Synthesis of a homochiral ketone having a pinguisane skeleton using phenylethylamine as a chiral auxiliary: A formal total synthesis of deoxopinguisone

Article abstract of DOI:10.1016/S0957-4166(01)00041-6

A homochiral bicyclic ketone having a pinguisane skeleton has been synthesised starting from homochiral methyl 3-[(1′S,6′R)-1′,6′-dimethyl-2′-oxo-1-yl] propionate prepared from pulegone using phenylethylamine as a chiral auxiliary. The five-membered ring was constructed by the Hosomi-Sakurai reaction of the allylsilane derived from the ketone. This synthesis can be considered a formal synthesis of deoxopinguisone.

Full text of DOI:10.1016/S0957-4166(01)00041-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 301–307
Synthesis of a homochiral ketone having a pinguisane skeleton
using phenylethylamine as a chiral auxiliary: a formal total
synthesis of deoxopinguisone
Motoo Tori,* Chiho Makino, Kenji Hisazumi, Masakazu Sono and Katsuyuki Nakashima
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Received 20 December 2000; accepted 19 January 2001
Abstract—A homochiral bicyclic ketone having a pinguisane skeleton has been synthesised starting from homochiral methyl
3-[(1%S,6%R)-1%,6%-dimethyl-2%-oxo-1-yl]propionate prepared from pulegone using phenylethylamine as a chiral auxiliary. The
five-membered ring was constructed by the Hosomi–Sakurai reaction of the allylsilane derived from the ketone. This synthesis can
be considered a formal synthesis of deoxopinguisone. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
precedence, the work reported herein can be considered
a formal total synthesis of deoxopinguisone 1.
Pinguisanes are unusual sesquiterpenes which most
commonly occur in liverworts.1 Many pinguisane type
terpenoids have been characterised so far, among which
deoxopinguisone 1 is representative.2 Interest in this
class of terpenoids is high due to their structural nov-
elty.3 They have four methyl groups, all of which are
b-oriented, and all four are attached to contiguous
chiral centres. We have reported the total synthesis of
trifarienols A and B4 and striatenic acid5 starting from
the homochiral ketone 2, which was prepared from
(3R)-2,3-dimethylcyclohexanone using phenylethy-
lamine as a chiral auxiliary.4 Key intermediate 2 is
easily prepared with a very high e.e. of >99.5%4 and
yields of 60–70%. To further extend the use of 2 in
terpene synthesis, we now describe the synthesis of
optically active bicyclic ketone 14 which has a basic
skeleton of the pinguisane type terpenoid. As conver-
sion of ketone 14 to doeoxopinguisone 1 has literature
2. Results and discussion
The cis-vicinal dimethyl group at the C-(4) and C-(9)
positions of 14 can be derived from the ketone 2. The
other dimethyl groups can be introduced by forming
the CꢀC bond between C-(8) and C-(1) positions,
accomplished by the Hosomi–Sakurai reaction. It was
thought that cis-stereochemistry between the C-(8) and
C-(9) positions would be realised when the C-(1)ꢀC-(8)
bond is formed because the cis-hydrindane system is
Scheme 1. Synthetic plan.
* Corresponding author. Tel.: +81-88-622-9611 (ext. 5631); fax: +81-88-655-3051; e-mail: tori@ph.bunri-u.ac.jp
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00041-6

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M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
Allylic oxidation of 9 with PDC and tert-butylhy-
droperoxide afforded the enone 10 in 43% yield. The
low yield was attributed to the fact that the allylic
position of the side chain was also oxidised to produce
the corresponding diketone. After construction of the
enone fragment of the six-membered ring, olefination
using (iodomethyl)trimethylsilane was unsuccessful.
Therefore cyclisation using the Hosomi–Sakurai
reaction8 of 10 was attempted and the results are shown
in Table 1.
usually much more energetically stable than the trans-
form (Scheme 1).
The silyl protected ketone 3 was prepared from ketone
24 in three steps, by reduction, chemoselective alcohol
protection, and then oxidation (85%). Methylation of
ketone 3 was initially difficult because 3 was unreactive
to methyl magnesium bromide in ether or THF. How-
6
ever, in the presence of dry CeCl3 the methylated
product 4 was obtained in 91% yield. These results are
presumably explained by the fact that the ketone is
easily enolizable and that the steric hindrance of the
cis-dimethyl groups is large. Dehydration of 4 with
POCl3 afforded a mixture of the endo- and exo-olefins
The use of titanium tetrachloride or boron trifluoride
etherate in the cyclisation step was unsuccessful owing
to the formation of vinyl compound 15 with the double
bond at the terminus of the side chain as a result of
proton abstraction from trace water present in the
reaction mixture. However, the use of anhydrous
TBAF dramatically changed the outcome of the reac-
tion and the desired 11 formed in excellent yield.8 The
presence or absence of HMPA did not alter the yield
significantly (entries 4 and 5).
1
5 and 6 in a 1:1 ratio (by H NMR, 93%), which were
not separated at this stage. However, brief treatment of
this mixture with CF3COOH only produced the endo-
olefin 5 in 81% yield. Deprotection (TBAF, 99%),
Swern oxidation (84%) and olefination using
(iodomethyl)trimethylsilane7 led to silyl ketone 9 in
84% yield; this was assigned from the 1H and 13C NMR
spectra as a 6:1 mixture of cis- and trans-olefin isomers.
This mixture was not separated because both isomers
were expected to yield the desired compound in the
cyclisation step (Scheme 2).
The stereochemistry of the product was determined by
the NOE experiment, as shown in Fig. 1. This result
can be explained by the transition state, as shown in
Fig. 2: the cis-isomer can approach the b-position of
Scheme 2. (a) LiAlH4; (b) TBDPSCl, NEt3; (c) Swern oxid.; (d) MeMgBr, CeCl3; (e) POCl3, Py; (f) CF3COOH, CH2Cl2; (g)
,
TBAF, THF; (h) Swern oxid.; (i) Ph3PMeBr, ICH2SiMe3, n-BuLi; (j) PDC, tBuOOH; (k) TBAF, 4 A molecular sieves; (l) O3,
CH2Cl2; then Me2S; (m) NaBH4; (n) TsCl, Py; (o) LiAlH4; (p) Jones oxid.

M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
Table 1. Results for the Hosomi–Sakurai reaction of 10
303
Entry
Reagents
Solvents
Temp. (°C)
Time (h)
Products (yields, %)
1
2
3
4
5
TiCl4
CH2Cl2
PhMe
THF
THF, HMPA MS 4A
THF MS 4A
−78 to 12
−78 to −70
−78 to rt
−78 to 5
5
3
24
2
15 (quant.)
10, 15 (1:1)
No reaction
11 (95%)
EtAlCl2
BF3·Et2O
TBAF
,
,
TBAF
−78 to 0
1
11 (99%)
diols 12. Direct reduction of the ozonide to the diol 12
using NaBH4 in MeOH was unsuccessful as a result of
the formation of a considerable amount of unwanted
highly polar products. Selective tosylation of the pri-
mary alcohol with tosyl chloride in pyridine and reduc-
tion with LiAlH4 afforded alcohol 13, which was
oxidised using Jones reagent to complete the synthesis
of the desired ketone 14. Because ketone 14 has previ-
ously been converted to deoxopinguisone 1 by Uye-
hara,3c,d the synthetic process developed can be
considered a formal total synthesis of deoxopinguisone.
Figure 1. The observed NOEs for 11.
In the CD spectrum of compound 14 the sign of the
Cotton effect was negative at 294 nm. If the conforma-
tion with a chair form is more stable than non-chair
forms, it can be assumed that conformer 2 is the most
stable by examination of the model (Fig. 3). However,
if it follows the Octant rule, the expected sign of the
Cotton effect of conformer 2 is positive. Therefore,
conformer 2 must be the energetically least stable. We
looked for stable conformers of 14 using CONFLEX.9
The results are shown in Fig. 3. There are eight con-
formers within 6 kcal/mol and, surprisingly, conformer
1, the twisted form, is the most stable one. However,
the difference in abundance of conformers 1 and 2
the enone from the back side of the dimethyl groups as
in Fig. 2(A) due to steric hindrance. If approach to the
b-position is as shown in Fig. 2(B), steric hindrance
between the trimethylsilyl group and the cyclohexenone
becomes severe. Thus, the main product 11, with all
substituents cis-oriented, is favoured.
Conversion of the vinyl group to a methyl group was
then undertaken to complete the synthesis. Ozonolysis
of 11 in CH2Cl2 at −78°C, followed by treatment with
Me2S afforded the corresponding aldehyde, which was
subsequently reduced with NaBH4 to give a mixture of
Figure 2. Transition states for cyclisations leading to 14.

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M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
Figure 3. Eight stable conformations for 14 calculated by CONFLEX and the signs of their expected Cotton effects.
differs by less than 2%. Judging from the sign of the
CD spectrum, the contribution of conformers 1 and 3 is
slightly more than that of conformer 2 and others,
providing that the absolute values of CD spectra are
almost the same. It is interesting to note that conform-
ers 1 and 2 have almost the same steric energies and
each contributes to the opposite sign of Cotton effect.
This explains the [q] value of the CD spectrum for 14,
which is relatively small compared to those of most
carbonyl compounds.10
were taken with a Varian Unity 200 (200 MHz), a
Unity 600 (600 MHz) or a JEOL JNM GX400 (400
MHz) spectrometer. The mass spectra including high-
resolution mass spectra were taken with a JEOL JMS
AX-500 spectrometer. The specific rotation was mea-
sured with a JASCO DIP-140 polarimeter and the CD
spectra were taken with a JASCO DIP-1000 spec-
trophotometer. Chemcopak Nucleosil 50-5 (10×250
mm) was used for HPLC (JASCO pump system). Silica
gel 60 (70–230 mesh, Merck) was used for column
chromatography and silica gel 60 F254 plates (Merck)
were used for TLC.
3. Experimental
3.1. General
3.2. Synthesis of 3
A solution of 2 (9.9 g, 47 mmol) in ether (550 mL) was
treated with LiAlH4 (3.3 g, 47 mmol) for 2 h at rt. The
reaction was quenched with wet ether, and the organic
The IR spectra were measured with a JASCO FT/IR-
1
5300 spectrophotometer. The H and 13C NMR spectra

M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
305
materials were extracted with ether. The ethereal solu-
tion was washed with brine, dried over anhydrous
magnesium sulfate, and evaporated under reduced pres-
sure to afford diol (9.5 g) as a colorless oil. TBDPSCl
(13.4 mL, 52 mmol) was added to a CH2Cl2 (250 mL)
solution of the diol (9.5 g) and triethylamine (13 mL, 94
mmol) at rt. After 24 h, the reaction mixture was
cooled to 0°C and quenched with water. The products
were extracted with CH2Cl2, and the organic solution
was washed with brine and dried over anhydrous mag-
nesium sulfate. The solution was filtered and concen-
trated to afford mono-silyl ether (21 g) as a colorless
oil. A solution of mono-silyl ether (21 g) in CH2Cl2
(300 mL) was oxidised with PDC (20 g, 54 mmol) at rt
for 24 h. After filtration and removal of CH2Cl2 in
vacuo, the organic materials were extracted with ether.
The ethereal solution was washed with brine and dried
over anhydrous magnesium sulfate. The products were
purified by silica gel flash chromatography (SiO2 300 g,
1–5% AcOEt in hexane) to afford 3 (17 g, 85%, three
steps).
HRMS (CI) found m/z 421.2917 [M−H2O+H]+, calcd
for C28H41OSi 421.2926.
Methyl b-isomer; FTIR 3500 cm−1; 1H NMR (200
MHz, CDCl3) l 0.74 (3H, s), 0.79 (3H, d, J=6.8 Hz),
1.05 (9H, s), 1.15 (3H, s), 1.2–2.1 (11H, m), 3.61 (2H, br
t, J=6.0 Hz), 7.3–7.45 (6H, m), 7.64–7.73 (4H, m); 13C
NMR (50 MHz, CDCl3) l 16.4 (CH3), 17.4 (CH3), 19.2
(C), 21.5 (CH2), 25.9 (CH3), 26.9 (CH3), 29.0 (CH2),
30.3 (CH2), 32.2 (CH2), 32.7 (CH), 37.0 (CH2), 42.1
(C), 65.1 (CH2), 76.1 (C), 127.6 (CH), 129.5 (CH), 134.1
(C), 135.6 (CH); MS (CI) m/z 421 [M−H2O+H]+, 405,
381, 363, 343, 303, 199, 181, 165 (base), 137, 123, 109,
95, 83; HRMS (CI) found m/z 421.2938 [M−H2O+H]+,
calcd for C28H41OSi 421.2926.
3.4. Synthesis of 5
To a pyridine (400 mL) solution of 4 (16 g, 36 mmol),
POCl3 (13.4 mL, 145 mmol) was added under an Ar
atmosphere at 0°C. After heating under reflux for 3 h,
the reaction was quenched with wet ether and the
organic materials were extracted with ether. The ethe-
real solution was washed with brine and dried over
anhydrous magnesium sulfate. The products were
purified by silica gel flash chromatography (SiO2 400 g,
1–10% AcOEt in hexane) to afford a mixture of 5 and
6 (14.1 g, 93%). To a CH2Cl2 (200 mL) solution of 5
and 6 (2.05 g, 6.05 mmol), CF3COOH (4 mL, 52 mmol)
was added under an Ar atmosphere at 0°C. After
stirring for 18 h at rt, the reaction was quenched with
satd NaHCO3 aq. and the organic materials were
extracted with ether. The ethereal solution was washed
with brine and dried over anhydrous magnesium sul-
fate. The products were purified by silica gel flash
chromatography (SiO2 250 g, 3–10% AcOEt in hexane)
to afford 5 (2.05 g, 81%).
1
3: FTIR 1708 cm−1; H NMR (200 MHz, CDCl3) l
0.89 (3H, d, J=6.6 Hz), 0.97 (3H, s), 1.05 (9H, s),
1.25–2.0 (9H, m), 2.34 (2H, br t, J=6.6 Hz), 3.54–3.76
(2H, m), 7.3–7.45 (6H, m), 7.62–7.7 (4H, m); 13C NMR
(50 MHz, CDCl3) l 15.5 (CH3), 19.0 (CH3), 19.2 (C),
23.8 (CH2), 26.9 (CH3), 27.3 (CH2), 28.6 (CH2), 32.7
(CH2), 38.3 (CH2), 38.7 (CH), 51.9 (C), 64.3 (CH2),
127.6 (CH), 129.6 (CH), 134.1 (C), 135.6 (CH), 216.2
(C); MS (CI) m/z 423 [M+H]+, 421, 405, 365, 345, 295,
283, 263, 199, 167 (base), 149; HRMS (CI) found m/z
421.2566 [M−H]+, calcd for C27H37O2Si 421.2563.
3.3. Synthesis of 4
A THF solution of MeMgBr (0.87 M, 62 mL, 54 mmol)
was added to a mixture of ketone 3 (17 g, 40 mmol)
and CeCl3 (250 mg, 0.92 mmol) in THF (550 mL) at
0°C. The reaction mixture was stirred for 96 h at rt and
quenched with satd NH4Cl aq. at 0°C. The organic
materials were extracted with ether, and the ethereal
solution was washed with brine and dried over anhy-
drous magnesium sulfate. The products were purified
by silica gel flash chromatography (SiO2 500 g, 1–10%
AcOEt in hexane) to afford 4 (16 g, 91%) as a colorless
oil. For the determination of the stereochemistry of 4,
the small amount of diastereomixture of 4 was purified
by MPLC (SiO2 50 g, 10% AcOEt in hexane) to afford
methyl a-isomer (less polar) and methyl b-isomer
(polar), respectively.
1
5: FTIR 1660 cm−1; H NMR (200 MHz, CDCl3) l
0.86 (3H, d, J=5.4 Hz), 0.87 (3H, s), 1.09 (9H, s),
1.1–1.8 (7H, m), 1.61 (3H, br s), 1.9–2.1 (2H, m), 3.66
(2H, m), 5.44 (1H, br s), 7.35–7.5 (6H, m), 7.7–7.8 (4H,
m); MS (CI) m/z 421 [M+H]+, 405, 363, 343, 285, 265,
239, 199, 163 (base), 149, 123, 109, 95, 83, 69; HRMS
(CI) found m/z 421.2914 [M+H]+, calcd for C28H41OSi
421.2927.
3.5. Synthesis of 7
To a THF (70 mL) solution of 5 (1.3 g, 310 mmol),
TBAF (1.0 M in THF, 8.6 mL) was added under an Ar
atmosphere at 0°C. After stirring for 10 h at rt, the
reaction was quenched with H2O and the organic mate-
rials were extracted with ether. The ethereal solution
was washed with brine and dried over anhydrous mag-
nesium sulfate. The products were purified by silica gel
flash chromatography (SiO2 50 g, 5–30% AcOEt in
hexane) to afford 7 (558 mg, 99%.).
1
4: Methyl a-isomer; FTIR 3500 cm−1; H NMR (200
MHz, CDCl3) l 0.90 (3H, d, J=6.4 Hz), 0.91 (3H, s),
1.10 (9H, s), 1.26 (3H, s), 1.15–1.95 (11H, m), 3.67 (2H,
br t, J=6.2 Hz), 7.36–7.5 (6H, m), 7.66–7.77 (4H, m);
13C NMR (50 MHz, CDCl3) l 12.8 (CH3), 16.9 (CH3),
19.2 (C), 22.7 (CH2), 23.6 (CH3), 26.9 (CH3), 29.0
(CH2), 30.5 (CH2), 33.5 (CH2), 37.9 (CH), 38.7 (CH2),
42.7 (C), 65.1 (CH2), 75.9 (C), 127.6 (CH), 129.5 (CH),
134.2 (C), 135.6 (CH); MS (CI) m/z 421 [M−H2O+H]+,
381, 363, 343, 199, 181, 165 (base), 123, 109, 95, 83;
7: FTIR 3330, 1660 cm−1; H NMR (200 MHz, CDCl3)
l 0.86 (3H, d, J=7.0 Hz), 0.87 (3H, s), 1.36–1.5 (2H,
m), 1.5–1.8 (5H, m), 1.60 (3H, br s), 1.83–2.1 (2H, m),
3.55–3.7 (3H, m), 5.42 (1H, br s); MS (EI) m/z 182
1

306
M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
(M+), 162, 135, 123 (base), 105, 81, 67, 55; HRMS (EI)
found m/z 182.1660, calcd for C12H22O 182.1671.
with brine and dried over anhydrous magnesium sulfate.
The products were purified by silica gel flash chro-
matography (SiO2 15 g, 5–10% AcOEt in hexane) to
afford 10 (17 mg, 43%).
3.6. Synthesis of 8
A solution of 7 (520 mg, 2.84 mmol) in CH2Cl2 (10 mL)
was oxidised with oxalyl chloride (0.37 mL, 4.3 mmol)
and DMSO (0.6 mL, 8.5 mmol) at −60 to −50°C for 15
min, followed by Et3N (3.2 mL, 23 mol). The organic
materials were extracted with CH2Cl2, and the solution
was washed with brine and dried over anhydrous mag-
nesium sulfate. The products were purified by silica gel
flash chromatography (SiO2 15 g, 1–10% AcOEt in
hexane) to afford 8 (430 mg, 84%).
10: Major Z-isomer; [h]2D1 +8.9 (c 0.66, CHCl3); FTIR
1670, 1615 cm−1; 1H NMR (200 MHz, CDCl3) 0.00 (9H,
s), 0.96 (3H, d, J=6.6 Hz), 0.95–1.0 (1H, m), 1.01 (3H,
s), 1.43–1.6 (5H, m), 1.92 (3H, d, J=1.2 Hz), 2.25–2.35
(3H, m), 5.2 (1H, br dt, J=9.1, 6.2 Hz), 5.4 (1H, dtt,
J=9.1, 9.1, 6.2 Hz), 5.88 (1H, br q, J=1.2 Hz); 13C
NMR (50 MHz, CDCl3) −1.8 (CH3), 15.5 (CH3), 18.6
(CH2), 19.5 (CH3), 20.3 (CH3), 21.9 (CH2), 33.7 (CH),
36.4 (CH2), 42.1 (CH2), 42.3 (C), 126.2 (CH), 126.5
(CH), 128.4 (CH), 168.8 (C), 199.2 (C); MS (EI) m/z 278
(M+), 263, 250, 223, 209, 195, 182, 138, 73 (base);
HRMS (EI) found m/z 278.2072, calcd for C17H30OSi
278.2066.
8: FTIR 1730 cm−1; 1H NMR (200 MHz, CDCl3) l 0.87
(3H, d, J=6.4 Hz), 0.91 (3H, s), 1.4–1.8 (2H, m), 1.58
(3H, br s), 1.85–2.05 (3H, m), 2.05–2.6 (4H, m), 5.47
(1H, br s), 9.78 (1H, br t, J=1.7 Hz); MS (CI) m/z 180
(M+), 163, 137, 123 (base), 107, 95, 81, 67; HRMS (CI)
found m/z 180.1518, calcd for C12H20O 180.1514.
3.9. Attempted cyclisation reaction of 10 with TiCl4
TiCl4 (4 mL, 0.04 mmol) was added to the CH2Cl2 (200
mL) solution of 10 (5.4 mg, 0.019 mmol) at −78°C. The
reaction mixture was allowed to stir at rt (12°C) for 5 h
and quenched with water. The mixture was extracted
with ether, and the ethereal solution washed with brine,
dried over anhydrous magnesium sulfate and concen-
trated to afford 15 (4.1 mg, quant.).
3.7. Synthesis of 9
A stirred suspension of methyltriphenylphosphonium
bromide (3.2 g, 9.1 mmol) in dry THF (30 mL) was
cooled to 0°C, treated with n-BuLi (1.54 M in hexane,
5.1 mL, 7.8 mmol), warmed to rt, stirred for 1 h and
recooled to 0°C. After the addition of (iodomethyl)-
trimethylsilane (1.4 mL, 9.1 mmol), the mixture was
again allowed to warm to rt, stirred for 1 h, cooled to
−78°C and treated again with n-BuLi (1.54 M in hexane,
5.1 mL, 7.8 mmol). The dark red solution was stirred for
1.5 h at 20°C, cooled to 0°C and treated for 30 min with
a solution of 8 (280 mg, 1.6 mmol) in dry THF (3 mL).
The mixture was allowed to warm slowly to rt within 1
h and quenched with satd NH4Cl aq. (10 mL). The
organic materials were extracted with ether, and the
ethereal solution was washed with brine and dried over
anhydrous magnesium sulfate. The products were
purified by silica gel flash chromatography (SiO2 40 g,
1–7% AcOEt in hexane) to afford 9 (344 mg, 84%).
15: FTIR 1670, 1620 cm−1; 1H NMR (200 MHz, CDCl3)
l 1.90 (3H, d, J=1.2 Hz), 4.93–5.08 (2H, m), 5.67–5.9
(1H, m), 5.86 (1H, d, J=1.2 Hz); MS (EI) m/z 206 (M+),
191, 163, 137, 123, 109 (base), 95, 81, 67, 55; HRMS
(EI) found m/z 206.1651, calcd for C14H22O 206.1671.
3.10. Synthesis of 11
,
To a THF (5 mL) suspension of MS 4A (350 mg) and
10 (79.3 mg, 0.29 mmol), TBAF (7 mL, 1.0 M in THF),
,
dried previously over MS 4A (350 mg), was added under
an Ar atmosphere at −78°C. The reaction mixture was
allowed to reach 0°C over 1 h and the reaction was
quenched with water. The organic materials were
extracted with ether, and the solution was washed with
brine and dried over anhydrous magnesium sulfate. The
products were purified by silica gel flash chromatogra-
phy (SiO2 5 g, 0–10% AcOEt in hexane) to afford 11
(58.4 mg, 99%).
9: [h]2D1 +43.0 (c 0.86, CHCl3); FTIR 1645 cm−1; 1H
NMR (200 MHz, CDCl3) l 0.01 (9H, s), 0.86 (3H, s),
0.88 (3H, d, J=6.2 Hz), 1.35–1.5 (6H, m), 1.62 (3H, br
s), 1.85–2.05 (3H, m), 2.02 (2H, br s), 5.2–5.4 (2H, m),
5.42 (1H, br s); 13C NMR (50 MHz, CDCl3) l −1.7
(CH3), 16.0 (CH3), 18.4 (CH2), 19.2 (CH3), 21.0 (CH3),
21.8 (CH2), 25.6 (CH2), 27.1 (CH2), 33.3 (CH), 36.6
(CH2), 40.5 (C), 124.0 (CH), 125.0 (CH), 128.1 (CH),
139.7 (C); MS (EI) m/z 264 (M+), 249, 221, 163, 140
(base), 123, 109, 95, 81, 73; HRMS (EI) found m/z
264.2291, calcd for C17H32Si 264.2273.
11: [h]2D0 −18.0 (c 1.18, CHCl3); CD [q] 94 nm −1330
1
(CHCl3); Dm=−0.40; FTIR 1720, 1640 cm−1; H NMR
(200 MHz, CDCl3) l 0.79 (3H, s), 0.95 (3H, d, J=6.3
Hz), 0.98 (3H, s), 1.5–1.65 (2H, m), 1.7–1.9 (2H, m),
2.08 (1H, br t, J=5.5 Hz), 2.15 (2H, br s), 2.24 (2H, m),
2.46 (1H, br q, J=8 Hz), 4.99 (1H, ddd, J=17, 2, 1 Hz),
5.04 (1H, ddd, J=10.4, 2, 0.6 Hz), 5.63 (1H, ddd, J=17,
10.4, 8 Hz); 13C NMR (50 MHz, CDCl3) l 13.8 (CH3),
17.3 (CH3), 19.4 (CH3), 26.2 (CH2), 33.5 (CH2),
36.7 (CH), 45.9 (CH2), 46.7 (C), 47.5 (CH2), 49.6 (CH),
52.1 (C), 116.7 (CH2), 138.8 (CH), 211.8 (C); MS (EI)
m/z 206 (M+), 191, 178, 163, 137, 121, 96, 82 (base);
HRMS (EI) found m/z 206.1691, calcd for C14H22O
206.1671.
3.8. Synthesis of 10
A solution of 9 (38 mg, 0.14 mmol) in benzene (20 mL)
was treated with PDC (265 mg, 0.72 mmol) and t-
BuOOH (5–6 M in decane, 0.14 mL, 0.72 mmol) at 5°C
and then stirred at rt for 24 h. After addition of satd
Na2S2O3 aq. and filtration, the organic materials were
extracted with ether. The ethereal solution was washed

M. Tori et al. / Tetrahedron: Asymmetry 12 (2001) 301–307
307
3.11. Synthesis of 12
MHz, CDCl3) l 0.76 (3H, s), 0.84 (3H, d, J=6.6 Hz),
0.94 (3H, d, J=6.3 Hz), 0.97 (3H, s), 1.4–2.2 (10H, m);
13C NMR (150 MHz, CDCl3) l 14.0, 14.5, 17.3, 18.7,
29.7, 33.4, 36.8, 38.9, 45.8, 46.9, 47.7, 50.7, 212.2; MS
(EI) m/z 194 (M)+ 179, 161, 151, 137, 123, 109 (base),
95, 82; HRMS (CI) found m/z 195.1746 [M+H]+, calcd
for C13H23O 195.1749.
A solution of 11 (23.9 mg, 0.116 mmol) in CH2Cl2 (10
mL) was treated with ozone at −78°C until a blue color
persisted. Me2S (1 mL) was added to the reaction
mixture and stirred for 24 h at rt. The reaction mixture
was concentrated and purified by silica gel flash chro-
matography (SiO2 5 g, AcOEt) to afford aldehyde (125
mg) as a colorless oil. A solution of aldehyde (125 mg)
in MeOH (2 mL) was treated with NaBH4 (85 mg, 2.2
mmol) for 2 h at 0°C. The reaction was quenched with
water and the organic materials were extracted with
ether. The ethereal solution was washed with brine and
dried over anhydrous magnesium sulfate to afford 12 as
a colorless oil (19.5 mg, two steps, 79%).
Acknowledgements
We thank Dr. M. Tanaka and Miss Y. Okamoto, this
university, for measurement of 600 MHz NMR and
MS spectra, respectively.
1
12: FTIR 3350 cm−1; H NMR (200 MHz, CDCl3) l
References
0.71 (3H, s), 0.73 (3H, s), 0.84 (3H, d, J=7 Hz), 1.2–2.0
(11H, m), 3.19 (1H, m), 3.61 (1H, dd, J=10.1, 5 Hz),
3.74 (1H, dd, J=10.1, 8.4 Hz), 4.08 (1H, quint, J=2.8
Hz); MS (EI) m/z 211 [M−1]+, 194, 176, 161 (base),
147, 134, 121, 107, 95; HRMS (CI) found m/z 211.1691
[M−1]+, calcd for C13H23O2 211.1698.
1. (a) Asakawa, Y. In Chemical Constituents of the
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3.12. Synthesis of 13
To a pyridine (1 mL) solution of 12 (19.5 mg, 0.092
mmol), TsCl (35 mg, 0.18 mmol) was added under an
Ar atmosphere at rt. After stirring for 4 h at rt, the
reaction was quenched with H2O and the organic mate-
rials were extracted with ether. The ethereal solution
was washed with brine and dried over anhydrous mag-
nesium sulfate to afford tosylate (27.5 mg) as a color-
less oil. A solution of tosylate (27.5 mg, 0.075 mmol) in
THF (3 mL) was treated with LiAlH4 (57 mg, 1.5
mmol) for 4 h at rt. The reaction was quenched with
water and the organic materials were extracted with
ether. The solution was washed with brine and dried
over anhydrous magnesium sulfate. The products were
purified by silica gel flash chromatography (SiO2 5 g,
0–100% AcOEt in hexane) to afford 13 (6.2 mg, two
steps, 34%).
1
13: FTIR 3550 cm−1; H NMR (300 MHz, CDCl3) l
0.60 (3H, s), 0.75 (3H, s), 0.84 (3H, d, J=6.6 Hz), 0.86
(3H, d, J=6.3 Hz), 1.0–2.0 (11H, m), 4.04 (1H, quint,
J=3.6 Hz); MS (EI) m/z 195 [M−1]+, 178, 163, 149,
136, 121, 109 (base), 95, 81; HRMS (CI) found m/z
196.1850 [M−1]+, calcd for C13H24O 196.1828.
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3.13. Synthesis of 14
A solution of 13 (6.2 mg, 0.032 mmol) in acetone (3
mL) was oxidised with Jones’ reagent (0.3 mL) at 0°C
for 1.25 h. After removal of acetone in vacuo, the
organic materials were extracted with ether, and the
solution was washed with brine and dried over anhy-
drous magnesium sulfate. The product was purified by
silica gel flash chromatography (SiO2 5 g, 0–10%
AcOEt in hexane) to afford 14 (2.2 mg, 35%).
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14: [h]2D5 −22.6 (c 0.15, CHCl3); CD [q] 94 nm −1130
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1
(CHCl3); Dm=−0.34; FTIR 1750 cm−1; H NMR (300