Thermal intramolecular cycloaddition of 4-alkenylfulvene; Highly regio- and diastereoselective formation of [4+2] adduct

Article abstract of DOI:10.1016/S0040-4020(03)00297-7

4-Alkenylfulvenes were prepared by the annulation of 1,4-ynediones and allylidenetriphenylphosphorane and subjected to a thermal reaction. Highly regio- and stereoselective [4+2] cycloaddition is accomplished with 4-((R)-3-benzyloxypent-4-en-1-yl)fulvene and the resulting adduct is transformed into bicyclo[3.3.0]octene derivative.

Full text of DOI:10.1016/S0040-4020(03)00297-7

Tetrahedron 59 (2003) 2673–2677
Thermal intramolecular cycloaddition of 4-alkenylfulvene;
highly regio- and diastereoselective formation of [412] adduct
Hiroyoshi Kitano, Shinya Fujita, Yutaka Takehara, Masakazu Hattori, Toshio Morita,
*
†
Kazutsugu Matsumoto and Minoru Hatanaka
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan
Received 20 January 2003; accepted 20 February 2003
Abstract—4-Alkenylfulvenes were prepared by the annulation of 1,4-ynediones and allylidenetriphenylphosphorane and subjected to a
thermal reaction. Highly regio- and stereoselective [4þ2] cycloaddition is accomplished with 4-((R)-3-benzyloxypent-4-en-1-yl)fulvene and
the resulting adduct is transformed into bicyclo[3.3.0]octene derivative. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
cycloaddition is accomplished with 4-((R)-3-benzyloxy-
pent-4-en-1-yl)fulvene.
Construction of fused ring-systems has been an attractive
subject of organic chemists. A variety of pericycloaddition
reactions have been successfully employed in natural
product synthesis, such as intramolecular Diels–Alder
reaction. The 6p electrons of fulvene allowed thermal
[4þ2], [6þ2], and [6þ4] cycloaddition reactions with
dienophiles, 1,3-dipolarophiles and dienes to form a variety
of ring systems.1 The competition among these cyclo-
addition reactions has been a subject of several recent
publications.2 Intramolecular cycloaddition of fulvenes
could provide powerful tool as shown in the elegant
synthesis of triquinane sesquiterpenes,3 but the utility is
limited due to the general inaccessibility of substituted
fulvene, especially in a regioselective manner. Fulvenes
have been usually prepared by the base-catalyzed conden-
sation of cyclopentadienes with aldehydes and ketones but
this method leads to the formation of a regioisomeric
mixture in many cases.4 We have demonstrated a single-
step preparation of functionalized fulvenes by the conden-
sation of allylidenetriphenylphosphorane with 1,4-yne-
diones.5 The reaction proceeds smoothly at room
temperature and with the high regioselection. Thus, we set
out to study the regio- and stereoselectivity of intramolec-
ular cycloaddition of various alkenylfulvenes. We now
report synthesis and thermal intramolecular cycloaddition
of 4-alkenylfulvenes in which high diastereoselective
2. Results and discussion
Synthesis of the fulvene tethered by an alkenyl chain
bearing a chiral center was initiated from preparation of the
corresponding 1,4-ynedione, since a limited number of
1,4-ynediones has been reported so far. O-Benzyl-(R)-
pantolactone was converted into (3S)-3-benzyloxy-2,2-
dimethyl-pent-4-enal 1 in 63% overall yield via a straight-
forward sequence consisted of reduction with DIBAL,
Wittig olefination and then Swern oxidation.6 Carbon
elongation of 1 to 2 was carried out in 68% overall yield
by Wittig reaction with methoxymethylidenetriphenyl-
phosphorane and then acid hydrolysis. Conversion of
aldehyde 2 to the desired 1,4-ynedione 5 was accomplished
in a following manner. The aldehyde 2 was at first treated
with ethynylmagnesium bromide to give 3 in 80% yield.
The hydroxy group of 3 was protected with TMSCl and then
subjected to the Sonogashira reaction with benzoyl chloride
to afford 4 in 55% yield after deprotection. Oxidation of 4
with MnO2 furnished unstable 1,4-ynedione 5 in 47% yield
along with recovery of 4 (33%).
Preparation of fulvene 7 from 1,4-ynedione 5 was next
examined according to the method reported previously.5
When 5 was treated with 2-ethoxyallylidenetriphenyl-
phosphorane 6 in THF at 08C, cyclization underwent nicely
in a highly regioselective manner to give deep-red colored
fulvene as a mixture of Z-isomer Z-7 (56%) and E-isomer
E-7 (22%) (Scheme 1). The E- and Z-geometry were
estimated on the basis of H-6 chemical shift in their NMR
spectra (6.77 ppm for Z-7, 8.29 ppm for E-7). It is evident
that the fulvenes are formed via initial Michael addition of
Keywords: fulvene; intramolecular cycloaddition; allylidenetriphenyl-
phosphorane; 1,4-ynedione.
*
Corresponding author. Tel.: þ81-776-27-8631; fax: þ81-776-27-8747;
e-mail: hatanaka@acbio2.acbio.fukui-u.ac.jp
Present address: Department of Chemistry, College of Science and
†
Engineering, Meisei University, Hodokubo, Hino Tokyo 191-8506,
Japan.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00297-7

2674
H. Kitano et al. / Tetrahedron 59 (2003) 2673–2677
Scheme 1. Reagents and conditions: (i) (1) DIBAL, toluene, 2788C, 2 h; (2) Ph3PþCH3Br2, BuLi, room temperature, 3 h; (3) Swern Oxidation, 63% (3 steps).
(ii) (1) Ph3PþCH2OCH3Cl2, sec-BuLi, THF, 08C; (2) TsOH, acetone, H2O, 08C, 68% (2 steps). (iii) ethynylmagnesium bromide, THF, 08C, 1 h, 80%. (iv) (1)
TMSCl, Et3N, ether, room temperature, 12 h; (2) PhCOCl, (Ph3P)2PdCl2, CuI, Et3N, benzene, room temperature, 15 h; (3) citric acid, MeOH, room
temperature, 20 min, 55% (3 steps). (v) MnO2 (5 equiv.), CH2Cl2, room temperature, 24 h, 47%.
phosphorane 6 to the 3 position of 1,4-ynedinone 5 followed
by intramolecular Wittig reaction with the 4-keto group.
The low temperature conditions were found to be essential
for minimizing the generation of the by-products.
Thermal cycloaddition of Z-isomer Z-7 was effected by
heating in toluene at 1008C for 20 h and [4þ2] adduct Z-8
was obtained in 86% yield with a high diastereoselection
(ds 96:4) (Scheme 2). Other cyclization products involving
[6þ2] adduct were not detected in the reaction mixture. In
the NMR experiment the major product showed the NOE
between the C-11 vinyl proton and the C-4 benzyloxy-
methine proton, supporting to have the stereochemistry
depicted in the structure Z-8.
In an attempt to convert the adduct Z-8 into the
corresponding ketones 11, we found that the compound
Z-8 could be readily transformed into bicyclo[3.3.0]octene
10 by the mild acid treatment and no formation of 11 was
observed under the reaction conditions. The structure of 10
was confirmed by a combination of COSY, HMQC and
HMBC spectra in the NMR experiment. The stereochemical
feature was supported by the NOE observation depicted in
the structure 10. The ring opening would involve C–C bond
cleavage through an intermediary hemiacetal 9 and
proceeds faster than hydrolysis to form ketone 11. Easy
C–C bond cleavage may be addressed to release of ring
strain and existence of the two electron-withdrawing groups
at the 7 and 11 positions (Scheme 2).7
When the E-isomer E-7 was subjected to thermal reaction
under the same conditions, an inseparable mixture gener-
ated. Treatment of the mixture with aqueous TFA and
subsequent column chromatography allowed isolating
Scheme 2.
compound 10 in 17% yield, which could arise from [4þ2]

H. Kitano et al. / Tetrahedron 59 (2003) 2673–2677
2675
triphenylphosphonium bromide (3.41 g, 9.55 mmol) and a
1.59 M solution of BuLi in hexane (6.0 ml) in THF (30 ml).
The mixture was stirred for 3 h at 08C, poured into an aq
NH4Cl solution and extracted with EtOAc. The extract was
dried and evaporated. The residue was purified by flash
chromatography (hexane–EtOAc) to give (3S)-3-benzyl-
oxy-2,2-dimethyl-4-penten-1-ol as an oil (323 mg). dH
(CDCl3): 0.89 (s, 3H), 0.90 (s, 3H), 2.83 (bs, 1H), 3.46 (d,
1H, J¼10.9 Hz), 3.53 (d, 1H, J¼10.9 Hz), 3.62 (d, 1H,
J¼8.2 Hz), 4.29 (d, 1H, J¼11.9 Hz), 4.61 (d, 1H, J¼
11.9 Hz), 5.30 (m, 2H), 5.81 (m, 1H), 7.31 (m, 5H); dC
(CDCl3): 138.10, 134.91, 128.40, 127.76, 127.63, 119.67,
88.03, 71.15, 70.40, 38.58, 22.48, 19.80; [a]2D1¼20.288
(c¼0.645, CHCl3); nmax (neat): 3448, 2958, 2864, 1420,
Scheme 3.
adduct E-8 (Scheme 3). Thus, the both fulvenes Z-7 and E-7
proceeded intramolecular cycloaddition in a [4þ2] fashion
with high diastereoselection. The highly diastereoselective
formation of the [4þ2] adducts and subsequent transform-
ation of them to 10 may provide an access to quinane
skeleton.
1096, 698 cm21
.
To a solution of oxalyl chloride (0.31 ml, 1.47 mmol) in
CH2Cl2 (5 ml) was added a dry DMSO (0.52 ml,
1.47 mmol) at 2788C. The mixture was stirred for 2 min
at 2158C, mixed with a solution of the above oil (323 mg,
1.47 mmol) in CH2Cl2 (4 ml) and the stirring was then
continued for 15 min at the same temperature. The reaction
mixture was cooled at 2788C, treated with Et3N (1.42 ml,
7.34 mmol) and then warmed up gradually at room
temperature. The mixture was poured onto ice-water and
extracted with CH2Cl2. The extract was dried and
evaporated. The residue was purified by flash chroma-
tography (hexane–EtOAc) to give 1 as an oil (310 mg, 63%
(3 steps)). dH (CDCl3): 0.99 (s, 3H), 1.10 (s, 3H), 3.88 (d,
1H, J¼8.5 Hz), 4.30 (d, 1H, J¼11.9 Hz), 4.59 (d, 1H, J¼
11.9 Hz), 5.36 (m, 2H), 5.75 (m, 1H), 7.30 (m, 5H), 9.54 (s,
1H); dC (CDCl3): 205.57, 133.70, 133.47, 128.40, 127.79,
127.55, 120.65, 84.12, 70.75, 46.34, 19.50, 16.65;
[a]2D1¼20.858 (c¼0.495, CHCl3); nmax (neat): 1720, 1454,
930, 734, 696 cm21; HRMS (EI): calcd for C14H18O2:
218.1307. Found: 218.1274. Anal. calcd for C14H18O2: H,
8.31; C, 77.03. Found: H, 8.53; C, 77.21.
3. Conclusion
We have demonstrated that the thermal intramolecular
cycloaddition reaction of 4-alkenylfulvenes prepared from
1,4-ynedione and allylidenephosphorane proceeded in a
[4þ2] fashion with a high diastereoselection. The resulting
[4þ2] adduct could be converted into bicyclo[3.3.0]octene
skeleton by mild acid treatment. An application of this
strategy to synthesis of pentalenic acid is underway.
4. Experimental
4.1. General
All mps were measured on a Yanagimoto hot stage
apparatus and are uncorrected. IR spectra were recorded
1
on a Hitachi 270-30 spectrometer. H NMR spectra were
measured at 500 MHz in CDCl3 on a JEOL Lambda 500
spectrometer, using SiMe4 as the internal standard. J-Values
are given in Hz. 13C NMR spectra were recorded at
125 MHz on the spectrometer and solvent peak (CDCl3: dC
77.0) was used for the internal standard. Mass spectra were
recorded on a Shimadzu GCMS-QP5000 spectrometer or a
JEOL JMS-700T spectrometer. All reactions were carried
out under Ar in dried glassware. Flash chromatography was
performed on Wakogel C-300. Extracts were dried over
MgSO4 and evaporated under reduced pressure. THF was
distilled from sodium benzophenone ketyl under Ar prior to
use. All commercially available reagents were used as
received. MnO2 (Chemical treated) was purchased from
Wako Pure Chemical Industries Ltd.
4.1.2. (4S)-4-Benzyloxy-3,3-dimethyl-5-hexenal (2). To a
solution of methoxymethyltriphenylphosphonium chloride
(1.07 g, 3.12 mmol) in THF (10 ml) was added a 1.01 M
solution of sec-BuLi in hexane (3.19 ml, 3.12 mmol) at
2788C and the mixture was stirred for 1 h at 08C. The
mixture was cooled at 2788C, treated with a solution of 1
(568 mg, 2.60 mmol) in THF (3 ml) and then stirred for 3 h
at room temperature. The mixture was poured into an aq
NH4Cl solution at 08C and extracted with EtOAc. The
extract was dried and evaporated. The residue was purified
by passing through a short column of SiO2 with hexane–
EtOAc and dissolved in a 1:1 solution (6 ml) of acetone and
H2O containing TsOH (10 mg). The mixture was stirred for
2 h at 08C, diluted with water and extracted with EtOAc.
The extract was washed with brine, dried and evaporated.
The residue was purified by flash chromatography (hexane–
EtOAc) to give 2 as an oil (411 mg, 68%). dH (CDCl3): 0.98
(s, 3H), 1.00 (s, 3H), 2.17 (d, 1H, J¼14.8 Hz), 2.33 (d, 1H,
J¼14.8 Hz), 3.40 (d, 1H, J¼6.9 Hz), 4.18 (d, 1H, J¼
11.6 Hz), 4.48 (d, 1H, J¼11.6 Hz), 5.24 (m, 2H), 5.69 (m,
1H), 7.23 (m, 5H), 9.72 (s, 1H); dC (CDCl3): 202.87, 138.33,
134.70, 128.25, 127.75, 127.42, 120.00, 87.18, 70.29, 53.07,
38.10, 25.30, 23.21; [a]2D1¼20.828 (c¼0.487, CHCl3); nmax
(neat): 2956, 2864, 1712, 1066, 738, 698 cm21; m/z (EI) 233
(Mþþ1, 11), 126 (25), 107 (44), 91 (100); HRMS (EI):
4.1.1. (3S)-3-Benzyloxy-2,2-dimethyl-4-pentenal (1).6
To a solution of O-benzyl-(R)-pantolactone (500 mg,
2.26 mmol) in toluene (5 ml) was added a 1.01 M solution
of DIBAL in toluene (2.68 ml) at 2788C. The mixture was
stirred for 2 h at that temperature, poured into an aq NH4Cl
solution and extracted with EtOAc. The extract was dried
and evaporated. The residue was purified by flash chroma-
tography (hexane–EtOAc) to give an oil (484 mg,
2.19 mmol). The oil (424 mg, 1.91 mmol) was dissolved
in THF (5 ml) and the solution was added at 08C to a solution
of methylidenetriphenylphosphorane prepared from methyl-

2676
H. Kitano et al. / Tetrahedron 59 (2003) 2673–2677
calcd for C15H20O2: 232.1463. Found: 232.1471. Anal. calcd
for C15H20O2: H, 8.67; C, 77.55. Found: H, 8.73; C, 77.72.
2H); dC (CDCl3): 177.81, 177.76, 137.05, 136.47, 134.66,
134.09, 134.04, 129.63, 129.59, 129.52, 128.53, 128.48,
128.41, 128.37, 128.25, 128.10, 127.97, 127.93, 127.79,
127.69, 120.85, 120.69, 96.03, 88.10, 87.96, 81.34, 70.85,
70.44, 60.33, 59.84, 59.56, 46.89, 45.84, 37.37, 37.21,
27.56, 26.40, 24.15, 23.34, 20.97; nmax (neat): 3400, 2236,
1640, 1262, 1066, 700 cm21; m/z (EI) 361 (Mþ21, 5), 219
(5), 205 (5), 120 (24), 105 (100), 77 (100).
4.1.3. (3S,6RS)-3-Benzyloxy-4,4-dimethyl-6-hydroxy-1-
octen-7-yne (3). To a solution of 2 (176 mg, 0.76 mmol)
in THF (2 ml) was added a 0.6 M solution of ethynylmag-
nesium bromide (2.53 ml, 1.52 mmol) in THF at 08C. The
mixture was stirred for 1 h at the same temperature, poured
into an aq NH4Cl solution and then extracted with EtOAc.
The extract was washed with brine, dried and evaporated.
The residue was purified by flash chromatography (hexane–
EtOAc) to give 3 as an oil (157 mg, 80%). dH (CDCl3): 0.89
(s, 3H£1/2), 0.98 (s, 3H£1/2), 1.00 (s, 3H£1/2), 1.06 (s,
3H£1/2), 1.57 (dd, 1H£1/2, J¼15.0, 2.7 Hz), 1.79 (dd,
1H£1/2, J¼15.0, 8.5 Hz), 1.89 (dd, 1H£1/2, J¼15.0,
4.3 Hz), 2.04 (dd, 1H£1/2, J¼15.0, 9.8 Hz), 2.37 (d,
1H£1/2, J¼2.1 Hz), 2.42 (d, 1H£1/2, J¼2.1 Hz), 3.23 (bs,
1H£1/2), 3.44 (d, 1H£1/2, J¼8.6 Hz), 3.49 (d, 1H£1/2,
J¼8.6 Hz), 4.23 (bs, 1H£1/2), 4.29 (d, 1H£1/2, J¼
11.6 Hz), 4.31 (d, 1H£1/2, J¼11.9 Hz), 4.51 (m, 1H£1/2),
4.52 (m, 1H£1/2), 4.61 (d, 1H£1/2, J¼11.6 Hz), 4.63 (d,
1H£1/2, J¼11.9 Hz), 5.25 (m, 2H£1/2), 5.38 (m, 2H£1/2),
5.79 (m, 1H£1/2), 5.91 (m, 1H£1/2), 7.30 (m, 5H£1/2),
7.33 (m, 5H£1/2); dC (CDCl3): 137.98, 137.33, 135.02,
134.44, 128.48, 128.36, 128.09, 127.94, 127.89, 127.62,
120.60, 120.09, 88.22, 88.03, 86.25, 85.94, 72.04, 71.47,
70.79, 70.41, 59.60, 59.22, 47.82, 46.71, 37.20, 37.09,
27.54, 26.19, 24.16, 23.09; [a]2D2¼20.268 (c¼0.531,
CHCl3); nmax (neat): 3292, 2960, 2864, 1452, 1386, 736,
698 cm21; HRMS (EI): calcd for C17H20O [M2H2O]þ:
240.1514. Found: 240.1494.
The oil was taken into CH2Cl2 (2 ml) and mixed with MnO2
(activated) (500 mg, 0.52 mmol) for 24 h at room tempera-
ture The mixture was filtered through celite and the filtrate
was evaporated. The residue was purified by flash
chromatography (hexane–EtOAc) to give 5 (87 mg, 47%)
and 4 (54 mg, 33%).
Compound 5. Oil; dH (CDCl3): 1.04 (s, 6H), 2.59 (d, 1H,
J¼14.3 Hz), 2.79 (d, 1H, J¼14.3 Hz), 3.55 (d, 1H, J¼
8.2 Hz), 4.22 (d, 1H, J¼11.6 Hz), 4.50 (d, 1H, J¼11.6 Hz),
5.27 (m, 2H), 5.67 (m, 1H), 7.24 (m, 5H), 7.50 (t, 2H,
J¼7.6 Hz), 7.57 (t, 1H, J¼7.6 Hz), 7.95 (d, 2H, J¼7.6 Hz);
dC (CDCl3): 185.76, 165.34, 138.50, 135.74, 134.91,
134.61, 128.24, 127.60, 137.36, 120.23, 111.96, 88.15,
86.76, 82.67, 70.30, 53.77, 39.34, 26.01, 24.72, 23.11;
[a]2D7¼21.378 (c¼0.292, CHCl3); nmax (neat): 2956, 2920,
1648, 1594, 1258, 1174 cm21; m/z (EI) 269 (Mþ291, 11),
255 (15), 105 (100), 91 (98), 77 (89); HRMS (EI): calcd for
C24H24O3: 360.1726. Found: 360.1688.
4.1.5. Ethyl 4-((3S)-3-benzyloxy-2,2-dimethyl-pent-4-en-
1-yl)-2-ethoxy-5(Z)-benzoylmethylidene-1,3-cyclopenta-
diene-1-carboxylate (Z-7) and ethyl 4-((3S)-3-benzyloxy-
2,2-dimethyl-pent-4-en-1-yl)-2-ethoxy-5(E)-benzoyl-
methylidene-1,3-cyclopentadiene-1-carboxylate (E-7).
To a solution of (2-ethoxy-3-ethoxycarbonyl-2-propenyl-
idene)triphenylphosphorane 6 (58 mg, 0.137 mmol) in THF
(6 ml) was added a solution of 5 (45 mg, 0.125 mmol) in
THF (2 ml) at 08C and the mixture was stirred for 24 h at
08C. The mixture was filtered and the filtrate was
evaporated. The residue was purified by flash chroma-
tography (hexane–EtOAc) to give Z-7 (35 mg, 56%) and
E-7 (14 mg, 22%).
4.1.4. (7S)-7-Benzyloxy-6,6-dimethyl-1-phenylnon-8-en-
2-yne-1,4-dione (5). To
a solution of 3 (201 mg,
0.79 mmol) in dry ether (5 ml) were added Et3N (0.18 ml,
1.3 mmol) and TMSCl (0.16 ml, 1.3 mmol) at 08C. The
mixture was stirred for 12 h at room temperature, poured
onto ice-water and extracted with EtOAc. The extract was
dried and evaporated. The resulting silyl ether of 3 was
purified by passing through a short column of SiO2 and
dissolved in a mixture of Et3N (4 ml) and benzene (1 ml).
The solution was mixed with benzoyl chloride (88 ml,
0.87 mmol), CuI (18 mg, 0.093 mmol) and then (Ph3P)2
PdCl2 (18 mg, 0.025 mmol) and the stirring was continued
for 15 h at room temperature After the addition of MeOH
(2 ml), the mixture was evaporated and the residue was
taken into benzene. The benzene layer was washed with
brine, dried and evaporated. The residue was dissolved in
MeOH (5 ml) containing citric acid (2.6 mg, 1.7 mol%).
The mixture was stirred for 20 min at room temperature,
poured into water and extracted with EtOAc. The extract
was dried and evaporated. The residue was purified by flash
chromatography (hexane–EtOAc) to give crude 4 as an oil
(189 mg, 55%). dH (CDCl3): 0.92 (s, 3H£1/2), 1.02 (s,
3H£1/2), 1.06 (s, 3H£1/2), 1.13 (s, 3H£1/2), 1.70 (d,
1H£1/2, J¼15.2 Hz), 1.90 (d, 1H£1/2, J¼14.7 Hz), 2.17 (d,
1H£1/2, J¼15.2 Hz), 2.37 (d, 1H£1/2, J¼14.7 Hz), 3.49 (d,
1H£1/2, J¼8.6 Hz), 3.52 (d, 1H£1/2, J¼8.6 Hz), 4.28 (d,
1H£1/2, J¼11.3 Hz), 4.32 (d, 1H£1/2, J¼11.6 Hz), 4.64 (d,
1H£1/2, J¼11.3 Hz), 4.65 (d, 1H£1/2, J¼11.6 Hz), 4.68 (d,
1H£1/2, J¼11.3 Hz), 4.80 (d, 1H£1/2, J¼11.3 Hz), 5.29
(m, 2H£1/2), 5.34 (m, 2H£1/2), 5.82 (m, 1H£1/2), 5.93 (m,
1H£1/2), 7.32 (m, 5H), 7.46 (m, 2H), 7.58 (m, 1H), 8.14 (m,
Compound Z-7. Oil; dH (CDCl3): 0.88 (t, 3H, J¼7.4 Hz),
0.92 (s, 3H), 0.99 (s, 3H), 1.40 (t, 3H, J¼7.0 Hz), 2.54 (d,
1H, J¼13.7 Hz), 2.68 (d, 1H, J¼13.7 Hz), 3.46 (d, 1H, J¼
8.2 Hz), 3.75 (q, 2H, J¼7.0 Hz), 4.22 (q, 2H, J¼7.4 Hz),
4.27 (d, 1H, J¼12.2 Hz), 4.61 (d, 1H, J¼12.2 Hz), 5.32 (m,
2H), 5.81 (m, 1H), 6.21 (s, 1H), 6.77 (s, 1H), 7.26 (m, 5H),
7.49 (t, 2H, J¼7.6 Hz), 7.52 (t, 1H, J¼7.6 Hz), 7.94 (d, 2H,
J¼7.6 Hz); dC (CDCl3): 194.08, 171.88, 163.03, 145.36,
144.47, 138.79, 137.28, 135.25, 132.90, 129.45, 128.94,
128.50, 128.26, 127.41, 127.33, 121.94, 119.92, 98.10,
87.32, 70.10, 67.32, 59.60, 38.50, 34.43, 24.78, 23.37,
15.27, 13.88; [a]D20¼24.258 (c¼0.961, CHCl3); nmax (neat):
2968, 1678, 1594, 1240, 1104 cm21; m/z (EI) 500 (Mþ, 11),
395 (8), 105 (100), 91 (88), 77 (30); HRMS (EI): calcd for
C32H36O5: 500.2563. Found: 500.2609.
Compound E-7. Oil; dH (CDCl3): 0.66 (s, 3H), 0.72 (s, 3H),
1.34 (t, 3H, J¼7.3 Hz), 1.41 (t, 3H, J¼7.3 Hz), 2.45 (d, 1H,
J¼14.3 Hz), 2.50 (d, 1H, J¼14.3 Hz), 3.22 (d, 1H, J¼
8.2 Hz), 4.17 (q, 2H, J¼7.3 Hz), 4.15 (d, 1H, J¼11.9 Hz),

H. Kitano et al. / Tetrahedron 59 (2003) 2673–2677
2677
4.26 (q, 2H, J¼7.3 Hz), 4.49 (d, 1H, J¼11.9 Hz), 5.12 (m,
2H), 5.59 (m, 1H), 6.02 (s, 1H), 7.27 (m, 5H), 7.44 (t, 2H,
J¼7.5 Hz), 7.56 (t, 1H, J¼7.6 Hz), 7.98 (d, 2H, J¼7.5 Hz),
8.29 (s, 1H); dC (CDCl3): 194.87, 170.93, 163.91, 145.81,
144.58, 138.89, 137.33, 135.16, 133.91, 133.60, 129.30,
128.64, 128.18, 127.59, 127.25, 124.26, 119.44, 98.28,
87.63, 70.15, 67.18, 59.25, 38.95, 36.32, 23.47, 23.02,
15.18, 14.45; [a]D22¼20.408 (c¼0.801, CHCl3); nmax (neat):
2964, 1728, 1702, 1574, 1204, 1064 cm21; m/z (EI) 500
(Mþ, 8), 105 (100), 91 (84), 77 (63); HRMS (EI): calcd for
C32H36O5: 500.2563. Found: 500.2554.
73.61, 60.38, 60.01, 58.44, 49.86, 47.35, 44.38, 41.97,
37.87, 36.60, 28.31, 23.13, 14.03; [a]2D1¼21.298 (c¼0.680,
m/z (EI) 518 (Mþ, 21), 427 (7), 105 (100), 91 (74), 77 (38);
HRMS (EI): calcd for C32H38O6: 518.2668. Found:
518.2666.
CHCl3): nmax (neat): 2920, 1726, 1696, 1106, 730 cm21
;
4.1.8. Thermal reaction of ethyl 4-((3S)-3-benzyloxy-2,2-
dimethyl-pent-4-en-1-yl)-2-ethoxy-5(E)-benzoylmethyl-
idene-1,3-cyclopentadiene-1-carboxylate (E-7). A solu-
tion of Z-7 (34 mg, 0.068 mmol) in toluene was heated for
20 h at 1008C in a sealed tube. The cooled mixture was
evaporated and the residue was dissolved in a 4:4:1 mixture
(1 ml) of TFA, THF and H2O. The mixture was stirred for
5 h at room temperature, diluted with water, and extracted
with EtOAc. The extract was washed in turn with brine and
saturated aq NaHCO3 solution, dried, and then evaporated.
Flash chromatography (hexane–EtOAc) and preparative
GPC gave 10 as an oil (6 mg, 17%).
4.1.6. Ethyl (1R,4S,5R,7S)-4-benzyloxy-8-ethoxy-3,3-
dimethyl-10(Z)-benzoylmethylidene-tricyclo[5.2.1.01,5]-
dec-8-ene-7-carboxylate (Z-8). A solution of Z-7 (28 mg,
0.056 mmol) in toluene was heated for 20 h at 1008C in a
sealed tube. The cooled mixture was evaporated and the
residue was purified by flash chromatography (hexane–
EtOAc) to give Z-8 as a solid (24 mg, 86%). Mp 143–
1448C; dH (CDCl3): 0.95 (t, 3H, J¼7.0 Hz), 1.12 (s, 3H),
1.14 (s, 3H), 1.23 (t, 3H, J¼7.0 Hz), 1.84 (d, 1H, J¼
14.7 Hz), 1.93 (d, 1H, J¼14.7 Hz), 2.03 (dd, 1H, J¼11.9,
9.2 Hz), 2.33 (m, 2H), 3.25 (d, 1H, J¼11.1 Hz), 3.72 (m,
1H), 3.81 (m, 2H), 4.17 (m, 1H), 4.54 (d, 1H, J¼11.6 Hz),
4.62 (d, 1H, J¼11.6 Hz), 4.92 (s, 1H), 6.14 (s, 1H), 7.32 (m,
5H), 7.44 (t, 2H, J¼7.0 Hz), 7.54 (t, 1H, J¼7.0 Hz), 7.92 (d,
2H, J¼7.0 Hz); dC (CDCl3): 191.61, 169.03, 167.12,
161.34, 139.17, 132.90, 128.69, 128.47, 128.25, 128.20,
128.04, 127.29, 127.10, 104.28, 102.35, 91.15, 72.52, 64.84,
60.42, 56.97, 53.78, 43.75, 37.87, 30.25, 29.60, 25.60,
14.12, 13.81; [a]D22¼20.718 (c¼0.591, CHCl3); nmax
(Nujol): 1736, 1274, 1100 cm21; m/z (EI) 500 (Mþ, 15),
409 (8), 105 (100), 91 (96), 77 (38); HRMS (EI): calcd for
C32H36O5: 500.2563. Found: 500.2551. Anal. calcd for
C32H36O5: H, 7.25; C, 76.77. Found: H, 7.44; C, 77.07.
Acknowledgements
We are grateful to Dr Y. Takai and Professor M. Sawada,
the Material Analytical Center of ISIR, Osaka University,
and Professor Y. Tokunaga, Fukui University for their kind
discussion of NMR spectroscopic analysis.
References
1. (a) Rigby, J. H. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp
626–633. (b) Coe, J. W.; Vetelino, M. G.; Kemp, D. S.
Tetrahedron Lett. 1994, 35, 6627–6630.
4.1.7. Ethyl (1S,5R,6S)-2-benzoylmethyl-6-benzyloxy-1-
ethoxycarbonylmethyl-7,7-dimethyl-bicyclo[3.3.0]oct-2-
ene-3-carboxylate (10). A solution of Z-8 (24 mg,
0.048 mmol) in a 4:4:1 mixture (1 ml) of THF, CF3CO2H
and H2O was stirred for 5 h at room temperature The
mixture was diluted with water (5 ml) and extracted with
EtOAc. The extract was washed successively with brine and
saturated aq NaHCO3 solution, dried and evaporated. The
residue was purified by flash chromatography (hexane–
EtOAc) to give 10 as an oil (14 mg, 56%). dH (CDCl3): 1.06
(t, 3H, J¼7.3 Hz), 1.07 (s, 3H), 1.12 (s, 3H), 1.20 (t, 3H,
J¼7.3 Hz), 1.53 (d, 1H, J¼13.4 Hz), 1.80 (d, 1H, J¼
13.4 Hz), 2.53 (d, 1H, 14.0 Hz), 2.62 (d, 1H, J¼14.0 Hz),
2.63 (d, 1H, J¼16.8 Hz), 2.80 (t, 1H, J¼8.6 Hz), 2.89 (dd,
1H, J¼16.8, 8.6 Hz), 3.45 (d, 1H, J¼8.6 Hz), 3.76 (d, 1H,
J¼17.1 Hz), 4.05 (q, 2H, J¼7.3 Hz), 4.06 (q, 2H, J¼
7.3 Hz), 4.48 (d, 1H, J¼17.1 Hz), 4.68 (d, 2H, J¼1.5 Hz),
7.33 (m, 5H), 7.48 (t, 2H, J¼7.6 Hz), 7.57 (t, 1H, J¼
7.6 Hz), 8.01 (d, 2H, J¼7.6 Hz); dC (CDCl3): 196.06,
171.05, 165.38, 153.96, 139.18, 137.10, 133.01, 129.67,
128.59, 128.32, 128.30, 128.07, 127.41, 127.37, 94.30,
2. (a) Hong, B.-C.; Shr, Y.-J.; Liao, J.-H. Org. Lett. 2002, 55,
9171–9984. (b) Nair, V.; Anilkumar, G.; Radhakrishnan, K. V.;
Sheela, K. C.; Rath, N. P. Tetrahedron Lett. 1997, 53,
17361–17372. (c) Nair, V.; Kumar, S.; Williard, P. G.
Tetrahedron Lett. 1995, 36, 1605–1608.
3. (a) Wang, Y.; Mukherjee, D.; Birney, D.; Houk, K. N. J. Org.
Chem. 1990, 55, 4504–4506. (b) Stone, K. J.; Little, R. D.
J. Org. Chem. 1984, 49, 1849. (c) Little, R. D.; Carroll, G. L.;
Petersen, J. L. J. Am. Chem. Soc. 1983, 105, 928.
4. Bergmann, E. D. Chem. Rev. 1968, 68, 41.
5. Himeda, Y.; Ueda, I.; Hatanaka, M. Chem. Lett. 1996, 71–72.
6. After the completion of this work, the preparation of compound
1 in the similar manner was reported: O’Brien, M.; Taylor,
N. H.; Thomas, E. J. Tetrahedron Lett. 2002, 43, 5491–5494.
7. We have reported previously that an analogous compound
without benzoylmethylidene group, ethyl 8-ethoxy-3,3-
dimethyltricyclo[5.2.1.01,5]dec-8-ene-7-caboxylate, gave the
corresponding ketone quantitatively by the acid treatment and
did not undergo such a C–C bond cleavage Hatanaka, M.;
Ueno, F.; Ueda, I. Tetrahedron Lett. 1996, 37, 89–90.