Scalable synthesis of the pink gypsy moth Lymantria mathura sex pheromone (-)-mathuralure

Article abstract of DOI:10.1139/cjc-2012-0376

Mathuralure (1) is the major sex pheromone component of the pink gypsy moth Lymantria mathura, a potentially devastating invasive species to North America. To support population monitoring of this moth, a gram-scale synthesis of (-)-mathuralure (1) was developed. This process relies on coupling an alkynyl lithium species with a chloroepoxide and provides access to the natural product in a 10% yield over 10 steps.

Full text of DOI:10.1139/cjc-2012-0376

235
ARTICLE
Scalable synthesis of the pink gypsy moth Lymantria mathura sex
pheromone (–)-mathuralure
Jeffrey Mowat, James Senior, Baldip Kang, and Robert Britton
Abstract: Mathuralure (1) is the major sex pheromone component of the pink gypsy moth Lymantria mathura, a potentially
devastating invasive species to North America. To support population monitoring of this moth, a gram-scale synthesis of
(–)-mathuralure (1) was developed. This process relies on coupling an alkynyl lithium species with a chloroepoxide and provides
access to the natural product in a 10% yield over 10 steps.
Key words: mathuralure, Lymantria mathura, total synthesis, alkylative epoxide rearrangement.
Résumé : Le mathuralure (1) est le composant principal de la phéromone sexuelle de la spongieuse rose, Lymantria mathura, une
espèce qui pourrait éventuellement envahir l'Amérique du Nord avec des effets dévastateurs. Afin d'apporter un support au suivi
de la population de cette mite, on a mis au point une méthode de synthèse du (–)-mathuralure (1) permettant d'en obtenir des
quantités au niveau du gramme. Le procédé s'appuie sur le couplage d'une espèce alcynyl-lithium avec un chloroépoxyde et il
permet d'obtenir le produit naturel avec un rendement de plus de 10%, en dix étapes. [Traduit par la Rédaction]
Mots-clés : mathuralure, Lymantria mathura, synthèse totale, réarrangement alkylant d'époxyde.
m-chloroperbenzoic acid (m-CPBA) in dichloromethane then af-
forded racemic ( )-5 in a 75% yield. Alternatively, subjecting 4 to
Introduction
The pink gypsy moth (Lymantria mathura) is widespread in parts
of Asia, India, and Russia.1 Although it rarely reaches outbreak
levels in these areas, the introduction of L. mathura into North
America would threaten the integrity of forest ecosystems and
presents the potential for widespread defoliation.2 In recent
years, egg masses of L. mathura have been detected on ships bound
for North America, which has stimulated interest in the devel-
opment of an efficient monitoring system for this potentially
devastating insect pest. In this regard, gas chromatographic–
electroantennographic detection (GC–EAD) and GC–mass spec-
trometric analysis of extracts from the abdominal tip pheromone
glands of female L. mathura led to the identification of a 4:1 mix-
ture of (2R,3S):(2S,3R)-2-nonyl-3-((2Z,5Z)-octa-2,5-dienyl)oxirane
(1), (–)-mathuralure (Fig. 1), as the major sex pheromone component.3
Based on the effective employment of other insect sex pheromones
for the early detection, monitoring, and (or) eradication of pestif-
erous insects,4 several synthetic strategies have been reported
that provide access to 1 and structurally related pheromones.5–7
However, the development of a process capable of supplying
quantities of 1 needed to support population monitoring studies
of mathuralure (1) remains an important pursuit. Herein, we re-
port an operationally simple, gram-scale synthesis of mathuralure
(1) that can be used to support the growing demand for this pher-
omone.
Sharpless epoxidation conditions10 in the presence of Ti(O-i-Pr)4 and
(+)-diethyl tartrate gave rise to 5 in a 62% yield and 88% enantio-
meric excess (ee). With racemic and enantioenriched samples of
5 in hand, these materials were mixed in appropriate ratios to
give epoxyalcohol 5 in a 60% ee. Conversion of 5 to its correspond-
ing mesylate 6 was then followed by regioselective opening of the
epoxide by the addition of Et2AlCl.11 The crude chlorohydrin (not
shown) was subsequently treated with K2CO3, which effected ep-
oxidation and afforded epoxychloride 7 in a 63% isolated yield
over three steps. Notably, this route was carried out on >10 g scale
without complication.
With epoxychloride 7 in hand, completion of the synthesis of
mathuralure (1) then involved the treatment of 1,4-heptadiyne
(8)12 with n-BuLi for 60 s, followed immediately by the addition
of BF3·OEt2 and epoxychloride 7 to afford the chlorohydrin
9 (Scheme 2).13 Notably, the reaction of the diyne 8 with n-BuLi for
periods of time greater than 60 s led to the production of signifi-
cant amounts of byproducts, seriously compromising the overall
yield of the process and complicating the eventual purification
of 1.14 Treatment of the crude product with K2CO3 in ethanol
then affected epoxide formation, producing epoxydiyne 10 in a
32% yield over two steps. Finally, hydrogenation of the diyne
moiety in 10 with H2 and catalytic P-2 nickel in the presence of
1,2-diaminoethane and cyclohexene15 afforded (–)-mathuralure (1) in
an 81% yield. The addition of a large excess of cyclohexene to the
reaction mixture was crucial to avoid over reduction of the resulting
diene 1 and the production of side products that were difficult to
separate from 1 and complicated the final purification process.
Due to the low yield for the diyne addition step (i.e., 8 ¡ 10,
Scheme 2), and issues concerning the stability and handling of
1,4-heptadiyne (8) on a larger scale, an alternative approach to
mathuralure (1) was also developed that requires an additional
Results and discussion
As depicted in Scheme 1, the synthesis of mathuralure (1) initi-
ated with the hydroxymethylation of undecyne (2). Thus, the
treatment of 2 with n-BuLi followed by the reaction of the result-
ing anion with paraformaldehyde furnished the propargyl alco-
hol 3, which upon subsequent hydrogenation with P-2 nickel
catalyst8 poisoned with 1,2-diaminoethane afforded cis-dodec-
2-en-1-ol (4) in 85% over two steps.9 Epoxidation of 4 with
Received 24 September 2012. Accepted 17 December 2012.
J. Mowat, J. Senior, B. Kang, and R. Britton. Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5S 1S6, Canada.
Corresponding author: Robert Britton (e-mail: rbritton@sfu.ca).
Can. J. Chem. 91: 235–239 (2013) dx.doi.org/10.1139/cjc-2012-0376
Published at www.nrcresearchpress.com/cjc on 18 March 2013.

236
Can. J. Chem. Vol. 91, 2013
Scheme 1. Synthesis of epoxychloride 7.
•
Ni(OAc)2 4H2O
NaBH4, H2
1) n-BuLi
OH
5
1,2-diaminoethane
MeOH
2) (CHO)n
5
2
3
(85% over 2 steps)
m-CPBA
CH2Cl2
O
OH
5
(75%)
(–)-5
Ti(OiPr)4, TBHP
(+)-diethyl tartrate
CH2Cl2, -20 °C, 20h
OH
5
4
O
OH
5
(62% yield
88% ee)
5
MsCl, Et3N
CH2Cl2
Cl
O
1) Et2AlCl, CH2Cl2
2) K2CO3, MeOH
(63% over 3 steps)
OMs
5
5
O
6
7
Scheme 2. Synthesis of (–)-mathuralure (1).
Cl
OH
n-BuLi, BF3•OEt2
5
THF, -78 °C;
then 7
8
9
•
Ni(OAc)2 4H2O
NaBH4, H2
K2CO3, MeOH
O
(-)-1
(32% yield
over 2 steps)
1,2-diaminoethane
cyclohexene, MeOH
5
10
(81%)
In conclusion, we have developed a concise and scalable total
synthesis of the L. mathura insect sex pheromone mathuralure (1).
Key aspects of this synthesis include regioselective opening of an
epoxymesylate to afford epoxychloride 7, and the use of an al-
kylative epoxide rearrangement to furnish the epoxyalkynes 10
and 12. Additionally, the overall yield of 1 from undecyne (10%
over 10 steps) compares well with that reported for the previous
synthesis of mathuralure (1),5b and this strategy should also
provide reliable access to several structurally related insect
sex pheromones.6,7 Importantly, following this process, multi-
gram quantities of (–)-mathuralure have been prepared to support
ongoing field testing of this material in pheromone-baited traps
for L. mathura.
Fig. 1. (2R,3S)-2-Nonyl-3-((2Z,5Z)-octa-2,5-dienyl)oxirane,
(–)-mathuralure (1).
O
H
H
1: (-)-mathuralure
chemical transformation but is more reliable, and provides 1 in
higher overall yield. As depicted in Scheme 3, the treatment of
epoxychloride 7 with the lithium acetylide derived from the addi-
tion of n-BuLi to trimethylsilylacetylene (11) resulted in the forma-
tion of a chlorohydrin (not shown), which was directly treated
with K2CO3 to afford epoxyalkyne 12 in a 66% isolated yield over
two steps. Subsequent coupling of propargylmesylate 13 with the
terminal alkyne function in 12 in the presence of CuI afforded 10
in a 57% yield.16 Reduction of the diyne function in 10 with P-2
nickel (vide supra), afforded (–)-mathuralure (1). Notably, small
amounts of over and (or) under reduced impurities could be easily
removed by final purification of 1 over 20% AgNO3 impregnated
silica gel.17 Following this optimized process, (–)-mathuralure (1)
was routinely produced with a purity >95%, as determined by GC
analysis,18 and all spectral data recorded on synthetic 1 (1H nuclear
magnetic resonance (NMR), 13C NMR, infrared (IR), high-resolution
mass spectrometry (HR-MS), [␣]D) were in complete agreement with
that reported in the literature.5b,19,20
Experimental
Preparation of (Z)-dodec-2-en-1-ol (4)
It was prepared according to the procedure reported by
Gansäuer et al.9 To a cold (−78 °C), stirred solution of undec-1-yne
(2; 10.0 g, 65.7 mmol) in tetrahydrofuran (THF; 85 mL) was added
n-butyllithium (2.4 mol/L solution in hexanes, 27.4 mL, 65.7 mmol).
The reaction mixture was stirred at this temperature for 40 min,
after which time paraformaldehyde (1.97 g, 65.7 mmol) was added
portionwise. The reaction mixture was stirred with gradual warm-
ing to room temperature (rt) over 20 h. Saturated aqueous NH4Cl
(20 mL) was then added, the mixture was diluted with Et2O
Published by NRC Research Press

Mowat et al.
237
Scheme 3. Second generation synthesis of (–)-mathuralure (1).
afford the crude epoxide 5. Purification of the crude product by
flash chromatography (silica gel, 5:1 hexanes–EtOAc) afforded
((2S,3R)-3-nonyloxiran-2-yl)methanol (5; 8.57 g, 62%, 88% ee) as a
white solid.
The enantiomeric ratio of 5 ((2S,3R):(2R,3S) = 94:6) was measured
on a HP5890 GC equipped with a custom-made chiral GC column
coated with a 1:1 mixture of heptakis(2,6-di-O-methyl-3-O-pentyl)-
␤-cyclodextrin and OV-1701.22 Temperature program: 140 °C iso-
thermal. (2R,3S) tR = 34.5 min; (2S,3R) tR = 35.4 min.
1) n-BuLi, BF3•OEt2
THF, -78 °C;
then 7
O
TMS
5
2) K2CO3, MeOH
11
12
(66% yield
over 2 steps)
Preparation of ( )-(3-nonyloxiran-2-yl)methanol ( )-(5)
To a cold (0 °C), stirred solution of (Z)-dodec-2-en-1-ol (4; 8.00 g,
43.4 mmol) in CH2Cl2 (400 mL) was added m-CPBA (29.1 g,
130.1 mmol) portionwise over 30 min. The reaction mixture was
stirred at 0 °C for 1 h, warmed to rt and stirred for a further 16 h.
After this time, the reaction mixture was poured into a saturated
solution of Na2S2O3, the phases were separated, and the aqueous
phase was extracted with CH2Cl2 (2 × 100 mL). The combined
organic phases were washed with a saturated solution of NaHSO3
(100 mL), H2O (100 mL), and brine (100 mL), dried over MgSO4, and
concentrated to afford the crude epoxide 5. The crude product
was purified by flash chromatography (silica gel, 10:1 hexanes–
EtOAc) to afford ( )-(3-nonyloxiran-2-yl)methanol (( )-(5); 6.5 g,
75%) as a white solid; mp 46–48 °C (lit. value5b mp 58 °C (recorded
on optically pure material, 99% ee)). IR (neat, cm−1): 3393, 2953,
2910, 2915, 2850, 1467, 1323, 1031, 850. 1H NMR (600 MHz, CDCl3) ␦:
3.86 (m, 1H), 3.68 (m, 1H), 3.15 (dt, 1H, J = 7.0, 4.2 Hz), 3.03 (m, 1H),
1.90 (br s, 1H), 1.63–1.20 (m, 16H), 0.87 (t, 3H, J = 7.0 Hz). 13C NMR
(150 MHz, CDCl3) ␦: 60.9, 57.3, 56.8, 31.9, 29.5, 29.5, 29.4, 29.3, 28.0,
26.6, 22.6, 14.1. Exact mass calcd. for C12H25O2: 201.1849 (M + H);
found: 201.1851 (M + H).
OMs
O
13
CuI, NaI,
5
K2CO3, DMF
(57%)
10
Ni(OAc)2•4H2O
NaBH4, H2
O
5
1,2-diaminoethane
cyclohexene, MeOH
(-)-mathuralure (1)
(81%)
(100 mL), and the phases were separated. The aqueous phase was
extracted with Et2O (2 × 100 mL) and the combined organic phases
were washed with H2O (100 mL), brine (100 mL), dried (MgSO4), and
concentrated to give the crude propargyl alcohol that was used in
the subsequent reaction without further purification.
To a cold (0 °C), stirred solution of Ni(OAc)2·4H2O (3.25 g, 15.1 mmol)
in MeOH (60 mL) was added NaBH4 (570 mg, 15.1 mmol).
(Caution: vigorous gas evolution.) The reaction was allowed to warm
to rt and was stirred for 5 min. After this time, 1,2-diaminoethane
(2.0 mL, 30 mmol) was added and the reaction mixture was stirred
for a further 5 min. A solution of dodec-2-yn-1-ol (11.0 g, 60.3 mmol)
in MeOH (20 mL) was then added. The reaction vessel was evacu-
ated and backfilled with hydrogen three times and the reaction
mixture stirred under an atmosphere of hydrogen for 4 h. The
reaction mixture was then filtered through a pad of Celite, which
was then washed thoroughly with MeOH. The filtrate was evapo-
rated under reduced pressure, and the residue was dissolved in
Et2O (300 mL), and washed with H2O (2 × 100 mL) and brine (100 mL),
then dried over MgSO4, and concentrated. The crude product was
purified by flash chromatography (silica gel, 10:1 hexanes–EtOAc)
to provide (Z)-dodec-2-en-1-ol (4) (10.4 g, 85% over two steps). The
spectral data obtained for 4 was in complete agreement with lit-
erature reported values.21
Preparation of ((2S,3R)-3-nonyloxiran-2-yl) methyl
methanesulfonate (6)
To a cold (0 °C), stirred solution of ((2S,3R)-3-nonyloxiran-2-yl)
methanol (5; 60% ee; 13.5 g, 67.8 mmol) and Et3N (14.2 mL,
101.6 mmol) in CH2Cl2 (250 mL) was added methanesulfonyl chlo-
ride (6.8 mL, 88 mmol) dropwise over 10 min. The reaction mix-
ture was stirred at 0 °C for 30 min and then filtered. The filtrate
was washed with H2O (100 mL), a 1 mol/L aqueous solution of HCl
(100 mL), and brine (100 mL), dried over MgSO4, and concentrated
under reduced pressure to give the crude mesylate 6, which was
used in the subsequent reaction without further purification.
25
[␣]D –5.9° (c 1.0, CH2Cl2; optical rotation was recorded on a
4:1 mixture of enantiomers, 60% ee). IR (neat, cm−1): 2920, 2358,
2337, 1259, 1359, 1175, 954. 1H NMR (400 MHz, CDCl3) ␦: 4.45
(dd, 1H, J = 12.0, 4.0 Hz), 4.22 (dd, 1H, J = 12.0, 7.5 Hz), 3.26 (dt, 1H, J =
8.0, 4.0 Hz), 3.09 (s, 3H), 3.09–3.05 (m, 1H), 1.57–1.27 (m, 16H), 0.88
(t, 3H, J = 7.0 Hz). 13C NMR (100 MHz, CDCl3) ␦: 68.2, 56.8, 53.4, 37.9,
31.8, 29.4, 29.4, 29.3, 29.2, 27.9, 26.6, 22.6, 14.0. Exact mass calcd.
for C13H26SO4: 278.1558 (M+); found: 278.1552 (M+).
Preparation of ((2S,3R)-3-nonyloxiran-2-yl)methanol (5)
It was prepared according to the procedure reported by
Sharpless and co-workers.10 To a cold (−20 °C), stirred suspension
of activated 4 Å molecular sieves in CH2Cl2 (250 mL) was added
L-(+)-diethyl tartrate (2.83 mL, 16.5 mmol) and Ti(O-i-Pr)4 (4.08 mL,
13.8 mmol). tert-Butylhydrogenperoxide (5.25 mol/L solution in
hexanes, 26.3 mL, 138 mmol) was added and the resulting solution
was stirred for 30 min. After this time, (Z)-dodec-2-en-1-ol (4)
(12.7 g, 69 mmol) was added and the resulting mixture was stirred
for 18 h at –20 °C. The reaction mixture was then added to a beaker
containing a cooled (0 °C) solution of FeSO4 and tartaric acid,10
and the resulting mixture was stirred for 10 min. The phases were
separated and the aqueous phase was extracted with Et2O (2 × 50 mL).
The combined organic layers were added to a cooled (0 °C), stirred
solution of 30% NaOH in brine and the resulting mixture was
stirred for 1 h at 0 °C. The mixture was diluted with H2O (50 mL) and
the phases were separated. The aqueous phase was extracted
with Et2O (3 × 40 mL), and the combined organic phases were
washed with brine (100 mL), dried (MgSO4), and concentrated to
Preparation of (S)-2-((S)-1-chlorodecyl)oxirane (7)
To a cold (−20 °C), stirred solution of ((2S,3R)-3-nonyloxiran-2-yl)
methyl methanesulfonate (6; 60% ee; 18.9 g, 67.8 mmol) in CH2Cl2
(250 mL) was added Et2AlCl (1 mol/L in hexane, 74.6 mL,
74.6 mmol) dropwise over 30 min. The reaction mixture was
stirred at –20 °C for 4 h, after which time the reaction was
quenched by dropwise addition of a saturated aqueous solution of
tartaric acid (50 mL). The phases were separated and the aqueous
phase was extracted with CH2Cl2 (2 × 100 mL). The combined
organic phases were successively washed with 1 mol/L HCl
(100 mL), saturated aqueous solution of NaHCO3 (100 mL), and
brine (100 mL), dried (MgSO4), and concentrated under reduced
pressure to afford the crude chlorohydrin, which was used in the
subsequent reaction without further purification.
To a stirred solution of the crude chlorohydrin in MeOH (400 mL)
was added K2CO3 (14.1 g, 102 mmol). The reaction mixture was
Published by NRC Research Press

238
Can. J. Chem. Vol. 91, 2013
stirred at rt for 40 min, then filtered and concentrated under
reduced pressure. The crude residue was dissolved in Et2O (250 mL),
and washed with H2O (2 × 100 mL) and brine (100 mL), then dried
(MgSO4) and concentrated to afford the crude epoxychloride 7.
The crude product was purified by flash chromatography (silica
gel, 20:1 hexanes–EtOAc) to afford (S)-2-((S)-1-chlorodecyl)oxirane
The reaction mixture was stirred for 1 min, after which time
BF3·OEt2 (0.94 mL, 7.6 mmol) was added, and the resulting mixture
was stirred for 1 min, then a solution of (S)-2-((S)-1-chlorodecyl)oxirane
(7; 1.11 g, 5.06 mmol) in THF (10 mL) was added. The reaction
mixture was stirred at –78 °C for 45 min, then treated with a
saturated aqueous solution of NH4Cl (5 mL), and the mixture was
allowed to warm to rt. The phases were separated and the aqueous
phase was extracted with Et2O (3 × 100 mL), and the combined
organics phases were washed with H2O (100 mL) and brine
(100 mL), dried (MgSO4), and concentrated under reduced pressure
to afford the crude chlorohydrin 9 that was used in the subse-
quent reaction without further purification.
To a stirred solution of the chlorohydrin 9 in MeOH (50 mL) was
added K2CO3 (2.10 g, 15.2 mmol). The reaction mixture was stirred
at rt for 5 h, after which time the reaction mixture was filtered
and concentrated under reduced pressure. The crude residue was
dissolved in Et2O (250 mL), and the organic phase was washed
with H2O (2 × 100 mL) and brine (100 mL), dried (MgSO4), and
concentrated to afford the crude epoxydiyne 10. The crude product
was purified by flash chromatography (silica gel, 20:1 hexanes–
EtOAc) to afford (2R,3S)-2-nonyl-3-(octa-2,5-diynyl)oxirane (10; 444 mg,
32%). The spectral data obtained for 10 was in complete agreement
with that reported for this substance.5b
25
(7; 9.3 g, 63% over three steps) as a colourless oil. [␣]D –2.4°
(c 1.0, CH2Cl2; optical rotation was recorded on a 4:1 mixture of
enantiomers, 60% ee). IR (neat, cm−1): 2953, 2925, 2855, 1465, 1253.
1H NMR (400 MHz, CDCl3) ␦: 3.88 (ddd, 1H, J = 8.5, 7.0, 5.5 Hz), 3.13
(ddd, 1H, J = 7.0, 4.0, 2.5 Hz), 2.90 (dd, 1H, J = 5.0, 4.0 Hz), 2.72 (dd,
1H, J = 5.0, 2.5 Hz), 1.88–1.73 (m, 2H), 1.60–1.50 (m, 1H), 1.47–1.39
(m, 1H), 1.33–1.23 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz). 13C NMR (100 MHz,
CDCl3) ␦: 63.4, 55.4, 47.1, 34.8, 31.9, 29.5, 29.4, 29.3, 29.1, 26.2, 22.7,
14.1. Exact mass calcd. for C12H23OCl: 218.1446 (M+); found:
218.1437 (M+).
Preparation of (2R,3S)-2-nonyl-3-(prop-2-ynyl)oxirane (12)
To a cold (−78 °C), stirred solution of trimethylsilylacetylene
(11; 3.55 mL, 14.7 mmol) in THF (85 mL) was added n-butyllithium
(2.5 mol/L solution in hexanes, 9.4 mL, 32 mmol). The reaction
mixture was stirred for 5 min, after which time BF3·OEt2 (2.89 mL,
23.4 mmol) was added. The reaction mixture was stirred for an
additional 5 min, then a solution of (S)-2-((S)-1-chlorodecyl)oxirane
(7; 60% ee; 2.70 g, 12.3 mmol) in THF (10 mL) was added and the
resulting mixture was stirred at –78 °C for 30 min. After this time,
a saturated aqueous solution of NH4Cl (10 mL) was added, and the
mixture was allowed to warm to rt. The phases were separated
and the aqueous phase was washed with Et2O (3 × 100 mL), and the
combined organics phases were washed with H2O (100 mL) and
brine (100 mL), then dried (MgSO4) and concentrated under re-
duced pressure to afford the crude chlorohydrin that was used in
the subsequent reaction without further purification.
To a stirred solution of the chlorohydrin in MeOH (100 mL) was
added K2CO3 (5.97 g, 43.2 mmol). The reaction mixture was stirred
at rt for 5 h, then filtered and concentrated under reduced pres-
sure. The crude residue was dissolved in Et2O (250 mL) and washed
with H2O (2 × 100 mL) and brine (100 mL), then dried (MgSO4) and
concentrated to afford the crude epoxyalkyne. The crude product
was purified by flash chromatography (silica gel, 20:1 hexanes–
EtOAc) to afford (2R,3S)-2-nonyl-3-(prop-2-ynyl)oxirane (12; 1.72 g,
66% over two steps) as a colourless oil. IR (neat, cm−1): 3313, 2955,
2925, 2855, 1465. 1H NMR (400 MHz, CDCl3) ␦: 3.15 (ddd, 1H, J = 7.0,
5.5, 4.0 Hz), 2.99–2.95 (m, 1H), 2.58 (ddd, 1H, J = 17.0, 5.5, 2.5 Hz),
2.28 (ddd, 1H, J = 17.0, 7.0, 2.5 Hz), 2.05 (t, 1H, J = 2.5 Hz), 1.58–
1.21 (m, 16H), 0.88 (t, 3H, J = 7.0 Hz). 13C NMR (100 MHz, CDCl3) ␦: 79.5,
70.3, 57.0, 54.8, 31.9, 29.5, 29.5, 29.5, 29.3, 27.5, 26.5, 22.7, 18.5, 14.1.
Exact mass calcd. for C14H24O: 208.1835 (M+); found: 208.1827 (M+).
Preparation of (2R,3S)-2-nonyl-3-((2Z,5Z)-octa-2,5-dienyl)
oxirane (1)
To a cold (0 °C), stirred solution of Ni(OAc)2·4H2O (454 mg,
1.8 mmol) in MeOH (60 mL) was added NaBH4 (69 mg, 1.8 mmol).
(Caution: vigorous gas evolution.) The reaction mixture was al-
lowed to warm to rt and then stirred for 5 min. After this time,
1,2-diaminoethane (0.24 mL, 3.6 mmol) and cyclohexene (1.48 mL,
14.6 mmol) were added and the resulting mixture was stirred for a
further 5 min. A solution of (2R,3S)-2-nonyl-3-(octa-2,5-diynyl)
oxirane (10; 60% ee; 1 g, 3.6 mmol) in MeOH (20 mL) was then
added. The reaction vessel was then evacuated and backfilled with
hydrogen three times and the reaction mixture stirred under an
atmosphere of hydrogen for 4 h. The reaction mixture was then
filtered through a pad of Celite, which was washed thoroughly
with MeOH. The filtrate was evaporated under reduced pressure,
and the residue dissolved in Et2O (100 mL) and washed with H2O
(2 × 50 mL) and brine (50 mL), then dried (MgSO4) and concentrated
to afford the crude diene. The crude product was purified by flash
chromatography (20% AgNO3–silica gel, 40:1 hexanes–EtOAc) to
afford (2R,3S)-2-nonyl-3-((2Z,5Z)-octa-2,5-dienyl)oxirane (1; 803 mg,
25
81%, 60% ee) as a colourless oil. [␣]D –4.7° (c 8.5, CHCl3), lit.
value5b [␣]D25 –4.3° (c 1.15, CHCl3; optical rotation was recorded on
a 4:1 mixture of enantiomers, 60% ee). IR (neat, cm−1): 3013, 2959,
1
2924, 2854, 1730, 1463, 1380, 1272, 1070, 720. H NMR (400 MHz,
CDCl3) ␦: 5.55–5.37 (m, 3H), 5.34–5.26 (m, 1H), 2.97–2.90 (m, 2H),
2.81 (t, 2H, J = 7.0 Hz), 2.45–2.37 (m, 1H), 2.27–2.17 (m, 1H), 2.07
(dp, 2H, J = 7.6, 0.8 Hz), 1.54–1.22 (m, 16H), 0.98 (t, 3H, J = 7.5 Hz), 0.88
(t, 3H, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3) ␦: 132.2, 130.8, 126.7,
124.3, 57.2, 56.4, 31.9, 29.6, 29.5, 29.3, 27.8, 26.6, 26.3, 25.7, 22.7,
20.6, 14.2, 14.1. Exact mass calcd. for C19H35O: 279.2682 (M + H);
found: 279.2680 (M + H).
Preparation of (2R,3S)-2-nonyl-3-(octa-2,5-diynyl)oxirane (10)
Method A (from 12): K2CO3 (2.40 g, 17.4 mmol), CuI (3.31 g,
17.4 mmol), and NaI (2.60 g, 17.4 mmol) were charged to a flask and
the flask was then evacuated and backfilled with argon three
times. Dimethylformamide (DMF; 80 mL) was then added, fol-
lowed by a solution of (2R,3S)-2-nonyl-3-(prop-2-ynyl)oxirane (7;
60% ee; 1.81 g, 8.27 mmol) in DMF (10 mL) and pent-2-ynyl meth-
anesulfonate (13; 4.22 g, 26.0 mmol). The reaction mixture was
stirred at rt for 24 h, after which time the reaction mixture was
filtered and the filtrate was diluted with Et2O (100 mL) and washed
with H2O (50 mL) and brine (7 × 50 mL), dried (MgSO4), and con-
centrated to afford the crude epoxydiyne 10. The crude product
was purified by flash chromatography (silica gel, 20:1 hexanes–
EtOAc) to afford (2R,3S)-2-nonyl-3-(octa-2,5-diynyl)oxirane (10;
1.35 g, 57%). The spectral data obtained for 10 was in complete
agreement with that reported for this substance.5b
Supplementary data
Supplementary data (general experimental details and experimen-
tal procedures and characterization data for known compounds) are
available with the article through the journal Web site at http://
nrcresearchpress.com/doi/suppl/10.1139/cjc-2012-0376.
Acknowledgments
This research was supported by the Canadian Food Inspection
Agency, the Natural Sciences and Engineering Research Council
of Canada (NSERC) Canada Graduate Scholarship (CGS-D; B.K.), the
NSERC Postgraduate Scholarship (PGS-D; J.M.), and the Michael
Smith Foundation for Health Research (B.K., J.M.). We thank
Method B (from 7): To a cold (−78 °C), stirred solution of
hepta-1,4-diyne (8; 700 mg, 7.6 mmol) in THF (30 mL) was added
n-butyllithium (2.4 mol/L solution in hexanes, 2.98 mL, 7.6 mmol).
Published by NRC Research Press

Mowat et al.
239
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GC analysis.
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