Synthesis of (R)-japonilure and (4R,9Z)-9-octadecen-4-olide, pheromones of the Japanese beetle and currant stem girdler

Article abstract of DOI:10.1080/00397910701462344

Asymmetric total synthesis of the sex pheromones of Japanese beetle and currant stem girdler, (R)-japonilure (1) and (4R,9Z)-9-octadecen-4-olide (2), has been achieved. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701462344

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Synthesis of (R)‐Japonilure and
(4R,9Z)‐9‐Octadecen‐4‐olide, Pheromones
of the Japanese Beetle and Currant Stem
Girdler
a
a
a
a
Gowravaram Sabitha , V. Bhaskar , K. Yadagiri & J. S. Yadav
a
Organic Division I , Indian Institute of Chemical Technology , Hyderabad,
India
Published online: 09 Aug 2007.
To cite this article: Gowravaram Sabitha , V. Bhaskar , K. Yadagiri & J. S. Yadav (2007) Synthesis of
(R)‐Japonilure and (4R,9Z)‐9‐Octadecen‐4‐olide, Pheromones of the Japanese Beetle and Currant Stem
Girdler, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 37:15, 2491-2500, DOI: 10.1080/00397910701462344
To link to this article: http://dx.doi.org/10.1080/00397910701462344
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Synthetic Communications , 37: 2491–2500, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701462344
Synthesis of (R)-Japonilure and (4R,9Z)-9-
Octadecen-4-olide, Pheromones of the
Japanese Beetle and Currant Stem Girdler
Gowravaram Sabitha, V. Bhaskar, K. Yadagiri, and
J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: Asymmetric total synthesis of the sex pheromones of Japanese beetle
and currant stem girdler, (R)-japonilure (1) and (4R,9Z)-9-octadecen-4-olide (2), has
been achieved.
Keywords: japonilure, g-lactones, (4R,9Z)-9-octadecen-4-olide, pheromones
INTRODUCTION
Optically active 5-alkyl substituted (-lactones are attractive building blocks
[
in natural product synthesis and comprise structural moieties frequently
1]
[
2]
[3]
present in insect pheromones, cardenolides, and lignans, for example.
The Japanese beetle, Popillia japonica, is a notorious pest in the USA,
causing damage to a variety of ornamental trees and cultivated crops. Its
pheromone, japonilure (1), a g-lactone isolated from virgin females, has
[4]
been used in traps to attract males. The structure of japonilure was
assigned as (R,Z)-5-(1-decenyl) oxacyclopentan-2-one. Male response was
strongly inhibited by small amounts of its (S,Z)-isomer. Given the industrial
[5]
importance of japonilure, a large number of syntheses have been reported.
Most of these methods do not produce the pheromone in high optical purity.
Received December 7, 2006
Address correspondence to Gowravaram Sabitha, Organic Division I, Indian
Institute of Chemical Technology, Hyderabad
gowravaramsr@yahoo.com
500 007, India. E-mail:
2
491

2
492
G. Sabitha et al.
Therefore, a simple and efficient method for the synthesis of enantiomeri-
cally pure japonilure is useful. (4R,9Z)-9-Octadecen-4-olide (2) is the
female sex pheromone of the currant stem girdler, Janus integer. This
insect is a pest of red currant in North America. The g-lactone 2 was
[6]
isolated and identified by Cosse and his co-workers in the USA. They
synthesized racemic 2, demonstrated its pheromone properties by field exper-
iments, and showed by gas chromotography (GC) analysis that the natural 2
contains only a single enantiomer. The stereochemistry of the pheromone
was proposed as R. Until now there have been only two syntheses reported
[
7]
[8]
by Mori. As a part of our interest in the synthesis of lactones, we
have taken up the total synthesis of (R)-japonilure (1) and (4R,9Z)-9-
octadecane–4-olide (2). The retrosynthetic analysis of these two lactones is
outlined in Scheme 1.
RESULTS AND DISCUSSION
[9]
The synthesis of R-japonilure starts with the known 4-pentynol. The 4-
pentynol (5) was protected as its tetrahydropyranyl derivative by treatment
Scheme 1. Retrosynthetic analysis.

Synthesis for Pheromones
2493
with 3,4-dihydro-2H-pyran and a catalytic amout of p-toluene sulfonic acid
PTSA) in CH Cl to afford 10. Treatment of 10 with ethyl magnesium
(
2
2
bromide followed by quenching with para-formaldehyde in dry THF afforded
1 in 80% yield. In the next step, the alkyne function in 11 was reduced by
1
lithium aluminium hydride in THF to its trans allylic alcohol. The allylic
alcohol 12 was subjected to Sharpless epoxidation to afford the desired
epoxide 4 in 77% yield. Epoxy alcohol 4 was converted to the chiral epoxy
chloride 13 using PPh in refluxing CCl in the presence of NaHCO (Scheme 2).
3
4
3
The 2,3-epoxychloride 13 was directly converted into an alkylated chiral
acetylenic carbinol 14 in 81% yield in onepot by subjecting it to a base-
induced opening with Li metal in liq. NH in THF, and the resulted alkynol
3
without isolation was treated with 1-bromooctane at 2788C. The spectral
data of compound 14 was in good agreement with the assigned structure.
The secondary hydroxyl group of compound 14 was protected as its silyl
ether using TBDMSCl and imidazole in dry CH Cl at room temperature to
2
2
afford the compound 15 in 88% yield. Deprotection of tetrahydropyran
THP) group in 15 using pyridinium p-toluenesulfonate (PPTS) in MeOH at
room temperature afforded a primary hydroxy compound 16 in 67% yield.
(
Scheme 2. Reagents and conditions; a) DHP, PTSA, dry CH
2 2
Cl , 08C–rt 86%; b) (i)
2 5
C H
Mg Br, 08C, 30 min, ii) parafarmaldehyde, 08C–rt, 12 h, 80%; c) LAH dry THF,
i
˚
0
8C–rt, 3 h, 80%; d) (-)DET, Ti(O Pr) cumenehydroperoxide, 4 A dry
4
CH
NH
TBDMSCl, imidazole, dry CH Cl , 08C–rt, 83%; ii) recrystalized PPTS, MeOH, rt,
2
Cl
2
, 2 248C, 4 h, 77%, e) PPh
3
, NaHCO
3
, CCl
4
, reflux, 4 h, 79%; f) (i) Li/Liq
3
, Fe(N0
3
)
3
8
(catalyst), 2788C, dry THF, 2 h; C H17Br, dry THF, 70%, g) (i)
2
2
2
h, 63%; h) Dess–Martinperiodide, dry CH
NaH PO , 2H O, DMSO, 08C–rt, 1 h, 80%; j) PTSA, MeOH, rt, 3 h, 85%, (k) Lindlar
catalyst, H , quinoline, EtOAc, 2 h, 85%.
2
2
Cl2, 08C–rt, 2 h, 85%; i) NaClO ,
2
4
2
2

2
494
G. Sabitha et al.
Oxidation of primary alcohol with Dess–Martin periodide in dry
CH Cl afforded the corresponding aldehyde 17 in 94% yield. This was
further converted into the acid 3 in 82% yield using NaClO2 and
2
2
.
NaH PO 2H O in DMSO at rt. The cyclization was achieved in 85%
2
4
2
yield by PTSA in MeOH by in situ deprotection of the silyl group to
give acetylenic lactone 18. The catalytic hydrogenation of the triple bond
over Lindlar catalyst gave the target, Japanese beetle pheromone, R-japoni-
lure 1, in 96% yield. The optical rotation of the target molecule matched the
reported data.
The synthesis of (4R,9Z)-octadecane-4-olide was achieved as shown in
Scheme 3. The THP ether 8 of 5-bromo-1-pentanol, which in turn was
prepared from 1,5-pentanediol, was coupled with propargyl alcohol 9 using
LiNH in liquid ammonia to afford alcohol 19. Compound 19 on reduction
2
with LAH at 08C resulted in trans olefin 20, which when subjected to
Sharpless asymmetric epoxidation conditions, afforded epoxide 7. Epoxy
alcohol 7 was converted to the chiral epoxychloride 21 using PPh3 in
refluxing CCl4 in the presence of NaHCO . Base-induced opening by
3
Scheme 3. Reagents and conditions a) Li/Liq NH , Fe (N0 ) , (catalyst), dry THF,
3
3 3
i
6
oxide, 4A, dry CH
h, 70%; b) LAH, dry THF, 08C–rt, 3 h, 90%; c) (-)DET, Ti(O Pr)4, cumenehydroper-
˚
2
Cl
2
, 2248C, 6 h, 83%; d) PPh
3 3 4
, NaHCO , CCl , reflux, 4 h, 80%; e)
Li/Liq NH , Fe(N0 ) (catalyst), dry THF, 70%, 6 h; f) MOMCl, Hunig’s base, 08 C–
3
3 3
rt, 2 h, 90%; g) n-BuLi, methylchloroformate, dry THF, 2788C, 30 min, 73%; h) Pd/
þ
C, H
2
2
, MeOH, 6 h, 70% i) IBX, dry DMSO, dry DCM, rt, 2 h, 75 %; j) C
9
H
19 pph
3
Br
,
dry THF-HMPA, nBuLi, 2788C–rt, 75%; k) PTSA, MeOH, 12 h, 80%.

Synthesis for Pheromones
2495
LiNH of epoxy chloride 21 in liquid ammonia at –788C resulted exclusively
2
in the formation of chiral carbinol 22 in 70% yield.
Compound 22 was protected as its methoxymethyl (MOM) ether 23
2
using 2.5 eq of Hunig’s base (iPr EtN) and 2 eq of MOM-Cl in dry
CH Cl at room temperature in 90% yield. The acetylenic compound 23
2
2
was then subjected to methoxy carbonylation with 1 eq of methyl chlorofor-
mate in the presence of 1.2 eq of n-BuLi (1.6 M in hexane) at –788C to
furnish acetylenic ester 24 in 73% yield.
In the next step, the reduction of triple bond and subsequent deprotection
of THP group in compound 24 was achieved in one pot by hydrogenation over
10% Pd/C to furnish the corresponding compound 25 in 70% yield. The
alcohol 25 was oxidized to the aldehyde 26 in 75% yield with iodoxy
benzoic acid (IBX) in dry DMSO and dry CH Cl
2
2.
The aldehyde 26 was subjected to a Wittig olefination with nonyltripho-
sphonium bromide in tetrahydrofuran-hexamethylphosphoric acid triamide
(THF-HMPA) and n-butyl lithum at – 78 8C to give the Z olefin 6. Finally,
the cylization of compound 6 with PTSA in MeOH afforded the target
lactone 2 in 80% yield.
1
The synthetic material showed IR, H NMR, and C NMR spectral data
13
2
D
5
in good agreement with the natural lactone [[a] þ23.3 (c ¼ 1, CHCl ) lit.
3
2
D
5
[
a] þ24.2(c ¼ 3.20, CHCl ) Ref. 7(b)].
3
In conclusion, we have achieved a simple, short, and efficient total
synthesis of g-lactones R-japonilure and (4R,9Z)-9-octadecen-4-olide in
good yields.
EXPERIMENTAL
Reactions were conducted under a nitrogen atmosphere using anhydrous
solvents such as DCM, THF, CCl , benzene, and EtOAc. All reactions
4
were monitored by thin-layer chromatography (TLC) using silica-coated
plates and visualization under UV light. Light petroleum of the distillation
range 60–808C was used. Yields refer to chromaographically and spectro-
1
13
scopically ( H, C) homogeneous material. Air-sensitive reagents were
transferred by syringe or with a double-ended needle. Evaporation of
solvents was performed at reduced pressure, using a Buchi rotary evapor-
1
ator. H NMR spectra were recorded on Varian FT 200-MHz (Gemini)
and Bruker UXNMR FT 300-MHz (Avance) instruments in CDCl3.
Chemical shift values were reported in parts per million (d) relative to tetra-
methylsilane (d 0.0) as an internal standard. Mass spectra were recorded
under electron impact at 70eV on LC-MSD (Agilent technologies).
Column chromatography was performed on silica gel (60–120 mesh)
supplied by Acme Chemical Co., India. TLC, was performed on Merck
6
0 F-254 silica-gel plates. Optical rotations were measured with a Jasco
DIP-370 polarimeter at 208C.

2
496
G. Sabitha et al.
(2S)-3-[3-(Tetrahydro-2H-2-pyranyloxy)propyl]oxiran-2-
ylmethanol (4)
2
D
5
[
a] : þ20.60 (c ¼ 0.5, CHCl ). IR (neat): 3429, 2934, 2865, 1124, 1072,
3
2
028 cm . H NMR (CDCl , 300 MHz): d 1.46–1.61 (m, 4H), 1.62–1.90
1 1
1
3
(
(
m, 6H), 2.03 (brs, 1H), 2.86–2.90 (m, 1H), 2.94–2.99 (m, 1H), 3.35–3.52
m, 2H), 3.58–3.65 (m, 1H), 3.70–3.87 (m, 3H), 4.54 (brs, 1H). LCMS:
þ
m/z 239 (M þ 1).
2-3-[(3R)-3-(Chloromethyl)oxiran-2-yl]propoxytetrahydro-2H-
pyran (13)
2
D
5
[
a] : þ12.97 (c ¼ 0.5, CHCl ). IR (neat): 2942, 2868, 1447, 1124, 1074,
3
2
030 cm . H NMR (CDCl , 300 MHz): d 1.46–1.61 (m, 4H), 1.62-1.90
1 1
1
3
(
m, 6H), 2.83–2.89 (m, 1H), 2.93–3.00 (m, 1H), 3.35–3.52 (m, 3H), 3.56–
1
3
3
.64 (m, 1H), 3.70–3.86 (m, 2H), 4.55 (t, J ¼ 3.0 Hz, 1H). C NMR
(
CDCl , 75 MHz): d 98.7, 66.5, 58.5, 56.9, 44.5, 30.5, 28.2, 25.8, 25.2,
3
þ
1
9.5. LCMS: m/z 257 (M þ 1).
(
4S)-1-(Tetrahydro-2H-2-pyranyloxy)-5-tetradecyn-4-ol (14)
2
D
5
[
a] : þ7.32 (c ¼ 1.0, CHCl ). IR (neat): 3430, 2928, 2856, 1459, 1120, 1071,
3
2
1 1
1
028 cm . H NMR (CDCl , 200 MHz): d 0.89 (t, J ¼ 6.5 Hz, 3H), 1.28
3
(
brs, 7H), 1.34–143 (m, 3H), 1.46–1.65 (m, 6H), 1.65-1.87 (m, 5H), 2.18
td, J ¼ 1.6, 6.5 Hz, 2H), 2.31 (dd, J ¼ 5.7 Hz, 2H), 3.36–3.52 (m, 2H),
(
1
3
3
.70–3.86 (m, 2H), 4.36 (d, J ¼ 5.7 Hz, 1H), 4.59 (q, J ¼ 3.2 Hz, 1H).
C
NMR (CDCl , 75 MHz): d ¼ 98.7, 85.4, 81.1, 67.2, 62.3, 62.1, 35.4, 31.8,
3
3
0.6, 29.1, 29.0, 28.8, 28.7, 25.5, 25.4, 22.6, 19.40, 18.7, 14.0. LCMS: m/z
þ
3
33 (M þ 1).
tert-Butyl(dimethyl)((1S)-1-[3-(tetrahydro-2H-2-pyranyloxy)propyl]
-
2-undecynyloxy)silane (15)
2
D
5
[
a] : þ19.95 (c ¼ 0.5, CHCl ). IR (neat): 2930, 2857, 1464, 1120, 1072,
3
2
1 1
1
035, 837 cm
H NMR (CDCl , 200 MHz): d 0.10 (s, 6H), 0.89 (brs,
3
12H), 1.26 (brs, 13H), 1.37–1.62 (m, 2H), 1.62–1.94 (m, 7H), 2.16
(
t, J ¼ 5.4 Hz, 2H), 3.28–3.53 (m, 2H), 3.61–3.89 (m, 2H), 4.33 (s, 1H),
1
3
4
6
2
.55 (t, J ¼ 3.12 Hz, 1H). C NMR (CDCl , 75 MHz): d 98.6, 84.5, 81.7,
3
7.2, 63.0, 62.1, 35.8, 31.8, 30.7, 29.2, 29.0, 28.8, 28.6, 27.7, 25.8, 25.6,
5.5, 22.6, 19.5, 18.2, 14.0, 24.1. LCMS: m/z 447 (M þ Na).
þ

Synthesis for Pheromones
2497
(4S)-4-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-5-tetradecyn-1-ol (16)
2
D
5
[
a] : þ24.26 (c ¼ 0.5, CHCl ). IR (neat): 3383, 2929, 2856, 1465, 1097,
3
2
1 1
1
059, 836 cm
2H), 1.28 (brs, 6H), 1.36–1.56 (m, 2H), 1.60–1.81 (m, 6H), 2.17 (td,
H NMR (CDCl , 200 MHz): d 0.10 (s, 6H), 0.90 (brs,
3
1
J ¼ 1.57, 6.2 Hz, 2H), 3.63 (brs, 2H), 4.40 (brs, 1H). LCMS: m/z 363
þ
(
M þ 1).
(4S)-4-f[1-(tert-Butyl)-1,1-dimethyl silyl]oxyg-5-tetradecynal (17)
2
1
IR (Neat): 2929, 2856, 1711, 1464, 1092, 838 cm . H NMR (CDCl ,
1
3
3
00 MHz): d 0.10 (s, 6H), 0.89 (brs, 12H), 1.27 (brs, 8H), 1.42–1.56
(
m, 2H), 1.88–2.01 (m, 2H), 2.17 (td, J ¼ 1.7, 6.79 Hz, 2H), 2.50 (td,
J ¼ 2.2, 7.36 Hz, 2H), 4.38–4.46 (m, 1H), 9.77 (t, J ¼ 1.5 Hz, 1H). LCMS:
þ
m/z 393 (M þ Na).
(4S)-4-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-5-tetradecynal (3)
2
D
5
[
a] : þ12.65 (c ¼ 1.0, CHCl ). IR (neat): 3444, 2929, 2856, 1728, 1465,
3
2
095, 837 cm . H NMR (CDCl , 300 MHz): d 0.10 (s, 6H), 0.89 (brs,
1 1
1
3
1
2H), 1.28 (brs, 10H), 1.42–1.55 (m, 2H), 1.83–2.01 (m, 2H), 2.17 (td,
J ¼ 1.5, 6.79 Hz, 2H), 2.50 (td, J ¼ 2.26, 7.50 Hz, 2H), 4.42
1
3
(
t, J ¼ 6.0 Hz, 1H). C NMR (CDCl , 75 MHz): d 85.4, 80.8, 62.2, 33.7,
3
3
1.8, 30.1, 29.7, 29.2, 29.0, 28.9, 25.8, 22.6, 186, 18.2, 14.0, 24.6.
þ
LCMS: m/z 377 (M þ 1).
(5R)-5-(1-Decynyl)tetrahydro-2-furanone (18)
2
D
5
[
a] : 25.2 [c ¼ 1.0, CHCl ]. IR (neat): 2927, 2859, 2244, 1786, 1461, 1183,
3
2
1
1
1
150, 1018, 977, 926, 809 cm
. H NMR (CDCl , 300 MHz): d 0.88
3
(
t, J ¼ 6.5 Hz, 3H), 1.26 (brs, 10H), 1.42–1.59 (m, 2H), 2.21 (td, J ¼ 2.3,
1
3
7
.0 Hz, 2H), 2.32–2.72 (m, 4H), 5.07 (tdd, J ¼ 7.0, 6.0, 2.1 Hz, 1H).
C
NMR (CDCl , 75 MHz): d 176.1, 88.7, 76.4, 69.6, 31.7, 30.0, 29.0, 28.9,
3
þ
2
8.7, 28.2, 27.8, 22.5, 18.5, 13.9. LCMS: m/z 245.1 (M þ Na).
(R)-Japonilure (1)
2
D
5
[
a] : 269.2 [c ¼ 1.0, CHCl ]. IR (neat): 2940, 2855, 1778, 16458, 1461,
3
2
1
1
1
420, 1379, 1328, 1290, 1218, 1178, 1125, 1013, 977, 910, 870, 720 cm
.
H NMR (CDCl , 300 MHz): d 0.89 (t, J ¼ 6.7 Hz, 3H), 1.27 (brs, 10H),
3
1
.34–1.45 (m, 2H), 1.84–2.01 (m, 1H), 2.02–2.21 (m, 2H), 2.28–2.43

2
498
G. Sabitha et al.
(
m, 1H), 2.44–2.59 (m, 2H), 5.19 (q, J ¼ 8.3 Hz, 1H), 5.43 (t, J ¼ 10.5, 1H),
1
3
5
.64 (dt, J ¼ 7.5, 10.5, 1H). C NMR (CDCl 75 MHz); d 177.1, 136.0,
3
1
27.3, 76.5, 31.9, 29.5, 29.4, 29.3, 29.2, 29.17, 29.0, 27.8, 22.6, 14.3.
þ
LCMS: m/z 247 (M þ Na).
(2R,3R)-3-[5-(Tetrahydro-2H-2-pyranyloxy)pentyl]oxiran-2-
ylmethanol (7)
2
D
5
21 1
[
a] : þ19.1 (c ¼ 1.0, CHCl ). IR (neat): 3438, 2960, 2856, 1049 cm . H
3
NMR (CDCl , 200 MHz): d 1.24–1.87 (m, 16H), 2.85 (dt, J ¼ 2.2, 6.1 Hz,
3
1
4
5
H), 2.90 (dt J ¼ 2.2, 4.5 Hz, 1H), 3.30–3.52 (m, 2H), 3.56–3.87 (m, 2H),
1
3
.54 (t, J ¼ 3.1 Hz, 1H). C NMR (CDCl , 75 MHz): d 98.5, 67.6, 62.7, 61.8,
3
þ
8.7, 54.8, 31.7, 30.6, 29.3, 25.3, 23.4, 22.7, 19.5. EI mass: m/z 267 (M þ Na).
2
2
-(5-[(2R,3S)-3-(Chloromethyl)oxiran-2-yl]pentyloxy)tetrahydro-
H-pyran (21)
2
D
5
21 1
[
a] : þ10.5 (c ¼ 1.0, CHCl ). IR (neat): 2940, 2866, 1049 cm . H NMR
3
(
CDCl , 200 MHz): d 1.36–1.82 (m, 16H), 2.81 (dt, J ¼ 1.25, 6.2 Hz, 1H),
3
2
.93 (dt, J ¼ 1.5, 7.1 Hz, 1H), 3.28–3.50 (m, 2H), 3.56–3.87 (m, 2H), 4.54
1
3
(
t, J ¼ 3.1 Hz, 1H). C NMR (CDCl , 75 MHz): d 98.7, 67.2, 61.8, 59.3,
3
þ
5
6.8, 48.2, 31.7, 30.6, 29.3, 25.4, 23.2, 22.7, 19.5. ESIMS: m/z 263 (M þ 1).
(
3R)-8-(Tetrahydro-2H-2-pyranyloxy)-1-octyn-3-ol (22)
2
D
5
21 1
[
a] : þ2.2 (c ¼ 1.0, CHCl ). IR (neat): 3420, 3296, 2944, 1029 cm
H
NMR (CDCl , 200 MHz): d 1.17–2.0 (m, 14H), 2.37 (s, 1H), 3.28–3.52
3
3
(
m, 2H), 3.62–3.86 (m, 2H), 4.32 (t, J ¼ 6.2 Hz, 1H), 4.54 (t, J ¼ 3.1 Hz,
þ
1
H). EI mass: m/z 249 (M þ Na).
2
-[(6R)-6-(Methoxymethoxy)-7-octynyl]oxytetrahydro-2H-pyran (23)
2
D
5
1
[
(
(
(
a] : þ11.6 (c ¼ 1.0, CHCl ). H NMR (CDCl , 300 MHz): d 1.38–1.80
3
3
m, 14H), 2.32 (dd, J ¼ 0.56, 2.07 Hz, 1H), 3.35 (d, J ¼ 0.75 Hz, 3H), 3.45
m, 2H), 3.66–3.84 (m, 2H), 4.27 (dt, J ¼ 1.8, 6.4 Hz, 1H), 4.51 – 4.56
1
3
m, 2H), 4.90 (dd, J ¼ 0.5, 6.7 Hz, 1H). C NMR (CDCl , 75 MHz): d
3
1
9
9.5, 24.9, 25.4, 25.9, 29.6, 30.7, 35.4, 55.5, 62.2, 65.3, 67.3, 73.4, 82.6,
4.1, 98.7. ESIMS: 271 m/z (M þ 1).
þ

Synthesis for Pheromones
2499
Methyl (4R)-4-(methoxymethoxy)-9-(tetrahydro-2H-2-pyranyloxy)-
2
-nonynoate (24)
2
D
5
[
a] : þ8.4 (c ¼ 1.0, CHCl ). IR (neat): 2943, 2866, 1719, 1437, 1348, 1253,
3
2
031 cm . H NMR (CDCl , 300 MHz): d 1.42–1.82 (m, 14H), 3.36 (s, 3H),
1 1
1
3
1
3
3
.46 (m, 2H), 3.67–3.84 (m, 5H), 4.38 (t, J ¼ 3.7 Hz, 1H), 4.54 (t, J ¼ 3.7 Hz,
H) 4.56 (d, J ¼ 6.7 Hz, 1H), 4.85 (d, J ¼ 6.7 Hz, 1H). ESIMS: m/z
þ
51(M þ Na)
Methyl (4R)-9-hydroxy-4-(methoxymethoxy)nonanoate (25)
2
D
5
[
a] : þ9.5 (c ¼ 1.0, CHCl ). IR (neat): 3440, 2931, 2858, 1727, 1652, 1439,
3
1
2
1
1
150, 1037, 1098 cm
.
H NMR (CDCl 300 MHz): d ¼ 1.31–1.84
3
,
(
(
m, 9H), 2.36 (t, J ¼ 7.5 Hz, 3H), 3.34 (m, 3H), 3.54 (m, 1H), 3.61
þ
t, J ¼ 6 Hz, 2H), 3.66 (s, 3H), 4.58 (s, 3H). ESIMS; m/z 271(M þ Na)
Methyl (4R)-4-(methoxymethoxy)-9-oxononanoate (26)
2
D
5
[
a] : þ19.2 (c ¼ 1.0, CHCl ). IR (neat): 2928, 2722, 1724, 1647, 1439, 1150,
3
21 1
036 cm . H NMR (CDCl . 300 MHz): d 1.27–1.85 (m, 6H), 2.30–2.46
3
1
(
m, 4H), 3.35 (s, 3H), 3.54 (m, 1H), 3.66 (s, 3H), 3.71 (t, J ¼ 5.41 Hz, 2H),
1
3
.58 (s, 2H), 9.75 (s, 1H). C NMR (CDCl , 75 MHz): d 22.1, 24.7, 29.2,
4
3
þ
2
9.8, 33.9, 43.7, 51.5, 55.6, 76.2, 95.6, 173.9, 202.3. ESIMS: m/z 247 (M þ 1).
Methyl (4R,9Z)-4-(methoxymethoxy)-9-octadecenoate (6)
2
D
5
[
a] : –4.2 (c ¼ 1.0, CHCl ). IR (neat): 2926, 2854, 1740, 1459, 1449, 1100,
3
2
1 1
1
1
3
2
2
037 cm . H NMR (CDCl , 300 MHz): d 0.89 (t, J ¼ 6.1 Hz, 3H), 1.24–
3
.42 (m, 20H), 1.96–2.04 (m, 4H), 2.36 (t, J ¼ 7.5 Hz, 2H), 3.34 (s, 2H),
.53 (m, 1H), 3.66 (s, 3H). 4.58 (s, 2H), 5.30 (ddt, J ¼ 3.0, 5.2, 6.7 Hz,
1
H). C NMR (CDCl , 75 MHz): d 14.1, 22.6, 24.8, 27.1, 27.2, 29.2, 29.3,
3
3
9.4, 29.7, 29.8, 31.8, 34.1, 51.4, 55.5, 76.4, 95.4, 129.4, 130.1, 174.1.
þ
ESIMS: m/z 357 (M þ 1).
(4R, 9Z)-9-Octadecen-4- olide (2)
2
D
5
[
a] : þ23.3 (c ¼ 1.0, CHCl ), IR (neat): 2925, 2854, 1777, 1644, 1459, 1351,
3
2
1
1
1
176, 1017, 912, 721 cm
.
H NMR (CDCl , 300 MHz): d 0.89
3
(
t, J ¼ 6.79 Hz, 3H), 1.24–1.77 (m, 19H), 1.79–1.90 (m, 1H), 1.95–2.07
(
m, 4H), 2.30 (ddt, J ¼ 6.7, 7.5, 13 Hz, 1H), 2.49 (ddd, J ¼ 1.5, 7.5, 9.8 Hz,
1
1
H), 4.44 (quint, J ¼ 6.04 Hz, 1H), 5.31 (ddt, J ¼ 6.7, 11.3, 17.3 Hz, 2H).
3
C NMR (CDCl , 75 MHz): d 14.1, 22.6, 24.7, 26.8, 27.2, 27.9, 28.7, 29.2,
3

2
500
G. Sabitha et al.
2
9.3, 29.4, 29.7, 31.8, 35.4, 80.9, 129.1, 130.13, 177.1. ESIMS: m/z
81(M þ 1).
þ
2
ACKNOWLEDGEMENT
K. Y. and V. B. thank University Grants Commission (UGC), New Delhi, for
the fellowships.
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1
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4
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(
(
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(
(
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(
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1
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7
8
9
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