Synthesis of eleven-membered carbocycles via a homo-Cope type of five-carbon ring expansion reaction utilized β-(hydroxymethyl)allylsilane

Article abstract of DOI:10.1016/S0040-4020(03)00348-X

Eleven-membered carbocycles were synthesized from six-membered compounds fitted with a β-(hydroxymethyl)allylsilane unit via the title reaction. Namely, trans- and cis-(E)-2-(trimethylsilylmethyl)-3-(2-vinylcyclohex-1-yl)prop-2-en-1-ol were treated with Tf₂O in CH₂Cl₂ in the presence of 2,6-lutidine to afford (1E)-3-methylenecycloundeca-1,6-diene in good yield. The geometry of the product was shown to depend upon the trans- and cis-substitution pattern on the cyclohexane ring of the substrates; i.e. trans-isomer afforded (6E)-product exclusively and cis-isomer afforded the mixture of (6E)- and (6Z)-product in 1:2 ratio. The (Z)-substrate with respect to allylsilane moiety afforded the same ring expansion product, however, the yield was lower than the reaction with the (E)-substrate. The substrates bearing t-butyl or benzyloxy substituents on the cyclohexane ring also afforded the product analogously, indicating that the reaction depends upon the conformation of the substrate. On the other hand, the substrate bearing isopropenyl group instead of a simple vinyl group did not afford the ring expansion product but produced bicyclo[5.4.0]undecane via the ene reaction.

Full text of DOI:10.1016/S0040-4020(03)00348-X

Tetrahedron 59 (2003) 3157–3174
Synthesis of eleven-membered carbocycles via a homo-Cope type
of five-carbon ring expansion reaction utilized
b-(hydroxymethyl)allylsilane
*
Hideyuki Suzuki and Chiaki Kuroda
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Received 20 January 2003; accepted 28 February 2003
Abstract—Eleven-membered carbocycles were synthesized from six-membered compounds fitted with a b-(hydroxymethyl)allylsilane unit
via the title reaction. Namely, trans- and cis-(E)-2-(trimethylsilylmethyl)-3-(2-vinylcyclohex-1-yl)prop-2-en-1-ol were treated with Tf2O in
CH2Cl2 in the presence of 2,6-lutidine to afford (1E)-3-methylenecycloundeca-1,6-diene in good yield. The geometry of the product was
shown to depend upon the trans- and cis-substitution pattern on the cyclohexane ring of the substrates; i.e. trans-isomer afforded (6E)-
product exclusively and cis-isomer afforded the mixture of (6E)- and (6Z)-product in 1:2 ratio. The (Z)-substrate with respect to allylsilane
moiety afforded the same ring expansion product, however, the yield was lower than the reaction with the (E)-substrate. The substrates
bearing t-butyl or benzyloxy substituents on the cyclohexane ring also afforded the product analogously, indicating that the reaction depends
upon the conformation of the substrate. On the other hand, the substrate bearing isopropenyl group instead of a simple vinyl group did not
afford the ring expansion product but produced bicyclo[5.4.0]undecane via the ene reaction. q 2003 Elsevier Science Ltd. All rights
reserved.
1. Introduction
expansion reaction is reported by Takayanagi et al. based
on the rearrangement of silyl group.10
Eleven-membered carbocycles are grouped as medium-
sized rings and are basic carbocyclic systems in natural
terpenes, such as humulanes in sesquiterpenes and lathyrols
or dollabelanes in diterpenes.1,2 Particularly, many natural
dollabelanes3 have been found in the last two decades and
have been the focus of attention as interesting synthetic
targets by several chemists.4 For the synthesis of medium-
sized ring compounds,5,6 the ring expansion method is one
of the most important method, among which the Cope
rearrangement is widely utilized as the four-carbon ring
expansion reaction.7 Various germacrane type of com-
pounds were synthesized by this method,8 since the direct
cyclization to prepare ten-membered rings is not easy. One-,
two-, three-, and four-carbon ring expansion reactions have
been established as common synthetic methods fitted with a
high level of quality and availability,9 whereas, to our
knowledge, only one example of a five-carbon ring
b-(Hydroxymethyl)allylsilane is a versatile three-carbon
unit in organic synthesis, which can be used for the
synthesis of odd-membered ring compounds.11,12 For
example, Giguere et al. reported the synthesis of hydro-
azulene derivatives via intramolecular homo-Diels–Alder
reaction utilizing this unit as the dienophile.13 As the related
carbon 1,3-dipole, we have developed various synthetic
methods utilizing b-carbonylallylsilanes.11 For examples,
self-cyclization of 2-(trimethylsilylmethyl)pentadienal14
and intramolecular cyclization of (2-functionalized allyl)-
trimethylsilane with acid chloride15 were established as new
synthetic methods to spiro[4.5]decanes and a-methylene-g-
lactones, respectively. On the course of our continuous
study, we planned a new five-carbon ring expansion method
via the homo-Cope reaction. Namely, as depicted in
Scheme 1, the homo-Cope type of reaction (reaction B) is
Scheme 1.
Keywords: silicon and compounds; ring transformation; ene-reaction.
*
Corresponding author. Tel.: þ81-3-3985-2396; fax: þ81-3-5992-3434; e-mail: kuroda@rikkyo.ac.jp
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00348-X

3158
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
Scheme 2. Reagents: (a) PivCl, pyridine, CHCl3; (b) (COCl)2, DMSO, Et3N, CH2Cl2; (c) [Ph3PCH3]þBr2, n-BuLi, THF; (d) LiAlH4, THF;
(e) (EtO)2P(O)CH(CO2Et)CH2SiMe3, NaH, DME; (f) DIBAL-H, CH2Cl2.
expected to proceed by replacing one of the two CvC
double bonds in the Cope rearrangement (reaction A) with a
b-(hydroxymethyl)allylsilane unit. A formal homo-Cope
rearrangement of 1,6-heptadiene was reported by Hoshstrate
et al.16 but the reaction of 7-substituted-1,5-heptadiene is
not known. Here we report the synthesis of eleven-
membered carbocycles from a cyclohexane ring having
b-(hydroxymethyl)allylsilane moiety via a new homo-Cope
type of ring expansion reaction.17
unfortunately, the isomers with respect to the cyclohexane
ring could not be separated. The ratio of 6a to 6b was 6:5,
and each consisted of trans- and cis-substituted cyclo-
hexanes in 3:2 and 9:2 ratios, respectively. The geometry of
the double bond was determined from the chemical shifts of
the conjugated olefinic protons; i.e. d 5.41 for E-isomer (6a)
and d 6.40 for Z-isomer (6b).19 Preparation of cis-6a and
cis-6b from cis-1,4-cyclohexanedimethanol was also tried
according to the same reaction scheme, and resulted in
obtaining the same mixture of four diastereomers of 6a and
6b, which is the result of the isomerization during the HWE
reaction. Each 6a and 6b was reduced by DIBAL-H to
afford the substrates 1a and 1b, respectively (1a: 95%, 1b:
93%).
2. Results and discussion
On the above basis, we first studied the ring expansion
reaction using the most simple substrates 1a and 1b which
have a b-(hydroxymethyl)allylsilane unit and a vinyl
group on the cyclohexane ring. The substrates 1a,b were
prepared as shown in Scheme 2. Namely, trans-1,2-
cyclohexanedimethanol 2, prepared from trans-1,2-cyclo-
hexanedicarboxylic acid by esterification and LiAlH4
reduction, was first monoprotected with a pivaloyl group
to give alcohol 3 (93%), which was oxidized to the aldehyde
followed by the Wittig methylenation to afford alkene 4
(83% in two steps). Reductive deprotection of the pivaloyl
group in 4 gave alcohol 5 (98%), to which, after oxidation to
the aldehyde, a b-(ethoxycarbonyl)allylsilane unit was
introduced using (EtO)2P(O)CH(CO2Et)CH2SiMe3 as the
Horner–Wadsworth–Emmons (HWE) reagent18 giving
6a,b in 60% from 5. The NMR experiment showed that
the products 6a,b consists of four-isomers, among which
(E)-allylsilane (6a) and (Z)-allylsilane (6b) could be
separated by repetitive column chromatography, however,
The ring expansion reaction was performed following the
homo-Diels–Alder reaction reported by Giguere et al.13a
Thus, the substrate 1a was treated with Tf2O in the presence
of 2,6-lutidine in dry CH2Cl2 solvent at 2608C affording the
desired eleven-membered hydrocarbons 7a and 7b in a short
reaction time (within 30 min) in a 81% yield (Scheme 3).
The 1H NMR spectrum of the product showed that the two
compounds 7a and 7b (7a/7b¼3:1) were the isomers with
respect to the non-conjugated double bond and the geometry
was determined from their J-values (J¼15.5 Hz for 7a,
J¼10.6 Hz for 7b), whereas the conjugated double bond in
both compounds were of the E-form (J¼15.8 Hz for both 7a
and 7b). In contrast, the reaction of 1b resulted in the
formation of the same mixture of 7a and 7b (7a/7b¼3:1) in
low yield (24%). Such contrastive results indicate that the
isomerization from 1b to 1a prior to the ring expansion
reaction is a favorable pathway. As shown in Scheme 4, the
Scheme 3.

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3159
Scheme 4.
direct cyclization of 1b seemed to be of considerable
disadvantage compared with that of 1a, since the seven-
membered transition state B, generated from 1b, is included
in the highly strained trans-substituted double bond. On the
other hand, 1a leads more favorable transition state A which
includes a cis-substituted double bond. A related E/Z
isomerization of a functionalized allylsilane moiety was
observed previously for b-formylallylsilane14 and
b-(ethoxycarbonyl)allylsilane.19
our surprise, the reaction proceeded without isomerization
at the a-carbon giving only trans-6a exclusively (Scheme 5).
We carried out the ring expansion reaction using a pure
trans-1a in hand after the reduction. As expected, the
product 7a was obtained as the sole product in a 95% yield,
and thus we could display the evidence that trans-1a affords
7a as the only product. Also, the overall yield of the
synthesis from diol 2 to eleven-membered carbocycle (7a
and/or 7b) was much increased (50%) compared with our
first attempt (23%).
To explore the stereochemistry of the reaction, we next
prepared three mixtures of 1a with different trans/cis ratios
by repetitive column chromatography, however, the com-
plete separation of the two isomers was impossible. Each
diastereomer mixtures were exposed to the same reaction
conditions, respectively, and the results are shown in
Table 1. The extraporation of these data showed that
trans-1a affords 7a selectively, whereas cis-1a affords 7a
and 7b in a 1:2 ratio.
Since the homo-Cope reaction of the basic substrate 1a was
successful, we next studied the substituent effect on
cyclohexane ring with the substrates bearing a bulky
substituent (t-Bu) 8 or the oxygen functionality (BnO) 20,
expecting to obtain the stereochemical informations of this
reaction. The substrate 8 was first synthesized by the route
shown in Scheme 6. Ethoxycarbonylmethylation22 of
commercially available 4-t-butylcyclohexanone (9) fol-
lowed by the reduction of 10 afforded diol 11 (79% in two
steps). Though compound 11 was obtained as the mixture of
three diastereomers, monoprotection with a pivaloyl group
(12) and oxidation afforded cyclohexanone 13 (82% in two
steps) as the single diastereomer. It was found that the
diastereomer of 13 was also produced in these reactions,
however, isomerization occurred quickly during work-up of
the oxidation reaction to afford the thermodynamically more
stable product, 13. Ketone 13 was next methylenated via the
Wittig reaction followed by hydroboration using 9-BBN to
the alcohol, which was masked by a TBDMS group to
obtain 14 (92% in three steps). Deprotection of the pivaloyl
group by LiAlH4 afforded a mixture of 15a and 15b (94%)
in a 2:1 ratio, which could easily be separated by the usual
column chromatography. The stereochemistry of 15a,b was
determined from the chemical shifts and their half-band
widths of the methyne protons on the cyclohexane ring
bonding t-butyldimethylsilyloxymethyl group (d 1.12,
W1/2¼22 Hz for 15a and d 1.89, W1/2¼14 Hz for 15b).
The major isomer, 15a, was nitrophenylselenylated,23 and
exposed to the conditions of oxidative elimination followed
by the removal of the TBDMS group to afford alcohol 16
(78% in three steps). The alcohol was oxidized to the
aldehyde 17 (100%), followed by the (E)-selective intro-
duction of a silyl group with the Ando-HWE reagent20
giving (E)-b-(ethoxycarbonyl)allylsilane 18 (81%). Com-
pound 15b also afforded the same allylsilane 18 by the same
operations, which is the result of the isomerization from cis-
isomer to trans-isomer during oxidation (16 to 17) as well as
the HWE reaction (17 to 18). The unsaturated ester 18 was
finally reduced to obtain substrate 8 (100%).
Table 1.
Entry
Isomer ratio in 1a (trans/cis)
Ratio of 7a and 7b
1
2
3
4
88:12
68:32
60:40a
44:56
93:7
78:22
75:25
63:37
a
Original ratio.
We recently developed an (E)-selective synthesis of
b-(ethoxycarbonyl)allylsilane
utilizing
prepared from Ando-
(PhO)2-
20
P(O)CH(CO2Et)CH2SiMe3
phosphonate21 as the HWE reagent. From the above
study, it is obvious that the (E)-allylsilane is more suitable
than the (Z)-allylsilane as the substrate for this five-carbon
ring expansion reaction. Therefore, we applied this (E)-
selective synthesis to obtain intermediate 6a. When the
aldehyde prepared from alcohol 5 was treated with the
above phosphonate, allylsilane 6a was obtained preferen-
tially in an excellent yield (90%; 6a/6b¼94:6). Moreover, to
Scheme 5. Reagents: (a) (COCl)2, DMSO, Et3N, CH2Cl2; (b) (PhO)2-
P(O)CH(CO2Et)CH2SiMe3, NaH, THF.

3160
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
Scheme 6. Reagents: (a) LDA, BrCH2CO2Me, HMPA, THF; (b) LiAlH4, THF; (c) PivCl, pyridine, CHCl3; (d) (COCl)2, DMSO, Et3N, CH2Cl2;
(e) [Ph3PCH3]þBr2, t-BuOK, PhMe; (f) 9-BBN, NaOH, H2O2, THF; (g) TBDMSCl, DMAP, Et3N, CH2Cl2; (h) LiAlH4, THF; (i) o-NO2C6H4SeCN, n-Bu3P,
THF; (j) H2O2, THF; (k) TBAF, THF; (l) (COCl)2, DMSO, Et3N, CH2Cl2; (m) (PhO)2P(O)CH(CO2Et)CH2SiMe3, NaH, THF; (n) DIBAL-H, CH2Cl2; (o) Tf2O,
2,6-lutidine, CH2Cl2.
The substrate 8, in which all three side chains are fixed in
equatorial orientations on cyclohexane ring, was exposed to
the condition of the ring expansion reaction as described for
1a, giving the desired eleven-membered ring compound 19
in a 75% yield. As expected, product 19 was obtained as a
single diastereomer having E-form with respect to both the
conjugated and non-conjugated double bonds, which was
confirmed by J-value of its olefinic proton on 1H NMR (see
Section 3).
The ring expansion reaction of the substrates 20a and 20b
were carried out under the same reaction conditions as
described for both 1a and 8. The reaction of 20a proceeded
smoothly to afford the expected eleven-membered ring
compound 32 in an 88% yield. The product 32 was also
obtained as the single diastereomer with an E-form with
respect to both the conjugated and non-conjugated double
bonds. On the other hand, the ring expansion product was
not obtained from 20b in spite of the disappearance of 20b
on TLC. The detection of products from the complex
reaction mixture was unsuccessful.
The substrates 20a and 20b, having benzyloxy substituent,
were prepared by a similar route (Scheme 7). 4-Benzyl-
oxycyclohexanone 21, which was easily prepared from
commercially available 1,2-cyclohexanediol by mono-
benzylation and oxidation, was first converted to the diol
23 (69% in two steps) via 22. After monoprotection of 23
with a pivaloyl group (24), the ketone 25 (25a/25b¼3:1)
was prepared by a Swern oxidation (86% in two steps).
When the major isomer 25a was exposed to the condition of
Wittig olefination, the epimerization at the a-position of the
carbonyl group occurred to give an inseparable mixture of
26 and its diastereomer in a 3:1 ratio. This undesired result
was improved by the usage of the Nozaki–Lombardo
procedure24 to give the alkene 26 (88%) as a single isomer.
Then, the same reaction sequence described for the substrate
having a t-butyl group afforded a mixture of 31a and 31b
(31a/31b¼1:2) after an Ando-HWE reaction. When the
introduction of allylsilane was carried out under weak-base
conditions (DBU/NaI),25 31a (74%) was obtained as the
single isomer. These compounds, 31a and 31b, were then
reduced to obtain the substrates 20a and 20b, respectively
(20a: 96%, 20b: 100%).
As a further study of the substituent effect, we next designed
substrate 33 with an isopropenyl group instead of a simple
vinyl group. Substrate 33 was synthesized from com-
mercially available 2-cyclohexene-1-carbaldehyde (34) as
shown in Scheme 8. Namely, 34 was exposed to the
condition reported by Kuwajima et al.26 to give the 1,4-
adduct (48%) as trans/cis mixture of 7:3 ratio, which was
easily isomerized to 35 (92%) by the treatment with DBU.
The (E)-selective introduction of b-(ethoxycarbonyl)allyl-
silane afforded 36 in a 51% yield. The substrate 33 (97%)
was obtained by a reduction using DIBAL-H.
When 33 was exposed to the reaction condition described
above, bicyclo[5.4.0]undecane 37 was afforded as the sole
product in a 62% yield, and the structure of which was
confirmed by the 1H and 13C NMR spectra including COSY
experiments. Compound 37 is obviously the product of an
ene reaction, which indicates that the cleavage of the C–C
single bond to give the eleven-membered ring did not take
place but deprotonation occurred from the seven-membered

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3161
Scheme 7. Reagents: (a) LDA, BrCH2CO2Me, HMPA, THF; (b) LiAlH4, THF; (c) PivCl, pyridine, CHCl3; (d) (COCl)2, DMSO, Et3N, CH2Cl2; (e) CH2Br2,
Zn, TiCl4, CH2Cl2, THF; (f) 9-BBN, NaOH, H2O2, THF; (g) TBDMSCl, DMAP, Et3N, CH2Cl2; (h) LiAlH4, THF; (i) o-NO2C6H4SeCN, n-Bu3P, THF; (j)
H2O2, THF; (k) TBAF, THF; (l) (COCl)2, DMSO, Et3N, CH2Cl2; (m) (PhO)2P(O)CH(CO2Et)CH2SiMe3, NaH (or DBU/NaI), THF; (n) DIBAL-H, CH2Cl2; (o)
Tf2O, 2,6-lutidine, CH2Cl2.
intermediate carbocation C (Scheme 9). From this result, it
is estimated that the pathway of five-carbon ring expansion
reaction is stepwise via the cation D as the intermediate,
however, the concerted mechanism for vinyl substituted
compounds such as 1 cannot be ruled out. This ene reaction
is expected to be a novel synthetic method to form seven-
membered ring compounds.
The explanations of the stereochemical outcome of
the homo-Cope reaction are as follows. As shown in
Scheme 8. Reagents: (a) H2CvCMeMgBr, CuBrSMe2, TMSCl, HMPA, HCl, THF; (b) DBU, CH2Cl2; (c) (PhO)2P(O)CH(CO2Et)CH2SiMe3, NaH, THF;
(d) DIBAL-H, CH2Cl2; (e) Tf2O, 2,6-lutidine, CH2Cl2.

3162
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
Scheme 9.
Scheme 10, the stereoselective formation of the EE-product
(EE) from trans-1a, 8, and 20a can be rationalized by the
intermediate I (and II for stepwise mechanism) in which
two side chains, the vinyl group and the allylsilane group,
take equatorial orientations on the chair conformation of the
cyclohexane ring. Three related conformations III–V are
possible by the rotation of two C(sp3)–C(sp2) single bonds,
which lead EZ, ZE, and ZZ, respectively. However, among
four conformers, only I is suitable for the reaction, since the
reaction sites of the other three conformers are too distant to
react (indicated in dotted line). Following the stepwise
mechanism, the reaction from cis-1a is interpreted in
accordance with Scheme 11. Two conformers VI and VII
can be considered as the intermediates based on the
assumption that the distance of the two reaction sites is
the same for conformer I but not for III–V. The expected
products from VI and VII are ZE and EZ, respectively,
however, EZ and EE were the products from cis-1a. This
means that the major product EZ can be rationalized by the
conformers VII and VIII. The minor product EE must be
formed via IX, which is the flipped conformer of VIII. The
disadvantage of VI is understood by the sterical hinderance
Scheme 10.

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3163
conjugated double bond, whereas the trans-substrate
produces the product having an E-configuration with respect
to the non-conjugated double bond, and the cis-substrate
produces the product having a Z-double bond as the major
component along with the minor E-product. On the other
hand, the substrate having an isopropenyl group did not
afford an eleven-membered ring compound but the
bicyclo[5.4.0]undecene derivative was obtained via the
ene reaction. The establishment of such a ring expansion
reaction from the present study enables the ring-size control,
i.e. the production of different sized compounds from the
same sized ring substrate, and thus offers a new strategy in
organic synthesis.
3. Experimental
3.1. General procedure
Melting points were measured on a Laboratory Devises
Mel-Temp apparatus and are uncorrected. IR spectra were
1
recorded on a Jasco FT/IR-230 spectrometer. Both H and
13C NMR spectra were measured on a Jeol GSX-400
1
(400 MHz for H; 100 MHz for 13C) spectrometer. Chemi-
cal shifts were reported on the d scale (ppm) with solvent
(CHCl3¼7.26) as an internal standard. The signal of the
solvent (CDCl3¼77.00) was used as a standard for 13C
NMR spectra. Both low-resolution mass spectra (LRMS)
and high-resolution mass spectra (HRMS) were obtained on
a Jeol SX-102A, JMS-DX303, Shimadzu GCMS-QP5050,
or JMS-GCMATE II mass spectrometer with the CI method
unless otherwise noted. Analytical TLC was done on
precoated TLC plates (Kieselgel 60 F254, layer thickness
0.2 mm). Wakogel C-200 was used for column chromato-
graphy. Anhydrous Na2SO4 or MgSO4 was used for drying
of extracted organic layers. For dry solvents, tetrahydro-
furan (THF), Et2O, and 1,2-dimethoxyethane (DME) were
distilled from LiAlH4; CHCl3 and CH2Cl2 were distilled
from CaH2 before use.
Scheme 11.
Scheme 12.
3.2. Synthesis and homo-Cope reaction of 1a
of the reacting carbon (indicated as carbocation) which
comes over the cyclohexane ring together with a large
trifluoromethanesulfonyloxy group. If the reaction is not
stepwise but concerted, the formation of EE must be
explained by X, which has a boat like (or twist chair)
conformation for the cyclohexane ring (Scheme 12). The
fact that no reaction proceeded from 20b is considered to be
the conformational disadvantage of both VII and X as well
as VI, namely, that the benzyloxy substituent takes axial
orientation in both VII and X.
3.2.1. [(1RS,2RS)-2-(Hydroxymethyl)cyclohex-1-
yl]methyl pivalate (3). In a 200 cm3 round bottomed flask
attached to a CaCl2 drying tube was placed a solution of 2
(3.173 g, 22.00 mmol) in dry pyridine (8.9 cm3, 110 mmol;
distilled from CaH2) and dry CHCl3 (150 cm3). After being
cooled to 2608C, pivaloyl chloride (3.3 cm3, 26.8 mmol)
was added dropwise, and the mixture was allowed to warm
slowly to room temperature over 8 h. The reaction was
quenched by addition of a small amount of water. 2 M HCl
(60 cm3) was added, and the mixture was extracted with
CHCl3 followed by drying and concentration. The residue
was purified by silica gel (150 g) column chromatography
using hexane/AcOEt (70:30) as eluent to give 3 (4.659 g,
93%) as an oil; IR (neat) 1728 (CvO) and 3447
In conclusion, eleven-membered carbocycles were syn-
thesized from six-membered carbocycle through a homo-
Cope type of new five-carbon ring expansion reaction using
b-(hydroxymethyl)allylsilane unit in place of CvC double
bond of Cope rearrangement. The ring expansion product
was obtained more efficiently when (E)-allylsilane was used
as the substrate than (Z)-allylsilane. It was found that the
geometry of double-bond in the product was determined by
the cis/trans substitution pattern of the two reaction units on
the cyclohexane ring. Namely, the reaction product has the
triene system with only E-configuration with respect to the
(OH) cm21
;
1H NMR (CDCl3) d¼1.09–1.29 (4H, m),
1.21 (9H, s), 1.30–1.40 (1H, m), 1.51–1.62 (1H, m), 1.70–
1.83 (5H, m), 3.64 (2H, d, J¼4.5 Hz), 4.00 (1H, dd, J¼6.0,
11.0 Hz), and 4.12 (1H, dd, J¼4.5, 11.0 Hz); 13C NMR
(CDCl3) d¼25.77, 25.83, 27.19 (3C), 29.49, 29.93, 38.54,
38.85, 42.15, 65.68, 67.56, and 178.67; LRMS (EI) m/z 228
(Mþ; 6%), 198 (100), 171 (93), 141 (86), 104 (90), 78 (95),

3164
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
66 (99), 65 (96), and 59 (84); HRMS [Found: m/z 228.1736
(Mþ). Calcd for C13H24O3: M, 228.1726].
3.2.4. Ethyl (E)-2-(trimethylsilylmethyl)-3-(2-vinylcyclo-
hex-1-yl)prop-2-enoate (6a) and ethyl (Z)-2-(trimethyl-
silylmethyl)-3-(2-vinylcyclohex-1-yl)prop-2-enoate (6b).
Swern oxidation. According to the same procedure shown in
the synthesis of 4, compound 5 (1.625 g, 11.59 mmol) was
oxidized. The resultant crude aldehyde (2.488 g) was used
for the next reaction without purification.
3.2.2. [(1RS,2SR)-2-Vinylcyclohex-1-yl]methyl pivalate
(4). Swern oxidation. To a stirred solution of (COCl)2
(3.9 cm3, 44.7 mmol) in dry CH2Cl2 (80 cm3) was added
dropwise DMSO (4.3 cm3, 60.6 mmol) at 2608C under Ar
atmosphere. After being stirred for 5 min, a solution of 3
(3.421 g, 14.98 mmol) in dry CH2Cl2 (15 cm3) was added
dropwise to this solution. The solution was stirred for 1.5 h
at the same temperature, Et3N (12.6 cm3, 89.7 mmol) was
added, and the reaction mixture was allowed to warm to
room temperature. The stirring was continued for 1 h, and the
reaction was quenched by the addition of water. Extraction
with CH2Cl2 followed by drying and concentration gave an
oily residue (5.054 g), which was not purified.
HWE reaction. To a stirred suspension of NaH (1.069 g,
24.50 mmol; 55% in mineral oil which was removed by
washing with dry hexane) in dry DME (90 cm3) was added
(EtO)2P(O)CH2CO2Et (4.6 cm3, 23.0 mmol) dropwise at
08C under Ar atmosphere. After being stirred at 08C for 4 h,
(iodomethyl)trimethylsilane (3.85 cm3, 25.7 mmol) was
added and the mixture was heated to 708C for 3 h. This
was recooled to 08C, and a second portion of NaH
(691.0 mg, 15.84 mmol; mineral oil was not removed) was
added. After the mixture had been warmed slowly to room
temperature, the stirring was continued for 1 h. This was
cooled to 08C again, a solution of the above aldehyde
(2.488 g) in dry DME (10 cm3) was added dropwise, and the
mixture was stirred at room temperature for 14 h. A
saturated NH4Cl aq. (100 cm3) was added, the mixture
was extracted with Et2O, and dried. Evaporation of the
solvent followed by silica gel (100 g) column chromatog-
raphy using hexane/Et2O (99:1) as eluent afforded a mixture
of 6a and 6b (2.045 g, 60%), which could be separated by
the repetition of the chromatography.
Wittig reaction. To a stirred suspension of methyltri-
phenylphosphonium bromide (10.71 g, 29.97 mmol) in dry
THF (60 cm3) was added n-BuLi (19.0 cm3, 28.5 mmol;
1.50 M solution in hexane) dropwise at 08C under Ar
atmosphere. After being stirred at room temperature for 4 h,
the clear yellow solution was recooled to 08C and a solution
of the above residue (5.054 g) in dry THF (15 cm3) was
added dropwise. The mixture was stirred for 20 h at room
temperature, and to this was added a saturated aqueous
solution of NH4Cl (100 cm3). This was extracted with Et2O
and dried. Evaporation of the solvent followed by silica gel
(100 g) column chromatography using hexane/AcOEt
(95:5) as eluent afforded 4 (2.835 g, 83%) as an oil; IR
Compound 6a. An oil; IR (neat) 1673 (CvC) and 1714
(CvO) cm21
(neat) 1640 (CvC) and 1731 (CvO) cm21
;
1H NMR
;
1H NMR (CDCl3) for trans-6a d¼20.03
(CDCl3) d¼1.06–1.29 (4H, m), 1.20 (9H, s), 1.39–1.49
(1H, m), 1.63–1.91 (5H, m), 3.84 (1H, dd, J¼6.5, 11.0 Hz),
4.06 (1H, dd, J¼3.5, 11.0 Hz), 4.92–5.01 (2H, m), and 5.63
(1H, ddd, J¼9.3, 10.1, 17.1 Hz); 13C NMR (CDCl3)
d¼25.75, 25.79, 27.23 (3C), 29.40, 33.31, 38.84, 41.11,
45.02, 67.60, 114.42, 142.38, and 178.55; LRMS m/z 225
(MþþH; 100%), 223 (2), 167 (2), 143 (4), 123 (71), 122
(48), 85 (22), 81 (15), and 67 (6); HRMS [Found: m/z
225.1841 (MþþH). Calcd for C14H25O2: M, 225.1856].
(9H, s), 1.01–1.11 (1H, m), 1.14–1.30 (3H, m), 1.30 (3H, t,
J¼7.0 Hz), 1.70 (2H, AB), 1.67–1.78 (5H, m), 2.78 (1H,
ddt, J¼3.6, 11.2, 10.0 Hz), 4.16 (2H, q, J¼7.0 Hz), 4.85
(1H, dd, J¼2.0, 10.0 Hz), 4.92 (1H, dd, J¼2.0, 17.2 Hz),
5.41 (1H, d, J¼10.0 Hz), and 5.64 (1H, ddd, J¼7.8, 10.0,
17.2 Hz); for cis-6a d¼20.03 (9H, s), 1.14–1.30 (3H, m),
1.30 (3H, t, J¼7.0 Hz), 1.36–1.45 (1H, m), 1.51–1.64 (4H,
m), 1.72 (2H, br s), 2.31–2.39 (1H, m), 3.15 (1H, br dq,
J¼10.0, 4.6 Hz), 4.17 (2H, q, J¼7.0 Hz), 4.97 (1H, ddd,
J¼1.2, 2.1, 17.0 Hz), 4.99 (1H, ddd, J¼1.1, 2.1, 10.3 Hz),
5.68 (1H, d, J¼10.0 Hz), and 5.92 (1H, ddd, J¼7.8, 10.3,
17.0 Hz); 13C NMR (CDCl3) for trans-6a d¼21.62 (3C),
14.22, 23.97, 25.63, 25.83, 32.59, 32.90, 42.67, 48.16,
59.93, 113.19, 127.99, 143.45, 144.08, and 168.44;
LRMS (EI) m/z 294 (Mþ; 99%), 279 (95), 212 (92), 211
(91), 147 (86), 94 (100), 75 (98), and 73 (95); HRMS
[Found: m/z 294.1973 (Mþ). Calcd for C17H30O2Si: M,
294.1996].
3.2.3. (1RS,2SR)-2-Vinylcyclohexanemethanol (5). In a
200 cm3 round bottomed flask attached to a CaCl2 drying
tube was placed a suspension of LiAlH4 (554.8 mg,
14.62 mmol) in dry Et2O (40 cm3). After being cooled to
08C, a solution of 4 (2.699 g, 12.03 mmol) in dry Et2O
(20 cm3) was added, and the mixture was stirred at room
temperature for 20 h. The reaction was quenched by the
addition of a small amount of moistured Et2O. 2 M HCl
(70 cm3) was added to clear solution, and the mixture was
extracted with Et2O and dried. Evaporation of the solvent
followed by silica gel (80 g) column chromatography using
pentane/Et2O (80:20 to 60:40) as eluent gave 5 (1.658 g,
Compound 6b. An oil; IR (neat) 1637 (CvC) and 1709
(CvO) cm21; 1H NMR (CDCl3) for trans-6b d¼0.00 (9H,
s), 1.11–1.33 (4H, m), 1.28 (3H, t, J¼7.1 Hz), 1.56–1.67
(2H, m), 1.72 (1H, d, J¼13.0 Hz), 1.71–1.82 (2H, m), 1.78
(1H, d, J¼13.0 Hz), 1.82–1.90 (1H, m), 2.00 (1H, dq,
J¼3.2, 10.2 Hz), 4.16 (2H, q, J¼7.1 Hz), 4.87 (1H, ddd,
J¼0.8, 1.9, 10.3 Hz), 4.94 (1H, ddd, J¼1.3, 1.9, 17.2 Hz),
5.63 (1H, ddd, J¼7.3, 10.3, 17.2 Hz), and 6.40 (1H, d,
J¼10.2 Hz); 13C NMR (CDCl3) for trans-6b d¼20.86
(3C), 14.27, 17.29, 25.52, 25.63, 31.66, 31.88, 42.83, 46.83,
60.34, 113.48, 129.15, 142.32, 142.54, and 168.62; LRMS
(EI) m/z 294 (Mþ; 91%), 280 (100), 249 (100), 213 (94), 185
(98), 175 (93), 119 (99), 93 (98), 74 (94), and 67 (92);
98%) as an oil; IR (neat) 1639 (CvC) and 3338 (OH) cm21
;
1H NMR (CDCl3) d¼1.00–1.36 (5H, m), 1.62–1.87 (6H,
m), 3.44 (1H, dd, J¼5.8, 11.0 Hz), 3.62 (1H, dd, J¼4.7,
11.0 Hz), 4.96 (1H, dd, J¼2.1, 10.0 Hz), 5.05 (1H, ddd,
J¼0.8, 2.1, 17.0 Hz), and 5.72 (1H, ddd, J¼9.1, 10.0,
17.0 Hz); 13C NMR (CDCl3) d¼25.73, 25.77, 29.07, 33.41,
44.26, 45.97, 67.15, 114.05, and 143.77; LRMS (EI) m/z
122 (Mþ2H2O; 93%), 110 (86), 94 (97), 91 (97), 65 (100),
and 52 (99); HRMS [Found: m/z 122.1094 (Mþ2H2O).
Calcd for C9H14: M, 122.1096].

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3165
HRMS [Found: m/z 294.1992 (Mþ). Calcd for C17H30O2Si;
M, 294.1996].
silica gel (4 g) column chromatography using hexane as
eluent afforded a mixture of 7a and 7b (39.8 mg, 81%) as an
;
oil; IR (neat) 1603 (CvC) and 1655 (CvC) cm21 1H
3.2.5. (E)-2-(Trimethylsilylmethyl)-3-(2-vinylcyclohex-1-
yl)prop-2-en-1-ol (1a). To a stirred solution of DIBAL-H
(3.8 cm3, 3.80 mmol; 1.0 M solution in cyclohexane) in dry
CH2Cl2 (10 cm3) was added a solution of 6a (366.0 mg,
1.24 mmol) in dry CH2Cl2 (5 cm3) at 2608C under Ar
atmosphere. After the mixture had been stirred for 1 h at
2608C, MeOH (1 cm3) was added, and the mixture was
further stirred for 30 min at room temperature. The resultant
gel was filtrated and washed with CH2Cl2. Evaporation of
the solvent followed by silica gel (15 g) column chroma-
tography using hexane/Et2O (97:3 to 85:15) as eluent
afforded 1a (297.1 mg, 95%); an oil; IR (neat) 1639 (CvC)
NMR (CDCl3) for 7a d¼1.44–1.51 (2H, m), 1.58–1.63
(2H, m), 1.93–2.00 (2H, m), 2.01–2.08 (2H, m), 2.12–2.19
(2H, m), 2.31–2.37 (2H, m), 4.81 (1H, d, J¼2.0 Hz), 4.85
(1H, d, J¼2.0 Hz), 5.11 (1H, dt, J¼15.5, 7.7 Hz), 5.34 (1H,
dt, J¼15.5, 7.6 Hz), 5.40 (1H, dt, J¼15.8, 7.3 Hz), and 5.91
(1H, br d, J¼15.8 Hz); for 7b d¼1.44–2.37 (12H, m), 4.73
(2H, br s), 5.24–5.32 (1H, m), 5.49 (1H, dtt, J¼10.6, 8.6,
1.7 Hz), 5.88 (1H, dt, J¼15.8, 6.8 Hz), and 6.03 (1H, br d,
J¼15.8 Hz); 13C NMR (CDCl3) for 7a d¼27.55, 29.88,
32.27, 33.98, 34.76, 34.88, 112.64, 130.82, 130.92, 134.45,
137.83, and 148.78; for 7b d¼25.56, 26.64, 26.80, 28.64,
29.69, 32.85, 111.21, 129.52, 130.18 (2C), 135.66, and
149.65; LRMS (EI) m/z 162 (Mþ; 66%), 160 (23), 133 (35),
119 (51), 105 (56), 91 (83), 73 (100), 58 (91), and 57 (26);
HRMS [Found: m/z 162.1389 (Mþ). Calcd for C12H18: M,
162.1409]. The ratio of 7a and 7b was determined from the
integral values of each olefinic protons (e.g. 7a: d 5.91, 7b: d
6.03).
and 3334 (OH) cm21 1H NMR (CDCl3) for trans-1a
;
d¼20.01 (9H, s), 1.06–1.29 (5H, m), 1.56 (2H, AB), 1.57–
1.64 (1H, m), 1.66–1.77 (4H, m), 2.05 (1H, dq, J¼3.7,
10.1 Hz), 3.93 (1H, br d, J¼11.4 Hz), 4.04 (1H, br d,
J¼11.4 Hz), 4.87 (1H, d, J¼10.1 Hz), 4.88–4.94 (2H, m),
and 5.64 (1H, ddd, J¼7.6, 10.3, 17.2 Hz); for cis-1a d¼0.01
(9H, s), 1.06–1.77 (9H, m), 1.60 (2H, br s), 2.22 (1H, tt,
J¼4.8, 8.0 Hz), 2.65 (1H, dq, J¼10.1, 4.8 Hz), 3.99 (1H, br
d, J¼11.5 Hz), 4.05 (1H, br d, J¼11.5 Hz), 4.93–4.99 (2H,
m), 5.28 (1H, d, J¼10.1 Hz), and 5.76–5.85 (1H, m); 13C
NMR (CDCl3) for trans-1a d¼21.22 (3C), 24.71, 25.80,
25.85, 32.16, 34.22, 42.01, 47.39, 62.07, 113.41, 131.88,
134.94, and 143.65; for cis-1a d¼21.22 (3C), 22.58, 24.27,
25.03, 28.51, 31.78, 37.91, 44.89, 61.71, 113.91, 127.22,
135.92, and 142.01; LRMS m/z 235 (Mþ2OH; 37%), 162
(24), 161 (33), 147 (10), 133 (14), 121 (20), 107 (22), 81
(31), and 73 (100); HRMS [Found: m/z 235.1832
(Mþ2OH). Calcd for C15H27Si: M, 235.1863].
3.3. Synthesis and homo-Cope reaction of 8
3.3.1. Methyl 2-[(1SR,5SR)-5-t-butyl-2-oxocyclohex-1-
yl]acetate (10a) and methyl 2-[(1RS,5SR)-5-t-butyl-2-
oxocyclohex-1-yl]acetate (10b). To a stirred solution of
i-Pr2NH (3.4 cm3, 24.2 mmol) in dry THF (30 cm3) was
added n-BuLi (15.5 cm3, 24.2 mmol; 1.56 M solution in
hexane) at 2608C under Ar atmosphere. After being stirred
for 20 min, a solution of 9 (3.088 g, 20.02 mmol) in dry
THF (15 cm3) was added dropwise to this solution. The
solution was stirred for 30 min at the same temperature, then
HMPA (4.2 cm3, 24.1 mmol) and BrCH2CO2Et (3.7 cm3,
40.2 mmol) were added subsequently. After the reaction
mixture had been stirred for 20 min, a saturated NH4Cl aq.
(50 cm3) was added, and the mixture was extracted with
AcOEt and dried. Evaporation of the solvent followed by
silica gel (120 g) column chromatography using hexane/
AcOEt (97:3 to 90:10) as eluent afforded 10 (4.016 g, 89%)
as a diastereomer mixture. The following spectral data were
obtained after partial separation into cis- and trans-isomers
by silica gel column chromatography.
3.2.6. (Z)-2-(Trimethylsilylmethyl)-3-(2-vinylcyclohex-1-
yl)prop-2-en-1-ol (1b). According to the same procedure,
compound 6b (467.2 mg, 1.59 mmol) was reduced to give
1b (373.4 mg, 93%); an oil; IR (neat) 1639 (CvC) and 3334
(OH) cm21; 1H NMR (CDCl3) for trans-1b d¼0.03 (9H, s),
1.02–1.13 (1H, m), 1.13–1.30 (3H, m), 1.40 (1H, br s), 1.47
(1H, br d, J¼13.8 Hz), 1.60 (1H, dd, J¼1.0, 13.8 Hz), 1.50–
1.79 (5H, m), 1.83–1.93 (1H, m), 3.92 (2H, br s), 4.85 (1H,
ddd, J¼0.8, 2.2, 10.3 Hz), 4.90 (1H, ddd, J¼1.1, 2.2,
17.2 Hz), 5.07 (1H, br d, J¼9.8 Hz), and 5.67 (1H, ddd,
J¼7.3, 10.3, 17.2 Hz); 13C NMR (CDCl3) for trans-1b
d¼20.59 (3C), 19.08, 25.81, 25.86, 32.05, 32.99, 41.47,
47.58, 68.83, 112.84, 128.56, 136.16, and 143.25; LRMS
m/z 235 (Mþ2OH; 43%), 162 (44), 161 (40), 147 (16), 134
(16), 133 (20), 121 (23), 107 (23), 81 (24), and 73 (100);
HRMS [Found: m/z 235.1824 (Mþ2OH). Calcd for
C15H27Si: M, 235.1863].
Compound 10a. An oil; IR (neat) 1714 (CvO) and 1738
(CvO) cm21; 1H NMR (CDCl3) d¼0.91 (9H, s), 1.44–1.53
(1H, m), 1.55–1.72 (3H, m), 1.83–1.95 (2H, m), 2.31 (1H,
dd, J¼7.0, 15.6 Hz), 2.40–2.49 (1H, m), 2.72 (1H, dd,
J¼7.0, 15.6 Hz), 2.94 (1H, quint, J¼7.3 Hz), and 3.68 (3H,
s); 13C NMR (CDCl3) d¼23.74, 27.08 (3C), 29.35, 32.93,
34.59, 38.57, 42.34, 43.50, 51.71, 172.39, and 213.42;
LRMS m/z 227 (MþþH; 11%), 196 (13), 195 (100), 194 (5),
179 (6), 169 (8), 138 (6), 137 (7), 57 (15), and 55 (6); HRMS
[Found: m/z 227.1662 (MþþH). Calcd for C13H23O3: M,
227.1648].
3.2.7. (1E,6E)-3-Methylenecycloundeca-1,6-diene (7a)
and (1E,6Z)-3-methylenecycloundeca-1,6-diene (7b)—
homo-Cope reaction of 1a. To a stirred solution of 1a
(76.3 mg, 0.30 mmol) in dry CH2Cl2 (5 cm3) were added
2,6-lutidine (0.085 cm3, 0.73 mmol) and Tf2O (0.075 cm3,
0.45 mmol) at 2608C under Ar atmosphere, and the stirring
was continued for 30 min. The reaction was quenched by
addition of a saturated Na2CO3 aq. (40 cm3), and the
mixture was extracted with CH2Cl2. The organic layer was
washed successively with saturated Na2CO3 aq. and 2 M
HCl, and dried. Evaporation of the solvent followed by
Compound 10b. An oil; IR (neat) 1716 (CvO) and 1739
(CvO) cm21; 1H NMR (CDCl3) d¼0.91 (9H, s), 1.23 (1H,
dt, J¼12.1, 12.5 Hz), 1.43 (1H, ddt, J¼5.6, 12.1, 12.5 Hz),
1.65 (1H, tt, J¼2.9, 12.1 Hz), 2.08–2.15 (2H, m), 2.15 (1H,
dd, J¼5.8, 16.4 Hz), 2.33–2.46 (2H, m), 2.78 (1H, dd,
J¼7.2, 16.4 Hz), 2.84–2.93 (1H, m), and 3.68 (3H, s); 13C
NMR (CDCl3) d¼27.53 (3C), 28.42, 32.33, 34.20, 34.76,

3166
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
41.02, 46.19, 46.85, 51.59, 172.98, and 211.32; LRMS m/z
227 (MþþH; 94%), 226 (7), 196 (13), 195 (100), 181 (6),
179 (5), 169 (11), 138 (5), 137 (9), and 57 (9); HRMS
[Found: m/z 227.1662 (MþþH). Calcd for C13H23O3: M,
227.1648].
AcOEt (97:3 to 70:30) as eluent to give 12 (3.474 g, 94%) as
a diastereomer mixture. The following spectral data were
collected after partial purification.
Compound 12a. Mp. 66–688C; IR (CH2Cl2) 1726 (CvO)
and 3427 (OH) cm21; 1H NMR (CDCl3) d¼0.71–0.85 (1H,
m), 0.80 (9H, s), 0.94–1.02 (2H, m), 1.14 (9H, s), 1.17–
1.33 (2H, m), 1.45 (1H, dq, J¼13.8, 6.8 Hz), 1.68–1.79
(2H, m), 1.93–2.01 (1H, m), 2.04 (1H, ddt, J¼4.2, 13.8,
6.8 Hz), 2.32 (1H, br s), 3.13 (1H, dt, J¼4.4, 10.8 Hz), and
4.12 (2H, br t, J¼6.8 Hz); 13C NMR (CDCl3) d¼25.66,
27.16 (3C), 27.57 (3C), 31.81, 31.85, 32.24, 35.93, 38.62,
42.67, 47.27, 63.12, 74.61, and 178.49; LRMS m/z 285
(MþþH; 96%), 267 (90), 183 (65), 165 (99), 149 (21), 109
(72), 95 (65), and 57 (100); HRMS [Found: m/z 285.2398
(MþþH). Calcd for C17H33O3: M, 285.2430].
3.3.2. (1SR,2RS,4SR)-4-t-Butyl-2-(2-hydroxyethyl)cyclo-
hexan-1-ol (11a), (1RS,2RS,4SR)-4-t-butyl-2-(2-hydro-
xyethyl)cyclohexan-1-ol (11b), and (1SR,2SR,4SR)-4-t-
butyl-2-(2-hydroxyethyl)cyclohexan-1-ol (11c). Accord-
ing to the same procedure described for the synthesis of 5,
the above g-ketoester (4.280 g, 18.91 mmol) was reduced
by LiAlH4. The crude product was purified by silica gel
(100 g) column chromatography using hexane/AcOEt
(70:30 to 80:20) as eluent to give diol 11 (3.369 g, 89%)
as a diastereomer mixture. The following spectral data were
obtained after partial purification.
Compound 12b. An oil; IR (neat) 1730 (CvO) and 3477
(OH) cm21; 1H NMR (CDCl3) d¼0.78–0.88 (1H, m), 0.84
(9H, s), 0.97–1.35 (3H, m), 1.18 (9H, s), 1.41–1.55 (4H,
m), 1.59 (1H, dq, J¼13.8, 6.8 Hz), 1.74 (1H, dq, J¼13.8,
6.8 Hz), 1.86–1.93 (1H, m), 3.85 (1H, br q-like, J¼2.5 Hz),
and 4.12 (2H, br t, J¼6.8 Hz); 13C NMR (CDCl3) d¼20.55,
27.22 (3C), 27.39, 27.54 (3C), 31.89, 32.51, 33.85, 38.74,
39.13, 47.85, 62.75, 67.73, and 178.50; LRMS m/z 285
(MþþH; 6%), 267 (11), 183 (27), 165 (48), 109 (63), 95
(56), and 57 (100); HRMS [Found: m/z 285.2394 (MþþH).
Calcd for C17H33O3: M, 285.2430].
Compound 11a. Mp. 72–758C; IR (CH2Cl2) 3336
(OH) cm21
;
1H NMR (CDCl3) d¼0.76–0.89 (1H, m),
0.83 (9H, s), 0.94–1.09 (2H, m), 1.18–1.37 (2H, m), 1.48–
1.56 (1H, m), 1.64–1.76 (3H, m), 1.96–2.03 (1H, m), 3.16
(1H, dt, J¼4.3, 10.5 Hz), 3.59 (1H, ddd, J¼3.4, 10.0,
10.5 Hz), 3.75 (1H, dt, J¼10.5, 4.3 Hz), and 4.46 (2H, br s);
13C NMR (CDCl3) d¼25.57, 27.56 (3C), 32.19, 33.82,
35.47, 38.46, 44.42, 47.20, 61.47, and 75.06; LRMS m/z 201
(MþþH; 36%), 183 (72), 165 (52), 149 (12), 139 (36), 125
(24), 109 (100), 101 (15), 95 (59), 83 (33), and 57 (87);
HRMS [Found: m/z 201.1791 (MþþH). Calcd for
C12H25O2: M, 201.1856].
Compound 12c. Mp. 41–448C; IR (CH2Cl2) 1726 (CvO)
1
and 3438 (OH) cm21; H NMR (CDCl3) d¼0.84 (9H, s),
Compound 11b. Mp. 87–908C; IR (CH2Cl2) 3365
1
0.99–1.28 (2H, m), 1.20 (9H, s), 1.38–1.80 (7H, m), 1.90–
2.07 (2H, m), 3.73 (1H, dt, J¼12.0, 4.5 Hz), 4.08 (1H, dt,
J¼10.8, 7.1 Hz), and 4.13–4.21 (1H, m); 13C NMR
(CDCl3) d¼24.71, 25.67, 27.28 (3C), 27.62 (3C), 29.56,
30.08, 32.10, 36.90, 38.77, 40.46, 63.91, 72.76, and 178.62;
LRMS m/z 285 (MþþH; 7%), 267 (9), 183 (25), 165 (24),
109 (33), 95 (28), and 57 (100); HRMS [Found: m/z
285.2336 (MþþH). Calcd for C17H33O3: M, 285.2430].
(OH) cm21; H NMR (CDCl3) d¼0.86 (9H, s), 1.05 (1H,
tt, J¼2.8, 12.0 Hz), 1.16 (1H, q, J¼12.0 Hz), 1.23–1.72
(7H, m), 1.87–1.94 (1H, m), 2.48 (1H, br s), 2.55 (1H, br s),
3.65–3.78 (2H, m), and 3.91 (1H, br q-like, J¼3 Hz); 13C
NMR (CDCl3) d¼20.67, 27.20, 27.58 (3C), 32.54, 33.75,
36.17, 39.69, 48.00, 60.26, and 68.01; LRMS m/z 201
(MþþH; 58%), 183 (100), 165 (31), 139 (22), 125 (19), 109
(59), 95 (35), 81 (16), and 57 (42); HRMS [Found: m/z
201.1768 (MþþH). Calcd for C12H25O2: M, 201.1856].
3.3.4. 2-[(1RS,5SR)-5-t-Butyl-2-oxocyclohex-1-yl]ethyl
pivalate (13). According to the same procedure shown in
the synthesis of 4, compound 12 was oxidized by the Swern
method. The crude ketone was purified by silica gel (100 g)
column chromatography using hexane/AcOEt (98:2 to
90:10) as eluent to give 13 (2.989 g, 87%) as an oil; IR
Compound 11c. Mp. 103–1068C; IR (CH2Cl2) 3267
1
(OH) cm21; H NMR (CDCl3) d¼0.82 (9H, s), 0.97–1.09
(1H, m), 1.10 (1H, tt, J¼3.0, 12.1 Hz), 1.25 (1H, dt, J¼3.6,
12.4 Hz), 1.42–1.55 (2H, m), 1.67 (1H, dq, J¼13.0,
3.0 Hz), 1.69–1.79 (2H, m), 1.90–2.01 (1H, m), 2.07–
2.14 (1H, m), 3.47 (2H, br s), 3.57 (1H, dt, J¼3.6, 10.4 Hz),
3.72 (1H, dt, J¼11.8, 4.0 Hz), and 3.78 (1H, dt, J¼10.4,
4.7 Hz); 13C NMR (CDCl3) d¼25.85, 27.58 (3C), 30.32,
30.83, 32.05, 32.30, 39.20, 40.85, 62.66, and 72.38; LRMS
m/z 201 (MþþH; 8%), 183 (36), 165 (30), 139 (27), 125 (20),
109 (85), 95 (57), 83 (27), and 57 (100); HRMS [Found: m/z
201.1924 (MþþH). Calcd for C12H25O2: M, 201.1856].
1
(neat) 1727 (CvO) cm21; H NMR (CDCl3) d¼0.91 (9H,
s), 1.13–1.24 (1H, m), 1.18 (9H, s), 1.44 (1H, dq, J¼4.7,
12.6 Hz), 1.49 (1H, dq, J¼13.8, 6.4 Hz), 1.59 (1H, tt, J¼3.0,
12.2 Hz), 2.07–2.14 (1H, m), 2.14 (1H, dt, J¼13.8, 3.3 Hz),
2.17 (1H, dq, J¼13.8, 6.4 Hz), 2.28–2.44 (3H, m), 4.07
(1H, dt, J¼10.8, 6.4 Hz), and 4.13 (1H, dt, J¼10.8, 6.4 Hz);
13C NMR (CDCl3) d¼27.18 (3C), 27.62 (3C), 28.37, 28.67,
32.43, 35.14, 38.69, 41.54, 46.63, 47.17, 62.57, 178.51, and
212.48; LRMS m/z 283 (MþþH; 5%), 221 (5), 181 (100),
180 (25), 154 (20), 139 (6), 89 (79), and 61 (7); HRMS
[Found: m/z 283.2258 (MþþH). Calcd for C17H31O3: M,
283.2274].
3.3.3. 2-[(1RS,2SR,5SR)-5-t-Butyl-2-hydroxycyclohex-1-
yl]ethyl pivalate (12a), 2-[(1RS,2RS,5SR)-5-t-butyl-2-
hydroxycyclohex-1-yl]ethyl pivalate (12b), and 2-
[(1SR,2SR,5SR)-5-t-butyl-2-hydroxycyclohex-1-yl]ethyl
pivalate (12c). According to the same procedure described
for the synthesis of 3, compound 11 (2.615 g, 13.05 mmol)
was monopivalated. The crude product was purified by
silica gel (50 g) column chromatography using hexane/
3.3.5. 2-[(1RS,2SR,5SR)-5-t-Butyl-2-(t-butyldimethylsily-
loxymethyl)cyclohex-1-yl]ethyl pivalate (14a) and 2-
[(1RS,2RS,5SR)-5-t-butyl-2-(t-butyldimethylsilyloxy-
methyl)cyclohex-1-yl]ethyl pivalate (14b). Wittig

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3167
reaction. To a stirred suspension of methyltriphenyl-
phosphonium bromide (10.64 g, 29.78 mmol) in toluene
(60 cm3) were added t-BuOK (3.311 mg, 29.51 mmol) and
the mixture was refluxed for 3 h under Ar atmosphere. After
being cooled to room temperature, the mixture was filtrated,
and the filtrate was added to a solution of 13 (2.098 g,
7.43 mmol) in toluene (20 cm3). The reaction mixture was
stirred at room temperature for 1 h, and then water
(100 cm3) was added. Extraction with AcOEt followed by
drying and evaporation of the solvent afforded an oily
residue, from which the polar by-product was removed by
silica gel (80 g) column chromatography using hexane/Et2O
(199:1 to 97:3) as eluent. The resultant crude oily product
(2.055 g) was used in the next hydroboration reaction
without purification.
1.85 (1H, m), 1.99 (1H, dq-like, J¼13, 2.5 Hz), 3.53 (1H,
dd, J¼8.4, 10.0 Hz), 3.66 (1H, dd, J¼6.0, 10.0 Hz), and
4.06–4.16 (2H, m); 13C NMR (CDCl3) d¼25.33, 25.26,
18.32, 21.55, 26.01 (3C), 27.27 (3C), 27.55 (3C), 28.59,
29.02, 32.55, 33.25, 37.09, 38.60, 38.75, 48.25, 60.65,
63.26, and 178.51; LRMS m/z 413 (MþþH; 48%), 355 (38),
311 (100), 179 (61), 159 (69), 123 (86), 109 (70), 95 (30),
and 57 (86); HRMS [Found: m/z 413.3535 (MþþH). Calcd
for C24H49O3Si: M, 413.3451].
3.3.6. 2-[(1RS,2SR,5SR)-5-t-Butyl-2-(t-butyldimethylsilyl-
oxymethyl)cyclohex-1-yl]ethanol (15a) and 2-[(1RS,
2RS,5SR)-5-t-butyl-2-(t-butyldimethylsilyloxymethyl)-
cyclohex-1-yl]ethanol (15b). According to the same pro-
ceduredescribed for the synthesis of5, compound14(2.529 g,
12.03 mmol) was deprotected to 15. The crude alcohol was
purified by silica gel (50 g) column chromatography using
hexane/AcOEt (95:5 to 80:20) as eluent. Purification by silica
gel column chromatography was repeated until 15a (1.243 g,
62%) and 15b (649.2 mg, 32%) were obtained.
Hydroboration. The above oil (2.055 g) was dissolved in
dry THF (10 cm3) and to this was added 9-BBN with stirring
(30.0 cm3, 15.0 mmol; 0.5 M solution in THF) at 08C under
Ar atmosphere. The stirring was continued for 24 h at room
temperature. The reaction mixture was cooled to 08C, and
water (1 cm3), 6 M NaOH (1.5 cm3), and 35% H2O2
(2.6 cm3) were added carefully. After the stirring had been
continued for 1 h at room temperature, 2 M HCl (5 cm3) and
a saturated aqueous solution of NH4Cl (20 cm3) were added.
The mixture was extracted with AcOEt, dried, and the
solvent was evaporated. The polar by-product was removed
by silica gel (60 g) column chromatography using hexane/
AcOEt (97:3 to 70:30) as eluent to give crude product of
alcohol (3.013 g), however to obtain pure compound was
not possible. This was used in the next step without
characterization.
1
Compound 15a. An oil; IR (neat) 3327 (OH) cm21; H
NMR (CDCl3) d¼0.04 (6H, s), 0.73–0.86 (1H, m), 0.83
(9H, s), 0.89 (9H, s), 0.92–1.03 (2H, m), 1.06–1.18 (2H, m,
W1/2¼22 Hz), 1.25–1.35 (1H, m), 1.40–1.49 (1H, m),
1.73–1.84 (4H, m), 1.87 (1H, br s), 3.59 (2H, br s), and
3.61–3.76 (2H, m); 13C NMR (CDCl3) d¼25.41, –5.37,
18.30, 21.62, 25.95 (3C), 27.47 (3C), 28.86, 29.32, 32.47,
37.12, 37.39, 38.57, 48.19, 61.10, and 61.63; LRMS m/z 329
(MþþH; 10%), 311 (2), 271 (3), 197 (2), 179 (3), 109 (4),
89 (100), and 61 (10); HRMS [Found: m/z 329.2874
(MþþH). Calcd for C19H41O2Si: M, 329.2857].
1
t-Butyldimethylsilylation. To a stirred solution of the above
residue (3.013 g) in CH2Cl2 (20 cm3) was added Et3N
(3.00 cm3, 21.3 mmol), DMAP (87.5 mg, 0.716 mmol), and
TBDMSCl (3.282 g, 21.78 mmol) at room temperature.
After stirring for 19 h, the reaction mixture was diluted with
Et2O (150 cm3), washed with saturated NaHCO3 aq. and
NH4Cl aq., and dried. Evaporation of the solvent followed
by silica gel (50 g) column chromatography using hexane/
AcOEt (99:1) as eluent afforded 14 (2.811 g, 92% in three
steps from 13). The following spectral data were collected
after partial purification.
Compound 15b. An oil; IR (neat) 3328 (OH) cm21; H
NMR (CDCl3) d¼0.05 (6H, s), 0.83 (9H, s), 0.89 (9H, s),
0.98–1.10 (2H, m), 1.31 (1H, tt, J¼3.6, 13.3 Hz), 1.40–
1.53 (3H, m), 1.61–1.73 (3H, m), 1.74 (1H, br s), 1.85–1.93
(1H, m, W1/2¼14 Hz), 1.96 (1H, dq, J¼13.3, 3.0 Hz), 3.53
(1H, dd, J¼7.6, 10.0 Hz), and 3.65–3.77 (3H, m); 13C NMR
(CDCl3) d¼25.45, 25.43, 18.33, 25.93 (3C), 26.88, 27.53
(3C), 30.80, 32.39, 33.76, 36.40, 36.81, 44.42, 47.80, 61.18,
and 66.11; LRMS m/z 329 (MþþH; 16%), 311 (1), 271 (2),
197 (3), 179 (9), 123 (8), 109 (7), 89 (100), and 61 (9);
HRMS [Found: m/z 329.2869 (MþþH). Calcd for
C19H41O2Si: M, 329.2857].
1
Compound 14a. An oil; IR (neat) 1730 (CvO) cm21; H
NMR (CDCl3) d¼0.03 (6H, s), 0.74 (1H, q, J¼11.8 Hz),
0.83 (9H, s), 0.88 (9H, s), 0.90–1.01 (2H, m), 1.05–1.17
(2H, m), 1.19 (9H, s), 1.24–1.36 (1H, m), 1.38–1.48 (1H,
m), 1.74–1.85 (3H, m), 1.92 (1H, ddt, J¼3.2, 13.6, 7.6 Hz),
3.50 (1H, dd, J¼4.8, 10.0 Hz), 3.60 (1H, dd, J¼2.8,
10.0 Hz), and 4.06–4.13 (2H, m); 13C NMR (CDCl3)
d¼25.37, 25.35, 18.35, 25.99 (3C), 26.93, 27.26 (3C),
27.60 (3C), 30.68, 32.31, 32.46, 33.09, 36.52, 38.71, 44.41,
47.88, 62.82, 65.75, and 178.51; LRMS m/z 413 (MþþH;
40%), 355 (25), 311 (100), 179 (33), 159 (33), 123 (41), 109
(35), 95 (14), and 57 (41); HRMS [Found: m/z 413.3412
(MþþH). Calcd for C24H49O3Si: M, 413.3451].
3.3.7. (1SR,2RS,4SR)-4-t-Butyl-2-vinylcyclohexane-
methanol (16). To a stirred mixture of 15a (390.6 mg,
1.189 mmol) and 2-nitrophenylselenocyanate (324.4 mg,
1.427 mmol) in THF (4 cm3) was added dropwise n-Bu3P
(0.35 cm3, 1.419 mmol) at room temperature under Ar
atmosphere and the stirring was continued for 2 h. After
evaporation of the solvent, the residue was roughly purified
by silica gel (20 g) column chromatography using
hexane/Et2O (100:0 to 97:3) as eluent to give a yellow oil
(522.9 mg) containing the nitrophenylselenylated com-
pound as the major component, which was dissolved in
THF (10 cm3) with stirring. To this was added 35% H2O2
(3 cm3) at 08C and the stirring was continued for 17 h at
room temperature. Water (50 cm3) was added and the
mixture was extracted with hexane, and dried. Evaporation
of the solvent afforded a residue which contains 16 and its
silylated compound. In order to complete the desilylation,
1
Compound 14b. An oil; IR (neat) 1730 (CvO) cm21; H
NMR (CDCl3) d¼0.04 (6H, br s), 0.85–0.92 (1H, m), 0.83
(9H, s), 0.89 (9H, s), 1.00–1.07 (2H, m), 1.19 (9H, s), 1.22–
1.32 (1H, m), 1.47–1.56 (3H, m), 1.58–1.76 (2H, m), 1.78–

3168
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
this mixture was dissolved in THF (10 cm3) to which was
added TBAF (801.2 mg, 3.06 mmol) at the room tempera-
ture with stirring. After stirring for 3.5 h, the reaction was
quenched by the addition of a saturated NH4Cl aq. followed
by extraction with Et2O and drying. Evaporation of the
solvent followed by silica gel (15 g) column chromatography
using pentane/Et2O (95:5 to 60:40) as eluent gave 16
(181.0 mg, 78%) as an oil; IR (neat) 1638 (CvC) and 3337
4.15 (2H, q, J¼6.8 Hz), 4.86 (1H, dd, J¼2.0, 10.4 Hz), 4.92
(1H, dd, J¼2.0, 17.2 Hz), 5.40 (1H, d, J¼10.0 Hz), and 5.64
(1H, ddd, J¼8.2, 10.4, 17.2 Hz); 13C NMR (CDCl3)
d¼21.61 (3C), 14.24, 23.96, 26.46, 27.49 (3C), 32.38,
33.19, 33.68, 42.57, 47.31, 48.64, 59.91, 113.17, 128.15,
143.61, 144.27, and 168.39; LRMS m/z 351 (MþþH;
100%), 335 (32), 305 (6), 293 (3), 212 (25), 211 (13), 185
(5), 147 (3), 94 (6), and 73 (10); HRMS [Found: m/z
351.2710 (MþþH). Calcd for C21H39O2Si: M, 351.2701].
1
(OH) cm21; H NMR (CDCl3) d¼0.85 (9H, s), 0.87–1.12
(4H, m), 1.19–1.31 (1H, m), 1.46 (1H, br s), 1.68 (1H, dq-like,
J¼3, 13 Hz), 1.77–1.90 (3H, m), 3.43 (1H, dd, J¼5.8,
11.0 Hz), 3.62 (1H, dd, J¼4.8, 11.0 Hz), 4.97 (1H, dd, J¼2.2,
10.2 Hz), 5.05 (1H, dd, J¼2.2, 17.2 Hz), and 5.72 (1H, ddd,
J¼9.5, 10.2, 17.2 Hz); 13C NMR (CDCl3) d¼26.58, 27.49
(3C), 29.46, 32.34, 34.50, 44.19, 46.43, 47.21, 67.14, 114.05,
and 143.99; LRMS m/z 197 (MþþH; 77%), 179 (100), 139
(44), 123 (77), 109 (69), 95 (27), 81 (24), and 67 (11); HRMS
[Found: m/z 197.1888 (MþþH). Calcd for C13H25O: M,
197.1907].
3.3.10. (E)-3-[(1SR,2RS,4SR)-4-t-Butyl-2-vinylcyclohex-
1-yl]-2-(trimethylsilylmethyl)prop-2-en-1-ol (8). Accord-
ing to the same procedure shown in the synthesis of 1a and
1b, compound 18 (73.0 mg, 0.208 mmol) was reduced to
afford 8 (64.0 mg, 100%); an oil; IR (neat) 1637 (CvC) and
3336 (OH) cm21
;
1H NMR (CDCl3) d¼20.01 (9H, s),
0.80–1.27 (5H, m), 0.85 (9H, s), 1.56 (2H, AB), 1.65–1.79
(4H, m), 1.99 (1H, ddt, J¼3.8, 11.3, 10.0 Hz), 3.93 (1H, d,
J¼11.5 Hz), 4.03 (1H, d, J¼11.5 Hz), 4.84 (1H, d,
J¼9.8 Hz), 4.89–4.95 (2H, m), and 5.62 (1H, ddd, J¼7.8,
10.2, 17.3 Hz); 13C NMR (CDCl3) d¼21.33 (3C), 24.69,
26.59, 27.49 (3C), 32.37, 33.23, 34.47, 41.85, 47.18, 47.86,
62.07, 113.48, 131.86, 135.23, and 143.91; LRMS m/z 308
(Mþ; 2%), 218 (14), 217 (4), 161 (17), 119 (5), 105 (4), 89
(100), 73 (11), and 61 (10); HRMS [Found: m/z 308.2520
(Mþ). Calcd for C19H36OSi: M, 308.2517].
3.3.8. (1SR,2RS,4SR)-4-t-Butyl-2-vinylcyclohexane-1-
carbaldehyde (17). According to the same procedure
described for the synthesis of 4, compound 16 (102.0 mg,
0.520 mmol) was oxidized by the Swern method. The crude
product was purified by silica gel (5 g) column chromato-
graphy using hexane/Et2O (99:1) as eluent to give 17
(100.6 mg, 100%) as an oil; IR (neat) 1651 (CvC), 1728
(CvO), and 2711 (CHO) cm21; 1H NMR (CDCl3) d¼0.86
(9H, s), 0.89–1.05 (2H, m), 1.09 (1H, tt, J¼2.7, 12.0 Hz),
1.27–1.38 (1H, m), 1.79–1.92 (3H, m), 2.05 (1H, tt, J¼3.7,
11.8 Hz), 2.24 (1H, ddt, J¼3.7, 8.0, 11.8 Hz), 5.00 (1H, dd,
J¼1.7, 10.1 Hz), 5.03 (1H, br d, J¼17.0 Hz), 5.71 (1H, ddd,
J¼8.0, 10.1, 17.0 Hz), and 9.55 (1H, d, J¼3.7 Hz); 13C
NMR (CDCl3) d¼25.52, 26.28, 27.41 (3C), 32.38, 33.28,
42.93, 46.88, 54.36, 114.91, 141.28, and 205.35; LRMS (EI)
m/z 194 (Mþ; 3%), 179 (4), 167 (8), 149 (22), 138 (25), 137
(16), 109 (27), 91 (16), 81 (15), 67 (20), 57 (100), and 55
(18); HRMS [Found: m/z 194.1680 (Mþ). Calcd for
C13H22O; M, 194.1672]; Analysis as semicarbazone (Mp
185–1878C) [Found: C, 67.00; H, 9.80; N, 16.61%. Calcd
for C14H25N3O: C, 66.89; H, 10.02; N, 16.72%].
3.3.11. (1E,6E)-9-t-Butyl-3-methylenecycloundeca-1,6-
diene (19)—homo-Cope reaction of 8. According to the
same procedure shown in the synthesis of 7a and 7b,
compound 8 (14.9 mg, 0.048 mmol) was converted to the
eleven-membered carbocycle. The purification of the
product was performed by silica gel (1 g) column
chromatography using pentane as eluent to afford 19
(7.9 mg, 75%) as an oil; IR (neat) 1603 and 1651
1
(CvC) cm21; H NMR (CDCl3) d¼0.87–0.95 (1H, m),
0.87 (9H, s), 1.04 (1H, ddt, J¼12.1, 14.3, 3.0 Hz), 1.46 (1H,
dt, J¼12.1, 9.8 Hz), 1.69 (1H, ddt, J¼2.5, 9.5, 12.1 Hz),
1.95 (1H, ddt, J¼5.5, 14.3, 3.0 Hz), 2.01–2.12 (1H, m),
2.19–2.34 (4H, m), 2.38–2.46 (1H, m), 4.84 (1H, br s), 4.85
(1H, br s), 5.14 (1H, ddd, J¼5.5, 9.8, 15.2 Hz), 5.25–5.35
(1H, m), 5.48 (1H, ddd, J¼6.5, 9.5, 15.8 Hz), and 5.89 (1H,
br d, J¼15.8 Hz); 13C NMR (CDCl3) d¼27.21 (3C), 32.25,
32.53, 33.92, 34.36, 34.87, 35.25, 49.22, 112.64, 131.12,
131.20, 132.89, 137.28, and 148.70; LRMS (EI) m/z 218
(Mþ; 5%), 175 (2), 161 (7), 147 (4), 133 (7), 119 (17), 105
(22), 91 (33), 80 (39), 57 (97), and 41 (100); HRMS [Found:
m/z 218.2026 (Mþ). Calcd for C16H26: M, 218.2036].
3.3.9. Ethyl (E)-3-[(1SR,2RS,4SR)-4-t-butyl-2-vinylcyclo-
hex-1-yl]-2-(trimethylsilylmethyl)prop-2-enoate (18). To
a stirred suspension of NaH (26.7 mg, 0.612 mmol; 55% in
mineral oil which was not removed) in THF (2 cm3) was
added dropwise at 08C a solution of (PhO)2P(O)CH(CO2-
Et)CH2SiMe3 (293.2 mg, 0.721 mmol) in THF (2 cm3),
20
and the stirring was continued at 08C for 30 min. The
solution was cooled to 2608C, and to this was added
dropwise a solution of 17 (85.0 mg, 0.437 mmol) in THF
(2 cm3). After stirring for 30 min at 2608C, the reaction
mixture was allowed to warm slowly to room temperature
over 17 h. The reaction was quenched by the addition of a
saturated NH4Cl aq. (20 cm3), and the mixture was
extracted with AcOEt. The combined extract was washed
with water and brine, and then dried. Evaporation of the
solvent followed by silica gel (8 g) column chromatography
using hexane/Et2O (199:1) as eluent gave 18 (123.5 mg,
81%) as an oil; IR (neat) 1637 (CvC) and 1714
3.4. Synthesis and homo-Cope reaction of 20a
3.4.1. Methyl 2-[(1SR,5SR)-5-benzyloxy-2-oxocyclohex-
1-yl]acetate (22a) and methyl 2-[(1RS,5SR)-5-benzyloxy-
2-oxocyclohex-1-yl]acetate (22b). According to the same
procedure described for the synthesis of 10, compound 21
(4.663 g, 22.83 mmol) was converted to 22 (4.952 g, 78%),
which was obtained as a diastereomer mixture. The
following spectral data were obtained after partial
separation into 22a and 22b.
1
(CvO) cm21; H NMR (CDCl3) d¼20.04 (9H, s), 0.80–
Compound 22a. An oil; IR (neat) 1712 (CvO) and 1738
1
1.13 (5H, m), 0.84 (9H, s), 1.29 (3H, t, J¼6.8 Hz), 1.69 (2H,
br s), 1.68–1.85 (3H, m), 2.73 (1H, br dq-like, J¼4, 10 Hz),
(CvO) cm21; H NMR (CDCl3) d¼1.61 (1H, dt, J¼2.3,
13.4 Hz), 1.80 (1H, ddt, J¼2.3, 4.4, 13.7 Hz), 2.21 (1H, dd,

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3169
1
J¼6.4, 16.8 Hz), 2.26–2.45 (3H, m), 2.74 (1H, dd, J¼6.8,
16.8 Hz), 2.81 (1H, dt, J¼6.4, 13.7 Hz), 3.33 (1H, dq,
J¼13.2, 6.4 Hz), 3.68 (3H, s), 3.87 (1H, quint-like,
J¼2.5 Hz), 4.60 (1H, d, J¼12.0 Hz), 4.67 (1H, d,
J¼12.0 Hz), 7.28–7.33 (1H, m), and 7.34–7.41 (4H, m);
13C NMR (CDCl3) d¼31.08, 33.68, 36.54, 36.84, 41.40,
51.62, 70.17, 71.35, 127.46 (2C), 127.62, 128.41 (2C),
138.36, 172.75, and 210.80; LRMS m/z 277 (MþþH; 26%),
245 (18), 227 (17), 197 (9), 181 (14), 169 (20), 155 (13), 137
(20), 119 (7), and 91 (100); HRMS [Found: m/z 277.1494
(MþþH). Calcd for C16H21O4: M, 277.1440].
Compound 23c. An oil; IR (CH2Cl2) 3363 (OH) cm21; H
NMR (CDCl3) d¼1.36–1.80 (7H, m), 1.85–1.94 (2H, m),
3.05 (2H, br s), 3.38 (1H, tt, J¼4.4, 10.6 Hz), 3.57–3.76
(2H, m), 3.86 (1H, br q-like, J¼2.5 Hz), 4.57 (2H, AB), and
7.25–7.37 (5H, m); 13C NMR (CDCl3) d¼25.90, 31.10,
32.03, 35.35, 38.00, 59.85, 67.37, 69.75, 77.08, 127.34,
127.46 (2C), 128.26 (2C), and 138.79; LRMS m/z 251
(MþþH; 8%), 197 (13), 126 (12), 125 (57), 119 (10), 108
(12), 107 (45), and 91 (100); HRMS [Found: m/z 251.1642
(MþþH). Calcd for C15H23O3: M, 251.1648].
3.4.3. 2-[(1RS,2RS,5SR)-5-Benzyloxy-2-hydroxycyclo-
hex-1-yl]ethyl pivalate (24a), 2-[(1SR,2SR,5SR)-5-
benzyloxy-2-hydroxycyclohex-1-yl]ethyl pivalate (24b),
and 2-[(1SR,2RS,5SR)-5-benzyloxy-2-hydroxycyclohex-
1-yl]ethyl pivalate (24c). According to the same procedure
described for the synthesis of 12, compound 23 (3.752 g,
13.05 mmol) was pivaloylated to afford 24 (4.722 g, 94%)
as the diastereomer mixture. The following spectral data
were obtained after partial purification.
Compound 22b. An oil; IR (neat) 1716 (CvO) and 1738
1
(CvO) cm21; H NMR (CDCl3) d¼1.55 (1H, dt, J¼11.2,
12.8 Hz), 1.69–1.81 (1H, m), 2.19 (1H, dd, J¼6.0,
16.4 Hz), 2.35–2.44 (4H, m), 2.80 (1H, dd, J¼7.0,
16.4 Hz), 2.90 (1H, dq, J¼12.8, 6.6 Hz), 3.68 (3H, s),
3.90 (1H, tt, J¼4.2, 12.8 Hz), 4.60 (2H, br s), and 7.27–7.39
(5H, m); 13C NMR (CDCl3) d¼31.80, 33.93, 37.78, 38.01,
43.47, 51.72, 70.65, 74.59, 127.50 (2C), 127.69, 128.44
(2C), 138.23, 172.67, and 209.22; LRMS m/z 277 (MþþH;
7%), 245 (5), 181 (10), 170 (6), 169 (6), 155 (6), 137 (8),
and 91 (100); HRMS [Found: m/z 277.1441 (MþþH). Calcd
for C16H21O4: M, 277.1440].
Compound 24a. An oil; IR (neat) 1726 (CvO) and 3440
(OH) cm21; 1H NMR (CDCl3) d¼1.13–1.22 (1H, m), 1.19
(9H, s), 1.39–1.54 (2H, m), 1.59 (1H, br s), 1.66–1.88 (3H,
m), 1.97–2.10 (3H, m), 3.31 (1H, dt, J¼4.8, 10.0 Hz), 3.64
(1H, quint, J¼3.0 Hz), 4.10–4.21 (2H, m), 4.49 (2H, AB),
7.24–7.30 (1H, m), and 7.31–7.36 (4H, m); 13C NMR
(CDCl3) d¼27.13 (3C), 28.17, 29.86, 31.37, 34.13, 36.66,
38.63, 62.79, 69.61, 71.96, 74.08, 127.21 (2C), 127.27,
128.22 (2C), 138.95, and 178.65; LRMS m/z 335 (MþþH;
100%), 317 (44), 233 (62), 231 (13), 215 (18), 197 (45),
141 (17), 125 (21), 107 (32), and 91 (31); HRMS
[Found: m/z 335.2287 (MþþH). Calcd for C20H31O4: M,
335.2223].
3.4.2. (1RS,2RS,4SR)-4-Benzyloxy-2-(2-hydroxyethyl)-
cyclohexan-1-ol (23a), (1SR,2SR,4SR)-4-benzyloxy-2-(2-
hydroxyethyl)cyclohexan-1-ol (23b), and (1RS,
2SR,4SR)-4-benzyloxy-2-(2-hydroxyethyl)cyclohexan-1-
ol (23c). According to the same procedure described for the
synthesis of 11, compound 22 (3.784 g, 18.91 mmol) was
reduced to the diol 23 (3.044 g, 89%). Although the mixture
of diastereomer was used in the next reaction, partial
purification was made to obtain 23a–c.
Compound 23a. An oil; IR (CH2Cl2) 3330 (OH) cm21; H
1
Compound 24b. An oil; IR (neat) 1726 (CvO) and 3442
(OH) cm21; 1H NMR (CDCl3) d¼1.04–1.17 (1H, m), 1.20
(9H, s), 1.25–1.45 (3H, m), 1.49–1.60 (1H, m), 1.76 (1H, br
s), 1.98–2.19 (4H, m), 3.30 (1H, dt, J¼4.3, 10.0 Hz), 3.36
(1H, tt, J¼4.1, 10.8 Hz), 4.13 (1H, dt, J¼10.8, 7.0 Hz), 4.18
(1H, ddd, J¼6.2, 7.2, 10.8 Hz), 4.54 (2H, s), 7.25–7.30 (1H,
m), and 7.31–7.36 (4H, m); 13C NMR (CDCl3) d¼27.23
(3C), 30.39, 31.55, 33.29, 36.22, 38.72, 40.47, 62.71, 70.19,
73.89, 76.34, 127.40 (3C), 128.29 (2C), 138.62, and 178.50;
LRMS m/z 335 (MþþH; 12%), 317 (30), 233 (36), 231 (29),
215 (19), 197 (48), 141 (27), 125 (60), 114 (14), 107 (55),
and 91 (100); HRMS [Found: m/z 335.2207 (MþþH). Calcd
for C20H31O4: M, 335.2223].
NMR (CDCl3) d¼1.20 (1H, ddd, J¼2.4, 12.4, 14.4 Hz),
1.39 (1H, ddt, J¼2.4, 4.8, 13.8 Hz), 1.49–1.57 (1H, m),
1.65–1.83 (4H, m), 1.95 (1H, dq, J¼14.0, 3.2 Hz), 1.99–
2.06 (1H, m), 2.76 (2H, br s), 3.29 (1H, dt, J¼4.8, 10.4 Hz),
3.60–3.67 (2H, m), 3.75 (1H, ddd, J¼4.1, 5.1, 10.8 Hz),
4.46 (1H, d, J¼12.0 Hz), 4.52 (1H, d, J¼12.0 Hz), 7.24–
7.29 (1H, m), and 7.31–7.36 (4H, m); 13C NMR (CDCl3)
d¼27.91, 29.31, 36.23, 37.69, 38.42, 61.17, 69.67, 72.21,
74.31, 127.25, 127.32 (2C), 128.17 (2C), and 138.75;
LRMS m/z 251 (MþþH; 36%), 233 (37), 215 (31), 197 (25),
185 (11), 141 (14), 125 (29), 107 (22), and 91 (100); HRMS
[Found: m/z 251.1634 (MþþH). Calcd for C15H23O3: M,
251.1648].
Compound 23b. Mp. 121.5–124.58C; IR (CH2Cl2) 3261
1
Compound 24c. An oil; IR (neat) 1726 (CvO) and 3481
1
(OH) cm21; H NMR (CDCl3) d¼1.18 (1H, dt, J¼10.8,
(OH) cm21; H NMR (CDCl3) d¼1.19 (9H, s), 1.10–1.25
12.8 Hz), 1.26–1.38 (2H, m), 1.39–1.49 (1H, m), 1.55–
1.62 (1H, m), 1.70–1.79 (1H, m), 1.98–2.07 (2H, m), 2.08–
2.14 (1H, m), 3.30 (1H, dt, J¼4.2, 9.7 Hz), 3.38 (1H, tt,
J¼4.0, 10.4 Hz), 3.63 (1H, dt, J¼3.3, 10.4 Hz), 3.69 (2H, br
s), 3.80 (1H, ddd, J¼4.3, 5.0, 10.5 Hz), 4.54 (2H, AB),
7.25–7.30 (1H, m), and 7.31–7.37 (4H, m); 13C NMR
(CDCl3) d¼30.26, 32.90, 37.70, 38.05, 42.25, 61.46, 70.24,
74.22, 76.41, 127.43, 127.45 (2C), 128.31 (2C), and 138.63;
LRMS m/z 251 (MþþH; 9%), 233 (17), 140 (14), 126 (12),
125 (48), 107 (27), and 91 (100); HRMS [Found: m/z
251.1551 (MþþH). Calcd for C15H23O3: M, 251.1648].
(1H, m), 1.40–1.54 (3H, m), 1.58–1.94 (6H, m), 3.35 (1H,
tt, J¼4.1, 10.8 Hz), 3.83 (1H, br q-like, J¼2.5 Hz), 4.11–
4.15 (2H, m), 4.57 (2H, s), 7.25–7.29 (1H, m), and 7.31–
7.36 (4H, m); 13C NMR (CDCl3) d¼25.85, 27.21 (3C),
31.26, 31.34, 32.36, 37.36, 38.74, 62.50, 66.93, 69.71,
76.72, 127.31, 127.39 (2C), 128.24 (2C), 138.81, and
178.45; LRMS m/z 335 (MþþH; 37%), 317 (20), 233
(42), 231 (29), 215 (27), 197 (58), 152 (22), 141 (34),
125 (73), 119 (35), 107 (100), and 91 (87); HRMS
[Found: m/z 335.2147 (MþþH). Calcd for C20H31O4: M,
335.2223].

3170
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3.4.4. 2-[(1RS,5SR)-5-Benzyloxy-2-oxocyclohex-1-
yl]ethyl pivalate (25a) and 2-[(1SR,5SR)-5-benzyloxy-2-
oxocyclohex-1-yl]ethyl pivalate (25b). According to the
same procedure described for the synthesis of 13, the
diastereomer mixture of 24 (4.722 g, 14.12 mmol) was
oxidized to a mixture of 25a and 25b. The crude product
was purified by the repetition of silica gel (100, 40, 20, and
5 g) column chromatography using hexane/AcOEt (95:5 to
80:20) as eluent to give 25a (3.244 g, 69%) and 25b
(1.037 g, 22%).
7.25–7.36 (5H, m); 13C NMR (CDCl3) d¼27.22 (3C),
30.25, 31.13, 32.87, 36.67, 38.01, 38.71, 62.63, 69.92,
73.07, 107.31, 127.27 (2C), 127.28, 128.22 (2C), 138.87,
149.93, and 178.42; LRMS m/z 331 (MþþH; 12%), 253 (2),
211 (10), 210 (45), 163 (13), 121 (100), 120 (63), 91 (47),
and 79 (5); HRMS [Found: m/z 331.2278 (MþþH). Calcd
for C21H31O3: M, 331.2274].
3.4.6. 2-[(1RS,2SR,5SR)-5-Benzyloxy-2-(hydroxy-
methyl)cyclohex-1-yl]ethyl pivalate (27a) and 2-
[(1RS,2RS,5SR)-5-benzyloxy-2-(hydroxymethyl)cyclo-
hex-1-yl]ethyl pivalate (27b). According to the same
procedure described for the synthesis of 14, compound 26
(1.254 g, 3.795 mmol) was treated with 9-BBN. The crude
product was purified by silica gel (40 g) column chroma-
tography using hexane/AcOEt (90:10 to 50:50) as eluent to
afford 27 (1.203 g, 91%) as the diastereomer mixture. The
following spectral data were obtained after partial
separation into 27a and 27b.
Compound 25a. An oil; IR (neat) 1712 (CvO) and 1726
(CvO) cm21; 1H NMR (CDCl3) d¼1.16 (9H, s), 1.48 (1H,
dq, J¼13.5, 7.2 Hz), 1.54 (1H, dt, J¼2.4, 13.2 Hz), 1.79
(1H, ddt, J¼2.6, 4.8, 13.8 Hz), 2.18 (1H, dq, J¼13.5,
7.2 Hz), 2.27 (1H, ddd, J¼2.5, 4.6, 13.5 Hz), 2.30–2.44
(2H, m), 2.75 (1H, dt, J¼6.0, 13.5 Hz), 2.91 (1H, dq,
J¼13.0, 6.8 Hz), 3.86 (1H, quint-like, J¼2.5 Hz), 4.07 (1H,
dt, J¼10.6, 7.0 Hz), 4.13 (1H, dt, J¼10.6, 7.0 Hz), 4.60 (2H,
AB), and 7.27–7.38 (5H, m); 13C NMR (CDCl3) d¼27.14
(3C), 27.92, 31.20, 37.00, 37.45, 38.67, 41.47, 62.25, 70.18,
71.59, 127.28 (2C), 127.58, 128.39 (2C), 138.44, 178.46,
and 211.93; LRMS m/z 333 (MþþH; 9%), 231 (100), 204
(7), 183 (2), 139 (10), 124 (22), 89 (32), and 61 (3); HRMS
[Found: m/z 333.2061 (MþþH). Calcd for C20H29O4: M,
333.2067].
Compound 27a. An oil; IR (neat) 1726 (CvO) and 3388
1
(OH) cm21; H NMR (CDCl3) d¼1.19 (9H, s), 1.24–1.35
(1H, m), 1.38–1.52 (3H, m), 1.62 (1H, ddt, J¼5.1, 12.3,
7.4 Hz), 1.68 (1H, ddt, J¼5.6, 13.2, 3.6 Hz), 1.74–1.82 (1H,
m), 1.85–1.93 (1H, m), 1.95–2.02 (1H, m), 2.10–2.19 (1H,
m), 3.50–3.59 (3H, m), 4.08 (1H, br), 4.04–4.15 (2H, m),
4.51 (1H, d, J¼12.0 Hz), 4.57 (1H, d, J¼12.0 Hz), and
7.24–7.35 (5H, m); 13C NMR (CDCl3) d¼22.45, 27.04,
27.19 (3C), 29.95, 30.97, 34.45, 38.74, 41.60, 63.18, 63.45,
69.96, 73.30, 127.32, 127.39 (2C), 128.22 (2C), 138.72, and
178.73; LRMS m/z 349 (MþþH; 15%), 241 (32), 229 (11),
155 (15), 139 (100), 121 (77), 103 (23), 91 (94), and 57 (32);
HRMS [Found: m/z 349.2383 (MþþH). Calcd for
C21H33O4: M, 349.2380].
Compound 25b. An oil; IR (neat) 1714 (CvO) and 1722
(CvO) cm21; 1H NMR (CDCl3) d¼1.18 (9H, s), 1.48–1.59
(2H, m), 1.70–1.83 (1H, m), 2.19 (1H, dq, J¼14.0, 6.8 Hz),
2.29–2.49 (5H, m), 3.84 (1H, tt, J¼4.0, 10.8 Hz), 4.07 (1H,
dt, J¼11.5, 6.8 Hz), 4.12 (1H, dt, J¼11.5, 6.8 Hz), 4.60 (2H,
s), and 7.27–7.38 (5H, m); 13C NMR (CDCl3) d¼27.16
(3C), 28.38, 31.90, 37.92, 38.26, 38.68, 43.88, 62.23,
70.58, 74.67, 127.48 (2C), 127.70, 128.46 (2C), 138.29,
178.43, and 210.39; LRMS (EI) m/z 230 (Mþ2PivOH;
26%), 204 (11), 139 (24), 124 (88), 122 (16), 91 (100),
85 (17), 65 (9), 57 (51), and 55 (10); HRMS [Found:
m/z 230.1307 (Mþ2PivOH). Calcd for C15H18O2:M,
230.1307].
Compound 27b. An oil; IR (neat) 1720 (CvO) and 3438
1
(OH) cm21; H NMR (CDCl3) d¼1.19 (9H, s), 1.20–1.30
(1H, m), 1.30–1.38 (1H, m), 1.42–1.52 (2H, m), 1.55–1.69
(2H, m), 1.69 (1H, br s), 1.78–2.03 (4H, m), 3.58 (1H, dd,
J¼6.4, 10.8 Hz), 3.67–3.71 (1H, m), 3.72 (1H, dd, J¼4.0,
10.8 Hz), 4.06 (1H, dt, J¼7.2, 11.2 Hz), 4.14 (1H, ddd,
J¼6.4, 7.2, 11.0 Hz), 4.50 (2H, AB), and 7.24–7.35 (5H,
m); 13C NMR (CDCl3) d¼23.48, 27.14 (3C), 28.95, 30.11,
31.80, 34.86, 38.65, 43.30, 62.36, 65.37, 69.62, 72.71,
127.26 (3C), 128.23 (2C), 139.08, and 178.70; LRMS m/z
349(MþþH;8%),247(9), 229(8), 211(9), 155(11), 140(12),
139 (52), 121 (76), 91 (100), and 57 (24); HRMS [Found: m/z
349.2318 (MþþH). Calcd for C21H33O4: M, 349.2380].
3.4.5. 2-[(1RS,5SR)-5-Benzyloxy-2-methylenecyclohex-1-
yl]ethyl pivalate (26). To a stirred suspension of Zn powder
(2.879 g, 44.04 mmol) and CH2Br2 (1.00 cm3, 14.4 mmol)
in THF (25 cm3) was added dropwise TiCl4 (10.0 cm3,
10.0 mmol; 1.0 M solution in CH2Cl2) over 10 min at
2608C under Ar atmosphere. The mixture was allowed to
warm to 58C, and the stirring was continued for 72 h. The
resulting slurry was quickly poured into a solution of 25a
(1.437 g, 4.32 mmol) in CH2Cl2 (20 cm3) at room tempera-
ture, and the stirring was continued for 1 h. The reaction was
quenched by careful addition of a saturated Na2CO3 aq.
(50 cm3), and diluted by water (100 cm3) and Et2O
(200 cm3). The mixture was extracted with Et2O and
dried. Evaporation of the solvent followed by silica gel
(30 g) column chromatography using hexane/AcOEt (98:2
to 97:3) as eluent gave 26 (1.254 g, 88%) as an oil; IR (neat)
3.4.7. 2-[(1RS,2SR,5SR)-5-Benzyloxy-2-(t-butyldimethyl-
silyloxymethyl)cyclohex-1-yl]ethyl pivalate (28a) and 2-
[(1RS,2RS,5SR)-5-benzyloxy-2-(t-butyldimethylsilyloxy-
methyl)cyclohex-1-yl]ethyl pivalate (28b). According to
the same procedure described for the synthesis of 14, the
above alcohol (1.203 g, 3.45 mmol) was converted to 28
(1.530 g, 96%), which was obtained as the diastereomer
mixture. The following spectral data were obtained after
partial separation into 28a and 28b.
1
1647 (CvC) and 1728 (CvO) cm21; H NMR (CDCl3)
d¼1.19 (9H, s), 1.58–1.67 (2H, m), 1.68–1.75 (1H, m),
1.79–1.94 (3H, m), 2.12–2.19 (1H, m), 2.29–2.39 (1H, m),
2.55 (1H, br quint-like, J¼7 Hz), 3.71 (1H, tt, J¼3.6,
7.2 Hz), 4.02 (1H, dt, J¼10.8, 6.8 Hz), 4.10 (1H, dt, J¼10.8,
6.8 Hz), 4.55 (2H, AB), 4.64 (1H, br s), 4.74 (1H, br s), and
1
Compound 28a. An oil; IR (neat) 1728 (CvO) cm21; H
NMR (CDCl3) d¼0.03 (6H, s), 0.88 (9H, s), 1.19 (9H, s),
1.23–1.32 (1H, m), 1.35–1.50 (3H, m), 1.56–1.68 (2H, m),
1.70–1.79 (1H, m), 1.85–2.02 (2H, m), 2.11–2.18 (1H, m),

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3171
3.47–3.55 (3H, m), 4.05 (1H, dt, J¼10.8, 7.2 Hz), 4.11 (1H,
ddd, J¼6.0, 7.2, 10.8 Hz), 4.51 (1H, d, J¼12.0 Hz), 4.54
(1H, d, J¼12.0 Hz), 7.25–7.28 (1H, m), and 7.30–7.35 (4H,
m); 13C NMR (CDCl3) d¼25.36, 25.34, 18.29, 22.60,
25.95 (3C), 26.91, 27.24 (3C), 30.27, 31.15, 34.50, 38.72,
41.54, 63.24, 63.93, 69.93, 73.46, 127.26, 127.37
(2C), 128.22 (2C), 138.93, and 178.43; LRMS m/z 405
(Mþ2t-Bu; 7%), 355 (16), 253 (28), 159 (20), 121 (100), 91
(63), and 57 (18); HRMS [Found: m/z 405.2378 (Mþ2t-
Bu). Calcd for C23H37O4Si: M, 405.2442].
procedure described for the synthesis of 16, compound 29
(509.1 mg, 1.485 mmol) was converted to 30a and 30b
(273.6 mg, 83% in three steps from 29). Two products, 30a
and 30b, were separated by the repetition of column
chromatography.
Compound 30a. An oil; IR (neat) 1635 (CvC) and 3421
(OH) cm21; 1H NMR (CDCl3) d ¼1.23–1.34 (1H, m), 1.41
(1H, ddt, J¼3.4, 10.0, 12.6 Hz), 1.47 (1H, br s), 1.62 (1H,
ddd, J¼4.3, 10.5, 12.8 Hz), 1.66–1.80 (2H, m), 2.04 (1H,
ddt, J¼2.2, 12.6, 4.1 Hz), 2.07–2.14 (1H, m), 2.74 (1H, dq,
J¼8.8, 4.0 Hz), 3.45 (1H, dd, J¼6.5, 10.8 Hz), 3.50 (1H, dd,
J¼7.2, 10.8 Hz), 3.62 (1H, tt, J¼4.0, 10.3 Hz), 4.54 (2H, s),
5.06 (1H, dd, J¼2.2, 10.3 Hz), 5.12 (1H, ddd, J¼1.1, 2.2,
16.9 Hz), 5.91 (1H, ddd, J¼8.8, 10.3, 16.9 Hz), and 7.24–
7.36 (5H, m); 13C NMR (CDCl3) d¼22.92, 31.11, 37.06,
40.17, 41.98, 65.16, 69.99, 73.59, 116.14, 127.38, 127.49
(2C), 128.32 (2C), 138.19, and 138.96; LRMS m/z 247
(MþþH; 11%), 229 (12), 211 (22), 199 (9), 173 (22), 155
(20), 139 (64), 121 (47), and 91 (100); HRMS [Found: m/z
247.1701 (MþþH). Calcd for C16H23O2: M, 247.1699].
1
Compound 28b. An oil; IR (neat) 1728 (CvO) cm21; H
NMR (CDCl3) d¼0.04 (6H, br s), 0.89 (9H, s), 1.17 (9H, s),
1.20–1.61 (6H, m), 1.78–1.99 (4H, m), 3.51 (1H, dd,
J¼6.4, 10.0 Hz), 3.65 (1H, dd, J¼4.4, 10.0 Hz), 3.65–3.69
(1H, m), 4.02–4.13 (2H, m), 4.49 (2H, AB), 7.23–7.28 (1H,
m), and 7.29–7.35 (4H, m); 13C NMR (CDCl3) d¼25.45,
25.44, 18.26, 23.65, 25.91 (3C), 27.17 (3C), 29.05, 30.45,
31.90, 34.76, 38.64, 43.35, 62.55, 65.58, 69.52, 72.91,
127.18, 127.23 (2C), 128.21 (2C), 139.25, and 178.62;
LRMS m/z 405 (Mþ2t-Bu; 9%), 361 (14), 355 (10), 331
(12), 253 (14), 211 (11), 159 (16), 121 (100), 91 (96), and 75
(13); HRMS [Found: m/z 405.2456 (Mþ2t-Bu). Calcd for
C23H37O4Si: M, 405.2442].
Compound 30b. An oil; IR (neat) 1637 (CvC) and 3392
(OH) cm21; 1H NMR (CDCl3) d¼1.31–1.58 (4H, m), 1.63
(1H, dq, J¼12.4, 3.5 Hz), 1.65 (1H, br s), 1.92 (1H, ddt,
J¼2.6, 13.8, 3.4 Hz), 2.03 (1H, d quint, J¼13.5, 3.0 Hz),
2.29 (1H, ddt, J¼3.8, 12.6, 9.5 Hz), 3.45 (1H, dd, J¼5.9,
11.0 Hz), 3.67 (1H, dd, J¼5.1, 11.0 Hz), 3.72 (1H, quint,
J¼3.0 Hz), 4.51 (2H, AB), 4.99 (1H, dd, J¼1.8, 10.3 Hz),
5.08 (1H, ddd, J¼0.7, 1.8, 17.2 Hz), 5.70 (1H, ddd, J¼9.2,
10.3, 17.2 Hz), and 7.25–7.38 (5H, m); 13C NMR (CDCl3)
d¼23.01, 28.94, 36.58, 39.96, 43.92, 66.97, 69.71, 72.36,
114.64, 127.30, 127.34 (2C), 128.28 (2C), 139.14, and
143.15; LRMS m/z 247 (MþþH; 65%), 229 (34), 211 (63),
199 (36), 155 (75), 121 (69), 91 (100), and 81 (13); HRMS
[Found: m/z 247.1693 (MþþH). Calcd for C16H23O2: M,
247.1699].
3.4.8. 2-[(1RS,2SR,5SR)-5-Benzyloxy-2-(t-butyldimethyl-
silyloxymethyl)cyclohex-1-yl]ethanol (29a) and 2-
[(1RS,2RS,5SR)-5-benzyloxy-2-(t-butyldimethylsilyloxy-
methyl)cyclohex-1-yl]ethanol (29b). According to the
same procedure described for the synthesis of 5, compound
28 (654.6 mg, 1.415 mmol) was deprotected to afford 29
(503.6 mg, 94%) as the diastereomer mixture. The follow-
ing spectral data were obtained after partial separation into
29a and 29b.
Compound 29a. An oil; IR (neat) 3421 (OH) cm21 1H
;
NMR (CDCl3) d¼0.05 (6H, br s), 0.89 (9H, s), 1.15–1.49
(4H, m), 1.52–1.62 (2H, m), 1.68–2.03 (4H, m), 2.10–2.18
(1H, m), 3.47–3.73 (5H, m), 4.51 (1H, d, J¼12.4 Hz), 4.55
(1H, d, J¼12.4 Hz), and 7.24–7.37 (5H, m); 13C NMR
(CDCl3) d¼25.46, 25.37, 18.23, 22.59, 25.87 (3C), 30.37,
31.14 (2C), 35.61, 41.66, 62.00, 64.18, 69.92, 73.69, 127.37,
127.47 (2C), 128.31 (2C), and 139.00; LRMS m/z 379
(MþþH; 17%), 271 (21), 213 (11), 139 (67), 121 (100), and
91 (96); HRMS [Found: m/z 379.2682 (MþþH). Calcd for
C22H39O3Si: M, 379.2650].
3.4.10. Ethyl (E)-3-[(1RS,2SR,4SR)-4-benzyloxy-2-vinyl-
cyclohex-1-yl]-2-(trimethylsilylmethyl)prop-2-enoate
(31a) and ethyl (E)-3-[(1SR,2SR,4SR)-4-benzyloxy-2-
vinylcyclohex-1-yl]-2-(trimethylsilylmethyl)prop-2-eno-
ate (31b). According to the same procedure described for
the synthesis of 4, compound 30a (119.5 mg, 0.485 mmol)
was oxidized by the Swern method. Then, this mixture was
converted to the silylated compounds 31a and 31b in
accordance with the synthesis of 18. The crude product was
purified by the repetition of silica gel (10 g) column
chromatography using hexane/Et2O (100:0 to 97:3) as
eluent to give 31a (58.8 mg, 30%) and 31b (113.9 mg,
59%).
1
Compound 29b. An oil; IR (neat) 3446 (OH) cm21; H
NMR (CDCl3) d¼0.06 (6H, s), 0.91 (9H, s), 1.25–1.39 (2H,
m), 1.41–1.52 (2H, m), 1.53–1.60 (2H, m), 1.71–1.86 (2H,
m), 1.87–1.95 (3H, m), 3.56 (1H, dd, J¼6.0, 10.0 Hz),
3.59–3.71 (4H, m), 4.47 (1H, d, J¼12.0 Hz), 4.53 (1H, d,
J¼12.0 Hz), and 7.24–7.39 (5H, m); 13C NMR (CDCl3)
d¼25.43 (2C), 18.30, 23.85, 25.91 (3C), 28.96, 30.53,
35.39, 36.07, 43.36, 60.85, 65.96, 69.64, 73.15, 127.27,
127.36 (2C), 128.27 (2C), and 139.22; LRMS m/z 379
(MþþH; 14%), 271 (11), 213 (19), 139 (45), 121 (89), and
91 (100); HRMS [Found: m/z 379.2626 (MþþH). Calcd for
C22H39O3Si: M, 379.2650].
Compound 31a. An oil; IR (neat) 1637 (CvC) and 1712
1
(CvO) cm21; H NMR (CDCl3) d¼20.03 (9H, s), 1.30
(3H, t, J¼7.0 Hz), 1.25–1.37 (1H, m), 1.40–1.51 (1H, m),
1.52–1.59 (2H, m), 1.71 (2H, AB), 1.95–2.03 (2H, m), 2.24
(1H, ddt, J¼3.4, 8.2, 11.8 Hz), 2.80–2.90 (1H, m), 3.73
(1H, quint, J¼2.6 Hz), 4.16 (2H, q, J¼7.0 Hz), 4.52 (2H,
AB), 4.89 (1H, dd, J¼1.8, 10.2 Hz), 4.95 (1H, ddd, J¼0.8,
1.8, 17.1 Hz), 5.49 (1H, d, J¼10.0 Hz), 5.64 (1H, ddd,
J¼8.2, 10.2, 17.1 Hz), and 7.25–7.39 (5H, m); 13C NMR
(CDCl3) d¼21.62 (3C), 14.20, 23.94, 26.63, 28.84, 35.77,
41.78, 42.19, 59.92, 69.70, 72.46, 113.66, 127.28, 127.33
3.4.9. (1SR,2SR,4SR)-4-Benzyloxy-2-vinylcyclohexane-
methanol (30a) and (1RS,2SR,4SR)-4-benzyloxy-2-vinyl-
cyclohexanemethanol (30b). According to the same

3172
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
(2C), 128.15, 128.27 (2C), 139.18, 142.89, 143.85, and
168.36; LRMS m/z 401 (MþþH; 100%), 385 (30), 355 (8),
309 (30), 293 (35), 212 (39), 174 (7), 145 (6), 91 (22), and
73 (12); HRMS [Found: m/z 401.2491 (MþþH). Calcd for
C24H37O3Si: M, 401.2493].
to the same procedure described for the synthesis of 7, 20a
(28.0 mg, 0.078 mmol) was treated with trifluoromethane-
sulfonic anhydride and 2,6-lutidine in CH2Cl2. The crude
product was purified by silica gel (1 g) column chromato-
graphy using pentane/Et2O (98:2) as eluent to afford 32
(18.5 mg, 88%) as an oil; IR (neat) 1603 (CvC) and 1650
1
Compound 31b. An oil; IR (neat) 1635 (CvC) and 1712
1
(CvC) cm21; H NMR (CDCl3) d¼1.68–1.77 (1H, m),
(CvO) cm21; H NMR (CDCl3) d¼20.03 (9H, s), 1.30
1.94 (1H, ddt, J¼2.6, 9.9, 12.8 Hz), 2.00–2.18 (3H, m),
2.25–2.34 (2H, m), 2.34–2.46 (2H, m), 2.54 (1H, br dd,
J¼5.5, 12.5 Hz), 3.22 (1H, br t-like, J¼8 Hz), 4.52 (2H, s),
4.84 (2H, AB), 5.12 (1H, ddd, J¼5.5, 9.5, 15.6 Hz), 5.35
(1H, ddd, J¼5.1, 9.9, 16.1 Hz), 5.36–5.46 (1H, m), 5.84
(1H, br d, J¼16.1 Hz), and 7.25–7.38 (5H, m); 13C NMR
(CDCl3) d¼31.52, 32.21, 34.70, 37.19, 39.90, 70.35, 80.40,
113.07, 127.42, 127.49 (2C), 128.35 (2C), 128.65, 131.01,
133.84, 137.07, 138.79, and 148.30; LRMS (EI) m/z 177
(Mþ2CH2Ph; 20%), 160 (58), 159 (49), 133 (63), 131 (42),
105 (51), 91 (100), 79 (56), 65 (37), and 55 (19); HRMS
[Found: m/z 177.1236 (Mþ–CH2Ph). Calcd for C12H17O:
M, 177.1280].
(3H, t, J¼7.2 Hz), 1.39–1.56 (2H, m), 1.66–1.79 (2H, m),
1.72 (2H, AB), 1.92–2.00 (2H, m), 2.69 (1H, br dq, J¼8.2,
5.0 Hz), 3.11 (1H, tt, J¼5.0, 10.0 Hz), 3.66 (1H, tt, J¼3.7,
8.7 Hz), 4.18 (2H, q, J¼7.2 Hz), 4.53 (2H, s), 4.99–5.06
(2H, m), 5.59 (1H, d, J¼10.0 Hz), 5.88 (1H, ddd, J¼8.2,
10.5, 17.0 Hz), and 7.24–7.36 (5H, m); 13C NMR (CDCl3)
d¼21.68 (3C), 14.21, 24.30, 26.83, 30.09, 35.62, 39.37,
41.93, 60.14, 69.87, 72.95, 115.72, 127.34, 127.46
(2C), 128.31 (2C), 129.34, 139.07, 139.11, 140.08, and
168.39; LRMS m/z 401 (MþþH; 100%), 385 (30), 355
(10), 309 (55), 293 (94), 277 (9), 212 (39), 211 (13), 191 (8),
145 (7), 133 (5), 91 (28), and 73 (15); HRMS [Found:
m/z 401.2494 (MþþH). Calcd for C24H37O3Si: M,
401.2493].
3.5. Synthesis and ene-reaction of 33
3.4.11. (E)-3-[(1RS,2SR,4SR)-4-Benzyloxy-2-vinylcyclo-
hex-1-yl]-2-(trimethylsilylmethyl)prop-2-en-1-ol (20a).
According to the same procedure described for the synthesis
of 1a and 1b, compound 31a (53.3 mg, 0.133 mmol) was
reduced to 20a (45.8 mg, 96%); an oil; IR (neat) 1637
3.5.1. (1RS,2RS)-2-Isopropenylcyclohexane-1-carbalde-
hyde (35). To a vigorously stirred mixture of Mg
(483.1 mg, 20.13 mmol) and dry THF (2 cm3) was added
dropwise 2-bromoprop-2-ene (1.80 cm3, 21.3 mmol) at 08C
under Ar atmosphere. After the beginning of the formation
of the Grignard reagent, the mixture was diluted with THF
(18 cm3), and the stirring was continued for 30 min at room
temperature. To a stirred suspension of CuBrMe2S
(754.1 mg, 3.668 mmol) in dry THF (20 cm3) was added
the above Grignard reagent by a syringe at 2508C under Ar
atmosphere, and HMPA (7.0 cm3, 40.2 mmol) was also
added. Then to this mixture was added dropwise at the same
temperature a solution of 34 (1.475 g, 13.39 mml) in dry
THF (10 cm3) containing TMSCl (3.40 cm3, 26.8 mmol),
and the stirring was continued for 1 h. The mixture was
treated with 1 M HCl (40 cm3) at 2508C, and was allowed
to warm to room temperature. This was extracted with Et2O,
the combined organic layer was washed with water, and
dried. Evaporation of the solvent followed by silica gel
(20 g) column chromatography using pentane/Et2O (100:0
to 199:1) as eluent afforded trans- and cis-35 (984.6 mg,
48%) as an inseparable mixture (trans-35:cis-35¼3:7). This
resultant oil was dissolved in CH2Cl2 and to this was added
DBU (1.0 cm3, 6.70 mmol) at room temperature with
stirring which was continued for 24 h. Evaporation of the
solvent followed by silica gel (20 g) column chromato-
graphy using pentane/Et2O (199:1 to 99:1) as eluent
afforded 35 (902.9 mg, 92%) as an oil; IR (neat) 1643
1
(CvC) and 3392 (OH) cm21; H NMR (CDCl3) d¼0.00
(9H, s), 1.18 (1H, br s), 1.25–1.47 (3H, m), 1.58 (2H, AB),
1.57–1.67 (1H, m), 1.95–2.06 (2H, m), 2.06–2.16 (1H, m),
2.22 (1H, ddt, J¼3.5, 8.0, 11.5 Hz), 3.75 (1H, quint-like,
J¼3 Hz), 3.95 (1H, d, J¼11.2 Hz), 4.05 (1H, d, J¼11.2 Hz),
4.51 (2H, AB), 4.91–4.98 (3H, m), 5.65 (1H, ddd, J¼8.0,
10.4, 17.2 Hz), and 7.25–7.38 (5H, m); 13C NMR (CDCl3)
d¼21.32 (3C), 24.71, 27.89, 28.94, 35.28, 41.08, 41.59,
62.06, 69.70, 72.37, 113.86, 127.30, 127.34 (2C), 128.28
(2C), 131.55, 135.23, 139.16, and 143.21; LRMS m/z 341
(Mþ2OH; 11%), 251 (12), 235 (23), 233 (27), 177 (16), 161
(42), 159 (35), 133 (15), 119 (20), 91 (100), and 73 (45);
HRMS [Found: m/z 341.2262 (Mþ2OH). Calcd for
C22H33OSi: M, 341.2282].
3.4.12. (E)-3-[(1SR,2SR,4SR)-4-Benzyloxy-2-vinylcyclo-
hex-1-yl]-2-(trimethylsilylmethyl)prop-2-en-1-ol (20b).
Similarly, 31b (38.8 mg, 0.097 mmol) was reduced to 20b
(34.6 mg, 100%); an oil; IR (neat) 1637 (CvC) and 3421
(OH) cm21; 1H NMR (CDCl3) d¼0.01 (9H, s), 1.16 (1H, br
s), 1.34–1.43 (1H, m), 1.54–1.64 (1H, m), 1.60 (2H, br s),
1.73 (1H, ddt, J¼4.0, 7.4, 13.0 Hz), 1.78–1.91 (3H, m),
2.56–2.67 (2H, m), 3.68 (1H, tt, J¼3.4, 7.2 Hz), 4.04 (2H,
br s), 4.53 (2H, s), 4.97–5.03 (2H, m), 5.19 (1H, d,
J¼9.7 Hz), 5.75–5.85 (1H, m), and 7.24–7.37 (5H, m); 13C
NMR (CDCl3) d¼21.32 (3C), 24.89, 27.40, 28.35, 34.20,
37.68, 41.56, 61.72, 69.85, 72.89, 115.02, 127.09, 127.34,
127.43 (2C), 128.31 (2C), 136.49, 139.09, and 140.56;
LRMS m/z 358 (Mþ; 7%), 341 (30), 323 (5), 249 (24), 214
(10), 177 (17), 159 (48), 133 (20), 131 (17), 91 (100), and 73
(44); HRMS [Found: m/z 358.2320 (Mþ). Calcd for
C22H34O2Si: M, 358.2309].
1
(CvC), 1726 (CvO), and 2710 (CHO) cm21; H NMR
(CDCl3) d¼1.22–1.39 (4H, m), 1.70 (3H, dd, J¼0.8,
1.2 Hz), 1.73–1.84 (4H, m), 2.16–2.25 (1H, m), 2.29 (1H,
tt, J¼3.6, 11.2 Hz), 4.72 (1H, br s), 4.74 (1H, quint,
J¼1.2 Hz), and 9.45 (1H, d, J¼3.6 Hz); 13C NMR (CDCl3)
d¼19.97, 24.69, 25.69, 26.22, 31.35, 46.25, 52.74, 111.43,
147.33, and 204.84; LRMS (EI) m/z 123 (Mþ–CHO;
100%), 109 (54), 95 (34), 81 (85), 67 (63), 55 (42), and 53
(18); HRMS [Found: m/z 123.1136 (Mþ2CHO). Calcd for
C9H15: M, 123.1175]; Analysis as semicarbazone (Mp 161–
1638C) [Found: C, 62.91; H, 9.07; N, 19.86%. Calcd for
C14H25N3O: C, 63.13; H, 9.15; N, 20.08%].
3.4.13. (1E,6E)-9-Benzyloxy-3-methylenecycloundeca-
1,6-diene (32)—homo-Cope reaction of 20a. According

H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
3173
3.5.2. Ethyl (E)-3-[(1RS,2RS)-2-isopropenylcyclohex-1-
References
yl]-2-(trimethylsilylmethyl)prop-2-enoate (36). Accord-
ing to the same procedure described for the synthesis of 18,
compound 35 (161.0 mg, 1.058 mmol) was converted to the
silylated compound 36 (165.1 mg, 51%); an oil; IR (neat)
1. Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds; Academic: New York, 1972; Vol. II.
2. For recent examples: (a) Hanson, J. R. Nat. Prod. Rep. 2000,
17, 165–174. Hanson, J. R. Nat. Prod. Rep. 2002, 19,
125–132. (b) Fraga, B. M. Nat. Prod. Rep. 2000, 17, 483–504.
3. For examples on the isolation or the structural determination
of dolabellanes, see: (a) Look, S. A.; Fenical, W. J. Org.
1
1643 (CvC) and 1712 (CvO) cm21; H NMR (CDCl3)
d¼20.05 (9H, s), 1.07 (1H, ddt, J¼3.0, 9.6, 12.1 Hz), 1.19–
1.37 (3H, m), 1.30 (3H, t, J¼7.2 Hz), 1.58 (3H, br s),
1.58–1.83 (5H, m), 1.67 (2H, br s), 2.98 (1H, ddt, J¼3.6,
10.8, 9.8 Hz), 4.17 (2H, q, J¼7.2 Hz), 4.60 (1H, br s), 4.65
(1H, d, J¼2.0 Hz), and 5.39 (1H, d, J¼9.8 Hz); 13C NMR
(CDCl3) d¼21.68 (3C), 14.24, 18.82, 23.95, 25.87, 26.29,
31.87, 33.09, 40.74, 52.62, 59.89, 110.49, 127.54, 144.03,
149.28, and 168.42; LRMS m/z 309 (MþþH; 100%), 293
(80), 263 (11), 226 (57), 225 (5), 190 (6), 161 (6), 135 (3),
108 (10), and 73 (14); HRMS [Found: m/z 309.2231
(MþþH). Calcd for C18H33O2Si: M, 309.2231].
´
Chem. 1982, 47, 4129–4134. (b) Gonzalez, A. G.; Martın,
´
´
J. D.; Norte, M.; Perez, R.; Weyler, V.; Rafii, S.; Clardy, J.
Tetrahedron Lett. 1983, 24, 1075–1076. (c) Baxter, G. A.;
Cameron, A. F.; Connolly, J. D.; Harrison, L. J.; Phillips,
W. R.; Rycroft, D. S.; Sim, G. A. J. Chem. Soc., Perkin Trans.
1 1986, 809–814. (d) Mori, K.; Iguchi, K.; Yamada, N.;
Yamada, Y.; Inouye, Y. Chem. Pharm. Bull. 1988, 36,
2840–2852. (e) Su, J.; Zhong, Y.; Shi, K.; Cheng, Q.; Snyder,
J. K.; Hu, S.; Huang, Y. J. Org. Chem. 1991, 56, 2337–2344.
(f) Shin, J.; Fenical, W. J. Org. Chem. 1991, 56, 3392–3398.
4. For examples on the synthesis of dolabellanes, see:
(a) Hutchinson, J. H.; Money, T.; Piper, S. E. Can. J. Chem.
1986, 64, 854–860. (b) Williams, D. R.; Coleman, P. J.;
Henry, S. S. J. Am. Chem. Soc. 1993, 115, 11654–11655.
(c) Kato, N.; Higo, A.; Nakanishi, K.; Wu, X.; Takeshita, H.
Chem. Lett. 1994, 1967–1970.
3.5.3. (E)-3-[(1RS,2RS)-2-Isopropenylcyclohex-1-yl]-2-
(trimethylsilylmethyl)prop-2-en-1-ol (33). According to
the same procedure described for the synthesis of 1a and 1b,
compound 36 (161.0 mg, 0.522 mmol) was reduced to 33
(134.2 mg, 97%); an oil; IR (neat) 1643 (CvC) and 3344
(OH) cm21; 1H NMR (CDCl3) d¼20.02 (9H, s), 1.06–1.18
(1H, m), 1.21–1.34 (3H, m), 1.54 (2H, br s), 1.61 (3H, br s),
1.57–1.79 (6H, m), 2.22 (1H, ddt, J¼3.6, 10.0, 10.4 Hz),
3.96 (1H, d, J¼11.3 Hz), 4.05 (1H, d, J¼11.3 Hz), 4.65–
4.68 (2H, m), and 4.85 (1H, d, J¼10.0 Hz); 13C NMR
(CDCl3) d¼21.37 (3C), 20.31, 24.51, 25.98, 26.27, 32.15,
34.67, 40.48, 51.92, 61.99, 110.12, 131.94, 134.48, and
150.10; LRMS m/z 267 (MþþH; 6%), 249 (100), 248 (10),
176 (21), 161 (23), 133 (15), 93 (12), and 73 (32); HRMS
[Found: m/z 267.2130 (MþþH). Calcd for C16H31OSi: M,
267.2125].
5. For a review on the synthesis of carbocyclic systems, see: Ho,
T.-L. Carbocycle Construction in Terpene Synthesis; VCH:
New York, 1988.
6. For examples on the synthesis of eleven-membered carbo-
cycles, see: (a) McMurry, J. E.; Matz, J. R.; Kees, K. L.
Tetrahedron 1987, 43, 5489–5498. (b) Takahashi, T.;
Kitamura, K.; Tsuji, J. Tetrahedron Lett. 1983, 24,
4695–4698. (c) Miyaura, N.; Suginome, H.; Suzuki, A.
Tetrahedron Lett. 1984, 25, 761–764. (d) Corey, E. J.;
Daigneault, S.; Dixon, B. R. Tetrahedron Lett. 1993, 34,
3675–3678. (e) Williams, D. R.; Coleman, P. J. Tetrahedron
Lett. 1995, 36, 35–38. (f) Winkler, J. D.; Holland, J. M.;
Kasparec, J.; Axelsen, P. H. Tetrahedron 1999, 55,
8199–8214. (g) Kato, N.; Higo, A.; Wu, X.; Takeshita, H.
Heterocycles 1997, 46, 123–127.
3.5.4. (2Z,5E)-2-Methyl-5-(trimethylsilylmethyl)bicy-
clo[5.4.0]nona-2,5-diene (37). Compound 33 (29.6 mg,
0.111 mmol) was treated with trifluoromethanesulfonic
anhydride and 2,6-lutidine in CH2Cl2 as the case of the
synthesis of 7a and 7b. The crude product was purified by
silica gel (5 g) column chromatography using pentane as
eluent to afford 37 (17.0 mg, 62%); an oil; IR (neat) 1641
(CvC) cm21; 1H NMR (CDCl3) d¼0.00 (9H, s), 1.04–1.33
(3H, m), 1.46 (1H, d, J¼13.3 Hz), 1.51 (1H, d, J¼13.3 Hz),
1.63 (3H, br s), 1.68–1.78 (4H, m), 1.91–2.01 (2H, m),
2.12–2.22 (1H, m), 2.38 (1H, dd, J¼7.4, 16.0 Hz), 2.77
(1H, br d, J¼16.0 Hz), 4.85 (1H, dd, J¼1.0, 4.8 Hz), and
5.54 (1H, m); 13C NMR (CDCl3) d¼21.42, 22.89, 26.38,
26.69, 30.36, 30.82, 32.22, 34.60, 40.46, 44.82, 122.97,
127.21, 139.57, and 140.30; LRMS m/z 248 (Mþ; 34%), 233
(17), 174 (7), 161 (9), 147 (9), 134 (5), 105 (7), 91 (7), 74
(10), and 73 (100); HRMS [Found: m/z 248.1875 (Mþ).
Calcd for C16H28Si: M, 248.1941].
7. Hill, R. K. Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 5, pp 785–826.
8. Pirrung, M. C.; Morehead, A. T., Jr. The Total Synthesis of
Natural Products, Part A: Acyclic and Monocyclic
Sesquiterpenes; Goldsmith, D., Ed.; Wiley: New York,
1997; Vol. 10.
9. For reviews on ring expansion reaction, see: (a) Dowd, P.;
Zhang, W. Chem. Rev. 1993, 93, 2091–2115. (b) Wovkulich,
P. M. Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon: Oxford, 1991; Vol. 1, pp 843–899. See also Ref. 5.
10. Takayanagi, M.; Tanino, K.; Kuwajima, I. Proc. 70th Natl
Meet. Chem. Soc. Jpn 1996, 1194.
11. (a) Kuroda, C. Recent Res. Dev. Pure Appl. Chem. 1998, 2,
189–198. (b) Kuroda, C.; Suzuki, H. Curr. Org. Chem. 2003,
7, 115–131.
Acknowledgements
12. For reviews, see: (a) Trost, B. M. Angew. Chem. Int. Ed. Engl.
1986, 25, 1–20. (b) Harmata, M. Tetrahedron 1997, 53,
6235–6280. (c) Chan, D. M. T. In Cycloaddition Reactions in
Organic Synthesis; Kobayashi, S., Jørgensen, K. A., Eds.;
Wiley: Weinheim, 2002; pp 57–84.
We are grateful to Professor M. Tori of Tokushima Bunri
University and Professor H. Nagano of Ochanomizu
University for recording high-resolution mass spectral
data. Also, we must thank Miss A. Monda for her help in
the experiment. Thanks are also due to Professor E. Horn,
Rikkyo University, for help in writing of this article.
13. (a) Giguere, R. J.; Duncun, S. M.; Bean, J. M.; Purvis, L.
Tetrahedron Lett. 1988, 29, 6071–6074. (b) Giguere, R. J.;

3174
H. Suzuki, C. Kuroda / Tetrahedron 59 (2003) 3157–3174
Tassely, S. M.; Rose, M. I. Tetrahedron Lett. 1990, 31,
4577–4580.
(b) Ando, K. J. Org. Chem. 1997, 62, 1934–1939. (c) Ando,
K. J. Org. Chem. 1998, 63, 8411–8416. (d) Ando, K. J. Org.
Chem. 1999, 64, 8406–8408.
14. Kuroda, C.; Koshio, H. Chem. Lett. 2000, 962–963.
15. Kuroda, C.; Kobayashi, K.; Koito, A.; Anzai, S. Bull. Chem.
Soc. Jpn 2001, 74, 1947–1961.
22. Mander, L. N.; Sethi, S. P. Tetrahedron Lett. 1983, 24,
5425–5428.
¨
16. Hochstrate, D.; Klarner, F.-G. Liebigs Ann. 1995, 745–754.
23. Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976,
41, 1485–1486.
17. Preliminary communication, see: Suzuki, H.; Monda, A.;
Kuroda, C. Tetrahedron Lett. 2001, 42, 1915–1917.
18. Kuroda, C.; Koshio, H.; Koito, A.; Sumiya, H.; Murase, A.;
Hirono, Y. Tetrahedron 2000, 56, 6441–6455.
24. (a) Takai, K.; Hotta, Y.; Oshima, K.; Nozaki, H. Bull. Chem.
Soc. Jpn 1980, 53, 1698–1702. (b) Lombardo, L. Tetrahedron
Lett. 1982, 23, 4293–4296.
19. Kuroda, C.; Mitsumata, N.; Tang, C. Y. Bull. Chem. Soc. Jpn
1996, 69, 1409–1416.
25. Ando, K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T. J. Org.
Chem. 2000, 65, 4745–4749.
20. Suzuki, H.; Kuroda, C. J. Chem. Res. (S) 2003, in press.
21. (a) Ando, K. Tetrahedron Lett. 1995, 36, 4105–4108.
26. Horiguchi, Y.; Matsuzawa, S.; Nakamura, E.; Kuwajima, I.
Tetrahedron Lett. 1986, 27, 4025–4028.