Synthesis of all the stereoisomers of 6-methyl-2-octadecanone, 14-methyl-2-octadecanone, and 6,14-dimethyl-2-octadecanone, sex pheromone components of the Lyclene dharma dharma moth, from the enantiomers of citronellal

Article abstract of DOI:10.1271/bbb.120436

The enantiomers of citronellal were converted to all the stereoisomers of 6-methyl-2-octadecanone, 14-methyl-2-octadecanone, and 6,14-dimethyl-2- octadecanone, the female-produced sex pheromone components of the Lyclene dharma dharma moth. Three wellestablished procedures, the Wittig reaction, alkylation of alkynes, and acetoacetic ester synthesis, were employed for the carbon-carbon bond formation to connect the building blocks.

Full text of DOI:10.1271/bbb.120436

Biosci. Biotechnol. Biochem., 76 (10), 1943–1951, 2012
Synthesis of All the Stereoisomers of 6-Methyl-2-octadecanone,
14-Methyl-2-octadecanone, and 6,14-Dimethyl-2-octadecanone,
Sex Pheromone Components of the Lyclene dharma dharma Moth,
*
from the Enantiomers of Citronellal
y
Yasumasa SHIKICHI and Kenji MORI
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd., 4-2-1 Wakahagi, Inzai, Chiba 270-1609, Japan
Received June 8, 2012; Accepted June 29, 2012; Online Publication, October 7, 2012
[doi:10.1271/bbb.120436]
The enantiomers of citronellal were converted to all
the stereoisomers of 6-methyl-2-octadecanone, 14-
methyl-2-octadecanone, and 6,14-dimethyl-2-octadeca-
none, the female-produced sex pheromone components
of the Lyclene dharma dharma moth. Three well-
established procedures, the Wittig reaction, alkylation
of alkynes, and acetoacetic ester synthesis, were em-
ployed for the carbon-carbon bond formation to connect
the building blocks.
O
Me(CH2)11
6-methyl-2-octadecanone (1)
(50 ng / female)
O
Me(CH2)3
(CH2)11
14-methyl-2-octadecanone (2)
O
Key words: citronellal;
enantioselective
Lyclene dharma dharma; methyl-branched
synthesis;
Me(CH2)3
(CH2)7
6,14-dimethyl-2-octadecanone (3)
1 : 2 : 3 = 2 : 1 :1
aliphatic ketone; pheromone
In 2007, Ando and his co-workers identified three
antennographically active components of the female-
produced sex pheromone of the Lithosiinae moth,
Lyclene dharma dharma, as 6-methyl-2-octadecanone
(1), 14-methyl-2-octadecanone (2), and 6,14-dimethyl-
2-octadecanone (3, Fig. 1).2) They then synthesized
mixtures of all the possible stereoisomers of 1, 2, and
3,2,3) and found that a mixture of 1, 2 and 3 in a ratio of
2:1:1 as well as a 2:1 mixture of 1 and 2 were
pheromonally active, showing that 3 was not indispen-
sable for bioactivity.3) The absolute configuration of
naturally occurring 1, 2 and 3 was not known at the time
when the present work was started.
It is well known that the absolute configuration of a
pheromone is often very important for the expression of
its pheromone activity.4) Synthesis and a bioassay of all
the possible stereoisomers of a pheromone are the
widely accepted paradigm for determining the absolute
configuration of a pheromone.4) In this context, one of
the authors has synthesized all the possible stereo-
isomers of 1, 2 and 3 by means of olefin cross
metathesis.5) In order to secure additional amounts of
the stereoisomers of 1, 2 and 3, we planned their
alternative synthesis based on classical carbon-carbon
bond formation reactions employing the commercially
available enantiomers of citronellal, whose use in
enantioselective synthesis has recently been reviewed.6)
This paper describes our second synthesis of all the
possible stereoisomers of 1, 2 and 3.
Fig. 1. Structures of the Components of the Female-Produced Sex
Pheromone of the Lyclene dharma dharma Moth.
A female moth produced about 50 ng of 1.
Results and Discussion
Scheme 1 shows the retrosynthetic analysis of 6,14-
dimethyl-2-octadecanone (3). Target ketone 3 could be
prepared by acetoacetic ester synthesis, using iodide A
and ethyl acetoacetate (B) as the building blocks. Iodide
A would be synthesized from C, D and E, employing
alkylation of the carbanion derived from D with E as the
key reaction. Subsequent replacement of the terminal
isopropylidene group with a methylene group could be
achieved by cleaving the double bond and subsequent
Wittig reaction using C. Both D and E can be readily
prepared from citronellal [F, Takasago, 97% ee for both
(R)- and (S)-isomers]. The enantiomers of F will lead to
the four steroisomers of 3 by the appropriate combina-
tion of D and E. Similarly, the two other ketones, 1 and
2, can be respectively synthesized by employing A0 and
A00, instead of A in the case for the preparation of 3.
The synthesis of (S)-5,9-dimethyl-8-decen-1-yne (8),
the left-hand portion of 3, is summarized in Scheme 2.
We adopted the procedure previously reported for the
synthesis of (R)-87,8) with slight modifications to
improve the yield in the conversion of 6 to 8.
Accordingly, (S)-citronellal was converted to (S)-citro-
nellyl iodide (6) via 4 and 5. Alkylation of lithium
*
y
Pheromone Synthesis, Part 252. See Ref. 1 for Part 251.
To whom correspondence should be addressed. Fax: +81-3-3813-1516; E-mail: kjk-mori@arion.ocn.ne.jp

1944
Y. SHIKICHI and K. MORI
O
Me(CH2)3
(CH2)7
3
O
Me(CH2)3
(CH2)7
I
CO2Et
A
ethyl acetoacetate (B)
Ph3P=CH2
I
OBn
C
D
E
CHO
(R)- or (S)-citronellal (F)
Me(CH2)3
(CH2)7
I
Me(CH2)11
I
A' for 1
A" for 2
Scheme 1. Retrosynthetic Analysis of 6,14-Dimethyl-2-octadecanone (3).
c
f
b
d
a
c
CHO
(S)-citronellal
OBn
OR
OR
(S)-4 R = H
(S)-9 R = Bn
O
(S)-4 R = H
(S)-5 R = Ts
(3S,6RS)-10
(Bn = CH2Ph)
b
a
d
RO
e
I
OHC
OBn
OBn
R
(S)-11
(S)-12 R = H
(S)-13 R = Ts
(S)-7 R = TMS
(S)-8 R = H (= D)
(S)-6
e
Similarly:
I
OBn
(S)-14 (= E)
Similarly:
CHO
(R)-citronellal
(R)-8 (= D)
I
Scheme 2. Synthesis of 8.
OH
OBn
Reagents: (a) LiAlH4, Et2O (94%); (b) TsCl, C5H5N (97%);
(c) NaI, DMF (83%); (d) HCꢀCTMS, n-BuLi, THF, HMPA (80%);
(e) K2CO3, MeOH, H2O (quant.).
(R)-14 (= E)
(R)-4
a
f
e
HO(CH2)6OBn
HO(CH2)6OH
15
16
trimethylsilylacetylenide with 6 was best carried out by
employing 1.5 eq. of the acetylenide in THF/HMPA
(5:1) and then heating the reaction mixture under reflux
for 2 h to give (S)-7 in an 80% yield. Treatment of (S)-7
with potassium carbonate in methanol furnished (S)-8 in
a quantitative yield. The overall yield of (S)-8 was 61%
based on (S)-citronellal in 5 steps. (R)-citronellal was
similarly converted to known (R)-8.
TsO(CH2)6OBn
I(CH2)6OBn
17
18
Scheme 3. Synthesis of 14 and 18.
Reagents: (a) BnCl, t-BuOK, DMSO [75% for (S)-9; 37% for 16];
.
(b) MCPBA, CH2Cl2 (quant.); (c) HIO4 2H2O, THF, Et2O (73%);
(d) LiAlH4, Et2O (83%); (e) TsCl, C5H5N [91% for (S)-13; 92% for
17]; (f) NaI, DMF [75% for (S)-14; 86% for 18].
(S)-6-Benzyloxy-4-methylhexyl iodide (14), the cen-
tral part of 3, was prepared as shown in Scheme 3.
Benzylation of (S)-citronellol (4) afforded (S)-9 which
was epoxidized with m-chloroperbenzoic acid
(MCPBA) to give (3S,6RS)-10. Periodic acid dihydrate
cleaved epoxide (3S,6RS)-10 to give aldehyde (S)-11.
Reduction of (S)-11 with lithium aluminum hydride
furnished alcohol (S)-12 which was converted to iodide
(S)-14 via (S)-13. The overall yield of (S)-14 was 29%
based on (S)-citronellal in 7 steps. (R)-4 was similarly
converted to (R)-14.
with sodium iodide in DMF finally afforded 18. The
overall yield of 18 was 29% based on 15.
With all the required building blocks in hand, we then
started the synthesis of the enantiomers of 6-methyl-2-
octadecanone (1) as shown in Scheme 4. Commercially
available 1-nonyne (19) was alkylated with (S)-14,
employing n-butyllithium in THF/HMPA as the base to
give (S)-20. Hydrogenation of (S)-20 over palladium-
charcoal in acetic acid afforded (S)-3-methyl-1-penta-
decanol (21). Corresponding tosylate (S)-22 was treated
with sodium iodide to furnish iodide (S)-23.
It was necessary to provide iodide 18 for the synthesis
of 14-methyl-2-octadecanone (2). Its synthesis started
from hexane-1,6-diol (15). Monobenzylation of 15 gave
16 which was tosylated to furnish 17. Treatment of 17
Alkylation of ethyl acetoacetate with (S)-23 was
achieved by using potassium carbonate in DMF as the
base to give a mixture of desired C-alkylation product

Synthesis of the Sex Pheromone of Lyclene dharma dharma
1945
Me(CH2)6
a
I
Me(CH2)6C CH
+
OBn
OBn
(S)-14
(S)-20
19
b
d
e
Me(CH2)11
OR
Me(CH2)11
I
(S)-21 R = H
(S)-22 R = Ts
(S)-23
c
O
f
+
CO2Et
Me(CH2)11
Me(CH2)11
O
CO2Et
(3RS,6S)-24
(S)-25
OH
O
g
h
impurity
(S)-1
+
Me(CH2)11
(2RS,6S)-26
Me(CH2)11
(S)-1
Similarly:
O
+
19
I
OBn
Me(CH2)11
(R)-14
(R)-1
Scheme 4. Synthesis of 1.
Reagents: (a) n-BuLi, THF, HMPA (87%); (b) H2, Pd–C, AcOH (89%); (c) TsCl, C5H5N (94%); (d) NaI, DMF (92%); (e) MeCOCH2CO2Et,
K2CO3, DMF; (f) NaOH, MeOH, H2O (81%, 2 steps); (g) LiAlH4, THF; then SiO2 chromatography (65%); (h) Jones CrO3, acetone (82%).
(3RS,6S)-24 and unwanted O-alkylation product (S)-25
(84:16). The structure of contaminant (S)-25 was
supported by its 1H-NMR spectrum to respectively
exhibit the presence of C=CH and C=CCH3 at ꢀ ¼ 5:01
and 2.29. The mixture was treated with sodium
hydroxide in aqueous methanol to give (S)-1 contami-
nated with (S)-25 which resisted hydrolysis under these
conditions. Unfortunately, (S)-1 and (S)-25 could not be
separated by column chromatography. To remove (S)-
25, the mixture was reduced with lithium aluminum
hydride, yielding alcohol (2RS,6S)-26. Curiously, (S)-25
could not be reduced under these conditions. These two
compounds, however, could be separated by chroma-
tography to give pure (S)-25 first, and then desired
(2RS,6S)-26. Finally, oxidation of (2RS,6S)-26 with
Acetoacetic ester synthesis employed (S)-33 and ethyl
acetoacetate in the presence of potassium carbonate in
DMF to give an inseparable mixture of (3RS,14S)-34
and (S)-35. After saponification and decarboxylation,
resulting (S)-2 and unchanged (S)-35 (85:15) were
reduced with lithium aluminum hydride for the purpose
of purification at this stage. Alcohol (2RS,14S)-36 could
be separated from unreduced by-product (S)-35 by silica
gel chromatography. Finally, oxidation of (2RS,14S)-36
25
with Jones chromic acid gave pure (S)-2, ½ꢁꢁD þ1:07
(c 1.09, hexane). Its IR, 1H- and 13C-NMR, and MS data
were identical with those previously reported.5) The
overall yield of (S)-2 based on (S)-citronellal was 10%
via (S)-8 in 16 steps or 4.8% based on hexane-1,6-diol
(15) in 14 steps.
25
Jones chromic acid furnished pure (S)-1, ½ꢁꢁD ꢂ0:39
(S)-8 was alkylated with (S)-14 for the synthesis of
(6S,14S)-3. Product (3S,11S)-37 was converted to
(6S,14S)-3 in the same manner as that just described
for (S)-2 via (3S,11S)-38, 39, 40, 41, 42, 43, 44, and
(c 1.15, hexane). Its IR, 1H- and 13C-NMR, and MS data
were identical with those previously reported.5) The
overall yield of (S)-1 based on (S)-citronellal was 8.4%
in 15 steps. (R)-14 was similarly converted to (R)-1,
24
(2RS,6S,14S)-46. Final product (6S,14S)-3, ½ꢁꢁD þ0:59
½ꢁꢁD þ0:39 (c 1.13, hexane). The overall yield of (R)-1
(c 1.01, hexane), showed IR, 1H- and 13C-NMR, and MS
data identical with those previously reported.5) The
overall yield of (6S,14S)-3 based on (S)-citronellal was
7.0% via (S)-8 in 16 steps or 3.3% via (S)-14 in 18 steps.
25
was 10% based on (R)-citronellal in 15 steps.
Scheme 5 summarizes the synthesis of the stereo-
isomers of 14-methyl-2-octadecanone (2) and 6,14-
dimethyl-2-octadecanone (3). Alkylation of (S)-8 with
18 yielded (S)-27 which was epoxidized with MCPBA
to give (11S,14RS)-28. Epoxide cleavage of (11S,14RS)-
28 with periodic acid dihydrate furnished aldehyde (R)-
29 which was treated with methylenetriphenylphospho-
rane to give (S)-30. Hydrogenation of (S)-30 over
palladium-charcoal in acetic acid effected both satura-
tion of the double and triple bonds as well as hydro-
genolytic removal of the benzyl protective group to give
alcohol (S)-31 in a 69% yield. A small amount of the
acetate of (S)-31 was also isolated which, after alkaline
hydrolysis, gave an additional amount of (S)-31 [15%
based on (S)-30]. Corresponding tosylate (S)-32 was
treated with sodium iodide, yielding (S)-33.
25
(6R,14R)-3, ½ꢁꢁD ꢂ0:42 (c 1.03, hexane), was sim-
ilarly prepared from (R)-8 and (R)-14; (6S,14R)-3,
25
½ꢁꢁD ꢂ1:39 (c 1.09, hexane) was prepared from (R)-
23
8 and (S)-14; and (6R,14S)-3, ½ꢁꢁD þ1:48 (c 1.01,
hexane), was synthesized from (S)-8 and (R)-14.
Conclusion
All of the eight possible stereoisomers of 1, 2 and 3,
the components of the female sex pheromone of the
Lyclene dharma dharma moth, were synthesized from
the enantiomers of citronellal by using classical reac-
tions. In retrospect, Mori’s 2009 synthesis based on
olefin cross metathesis was less time-consuming.5)

1946
Y. SHIKICHI and K. MORI
R
b
d
a
R
I
+
OBn
OBn
(S)-8
18 R = H
(S)-14 R = Me
(S)-27 R = H
(3S,11S)-37 R = Me
c
R
R
OHC
O
OBn
OBn
(11S,14RS)-28 R = H
(R)-29 R = H
(3S,11S, 14RS)-38 R = Me
(4R,12S)-39 R = Me
R
e
g
R
Me(CH2)3
f
(CH2)7
OR'
OBn
(S)-30 R = H
(3S,11S)-40 R = Me
(S)-31 R = H, R' = H
(S)-32 R = H, R' = Ts
(3S,11S)-41 R = Me, R' = H
(3S,11S)-42 R = Me, R' = Ts
f
R
O
R
h
Me(CH2)3
(CH2)7
Me(CH2)3
(CH2)7
I
CO2Et
(S)-33 R = H
(3S,11S)-43 R = Me
(3RS,14S)-34 R = H
(3RS,6S,14S)-44 R = Me
R
(S)-2 or
i
impurity
O
+
+
CO2Et
Me(CH2)3
(CH2)7
O
(6S,14S)-3
(S)-35 R = H
(3S,11S)-45 R = Me
Me(CH2)3
(CH2)11
(S)-2
R
OH
j
k
Me(CH2)3
(CH2)7
O
(2RS,14S)-36 R = H
(2RS,6S,14S)-46 R = Me
Me(CH2)3
(CH2)7
(6S,14S)-3
Similarly:
O
(CH2)11
(R)-2
Me(CH2)3
(R)-8
O
(R)-8
+
+
(R)-14
(S)-14
Me(CH2)3
Me(CH2)3
(CH2)7
(6R,14R)-3
O
O
(R)-8
(S)-8
(CH2)7
(6S,14R)-3
+
(R)-14
Me(CH2)3
(CH2)7
(6R,14S)-3
Scheme 5. Synthesis of 2 and 3.
Reagents: (a) n-BuLi, THF, HMPA [86% for (S)-27; 77% for (3S,11S)-37]; (b) MCPBA, CH2Cl2ꢂ[quant. for (11S,14RS)-28; 99% for
þ
.
(3S,11S,14RS)-38]; (c) HIO4 2H2O, THF, Et2O [65% for (R)-29; 76% for (4R,12S)-39]; (d) Ph3P MeBr , n-BuLi, THF [83% for (S)-30; 91%
(3S,11S)-40]; (e) H2/Pd–C, AcOH; then NaOH, MeOH, H2O [84% for (S)-31; 82% for (3S,11S)-41]; (f) TsCl, C5H5N [87% for (S)-32; 88% for
(3S,11S)-42]; (g) NaI, DMF [84% for (S)-33; 85% for (3S,11S)-43]; (h) MeCOCH2CO2Et, K2CO3, DMF; (i) NaOH, MeOH, H2O [84% for (S)-2;
92% for (6S,14S)-3, 2 steps]; (j) LiAlH4, THF; then SiO2 chromatography [82% for (2RS,14S)-36; 68% for (2RS,6S,14S)-46]; (k) Jones CrO3,
acetone [84% for (S)-2; 57% for (6S,14S)-3].
ogies 5975 Inert XL instrument, and HRMS data were recorded on an
Agilent Technologies 6530 Accurate Mass Q-TOF LC/MS instrument.
A bioassay of these stereoisomers of 1, 2 and 3 has
been carried out by Ando and his co-workers,9) the
results showing that (S)-1 and (S)-2 were bioactive. The
absolute configuration and the biological role of natural
3 have remained unknown.9)
Column chromatography was carried out on Merck Kieselgel 60 Art.
1.07734.
All HRMS data was measured under the following conditions:
APCI ionization; positive polarity; 6 mA corona current; N2 (50 psi)
nebulizer; N2 (5 L/min, 350 ꢃC) drying gas; 350 ꢃC vaporizer; 3000 V
capillary current; 0.01 M HCO2H aq./MeOH (10/90) eluent.
Experimental
Refractive indices (nD) were measured with an Atago DR-M2
refractometer, and optical rotation values were measured with a Jasco
P-1020 polarimeter. IR spectra were measured with a Jasco FT/IR-410
spectrometer, and 1H-NMR spectra (400 MHz, TMS at ꢀ ¼ 0:00 as the
internal standard) and 13C-NMR spectra (100 MHz, CDCl3 at ꢀ ¼ 77:0
as the internal standard) were recorded by a Jeol JNM-AL 400
spectrometer. GC-MS data were measured with an Agilent Technol-
(3S,6RS)-1-Benzyloxy-6,7-epoxy-3,7-dimethyloctane [(3S,6RS)-10].
In the usual manner, (S)-910) {5.01 g, 20.3 mmol, prepared in the same
19
manner as that described in ref. 8, ½ꢁꢁD ꢂ3:49 (c 4.18, hexane)} in
CH2Cl2 (50 mL) was treated with MCPBA (69% purity, 5.58 g,
22.3 mmol) to give 5.60 g (quant.) of crude (3S,6RS)-10 as an oil; IR
ꢂ
max (film) cmꢂ1: 1250 (m), 1203 (w, C–O–C), 1101 (s, C–O), 872 (w),
737 (s), 698 (s); 1H-NMR ꢀH (CDCl3): 0.90 (3H, d, J ¼ 6:4 Hz, CH3),

Synthesis of the Sex Pheromone of Lyclene dharma dharma
1947
1.20–1.60 (5H, m), 1.25 (3H, s, CH3), 1.30 (3H, s, CH3), 1.60–1.72
(2H, m), 2.68 (1H, t, J ¼ 6:4 Hz), 3.46–3.56 (2H, m, CH2OBn), 4.50
(2H, s, C6H5CH2), 7.26–7.34 (5H, m, C6H5). This compound was
employed for the next step without further purification.
6-Benzyloxyhexyl iodide (18). In the same manner as that described
for (S)-14, 17 (19.7 g, 54.3 mmol) gave 14.8 g (86%) of 18 as an oil,
23
nD 1.5434; IR ꢂmax (film) cmꢂ1: 1205 (m, C–O–C), 1169 (w) 1103
(s, C–O), 735 (s), 696 (s), 600 (w); 1H-NMR ꢀH (CDCl3): 1.35–1.46
(4H, m), 1.68–1.76 (2H, m), 1.79–1.86 (2H, m), 3.18 (2H, t,
J ¼ 7:2 Hz, CH2I), 3.47 (2H, t, J ¼ 6:6 Hz, CH2OBn), 4.50 (2H, s,
C6H5CH2), 7.26–7.35 (5H, m, C6H5); HRMS of 18: calcd. for
(S)-6-Benzyloxy-4-methylhexanal [(S)-11]. A solution of crude
(3S,6RS)-10 (5.60 g, <20:3 mmol) in Et2O (30 mL) was added to a
C
13H20IO [ðM þ HÞþ], 319.0553; found, 319.0547.
.
stirred and ice-cooled solution of HIO4 2H2O (7.02 g, 30.8 mmol) in
THF (30 mL) at 0–10 ꢃC. The mixture was stirred for 1 h at room
temperature, before being diluted with water and extracted with Et2O.
The Et2O solution was successively washed with water, dil. Na2S2O3,
water, an NaHCO3 solution, and brine, dried (MgSO4), and concen-
trated in vacuo. The residue (4.88 g) was chromatographed over SiO2
(100 g). Elution with hexane/EtOAc (9:1) gave 3.29 g (73%) of (S)-11
1-Benzyloxy-3-methyl-7-pentadecyne (20).
(i) (S)-isomer. In the same manner as that previously described,11)
(S)-14 (4.00 g, 12.0 mmol) and 19 (2.75 g, 22.1 mmol) gave 3.46 g
20
24
(87%) of (S)-20 as an oil, nD 1.4889; ½ꢁꢁD ꢂ6:05 (c 4.05, hexane);
IR ꢂmax (film) cmꢂ1: 1203 (w, C–O–C), 1101 (s, C–O), 735 (s), 696 (s);
1H-NMR ꢀH (CDCl3): 0.82–1.02 (6H, m), 1.16–1.77 (17H, m), 2.06–
2.28 (4H, br, CꢀCCH2 ꢄ 2), 3.46–3.62 (2H, m, CH2OBn), 4.50 (2H,
s, C6H5CH2), 7.24–7.50 (5H, m, C6H5); HRMS of (S)-20: calcd. for
C23H37O [ðM þ HÞþ], 329.2839; found, 329.2843.
25
25
as a colorless oil, nD 1.5156; ½ꢁꢁD ꢂ2:60 (c 4.11, hexane); IR ꢂmax
(film) cmꢂ1: 1724 (s, C=O), 1203 (w, C–O–C), 1111 (s, C–O), 737 (s),
698 (s); 1H-NMR ꢀH (CDCl3): 0.90 (3H, d, J ¼ 6:4 Hz, CH3), 1.40–
1.55 (2H, br), 1.58–1.77 (3H, br), 2.38–2.53 (2H, br), 3.46–3.56 (2H,
m, CH2OBn), 4.50 (2H, s, C6H5CH2), 7.26–7.34 (5H, m, C6H5), 9.76
(1H, CHO); HRMS of (S)-11: calcd. for C14H21O2 [ðM þ HÞþ],
221.1536; found, 221.1542.
(ii)
(R)-isomer. Similarly, (R)-14 (3.00 g, 9.03 mmol) and 19
18
(2.13 g, 17.1 mmol) gave (R)-20 (2.88 g, 97%) as an oil, nD 1.4935;
20
½ꢁꢁD þ5:80 (c 0.159, hexane). Its IR and 1H-NMR spectra were
identical with those of (S)-20; HRMS of (R)-20: calcd. for C23H37
[ðM þ HÞþ], 329.2839; found, 329.2839.
O
(S)-6-Benzyloxy-4-methyl-1-hexanol [(S)-12]. Reduction of (S)-11
(3.29 g, 14.8 mmol) with LiAlH4 (360 mg, 9.49 mmol) in dry Et2O
(48 mL) gave 3.3 g of crude (S)-12. This was combined with 11.5 g of
crude (S)-12 which had been prepared by extra runs, and the mixture
chromatographed over SiO2 (200 g). Elution with hexane/EtOAc
3-Methyl-1-pentadecanol (21).
(i) (S)-isomer. In the usual manner, (S)-20 (3.96 g, 12.1 mmol) in
AcOH (35 mL) treated with palladium on charcoal (10%, 880 mg)
21
23
23
24
under H2 gave 2.59 g (89%) of (S)-21 as an oil, nD 1.4510; ½ꢁꢁD
(10:1–3:1) gave 13.5 g (83%) of (S)-13 as an oil, nD 1.5013; ½ꢁꢁD
ꢂ3:48 (c 3.94, hexane); IR ꢂmax (film) cmꢂ1: 3330 (s, O–H), 1059
(s, C–O); 1H-NMR ꢀH (CDCl3): 0.85–0.94 (6H, m), 1.09–1.45
(23H, m), 1.50–1.65 (3H, m), 3.62–3.74 (2H, m, CH2OH). HRMS
data for (S)-21 could not be directly measured, so it was measured after
silylation with N-methyl-N-trimethylsilyltrifluoroacetamide. HRMS of
silylated (S)-21: calcd. for C19H43OSi [ðM þ HÞþ], 315.3078; found,
315.3076.
ꢂ2:24 (c 4.03, hexane); IR ꢂmax (film) cmꢂ1: 3383 (s, OH), 1205 (w,
C–O–C), 1097 (s, C–O), 1057 (m, C–O), 737 (s), 698 (s); 1H-NMR ꢀH
(CDCl3): 0.90 (3H, d, J ¼ 6:4 Hz, CH3), 1.12–1.70 (8H, m), 3.45–3.55
(2H, m, CH2OBn), 3.61 (2H, t, J ¼ 6:4 Hz, CH2OH), 4.50 (2H, s,
C6H5CH2), 7.26–7.34 (5H, m, C6H5); HRMS of (S)-12: calcd. for
C14H23O2 [ðM þ HÞþ], 223.1693; found, 223.1692.
(ii) (R)-isomer. Similarly, (R)-20 (2.88 g, 8.77 mmol) gave 1.41 g
(S)-6-Benzyloxy-4-methylhexyl tosylate [(S)-13]. In the same
manner as that described previously,11) (S)-12 (6.88 g, 30.9 mmol)
gave 10.6 g (91%) of (S)-13 as an oil; IR ꢂmax (film) cmꢂ1: 1599 (m,
arom. C=C), 1358 (s, SO2), 1176 (s, SO2), 1097 (s), 964 (s), 916 (s),
816 (s),737 (s), 698 (m), 663 (s), 553 (s); 1H-NMR ꢀH (CDCl3): 0.83
(3H, d, J ¼ 6:4 Hz, CH3), 1.08–1.17 (1H, m), 1.26–1.42 (2H, m), 1.50–
1.74 (4H, m), 2.44 (3H, s, C6H4CH3), 3.41–3.50 (2H, m, CH2OBn),
4.00 (2H, t, J ¼ 6:6 Hz, CH2OTs), 4.48 (2H, s, C6H5CH2), 7.26–7.36
(7H, m), 7.78 (2H, d, J ¼ 8:0). This compound was used in the next
step without further purification.
15
25
(66%) of (R)-21 as a colorless oil, nD 1.4515; ½ꢁꢁD þ3:51 (c 4.23,
hexane). Its IR and 1H-NMR spectra were identical with those reported
for (S)-21. HRMS of silylated (R)-21: calcd. for C19H43OSi
[ðM þ HÞþ], 315.3078; found, 315.3078.
3-Methylpentadecyl tosylate (22).
(i) (S)-isomer. In the same manner as that described for (S)-13,
23
(S)-21 (2.59 g, 10.7 mmol) gave 4.00 g (94%) of (S)-22 as an oil, ½ꢁꢁD
ꢂ2:42 (c 4.06, hexane); IR ꢂmax (film) cmꢂ1: 1599 (m, arom. C=C),
1365 (s, SO2), 1178 (s, SO2), 1097 (m), 945 (s), 889 (m), 814 (m), 663
(s), 553 (s); 1H-NMR ꢀH (CDCl3): 0.80 (3H, d, J ¼ 6:4 Hz, CH3), 0.88
(3H, t, J ¼ 6:8 Hz, CH3), 0.99–1.57 (24H, m), 1.60–1.72 (1H, m), 2.45
(3H, s, C6H4CH3), 4.00–4.10 (2H, m, CH2OTs), 7.34 (2H, d,
J ¼ 8:0 Hz, arom. H), 7.79 (2H, d, J ¼ 8:0 Hz, arom. H).
(S)-6-Benzyloxy-4-methylhexyl iodide [(S)-14]. In the same manner
as that described previously,11) (S)-13 (10.2 g, 27.1 mmol) gave 6.71 g
25
23
(75%) of (S)-14 as a colorless oil, nD 1.5373; ½ꢁꢁD ꢂ7:28 (c 4.29,
hexane); IR ꢂmax (film) cmꢂ1: 1211 (w, C–O–C), 1174 (w) 1099 (s, C–
O), 735 (s), 698 (s), 600 (w); 1H-NMR ꢀH (CDCl3): 0.89 (3H, d,
J ¼ 6:4 Hz, CH3), 1.18–1.28 (1H, m), 1.36–1.48 (2H, m), 1.59–1.69
(2H, m), 1.73–1.92 (2H, m), 3.11–3.20 (2H, m, CH2I), 3.46–3.55 (2H,
m, CH2OBn), 4.50 (2H, s, C6H5CH2), 7.26–7.35 (5H, m, C6H5);
HRMS of (S)-14: calcd. for C14H22IO [ðM þ HÞþ], 333.0710; found,
333.0710.
(ii) (R)-isomer. Similarly, (R)-21 (1.38 g, 5.69 mmol) gave 2.03 g
26
(90%) of (R)-22 as an oil, ½ꢁꢁD þ2:40 (c 4.14, hexane). Its IR and
1H-NMR spectra were identical with those of (S)-22.
3-Methylpentadecyl iodide (23).
(i) (S)-isomer. In the same manner as that described for (S)-14,
crude (S)-22 (4.00 g, 10.1 mmol) gave 3.27 g (92%) of (S)-23 as a
18
25
colorless oil, nD 1.4828; ½ꢁꢁD þ6:11 (c 4.07, hexane); IR ꢂmax
(film) cmꢂ1: 1178 (w), 606 (w); 1H-NMR ꢀH (CDCl3): 0.84–0.91 (6H,
m), 1.08–1.35 (22H, br), 1.48–1.57 (1H, br), 1.60–1.69 (1H, m), 1.83–
1.92 (1H, m), 3.14–3.28 (2H, m, CH2I).
(R)-6-Benzyloxy-4-methylhexyl iodide [(R)-14]. Similarly, (R)-4
22
24
was converted to (R)-14 [45%, 6 steps from (R)-4]; nD 1.5219; ½ꢁꢁD
þ6:39 (c 3.58, hexane); its IR and 1H-NMR spectra were identical with
those of (S)-14; HRMS of (R)-14: calcd. for C14H22IO [ðM þ HÞþ],
333.0710; found, 333.0710.
(ii) (R)-isomer. Similarly, crude (R)-22 (2.00 g, 5.04 mmol) gave
18
26
1.46 g (82%) of (R)-23 as a colorless oil, nD 1.4833; ½ꢁꢁD ꢂ6:16
(c 4.05, hexane). Its IR and 1H-NMR spectra were identical with those
of (S)-23.
6-Benzyloxyhexyl tosylate (17). In the same manner as that
described for (S)-13, 1612) (12.7 g, 61.0 mmol, which had been
prepared in the same manner as that described in ref. 8 gave 20.3 g
(92%) of 17 as a colorless oil; IR ꢂmax (film) cmꢂ1: 1599 (m, arom.
C=C), 1360 (s, SO2), 1176 (s, SO2), 1097 (s), 960 (m), 928 (m), 816
(m), 739 (m), 698 (m), 663 (s), 555 (s); 1H-NMR ꢀH (CDCl3): 1.28–
1.37 (4H, br), 1.51–1.70 (4H, br), 2.44 (3H, s, C6H4CH3), 3.43 (2H, t,
J ¼ 6:6 Hz, CH2OBn), 4.02 (2H, t, J ¼ 6:4 Hz, CH2OTs), 4.48 (2H, s,
C6H5CH2), 7.26–7.40 (7H, m), 7.78 (2H, d, J ¼ 8:0 Hz).
6-Methyl-2-octadecanone (1) as a crude mixture contaminated
with 25.
(i) (S)-isomer. Powdered K2CO3 (4.10 g, 29.7 mmol) was added
portionwise to a solution of (S)-23 (1.20 g, 3.41 mmol) and ethyl
acetoacetate (2.00 g, 15.4 mmol) in DMF (50 mL). The mixture was
vigorously stirred at room temperature for 3 h, before being diluted
with water and extracted with hexane and Et2O. The organic layer was

1948
Y. SHIKICHI and K. MORI
successively washed with water and brine, dried (MgSO4), and
concentrated in vacuo to give 1.40 g (quant.) of crude (3RS,6S)-24 as
an oil. This oil was dissolved in MeOH (10 mL), and 15% NaOH aq
(10 g) was added to the solution. The mixture was stirred at reflux for
2 h and, after cooling, it was diluted with water and extracted with
hexane. The hexane solution was successively washed with water and
brine, dried (MgSO4), and concentrated in vacuo. The residue (1.17 g)
was chromatographed over SiO2 (20 g). Elution with hexane/EtOAc
loxane, 30 m ꢄ 0:25 mm i.d.; 60.7 kPa pressure; 70–230 ꢃC temper-
ature (þ10 ꢃC/min); He carrier gas] tR: 17.2 min (3%), 18.3 min [96%,
(S)-1], 18.9 min (1%). MS of (S)-1 (70 eV, EI) m=z: 282 (4) [Mþ,
C
19H38O], 264 (66), 239 (16), 123 (15), 110 (30), 109 (34), 95 (29), 85
O
(42), 71 (56), 58 (100), 43 (85). HRMS of (S)-1: calcd. for C19H39
[ðM þ HÞþ], 283.2995; found, 283.2994.
(ii) (R)-isomer. Similarly, (2RS,6R)-26 (600 mg, 2.11 mmol) gave
22
440 mg (74%) of (R)-1 as an oil which solidified in a refrigerator, nD
25
26
(20:1) gave 780 mg (81%,
2
steps) of crude (S)-1 as an oil
1.4462; ½ꢁꢁD þ0:39 (c 1.13, hexane) {ref. 5, ½ꢁꢁD þ0:35 (c 4.08,
hexane)}; GC-MS [same conditions as those for (S)-1] tR: 18.3 min
[98%, (R)-1], 18.9 min (2%). Its spectral data (IR, 1H- and 13C-NMR,
and MS) were identical with those of (S)-1. HRMS of (R)-1: calcd. for
contaminated with 16% of (S)-25 which had been generated by O-
alkylation of ethyl acetoacetate with (S)-23. Ester (S)-25 could not be
separated from (S)-1 by chromatographic purification.
(3RS,6S)-24. IR ꢂmax (film) cmꢂ1: 1743 (s, C=O), 1718 (s, C=O),
1624 (m), 1240 (m), 1144 (m, C–O), 1053 (m, C–O); 1H-NMR ꢀH
(CDCl3): 0.84–0.92 (6H, m), 1.02–1.45 (28H, m), 1.74–1.94 (2H, m),
2.22 (3H, s, CH3C=O), 3.35 (1H, t, J ¼ 7:4 Hz, CHC=O), 4.16–4.24
(2H, m, CH3CH2O).
C
19H39O [ðM þ HÞþ], 283.2995; found, 283.2995.
1-Benzyloxy-11,15-dimethyl-14-hexadecen-7-yne(27).
(i) (S)-isomer. In the same manner as that described for (S)-20,
(S)-8 (4.17 g, 25.4 mmol) and 18 (6.20 g, 19.5 mmol) gave 5.96 g (86%)
18
26
(ii) (R)-isomer. Similarly, (R)-23 (1.42 g, 4.03 mmol) gave
960 mg (84%, 2 steps) of crude (R)-1 contaminated with 18% of
of (S)-27 as an oil, nD 1.4984; ½ꢁꢁD ꢂ4:69 (c 3.43, hexane); IR ꢂmax
(film) cmꢂ1: 2117 (w, CꢀC), 1672 (w, C=C), 1203 (w, C–O–C), 1103
(m, C–O), 827 (w), 735 (m), 696 (m); 1H-NMR ꢀH (CDCl3): 0.87 (3H,
d, J ¼ 6:8 Hz, CH3), 1.08–1.18 (1H, m), 1.23–1.76 (12H, m), 1.60 (3H,
s, CH3), 1.68 (3H, s, CH3), 1.91–2.05 (2H, m), 2.05–2.24 (4H, m,
CꢀCCH2 ꢄ 2), 3.47 (2H, t, J ¼ 6:6 Hz, CH2OBn), 4.50 (2H, s,
C6H5CH2), 5.07–5.12 (1H, m, C=CH), 7.26–7.34 (5H, m, C6H5).
HRMS of (S)-27: calcd. for C25H39O [ðM þ HÞþ], 355.2995; found,
355.2996.
(R)-25.
(3RS,6R)-24. Its IR and 1H-NMR spectra were identical with those
of (3RS,6S)-24.
6-Methyl-2-octadecanol (26).
(i) (2RS,6S)-isomer. Crude (S)-1 contaminated with 16% of (S)-
25 (550 mg, <1:95 mmol) was dissolved in dry THF (2 mL), and added
dropwise to a stirred and ice-cooled suspension of LiAlH4 (46 mg,
1.2 mmol) in dry THF (8 mL) at 5–10 ꢃC. The mixture was stirred for
1 h at 5–10 ꢃC, and excess LiAlH4 was destroyed by dropwise addition
of water to the stirred and ice-cooled mixture. It was then poured into
ice-cooled dil. HCl and extracted with Et2O. The Et2O solution was
successively washed with water, an NaHCO3 solution, and brine, dried
(MgSO4), and concentrated in vacuo. The residue (516 mg) was
chromatographed over SiO2 (50 g). Elution with hexane/EtOAc (9:1)
gave 68 mg of (S)-25 which could not be reduced under these
conditions. Further elution with hexane/EtOAc (5:1) afforded 359 mg
(65%) of (2RS,6S)-26 as an oil.
(S)-25. IR ꢂmax (film) cmꢂ1: 1712 (s, C=O), 1626 (s, C=C), 1344
(m), 1275 (s, C–O–C), 1140 (s, C–O), 1055 (s, C–O), 820 (m, C=CH);
1H-NMR ꢀH (CDCl3): 0.84–0.92 (6H, m), 1.11–1.35 (24H, br), 1.47–
1.59 (3H, m), 1.68–1.78 (1H, m), 2.29 (3H, s, CH3C=C), 3.73–3.82
(2H, m, CH2O), 4.13 (2H, q, J ¼ 7:2 Hz, CH3CH2O), 5.01 (1H, s,
C=CH); HRMS of (S)-25: calcd. for C22H43O3 [ðM þ HÞþ], 355.3207;
found, 355.3209.
(ii)
(7.00 g, 22.0 mmol) gave 6.76 g (87%) of (R)-27 as an oil, nD 1.4991;
(R)-isomer. Similarly, (R)-8 (4.70 g, 28.6 mmol) and 18
18
25
½ꢁꢁD þ3:89 (c 4.13, hexane). Its IR and 1H-NMR data were identical
with those of (S)-27. HRMS of (R)-27: calcd. for C25H39O [ðM þ HÞþ],
355.2995; found, 355.2995.
1-Benzyloxy-14,15-epoxy-11,15-dimethyl-7-hexadecyne (28).
(i) (11S,14RS)-isomer. In the same manner as that described for
(3S,6RS)-10, (S)-27 (5.84 g, 16.5 mmol) gave 6.24 g (quant.) of crude
(11S,14RS)-28 as an oil; IR ꢂmax (film) cmꢂ1: 2117 (w, CꢀC), 1250
(w), 1205 (w, C–O–C), 1115 (m, C–O), 870 (w), 737 (m), 698 (m);
1H-NMR ꢀH (CDCl3): 0.89 (3H, d, J ¼ 6:4 Hz, CH3), 1.10–1.72 (15H,
m), 1.27 (3H, s, CH3), 1.31 (3H, s, CH3), 2.05–2.25 (4H, m,
CꢀCCH2 ꢄ 2), 2.69 (1H, t, J ¼ 6:0 Hz), 3.47 (2H, t, J ¼ 6:6 Hz,
CH2OBn), 4.50 (2H, s, C6H5CH2), 7.26–7.40 (5H, m, C6H5).
(ii)
(11R,14RS)-isomer. Similarly, (R)-27 (6.70 g, 18.9 mmol)
gave 6.86 g (98%) of crude (11R,14RS)-28 as an oil. Its IR and 1H-
NMR spectra were identical with those of (11S,14RS)-28.
(2RS,6S)-26. nD18 1.4528; IR ꢂmax (film) cmꢂ1: 3338 (s, O–H), 1119
(m, C–O), 1077 (w); 1H-NMR ꢀH (CDCl3): 0.85 (3H, d, J ¼ 6:8 Hz,
CH3), 0.88 (3H, t, J ¼ 6:8 Hz, CH3), 1.06–1.50 (30H, br), 1.19 (3H, d,
J ¼ 6:0 Hz, CH3), 3.75–3.85 (1H, br, CHOH).
14-Benzyloxy-4-methyl-7-tetradecynal (29).
(i) (R)-isomer. In the same manner as that described for (S)-11,
crude (11S,14RS)-28 (6.11 g, 16.5 mmol) gave 3.52 g (65%) of (R)-29
17
23
(ii) (2RS,6R)-isomer. Similarly, crude (R)-1 (960 mg) contami-
nated with 18% of (R)-25 gave 780 mg (80%) of (2RS,6R)-26.
as an oil, nD 1.5110; ½ꢁꢁD ꢂ2:53 (c 3.92, hexane); IR ꢂmax (film)
cmꢂ1: 2117 (w, CꢀC), 1726 (s, C=O), 1203 (w, C–O–C), 1101 (s, C–
O), 737 (m), 698 (m); 1H-NMR ꢀH (CDCl3): 0.89 (3H, d, J ¼ 6:4 Hz,
CH3), 1.20–1.80 (13H, m), 2.08–2.30 (4H, m, CꢀCCH2 ꢄ 2), 2.34–
2.50 (2H, m), 3.47 (2H, t, J ¼ 6:6 Hz, CH2OBn), 4.50 (2H, s,
C6H5CH2), 7.26–7.45 (5H, m, C6H5), 9.77 (1H, t-like, CHO). HRMS
18
(2RS,6R)-26. nD 1.4522. Its IR and 1H-NMR spectra were
identical with those of (2RS,6S)-26.
6-Methyl-2-octadecanone (1).
(i)
of (R)-29: calcd. for
329.2474.
C
22H33O2 [ðM þ HÞþ], 329.2475; found,
(S)-isomer. Jones chromic acid reagent (8 N, 0.5 mL) was
added to a stirred and ice-cooled solution of (2RS,6S)-26 (359 mg,
1.26 mmol) in acetone (18 mL). The addition was continued until the
green mixture had turned orange in color. After stirring for 20 min at
5–10 ꢃC, 2-propanol was added to the ice-cooled mixture until the
excess chromic acid had been destroyed. It was then diluted with water
and extracted with Et2O. The Et2O solution was successively washed
with water, an NaHCO3 solution, and brine, dried (MgSO4), and
concentrated in vacuo. The residue (378 mg) was chromatographed
over SiO2 (30 g), and elution with hexane/EtOAc (20:1) gave 291 mg
(ii)
18.4 mmol) gave 4.42 g (73%) of (S)-29 as an oil, nD 1.5122;
(S)-isomer. Similarly, crude (11R,14RS)-28 (6.80 g,
17
25
½ꢁꢁD þ2:42 (c 4.14, hexane). Its IR and 1H-NMR spectra were
identical with those of (R)-29. HRMS of (S)-29: calcd. for C22H33O2
[ðM þ HÞþ], 329.2475; found, 329.2479.
1-Benzyloxy-11-methyl-14-pentadecen-7-yne (30).
(i) (S)-isomer. A solution of n-butyllithium in hexane (1.6 M,
12 mL, 19 mmol) was added dropwise to a stirred and cooled
23
(82%) of (S)-1 as an oil. This oil solidified in a refrigerator, nD
25
28
1.4455; ½ꢁꢁD ꢂ0:39 (c 1.15, hexane) {ref. 5, ½ꢁꢁD ꢂ0:38 (c 3.63,
hexane)}; IR ꢂmax (film) cmꢂ1: 2925 (s), 2854 (s), 1720 (s, C=O), 1464
(m), 1360 (m), 1165 (m), 721 (m); 1H-NMR ꢀH (CDCl3): 0.85 (3H, d,
J ¼ 6:8 Hz, CH3), 0.88 (3H, t, J ¼ 6:8 Hz, CH3), 1.04–1.15 (2H, br),
1.18–1.45 (23H, br), 1.48–1.67 (2H, br), 2.13 (3H, s, CH3C=O), 2.40
(2H, t, J ¼ 7:4 Hz, CH2C=O); 13C-NMR ꢀC (CDCl3): 14.1, 19.5, 21.4,
22.7, 27.0, 29.3, 29.60, 29.67, 29.69, 29.8, 30.0, 31.9, 32.6, 36.5, 36.9,
44.1, 209.1 (C=O); GC-MS [HP-5MS column, 5% phenylmethylsi-
suspension of methyltriphenylphosphonium bromide (7.85 g,
22.0 mmol) in dry THF (70 mL) at between ꢂ50 and ꢂ40 ꢃC under
Ar. The temperature was gradually raised to room temperature. After
stirring for 4.5 h, the mixture was cooled to ꢂ65 ꢃC. A solution of (R)-
29 (3.47 g, 10.6 mmol) in dry THF (15 mL) was added dropwise to the
stirred and cooled solution at ꢂ65 ꢃC, and the mixture was gradually
warmed to room temperature. It was stirred overnight, poured into an
ice-cooled NH4Cl solution and then extracted with hexane. The hexane

Synthesis of the Sex Pheromone of Lyclene dharma dharma
1949
14-Methyl-2-octadecanone (2) as a crude mixture contaminated
with 35.
solution was successively washed with an MeOH/H2O mixture (3:2),
water and brine, dried (MgSO4), and concentrated in vacuo. The
residue (4.03 g) was chromatographed over SiO2 (70 g). Elution with
(i) (S)-isomer. In the same manner as that described for crude
(S)-1, (S)-33 (680 mg, 1.93 mmol) and ethyl acetoacetate (1.14 g,
8.76 mmol) gave 740 mg (quant.) of crude (3RS,14S)-34 as an oil
which contained 15% of (S)-35. This was treated with 15% NaOH to
give 460 mg (84%, 2 steps) of crude (S)-2 contaminated with 15% of
(S)-35.
(3RS,14S)-34. IR ꢂmax (film) cmꢂ1: 1743 (s, C=O), 1718 (s, C=O),
1626 (m), 1240 (m), 1147 (m, C–O), 1043 (m, C–O); 1H-NMR ꢀH
(CDCl3): 0.84 (3H, d, J ¼ 6:4 Hz, CH3), 0.89 (3H, t, J ¼ 6:8 Hz, CH3),
1.01–1.42 (28H, br), 1.75–1.92 (2H, m), 2.22 (3H, s, CH3C=O), 3.39
(1H, t, J ¼ 7:4 Hz, CHC=O), 4.16–4.24 (2H, m, CH3CH2O).
(ii) (R)-isomer. Similarly, (R)-33 (1.77 g, 5.02 mmol) and ethyl
acetoacetate (3.0 g, 22.7 mmol) gave 1.23 g (87%, 2 steps) of crude
(R)-2 contaminated with 18% of (R)-35. The IR and 1H-NMR spectra
of (3RS,14R)-34 were identical with those for (3RS,14S)-34.
16
hexane/EtOAc (15:1) gave 2.87 g (83%) of (S)-30 as an oil, nD
26
1.5020; ½ꢁꢁD ꢂ2:69 (c 4.06, hexane); IR ꢂmax (film) cmꢂ1: 1639 (m,
C=C), 1203 (w, C–O–C), 1101 (s, C–O), 995 (w), 908 (m), 735 (m),
696 (m); 1H-NMR ꢀH (CDCl3): 0.87 (3H, d, J ¼ 6:4 Hz, CH3), 1.15–
1.67 (13H, m), 1.96–2.22 (6H, m), 3.47 (2H, t, J ¼ 6:6 Hz, CH2OBn),
4.50 (2H, s, C6H5CH2), 4.90–5.03 (2H, m, H2C=CH), 5.75–5.86 (1H,
m, H2C=CH), 7.26–7.40 (5H, m, C6H5). HRMS of (S)-30: calcd. for
C23H35O [ðM þ HÞþ], 327.2682; found, 327.2684.
(ii) (R)-isomer. Similarly, (S)-29 (3.45 g, 10.5 mmol) gave 3.05 g
22
(89%) of (R)-30 as an oil, nD15 1.5022; ½ꢁꢁD þ2:51 (c 0.108, hexane).
Its IR and 1H-NMR spectra were identical with those of (S)-30. HRMS
of (R)-30: calcd. for C23H35O [ðM þ HÞþ], 327.2682; found, 327.2686.
11-Methyl-1-pentadecanol (31).
(i) (S)-isomer. Palladium on charcoal (10%, 710 mg) was added
to a solution of (S)-30 (2.87 g, 8.79 mmol) in AcOH (29 mL). The
suspension was stirred under H2 (balloon) at room temperature. After
stirring overnight, a GC analysis of the solution showed that the
reaction had not been completed. Additional palladium on charcoal
(10%, 640 mg) was added to the mixture, and it was stirred overnight
under H2 at room temperature. The mixture was then filtered through
Celite, and the catalyst and Celite were washed with Et2O. The filtrate
and washings were diluted with Et2O and then washed with water. The
Et2O solution was successively washed with water, an NaHCO3
solution (3 times) and brine, dried (MgSO4), and concentrated
in vacuo. The residue (2.14 g) was chromatographed over SiO2
(40 g). Elution with hexane/EtOAc (3:1) gave 430 mg of acetylated
(S)-31 and 1.48 g (69%) of (S)-31. This acetate was dissolved in MeOH
(1 mL) and treated with a 20% NaOH solution (5.3 g) for 1 h at 65 ꢃC.
Subsequent workup and chromatographic purification over SiO2 [8 g,
elution with hexane/EtOAc (3:1)] gave 310 mg [15% from (S)-30] of
14-Methyl-2-octadecanol (36).
(i) (2RS,14S)-isomer. In the same manner as that described for
(2RS,6S)-26, crude (S)-2 (460 mg, <1:63 mmol) contaminated with
19
18% of (S)-35 gave 380 mg (82%) of (2RS,14S)-36 as an oil, nD
1.4525; IR ꢂmax (film) cmꢂ1: 3343 (s, O–H), 1120 (m, C–O), 1077 (w);
1H-NMR ꢀH (400 MHz, CDCl3): 0.84 (3H, d, J ¼ 6:4 Hz, CH3), 0.89
(3H, t, J ¼ 6:8 Hz, CH3), 1.02–1.52 (30H, br), 1.19 (3H, d, J ¼ 6:1 Hz,
CH3), 3.74–3.84 (1H, m).
(ii)
<4:35 mmol) contaminated with 18% of (R)-35 gave (2RS,14R)-36
(2RS,14R)-isomer. Similarly, crude (R)-2 (1.23 g,
18
(970 mg, 78%) as an oil, nD 1.4522. Its IR and 1H-NMR spectra were
identical with those of (2RS,14S)-36.
14-Methyl-2-octadecanone (2).
(i) (S)-isomer. In the same manner as that described for (S)-1,
(2RS,14S)-36 (310 mg, 1.09 mmol) gave 260 mg (84%) of (S)-2 as an
16
22
25
(S)-31 as a colorless oil. The total yield of (S)-31 was 84%, nD
25
oil which solidified in a refrigerator, nD 1.4472; ½ꢁꢁD þ1:07 (c
1.4506; ½ꢁꢁD þ1:16 (c 4.28, hexane); IR ꢂmax (film) cmꢂ1: 3330 (s,
24
1.09, hexane), {ref. 5, ½ꢁꢁD þ1:05 (c 3.13, hexane)}; IR ꢂmax (film)
O–H), 1057 (m, C–O); 1H-NMR ꢀH (CDCl3): 0.84 (3H, d, J ¼ 6:4 Hz,
CH3), 0.89 (3H, t, J ¼ 6:6 Hz, CH3), 1.02–1.40 (24H, m), 1.53–1.60
(2H, m), 3.62–3.67 (2H, m, CH2OH). HRMS of silylated (S)-31: calcd.
for C19H43OSi [ðM þ HÞþ], 315.3078; found, 315.3073.
cmꢂ1: 2925 (s), 2854 (s), 1720 (s, C=O), 1466 (m), 1358 (m), 1163
(m), 717 (w); 1H-NMR ꢀH (CDCl3): 0.84 (3H, d, J ¼ 6:8 Hz, CH3),
0.89 (3H, t, J ¼ 6:8 Hz, CH3), 1.02–1.16 (2H, br), 1.18–1.46 (23H, br),
1.52–1.62 (2H, br), 2.13 (3H, s, CH3C=O), 2.41 (2H, t, J ¼ 7:6 Hz,
CH2C=O); 13C-NMR ꢀC (CDCl3): 14.2, 19.7, 23.0, 23.9, 27.1, 29.2,
29.31, 29.38, 29.44, 29.58, 29.62, 29.7, 29.8, 30.0, 32.7, 36.7, 37.1,
43.8, 209.2 (C=O); GC-MS [same conditions as those for (S)-1] tR:
17.4 min (3%), 18.3 min [95%, (S)-2], 19.0 min (1%), 20.1 min (1%).
MS of (S)-2 (70 eV, EI): m=z: 282 (23) [Mþ, C19H38O], 264 (16), 222
(11), 127 (8), 109 (12), 96 (22), 85 (28), 71 (63), 59 (72), 58 (100), 43
(91). HRMS of (S)-2: calcd. for C19H39O [ðM þ HÞþ], 283.2995;
found, 283.2993.
(ii) (R)-isomer. Similarly, (R)-30 (3.04 g, 9.31 mmol) gave 1.99 g
16
25
(88%) of (R)-31 as a colorless oil, nD 1.4514; ½ꢁꢁD ꢂ1:15 (c 4.07,
hexane). Its IR and 1H-NMR spectra were identical with those of (S)-
31. HRMS of silylated (R)-31: calcd. for C19H43OSi [ðM þ HÞþ],
315.3078; found, 315.3085.
11-Methylpentadecyl tosylate (32).
(i) (S)-isomer. In the same manner as that described for (S)-13,
(S)-31 (1.79 g, 7.38 mmol) gave 2.55 g (87%) of (S)-32 as a colorless
(ii)
gave 630 mg (92%) of (R)-2 as an oil which solidified in a refrigerator,
(R)-isomer. Similarly, (2RS,14R)-36 (690 mg, 2.43 mmol)
24
oil which solidified in a refrigerator, ½ꢁꢁD þ0:77 (c 4.09, hexane); IR
ꢂmax (film) cmꢂ1: 1599 (m, arom. C=C), 1365 (s, SO2), 1178 (s, SO2),
1097 (m), 957 (m), 926 (m), 814 (s), 663 (s), 555 (s); 1H-NMR ꢀH
(CDCl3): 0.84 (3H, d, J ¼ 6:4 Hz, CH3), 0.89 (3H, t, J ¼ 6:6 Hz, CH3),
1.00–1.40 (23H, br), 1.58–1.68 (2H, m), 2.45 (3H, s, C6H4CH3), 4.02
(2H, t, J ¼ 6:6 Hz, CH2OTs), 7.34 (2H, d, J ¼ 8:0 Hz), 7.79 (2H, d,
J ¼ 8:0 Hz).
21
25
25
nD 1.4470; ½ꢁꢁD ꢂ1:07 (c 1.04, hexane) {ref. 5, ½ꢁꢁD ꢂ0:60
(c 3.07, hexane)}; GC-MS [same conditions as those for (S)-1] tR: 17.4
(2%), 18.3 [95%, (R)-2], 19.1 (3%). Its spectral data (IR, 1H and 13C-
NMR, and MS) were identical with those of (S)-2. HRMS of (R)-2:
calcd. for C19H39O [ðM þ HÞþ], 283.2995; found, 283.2995.
(ii) (R)-isomer. Similarly, (R)-31 (1.94 g, 8.00 mmol) gave 2.44 g
(77%) of (R)-32 as a colorless oil which solidified in a refrigerator,
1-Benzyloxy-3,11,15-trimethyl-14-hexadecen-7-yne (37).
(i) (3S,11S)-isomer. In the same manner as that described for (S)-
20, (S)-8 (2.12 g, 12.9 mmol) and (S)-14 (3.30 g, 9.93 mmol) gave
26
½ꢁꢁD ꢂ0:79 (c 4.31, hexane). Its IR and 1H-NMR spectra were
identical with those of (S)-32.
21
25
2.82 g (77%) of (3S,11S)-37 as a colorless oil, nD 1.4989; ½ꢁꢁD
ꢂ9:46 (c 3.93, hexane); IR ꢂmax (film) cmꢂ1: 2117 (w, CꢀC), 1672 (w,
C=C), 1203 (w, C–O–C), 1101 (s, C–O), 825 (w), 735 (s), 696 (s); 1H-
NMR ꢀH (CDCl3): 0.84–0.92 (6H, m), 1.04–1.88 (12H, m), 1.60 (3H, s,
CH3), 1.68 (3H, s, CH3), 1.89–2.05 (2H, m), 2.05–2.30 (4H, m,
CꢀCCH2 ꢄ 2), 3.46–3.55 (2H, m, CH2OBn), 4.50 (2H, s, C6H5CH2),
5.06–5.13 (1H, br, C=CH), 7.26–7.36 (5H, m, C6H5). HRMS of
11-Methylpentadecyl iodide (33).
(i) (S)-isomer. In the same manner as that described for (S)-14,
(S)-32 (800 mg, 2.02 mmol) gave 600 mg (84%) of (S)-33 as a colorless
19
25
oil, nD 1.4831; ½ꢁꢁD þ1:00 (c 4.01, hexane); IR ꢂmax (film) cmꢂ1
:
1180 (m), 600 (w); 1H-NMR ꢀH (CDCl3): 0.84 (3H, d, J ¼ 6:4 Hz,
CH3), 0.89 (3H, t, J ¼ 6:8 Hz, CH3), 1.01–1.45 (23H, br), 1.78–1.86
(2H, m), 3.19 (2H, t, J ¼ 7:1 Hz, CH2I).
(3S,11S)-37: calcd. for C26H41
369.3153.
O
[ðM þ HÞþ], 369.3152; found,
(ii) (R)-isomer. Similarly, (R)-32 (2.42 g, 6.10 mmol) gave 1.81 g
(ii) (3R,11R)-isomer. Similarly, (R)-8 (3.82 g, 23.3 mmol) and
(R)-14 (5.61 g, 16.9 mmol) gave 5.85 g (94%) of (3R,11R)-37 as an oil,
18
25
(84%) of (R)-33 as a colorless oil, nD 1.4831; ½ꢁꢁD ꢂ0:87 (c 4.03,
hexane). Its IR and 1H-NMR spectra were identical with those of (S)-
33.
20
25
nD 1.4989; ½ꢁꢁD þ8:27 (c 4.18, hexane). Its IR and 1H-NMR
spectra were identical with those of (3S,11S)-37. HRMS of (3R,11R)-
37: calcd. for C26H41O [ðM þ HÞþ], 369.3152; found, 369.3152.

1950
(iii) (3S,11R)-isomer. Similarly, (R)-8 (2.11 g, 12.8 mmol) and
(S)-14 (3.28 g, 9.87 mmol) gave 2.94 g (81%) of (3S,11R)-37 as an oil,
Y. SHIKICHI and K. MORI
(iii) (3S,11R)-isomer. Similarly, (4S,12S)-39 (1.64 g, 4.79 mmol)
18
24
gave 1.48 g (91%) of (3S,11R)-40 as an oil, nD 1.5009; ½ꢁꢁD ꢂ2:51
nD 1.4975; ½ꢁꢁD ꢂ1:12 (c 4.10, hexane). Its IR and 1H-NMR
(c 4.09, hexane). Its IR and 1H-NMR spectra were indistinguishable
19
25
spectra were indistinguishable from those of (3S,11S)-37. HRMS of
[ðM þ HÞþ], 369.3152; found,
from those of (3S,11S)-40. HRMS of (3S,11R)-40: calcd. for C24H37
[ðM þ HÞþ], 341.2839; found, 341.2837.
O
(3S,11R)-37: calcd. for
369.3151.
(iv) (3R,11S)-isomer. Similarly, (S)-8 (4.00 g, 24.3 mmol) and
C
26H41
O
(iv) (3R,11S)-isomer. Similarly, (4R,12R)-39 (2.19 g, 6.39 mmol)
17
25
gave 1.81 g (83%) of (3R,11S)-40 as an oil, nD 1.5002; ½ꢁꢁD þ2:39
(R)-14 (6.22 g, 18.7 mmol) gave 5.09 g (74%) of (3R,11S)-37 as an oil,
(c 4.03, hexane). Its IR and 1H-NMR spectra were identical with those
19
26
nD 1.4992; ½ꢁꢁD þ1:43 (c 4.07, hexane). Its IR and 1H-NMR
spectra were identical with those of (3S,11R)-37. HRMS of (3R,11S)-
37: calcd. for C26H41O [ðM þ HÞþ], 369.3152; found, 369.3152.
of (3S,11R)-40. HRMS of (3R,11S)-40: calcd. for C24H37
[ðM þ HÞþ], 341.2839; found, 341.2837.
O
3,11-Dimethyl-1-pentadecanol (41).
(i) (3S,11S)-isomer. In the same manner as that described for (S)-
31, (3S,11S)-40 (1.70 g, 4.99 mmol) gave 1.05 g (82%) of (3S,11S)-41
1-Benzyloxy-14,15-epoxy-3,11,15-trimethyl-7-hexadecyne (38).
(i) (3S,11S,14RS)-isomer. In the same manner as that described
for (3S,6RS)-10, (3S,11S)-37 (2.80 g, 7.60 mmol) gave 2.88 g (99%) of
(3S,11S,14RS)-38 as an oil; IR ꢂmax (film) cmꢂ1: 2116 (w, CꢀC), 1250
(w), 1205 (w, C–O–C), 1101 (s, C–O), 870 (w), 737 (m), 698 (m);
1H-NMR ꢀH (400 MHz, CDCl3): 0.87–0.90 (6H, m), 1.14–1.74 (14H,
m), 1.27 (3H, s, CH3), 1.31 (3H, s, CH3), 2.08–2.25 (4H, m,
CꢀCCH2 ꢄ 2), 2.69 (1H, t-like), 3.44–3.57 (2H, m, CH2OBn), 4.50
(2H, s, C6H5CH2), 7.26–7.40 (5H, m, C6H5).
18
22
as an oil, nD 1.4520; ½ꢁꢁD ꢂ2:39 (c 4.00, hexane); IR ꢂmax (film)
cmꢂ1: 3325 (s, O–H), 1057 (m, C–O); 1H-NMR ꢀH (CDCl3): 0.82–
0.94 (9H, m), 1.02–1.45 (23H, m), 1.50–1.67 (2H, m), 3.62–3.75 (2H,
br, CH2OH). HRMS of silylated (3S,11S)-41: calcd. for C20H45OSi
[ðM þ HÞþ], 329.3234; found, 329.3237.
(ii) (3R,11R)-isomer. Similarly, (3R,11R)-40 (2.30 g, 6.75 mmol)
17
26
gave 1.60 g (92%) of (3R,11R)-41 as an oil, nD 1.4523; ½ꢁꢁD þ2:44
(c 4.03, hexane). Its IR and 1H-NMR spectra were identical with those
of (3S,11S)-41. HRMS of silylated (3R,11R)-41: calcd. for C20H45OSi
[ðM þ HÞþ], 329.3234; found, 329.3235.
(ii)
(3R,11R,14RS)-isomer. Similarly, (3R,11R)-37 (5.78 g,
15.7 mmol) gave 4.69 g (78%) of (3R,11R,14RS)-38 as an oil. Its IR
and 1H-NMR spectra were identical with those of (3S,11S,14RS)-38.
(iii)
(3S,11R,14RS)-isomer. Similarly, (3S,11R)-37 (2.92 g,
(iii) (3S,11R)-isomer. Similarly, (3S,11R)-40 (1.44 g, 4.23 mmol)
16
24
7.92 mmol) gave 2.80 g (92%) of (3S,11R,14RS)-38 as an oil. Its IR
and 1H-NMR were indistinguishable from those of (3S,11S,14RS)-38.
gave 910 mg (84%) of (3S,11R)-41 as an oil, nD 1.4521; ½ꢁꢁD
ꢂ4:54 (c 4.01, hexane). Its IR and 1H-NMR spectra were indistin-
guishable from those of (3S,11S)-41. HRMS of silylated (3S,11R)-41:
calcd. for C20H45OSi [ðM þ HÞþ], 329.3234; found, 329.3235.
(iv) (3R,11S)-isomer. Similarly, (3R,11S)-40 (1.80 g, 5.29 mmol)
(iv)
(3R,11S,14RS)-isomer. Similarly, (3R,11S)-37 (5.00 g,
13.6 mmol) gave 4.23 g (81%) of (3R,11S,14RS)-38 as an oil. Its IR
and 1H-NMR spectra were identical with those of (3S,11R,14RS)-38.
16
25
gave 1.12 g (82%) of (3R,11S)-41 as an oil, nD 1.4523; ½ꢁꢁD þ4:64
(c 4.36, hexane). Its IR and 1H-NMR spectra were identical with those
of (3S,11R)-41. HRMS of silylated (3R,11S)-41: calcd. for C20H45OSi
[ðM þ HÞþ], 329.3234; found, 329.3237.
14-Benzyloxy-4,12-dimethyl-7-tetradecynal (39).
(i) (4R,12S)-isomer. In the same manner as that described for (S)-
11, crude (3S,11S,14RS)-38 (2.88 g, 7.49 mmol) gave 1.94 g (76%) of
19
26
(4R,12S)-39 as a colorless oil, nD 1.5096; ½ꢁꢁD ꢂ8:75 (c 3.96,
hexane); IR ꢂmax (film) cmꢂ1: 2116 (w, CꢀC), 1726 (s, C=O), 1203
(w, C–O–C), 1101 (s, C–O), 737 (s), 698 (s); 1H-NMR ꢀH (CDCl3):
0.85–0.91 (6H, m), 1.15–1.76 (12H, m), 2.06–2.26 (4H, m,
CꢀCCH2 ꢄ 2), 2.39–2.48 (2H, m), 3.45–3.55 (2H, m, CH2OBn),
4.50 (2H, s, C6H5CH2), 7.26–7.40 (5H, m, C6H5), 9.77 (1H, t-like,
CHO). HRMS of (4R,12S)-39: calcd. for C23H35O2 [ðM þ HÞþ],
343.2632; found, 343.2635.
3,11-Dimethylpentadecyl tosylate (42).
(i) (3S,11S)-isomer. In the same manner as that described for (S)-
13, (3S,11S)-41 (1.03 g, 4.02 mmol) gave 1.45 g (88%) of (3S,11S)-42
23
as an oil, ½ꢁꢁD ꢂ2:11 (c 0.132, hexane); IR ꢂmax (film) cmꢂ1: 1599
(w, arom. C=C), 1365 (s, SO2), 1178 (s, SO2), 1097 (m), 947 (s), 889
(m), 814 (m), 665 (m), 555 (m); 1H-NMR ꢀH (CDCl3): 0.80 (3H, d,
J ¼ 6:4 Hz, CH3), 0.84 (3H, d, J ¼ 6:4 Hz, CH3), 0.89 (3H, t,
J ¼ 6:8 Hz, CH3), 1.02–1.57 (23H, m), 1.61–1.70 (1H, m), 2.45 (3H,
s, C6H4CH3), 4.02–4.10 (2H, m, CH2OTs), 7.34 (2H, d, J ¼ 8:0 Hz),
7.79 (2H, d, J ¼ 8:0 Hz).
(ii)
12.1 mmol) gave 2.71 g (65%) of (4S,12R)-39 as a colorless oil, nD
(4S,12R)-isomer. Similarly, (3R,11R,14RS)-38 (4.67 g,
18
25
1.5109; ½ꢁꢁD þ8:09 (c 4.15, hexane). Its IR and 1H-NMR spectra
were identical with those of (4R,12S)-39. HRMS of (4S,12R)-39: calcd.
for C23H35O2 [ðM þ HÞþ], 343.2632; found, 343.2633.
(ii) (3R,11R)-isomer. Similarly, (3R,11R)-41 (1.57 g, 6.12 mmol)
27
gave 1.92 g (76%) of (3R,11R)-42 as an oil, ½ꢁꢁD þ1:76 (c 4.04,
(iii)
7.23 mmol) gave 1.67 g (67%) of (4S,12S)-39 as a colorless oil, nD
(4S,12S)-isomer. Similarly, (3S,11R,14RS)-38 (2.78 g,
18
hexane). Its IR and 1H-NMR spectra were identical with those of
(3S,11S)-42.
24
1.5007; ½ꢁꢁD ꢂ2:56 (c 4.00, hexane). Its IR and 1H-NMR spectra
(iii)
(3S,11R)-isomer. Similarly, (3S,11R)-41 (910 mg, 3.55
25
were indistinguishable from those of (4R,12S)-39. HRMS of (4S,12S)-
39: calcd. for C23H35O2 [ðM þ HÞþ], 343.2632; found, 343.2635.
mmol) gave 1.33 g (91%) of (3S,11R)-42 as an oil, ½ꢁꢁD ꢂ3:19
(c 4.10, hexane). Its IR and 1H-NMR spectra were indistinguishable
from those of (3S,11S)-42.
(iv)
10.9 mmol) gave 2.24 g (60%) of (4R,12R)-39 as a colorless oil, nD
(4R,12R)-isomer. Similarly, (3R,11S,14RS)-38 (4.20 g,
17
(iv) (3R,11S)-isomer. Similarly, (3R,11S)-41 (1.10 g, 4.29 mmol)
25
24
1.5098; ½ꢁꢁD þ2:33 (c 4.08, hexane). Its IR and 1H-NMR spectra were
gave 1.48 g (84%) of (3R,11S)-42 as an oil, ½ꢁꢁD þ3:28 (c 4.15,
idetical with those of (4S,12S)-39. HRMS of (4R,12R)-39: calcd. for
23H35O2 [ðM þ HÞþ], 343.2632; found, 343.2623.
hexane). Its IR and 1H-NMR spectra were identical with those of
(3S,11R)-42.
C
1-Benzyloxy-3,11-dimethyl-14-pentadecen-7-yne (40).
(i) (3S,11S)-isomer. In the same manner as that described for (S)-
30, (4R,12S)-39 (1.90 g, 5.55 mmol) gave 1.72 g (91%) of (3S,11S)-40
3,11-Dimethylpentadecyl iodide (43).
(i) (3S,11S)-isomer. In the same manner as that described for (S)-
14, (3S,11S)-42 (700 mg, 1.70 mmol) gave 530 mg (85%) of (3S,11S)-
20
25
17
26
as an oil, nD 1.5005; ½ꢁꢁD ꢂ9:29 (c 4.04, hexane); IR ꢂmax (film)
cmꢂ1: 1639 (m, C=C), 1203 (w, C–O–C), 1099 (s, C–O), 995 (m), 910
(m), 735 (s), 696 (s); 1H-NMR ꢀH (CDCl3): 0.86–0.89 (6H, m), 1.15–
1.70 (12H, m), 1.98–2.22 (6H, m), 3.47–3.54 (2H, m, CH2OBn), 4.50
(2H, s, C6H5CH2), 4.91–5.02 (2H, m, H2C=CH), 5.76–5.86 (1H, m,
H2C=CH), 7.26–7.37 (5H, m, C6H5). HRMS of (3S,11S)-40: calcd. for
43 as an oil, nD 1.4827; ½ꢁꢁD þ6:87 (c 4.07, hexane); IR ꢂmax (film)
cmꢂ1: 1178 (m), 604 (w); 1H-NMR ꢀH (CDCl3): 0.82–0.97 (9H, m),
1.00–1.59 (22H, br), 1.60–1.69 (1H, m), 1.83–1.92 (1H, m), 3.12–3.28
(2H, m, CH2I).
(ii) (3R,11R)-isomer. Similarly, (3R,11R)-42 (1.90 g, 4.63 mmol)
17
25
gave 1.44 g (85%) of (3R,11R)-43 as an oil, nD 1.4832; ½ꢁꢁD ꢂ6:96
(c 4.01, hexane). Its IR and 1H-NMR spectra were identical with those
of (3S,11S)-43.
C
24H37O [ðM þ HÞþ], 341.2839; found, 341.2839.
(ii) (3R,11R)-isomer. Similarly, (4S,12R)-39 (2.69 g, 7.85 mmol)
19
25
gave 2.35 g (88%) of (3R,11R)-40 as an oil, nD 1.4990; ½ꢁꢁD þ8:91
(iii) (3S,11R)-isomer. Similarly, (3S,11R)-42 (1.30 g, 3.17 mmol)
17
(c 4.04, hexane). Its IR and 1H-NMR spectra were identical with those
gave 940 mg (81%) of (3S,11R)-43 as an oil, nD 1.4822; ½ꢁꢁD
25
of (3S,11S)-40. HRMS of (3R,11R)-40: calcd. for
[ðM þ HÞþ], 341.2839; found, 341.2838.
C24H37
O
þ5:33 (c 4.01, hexane). Its IR and 1H-NMR spectra were indistin-
guishable from those of (3S,11S)-43.

Synthesis of the Sex Pheromone of Lyclene dharma dharma
1951
(iv)
mmol) gave 530 mg (87%) of (3R,11S)-43 as an oil, nD 1.4834;
(3R,11S)-isomer. Similarly, (3R,11S)-42 (680 mg, 1.66
17
(6S,14S)-3 (70 eV, EI) m=z: 296 (4) [Mþ, C20H40O], 278 (62), 253
(16), 236 (12), 123 (19), 110 (34), 109 (41), 95 (32), 85 (45), 71 (55),
½ꢁꢁD ꢂ5:30 (c 4.05, hexane). Its IR and 1H-NMR spectra were
58 (93), 43 (100). HRMS of (6S,14S)-3: calcd. for C20H41
[ðM þ HÞþ], 297.3152; found, 297.3152.
O
25
identical with those of (3S,11R)-43.
(ii) (6R,14R)-isomer. Similarly, (2RS,6R,14R)-46 (580 mg,
23
1.9 mmol) gave 520 mg (90%) of (6R,14R)-3 as an oil, nD 1.4476;
6,14-Dimethyl-2-octadecanone (3) as a crude mixture contaminated
with 45.
25
27
½ꢁꢁD ꢂ0:42 (c 1.03, hexane) {ref. 5, ½ꢁꢁD ꢂ0:50 (c 2.65, hexane)};
GC-MS [same conditions as those for (S)-1] tR: 17.8 min (4%),
18.8 min [94%, (6R,14R)-3], 19.5 min (2%). Its spectral data (IR, 1H-
and 13C-NMR, and MS) were identical with those of (6S,14S)-3.
HRMS of (6R,14R)-3: calcd. for C20H41O [ðM þ HÞþ], 297.3152;
found, 297.3153.
(i) (6S,14S)-isomer. In the same manner as that described for
crude (S)-1, (3S,11S)-43 (470 mg, 1.28 mmol) and ethyl acetoacetate
(750 mg, 5.76 mmol) gave 530 mg (quant.) of crude (3RS,6S,14S)-44 as
an oil. This oil was treated with 15% NaOH to give 350 mg (92%, 2
steps) of (6S,14S)-3 contaminated with 20% of (3S,11S)-45.
(3RS,6S,14S)-44. IR ꢂmax (film) cmꢂ1: 1743 (s, C=O), 1718 (s,
C=O), 1624 (m), 1242 (m), 1142 (m, C–O), 1055 (m, C–O); 1H-NMR
ꢀH (400 MHz, CDCl3): 0.82–0.93 (9H, m), 1.02–1.45 (27H, br), 1.70–
1.94 (2H, m), 2.22 (3H, s, CH3C=O), 3.35 (1H, t, J ¼ 7:4 Hz,
CHC=O), 4.16–4.24 (2H, m, CH3CH2O).
(iii)
1.64 mmol) gave 330 mg (68%) of (6S,14R)-3 as an oil, nD 1.4486;
(6S,14R)-isomer. Similarly, (2RS,6S,14R)-46 (490 mg,
21
25
27
½ꢁꢁD ꢂ1:39 (c 1.09, hexane) {ref. 5, ½ꢁꢁD ꢂ1:16 (c 3.07, hexane)};
GC-MS [same conditions as those for (S)-1] tR: 17.8 min (3%),
18.8 min [93%, (6S,14R)-3], 19.5 min (2%), 22.1 min (2%). Its spectral
data (IR, 1H- and 13C-NMR, and MS) were indistinguishable from
(ii) (6R,14R)-isomer. Similarly, (3R,11R)-43 (1.41 g, 3.85 mmol)
gave 1.51 g (quant.) of crude (3RS,6R,14R)-44 as an oil. This oil
yielded 1.04 g (91%, 2 steps) of crude (6R,14R)-3 contaminated with
18% of (3R,11S)-45. The IR and 1H-NMR spectra of (3RS,6R,14R)-44
were identical with those of (3RS,6S,14S)-44.
those of (6S,14S)-3. HRMS of (6S,14R)-3: calcd. for C20H41
[ðM þ HÞþ], 297.3152; found, 297.3152.
O
(iv)
0.871 mmol) gave 230 mg (89%) of (6R,14S)-3 as an oil, nD
(6R,14S)-isomer. Similarly, (2RS,6R,14S)-46 (260 mg,
22
23
24
1.4463; ½ꢁꢁD þ1:48 (c 1.01, hexane) {ref. 5, ½ꢁꢁD þ1:54 (c 3.07,
hexane)}; GC-MS [same conditions as those for (S)-1] tR: 17.8 min
(4%), 18.8 min [93%, (6R,14S)-3], 19.5 min (1%), 20.6 min (2%). Its
spectral data (IR, 1H- and 13C-NMR, and MS) were identical with
(iii)
(6S,14R)-isomer. Similarly, (3S,11R)-43 (940 mg, 2.57
mmol) gave 1.03 g (quant.) of crude (3RS,6S,14R)-44 as an oil. This
oil yielded 700 mg (92%, 2 steps) of crude (6S,14R)-3 contaminated
with 22% of (3S,11R)-45. The IR and 1H-NMR spectra of
(3RS,6S,14R)-44 were indistinguishable from those of (3RS,6S,14S)-44.
those of (6S,14R)-3. HRMS of (6R,14S)-3: calcd. for C20H41
[ðM þ HÞþ], 297.3152; found, 297.3154.
O
(iv)
(6R,14S)-isomer. Similarly, (3R,11S)-43 (510 mg, 1.39
mmol) gave 550 mg (quant.) of crude (3RS,6R,14S)-44 as an oil. This
oil yielded 380 mg (92%, 2 steps) of crude (6R,14S)-3 contaminated
with 23% of (3R,11S)-45. The IR and 1H-NMR spectra of
(3RS,6R,14S)-44 were identical with those of (3RS,6S,14R)-44.
Acknowledgments
Our thanks are due to Mr. M. Kimura (President,
Toyo Gosei Co., Ltd.) for his support. We are grateful to
Prof. T. Ando (Tokyo University of Agriculture and
Technology) for discussions and also for the bioassay of
our synthetic samples. The enantiomers of citronellal
were kindly supplied by Takasago International Corpo-
ration.
6,14-Dimethyl-2-octadecanol (46).
(i) (2RS,6S,14S)-isomer. In the same manner as that described
for (S)-26, crude (6S,14S)-3 (350 mg, <1:18 mmol) gave 240 mg (68%)
20
of (2RS,6S,14S)-46 as an oil, nD 1.4534; IR ꢂmax (film) cmꢂ1: 3338
(s, O–H), 1120 (m, C–O), 1077 (w); 1H-NMR ꢀH (CDCl3): 0.82–0.92
(9H, m), 0.98–1.49 (29H, br), 1.19 (3H, d, J ¼ 6:1 Hz, CH3), 3.74–
3.86 (1H, br).
(ii) (2RS,6R,14R)-isomer. Similarly, crude (6R,14R)-3 (1.04 g,
19
References
<3:51 mmol) gave 830 mg (79%) of (2RS,6R,14R)-46, nD 1.4528. Its
IR and 1H-NMR spectra were identical with those of (2RS,6S,14S)-46.
(iii) (2RS,6S,14R)-isomer. Similarly, crude (6S,14R)-3 (700 mg,
1) Shikichi Y and Mori K, Biosci. Biotechnol. Biochem., 76, 1419–
1421 (2012).
21
<2:36 mmol) gave 490 mg (70%) of (2RS,6S,14R)-46, nD 1.4529. Its
IR and 1H-NMR spectra were indistinguishable from those of
(2RS,6S,14S)-46.
2) Yamamoto M, Kamata T, Nguyen DD, Adachi Y, Kinjo M, and
Ando T, Biosci. Biotechnol. Biochem., 71, 2860–2863 (2007).
3) Nguyen DD, Kinjo M, Taguri T, Adachi Y, Yamakawa R, and
Ando T, Biosci. Biotechnol. Biochem., 73, 1618–1622 (2009).
4) Mori K, Bioorg. Med. Chem., 15, 7505–7523 (2007).
5) Mori K, Tetrahedron, 65, 2798–2805 (2009).
6) Lenarda˜o EJ, Botteselle GV, de Azanbuja F, Perin G, and Jacob
RG, Tetrahedron, 63, 6671–6712 (2007).
(iv) (2RS,6R,14S)-isomer. Similarly, crude (6R,14S)-3 (380 mg,
20
<1:28 mmol) gave 260 mg (68%) of (2RS,6R,14S)-46, nD 1.4532. Its
IR and 1H-NMR spectra were identical with those of (2RS,6S,14R)-46.
6,14-Dimethyl-2-octadecanone (3).
(i) (6S,14S)-isomer. In the same manner as that described for (S)-
1, (2RS,6S,14S)-46 (210 mg, 0.703 mmol) gave 120 mg (57%) of
7) Mori K, Masuda S, and Suguro T, Tetrahedron, 37, 1329–1340
(1981).
21
24
(6S,14S)-3 as an oil, nD 1.4471; ½ꢁꢁD þ0:59 (c 1.01, hexane)
8) Mori K, Tetrahedron, 64, 4060–4071 (2008).
9) Adachi Y, Nguyen DD, Kinjo M, Makisako S, Yamakawa R,
Mori K, and Ando T, J. Chem. Ecol., 36, 814–823 (2010).
10) Mori K, Masuda S, and Matsui M, Agric. Biol. Chem., 42,
1015–1018 (1978).
26
{ref. 5, ½ꢁꢁD þ0:65 (c 3.81, hexane)}; IR ꢂmax (film) cmꢂ1: 2954 (m),
2925 (s), 2854 (s), 1720 (s, C=O), 1462 (m), 1377 (m), 1360 (m), 1163
(m), 725 (w); 1H-NMR ꢀH (CDCl3): 0.82–0.92 (9H, m), 1.02–1.15
(4H, br), 1.15–1.44 (20H, br), 1.48–1.66 (2H, m), 2.13 (3H, s,
CH3C=O), 2.40 (2H, t, J ¼ 7:6 Hz, CH2C=O); 13C-NMR ꢀC (CDCl3):
14.2, 19.6, 19.8, 21.5, 23.1, 27.09, 27.15, 29.4, 29.8, 30.05, 30.09, 32.7,
32.8, 36.6, 36.8, 36.9, 37.1, 44.2, 209.2 (C=O); GC-MS [same
conditions as those for (S)-1] tR: 17.8 min (3%), 18.8 min [89%,
(6S,14S)-3], 19.5 min (2%), 20.6 min (1%), 22.1 min (5%). MS of
11) Mori K, Shikichi Y, Shankar S, and Yew JY, Tetrahedron, 66,
7161–7168 (2010).
12) Mori K and Qian ZH, Liebigs Ann. Chem., 1994, 291–295
(1994).