Radical mediated stereoselective synthesis of (4R,8R)-4,8-dimethyldecanal, an aggregation pheromone of Tribolium flour beetles

Article abstract of DOI:10.1016/j.tet.2006.07.054

(4R,8R)-4,8-Dimethyldecanal, a common aggregation pheromone of Tribolium flour beetles, has been synthesized from (R)-2,3-O-isopropylideneglyceraldehyde in 11 steps and 7% overall yield. The key step in the synthesis is the highly diastereoselective chela

Full text of DOI:10.1016/j.tet.2006.07.054

Tetrahedron 62 (2006) 9751–9757
Radical mediated stereoselective synthesis of (4R,8R)-
4,8-dimethyldecanal, an aggregation pheromone of
Tribolium flour beetles
*
Yoko Kameda and Hajime Nagano
Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
Received 22 June 2006; revised 14 July 2006; accepted 14 July 2006
Available online 21 August 2006
Abstract—(4R,8R)-4,8-Dimethyldecanal, a common aggregation pheromone of Tribolium flour beetles, has been synthesized from (R)-2,3-O-
isopropylideneglyceraldehyde in11steps and7%overall yield. Thekey stepinthesynthesisisthehighly diastereoselectivechelation-controlled
radical reaction of ethyl (4S,5R)-4-benzyloxy-5,6-(isopropylidenedioxy)-2-methylenehexanoate with ethyl (R)-5-iodo-3-methylpentanoate
performed in the presence of 7 equiv of MgBr2$OEt2.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
synthesized by using the radical addition of alkyl iodide
IV to optically active g-benzyloxy-a-methylenecarboxylic
acid ester I followed by the reduction of the ethoxycarbonyl
group to a methyl group (Scheme 2).
The 1,5-syn-dimethylalkyl motif is ubiquitous in many natu-
ral products such as tocopherols, several insect pheromones,
and membrane lipids of archaebacteria. The stereoselective
construction of the structural motif is therefore of particular
interest1–3 and we intend to apply the chelation-controlled
radical reaction of g-benzyloxy-a-methylenecarboxylic
acid ester I yielding syn-adduct III, recently developed in
our laboratory,4 to the synthesis of these natural products
(Scheme 1). The highly syn-selective addition of alkyl iodide
R2I to I is referred to the H-atom transfer to the outside face of
radical center in the sharply folded seven-membered chelate
intermediate II.4c–e
The first synthesis of (4R,8R)-4,8-dimethyldecanal (1) and
three other stereoisomers from (R)-citronellol and (R)-citro-
nellic acid has established that the absolute configuration of
the pheromone is (4R,8R).7,8 Since the identification of the
structure, several stereoselective syntheses of the pheromone
1 have been reported.9
2. Results and discussion
We now report the radical mediated stereoselective synthesis
of (4R,8R)-4,8-dimethyldecanal (1), a common aggregation
pheromone produced by the male flour beetles of Tribolium
castaneum, Tribolium confusum, Tribolium freemani, and
Tribolium madens (Coleoptera: Tenebrionidae).5,6 The phero-
mone possessing a 1,5-dimethylalkyl motif would be
Scheme 3 shows the synthetic route of (4R,8R)-4,8-di-
methyldecanal (1) starting from (R)-2,3-O-isopropylidene-
glyceraldehyde (2), which is prepared from 1,2:5,6-di-O-
isopropylidene-D-mannitol.10 The Reformatsky reaction of
aldehyde 2 with ethyl 2-(bromomethyl)propeonate (3)
gave an inseparable diastereomeric mixture of g-hydroxy
Br
O
Br
Mg
n-Bu3SnH
Et3B / O2
Bn
R1
Bn
R2
Bn
R1
O
O
O
R2I
O
+
R1
CO2Et
CO2Et
MgBr2•OEt2
CH2Cl2, 0 °C
γ
α
H
syn-III
R2
I
II
Scheme 1. Chelation-controlled diastereoselective radical reactions of a-methylene-g-oxycarboxylic acid esters I with alkyl iodides R2I yielding syn-
adducts III.
Keywords: Tribolium flour beetle; Pheromone; (4R,8R)-4,8-Dimethyldecanal; Radical reaction; 1,3-Asymmetric induction.
* Corresponding author. Fax: +81 3 5978 5715; e-mail: nagano@cc.ocha.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.054

9752
Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
R3
n-Bu3SnH
Et3B / O2
Bn
Bn
R1
O
O
+
R3
MgBr2•OEt2
R1
CO2Et
I
CO2Et
CH2Cl2, 0 °C
I
IV
V
Bn
R1
CO2Et
O
H
O
R3
(4R,8R)-4,8-dimethyldecanal (1)
Scheme 2. Synthetic plan of (4R,8R)-4,8-dimethyldecanal (1).
R
R
O
O
O
a
Br
H
+
CO2Et
+
CO2Et
O
b
O
O
CO2Et
O
O
O
2
3
4 (R = H)
5 (R = H)
b
6 (R = Bn)
7 (R = Bn)
Bn
O
X
d
CO2Et
O
O
11 (X = Me)
14 (X = CH2CO2Et)
c
g
k
+
6
I
X
10 (X = Me)
Bn
O
X
13 (X = CH2CO2Et)
CO2Et
O
O
O
12 (X = Me)
15 (X = CH2CO2Et)
X
Bn
O
X
j
X
O
O
O
16 (X = OH)
17 (X = OTs)
18 (X = H)
19 (X = OH)
e
f
h
i
20 (X = OC(=S)OPh)
21 (X = H)
H
HO
HO
O
(4R,8R)-4,8-dimethyldecanal (1)
22
Scheme 3. Synthetic route of (4R,8R)-4,8-dimethyldecanal (1). Reagents: (a) Zn, THF, aq NH4Cl; (b) PhCH2Br, Ag2O, toluene; (c) n-Bu3SnH, Et3B,
MgBr2$OEt2, CH2Cl2; (d) LiAlH4, diethyl ether; (e) p-TsCl, pyridine, CH2Cl2; (f) LiAlH4, diethyl ether; (g) H2, Pd–C, ethanol; (h) PhOC(]S)Cl, pyridine,
CH2Cl2; (i) n-Bu3SnH, AIBN, toluene, 85 ꢀC; (j) 1 mol dmꢁ3 HCl, THF–H2O (1:1); (k) NaIO4, aq CH3CN.

Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
9753
esters 4 and 5 in a ratio of 2.8:1.11 Treatment of the mixture
+0.09
+0.53
+0.10
H
with benzyl bromide and silver oxide gave a mixture of
benzyl ethers 6 and 7, which was easily separated by silica
gel column chromatography to give 6 in 26% yield from
1,2:5,6-di-O-isopropylidene-D-mannitol. To assign unam-
biguously the stereochemistry of the newly formed chiral
center in the Reformatsky reaction,11 the benzyl ethers 6
and 7 were transformed into d-lactones 8 and 9, respectively,
and their NOE experiments were performed (Scheme 4). For
the lactone 9, NOE enhancements of g-H (6.2%) and d-H
(8.5%) were observed by irradiating d-H and g-H, respec-
tively, while for the lactone 8, irradiation of g-H and d-H
did not enhance the signals of their vicinal methine protons.
The NOE difference spectra of the d-lactones 8 and 9 thus
established the stereochemistry of 6 and 7 as 4,5-anti and
4,5-syn, respectively.
H
Ph
CH
-0.04
-0.01
O
H
H
2 -0.07
H
+0.03
O
CO2CH2CH3
+0.18
H H H
+0.11
O
H3C
CH3
-0.07
+0.12
+0.11
+0.18
Figure 1. Dd values (ppm) for the substrate 6. DdH¼dH (substrate
6+MgBr2$OEt2)ꢁdH (substrate 6). The dH (substrate 6+MgBr2$OEt2) value
was obtained after sonication of 6 with 7 equiv of MgBr2$OEt2 in CDCl3.
dimethyldecanal (1), was carried out using 7 equiv of
MgBr2$OEt2. The desired 2,4-syn-adduct 14 was obtained
in 71% yield and >96% de. The H NMR and 13C NMR
1
spectra of a-methoxy-a-(trifluoromethyl)phenylacetates 24
and 25, which were transformed from 14 via the correspond-
ing alcohol 23, did not show the epimerization of aldehyde 2
during the Reformatsky reaction of 2 with 3 (Scheme 5).
HO
Bn
O
O
O
1) CF3COOH
H
H
δ
γ
CO2Et
O
2) p-TsOH
O
O
Bn
6
8
CO2Et
OR
CO2Et
O
NOE
O
HO
H
Bn
O
O
O
O
1) CF3COOH
14 R = Bn
23 R = H
24 R = -(O=)C(CF3)(OCH3)C6H5-(S)
CO2Et
6.2%
O
2) p-TsOH
H
8.5%
O
Bn
7
25 R = -(O=)C(CF3)(OCH3)C6H5-(R)
9
Scheme 4. Determination of the configurations of 6 and 7.
24
b
a
14
23
The radical reaction of the major diastereomer 6 with 1-
iodo-3-methylbutane (10) was at first performed under the
reaction conditions used in our previous work4 [iodide 10
(3 equiv), n-Bu3SnH (2 equiv), Et3B (1 equiv), MgBr2$OEt2
(3 equiv) in CH2Cl2 at 0 ꢀC] to give the 2,4-syn-adduct 11
and 2,4-anti-adduct 12 in 63% yield and 14:1 diastereomer
ratio. In order to ameliorate the stereoselectivity, the radical
reaction was then performed using 7 equiv of MgBr2$OEt2.
The diastereoselectivity and yield were improved to 11/
12>50:1 and 73%, respectively.
c
25
Scheme 5. Reagents: (a) H2, Pd–C, ethanol; (b) (R)-(ꢁ)-a-methoxy-a-(tri-
fluoromethyl)phenylacetyl chloride, 4-dimethylaminopyridine, pyridine;
(c)(S)-(+)-a-methoxy-a-(trifluoromethyl)phenylacetylchloride, 4-dimethyl-
aminopyridine, pyridine.
The diester 14 was then reduced with lithium aluminium
hydride to give the corresponding diol 16 in 89% yield.
The tosylation of the diol with p-toluenesulfonyl chloride
followed by the reduction with lithium aluminium hydride
gave compound 18 in 76% yield. The hydrogenolysis of
18 over Pd–C gave alcohol 19 quantitatively. The alcohol
was then treated with phenyl chlorothionoformate to give
phenoxythiocarbonyl ester 20, which was then reduced
under radical conditions using AIBN and n-Bu3SnH to
give compound 21 in 71% two-step yield. The acid catalyzed
hydrolysis of 21 followed by the oxidative cleavage of the
resulting diol 22 with sodium periodate gave (4R,8R)-4,8-
dimethyldecanal (1), as an oil, [a]2D3 ꢁ5.7 (c 1.0, CHCl3)
(lit.7b [a]D22.5 ꢁ7.3 (c 2.04, CHCl3)), in 85% two-step yield.
In our previous work,4c we confirmed the seven-membered
chelate ring formation of the starting material I (R1¼Ph)
by the complexation experiment with 3 equiv of
MgBr2$OEt2 in CDCl3. The largedifference in chemical shift
increments Dd¼[dH (substrate+MgBr2$OEt2)ꢁdH (sub-
strate)] by adding the Lewis acid between the diastereotopic
b-methylene protons suggests the formation of bidentate
complexation. However, in the complexation experiment of
6 with 3 equiv of MgBr2$OEt2, only slight chemical shift
increments were observed. The results of the complexation
experiment of 6 with 7 equiv of MgBr2$OEt2 are shown in
Figure 1. The large Dd values suggest that the addition of
7 equiv of the Lewis acid is required to achieve the chelate
ring formation and the highly diastereoselective radical addi-
tion reaction.12
The IR, H NMR, 13C NMR, and MS spectral data of the
1
synthetic aldehyde 1 were identical with those of (4R,8R)-
and (4S,8S)-4,8-dimethyldecanals reported in the litera-
tures.7,9,14
We have thus synthesized (4R,8R)-4,8-dimethyldecanal (1)
from (R)-2,3-O-isopropylideneglyceraldehyde (2) in 11
steps and 7% overall yield.
The radical addition of ethyl (R)-5-iodo-3-methylpentanoate
(13)13 to 6, i.e., the key step in the synthesis of (4R,8R)-4,8-

9754
Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
3. Conclusion
d 14.22, 25.30, 26.58, 36.77, 60.93, 66.00, 70.62, 78.40,
109.36, 127.69, 136.64, 167.08.
We have synthesized (4R,8R)-4,8-dimethyldecanal (1) from
(R)-2,3-O-isopropylideneglyceraldehyde (2), easily pre-
pared from D-mannitol, in 11 steps and 7% overall yield.
The key step in the synthesis is the highly diastereoselective
chelation-controlled radical reaction of g-benzyloxy-a-
methylenecarboxylic acid ester 6 and ethyl (R)-5-iodo-3-
methylpentanoate (13) performed in the presence of 7 equiv
of MgBr2$OEt2.
4.1.2. Ethyl (4S,5R)- and (4R,5R)-4-benzyloxy-5,6-(iso-
propylidenedioxy)-2-methylenehexanoates (6) and (7).
To a solution of alcohols 4 and 5 (29.2 mg, 0.12 mmol) in
toluene (2 cm3) were added benzyl bromide (0.05 cm3,
0.36 mmol) and freshly prepared silver oxide (84.5 mg,
0.36 mmol). The mixture was stirred at room temperature
for 48 h and then filtered through a pad of Celite. The filtrate
was evaporated in vacuo and the residue was purified by col-
umn chromatography on silica gel [eluent: hexane–ethyl
acetate (20:1)] to give 6 (14 mg) and 7 (8.3 mg), and 6
(12.3 mg). Major diastereomer 6. [a]2D3 +22.0 (c 1.95,
CHCl3); 1H NMR d 1.28 (3H, t, J¼7.0 Hz, CH3), 1.35
(3H, s, CH3), 1.43 (3H, s, CH3), 2.46 (1H, dd, J¼14.2,
7.8 Hz, CHHC]CH2), 2.72 (1H, ddd, J¼14.2, 4.4, 0.8 Hz,
CHHC]CH2), 3.73 (1H, m, CH–O), 3.90 (1H, dd, J¼7.8,
6.0 Hz, CHH–O), 4.03 (1H, d, J¼7.8, 6.4 Hz, CHH–O),
4.12 (1H, dd, J¼10.5, 6.0 Hz, CH–O), 4.16 (2H, q,
J¼7.0 Hz, CH2–O), 4.59 (2H, s, PhCH2O), 5.68 (1H, d,
J¼1.2 Hz, C]CHH), 6.23 (1H, d, J¼1.2 Hz, C]CHH),
7.28–7.32 (5H, m, Ph); 13C NMR d 14.24, 25.36, 26.56,
34.25, 60.72, 66.00, 72.98, 77.42, 77.82, 109.12, 127.50,
127.63, 127.78, 128.17, 136.91, 138.16, 166.91; MS m/z
319 (M+ꢁMe, 26%), 233 (95), 101 (58), 91 (100); HRMS
calcd for C18H23O5 [M+ꢁMe] 319.1545, found 319.1552.
4. Experimental
4.1. General
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).
IR spectra were taken on a SIMADZU FTIR-8700 spectro-
meter. 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, respec-
tively.
1
Minor diastereomer 7. H NMR d 1.28 (3H, t, J¼7.2 Hz,
4.1.1. Ethyl (4S,5R)- and (4R,5R)-4-hydroxy-5,6-(iso-
propylidenedioxy)-2-methylenehexanoates (4) and (5).
(R)-2,3-O-Isopropylideneglyceraldehyde (2) was prepared
from 1,2:5,6-di-O-isopropylidene-D-mannitol (2.87 g,
10.9 mmol) following the reported procedures.10 To a solu-
tion of the aldehyde 2 in THF (36 cm3) were added ethyl
2-(bromomethyl)propeonate (3) (5.95 g, 30.8 mmol), satu-
rated aqueous NH4Cl (57 cm3), and activated zinc powder
(3.34 g, 51.3 mmol) and the mixture was stirred at 0 ꢀC for
3 h. The product was extracted with ethyl acetate and the
extract was washed with saturated brine and then dried
over anhydrous sodium sulfate. The solvent was evaporated
in vacuo and the residue was purified by column chromato-
graphy on silica gel [eluent: hexane–ethyl acetate (8:1)] to
give an inseparable mixture of 4 and 5 (3.38 g, 63% yield
from 1,2:5,6-di-O-isopropylidene-D-mannitol; 4/5¼2.8:1)
as an oil. MS m/z 229 (M+ꢁMe, 68%), 143 (94), 123 (71),
101 (100); HRMS calcd for C11H17O5 [M+ꢁMe]
229.1076, found 229.1082. Major diastereomer 4. 1H
NMR d 1.32 (3H, t, J¼7.2 Hz, CH3), 1.36 (3H, s, CH3),
1.43 (3H, s, CH3), 2.37 (1H, ddd, J¼14.2, 8.4, 0.8 Hz,
CHHC]CH2), 2.70 (1H, ddd, J¼14.2, 3.6, 0.8 Hz,
CHHC]CH2), 2.86 (1H, d, J¼3.6 Hz, OH), 3.75–4.10
(4H, m, CH(–O)CHOH, CO2CH2CH3), 4.21 (1H, dd,
J¼14.2, 7.0 Hz, CHHO), 4.25 (1H, dd, J¼14.2, 7.0 Hz,
CHHO), 5.74 (1H, d, J¼1.6 Hz, C]CHH), 6.29 (1H, d,
J¼1.2 Hz, C]CHH); 13C NMR d 14.20, 25.30, 26.67,
36.15, 61.19, 65.94, 71.28, 78.10, 109.12, 128.00, 136.92,
167.89. Minor diastereomer 5. 1H NMR d 1.31 (3H, t,
J¼7.2 Hz, CH3), 1.37 (3H, s, CH3), 1.44 (3H, s, CH3),
2.41–2.49 (2H, m, CH2C]CH2), 2.86 (1H, d, J¼3.6 Hz,
OH), 3.75–4.10 (4H, m, CH(–O)CHOH, CO2CH2CH3),
4.20 (1H, dd, J¼14.2, 6.8 Hz, CHHO), 4.23 (1H, dd,
J¼14.2, 6.8 Hz, CHHO), 5.72 (1H, d, J¼1.6 Hz,
C]CHH), 6.28 (1H, d, J¼1.2 Hz, C]CHH); 13C NMR
CH3), 1.37 (3H, s, CH3), 1.45 (3H, s, CH3), 2.42–2.52
(2H, m, CH2C]CH2), 3.63 (1H, m, CH–O), 3.79 (1H, dd,
J¼8.0, 7.3 Hz, CHH–O), 3.99 (1H, d, J¼8.0, 6.5 Hz,
CHH–O), 4.13–4.23 (3H, m, CH–O, CH2–O), 4.59 (1H, d,
J¼11.7 Hz, PhCHH–O), 4.70 (1H, d, J¼11.7 Hz, PhCHH–
O), 5.69 (1H, d, J¼1.2 Hz, C]CHH), 6.23 (1H, d,
J¼1.6 Hz, C]CHH), 7.26–7.36 (5H, m, Ph); 13C NMR
d 14.24, 25.47, 26.53, 34.09, 60.72, 65.88, 72.93, 77.95,
78.05, 109.30, 127.41, 127.83, 127.88, 128.11, 136.64,
138.38, 166.80. MS m/z 319 (M+ꢁMe, 25%), 233 (94),
101 (54), 91 (100); HRMS calcd for C18H23O5 [M+ꢁMe]
319.1545, found 319.1597.
4.1.3. (5S,6R)-5-Benzyloxy-6-hydroxymethyl-3-methyl-
enetetrahydropyran-2-one (8). To a solution of
6
(18.2 mg, 0.054 mmol) in THF–H2O (4:1, 1 cm3) was added
trifluoroacetic acid at 0 ꢀC. The solution was stirred at room
temperature overnight and then the product was extracted
with ethyl acetate and the extract was washed with saturated
brine and dried over anhydrous sodium sulfate. Concentra-
tion of the solution gave a crude product, which was used
without further purification. To a solution of the crude
product in benzene (1 cm3) was added catalytic amount of
p-toluenesulfonic acid. The mixture was stirred at room
temperature overnight. The solvent was evaporated in vacuo
and the residue was purified by column chromatography on
silica gel [eluent: hexane–ethyl acetate (2:1)] to give 8
(6.9 mg, 51%) as an oil. 1H NMR d 2.66 (1H, m,
CHHCHOBn), 3.03 (1H, m, CHHCHOBn), 3.85 (1H, m,
CHOBn), 3.86 (1H, dd, J¼12.3, 3.4 Hz, CHHOH), 3.93
(1H, dd, J¼12.3, 3.4 Hz, CHHOH), 4.34 (1H, dt, J¼7.8,
3.4 Hz, CHCH2OH), 4.60 (1H, d, J¼11.5 Hz, PhCHH),
4.68 (1H, d, J¼11.5 Hz, PhCHH), 5.65 (1H, m, C]CHH),
6.46 (1H, m, C]CHH), 7.30–7.39 (5H, m, Ph); 13C NMR
d 33.16, 61.74, 70.14, 71.50, 82.14, 127.72, 128.06,

Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
9755
128.52, 130.18, 131.19, 137.20, 164.53; MS m/z 248 (M+,
14%), 124 (15), 97 (41), 91 (100); HRMS calcd for
C14H16O4 [M+] 248.1049, found 248.1055.
13 (210 mg, 0.78 mmol) in the presence of MgBr2$OEt2
(453 mg, 1.75 mmol) as described above gave 14 (85 mg,
71% yield; 96% de) as an oil. [a]2D3 ꢁ3.0 (c 2.0, CHCl3);
1H NMR d 0.91 (3H, d, J¼6.3 Hz, CH3), 1.22 (3H, t,
J¼7.3 Hz, CH3), 1.25 (3H, t, J¼7.3 Hz, CH3), 1.35 (3H, s,
CH3), 1.42 (3H, s, CH3), 1.13–1.62 (7H, m), 1.92–1.99
(2H, m, CH2C]O), 2.07 (1H, dd, J¼14.7, 7.8 Hz, CHH),
2.26 (1H, dd, J¼14.7, 5.8 Hz, CHH), 2.65 (1H, m,
CHC]O), 3.52 (1H, m, CHOBn), 3.86 (1H, dd, J¼8.0,
6.5 Hz, CHH–O), 4.00–4.16 (6H, m, CH–O, CHH–O,
2ꢂCH2–O), 4.55 (1H, d, J¼11.0 Hz, PhCHH), 4.64 (1H,
d, J¼11.0 Hz, PhCHH), 7.27–7.34 (5H, m, Ph); 13C NMR
d 14.41, 19.75, 24.64, 25.36, 26.65, 30.30, 33.59, 33.95,
36.57, 41.49, 41.87, 60.13, 60.20, 66.08, 73.34, 77.59,
77.68, 109.02, 127.51, 127.80, 128.19, 138.25, 172.94,
175.85; MS m/z 463 (M+ꢁMe, 22%), 377 (95), 285 (46),
101 (45), 91 (100); HRMS calcd for C26H39O7 [M+ꢁMe]
463.2695, found 463.2740.
4.1.4. (5R,6R)-5-Benzyloxy-6-hydroxymethyl-3-methyl-
enetetrahydropyran-2-one (9). To a solution of
7
(12.9 mg, 0.039 mmol) in THF–H2O (4:1, 1 cm3) was added
trifluoroacetic acid at 0 ꢀC. The solution was stirred at room
temperature overnight and then the product was extracted
with ethyl acetate and the extract was washed with saturated
brine and dried over anhydrous sodium sulfate. Evaporation
of the solvent in vacuo gave the product, which was used
without further purification. To a solution of the product in
benzene (1 cm3) was added catalytic amount of p-toluene-
sulfonic acid. The mixture was stirred at room temperature
overnight. The solvent was evaporated in vacuo and the resi-
due was purified by column chromatography on silica gel
[eluent: hexane–ethyl acetate (2:1)] to give 9 (3.5 mg,
1
37%) as an oil. H NMR d 2.65 (1H, m, CHHCHOBn),
3.07 (1H, dd, J¼16.4, 3.9 Hz, CHHCHOBn), 3.78 (1H, dd,
J¼11.9, 5.1 Hz, CHHOH), 3.93 (1H, m, CHOBn), 3.99
(1H, dd, J¼11.9, 6.6 Hz, CHHOH), 4.42 (1H, d,
J¼12.1 Hz, PhCHH), 4.45 (1H, m, CHCH2OH), 4.66 (1H,
d, J¼12.1 Hz, PhCHH), 5.63 (1H, m, C]CHH), 6.52 (1H,
m, C]CHH), 7.28–7.38 (5H, m, Ph); 13C NMR d 31.88,
62.42, 69.33, 70.22, 82.00, 127.69, 128.09, 128.53,
130.31, 130.57, 137.03, 164.16; MS m/z 248 (M+, 7%),
124 (18), 97 (27), 91 (100); HRMS calcd for C14H16O4
[M+] 248.1049, found 248.1058.
4.1.7. (2R,6S)-2-[(2S,3R)-2-Benzyloxy-3,4-(isopropylid-
enedioxy)butyl]-6-methyloctane-1,8-diol (16). To a solu-
tion of diester 14 (248 mg, 0.52 mmol) in dry diethyl ether
(13 cm3) was added lithium aluminium hydride (3.3 equiv)
at 0 ꢀC and the mixture was stirred at room temperature
for 12 h. To the mixture cooled to 0 ꢀC were added dropwise
water, then 15% aqueous sodium hydroxide. After filtration
through a pad of Celite, the filtrate was dried over anhydrous
sodium sulfate. The solvent was evaporated in vacuo and the
residue was purified by column chromatography on silica gel
[eluent: hexane–ethyl acetate (2:1)] to give diol 16 (181 mg,
89%) as an oil. [a]D23 ꢁ0.52 (c 2.2, CHCl3); 1H NMR d 0.88
(3H, d, J¼6.3 Hz, CH3), 1.36 (3H, s, CH3), 1.11–1.40 (7H,
m, (CH2)3CH), 1.43 (3H, s, CH3), 1.44–1.64 (4H, m,
2ꢂCH2), 1.73 (1H, m, CH), 3.42 (1H, dd, J¼11.2, 6.4 Hz,
CH–O), 3.51 (1H, dd, J¼11.2, 4.4 Hz, CH–O), 3.63–3.72
(3H, m, CH–O, CH2–O), 3.86–4.18 (3H, m, CH–O, CH2–
O), 4.61 (1H, d, J¼11.3 Hz, PhCHH), 4.71 (1H, d,
J¼11.3 Hz, PhCHH), 7.26–7.37 (5H, m, Ph); 13C NMR
d 19.71, 24.26, 25.28, 26.55, 29.36, 32.26, 33.54, 37.18,
39.91, 61.10, 65.63, 66.31, 72.80, 78.05, 109.02, 127.79,
127.96, 128.38, 137.87; MS m/z 379 (M+ꢁMe, 4%), 185
(91), 101 (24), 91 (100); HRMS calcd for C22H35O5
[M+ꢁMe] 379.2485, found 379.2516.
4.1.5. Ethyl (2R)-2-[(2S,3R)-2-benzyloxy-3,4-(isopropyl-
idenedioxy)butyl]-6-methyl-heptanoate (11). To a solution
of a-methylene ester 6 (21.5 mg, 0.064 mmol) in dry
CH2Cl2 (1.3 cm3) was added MgBr2$OEt2 (117 mg,
0.45 mmol) under N2 and the mixture was stirred at room
temperature for 15 min. To the suspension cooled to 0 ꢀC
were added 1-iodo-3-methylbutane (10) (0.026 cm3,
0.19 mmol), n-Bu3SnH (0.036 cm3, 0.13 mmol), and Et3B
(0.064 cm3, 1.0 mol dmꢁ3 in hexane). The mixture was
stirred at 0 ꢀC for 6 h. KF and water were added and the mix-
ture was stirred at room temperature overnight. After filtra-
tion through a pad of Florisil, the filtrate was evaporated
in vacuo and the residue was purified by column chromato-
graphy on silica gel [2 g; eluent: hexane then hexane–ethyl
acetate (30:1)] to give a mixture of 11 and 12 (19 mg, 73%
yield; 11/12>50:1) as an oil. 1H NMR d 0.85 (6H, d,
J¼6.3 Hz, 2ꢂCH3), 1.22 (3H, t, J¼7.0 Hz, CH3), 1.13–
1.65 (8H, m, CHHCH(CH2)3CH(CH3)2), 1.35 (3H, s,
CH3), 1.42 (3H, s, CH3), 1.95 (1H, ddd, J¼14.2, 11.3,
3.0 Hz, CHH), 2.68 (1H, m, CHC]O), 3.52 (1H, m, CH–
O), 3.88 (1H, dd, J¼8.0, 7.6 Hz, CHH–O), 4.00–4.14 (4H,
m, CHH–O, CH–O, CH2–O), 4.55 (1H, d, J¼11.0 Hz,
PhCHH), 4.65 (1H, d, J¼11.0 Hz, PhCHH), 7.26–7.34
(5H, m, Ph); 13C NMR d 14.39, 22.57, 22.66, 25.02, 25.33,
26.59, 27.84, 33.72, 33.98, 38.77, 41.54, 60.13, 66.06,
73.36, 77.62, 77.73, 109.04, 127.54, 127.85, 128.23,
138.34, 176.09; MS m/z 391 (M+ꢁMe, 13%), 305 (76),
101 (32), 91 (100); HRMS calcd for C23H35O5 [M+ꢁMe]
391.2485, found 391.2504.
4.1.8. (2R,3S,5R,9S)-3-Benzyloxy-1,2-(isopropylidene-
dioxy)-9-methyl-11-(p-toluenesulfonyloxy)-5-(p-toluene-
sulfonyloxymethyl)undecane (17). To a solution of diol 16
(181 mg, 0.46 mmol) in dry CH2Cl2 (7 cm3) were added
pyridine (0.3 cm3) and p-toluenesulfonyl chloride (879 mg,
4.6 mmol) at 0 ꢀC. The solution was stirred at room temper-
ature overnight. After dilution with water, the product was
extracted with chloroform. The extract was washed with
water, saturated sodium hydrogencarbonate solution, and
saturated brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the resi-
due was purified by column chromatography on silica gel
[eluent: hexane–ethyl acetate (6:1)] to give tosylate 17
1
(294 mg, 91%) as an oil. [a]2D3 ꢁ7.5 (c 2.1, CHCl3); H
NMR d 0.74 (3H, d, J¼6.1 Hz, CH3), 0.97–1.48 (10H, m),
1.34 (3H, s, CH3), 1.41 (3H, s, CH3), 1.60 (1H, m, CH),
1.80 (1H, m, CH), 2.44 (3H, s, CH3), 2.45 (3H, s, CH3),
3.49 (1H, m, CH–O), 3.77 (1H, dd, J¼9.8, 4.9 Hz, CH–O),
3.83 (2H, m, CH–O), 3.97–4.11 (4H, m, CH–O), 4.45 (1H,
4.1.6. Diethyl (2R,6S)-2-[(2S,3R)-2-benzyloxy-3,4-(iso-
propylidenedioxy)butyl]-6-methyl-1,8-octanedioate (14).
The radical reaction of 6 (83 mg, 0.25 mmol) with iodide

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Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
1
d, J¼11.7 Hz, PhCHH), 4.67 (1H, d, J¼11.7 Hz, PhCHH),
7.25–7.38 (9H, m, Ar), 7.73 (2H, d, J¼8.3 Hz, Ar), 7.78
(2H, d, J¼8.3 Hz, Ar); 13C NMR d 19.01, 21.69, 23.74,
25.23, 26.45, 29.10, 31.78, 32.44, 33.91, 35.67, 36.61,
65.70, 68.88, 71.92, 72.88, 76.06, 78.11, 108.98, 127.66,
127.77, 127.78, 127.84, 128.29, 129.75, 132.75, 133.01,
138.13, 144.58, 144.66.
(c 1.74, CHCl3); H NMR d 0.85 (3H, d, J¼6.4 Hz, CH3),
0.86 (3H, d, J¼6.4 Hz, CH3), 0.98 (3H, d, J¼6.8 Hz,
CH3), 1.22–1.43 (10H, m, 4ꢂCH2, 2ꢂCH), 1.39 (3H, s,
CH3), 1.48 (3H, s, CH3), 1.62 (1H, m, CH), 1.84 (1H, ddd,
J¼14.1, 10.0, 3.9 Hz, CH), 3.94 (1H, dd, J¼8.3, 6.4 Hz,
CH–O), 4.12 (1H, m, CH–O), 4.33 (1H, m, CH–O), 5.69
(1H, m, PhOC(]S)OCH), 7.09–7.44 (5H, m, Ph); 13C
NMR d 11.49, 19.32, 19.78, 24.37, 25.32, 26.32, 29.03,
29.51, 34.42, 36.83, 37.36, 37.86, 65.55, 76.91, 82.48,
109.86, 121.87, 126.47, 129.41, 153.28, 195.09; MS m/z
393 (M+ꢁMe, 10%), 254 (54), 239 (56), 197 (32), 179
(47), 149 (48), 127 (100), 123 (45), 101 (55), 97 (47), 69
(95); HRMS calcd for C22H33O4S [M+ꢁMe] 393.2099,
found 393.2053.
4.1.9. (2R,3S,5R,9R)-3-Benzyloxy-1,2-(isopropylidene-
dioxy)-5,9-dimethylundecane (18). To a solution of
tosylate 17 (134.3 mg, 0.19 mmol) in dry diethyl ether
(10 cm3) was added lithium aluminium hydride (3.3 equiv)
at 0 ꢀC. The mixture was stirred at room temperature for
12 h. To the mixture cooled to 0 ꢀC were added dropwise
water and then 15% aqueous sodium hydroxide. After filtra-
tion through a pad of Celite, the filtrate was dried over anhy-
drous sodium sulfate. The solvent was evaporated in vacuo
and the residue was purified by column chromatography
on silica gel [eluent: hexane–ethyl acetate (40:1)] to give
18 (57.3 mg, 83%) as an oil. [a]2D3 ꢁ6.6 (c 1.8, CHCl3); 1H
NMR d 0.83 (6H, d, J¼6.4 Hz, 2ꢂCH3), 0.85 (3H, t,
J¼7.3 Hz, CH3), 1.03–1.66 (12H, m, 5ꢂCH2, 2ꢂCH),
1.37 (3H, s, CH3), 1.43 (3H, s, CH3), 3.70 (1H, dt, J¼10.0,
3.4 Hz, CHOBn), 3.94 (1H, dd, J¼7.8, 7.3 Hz, CHH–O),
4.02 (1H, dd, J¼7.8, 6.3 Hz, CHH–O), 4.10 (1H, m, CH–
O), 4.59 (1H, d, J¼11.2 Hz, PhCHH), 4.77 (1H, d,
J¼11.2 Hz, PhCHH), 7.27–7.34 (5H, m, Ph); 13C NMR
d 11.47, 19.31, 19.41, 24.42, 25.43, 26.53, 29.12, 29.49,
34.42, 36.87, 38.25, 39.43, 65.59, 73.41, 76.62, 79.08,
108.84, 127.47, 127.74, 128.23, 138.66; MS m/z 347
(M+ꢁMe, 16%), 261 (23), 101 (73), 91 (100); HRMS calcd
for C22H35O3 [M+ꢁMe] 347.2587, found 347.2578.
4.1.12. (2S,5R,9R)-1,2-(Isopropylidenedioxy)-5,9-
dimethylundecane (21). To a solution of 20 (23.8 mg,
0.059 mmol) in dry toluene (2 cm3) were added n-Bu3SnH
(0.027 cm3, 0.12 mmol) and AIBN (12.8 mg, 0.064 mmol).
The mixture was stirred at 85 ꢀC for 3 h. KF and water
were then added and the reaction mixture was stirred at
room temperature overnight. After filtration though a pad
of Florisil, the filtrate was evaporated in vacuo and the resi-
due was purified by column chromatography on silica gel to
give 21 (14.1 mg, 95%) as an oil. [a]2D3 +10.8 (c 1.95,
1
CHCl3); H NMR d 0.84 (3H, d, J¼6.9 Hz, CH3), 0.85
(3H, t, J¼7.6 Hz, CH3), 0.87 (3H, d, J¼6.3 Hz, CH3),
1.08–1.45 (13H, m, 5ꢂCH2, 3ꢂCH), 1.36 (3H, s, CH3),
1.41 (3H, s, CH3), 1.68 (1H, m, CH), 3.52 (1H, m, CH–O),
4.02–4.07 (2H, m, CH2–O); 13C NMR d 11.48, 19.32,
19.67, 24.47, 25.81, 27.02, 29.50, 31.17, 32.82, 32.90,
34.44, 36.95, 37.19, 69.58, 76.49, 108.52; MS m/z 241
(M+ꢁMe, 100%), 101 (9); HRMS calcd for C15H29O2
[M+ꢁMe] 241.2246, found 241.2218.
4.1.10. (2R,3S,5R,9R)-1,2-(Isopropylidenedioxy)-5,9-
dimethylundecan-3-ol (19). A solution of 18 (47.2 mg,
0.13 mmol) in dry ethanol (5 cm3) was stirred with Pd–C
(35.5 mg, 0.032 mmol) under hydrogen atmosphere at
room temperature for 12 h. The mixture was filtered through
a pad of Celite and the filtrate was concentrated in vacuo to
give 19 in quantitative yield. [a]2D3 ꢁ0.73 (c 1.86, CHCl3); 1H
NMR d 0.84 (3H, d, J¼6.4 Hz, CH3), 0.85 (3H, t, J¼7.3 Hz,
CH3), 0.90 (3H, d, J¼6.8 Hz, CH3), 1.05–1.69 (12H, m,
5ꢂCH2, 2ꢂCH), 1.37 (3H, s, CH3), 1.43 (3H, s, CH3),
1.92 (1H, br s, OH), 3.87–4.02 (4H, m, CH2–O, CH–O,
CHOH); 13C NMR d 11.47, 19.09, 19.30, 24.43, 25.37,
26.52, 29.18, 29.48, 34.42, 36.88, 38.24, 39.70, 64.44,
68.29, 79.15, 108.83; MS m/z 257 (M+ꢁMe, 100%), 229
(18), 101 (13); HRMS calcd for C15H29O3 [M+ꢁMe]
257.2117, found 257.2121.
4.1.13. (2S,5R,9R)-5,9-Dimethyl-1,2-undecanediol (22).
To a solution of 21 (32.1 mg, 0.12 mmol) in THF–H2O
(1:1, 2 cm3) was added 1 mol dmꢁ3 HCl at 0 ꢀC. The solution
was stirred at room temperature overnight. The reaction mix-
ture was then extracted with ethyl acetate. The extract was
washed with saturated brine, and then dried over anhydrous
sodium sulfate. The solvent was evaporated in vacuo and
the residue was purified by column chromatography on silica
gel [eluent: hexane–ethyl acetate (3:1)] to give 22 (24.0 mg,
89%) as an oil. [a]D23 ꢁ3.4 (c 1.0, CHCl3); 1H NMR d 0.84
(3H, d, J¼5.9 Hz, CH3), 0.85 (3H, t, J¼7 Hz, CH3), 0.87
(3H, d, J¼6.8 Hz, CH3), 1.06–1.45 (14H, m, 6ꢂCH2,
2ꢂCH), 2.02 (1H, br s, OH), 2.13 (1H, br s, OH), 3.45 (1H,
m, CHOH), 3.66–3.68 (2H, m, CH2OH); 13C NMR
d 11.48, 19.32, 19.63, 24.51, 29.50, 30.75, 32.73, 32.87,
34.44, 36.96, 37.34, 66.89, 72.66; MS m/z 185 (M+ꢁCH2OH,
100%), 111 (43), 97 (64), 83 (56), 69 (50); HRMS calcd for
C12H25O [M+ꢁCH2OH] 185.1905, found 185.1854.
4.1.11. (2R,3S,5R,9R)-3-Phenoxythiocarbonyloxy-1,2-
(isopropylidenedioxy)-5,9-dimethylundecane (20). To
a solution of alcohol 19 (55.5 mg, 0.20 mmol) in dry
CH2Cl2 (3 cm3) were added dry pyridine (0.050 cm3,
0.60 mmol) and O-phenyl chlorothionoformate (0.032 cm3,
0.23 mmol) at 0 ꢀC. The solution was stirred at room tem-
perature for 3 h. The reaction mixture was then washed
with water, saturated sodium hydrogencarbonate solution,
and saturated brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the residue
was purified by column chromatography on silica gel [elu-
ent: hexane–ethyl acetate (60:1)] to give phenoxythio-
carbonyl ester 20 (62.1 mg, 75%) as an oil. [a]2D3 ꢁ18.7
4.1.14. (4R,8R)-4,8-Dimethyldecanal (1). To a solution of
22 (24.0 mg, 0.11 mmol) in aqueous acetonitrile (60%,
2 cm3) was added NaIO4 (18.4 mg, 0.079 mmol) at 0 ꢀC
and the mixture was stirred at 0 ꢀC for 1 h. The reaction mix-
ture was then filtered through a pad of Celite and extracted
with chloroform. The extract was washed with water and
saturated brine, and then dried over anhydrous sodium
sulfate. The solvent was evaporated in vacuo and the resi-
due was purified by column chromatography on silica gel

Y. Kameda, H. Nagano / Tetrahedron 62 (2006) 9751–9757
9757
4. (a) Nagano, H.; Toi, S.; Yajima, T. Synlett 1999, 53–54; (b)
Nagano, H.; Matsuda, M.; Yajima, T. J. Chem. Soc., Perkin
Trans. 1 2001, 174–182; (c) Nagano, H.; Toi, S.; Hirasawa,
T.; Matsuda, M.; Hirasawa, S.; Yajima, T. J. Chem. Soc.,
Perkin Trans. 1 2002, 2525–2538; (d) Nagano, H.; Ohkouchi,
H.; Yajima, T. Tetrahedron 2003, 59, 3649–3663; (e) Yajima,
T.; Okada, K.; Nagano, H. Tetrahedron 2004, 60, 5683–5693.
5. For the isolation of (4R,8R)-4,8-dimethyldecanal (1), see:
(a) Suzuki, T. Agric. Biol. Chem. 1980, 44, 2519–2520;
(b) Suzuki, T. Agric. Biol. Chem. 1981, 45, 1357–1363;
(c) Suzuki, T.; Nakakita, H.; Kuwahara, Y. Appl. Entomol.
Zool. 1987, 22, 340–347; (d) Arnaud, L.; Lognay, G.;
Verscheure, M.; Leenaers, L.; Gaspar, C.; Haubruge, E.
J. Chem. Ecol. 2002, 28, 523–532.
6. For the biosynthesis of (4R,8R)-4,8-dimethyldecanal (1), see:
Kim, J.; Matsuyama, S.; Suzuki, T. J. Chem. Ecol. 2005, 31,
1381–1400.
7. For the synthesis of four possible stereoisomers of 4,8-di-
methyldecanal and the absolute configuration of the pheromone,
see: (a) Suzuki, T.; Mori, K. Appl. Entomol. Zool. 1983, 18,
134–136; (b) Mori, K.; Kuwahara, S.; Ueda, H. Tetrahedron
1983, 39, 2439–2444; (c) Levinson, H. Z.; Mori, K.
Naturwissenschaften 1983, 70, 190–192.
[eluent: hexane–ethyl acetate (60:1)] to give (4R,8R)-4,8-di-
methyldecanal (1) (18.5 mg, 91%) as an oil. [a]2D3 ꢁ5.6 (c
1.1, CHCl3); IR (neat) 2961, 2929, 2714, 1712, 1463,
1
1379 cmꢁ1; H NMR d 0.84 (3H, d, J¼6.3 Hz, CH3), 0.85
(3H, d, J¼7.2 Hz, CH3), 0.88 (3H, d, J¼5.6 Hz, CH3),
1.04–1.14 (12H, m, 5ꢂCH2, 2ꢂCH), 2.40–2.46 (2H, m,
CH2CH]O), 9.78 (1H, t, J¼1.2 Hz, CH]O); 13C NMR
d 11.47, 19.30, 19.45, 24.43, 28.92, 29.48, 32.46, 34.43,
36.88, 37.07, 41.77, 202.95; MS m/z 184 (M+, 1%), 140
(67), 111 (42), 85 (54), 81 (57), 70 (90), 57 (100); HRMS
calcd for C12H24O [M+] 184.1827, found 184.1802.
4.1.15. a-Methoxy-a-(trifluoromethyl)phenylacetate 24.
1H NMR d 0.88 (3H, d, J¼6.3 Hz, CH3), 1.00–1.40 (4H,
m), 1.25 (3H, t, J¼7.3 Hz, CH3), 1.29 (3H, t, J¼7.0 Hz,
CH3), 1.33 (3H, s, CH3), 1.41 (3H, s, CH3), 1.46–1.60
(1H, m), 1.65 (1H, ddd, J¼14.1, 10.7, 3.4 Hz), 1.89 (1H,
m), 1.99 (1H, ddd, J¼14.1, 11.9, 2.4 Hz), 2.05 (1H, dd,
J¼15.1, 7.8 Hz), 2.15–2.25 (1H, m), 2.23 (1H, dd, J¼14.6,
5.9 Hz), 3.59 (3H, s, OCH3), 3.76 (1H, dd, J¼8.3, 6.4 Hz,
CHH–O), 3.99 (1H, dd, J¼8.3, 6.4 Hz, CHH–O), 4.12
(2H, q, J¼7.3 Hz, CH2–O), 4.17 (2H, q, J¼7.0 Hz, CH2–
O), 4.22 (1H, m, CH–O), 5.13 (1H, m, CH–O), 7.39–7.43
(3H, m, Ph), 7.57–7.60 (2H, m, Ph); 13C NMR d 14.30,
14.34, 19.61, 24.34, 24.94, 26.21, 30.14, 32.28, 33.18,
36.26, 41.02, 41.78, 55.54, 60.15, 60.59, 65.58, 74.30,
76.23, 77.20, 109.75, 127.36, 128.31, 129.58, 132.03,
165.90, 173.01, 175.06.
8. The natural pheromone of T. castaneum is suggested to be an
8:2 mixture of (4R,8R)- and (4R,8S)-4,8-dimethyldecanals be-
cause the mixture is about 10 times more active than (4R,8R)-
isomer alone. Suzuki, T.; Kozaki, J.; Sugawara, R.; Mori, K.
Appl. Entomol. Zool. 1984, 19, 15–20.
9. For other syntheses of (4R,8R)-4,8-dimethyldecanal (1), see:
(a) Mori, K.; Kato, M.; Kuwahara, S. Liebigs Ann. Chem.
1985, 861–865; (b) Nguyen, Kong Hao; Ceskis, B.; Mavrov,
M. V.; Moiseenkov, A. M.; Serebryakov, E. P. Zh. Org. Khim.
1987, 23, 498–503; (c) Nguyen, Kong Hao; Mavrov, M. V.;
Serebryakov, E. P. Zh. Org. Khim. 1987, 23, 1649–1653; (d)
Ceskis, B.; Lebedeva, K. V.; Moiseenkov, A. M. Izv. Akad.
Nauk SSSR, Ser. Khim. 1988, 865–871; (e) Mavrov, M. V.;
Nguyen, Cong Hao; Serebryakov, E. P. Bioorg. Khim. 1989,
15, 123–126; (f) Fuganti, C.; Grasselli, P.; Servi, S.;
Hoegberg, H. E. J. Chem. Soc., Perkin Trans. 1 1988, 3061–
4.1.16. a-Methoxy-a-(trifluoromethyl)phenylacetate 25.
1H NMR d 0.91 (3H, d, J¼6.4 Hz, CH3), 1.13 (1H, m),
1.25 (3H, t, J¼7.0 Hz, CH3), 1.20–1.35 (3H, m), 1.27 (3H,
t, J¼67.0 Hz, CH3), 1.30 (3H, s, CH3), 1.36 (3H, s, CH3),
1.43 (1H, m), 1.56–1.64 (1H, m), 1.69 (1H, ddd, J¼14.1,
10.2, 39 Hz), 1.92 (1H, m), 2.03–2.13 (2H, m), 2.25 (1H,
dd, J¼15.0, 6.0 Hz), 2.39 (1H, m), 3.69 (1H, dd, J¼8.5,
6.9 Hz, CHH–O), 3.52 (3H, s, OCH3), 3.91 (1H, dd,
J¼8.5, 6.4 Hz, CHH–O), 4.10 (1H, m, CH–O), 4.12 (2H,
q, J¼6.4 Hz, CH2–O), 4.16 (2H, q, J¼7.0 Hz, CH2–O),
5.14 (1H, m, CH–O), 7.39–7.43 (3H, m, Ph), 7.57–7.60
(2H, m, Ph); 13C NMR d 14.29, 14.35, 19.67, 24.43, 25.17,
26.26, 30.18, 33.08, 33.27, 36.37, 41.26, 41.81, 55.36,
60.16, 60.63, 65.93, 74.34, 76.35, 109.69, 127.55, 128.26,
128.38, 129.66, 131.62, 165.90, 173.01, 174.96.
^
3065; (g) Chenevert, R.; Desjardins, M. J. Org. Chem. 1996,
61, 1219–1222; (h) Sankaranarayanan, S.; Sharma, A.;
Chattopadhyay, S. Tetrahedron: Asymmetry 2002, 13, 1373–
1378.
10. Schmid, C. R.; Bryant, J. D.; Dowlatzedah, M.; Phillips, J. L.;
Prather, D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C. S. J. Org.
Chem. 1991, 56, 4056–4058.
References and notes
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