Asymmetric dihydroxylation and one-pot epoxidation routes to (+)- and (-)-posticlure: A novel trans-epoxide as a sex pheromone component of Orgyia postica (Walker)

Article abstract of DOI:10.1016/S0040-4020(02)00685-3

A highly enantioselective synthesis of (+)- and (-)-posticlure has been achieved. The synthesis features the Sharpless asymmetric dihydroxylation and one-pot epoxidation as the key steps.

Full text of DOI:10.1016/S0040-4020(02)00685-3

Tetrahedron 58 (2002) 6685–6690
Asymmetric dihydroxylation and one-pot epoxidation routes to
(1)- and (2)-posticlure: a novel trans-epoxide as a sex pheromone
component of Orgyia postica (Walker)
*
Rodney A. Fernandes and Pradeep Kumar
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India
Received 2 April 2002; revised 28 May 2002; accepted 20 June 2002
Abstract—A highly enantioselective synthesis of (þ)- and (2)-posticlure has been achieved. The synthesis features the Sharpless
asymmetric dihydroxylation and one-pot epoxidation as the key steps. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
(þ)-juvenile hormones I and II.15 Another recent paper
describes the use of asymmetric dihydroxylation route to the
synthesis of (3R,5E )-2,6-dimethyl-2,3-epoxyocta-5,7-
diene.16 Sharpless has reported a simple one-pot sequence
for the conversion of vicinal diols into epoxides17 via
halohydrin ester intermediates. This method tolerates a wide
range of functionality including acid sensitive functional
groups and the transformation proceeds without epimeriza-
tion even with benzylic substrates in high stereospecificity
and yields.
The need for pure enantiomers is particularly apparent in the
field of insect pheromone chemistry, since insect chemor-
eception can be highly stereoselective.1–3 Optically active
epoxides are an important class of natural products
commonly encountered as sex attractants of Lepidopteran
pests,4 and self defensive substances against rice blast
disease.5 The advent of Sharpless asymmetric epoxidation
(SAE) in 19806 dramatically facilitated the synthesis of
optically active epoxides.7 Since then several synthesis of
pheromone epoxides such as (þ)-disparlure,8 (3Z,6Z)-cis-
9,10-epoxy-3,6-henicosadiene,8 (6Z,9Z,3S,4R )-cis-epoxy-
6,9-nonadecadiene,9 (3Z,6Z )-cis-9,10-epoxy-1,3,6-henico-
satriene and (3Z,6Z )-cis-9,10-epoxy-1,3,6-icosatriene10
were reported by employing the SAE reaction. However,
there are quite a few methods available for the direct
enantioselective epoxidation of olefins bearing no directing
functional groups in close proximity to the double bond.11
In contrast the Sharpless asymmetric dihydroxylation
(SAD) of olefins, needless of directing groups has reached
a high level of efficiency due to recent advances in reaction
conditions and ligands employed.12 Thus, enantiomeric
excesses of greater than 90% can now be achieved with a
number of olefins representing four of the six olefin
substitution classes. The chiral 1,2-diol provides varied
opportunities to achieve different functionalities in asym-
metric synthesis.
Many mono-epoxy compounds derived from (Z )-ene,
(Z,Z )-dienes, (Z,Z,Z )-trienes, and saturated analogues like
disparlure, identified as attractant pheromones have a
unique and common feature i.e. cis-epoxide functionality.18
No trans-epoxide pheromone was known in the literature
until Wakamura et al.19 isolated for the first time, a novel
trans-epoxide pheromone from the virgin females of
the tussock moth, Orgyia postica and identified it
as (6Z,9Z,11S,12S )-trans-11,12-epoxyhenicosa-6,9-diene
1a. This novel trans-oxirane pheromone was named
‘posticlure’ in reference to the species name. The coupling
constant of J¼2.2 Hz between the epoxide protons con-
firmed the trans-epoxide structure. Wakamura has also
reported the synthesis19 of natural posticlure and its optical
antipode by employing the SAE reaction with 59% ee and
obtained the pure samples by preparative HPLC. Thus,
there is a need for an efficient method to synthesize this
pheromone in both large scale and high enantiomeric excess
as well.
The diols prepared by the SAD process have recently been
used as a precursor for making the cis-epoxide in the
synthesis of (6Z,9S,10R)-cis-9,10-epoxyhenicosa-6-ene,13
eicosanoid (11R,12S)-oxidoarachidonic acid,14 (10R,11S)-
Keywords: asymmetric synthesis; dihydroxylation; one-pot epoxidation;
pheromone; posticlure.
*
Corresponding author. Tel.: þ91-20-5893300; fax: þ91-20-5893614;
e-mail: tripathi@dalton.ncl.res.in
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00685-3

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R. A. Fernandes, P. Kumar / Tetrahedron 58 (2002) 6685–6690
Scheme 2. (i) DIBAL-H, Et2O, 08C, 0.5 h, 90%; (ii) (a) PCC, CH2Cl2, rt,
8 h. (b) (Z)-C5H11CHvCHCH2CH2PþPh3I2 7, LiHMDS, THF, 2808C,
8 h, 74%; (iii) (DHQ)2-PHAL, OsO4, MeSO2NH2, K3Fe(CN)6, K2CO3, t-
BuOH/H2O [1:1], 10 h, 08C, 78%; (iv) (DHQD)2-PHAL, OsO4, MeSO2-
NH2, K3Fe(CN)6, K2CO3, t-BuOH/H2O [1:1], 10 h, 08C, 79%.
Scheme 1. (i) Ph3PvCHCO2Et, THF, rt, 12 h, 86%; (ii) (DHQ)2-PHAL,
OsO4, MeSO2NH2, K3Fe(CN)6, K2CO3, t-BuOH/H2O [1:1], 24 h, 08C,
94%; (iii) 2,2-DMP, (CH3)2CO, p-TsOH, rt, 8 h, 99%; (vi) LiAlH4, Et2O,
08C to rt, overnight, 97%; (v) (a) (COCl)2, DMSO, CH2Cl2, Et3N, 278 to
2608C; (b) (Z )-C5H11CHvCHCH2CH2PþPh3I2 7, n-BuLi, THF, 2808C,
8 h, 76%; (vi) 3N HCl, MeOH, rt, 12 h, 90%.
both by electronic and steric effects. It has been shown that
the rate constants of the dihydroxylation of isolated double
bonds are much larger with trans-1,2-disubstituted and
trisubstituted olefins than with cis-1,2-disubstituted and
terminal olefins.23 Taking advantage of trans-olefin dihy-
droxylation to be faster than the cis-olefin, we thought of
preparing compounds 9 and 10 via an alternative approach
by employing selective mono-dihydroxylation of the trans-
olefin bond of a (Z,Z,E)-triene system like 12. Toward this
end, the synthesis of (Z,Z,E)-triene (12) was attempted
starting from the trans-olefin (3) and using the Wittig
approach as illustrated in Scheme 2. Thus, the DIBAL-H
reduction of the ester 3 afforded the allylic alcohol 1113 in
90% yield which on PCC oxidation followed by the Wittig
reaction of the corresponding aldehyde with 7 furnished the
(6Z,9Z,11E )-triene 12 in 74% yield. The triene 12 was
subjected to the dihydroxylation reaction with osmium
tetroxide (0.2 mol%) and potassium ferricyanide as
co-oxidant in the presence of (DHQ)2-PHAL ligand
(1 mol%) under the SAD reaction conditions to give the
diol 924 in 78% yield. Similarly compound 1024 was
obtained from 12 by SAD reaction using (DHQD)2-PHAL
ligand in 79% yield.
As part of our ongoing research aimed at developing
enantioselective synthesis of naturally occurring lac-
tones,20a,b amino alcohols20c–e and diolmycin A2,20f we
have employed the SAD reaction and the regioselective
nucleophilic opening of cyclic sulfites/sulfates as the key
steps. Herein we report a highly enantioselective synthesis
of the novel first trans-epoxide pheromone (þ)- and
(2)-posticlure by employing the SAD reaction and one-
pot epoxidation sequence as the key steps.
2. Results and discussion
The synthesis of target molecule posticlure involves the
preparation of enantiomerically pure diols 9 and 10 by
employing the SAD reaction and their subsequent one-pot
conversion to the trans-epoxides via acetoxy bromides.
Scheme 1 summarizes our synthesis of the intermediate diol
9, a precursor for one-pot epoxidation. The commercially
available decanal (2) was treated with (ethoxycarbonyl-
methylene)triphenylphosphorane in THF to give the trans-
Wittig product 321 in 86% yield. The dihydroxylation of
olefin 3 with osmium tetroxide and potassium ferricyanide
as co-oxidant in the presence of (DHQ)2-PHAL ligand
under the SAD reaction conditions12 gave 4 in 94% yield,
with [a ]2D0¼210.54 (c 1, CHCl3). The hydroxyl group
protection of 4 with 2,2-dimethoxypropane (!5) and
subsequent ester group reduction with LiAlH4 furnished
the primary alcohol 6 in essentially quantitative yield. The
enantiomeric purity of greater than 99% ee for 6 was
determined by preparing the corresponding Mosher’s ester
and analyzing the 19F NMR spectrum. Compound 6 was
oxidized to the aldehyde under the normal Swern oxidation
conditions which on subsequent Wittig reaction with 7
furnished the (Z,Z )-diene 8 in 76% yield. Deprotection of
acetonide 8 was effected with 3N HCl in MeOH to give the
desired diol 9 in 90% yield. The enantiomer of 9 i.e 10 was
synthesized by employing the (DHQD)2-PHAL ligand in
SAD reaction on 3 and following the same reaction
sequence as shown in Scheme 1.
With the enantiomerically pure diols 9 and 10 in hand we
then proceeded with the synthetic strategy (Scheme 3) to
install the trans-epoxide moiety. While a variety of methods
have been developed for making the cis-epoxide13–15 from
diols, prepared by the SAD process, the literature describing
It is known that under the heterogeneous ferricyanide
conditions, the SAD reaction may be controlled to
selectively produce ene diols from conjugated polyenes.22
The regioselectivity of mono-dihydroxylation is determined
Scheme 3. (i) CH3C(OMe)3, p-TsOH (cat), CH2Cl2, rt, 30 min; (ii)
CH3COBr, CH2Cl2, rt, 4 h; (iii) K2CO3, MeOH, rt, 4 h, 86–88% overall.

R. A. Fernandes, P. Kumar / Tetrahedron 58 (2002) 6685–6690
6687
a one-pot method for the trans-epoxide25 is rather scarce.
We have employed a one-pot synthetic approach17 for
preparing the trans-epoxide from enantiomerically pure
diols 9 and 10 via acetoxy bromides as illustrated in Scheme
3. Thus, the treatment of diol 9 with trimethylorthoacetate in
the presence of catalytic amount of p-TsOH at room
temperature followed by subsequent removal of the
volatiles gave the cyclic orthoester 13. The subsequent
treatment of compound 13 with 1.3 equiv. of acetyl bromide
afforded a mixture of virtually pure acetoxy bromides 14a
and b. Base mediated ester saponification with K2CO3 in dry
MeOH resulted in concomitant cyclization to furnish the
trans-epoxide, (2)-posticlure 1a, [a ]2D0¼211.1 (c 1,
CHCl3) in 88% yield.
ether. The filtrate was concentrated and the residue was
purified by silica gel column chromatography using
petroleum ether/EtOAc (9:1) to give 3 (6.23 g, 86%) as a
colorless oil. Spectroscopic data are in consistence with the
literature data.21
4.1.2. (2R,3S)-Ethyl-2,3-dihydroxydodecanoate (4). To
a mixture of K3Fe(CN)6 (13.06 g, 39.76 mmol), K2CO3
(5.49 g, 39.76 mmol) and (DHQ)2-PHAL (104 mg,
0.133 mmol, 1 mol%) in t-BuOH–H2O (1:1, 140 mL)
cooled at 08C was added osmium tetroxide (536 mL,
0.1 M solution in toluene, 0.4 mol%) followed by methane-
sulfonamide (1.26 g, 13.25 mmol). After stirring for 5 min
at 08C, the olefin 3 (3 g, 13.25 mmol) was added in one
portion. The reaction mixture was stirred at 08C for 24 h and
then quenched with solid sodium sulfite (5 g). The stirring
was continued for an additional 45 min and then the solution
was extracted with EtOAc (5£30 mL). The combined
organic phases were washed with 10% aq KOH, brine,
dried (Na2SO4) and concentrated. Silica gel column
chromatography of the crude product using petroleum
ether/EtOAc (3:2) as eluent gave 4 (3.24 g, 94%) as a white
solid; mp 52–538C; [a ]2D0¼210.54 (c 1, CHCl3); IR
This stereospecific one-pot epoxidation sequence involved
the first inversion at the bromide-receiving center followed
by a second inversion at the bromide-leaving center to give
the trans-epoxide. Thus, this transformation resulted in
overall retention of configuration and therefore the regio-
selectivity of the acetyl bromide formation is immaterial.
The unnatural antipode was synthesized following the
above one-pot epoxidation sequence on 10 to give (þ)-
posticlure 1b, [a ]2D0¼þ11.33 (c 1, CHCl3) in 86% yield.
1
(CHCl3): nmax 3377, 1736, 1460 cm21; H NMR (CDCl3):
d 0.85 (t, J¼7 Hz, 3H), 1.2–1.3 (m, 14H), 1.31 (t, J¼8 Hz,
3H), 1.52–1.59 (m, 2H), 3.06 (br s, 2H), 3.84 (br t, J¼6 Hz,
1H), 4.0–4.1 (m, 1H), 4.24 (q, J¼8 Hz, 2H); 13C NMR
(CDCl3): d 13.81, 13.82, 22.38, 25.54, 29.07, 29.33
(overlapping 3C), 31.64, 33.29, 61.41, 72.44, 73.25,
173.45; EIMS m/z (%): 187 [Mþ2CO2Et] (3.3), 157 (1.4),
133 (2.4), 104 (100), 95 (4.7), 76 (88.4), 55 (23.1). Anal.
Calcd for C14H28O4 (260.37): C, 64.58; H, 10.84. Found: C,
64.66; H, 10.71.
3. Conclusion
In summary we have employed an alternative sequence of
reaction to SAE involving a two-step process, SAD and
stereospecific one-pot epoxidation. Although two steps, it is
much compatible in terms of both yields and enantio-
selectivity. Thus, a highly enantioselective synthesis of
a novel first trans-epoxide pheromone posticlure has
been achieved. This alternative route will provide an
easy excess to the large-scale synthesis of posticlure,
both (þ)- and (2)-isomers for biological studies and pest
control.
4.1.3. (2R,3S )-Ethyl-2,3-O-isopropylidenedodecanoate-
2,3-diol (5). To a solution of the diol 4 (5 g, 19.2 mmol),
p-TsOH (cat) in acetone (100 mL) was added 2,2-di-
methoxypropane (4 g, 38.4 mmol) and stirred at room
temperature for 8 h. Solid NaHCO3 (1 g) was added and
stirred for 30 min. The reaction mixture was filtered through
a pad of neutral alumina and concentrated. Silica gel column
chromatography of the residue using petroleum ether/
EtOAc (24:1) gave 5 (5.71 g, 99%) as a colorless liquid;
[a ]2D0¼215 (c 1, CHCl3); IR (neat): nmax 1758, 1460, 1376,
1097 cm21; 1H NMR (CDCl3): d 0.85 (t, J¼7 Hz, 3H), 1.2–
1.26 (m, 14H), 1.30 (t, J¼7.5 Hz, 3H), 1.41 (s, 3H), 1.43 (s,
3H), 1.60–1.70 (m, 2H), 4.06–4.10 (m, 2H), 4.23 (q,
J¼7.5 Hz, 2H); 13C NMR (CDCl3): d 13.5, 13.52, 22.08,
25.02 (overlapping 2C), 26.57, 28.74, 28.96 (overlapping
3C), 31.35, 33.04, 60.31, 78.69, 78.7, 109.97, 170.18; EIMS
m/z (%): 285 [Mþ215] (100), 271 (4.8), 227 (29.3), 197
(2.7), 144 (17), 109 (15), 95 (38.1), 69 (22.4), 59 (59.2), 55
(40.8). Anal. Calcd for C17H32O4 (300.43): C, 67.96; H,
10.73. Found: C, 67.88; H, 10.93.
4. Experimental
4.1. General information
Solvents were purified and dried by standard procedures
before use; petroleum ether of boiling range 60–808C was
used. Melting points are uncorrected. Optical rotations were
measured using sodium D line on a JASCO P-1020
microprocessor based polarimeter. Infrared spectra were
recorded on ATI MATTSON RS-1 FT-IR spectrometer. 1H
NMR and 13C NMR spectra were recorded on Bruker
AC-200 spectrometer or otherwise indicated. Mass spectra
were obtained with a TSQ 70, Finningen MAT mass
spectrometer. Elemental analyses were carried on a Carlo
Erba CHNS-O analyzer.
4.1.4. (2S,3S )-2,3-O-Isopropylidenedodecane-1,2,3-triol
(6). To
a stirred suspension of LiAlH4 (0.615 g,
4.1.1. (2E)-Ethyl dodec-2-enoate (3). To a solution of
(ethoxycarbonylmethylene) triphenylphosphorane (12.2 g,
35 mmol) in dry THF (100 mL) was added decanal 2 (5 g,
32 mmol) in THF (10 mL). The reaction mixture was stirred
at room temperature for 12 h and then concentrated. To the
residue was added ether and the precipitated solids of
triphenylphosphine oxide were filtered off and washed with
16.2 mmol) in dry Et2O (100 mL) at 08C was added the
solution of 5 (3.25 g, 10.81 mmol) in Et2O (10 mL)
dropwise. The reaction mixture was allowed to warm to
room temperature and stirred overnight. Excess LiAlH4 was
destroyed by slow addition of 10% aq NaOH (2 mL) and
EtOAc (20 mL). The white precipitate was filtered through

6688
R. A. Fernandes, P. Kumar / Tetrahedron 58 (2002) 6685–6690
a pad of neutral alumina and washed with MeOH
(3£100 mL). The filtrate was concentrated and the residue
was purified by silica gel column chromatography using
petroleum ether/EtOAc (4:1) as eluent to give 6 (2.71 g,
97%) as a colorless oil; [a ]2D0¼221.16 (c 1, CHCl3); IR
(neat): nmax 3460, 1462, 1378, 1246 cm21 1H NMR
;
(CDCl3): d 0.85 (t, J¼7.5 Hz, 3H), 1.2–1.35 (m, 14H),
1.38 (s, 6H), 1.49–1.54 (m, 2H), 2.58 (s, 1H), 3.54–3.60
(m, 1H), 3.69–3.73 (m, 2H), 3.78–3.84 (m, 1H); 13C NMR
(CDCl3): d 13.52, 22.16, 25.5, 26.53, 26.86, 28.85, 29.07,
29.25 (overlapping 2C), 31.42, 32.82, 61.89, 77.00, 81.45,
107.95; EIMS m/z (%): 243 [Mþ215] (97.4), 227 (21.7),
155 (1.6), 109 (17.8), 95 (28.3), 81 (19), 69 (19), 59 (100),
55 (44). Anal. Calcd for C15H30O3 (258.4): C, 69.72; H,
11.70. Found: C, 69.63; H, 11.82.
trated to give the crude aldehyde, which was used in the next
step without further purification.
To a stirred suspension of the Wittig salt 7 (19.4 g,
37.7 mmol) in dry THF (100 mL) was added n-BuLi
(20 mL, 40 mmol, 2 M in hexane) dropwise at 08C. The
reaction mixture was stirred till all solids dissolved
(30 min). To the dark red solution was added the above
aldehyde in dry THF (20 mL) dropwise at 2808C. The
reaction mixture was stirred for 8 h at 2808C and then
allowed to warm to room temperature. It was quenched with
sat. aq NH4Cl and extracted with EtOAc (3£50 mL). The
combined organic layers were washed (brine), dried
(Na2SO4) and concentrated. The residue was purified by
silica gel column chromatography using petroleum ether/-
EtOAc (9:1) as eluent to give 8 (8.58 g, 76%) as a colorless
oil; [a]2D0¼28.37 (c 1, CHCl3); IR (neat): nmax 1723, 1464,
1378, 1221, 1052 cm21; 1H NMR (CDCl3): d 0.85–0.92 (m,
6H), 1.2–1.35 (m, 20H), 1.42 (s, 3H), 1.43 (s, 3H), 1.51–
1.53 (m, 2H), 2.00–2.07 (m, 2H), 2.83–2.92 (m, 2H), 3.64–
3.70 (m, 1H), 4.4 (t, J¼8 Hz, 1H), 5.3–5.5 (m, 3H), 5.7 (dt,
J¼8, 4 Hz, 1H); 13C NMR (CDCl3): d 13.8, 13.81, 22.3,
22.45, 25.83, 25.98, 26.83, 27.01 (overlapping 2C), 29.1,
29.33 (overlapping 3C), 29.55, 31.27, 31.68 (overlapping
2C), 76.38, 80.68, 107.91, 126.45, 126.51, 130.63, 133.57;
EIMS m/z (%): 364 [Mþ] (1.3), 349 [Mþ215] (11), 289
(2.6), 208 (11.3), 155 (9.7), 97 (92.3), 80 (51.6), 69 (40.3),
55 (100). Anal. Calcd for C24H44O2 (364.61): C, 79.06; H,
12.16. Found: C, 79.32; H, 11.88.
4.1.5. (3Z )-Non-3-ene-triphenylphosphoniumiodide (7).
To a solution of triphenylphosphine (13.72 g, 52.3 mmol) in
dry CH2Cl2 (50 mL) was added iodine (13.27 g,
52.3 mmol). The orange precipitate was stirred for 30 min
and a solution of cis-3-nonen-1-ol (6.2 g, 43.58 mmol) and
imidazole (3.56 g, 52.3 mmol) was added dropwise. The
reaction mixture was stirred at room temperature for 1.5 h
and then CH2Cl2 was evaporated. The residue was diluted
with water and the solution was extracted with EtOAc
(3£50 mL). The combined organic extracts were washed
with 20% aq Na2S2O3, brine, dried (Na2SO4) and concen-
trated. The residue was purified by silica gel column
chromatography using petroleum ether/ether (9.8:0.2) to
give cis-3-nonen-1-iodide (10.77 g, 98%) as a colorless oil;
IR (neat): nmax 1648, 1457 cm21; 1H NMR (CDCl3): d 0.88
(t, J¼7 Hz, 3H), 1.25–1.35 (m, 6H), 1.97–2.04 (m, 2H),
2.65 (dd, J¼8, 6 Hz, 2H), 3.14 (t, J¼7 Hz, 2H), 5.34 (dt,
J¼11, 6 Hz, 1H), 5.55 (dt, J¼11, 6 Hz, 1H); 13C NMR
(CDCl3): d 5.18, 13.96, 22.41, 27.30, 29.07, 31.35
(overlapping 2C), 127.62, 132.47; EIMS m/z (%): 252
[Mþ] (1.6), 155 (2.6), 127 (5.9), 83 (29.4), 69 (71.2), 55
(100).
4.1.7. (6Z,9Z,11S,12S )-11,12-Dihydroxyhenicosa-6,9-
diene (9). To a solution of 8 (2.6 g, 7.13 mmol) in MeOH
(50 mL) was added 3N HCl (6 mL) and stirred at room
temperature for 12 h. Excess HCl was quenched by adding
solid NaHCO3 and the reaction mixture diluted with water
(50 mL). The solution was extracted with EtOAc
(4£50 mL), washed (brine), dried (Na2SO4) and concen-
trated. Silica gel column chromatography of the residue
with petroleum ether/EtOAc (3:2) as eluent gave 9 (2.09 g,
90%) as a colorless syrup; [a]2D0¼25.93 (c 1, CHCl3); IR
To a solution of triphenylphosphine (10.4 g, 39.65 mmol) in
dry benzene (50 mL) was added the above iodide (10 g,
39.65 mmol) and the solution refluxed for 24 h. The reaction
mixture was cooled to room temperature and benzene
removed under reduced pressure. The sticky solid was
triturated with dry Et2O to remove unreacted starting
materials. The residue was dried under high vacuum to a
white sticky solid of (3Z)-non-3-ene-triphenylphosphonium-
iodide 719 (19.4 g, 95%) and was used as such immediately.
1
(neat): nmax 3384, 1723, 1714, 1465, 1067 cm21; H NMR
(CDCl3): d 0.85–0.90 (m, 6H), 1.2–1.35 (m, 22H), 2.00–
2.07 (m, 2H), 2.34 (br s, 2H), 2.84–2.91 (m, 2H), 3.4–3.5
(m, 1H), 4.23 (t, J¼8 Hz, 1H), 5.34–5.46 (m, 3H), 5.61 (dt,
J¼8, 4 Hz, 1H); 13C NMR (CDCl3): d 13.81, 13.82, 22.49
overlaping 2C), 25.69, 26.16, 27.05, 29.10 (overlapping
2C), 29.51 (overlapping 3C), 31.31, 31.75, 32.67, 70.9,
74.79, 126.66, 129.12, 130.63, 131.84; EIMS m/z (%): 324
[Mþ] (1.7), 306 (8.7), 290 (3.3), 213 (11.4), 157 (17.4), 97
(27.5), 83 (65.7), 69 (53.7), 57 (100). Anal. Calcd for
C21H40O2 (324.54): C, 77.72; H, 12.42. Found: C, 77.98; H,
12.26.
4.1.6. (6Z,9Z,11S,12S )-11,12-O-Isopropylidenehenicosa-
6,9-diene (8). To a solution of oxalyl chloride (5.89 g,
4.05 mL, 46.42 mmol) in dry CH2Cl2 (250 mL) cooled at
2788C was added dropwise DMSO (6.6 mL, 92.84 mmol)
in CH2Cl2 (15 mL) over 20 min. The reaction mixture was
stirred for 30 min at 2788C and the solution of alcohol 6
(8 g, 30.95 mmol) in CH2Cl2 (15 mL) was added dropwise
at 2608C over 20 min. The reaction mixture was stirred for
30 min when a copious white precipitate was obtained. Et3N
(16 mL) was added dropwise and stirred for 1 h allowing the
temperature to rise to room temperature. The reaction
mixture was quenched with 2% aq HCl (200 mL) and the
new phase extracted with EtOAc. The combined organic
phases were washed (brine), dried (Na2SO4) and concen-
4.1.8. (2E )-Dodec-2-ene-1-ol (11). To a solution of 3 (2 g,
8.83 mmol) in dry Et2O (70 mL) at 08C was added dropwise
DIBAL-H (19.5 mL, 19.5 mmol, 1 M in toluene) through a
syringe. The reaction mixture was allowed to warm to room
temperature over 0.5 h, then recooled to 08C and treated
with 1N HCl (50 mL). The resulting gel was dissolved by
dropwise addition of 6N HCl. The ethereal phase was
separated and the aqueous layer was extracted with CH2Cl2
(3£50 mL). The combined organic extracts were washed
with sat. aq NaHCO3, dried (Na2SO4), filtered and

R. A. Fernandes, P. Kumar / Tetrahedron 58 (2002) 6685–6690
6689
concentrated. Silica gel column chromatography of the
crude product using petroleum ether/EtOAc (8:2) as eluent
gave 11 (1.47 g, 90%) as a colorless oil. Spectroscopic data
are in consistence with the literature data.13
removed under high vacuum. The residue was taken in
CH2Cl2 (5 mL) and acetyl bromide (0.237 mL, 3.2 mmol)
was added dropwise at room temperature. The reaction
mixture was stirred for 4 h and concentrated to give a
1
mixture of virtually pure acetoxy bromides 14a and b: H
4.1.9. (6Z,9Z,11E )-Henicosatriene (12). To a stirred
suspension of PCC (11.76 g, 54.55 mmol) and powdered
NMR (CDCl3): d 0.85–0.91 (m, 6H), 1.2–1.35 (m, 20H),
1.62–1.7 (m, 2H), 2.03–2.85 (m, 2H), 2.09 (s, 3H), 2.87 (br
t, J¼7 Hz, 2H), 4.91–4.98 (m, 1H), 5.06–5.2 (m, 1H), 5.4–
5.75 (m, 4H); EIMS m/z (%): 429 [Mþ] (0.3), 369 (0.7), 349
(0.5), 307 (6.6), 289 (11.9), 195 (4.6), 155 (15.5), 109
(13.2), 95 (29.8), 81 (47.7), 67 (56.3), 55 (100).
˚
molecular sieves (3 A, 4 g) in dry CH2Cl2 (200 mL) was
added 11 (6.7 g, 36.35 mmol) in CH2Cl2 (10 mL). The
reaction mixture was stirred at room temperature for 8 h and
then concentrated. The residue was triturated with ether and
filtered through a pad of celite and washed with ether
(3£50 mL). The filtrate was concentrated to give virtually
pure aldehyde (5.62 g, 85%) as colorless oil. This was used
as such in subsequent reaction.
To a solution of the mixture of 14a and b in dry MeOH
(4 mL) was added powdered K2CO3 (0.443 g, 3.2 mmol)
and the mixture was stirred for 4 h at room temperature. The
reaction mixture was filtered through a pad of neutral
alumina and the pad washed with Et2O (3£50 mL). The
filtrate was concentrated and the residue purified by silica
gel column chromatography using petroleum ether/ether
(9:1) as eluent to give 1a (0.665 g, 88%) as a colorless oil;
[a ]2D0¼211.1 (c 1, CHCl3); IR (neat): nmax 2956, 1725,
To a suspension of the Wittig salt 7 (19.4 g, 37.7 mmol) in
dry THF (100 mL) was added LiHMDS (45 mL, 45 mmol,
1 M solution in THF) dropwise at 08C. The reaction mixture
was stirred till all solids dissolved (30 min). To the dark red
solution was added the above aldehyde in dry THF (20 mL)
dropwise at 2808C. The reaction mixture was stirred for 8 h
at 2808C and then allowed to warm to room temperature. It
was quenched with sat. aq NH4Cl and extracted with EtOAc
(3£50 mL). The combined organic layers were washed
(brine), dried (Na2SO4) and concentrated. The residue was
purified by silica gel column chromatography using
petroleum ether/ether (99:1) as eluent to give 12 (7.81 g,
74%) as a colorless oil; IR (neat): nmax 1680, 1642,
1465 cm21; 1H NMR (CDCl3): d 0.84–0.93 (m, 6H), 1.25–
1.3 (m, 20H), 2.01–2.22 (m, 6H), 5.38–5.63 (m, 4H), 5.94–
6.10 (m, 1H), 6.24 (dd, J¼15, 4 Hz, 1H); 13C NMR
(CDCl3): d 13.96, 14.07, 22.27, 22.78, 29.36, 29.47, 29.66
(overlapping 3C), 31.53, 32.01, 32.34, 32.71, 33.00, 34.8,
125.81, 128.98, 129.49, 130.48, 130.81, 134.53; EIMS m/z
(%): 290 [Mþ] (3.3), 247 (1.3), 193 (2.6), 109 (14.4), 95
(34.6), 81 (56.2), 67 (100), 55 (78.4). Anal. Calcd for
C21H38 (290.53): C, 86.81; H, 13.18. Found: C, 87.01; H,
12.98.
1
1708, 1465, 1389 cm21; H NMR (500 MHz, CDCl3): d
0.85–0.90 (m, 6H), 1.2–1.45 (m, 20H), 1.56–1.62 (m, 2H),
2.04–2.09 (m, 2H), 2.80–2.84 (dt, J¼2.1 Hz, 1H), 2.97 (dd,
J¼7.1, 7.5 Hz, 2H), 3.36 (dd, J¼2.1, 8.7 Hz, 1H), 5.08 (ddd,
J¼8.7, 10.8 Hz, 1H), 5.37 (dtt, J¼7.1, 10.7 Hz, 1H), 5.44
(dtt, J¼7.5, 10.7 Hz, 1H), 5.67 (dt, J¼7.5, 10.8 Hz, 1H); 13C
NMR (CDCl3): d 13.74, 13.75, 22.3, 22.41, 25.76, 26.94,
29.07 (overlapping 2C), 29.21, 29.33 (overlapping 3C),
31.24, 31.64, 31.82, 53.77, 59.5, 126.59, 127.28, 130.59,
133.53; EIMS m/z (%): 306 [Mþ] (15), 290 (3.4), 235 (1.4),
209 (2), 195 (17), 179 (4.1), 155 (16.3), 136 (8.1), 109
(12.2), 95 (32), 79 (76.8), 71 (47.6), 67 (58.5), 55 (100).
Anal. Calcd for C21H38O (306.53): C, 82.28; H, 12.49.
Found: C, 82.32; H, 12.43.
4.1.12. (1)-Posticlure (1b). Prepared by following the
same procedure as described for compound 1a. Yield 86%;
colorless oil; [a ]2D0¼þ11.33 (c 2, CHCl3).
4.1.10. Monodihydroxylation of triene 12 to 9. To a
mixture of K3Fe(CN)6 (3.4 g, 10.33 mmol), K2CO3 (1.43 g,
10.33 mmol) and (DHQ)2-PHAL (27 mg, 0.0344 mmol,
1 mol%) in t-BuOH–H2O (1:1, 40 mL) cooled at 08C was
added osmium tetroxide (68 mL, 0.1 M solution in toluene,
0.2 mol%) followed by methanesulfonamide (0.327 g,
3.44 mmol). After stirring for 5 min at 08C, the triene 12
(1 g, 3.44 mmol) was added in one portion. The reaction
mixture was stirred at 08C for 10 h and then quenched with
solid sodium sulfite (5 g). The stirring was continued for an
additional 45 min and then the solution was extracted with
EtOAc (5£30 mL). The combined organic phases were
washed with 10% aq KOH, brine, dried (Na2SO4) and
concentrated. Silica gel column chromatography of the
crude product using petroleum ether/EtOAc (3:2) as eluent
gave 9 (0.87 g, 78%) as colorless syrup; [a]2D0¼25.69 (c 1,
CHCl3).
Acknowledgments
R. A. F. thanks CSIR, New Delhi, for financial assistance.
We are grateful to Dr M. K. Gurjar, Head, Organic
Chemistry: Technology division for his support and
encouragement. This is NCL Communication No. 6622.
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