Synthesis of spirocyclic β-methylene-γ-lactone utilizing hydroxymethylation of functionalized allylsilane

Article abstract of DOI:10.1016/S0040-4020(02)00403-9

A new spiro-β-methylene-γ-lactone annulation reaction is addressed for the synthesis of 4-methylene-2-oxaspiro[4.5]decan-1-one and its derivatives. 2-Cyclohexylidene-3-trimethylsilylprop-1-yl pivalate, obtained from cyclohexanone, was hydroxymethylated followed by desilylation to afford 2-[(1-hydroxymethyl)cyclohexyl]prop-2-en-1-yl pivalate and its -1-en-1-yl isomer. The former was oxidized to carboxylic acid followed by lactonization to the above compound. It was found that the stereochemistry of the hydroxymethylation reaction depends on the substituent on the cyclohexane ring.

Full text of DOI:10.1016/S0040-4020(02)00403-9

TETRAHEDRON
Pergamon
Tetrahedron 58 ,2002) 4493±4504
Synthesis of spirocyclic b-methylene-g-lactone utilizing
hydroxymethylation of functionalized allylsilane
Chiaki Kuroda,p Takahiro Kasahara, Kouki Akiyama, Takuma Amemiya, Takashi Kunishima
and Yoshihiro Kimura
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Received 1 March 2002; accepted 8 April 2002
AbstractÐA new spiro-b-methylene-g-lactone annulation reaction is addressed for the synthesis of 4-methylene-2-oxaspiro[4.5]decan-1-
one and its derivatives. 2-Cyclohexylidene-3-trimethylsilylprop-1-yl pivalate, obtained from cyclohexanone, was hydroxymethylated
followed by desilylation to afford 2-[,1-hydroxymethyl)cyclohexyl]prop-2-en-1-yl pivalate and its -1-en-1-yl isomer. The former was
oxidized to carboxylic acid followed by lactonization to the above compound. It was found that the stereochemistry of the hydroxymethyl-
ation reaction depends on the substituent on the cyclohexane ring. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
Substituted allylsilanes with carbonyl group at the
b-position ,b-carbonylallylsilanes) and their reduced form
,b-,hydroxymethyl)allylsilanes) are useful precursors for
the synthesis of odd-membered rings,1,2 since these moieties
can formally react with both nucleophiles and electrophiles
at the same carbon as shown in Scheme 1 ,arrow `a' is for an
Scheme 2.
electrophile and arrow `b' is for a nucleophile). We3,4 and
Nishitani's group5,6 independently developed a synthetic
allylsilanes, such as b-,dialkoxymethyl)-,10,11 b-,halo-
strategy towards fused a-methylene-g-lactones, basic
methyl)-,12±15
and
b-,hydroxymethyl)allylsilanes16,17
structure of terpenoids, utilizing an intramolecular reaction
of b-,ethoxycarbonyl)allylsilane with aldehyde ,Scheme 2,
XˆO). We also reported a synthesis of a ®ve-membered
carbocycle by the same strategy ,XˆCHCOCH3),7 as well
as the synthesis of a-methylene-g-lactone via a different
mode from related functionalized allylsilane.8,9 While a
number of synthesis of ®ve- and seven-membered rings
are reported with the use of b-,functionalizedmethyl)-
including trimethylenemethane developed by Trost's
group.18
Although a-methylene-g-lactone is the major unit in natural
terpenes, a-methylene-d-lactone and b-methylene-g-
lactone are also found in nature.19 Nishitani et al. reported
a synthesis of a-methylene-d-lactone from the related
methodoloy,20 i.e. by replacing the CˆX group in Scheme
2 with epoxide. Based on these backgrounds, we currently
focus on the synthesis of the third type of methylenelactone,
b-methylene-g-lactone, by the related strategy. a,a0-Spiro-
cyclic b-methylene-g-lactones are found as a part of
bakkenolide A or related sesquiterpenes19 having some
biological activity.21 These natural sesquiterpenes have a
2-oxaspiro[4.4]nonan-1-one skeleton, however a natural
product having a 2-oxaspiro[4.5]decan-1-one skeleton was
also found recently.22 To date, several syntheses have been
reported focusing on this interesting structure.23±27 Our
basic strategy is to use exocyclic b-,hydroxymethyl)allyl-
silane derivative 1, which can easily be obtained from
cycloalkanone and had been used previously as the key
intermediate for the synthesis of spiro[4.5]decane 2 or
spiro[4.4]nonane 3.9b ,Scheme 3). Spirolactones are
Scheme 1.
Keywords: lactones; silicon and compounds; spiro compounds.
Corresponding author. Tel: 181-3-3985-2396; fax: 181-3-5992-3434;
e-mail: kuroda@rikkyo.ac.jp
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,02)00403-9

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C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
Scheme 5. Reagents and conditions: ,i) PivCl, pyridine, rt; ,ii) ,CH2O)n,
Et2AlCl, CH2Cl2, 2608C, see Table 1.
2. Results and discussion
Our ®rst idea was to cyclize carbonate 9 from which lactone
4 can be obtained directly as described in Scheme 4. The
substrate 9 was prepared from 89b by treatment with methyl
chloroformate in pyridine ,95%). However, no desired
lactone 4 was obtained when 9 was treated with Lewis
acids, such as BF3OEt2, SnCl4, and TiCl4. While, the desilyl-
ated product 10 was afforded in 69% yield from a Bu4NF
treatment. The product of the Lewis acid treatment could
not be identi®ed, however, it was shown by TLC monitoring
that a non-polar product was produced. This can be under-
stood by the elimination of carbonate under an acidic
condition giving a stable allylic carbocation.
Scheme 3.
Then our strategy was changed to introduce a one carbon
unit prior to the lactonization ,Scheme 5). The hydroxyl
group of 8 was ®rst protected as a pivalate to give 11.
Since the reaction site of 11 ,i.e. the g-position of the allyl-
silane) is sterically hindered, hydroxymethylation using
formaldehyde, the smallest molecule for this purpose, was
studied. Reaction of b-,trimethylsilyloxymethyl)allylsilane
with formaldehyde in the presence of various Lewis acids as
Scheme 4. Reagents and conditions: ,i) ClCOOMe, pyridine, 08C;
,ii) Bu4NF, THF, rt.
the catalyst was studied by Marko et al.28 among which the
Â
Hosomi±Sakurai type of reaction occurred when TiCl4 was
used as the catalyst. Therefore, we ®rst attempted the
hydroxymethylation of 11 with paraformaldehyde29 in the
presence of TiCl4, but the result was unsatisfactory. Et2AlCl
was then used as the Lewis acid, expecting that the same
product would be obtained after desilylation. The results are
summarized in Table 1. When the reaction was carried out at
expected to be obtained from 1 via a Hosomi±Sakurai type
of one carbon introduction as the key step, and thus the total
reaction of the present method forms a spiro-b-methylene-
g-lactone annulation. Here we report the synthesis of spiro-
cyclic b-methylene-g-lactones 4, 5, 6a, b, and 7a, b from
the corresponding cycloalkanones by this strategy.
Table 1. Hydroxymethylation of 11
Entry
Temperature ,8C)
Time
Concentration ,mol/l)
Yield of 12a ,%)
Recovered 11 ,%)
1
2
3
4
5
rt
30 min
15 min
17 h
40 min
15 min
0.01
0.04
0.01
0.04
0.07
±
±
220
260
260
260
7 ,26)
10 ,63)
14 ,69)
26 ,94)
73
84
80
72
All reactions were carried out with excess amount ,ca. 10 equiv.) of paraformaldehyde in the presence of Et2AlCl ,ca. 3 equiv.) in CH2Cl2.
Yield based on consumed material is shown in parenthesis.
a

C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
4495
room temperature, only a complex mixture was afforded,
among which 12 was detected by TLC but could not be
isolated ,entry 1). Then the reaction was carried out at
lower temperature. In all cases ,entries 2±5), a considerable
amount of unreacted substrate 11 was recovered. The yield
of 12 was increased when the reaction was carried out in
more concentrated solutions, and ®nally 12 was obtained in
94% yield based on the consumed material ,entry 5). Some
other Lewis acids, such as EtAlCl2, SnCl4, and BF3OEt2
were also tested in the hydroxymethylation reaction but
no desired product was obtained. Tetrabutylammonium
¯uoride promoted anionic reaction conditions also did not
afford the alkylated product. Compound 12 was obtained as
the single isomer, however, the geometry of the double bond
was not determined.28
Scheme 7. See Scheme 6 for the reagents and conditions.
Desilylation of 12 with Bu4NF was carried out next expect-
ing to produce the exo-methylenic product 13. However, 13
was obtained together with its double-bond isomer 14 ,13/
14ˆca. 2:1) in a total product yield of 86% ,Scheme 6)
which could be separated by repeated silica-gel column
chromatography. The alcohol 13 was then converted to
carboxylic acid 15 by Swern oxidation followed by chlorite
oxidation ,94% yield in two oxidation steps). Alkali
hydrolysis of pivalates 15 did not afford the corresponding
hydroxy acid, but the desired lactone 4 was obtained in an
85% yield after the acidic work up.
double-bond isomer 22 ,totally 96%), which was then
hydrolyzed to afford lactone 4 and hemiacetal 23, derived
from 22 ,Scheme 7). This mixture could easily be separated,
and 4 and 23 were obtained in 58 and 27% yields, respec-
tively. It was found that hemiacetal 23 consisted of ca. a 3:1
mixture of diastereomeres, however, the stereochemistry of
the isomers was not determined.
To study the substituent effect on the cyclohexane ring,
spirolactones 6a, b were synthesized from 4-tbutylcyclo-
hexanone. Compound 25, obtained by pivaloylation of
24,9b was subjected to the hydroxymethylation, in which
medium stereoselectivity was observed giving a mixture
of two diastereomers, 26a and 26b, in a 2:5 ratio ,97%
yield based on the consumed material) ,Scheme 8). These
isomers could be separated by silica-gel column chromato-
graphy, however, the stereochemistry of the products was
determined at the latest stage. When Me2AlCl29 was used
for the hydroxymethylation, instead of Et2AlCl, the
substrate 25 was consumed within 1 h, and the products
26a, b were obtained in a 66% yield with the same ratio
,26a/26bˆ2:5). Desilylation of 26a afforded an inseparable
mixture of double-bond isomers 27a and 28a in a 93% yield
In the same way, spiro-b-methylene-g-lactone fused to the
cyclopentane ring 5 was synthesized. Thus, hydroxymethyl-
ation of compound 17, prepared from 169b as above,
afforded 18 in an 80% yield based on the consumed
material. Desilylation of 18 gave 19 and 20 ,totally 90%),
the former of which was oxidized to 21 ,89%, in two oxida-
tion steps) followed by lactonization to yield 5 in an 88%
yield ,Schemes 5 and 6).
Since the separation of the double-bond isomers 13 and 14
was not easy, puri®cation of the lactone in the last stage was
also examined. Namely, a mixture of 13 and 14 was
oxidized as described above giving a mixture of 15 and its
Scheme 6. Reagents and conditions: ,i) Bu4NF, THF or DMF, rt;
,ii) DMSO, ,COCl)2, Et3N, CH2Cl2, rt; ,iii) NaClO2, NaH2PO4, 2-methyl-
2-butene, tBuOH, rt; ,iv) NaOH aq, THF, rt, then HCl aq, rt.
Scheme 8. Reagents and conditions: ,i) PivCl, pyridine, rt; ,ii) ,CH2O)n,
Et2AlCl, CH2Cl2, 2608C.

4496
C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
Figure 1.
Spirolactones having an oxygen-functionality, 7a and 7b,
were also synthesized from 4-benzyloxycyclohexanone.
Compound 32 was prepared by the Horner±Emmons
reaction followed by LiAlH4 reduction, as reported
previously ,see Section 3). Although the stereoselectivity
of the hydroxymethylation of 33 was lower, it is interesting
that the selectivity was opposite to the case of 25, giving 34a
and 34b in ca. 3:2 ratio ,91% yield based on the consumed
material) ,Scheme 8). This inseparable mixture of stereo-
isomers, 34a and 34b, was desilylated to afford a mixture of
four isomers 35a, b/36a, b ,totally 92%) ,Scheme 10).
Scheme 9. Reagents and conditions: ,i) Bu4NF, THF, rt; ,ii) DMSO,
,COCl)2, Et3N, CH2Cl2, rt; ,iii) NaClO2, NaH2PO4, 2-methyl-2-butene,
tBuOH, rt; ,iv) NaOH aq, THF, rt, then HCl aq, rt.
,27a/28aˆca. 3:2) ,Scheme 9). Similarly, 26b afforded a
mixture of 27b and 28b in a 99% yield. Two-step oxidation
of these mixtures of alcohols afforded corresponding
carboxylic acids as above, however, the separation of the
double-bond isomers was successfully made at the inter-
mediate aldehydes. Namely, Swern oxidation of the mixture
of 27a and 28a gave corresponding aldehydes, which were
separated by silica-gel column chromatography to yield 29a
and 30a in 56 and 35% yields, respectively. Similarly, 29b
and 30b were obtained in 47 and 37% yields, respectively,
after separation. The aldehydes 29a and 29b were then
converted to lactones 6a and 6b, respectively, by chlorite
oxidation ,31a: 93%, 31b: 80%) followed by hydrolysis ,6a:
96%, 6b: 93%).
The stereochemistry of 6a and 6b were determined from 1H
NMR spectra including an NOE experiment. Thus, the NOE
signal was observed between one of methylenic proton and
6,axial)-H for 6b, and 7,axial)-H for 6a ,Fig. 1). From this,
the stereochemistry of 26a, b, 27a, b, 29a, b, and 31a, b was
also established.
Scheme 10. Reagents and conditions: ,i) Bu4NF, THF, rt; ,ii) DMSO,
,COCl)2, Et3N, CH2Cl2, rt; ,iii) NaClO2, NaH2PO4, 2-methyl-2-butene,
tBuOH, rt; ,iv) NaOH aq, THF, rt, then HCl aq, rt.

C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
4497
mation from the related compound 6a ,see Fig. 1). This
indicates that exo-methylene group in conformer ii comes
over the cyclohexane ring, which makes ii less stable than i.
The preferential formation of 26b over 26a in the hydroxy-
methylation reaction of 25 can be rationalized by steric
effects based on the assumption that the tBu substituent
takes an equatorial orientation ,Scheme 11). It is known
that the equatorial attack on the exo-cyclic double-bond
,direction `a', the less-hindered side attack) is normally
more favored over the axial attack ,direction `b', the more
hindered side attack).30 However, in this case, attacking
from the `b' side is more favorable than from the `a' side,
since the exocyclic double-bond have bigger substituents
than the attacking reagent. Thus, attacking the activated
formaldehyde to 25 from direction `a' gives the sterically
congested intermediate A in which the bigger substituent is
located in the axial orientation. This makes intermediate B,
generated from the `b' side attack, more favored. The
related stereoselectivity was also observed in the synthesis
of 2 via the Nazarov cyclization.9b The reversed stereoselec-
tivity for 33 can be justi®ed by the ¯ip of the cyclohexane
ring from A to C, in which the biggest substituent takes the
equatorial conformation. Thus, in contrast to 26a, the
product of the less-hindered side attack ,direction `a') 34a
is not sterically congested. The related ¯ipping of cyclo-
hexane ring is also observed for the conformation of the
four lactones 6a, b and 7a, b ,see Figs. 1 and 2). The forma-
tion of the sterically hindered transition state also explains
the low reactivity of 11, 17, 25, and 33.
Figure 2.
Without puri®cation, these were subjected to the Swern
oxidation to yield a mixture of aldehydes 37a, b/38a, b in
a 75% yield from 34a, b. As in the case of 29/30, regio- and
stereoisomers could be separated from each other at this
stage to obtain 37a and 37b, which were then oxidized to
the carboxylic acids, 39a ,96%) and 39b ,82%), followed by
lactonization to afford 7a ,94%) and 7b ,94%), respectively.
The structure of 7a and 7b was determined from the J-value
of 8-H, the benzyloxy-bearing position, together with the
NOE measurements ,Fig. 2). Namely, the J-value of 8-H
indicates that the benzyloxy group is axial for 7a ,tt, Jˆ3.1,
6.0 Hz; conformer i) and equatorial for 7b ,tt-like, Jˆ3.9,
9.3 Hz). The NOE was observed between 6-H and 8-H for
7b but not for 7a, while the NOE between 6-H and one of
the exo-methylene was observed for both 7a and 7b. From
these data, it was established that 8-H and exo-methylene
are located on the same side of the cyclohexane ring for 7b
and opposite side for 7a. It is interesting that the spectral
data of 7a are explained by conformer i, a `¯ipped' confor-
In conclusion, a new spiroannulation strategy for the
synthesis of a,a-spirocyclic b-methylene-g-lactone from
cycloalkanone was established via a hydroxymethylation
of b-,acyloxymethyl)allylsilane derivative. It was shown
that b-,functionalizedmethyl)allylsilane is a useful organic
bifunctional unit by which three types of methylenelactones,
a-methylene-g-lactones, b-methylene-g-lactones, and
a-methylene-d-lactones could be synthesized based on the
Scheme 11.

4498
C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
same concept. In addition, the b-,acyloxymethyl)allylsilane
derivative 1 was shown to be a good intermediate for the
synthesis of two types of spirocyclic compounds, carbo-
cycles ,2, 3) and lactones ,4, 5), from cycloalkanone. More-
over, it was found that the stereochemistry of the
hydroxymethylation of the cyclohexylidene system depends
on the substitution pattern, as well as, the possibility to
adopt the ¯ipped conformation.
[Found: m/z 360.2094 ,M1). Calcd for C21H32O3Si: M,
360.2122].
3.2.2. 2-.4-Benzyloxy)cyclohexylidene-3-trimethylsilyl-
propanol .32). An oil; IR ,neat) 3390 ,OH), 1453, 1246,
1094, 847, and 696 cm21; 1H NMR ,CDCl3) dˆ0.02 ,9H, s,
SiMe3), 1.27 ,1H, br, OH), 1.47±1.59 ,2H, m), 1.70 ,2H, br
s, CH2SiMe3), 1.87±2.06 ,4H, m), 2.40±2.48 ,1H, m),
2.60±2.68 ,1H, m), 3.56 ,1H, tt, Jˆ3.4, 8.5 Hz, CHOBn),
4.04 ,1H, d, Jˆ11.4 Hz, CHHOH), 4.07 ,1H, d, Jˆ11.4 Hz,
CHHOH), 4.58 ,2H, s, OCH2Ph), and 7.25±7.39 ,5H, m,
Ph); 13C NMR ,CDCl3) dˆ20.85 ,3C), 21.45, 26.33, 27.46,
32.31, 32.98, 63.32, 69.81, 75.95, 127.32, 127.42 ,2C),
127.93, 128.27 ,2C), 133.09, and 139.03; MS m/z 318
,M1, 90%), 298 ,100), 242 ,12), 229 ,12), 160 ,15), and
63 ,15); HRMS [Found: m/z 318.2032 ,M1). Calcd for
C19H30O2Si: M, 318.2016].
3. Experimental
3.1. General procedure
Melting points were collected on a Laboratory Devices Mel-
Temp apparatus. IR spectra were taken on a Jasco FT/IR-
1
230 spectrometer. Both H and 13C NMR spectra were
1
measured on a Jeol GSX-400 ,400 MHz for H; 100 MHz
for 13C) spectrometer. Chemical shifts were reported on the
d scale ,ppm) with solvent ,CHCl3ˆ7.26) as an internal
standard, unless otherwise noted. The signal of the solvent
,CDCl3ˆ77.00) 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-700, JMS-HX100, 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 were used for column chromato-
graphy. Anhydrous Na2SO4 or MgSO4 was used for drying
the extracted organic layers.
3.3. Pivaloylation
In a 100 cm3 round bottomed ¯ask attached to a CaCl2
drying tube was placed a solution of 8 ,991.3 mg,
4.67 mmol) in dry pyridine ,50 cm3; distilled from CaH2).
After being cooled to 08C, pivaloyl chloride ,0.69 cm3) was
added, and the mixture was stirred at room temperature
overnight. Subsequently, water was added, and the mixture
was extracted with ether and dried. Evaporation of the
solvent followed by silica gel ,20 g) column chromato-
graphy using hexane±AcOEt ,99:1) as eluent afforded 11
,1247.1 mg, 90%).
Compounds 17, 25, and 33 were obtained by the same
procedure in 92, 94, and 94% yields, respectively.
3.2. Horner±Emmons reaction and reduction
See Ref. 9b for the preparation and spectral data of 8, 16,
and 24. Compound 32 was prepared from 4-benzyloxy-
cyclohexanone by the same way ,Scheme 12).
3.3.1. 2-Cyclohexylidene-3-trimethylsilylprop-1-yl piva-
late .11). An oil; IR ,neat) 1727 ,CvO), 1479, 1247, 1153,
1
and 849 cm21; H NMR ,CDCl3) dˆ0.00 ,9H, s, SiMe3),
1.19 ,9H, s, tBu), 1.45±1.58 ,6H, m), 1.62 ,2H, s,
CH2SiMe3), 2.07±2.18 ,4H, m), and 4.48 ,2H, s, CH2OPiv);
13C NMR ,CDCl3) dˆ20.93 ,3C), 21.88, 26.75, 27.24 ,3C),
27.80, 28.45, 30.64, 31.16, 38.79, 65.46, 121.79, 137.39,
and 178.69; MS m/z 296 ,M1, 14%), 176 ,9), 144 ,14),
113 ,96), and 65 ,100); HRMS [Found: m/z 296.2141
,M1). Calcd for C17H32O2Si: M, 296.2173]; Analysis
[Found: C, 68.81; H, 10.76%. Calcd for C17H32O2Si: C,
68.86; H, 10.88%].
Scheme 12.
3.3.2. 2-Cyclopentylidene-3-trimethylsilylprop-1-yl piva-
late .17). An oil; IR ,neat) 1731 ,CvO), 1480, 1283, 1156,
1
and 840 cm21; H NMR ,CDCl3) dˆ0.01 ,9H, s, SiMe3),
3.2.1. Ethyl 2-.4-benzyloxy)cyclohexylidene-3-trimethyl-
silylpropanoate .40). An oil; IR ,neat) 1711 ,CvO), 1453,
1248, 1102, and 852 cm21; 1H NMR ,CDCl3) dˆ0.00 ,9H,
s, SiMe3), 1.30 ,3H, t, Jˆ7.1 Hz, OCH2CH3), 1.58±1.68
,2H, m), 1.81 ,2H, br s, CH2SiMe3), 1.87±2.04 ,3H, m),
2.20 ,1H, ddd, Jˆ3.9, 5.7, 14.0 Hz), 2.41±2.50 ,1H, m),
2.75 ,1H, ddd, Jˆ3.6, 6.6, 13.3 Hz), 3.59 ,1H, tt, Jˆ3.6,
7.9 Hz, CHOBn), 4.17 ,2H, q, Jˆ7.1 Hz, OCH2CH3), 4.55
,1H, d, Jˆ12.0 Hz, OCHHPh), 4.58 ,1H, d, Jˆ12.0 Hz,
OCHHPh), and 7.24±7.38 ,5H, m, Ph); 13C NMR ,CDCl3)
dˆ21.23 ,3C), 14.20, 20.03, 27.55, 28.31, 32.06, 32.40,
60.14, 69.89, 75.32, 123.52, 127.36, 127.43 ,2C), 128.31
,2C), 139.01, 140.98, and 170.69; MS m/z 360 ,M1,
85%), 315 ,43), 205 ,84), 145 ,100), and 65 ,79); HRMS
1.20 ,9H, s, tBu), 1.55 ,2H, br s, CH2SiMe3), 1.60±1.67
,4H, m), 2.12±2.18 ,2H, m), 2.24±2.30 ,2H, m), and 4.49
,2H, s, CH2OPiv); 13C NMR ,CDCl3) dˆ20.67 ,3C), 22.05,
26.40, 26.91, 27.30 ,3C), 30.14, 31.52, 38.92, 66.44, 122.41,
140.16, and 178.65; MS m/z 180 ,M12PivOH, 5%), 165
,6), 159 ,9), 93 ,23), and 73 ,100); HRMS [Found: m/z
180.1291 ,M12PivOH). Calcd for C11H20Si: M, 180.1335].
3.3.3. 2-4-tButylcyclohexylidene-3-trimethylsilylprop-1-
yl pivalate .25). An oil; IR ,neat) 1727 ,CvO), 1479,
1365, 1282, 1247, 1151, and 849 cm21; H NMR ,CDCl3)
1
dˆ0.01 ,9H, s, SiMe3), 0.84 ,9H, s, tBu), 0.91±1.19 ,3H,
m), 1.20 ,9H, s, tBu), 1.63 ,1H, d, Jˆ14.3 Hz, CHHSiMe3),

C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
4499
1.65 ,1H, d, Jˆ14.3 Hz, CHHSiMe3), 1.66±1.87 ,4H, m),
2.57 ,1H, dq, Jˆ13.5, 2.7 Hz), 2.66 ,1H, dq, Jˆ13.5,
2.7 Hz), 4.48 ,1H, d, Jˆ11.8 Hz, CHHOPiv), and 4.51
,1H, d, Jˆ11.8 Hz, CHHOPiv); 13C NMR ,CDCl3)
dˆ20.90 ,3C), 21.85, 27.26 ,3C), 27.54 ,3C), 28.35,
28.99, 30.39, 30.99, 32.39, 38.82, 48.16, 65.51, 121.54,
137.22, and 178.75; MS m/z 250 ,M12PivOH, 4%), 235
,2), 193 ,5), 159 ,11), 73 ,85), and 57 ,100); HRMS [Found:
m/z 250.2081 ,M12PivOH). Calcd for C16H30Si: M,
250.2118].
3.4.2. 2-[.1-Hydroxymethyl)cyclopentyl]-3-trimethylsilyl-
prop-1-en-1-yl pivalate .18). Mp 61±628C; IR ,neat) 3450
,OH), 1730 ,CvO), 1655 ,CvC), 1266, 1144, and
1
741 cm21; H NMR ,CDCl3) dˆ0.08 ,9H, s, SiMe3), 1.26
,9H, s, tBu), 1.52±1.69 ,8H, m), 1.56 ,2H, br s, CH2SiMe3),
1.76 ,1H, br OH), 3.30 ,2H, s, CH2OH), and 6.85 ,1H, s,
CvCH); 13C NMR ,CDCl3) dˆ0.02 ,3C), 16.72, 23.43
,2C), 27.22 ,3C), 32.89 ,2C), 38.78, 52.53, 65.24, 128.44,
130.58, and 175.87; MS m/z 209 ,M12PivOH±H, 2%), 195
,2), 180 ,5), 159 ,9), 125 ,10), 73 ,68), and 57 ,100); HRMS
[Found: m/z 209.1346 ,M12PivOH±H). Calcd for
C12H21OSi: M, 209.1362].
3.3.4. 2-.4-Benzyloxy)cyclohexylidene-3-trimethylsilyl-
prop-1-yl pivalate .33). An oil; IR ,neat) 1725 ,CvO),
1479, 1282, 1247, 1152, 849, and 696 cm21
;
1H NMR
3.4.3. 2-[.trans-4-tButyl-1-hydroxymethyl)cyclohexyl]-3-
trimethylsilylprop-1-en-1-yl pivalate .26a). An oil; IR
,neat) 3450 ,OH), 1739 ,CvO), 1654 ,CvC), 1141, and
,CDCl3) dˆ0.02 ,9H, s, SiMe3), 1.20 ,9H, s, tBu), 1.47±
1.59 ,2H, m), 1.64 ,1H, d, Jˆ14.3 Hz, CHHSiMe3), 1.66
,1H, d, Jˆ14.3 Hz, CHHSiMe3), 1.87±2.01 ,4H, m), 2.41±
2.57 ,2H, m), 3.55 ,1H, tt, Jˆ3.4, 8.5 Hz, CHOBn), 4.48
,1H, d, Jˆ11.9 Hz, OCHHPh), 4.51 ,1H, d, Jˆ11.9 Hz,
OCHHPh), 4.57 ,2H, s, CH2OPiv), and 7.25±7.38 ,5H, m,
Ph); 13C NMR ,CDCl3) dˆ20.94 ,3C), 22.19, 26.82, 27.24
,3C), 27.48, 32.35, 32.85, 38.82, 65.43, 69.91, 75.96,
123.02, 127.37, 127.48 ,2C), 128.32 ,2C), 135.39, 139.07,
and 178.67; MS m/z 402 ,M1, 7%), 345 ,7), 302 ,92), 283
,94), 239 ,100), 191 ,95), and 102 ,98); HRMS [Found: m/z
402.2599 ,M1). Calcd for C24H38O3Si: M, 402.2591].
1
852 cm21; H NMR ,CDCl3) dˆ0.09 ,9H, s, SiMe3), 0.82
,9H, s, tBu), 0.95±1.61 ,8H, m), 1.28 ,9H, s, tBu), 1.55
,2H, br s, CH2SiMe3), 1.98±2.05 ,2H, m), 3.23 ,2H, br d,
Jˆ4 Hz, CH2OH), and 6.92 ,1H, s, CvCH); 13C NMR
,CDCl3) dˆ0.00 ,3C), 15.16, 23.46 ,2C), 27.26
,3C), 27.55 ,3C), 31.97 ,2C), 32.43, 38.82, 43.90, 48.82,
70.56, 124.29, 133.22, and 175.66; MS m/z 280
,M12PivOH, 0.1%), 279 ,0.2), 251 ,0.5), 195 ,3), 159
,2), 85 ,13), 73 ,21), and 57 ,100); HRMS [Found: m/z
280.2286 ,M12PivOH). Calcd for C17H32OSi: M,
280.2224].
3.4. Hydroxymethylation
3.4.4. 2-[.cis-4-tButyl-1-hydroxymethyl)cyclohexyl]-3-
trimethylsilylprop-1-en-1-yl pivalate .26b). Mp 103±
1048C; IR ,CH2Cl2) 3520 ,OH), 1733 ,CvO), 1654
To a stirred solution of paraformaldehyde ,502.3 mg,
16.73 mmol) in dry CH2Cl2 ,15 cm3; distilled from CaH2)
was added a solution of Et2AlCl ,5.8 cm3, 5.4 mmol;
0.93 mol/l solution in hexane) at 2608C under Ar. After
30 min stirring, a solution of 11 ,557.3 mg, 1.879 mmol)
in CH2Cl2 ,5 cm3) was added, and the mixture was stirred
at the same temperature. A dilute HCl aq ,2 mol/l) was
added and the mixture was warmed to room temperature,
and then extracted with CH2Cl2. Drying the organic layer
followed by evaporation of the solvent gave an oily residue,
which was chromatographed on silica gel ,13 g) using
hexane±AcOEt ,97:3, 95:5, and 90:10) as eluent to yield
recovered 11 ,400.7 mg, 72%) and 12 ,162.1 mg, 26%; 94%
based on the consumed material) ,entry 5 of Table 1).
,CvC), 1479, 1146, and 849 cm21 1H NMR ,CDCl3)
;
dˆ0.07 ,9H, s, SiMe3), 0.84 ,9H, s, tBu), 0.90±1.37
,5H, m), 1.26 ,9H, s, tBu), 1.55±1.68 ,3H, m), 1.56 ,2H,
br s, CH2SiMe3), 1.87±1.93 ,2H, m), 3.52 ,2H, br d,
Jˆ5 Hz, CH2OH), and 6.91 ,1H, s, CvCH); 13C NMR
,CDCl3) dˆ0.10 ,3C), 14.83, 22.51, 27.21 ,3C), 27.45
,3C), 31.68, 32.34, 38.78, 41.55, 47.64, 61.93, 129.73,
130.97, and 175.72; MS m/z 280 ,M12PivOH,
0.4%), 279 ,M12PivO, 0.3), 251 ,0.5), 195 ,3), 159
,2), 85 ,11), 73 ,23), and 57 ,100); Analysis [Found: C,
68.85; H, 10.78%. Calcd for C22H42O3Si: C, 69.05; H,
11.06%].
3.4.5. 2-[.4-Benzyloxy-1-hydroxymethyl)cyclohexyl]-3-
trimethylsilylprop-1-en-1-yl pivalate .34a, b). Mp 84±
868C; IR ,neat) 3450 ,OH), 1737 ,CvO), 1654 ,CvC),
Similarly, compounds 18, 26a, b, and 34a, b were obtained
in 80, 97, and 91% yields based on the consumed materials,
respectively. The isomers 26a and 26b were separated by
repeated column chromatography. The isomers 34a and 34b
could not be separated.
1
1479, 1280, 1249, 1144, and 852 cm21; H NMR ,CDCl3)
assigned for 34a: dˆ0.09 ,9H, s, SiMe3), 1.27 ,9H, s, tBu),
1.41±1.98 ,9H, m), 1.58 ,2H, br s, CH2SiMe3), 3.31 ,2H, s,
CH2OH), 3.38±3.50 ,1H, m, CHOBn), 4.53 ,2H, s,
OCH2Ph), 6.98 ,1H, s, CvCH), and 7.26±7.35 ,5H, m,
Ph); assigned for 34b: dˆ0.07 ,9H, s, SiMe3), 1.27 ,9H, s,
tBu), 1.41±1.98 ,9H, m), 1.57 ,2H, br s, CH2SiMe3), 3.38±
3.50 ,1H, m, CHOBn), 3.47 ,2H, s, CH2OH), 4.53 ,2H, s,
OCH2Ph), 6.93 ,1H, s, CvCH), and 7.26±7.35 ,5H, m, Ph);
13C NMR ,CDCl3; assignment was not made) dˆ20.03
3.4.1. 2-[.1-Hydroxymethyl)cyclohexyl]-3-trimethylsilyl-
prop-1-en-1-yl pivalate .12). Mp 44±468C; IR ,neat) 3460
,OH), 1738 ,CvO), 1654 ,CvC), 1479, 1280, 1249, 1142,
1
and 853 cm21; H NMR ,CDCl3) dˆ0.08 ,9H, s, SiMe3),
1.27 ,9H, s, tBu), 1.39±1.50 ,7H, m), 1.56 ,2H, br s,
CH2SiMe3), 1.54±1.66 ,4H, m), 3.38 ,2H, s, CH2OH), and
6.92 ,1H, s, CvCH); 13C NMR ,CDCl3) dˆ0.00 ,3C),
14.95, 22.14 ,2C), 26.32, 27.23 ,3C), 31.60 ,2C), 38.79,
43.04, 66.6 ,br), 126.80, 132.24, and 175.67; MS m/z 326
,M1, 2%), 295 ,M12CH2OH, 10), 223 ,9), 195 ,13), 139
,24), 73 ,53), and 57 ,100); HRMS [Found: m/z 295.2106
,M12CH2OH). Calcd for C17H31O2Si: M, 295.2094].
²
²
,3C), 0.00 ,3C), 15.05, 27.08 ,2C), 27.17 ,3C), 27.71
²
,2C), 27.91 ,2C), 28.69 ,2C), 38.74, 42.31, 42.97, 65.1
,br), 67.9 ,br), 69.72, 69.78, 75.35, 76.39, 127.31, 127.34,
127.40 ,2C), 127.42 ,2C), 128.26 ,2C), 128.28 ,2C),
²
The signal for both isomers.

4500
C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
²
²
²
131.80, 132.65, 138.93, 175.47, and 175.65; GC±MS
for 34a: m/z 330 ,M12PivOH, 0.5%), 227 ,1), 221
,1), 209 ,2), 91 ,42), 73 ,26), and 57 ,100); for 34b: m/z
345 ,M12CH2SiMe3, 0.4%), 222 ,1), 209 ,1), 91 ,45),
73 ,19), and 57 ,100); HRMS [Found: m/z
330.2001 ,M12PivOH). Calcd for C20H30O2Si: M,
330.2016].
64.80, 67.13, 112.91, 147.77, and 178.49; MS m/z 125
,M12CH2OPiv, 5%), 108 ,52), 93 ,40), 79 ,50), and 57
,100); HRMS [Found: m/z 125.0956 ,M12CH2OPiv).
Calcd for C8H13O: M, 125.0967].
3.5.4. 2-[.1-Hydroxymethyl)cyclopentyl]prop-1-en-1-yl
pivalate .20). An oil; IR ,neat) 3450 ,0H), 1737 ,CvO),
1
1671 ,CvC), 1480, 1281, 1150, and 739 cm21; H NMR
,CDCl3) dˆ1.26 ,9H, s, tBu), 1.60±1.68 ,9H, m), 1.68
,3H, d, Jˆ1.3 Hz, Me), 3.38 ,2H, s, CH2OH), and 6.93
,1H, q, Jˆ1.3 Hz, CvCH); 13C NMR ,CDCl3) dˆ11.4,
23.5 ,2C), 27.1 ,3C), 32.5 ,2C), 38.9, 52.3, 65.5, 125.2,
132.4, and 175.8; MS m/z 209 ,M12CH2OH, 1%), 138
,3), 125 ,39), 108 ,9), 85 ,10), and 57 ,100); HRMS
[Found: m/z 209.1555 ,M12CH2OH). Calcd for
C13H21O2: M, 209.1542].
3.5. Desilylation
Vacuum dried tetrabutylammonium ¯uoride ,1.565 g) was
prepared in a 100 cm3 two-necked round bottomed ¯ask
under an Ar atmosphere. Dry DMF ,20 cm3; distilled from
4A molecular sieve) was then added, and the resulting
solution was cooled to 08C. A solution of 12 ,474.9 mg,
1.454 mmol) in DMF ,30 cm3) was added, the mixture
was stirred at 08C for 15 min, and then water was added.
Extraction with ether followed by drying and evaporation of
the solvent gave an oily residue, which was chromato-
graphed on silica gel ,20 g) using hexane±AcOEt ,99:5)
to afforded a mixture of 13 and 14 ,338.9 mg, 86%, ratio
2:1). Further separation of 13 and 14 was carried out by
repeated silica gel chromatography.
3.5.5. 2-[.trans-4-tButyl-1-hydroxymethyl)cyclohexyl]-
prop-2-en-1-yl pivalate and 2-[.trans-4-tbutyl-1-
hydroxymethyl)cyclohexyl]prop-1-en-1-yl pivalate .27a,
28a). Mp 59±618C; IR ,CH2Cl2) 3480 ,OH), 1729 ,CvO),
1
1637 ,CvC), 1479, 1365, 1282, and 1155 cm21; H NMR
,CDCl3) dˆ0.81 ,9H, s, tBu of 27a), 0.81 ,9H, s, tBu of
28a), 0.96±1.26 ,5H£2, m), 1.23 ,9H, s, tBu of 27a), 1.27
,9H, s, tBu of 28a), 1.56±1.66 ,2H£2 plus 1H, m), 1.60 ,3H,
d, Jˆ1.1 Hz, Me of 28a), 1.98±2.08 ,2H£2 plus 1H, m),
3.23 ,2H, s, CH2OH of 28a), 3.34 ,2H, s, CH2OH of 27a),
4.54 ,2H, s, CH2OPiv of 27a), 5.12 ,1H, br s, CvCHH of
27a), 5.38 ,1H, br s, CvCHH of 27a), and 6.87 ,1H, q,
Jˆ1.1 Hz, CvCH of 28a); 13C NMR ,CDCl3) assigned
for 27a: dˆ23.02 ,2C), 27.16 ,3C), 27.49 ,3C), 32.13
,2C), 32.38, 38.79, 44.94, 48.49, 64.42, 71.82, 115.33,
143.51, and 178.56; assigned for 28a: dˆ9.95, 22.83
,2C), 27.09 ,3C), 27.49 ,3C), 31.75 ,2C), 32.38, 38.88,
43.45, 48.62, 70.34, 121.73, 135.19, and 175.93; GC-MS
for 27a: m/z 178 ,M12PivOH±CH2OH, 12%), 135 ,5),
121 ,11), 107 ,14), and 57 ,100); for 28a: m/z 279
,M12CH2OH, 1%), 208 ,M12PivOH, 2), 195 ,7), 178
,4), 85 ,11), and 57 ,100). Analysis [Found: C, 73.45; H,
10.98%. Calcd for C19H34O3: C, 73.50; H, 11.04%].
For the synthesis of related compounds, dry THF ,distilled
from CaH2) was used instead of DMF. Compounds 19/20,
27a/28a, and 27b/28b were obtained in 90, 93, and 99%
yields, respectively. A mixture of four isomers 35a, b/36a,
b were inseparable and not puri®ed at this stage.
3.5.1. 2-[.1-Hydroxymethyl)cyclohexyl]prop-2-en-1-yl
pivalate .13). An oil; IR ,neat) 3450 ,OH), 1729 ,CvO),
1637 ,CvC), 1480, 1283, 1151, and 1042 cm21; H NMR
1
,CDCl3) dˆ1.23 ,9H, s, tBu), 1.26±1.57 ,8H, m), 1.75±1.82
,2H, m), 1.90 ,1H, br, OH), 3.44 ,2H, s, CH2OH), 4.56 ,2H,
t, Jˆ1.1 Hz, CH2OPiv), 5.11 ,1H, q, Jˆ1.0 Hz, CvCHH),
and 5.34 ,1H, q, Jˆ1.0 Hz, CvCHH); 13C NMR ,CDCl3)
dˆ22.05 ,2C), 26.36, 27.17 ,3C), 31.67 ,2C), 38.81, 44.62,
64.29, 69.5 ,br), 114.53, 145.20, and 178.54; MS m/z 152
,M12PivOH, 4%), 122 ,76), 107 ,27), 93 ,58), 79 ,57), and
57 ,100); HRMS [Found: m/z 152.1220 ,M12PivOH).
Calcd for C10H16O: M, 152.1202].
3.5.6. 2-[.cis-4-tButyl-1-hydroxymethyl)cyclohexyl]prop-
2-en-1-yl pivalate and 2-[.cis-4-tbutyl-1-hydroxymethyl)-
cyclohexyl]prop-1-en-1-yl pivalate .27b, 28b). Mp 78±
818C; IR ,CH2Cl2) 3450 ,OH), 1728 ,CvO), 1637
3.5.2. 2-[.1-Hydroxymethyl)cyclohexyl]prop-1-en-1-yl
pivalate .14). An oil; IR ,neat) 3450 ,OH), 1740 ,CvO),
1
,CvC), 1480, 1154, and 1039 cm21; H NMR ,CDCl3)
1669 ,CvC), 1480, 1281, 1149, and 1045 cm21; H NMR
1
dˆ0.84 ,9H£2, s, tBu), 0.90±1.36 ,5H£2, m), 1.22 ,9H,
s, tBu of 27b), 1.26 ,9H, s, tBu of 28b), 1.59±1.66 ,2H£2
plus 1H, m), 1.66 ,3H, d, Jˆ1.2 Hz, Me of 28b), 1.90±2.02
,2H£2 plus 1H, m), 3.58 ,2H, br s, CH2OH of 28b), 3.66
,2H, d, Jˆ5.5 Hz, CH2OH of 27b), 4.59 ,2H, s, CH2OPiv of
27b), 5.07 ,1H, s, CvCHH of 27b), 5.19 ,1H, s, CvCHH
of 27b), and 6.93 ,1H, q, Jˆ1.2 Hz, CvCH of 28b); 13C
NMR ,CDCl3) assigned for 27b: dˆ22.50 ,2C), 27.16 ,3C),
27.46 ,3C), 31.49 ,2C), 32.36, 38.79, 42.68, 47.70, 63.16,
64.05, 112.66, 149.40, and 178.56; assigned for 28b:
dˆ9.67, 22.50 ,2C), 27.10 ,3C), 27.46 ,3C), 31.29 ,2C),
32.36, 38.90, 41.41, 47.81, 61.90, 127.08, 132.86, and
175.77; GC-MS for 27b: m/z 208 ,M12PivOH, 1%), 178
,11), 135 ,6), 121 ,11), 107 ,13), and 57 ,100); for 28b: m/z
279 ,M12CH2OH, 0.5%), 208 ,3), 195 ,5), 109 ,6), 96 ,7),
85 ,9), and 57 ,100). Analysis [Found: C, 73.40; H, 10.99%.
Calcd for C19H34O3: C, 73.50; H, 11.04%].
,CDCl3) dˆ1.27 ,9H, s, tBu), 1.23±1.56 ,9H, m), 1.62 ,3H,
d, Jˆ1.3 Hz, Me), 1.72±1.80 ,2H, m), 3.35 ,2H, s, CH2OH),
and 6.92 ,1H, q, Jˆ1.3 Hz, CvCH); 13C NMR ,CDCl3)
dˆ9.84, 21.88 ,2C), 26.39, 27.11 ,3C), 31.32 ,2C), 38.89,
43.19, 68.0 ,br), 123.21, 134.62, and 175.88; MS m/z 153
,M12PivO, 6%), 139 ,26), 122 ,8), 85 ,11), 71 ,11), and 57
,100); HRMS [Found: m/z 153.1306 ,M12PivO). Calcd for
C10H17O: M, 153.1280].
3.5.3. 2-[.1-Hydroxymethyl)cyclopentyl]prop-2-en-1-yl
pivalate .19). An oil; IR ,neat) 3470 ,OH), 1724 ,CvO),
1
1639 ,CvC), 1480, 1284, 1156, and 739 cm21; H NMR
,CDCl3) dˆ1.23 ,9H, s, tBu), 1.62±1.67 ,8H, m), 1.94 ,1H,
br, OH), 3.44 ,2H, s, CH2OH), 4.57 ,2H, dd, Jˆ0.7, 1.3 Hz,
CH2OPiv), 5.07 ,1H, dt, Jˆ1.0, 0.7 Hz, CvCHH), and 5.19
,1H, dt, Jˆ1.0, 1.3 Hz, CvCHH); 13C NMR ,CDCl3)
dˆ23.47 ,2C), 27.17 ,3C), 32.77 ,2C), 38.79, 53.50,

C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
4501
3.6. Oxidation
,2C), 27.11 ,3C), 34.66 ,2C), 38.75, 58.05, 65.37, 114.23,
144.24, 178.08, and 180.37; MS m/z 254 ,M1, 100%), 214
,96), 209 ,97), 135 ,90), and 114 ,95); HRMS [Found: m/z
254.1539 ,M1). Calcd for C14H22O4: M, 254.1519].
To a stirred solution of ,COCl)2 ,0.21 cm3) in dry CH2Cl2
,15 cm3) was added DMSO ,0.34 cm3) at 2608C under Ar.
After this had been stirred for 30 min, a solution of 13
,151.1 mg, 0.594 mmol) in CH2Cl2 ,10 cm3) was added,
and the mixture was stirred at 2608C for 21 h. Et3N
,1.1 cm3) was added, and the ¯ask was allowed to warm
to room temperature slowly with stirring. The reaction
was quenched by the addition of water ,30 cm3) followed
by extraction with CH2Cl2 and drying. Evaporation of the
solvent afforded an oily residue, which was dissolved in a
mixed solvent prepared from tBuOH ,15 cm3) and H2O
,4 cm3). To this was added 2-methyl-2-butene ,0.65 cm3)
and NaH2PO4´2H2O ,182.8 mg) with stirring at room
temperature. After 20 min of stirring, NaClO2 ,415.0 mg)
was added, and the stirring was continued for an additional
1 h. The reaction was quenched by the addition of HCl aq
,20 cm3; ca. 1 mol/l), and the mixture was extracted with
CH2Cl2 and dried. Evaporation of the solvent followed by
silica gel ,20 g) column chromatography using hexane±
AcOEt ,99:5, 90:10, 85:15, and 80:20) as eluent yielded
15 ,150.3 mg, 94% from 13).
3.6.3. trans-4-tButyl-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarbaldehyde .29a). An oil; IR ,neat) 2697
,CHO), 1730 ,CvO), 1637 ,CvC), 1479, 1458, 1365,
1
1281, and 1146 cm21; H NMR ,CDCl3) dˆ0.82 ,9H, s,
tBu), 0.97±1.18 ,3H, m), 1.17 ,9H, s, tBu), 1.46 ,2H, dt,
Jˆ2.3, 13.3 Hz), 1.69 ,2H, dm, Jˆca. 13 Hz), 2.09 ,2H, dm,
Jˆca. 14 Hz), 4.49 ,2H, s, CH2OPiv), 5.33 ,1H, s,
CvCHH), 5.61 ,1H, s, CvCHH), and 9.25 ,1H, s, CHO);
13C NMR ,CDCl3) dˆ22.29 ,2C), 27.09 ,3C), 27.42 ,3C),
28.69 ,2C), 32.39, 38.76, 47.84, 54.88, 65.77, 119.75,
139.83, 178.02, and 202.25; MS m/z 207 ,M12PivO,
0.8%), 178 ,4), 135 ,5), 121 ,10), 107 ,13), and 57 ,100);
HRMS [Found: m/z 206.1571 ,M12PivOH). Calcd for
C14H22O: M, 206.1672].
3.6.4. cis-4-tButyl-1-[1-.pivaloyloxymethyl)ethenyl]cyclo-
hexanecarbaldehyde .29b). Mp 74±768C; IR ,CH2Cl2)
2705 ,CHO), 1724 ,CvO), 1719 ,CvO), 1636 ,CvC),
1
1479, 1365, and 1152 cm21; H NMR ,CDCl3) dˆ0.80
,9H, s, tBu), 0.88±1.09 ,3H, m), 1.20 ,9H, s, tBu), 1.44
,2H, dt, Jˆ3.2, 13.3 Hz), 1.73 ,2H, dm, Jˆca. 13 Hz),
2.34 ,2H, dm, Jˆca. 13 Hz), 4.49 ,2H, br s, CH2OPiv),
5.17 ,1H, s, CvCHH), 5.32 ,1H, s, CvCHH), and 9.25
,1H, s, CHO); 13C NMR ,CDCl3) dˆ23.89 ,2C), 27.13
,3C), 27.37 ,3C), 30.46 ,2C), 32.30, 38.76, 47.27, 54.30,
64.10, 116.41, 143.22, 177.86, and 201.84; MS m/z 207
,M12PivO, 2%), 178 ,5), 163 ,2), 149 ,2), 135 ,5), 121
,11), 107 ,12), and 57 ,100); Analysis [Found: C, 73.63; H,
10.29%. Calcd for C19H32O3: C, 73.98; H, 10.46%].
Starting from a mixture of 13 and 14 ,29.7 mg, 0.117 mmol)
a mixture of 15 and 22 ,30.3 mg, 96%) was obtained.
Compounds 21 was obtained from 19 in a 89% yield. For the
synthesis of 31a, b and 39a, b, intermediate aldehydes 29a,
b and 37a, b were isolated for the separation purpose from
their isomers 30a, b and 38a, b, respectively. Namely, a
mixture of 27a/28a afforded 29a and 30a in 56 and 35%
yields, respectively, after separation by silica-gel column
chromatography. A mixture of 27b/28b afforded 29b and
30b in 54, and 41% yields. The carboxylic acids 31a and
31b were then synthesized from 29a and 29b in 93 and 80%
yields, respectively. In the same way, a crude mixture of
35a, b/36a, b were oxidized to yield a mixture of 37a,
b/38a, b ,75% from 34a, b), which were separated from
each other. The carboxylic acids 39a and 39b were then
obtained from 37a and 37b in 96 and 82% yields,
respectively.
3.6.5. trans-4-tButyl-1-.1-methyl-2-pivaloyloxyethenyl)-
cyclohexanecarbaldehyde .30a). An oil; IR ,neat) 1745
,CvO), 1725 ,CvO), 1479, 1457, 1365, 1279, and
1
1136 cm21; H NMR ,CDCl3) dˆ0.81 ,9H, s, tBu), 1.01
,1H, m), 1.14 ,2H, dq, Jˆ2.6, 12.7 Hz), 1.28 ,9H, s, tBu),
1.40 ,2H, dt, Jˆ2.6, 13.5 Hz), 1.59 ,3H, d, Jˆ1.5 Hz, Me),
1.68 ,2H, dm, Jˆca. 13 Hz), 2.13 ,2H, dm, Jˆca. 14 Hz),
7.17 ,1H, q, Jˆ1.5 Hz, CvCH), and 9.17 ,1H, s, CHO); 13C
NMR ,CDCl3) dˆ11.14, 22.17 ,2C), 27.06 ,3C), 27.48
,3C), 28.41 ,2C), 32.41, 38.94, 48.07, 53.61, 116.77,
136.26, 175.44, and 201.75; MS m/z 308 ,M1, 0.3%), 279
,1), 195 ,5), 83 ,11), and 57 ,100); HRMS ,FAB) [Found:
m/z 331.2247 ,M11Na). Calcd for C19H32O3Na: M,
331.2250].
3.6.1. 1-[1-.Pivaloyloxymethyl)ethenyl]cyclohexanecar-
boxylic acid .15). An oil; IR ,neat) 2400±3600 ,OH),
1733 ,CvO), 1700 ,CvO), 1640 ,CvC), 1282, and
1
1148 cm21; H NMR ,CDCl3) dˆ1.19 ,9H, s, tBu), 1.42±
1.67 ,8H, m), 2.11±2.19 ,2H, m), 4.62 ,2H, d, Jˆ0.7 Hz,
CH2OPiv), 5.29 ,1H, br s, CvCHH), and 5.35 ,1H, t,
Jˆ0.7 Hz, CvCHH); 13C NMR ,CDCl3) dˆ23.00 ,2C),
25.52, 27.14 ,3C), 32.54 ,2C), 38.76, 50.52, 64.66,
115.90, 144.34, 178.08, and 180.95; MS m/z 268 ,M1,
82%), 256 ,94), 200 ,97), 182 ,94), 147 ,100), and 100
,99); HRMS [Found: m/z 268.1724 ,M1). Calcd for
C15H24O4: M, 268.1675].
3.6.6. cis-4-tButyl-1-.1-methyl-2-pivaloyloxyethenyl)cy-
clohexanecarbaldehyde .30b). Mp 74±768C; IR ,CH2Cl2)
2698 ,CHO), 1744 ,CvO), 1723 ,CvO), 1662 ,CvC),
1480, 1366, 1278, and 1072 cm21 1H NMR ,CDCl3)
;
dˆ0.80 ,9H, s, tBu), 0.88±1.04 ,3H, m), 1.25 ,9H, s,
tBu), 1.36 ,2H, br t, Jˆca. 13 Hz), 1.56 ,3H, d, Jˆ1.4 Hz,
Me), 1.73 ,2H, m), 2.34 ,2H, dm, Jˆca. 13 Hz), 7.11 ,1H, q,
Jˆ1.4 Hz, CvCH), and 9.13 ,1H, s, CHO); 13C NMR
,CDCl3) dˆ10.34, 23.96 ,2C), 27.03 ,3C), 27.40 ,3C),
30.07 ,2C), 32.31, 38.93, 47.45, 53.41, 120.90, 133.88,
175.40, and 201.54; MS m/z 308 ,M1, 0.4%), 279 ,1), 195
,5), 85 ,10), and 57 ,100); Analysis [Found: C, 73.70; H,
10.27%. Calcd for C19H32O3: C, 73.98; H, 10.46%].
3.6.2. 1-[1-.Pivaloyloxymethyl)ethenyl]cyclopentanecar-
boxylic acid .21). An oil; IR ,neat) 2400±3600 ,OH), 1733
,CvO), 1701 ,CvO), 1647 ,CvC), 1282, and 1147 cm21
;
1H NMR ,CDCl3) dˆ1.21 ,9H, s, tBu), 1.68±1.85 ,6H, m),
2.26±2.34 ,2H, m), 4.63 ,2H, dd, Jˆ0.6, 1.2 Hz, CH2OPiv),
5.25 ,1H, br s, CvCHH), 5.27 ,1H, t, Jˆ1.2 Hz, CvCHH),
9.7±11.2 ,1H, very br, CO2H); 13C NMR ,CDCl3) dˆ23.47

4502
C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
3.6.7. trans-4-tButyl-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarboxylic acid .31a). Mp 135±1388C; IR
,CH2Cl2) 3420 ,OH), 1720 ,CvO), 1699 ,CvO), 1638
2.00 ,8H, m), 1.58 ,3H, d, Jˆ1.5 Hz, Me), 3.53 ,1H, br tt,
Jˆ2.9, 5.2 Hz, CHOBn), 4.50 ,2H, s, OCH2Ph), 7.19 ,1H, q,
Jˆ1.5 Hz, CvCH), 7.24±7.36 ,5H, m, Ph), and 9.18 ,1H, s,
CHO); 13C NMR ,CDCl3) dˆ10.55, 24.50 ,2C), 26.73 ,2C),
27.02 ,3C), 38.92, 53.28, 69.87, 73.6 ,br), 118.7 ,br), 127.40
,3C), 128.33 ,2C), 134.95, 138.82, 175.24, and 201.16; MS
m/z 137 ,M12PivO±CHO±Bn, 3%), 91 ,31), 57 ,100), and
41 ,24); HRMS [Found: m/z 137.0880 ,M12PivO±CHO±
Bn). Calcd for C9H13O: M, 137.0967].
1
,CvC), and 1154 cm21; H NMR ,CDCl3) dˆ0.81 ,9H,
s, tBu), 0.99±1.18 ,3H, m), 1.18 ,9H, s, tBu), 1.60±1.74
,4H, m), 2.26 ,2H, br d, Jˆca. 13 Hz), 4.59 ,2H, s,
CH2OPiv), 5.34 ,1H, s, CvCHH), and 5.54 ,1H, s,
CvCHH); 13C NMR ,CDCl3) dˆ22.70 ,2C), 27.02 ,3C),
27.40 ,3C), 31.58 ,2C), 32.33, 38.73, 47.64, 49.33, 65.72,
118.75, 140.52, 178.15, and 181.83; MS m/z 267 ,M12tBu,
0.8%), 222 ,2), 194 ,2), 165 ,4), 57 ,100), and 41 ,40);
Analysis [Found: C, 70.27; H, 9.69%. Calcd for C19H32O4:
C, 70.33; H, 9.94%].
3.6.12. cis-4-Benzyloxy-1-.1-methyl-2-pivaloyloxyethenyl)-
cyclohexanecarbaldehyde .38b). An oil; IR ,CH2Cl2) 2695
,CHO), 1742 ,CvO), 1724 ,CvO), 1637 ,CvC), 1456,
1
1279, and 1140 cm21; H NMR ,CDCl3) dˆ1.26 ,9H, s,
tBu), 1.37±2.30 ,8H, m), 1.58 ,3H, d, Jˆ1.1 Hz, Me),
3.36 ,1H, tt, Jˆ3.7, 8.9 Hz, CHOBn), 4.52 ,2H, s,
OCH2Ph), 7.13 ,1H, q, Jˆ1.1 Hz, CvCH), 7.23±7.35
,5H, m, Ph), and 9.15 ,1H, s, CHO); 13C NMR ,CDCl3)
dˆ10.60, 26.58 ,2C), 27.01 ,3C), 28.07 ,2C), 38.92,
53.15, 69.87, 75.66, 119.33, 127.46 ,3C), 128.34 ,2C),
134.47, 138.80, 175.37, and 200.66; MS m/z 166
,M12PivO±Bn, 1%), 137 ,4), 91 ,32), 57 ,100), and 41
,24); HRMS [Found: m/z 137.0867 ,M12PivO±CHO±
Bn). Calcd for C9H13O: M, 137.0967].
3.6.8.
cis-4-tButyl-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarboxylic acid .31b). Mp 88±928C; IR
,Nujol) 2300±3400 ,OH), 1740 ,CvO), 1697 ,CvO),
1
1643 ,CvC), and 1142 cm21; H NMR ,CDCl3) dˆ0.68
,9H, s, tBu), 0.83 ,1H, m), 1.02 ,2H, m), 1.07 ,9H, s,
tBu), 1.25 ,2H, dt, Jˆ2.5, 12.7 Hz), 1.61 ,2H, br d, Jˆca.
13 Hz), 2.30 ,2H, br d, Jˆca. 13 Hz), 4.50 ,2H, s,
CH2OPiv), 5.11 ,1H, s, CvCHH), and 5.13 ,1H, s,
CvCHH); 13C NMR ,CDCl3) dˆ24.52 ,2C), 27.14 ,3C),
27.40 ,3C), 32.28, 33.37 ,2C), 38.75, 47.24, 50.71, 64.14,
114.37, 145.89, 178.02, and 179.78; MS m/z 222
,M12PivOH, 2%), 207 ,2), 165 ,5), 57 ,100), and 41
,44); HRMS [Found: m/z 222.1629 ,M12PivOH). Calcd
for C14H22O2: M, 222.1621].
3.6.13.
trans-4-Benzyloxy-1-[1-.pivaloyloxymethyl)-
ethenyl]cyclohexanecarboxylic acid .39a). Mp 90±928C;
IR ,CH2Cl2) 2400±3400 ,OH), 1724 ,CvO), 1700 ,CvO),
1641 ,CvC), 1455, 1154, and 702 cm21; 1H NMR ,CDCl3)
dˆ1.19 ,9H, s, tBu), 1.71±1.80 ,4H, m), 1.94±2.09 ,4H,
m), 3.55 ,1H, quint, Jˆ4.8 Hz, CHOBn), 4.51 ,2H, s,
OCH2Ph), 4.63 ,2H, s, CH2OPiv), 5.34 ,1H, s, CvCHH),
5.41 ,1H, br s, CvCHH), and 7.24±7.36 ,5H, m, Ph); 13C
NMR ,CDCl3) dˆ27.08 ,3C), 27.42 ,2C), 27.99 ,2C),
38.72, 49.90, 64.72, 69.87, 75.6 ,br), 116.7 ,br), 127.40
,3C), 128.32 ,2C), 138.84, 143.2 ,br), 178.03 and 180.67;
MS m/z 181 ,M12PivOH±Bn, 39%), 152 ,1), 111 ,5), and
91 ,100); HRMS [Found: m/z 181.0868 ,M12PivOH±Bn).
Calcd for C10H13O3: M, 181.0865].
3.6.9. trans-4-Benzyloxy-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarbaldehyde .37a). An oil; IR ,CH2Cl2) 2697
,CHO), 1728 ,CvO), 1637 ,CvC), 1457, 1281, and
1
1148 cm21; H NMR ,CDCl3) dˆ1.18 ,9H, s, tBu), 1.65±
2.04 ,8H, m), 3.51 ,1H, quint, Jˆ4.7 Hz, CHOBn), 4.51
,4H, s, CH2OPiv and OCH2Ph), 5.28 ,1H, s, CvCHH),
5.49 ,1H, s, CvCHH), 7.24±7.37 ,5H, m, Ph), and 9.28
,1H, s, CHO); 13C NMR ,CDCl3) dˆ25.01 ,2C), 26.82
,2C), 27.06 ,3C), 38.73, 54.27, 64.77, 69.85, 73.7 ,br),
118.7 ,br), 127.38, 127.40 ,2C), 128.31 ,2C), 138.78,
141.33, 177.87, and 201.51; MS m/z 228 ,M12PivO±
CHO, 1%), 210 ,1), 150 ,3), 91 ,100), 57 ,77), and 41
,48); HRMS ,FAB) [Found: m/z 381.2012 ,M11Na).
Calcd for C22H30O4Na: M, 381.2043].
3.6.14. cis-4-Benzyloxy-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarboxylic acid .39b). Mp 82±848C; IR
,CH2Cl2) 2600±3600 ,OH), 1730 ,CvO), 1702 ,CvO),
1637 ,CvC), 1455, 1282, and 1154 cm21 1H NMR
;
,CDCl3) dˆ1.20 ,9H, s, tBu), 1.48±1.63 ,4H, m), 1.93±
2.04 ,2H, m), 2.36±2.44 ,2H, m), 3.35±3.43 ,1H, m,
CHOBn), 4.56 ,2H, s, OCH2Ph), 4.62 ,2H, br s, CH2OPiv),
5.28 ,1H, s, CvCHH), 5.32 ,1H, s, CvCHH), and 7.24±
7.35 ,5H, m, Ph); 13C NMR ,CDCl3) dˆ27.11 ,3C), 28.77
,2C), 30.13 ,2C), 38.74, 50.14, 64.33, 69.87, 75.6 ,br),
115.62, 127.48, 127.57 ,2C), 128.34 ,2C), 138.60, 144.1
,br), 178.05 and 179.09; MS m/z 166 ,M12PivO±BnO,
18%), 138 ,14), 121 ,7), 107 ,11), and 91 ,100); HRMS
[Found: m/z 166.0954 ,M12PivO±BnO). Calcd for
C10H14O2: M, 166.0994].
3.6.10. cis-4-Benzyloxy-1-[1-.pivaloyloxymethyl)ethenyl]-
cyclohexanecarbaldehyde .37b). An oil; IR ,CH2Cl2)
2704 ,CHO), 1727 ,CvO), 1637 ,CvC), 1456, and
1
1149 cm21; H NMR ,CDCl3) dˆ1.19 ,9H, s, tBu), 1.45±
2.28 ,8H, m), 3.39 ,1H, tt, Jˆ3.7, 8.5 Hz, CHOBn), 4.48
,2H, s, CH2OPiv), 4.52 ,2H, s, OCH2Ph), 5.23 ,1H, br s,
CvCHH), 5.42 ,1H, br s, CvCHH), 7.24±7.36 ,5H, m,
Ph), and 9.26 ,1H, s, CHO); 13C NMR ,CDCl3) dˆ26.54
,2C), 27.10 ,3C), 27.77 ,2C), 38.74, 54.10, 64.44, 69.82,
75.06, 117.73, 127.41 ,3C), 128.33 ,2C), 138.76, 141.53,
177.86, and 201.02; MS m/z 165 ,M12PivOH±Bn, 2%),
120 ,7), 91 ,100), 57 ,78), and 41 ,50); HRMS ,FAB)
[Found: m/z 381.2071 ,M11Na). Calcd for C22H30O4Na:
M, 381.2043].
3.7. Lactonization
To a stirred solution of 15 ,93.0 mg, 0.347 mmol) in THF
,10 cm3) was added an aqueous solution of NaOH ,15 cm3;
2 mol/l) and water ,20 cm3). After being stirred for 26 h at
room temperature, HCl aq ,20 cm3; 2 mol/l) was added,
and the mixture was extracted with CH2Cl2 followed by
3.6.11.
trans-4-Benzyloxy-1-.1-methyl-2-pivaloyloxy-
ethenyl)cyclohexanecarbaldehyde .38a). An oil; IR
,CH2Cl2) 2694 ,CHO), 1741 ,CvO), 1456, 1279, and
1143 cm21; H NMR ,CDCl3) dˆ1.26 ,9H, s, tBu), 1.56±
1

C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
4503
drying. The solvent was evaporated to give an oily residue,
which was chromatographed on silica gel ,18 g) using
hexane±AcOEt ,85:15) as eluent to afford 4 ,48.9 mg,
85%).
3.7.5. trans-8-Benzyloxy-4-methylene-2-oxaspiro[4.5]de-
can-1-one .7a). An oil; IR ,neat) 1769 ,CvO), 1670
,CvC), 1452, 1352, 1095, and 1029 cm21 1H NMR
;
,CDCl3) dˆ1.70±1.85 ,4H, m, 6eq-H2, 7eq-H2), 1.90 ,2H,
br ddd-like, Jˆ3, 9, 13 Hz, 6ax-H2), 2.11±2.20 ,2H, m,
7ax-H2), 3.66 ,1H, tt, Jˆ3.1, 6.0 Hz, 8-H), 4.55 ,2H, s,
OCH2Ph), 4.78 ,2H, dd, Jˆ2.0, 2.4 Hz, 3-H2), 5.10 ,1H,
dt, Jˆ0.7, 2.0 Hz, CvCHH), 5.24 ,1H, dt, Jˆ0.7, 2.4 Hz,
CvCHH), and 7.26±7.38 ,5H, m, Ph); 13C NMR ,CDCl3)
dˆ25.85 ,2C), 29.22 ,2C), 44.19, 69.48, 69.95, 73.35,
107.84, 127.42 ,2C), 127.47, 128.38 ,2C), 138.92, 148.70,
and 179.85; MS m/z 181 ,M12CH2Ph, 26%), 111 ,4), 91
,100), and 65 ,14); MS ,CI method) m/z 273 ,M11H, 66%),
181 ,23), 165 ,42), 85 ,62), and 69 ,100); HRMS [Found: m/
z 181.0875 ,M12CH2Ph). Calcd for C10H13O3: M,
181.0865].
A mixture of 15 and 22 ,30.2 mg, 0.113 mmol) afforded 15
,10.9 mg, 58%) and 23 ,5.7 mg, 27%).
Compounds 5, 6a, 6b, 7a and 7b were obtained in 88, 96,
93, 94, 94% yields, respectively, from corresponding
carboxylic acids.
3.7.1. 4-Methylene-2-oxaspiro[4.5]decan-1-one .4). An
oil; IR ,neat) 1776 ,CvO), 1669 ,CvC), 1449, 1351,
1171, 1116, 1031, and 901 cm21 1H NMR ,CDCl3)
;
dˆ1.38±1.96 ,10H, m), 4.77 ,2H, t, Jˆ2.2 Hz, CH2O),
5.08 ,1H, dt, Jˆ0.7, 2.2 Hz, CvCHH), and 5.17 ,1H, dt,
Jˆ0.7, 2.2 Hz, CvCHH); 13C NMR ,CDCl3) dˆ21.03
,2CH2), 25.10 ,CH2), 33.37 ,2CH2), 44.70 ,C), 69.34
,CH2), 107.24 ,CH2), 149.33 ,C), and 179.89 ,CO); MS
m/z 166 ,M1, 93%), 121 ,16), 111 ,9), 78 ,93), and 66
,100); HRMS [Found: m/z 166.1018 ,M1). Calcd for
C10H14O2: M, 166.0994].
3.7.6. cis-8-Benzyloxy-4-methylene-2-oxaspiro[4.5]decan-
1-one .7b). An oil; IR ,neat) 1765 ,CvO), 1671 ,CvC),
1450, 1350, 1097, and 1029 cm21 1H NMR ,CDCl3)
;
dˆ1.52 ,2H, br ddd-like, Jˆ4, 11, 14 Hz, 6ax-H2), 1.88±
2.15 ,6H, m, 7-H4, 6eq-H2), 3.49 ,1H, tt-like, Jˆ3.9,
9.3 Hz, 8-H), 4.58 ,2H, s, OCH2Ph), 4.78 ,2H, t,
Jˆ2.2 Hz, 3-H2), 5.07 ,1H, dt, Jˆ0.7, 2.2 Hz, CvCHH),
5.08 ,1H, dt, Jˆ0.7, 2.2 Hz, CvCHH), and 7.25±7.38 ,5H,
m, Ph); 13C NMR ,CDCl3) dˆ26.62 ,2C), 31.51 ,2C),
43.80, 69.28, 69.71, 75.31, 106.87, 127.39, 127.46 ,2C),
128.34 ,2C), 138.96, 148.89, and 178.93; MS m/z 181
,M12CH2Ph, 89%), 167 ,99), 136 ,100), 121 ,99), and
107 ,99); HRMS [Found: m/z 181.0842 ,M12CH2Ph).
Calcd for C10H13O3: M, 181.0865].
3.7.2. 4-Methylene-2-oxaspiro[4.4]nonan-1-one .5). An
oil; IR ,neat) 1782 ,CvO), 1671 ,CvC), 1466, 1139, and
1
1028 cm21; H NMR ,CDCl3, TMSˆ0.00) dˆ1.75±2.18
,8H, m), 4.81 ,2H, dd, Jˆ2.0, 2.4 Hz, CH2O), 5.02 ,1H,
dt, Jˆ0.6, 2.0 Hz, CvCHH), and 5.04 ,1H, dt, Jˆ0.6,
2.4 Hz, CvCHH); 13C NMR ,CDCl3) dˆ26.05 ,2C),
38.41 ,2C), 51.80, 70.14, 105.89, 150.12, and 182.02; MS
m/z 152 ,M1, 13%), 124 ,6), 111 ,24), 93 ,94), and 79 ,100);
HRMS [Found: m/z 152.0820 ,M1). Calcd for C9H12O2: M,
152.0838].
3.7.7. 3-Hydroxy-4-methyl-2-oxaspiro[4.5]decan-1-one
.23). An oil; IR ,neat) 3398 ,OH), 1763 ,CvO), 1743
1
,CvO), 1451, 1190, 1151, 1134, and 959 cm21; H NMR
3.7.3. trans-8-tButyl-4-methylene-2-oxaspiro[4.5]decan-
1-one .6a). Mp 74±768C; IR ,CH2Cl2) 1769 ,CvO), 1670
,CDCl3) dˆ1.03 ,3H£1/4, d, Jˆ7.2 Hz, Me of the minor
isomer), 1.06 ,3H£3/4, d, Jˆ7.2 Hz, Me of the major
isomer), 1.22±2.09 ,10H, m), 2.18 ,1H£3/4, dq, Jˆ3.9,
7.2 Hz, CHMe of the major isomer), 2.26 ,1H£1/4, dq,
Jˆ5.3, 7.2 Hz, CHMe of the minor isomer), 3.9±4.6
,1H, very br, OH), 5.40 ,1H£3/4, d, Jˆ3.9 Hz, CHOH
of the major isomer), 5.72 ,1H£1/4, d, Jˆ5.3 Hz,
CHOH of the minor isomer); 13C NMR ,CDCl3)
assigned for the major isomer: dˆ12.01, 21.78, 21.88,
25.20, 28.26, 33.81, 45.65, 46.37, 102.18, and 180.58;
assigned for the minor isomer: dˆ8.13, 21.32, 21.69,
25.26, 29.49, 33.26, 44.37, 45.65, 97.76, and 180.78;
MS m/z 184 ,M1, 93%), 166 ,86), 156 ,100), 142
,91), 108 ,93), 100 ,99), and 78 ,96); HRMS
[Found: m/z 184.1069 ,M1). Calcd for C10H16O3:, M,
184.1100].
1
,CvC), 1169, and 1025 cm21; H NMR ,CDCl3) dˆ0.88
,9H, s, tBu), 1.14 ,1H, tt, Jˆ3.2, 12.2 Hz, 8-H), 1.33 ,2H,
ddt, Jˆ7.4, 10.0, 12.6 Hz, 7ax-H2), 1.71±1.86 ,6H, m, 6-H4
and 7eq-H2), 4.72 ,2H, t, Jˆ2.2 Hz, 3-H2), 5.11 ,1H, t,
Jˆ2.0 Hz, CvCHH), and 5.34 ,1H, t, Jˆ2.4 Hz,
CvCHH); 13C NMR ,CDCl3) dˆ21.88 ,2C), 27.32 ,3C),
32.38 ,2C), 32.48, 45.34, 46.54, 69.63, 109.08, 147.89, and
181.30; MS m/z 207 ,M12Me, 7%),194 ,2), 177 ,3), 165
,22), 93 ,23), 79 ,26), 57 ,100), and 41 ,82); HRMS [Found:
m/z 207.1338 ,M12Me). Calcd for C13H19O2: M,
207.1386].
3.7.4. cis-8-tButyl-4-methylene-2-oxaspiro[4.5]decan-1-
one .6b). Mp 55±578C; IR ,CH2Cl2) 1763 ,CvO), 1671
1
,CvC), 1110, and 1035 cm21; H NMR ,CDCl3) dˆ0.89
,9H, s, tBu), 1.05 ,1H, tt, Jˆ3.3, 12.1 Hz, 8-H), 1.46 ,2H, dt,
Jˆ3.9, 13.4 Hz, 6ax-H2), 1.64 ,2H, dm, Jˆca. 13 Hz, 7eq-
H2), 1.78 ,2H, dq, Jˆ3.3, 12.9 Hz, 7ax-H2), 1.95 ,2H, dm,
Jˆca. 13 Hz, 6eq-H2), 4.78 ,2H, t, Jˆ2.2 Hz, 3-H2), 5.01
,1H, dt, Jˆ0.5, 2.4 Hz, CvCHH), and 5.03 ,1H, dt,
Jˆ0.5, 2.0 Hz, CvCHH); 13C NMR ,CDCl3) dˆ22.18
,2C), 27.55 ,3C), 32.50, 35.05 ,2C), 43.95, 47.42, 69.18,
105.95, 150.06, and 179.21; MS m/z 207 ,M12Me, 7%),
194 ,7), 177 ,12), 166 ,45), 138 ,40), 57 ,64), and 41 ,100);
HRMS [Found: m/z 207.1333 ,M12Me). Calcd for
C13H19O2: M, 207.1386].
Acknowledgements
We must thank Professor H. Nagano of Ochanomizu
University and Professor M. Ishibashi of Chiba University
for the measurement of mass spectra. Thanks are also due to
Professor E. Horn of Rikkyo University for help in the
writing of this article. This work was partly supported by
the Rikkyo University Grant for the Promotion of
Research.

4504
C. Kuroda et al. / Tetrahedron 58 '2002) 4493±4504
12. Knapp, S.; O'Connor, U.; Mobilio, D. Tetrahedron Lett. 1980,
21, 4557±4560.
References
13. Schinzer, D.; Panke, G. J. Org. Chem. 1996, 61, 4496±4497.
14. D'Aniello, F.; Mattii, D.; Taddei, M. Synlett 1993, 119±121.
15. Molander, G. A.; Eastwood, P. R. J. Org. Chem. 1995, 60,
4559±4565.
1. For review on the reaction of allylsilanes: ,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 Appli-
cation; Hudlicky, T., Ed.; JAI: Greenwich, 1989; Vol. 1,
pp 173±240.
16. Giguere, R. J.; Duncan, S. M.; Bean, J. M.; Purvis, L.
Tetrahedron Lett. 1988, 29, 6071±6074.
17. Hoffmann, H. M. R.; Eggert, U.; Gibbels, U.; Giesel, K.;
Koch, O.; Lies, R.; Rabe, J. Tetrahedron 1988, 44, 3899±
3918.
2. For review on the synthesis of cyclic compounds: ,a) Ho, T.-L.
Carbocycle Construction in Terpene Synthesis; VCH: New
York, 1998. ,b) Thebtaranonth, C.; Thebtaranonth, Y.
Cyclization Reactions; CRC: Boca Raton, 1994.
18. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1±20.
19. Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Componds, Vol. II; Academic: New York, 1972.
20. Nishitani, K.; Harada, Y.; Nakamura, Y.; Yokoo, K.;
Yamakawa, K. Tetrahedron Lett. 1994, 35, 7809±7812.
21. Harborne, J. F.; Baxter, H. Dictionary of Plant Toxins; Wiley:
Chichester, 1996.
3. Kuroda, C. Recent Res. Dev. Pure Appl. Chem. 1998, 2, 189±
198.
4. ,a) Kuroda, C.; Anzai, S. Chem. Lett. 1998, 875±876.
,b) Kuroda, C.; Kobayashi, K.; Koito, A.; Anzai, S. Bull.
Chem. Soc. Jpn. 2001, 74, 1947±1961.
22. Oh, H.; Swenson, D. C.; Gloer, J. B.; Shearer, C. A.
Tetrahedron Lett. 2001, 42, 975±977.
5. Nishitani, K.; Nakamura, Y.; Orii, R.; Arai, C.; Yamakawa, K.
Chem. Pharm. Bull. 1993, 41, 822±831.
23. ,a) Back, T. G.; Payne, J. E. Org. Lett. 1999, 1, 663±665.
,b) Back, T. G.; Gladstone, P. L.; Parvez, M. J. Org. Chem.
1996, 61, 3806±3814.
Â
24. Hamelin, O.; Depres, J.-P.; Greene, A. W.; Tinant, B.;
Declercq, J.-P. J. Am. Chem. Soc. 1996, 118, 9992±9993.
6. Nishitani, K.; Suzuki, J.; Ishibashi, H.; Saitoh, Y.; Kariya, S.;
Yamakawa, K. Heterocycles 1994, 39, 43±46.
7. Kuroda, C.; Nogami, H.; Ohnishi, Y.; Kimura, Y.; Satoh, J. Y.
Tetrahedron 1997, 53, 839±858.
8. ,a) Kuroda, C.; Mitsumata, N.; Tang, C. Y. Bull. Chem. Soc.
Jpn. 1996, 69, 1409±1416. ,b) Kuroda, C.; Tang, C. Y.;
Tanabe, M.; Funakoshi, M. Bull. Chem. Soc. Jpn. 1999, 72,
1583±1587.
Â
25. Greene, A. G.; Coelho, F.; Depres, J.-P.; Brocksom, T. J.
J. Org. Chem. 1985, 50, 1973±1975.
26. ,a) Srikrishna, A.; Viswajanani, R.; Sattigeri, J. A. Chem.
Commun. 1995, 469±470. ,b) Srikrishna, A.; Nagaraju, S.;
Sharma, G. V. R. Chem. Commun. 1993, 285±288.
9. For related work on the reaction of functionalized allylsilane
reported from our laboratory: ,a) Kuroda, C.; Kimura, Y.;
Nogami, H. J. Chem. Res. 'S) 1998, 174±175. ,b) Kuroda,
C.; Koshio, H.; Koito, A.; Sumiya, H.; Murase, A.; Hirono,
Y. Tetrahedron 2000, 56, 6441±6455. ,c) Kuroda, C.; Koshio,
H. Chem. Lett. 2000, 962±963. ,d) Suzuki, H.; Monda, A.;
Kuroda, C. Tetrahedron Lett. 2001, 42, 1915±1917.
10. Harmata, M. Recent Res. Dev. Org. Chem. 1997, 1, 523±535.
11. Lee, T. V.; Boucher, R. J.; Porter, J. R.; Taylor, D. A.
Tetrahedron 1988, 44, 4233±4242.
27. Okabe, M.; Tada, M. J. Org. Chem. 1982, 47, 5382±5384.
Â
28. Marko, I. E.; Bayston, D. J. Tetrahedron Lett. 1993, 34, 6595±
6598.
29. Snider, B. B.; Rodini, D. J.; Kirk, T. C.; Cordova, R. J. Am.
Chem. Soc. 1982, 104, 555±563.
30. Caine, D. Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 3, pp 1±63.