Synthesis and enantioselective gas chromatography of stereoisomers of 7,11-dimethylheptadecane - A pheromone component of Lambdina species

Article abstract of DOI:10.1002/ejoc.200300643

The stereoisomers of 7,11-dimethylheptadecane exhibit a useful level of separation under enantioselective gas chromatographic conditions, using a modified cyclodextrin phase. Synthesis of the (7R,11R) isomer and coinjection studies establish the order of elution as (7S,11S), (7R,11R), and finally the meso form, the latter being a sex-pheromone component of Lambdina species. Enantiomeric assays of natural samples containing this hydrocarbon system will now be possible. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300643

FULL PAPER
Synthesis and Enantioselective Gas Chromatography of Stereoisomers of
,11-Dimethylheptadecane ؊ A Pheromone Component of Lambdina Species
7
[a]
[b]
[a]
Sharon Chow, Wilfried A. Koenig, and William Kitching*
Keywords: Enantioselective gas chromatography / Lambdina athasaria / Lambdina pellucidaria / Pheromones /
Hydrocarbons
The stereoisomers of 7,11-dimethylheptadecane exhibit a
the meso form, the latter being a sex-pheromone component
useful level of separation under enantioselective gas chroma- of Lambdina species. Enantiomeric assays of natural samples
tographic conditions, using a modified cyclodextrin phase.
Synthesis of the (7R,11R) isomer and coinjection studies es-
tablish the order of elution as (7S,11S), (7R,11R), and finally
containing this hydrocarbon system will now be possible.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Hydrocarbons are considered to have diverse roles in the
life-cycles of insects, and cuticular hydrocarbons have been
studied in considerable detail.[1] Recognition and phero-
monal functions have been assigned to hydrocarbon com-
[
2]
ponents and any chirality therein is usually, but not al-
[
3]
ways, associated with methyl branching. Although there
is a perception, sometimes unwarranted, that insect hydro-
carbons are unchallenging synthetically, this is certainly not
the case for stereochemical determinations. With respect to
absolute stereochemistry, enantiomer separation on chiral
phases (GC or HPLC) is generally difficult[4] and bioassays
of synthesised stereoisomers are then required.[
The hydrocarbons 7-methylheptadecane (1) and 7,11-di-
methylheptadecane (2) have been identified as constituents
of the female-generated sex pheromone of the spring hem-
Results and Discussion
Recently, we demonstrated that hydrolytic kinetic resolu-
tion (HKR) of terminal bis(epoxides) delivered the enanti-
omerically enriched epoxides, epoxydiols, and tetrols, which
served as useful intermediates for a range of oxygenated
5]
[
12]
insect sex pheromones.
We have further developed this
lock looper (Lambdina athasaria) and the pitch pine looper
approach and now describe the conversion of racemic 1,3-
bis(oxiranyl)propane to stereoisomers of 7,11-dimethylhep-
tadecane and demonstrate for the first time that the three
stereoisomers are separable on a cyclodextrin-based phase.
A mixture of rac- and meso-3, from peracid epoxidation
of hepta-1,6-diene, was treated with n-pentylmagnesium
bromide and CuI (in diethyl ether) to provide 7,11-heptade-
canediol (4), as an isomeric mixture. Oxidation of this diol
with Jones reagent provided the 7,11-diketone 5, which was
treated with an excess of MeMgI to furnish the tertiary al-
cohol 6. Heating of diol 6 in DMSO generated a mixture
of dienes which was immediately hydrogenated to a mixture
of the (Ϯ)- and meso-7,11-dimethylheptadecanes. A dia-
stereomeric mixture of bis(epoxide) 3 was subjected to
(
(
L. pellucidaria).[ Subsequently, bioassays confirmed that
6,7]
S)-1 and meso-2, that is (7S,11R), were the bioactive ster-
eoisomers. A number of syntheses of these components
have been described, with comments that stereoisomers of
[
8]
1
and 2 are not amenable to separation on chiral stationary
[
9Ϫ11]
phases.
An additional problem for comparisons of ee
values was the very low specific rotations for enantiomers
of 1 and 2. For example, for (7R,11R)-2, values of
[
9]
[11]
Ϫ1.26Ϯ0.04 and Ϫ1.48
have been reported as well as
[
9]
[11]
[10]
for (7S,11S)-2, ϩ1.77Ϯ0.04, ϩ1.74, and ϩ1.63. For
the enantiomers of 1, [α] values are reported to be between
D
[
9Ϫ11]
0.26 and 0.29.
[
[
a]
Department of Chemistry, School of Molecular and Microbial
Science, The University of Queensland,
[
12]
HKR
with 1.4 % equiv. of [(R,R)-(salen)Co(OAc)] com-
Brisbane 4072, Australia
plex and 1.0 equiv. of H O to furnish epoxide enantiomer
2
Email: w.kitching@mailbox.uq.edu.au
b]
(R,R)-3, which was ‘‘scrubbed’’ with additional (R,R) cata-
Institut fur Organische Chemie, Universitat Hamburg,
20146 Hamburg, Germany
lyst and H O to ensure complete enantiomeric integrity.
2
1198
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300643
Eur. J. Org. Chem. 2004, 1198Ϫ1201

Gas Chromatography of Stereoisomers of 7,11-Dimethylheptadecane
FULL PAPER
This bis(epoxide) was converted through the crystalline
diol, (S,S)-4 and then bis(mesylate), to (R,R)-7,11-dimeth-
2
0
ylheptadecane, [α]D ϭ Ϫ1.44 (CHCl ), exhibiting a mass
3
1
spectrum identical with those reported with consistent H
and C NMR spectra. The displacement of the mesylate
1
3
[9]
groups by Me CuLi [step iv, Scheme 1 (b)] affords, in ad-
2
dition to the desired (7R,11R)-2, monomethyl and alkenyl
by-products which were separated by ozonolysis and then
flash chromatography. These side-reactions resulted in a
low yield of (7R,11R)-2. These procedures are summarised
in Scheme 1 (a) and (b).
Figure 1. Enantioselective gas chromatography of 7,11-dimethylhe-
ptadecane: (a) a mixture of (Ϯ) and meso isomers; (b) (R,R)-iso-
mer; (c) co-injection of isomeric mixture and the (R,R) isomer
The enantiomers of a few methyl-substituted alkanes
have been separated under enantioselective gas chromato-
[
4]
graphic conditions and these are shown below (Figure 2).
Although 3-methylhexane responds well, separation is an-
ticipated to be more difficult for longer chain 3-methylal-
kanes and bioassays would be necessary to establish the
[
5]
natural isomer.
These considerations apply also to
Lambdina component 1. Considerable variety is now being
demonstrated in insect-derived methyl-branched hydro-
carbons and establishing the absolute stereochemistry of
such low-level hydrocarbons with multiple stereogenic
centres is very demanding, for many of the reasons sum-
marised in this report.
Scheme 1. (a) Synthesis of racemic 7,11-dimethylheptane, (Ϯ)- and
meso-2: (i) m-CPBA, DCM; (ii) n-pentylMgBr, CuI, diethyl ether;
(
iii) Jones reagent; (iv) MeMgI, diethyl ether; (v) DMSO; (vi) H ,
2
III
Pd/C; (b) synthesis of (R,R)-2: (i) [(R,R)-salenCo OAc], H
2
O; (ii)
n-pentylMgBr, CuI; (iii) MsCl, Et N; (iv) Me CuLi, diethyl ether
3
2
Figure 2. Examples of methylated alkanes whose enantiomers have
been separated by enantioselective gas chromatography
Attention was then directed to the gas-chromatographic
separation of the three stereoisomers, (7R,11R)-, (7S,11S)-,
and meso-7,11-dimethylheptadecane. It was pleasing that
useful separation was achievable, using a 25 m heptakis(6-
O-TBDMS-2,3-di-O-methyl)-β-cyclodextrin phase (50 % in Experimental Section
polysiloxane PS 086) at 115 °C. This is shown in Figure 1
General: NMR spectra were obtained with a Bruker AV400 spec-
trometer and signals were referenced to the corresponding residual
solvent signal, i.e. δ ϭ 7.24 and δ ϭ 77.0 ppm for CDCl . The
H C 3
mass spectra were recorded with either a HewlettϪPackard 5890A
GC/Mass Detector at 70 eV or a Shimadzu QP5100 gas chromatog-
raphy mass spectrometer both using a J & W Scientific DB-5 col-
umn. Flash chromatography was carried out using either Merck or
Scharlau silica gel (230Ϫ400 mesh). Optical rotations were meas-
(
a). The synthesised (7R,11R) isomer provided a single
peak, with no detectable presence of the (7S,11S) or meso
forms [Figure 1 (b)]. Coinjection of this (7R,11R) isomer
with the (Ϯ) and meso isomers [Figure 1 (c)] established that
the order of elution was (7S,11S) then (7R,11R) followed
by the meso isomer. It will now be possible to determine
directly, with reasonable precision, the enantiomeric com-
position of samples of 7,11-dimethylheptadecane from ured at 589 nm using a 1-dm cell with a PerkinϪElmer 241 MC
natural sources.
polarimeter. Melting points were recorded with
a
Büchi
Eur. J. Org. Chem. 2004, 1198Ϫ1201
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1199

S. Chow, W. A. Koenig, W. Kitching
FULL PAPER
Schmelzpunktbestimmungs-Apparat and are uncorrected. Anhy-
drous diethyl ether and THF used in the moisture-sensitive reac-
tions were freshly distilled from sodium wire and dry dichlorometh-
1H NMR (400 MHz, CDCl
6 H, 1-, 17-H), 1.22Ϫ1.29 (m, 12 H, 2-, 3-, 4-, 14-, 15-, 16-H), 1.50
3
, 28 °C): δ ϭ 0.85 (t, 3JH,H ϭ 6.7 Hz,
3
(m, 4 H, 5-, 13-H), 1.80 (p,
JH,H ϭ 7.1 Hz, 2 H, 9-H), 2.35 (t,
3
3
ane (DCM) was distilled from CaH
2
.
JH,H ϭ 7.4 Hz, 4 H, 6-, 12-H), 2.40 (t, JH,H ϭ 7.1 Hz, 4 H, 8-,
0-H) ppm. C NMR (100 MHz, CDCl
1
3
1
3
, 28 °C): δ ϭ 14.0, 17.8,
1,3-Bis(oxiranyl)propane (3): Commercially available 1,6-hep-
2
2.5, 23.8, 28.9, 31.6, 41.5, 42.8, 210.9 ppm. The spectroscopic data
tadiene (3.0 g, 31.3 mmol) in DCM (60 mL) was cooled to 0 °C
and m-chloroperbenzoic acid (50 %, 23.7 g, 68.7 mmol) was added
[6]
agree with those reported.
2 3
portionwise followed by K CO (0.70 g, 5.1 mmol). After stirring (؎)- and meso-7,11-Dimethylheptadecane-7,11-diol (6): Diketone 5
at 0 °C for 30 min and at room temperature for 4 h, the mixture
was filtered and the precipitate was rinsed thoroughly with cold
(0.13 g, 0.48 mmol) in dry diethyl ether (3 mL) was slowly added
to MeMgI (1.2  in diethyl ether, 2.5 mL) at 0 °C under an inert
DCM (40 mL). The combined filtrates were washed successively gas. After 1.5 h of stirring, the reaction mixture (at 20 °C) was
with Na SO (5 % solution, 30 mL), saturated NaHCO (3 ϫ diluted with diethyl ether (15 mL) and quenched by cautious ad-
0 mL), and brine (30 mL). The organic layer was dried with dition of saturated NH Cl (8 mL). The standard reaction workup
yielded diol 6 as an oil (0.11 g, 85 %) after column purification
2
3
3
2
4
4
MgSO , concentrated until solvent-free and purified by flash chro-
matography, eluting with 10% diethyl ether in petroleum spirit, to
ϩ
(30% DCM in hexane). EIMS: m/z (%) ϭ 249 (3) [M Ϫ (CH
3
,
give 3.0 g of the titled bis(epoxide) in 75 % yield. EIMS: m/z (%) ϭ
H O)], 197 (47), 179 (57), 154 (9), 138 (13), 129 (84), 109 (50), 95
2
ϩ
1
1
09 (1) [M Ϫ H
3
O], 97 (8), 83 (10), 79 (11), 69 (38), 54 (66), 43
3
(64), 84 (54), 69 (100), 55 (82). H NMR (400 MHz, CDCl , 28
1
3
(
(
31), 41 (100). H NMR (400 MHz, CDCl , 28 °C): δ ϭ 1.42Ϫ1.64 °C): δ ϭ 0.83 (t, JH,H ϭ 6.6 Hz, 6 H, 1-, 17-H), 1.09 (s, 6 H, 7-,
m, 6 H, 1-, 2-, 3-H), 2.45 (dt,
3
2,3
J
H,H ϭ 2.7, 5.2 Hz, 2 H, one of
11-H), 1.23Ϫ1.38 (m, 26 H, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10-, 12-, 13-,
), 2.72 (dt, 2
,3
J
H,H ϭ 0.5, 4.5 Hz, 2 H, one of oxiranyl
14-, 15-, 16-H), 1.69 (br. s, 2 H, OH) ppm. C NMR (100 MHz,
13
oxiranyl CH
CH
CDCl
2
13
2
), 2.89 (m, 2 H, oxiranyl CH) ppm. C NMR (100 MHz, CDCl
, 28 °C): δ ϭ 22.4, 22.5, 32.3, 46.91, 46.94, 52.00, 52.04 ppm. 42.2, 72.7 ppm.
7 12 2
C H O (128.02): calcd. C 65.60, H 9.44; found C 65.23, H 10.14.
3
, 28 °C): δ ϭ 14.0, 18.1, 22.5, 23.8, 26.8, 29.8, 31.8, 42.0,
3
(
؎)- and meso-7,11-Dimethylheptadecane (2): Racemic diol 6
؎)- and meso-Heptadecane-7,11-diol (4): Under an inert gas, a few (0.10 g, 0.33 mmol) in dry DMSO (0.4 mL) was heated to ca. 130
°C for 15 h. The chocolate-brown solution was poured into H
(40 mL) and extracted with hexane (3 ϫ 15 mL). The combined
organic layers were washed with brine, dried (MgSO ), and concen-
(
drops of neat n-pentyl bromide (0.58 mL, 4.7 mmol) was added to
2
O
predried Mg turnings (0.15 g, 6.2 mmol) in anhydrous diethyl ether
(2 mL) to initiate the formation of the organometallic species. The
4
remaining bromide was diluted with diethyl ether (3 mL) and added
dropwise to the Mg mixture to maintain gentle reflux. Upon com-
pletion of addition, the Grignard solution was stirred for another
trated under reduced pressure. The product was purified by flash
chromatography (hexane) to give a clear liquid (50 mg, 57 %). The
diene mixture (36 mg, 0.13 mmol) was then taken up in hexane
(1.5 mL) and stirred with a catalytic amount of Pd/C (10 % active,
4
8
0 min before cannulating it into a suspension of CuI (17 mg,
9.3µmol) in diethyl ether (0.5 mL) at Ϫ40 °C. After 10 min of ca 5 mg) in the presence of H
through Celite, removal of solvent under vacuum and flash chro-
ether (1 mL) was added dropwise to the above and the dark blue matography (hexane) produced the required hydrocarbon as a mix-
2
(balloon) overnight. Upon filtration
stirring, a mixture of (Ϯ)- and meso-3 (0.10 g, 0.78 mmol) in diethyl
solution was stirred overnight while gradually warming to room
temperature. The reaction mixture was recooled to 0 °C and care-
ture of diastereomers (35 mg) in quantitative yield based on the
diene. EIMS: m/z (%) ϭ 268 (Ͻ 1) [M ], 253 (Ͻ 1), 183 (3), 155
ϩ
fully quenched with saturated NH
ous layer was re-extracted with diethyl ether (3 ϫ 8 mL) and the
combined extracts were washed with brine (10 mL), dried 6.46 Hz, 3 H, 1-, 17-H or 7-, 11-Me), 0.822 (d, JH,H ϭ 6.5 Hz, 3
4
Cl (10 mL). The separated aque-
(1), 127 (2), 113 (4), 99 (5), 85 (13), 71(44), 57 (100), 43 (91), 41
1
3
(53). H NMR (400 MHz, CDCl
3
, 28 °C): δ ϭ 0.821 (t, JH,H
ϭ
3
3
(MgSO
4
), and concentrated. A diastereomeric mixture of diol 4
H, 1- or 17-H or 7- or 11-Me), 0.87 (t, JH,H ϭ 7.0 Hz, 3 H, 1- or
17-H or 7- or 11-Me), 1.01Ϫ1.38 (m, 28 H, 2-, 3-, 4-, 5-, 6-, 7-, 8-
was obtained as a white solid (0.18 g) in 81 % yield after flash chro-
matography (DCM, then 5% MeOH in DCM). H NMR
1
13
, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-H) ppm. C NMR (100 MHz,
3
(400 MHz, CDCl
3
, 28 °C): δ ϭ 0.86 (t, JH,H ϭ 6.6 Hz, 6 H, 1-, CDCl
3
, 28 °C): δ ϭ 14.1, 19.7, 19.8, 22.7, 24.5, 27.1, 29.7, 32.0,
1
1
7-H), 1.27Ϫ1.42 (m, 28 H, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10-, 12-, 13-,
4-, 15-, 16-H), 3.59 (m, 2 H, 7-, 11-H) ppm. 13C NMR (100 MHz,
, 28 °C): δ ϭ 14.1, 21.6, 22.6, 25.6, 29.3, 31.8, 37.4, 37.5,
1.9 ppm. M.p. 82.0 Ϫ86.0 °C. The spectroscopic data are in agree-
32.74, 32.77, 37.1, 37.1, 37.37, 37.42 ppm. The spectroscopic data
agree with those reported.
[6]
CDCl
7
3
(
1R,3R)-Bis(oxiranyl)propane [(R,R)-3], (2S,5R)-5-Oxiranylpen-
[6]
tane-1,2-diol and (2S,6S)-Heptane-1,2,6,7-tetrol: A diastereomeric
mixture of bis(epoxide) 3 (2.9 g, 30.2 mmol) was stirred with Ja-
ment with those reported.
Heptadecane-7,11-dione (5): To a solution of a diastereomeric mix-
2
cobsen catalyst [(R,R), 0.23 g, 0.32 mmol] and H O (0.55 mL,
ture of the diol 4 (0.15 g, 0.55 mmol) in acetone (5 mL) was slowly 30.6 mmol) for 3 d. The mixture was separated by flash chromatog-
added Jones reagent (8  in H
reaction mixture was stirred overnight and allowed to warm to
room temperature. After consuming the excess oxidising reagent
2
O/H
2
SO
4
, 1.0 mL) at 0 °C. The
raphies to give (R,R)-3 (0.73 g, 14 %), (2S,5R)-5-oxiranylpentane-
1,2-diol (1.7 g, 40 %) and (2S,6S)-heptane-1,2,6,7-tetrol (0.93 g,
18 %). To ensure a high enantiopurity of the chiral bis(epoxide),
with 2-propanol (1 mL), the mixture was filtered through Celite, (R,R)-3 was then stirred with additional (R,R) catalyst (20 mg,
where the precipitate was washed thoroughly with diethyl ether 28 µmol) and H O (80 µL, 4.4 µmol), followed by the same workup.
20 mL). After concentrating under reduced pressure, saturated (R,R)-3: EIMS: m/z (%) ϭ 109 (1) [M Ϫ H
NaHCO (10 mL) was carefully added, followed by extraction with
diethyl ether (3 ϫ 10 mL). The combined organic layers were
washed with brine (10 mL) and dried (MgSO ). After solvent re-
moval, diketone 5 was revealed as a white paste (0.13 g, 87 %). 4.9 Hz, 2 H, one of oxiranyl CH
2
ϩ
(
3
O], 97 (8), 83 (10), 79
1
3
(11), 69 (39), 54 (68), 43 (30), 41 (100). H NMR (400 MHz,
CDCl , 28 °C): δ ϭ 1.48Ϫ1.62 (m, 6 H, 1-, 2-, 3-H), 2.43 (dd,
3
2
,3
2,3
4
J
H,H ϭ 2.7, 5.0 Hz, 2 H, one of oxiranyl CH
), 2.88 (m, 2 H, oxiranyl CH)
, 28 °C): δ ϭ 22.4, 32.0, 46.8,
51.9 ppm. The spectroscopic data agree with those of the mixture
2
), 2.71 (t,
H,H
J ϭ
2
ϩ
13
EIMS: m/z (%) ϭ 268 (2) [M ], 211 (4), 198 (22), 183 (15), 155 ppm. C NMR (100 MHz, CDCl
55), 141 (39), 128 (100), 113 (62), 95 (25), 85 (52), 71 (39), 55 (61).
3
(
1200
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1198Ϫ1201

Gas Chromatography of Stereoisomers of 7,11-Dimethylheptadecane
FULL PAPER
min before the crude bis(mesylate) in diethyl ether (2 mL) was ad-
of diastereomers. [α]2
0
ϭ ϩ24.9 (c ϭ 1.7, CHCl
). (2S,5R)-5-Oxir-
D
3
anylpentane-1,2-diol: 1H NMR (400 MHz, CDCl
, 28 °C): δ ϭ ded dropwise. The reaction mixture was stirred at 0 °C for 5 h and
3
2,3
1
5
.42Ϫ1.62 (m, 8 H, 3-, 4-, 5-H, 2 OH), 2.43 (dd,
J
H,H ϭ 2.8,
H,H ϭ 4.9 Hz, 1 H, extraction of the aqueous layer with diethyl ether (3 ϫ 10 mL), the
), 2.87 (m, 1 H, oxiranyl CH), 3.36 [dd, combined ethereal extracts were then washed with brine (8 mL),
H,H ϭ 7.5, 10.9 Hz, 1 H, one of CH (OH)CH], 3.54 [m, 2 H, dried (MgSO ), and concentrated. Flash chromatography (hexane)
one of CH , 28 provided a mixture of hydrocarbons (ca. 70 mg) including the de-
(OH), CH(OH)] ppm. 13C NMR (100 MHz, CDCl
C): δ ϭ 22.0, 32.2, 32.6, 37.0, 52.3, 66.6, 71.9 ppm. Acetonide
4
worked up carefully by addition of saturated NH Cl (10 mL). After
2
.0 Hz, 1 H, one of oxiranyl CH J
), 2.71 (t, 2
,3
one of oxiranyl CH
2
2,3
J
2
4
2
3
°
sired alkane, plus the monomethylated alkene and diene. A portion
of the mixture (20 mg) was treated with ozone to convert the al-
kenes into carbonyl compounds and thereby assist flash chroma-
20
derivative: [α]
D 3 18 3
ϭ ϩ21.7 (c ϭ 0.6, CHCl ). C10H O (186.13):
calcd. C 64.49, H 9.74; found C 64.40, H 9.89. (2S,6S)-Heptane-
1
,2,6,7-tetrol: This was converted into the bis(acetonide) derivative, tography purification. Pure dimethyl alkane was obtained (13 mg,
ϩ
by stirring with excess 2,2-dimethoxypropane and p-toluenesulfonic
ca. 19 % from the diol). EIMS: m/z (%) ϭ 268 (Ͻ 1) [M ], 253 (Ͻ
acid in DCM, for ease in data analyses. EIMS: m/z (%) ϭ 229 (14) 1), 211 (Ͻ 1), 183 (3), 155 (2), 127 (2), 112 (9), 99 (5), 85 (16), 71
ϩ
1
[
(
1
2
M
Ϫ CH
3
], 171 (3), 141 (Ͻ 1), 129 (Ͻ 1), 111 (12), 93 (13), 72
(49), 57 (100), 43 (76). H NMR (400 MHz, CDCl
3
, 28 °C): δ ϭ
, 28 °C): δ ϭ 0.82 (d, JH,H ϭ 6.5 Hz, 6 H, Me), 0.86 (t, JH,H ϭ 6.6 Hz, 6 H,
.32 (s, 6 H, Me), 1.37 (s, 6 H, Me), 1.42 (m, 2 H, CH ), 1.51 (m, Me), 0.99Ϫ1.39 (m, 28 H, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-,
H, CH ), 1.63 (m, 2 H, CH H,H ϭ 7.1 Hz, 2 H, 13-, 14-, 15-, 16-H) ppm. C NMR (100 MHz, CDCl
), 3.48 (t, 3
O), 4.00 (d, 3
H,H ϭ 12.3 Hz, 1 H, one of CH
1
3
3
25), 59 (10), 43 (100). H NMR (400 MHz, CDCl
3
2
13
2
2
J
3
, 28 °C): δ ϭ
O), 4.01 (d, 14.1, 19.7, 22.7, 24.5, 27.1, 29.7, 32.0, 32.7, 37.2, 37.4 ppm. The
spectroscopic data agree with those of the mixture of diastereomers
, 28 °C): δ ϭ 22.2, and those reported. [α]
). (c ϭ 0.9, hexane).
CH
2
J
2
3
3
J
H,H ϭ 7.4 Hz, 1 H, one of CH
2
O), 4.04 (ds, JH,H ϭ 1.0, 6.9 Hz,
H, CHO) ppm. 1 C NMR (100 MHz, CDCl
3
[9]
20
2
2
3
D 3
ϭ Ϫ1.44 (c ϭ 0.9, CHCl ) or Ϫ1.22
5.7, 33.6, 69.4, 75.9, 108.7. [α]2
0
ϭ ϩ24.1 (c ϭ 2.8, CHCl
D
3
(
4
7S,11S)-Heptadecane-7,11-diol [(S,S)-4]: The preparation of (S,S)-
followed the procedure described for the racemate, listed above,
but starting with the chiral bis(epoxide) (R,R)-3. EIMS: m/z (%) ϭ
[1] [1a]
T. L. Singer, Am. Zool. 1998, 38, 394. [1b] R. W. Howard,
C. A. McDaniel, G. T. Blomquist, J. Chem. Ecol. 1978, 4, 233.
W. Francke, Pheromones in Comprehensive Natural Products
Chemistry, vol. 8 (Ed.: K. Mori), Elsevier, Oxford, 1999, pp.
247Ϫ249.
See, for example: M. J. McGrath, M. T. Fletcher, W. A. Konig,
C. J. Moore, B. W. Cribb, P. G. Allsopp, W. Kitching, J. Org.
Chem. 2003, 68, 3739.
For some examples, see: W. A. Koenig, Gas Chromatographic
Enantiomer Separation with Modified Cyclodextrins, Hüthig,
Heidelberg, 1992, especially pp. 27Ϫ29. Also see: U. J. Mei-
erhenrish, M. Nguyen, B. Barbier, A. Brack, W. H. Thiemann,
Chirality 2003, 15, S13ϪS16.
For a summary, see: K. Marukawa, H. Takikawa, K. Mori,
Biosci. Biotechnol. Biochem. 2001, 65, 305.
R. Gries, G. Gries, J. Li, C. T. Maier, C. R. Lemmon, K. N.
Slessor, J. Chem. Ecol. 1994, 20, 2501.
C. T. Maier, R. Gries, G. Gries, J. Chem. Ecol. 1998, 24, 491.
C. M. Duff, G. Gries, K. Mori, Y. Shirai, M. Seki, H. Taki-
kawa, T. Sheng, K. N. Slessor, R. Gries, C. T. Maier, J. Chem.
Ecol. 2001, 27, 431.
Y. Shirai, M. Seki, K. Mori, Eur. J. Org. Chem. 1999, 3139.
D. D. Diaz, V. S. Martin, J. Org. Chem. 2000, 65, 7896.
D. Enders, T. Schusseler, Tetrahedron Lett. 2002, 43, 3467.
S. Chow, W. Kitching, Tetrahedron: Asymmetry 2002, 13, 779.
Received October 10, 2003
ϩ
[2]
2
8
29 (2) [M Ϫ CH
3
], 187 (4), 169 (24), 151 (19), 115 (17), 95 (62),
1
3 (30), 79 (42), 55 (100), 43 (75). H NMR (400 MHz, CDCl
3
, 28
3
°
C): δ ϭ 0.86 (t, JH,H ϭ 6.6 Hz, 6 H, 1-, 17-H), 1.27Ϫ1.55 (m, 26
H, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10-, 12-, 13-, 14-, 15-, 16-H, 2OH), 3.57
m, 2 H, 7-, 11-H) ppm. 13C NMR (100 MHz, CDCl
, 28 °C):
[3]
(
3
δ ϭ 14.1, 21.8, 22.6, 25.6, 29.4, 31.8, 37.2, 37.6, 71.8 ppm. The
[4]
[5]
spectroscopic data agree with those of the diastereomeric mixture.
M.p. 85.0Ϫ86.0 °C. [α]2
0
ϭ ϩ2.4 (c ϭ 0.5, CHCl
).
D
3
(7R,11R)-7,11-Dimethylheptadecane [(R,R)-2]: To a solution of diol
(S,S)-4 (0.15 g, 0.55 mmol) in dry DCM (2 mL) was added Et
(0.79 mL, 5.4 mmol) under an inert gas. After stirring for 10 min,
3
N
[6]
mesyl chloride (0.21 mL, 2.6 mmol) was added at 0 °C. The reac-
tion mixture was stirred for a further 15 min and then at room
temperature for 2 h. Diethyl ether (8 mL) was added and the pre-
cipitate was filtered off. The filtrate was washed with dilute
NaHCO (4 mL) and brine (4 mL), dried (MgSO ), and solvent
3 4
was removed in vacuo. In a separate flask, MeLi (1.4  in diethyl
ether, 4.0 mL) was added dropwise to a suspension of CuI (0.56 g,
2
The initial bright orange colour faded upon the completion of ad-
dition. The resulting colourless solution was stirred for another 10
[
[
7]
8]
[9]
[10]
[11]
2
.9 mmol) in anhydrous diethyl ether (15 mL) at Ϫ10 °C under N .
[12]
Eur. J. Org. Chem. 2004, 1198Ϫ1201
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1201