Radical mediated stereoselective synthesis of meso-7,11-dimethylheptadecane, a female sex pheromone component of the spring hemlock looper and the pitch pine looper

Article abstract of DOI:10.1016/j.tet.2007.06.027

meso-7,11-Dimethylheptadecane, a female sex pheromone component of the spring hemlock looper and the pitch pine looper, was synthesized from ethyl 2-(bromomethyl)propenoate in nine steps and 14% overall yield. The key step in the synthesis is the highly d

Full text of DOI:10.1016/j.tet.2007.06.027

Tetrahedron 63 (2007) 8810–8814
Radical mediated stereoselective synthesis of meso-7,11-
dimethylheptadecane, a female sex pheromone component
of the spring hemlock looper and the pitch pine looper
*
Hajime Nagano, Rie Kuwahara and Fumika Yokoyama
Department of Chemistry, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
Received 8 May 2007; revised 8 June 2007; accepted 9 June 2007
Available online 15 June 2007
Abstract—meso-7,11-Dimethylheptadecane, a female sex pheromone component of the spring hemlock looper and the pitch pine looper, was
synthesized from ethyl 2-(bromomethyl)propenoate in nine steps and 14% overall yield. The key step in the synthesis is the highly diastereo-
selective chelation-controlled radical reaction of diethyl 4-benzyloxy-2,6-dimethyleneheptanedioate with pentyl iodide performed in the pres-
ence of 6 equiv of MgBr2$OEt2.
Ó 2007 Elsevier Ltd. All rights reserved.
BnO
1. Introduction
CO2Et
CO2Et
O
I
O
n-Bu3SnH, Et3B,
CO2Et
1
The stereoselective construction of the 1,5-syn-dimethyl-
alkyl motif is of particular interest because of the ubiquitous
presence of the structural motif in many natural products
such as tocopherols, insect pheromones and membrane
lipids of archaebacteria.1–3 Recently, we reported the stereo-
selective synthesis of (4R,8R)-4,8-dimethyldecanal (4),
a common aggregation pheromone of Tribolium flour beetles
(Scheme 1).4 The key step in the synthesis is the highly dia-
stereoselective chelation-controlled radical reaction of ethyl
(4S,5R)-4-benzyloxy-5,6-(isopropylidenedioxy)-2-methylene-
hexanoate (1) with ethyl (R)-5-iodo-3-methylpentanoate (2)
performed in the presence of 7 equiv of MgBr2$OEt2
(Scheme 1).5 The highly syn-selective addition of alkyl
iodide 2 yielding compound 3 is referred to the H-atom
transfer to the outside face of radical centre in the sharply
folded seven-membered chelate intermediate.5c
BnO
O
MgBr2•OEt2, CH2Cl2
CO2Et
O
3
2
H
O
(4R,8R)-4,8-dimethyldecanal (4)
Scheme 1. Stereoselective synthesis of (4R,8R)-4,8-dimethyldecanal (4) via
the chelation-controlled diastereoselective radical reaction of a-methylene-
g-oxycarboxylic acid ester 1 with alkyl iodide 2 yielding syn-adduct 3.
(5), and (S)-7-methylheptadecane (6) was identified as the
pheromone of the loopers.7
7,11-Dimethylheptadecane and 7-methylheptadecane have
been reported as female sex pheromone components of the
spring hemlock looper (Lambdina athasaria) and the pitch
pine looper (Lambdina pellucidaria), forest pests in north-
eastern America.6 All the stereoisomers of the methylated
heptadecanes were synthesized and a mixture of meso-7,11-di-
methylheptadecane, that is (7R,11S)-7,11-dimethylheptadecane
meso-7,11-dimethylheptadecane (5)
(S)-7-methylheptadecane (6)
Keywords: Pheromone; meso-7,11-Dimethylheptadecane; Radical reaction;
1,3-Asymmetric induction.
We now report the radical mediated stereoselective synthesis
of meso-7,11-dimethylheptadecane (5).8 The pheromone 5
* Corresponding author. Fax: +81 3 5978 5715; e-mail: nagano.hajime@
ocha.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.06.027

H. Nagano et al. / Tetrahedron 63 (2007) 8810–8814
8811
possessing a 1,5-dimethylalkyl motif would be synthesized
by using the radical addition of pentyl iodide to diester 7
followed by the reduction of the oxygen functional groups
in the radical adduct 8 (Scheme 2). Both the two newly
formed hexyl chains located at the positions a to the ethoxy
carbonyl groups in 8 are expected to be syn to the benzyloxy
group.9,10
to 6 equiv, the diastereomeric ratio increased to 20:1. Fur-
thermore, when the reaction of 7 using 6 equiv of
MgBr2$OEt2 was performed at ꢀ60 ꢁC, adduct 8 was
obtained exclusively in 59% yield.
syn
anti
n-C5H11
n-C5H11
OBn
EtO2C
CO2Et
n-C5H11I, n-Bu3SnH, Et3B,
MgBr2•OEt2, CH2Cl2
16
n-C5H11
n-C5H11
OBn
OBn
EtO2C
CO2Et
EtO2C
CO2Et
syn-addition
7
8
anti anti
n-C5H11
n-C5H11
OBn
EtO2C
CO2Et
meso-7,11-dimethylheptadecane
17
Scheme 2. Synthetic plan of meso-7,11-dimethylheptadecane (5).
The stereochemistry of the products was assigned on the
basis of chemical shift values of the methine protons a to
the ester carbonyl groups. The methine proton of syn-adduct
resonates in lower field than that of anti-adduct.4,5 The
signal at d 2.58 was thus assigned to both the two methine
protons in syn,syn-adduct 8 (major product) and one of the
methine protons of syn,anti-adduct 16 (minor product),
while the signal at d 2.41 was assigned to the other methine
proton of syn,anti-adduct 16. In this case, syn,syn, syn,anti
and anti,anti denote the stereochemical relations between
the two hexyl groups and the benzyloxy group. The compar-
ison of the syn/anti ratio of methine protons with the inte-
gration ratio of benzyl methylene signals suggested the
formation of two diastereomers 8 and 16, but not anti,anti-
adduct 17 bearing two hexyl groups anti to the benzyloxy
group. Furthermore, the 13C NMR spectrum supported the
formation of the two diastereomers 8 and 16 (d 176.1,
75.7, 60.0, 41.6, 37.1, 33.2 for 8 and d 176.0, 75.6, 60.1,
42.1, 37.0, 33.0 for 16).
2. Results and discussion
The substrate 7 for the key radical reaction mentioned
above was prepared as follows. The Reformatsky reaction
of bromomethacrylate 911 and formaldehyde using indium
gave alcohol 1012 in 79% yield. The oxidation of 10 with
pyridinium chlorochromate yielding the corresponding
aldehyde 11, followed by the Reformatsky reaction with
bromide 9, gave hydroxy ester 12 (54% yield for two steps).
Treatment of 12 with benzyl 2,2,2-trichloroacetimidate
(2 equiv) and trifluoromethanesulfonic acid (0.2 equiv)
gave the corresponding benzyl ether 7 in 70% yield
(Scheme 3).
b
c
a
CH=O
Br
EtO2C
EtO2C
EtO2C
OH
9
10
11
syn syn
n-C5H11
n-C5H11
OR
OBn
In our previous work,4,5c we confirmed the seven-membered
chelate ring formation of the starting material 1 by the
complexation experiment with MgBr2$OEt2 in CDCl3. The
large difference of chemical shift increments, Dd values
[dH (substrate+MgBr2$OEt2)ꢀdH (substrate)] between the
diastereotopic b-methylene protons suggests the formation
of bidentate complexation. However, in the complexation
experiment of 6 with 3 equiv of MgBr2$OEt2, only slight
chemical shift increments were observed. The large DdH
values as shown in Figure 1 suggest that the addition of
6 equiv of Lewis acid is required to achieve the chelate
f
e
EtO2C
d
CO2Et
EtO2C
CO2Et
8
12 R = H
7
R = Bn
OR
X
X
i
R = Bn, X = OH
R = H, X = OH
R = Ms, X = OMs
13
14
15
5
g
h
Scheme 3. Synthesis of meso-7,11-dimethylheptadecane (5). Reagents: (a)
HCH]O, In, H2O–EtOH (1:1), 79%; (b) PCC, AcONa, CH2Cl2; (c) 9, Zn,
aq NH4Cl, 54% yield from 10; (d) BnC(]NH)CCl3, TfOH, cyclohexane–
CH2Cl2 (2:1), 70%; (e) n-C5H11I, n-Bu3SnH, Et3B, MgBr2$OEt2, CH2Cl2,
ꢀ60 ꢁC, 59%, 8:16¼>50:1; (f) DIBAL-H, CH2Cl2, 91%; (g) H2, Pd–C,
ethanol, 100%; (h) MsCl, pyridine, CH2Cl2, 96% and (i) LiAlH4, diethyl
ether; 88%.
+0.09 -0.11
H
+0.25
H
H
H
O
O
O
The radical reaction of 7 with pentyl iodide in the presence
of MgBr2$OEt2 (3 equiv) at 0 ꢁC gave an inseparable dia-
stereomeric mixture of 8 and 16 in 55% yield with a ratio
of 11:1.5 The diastereomeric ratio was determined on the
basis of the integration of 1H NMR signals of benzyl meth-
ylene groups [d 4.43 (major product 8) and 4.46 (minor prod-
uct 16)]. When the amount of the Lewis acid was increased
H
O
HH
O
HH
+0.30
+0.17
+0.40
+0.04
Figure 1. DdH values (ppm) for the substrate 7. DdH¼dH (substrate
7+6 equiv of MgBr2$OEt2)ꢀdH (substrate 7). The dH values were obtained
after sonication of 7 with MgBr2$OEt2 in CDCl3.

8812
H. Nagano et al. / Tetrahedron 63 (2007) 8810–8814
ring formation and the highly diastetreoselective radical
addition reaction.
(25 ml) were added pyridinium chlorochromate (1.7 g,
7.9 mmol) and sodium acetate (130 mg, 1.6 mmol) at
room temperature and the mixture was stirred at room tem-
perature for 4.5 h. The reaction mixture was passed through
a short pad of Florisil, and the eluate was concentrated in va-
cuo until ca. 5 ml. The product containing 11 was used for
the next step without further purification.
The transformation of diester 8 into the pheromone 5 was
performed as follows. The reduction of 8 with diisobutylalu-
minium hydride (DIBAL-H) gave diol 13 in 90% yield. The
hydrogenolysis of the diol over Pd–C gave triol 14 quantita-
tively. Finally, mesylate 15 derived from the triol in 96%
yield was reduced with lithium aluminium hydride to give
4.1.3. Diethyl 4-hydroxy-2,6-dimethyleneheptanedioate
(12). To a solution of the above aldehyde 11 in THF–satd
aq NH4Cl (1:3; 40 ml) was added bromide 9 (1.49 g,
10.5 mmol) at room temperature. To the suspension cooled
to 0 ꢁC was added activated zinc powder (345 mg,
10.5 mmol). After stirring at 0 ꢁC for 10 h, the mixture
was extracted with diethyl ether and the organic layer was
washed with brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the residue
was purified by chromatography on silica gel [eluent: hex-
ane–AcOEt (1:1)] to afford diethyl 4-hydroxy-2,6-dimethyl-
eneheptanedioate (12) (739 mg, 55% yield from alcohol 10)
1
meso-7,11-dimethylheptadecane (5) in 88% yield. The H
and 13C NMR and MS spectral data of the synthetic hydro-
carbon 5 were identical with those reported in the litera-
tures.8
3. Conclusion
meso-7,11-Dimethylheptadecane, a female sex pheromone
component of the spring hemlock looper and the pitch
pine looper, has been synthesized from ethyl 2-(bromo-
methyl)propenoate in nine steps and 14% overall yield. The
key step in the synthesis is the highly diastereoselective
chelation-controlled radical reaction of diethyl 4-benzyl-
oxy-2,6-dimethyleneheptanedioate with pentyl iodide per-
formed in the presence of 6 equiv of MgBr2$OEt2.
1
as an oil; H NMR d 6.27 (2H, d, J¼1.5 Hz, ]CHHꢂ2),
5.68 (2H, d, J¼1.5 Hz, ]CHHꢂ2), 4.22 (4H, q, J¼7.3
Hz, CO2CH2ꢂ2), 3.95 (1H, m, CHOH), 2.64 (1H, d,
J¼4.2 Hz, OH), 2.58 (2H, dd, J¼14.1, 3.9 Hz, CHHC
]Cꢂ2), 2.42 (2H, dd, J¼14.1, 8.3 Hz, CHHC]Cꢂ2), 1.31
(6H, t, J¼7.3 Hz, CH2CH3ꢂ2); 13C NMR d 167.3, 137.3,
127.5, 69.3, 60.9, 39.9, 14.2; MS m/z 239 (M+ꢀOH, 1.4),
211 (M+ꢀOEt, 5.5), 165 (25), 143 (86), 97 (100), 86 (50).
4. Experimental
4.1. General
4.1.4. Diethyl 4-benzyloxy-2,6-dimethyleneheptanedioate
(7). To a solution of alcohol 12 (119 mg, 0.47 mmol) in
cyclohexane–CH2Cl2 (2:1; 4.5 ml) were added benzyl
2,2,2-trichloroacetimidate (0.18 ml, 0.94 mmol) and trifluoro-
methanesulfonic acid (8 ml, 0.09 mmol) at 0 ꢁC. The solution
was stirred at 0 ꢁC for 2.5 h. The product was extracted with
diethyl ether and the organic layer was washed with satd aq
NaHCO3 and brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the residue
was purified by chromatography on silica gel [eluent: hex-
ane–AcOEt (10:1)] to afford diethyl 4-benzyloxy-2,6-di-
methyleneheptanedioate (7) (113 mg, 70% yield) as an oil;
1H NMR d 7.32–7.22 (5H, m, C6H5), 6.22 (2H, d, J¼
1.8 Hz, ]CHHꢂ2), 5.64 (2H, d, J¼1.8 Hz, ]CHHꢂ2),
4.51 (2H, s, CH2C6H5), 4.16 (4H, q, J¼7.3 Hz, CO2CH2ꢂ2),
3.80 (1H, m, OCH), 2.58 (2H, dd, J¼13.7, 7.0 Hz,
]CH2CHHꢂ2), 2.52 (2H, dd, J¼13.7, 5.5 Hz,
]CH2CHHꢂ2), 1.27 (6H, t, J¼7.3 Hz, CH2CH3ꢂ2); 13C
NMR d 166.9, 138.4, 137.3, 128.1, 127.7, 127.3, 76.20,
71.4, 60.7, 37.1, 14.2; MS m/z 347 (M++H, 1.7), 254 (9),
239 (19), 233 (47), 91 (100); HRMS calcd for C20H27O5
[M++H] 347.1858, found 347.1819.
1H NMR spectra were recorded on a JEOL GSX-400
(400 MHz) spectrometer with CDCl3 as the solvent and
tetramethylsilane as an internal standard. 13C NMR spectra
were recorded on the instrument operating at 100.5 MHz
with CDCl3 as the solvent and internal standard (d 77.0).
Mass spectra (EI+) were obtained on a JEOL JMS-700
mass spectrometer. Precoated Merck Kieselgel 60 F254
and Kanto silica gel 60 (spherical neutral) were used for
thin layer chromatography and column chromatography,
respectively.
4.1.1. Ethyl 2-(2-hydroxyethyl)propenoate (10). To a solu-
tionofbromide9(200 mg, 1.0 mmol)ina mixtureofethanol–
H2O (1:1; 2 ml) were added formalin (0.18 ml, 1.8 mmol)
and indium powder (131 mg, 1.1 mmol), and the mixturewas
stirred at room temperature for 22 h. Dilute HCl (1 mol/dm3;
5 ml) was then added. The mixture was stirred for 15 min,
and then the product was extracted with ethyl acetate. The or-
ganic layer was washed with satd aq NaHCO3 and brine, and
then dried over anhydrous sodium sulfate. The solvent was
evaporated in vacuo and the residue was purified by chroma-
tography on silica gel [eluent: AcOEt] to afford ethyl 2-(2-
hydroxyethyl)propenoate (10) (117 mg, 79% yield) as an
oil; 1H NMR d 6.25 (1H, d, J¼1.5 Hz, C]CHH), 5.67 (1H,
d, J¼1.5 Hz, C]CHH), 4.23 (2H, q, J¼6.8 Hz, CH2CH3),
3.75 (2H, q, J¼6.3 Hz, CH2OH), 2.59 (2H, t, J¼6.3 Hz,
CH2CH2OH), 1.31 (3H, t, J¼6.8 Hz, CH3); 13C NMR
d 167.2, 137.4, 126.9, 61.5, 60.9, 35.5, 14.1; MS: m/z 144
(M+, 1), 114 (100), 99 (36), 86 (66), 68 (33).
4.1.5. Diethyl (2R*,4R*,6S*)-4-benzyloxy-2,6-dihexyl-
heptanedioate (8). To a solution of ester 7 (173 mg,
0.5 mmol) in dry CH2Cl2 (8 ml) was added MgBr2$OEt2
(774 mg, 3.0 mmol) and the mixture was stirred at room
temperature for 15 min. To the suspension cooled to
ꢀ60 ꢁC were added pentyl iodide (541 ml, 3.0 mmol),
n-Bu3SnH (540 ml, 2.0 mmol) and Et3B (980 ml, 1.0 mmol).
The mixture was stirred at ꢀ60 ꢁC for 12 h. KF and water
were added and the mixture was stirred at room temperature
for 24 h. After filtration, the solvent was evaporated in vacuo
and the residue was purified by chromatography on silica
4.1.2. Ethyl 2-(formylmethyl)propenoate (11). To a solu-
tion of alcohol 10 (760 mg, 5.3 mmol) in dry CH2Cl2

H. Nagano et al. / Tetrahedron 63 (2007) 8810–8814
8813
gel [eluent: hexane–AcOEt (20:1)] to afford diethyl
(2R*,4R*,6S*)-4-benzyloxy-2,6-dihexylheptanedioate (8)
(146 mg, 59% yield; diastereomeric ratio: >50:1) as an oil;
1H NMR d 7.35–7.25 (5H, m, C6H5), 4.44 (2H, s, CH2C6H5),
4.20–4.10 (4H, m, CO2CH2ꢂ2), 3.37 (1H, m, OCH), 2.58
(2H, m, CHCO2ꢂ2), 1.87 (2H, ddd, J¼14.1, 10.2, 3.9 Hz,
OCHCHHꢂ2), 1.69–1.54 (4H, m, C5H11CHHꢂ2,
OCHCHHꢂ2), 1.45–1.35 (2H, m, C5H11CHHꢂ2), 1.35–
1.20 (16H, m, C4H8CH3ꢂ2), 1.21 (6H, t, J¼6.8 Hz,
CH3ꢂ2), 0.87 (6H, t, J¼7.3 Hz, CH3ꢂ2); 13C NMR
d 176.1, 138.4, 128.1, 127.9, 127.3, 75.7, 71.7, 60.0, 41.6,
37.1, 33.2, 31.6, 29.1, 27.1, 22.5, 14.3, 14.1; MS m/z 491
(M++H, 0.5), 445 (7), 384 (12), 353 (7), 305 (8), 279 (10),
213 (65), 172 (67), 101 (19), 91 (100); HRMS calcd for
C30H51O5 [M++H] 491.3737, found 491.3714.
with water and brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the residue
was purified by chromatography on silica gel [eluent:
hexane–AcOEt (1:1)] to afford (2R*,4R*,6S*)-2-hexyl-4-
methanesulfonyloxy-6-(methanesulfonyloxymethyl)dodecyl
1
methanesulfonate (15) (53.1 mg, 96% yield) as an oil; H
NMR d 5.01 (1H, m, CHOMs), 4.32 (2H, dd, J¼10.2, 4.2 Hz,
CHHOMs), 4.18 (2H, dd, J¼10.2, 4.9 Hz, CHHOMs), 3.06
(3H, s, OSO2CH3), 3.04 (6H, s, OSO2CH3ꢂ2), 1.95 (2H, m,
CHCH2OMsꢂ2), 1.74 (4H, m, CH2COMsꢂ2), 1.35–1.22
(20H, m, C5H10ꢂ2), 0.89 (6H, t, J¼6.8 Hz, CH3ꢂ3); 13C
NMR d 78.5, 71.3, 38.9, 37.2, 36.9, 34.2, 31.7, 31.5, 29.3,
26.6, 22.6, 14.1.
4.1.9. meso-7,11-Dimethylheptadecane (5). To a suspen-
sion of lithium aluminium hydride (18.9 mg, 0.46 mmol)
in dry ether (0.5 ml) was added a solution of mesylate 15
(28 mg, 0.051 mmol) in dry diethyl ether (1.5 ml) at 0 ꢁC.
The mixture was stirred at room temperature, and then water
was added. After filtration through a pad of Celite, the filtrate
was dried over anhydrous sodium sulfate. The solvent was
evaporated in vacuo to afford meso-7,11-dimethylheptade-
4.1.6. (2R*,4R*,6S*)-4-Benzyloxy-2,6-dihexylheptane-
1,7-diol (13). To
a solution of ester 8 (42.2 mg,
0.086 mmol) in dry CH2Cl2 (4 ml) was added DIBAL-H
(0.93 mol/dm3 in hexane; 0.74 ml, 0.69 mmol) at 0 ꢁC.
The mixture was stirred at room temperature for 4 h. Aq
NaOH (10% w/v in water) was added. The product was ex-
tracted with diethyl ether and the organic layer was washed
with aq NaOH (10% w/v in water) and brine, and then dried
over anhydrous sodium sulfate. The solvent was evaporated
in vacuo and the residue was purified by chromatography
on silica gel [eluent: hexane–AcOEt (3:1)] to afford
(2R*,4R*,6S*)-4-benzyloxy-2,6-dihexylheptane-1,7-diol (13)
(31.6 mg, 91% yield) as an oil; 1H NMR d 7.38–7.28 (5H, m,
C6H5), 4.54 (2H, s, PhCH2), 3.70 (1H, m, OCH), 3.53 (2H,
dd, J¼11.0, 3.9 Hz, CHHOHꢂ2), 3.43 (2H, dd, J¼11.0,
6.4 Hz, CHHOHꢂ2), 2.39 (2H, br s, OHꢂ2), 1.74–1.64 (4H,
m, OCHCH2ꢂ2), 1.64–1.54 (2H, m, CHCH2OHꢂ2), 1.27
(20H, m, C5H10ꢂ2), 0.88 (6H, t, J¼6.8 Hz, CH3ꢂ2); 13C
NMR d 137.5, 128.3, 128.0, 127.8, 75.5, 70.7, 66.1, 37.1,
35.9, 31.84, 31.79, 29.6, 26.9, 22.7, 14.1; MS m/z 407
(M++H, 0.1), 297 (12), 252 (9), 155 (61), 91 (100); HRMS
calcd for C26H47O3 [M++H] 407.35.27, found 407.3520.
1
cane (5) (12 mg, 88% yield) as an oil; H NMR d 1.40–
1.02 (28H, m), 0.88 (6H, t, J¼6.8 Hz, CH3ꢂ2), 0.85 (6H, d,
J¼6.8 Hz, CH3ꢂ2); 13C NMR d 37.5, 37.1, 32.8, 32.0, 29.7,
27.1, 24.5, 22.8, 19.8, 14.2; MS m/z 268 (M+, 3.5), 266 (5),
253 (3), 239 (3.5), 225 (2), 211 (3), 197 (2), 183 (42), 112
(35), 85 (44), 71 (100); HRMS calcd for C19H40 [M+]
268.3130, found 268.3085.
References and notes
1. Bell, S.; W€ustenberg, B.; Kaiser, S.; Menges, F.; Netscher, T.;
Pfaltz, A. Science 2006, 311, 642.
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Synthesis of Natural Products; ApSimon, J., Ed.; John Wiley:
New York, NY, 1992; Vol. 9, pp 1–534.
3. (a) Boucher, Y.; Kamekura, M.; Doolittle, W. F. Mol.
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Kyokaishi 2005, 63, 1069.
4.1.7. (2R*,4R*,6S*)-2,6-Dihexylheptane-1,4,7-triol (14).
To a solution of diol 13 (172 mg, 0.43 mmol) in dry ethanol
(8 ml) was added Pd–C (113 mg). After hydrogenation at
room temperature for 24 h, the mixture was filtered through
a pad of Celite. The filtrate was evaporated in vacuo to afford
(2R*,4R*,6R*)-2,6-dihexylheptane-1,4,7-triol (14) (145 mg,
quant.) as an oil. The product was used in the next step with-
4. Kameda, Y.; Nagano, H. Tetrahedron 2006, 62, 9751.
5. (a) Nagano, H.; Toi, S.; Yajima, T. Synlett 1999, 53; (b)
Nagano, H.; Matsuda, M.; Yajima, T. J. Chem. Soc., Perkin
Trans. 1 2001, 174; (c) Nagano, H.; Toi, S.; Hirasawa, T.;
Matsuda, M.; Hirasawa, S.; Yajima, T. J. Chem. Soc., Perkin
Trans. 1 2002, 2525; (d) Nagano, H.; Ohkouchi, H.; Yajima,
T. Tetrahedron 2003, 59, 3649; (e) Yajima, T.; Okada, K.;
Nagano, H. Tetrahedron 2004, 60, 5683.
6. For the isolation of the pheromone, see: (a) Gries, R.; Gries, G.;
Li, J.; Maier, C. T.; Lemmon, C. R.; Slessor, K. N. J. Chem.
Ecol. 1994, 20, 2501; (b) Maier, C. T.; Gries, R.; Gries, G.
J. Chem. Ecol. 1998, 24, 491; (c) Duff, C. M.; Gries, G.;
Mori, K.; Shirai, Y.; Seki, M.; Takikawa, H.; Sheng, T.;
Slessor, K. N.; Gries, R.; Maier, C. T.; Ferguson, D. C.
J. Chem. Ecol. 2001, 27, 431.
1
out further purification. H NMR d 3.99 (1H, m, CHOH),
3.66 (2H, dd, J¼10.5, 3.2 Hz, CHHOHꢂ2), 3.56 (2H, dd,
J¼10.5, 6.8 Hz, CHHOHꢂ2), 1.77 (2H, m, CHCH2OHꢂ2),
1.66–1.43 (4H, m, CH2CHOHꢂ2), 1.40–1.20 (20H, m,
C5H10ꢂ2), 0.88 (6H, t, J¼7.3 Hz, CH3ꢂ2); 13C NMR
d 66.2, 65.2, 40.9, 37.2, 31.9, 31.3, 29.6, 27.3, 22.7, 14.2;
MS m/z 299 (M+ꢀOH, 7), 173 (23), 155 (100); HRMS calcd
for C29H39O2 [M+ꢀOH] 299.2960, found 299.2953.
4.1.8. (2R*,4R*,6S*)-2-Hexyl-4-methanesulfonyloxy-6-
(methanesulfonyloxymethyl)dodecyl methanesulfonate
(15). To a solution of triol 14 (32.1 mg, 0.10 mmol) in dry
CH2Cl2 (1 ml) was added Et3N (47 ml, 0.33 mmol) at 0 ꢁC.
To the mixture was added dropwise methanesulfonyl chlo-
ride (26 ml, 0.33 mmol) over 5 min. The resulting mixture
was stirred at room temperature for 24 h. The mixture was
extracted with CH2Cl2 and the organic layer was washed
7. Shirai, Y.; Seki, M.; Mori, K. Eur. J. Org. Chem. 1999, 3139.
8. For the synthesis of the pheromone, see: (a) Diaz, D. D.;
Martin, V. S. J. Org. Chem. 2000, 65, 7896; (b) Enders, D.;
Schusseler, T. Tetrahedron Lett. 2002, 43, 3467; (c) Chow, S.;
Koenig, W. A.; Kitching, W. Eur. J. Org. Chem. 2004, 1198.
9. Recently we reported the chelation-controlled highly syn-
selective
catalytic
hydrogenation
of
g-hydroxy-a-

8814
H. Nagano et al. / Tetrahedron 63 (2007) 8810–8814
methylenecarboxylic acid esters. We attempted the catalytic
10. For the stereoselective synthesis of syn-4,8-dimethyldecanal,
see: Schreiber, S. L.; Hulin, B. Tetrahedron Lett. 1986, 27, 4561.
11. (a) Villieras, J.; Ranbaud, M. Synthesis 1982, 924; (b)
Hanessian, S.; Park, H.; Yang, R.-Y. Synlett 1997, 351.
12. Grigg, R.; Markandu, J.; Perrior, T.; Surendrakumar, S.;
Warnock, W. J. Tetrahedron 1992, 48, 6829.
hydrogenation of 12 under the reaction conditions yielding
diethyl 4-hydroxy-2,6-dimethylheptanedioate, an alternative
intermediate for the synthesis of the pheromone 5, but the dia-
stereoselectivity of the reaction was not satisfactory. Nagano,
H.; Yokota, M.; Iwazaki, Y. Tetrahedron Lett. 2004, 45, 3035.