Synthesis of (+)-disparlure from diethyl (-)-malate via opening and fragmentation of the three-membered ring in tertiary cyclopropanols

Article abstract of DOI:10.1134/S1070428009090036

(+)-Disparlure [(7R,8S)-7,8-epoxy-2-methyloctadecane, pheromone of the gypsy moth Lymantria dispar L.] was synthesized starting from diethyl (-)-malate via cyclopropanation of the ester groups, selective protection of the 1,3-diol functionality, and succe

Full text of DOI:10.1134/S1070428009090036

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 9, pp. 1318–1324. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.N. Kovalenko, N.V. Masalov, O.G. Kulinkovich, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 9,
pp. 1333–1339.
Synthesis of (+)-Disparlure from Diethyl (–)-Malate
via Opening and Fragmentation of the Three-Membered Ring
in Tertiary Cyclopropanols
V. N. Kovalenko, N. V. Masalov, and O. G. Kulinkovich
Belarus State University, pr. Nezavisimosti 4, Minsk, 220030 Belarus
e-mail: kulinkovich@bsu.by
Received May 20, 2008
Abstract— (+)-Disparlure [(7R,8S)-7,8-epoxy-2-methyloctadecane, pheromone of the gypsy moth Lymantria
dispar L.] was synthesized starting from diethyl (–)-malate via cyclopropanation of the ester groups, selective
protection of the 1,3-diol functionality, and successive opening and fragmentation of the three-membered rings
in the corresponding tertiary cyclopropanols as key stages.
DOI: 10.1134/S1070428009090036
Cyclopropanols and their derivatives undergo open-
ing of the three-membered ring with formation of al-
dehydes, ketones, carboxylic acids, allyl halides, and
some other compounds [1]. These transformations
often occur under mild conditions and with high selec-
tivity, so that substituted cyclopropanols attract con-
siderable interest as intermediate products in organic
synthesis. A convenient synthetic approach to cyclo-
propanols having chiral substituents is based on
titanium(IV) alkoxide-catalyzed reactions of natural
hydroxy- and aminocarboxylic acid esters with alkyl-
magnesium halides [2, 3]. The key step in the stereo-
selective syntheses of branched carbon skeletons of
pheromones of the pine sawfly (Diprion pini L.) [4],
alkaloid Heliotridane [5], and C13–C21 fragments of
Epothilones [6] was cleavage of the three-membered
carbon ring in chiral cyclopropanols.
gypsy moth Lymantria dispar L., The stereogenic
structural fragment in molecule I is oxirane ring [7, 8].
The key intermediate was THP-protected bis-cyclo-
propanol II; it was synthesized by titanium(IV) iso-
propoxide-catalyzed reaction of ethylmagnesium bro-
mide with O-tetrahydropyranyl derivative of diethyl
(S)-malate (III) [6], and the necessary carbon chain
was built up via alkylation of products of successive
oxidative cleavage and fragmentation of the three-
membered rings (Scheme 1; for other synthetic ap-
proaches to (+)-disparlure (I) based on natural hy-
droxy carboxylic acids, see [9]).
Differentiation of the cyclopropanol fragments in
molecule II is readily attained via its selective trans-
formation into 1,3-dioxane derivative IV [6] as shown
in Scheme 2. Treatment of acetonide IV with sodium
hypobromite in water–diethyl ether gave vinyl ketone
V whose concentration in the products was more than
90% (according to the 1H NMR data). The use of other
brominating agents, such as Br2–MeOH, N-bromosuc-
In the present work we used the cyclopropanol
strategy to synthesize (+)-disparlure [I, (7R,8S)-7,8-ep-
oxy-2-methyloctadecane] which is sex attractant of the
Scheme 1.
Me
(7R)
OH
OTHP
O
OTHP
O
Me
O
7
8
OEt
(8S)
EtO
OH
Me
I
II
III
THP is tetrahydropyran-2-yl.
1318

SYNTHESIS OF (+)-DISPARLURE FROM DIETHYL (–)-MALATE
1319
Scheme 2.
Me
O
Me
O
Me
O
Me
O
(1) EtMgBr, Ti(OPr-i)4
(2) MeOH, Py·TsOH
(3) Me2CO, CuSO4
NaOBr, Et2O–H2O
III
CH2
OH
O
IV
V
Me
O
Me
O
Me
Me2CHCH2CH2MgBr, CuI
47% (calculated on IV)
Me
O
VI
Me
O
Me
O
Me
Me
O
Me
O
Me
Al(OPr-i)3, i-PrOH
+
98%
Me
Me
OH
VIIa
OH
VIIb
4:1
cinimide, and pyridine–bromine complex, resulted in
the formation of intractable mixtures of products.
Taking into account low stability of vinyl ketone V, it
was brought (without additional purification) into the
copper(I) iodide-catalyzed reaction with isopentyl-
magnesium bromide. The reduction of the carbonyl
group in compound VI with lithium tetrahydridoalu-
minate or diisobutylaluminum hydride at room tem-
perature was characterized by low stereoselectivity,
and diastereoisomeric alcohols VIIa and VIIb were
obtained at a ratio close to equimolar. When compound
VI was treated with LiAlH4 in diethyl ether at –78°C,
anti isomer VIIb was formed as the major product
(VIIa:VIIb = 1:4), while aluminum(III) isopropoxide
as reducing agent in a mixture of benzene with iso-
propyl alcohol ensured the reverse isomer ratio; pure
stereoisomers VIIa and VIIb were separated by col-
umn chromatography on silica gel.
similar chromatographic mobilities. They were treated
with methanesulfonyl chloride, and a mixture of sulfo-
nates XI and XII thus obtained was brought into
reaction with octylmagnesium bromide in the presence
of dilithium tetrachlorocuprate(II). Selective replace-
ment of sulfonate groups at primary carbon atoms
afforded syn-diol derivative XIII and nonylbenzene,
which were readily separated by chromatography. The
best yield of XIII was obtained when Li2CuCl4 was
added to the reaction mixture in several portions. The
overall yield of key intermediate XIII was not im-
proved by carrying out the reaction with preliminarily
isolated (by chromatography) bis-sulfonate XI. Re-
moval of the THP protection from compound XIII
gave monosulfonate XIV with an ee (enantiomeric
excess) value of 90%. The optical purity was deter-
mined from the intensity ratio of signals from protons
in the methoxy and methylsulfonyl groups in the
1H NMR spectrum of its acylation product with
(S)-Mosher acid chloride [(S)-3,3,3-trifluoro-2-me-
thoxy-2-phenylpropanoyl chloride] [11]. The assign-
ment of proton signals to the minor diastereoisomer
was confirmed by comparison of chemical shifts with
those in the spectrum of the corresponding ester
obtained from racemic Mosher acid. Treatment of XIV
with anhydrous potassium carbonate in methanol
smoothly afforded (+)-disparlure (I) as a result of
closure of oxirane ring.
Benzoylation of the hydroxy group in alcohol VIIa,
subsequent removal of the acetonide protection, and
fragmentation of the three-membered ring in cyclo-
propanol VIII by the action of (diacetoxy-λ3-iodanyl)-
benzene [10] gave methyl 4-benzoyloxy-3-hydroxy-9-
methyldecanoate (IX) in a good yield (Scheme 3).
Compound IX was converted into 3-O-tetrahydro-
pyranyl derivative X which was reduced with lithium
tetrahydridoaluminate to the corresponding triol with
one protected hydroxy group and benzyl alcohol
formed as a result of reduction of the benzoate frag-
ment. The reduction products were characterized by
To conclude, it should be noted that the proposed
scheme of synthesis of (+)-disparlure (I) from natural
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

KOVALENKO et al.
1320
Scheme 3.
OH
OH
Me
O
OH
Me
(1) PhCOCl, Py, DMAP
PhI(OAc)2, MeOH
82%
(2) MeOH, Py·TsOH
VIIa
Me
MeO
Me
87%
OCOPh
OCOPh
VIII
IX
O
OTHP
Me
OTHP
Me
(1) LiAlH4
DHP, Py· TsOH
94%
(2) MeSO2Cl, Et3N
MeO
Me
MsO
Me
–PhCH2OSO2Me (XII)
OCOPh
OSO2Me
X
XI
Me
Me
MsO
MsO
HO
Me
Me
C8H17MgBr, Li2CuCl4
MeOH, TsOH
Me
Me
50% (calculated on X)
64%
THPO
XIII
XIV
MeOH, K2CO3
89%
I
O
Me
F3C
MeO
MsO
O
, Py
Cl
Me
Ph
F3C
Me
O
MeO
Ph
XV
DHP is dihydropyran.
(S)-malic acid [12] is experimentally simple. It demon-
strates synthetic utility of cyclopropanols as equiv-
alents of vinyl ketone and ester moieties.
was stirred for 5–10 min at room temperature, a solu-
tion of 0.15 g (3.75 mmol) of sodium hydroxide in
5 ml of water was added, and the mixture was stirred
for 5 min more. The organic phase was separated,
the aqueous phase was extracted with diethyl ether
(3×10 ml), the extracts were combined with the organ-
ic phase, washed with a saturated aqueous solution of
Na2SO3, and dried over Na2SO4, and the solvent was
distilled off under reduced pressure to isolate 0.55 g
(2.80 mmol) of crude vinyl ketone V which was
brought into the next step without additional purifica-
tion. IR spectrum, ν, cm–1: 3088 (C–H, cyclopropane),
1701 (C=O), 1613 (C=C). 1H NMR spectrum (CDCl3),
δ, ppm: 0.45 d.d.d (1H, CH2CH2, J = 10.3, 6.4,
5.5 Hz), 0.66 d.d.d (1H, CH2CH2, J = 10.3, 6.4,
4.8 Hz), 0.73–0.79 m (1H, CH2CH2), 0.82–0.88 m
(1H, CH2CH2), 1.25 d.d (1H, 8′-H, J = 13.3, 3.0 Hz),
1.44 s and 1.56 s (3H each, CH3), 2.18–2.24 m (1H,
8′-H), 4.64 d.d (1H, 7′-H, J = 11.9, 3.0 Hz), 5.79 d.d
(1H, CH=CH2, J = 10.6, 1.7 Hz), 6.43 d.d (1H,
CH=CH2, J = 17.5, 1.7 Hz), 6.86 d.d (1H, CH=CH2,
J = 17.5, 10.6 Hz). 13C NMR spectrum (CDCl3), δC,
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded from
solutions in CDCl3 on a Bruker AC-400 instrument at
400 and 100 MHz, respectively. The IR spectra were
recorded on a Bruker Vertex 70 spectrometer from thin
films. Individual compounds were isolated by column
chromatography on silica gel (70–230 mesh). All sol-
vents were dried according to standard procedures and
distilled before use.
1-{(7S)-5,5-Dimethyl-4,6-dioxaspiro[2.5]oct-7-
yl}prop-2-en-1-one (V). An aqueous solution of sodi-
um hypobromite prepared from 0.27 ml (5.30 mmol)
of bromine and 0.25 g (6.30 mmol) of sodium hydrox-
ide in 20 ml of water was added dropwise under
vigorous stirring to a solution of 0.70 g (3.53 mmol) of
acetonide IV [6] in 30 ml of diethyl ether. The mixture
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

SYNTHESIS OF (+)-DISPARLURE FROM DIETHYL (–)-MALATE
1321
ppm: 10.0 (CH2), 13.4 (CH2), 21.0 (CH3), 29.6 (CH3),
33.2 (CH2), 53.4 (C), 73.5 (CH), 100.5 (C), 129.9
(CH2), 130.8 (CH), 198.1 (C).
phase was extracted with ethyl acetate (3×10 ml). The
extracts were combined with the organic phase and
filtered through a thin layer of silica gel, the solvent
was distilled off under reduced pressure, and the
residue was subjected to chromatography on silica gel
using petroleum ether–ethyl acetate (40:1 to 30:1) as
eluent. Yield 0.75g (50%), [α]D = 25.3° (c = 3.8, Et2O).
IR spectrum, ν, cm–1: 3485 (OH), 3086 (C–H, cyclo-
1-{(7S)-5,5-Dimethyl-4,6-dioxaspiro[2.5]oct-7-
yl}-6-methylheptan-1-one (VI). A solution of iso-
pentylmagnesium bromide, prepared from 0.32 g
(13.3 mmol) of magnesium and 2.10 g (14.0 mmol) of
isopentyl bromide in 12 ml of THF, was added with
stirring under argon to a suspension of 0.90 g
(4.7 mmol) of CuI in 15 ml of THF, cooled to –25°C.
The mixture was stirred for 30 min at –20 to –25°C
and cooled to –70°C, and a solution of 0.55 g
(2.80 mmol) of crude vinyl ketone V in 15 ml of THF
was added dropwise under stirring over a period of 1 h.
The mixture was treated with 10 ml of a saturated
aqueous solution of sodium carbonate and diluted with
25 ml of petroleum ether, and the precipitate was fil-
tered off and washed with petroleum ether (2×10 ml).
The organic phase was washed with a saturated aque-
ous solution of Na2CO3 and dried over Na2SO4. The
solvent was distilled off under reduced pressure, and
the residue was subjected to chromatography on silica
gel using petroleum ether–ethyl acetate (50:1) as
eluent. Yield 0.45 g (47%, calculated on acetonide IV),
[α]D = 5.5° (c = 7.3, Et2O). IR spectrum, ν, cm–1: 3084
(C–H, cyclopropane), 1719 (C=O). 1H NMR spectrum,
δ, ppm: 0.41 d.d.d (1H, 2′-H or 3′-H, J = 10.2, 6.4,
5.4 Hz), 0.62 d.d.d (1H, 2′-H or 3′-H, J = 10.2, 6.1,
5.0 Hz), 0.73 d.d.d (1H, 2′-H or 3′-H, J = 10.8, 6.1,
5.6 Hz), 0.70–0.76 m (1H, 2′-H or 3′-H), 0.83 d [6H,
CH(CH3)2, J = 6.7 Hz], 1.12–1.31 m (5H, CH2, 8′-H),
1.41 s and 1.51 s [3H each, C(CH3)2], 1.47–1.56 m
(3H, 6-H, CH2), 2.07–2.14 m (1H, 8′-H), 2.51–2.66 m
(2H, CH2), 4.42 d.d (1H, 7′-H, J = 12.0, 2.8 Hz).
13C NMR spectrum, δC, ppm: 10.0 (CH2), 14.4 (CH2),
20.9 (CH3), 22.50 (CH3), 22.51 (CH3), 23.2 (CH2),
26.9 (CH2), 27.8 (CH), 29.6 (CH3), 33.4 (CH2), 37.6
(CH2), 38.7 (CH2), 53.5 (C), 74.2 (CH), 100.3 (C),
210.9 (C). Found, %: C 71.46; H 10.59. C16H28O3. Cal-
culated, %: C 71.60; H 10.52.
1
propane). H NMR spectrum, δ, ppm: 0.40 d.d.d (1H,
2′-H or 3′-H, J = 10.2, 6.3, 5.7 Hz), 0.59 d.d.d (1H,
2′-H or 3′-H, J = 10.2, 6.0, 4.9 Hz), 0.72–0.78 m (1H,
2′-H or 3′-H), 0.80–0.85 m (1H, 2′-H or 3′-H), 0.85 d
[6H, CH(CH3)2, J = 6.7 Hz], 0.90 d.d (1H, 8′-H, J =
12.9, 2.5 Hz), 1.14–1.55 m (9H, 6-H, CH2), 1.40 s and
1.52 s [3H each, C(CH3)2], 2.06–2.14 m (1H, 8′-H),
2.50 d (1H, OH, J = 3.7 Hz), 3.43 m (1H, CHOH),
3.87 d.d.d (1H, 7′-H, J = 11.6, 6.3, 2.5 Hz). 13C NMR
spectrum, δC, ppm: 9.8 (CH2), 14.7 (CH2), 21.3 (CH3),
22.5 (CH3), 22.6 (CH3), 25.6 (CH2), 27.4 (CH2), 27.9
(CH), 29.7 (CH3), 32.1 (CH2), 33.4 (CH2), 38.9 (CH2),
53.1 (C), 71.7 (CH), 73.9 (CH), 100.2 (C). Found, %:
C 70.91; H 11.25. C16H30O3. Calculated, %: C 71.07;
H 11.18.
(1S)-1-{(7S)-5,5-Dimethyl-4,6-dioxaspiro[2.5]oct-
7-yl}-6-methylhept-1-yl benzoate. Alcohol VIIa,
1.16 g (4.30 mmol), was dissolved in a mixture of
20 ml of methylene chloride and 3 ml (37.2 mmol) of
pyridine, 0.74 ml (6.37 mmol) of benzoyl chloride and
0.03 g (0.24 mmol) of 4-dimethylaminopyridine
(DMAP) were added, and the mixture was kept for
12 h at room temperature. The solvent was distilled off
under reduced pressure, the residue was dissolved in
20 ml of methanol, 1 ml (7.2 mmol) of triethylamine
was added, and the mixture was kept for 10 h. The
mixture was then diluted with water and extracted with
diethyl ether (3×20 ml), the extracts were combined
and dried over Na2SO4, the solvent was distilled off
under reduced pressure, and the residue was subjected
to chromatography on silica gel using petroleum ether–
ethyl acetate (25:1) as eluent. Yield 1.58 g (98%),
[α]D = 12.4° (c = 7.6, Et2O). IR spectrum, ν, cm–1:
3087 (C–H, cyclopropane), 1720 (C=O). 1H NMR spec-
trum, δ, ppm: 0.38 d.d.d (1H, 2′-H or 3′-H, J = 10.2,
6.3, 5.6 Hz), 0.56–0.61 m (1H, 2′-H or 3′-H), 0.70–
0.75 m (1H, 2′-H or 3′-H), 0.80–0.85 m (1H, 2′-H or
3′-H), 0.84 d [6H, CH(CH3)2, J = 6.7 Hz], 0.90 d.d
(1H, 8′-H, J = 12.8, 2.3 Hz), 1.10–1.17 m (2H, CH2),
1.25–1.42 m (4H, CH2), 1.46–1.55 m [1H, CH(CH3)2],
1.39 s and 1.52 s [3H each, C(CH3)2], 1.71–1.79 m
(2H, CH2), 2.25 d.d.d (1H, 8′-H, J = 12.8, 12.0,
1.3 Hz), 4.27 d.d.d (1H, 7′-H, J = 12.0, 3.7, 2.3 Hz),
(1S)-1-{(7S)-5,5-Dimethyl-4,6-dioxaspiro[2.5]oct-
7-yl}-6-methylheptan-1-ol (VIIa). A 1.3 M solution
of aluminum(III) isopropoxide in benzene, 12.9 ml
(16.8 mmol), was added to a solution of 1.50 g
(5.60 mmol) of ketone VI in 45 ml of isopropyl alco-
hol, and the mixture was kept for 36 h at room tem-
perature. The mixture was evaporated under reduced
pressure to 1/3 of the initial volume, 80 ml of water
and 50 ml of ethyl acetate were added to the residue,
the organic phase was separated, and the aqueous
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

KOVALENKO et al.
1322
5.16 d.d.d (1H, 1-H, J = 6.9, 6.5, 3.7 Hz), 7.42–7.48 m
(2H, Harom), 7.56–7.60 m (1H, Harom), 8.04–8.08 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 9.8 (CH2),
14.4 (CH2), 21.0 (CH3), 22.5 (CH3), 22.6 (CH3), 25.7
(CH2), 27.3 (CH2), 27.8 (CH), 29.6 (CH2), 29.8 (CH3),
32.8 (CH2), 38.8 (CH2), 53.4 (C), 69.0 (CH), 75.5
(CH), 100.3 (C), 128.3 (2CH), 129.5 (2CH), 130.4 (C),
132.8 (CH), 166.3 (C). Found, %: C 73.90; H 9.07.
C23H34O4. Calculated, %: C 73.76; H 9.15.
H
H
arom), 7.54–7.60 m (1H, Harom), 8.02–8.08 m (2H,
arom). 13C NMR spectrum, δC, ppm: 22.50 (CH3),
22.54 (CH3), 25.7 (CH2), 27.2 (CH2), 27.8 (CH), 30.2
(CH2), 37.8 (CH2), 38.7 (CH2), 51.8 (CH3), 68.8 (CH),
76.2 (CH), 128.3 (2CH), 129.7 (2CH), 129.9 (C),
133.1 (CH), 166.2 (C), 172.8 (C). Found, %: C 67.98;
H 8.32. C19H28O5. Calculated, %: C 67.83; H 8.39.
(3S,4S)-1-Methoxy-9-methyl-1-oxo-3-(tetra-
hydro-2H-pyran-2-yloxy)decan-4-yl benzoate (X).
A solution of 0.50 g (1.48 mmol) of ester IX, 0.19 g
(2.26 mmol) of dihydropyran, and 0.02 g (0.079 mmol)
of pyridinium p-toluenesulfonate in 6 ml of methylene
chloride was heated for 2–4 h under reflux. The mix-
ture was washed with a saturated aqueous solution of
NaHCO3, the organic phase was dried over Na2SO4,
the solvent was distilled off under reduced pressure,
and the residue was subjected to chromatography on
silica gel using petroleum ether–ethyl acetate (10:1) as
eluent. Yield 0.59 g (94%), 1:1 mixture of diastereo-
isomers. IR spectrum, ν, cm–1: 1745 (C=O), 1722
(2S,3S)-2-Hydroxy-1-(1-hydroxycyclopropyl)-8-
methylnonan-3-yl benzoate (VIII). A solution of
1.06 g (2.83 mmol) of (1S)-1-{(7S)-5,5-dimethyl-4,6-
dioxaspiro[2.5]oct-7-yl}-6-methylhept-1-yl benzoate
and 0.10 g (0.39 mmol) of pyridinium p-toluenesulfo-
nate in 30 ml of methanol was heated for 30 min under
reflux. The solvent was distilled off under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(5:1) as eluent. Yield 0.84 g (89%), [α]D = –20.0° (c =
4.3, MeOH). IR spectrum, ν, cm–1: 3418 (OH), 3086
(C–H, cyclopropane), 1717 (C=O). 1H NMR spectrum,
δ, ppm: 0.35–0.52 m and 0.75–0.84 m (2H each, 2′-H,
3′-H), 0.83 d [6H, CH(CH3)2, J = 6.5Hz], 1.10–1.16 m
(2H, CH2), 1.25–1.38 m (5H, CH2, 1-H), 1.42–1.53 m
(1H, 8-H), 1.71–1.79 m (2H, CH2), 2.10 d.d (1H, 1-H,
J = 14.5, 10.5 Hz), 3.15 d (1H, OH, J = 5.2 Hz),
3.61 br.s (1H, OH), 4.16–4.20 m (1H, 2-H), 5.11 d.t
(1H, 3-H, J = 6.6, 4.2 Hz), 7.41–7.46 m (2H, Harom),
7.55–7.60 m (1H, Harom), 8.04–8.08 m (2H, Harom).
13C NMR spectrum, δC, ppm: 12.5 (CH2), 14.0 (CH2),
22.5 (CH3), 22.6 (CH3), 25.7 (CH2), 27.2 (CH2), 27.8
(CH), 30.4 (CH2), 38.7 (CH2), 40.4 (CH2), 55.3 (C),
73.1 (CH), 77.3 (CH), 128.4 (CH), 129.7 (CH), 130.0
(C), 133.1 (CH), 166.6 (C). Found, %: C 71.67;
H 9.11. C20H30O4. Calculated, %: C 71.82; H 9.04.
1
(C=O). H NMR spectrum, δ, ppm: 0.83 d (6H, CH3,
J = 6.7 Hz), 1.12–1.85 m (15H), 2.58–2.75 m (2H,
2-H), 3.43–3.57 m (1H), 3.61 s (3H, OCH3), 3.79–
3.91 m (1H), 4.31–4.38 m (1H), 4.71–4.75 m (1H),
5.24 d.t (0.5H, 4-H, J = 8.7, 3.9 Hz), 5.36 d.t (0.5H,
4-H, J = 9.5, 3.9 Hz), 7.44 m (2H, Harom), 7.56 m (1H,
Harom), 8.03 m (2H, Harom). 13C NMR spectrum, δC,
ppm: 19.8 (CH2), 22.5 (CH3), 22.6 (CH3), 25.3 (CH2),
25.8 (CH2), 26.0 (CH2), 27.1 (CH2), 27.8 (CH), 28.9
(CH2), 29.3 (CH2), 30.9 (CH2), 35.5 (CH2), 37.2 (CH2),
38.6 (CH2), 38.7 (CH2), 51.5 (CH3), 51.6 (CH3), 62.9
(CH2), 63.0 (CH2), 74.3 (CH), 74.8 (CH), 75.0 (CH),
75.4 (CH), 99.4 (CH), 100.4 (CH), 128.3 (CH), 129.6
(CH), 130.1 (C), 130.3 (C), 132.8 (CH), 132.9 (CH),
165.9 (C), 166.0 (C), 171.6 (C), 171.8 (C). Found, %:
C 68.41; H 8.69. C24H36O6. Calculated, %: C 68.54;
H 8.63.
(3S,4S)-3-Hydroxy-1-methoxy-9-methyl-1-oxo-
decan-4-yl benzoate (IX). Diacetoxy(phenyl)-λ3-
iodane, 0.38 g (1.20 mmol), was added to a solution of
0.40 g (1.20 mmol) of diol VIII in 10 ml of methanol,
the mixture was kept for 10 min at room temperature,
the solvent was distilled off under reduced pressure,
and the residue was subjected to chromatography on
silica gel using petroleum ether–ethyl acetate (10:1) as
eluent. Yield 0.33 g (82%), [α]D = –20.0° (c = 3.5,
CHCl3). IR spectrum, ν, cm–1: 3494 (OH), 1730
(7S,8S)-2-Methyl-8-(tetrahydro-2H-pyran-2-yl-
oxy)octadecan-7-yl methanesulfonate (XIII).
Lithium tetrahydridoaluminate, 0.095 g (2.5 mmol),
was added at room temperature to a solution of 0.40 g
(0.97 mmol) of ester X in 8 ml of anhydrous diethyl
ether. The mixture was stirred for 30 min at room
temperature and treated in succession with 5 ml of
ethyl acetate and 0.5 ml of water. The precipitate was
filtered off and washed with ethyl acetate (3×5 ml),
and the solvent was distilled off from the filtrate under
reduced pressure. The residue was dissolved in 8 ml of
anhydrous diethyl ether, 1 ml (7.2 mmol) of triethyl-
amine was added, the mixture was cooled to 0°C, and
1
(C=O), 1717 (C=O). H NMR spectrum, δ, ppm:
0.83 d (6H, CH3, J = 6.6 Hz), 1.11–1.17 m (2H, CH2),
1.25–1.40 m (4H, CH2), 1.44–1.54 m (1H, 9-H), 1.77–
1.83 m (2H, CH2), 2.50–2.61 m (2H, 2-H), 3.22 br.s
(1H, OH), 3.63 s (3H, OCH3), 4.22–4.28 m (1H, 3-H),
5.15 d.t (1H, 4-H, J = 6.7, 3.5 Hz), 7.42–7.50 m (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

SYNTHESIS OF (+)-DISPARLURE FROM DIETHYL (–)-MALATE
1323
0.39 ml (5.0 mmol) of methanesulfonyl chloride was
added dropwise. The mixture was stirred for 30 min at
0°C and poured into water, the organic phase was sep-
arated, and the aqueous phase was extracted with ethyl
acetate (2×10 ml). The extracts were combined with
the organic phase, washed with a saturated aqueous so-
lution of NaHCO3, and dried over Na2SO4, the solvent
was distilled off under reduced pressure, the residue
was passed through a thin layer of silica gel, and the
sorbent was washed with petroleum ether–ethyl acetate
(5:1). The solvent was distilled off to isolate 0.52 g of
a mixture of methanesulfonates XI and XII. The prod-
uct mixture was dissolved in a mixture of 6 ml of THF
and 2 ml of benzene, the solution was cooled to 0°C,
and 8 ml of a solution of octylmagnesium bromide,
prepared from 1.38 ml (8.0 mmol) of n-octyl bromide
and 0.30 g (12.5 mmol) of magnesium in a mixture of
5.5 ml of THF and 1.5 ml of benzene, was added under
argon. A solution of Li2CuCl4 prepared from 0.032 g
(0.76 mmol) of LiCl and 0.051 g (0.38 mmol) of CuCl2
in 1.8 ml of THF was added in 0.3-ml portions over
a period of 40 min under stirring at 0°C. After addition
of the catalyst, the mixture was stirred for 20 min and
treated with water and 10 ml of petroleum ether. The
organic phase was separated, the aqueous phase was
extracted with petroleum ether (2×10 ml), the extracts
were combined with the organic phase, washed with
a saturated aqueous solution of Na2CO3, and dried over
Na2SO4. The solvent was distilled off under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(20:1) as eluent. Yield 0.22 g (50%), 1.5:1 mixture of
diastereoisomers. IR spectrum, ν, cm–1: 1354, 1176
(0.11 mmol) of p-toluenesulfonic acid in 5 ml of meth-
anol was kept for 2 h at room temperature. The mix-
ture was diluted with water and extracted with diethyl
ether (5×5 ml), the extracts were combined and dried
over Na2SO4, the solvent was distilled under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(10:1) as eluent. Yield 0.17 g (94%), [α]D = –12.3°
(c = 2.5, CHCl3). IR spectrum, ν, cm–1: 3532 (OH);
1
1342, 1174 (SO2). H NMR spectrum, δ, ppm: 0.85 d
[6H, CH(CH3)2, J = 6.6 Hz], 0.86 t (3H, CH3, J =
6.7 Hz), 1.38–1.80 m (27H), 2.03 d (1H, OH, J =
6.3 Hz), 3.07 s (3H, CH3SO2), 3.64–3.70 m (1H, 8-H),
4.57 d.t (1H, 7-H, J = 5.2, 7.4 Hz). 13C NMR spectrum,
δC, ppm: 14.1 (CH3), 22.5 (2CH3), 22.6 (CH2), 25.2
(CH2), 25.3 (CH2), 27.1 (CH2), 27.8 (CH), 29.3 (CH2),
29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 31.1 (CH2), 31.9
(CH2), 33.1 (CH2), 38.7 (CH3), 72.1 (CH), 86.6 (CH).
Found, %: C 63.60; H 11.24. C20H42O4S. Calculated,
%: C 63.45; H 11.18.
(7S,8S)-2-Methyl-7-methylsulfonyloctadecan-8-
yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropan-
oate (XV). Compound XIV, 17 mg (0.045 mmol), was
dissolved in 0.5 ml of carbon tetrachloride, 50 mg
(0.62 mmol) of pyridine and 23 mg (0.090 mmol) of
(2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl
chloride were added, and the mixture was kept for 24 h
at room temperature, diluted with 2 ml of petroleum
ether, treated with 10% sulfuric acid, washed with
water and a saturated aqueous solution of NaHCO3,
and dried over Na2SO4. The solvent was distilled off
under reduced pressure, and the residue was subjected
to chromatography on silica gel using petroleum ether–
ethyl acetate (20:1) as eluent. Yield quantitative; the
product contained 5% of minor diastereoisomer.
1H NMR spectrum, δ, ppm: 0.85 m (9H, CH3), 1.15–
1.70 m (27H), 2.93 s (0.15H, CH3SO2), 3.00 s (2.85H,
CH3SO2), 3.52 s (2.85H, CH3O), 3.56 s (0.15H, CH3O),
4.71–4.75 m (1H, 7-H), 5.20–5.25 m (1H, 8-H), 7.40–
7.43 m (3H, Harom), 7.53–7.55 m (2H, Harom).
1
(SO2). H NMR spectrum, δ, ppm: 0.85 d [6H,
CH(CH3)2, J = 6.4 Hz], 0.86 t (3H, CH3, J = 6.7 Hz),
1.13–1.80 m (33H), 3.00 s (1.2H, CH3SO2), 3.03 s
(1.8H, CH3SO2), 3.46–3.51 m (1H), 3.77–3.82 m (1H),
3.84–3.90 m (1H), 4.55–4.57 m (0.6H), 4.62–4.66 m
(0.8H), 4.76–4.81 m (0.6H). 13C NMR spectrum, δC,
ppm: 14.1 (CH3), 20.0 (CH2), 20.5 (CH2), 22.5 (CH3),
22.6 (CH3), 25.0 (CH2), 25.2 (CH2), 25.3 (CH2), 25.7
(CH2), 27.1 (CH2), 27.9 (CH), 28.9 (CH2), 29.3 (CH2),
29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.7 (CH2), 29.8
(CH2), 30.4 (CH2), 31.0 (CH2), 31.8 (CH2), 38.3 (CH3),
38.6 (CH2), 38.7 (CH2), 63.2 (CH2), 63.7 (CH2), 77.1
(CH), 78.3 (CH), 83.4 (CH), 84.1 (CH), 99.4 (CH),
100.3 (CH). Found, %: C 65.03; H 10.81. C25H50O5S.
Calculated, %: C 64.89; H 10.89.
(7R,8S)-7,8-Epoxy-2-methyloctadecane (I).
Potassium carbonate, 0.55 g (4.0 mmol), was added at
room temperature to a solution of 0.43 g (1.14 mmol)
of compound XIV in 10 ml of methanol. The mixture
was stirred for 10 min, diluted with water, and ex-
tracted with diethyl ether (3×10 ml), the extracts were
combined and dried over Na2SO4, the solvent was
distilled off under reduced pressure, and the residue
was subjected to chromatography on silica gel using
petroleum ether–ethyl acetate (30:1) as eluent. Yield
(7S,8S)-8-Hydroxy-2-methyloctadecan-7-yl
methanesulfonate (XIV). A solution of 0.22 g
(0.48 mmol) of compound XIII and 0.02 g
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 9 2009

KOVALENKO et al.
1324
7. Lebedeva, K.V., Minyailo, V.A., and Pyatnova, Yu.B.,
Feromony nasekomykh (Insect Pheromones), Moscow:
Nauka, 1984, p. 91; Mori, K., Top. Curr. Chem., 2004,
vol. 239, p. 1; Mori, K., Tetrahedron, 1989, vol. 45,
p. 3233.
0.29 g (89%). The spectral parameters and optical
rotation value of compound I coincided with the data
given in [9].
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