Synthesis of the (5S,9R)-isomer of 5,9-dimethylpentadecane, the major component of the female sex pheromone of the coffee leaf miner moth, Leucoptera coffeella

Article abstract of DOI:10.1016/j.tetasy.2008.03.016

(5S,9R)-5,9-Dimethylpentadecane, one of the stereoisomers of the major component of the female sex pheromone of the coffee leaf miner moth (Leucoptera coffeella), was synthesized by starting from (R)-3-methyl-4-butanolide and (S)-citronellal.

Full text of DOI:10.1016/j.tetasy.2008.03.016

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 857–861
Synthesis of the (5S,9R)-isomer of 5,9-dimethylpentadecane,
the major component of the female sex pheromone of the coffee
leaf miner moth, Leucoptera coffeellaI
Kenji Mori*
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd, Wakahagi 4-2-1, Inba-mura, Inba-gun, Chiba 270-1609, Japan
Received 13 February 2008; accepted 17 March 2008
Available online 15 April 2008
Abstract—(5S,9R)-5,9-Dimethylpentadecane, one of the stereoisomers of the major component of the female sex pheromone of the coffee
leaf miner moth (Leucoptera coffeella), was synthesized by starting from (R)-3-methyl-4-butanolide and (S)-citronellal.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
of 1 attracted the insects, while other stereoisomers
[(5R,9S)- and (5S,9R)-1] did not.4 Very recently, however,
we were informed that (5S,9R)-1 showed the highest activ-
ity in a field test, while (5S,9S)-1 was about one thirds as
active as (5S,9R)-1.8 The other two isomers were almost
inactive. Therefore, we decided to develop a new synthesis
for (5S,9R)-1.
In 1988, Francke et al. identified 5,9-dimethylpentadecane
1 (Fig. 1) as the major component of the female sex pher-
omone of the coffee leaf miner moth, Leucoptera coffeella.2
Since then, three syntheses of 1 as a racemic and diastereo-
meric mixture3,4 or the (5RS,9S)-isomer5 were reported. In
2000, Kuwahara et al. described the synthesis of all four
stereoisomers of 1,6 while in 2003 Moreira and Correˆa
reported the synthesis of (5S,9S)-, (5R,9S)-, and (5S,9R)-1.7
As shown in Scheme 1, Kuwahara et al. converted the
enantiomers of methyl 3-hydroxy-2-methylpropanoate to
(R)-2 and (S)-4, and employed methyl phenyl sulfone 3
as the linchpin to connect 2 and 4 as reported by us.9 This
was a reliable route, but rather complicated. Correˆa’s route
was straightforward by starting from neoisopulegol 5, but
quite lengthy via 6. Accordingly, their syntheses provided
only small amounts of (5S,9R)-1.6,7
Despite these efforts, the absolute configuration of the nat-
ural pheromone still remains unknown. It was mentioned
in Zarbin’s paper that a mixture of (5S,9S)-1 and
(5R,9S)-1, as well as a racemic and diastereomeric mixture
2. Results and discussion
Me(CH2)5
Me(CH2)5
(CH2)3Me Me(CH2)5
(CH2)3Me
(CH2)3Me
(5S,9R)-1
(5R,9S)-1
(5S,9S)-1
(5R,9R)-1
In our synthetic plan, as shown in Scheme 1, (R)-3-methyl-
4-butanolide 7 and (S)-citronellal 8 were chosen as the
starting materials. The former 7 (>99% ee10) was given to
us by Dr. Sakashita of Mitsubishi Rayon Co., while the
latter 8 (97% ee) was a commercial product of Takasago
International Corporation. Both enantiomers of 8 are
employed frequently in enantioselective synthesis.11 Lac-
tone 7 would give (R)-2, whose combination with (S)-8
would eventually furnish (5S,9R)-1.
Me(CH2)5
(CH2)3Me
Figure 1. Structures of the stereoisomers of 5,9-dimethylpentadecane, the
major component of the female sex pheromone of the coffee leaf miner
moth.
q Pheromone synthesis, Part 236. For Part 235, see Ref. 1.
*
Scheme 2 summarizes our synthesis of (5S,9R)-1. The
reduction of the lactone (R)-7 with diisobutylaluminum
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doi:10.1016/j.tetasy.2008.03.016

858
K. Mori / Tetrahedron: Asymmetry 19 (2008) 857–861
a
b
I
I
+
+
MeSO2Ph
Me(CH2)5
(R)-2
(CH2)3Me
OH
O
O
(S)-4
3
O
HO
(2RS,4R)-9
(R)-10
(R)-7
(5S,9R)-1
c
e
I
OR
OTs
Me(CH2)5
Me(CH2)5
(5S,9R)-1
(R)-11 R = H
(R)-12 R = Ts
OH
(R)-13
d
OBn
neoisopulegol 5
6
OR
f
h
The present work
Me(CH2)5
(6S,8RS,10R)-14 R = H
(6S,8RS,10R)-15 R = Ms
g
I
Me(CH2)5
(R)-2
O
O
i or j,k
(R)-3-methyl-
(5S,9R)-1
4-butanolide 7
Me(CH2)5
Me(CH2)5
Me(CH2)5
Me(CH2)5
(6R,10R)-16
OHC
(S)-citronellal 8
l
CHO
Scheme 1. Various syntheses of (5S,9R)-5,9-dimethylpentadecane.
(4R,8R)-17
(5R,9R)-18
hydride (DIBAL-H) gave lactol (2RS,4R)-9. This was trea-
ted with the Wittig reagent prepared from n-butyltriphenyl-
phosphonium iodide and n-butyllithium in THF to give
alkene (R)-10 as an E/Z-mixture (E/Z = ca. 1:4 as judged
by 13C NMR analysis). The hydrogenation of (R)-10
m
over palladium-charcoal afforded the known (R)-2-
24
methyl-1-octanol 11, ½aꢀD ¼ þ12:1 (c 2.43, EtOH){Ref.
(CH2)3Me
25
12 ½aꢀD ¼ þ13:2 (c 1.63, EtOH)}. The corresponding tosyl-
(5S,9R)-1
ate 12 was subjected to the Finkelstein reaction with lith-
ium bromide in N,N-dimethylformamide (DMF) to give
the corresponding bromide. Unfortunately, conversion of
this bromide to the Grignard reagent afforded a poor yield
under conventional conditions with magnesium in THF.
Ts =
Ms = —SO2Me
SO2
Scheme 2. Synthesis of (5S,9R)-5,9-dimethylpentadecane 1. Reagents and
conditions: (a) DIBAL-H, THF, ꢁ60 to ꢁ55°C, 45 min, 92%; (b) Ph3P(n-
Bu)I, n-BuLi, THF, 10–20 °C, 1.25 h, 47%; (c) H2, Pd–C, EtOH, room
temp, 2 h, 92%; (d) TsCl, C5H5N, DMAP, 0–5 °C, 2 h, quant.; (e) NaI,
DMF, 55–60 °C, 2 h, 97%; (f) t-BuLi (2 equiv), Et2O, ꢁ70 to ꢁ50 °C,
20 min, then room temp, ꢁ70 to ꢁ40 °C, (S)-8, room temp, 1.5 h, 83%; (g)
MsCl, CH2Cl2, C5H5N, 0–5 °C, 3 d, quant.; (h) LiAlH4, THF, reflux, 1 h,
77%; (i) OsO4, NaIO4, THF, H2O, room temp, 2 d, quant. (70% purity); (j)
MCPBA, CH2Cl2, 0–5 °C, 45 min, quant.; (k) HIO4ꢂ2H2O, THF, Et2O,
0–5 °C, 20 min, 85%; (l) Ph3P(Me)Br, n-BuLi, THF, 0–5 °C, 1 h, 81%; (m)
H2, PtO2, EtOAc, room temp, 30 min, 96%.
Accordingly, we decided to employ (R)-2-methyloctyl-
lithium instead of the Grignard reagent. Tosylate 12 was
treated with sodium iodide in DMF to give iodide (R)-13.
Transmetallation of 13 with t-butyllithium in pentane/
ether13,14 gave the lithio derivative, which was treated with
(S)-citronellal 8 to give alcohol (6S,8RS,10R)-14. The cor-
responding mesylate 15 was reduced with lithium alumi-
num hydride to give alkene (6R,10R)-16 in 64% yield
based on (R)-13.
1
CHCl3)}. Its IR, H, and 13C NMR spectroscopic proper-
Lemieux–Johnson oxidation of 16 with osmium tetroxide
and sodium periodate in aqueous THF furnished aldehyde
(4R,8R)-17. An excessive reaction time (2–3 days) at this
stage resulted in the further oxidation of 17 to the corres-
ponding carboxylic acid. Purer 17 could be obtained in a
better yield by the epoxidation of 16 with m-chloroperben-
zoic acid (MCPBA) followed by the treatment of the result-
ing epoxide with periodic acid dihydrate in THF/Et2O. The
treatment of 17 with methylene triphenylphosphorane gave
terminal alkene (5R,9R)-18. Finally, the hydrogenation of
18 over Adams platinum oxide in ethyl acetate afforded
the desired (5S,9R)-5,9-dimethylpentadecane 1 as an oil,
ties were in good agreement with those reported previ-
ously.6,7 Although modern GC analysis on a chiral
stationary phase does not allow the determination of the
enantiomeric purity of synthetic 1, it was thought to be
97% ee, reflecting the enantiomeric purity of the starting
(S)-citronellal 8.
3. Conclusion
In conclusion, (5S,9R)-5,9-dimethylpentadecane 1 was syn-
thesized in 16% overall yield (12 steps) based on (R)-3-
25
21
½aꢀD ¼ þ1:0 (c 2.23, CHCl3) {Ref. 6 ½aꢀD ¼ þ1:1 (c 3.81,

K. Mori / Tetrahedron: Asymmetry 19 (2008) 857–861
859
methyl-4-butanolide 7 or 42% (7 steps) in turn based on
(S)-citronellal 8. The present synthesis was more efficient
than the previous ones.6,7 Since both the enantiomers of
citronellal 8 are commercially available, the present route
can also provide (5R,9R)-1.
After stirring for 1 h at 15–20 °C, the mixture was diluted
with MeOH/H2O (3:2, 100 mL), and extracted with hex-
ane. The hexane extract was washed with MeOH/H2O
(3:2, 100 mL), water and brine, dried over MgSO4, and
concentrated in vacuo. The residue was distilled to give
5.9 g (47%) of 10 as an oil, bp 122–125 °C/55 Torr;
22
At the time when the synthesis of (5S,9R)-1 was completed,
we were informed that a racemic and diastereomeric mix-
ture of 1 showed sufficient pheromone activity for practical
use in Brazil.8 Zarbin et al. published the same biological
observation.4 The bioassay results of the four stereoisomers
of 1 are unfortunately not reproducible but fluctuate. The
absolute configuration of natural 1 therefore remains
unknown.
n2D3 ¼ 1:4490; ½aꢀD ¼ þ7:8 (c 3.26, EtOH); mmax (film):
3338 (s, O–H), 1039 (s, C–O); dH (CDCl3): 0.87–0.94
(6H, m, 2 ꢃ CH3), 1.33–1.42 (2H, m, 7-CH2), 1.56 (1H,
br s, O–H), 1.65–1.75 (1H, m, 2-CH), 1.85–2.18 (4H, m),
3.40–3.54 (2H, m, 1-CH2), 5.35–5.50 (2H, CH@CH); dC
(CDCl3): 13.8, 16.5, 22.6, 29.3, 30.9, 34.7, 36.3, 68.0,
127.5 (Z), 128.0 (E), 131.0 (Z), 132.0 (E) (Z/E = ca. 4:1).
HRMS calcd for C9H18O (M+) 142.1358; found, 142.1357.
4.4. (R)-2-Methyl-1-octanol 11
4. Experimental
4.1. General
Palladium-charcoal (0.4 g, 10%) was added to a solution of
10 (5.85 g, 41 mmol) in EtOH (20 mL). The suspension was
stirred under H2 (balloon) for 2 h at room temperature.
The catalyst was filtered off through Celite, and the solid
was washed with EtOH. The combined solution was
concentrated in vacuo. The residue was distilled to give
Boiling points are uncorrected values. Refractive indices
(nD) were measured on an Atago DMT-1 refractometer.
The optical rotations were measured on a Jasco P-1020
polarimeter. IR spectra were measured on a Jasco FT/
5.41 g (92%) of 11 as an oil, bp 128–133 °C/73 Torr or
24
119–121 °C/45 Torr; nD22 ¼ 1:4338; ½aꢀD ¼ þ12:1 (c 2.43,
25
1
IR-410 spectrometer. H NMR spectra (400 MHz, TMS
at d = 0.00 as an internal standard) and 13C NMR spectra
(100 MHz, CDCl3 at d = 77.0 as an internal standard) were
recorded on a Jeol JNM-AL 400 spectrometer. GC–MS
were measured on Agilent Technologies 5975 inert XL.
HRMS were recorded on a Jeol JMS-SX102A. Column
chromatography was carried out on Merck Kieselgel 60
Art 1.07734.
EtOH); {Ref. 12: ½aꢀD ¼ þ13:2 (c 1.63, EtOH)}; mmax (film):
3354 (s, O–H), 1034 (s, C–O); dH (CDCl3): 0.88 (3H, t, J
6.8; CH2CH3), 0.91 (3H, d, J 6.8, CHCH3), 1.05–1.92
[12H, m (1.27, br s)], 1.48 (1H, br s), 1.60 (1H, m), 3.41
(1H, dd, J 6.8, 10.8 CHHOH), 3.50 (1H, dd, J 6.8, 10.8,
CHHOH). HRMS calcd for C9H18(M+ꢁH2O) 126.1409;
found 126.1417.
4.2. (2RS,4R)-4-Methyloxacyclopentan-2-ol 9
4.5. (R)-2-Methyloctyl tosylate 12
A solution of DIBAL-H (0.97 M in hexane, 45 mL
43.7 mmol) was added dropwise to a cooled and stirred
Tosyl chloride (9.5 g, 50 mmol) was added portionwise to a
stirred and ice-cooled solution of 11 (6.1 g, 42 mmol) in dry
C5H5N (30 mL). A small amount (ca. 10 mg) of DMAP
was added and the mixture was stirred at 0–5 °C for 2 h.
Then Et2O and ice-water were added to the mixture. The
Et2O layer was separated and the aqueous layer was
extracted with Et2O. The combined Et2O solution was
washed with H2O, dil HCl, aq NaHCO3 solution and brine,
dried over MgSO4, and concentrated in vacuo to give
12.9 g (quant.) of 12 as an oil, mmax (film): 1599 (w, arom
C@C), 1362 (s), 1178 (s), 1188 (s), 966 (s); dH (CDCl3):
0.87 (3H, t, J 7.2, CH2CH3), 0.88 (3H, d, J 6.8, CHCH3),
1.05–1.35 (10H, m), 1.76 (1H, m), 2.45 (3H, s,
C6H4CH3), 3.80 (1H, dd, J 6.8, 10.0, CHHOTs), 3.88
(1H, dd, J 6.8, 10.0, CHHOTs), 7.34 (2H, d, J 8.8, arom
H), 7.79 (2H, d, J 8.8, arom H). This was employed for
the next step without further purification.
solution of (R)-3-methyl-4-butanolide (8, Mitsubishi
18
Rayon Co., >99% ee; bp 118–119 °C/42 Torr; ½aꢀD
¼
24
þ25:8 (c 3.72, MeOH), ½aꢀD ¼ þ3:6 (c 4.82, hexane),
4.0 g, 40 mmol) in dry THF (60 mL) at ꢁ60 to ꢁ55 °C over
15 min under Ar. After stirring for 30 min at ꢁ60 °C, the
reaction was quenched by the addition of saturated NH4Cl
solution (15 mL) with stirring at ꢁ60 °C. The mixture was
diluted with Et2O (200 mL). Stirring was continued for
40 min at room temperature, when gelatinous precipitates
of Al(OH)3 appeared. The suspension was mixed with
MgSO4, and filtered through Celite. The filtrate was
concentrated in vacuo to give 3.7 g (92%) of crude 9; mmax
(film): 3402 (s, O–H), 1055 (s, C–O), 1001 (s, C–O). This
was employed for the next step without further
purification.
4.3. (2R,4EZ)-2-Methyl-4-octen-1-ol 10
4.6. (R)-2-Methyloctyl iodide 13
To an ice-cooled and stirred suspension of Ph3P(n-Bu)I
(90.0 g, 202 mmol) in dry THF (240 mL) was added a solu-
tion of n-BuLi in hexane (1.6 M, 126 mL, 202 mmol) drop-
wise over 15 min at 10–15 °C under Ar. Then a solution of
crude 9 (8.9 g, 87 mmol) in dry THF was added dropwise
over 15 min to the ice-cooled and red solution of the result-
ing Wittig reagent at 10–15 °C with vigourous stirring.
Sodium iodide (15.0 g, 100 mmol) was added to a solution
of 12 (12.8 g, 43 mmol) in DMF (75 mL). The mixture was
stirred and heated at 55–60 °C for 2 h. After cooling, the
mixture was diluted with water, and extracted with hexane.
The hexane extract was washed with water containing a
trace amount of Na2S2O3 and brine, dried over MgSO4,
and concentrated in vacuo. The residue was distilled to give

860
K. Mori / Tetrahedron: Asymmetry 19 (2008) 857–861
10.6 g (97%) of 13 as an oil, bp 107–109 °C/10 Torr;
reflux for 1 h. The reaction was quenched by the addition
of water to a stirred and ice-cooled mixture. Next Et2O
and ice-dil HCl were added, and the mixture was extracted
with Et2O. The extract was washed with water, satd NaH-
CO3 solution and brine, dried over MgSO4, and concen-
trated in vacuo. The residue (2.4 g) was chromatographed
21
n2D3 ¼ 1:4822; ½aꢀD ¼ ꢁ2:3 (c 4.75, hexane); mmax (film):
2956 (s), 2925 (s), 2854 (m), 1458 (m), 1377 (w), 1194
(m); dH (CDCl3): 0.88 (3H, t, J 6.8, CH2CH3), 0.97
(3H, d, J 6.4, CHCH3), 1.15–1.40 (10H, m), 1.44 (1H,
m), 3.15 (1H, dd, J 5.6, 5.6, CHHI), 3.24 (1H, dd, J 5.6,
5.6, CHHI). HRMS calcd for C9H19I 254.0531; found
254.0522.
over SiO2 (20 g). Elution with hexane gave 1.79 g (77%)
16
of 16, n2D2 ¼ 1:4514; ½aꢀD ¼ þ1:85 (c 3.23, hexane); mmax
(film): 2956 (s), 2925 (s), 2856 (s), 1460 (m), 1377 (m),
970 (w), 829 (w), 725 (w); dH (CDCl3): 0.83 (3H, d, J 6.4,
CHCH3), 0.86 (3H, d, J 6.8, CHCH3), 0.88 (3H, t, J 6.4,
CH2CH3), 1.00–1.42 (20H, m), 1.60 (3H, s), 1.68 (3H, s),
1.96 (2H, m, 4-CH2), 5.10 (1H, t-like, C@CH). HRMS
calcd for C19H38 266.2974; found 266.2976.
4.7. (6S,8RS,10R)-2,6,10-Trimethyl-2-hexadecen-8-ol 14
A solution of t-BuLi in pentane (1.7 M, 12.5 mL, 21 mmol)
was added dropwise to a stirred and cooled solution of 13
(2.54 g, 10 mmol) in dry Et2O (20 mL) over 10 min at ꢁ70
to ꢁ50 °C under Ar. The mixture was stirred for 10 min at
ꢁ70 °C, then warmed to room temperature, and left to
stand for 30 min. The mixture was cooled again at
ꢁ70 °C. A solution of (S)-8 (Takasago, 97% ee, 1.39 g,
9 mmol) in dry Et2O (5 mL) was added to the stirred and
cooled mixture at ꢁ70 to ꢁ40°C over 5 min. Then the cool-
ing bath was removed, and the stirred mixture was left to
stand for 1.5 h at room temperature. The reaction was
quenched with dil HCl–NH4Cl and the mixture was
extracted with Et2O. The extract was washed with sat.
NaHCO3 solution and brine, dried over MgSO4, and
concentrated in vacuo. The crude product (2.87 g) was
chromatographed over SiO2 (20 g). Hydrocarbon impuri-
ties (0.3 g) were removed by elution with hexane. Subse-
4.10. (4R,8R)-4,8-Dimethyltetradecanal 17
4.10.1. Lemieux–Johnson oxidation of 16. A solution of
OsO4 (50 mg) in t-BuOH (5 mL) and powdered NaIO4
(4.8 g, 22 mmol) were added to a stirred solution of 16
(1.70 g, 6.4 mmol) in a mixture of THF (30 mL) and water
(10 mL) at room temperature under Ar. The stirring was
continued for 2 d at room temperature, while the tan-
colored mixture turned colorless. It was then diluted with
water, and extracted with hexane. The extract was washed
with water and brine, dried over MgSO4, and concentrated
in vacuo. The residue was chromatographed over SiO2
(20 g). Elution with hexane/EtOAc (10:1) gave 17 (1.66 g,
quant), whose IR spectrum revealed contamination with
the corresponding carboxylic acid. Further NMR analysis
indicated that 17 was only of ca. 70% purity.
quent elution with hexane/EtOAc (20:1) afforded 2.35 g
21
(83%) of 14 as an oil, nD23 ¼ 1:4585; ½aꢀD ¼ þ1:7 (c 2.64,
hexane); mmax (film): 3346 (s, O–H), 1061 (m), 1020 (m);
dH (CDCl3): 0.85–0.94 (9H, m, CH3), 1.00–1.50 [18H,
m(1.18 br s)], 1.55–1.65 (1H), 1.60 (3H, s, C@CCH3),
1.68 (3H, s, C@CCH3), 1.90–2.10 (2H, m, 3-CH2), 3.74–
3.82 (1H, m, CHOH), 5.10 (1H, t-like, C@CH). HRMS
calcd for C19H38O 282.2923; found 282.2924.
4.10.2. Epoxidation of 16 followed by cleavage of the
epoxide. MCPBA (77% purity, 1.2 g, 5.4 mmol) was
added portionwise to a stirred and ice-cooled solution of
16 (1.20 g, 4.5 mmol) in dry CH2Cl2 (20 mL) at 0–5 °C.
After stirring for 45 min at 0–5 °C, the mixture was diluted
with Et2O. The solution was washed with K2CO3 solution
containing a small amount of Na2S2O3 and brine, dried
over MgSO4, and concentrated in vacuo to give 1.3 g
(quant.) of the epoxide, mmax (film): 1122 (m), 739 (w); dH
(CDCl3): 0.80–0.90 (9H, m, CH3), 1.00–1.60 (22H, m),
1.27 [3H, s, CH3C(O)], 1.31[3H, s, CH3C(O)], 2.70 (1H, t,
J 6, OCH). A solution of this epoxide (1.3 g, 4.5 mmol)
in Et2O (5 mL) was added dropwise to a stirred and ice-
cooled solution of HIO4ꢂ2H2O (1.3 g, 5.7 mmol) in THF
(25 mL) at 0–5 °C. After stirring for 20 min at 0–5 °C,
the mixture was diluted with water, and extracted with
Et2O. The extract was washed with water, satd NaHCO3
solution and brine, dried over MgSO4, and concentrated
in vacuo. The residue was chromatographed over SiO2
4.8. (6S,8RS,10R)-8-Methanesulfonyloxy-2,6,10-trimethyl-
2-hexadecene 15
Methanesulfonyl chloride (2 mL = ca. 3.0 g, 26 mmol) was
added dropwise to a stirred and ice-cooled solution of 14
(2.11 g, 7.5 mmol) in dry CH2Cl2 (10 mL) and dry pyridine
(10 mL). The mixture was left to stand for three days in a
refrigerator. The mixture was then diluted with ice-water,
and extracted with Et2O. The extract was washed with dil
HCl, water, satd NaHCO3 solution and brine, dried over
MgSO4, and concentrated in vacuo to give 2.8 g (quant.)
of crude 15 as an oil, mmax (film): 1338 (s), 1174 (s), 902
(s), dH (CDCl3): 0.85–1.00 (9H, m, CH3), 1.10–1.50 [16H,
m (1.19 br s)], 1.58 (1H, m), 1.61 (3H, s, C@CCH3), 1.68
(3H, s, C@CCH3), 1.70–1.80 (1H, m), 1.90–2.10 (2H, m),
2.98 (3H, s, SO2CH3), 4.85–4.95 (1H, m, CHOMs), 5.10
(1H, m, C@CH). This was employed for the next step
without further purification.
(15 g). Elution with hexane/EtOAc (10:1) gave 0.87 g
22
(85%) of 17 as an oil, nD18 ¼ 1:4490; ½aꢀD ¼ þ1:33 (c 3.41,
hexane); mmax (film): 2956 (s), 2925 (s), 2856 (s), 2713 (m,
O@C–H), 1728 (s, C@O), 1462 (m), 1412 (w), 1379 (m),
1020 (w), 970 (w), 902 (w), 725 (w); dH (CDCl3): 0.84
(3H, d, J 7.2, CHCH3), 0.87 (3H, d, J 6.8 CHCH3), 0.88
(3H, t, J 6.8, CH2CH3),0.90–1.70 (20H, m), 2.35–2.50
(2H, m, CH2CHO), 9.77 (1H, t, J 2, CHO). HRMS calcd
for C16H32O 240.2453; found 240.2455.
4.9. (6S,10R)-2,6,10-Trimethyl-2-hexadecene 16
A solution of 15 (2.8 g, 7.5 mmol) in dry THF (10 mL) was
added to a stirred suspension of LiAlH4 (0.8 g, 21 mmol) in
dry THF (10 mL). The mixture was stirred and heated at

K. Mori / Tetrahedron: Asymmetry 19 (2008) 857–861
861
4.11. (5R,9R)-5,9-Dimethyl-1-pentadecene 18
Acknowledgments
A solution of methylene triphenylphosphorane was pre-
pared by adding a solution of n-BuLi in hexane (1.6 M,
4.5 mL, 7.2 mmol) to a stirred and ice-cooled suspension
of Ph3PMeBr (2.70 g, 7.2 mmol) in dry THF (30 mL) at
5–10 °C under Ar. A solution of 17 (0.87 g, 3.6 mmol) in
dry THF (10 mL) was added dropwise to the stirred and
ice-cooled Wittig reagent. The mixture was stirred at
0–5 °C for 1 h, quenched with a mixture of MeOH/water
(3:2), and extracted with hexane. The hexane extract was
washed with a mixture of MeOH/water (3:2), water and
brine, dried over MgSO4, and concentrated in vacuo. The
residue was chromatographed over SiO2 (15 g). Elution
Thanks are due to Mr. M. Kimura (President, Toyo Gosei
Co., Ltd) for his support. Mr. K. Ogawa (Shin-etsu Chem-
ical Co.) provided useful information on the pheromone
activity of 1. Dr. T. Tashiro (RIKEN) kindly prepared
the Figure and Schemes. Mr. Y. Shikichi (Toyo Gosei
Co.) and Mr. H. Tawaragi (RIKEN) are thanked for
NMR and HRMS analyses, respectively. Thanks are due
to Mitsubishi Rayon Co. and Takasago International
Corporation for the kind supply of (R)-7 and (S)-8,
respectively.
References
with hexane gave 0.70 g (81%) of 18 as a colorless oil,
21
n2D0 ¼ 1:4426; ½aꢀD ¼ þ2:3 (c 2.89, hexane); mmax (film):
1. Mori, K. Tetrahedron 2008, 64, 4060–4071.
3078 (w), 2956 (s), 2925 (s), 2856 (s), 1641 (w, C@C),
1462 (m), 1377 (m), 993 (w), 908 (m, C@CH2); dH (CDCl3):
0.84 (3H, d, J 6.8, CHCH3), 0.86 (3H, d, J 6.4 CHCH3),
0.88 (3H, t, J 6.8, CH2CH3), 1.00–1.50 (20H, m), 2.05
(2H, m, C@CCH2), 4.92 (1H, d-like, J 10, C@CHH),
4.98 (1H, d-like, J 17.2, C@CHH). HRMS calcd for
C17H34 238.2661; found 238.2656.
´
2. Francke, W.; Toth, M.; Szo¨cs, G.; Krieg, W.; Ernst, H.;
Buschmann, E. Z. Naturforsch 1988, 43c, 787–789.
3. Liang, T.; Kuwahara, S.; Hasegawa, M.; Kodama, O. Biosci.
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A. A.; Ambrogio, B. G.; de Oliveira, A. R. M. Tetrahedron
Lett. 2004, 45, 239–241.
´
´ ´
´
5. Poppe, L.; Novak, L.; Devenyi, J.; Szantay, Cs. Tetrahedron
Lett. 1991, 32, 2643–2646.
4.12. (5S,9R)-5,9-Dimethylpentadecane 1
6. Kuwahara, S.; Liang, T.; Leal, W. S.; Ishikawa, J.; Kodama,
O. Biosci. Biotechnol. Biochem. 2000, 64, 2723–2726.
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8. Ogawa, K. Shin-etsu Chemical Co., personal communication.
9. Mori, K.; Wu, J. Liebigs Ann. Chem. 1991, 439–443.
Adams PtO2 (100 mg) was added to a solution of 18 (0.60 g,
2.5 mmol) in EtOAc (10 mL). The suspension was vigor-
ously stirred under H2 (balloon) for 30 min at room temper-
ature. The catalyst was removed by filtration through SiO2
(3 g). The SiO2 column was washed with hexane. The com-
10. Sakashita,
K.
Mitsubishi
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Co.,
personal
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bined filtrate and washings were concentrated in vacuo to
11. Lenardao, E. J.; Botteselle, G. V.; de Azambuja, F.; Perin, G.;
˜
Jacob, R. G. Tetrahedron 2007, 63, 6671–6712.
12. Shirai, Y.; Seki, M.; Mori, K. Eur. J. Org. Chem. 1999, 3139–
23
give 0.58 g (96%) of 1 as an oil, n2D0 ¼ 1:4371; ½aꢀD ¼ þ1:0
21
(c 2.23, CHCl3); {Ref. 6 ½aꢀD ¼ þ1:1 (c 3.81, CHCl3)}; mmax
(film): 2956 (s), 2925 (s), 2856 (s), 1464 (m), 1377 (m), 727
(w); dH (CDCl3): 0.84 (6H, d, J 6.4, 2 ꢃ CHCH3), 0.882
(3H, t, J 6.8, CH2CH3), 0.887 (3H, t, J 6.8, CH2CH3),
1.00–1.45 (24H, m); dC (CDCl3): 14.21, 14.26, 19.84,
22.78, 23.13, 24.54, 27.12, 29.42, 29.77, 32.03, 32.80,
32.82, 36.82, 37.14, 37.50. HRMS calcd for C17H36
240.2817; found 240.2812.
3145.
13. Bailey, W. F.; Punzalan, E. R. J. Org. Chem. 1990, 55, 5404–
5406.
14. Negishi, E.; Swanson, D. R.; Rousset, C. J. J. Org. Chem.
1990, 55, 5406–5409.