromatography-mass spectrometry (GC-MS)
analyses were carried out with Hewlett-Packard 6890 and
5973 system (Agilent, Santa Clara, USA).
Pentadec-3-yn-1-ol (7). Catalytic Fe(NO3)3ꢀ9H2O was
added to an ammonia solution (100 mL) (appearing in an
ammonia condenser) and stirred for 30 min. Lithium metal
(1.48 g, 212.8 mmol, 4.0 equiv) was added slowly to the reac-
tion mixture, and brown color turned into white-gray after 30
min. Then, butyn-1-ol 9 (4.8 mL, 63.8 mmol, 1.2 equiv) in dry
tetrahydrofuran (THF) was added dropwise and stirred for 1 h,
compound 8 (12.5 g, 53 mmol, 1.0 equiv) in THF (16 mL) was
added slowly, and stirring was continued for 16 h at −45 ꢁC.
Thin Layer Chromatography (TLC) was used to monitor the
complete consumption of the starting alcohol. Saturated
NH4Cl (150 mL) was added to the reaction mixture and then
extracted with ethyl ether (2 × 100 mL). The combined
organic layers were washed with water and dried over anhy-
drous Na2SO4. The crude compound was purified by column
chromatography to get the pure alcohol compound 7 (8.44 g,
76%) as a white solid. M.p. 42–43 ꢁC; IR (KBr) νmax 3327,
2-(4S,5R)-2,2-Dimethyl-5-undecyl-1,3-dioxolan-4-yl)etha-
nol (12). A mixture of compound 11 (7.00 g, 26.8 mmol, 1.0
equiv) and pTsOHꢀH2O (1.02 g, 5.37 mmol, 0.2 equiv) in ace-
tone (250 mL) was stirred at RT for 24 h. The reaction was
quenched with NaHCO3. After filtration, the solvent was con-
centrated under reduced pressure. The residue was purified by
columnchromatography(hexane/EtOAc, 1:1)togivetheacet-
onide-protected compound 12 (7.43 g, 92%) as a colorless oil.
1
2918, 2850, 2106, 1629, 1471, 1048, 1018, 885 cm−1; H
NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H),
1.22–1.38 (m, 16H), 1.44–1.53 (m, 2H), 2.13–2.20 (m, 2H),
2.41–2.47 (m, 2H), 3.69 (q, J = 6.0 and 12.3, 2H) ppm; 13C
NMR (100 MHz, CDCl3): δ 82.8, 76.2, 61.3, 31.9, 29.6,
29.5, 29.1, 29.0, 28.9, 23.2, 22.7, 18.7, 14.1 ppm; GC-MS
(m/z): 224 [M]+; Anal. calcd for C15H28O: C, 73.36; H,
11.17. Found: C, 73.07; H, 10.87.
(Z)-Pentadec-3-en-1-ol (10). To a suspension of compound 7
(8.0 g, 35 mmol, 1.0 equiv) in ethyl acetate (100 mL) was
added a catalytic amount of Lindlar's catalyst in a Parr reaction
bottle and quinoline (70 mg) was added. The reaction mixture
was shaken under H2 atmosphere (40 psi, 6 h) using a Parr
hydrogenation apparatus. After completion of the reaction,
½αꢂ2D5 = +44:5 (c 1.0, methanol); IR (neat) νmax 3440, 2927,
1418, 1375, 1074, 909, 796, 674, 448 cm−1; H NMR (400
1
MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H), 1.21–1.32 (m,
16H), 1.34 (d, J = 8.3 Hz, 6 H), 1.47–1.64 (m, 4H),
1.66–1.88 (m, 2H), 3.61–3.89 (m, 2H), 4.04–4.13 (m, 1H),
4.21–4.30 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ
107.8, 81.0, 80.9, 61.3, 38.8, 32.1, 31.9, 29.8, 29.7, 29.6,
29.6, 29.3, 29.3, 28.4, 27.2, 26.3, 22.7, 14.1 ppm; GC-MS
(m/z): 300 [M]+; Anal. calcd for C18H36O3: C, 71.95; H,
12.08. Found: C, 72.25; H, 12.38.
Bull. Korean Chem. Soc. 2015, Vol. 36, 1245–1249
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Practical synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene
KOREAN CHEMICAL SOCIETY
2-((4S,5R)-2,2-Dimethyl-5-undecyl-1,3-dioxolan-4-yl)acet-
aldehyde (13). 2-Iodoxybenzoic acid (IBX) (12.68 g, 45.2
mmol, 2.0 equiv) was dissolved in a minimum amount of
dry Dimethyl sulfoxide (DMSO) and stirred for 15 min. Then
the starting material 12 (6.80 g, 22.6 mmol, 1.0 equiv) dis-
solved in THF (80 mL) was added. Then reaction was stirred
for 3 h at RT and filtered through a Celite pad. The reaction
mixture was dissolved in ethyl acetate and washed with aque-
ous sodium bicarbonate solution. The organic layer was dried
over Na2SO4 and concentrated, followed by column chroma-
tography purification to get the pure aldehyde compound 13
(6.01 g, 89%)asacolorless oil. ½αꢂ2D5 = −10:1(c1.0, methanol);
IR (Neat) νmax 3404, 2924, 2847, 1398, 1085, 910, 789, 674
cm−1; 1H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H),
1.16–1.50 (m, 26H), 2.44–2.77 (m, 2H), 4.14–4.21 (m, 1H),
4.54–4.63 (m, 1H ), 9.82–9.84 (m, 1H) ppm; 13C NMR
(100 MHz, CDCl3): δ 200.9, 108.1, 77.4, 72.8, 44.7, 31.9,
29.6, 29.6, 29.6, 29.6, 29.5, 29.5, 28.3, 26.3, 25.7, 22.7,
14.1 ppm; GC-MS (m/z): 299 [M]+; Anal. calcd for
C18H34O3: C, 72.44; H, 11.48. Found: C, 72.02; H, 11.04.
6H), 1.48–1.58 (m, 2H), 2.02–2.38 (m, 4H), 2.71–2.86
(m, 2H), 3.55–3.71 (m, 1H), 4.04–4.12 (m, 1H), 5.26–5.56
(m, 4H) ppm; 13C NMR (100 MHz, CDCl3): δ 132.8,
132.3, 132.1, 126.6, 125.3, 73.973.8, 31.9,31.6, 30.9,
29.6, 29.6, 29.6, 29.6, 29.3, 29.0, 26.0, 25.6, 22.7,
20.6, 20.5, 14.2, 14.1 ppm; GC-MS (m/z): 365 [M]+; Anal.
calcd for C24H44O2: C, 79.06; H, 12.16. Found: C, 79.41;
H, 12.42.
(3Z,6Z,9S,10R)-Henicosa-3,6-diene-9,10-diol
(15).
Compound 6 (4.2 g, 11.5 mmol, 1.0 equiv) was dissolved
in methanol, and a catalytic amount of p-Toluenesulfonic acid
(PTSA)wasadded. Thereactionmixture wasstirredfor24 hat
RT and passed through silica gel with CH2Cl2 solvent to get
the diol product 15 (3.25 g, 87%) as a colorless oil.
½αꢂ2D5 = +41:5 (c 1.0, methanol); IR (Neat) νmax 3422, 3290,
3013, 2958, 2925, 2872, 2850, 1632, 1464, 1060, 1044,
1
722 cm−1; H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8
Hz, 3H), 0.97 (t, J = 7.5 Hz, 3H), 1.23–1.29 (m, 18H),
1.45–1.54 (m, 2H), 2.04–2.12 (m, 2H), 2.19–2.25 (m, 1H),
2.35–2.45 (m, 1H), 2.76–2.91 (m, 2H), 3.58–3.68 (m, 1H),
3.79–3.87 (m, 1H), 5.19–5.54 (m, 4H) ppm; 13C NMR
(100 MHz, CDCl3): δ 132.10, 132.27, 132.1, 126.83,
125.52, 77.97, 77.77, 33.05, 32.99, 31.93, 30.9, 29.72,
29.67, 29.61, 29.57, 25.81, 25.71, 22.71, 20.58, 14.28,
14.15 ppm; GC-MS (m/z): 324 [M]+; Anal. calcd for
C21H40O2: C, 77.72; H, 12.42. Found: C, 78.12; H, 12.10.
(Z)-Hex-3-en-1-yltriphenylphosphonium iodide (14). Into
a round-bottomed flask was added (Z)-1-iodohex-3-ene (14.0
g, 66.4 mmol, 1.0 equiv), triphenyl phosphine (19.20 g, 73.5
mmol, 1.1 equiv), and toluene (100 mL). The mixture was stir-
red at reflux condition for 24 h and then monitored by TLC.
The reaction mixture was then cooled to RT and filtered,
and washed with hexane (300 mL) to get the pure Wittig salt
(30 g, 95%) as a white solid. M.p. 120–122 ꢁC. IR (KBr) νmax
3429, 3016, 2963, 2865, 1627, 1578, 1486, 1438, 1336,
(9S,10R)-9,10-Epoxy-(3Z,6Z)-henicosa-3,6-diene (1). To a
solution of 15 (2.60 g, 8.0 mmol, 1.0 equiv) in freshly distilled
CH2Cl2 was added trimethyl orthoacetate (5.1 mL, 40.1
mmol, 5.0 equiv) and PPTS (0.20 g, 0.80 mmol, 0.1 equiv)
at RT for 10 h; most of the volatile components were removed
by rotary evaporation. The residue was dissolved in freshly
distilled CH2Cl2 and cooled to 0 ꢁC. Trimethylsilyl chloride
(5.0 mL, 40.1 mmol, 5.0 equiv) was added via a syringe,
and the mixture was allowed to warm to room temperature
and stirred for 1.5 h. Most of the volatiles were removed in
vacuo, and the resulting residue was dissolved in methanol.
K2CO3 (3.30 g, 24.0 mmol, 3.0 equiv) was added in one por-
tion, and the mixture was stirred at room temperature for 1 h.
The reaction mixture was poured into saturated ammonium
chloride, extracted with ethyl acetate, dried, concentrated,
and chromatographed to get the final epoxide product 1
(1.59 g, 65% yield for three steps) as a colorless oil.
1
1163,1111, 996, 808, 743, 720 cm−1; H NMR (400 MHz,
CD3COCD3): δ 0.92 (t, J = 7.5 Hz, 3H), 1.88–2.04 (m, 2H),
2.35–2.50 (m, 2H), 3.47–3.60 (m, 2H), 5.34–5.57 (m, 2H),
7.77–7.94 (m, 15H) ppm; 13C NMR (100 MHz, CD3OCD3):
δ 136.4, 136.3, 136.3, 136.3, 135.4, 135.4, 135.0, 134.9,
134.9, 134.9, 134.8, 131.6, 131.5, 126.5, 119.5, 119.5,
30.8, 21.5, 14.1; ESI-MS (m/z): 473 [M + H]+. Anal. calcd
for C24H26IP: C, 61.03; H, 5.55. Found: C, 61.32; H, 5.26.
(4S,5R)-2,2-Dimethyl-4-((2Z,5Z)-octa-2,5-dien-1-yl)-5-
undecyl-1,3-dioxolane (6). A solution of the Wittig salt 14
(17.4 g, 36.9 mmol, 2.0 equiv) in THF (60 mL) at −78 ꢁC was
treated dropwise with n-BuLi (18.4 mL, 1.6 M solution in
THF, 29.5 mmol, 1.6 equiv). The bright orange-red reaction
mixture was warmed to 25 ꢁC and stirred for 10 min. The reac-
tion mixture was recooled to −78 ꢁC, treated with compound
13 (5.5 g, 18.4 mmol, 1.0 equiv), and brought to 25 ꢁC. After
stirring at 25 ꢁC for 30 min, the reaction mixture was treated
with saturated aqueous NH4Cl solution and partitioned
between EtOAc (100 mL) and H2O (100 mL). The organic
layer was dried over Na2SO4 and concentrated under reduced
pressure and purified by column chromatography afford pure
6 (5.20 g, 78%) as a colorless oil. ½αꢂ2D5 = +10:9 (c 1.0, meth-
anol); IR (Neat) νmax 3009, 2925, 2858, 1743, 1645, 1466,
1375, 1244, 1220, 1171, 1069, 1033, 865,721 cm−1; 1H
NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3H), 0.97 (t,
J = 7.5 Hz, 3H), 1.20–1.31 (m, 18H), 1.36 (d, J = 19.7Hz,
½αꢂ2D5 = +3:9 (c 1.7, CCl4) [Refs 7g and 7h ½αꢂ28 = +3:9 (c
D
1.8, CCl4 ), ½αꢂ22 = +3:99 (c 1.65, CCl4)]; IR (Neat) νmax
D
3012, 2960, 2925, 2854, 1650, 1464, 1382, 1076, 1025
1
cm−1; H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz,
3H), 0.98 (t, J = 7.4 Hz, 3H), 1.22–1.32 (m, 18
H),1.50–1.56 (m, 2H), 2.03–2.12 (m, 2H), 2.18–2.27 (m,
1H), 2.35–2.46 (m, 1H), 2.73–2.84 (m, 2H), 2.90–2.97 (m,
2H), 5.26–5.56 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3)
δ 132.2, 130.7, 126.7, 124. 2, 57.2, 56.4, 31.9, 29.6, 29.6,
29.5, 29.3, 27.7, 26.6, 26.2, 25.7, 22.7, 20.5, 14.2, 14.1
ppm; GC-MS (m/z): 306 [M]+; Anal. calcd. for C21H38O: C,
82.28; H, 12.50. Found: C, 82.59; H, 12.11.
Bull. Korean Chem. Soc. 2015, Vol. 36, 1245–1249
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Practical synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene
Results and Discussion
KOREAN CHEMICAL SOCIETY
The retrosynthetic analysis of pheromone 1 starting from
commercially available 1-bromoundecane (8) and 3-butyn-
1-ol (9) is shown in Scheme 1. The target pheromone 1 can
be achieved from the intermediate 6 in four synthetic steps.
Compound 6 can be obtained from 7 by partial hydrogena-
tion, Sharpless asymmetric hydroxylation, and Wittig olefina-
tion as key steps. The intermediate 7 can be synthesized by
metal-based coupling reaction in liquid ammonia between 8
and 9.
Our synthetic strategy involves Sharpless asymmetric dihy-
droxylation on cis-olefin as the key step, for the first time,
to achieve chirality in 1.
The asymmetric synthesis of pheromone 1 is outlined in
Scheme 2. Here, we have carried out a metal dissolving cou-
pling reaction between 8 and 9, which generates lithium amide
in liquid ammonia at −45 ꢁC in the presence of catalytic
Fe(NO3)3ꢀ9H2O in 76% yield. This reaction successfully
afforded pentadec-3-yn-1-ol (7) and was further preceded
for hydrogenation using Lindlar's catalyst (5% Pd on CaCO3
poisoned with lead) in presence of catalytic quinoline under 1
atm H2 gas. Partial hydrogenation of 7 afforded the cis-olefin
10 in 94% yield, which was confirmed by IR absorption bands
at1048 cm−1 ( C Hbending) forcis-olefin. Carbons appear-
ing at δ 125.6 and 124.9 in 13C NMR spectrum also confirmed
the same. This cis-olefin 10 was subjected to Sharpless asym-
metric dihydroxylation using AD-mix-β to afford triol 11 in
96% yield with 86.5% ee. The vicinal diol of 11 was protected
by acetone in presence of catalytic PTSA to achieve acetonide
Scheme 1. Retrosynthetic analysis of pheromone 1.
Scheme 2. Synthesis of pheromone 1.
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Practical synthesis of (9S,10R)-9,10-epoxy-(3Z,6Z)-henicosadiene
KOREAN CHEMICAL SOCIETY
12 in 92% yield. The primary alcohol of 12 was oxidized in
presence of IBX in DMSO/THF to obtain the key intermediate
aldehyde 13 in 89% yield. This aldehyde can be used for Wit-
tig olefination to achieve different pheromone components
depending on the appropriate Wittig counterpart. We have
taken the known Wittig salt 1410 to make phosphonium ylide
in presence of n-BuLi, which was then used for the Wittig ole-
fination in THF at −78 ꢁC to obtain 6 in 78% yield. The Wittig
olefin 6 was treated with PTSA to afford diol 15 in 87% yield.
Finally, the epoxide was then obtained in a one-pot, three-step
synthesis from diol 15. At first, 15 was treated with trimethyl
orthoacetate in presence of PPTS to achieve the corresponding
cyclic orthoacetate, which was directly treated with TMSCl
for 1 h and then with K2CO3 in MeOH affording the target
pheromone 1 in 65% yield (three steps).
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Conclusion
In summary, we have accomplished concise and practical syn-
thesis of (3Z,6Z)-cis-9,10-epoxy-3,6-henicosadiene (1), the
major sex pheromone of E. acrea (Drury) starting from com-
mercially available but-3-yn-1-ol and 1-bromoundecane in
24.7% overall yield in eight steps. The simplicity of the
method and purity of the products in this synthetic approach
allow the potential and practical use of pheromone 1 in field
studies to understand the responses of pest management
programs.
Acknowledgments. This work was supported by the grants
from the Ministry of Environment (KME, 412-111-008) and
the National Research Foundation (NRF-2009-0094063),
South Korea.
Bull. Korean Chem. Soc. 2015, Vol. 36, 1245–1249
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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