A concise, protection-free and divergent approach for the enantioselective syntheses of two pheromonal epoxide components of the fall webworm moth and other species

Article abstract of DOI:10.1021/jo1007042

(Figure presented) On the basis of Zhous modified Sharpless asymmetric epoxidation, sequential coupling reactions, and a divergent strategy, the protection-free syntheses of two main pheromonal components 1 and 5, found in the fall webworm moth, Hyphantria cunea, and other species have been accomplished in 10 steps (for two compounds). The overall yields are 31% for 1, 28% for 5, and 25% for both 1 and 5, respectively. The ee values of the final products 1 and 5 are at least 99%.

Full text of DOI:10.1021/jo1007042

pubs.acs.org/joc
A Concise, Protection-Free and Divergent Approach
for the Enantioselective Syntheses of Two
Pheromonal Epoxide Components of the Fall
Webworm Moth and Other Species
Yu Du, Jian-Feng Zheng, Zhi-Gang Wang, Li-Jiao Jiang,
Yuan-Ping Ruan, and Pei-Qiang Huang*
Department of Chemistry and Key Laboratory for Chemical
Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen, Fujian
3
61005, People’s Republic of China
pqhuang@xmu.edu.cn
Received April 12, 2010
FIGURE 1. Structures of the pheromone of the fall webworm moth
Hyphantria cunea).
(
4
epoxide in at least five species. Moreover, epoxides 1 and
were also two pheromonal components of Diacrisia obliqua
Bihar hairy caterpillar, Arctiidae), a polyphagous pest
5
(
attacking as many as 33 host plants particularly oil seed
5
crops. This pest has been recorded in many Asian countries
including Indian, China, and Japan. Roelofs and co-workers
suggested (9S,10R) absolute configuration for pheromones
3
of E. acrea. Arn and co-workers showed that the synthetic
(
9S,10R)-enantiomers of 4 and 5 were biologically active,
2
while the (9R,10S) forms were inactive. Thus the (9S,10R)-
enantiomers are the natural and biologically active pheromones.
Field tests showed that a mixture of synthetic 1-5 in the
approximate proportions found in the H. cunea and Diacrisia
obliqua female attracted males. Latter, Senda and co-workers
found that a blend of 1, 3, and5 was able to attract H. cunea, and
On the basis of Zhou’s modified Sharpless asymmetric
epoxidation, sequential coupling reactions, and a divergent
strategy, the protection-free syntheses of two main phero-
monal components 1 and 5, found in the fall webworm moth,
Hyphantria cunea, and other species have been accomplished
in 10 steps (for two compounds). The overall yields are 31%
for 1, 28% for 5, and 25% for both 1 and 5, respectively. The
ee values of the final products 1 and 5 are at least 99%.
2
5b
6
this blend was commercialized for H. cunea monitoring.
It has been demonstrated that the 1, 3, and 5-containing
blend of female H. cunea and Diacrisia obliqua is active in the
field test, and the epoxide components 1 and 5 play a key role
for the biological activity. Because component 3 can be
1
,7
prepared readily from linolenic acid, the synthesis of these
pheromonal components were focused on the asymmetric
The fall webworm moth, Hyphantria cunea, also known as
the American white moth and Amerika-Shirohitori, is a
notorious pest widely distributed throughout the northern
hemisphere and in many Asian countries such as Japan and
China. Its larva attacks many crops, fruit trees, and orna-
mental trees. A total of five pheromone components (1-5,
Figure 1) have been identified with three of them being
5
b,8
2,5,8g,9
synthesis of epoxides components 1
tively. Nevertheless, considering the synthesis of both
and 5,
respec-
(4) Bell, T. W.; Meinwald, J. J. Chem. Ecol. 1986, 12, 385–409.
(5) (a) Yadav, J. S.; Valli, M. Y.; Prasad, A. R. Tetrahedron 1998, 54,
551–7562. (b) Yadav, J. S.; Valli, M. Y.; Prasad, A. R. Pure Appl. Chem.
7
1
,2
2001, 73, 1157–1162.
6) Senda, S.; Saika, T.; Furumori, K. Nitto Giho 1993, 31, 97–102.
optically active epoxides.
pheromones have been found in other species. For example,
3Z,6Z)-cis-9,10-epoxy-3,6-henicosadiene (1) is also identi-
Interestingly, some of these
(
(7) (a) Naomi, C. D.; Gerhard, G.; Reging, G. J. Chem. Ecol. 1999, 25,
229–2245. (b) Rule, G. S.; Roelofs, W. L. Arch. Insect. Biochem. Physiol.
989, 12, 89–97. (c) Yan, Z.-K.; He, J.; Zhang, Z.-N. Chin. J. Pesticide Sci.
002, 4, 85–88.
2
1
2
(
fied as the major pheromone component of the saltmarsh
3
caterpillar moth Estigment acrea Drury. Further study on
the female arctiids has uncovered this same 21-carbon
(8) For the asymmetric synthesis of 1, see: (a) Wong, J. W.; Underhill,
E. W.; Mackenzie, S. L.; Chisholm, M. D. J. Chem. Ecol. 1985, 11, 727–756.
b) Mori, K.; Ebata, T. Tetrahedron 1986, 42, 3471–3478. (c) Bell, T. W.;
(
Ciaccio, J. A. Tetrahedron Lett. 1988, 883–888. (d) Lin, G. Q.; Zeng, C. M.
Acta Chim. Sin. 1993, 51, 197–201. (e) Zhang, Z. B.; Wang, Z. M.; Wang,
Y. X.; Liu, H. Q.; Lei, G. X.; Shi, M. Tetrahedron: Asymmetry 1999, 10, 837–
840. (f) Bell, T. W.; Ciaccio, J. A. J. Org. Chem. 1993, 58, 5153–5162.
(g) Mori, K.; Nakanishi, A. Biosci. Biotechnol. Biochem. 2005, 69, 1007–
1013. (h) Che, C.; Zhang, Z.-N. Chin. Chem. Lett. 2005, 16, 420–421.
(
1) Hill, A. S.; Kovalev, B. G.; Nikolaeva, L. N.; Roelofs, W. L. J. Chem.
Ecol. 1982, 8, 383–396.
2) T oꢀ th, M.; Buser, H. R.; Pena, A.; Arn, H.; Mori, K.; Takeuchi, T.;
Nikolaeva, L. N.; Kovalev, B. G. Tetrahedron Lett. 1989, 30, 3405–3408.
3) Hill, A. S.; Roelofs, W. L. J. Chem. Ecol. 1981, 7, 655–668.
(
(
DOI: 10.1021/jo1007042
r 2010 American Chemical Society
Published on Web 05/27/2010
J. Org. Chem. 2010, 75, 4619–4622 4619

Du et al.
JOCNote
SCHEME 1. Retrosynthetic Analysis of the Pheromonal
Components 1 and 5
SCHEME 2
components 1 and 5, the known approaches are inefficient,
because the two triene and diene side chains in both components
1
and 5 need to be synthesized separately. On the basis of these
considerations, we decided to develop an inherently divergent
approach to the key pheromonal components 1 and 5, and the
results are reported herein.
SCHEME 3
Considering the structural similarity of epoxides 1 and 5,
bromide 6 was designed as a common precursor. Accord-
ingly, the retrosynthetic analysis of both components 1 and 5
is outlined in Scheme 1. Given the epoxide as the key
structural feature of both 1 and 5, the Sharpless asymmetric
1
0
epoxidation (AE) appeared to be a convenient method for
their asymmetric synthesis. A direct use of the Sharpless
8
b
asymmetric epoxidation (AE) has been reported by Mori,
2
and adopted by Kovalev and co-workers for the synthesis of
components 1, 4, and 5. The drawback of the approach,
featuring the first installation of the shorter unsaturated side
chain, resided in the fact that the enantiomeric excess (% ee)
of the AE product was only 87-88% that required addi-
tional steps including derivation, repeated recrystallizations,
and release of the hydroxyl group. This was expected to be
avoided by using allylic alcohol 9, bearing a longer side
10,11
alcohol
tion (AE) conditions [Ti(OiPr) , L-(þ)-DIPT, t-BuO H,
9, Zhou’s modified Sharpless asymmetric oxida-
13
4
2
CaH , SiO , CH Cl , -25 °C, 4 days) turned out to give a
2
2
2
2
better result (Scheme 2). In such a manner, the epoxide 12
was obtained in at least 85% ee and 92% yield, which was
enriched to >99% ee after one recrystallization from n-hexane.
The enantiomeric excess of epoxide alcohol 12 was deter-
mined by chiral HPLC analysis of its 3,5-dinitrobenzoyl
ester. The racemic epoxide (()-12 for comparison was
obtained by epoxidation of allylic alcohol 9 with mCPBA.
For an efficient coupling of epoxide 12 with propargyl
alcohol, the former was converted into the corresponding
1
0
chain, as a substrate for the AE. Indeed, in the synthesis of
another pheromone, Mori and co-workers showed that the
enantiomeric purity of the AE product of 9 can be enriched
1
1
simply by one recrystallization. However, a low yield
42%) was obtained in the subsequent coupling reaction
(
via tosylate derivative. Thus triflate 8 was selected as our key
intermediate.
Our synthesis started withpropargyl alcohol (10), whichwas
14
triflate 8 by treating with triflic anhydride (Tf O, NEt ,
2
3
CH Cl , -78 to -45 °C, yield 98%).
2
2
1
1,12
converted to (Z)-allylic alcohol 9 by Ames’s procedure.
In the event, treatment of 1-bromoundecane with LiCt
15
Successive treatment of propargyl alcohol TMS ether 13
with n-BuLi and triflate 8 in a mixed HMPA/Et O solvent
2
CCH OLi in a mixed solvent system HMPA/THF pro-
2
duced propargylic alcohol 11 in 92% yield. Partial hydro-
genation of propargylic alcohol 11 over Lindlar catalyst
system at -78 °C afforded the desired coupling product,
which, without purification, was treated with K CO in
2
3
MeOH to give the propargylic alcohol 14 in 85% yield over
two steps (Scheme 3). It was found that when 2 equiv of
n-BuLi was used, the coupling of triflate 8 with propargyl
alcohol (10) proceeded chemoselectively to produce di-
rectly the coupling product 14 in 84% yield.
(
H , 5% Pd/CaCO , poisoned with 3.5% Pb, n-hex., 0-5 °C)
2
3
gave (Z)-allylic alcohol 9 in 98% yield. The Z/E ratio of 9 was
at least 49:1 as determined by GC analysis of the crude
product. For the asymmetric epoxidation of (Z)-allylic
8g
Chemoselective bromination of propargylic alcohol 14
6
1
(9) For the asymmetric synthesis of 5, see: (a) Mori, K.; Takeuchi, T.
Liebigs Ann. Chem. 1989, 453–457. (b) Che, C.; Zhang, Z.-N. Tetrahedron
by Appel-Lee reaction (CBr , PPh , CH Cl , rt) gave
4
3
2
2
2
005, 61, 2187–2193.
10) Rossiter, B. E.; Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1981,
03, 464–465.
(
(14) Kotsuki, H.; Kadota, I.; Ochi, M. J. Org. Chem. 1990, 55, 4417–4422.
(15) (a) Aizpurua, J. M.; Palomo, C. Bull. Soc. Chim. Fr. 1982, 11, 265–
268. (b) Jin, B.; Liu, Q. S.; Sulikowski, G. A. Tetrahedron 2005, 61, 401–408.
(16) (a) Lee, J. B. J. Am. Chem. Soc. 1966, 88, 3440–3441. (b) Appel, R.;
Kleinst u€ ck, R.; Ziehn, K. D. Angew. Chem., Int. Ed. Engl. 1971, 10, 132.
(c) Hayashi, H.; Nakanishi, K.; Brandon, C.; Marmur, J. J. Am. Chem. Soc.
1973, 95, 8749–8757. For a review, see: (d) Appel, R. Angew. Chem., Int. Ed.
Engl. 1975, 14, 801–811.
1
(
(
11) Ebata, T.; Mori, K. Agric. Biol. Chem. 1989, 53, 801–804.
12) Ames, D. E.; Covell, A. N.; Goodburn, T. G. J. Chem. Soc. 1963,
5
889–5893.
(13) (a) Wang, Z.-M.; Zhou, W.-S.; Lin, G.-Q. Tetrahedron Lett. 1985, 26,
221–6224. (b) Wang, Z.-M.; Zhou, W.-S. Synth. Commun. 1989, 19, 2627–
632.
6
2
4
620 J. Org. Chem. Vol. 75, No. 13, 2010

Du et al.
JOCNote
SCHEME 4
SCHEME 6
SCHEME 5
In summary, we have developed a strategically conver-
gent and product divergent, yet protection-deprotection-
free approach to the two pheromone principle components
of H. cunea and Diacrisia obliqua, which are also present in
several other species. Considering the total steps (10 steps)
required for the synthesis of the two most active and
challenging pheromone components of the useful blend,
this approach is quite efficient. The concept of developing
a divergent synthesis in the last step in a target-oriented
synthesis (TOS) is of value in organic synthesis.
8
g,9b
bromide 15 in 84% yield without affecting the epoxide
(Scheme 4). Further chemoselective coupling of propargyl
bromide 15 with 3-butynyl alcohol (16) was achieved by
1
using Spinella’s conditions (Cs CO , CuI, NaI, DMF, rt),
7
2
3
which afforded the coupling product 7 in 82% yield.
Alternatively, a convergent coupling approach was also
explored. For this purpose, the requisite diyne 17 was pre-
pared from 3-butynyl alcohol (16) by deprotonation with
ethyl magnesium bromide, followed by CuCl-mediated che-
moselective coupling with propargyl bromide (Scheme 5).
The coupling of triflate 8 with the alkynide generated in situ
from diyne 17 and 2 mol equiv of n-BuLi at -78 °C produced
the desired coupling product 7 in 85% yield. To prove the
chemoselectivity of the reaction, the coupling of 8 with the
lithium alkynide, derived in situ from O-TMS protected 17 and 1
equiv of n-BuLi at -78 °C, was also tested. After cleavage of
TMS with K CO in MeOH compound 7 was obtained.
Chemoselective partial hydrogenation of the diyne 7 was
achieved by using the Lindlar catalyst (H , 5% Pd-CaCO ,
poisoned with 3.5% Pb, n-hexane, 18-19 °C, 35 min), which
gave the known diene 18 in 96% yield (Scheme 6). Chemo-
selective bromination of alcohol 18 afforded bromide 6 in
7% yield. Compound 6 was considered to be a ready
precursor of both 1 and 5. Indeed, treatment of bromide 6
Experimental Section
(
2S,3R)-2,3-Epoxytetradecan-1-ol (12). To a mixture of tita-
nium tetraisopropoxide (10.9 mL, 35.8 mmol), 150 mg of calcium
hydride, and 200 mg of silica gel in 280 mL of anhydrous CH Cl
8
a
2
2
was injected L-(þ)-diisopropyl tartrate (9.8 g, 41.1 mmol) dis-
solved in anhydrous CH Cl (15 mL) via syringe under N in a
2
2
2
cooling bath (-35 °C). After stirring for 30 min, (Z)-tetradec-2-
en-1-ol (9, 6.6 g, 31.1 mmol) dissolved in anhydrous CH Cl
15 mL) was injected. After stirring for another 30 min, 12.5 mL
2
2
(
(68.5 mmol) of anhydrous TBHP (5.5 M) was then injected at
-35 °C. The resulting mixture was allowed to stir at -30 °C for
3 days. The reaction was quenched with 80 mL of 10% aq tartaric
acid. The mixture was stirred at -20 °C for 1 h, then warmed to
room temperature until the aqueous layer became clear. After
separation of the organic layer, the aqueous layer was extracted
2
3
2
3
9
b
with CH
dried over anhydrous Na
reduced pressure. The residue was purified by flash column
chromatography on silica gel (R 0.25, eluent: ethyl acetate:
2 2
Cl
(2 ꢀ 50 mL) and the combined organic layers were
SO , filtered, and concentrated under
4
8
g
2
8
f
petroleum ether = 1:5) to afford epoxide 12 (6.55 g, 92%) as a
white solid, which was recrystallized from petroleum ether to give
9
b
with K CO in MeOH at rt for 24 h gave the desired triene 5
2
3
2
8
8g
11
in 82% yield. The physical {[R]
-0.9 (c 1.9, CHCl ); lit.
4.62 g (65%) of epoxide 12. Mp 69-70 °C (petroleum ether) (lit.
D
3
2
1
9b
25
D
28
19
[R]
-0.38 (c 1.04, CHCl ); lit. [R]
-0.6 (c 3.0, CHCl )}
mp 62.5-63.5 °C); [R]
D
3
-4.2 (c 1.0, CHCl ) {enantiomer lit.
D
3
3
2
2
D
11
23
[
R]
D
þ4 (c 1.3, CH Cl
2 2
)}; [R]
þ8.4 (c 2.0, EtOH) {lit. [R]
D
and spectral data of the synthetic compound were identical
2
,5,8g,9
þ8.3 (c0.7, EtOH)};IR(film) ν 3301 (br, OH), 2914, 2849, 1470,
max
with those reported.
On the other hand, cleavage of the
1
-
1 1
1035 cm ; H NMR (400 MHz, CDCl ) δ0.88 (t, J=6.8 Hz, 3H),
8
3
C-Br bond in 6 with Zn-Cu/NH Cl in MeOH at 68 °C for
4
2
8
D
1.20-1.62 (m, 20H), 2.12 (dd, J = 4.6, 7.5 Hz, 1H), 3.01-3.06
4
0 min afforded diene 1 in 90% yield. The physical {[R]
þ
(
ddd, J = 6.7, 5.5, 4.4 Hz, 1H), 3.16 (ddd, J = 3.9, 4.4, 7.0 Hz, 1H),
8
g
22
3 þ4.0 (c 1.6, CCl )} and spectral
data of the synthetic compound were identical with those
.9 (c 1.8, CCl ); lit. [R]
4
D
4
3
.67 (ddd, J = 4.6, 7.0, 11.9 Hz, 1H), 3.86 (ddd, J = 3.9, 7.5, 11.9
13
3
Hz, 1H) ppm; C NMR (100 MHz, CDCl ) δ14.1, 22.7, 26.6, 27.9,
5
b,8
reported.
2
9.3, 29.4, 29.48, 29.5, 29.58, 29.59, 31.9, 56.9, 57.3, 60.9 ppm; MS
þ
(
ESI) m/z 251.2 (M þ Na , 100%). Anal. Calcd for C H O : C,
1
4
28 2
73.63; H, 12.36. Found: C, 73.66; H, 12.36. The enantiomeric excess
(ee) of epoxide (2S,3R)-12 was determined by HPLC analysis of the
(17) For copper-mediated coupling of 1-alkynes and propargylic halides,
see: Caruso, T.; Spinella, A. Tetrahedron 2003, 59, 7787–7790. and refer-
ences cited therein.
(
18) This reagent is efficient for the debromination of R-bromo ketones:
Takaya, H.; Makino, S.; Hayakawa, Y.; Noyori, R. J. Am. Chem. Soc. 1978,
00, 1765–1777.
(19) Souli ꢀe , J.; Boyer, T.; Lallemand, J. Y. Tetrahedron: Asymmetry 1995,
6, 625–636.
1
J. Org. Chem. Vol. 75, No. 13, 2010 4621

Du et al.
JOCNote
corresponding 3,5-dinitrobenzoyl ester (column, Chiralpak AD-H
filtered and concentrated in vacuo. The residue was purified
4
.6 ꢀ 250 mm; n-hexane/ethanol = 60:40; flow rate, 1.0 mL/min) t
R
f
by flash column chromatography on silica gel (R 0.35, eluent:
(
(
min): the product before recrystallization, (2R,3S)-ester: 19.9
5.4%), (2S,3R)-ester: 24.2 (94.6%), ee 89.0%; the product after
ethyl acetate:petroleum ether = 1:50) to give (9S,10R)-5 (44 mg,
82%) as a colorless oil. [R]
2
8
D
b
8g
-0.9 (c 1.9, CHCl ) {lit. [R]
21
3
D
9
25
one recrystallization, (2R,3S)-ester: 19.9 (0.2%), (2S,3R)-ester: 24.0
99.8%), ee 99.5%.
2S,3R)-2,3-Epoxytetradecyl Trifluoroacetate (8). To a vigo-
rously stirred suspension of epoxide 12 (502 mg, 2.2 mmol) in
anhydrous CH Cl (146 mL) were added dropwise triethyl-
-0.38 (c 1.04, CHCl
3
); lit. [R]
D
3
-0.6 (c 3.0, CHCl )}; IR
(
(film) νmax 3014, 2924, 2854, 1635 (w, CdC), 1466, 1080, 1051,
-
1 1
(
3
1035, 1018 cm ; H NMR (400 MHz, CDCl ) δ 0.88 (t, J =
6.8 Hz, 3H), 1.20-1.57 (m, 20H), 2.24 (dt, J = 14.5, 6.4 Hz, 1H),
2.40 (dt, J = 14.5, 6.4 Hz, 1H), 2.90-3.00 (m, 4H), 5.13 (d, J =
10.1Hz, 1H), 5.22 (d, J = 16.8Hz, 1H), 5.41 (dt, J = 10.4, 8.0 Hz,
1H), 5.45-5.58 (m, 2H), 6.03 (dd, J = 10.8, 10.4 Hz, 1H), 6.65
2
2
amine (1.1 mL, 7.9 mmol) and trifluoromethanesulfonic anhy-
dride (1.1 mL, 6.6 mmol) under argon atmosphere at -78 °C.
The suspension was allowed to warm slowly to about -35 °C
and stirred. Once the solution became clear, the reaction was
recooled to -78 °C and stirred for 30 min, then quenched with
1
3
(ddd, J = 16.8, 10.8, 10.1 Hz, 1H) ppm; C NMR (100 MHz,
CDCl ) δ 14.1, 22.7, 26.25, 26.28, 26.6, 27.8, 29.3, 29.55, 29.63,
3
31.9, 56.3, 57.2, 117.7, 124.9, 129.5, 129.83, 129.88, 131.8 ppm;
MS (ESI) m/z 327.2 (M þ Na , 100%). Anal. Calcd for C H O:
21 36
þ
an aqueous NH Cl solution (30 mL). The aqueous layer was
4
extracted with CH
layers were washed with brine, dried over anhydrous Na
2
Cl
2
(2 ꢀ 20 mL). The combined organic
C, 82.83; H, 11.92. Found: C, 82.94; H, 11.63.
(9S,10R)-9,10-Epoxy-(3Z,6Z)-henicosa-3,6-diene (1). To a
2
SO
4
,
filtered, and concentrated under vacuum. The residue was puri-
4
stirring aqueous solution (20 mL) of CuSO (400 mg) was added
fied by flash column chromatography on silica gel (R 0.33,
f
Zn dust (3.0 g). The resulting couple was allowed to settle, the
supernatant was decanted, and the residue was washed succes-
sively with water and MeOH. The couple was suspended in
eluent: ethyl acetate:petroleum ether = 1:40) to afford crude
triflate 8 (775 mg, 98%) as a colorless oil, which was used in the
subsequent step without further purification.
NH Cl saturated MeOH (15 mL), and (9S,10R)-6 (77 mg, 0.20
4
(
A solution of n-BuLi (1.6 M in hexane, 5.1 mL, 8.2 mmol) was
9S,10R)-9,10-Epoxyhenicosan-3,6-diyn-1-ol (7). Method 1:
mmol) was added. The mixture was refluxed with stirring for
40 min. The mixture was filtered through Celite, and the filter
cake was washed with diethyl ether. The combined filtrates
were concentrated, washed with water (5 mL), and extracted
with diethyl ether (3 ꢀ 5 mL). The combined organic layers
added slowly to a solution of freshly prepared 3,6-heptadiyn-1-ol
(
17, 444 mg, 4.1 mmol) in anhydrous diethyl ether (60 mL) at
-
78 °C under argon. After stirring for 30 min at the same temp-
erature, a solution of (2S,3R)-8 (755 mg, 2.1 mmol) in anhydrous
diethyl ether (5 mL) and anhydrous HMPA (1.4 mL) were added.
After stirring for 60 min at -78 °C, the reaction was quenched
2 4
were washed with brine, dried over anhydrous Na SO , fil-
tered, and concentrated under reduced pressure. The residue
was purified by flash column chromatography on silica gel
with a saturated aqueous NH
4
Cl solution. The aqueous layer was
(R
f
0.35, eluent: ethyl acetate:petroleum ether = 1:50) to give
2
8
extracted with diethyl ether (3 ꢀ 30 mL). The combined organic
layers were washed with brine, dried over anhydrous Na SO
filtered, and concentrated under reduced pressure. The residue
was purified by flash column chromatography on silica gel (R 0.25,
eluent: ethyl acetate:petroleum ether = 1:4) to give (9S,10R)-7
567 mg, 85%) as a white solid. Mp 72-73 °C (ethyl acetate/
(9S,10R)-epoxide 1 (55 mg, 90%) as a colorless oil. [R]
D
þ3.9
)}; IR (film) νmax
3012, 2960, 2925, 2854, 1648 (w, CdC), 1463, 1381, 1069, 1026
8
g
22
2
4
,
(c 1.8, CCl
4
) {lit. [R]
D
þ3.99 (c 1.65, CCl
4
-
1 1
f
cm ; H NMR (400 MHz, CDCl
3
) δ 0.88 (t, J = 6.8 Hz, 3H),
0.98 (t, J = 7.4 Hz, 3H), 1.20-1.60 (m, 20H), 2.08 (quint, J =
7.4 Hz, 2H), 2.22 (dt, J = 15.1, 6.4 Hz, 1H), 2.40 (dt, J = 15.1,
(
9
b
28
D
n-hexane) (lit. mp 48-50 °C); [R]
{
2
þ32.5 (c 1.0, CHCl )
6.4 Hz, 1H), 2.81 (t, J = 7.0 Hz, 2H), 2.90-2.97 (m, 2H),
3
9
b
25
D
13
lit. [R]
þ23.5 (c 1, CHCl
3
)}; IR (film) νmax 3311 (br, OH),
3
5.26-5.56 (m, 4H) ppm; C NMR (100 MHz, CDCl ) δ 14.1,
-
1 1
954, 2916, 2849, 2285 (w, CtC), 1470, 1318, 1049 cm ; H
14.2, 20.5, 22.7, 25.7, 26.2, 26.6, 27.8, 29.3, 29.5, 29.6, 29.61,
31.9, 56.4, 57.2, 124.2, 126.7, 130.7, 132.2 ppm; MS (ESI) m/z
NMR (400 MHz, CDCl ) δ 0.88 (t, J = 6.8 Hz, 3H), 1.20-1.55
3
þ
(
m, 20H), 1.72 (t, J = 6.3 Hz, 1H), 2.28(ddt, J = 17.0, 7.0, 2.4 Hz,
329.2 (M þ Na , 100%). Anal. Calcd for C21
H38O: C, 82.28; H,
1
1
1
2
2
6
1
7
H), 2.45 (tt, J = 6.2, 2.4 Hz, 2H), 2.55(ddt, J = 17.0, 5.7, 2.4 Hz,
H), 2.96 (dt, J = 4.2, 5.9 Hz, 1H), 3.12 (ddd, J = 4.2, 5.7, 7.0 Hz,
H), 3.16 (ddt, J = 2.4, 2.4, 2.4 Hz, 2H), 3.71 (dt, J = 6.3, 6.2 Hz,
12.50. Found: C, 82.52; H, 12.33.
Acknowledgment. The authors are grateful to the NSF of
China (No. 20832005) and the National Basic Research Pro-
gram (973 Program) of China (Grant No. 2010CB833206) for
financial support.
13
3
H) ppm; C NMR (100 MHz, CDCl ) δ 9.8, 14.1, 18.7, 22.6,
3.0, 26.4, 27.5, 29.3, 29.4, 29.5 (2C), 29.59, 29.6, 31.9, 55.0, 57.1,
1.0, 75.7, 76.22, 76.23, 77.1 ppm; MS (ESI) m/z 341.3 (M þ Na ,
þ
þ
00%), 357.3 (M þ K , 70%). Anal. Calcd for C H O : C,
2
1
34 2
9.19; H, 10.76. Found: C, 78.95; H, 11.03.
(
9S,10R)-9,10-Epoxy-(3Z,6Z)-henicosa-1,3,6-triene (5). To a
solution of (9S,10R)-6 (66 mg, 0.17 mmol) in 2 mL of anhydrous
methanol was added anhydrous K CO (70 mg) with stirring
at room temperature. After 48 h, the reaction mixture was
Supporting Information Available: Experimental proce-
dures, characterization for all new compounds, and copies of
H, C NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
13
2
3
4
622 J. Org. Chem. Vol. 75, No. 13, 2010