Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring systems by self-cyclization of (Z)- and (E)-2-(trimethylsilylmethyl)pentadienal derivative

Article abstract of DOI:10.1016/j.tet.2003.11.024

The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4- cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product, 2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2- (trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products as a complex mixture.

Full text of DOI:10.1016/j.tet.2003.11.024

Tetrahedron 60 (2004) 319–331
Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring
systems by self-cyclization of (Z)- and
(E)-2-(trimethylsilylmethyl)pentadienal derivative
*
Chiaki Kuroda, Shigenobu Honda, Yuki Nagura, Hiroyuki Koshio, Taku Shibue
and Tokio Takeshita
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Received 23 July 2003; accepted 7 November 2003
Abstract—The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of
2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4-cyclohexylidene-2-(trimethyl-
silylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product,
2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2-
(trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al
cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products
as a complex mixture.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
activated by an allylic trimethylsilyl group. The formal
reaction mechanism from 1 to 2 is illustrated in Scheme 1.
Related silicon directed Nazarov cyclization is well
documented by Denmark et al.11
a-(Trialkylsilylmethyl)-a,b-unsaturated carbonyl is a
unique building block in organic synthesis since the
b-carbon reacts as an allylsilane1 but not as an unsaturated
carbonyl, and therefore, this moiety acts as a carbon 1,3-
dipole based on the nucleophilicity of the b-carbon and the
electrophilicity of the carbonyl carbon.2 By using this unit,
various five-membered compounds were synthesized.3,4 For
example, we obtained g-lactones by the reaction with
aldehyde5 or ketone.6 Cyclopentane ring was also syn-
thesized by the reaction with an enone.7 Nishitani et al.
prepared g- and d-lactones by the reaction with either an
aldehyde8 or an epoxide,9 respectively.
Scheme 1.
In contrast to the classic Nazarov cyclization of cross-
conjugated divinyl ketone, linearly conjugated a,b,g,d-
unsaturated carbonyl compounds, such as penta-2,4-dienal,
are not suitable substrates for the Nazarov or related type of
self-cyclization, since the d-carbon is too electron deficient
to react with the carbonyl group. We envisioned that the
a,b,g,d-unsaturated carbonyl can also cyclize with itself if
this moiety is substituted by a trimethylsilylmethyl group at
b-position. Namely, by the presence of this substituent, the
d-carbon of 3 becomes nucleophilic, as a part of allylsilane,
which is expected to react with the carbonyl to form the five-
membered ring compound 4 (Scheme 2, Eq. A). However,
in our previous study, ethyl 2-(trimethylsilylmethyl)penta-
Further conjugation of CvC double bond to this moiety
enables self-cyclization to form a five-membered ring
compound, and therefore, the reaction is not expected to
be a simple extension. There are two ways for further
conjugation, namely on the CvC side or on the carbonyl
side, leading to b-(trialkylmethyl)-a,b,g,d-unsaturated car-
bonyl or a-(trialkylmethyl)divinyl ketone, respectively. We
previously reported the synthesis of spiro[4.5]decane 2 by
Lewis acid promoted Nazarov cyclization of a-(trimethyl-
silylmethyl)divinyl ketone 1,10 in which the reaction was
Keywords: Spiro[4.5]decane; Bicyclo[4.3.0]nonane; Allylsilane;
Pentadienal; Cyclization.
2,4-dienoate 5 or -dienoic acid
6
(R1¼R2¼CH3,
*
Corresponding author. Tel.: þ81-3-3985-2396; fax: þ81-3-5992-3434;
R1,R2¼(CH2)4) did not cyclize in this way but produced
e-mail address: kuroda@rikkyo.ac.jp
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.11.024

320
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
Section 4). The DIBAL-H reduction of 10a afforded 11a in
a 92% yield, which was subsequently oxidized by MnO2
giving substrate 8a (89%).
The cyclization of 8a was carried out by the same procedure
reported for the Nazarov cyclization.10 Namely, 8a was
treated with ca. 2 equiv. of FeCl3 in CH2Cl2 at 260 8C
followed by slow warming to room temperature over 7 h. As
a result, a spiro[4.5]decane compound was obtained but this
was not the expected dienol but enone 12a (78% yield,
Scheme 4). Some other Lewis acids, such as AlCl3, Et2AlCl
and BF3OEt2 were also used but without success.
Scheme 2.
g-lactone 7 via a protonic acid treatment (Eq. B).12 This is
probably due to the low reactivity of the ester group. Thus,
we planned to use an aldehyde instead of an ester in order to
obtain a five-membered carbocycle via the reaction mode
shown in Eq. A.
To compare this new type of cyclization with the Nazarov
cyclization of our previous report, we first chose the
spiro[4.5]decane ring as the synthetic target. Spiro[4.5]-
decane is one of the basic ring systems in natural
sesquiterpenes such as acoranes or vetispiranes.13,14 Here
we report the synthesis of the spiro[4.5]decane ring system
by a new spiro-cyclopentannulation using the cyclization of
linearly conjugated pentadienal.15 Synthesis of
bicyclo[4.3.0]nonane ring system by the same method is
also described.
Scheme 4. Reagents and conditions: (i) FeCl3, CH2Cl2, 260 8C to rt.
The stereochemistry of the cyclization reaction was then
studied using the substrates 8b and 8c, which were prepared
analogously from 4-t-butyl- and 4-methylclohexanone,
respectively, in accordance to Scheme 3. When 8b was
treated under the same reaction conditions, spiro[4.5]deca-
none 12b was obtained as a single diastereomer in 80%
yield (Scheme 4). The stereostructure of 12b was deter-
mined from the NOE signal observed between allylic
methylene and the axial protons on the cyclohexane ring as
shown in Figure 1. Similarly, 8c afforded 12c in a 70%
yield, which was again obtained as a single diastereomer,
and its structure was determined independently in the same
way (Fig. 1).
2. Results and discussion
2.1. Synthesis of spiro[4.5]decane ring system
As the initial study, compound 8a was designed as the
cyclization precursor. The substrate was synthesized as
shown in Scheme 3. Namely, to 2-cyclohexylideneacetal-
dehyde (9a), prepared from cyclohexanone by Horner–
Emmons reaction followed by DIBAL-H reduction and
MnO2 oxidation, a b-(ethoxycarbonyl)allylsilane unit was
introduced by using Hoffman’s reagent4 (EtO)2-
P(O)CH(CO2Et)CH2SiMe3 giving 10a in a 51% yield.
The geometry of the double bond in 10a was determined to
be Z based on the chemical shift of the olefinic proton (see
Figure 1.
Scheme 3. Reagents and conditions: (i) for 10a–c: (EtO)2P(O)CH(CO2Et)CH2SiMe3, NaH, DME, rt; for 14: (EtO)2P(O)CH(CO2Et)CH3, NaH, DME, rt;
(ii) DIBAL-H, CH2Cl2, 260 8C; (iii) MnO2, CH2Cl2, rt.

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
321
To demonstrate whether the reaction proceeds via a silicon-
stabilized carbocation as the intermediate, the desilylated
substrate 13 was prepared (Scheme 3). Under the same
reaction conditions described above, 13 did not afford any
cyclization product, as expected, but was recovered without
reaction (Scheme 4). From this result, it is obvious that the
cyclization from 8a to 12a proceeds via the silicon-
stabilized carbocation 16 as the intermediate (Scheme 5).
Since the two reaction sites in 8a are too far apart to react
(cf. two sites are close for its (E)-isomer 17a), it is easily
expected that 8a could cyclize after isomerization to (E)-
intermediate (vide infra) by the aid of Lewis acid. The
related isomerization from (Z)-b-carbonylallylsilane to its
(E)-isomer was also observed previously in the reaction of
a-(trimethylsilylmethyl)-a,b,g,d-unsaturated carboxylic
acid.12 From 16, the initial cyclization product via the
expected mode should be dienol 18a (see also Scheme 1).
Although, the reaction mechanism cannot be specified at
this stage, isomerization from 18a to the enone 12a is
considered to be a plausible pathway.
The result of the cyclization reaction of 17a is listed in
Table 1 and Scheme 7. As expected, the reaction was much
faster than in the case of 8a. When 17a was treated with
FeCl3 in CH2Cl2 at 0 8C, the reaction proceeded within
20 min and b,g-unsaturated enone 21a was afforded instead
of the conjugated compound 12a (Entries 1,2) Interestingly,
when the reaction was carried out at 260 8C, the originally
expected dienol 18a was obtained in good yield (Entry 4).
Table 1. Cyclization of 17aa
Entry
FeCl3 (equiv.)
Temp (8C)
Product
Yield (%)
1
2
3
4
1
0
0
260
260
21a
21a
18a
18a
41
83
34
78
Excessb
1
Excessb
a
All reactions were carried out in CH2Cl2 for 20 min under Ar atmosphere.
About 10 equiv.
b
From these results, it could be considered that the initial
cyclization product from 17a or 8a is 18a, the originally
expected product. Also, it is very likely that 21a is the
isomerization product at higher temperature, and in
addition, that 12a is the final isomerization product with a
longer reaction time. To demonstrate this, 18a was treated
with the same reagent except that the reaction was carried
out at 0 8C for 20 min to afford 21a in 97% yield. Similarly,
when 21a was treated under the same reaction condition as
for 8a (260 8C to room temperature, 2 days), 12a was
obtained in an 87% yield. These results clearly indicate that
the cyclization of 8a or 17a proceeded via the intermediates
18a and 21a.
Cyclization of the substituted compounds 17b and 17c were
also studied and the results are shown in Table 2. From 17b,
the initial cyclization product 18b could not be isolated
when the reaction was carried out at 260 8C. Under this
condition, the desilylated product 22 (a mixture of E- and
Z-isomers) was detected together with 21b (Entry 3). The
isomerization reaction of 21b was also carried out under the
same reaction conditions as Entry 4 affording 12b in a 71%
yield. The results of the cyclization of 17c (Entries 5–7)
were almost consistent with those of 17b, except that 18c
was obtained in a low yield at 260 8C and a lack of
experimental reproducibility (Entry 6). These results
indicate that dienols 18b,c are not stable enough for
handling.
Scheme 5.
Recently, we established a new method to prepare (E)-b-
(ethoxycarbonyl)allylsilanes from aldehydes via the Ando-
HWE (Horner–Wadsworth–Emmons) reaction.16 In order
to clarify the above reaction mechanism, we prepared the
(E)-substrate 17a by this method (Scheme 6). Namely, 19a
was synthesized from 9a by using (PhO)2P(O)CH(CO2-
Et)CH2SiMe3 giving a mixture of both the (E)-isomer 19a
and the (Z)-isomer 10a in an 89% yield (19a/10a¼9:1).
DIBAL-H reduction (20a, 86%) followed by MnO2
oxidation afforded 17a in a 71% yield after separation
from its (Z)-isomer.
The stereoselectivity of the cyclization reaction from 17b or
17c (so as 8b and 8c) can be rationalized by a preferential
equatorial attack to the exocyclic double bond (Scheme 8).17
Scheme 6. Reagents and conditions: (i) (PhO)2P(O)CH(CO2Et)CH2SiMe3, NaH, THF, rt; (ii) DIBAL-H, CH2Cl2, 260 8C; (iii) MnO2, CH2Cl2, rt.

322
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
Scheme 7. Reagents and conditions: (i) see Table 1; (ii) FeCl3, CH2Cl2, 0 8C; (iii) FeCl3, CH2Cl2, 260 8C to rt.
Table 2. Cyclization of 17b and 17ca
decane carbon skeleton, we next focused on the use of this
method to synthesize the hydrindane, or bicyclo[4.3.0]-
nonane, carbon framework from cyclohexane derivatives.
Hydrindane is one of the key structures in various
terpenoid,13,14 which also appears as the CD rings of
steroids.
Entry
Substrate
Temp (8C)
Time
Product
Yield (%)
1
2
3
4
5
6
7
17b
17b
17b
17b
17c
17c
17c
0
215
260
260 to rt
0
260
20 min
20 min
20 min
2 days
20 min
20 min
2 days
21b
21b
21b, 22
12b
21c
93
89
Not determined
81
74
18b
64
The cyclization of both (Z)- and (E)-allylsilanes were
studied. The substrates were synthesized in accordance to
Scheme 9. Namely, to the a,b-unsaturated aldehyde 23 was
introduced the b-(ethoxycarbonyl)allylsilane moiety by
treatment with (EtO)2P(O)CH(CO2Et)CH2SiMe3/NaH in
DME to afford 24 and 25 in a 61% yield (24/25¼6:1).
Reduction of the ester group with DIBAL-H yielded
alcohols 26 and 27 after separation by column chromatog-
raphy. The (Z)-isomer 26 was oxidized by MnO2 to afford
28 in a 92% yield. When (PhO)2P(O)CH(CO2Et)CH2SiMe3
was used as the Horner–Wadsworth–Emmons reagent, 25
was obtained preferentially (E/Z¼97:3, 95% yield). The
alcohol 27 was then obtained by DIBAL-H reduction
followed by purification.
18c
12c
260 to rt
a
All reactions were carried out in CH2Cl2 under Ar atmosphere with about
4 equiv. of FeCl3.
The result was not reproducible.
b
Namely, transition state B is less favorable than A since the
carbonyl oxygen, together with bulky Lewis acid, comes
over the cyclohexane ring. From the transition state A, 21b,c
is considered to be obtained via 18b,c. It is interesting that
this stereoselectivity was much higher than the related
Nazarov cyclization.10
2.2. Synthesis of bicyclo[4.3.0]nonane ring system
In contrast to the oxidation of 26, when 27 was subjected to
Following the success of the synthesis of the spiro[4.5]-
Scheme 8.

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
323
Figure 2.
Scheme 9. Reagents and conditions: (i) for 24: (EtO)2P(O)CH(CO2-
Et)CH2SiMe3, NaH, DME, rt; for 25: (PhO)2P(O)CH(CO2Et)CH2SiMe3,
NaH, THF, rt; (ii) DIBAL-H, CH2Cl2, 260 8C; (iii) MnO2, CH2Cl2, rt.
MnO2 oxidation, the corresponding aldehyde 29 was not
obtained but the cyclization product 30 (20%) was afforded
together with its trimethylsilyl ether 31 (63%) (Scheme 10).
However, the yields of the two products varied, and in some
case, only 30 was afforded in good yield (93%). Since 31
was too volatile to isolate, the reaction mixture was treated
with Bu4NF giving 30 effectively without being
accompanied by 31. The formation of the aldehyde 29
could not be detected on a TLC, which indicates that the
oxidation product was immediately cyclized. The stereo-
chemistry of 30 was determined from the 1H NMR spectrum
including NOE which was observed between the proton
attached to the hydroxy-bearing carbon (7-H) and one of the
axial protons on the cyclohexane ring (5-H) as shown in
Figure 2.
Scheme 11.
respect to the enone moiety, conformer C is favorable over
D, since the carbonyl oxygen takes on a congested position
in D.
The cyclization of 28 was also studied by the treatment with
ca. 1.5 equiv. of FeCl3 in CH2Cl2 at room temperature. The
reaction proceeded slowly, and after for 4 days, many
products were detected on a TLC. This complex mixture of
the products was roughly separated by silica-gel column
chromatography, and five compounds 32–36 could be
The stereoselective formation of 30 can easily be explained
by the s-trans conformation of the enone moiety in the
precursor enal 29 (Scheme 11). Although both the s-trans
conformer C and the s-cis conformer D are possible with
Scheme 10. Reagents and conditions: (i) MnO2, CH2Cl2, rt, (ii) Bu4NF,
Et2O, rt.
Scheme 12. Reagents and conditions: (i) FeCl3, CH2Cl2, rt.

324
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
promoted cyclization of 39a and 39b proceeded slower than
the case of 27, and the reaction completed after stirring with
silica gel to afford 42a (94%) and 42b (94%), respectively,
after treatment with Bu4NF. In contrast to the synthesis of
spiro[4.5]decane ring, no stereoselectivity was observed.
Namely, both dienols 42a and 42b were obtained in 1:1
mixture of diastereomers.
As mentioned above, a remarkable difference in reactivity
based on the geometry of 2-(trimethylsilylmethyl)penta-
dienal was observed for the case of (Z)-isomer 28 and
(E)-isomer 29. While in contrast, the same spiro[4.5]decane
ring compounds 12a–c were obtained from both (Z)-
isomers 8a–c and (E)-isomers 17a–c. This difference can
be rationalized by an easier isomerization from 8 to (E)-
intermediate (i.e., 43–44) than from 28 (i.e., 45–46) in the
presence of Lewis acid (Scheme 14). Namely, the
intermediate carbocation is tertiary for 43 (and 44) and
secondary for 45 (and 46). Since 18 and 21, the products
from 17 at lower temperature, were not obtained from 8, it
can be predicted that Z/E isomerization requires more
energy than the cyclization.
Scheme 13. Reagents and conditions: (i) (PhO)2P(O)CH(CO2Et)CH2-
SiMe3, NaH, THF, rt; (ii) DIBAL-H, CH2Cl2, 260 8C; (iii) (a) MnO2,
CH2Cl2, rt; (b) SiO2, Et2O, rt; (c) Bu4NF, Et2O, rt.
identified from the 1H NMR and mass spectra (Scheme 12),
among which 32 was found to be the major product (ca. 36%
yield). The other compounds include isomeric enone 33,
dienone 34, and two chlorides 35 and 36. The structure of
1
these products was determined by H and 13C NMR and
mass spectra. The stereochemistry of two chlorides 35 and
36 were established by NOE experiment. Namely, NOE was
observed between CHCl (2-H) and 9b-H for 35; between
CHCl and 9a-H for 36. The cis-fused structure for 33 was
deduced from J-value of methine proton (6-H). Compound
34 is considered to be formed from 33 by further oxidation
caused by FeCl3.11b Two chlorides must be chlorination
products from 32. When the reaction was carried out with
ca. 4 equiv. of FeCl3, the two oxidized products 37 and 38
were also found in the mixture. Some other Lewis acids
such as Et2AlCl, AlCl3, and TiCl4 were tested instead of
FeCl3 but none of them gave us satisfactory results.
3. Conclusion
A new cyclization reaction of linearly conjugated penta-
dienal assisted by allylic trimethylsilyl group was estab-
lished. Both spiro[4.5]decane and bicyclo[4.3.0]nonane
carbon frameworks were synthesized by this method. In
the synthesis of spiro[4.5]decane, it was found that (1) both
(Z)- and (E)-precursors afford the same product enone in
good yields under appropriate conditions, (2) the reaction
proceeds via a silicon-stabilized carbocation as the inter-
mediate to afford the initial product dienol, (3) isomeriza-
tion reaction occurs from dienol to conjugated enone, and
(4) the cyclization reaction is stereoselective. While, a
remarkable difference in reactivity based on (Z)- or (E)-
precursor was observed for the synthesis of bicyclo[4.3.0]-
nonane. Therefore, (E)-precursor is required for the
The substituent effect for the cyclization of (E)-isomer was
examined. The cyclization precursor, alcohols 39a and 39b,
were prepared in same way (Scheme 13). The MnO2
Scheme 14. LA¼Lewis acid.

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
325
cyclization of 4,5-disubstituted-2-(trimethylsilylmethyl)-
pentadienal, while geometry of the functionalized allyl-
silane is not an important factor for the cyclization reaction
of 5,5-disubstituted derivative.
(Mþ, 34%), 265 (18), 235 (11), 162 (32), 133 (40), 91 (54),
and 73 (100); HRMS [Found: m/z 280.1907 (Mþ). Calcd for
C16H28O2Si: M, 280.1859].
4.2.2. (Z)-Ethyl 4-(4-t-butylcyclohexylidene)-2-(tri-
methylsilylmethyl)but-2-enoate (10b). An oil; IR (neat)
1
1704 (CvO), 1633, 1365, 1250, 852, and 755 cm21; H
4. Experimental
NMR d¼0.00 (9H, s, SiMe3), 0.85 (9H, s, tBu), 0.99–1.28
(3H, m), 1.30 (3H, t, J¼7.1 Hz, OCH2CH3), 1.80–1.98 (3H,
m), 1.93 (2H, br s, CH2SiMe3), 2.12–2.21 (1H, m), 2.31–
2.38 (1H, m), 2.96–3.01 (1H, m), 4.19 (2H, q, J¼7.1 Hz,
OCH2CH3), 5.93 (1H, br d, J¼10.8 Hz, CringvCH), and
7.40 (1H, d, J¼10.8 Hz, CHvCCO2Et); 13C NMR
d¼21.05 (3C), 14.36, 17.32, 27.59 (3C), 28.63, 29.43,
29.48, 32.46, 38.01, 48.27, 60.38, 118.33, 127.52, 130.42,
150.67, and 169.05; MS m/z 336 (Mþ, 100%), 205 (7), 189
(89), and 107 (15); HRMS [Found: m/z 336.2438 (Mþ).
Calcd for C20H36O2Si: M, 336.2486].
4.1. General procedure
Melting points were measured on a Laboratory Devices
Mel-Temp apparatus. IR spectra were recorded on a Jasco
FT/IR-230 spectrometer. Both H and 13C NMR spectra
1
were measured on a Jeol GSX-400 (400 MHz for 1H;
100 MHz for 13C) spectrometer. Chemical shifts were
reported on the d scale (ppm) with solvent (CHCl3¼7.26)
as an internal standard, unless otherwise noted. The signal
of the solvent (CDCl3¼77.0) was used as a standard for all
13C NMR spectra. Both low-resolution mass spectra (MS)
and high-resolution mass spectra (HRMS) were obtained on
a Jeol SX-102A, JMS-DX303, CMATE II, or Shimadzu
GCMS-QP5050 mass spectrometer with the EI method
unless otherwise noted. Analytical TLC was done on
precoated TLC plates (Kieselgel 60 F254, layer thickness
0.2 mm). Wakogel C-200 or C-300 was used for column
chromatography. Anhydrous Na2SO4 or MgSO4 was used
for drying the extracted organic layers.
4.2.3. (Z)-Ethyl 4-(4-methylcyclohexylidene)-2-(tri-
methylsilylmethyl)but-2-enoate (10c). An oil; IR (neat)
1704 (CvO), 1632, 1260, and 852 cm21
;
1H NMR
d¼20.01 (9H, s, SiMe3), 0.91 (3H, d, J¼6.5 Hz, Me),
0.95–1.11 (2H, m), 1.30 (3H, t, J¼7.1 Hz, OCH2CH3),
1.54–1.66 (1H, m), 1.77–1.97 (3H, m), 1.93 (2H, br s,
CH2SiMe3), 2.14–2.33 (2H, m), 2.85–2.92 (1H, m), 4.19
(2H, q, J¼7.1 Hz, OCH2CH3), 5.95 (1H, br d, J¼10.8 Hz,
CringvCH), and 7.40 (1H, d, J¼10.8 Hz, CHvCCO2Et);
13C NMR d¼21.06 (3C), 14.36, 17.32, 21.81, 28.92, 32.70,
35.99, 36.81, 37.48, 60.38, 118.77, 127.58, 130.41, 150.24,
and 169.05; MS m/z 294 (Mþ, 100%), 279 (7), 237 (7), 147
(97), 143 (91), and 75 (98); HRMS [Found: m/z 294.1990
(Mþ). Calcd for C17H30O2Si: M, 294.2016].
4.2. (Z)-Selective HWE reaction
To a stirred suspension of NaH (1018 mg, 23.3 mmol; 55%
in mineral oil which was removed by washing with dry
hexane) in dry DME (80 cm3; distilled from CaH2) was
added (EtO)2P(O)CH2CO2Et (4.2 cm3, 21.2 mmol) drop-
wise at 0 8C under Ar. After being stirred for 40 min,
iodomethyltrimethylsilane (3.6 cm3, 24.3 mmol) was
added, and the mixture was heated to 70 8C for 4 h. The
flask was cooled to 0 8C again, and a second portion of NaH
(960 mg, 22.0 mmol; mineral oil was not removed) was
added. After being stirred at 0 8C for 2 h, a solution of
2-cyclohexylideneacetaldehyde (1.648 g, 13.3 mmol) in
DME (28 cm3) was added, and the mixture was stirred at
room temperature for 14 h. An aqueous solution of NH4Cl
was added, and the resulting aqueous mixture was extracted
with Et2O, and dried. Evaporation of the solvent followed
by silica gel (80 g) column chromatography using hexane/
AcOEt (99.5:0.5) as eluent afforded 10a (1.891 g, 51%).
Similarly, 10b and 10c were obtained in 35 and 58% yields,
respectively. For the preparation of 14, methyl iodide was
used instead of iodomethyltrimethylsilane (32% yield). See
Ref. [12] for the synthesis and the spectral data of 24.
4.2.4. (E)-Ethyl 4-cyclohexylidene-2-methylbut-2-enoate
(14). An oil; IR (neat) 1704 (CvO), 1635, 1447, 1256,
1112, and 752 cm21; 1H NMR (Me4Si¼0.00) d¼1.31 (3H,
t, J¼7.1 Hz, OCH2CH3), 1.55–1.68 (6H, m, (CH2)3), 1.93
(3H, d, J¼2.1 Hz, CvCCH3), 2.20–2.27 (2H, m,
CvCCH2), 2.37–2.43 (2H, m, CvCCH2), 4.21 (2H, q,
J¼7.1 Hz, OCH2CH3), 6.07 (1H, br d, J¼11.8 Hz,
CringvCH), and 7.51 (1H, dq, J¼11.8, 1.3 Hz, CHvCCO2-
Et); 13C NMR d¼12.31, 14.37, 26.64, 27.93, 28.67, 29.72,
38.16, 60.38, 117.97, 124.67, 133.59, 152.39, and 169.07;
MS m/z 208 (Mþ, 88%), 196 (100), 182 (93), 150 (90), 137
(100), 96 (99), and 68 (99); HRMS [Found: m/z 208.1427
(Mþ). Calcd for C13H20O2: M, 208.1464].
4.3. (E)-Selective HWE reaction
To a stirred suspension of NaH (242 mg, 5.57 mmol; 55% in
mineral oil) in dry THF (20 cm3; distilled from LiAlH4) was
added a solution of (PhO)2P(O)CH(CO2Et)CH2SiMe3
(1.98 g, 4.87 mmol) in THF (15 cm3) dropwise at 0 8C
under Ar. After being stirred for 30 min, the mixture was
cooled to 260 8C, and a solution of 2-cyclohexylidene-
acetaldehyde (446.1 mg, 3.59 mmol) in THF (20 cm3) was
added. The stirring was continued at 260 8C for 4 h, then
the mixture was allowed to warm to room temperature
followed by stirring at room temperature for 12 h. An
aqueous solution of NH4Cl was added, and the resulting
aqueous mixture was extracted with AcOEt, and dried.
Evaporation of the solvent followed by silica gel (40 g)
4.2.1. (Z)-Ethyl 4-cyclohexylidene-2-(trimethylsilyl-
methyl)but-2-enoate (10a). An oil; IR (neat) 1702
(CvO), 1630, 1258, 851, and 754 cm21
;
1H NMR
d¼20.01 (9H, s, SiMe3), 1.30 (3H, t, J¼7.1 Hz,
OCH2CH3), 1.54–1.62 (6H, m, (CH2)3), 1.93 (2H, br s,
CH2SiMe3), 2.19–2.24 (2H, m, CvCCH2), 2.36–2.41 (2H,
m, CvCCH2), 4.19 (2H, q, J¼7.1 Hz, OCH2CH3), 5.94
(1H, br d, J¼11.9 Hz, CringvCH), and 7.40 (1H, d,
J¼11.9 Hz, CHvCCO2Et); 13C NMR d¼21.06 (3C),
14.36, 17.32, 26.70, 27.99, 28.80, 29.72, 38.19, 60.39,
118.68, 127.54, 130.33, 150.66, and 169.06; MS m/z 280

326
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
column chromatography using hexane/AcOEt (97:3) as
eluent afforded a mixture of 19a and 10a (1007.6 mg, 51%,
19a/10a¼9:1). Similarly, 19b, 19c, 41a, and 41b were
obtained in 62, 88, 97, and 96% yields, respectively. These
compounds were obtained together with a small amount of
corresponding (Z)-isomer (ca. 1–10%) which were
removed at later stage. See Ref. 16 for the synthesis of 25.
119 (17), 91 (19), and 73 (100); HRMS (CI) [Found: m/z
267.1758 (MþþH). Calcd for C15H27O2Si: M, 267.1780].
4.3.5. (E)-Ethyl 3-(4-t-butylcyclohex-1-en-1-yl)-2-(tri-
methylsilylmethyl)prop-2-enoate (41a). An oil; IR (neat)
1
1722 (CvO), 1632, 1365, 1248, 1088, and 854 cm21; H
NMR d¼0.03 (9H, s, SiMe3), 0.85 (9H, s, t-Bu), 1.05–1.17
(1H, m), 1.22–1.32 (1H, m), 1.29 (3H, t, J¼7.1 Hz,
OCH2CH3), 1.69 (1H, d, J¼13.8 Hz, CHHSiMe3), 1.76
(1H, d, J¼13.8 Hz, CHHSiMe3), 1.77–1.92 (2H, m), 2.02–
2.17 (3H, m), 4.14 (1H, dq, J¼11.0, 7.1 Hz, OCHHCH3),
4.19 (1H, dq, J¼11.0, 7.1 Hz, OCHHCH3), 5.63–5.68 (1H,
m, CvCHCH2), and 5.85 (1H, br s, CHvCCO2Et); 13C
NMR d¼21.56 (3C), 14.12, 24.10, 25.73, 27.11 (3C),
27.49, 28.19, 32.15, 43.67, 60.37, 128.48, 129.42, 133.23,
135.05, and 171.00; MS m/z 322 (Mþ, 3%), 307 (1), 277 (2),
204 (16), 175 (9), 147 (12), 119 (15), and 73 (100); HRMS
(CI) [Found: m/z 323.2341 (MþþH). Calcd for C19H35O2Si:
M, 323.2406].
4.3.1. (E)-Ethyl 4-cyclohexylidene-2-(trimethylsilyl-
methyl)but-2-enoate (19a). An oil; IR (neat) 1703
;
(CvO), 1630, 1198, 1159, and 852 cm21 1H NMR
d¼0.00 (9H, s, SiMe3), 1.32 (3H, t, J¼7.2 Hz,
OCH2CH3), 1.54–1.62 (6H, m, (CH2)3), 1.82 (2H, s,
CH2SiMe3), 2.18–2.23 (2H, m, CvCCH2), 2.29–2.34
(2H, m, CvCCH2), 4.20 (2H, q, J¼7.2 Hz, OCH2CH3),
6.51 (1H, d, J¼12.0 Hz, CHvCCO2Et), and 6.77 (1H, br d,
J¼12.0 Hz, CringvCH); 13C NMR d¼21.61 (3C), 14.30,
24.66, 26.77, 27.82, 28.51, 28.91, 37.97, 60.09, 119.28,
126.30, 132.29, 148.42, and 168.30; MS m/z 280 (Mþ,
36%), 265 (16), 235 (16), 162 (51), 133 (55), 91 (68), and 73
(100); HRMS [Found: m/z 280.1948 (Mþ). Calcd for
C16H28O2Si: M, 280.1859].
4.3.6. (E)-Ethyl 3-(4-methylcyclohex-1-en-1-yl)-2-(tri-
methylsilylmethyl)prop-2-enoate (41b). An oil; IR (neat)
1
1720 (CvO), 1624, 1248, 1219, and 852 cm21; H NMR
4.3.2. (E)-Ethyl 4-(4-t-butylcyclohexylidene)-2-(tri-
methylsilylmethyl)but-2-enoate (19b). An oil; IR (neat)
d¼0.03 (9H, s, SiMe3), 0.94 (3H, d, J¼6.3 Hz, Me), 1.18
(1H, ddt, J¼5.2, 12.4, 10.8 Hz), 1.28 (3H, t, J¼7.2 Hz,
OCH2CH3), 1.58–1.74 (3H, m), 1.70 (1H, d, J¼13.6 Hz,
CHHSiMe3), 1.74 (1H, d, J¼13.6 Hz, CHHSiMe3), 1.99–
2.20 (3H, m), 4.13 (1H, dq, J¼10.7, 7.2 Hz, OCHHCH3),
4.16 (1H, dq, J¼10.7, 7.2 Hz, OCHHCH3), 5.57–5.61 (1H,
m, CvCHCH2), and 5.83 (1H, br s, CHvCCO2Et); 13C
NMR d¼21.57 (3C), 14.11, 21.75, 25.68, 26.88, 28.01,
30.99, 34.39, 60.34, 128.17, 128.75, 133.31, 134.86, and
171.01; MS m/z 280 (Mþ, 2%), 235 (2), 162 (14), 133 (18),
91 (18), and 73 (100); HRMS (CI) [Found: m/z 281.1985
(MþþH). Calcd for C16H29O2Si: M, 281.1937].
1
1703 (CvO), 1631, 1365, 1178, 852, and 756 cm21; H
NMR d¼0.01 (9H, s, SiMe3), 0.85 (9H, s, tBu), 0.98–1.34
(3H, m), 1.32 (3H, t, J¼7.2 Hz, OCH2CH3), 1.75–1.94 (5H,
m), 2.09–2.18 (1H, m), 2.32–2.39 (1H, m), 2.85–2.92 (1H,
m), 4.20 (2H, q, J¼7.2 Hz, OCH2CH3), 6.51 (1H, d,
J¼11.6 Hz, CHvCCO2Et), and 6.77 (1H, br d, J¼11.6 Hz,
CringvCH); 13C NMR d¼21.60 (3C), 14.31, 24.65, 27.59
(3C), 28.45, 28.69, 29.10, 32.47, 37.79, 48.32, 60.10,
118.96, 126.32, 132.38, 148.40, and 168.29; MS m/z 336
(Mþ, 33%), 321 (15), 237 (21), 169 (29), 119 (45), and 73
(100); HRMS [Found: m/z 336.2441 (Mþ). Calcd for
C20H36O2Si: M, 336.2486].
4.4. DIBAL-H reduction
4.3.3. (E)-Ethyl 4-(4-methylcyclohexylidene)-2-(tri-
methylsilylmethyl)but-2-enoate (19c). An oil; IR (neat)
1693 (CvO), 1628, 1190, and 852 cm21; 1H NMR d¼0.00
(9H, s, SiMe3), 0.90 (3H, d, J¼6.5 Hz, Me), 0.95–1.14
(2H, m), 1.32 (3H, t, J¼7.1 Hz, OCH2CH3), 1.50–1.94 (6H,
m), 2.11–2.21 (1H, m), 2.26–2.33 (1H, m), 2.75–2.83 (1H,
m), 4.20 (2H, q, J¼7.1 Hz, OCH2CH3), 6.51 (1H, d,
J¼10.8 Hz, CHvCCO2Et), and 6.78 (1H, br d, J¼10.8 Hz,
CringvCH); 13C NMR d¼21.61 (3C), 14.11, 24.68, 28.14,
31.58, 32.77, 35.90, 36.59, 37.27, 60.08, 119.42, 126.41,
132.36, 147.93, and 168.29; MS m/z 294 (Mþ, 3%), 279 (1),
237 (3), 176 (9), 147 (12), 119 (18), and 73 (100); HRMS
[Found: m/z 294.2011 (Mþ). Calcd for C17H30O2Si: M,
294.2016].
In a 50 cm3 two-necked flask was placed a solution of 10a
(152.6 mg, 554.1 mmol) in dry CH2Cl2 (12 cm3; distilled
from CaH2) with stirring under Ar. To this was added
DIBAL-H (1.63 cm3, 1.63 mmol; 1 M solution in hexane) at
260 8C, and the stirring was continued for 30 min at the
same temperature. MeOH (2 cm3) was added, and the flask
was quickly warmed to room temperature. After being
stirred for 30 min, a saturated aqueous solution of Rochelle
salt (30 cm3) was added, and the mixture was extracted with
CH2Cl2 and dried. Evaporation of the solvent followed by
silica gel (1 g) column chromatography using hexane/
AcOEt (96:4) as eluent afforded 11a (120.1 mg, 93%).
Similarly, 10b, 10c, 14, 19a, 24, 25, 41a, and 41b afforded
11b, 11c, 15, 20a, 26, 27, 39a, and 39b in 96, 91, 74, 86, 91,
98, 82, and 81% yields, respectively.
4.3.4. (E)-Ethyl 3-(cyclohex-1-en-1-yl)-2-(trimethylsilyl-
methyl)prop-2-enoate (25). An oil; IR (neat) 1722 (CvO),
1626, 1373, 1219, and 850 cm21; 1H NMR d¼0.02 (9H, s,
SiMe3), 1.28 (3H, t, J¼7.1 Hz, OCH2CH3), 1.51–1.62 (4H,
m), 1.72 (2H, br s, CH2SiMe3), 2.01–2.11 (4H, m), 4.15
(2H, q, J¼7.1 Hz, OCH2CH3), 5.60–5.64 (1H, m,
CvCHCH2), and 5.82 (1H, br s, CHvCCO2Et); 13C
NMR d¼21.60 (3C), 14.08, 21.98, 22.68, 25.65, 25.76,
26.89, 60.33, 128.50, 128.62, 133.61, 135.23, and 171.00;
MS m/z 266 (Mþ, 2%), 251 (1), 237 (2), 221 (3), 148 (18),
Compounds 19b and 19c were reduced by LiAlH4 in Et2O
giving 20b and 20c in 99 and 92% yields, respectively.
4.4.1. (Z)-4-Cyclohexylidene-2-(trimethylsilylmethyl)-
but-2-en-1-ol (11a). An oil; IR (neat) 3320 (OH), 1608,
1
1447, 1248, 852, and 691 cm21; H NMR d¼0.04 (9H, s,
SiMe3), 1.49–1.58 (7H, m, (CH2)3 and OH), 1.71 (2H, br s,
CH2SiMe3), 2.13–2.18 (2H, m, CvCCH2), 2.24–2.30 (2H,
m, CvCCH2), 4.03 (2H, br s, CH2OH), 5.83 (1H, br d,

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
327
J¼11.2 Hz, CringvCH), and 6.20 (1H, br d, J¼11.2 Hz,
CHvCCH2OH); 13C NMR d¼20.71 (3C), 19.40, 26.87,
27.80, 28.79, 29.15, 37.77, 68.95, 118.01, 118.17, 137.25,
and 142.24; MS m/z 238 (Mþ, 9%), 193 (4), 148 (34), 133
(22), 105 (83), and 73 (199); HRMS [Found: m/z 238.1791
(Mþ). Calcd for C14H26OSi: M, 238.1754].
CH2SiMe3), 2.05–2.15 (1H, m), 2.24–2.31 (1H, m),
2.78–2.85 (1H, m), 4.18 (1H, d, J¼12.0 Hz, CHHOH),
4.21 (1H, d, J¼12.0 Hz, CHHOH), and 6.01 (2H, s,
CHvCH); 13C NMR d¼21.31 (3C), 26.04, 27.61 (3C),
28.32, 28.69, 29.14, 32.48, 37.45, 48.40, 61.91, 116.62,
121.78, 136.48, and 141.69; MS m/z 294 (Mþ, 4%), 276
(20), 204 (21), 105 (42), 73 (100), and 57 (100); HRMS
[Found: m/z 294.2336 (Mþ). Calcd for C18H34OSi: M,
294.2380].
4.4.2. (Z)-4-(4-t-Butylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-en-1-ol (11b). An oil; IR (neat) 3310 (OH),
1609, 1364, 1248, and 839 cm21; 1H NMR d¼0.04 (9H, s,
SiMe3), 0.85 (9H, s, tBu), 0.95–1.91 (7H, m), 1.71 (2H, br s,
CH2SiMe3), 2.05–2.15 (1H, m), 2.24–2.31 (1H, m), 2.82–
2.88 (1H, m), 4.03 (2H, br s, CH2OH), 5.83 (1H, br d,
J¼11.2 Hz, CringvCH), and 6.20 (1H, br d, J¼11.2 Hz,
CHvCCH2OH); 13C NMR d¼20.70 (3C), 19.40, 27.62
(3C), 28.43, 28.93, 29.39, 32.46, 37.60, 48.42, 68.95,
117.82, 118.09, 137.28, and 142.25; MS m/z 294 (Mþ,
42%), 275 (66), 247 (100), 213 (98), 198 (75), 116 (61), and
86 (80); HRMS [Found: m/z 294.2338 (Mþ). Calcd for
C18H34OSi: M, 294.2380].
4.4.7. (E)-4-(4-Methylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-en-1-ol (20c). An oil; IR (neat) 3320 (OH),
1
1604, 1454, 1246, 1011, and 849 cm21; H NMR d¼0.03
(9H, s, SiMe3), 0.85–1.88 (7H, m), 0.90 (3H, d, J¼6.6 Hz,
Me), 1.68 (2H, br s, CH2SiMe3), 2.06–2.26 (2H, m), 2.68–
2.77 (1H, m), 4.18 (1H, d, J¼11.9 Hz, CHHOH), 4.20 (1H,
d, J¼11.9 Hz, CHHOH), and 6.01 (2H, s, CHvCH); 13C
NMR d¼21.32 (3C), 21.99, 26.04, 28.13, 32.81, 35.81,
36.68, 36.92, 61.90, 117.06, 121.79, 136.53, and 141.26;
MS m/z 252 (Mþ, 2%), 162 (23), 147 (14), 105 (94), 91 (53),
and 57 (100); HRMS [Found: m/z 252.1918 (Mþ). Calcd for
C15H28OSi: M, 252.1910].
4.4.3. (Z)-4-(4-Methylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-en-1-ol (11c). An oil; IR (neat) 3310 (OH),
1608, 1456, 1248, and 839 cm21; 1H NMR d¼0.03 (9H, s,
SiMe3), 0.99 (3H, d, J¼6.5 Hz, Me), 0.82–1.88 (7H, m),
1.70 (2H, br s, CH2SiMe3), 2.07–2.26 (2H, m), 2.70–2.79
(1H, m), 4.02 (2H, br s, CH2OH), 5.84 (1H, br d, J¼11.2 Hz,
CringvCH), and 6.20 (1H, br d, J¼11.2 Hz, CHvCCH2-
OH); 13C NMR d¼20.71 (3C), 19.40, 22.00, 28.37, 32.84,
35.91, 36.90, 37.06, 68.93, 118.09, 118.29, 137.33, and
141.78; MS m/z 252 (Mþ, 86%), 193 (84), 147 (96), 135
(87), 121 (100), and 77 (97); HRMS [Found: m/z 252.1893
(Mþ). Calcd for C15H28OSi: M, 252.1910].
4.4.8. (Z)-3-(Cyclohex-1-en-1-yl)-2-(trimethylsilyl-
methyl)prop-2-en-1-ol (26). An oil; IR (neat) 3320 (OH),
1
1689, 1643, 1437, 1248, 1028, and 852 cm21; H NMR
d¼0.04 (9H, s, SiMe3), 1.53–1.68 (5H, m), 1.84 (2H, br s,
CH2SiMe3), 2.05–2.13 (4H, m), 3.98 (2H, br s, CH2OH),
5.60–5.64 (1H, m, CvCHCH2), and 5.71 (1H, br s,
CHvCCH2OH); 13C NMR d¼20.57 (3C), 19.76, 22.20,
22.96, 25.58, 29.37, 69.49, 125.44, 126.09, 128.97, and
135.13; MS m/z 224 (Mþ, 1%), 134 (12), 119 (44), 105 (57),
91 (100), and 73 (100); HRMS [Found: m/z 224.1590 (Mþ).
Calcd for C13H24OSi: M, 224.1597].
4.4.4. (E)-4-Cyclohexylidene-2-methylbut-2-en-1-ol (15).
Mp 38.5–40.5 8C; IR (Nujol) 3340 (OH), 1008, and
4.4.9. (E)-3-(Cyclohex-1-en-1-yl)-2-(trimethylsilyl-
methyl)prop-2-en-1-ol (27). An oil; IR (neat) 3325 (OH),
1
861 cm21; H NMR (Me4Si¼0.00) d¼1.00–1.75 (7H, m,
1
(CH2)3 and OH), 1.79 (3H, s, CvCCH3), 2.15–2.21 (2H, m,
CvCCH2), 2.26–2.32 (2H, m, CvCCH2), 4.08 (2H, s,
CH2OH), 5.97 (1H, br d, J¼11.4 Hz, CringvCH), and 6.30
(1H, d sext, J¼11.4, 1.2 Hz, CHvCCH2OH); 13C NMR
d¼13.96, 26.81, 27.77, 28.68, 29.13, 37.71, 69.22, 117.29,
120.78, 134.51, and 143.93; MS m/z 166 (Mþ, 6%), 165
(Mþ2H, 44), 148 (73), 121 (13), 105 (35), and 43 (100);
HRMS [Found: m/z 166.1322 (Mþ). Calcd for C11H18O: M,
166.1358].
1637, 1437, 1246, 1016, and 850 cm21; H NMR d¼0.01
(9H, s, SiMe3), 1.51–1.64 (4H, m), 1.63 (2H, br s,
CH2SiMe3), 1.77 (1H, br, OH), 1.95–2.01 (2H, m), 2.03–
2.10 (2H, m), 4.16 (2H, s, CH2OH), 5.40–5.44 (1H, m,
CvCHCH2), and 5.50 (1H, br s, CHvCCH2OH); 13C NMR
d¼1.27 (3C), 22.12, 22.81, 25.04, 25.48, 29.42, 62.89,
125.41, 128.96, 135.08, and 136.97; MS m/z 224 (Mþ, 1%),
134 (10), 119 (40), 105 (52), 91 (94), and 73 (100); HRMS
(CI) [Found: m/z 225.1576 (MþþH). Calcd for C13H25OSi:
M, 225.1675].
4.4.5. (E)-4-Cyclohexylidene-2-(trimethylsilylmethyl)-
but-2-en-1-ol (20a). An oil; IR (neat) 3390 (OH), 1624,
4.4.10. (E)-3-(t-Butylcyclohex-1-en-1-yl)-2-(trimethyl-
silylmethyl)prop-2-en-1-ol (39a). An oil; IR (neat) 3390
1448, 1248, and 852 cm21
;
1H NMR d¼0.03 (9H, s,
1
SiMe3), 1.50–1.58 (7H, m, (CH2)3 and OH), 1.68 (2H, s,
CH2SiMe3), 2.11–2.17 (2H, m, CvCCH2), 2.23–2.28 (2H,
m, CvCCH2), 4.19 (2H, br s, CH2OH), and 6.01 (2H, br s,
CvCH–CHvC); 13C NMR d¼21.32 (3C), 26.00, 26.83,
27.68, 28.56, 28.88, 37.60, 61.85, 116.95, 121.67, 136.46,
and 141.68; MS m/z 238 (Mþ, 4%), 148 (27), 133 (23), 105
(92), and 73 (199); HRMS [Found: m/z 238.1715 (Mþ).
Calcd for C14H26OSi: M, 238.1754].
(OH), 1637, 1467, 1365, 1245, and 854 cm21; H NMR
d¼0.03 (9H, s, SiMe3), 0.87 (9H, s, t-Bu), 1.10–1.30 (2H,
m), 1.45 (1H, br, OH), 1.63 (1H, d, J¼13.5 Hz,
CHHSiMe3), 1.67 (1H, d, J¼13.5 Hz, CHHSiMe3), 1.78–
1.92 (2H, m), 2.05–2.16 (3H, m), 4.12 (1H, d, J¼12.0 Hz,
OCHHOH), 4.24 (1H, d, J¼12.0 Hz, OCHHOH), 5.44–
5.48 (1H, m, CvCHCH2), and 5.55 (1H, br s, CHvCCH2-
OH); 13C NMR d¼21.26 (3C), 24.19, 25.14, 27.14, 27.18
(3C), 30.94, 32.19, 43.81, 62.70, 125.85, 128.54, 134.93,
and 137.01; MS m/z 280 (Mþ, 1%), 251 (1), 190 (4), 175 (5),
133 (26), 106 (34), 91 (52), 73 (89), and 57 (100); HRMS
(CI) [Found: m/z 281.2343 (MþþH). Calcd for C17H33OSi:
M, 281.2301].
4.4.6. (E)-4-(4-t-Butylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-en-1-ol (20b). An oil; IR (neat) 3360 (OH),
1604, 1365, 1248, and 850 cm21; 1H NMR d¼0.03 (9H, s,
SiMe3), 0.85 (9H, s, tBu), 0.97–1.92 (7H, m), 1.69 (2H, br s,

328
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
4.4.11. (E)-3-(Methylcyclohex-1-en-1-yl)-2-(trimethyl-
silylmethyl)prop-2-en-1-ol (39b). An oil; IR (neat) 3330
1.85 (2H, br s, CH2SiMe3), 2.19–2.39 (2H, m), 2.86–2.93
(1H, m), 6.17 (1H, br d, J¼11.6 Hz, CringvCH), 7.01 (1H,
d, J¼11.6 Hz, CHvCCHO), and 9.38 (1H, s, CHO); 13C
NMR d¼1.05 (3C), 14.74, 21.70, 29.08, 32.62, 36.00,
36.76, 37.67, 118.90, 138.94, 141.69, 153.56, and 194.95;
MS m/z 250 (Mþ, 100%), 235 (99), 193 (94), 180 (6), 147
(5), and 75 (94); HRMS [Found: m/z 250.1725 (Mþ). Calcd
for C15H26OSi: M, 250.1754].
1
(OH), 1637, 1458, 1248, 1012, and 856 cm21; H NMR
d¼0.03 (9H, s, SiMe3), 0.95 (3H, d, J¼6.6 Hz, Me), 1.16–
1.27 (1H, m), 1.56–1.74 (6H, m), 1.97–2.19 (3H, m), 4.13
(1H, d, J¼12.2 Hz, OCHHOH), 4.21 (1H, d, J¼12.2 Hz,
OCHHOH), 5.38–5.42 (1H, m, CvCHCH2), and 5.53 (1H,
br s, CHvCCH2OH); 13C NMR d¼21.29 (3C), 21.76,
24.98, 28.08, 29.47, 31.05, 34.07, 62.61, 125.00, 128.62,
134.67, and 136.99; MS m/z 238 (Mþ, 1%), 223 (1), 148
(12), 133 (23), 106 (64), 91 (86), and 73 (100); HRMS
[Found: m/z 238.1738 (Mþ). Calcd for C14H26OSi: M,
238.1753].
4.5.4. (E)-4-Cyclohexylidene-2-methylbut-2-enal (13).
An oil; IR (neat) 2708 (CHO), 1681 (CvO), 1629, 1447,
1234, 1223, 1187, and 1011 cm21; 1H NMR (Me4Si¼0.00)
d¼1.13–1.91 (6H, m, (CH2)3), 1.84 (3H, d, J¼1.0 Hz,
CvCCH3), 2.28–2.33 (2H, m, CvCCH2), 2.42–2.48 (2H,
m, CvCCH2), 6.28 (1H, br d, J¼11.8 Hz, CringvCH), 7.17
(1H, dq, J¼11.8, 1.1 Hz, CHvCCHO), and 9.45 (1H, s,
CHO); 13C NMR d¼9.19, 26.50, 27.99, 28.66, 29.89,
38.37, 118.09, 135.71, 144.46, 155.85, and 195.35; MS m/z
164 (Mþ, 97%), 149 (3), 135 (3), and 121 (100); HRMS
[Found: m/z 164.1161 (Mþ). Calcd for C11H16O: M,
164.1202].
4.5. MnO2 oxidation
In a 50 cm3 round-bottomed flask fitted with CaCl2 drying
tube was placed a solution of 11a (104.3 mg, 473.4 mmol)
in dry CH2Cl2 (15 cm3; distilled from CaH2) at room
temperature, and to this was added a suspension of MnO2
(2.1 g) in CH2Cl2 (3 cm3) with vigorous stirring. After this
had been stirred for 15 h, the mixture was filtered through
Celite, and the filtrate was concentrated. The resultant crude
oil was chromatographed on silica gel (1 g) using hexane/
AcOEt (99:1) as eluent to afford 8a (91.7 mg, 89%).
Similarly, 11b, 11c, 15, 20a, 20b, 20c, and 26 afforded 8b,
8c, 13, 17a, 17b, 17c, and 28 in 88, 81, 51, 71, 64, 75, and
85% yields, respectively. These compounds were purified
free from their geometrical isomers at this stage.
4.5.5. (E)-4-Cyclohexylidene-2-(trimethylsilylmethyl)-
but-2-enal (17a). An oil; IR (neat) 1660 (CvO), 1626,
1248, 856, and 739 cm21
;
1H NMR d¼20.02 (9H, s,
SiMe3), 1.57–1.66 (6H, m, (CH2)3), 1.72 (2H, s, CH2-
SiMe3), 2.22–2.27 (2H, m, CvCCH2), 2.33–2.38 (2H, m,
CvCCH2), 6.77 (1H, br d, J¼12.4 Hz, CringvCH), 7.07
(1H, d, J¼12.4 Hz, CHvCCHO), and 10.03 (1H, s, CHO);
13C NMR d¼21.60 (3C), 19.93, 26.62, 27.87, 28.56, 28.94,
38.18, 114.99, 134.89, 138.48, 151.04, and 190.11; MS m/z
236 (Mþ, 7%), 221 (8), 193 (19), 180 (7), 91 (12), 73 (100),
and 45 (37); HRMS [Found: m/z 236.1585 (Mþ). Calcd for
C14H24OSi: M, 236.1597].
4.5.1. (Z)-4-Cyclohexylidene-2-(trimethylsilylmethyl)-
but-2-enal (8a). An oil; IR (neat) 2705 (CHO), 1675
;
(CvO), 1627, 1447, 1249, and 854 cm21 1H NMR
d¼20.02 (9H, s, SiMe3), 1.60–1.67 (6H, m, (CH2)3),
1.85 (2H, br s, CH2SiMe3), 2.25–2.30 (2H, m, CvCCH2),
2.40–2.46 (2H, m, CvCCH2), 6.16 (1H, d quint, J¼11.6,
0.9 Hz, CringvCH), 7.02 (1H, d, J¼11.6 Hz, CHvCCHO),
and 9.39 (1H, s, CHO); 13C NMR d¼21.05 (3C), 14.74,
26.58, 28.05, 28.80, 29.87, 38.39, 118.81, 138.90,
141.62, 153.97, and 194.96; MS m/z 236 (Mþ, 30%), 221
(26), 193 (38), 180 (15), 91 (17), and 73 (100); HRMS
[Found: m/z 236.1565 (Mþ). Calcd for C14H24OSi: M,
236.1597].
4.5.6. (E)-4-(4-t-Butylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-enal (17b). An oil; IR (neat) 1662 (CvO),
1630, 1365, 1248, and 856 cm21; 1H NMR d¼20.02 (9H, s,
SiMe3), 0.87 (9H, s, tBu), 1.00–1.30 (3H, m), 1.69 (1H, d,
J¼13.0 Hz, CHHSiMe3), 1.74 (1H, d, J¼13.0 Hz,
CHHSiMe3), 1.79–2.00 (3H, m), 2.14–2.24 (1H, m),
2.36–2.41 (1H, m), 2.89–2.95 (1H, m), 6.77 (1H, br d,
J¼12.6 Hz, CringvCH), 7.07 (1H, d, J¼12.6 Hz,
CHvCCHO), and 10.30 (1H, s, CHO); 13C NMR
d¼21.60 (3C), 19.90, 27.57 (3C), 28.52, 28.71, 29.16,
32.48, 38.00, 48.21, 114.67, 134.86, 138.61, 151.03, and
190.12; MS m/z 292 (Mþ, 3%), 277 (4), 193 (32), and 73
(100); HRMS [Found: m/z 292.2223 (Mþ). Calcd for
C18H32OSi: M, 292.2224].
4.5.2. (Z)-4-(4-t-Butylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-enal (8b). An oil; IR (neat) 2707 (CHO),
1
1677 (CvO), 1628, 1365, 1248, 1226, and 855 cm21; H
NMR d¼20.02 (9H, s, SiMe3), 0.87 (9H, s, tBu), 1.02–1.32
(3H, m), 1.85 (2H, br s, CH2SiMe3), 1.88–2.02 (3H, m),
2.17–2.27 (1H, m), 2.38–2.44 (1H, m), 2.96–3.03 (1H, m),
6.15 (1H, br d, J¼11.5 Hz, CringvCH), 7.01 (1H, d,
J¼11.5 Hz, CHvCCHO), and 9.39 (1H, s, CHO); 13C
NMR d¼21.04 (3C), 14.74, 27.58 (3C), 28.70, 29.44,
29.63, 32.48, 38.20, 48.18, 118.48, 138.88, 141.72, 153.97,
and 194.94; MS m/z 292 (Mþ, 91%), 277 (87), 194 (98), 180
(86), and 73 (100); HRMS [Found: m/z 292.2202 (Mþ).
Calcd for C18H32OSi: M, 292.2224].
4.5.7. (E)-4-(4-Methylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-enal (17c). An oil; IR (neat) 1660 (CvO),
1626, 1248, 1146, and 856 cm21; 1H NMR d¼20.02 (9H, s,
SiMe3), 0.93 (3H, d, J¼6.5 Hz, Me), 0.98–1.16 (2H, m),
1.70 (1H, d, J¼12.8 Hz, CHHSiMe3), 1.73 (1H, d,
J¼12.8 Hz, CHHSiMe3), 1.58–1.96 (4H, m), 2.17–2.36
(2H, m), 2.79–2.86 (1H, m), 6.78 (1H, br d, J¼12.4 Hz,
CringvCH), 7.06 (1H, d, J¼12.4 Hz, CHvCCHO), and
10.29 (1H, s, CHO); 13C NMR d¼21.59 (3C), 19.97, 21.74,
28.18, 32.68, 35.88, 36.58, 37.48, 115.10, 134.98, 138.54,
150.61, and 190.11; MS m/z 250 (Mþ, 4%), 235 (5), 193
(25), 103 (16), and 73 (100); HRMS [Found: m/z 250.1758
(Mþ). Calcd for C15H26OSi: M, 250.1754].
4.5.3. (Z)-4-(4-Methylcyclohexylidene)-2-(trimethylsilyl-
methyl)but-2-enal (8c). An oil; IR (neat) 2707 (CHO),
1
1676 (CvO), 1626, 1248, 1223, and 855 cm21; H NMR
d¼20.02 (9H, s, SiMe3), 0.93 (3H, d, J¼6.5 Hz, Me),
0.99–1.15 (2H, m), 1.55–1.73 (1H, m), 1.82–2.04 (3H, m),

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
329
4.5.8. (Z)-3-(Cyclohex-1-en-1-yl)-2-(trimethylsilyl-
methyl)prop-2-enal (28). An oil; IR (neat) 1680 (CvO),
extracted with Et2O and dried. Evaporation of the solvent
followed by florisil (2 g) column chromatography using
hexane/Et2O (99:1) as eluent afforded 42a (23.2 mg, 94%).
Similarly, 39b (20.5 mg, 0.086 mmol) afforded 42b
(13.3 mg, 94%).
1615, 1249, and 856 cm21
;
1H NMR d¼20.01 (9H, s,
SiMe3), 1.58–1.74 (4H, m), 2.02 (2H, br s, CH2SiMe3),
2.20–2.26 (2H, m), 2.31–2.37 (2H, m), 6.12–6.17 (1H, m,
CvCHCH2), 6.53 (1H, br s, CHvCCHO), and 9.31 (1H, s,
CHO); 13C NMR d¼20.94 (3C), 15.53, 21.63, 22.59, 26.41,
28.33, 135.80, 136.61, 138.15, 150.66, and 196.19; MS m/z
221 (Mþ2 H, 3%), 207 (3), 180 (6), 131 (7), 117 (9), 104
(10), 91 (18), and 73 (100); HRMS [Found: m/z 222.1428
(Mþ). Calcd for C13H22OSi: M, 222.1441].
4.7.1. 4-t-Butyl-8-methylenebicyclo[4.3.0]non-9-en-7-ol
(42a). An oil; IR (neat) 3390 (OH), 1639, 1365, 1265,
1
1072, 866, and 737 cm21; H NMR d¼0.87 (9H of one
isomer, s, t-Bu), 0.87 (9H of one isomer, s, t-Bu), 0.79–2.69
(9H, m), 4.24–4.32 (1H, m, CHOH), 4.84–4.90 (2H, m,
CvCH2), 5.77 (1H of one isomer, s, CvCHCvCH2), and
5.82 (1H of one isomer, s, CvCHCvCH2); 13C NMR
d¼23.51, 25.92, 27.56 (3C), 27.64 (3C), 27.77, 29.21,
29.66, 32.49, 32.98, 33.72, 43.10, 43.31, 50.59, 54.60,
79.88, 81.24, 101.58, 102.36, 122.67, 123.68, 153.09,
153.60, 156.81, and 157.02; MS m/z 206 (Mþ, 1%), 188
(31), 173 (9), 131 (48), 104 (32), 57 (39), and 43 (100);
HRMS (CI) [Found: m/z 207.1652 (MþþH). Calcd for
C14H23O: M, 207.1749].
4.6. Cyclization of 27
By the same procedure described above, compound 27
(25.6 mg, 0.114 mmol) was treated with MnO2 (260 mg) in
dry CH2Cl2 (10 cm3) at room temperature for 75 min. After
filtration through Celite, the filtrate was concentrated and
chromatographed on silica gel (1 g) using pentane/Et2O
(99:1) as eluent to afford 30 (5.1 mg, 20%) and 31 (10.7 mg,
63%).
4.7.2. 4-Methyl-8-methylenebicyclo[4.3.0]non-9-en-7-ol
(42b). An oil; IR (neat) 3370 (OH), 1639, 1265, 1049,
4.6.1. 8-Methylenebicyclo[4.3.0]non-9-en-7-ol (30). An
oil; IR (neat) 3350 (OH), 1639, 1446, 1036, 868, and
1
868, and 739 cm21; H NMR d¼0.71–2.63 (9H, m), 0.93
1
739 cm21; H NMR d¼1.04 (1H, dq, J¼3.3, 12.5 Hz, 5b-
(3H of one isomer, d, J¼6.5 Hz, Me), 1.08 (3H of one
isomer, d, J¼7.1 Hz, Me), 4.25 (1H, br s, CHOH), 4.87–
4.92 (2H, m, CvCH2), and 5.79 (1H, s, CvCHCvCH2);
13C NMR d¼16.88, 22.14, 24.24, 27.75, 28.93, 31.99,
32.06, 35.25, 38.07, 41.04, 48.98, 54.22, 79.63, 80.01,
102.54 (for both isomers), 122.84, 123.12, 153.24, 153.86,
156.58, and 156.83; MS m/z 164 (Mþ, 48%), 149 (33), 131
(44), 122 (61), 91 (61), and 79 (100); HRMS (CI)
[Found: m/z 165.1274 (MþþH). Calcd for C11H17O: M,
165.1279].
H), 1.17–1.44 (2H, m, 3b-H and 4a-H), 1.68 (1H, br d,
J¼6 Hz, OH), 1.77–1.89 (2H, m, 3a-H and 4b-H), 2.06
(1H, br dt, J¼5, 13 Hz, 2a-H), 2.14–2.22 (1H, m, 5a-H),
2.34–2.41 (1H, m, 6-H), 2.49 (1H, ddt, J¼4.0, 13.9, 2.2 Hz,
2b-H), 4.26 (1H, br s, 7-H), 4.88 (1H, br s, CvCHH), 4.91
(1H, d, J¼1.5 Hz, CvCHH), and 5.79 (1H, br s, 9-H); 13C
NMR d¼25.57, 26.91, 29.47, 29.69, 32.75, 79.65, 102.55,
123.05, 153.61, and 156.61; MS m/z 150 (Mþ, 74%), 135
(17), 121 (81), 108 (81), 91 (79), and 79 (100); HRMS
[Found: m/z 150.1040 (Mþ). Calcd for C10H14O: M,
150.1045].
4.8. Cyclization of 8a–c and 17a–c
4.6.2. 8-Methylene-7-(trimethylsilyloxy)bicyclo[4.3.0]-
non-9-ene (31). An oil; IR (CH2Cl2) 1458, 1097, 1030,
To a stirred solution of FeCl3 (63.4 mg, 391 mmol) in dry
CH2Cl2 (6 cm3; distilled from CaH2) was added a solution
of 8a (42.8 mg, 181 mmol) in CH2Cl2 (10 cm3) dropwise at
260 8C under Ar. Monitoring on TLC, the mixture was
slowly warmed to room temperature over 7 h. A saturated
aqueous solution of NaHCO3 was added, and the mixture
was extracted with CH2Cl2 and dried. Evaporation of the
solvent followed by silica gel (15 g) column chromato-
graphy using hexane/AcOEt (98:2) afforded 12a (23.3 mg,
78%). Similarly, 8b and 8c gave 12b and 12c in 80 and 70%
yields, respectively. See Tables 1 and 2 for the modified
reaction conditions of the cyclization of 17a–c.
1
and 802 cm21; H NMR d¼0.18 (9H, s, SiMe3), 1.03 (1H,
dq, J¼3.3, 12.5 Hz), 1.16–1.44 (2H, m), 1.76–1.88 (2H,
m), 1.98–2.19 (2H, m), 2.35–2.50 (2H, m), 4.31 (1H, dt,
J¼3.4, 2.2 Hz, CHOSiMe3), 4.75 (1H, br s, CvCHH), 4.86
(1H, d, J¼1.6 Hz, CvCHH), and 5.78 (1H, br s, CHvC);
13C NMR d¼0.43 (3C), 25.61, 26.72, 29.47, 32.65, 53.56,
80.15, 102.17, 123.43, 152.43, and 155.70; MS m/z 222
(Mþ, 31%), 207 (10), 180 (18), 117 (23), 104 (27), 91 (32),
and 73 (100); HRMS [Found: m/z 222.1438 (Mþ). Calcd for
C13H22OSi: M, 222.1441].
4.7. Cyclization of 39a,b
4.8.1. 2-Methylspiro[4.5]dec-2-en-1-one (12a). An oil; UV
(EtOH) lmax 227.4 nm (1 1.0£1024); IR (neat) 1702
1
By the same procedure, compound 39a (34.2 mg,
0.122 mmol) was treated with MnO2 (450 mg) at room
temperature for 5 min. After the mixture had been filtered
through Celite, the solvent was evaporated off. The resultant
oily residue was dissolved in Et2O (5 cm3), silica gel (ca.
100 mg) was added, and the mixture was stirred for 3 days.
The silica gel was filtered off, washed with Et2O, and the
solvent was partly evaporated. Et2O was added to a volume
of ca. 5 cm3 again, and Bu4NF (31 mg) was added. After the
mixture had been stirred at room temperature for 4 h, an
aqueous solution of NH4Cl was added, and the mixture was
(CvO), 1640, 1261, 1098, 1021, and 804 cm21; H NMR
d¼1.20–1.40 (6H, m), 1.52–1.77 (4H, m), 1.77 (3H, dt,
J¼1.3, 2.3 Hz, Me), 2.42 (2H, quint, J¼2.3 Hz, CvCCH2),
and 7.23 (1H, tq, J¼2.3, 1.3 Hz, CvCH); 13C NMR
d¼10.39, 23.05 (2C), 25.25, 33.40 (2C), 39.97, 48.08,
139.65, 155.74, and 214.42; MS m/z 164 (Mþ, 16%), 149 (7),
121 (16), 109 (100), 96 (28), 79 (16), and 41 (31); HRMS
[Found: m/z164.1216(Mþ). Calcdfor C11H16O: M, 164.1202].
4.8.2. 8-t-Butyl-2-methylspiro[4.5]dec-2-en-1-one (12b).
1
An oil; IR (neat) 1706 (CvO), 1637, and 1009 cm21; H

330
C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
NMR d¼0.85 (9H, s, tBu), 1.00–1.11 (3H, m), 1.24–1.35
(2H, m), 1.53–1.66 (2H, m), 1.73–1.80 (2H, m), 1.77 (3H,
dt, J¼1.4, 2.2 Hz, Me), 2.39 (2H, quint, J¼2.2 Hz,
HRMS [Found: m/z 220.1818 (Mþ). Calcd for C15H24O: M,
220.1828].
1
CvCCH2), and 7.23 (1H, tq, J¼2.2, 1.4 Hz, CvCH); H
4.8.7. 2,8-Dimethylspiro[4.5]dec-3-en-1-one (21c). An oil;
IR (CH2Cl2) 1738 (CvO), 1450, 1377, 955, and 883 cm21
;
NMR (C6D6¼7.15) d¼0.79 (9H, s, tBu), 0.76–0.96 (3H, m,
7ax-H, 8-H, and 9ax-H), 1.15–1.21 (2H, m, 6eq-H and 10eq-
H), 1.52–1.59 (2H, m, 7eq-H and 9eq-H), 1.70 (3H, dt,
J¼1.4, 2.2 Hz, Me), 1.74 (2H, br dt, J¼3.5, 13 Hz, 6ax-H
and 10ax-H), 1.91 (2H, quint, J¼2.2 Hz, CvCCH2), and
6.57 (1H, tq, J¼2.2, 1.4 Hz, CvCH); 13C NMR d¼10.39
(CH3), 24.04 (2CH2), 27.43 (3CH3), 32.40 (C), 34.07
(2CH2), 39.90 (CH2), 46.93 (CH), 48.08 (C), 139.84 (C),
155.82 (CH), and 214.66 (CO); MS m/z 220 (Mþ, 7%), 205
(3), 163 (100), 109 (97), and 57 (98); HRMS [Found: m/z
220.1783 (Mþ). Calcd for C15H24O: M, 220.1828].
1H NMR d¼0.91 (3H, d, J¼6.5 Hz, Me), 1.00–1.69 (9H,
m), 1.13 (3H, d, J¼7.5 Hz, Me), 2.94 (1H, tq, J¼2.1,
7.5 Hz, COCHMe), 6.03 (1H, dd, J¼2.1, 7.1 Hz, CHvCH),
and 6.36 (1H, dd, J¼2.1, 7.1 Hz, CHvCH); 13C NMR
(C6D6¼128.00) d¼15.95, 22.65, 31.28, 31.42, 32.30, 33.97,
34.03, 46.90, 54.03, 132.63, 135.28, and 221.24; MS m/z
178 (Mþ, 4%), 150 (95), 135 (20), 121 (45), 93 (67), 79 (87),
and 41 (100); HRMS [Found: m/z 178.1366 (Mþ2H). Calcd
for C12H18O: M, 178.1358].
4.9. The cyclization products obtained from 28
4.8.3. 2,8-Dimethylspiro[4.5]dec-2-en-1-one (12c). An oil;
UV (EtOH) lmax 227.8 nm (1 1.0£1024); IR (neat) 1703
1
The following compounds were detected from H and 13C
(CvO), 1641, 1452, 1072, and 1021 cm21
;
1H NMR
NMR spectra and GC–MS after partial separation into
several groups, however, it was difficult to isolate each
compounds.
d¼0.90 (3H, d, J¼6.5 Hz, Me), 0.93–1.05 (2H, m, 7ax-H
and 9ax-H), 1.21–1.28 (2H, m, 6eq-H and 10eq-H), 1.36–
1.49 (1H, m, 8-H), 1.61 (2H, br dt, J¼3.5, 13 Hz, 6ax-H and
10ax-H), 1.66–1.72 (2H, m, 7eq-H and 9eq-H), 1.77 (3H, dt,
J¼1.4, 2.3 Hz, Me), 2.39 (2H, quint, J¼2.3 Hz, CvCCH2),
and 7.23 (1H, tq, J¼2.3, 1.4 Hz, CvCH); 13C NMR
d¼10.40, 22.64, 31.55, 31.87 (2C), 33.53 (2C), 39.84,
47.81, 139.80, 155.85, and 214.69; MS m/z 178 (Mþ, 18%),
121 (16), 109 (98), and 96 (100); HRMS [Found: m/z
179.1402 (Mþ2H). Calcd for C12H19O: M, 179.1437].
4.9.1. 8-Methylbicyclo[4.3.0]non-1(6)-en-7-one (32). 1H
NMR d¼1.17 (3H, d, J¼7.3 Hz, Me), 1.61–1.76 (4H, m,
3-H2 and 4-H2), 2.03–2.15 (3H, m, 2-H2 and 9-H), 2.26–
2.32 (2H, m, 5-H2), 2.38 (1H, d quint, J¼2.0, 7.3 Hz, 8-H),
and 2.72 (1H, dm, J¼ca. 18 Hz, 9-H); 13C NMR d¼16.58,
20.09, 21.71, 22.18, 28.43, 39.16, 39.81, 137.43, 171.82,
and 211.59; GC–MS m/z 150 (Mþ, 43%), 135 (91), 122
(23), 107 (45), 91 (30), and 79 (100).
4.8.4. 2-Methylenespiro[4.5]dec-3-en-1-ol (18a). An oil;
IR (neat) 3390 (OH), 1643, 1450, 1101, 1947, 870, 800, and
735 cm21; 1H NMR d¼1.24–1.68 (11H, m), 4.18 (1H, br s,
CHOH), 5.02–5.05 (2H, m, CvCH2), 6.12 (1H, d,
J¼6.4 Hz, CHvCH–CvC), and 6.21 (1H, br d,
J¼6.4 Hz, CHvCH–CvC); 13C NMR d¼22.93, 23.37,
26.00, 31.05, 36.04, 51.18, 80.80, 105.61, 129.40, 144.67,
and 155.81; MS m/z 164 (Mþ, 5%), 149 (14), 135 (23), 121
(100), 108 (54), 91 (60), 79 (59), 67 (51), and 41 (82);
HRMS [Found: m/z 164.1297 (Mþ). Calcd for C11H16O: M,
164.1202].
1
4.9.2. cis-8-Methylbicyclo[4.3.0]non-8-en-7-one (33). H
NMR d¼1.06–2.02 (8H, m), 1.78 (3H, t, J¼1.5 Hz, Me),
2.41 (1H, q, J¼6.4 Hz, 6-H), 2.80–2.88 (1H, m, 1-H), and
7.23 (1H, sextet, J¼1.5 Hz, 9-H); 13C NMR d¼10.26,
21.09, 21.27, 22.84, 28.09, 38.64, 45.50, 139.83, 161.31,
and 211.96; GC–MS m/z 150 (Mþ, 54%), 135 (12), 121
(39), 107 (29), 93 (28), 79 (80), 69 (94), and 41 (100).
4.9.3. 8-Methylbicyclo[4.3.0]nona-1,8-dien-7-one (34). 1H
NMR d¼1.06–2.02 (3H, m), 1.85 (3H, br s, Me), 2.08–2.19
(1H, m, 3-H), 2.25 (1H, ddt, J¼4.5, 12.7, 3.5 Hz, 5-H), 2.37
(1H, dm, J¼ca. 18 Hz, 3-H), 2.69 (1H, dd-like, J¼4.9,
12.0 Hz, 6-H), 5.77 (1H, br t, J¼3 Hz, 2-H), and 7.37 (1H,
br s, 9-H); 13C NMR d¼10.29, 22.13, 22.58, 25.73, 46.95,
121.83, 139.00, 140.90, 150.85, and 207.61; GC–MS m/z
148 (Mþ, 63%), 133 (26), 120 (25), 105 (95), 91 (100), 77
(47), and 51 (47).
4.8.5. 2-Methylspiro[4.5]dec-3-en-1-one (21a). An oil; IR
(neat) 1738 (CvO), 1676, 1624, 1452, and 1161 cm21; 1H
NMR d¼1.15 (3H, d, J¼7.5 Hz, Me), 1.20–1.78 (10H, m),
2.96 (1H, tq, J¼2.2, 7.5 Hz, CHMe), 6.03 (1H, dd, J¼2.2,
7.2 Hz, CHvCH), and 6.30 (1H, dd, J¼2.2, 7.2 Hz,
CHvCH); 13C NMR d¼15.96, 22.18, 22.34, 25.68, 33.48,
33.59, 46.51, 54.01, 132.15, 135.87, and 195.70; MS m/z
164 (Mþ, 5%), 136 (100), 121 (21), 107 (68), 94 (34), 79
(92), and 41 (68); HRMS [Found: m/z 164.1169 (Mþ).
Calcd for C11H16O: M, 164.1202].
4.9.4. trans-2-Chloro-8-methylbicyclo[4.3.0]non-1(6)-en-
7-one (35). 1H NMR d¼1.19 (3H, d, J¼7.3 Hz, Me), 1.69–
1.94 (2H, m, 4-H2), 2.03 (1H, dm, J¼ca. 18 Hz, 9b-H),
2.04–2.18 (3H, m, 3-H2 and 5-H), 2.27 (1H, dm, J¼ca.
18 Hz, 5-H), 2.46 (1H, d quint, J¼2.2, 7.3 Hz, 8a-H), 3.13
(1H, ddt, J¼6.7, 18.2, 2.2 Hz, 9a-H), and 4.69 (1H, br t,
J¼4.5 Hz, 2b-H); 13C NMR d¼16.38, 18.27, 19.99, 32.80,
36.38, 40.03, 54.94, 139.74, 165.89, and 211.54; GC–MS
m/z 186 (Mþ for 37Cl, 14%), 184 (Mþ for 35Cl, 39), 169
(44), 149 (30), 121 (65), 91 (90), and 79 (100).
4.8.6. 8-t-Butyl-2-methylspiro[4.5]dec-3-en-1-one (21b).
Mp 43–45 8C; IR (neat) 1739 (CvO), 1676, 1630, 1450,
1365, and 856 cm21; 1H NMR d¼0.87 (9H, s, tBu), 1.11–
1.77 (9H, m), 1.15 (3H, d, J¼7.6 Hz, Me), 2.96 (1H, tq,
J¼2.1, 7.6 Hz, CHMe), 6.05 (1H, dd, J¼2.0, 7.2 Hz,
CHvCH), and 6.37 (1H, dd, J¼2.2, 7.2 Hz, CHvCH);
13C NMR (C6D6¼128.00) d¼15.96, 23.54, 23.71, 27.46
(3C), 32.36, 34.40, 34.54, 46.44, 47.51, 54.31, 132.65,
135.32, and 221.13; MS m/z 220 (Mþ, 4%), 192 (43), 149
(11), 135 (28), 121 (28), 93 (38), 79 (57), and 57 (100);
4.9.5. cis-2-Chloro-8-methylbicyclo[4.3.0]non-1(6)-en-7-
1
one (36). H NMR d¼1.21 (3H, d, J¼7.4 Hz, Me), 1.70–
1.94 (2H, m, 4-H2), 2.03–2.17 (3H, m, 3-H2 and 5-H), 2.26

C. Kuroda et al. / Tetrahedron 60 (2004) 319–331
331
2. (a) Kuroda, C.; Suzuki, H. Curr. Org. Chem. 2003, 7,
115–131. (b) Kuroda, C. Recent Res. Dev. Pure Appl.
Chem. 1998, 2, 189–198.
(1H, dm, J¼ca. 18 Hz, 5-H), 2.42–2.50 (2H, m, 8a-H, 9a-
H), 2.69 (1H, m, 9b-H), and 4.70 (1H, br t, J¼4.5 Hz, 2a-
H); 13C NMR d¼16.22, 18.30, 19.96, 32.79, 36.45, 40.16,
54.91, 139.80, 166.09, and 211.33; GC–MS m/z 186 (Mþ
for 37Cl, 17%), 184 (Mþ for 35Cl, 44), 169 (45), 149 (29),
121 (69), 91 (96), and 79 (100).
3. For the synthesis of ring compounds: (a) Ho, T.-L. Carbocycle
Construction in Terpene Synthesis; VCH: New York, 1988.
(b) Thebtaranonth, C.; Thebtaranonth, Y. Cyclization
Reactions; CRC: Boca Raton, 1994.
4.9.6. 8-Methenebicyclo[4.3.0]non-1(6)-en-7-one (37). 1H
NMR d¼1.62–1.79 (4H, m, 3-H2 and 4-H2), 2.19–2.25
(2H, m, 2-H2 or 5-H2), 2.34–2.40 (2H, m, 5-H2 or 2-H2),
3.07 (2H, sept, J¼1.3 Hz, 9-H2), 5.34 (1H, q, J¼1.3 Hz,
CvCHH), and 6.05 (1H, q, J¼1.3 Hz, CvCHH); 13C NMR
d¼20.29, 21.64, 22.12, 28.05, 35.49, 115.20, 140.73,
142.05, 167.84, and 195.40; GC–MS m/z 148 (Mþ, 73%),
133 (11), 120 (26), 105 (51), and 91 (100).
4. For related work on the reaction of functionalized allylsilane
reported recently from our laboratory: (a) Suzuki, H.; Monda,
A.; Kuroda, C. Tetrahedron Lett. 2001, 42, 1915–1917.
(b) Suzuki, H.; Kuroda, C. Tetrahedron 2003, 59, 3157–3174.
(c) Kuroda, C.; Kasahara, T.; Akiyama, K.; Amemiya, T.;
Kunishima, T.; Kimura, Y. Tetrahedron 2002, 58,
4493–4504. (d) Kuroda, C.; Anzai, S. Chem. Lett. 1998,
875–876. (e) Kuroda, C.; Tang, C. Y.; Tanabe, M.; Funakoshi,
M. Bull. Chem. Soc. Jpn 1999, 72, 1583–1587.
4.9.7. 8-(Chloromethyl)bicyclo[4.3.0]non-1(6)-en-7-one
(38). 1H NMR d¼1.62–1.79 (4H, m, 3-H2 and 4-H2),
2.10–2.17 (2H, m, 2-H2 or 5-H2), 2.32–2.38 (2H, m, 5-H2
or 2-H2), 2.51 (1H, dm, J¼18 Hz, 9-H), 2.65–2.79 (2H, m,
8-H and 9-H), 3.73 (1H, dd, J¼6.6, 10.8 Hz, CHHCl), and
3.82 (1H, dd, J¼3.7, 10.8 Hz, CHHCl); 13C NMR d¼19.99,
21.54, 22.03, 28.48, 34.88, 44.75, 46.82, 138.54, 173.36,
and 206.15; GC–MS m/z 186 (Mþ for 37Cl, 7%), 184 (Mþ
for 35Cl, 21), 149 (35), 107 (100), and 79 (71).
5. Kuroda, C.; Kobayashi, K.; Koito, A.; Anzai, S. Bull. Chem.
Soc. Jpn 2001, 74, 1947–1961, and references cited therein.
6. Kuroda, C.; Ito, K. Bull. Chem. Soc. Jpn 1996, 69, 2297–2303.
7. Kuroda, C.; Nogami, H.; Ohnishi, Y.; Kimura, Y.; Satoh, J. Y.
Tetrahedron 1997, 53, 839–858.
8. Nishitani, K.; Nakamura, Y.; Orii, R.; Arai, C.; Yamakawa, K.
Chem. Pharm. Bull. 1993, 41, 822–831.
9. Nishitani, K.; Harada, Y.; Nakamura, Y.; Yokoo, K.;
Yamakawa, K. Tetrahedron Lett. 1994, 35, 7809–7812.
10. Kuroda, C.; Koshio, H.; Koito, A.; Sumiya, H.; Murase, A.;
Hirono, Y. Tetrahedron 2000, 56, 6441–6455.
Acknowledgements
11. (a) Denmark, S. E. Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon: Oxford, 1991; Vol. 5, pp 751–784.
(b) Denmark, S. E.; Klix, R. C. Tetrahedron 1988, 44,
4043–4060. (c) Denmark, S. E.; Wallace, M. A.; Walker,
C. B., Jr. J. Org. Chem. 1990, 55, 5543–5545.
We are grateful to Professor M. Tori of Tokushima Bunri
University for the measurement of high-resolution mass
spectra. Thanks are also due to Professor E. Horn of Rikkyo
University for help in the writing of this article.
12. Kuroda, C.; Mitsumata, N.; Tang, C. Y. Bull. Chem. Soc. Jpn
1996, 69, 1409–1416.
13. Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds; Academic: New York, 1972; Vol. II.
References and notes
14. Fraga, B. M. Nat. Prod. Rep. 1999, 16, 21–38, 1999, 16, 711–
730; 2000, 17, 483–504; 2001, 18, 650–673; 2002, 19, 650–
672.
1. For the reaction of allylsilanes, see: (a) Langkopf, E.;
Schinzer, D. Chem. Rev. 1995, 95, 1375–1408. (b) Fleming,
I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063–2192.
(c) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93,
2207–2293. (d) Majetich, G. Organic Synthesis: Theory and
Application; Hudlicky, T., Ed.; JAI: Greenwich, 1989; Vol. 1,
pp 173–240.
15. Preliminary communications: Kuroda, C.; Koshio, H. Chem.
Lett. 2000, 962–963.
16. Suzuki, H.; Kuroda, C. J. Chem. Res. 2003, 310–312.
17. Caine, D. Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 3, pp 1–63.