Synthesis of the enantiomers of 13-methylheptacosane, the sex pheromone of pear psylla, Cacopsylla pyricola

Article abstract of DOI:10.1002/chir.23307

An efficient and gram-scale enantioselective synthesis of (R)- and (S)-13-methylheptacosane, the sex pheromone of pear psylla, has been developed. The key steps of the approach included Evans' chiral auxiliaries and Wittig coupling of chiral phosphonium salt with aldehyde.

Full text of DOI:10.1002/chir.23307

Received: 9 October 2020
DOI: 10.1002/chir.23307
Revised: 12 February 2021
Accepted: 11 March 2021
R E S E A R C H A R T I C L E
Synthesis of the enantiomers of 13-methylheptacosane, the
sex pheromone of pear psylla, Cacopsylla pyricola
Gucheng Yuan | Yuxiong Yang | Jiawei Liu | Qinghua Bian | Min Wang |
Jiangchun Zhong
Department of Applied Chemistry, China
Abstract
Agricultural University, Beijing, China
An efficient and gram-scale enantioselective synthesis of (R)- and
Correspondence
Jiangchun Zhong, Department of Applied
Chemistry, China Agricultural University,
(S)-13-methylheptacosane, the sex pheromone of pear psylla, has been
developed. The key steps of the approach included Evans' chiral auxiliaries
and Wittig coupling of chiral phosphonium salt with aldehyde.
2
West Yuanmingyuan Road, 100193
Beijing, China.
Email: zhong@cau.edu.cn
K E Y W O R D S
1
3-methylheptacosane, chiral auxiliaries, enantioselective synthesis, pear psylla, sex pheromone
Funding information
National Key Technology Research and
Development Program of China, Grant/
Award Number: 2017YFD0201404
1
| INTRODUCTION
and (S)-1 from two kinds of chiral sources, the enantio-
11
15
mers of citronellal and citronellol. Herein, we reported
an efficient and gram-scale synthesis of both enantiomers
of the sex pheromone of pear psylla via Evans' chiral
auxiliaries. The key steps of our strategy involve
diastereoselective methylation of oxazolidinone amide and
Wittig reaction of chiral phosphonium salt with aldehyde.
Pear psylla (Cacopsylla pyricola) is a serious pest of pears,
which has caused significant economic damage in North
America and Europe.
relies mainly on insecticides. However, the increasing
1,2
Current control of this pest
3
4,5
resistance to many insecticides, such as pyrethroid
6,7
15
and orgno-phosphorous, has made the control more
difficult. Therefore, it is essential to search more efficient
and environment-friendly alternative control methods to
insecticides.
Compared with Mori's processes, our synthesis was
easier to scale up and afforded the sex pheromones of pear
psylla with higher enantiomeric purity.
The pest management based on sex pheromones is a
8
,9
safe, effective and promising technique. In 2009, the sex
pheromone produced by the female pear psylla was identi-
fied as 13-methylheptacosane (rac-1) by Guédot, mean-
while their bioassays indicated that males were attracted
2 | MATERIALS AND METHODS
2.1 | Instruments and materials
10
to synthetic racemic 1. Although this result opened a
new strategy to monitor and trap pear psylla, the absolute
configuration of the sex pheromone remains unknown.
Previous literatures reported that the bioactivity of sex
pheromones was often closely relayed to chirality.
stereochemistry on this sex pheromone still needs to be
assigned by further biological studies of (R)-1 and (S)-1
Figure 1), which promotes the synthesis of the enantio-
mers of 13-methylheptacosane. Mori has prepared (R)-1
All reactions were conducted under an argon atmosphere
with Schlenk techniques. The solvents were purified refer-
ring to the standard strategy and distilled before use. Other
commercial reagents were used directly. Melting points
were measured on a Beijing Tech X-4 melting point appa-
ratus without correction. Differential scanning calorimetry
(DSC) thermograms were recorded on EXSTAR6000. Opti-
cal rotations were determined by a Perkin–Elmer PE-341
11
12–14
The
(
1
13
polarimeter. H, C nuclear magnetic resonance (NMR),
274
© 2021 Wiley Periodicals LLC.
wileyonlinelibrary.com/journal/chir
Chirality. 2021;33:274–280.

YUAN ET AL.
275
2
2
.3 | Synthesis of (R)-4-benzyl-3-((R)-
-methyltetradecanoyl)oxazolidin-2-one
((R)-4) (new compound)
Under an argon atmosphere, the oxazolidinone amide
FIGURE 1 The structures of (R)-and
(
R)-3 (3.87 g, 10 mmol) was dissolved in dry THF (80 ml),
(
S)-13-methylheptacosane
ꢀ
and the solution was cooled to −78 C. Sodium
hexamethyldisilazide (NaHMDS, 7.12 ml, 2.0 M in THF,
14.25 mmol) was then added over 15 min via syringe
pump. The resulting mixture was stirred for 1 h at the
same temperature, and MeI (7.34 g, 3.22 ml, 52 mmol)
was added. After the reaction solution was stirred for
19
and F NMR spectra were obtained from a Bruker
DP-X300 MHz or ASCEND™500 spectrometer with
1
13
internal tetramethylsilane for H NMR and CDCl for
C
3
NMR. High-resolution mass spectrometry (HRMS) data
were recorded on Thermo Scientific Exactive Plus (EMR)
with a quadrupole mass analyzer. Mass spectrometry
ꢀ
additional 2 h at −78 C, it was quenched with saturated
aqueous NH Cl solution (75 ml). The layers were sepa-
4
(MS) data were collected from Exactive GC–MS (EI).
rated and the aqueous phase was extracted with EtOAc
(
3 × 75 ml). The combined organic layers were washed
with brine (300 ml). The combined organic phases were
dried over anhydrous Na SO and concentrated under
2
3
.2 | Synthesis of (R)-4-benzyl-
-tetradecanoyl-oxazolidin-2-one ((R)-3)
2
4
reduced pressure. The residue was purified by silica gel
column chromatography (EtOAc/petroleum ether 1:10)
to give oxazolidinone amide (R)-4 (3.41 g, 85% yield,
>99% ee, dr > 99:1) as a white solid. (R)-4 was rec-
rystallized from dry ether and DSC thermograms showed
that it was diastereomerically pure and different
from rac-4. Enantiomeric excess was determined by
high-performance liquid chromatography (HPLC) with a
Daicel Chiralcel OD-H column (5% 2-propanol in
n-hexane, 1.0 ml/min, 210 nm); major (R)-enantiomer
(new compound)
Tetradecanoic acid 2 (2.28 g, 10 mmol) was dissolved in
dichloromethane (DCM) (20 ml) at 0 C; the catalytic
amount of DMF was then added. After oxalyl chloride
ꢀ
(1.90 g, 15 mmol) was added slowly via syringe, the reac-
tion mixture was stirred for 1 h at the same temperature.
The solvent was removed under reduced pressure to give
the crude tetradecanoyl chloride as a slight yellow solid.
ꢀ
20
(R)-4-benzyloxazolidin-2-one (1.45 g, 8.25 mmol,
t = 9.73 min. mp 33–34 C; [α]
= −40.4 (c = 0.91 in
r
D
1
>
99% ee) was dissolved in tetrahydrofuran (THF)
CHCl3); H NMR (300 MHz, CDCl , δ): 7.42–7.13
3
(20 ml), NaH (0.50 g, 60% in mineral oil, 12.3 mmol) was
(m, 5H), 4.68 (ddt, J = 10.0, 6.7, 3.3 Hz, 1H), 4.29–4.07
(m, 2H), 3.72–3.68 (m, 1H), 3.28 (dd, J = 13.3, 3.3 Hz,
1H), 2.77 (dd, J = 13.3, 9.6 Hz, 1H), 1.84–1.65 (m, 1H),
ꢀ
then added slowly at 0 C. The resulting mixture was
warmed to 25 C and stirred for 2 h. The crude
tetradecanoyl chloride was added. After the reaction mix-
ture was stirred for another 3 h at 25 C, it was quenched
ꢀ
1.53–1.24 (m, 21H), 1.23 (d, J = 6.8 Hz, 3H), 0.89
ꢀ
13
(t, J = 6.7 Hz, 3H); C NMR (75 MHz, CDCl , δ): 177.51,
3
with saturated aqueous NH Cl solution (10 ml). The
153.19, 135.52, 129.58, 129.06, 127.46, 66.14, 55.50, 38.09,
4
layers were separated, and the aqueous phase was
37.86, 33.60, 32.05, 29.80, 29.78, 29.73, 29.65, 29.48, 27.40,
22.81, 17.49, 14.23; HRMS (ESI, m/z): [M + Na] calcd
+
extracted with Et O (3 × 50 ml). The combined organic
2
layers were washed with brine (50 ml) and dried over
anhydrous Na SO , concentrated under reduced pressure.
for C H O NNa, 424.2822; found, 424.2811.
25
39 3
2
4
The residue was purified by silica gel column chromatog-
raphy (EtOAc/petroleum ether 1:10) to provide
oxazolidinone amide (R)-3 as a white solid (2.99 g, 94%
2.4 | Synthesis of (R)-
2-methyltetradecan-1-ol ((R)-5) (CAS
108349-45-7)
ꢀ
20
yield). mp 58–59 C; [α]
= −28.2 (c = 2.14 in CHCl3);
D
1
H NMR (300 MHz, CDCl , δ): 7.38–7.18 (m, 5H), 4.68
3
(
(
(
ddt, J = 13.1, 7.0, 3.4 Hz, 1H), 4.32–4.04 (m, 2H), 3.31
Oxazolidinone amide (R)-4 (8.90 g, 22.16 mmol) was
dissolved in THF (80 ml), and the solution of NaBH4
(3.35 g, 88.65 mmol) in water (10 ml) was then added
dd, J = 13.3, 3.3 Hz, 1H), 3.03–2.71 (m, 3H), 1.80–1.53
13
m, 2H), 1.35–1.27 (m, 20H), 0.89 (t, J = 6.7 Hz, 3H);
C
ꢀ
NMR (75 MHz, CDCl , δ): 173.59, 153.60, 135.48, 129.56,
dropwise over 30 min at 0 C. The reaction mixture was
3
ꢀ
1
2
1
3
29.08, 127.47, 66.28, 55.29, 38.08, 35.68, 32.06, 29.82,
warmed to 25 C and stirred for 3 h, followed by the slow
9.80, 29.78, 29.76, 29.63, 29.54, 29.49, 29.28, 24.42, 22.83,
addition of 2-M aqueous HCl solution until pH
was 6. The resulting mixture was extracted with Et O
(3 × 30 ml), and the combined ether extracts were
+
4.25; HRMS (ESI, m/z): [M + H] calcd for C H O N,
24
38
3
2
88.2846; found, 388.2829.

276
YUAN ET AL.
washed with saturated aqueous NaHCO solution (20 ml)
and brine (2 × 20 ml) sequentially. The organic layer was
and stirred for 24 h. The reaction solution was cooled to
room temperature and concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography (dichloromethane/methanol 10:1) to
provide phosphonium salt (R)-7 (1.90 g, 50% yield) as a
3
then dried over anhydrous Na SO and concentrated
2
4
under reduced pressure. The residue was purified by sil-
ica gel column chromatography (EtOAc/petroleum ether
20
1
1
:5) to afford alcohol (R)-5 (4.30 g, 85% yield, >99% ee,
colorless oil. [α]D = −0.68 (c = 1.17 in CHCl3);
H
19
determined by F NMR analysis of its Mosher ester) as a
colorless oil. [α]D = +4.5 (c = 1.68 in CHCl ); H NMR
NMR (400 MHz, CDCl3, δ): 8.20–6.87 (m, 15H),
3.84–3.75 (m, 1H), 3.50–3.26 (m, 1H), 2.06–2.04 (m, 1H),
1.79–1.01 (m, 22H), 0.96 (d, J = 6.5 Hz, 3H), 0.80
20
1
3
(
300 MHz, CDCl , δ): 3.51 (dd, J = 10.5, 5.8 Hz, 1H), 3.41
3
13
(
(
3
dd, J = 10.5, 6.5 Hz, 1H), 1.69–1.47 (m, 2H), 1.42–1.17
(t, J = 6.4 Hz, 3H); C NMR (126 MHz, CDCl , δ):
3
m, 22H), 0.91 (d, J = 6.0 Hz, 3H), 0.87 (t, J = 6.8 Hz,
135.07, 135.05, 133.72, 133.64, 130.60, 130.50, 119.24,
118.56, 38.20, 38.13, 31.92, 29.66, 29.64, 29.62, 29.57,
13
H); C NMR (75 MHz, CDCl , δ): 68.56, 35.92, 33.31,
3
3
2.07, 30.10, 29.82, 29.80, 29.50, 27.14, 22.83, 16.72, 14.24;
29.50, 29.35, 29.30, 26.78, 22.69, 21.13, 21.07, 14.14;
+
+
HRMS (ESI, m/z):[M + Na] calcd for C H ONa,
HRMS (ESI, m/z): [M + H] calcd for C H BrP,
15
32
33 47
2
51.2345; found, 251.2345.
553.2593; found, 553.2607.
2
2
.5 | Synthesis of (R)-1-bromo-
-methyltetradecane ((R)-6) (new
2.7 | Synthesis of (R)-
13-methylheptacosane ((R)-1) (CAS
340006-05-5)
compound)
Under
3.12 g, 13.64 mmol) and triphenylphosphine (5.37 g,
0.46 mmol) were dissolved in CH Cl (40 ml); carbon
an
argon
atmosphere,
alcohol
(R)-5
Under an argon atmosphere, phosphonium salt
(R)-7 (2.72 g, 4.91 mmol) was dissolved in dry
1,2-dimethoxyethane (30 ml), and the solution of n-BuLi
(3.93 ml, 2.5 M in n-hexane, 9.83 mmol) was then added
dropwise via syringe at room temperature. The resulting
(
2
2
2
tetrabromide (6.78 g, 20.46 mmol) was then added in por-
ꢀ
ꢀ
tions over 30 min at 0 C. After the reaction mixture was
ꢀ
stirred for 20 min at 0 C, it was warmed to room temper-
mixture was stirred for 2 h at 25 C to obtain phosphorus
ature and stirred for additional 12 h. The solvent was
removed under reduced pressure, followed by the addi-
tion of n-hexane (100 ml). The resulting mixture was fil-
tered through a pad of Celite and washed with n-hexane
ylide solution. The resulting phosphorus ylid solution
was then cooled to −40 C, followed by the addition
ꢀ
of solution of n-tridecanal (1.46 g, 7.37 mmol) in dry
1,2-dimethoxyethane (15 ml) via syringe at the same tem-
perature. The reaction mixture was warmed gradually to
(100 ml). The combined filtrates were concentrated under
ꢀ
reduced pressure, and the residue was purified by silica
gel column chromatography (petroleum ether) to obtain
hydrocarbon bromide (R)-6 (3.89 g, 98% yield) as a color-
25 C and stirred for 5 h. After the reaction was quenched
with saturated aqueous NH Cl solution (10 ml), the
4
layers were separated, and the aqueous phase was
20
1
less oil. [α]D = +0.35 (c = 2.3 in CHCl3); H NMR
extracted with Et O (3 × 20 ml). The combined organic
2
(
(
300 MHz, CDCl , δ): 2.65 (dd, J = 9.8, 4.9 Hz, 1H), 2.57
phases were washed with brine (20 ml) sequentially, and
dried over anhydrous Na SO . The solvent was removed
under reduced pressure, and the residue was purified by
column silica gel chromatography (petroleum) to give
(R)-15-methylheptacos-13-ene (1.31 g) as a colorless
viscous liquid.
3
dd, J = 9.8, 6.2 Hz, 1H), 1.14–0.98 (m, 1H), 0.72–0.51 (m,
2
4
2
2H), 0.28 (d, J = 6.6 Hz, 3H), 0.16 (t, J = 6.7 Hz, 3H);
1
3
C NMR (75 MHz, CDCl , δ): 41.67, 35.39, 35.06, 32.09,
3
2
9.87, 29.81, 29.79, 29.74, 29.51, 27.04, 22.85, 18.95, 14.25;
+
HRMS (ESI, m/z): [M + H] calcd for C H Br,
1
5
32
2
91.1682; found, 291.1726.
In a three-neck 100-ml flask, 10% platinum on carbon
(
0.50 g) was placed and charged with hydrogen. The solu-
tion of (R)-15-methylheptacos-13-ene (1.31 g, 3.33 mmol)
in ethanol (20 ml) and catalytic amount of acetic acid
was then added slowly at room temperature. After the
reaction mixture was stirred for 12 h at the same temper-
ature under hydrogen, it was filtered and the filter was
washed with n-hexane (50 ml). The combined filtrate and
washing were concentrated under reduced pressure. The
residue was purified by silica gel column chromatogra-
phy (n-hexane) to obtain target pheromone (R)-1 (1.29 g,
2
.6 | Synthesis of (R)-2-methyl
tetradecyltriphenylphosphonium bromide
(R)-7) (new compound)
(
Under an argon atmosphere, hydrocarbon bromide (R)-6
2.00 g, 6.87 mmol) and triphenylphosphine (2.70 g,
(
1
0.30 mmol) were added to CH CN (40 ml) at room tem-
3
ꢀ
perature. The reaction solution was then heated to 85 C

YUAN ET AL.
277
ꢀ
+
6
[
7% yield two steps) as a white solid. mp 29–30 C;
22.83, 17.50, 14.25; HRMS (ESI, m/z): [M + Na] calcd for
C H O NNa, 424.2822; found, 424.2830.
25 39 3
20
1
α]D = −0.35 (c = 2.27 in CHCl ); H NMR (300 MHz,
3
13
CDCl , δ): 1.45–1.02 (m, 49H), 0.96–0.87 (m, 9H);
C
3
NMR (75 MHz, CDCl , δ): 37.34, 32.99, 32.16, 30.28,
3
2
9.94, 29.90, 29.60, 27.32, 22.91, 19.91, 14.28; EIMS (m/z
2.10 | Synthesis of (S)-
2-methyltetradecan-1-ol ((S)-5) (CAS
[
%]): 71 (60), 85 (58), 207 (100), 225 (33), 281 (38).
156394-18-2)
2
3
.8 | Synthesis of (S)-4-benzyl-
-tetradecanoyloxazolidin-2-one ((S)-3)
According to the similar procedure for alcohol (R)-5,
oxazolidinone amide (S)-4 (6.37 g, 15.86 mmol) and
(CAS 145816-90-6)
NaBH (2.4 g, 63.44 mmol) afforded alcohol (S)-5 (3.19 g,
4
19
8
8% yield, >99% ee, determined by F NMR analysis of
its Mosher ester) as a colorless oil. [α]
(c = 0.88 in CHCl ); H NMR (300 MHz, CDCl , δ): 3.51
20
According to the similar procedure for oxazolidinone
amide (R)-3, tetradecanoic acid (6.85 g, 30 mmol), oxalyl
chloride (5.71 g, 45 mmol) and (S)-4-benzyloxazolidin-
= −11.36
3
D
1
3
(dd, J = 10.5, 5.8 Hz, 1H), 3.41 (dd, J = 10.5, 6.5 Hz, 1H),
2
-one (3.54 g, 20 mmol, >99% ee) afforded oxazolidinone
1.83–1.55 (m, 2H), 1.38–1.18 (m, 22H), 0.92
13
amide (S)-3 as a white solid (7.51 g, 97% yield). mp
5
(d, J = 7.0 Hz, 3H), 0.89 (t, J = 6.8 Hz, 3H); C NMR
ꢀ
20
1
8–59 C; [α]
= +28.2 (c = 1.29 in CHCl ); H NMR
(75 MHz, CDCl , δ): 68.53, 35.90, 33.32, 32.07, 30.10,
D
3
3
(
(
(
(
300 MHz, CDCl3, δ): 7.44–7.10 (m, 5H), 4.68
ddt, J = 10.3, 6.8, 3.4 Hz, 1H), 4.30–4.10 (m, 2H), 3.31
dd, J = 13.3, 3.2 Hz, 1H), 3.09–2.64 (m, 3H), 1.72–1.65
29.83, 29.80, 29.50, 27.14, 22.83, 16.72, 14.23; HRMS (ESI,
+
m/z): [M + Na] calcd for C H ONa, 251.2345; found,
15
32
251.2351.
13
m, 2H), 1.35–1.27 (m, 20H), 0.89 (t, J = 6.7 Hz, 3H);
C
NMR (75 MHz, CDCl , δ): 173.59, 153.58, 135.49, 129.55,
3
1
2
29.07, 127.45, 66.27, 55.28, 38.09, 35.67, 32.05, 29.78,
2.11 | Synthesis of (S)-1-bromo-
2-methyltetradecane ((S)-6) (CAS
2410601-40-8)
9.75, 29.62, 29.53, 29.48, 29.28, 24.43, 22.81, 14.23;
+
HRMS (ESI, m/z): [M + Na] calcd for C H O NNa,
24
37 3
4
10.2666; found, 410.2670.
According to the similar procedure for hydrocarbon
bromide (R)-6, alcohol (S)-5 (8.76 g, 38.35 mmol),
carbon tetrabromide (19.08 g, 57.52 mmol), and
triphenylphosphine (15.09 g, 57.52 mmol) afforded
hydrocarbon bromide (S)-6 (10.94 g, 98% yield) as a color-
2
.9 | Synthesis of (S)-4-benzyl-3-((S)-
-methyltetradecanoyl)oxazolidin-2-one
2
(
(S)-4) (new compound)
20
1
less oil. [α]D = −0.31 (c = 5.23 in CHCl ); H NMR
3
According to the similar procedure for oxazolidinone
(300 MHz, CDCl , δ): 3.41 (dd, J = 9.8, 5.0 Hz, 1H),
3
amide (R)-4, oxazolidinone amide (R)-3 (3.87 g,
3.33 (dd, J = 9.8, 6.2 Hz, 1H), 1.86–1.74 (m, 1H),
1
0 mmol), MeI (7.10 g, 50 mmol) and sodium
1.50–1.27 (m, 21H), 1.02 (d, J = 6.6 Hz, 3H), 0.89
13
hexamethyldisilazide (NaHMDS, 2.0 M in THF, 10 ml,
(t, J = 6.7 Hz, 3H); C NMR (75 MHz, CDCl , δ): 41.69,
3
2
8
0 mmol) afforded oxazolidinone amide (S)-4 (3.49 g,
7% yield) as a white solid. (S)-4 was recrystallized from
35.39, 35.06, 32.09, 29.87, 29.82, 29.79, 29.74, 29.51, 27.04,
22.85, 18.96, 14.26; HRMS (ESI, m/z): [M + H] calcd for
+
dry ether and DSC thermograms showed that it was
diastereomerically pure and different from rac-4.
Enantiomeric excess was determined by HPLC with a
Daicel Chiralcel OD-H column (5% 2-propanol in
n-hexane, 1.0 ml/min, 210 nm); major (S)-enantiomer
C H Br, 291.1682; found, 291.1740.
15
32
2.12 | Synthesis of (S)-2-methyl
tetradecyltriphenylphosphonium bromide
((S)-7) (new compound)
ꢀ
20
t = 11.03 min. mp 33–34 C; [α]
= +40.73 (c = 5.5 in
r
D
1
CHCl3); H NMR (300 MHz, CDCl , δ): 7.40–7.16
3
(
(
1
m, 5H), 4.68 (ddt, J = 9.9, 6.7, 3.5 Hz, 1H), 4.26–4.07
m, 2H), 3.72–3.68 (m, 1H), 3.27 (dd, J = 13.3, 3.2 Hz,
H), 2.77 (dd, J = 13.3, 9.5 Hz, 1H), 1.83–1.59 (m, 2H),
.28–1.24 (m, 20H), 1.22 (d, J = 6.8 Hz, 3H), 0.89
According to the similar procedure for phosphonium salt
(R)-7, hydrocarbon bromide (S)-6 (6.00 g, 20.60 mmol)
and triphenylphosphine (21.09 g, 80.40 mmol) afforded
phosphonium salt (S)-7 (5.93 g, 52% yield) as a colorless
1
13
20
1
(d, J = 6.8 Hz, 3H); C NMR (75 MHz, CDCl , δ): 177.53,
oil. [α]D = +3.32 (c = 4.33 in CHCl3); H NMR
(400 MHz, CDCl3, δ): 8.02–7.08 (m, 15H), 3.76
(tt, J = 68.2, 34.2 Hz, 1H), 3.48–3.23 (m, 1H), 2.01
3
1
3
53.21, 135.53, 129.60, 129.07, 127.47, 66.16, 55.52, 38.10,
7.87, 33.61, 32.07, 29.81, 29.79, 29.75, 29.66, 29.50, 27.42,

278
YUAN ET AL.
(
d, J = 32.0 Hz, 1H), 1.73 (t, J = 33.3 Hz, 1H), 1.32–1.01
2.13 | Synthesis of (S)-
13-methylheptacosane ((S)-1) (CAS
340006-23-7)
(m, 21H), 0.96 (d, J = 6.5 Hz, 3H), 0.80 (t, J = 6.4 Hz,
13
3
1
3
2
[
5
H); C NMR (126 MHz, CDCl , δ): 135.07, 135.05,
3
33.72, 133.64, 130.60, 130.50, 119.23, 118.56, 38.20,
8.13, 31.92, 29.66, 29.64, 29.62, 29.57, 29.49, 29.35, 29.30,
According to the similar procedure for sex pheromone
(R)-1, (S)-7 (2.86 g, 5.17 mmol), n-tridecanal (1.54 g,
7.75 mmol) and 10% platinum on carbon (0.50 g)
afforded sex pheromone (S)-1 (1.37 g, 68% yield two
6.78, 22.69, 21.13, 21.07, 14.14; HRMS (ESI, m/z):
+
M + H]
calcd for C H BrP, 553.2593; found,
33 47
53.2675.
ꢀ
20
steps) as a white solid. mp 29–30 C. [α]
= +0.13
D
1
(
c = 3.02 in CHCl3); H NMR (300 MHz, CDCl δ):
3,
13
1
.45–1.10 (m, 49H), 0.94–0.85 (m, 9H);
C NMR
(
126 MHz, CDCl3, δ): 37.27, 32.92, 32.10, 30.21, 29.91,
9.88, 29.84, 29.54, 27.26, 22.86, 19.89, 19.87, 14.28; EIMS
m/z[%]): 71 (60), 85 (58), 207 (100), 225 (33), 281 (39).
2
(
3
| RESULTS AND DISCUSSION
The retrosynthetic analysis of (R)-13-methylheptacosane
is outlined in Scheme 1. The target sex pheromone (R)-1
could be prepared via the Wittig coupling of phospho-
nium salt (R)-7 with n-tridecanal and hydrogenation
reduction. The bromination of chiral alcohol (R)-5 and
reacting with triphenylphosphine were envisaged to
afford the key chiral intermediate (R)-7. Most
importantly, the chiral methyl of (R)-5 could be
introduced by Evans' chiral auxiliaries including
acylation of myristic acid 2, asymmetric methylation of
(R)-4-benzyl-3-tetradecanoyloxazolidin-2-one oxazolidinone
SCHEME 1 Retrosynthetic analysis of
R)-13-methylheptacosane
(
SCHEME 2 Synthesis of (R)- and (S)-13-methylheptacosane

YUAN ET AL.
279
amide ((R)-3) and the reduction of oxazolidinone
amide (R)-4. (S)-13-methylheptacosane ((S)-1) could
be obtained following the similar approach using
sex pheromone of pear psylla. Central to our approach
were Evans' chiral auxiliaries and Wittig coupling of chi-
ral phosphonium salt with aldehyde. The sex phero-
mones synthesized herein were valuable for the pest
management of pear psylla.
(S)-4-benzyloxazolidin-2-one.
As outlined in Scheme 2, our synthetic sequence
began with the reaction of myristic acid 2 with oxalyl
1
6
chloride to provide tetradecanoyl chloride. The subse-
quent acylation with (R)-4-benzyloxazolidin-2-one (>99%
ee) afforded (R)-4-benzyl-3-tetradecanoyloxazolidin-2-one
ACKNOWLEDGMENTS
We appreciate the National Key Technology
Research and Development Program of China
(No. 2017YFD0201404) for the financial support.
17
(
(R)-3) in 94% yield.
oxazolidinone amide (R)-3 with hexamethyldisilazide
NaHMDS) in THF, followed by diastereoselective
methylation with iodomethane gave oxazolidinone amide
Deprotonation of chiral
(
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are
available in the supporting information of this article.
18,19
(
R)-4 in 85% yield and with >99% ee.
DSC
thermograms and NMR spectra showed that (R)-4 was
diastereomerically pure. The governing precedents of
Evans' chiral auxiliaries favored the absolute configura-
tion of new stereocenter at the C2 position of (R)-4 as
ORCID
Jiangchun Zhong https://orcid.org/0000-0002-6594-
979X
20
(
R). The chiral auxiliary was then removed with
simultaneous reduction using NaBH4 provided
R)-2-methyltetradecan-1-ol ((R)-5) in 85% yield (>%99
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How to cite this article: Yuan G, Yang Y, Liu J,
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pheromone of pear psylla, Cacopsylla pyricola.
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