Highly stereoselective syntheses of the sex pheromone components of the southern green stink bug Nezara viridula (L.) and the green stink bug Acrosternum hilare (say)

Article abstract of DOI:10.1055/s-2000-6253

Diastereoisomeric (Z)-(1R,2S,4S)- and (Z)-(1S,2R,4S)-epoxybisabolenes (1 and 2), sex pheromone components of the stink bugs Nezara viridula and Acrosternum hilare were synthesized stereoselectively in three steps from commercially available (-)-limonene oxide 3. Two other stereoisomers, (E)- (1R,2S,4S)- and (E)-(1S,2R,4S)-epoxybisabolenes (7 and 9) were obtained in two steps from the same starting material. The other four stereoisomers are also accessible by simply substituting (+)-limonene oxide for 3, providing short, stereoselective routes to all eight possible stereoisomers.

Full text of DOI:10.1055/s-2000-6253

PAPER
269
Highly Stereoselective Syntheses of the Sex Pheromone Components of the
Southern Green Stink Bug Nezara viridula (L.) and the Green Stink Bug
Acrosternum hilare (Say)
Xin Chen, Levi Gottlieb, Jocelyn G. Millar
Department of Entomology, University of California Riverside CA 92521, USA
E-mail: jocelyn.millar@ucr.edu
Received 29 June 1999; revised 24 September 1999
assays and field tests. We report here the convenient syn-
theses of 1 and 2 in three steps from commercially
available (−)-limonene oxide 3.
Abstract: Diastereoisomeric (Z)-(1R,2S,4S)- and (Z)-(1S,2R,4S)-
epoxybisabolenes (1 and 2), sex pheromone components of the
stink bugs Nezara viridula and Acrosternum hilare were synthe-
sized stereoselectively in three steps from commercially available
(−)-limonene oxide 3. Two other stereoisomers, (E)-(1R,2S,4S)-
and (E)-(1S,2R,4S)-epoxybisabolenes (7 and 9) were obtained in
two steps from the same starting material. The other four stereoiso-
mers are also accessible by simply substituting (+)-limonene oxide
for 3, providing short, stereoselective routes to all eight possible ste-
reoisomers.
The biggest challenge in constructing both 1 and 2 proved
to be controlling the stereochemistry of the trisubstituted
double bond. Marron and Nicolaou5 used stereospecific
cuprate addition to an alkynoate to establish the required
Z-stereochemistry, but the overall synthetic route required
8 steps. In our hands, a much shorter alternate route was
developed that took advantage of the stability of the inter-
mediates formed from the Horner−Wittig reaction of a ke-
tone with a carbanion stabilized by an attached
diphenylphosphine oxide group.9 In particular, a mixture
of erythro- and threo-diastereomers results, the erythro-
isomers of which are stable enough to be isolated, whereas
under the reaction conditions, the threo intermediates col-
lapse to produce the trisubstituted (E)-alkene. Further-
more, the ratio of erythro:threo intermediates can be
manipulated; at lower reaction temperatures, the reaction
gives a preponderance of the desired erythro-diastere-
omer,10 which upon treatment with base, undergoes a ste-
reospecific syn elimination of diphenylphosphinic acid,
producing the desired (Z)-alkene.
Key words: stink bug, pheromone, Horner−Wittig reaction
The southern green stink bug Nezara viridula (L.), a noto-
rious agricultural pest with a worldwide distribution, at-
tacks a wide range of vegetable, fruit and cereal crops.1
The polyphagous nature and mobility of the bug have
made its control extremely difficult. The closely related
green stink bug Acrosternum hilare is found frequently
with N. viridula as part of a complex of stink bugs infest-
ing soybeans and other legumes, cotton, and alfalfa.1 Sex
attractant pheromones released by males of both species
attract conspecific females. The pheromone blend pro-
duced by A. hilare consists mainly of cis-(Z)-(1R,2S,4S)-
epoxybisabolene 1 mixed with lesser amounts of the cor-
responding trans-isomer 22 whereas the attractant blend of
N. viridula is composed of the opposite ratio, with 2 as the
major and 1 as the minor component.2-4 In view of the im-
portance of these insects as agricultural pests, and the im-
portant role that the pheromones could play in the
development of attractant-based methods of monitoring
and controlling these bugs, 1 and 2 have attracted the in-
terest of synthetic chemists, and at least six syntheses have
been described.3-8 However, all the reported syntheses
have major drawbacks, varying from the production of the
epoxybisabolenes as mixtures of several or all possible
stereoisomers,4,6 to the production of small quantities of
compounds from lengthy syntheses requiring highly toxic
and/or expensive reagents.3,5,7,8 The resulting lack of sig-
nificant quantities of stereochemically pure compounds
has delayed the determination of the optimal pheromone
blend for each species, and field testing of the blends to
assess their potential for development into pest manage-
ment tools. Our objective was to develop straightforward
preparative scale methods for synthesizing the target com-
pounds in high chemical and isomeric purity, to provide
sufficient quantities of pure materials for laboratory bio-
Our synthesis began with (−)-limonene oxide 3, commer-
cially available as a 42:58 mixture of α- and β-epoxides.
Phase transfer catalyzed oxidation of 3 with KMnO4 gave
the epoxy ketones 4a and 4b. Optimization of the catalyst
proved to be critical for this oxidative cleavage. The cata-
lysts triethylbenzylammonium chloride,11 18-crown-6, or
dibenzo-18-crown-6,7 when used alone, resulted in in-
complete conversion. However, when a mixture of 18-
crown-6 and dibenzo-18-crown-6 was used, the oxidation
went to completion, giving 4a and 4b (58:42) in an overall
yield of 67%. Compounds 4a and 4b12 were separated by
chromatography, and each isomer was processed sepa-
rately through the rest of the sequences (Scheme).
Horner−Wittig reaction between the lithium salt of (4-me-
thyl-3-pentenyl)diphenylphosphine oxide (5)7 and β-ep-
oxy ketone 4a in THF at −78 °C afforded the desired
erythro-adduct 6 as the major product,10 together with (E)-
(1R,2S,4S)-epoxybisabolene 7 as a minor product. How-
ever, the choice of base was critical: with n-butyllithium,7
the yield of 6 was poor, and most of the unreacted ketone
4a was racemized at C-4. An improvement in yield (61%)
was achieved by substituting LDA for n-BuLi, with no
epimerization of the small amounts of unreacted ketone
Synthesis 2000, No. 2, 269–272 ISSN 0039-7881 © Thieme Stuttgart · New York

270
X. Chen et al.
PAPER
products being formed readily. Employing the previously
reported standard conditions (NaH in DMF),7,13 consider-
able amounts of retro-addition products 5 and epimerized
4a resulted. After lengthy experimentation with different
bases (KOBut, KN(TMS)2, KOH, NaOH, BuLi, NaH),
solvents (THF, DMSO, DMF) and temperatures (75 °C,
50 °C and 25 °C), the optimal conditions for the elimina-
tion were determined to be the rapid addition of powdered
KOH to a DMSO solution of 6 at room temperature, and
quenching the reaction by adding ice-cold water as soon
as all the starting materials had been consumed (approxi-
mately 30 minutes). Under these conditions, pure cis-(Z)-
epoxybisabolene 1 was obtained in 58% yield, free of the
undesired cis-(E)-isomer or other diastereoisomers. Fur-
thermore, this result confirmed the stereochemistry of
erythro-6.
O
O
O
O
O
KMnO4, 18-crown-6
Dibenzo-18-crown-6
CH2Cl2, r.t., 10 h
+
67%
4b
3
4a
O
LDA, THF
4 h
4a
Ph2P
+
61% 6
12% 7
5
O
O
+
*
*
HO
O
O
Ph2P
The spectral data of 1 were identical with those reported
in the literature.3,8 The NMR spectra of (Z)-1 and (E)-7
display features allowing unambiguous differentiation be-
tween them. In the 1H spectra, a multiplet from the proton
at C-4 in (Z)-1 appears at 2.40 ppm, whereas in (E)-7, the
6
7
7
6
2
1
4
KOH, DMSO
r.t., 30 min
6
6'
58%
1'
corresponding proton is observed at 1.92 ppm. In the 13
C
7'
8'
NMR spectra, the diagnostic signals are those from C-4
and C-7′. The C-4 signal is significantly more shielded in
1 (34.60 ppm for 1, 42.50 ppm for 7), and the C-7′ signal
is deshielded by about 4 ppm in 1 (17.76 ppm for 1, 13.59
ppm for 7). These results agree well with those previously
reported.3
2'
4'
1
O
O
LDA, THF
4 h
+
4b
5
+
58% 8
9% 9
*
In an analogous manner, trans-(Z)-epoxybisabolene 2 and
its E-isomer 9 were prepared from α-epoxy ketone 4b
(Scheme). The NMR spectra of 2 and 9 were in good
agreement with literature data.3,7
*
HO
O
O
Ph2P
9
8
KOH, DMSO
r.t., 30 min
In conclusion, short, simple, and highly stereoselective
syntheses of cis-(Z)-epoxybisabolene 1 and the trans-(Z)-
isomer 2 have been developed. The corresponding cis-
(E)- and trans-(E)-epoxybisabolenes 7 and 9 have also
been synthesized in two steps from the same starting ma-
terial. Furthermore, the routes developed for 1, 2, 7 and 9
can be applied equally well to the syntheses of the other
four stereoisomers by substitution of (−)-limonene oxide
3 with commercially available (+)-limonene oxide.
8
62%
2
Scheme
4a. The crystalline adduct 6 was obtained as a pair of
erythro-diastereoisomers (ratio 3:1), which apparently
separated into pure crystals of each stereoisomer during
crystallization, as evidenced by two observed melting
ranges (172−174 °C and 181−183 °C). Preliminary at-
tempts to separate the two stereoisomers by fractional
crystallization or flash chromatography on silica were not
successful, and were not pursued because the two new
chiral centers would be lost anyway during the next elim-
ination step. The proton NMR spectra of the two diastere-
oisomers showed distinctly different signals for the proton
at C-2 (doublets at 3.00 and 2.90 ppm, respectively).
Mps are uncorrected. 1H NMR (300 MHz) and 13C NMR (75 MHz)
spectra were recorded on a General Electric QE-300 instrument, us-
ing CDCl3 as solvent. EIMS (70 eV) were recorded with a Hewlett−
Packard (HP, Palo Alto CA) 5970 mass selective detector interfaced
to a HP 5890 GC fitted with a DB-5 column (20m × 0.25mm i.d.;
J&W Scientific, Folsom CA). High resolution exact mass measure-
ments were made with a VG 7070E double focusing magnetic sec-
tor instrument (EI, 50 eV), using a direct insertion probe. Routine
GC analyses were carried out on an HP 5890 GC fitted with a DB-
5 column (20m × 0.32mm i.d.). THF was purified by distillation
from sodium/benzophenone ketyl under Ar. Solvents (hexane and
EtOAc) for flash chromatography were distilled prior to use. All
other solvents and reagents were used as received. Flash chroma-
tography was conducted on 32−63µ silica gel (Scientific Adsor-
bents Inc., Atlanta GA). Moisture-sensitive reactions were carried
out in oven-dried glassware under Ar atm. Unless otherwise stated,
extracts were dried over anhyd Na2SO4, and concentrated by rotary
The base-induced elimination of diphenylphosphinic
acid10,13 from 6 was highly stereoselective. However, the
reaction was very sensitive to the conditions used, with
unwanted isomers and other non-volatile degradation
Synthesis 2000, No. 2, 269–272 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Highly Stereoselective Syntheses of the Sex Pheromone Components
271
evaporation under reduced pressure. (4-Methyl-3-pentenyl) diphe-
Hz), 57.46, 59.70, 119.86, 124.33 (JPC = 8.0 Hz), 128.42 (JPC = 11.5
Hz), 128.81 (JPC = 11.0 Hz), 129.72 (JPC = 8.6 Hz), 130.70, 132.27,
135.82 (JPC = 90.8 Hz).
nylphosphine oxide (5) was prepared as previously described.7
HRMS: m/z calc for C27H36O3P (M+1+, from self-protonation on
probe) 439.2402. Found: 439.2388.
(1R,2S,4S)-4-Acetyl-1,2-epoxy-1-methylcyclohexane (4a) and
(1S,2R,4S)-4-Acetyl-1,2-epoxy-1-methylcyclohexane (4b)
To a stirred suspension of (−)-limonene oxide 3 (20.4 g, 132 mmol;
Aldrich) and KMnO4 (88 g, 556 mmol) in anhyd CH2Cl2 (900 mL)
was added 18-crown-6 (2.4 g, 9.1 mmol, 0.07 equiv) and dibenzo-
18-crown-6 (2.9 g, 8.0 mmol, 0.06 equiv) at r.t. Stirring was contin-
ued for 10h, then the resulting gray-brown suspension was filtered
through a pad of Celite, rinsing the solids with CH2Cl2 (200 mL)
and EtOAc (150 mL). The combined filtrate was concentrated, and
the residue was purified in batches by flash chromatography (4−
15% EtOAc in hexane) to afford 4b (5.9 g, 29% yield) followed by
4a (7.7 g, 38% yield) as colorless oils.
cis-(E)-Epoxybisabolene 7
1H NMR: δ = 1.32 (s, 3H, 7-Me), 1.41 (m, 1H, ring proton), 1.56 (s,
3H, 6′-Me), 1.62 (s, 3H, 7′-Me), 1.69 (d, 3H, J = 0.8 Hz, 8′-Me),
1.64−1.85 (m, 4H, ring protons), 1.92 (m, 1H, 4-H), 2.05 (m, 1H,
ring proton), 2.66 (t, 2H, J = 7.2 Hz, 3′-H), 2.98 (d, 1H, J = 5.2 Hz,
2-H), 5.07−5.12 (m, 2H, 2′, 4′-H).
13C NMR: δ = 13.59(C-7′), 17.71 (C-6′), 23.15 (C-5), 24.34 (C-7),
25.69 (C-8′), 26.87 (C-6), 29.79 (C-3′), 30.84 (C-3), 42.50 (C-4),
57.51 (C-1), 59.46 (C-2), 122.50 (C-4′), 123.22 (C-2′), 131.43 (C-
5′), 138.31 (C-1′).
MS: m/z = 220 (M+, 2), 205 (1), 187 (3), 176 (3), 151 (5), 133 (8),
125 (9), 109 (45), 93 (64), 81 (40), 67 (61), 55 (40), 43 (100).
4a: Rf = 0.14 (silica gel, 15% EtOAc in hexanes).
1H NMR: δ = 1.32 (s, 3H), 1.40−1.78 (m, 3H), 2.03−2.10 (m, 3H),
2.13 (s, 3H), 2.18−2.32 (m, 1H), 3.01 (d, 1H, J = 4.2 Hz).
HRMS: m/z calc for C15H24O (M+) 220.1827. Found: 220.1833.
13C NMR: δ = 21.62, 22.88, 25.87, 27.76, 29.53, 46.12, 57.31,
58.04, 210.20.
(Z)-(1R,2S,4S)-4-(1’,5’-Dimethylhexa-1’,4’-dienyl)-1,2-epoxy-
1-methylcyclohexane (1)
MS: m/z = 154 (M+, 1), 136 (1), 121 (2), 111 (8), 96 (12), 83 (13),
71 (8), 55 (9), 43 (100).
To a stirred solution of 6 (10.6 g, 24.2 mmol) in anhyd DMSO (120
mL) was added powdered KOH (1.8 g, 88% purity, 28.8 mmol) in
one portion at r.t., and the reaction solution was stirred at r.t. for 30
min. The reaction was quenched by adding ice-cold H2O (150 mL),
and the resulting mixture was diluted with brine (150 mL) and ex-
tracted with Et2O (500 mL). The ethereal solution was washed with
H2O (2 × 80 mL) and brine (100 mL), dried, and concentrated. The
crude products were purified by flash chromatography (5% Et2O in
hexane) to give 1 (3.1 g, 58% yield) as a colorless liquid.
4b: Rf = 0.20.
1H NMR: δ = 1.30 (s, 3H), 1.35−1.45 (m, 1H), 1.71−2.15 (m, 5H),
2.14 (s, 3H), 2.59 (m, 1H), 3.08 (br s, 1H).
13C NMR: δ = 22.80, 23.88, 26.62, 27.77, 28.17, 43.30, 57.25,
59.51, 211.15.
MS: m/z = 154 (M+,1), 136 (1), 121 (1), 111(4), 96 (9), 83 (6), 71
(3), 55 (7), 43 (100).
1H NMR: δ = 1.12−1.20 (m, 1H, ring proton), 1.33 (s, 3H, 7-Me),
1.49 (qd, 1H, J = 12.8, 4.2 Hz, ring proton), 1.56 (br s, 3H, 6′-Me),
1.63 (br s, 3H, 7′-Me), 1.69 (br s, 3H, 8′-Me), 1.65−1.82 (m, 3H,
ring protons), 2.02 (m, 1H, ring proton), 2.40 (m, 1H, 4-H), 2.67 (t,
2H, J = 7.0 Hz, 3′-H), 2.98 (d, 1H, J = 3.8 Hz, 2-H), 5.03−5.11 (m,
2H, 2′, 4′-H).
13C NMR: δ = 17.76 (C-7′), 19.10 (C-6′), 23.26 (C-7), 23.89 (C-8′),
25.75 (C-3′), 26.41 (C-5), 28.50 (C-3), 30.80 (C-6), 34.60 (C-4),
57.43 (C-1), 59.43 (C-2), 123.43 (C-4′), 123.91 (C-2′), 131.44 (C-
5′), 138.10 (C-1′).
1H and 13C spectra of 4a and 4b matched those previously report-
ed.12
erythro-(1R,2S,4S)-4-(1′,5′-Dimethyl-2′-diphenylphosphinoyl-
1′-hydroxyhex-4′-enyl)-1,2-epoxy-1-methylcyclohexane (6) and
(E)-(1R,2S,4S)-4-(1′,5′-Dimethylhexa-1′,4′-dienyl)-1,2-epoxy-1-
methylcyclohexane (7)
LDA (80 mL, 1.5M in hexanes; 120 mmol) was added dropwise to
a stirred soln of (4-methyl-3-pentenyl) diphenylphosphine oxide
(5)7 (25.5g, 90 mmol) in anhyd THF (450 mL) at 0 °C. The resulting
dark brown mixture was stirred at 0 °C for 30 min, then cooled to
−78 °C, and a solution of 4a (9.3 g, 60 mmol) in dry THF (50 mL)
was added dropwise over 1h, maintaining the reaction temperature
below −73 °C. After the addition was complete, the mixture was
stirred at −78 °C for 1h, then warmed gradually to r.t., and main-
tained at the same temperature for an additional 2h. The reaction
was quenched by addition of sat. NH4Cl (200 mL), and the resulting
mixture was extracted with EtOAc (500 mL). The EtOAc extract
was dried, concentrated and purified by flash chromatography (30%
EtOAc in hexanes), yielding (E)-epoxybisabolene 7 (1.58 g, 12%)
as a colorless liquid, followed by unreacted 4a (1.7 g). Further elu-
tion with 50% EtOAc in hexanes afforded 6 (16.1 g, 61% yield) as
a white solid. GC analysis indicated two diastereoisomeric products
in a ratio of 3:1. The solid was recrystallized from 20% EtOAc in
hexane (200 mL) at −20 °C, yielding a white crystalline product
(14.2 g) with two distinct melting ranges (172−174 °C and 181−183
°C).
MS: m/z = 220 (M+, 8), 205 (3), 202 (6), 187 (12), 176 (11), 151
(13), 133 (24), 121 (21), 109 (62), 93 (69), 81 (41), 67 (54), 55 (47),
43 (100).
HRMS: m/z calc for C15H24O (M+) 220.1827. Found: 220.1830.
erythro-(1S,2R,4S)-4-(1′,5′-Dimethyl-2′-diphenylphosphinoyl-
1′-hydroxyhex-4′-enyl)-1,2-epoxy-1-methylcyclohexane (8) and
(E)-(1S,2R,4S)-4-(1′,5′-dimethylhexa-1′,4′-dienyl)-1,2-epoxy-1-
methylcyclohexane (9)
Employing the same procedure used for 6, Horner−Wittig reaction
of α-epoxy ketone 4b (4.9 g, 32 mmol) with 5 (13.6 g, 48 mmol)
gave 8 (8.2 g, 58%) as a solid and 9 (0.68 g, 9%) as a colorless liq-
uid. Compound 8 was recrystallized from 30% EtOAc in hexane
(100 mL) at −20 °C to afford white crystals (7.2 g), mp 157−159 °C.
erythro Adduct 8 (the major isomer)
1H NMR: δ = 0.99 (s, 3H, 7′-Me), 1.19 (s, 3H, 7-Me), 1.23 (br s, 3H,
6′-Me), 1.54 (br s, 3H, 8′-Me), 1.77−2.75 (m, 10H, ring protons, 2′,
3′-H), 2.98 (br s, 1H, 2-H), 4.70 (br s, 1H, 4′-H), 4.81 (br s, 1H,
OH), 7.37−7.53 (m, 6H, Ar-H), 7.68−7.92 (m, 4H, Ar-H).
erythro Adduct 6 (the major isomer)
1H NMR: δ = 0.96 (s, 3H, 7′-Me), 1.16 (s, 3H, 7-Me), 1.55 (br s, 3H,
6′-Me), 1.71 (br s, 3H, 8′-Me), 1.70−2.72 (m, 10H, ring protons,
2′,3′-H), 3.00 (d, 1H, J = 5.4 Hz, 2-H), 4.69 (br s, 1H, OH), 4.87 (m,
1H, 4′-H), 7.37−7.51 (m, 6H, Ar-H), 7.68−7.88 (m, 4H, Ar-H).
13C NMR: δ = 17.60, 21.70, 23.23, 23.72, 24.42, 25.32, 25.82
(JPC = 8.1 Hz), 27.85, 29.07, 35.10 (JPC = 10.5 Hz), 43.68
(JPC = 66.9 Hz), 56.87, 60.54, 124.16 (JPC = 7.7 Hz), 128.22, 128.42
13C NMR: δ = 17.58, 17.94, 21.21, 23.04, 23.84, 24.12, 25.76,
25.81 (JPC = 8.5 Hz), 30.56, 39.34 (JPC = 9.6 Hz), 43.35 (JPC = 66.7
Synthesis 2000, No. 2, 269–272 ISSN 0039-7881 © Thieme Stuttgart · New York

272
X. Chen et al.
PAPER
(JPC = 11.1 Hz), 128.83 (JPC = 11.5 Hz), 129.88 (JPC = 8.4 Hz),
131.33, 132.68, 136.10 (JPC = 90.6 Hz).
HRMS: m/z calc for C27H35O3P (M+) 438.2324. Found: 438.2314.
Acknowledgement
We thank the University of California Integrated Pest Management
Program and the California Pistachio Commission for financial sup-
port of this work, and the UC Riverside Analytical Chemistry In-
strumentation Facility for the high resolution mass spectra.
trans-(E)-Epoxybisabolene 9
1H NMR: δ = 1.30 (s, 3H, 7-Me), 1.43−1.53 (m, 1H, ring proton),
1.58 (br s, 3H, 6′-Me), 1.63 (br s, 3H, 7′-Me), 1.70 (d, 3H, J = 0.8
Hz, 8′-Me), 1.75−1.92 (m, 4H, ring protons), 2.02−2.15 (m, 2H,
ring protons), 2.68 (t, 2H, J = 7.0 Hz, 3′-H), 3.04 (br s, 1H, 2-H),
5.05−5.14 (m, 2H, 2′, 4′-H).
References
(1) (a) Todd, J. W. Ann. Rev. Entomology 1989, 34, 273.
(b) Panizzi, A. R. Ann. Rev. Entomology 1997, 42, 99.
(c) Metcalf, R. L.; Metcalf, R. A. Destructive and Useful
Insects, 5th ed. McGraw-Hill: New York, 1993.
(2) (a) Aldrich, J. R.; Lusby, W. R.; Marron, B. E.; Nicolau, K. C.;
Hoffmann, M. P.; Wilson, L. T. Naturwissenschaften 1989,
76, 173.
(b) Millar, J. G.; McBrien, H. Unpublished data.
(3) Baker, R.; Borges, M.; Cooke, N. G.; Herbert, R. H., J. Chem.
Soc., Chem. Commun. 1987, 414.
13C NMR: δ = 14.54 (C-7′), 17.71 (C-6′), 24.32 (C-5), 25.67 (C-7),
26.05 (C-8′), 26.94 (C-6), 28.76 (C-3′), 30.71 (C-3), 37.67 (C-4),
57.32 (C-1), 60.73 (C-2), 122.35 (C-4′), 123.27 (C-2′), 131.39 (C-
5′), 137.91 (C-1′).
MS: m/z = 220 (M+, 1), 205 (1), 191 (3), 177 (4), 159 (10), 151 (5),
121 (15), 109 (52), 93 (50), 82 (60), 55 (35), 43 (100).
HRMS: m/z calc for C15H24O (M+) 220.1827. Found: 220.1826.
(Z)-(1S,2R,4S)-4-(1’,5’-Dimethylhexa-1’,4’-dienyl)-1,2-epoxy-
1-methylcyclohexane (2)
(4) Brézot, P.; Malosse, C.; Mori, K.; Renou, M. J. Chem. Ecol.
1994, 20, 3133.
Under the same reaction conditions used for 1, the base-induced
elimination of 8 (6.4 g, 14.6 mmol) gave 2 (2.0 g, 62% yield) as a
colorless liquid.
(5) Marron, B. E.; Nicolaou, K. C. Synthesis 1989, 537.
(6) Tomioka, H.; Mori, K. Biosci. Biotech. Biochem. 1992, 56,
1001.
(7) Baptistella, L. H. B.; Aleixo, A. M. Liebigs Ann. Chem. 1994,
785.
(8) (a) Kuwahara, S.; Itoh, D.; Leal, W. S.; Kodama, O.
Tetrahedron Lett. 1998, 39, 1183.
(b) Kuwahara, S.; Itoh, D.; Leal, W. S.; Kodama, O.
Tetrahedron 1998, 54, 11421-11430.
(9) Buss, A. D.; Warren, S. Tetrahedron Lett. 1983, 24, 3931.
(10) Buss, A. D.; Warren, S. J. Chem. Soc., Perkin Trans. I 1985,
2307.
(11) Ogino, T.; Mochizuki, K. Chem. Lett. 1979, 443.
(12) Delay, F.; Ohloff, G. Helv. Chim. Acta 1979, 62, 2168.
(13) Buss, A. D.; Greeves, N.; Mason, R.; Warren, S. J. Chem.
Soc., Perkin Trans. I 1987, 2569.
1H NMR: δ = 1.24−1.32 (m, 2H, ring protons), 1.31 (s, 3H, 7-Me),
1.58 (d, 3H, J = 1.0 Hz, 6′-Me), 1.62 (br s, 3H, 7′-Me), 1.67 (d, 3H,
J = 0.8 Hz, 8′-Me), 1.72−1.94 (m, 4H, ring protons), 2.68 (m, 3H,
3′,4-H), 3.04 (br s, 1H, 2-H), 5.03−5.14 (m, 2H, 2′,4′-H).
13C NMR: δ = 17.69 (C-7′), 19.20 (C-6′), 24.56 (C-7), 25.69 (C-8′),
26.19 (C-3′), 26.37 (C-5), 29.21 (C-3), 29.90 (C-6), 30.09 (C-4),
57.06 (C-1), 60.81 (C-2), 123.27 (C-4′), 124.48 (C-2′), 131.33 (C-
5′), 137.64 (C-1′).
MS: m/z = 220 (M+, 1), 205 (1), 191 (1), 177 (2), 164 (10), 159 (10),
149 (6), 131 (15), 121 (13), 109 (54), 93 (68), 82 (45), 67 (50), 55
(44), 43 (100).
HRMS: m/z calc for C15H24O (M+) 220.1827. Found: 220.1838.
Article Identifier:
1437-210X,E;2000,0,02,0269,0272,ftx,en;M01699SS.pdf
Synthesis 2000, No. 2, 269–272 ISSN 0039-7881 © Thieme Stuttgart · New York