A novel synthesis of tricyclo[5.1.0.03,5]octane-2,6-dione derivatives via double Michael addition-induced cyclopropanation reactions

Article abstract of DOI:10.1016/S0040-4020(01)00180-6

Tricyclo[5.1.0.0^3,5]octane-2,6-diones 1a-q were prepared in moderate yields by the reaction of α,β-unsaturated esters 2 with dihalomethane in the presence of butyllithium, and by the reaction of dichloromethyl α,β-unsaturated ketones 3 with sodium ethoxide, respectively. This reaction was newly explained by a mechanism involving intermolecular double Michael additions of enolate anion 4 of ketones 3 and the following cyclopropanation.

Full text of DOI:10.1016/S0040-4020(01)00180-6

TETRAHEDRON
Pergamon
Tetrahedron 57 =2001) 3035±3044
A novel synthesis of tricyclo[5.1.0.03,5]octane-2,6-dione derivatives
via double Michael addition-induced cyclopropanation reactions
Sadao Tsuboi,a,p Xuan Ye,a Katsushi Kunitob and Takashige Onob
aDepartment of Environmental Chemistry and Materials, Faculty of Environmental Science and Technology, Okayama University,
Tsushima, Okayama 700-8530, Japan
bDepartment of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama 700-8530, Japan
Received 11 January 2001; accepted 8February 2001
AbstractÐTricyclo[5.1.0.03,5]octane-2,6-diones 1a±q were prepared in moderate yields by the reaction of a,b-unsaturated esters 2 with
dihalomethane in the presence of butyllithium, and by the reaction of dichloromethyl a,b-unsaturated ketones 3 with sodium ethoxide,
respectively. This reaction was newly explained by a mechanism involving intermolecular double Michael additions of enolate anion 4 of
ketones 3 and the following cyclopropanation. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
synthesis of syn-bishomoquinone =syn-tricyclo[5.1.0.03,5]-
octane-2,6-dione), as shown in Fig. 2.
Michael addition is an important reaction in organic synthe-
sis for making carbon±carbon bonds. Recently, a number of
tandem reactions via Michael addition, which are useful for
the construction of carbon skeletons, have been reported.1 It
is well known that Michael addition of nucleophiles to a,b-
unsaturated esters and the following cyclopropanation
affords cyclopropanecarboxylic esters. Michael addition of
2-methylpropenyl magnesiumbromide to a-chloroisobutyl-
idenemalonate gave chrysanthemic acid derivate.2 The reac-
tion of 1,1-dipolar species with Michael acceptors can result
in three-membered ring compounds. Corey et al. reported
the synthesis of methyl chrysanthemate by the reaction of
sulfonium ylide with methyl 2,4-hexadienoate.3 Michael
additions of phosphonium ylides or a-lithiosulfones to
a,b-unsaturated esters give cyclopropanecarboxlyates.4,5
Dimerizative cyclopropanation of methyl a-bromoacrylate
by the action of nucleophiles has been reported.6
Christopher et al.9 reported the synthesis of tetramethyl-
bishomoquinones with anti-con®guration by the double
additions of dichlorocarbene and dibromocarbene to tetra-
methylquinone, as shown in Fig. 3.
The synthesis of 1,5-dihalotricyclo[5.1.0.03,5]octane-2,6-
dione 1 via intermolecular double Michael additions
between the same molecules has never been reported, to
the best of our knowledge. In this paper we report a novel
synthesis of tricyclo[5.1.0.0.3,5]octane-2,6-dione derivatives
via intermolecular double Michael addition-induced cyclo-
propanation reactions from 1,1-dichloro-3-alken-2-ones 3
and a,b-unsaturated esters 2.10±12 The intermediate of the
formation of 1 is also our concern.
Tricyclo[5.1.0.03,5]octane-2,6-dione is a unique and steri-
cally strained compound. Its synthesis via some steps is
reported in the following papers. Heller et al.7 reported
the ®rst preparation of anti-bishomoquinone =tricyclo-
[5.1.0.03,5]octane-2,6-dione) by bromination of cyclo-
octane-1,5-dione and the following dehydrobromination
reaction, as shown in Fig. 1.
Figure 1.
Buchanan et al.8 reported a convenient stereoselective
Keywords: tricyclo[5.1.0.03,5]octane-2,6-dione; cyclopropanation; tandem
reaction; Michael addition.
p
Corresponding author. Tel./fax: 181-86-251-8898;
e-mail: stsuboi6@cc.okayama-u.ac.jp
Figure 2.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020=01)00180-6

3036
S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
Figure 3.
2. Results and discussion
under an atmosphere of nitrogen and the following quench-
ing with cold water. The reaction afforded 1 in 50±70%
yields as white crystals.15 Yields of 1 are tabulated in
Table 2. In these reactions, other stereoisomers of 1 were
not detected. Formation of other stereoisomers seems to be
dif®cult due to steric hindrance. Although the reaction
mixture was puri®ed and analyzed carefully, any other
compounds were not isolated except decomposed resinous
materials. Compound 3 was prepared by the reaction of a,b-
unsaturated aldehydes with dichloromethane in the presence
of butyllithium and the following oxidation with manganese
dioxide.16 The formation of tricyclo[5.1.0.03,5]-octane-2,6-
dione 1 from two starting materials 2 and 3 is shown in
Scheme 1.
Various a,b-unsaturated esters 2 were treated with one
equivalent of lithiodihalomethane =BuLi1CH2X2) in
anhydrous THF at 2958C =10 min) under an atmosphere
of nitrogen, and then the reaction mixture was quenched
with water to give 1 as white crystals in moderate yields.
The yields and physical properties of 1 are tabulated in
Table 1. The yields of alkyl substituted 1 are lower than
those of aryl substituted 1. Due to the stereo-hindered effect
of halogen atom, the yields of bromo-substituted 1 are lower
than those of the chloro-substituted one.
Characteristic signals of the IR and NMR data were
identical with those of the samples, and the stereochemistry
was absolutely veri®ed by X-ray crystallographic
analysis.13±15 Because of the deshielding effect of the aryl
groups, the chemical shifts of the tricyclo-ring-proton of
aryl-substituted 1 are located in lower ®eld than those of
alkyl-substituted 1.
The formation of compound 1 is a process via the enolate 4
from 3, which is also introduced from the reaction between
a,b-unsaturated esters 2 with 1 equiv. of lithiodihalo-
methane, as shown in Scheme 3. On the other hand,
Normant et al.17 reported that the reaction of a,b-unsatu-
rated esters with dichloromethane in the presence of butyl-
lithium gave 1,1-dichloro-3-alken-2-one 3 predominantly
without the formation of tricyclo[5.1.0.03,5]octane-2,6-
dione 1. We clari®ed this discrepancy by the following
experiment. When the reaction mixture was quenched
In a similar way, compounds 1 were also obtained by the
treatment of 1,1-dichloro-3-alken-2-ones 3 with 1 equiv. of
sodium ethoxide in dry diethyl ether at low temperature
=278to 2608C for ca. 10 h, and 08C for a few days)
Table 1. Preparation of 1a±q by the reaction of various a,b-unsaturated esters with dichloromethane in the presence of butyllithium
R
X
Yields =%)
Mp =8C)
IR =cm21
)
NMR =d, CDCl3, ring H)
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
CH3
C2H5
n-C3H7
n-C4H9
n-C5H11
=CH3)2CHCH2
=CH3)2CH
C6H5
p-Cl±C6H4
p-CH3±C6H4
o-Cl±C6H4
CH3
C2H5
n-C3H7
C6H5
p-Cl±C6H4
p-CH3±C6H4
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
41
41
33
31
32
32
19
63
67
42
24
13
10.4
5.3
60.5
36
228a
145
109
105
1685
1705
1702
1690
1690
1700
2.00, 2.21
1.85, 2.25
1.84, 2.24
1.92, 2.24
1.86, 2.32
1.87, 2.23
101
220a
1281700
224a
225a
192a
274
1.60, 2.26
1700
1695
1705
1695
1675
1700
1685
1695
1680
1700
3.28, 3.89
3.48, 4.04b
3.05, 3.29
3.60, 3.94b
1.76, 2.28
1.91, 2.32
1.91, 2.32
3.14, 3.20
3.08, 3.15
3.10, 3.16
192
163
113a
224a
183a
215a
19
a
Decomposition temperature.
DMSO-d6 solvent.
b

S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
3037
Table 2. Preparation of 1 by the reaction of =E)-1,1-dichloro-3-alken-2-one
3 with NaOEt in THF
Namely, when an acid was added to the reaction mixture for
quenching the reaction, the reaction gave 3 as a major
product. However, the quenching by addition of water and
the subsequent stirring of the mixture with gradually warm-
ing up to room temperature for 10±30 min afforded tricyclo-
[5.1.0.03,5]octane-2,6-dione 1 as a main product. After the
addition of water, the reaction proceeds under alkaline
condition, giving 1 via Michael addition of enolate 4 and
the cyclopropanation as shown in Scheme 3.
There are two possible mechanisms of the formation of
tricyclo[5.1.0.03,5]octane-2,6-dione 1. One is through the
intermediate, anion 4, and the other is through the inter-
mediate, carbene 40 as shown in Scheme 3. Concerning
with the mechanism via 4, two pathways =path a and path
b) can be supposed. In order to determine which inter-
mediate is more reasonable for the formation of tri-
cyclo[5.1.0.03,5]octane-2,6-dione 1, the calculation
=AM1)18 of the heat formation of both intermediate states
4 and 40 was carried out and the result is illustrated in Table
3. This result shows carbene intermediate 40 state is at a
higher energy level than that of 4. Furthermore, the carbene
mechanism was rejected by a chemical reaction. When the
reaction of formation of 1 was carried out in the presence of
cyclohexene, no cycloaddition products of 40 to carbon±
carbon double bonds were detected. The possible
intermediate state should be 4.
R
X
Yield =%)
1a
1c
1r
1s
1h
CH3
n-C3H7
CH3CHˆCH
n-C6H13
C6H5
Cl
Cl
Cl
Cl
Cl
52.9
56.9
48
53.4
70.0
1t
Cl
71.0
When the formation of 1 as a by-product in the reaction of
a,a-dichloroacetoacetate with aldehydes in the presence of
alkoxides was reported in the previous paper,13 the forma-
tion of 4 and the following double Michael addition
mechanism was also postulated. In the course of this
research, Mamedov et al.19,20 reported the formation of 1
in a low yield by the reaction of some benzaldehydes
with a,a-dichloroacetone or 3,3-dichloro-2,4-pentanedione.
In these cases, formation of 1 can be explained by the
with water, tricyclo[5.1.0.03,5]octane-2,6-dione
1 was
formed, as described above. However, the reaction of
ethyl cinnamate and dichloromethane in the presence of
LDA in THF at 2958C and the following quenching with
2 M HCl afforded =E)-1,1-dichloro-4-phenyl-3-buten-2-one
=3h) in 41% yield, which was then treated with LiOH water
solution in THF at 2958C for 10 min to give 1h in 94%
yield. These results are summarized in Scheme 2.
Scheme 1. Syntheses of tricyclo[5.1.0.03,5]octane-2,6-dione 1.
Scheme 2. Preparation of 1h by the treatment of 3h with LiOH.

3038
S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
Scheme 3. Reaction mechanism of formation of tricyclo[5.1.0.03,5]octane-2,6-dione.
Table 3. Calculations of DHf with AM1 for 4 and 40
R
X
4 DHf =
) =kcal/mol)
40 DHf =
) =kcal/mol)
4a
4b
4c
4d
CH3
Cl
Cl
Cl
Cl
245.30
248.32
255.85
210.27
23.53
29.09
213.86
34.27
C2H5
n-C3H7
Ph
Figure 4.

S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
3039
Table 4. Preparation of 1a and 1h by the reaction of various a,b-unsaturated esters 5a±o with LiCHCl2
S.T.
R
R0
1a Yield =%)
S.T.
R
R0
1h Yield =%)
5a
5b
5c
5d
5e
5f
CH3
CH3
CH3
CH3
CH3
CH3
CH3
C2H5
49
49
50
28
45
23
8
5i
5j
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH3
C2H5
n-C3H7
n-C4H9
CH=CH3)2
63
71
65
72
45
43
36
n-C3H7
n-C4H9
CH=CH3)2
CH2CH=CH3)2
CH=CH3)CH2CH3
C=CH3)3
5k
5l
5m
5n
5o
CH2CH=CH3)2
CH=CH3)CH2CH3
5g
mechanism via the aldol product 3 and the intermediate 4, as
shown in Fig. 4.
3.2. Preparation of starting materials
All a,b-unsaturated esters were synthesized by Horner±
Emmons±Wardsworth reaction.10,11
To investigate the best leaving group in various esters for
synthesis of tricyclo[5.1.0.03,5]octane-2,6-dione compounds
=1a and 1h), various a,b-unsaturated esters 5a±o were used
to prepare 1a and 1h. The results are shown in Table 4. The
best leaving group is the n-butyl group.
3.3. General procedure for the preparation of tricyclo-
[5.1.0.03,5]octane-2,6-diones 1
Method ,a). To a solution of n-BuLi =1.61 M in hexane) in
THF was added slowly dichloromethane at 2958C. The
mixture was stirred for 30 min at the same temperature.
Then a,b-unsaturated ester =1 equiv.) was added to the
¯ask. The solution was stirred for 10 min, and then 10 mL
of water was added to the ¯ask. The cooling bath was
removed. After the reaction mixture was warmed up to
room temperature, 10% hydrochloric acid solution was
added to acidify the solution. After the solvent was removed
in vacuo, the precipitate was ®ltered and washed with
diethyl ether to give tricyclo[5.1.0.03,5]octane-2,6-diones.
3. Experimental
3.1. General techniques
All reactions were carried out under a nitrogen atmosphere
with dry, freshly distilled solvents under anhydrous con-
ditions, unless otherwise noted. Tetrahydrofuran =THF),
toluene, and diethyl ether were distilled from sodium benzo-
phenone; methylene chloride =CH2Cl2) was freshly distilled
from calcium hydride.
Reagents of the highest commercial quality were purchased
and used without further puri®cation, unless otherwise
stated. Reactions were monitored by thin-layer chromato-
graphy =TLC) carried out on 0.25 mm E. Merck silica gel
plates =60F-254) using UV light as a visualizing agent and
5% ethanolic phosphomolybdic acid or p-anisaldehyde
solution, and heat as developing agents. E. Merck silica
gel =60, particle size 0.040±0.050 mm) was used for ¯ash
column chromatography.
Method ,b). To a solution of n-BuLi =1.61 M in hexane) in
THF was added slowly dichloromethane at 2958C. The
mixture was stirred for 30 min at the same temperature.
Then a,b-unsaturated ester =1 equiv.) was added to the
¯ask. The solution was stirred for 10 min, and then 10 mL
of water was added to the ¯ask. After the cooling bath was
removed, the reaction mixture was allowed to warm up to
room temperature, and then 10% hydrochloric acid
solution was added to acidify the solution. The precipitate
was ®ltered and was washed with ethyl acetate to give
tricyclo[5.1.0.03,5]octane-2,6-diones.
NMR spectra were recorded on Varian Gemini 200 or
Varian Gemini 500 instruments and calibrated using resi-
dual undeuterated solvent as an internal reference. The
following abbreviations were used to explain the
multiplicities: sˆsinglet, dˆdoublet, tˆtriplet, qˆquartet,
septˆseptet, mˆmultiplet, bˆbroad, bsˆbroad singlet. IR
spectra were recorded on a JASCO model FT-IR 5000
spectrometer. The melting points and boiling points are
uncorrected. Mass spectra were measured on a Shimadzu
model GC-MS QP 5000 at 70 eV. Elementary analysis was
carried out on a PERKIN ELMER 2400 Series II CHNS/O
Analyzer. Calculations of DHf with AM1 was carried out on
SPARTAN M/P Plus.
3.3.1. 1,5-Dichloro-4,8-dimethyltricyclo[5.1.0.03,5]octane-
2,6-dione 11a). Method =a) was used. n-BuLi =12.4 mL of
1.6 M in hexane, 20 mmol), THF =50 mL), CH2Cl2 =2.13 g,
25 mmol), and ethyl crotonate =3.24 g, 28mmol) were
employed to give 1a: 0.944 g =41%) as a white solid: mp
2288C =decomposition); 1H NMR =200 MHz, CDCl3) d 1.46
=d, Jˆ6.0 Hz, 6H), 2.00 =dq, Jˆ6.0, 6.3 Hz, 2H), 2.21 =d,
Jˆ6.3 Hz, 2H); 13C NMR =50 MHz, CDCl3) d 13.4, 27.7,
40.6, 50.4, 192.8; IR =KBr): 3385, 3018, 2950, 2910, 2825,
1685, 1565 cm21. Anal. Calcd for C10H10O2Cl2: C, 51.53;
H, 4.34. Found: C, 51.50; H, 4.17.

3040
S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
3.3.2. 1,5-Dichloro-4,8-diethyltricyclo[5.1.0.03,5]octane-
2,6-dione 11b). Method =a) was used. n-BuLi =12.4 mL of
1.6 M in hexane, 20 mmol), THF =50 mL), CH2Cl2 =2.08g,
23 mmol), and ethyl =2E)-pentenoate =2.42 g, 18.9 mmol)
were employed to give 1b: 1.01 g =41%) as a white solid:
mp 145.5±146.58C; 1H NMR =200 MHz, CDCl3) d 1.10 =t,
Jˆ6.6 Hz, 6H), 1.62±1.91 =m, 6H), 2.25 =d, Jˆ5.6 Hz, 2H);
13C NMR =50 MHz, CDCl3) d 12.54, 22.38, 33.96, 39.76,
50.24, 192.7 27; IR =KBr): 3032, 2974, 2934, 2878, 1705,
3.3.7. 1,5-Dichloro-4,8-dipropyltricyclo[5.1.0.03,5]octane-
2,6-dione 11g). Method =a) was used. n-BuLi =1.24 mL of
1.6 M in hexane, 2.0 mmol), THF =5 mL), CH2Cl2 =0.213 g,
2.5 mmol), and ethyl =E)-4-methyl-2-pentenoate =0.342 g,
3.0 mmol) were employed to give 1g: 0.055 g =19%) as a
white solid: mp 1288C; 1H NMR =200 MHz, CDCl3) d 1.09
=d, Jˆ6.36 Hz, 6H), 1.17 =d, Jˆ6.36 Hz, 6H), 1.58±1.60 =m,
2H), 1.71±1.74 =m, 2H), 2.26 =d, Jˆ6.22 Hz, 2H); 13C NMR
=50 MHz, CDCl3) d 21.12, 21.48, 30.00, 39.27, 39.52,
50.35, 192.2; IR =KBr): 3380, 2950, 2850, 1700,
1460 cm21. Anal. Calcd for C14H18O2Cl2: C, 58.14; H,
6.27. Found: C, 57.92; H, 6.02.
1462, 1388, 1334, 1294, 1247, 1149, 1096, 1036, 784 cm21
.
Anal. Calcd for C12H14O2Cl2: C, 55.19; H, 5.40. Found: C,
55.33; H, 5.52; GC-MS 260 =M1), 225, 197, 155, 115, 105,
91, 65=100).
3.3.8. 1,5-Dichloro-4,8-diphenyltricyclo[5.1.0.03,5]octane-
2,6-dione 11h). Method =b) was used. n-BuLi =1.21 mL of
1.6 M in hexane, 2.0 mmol), THF =5 mL), CH2Cl2 =0.213 g,
2.5 mmol), and ethyl =E)-cinnamate =0.441 g, 2.5 mmol)
were employed to give 1h: 0.226 g =63%) as a white
solid: mp 2248C =decomposition); 1H NMR =200 MHz,
DMSO): d 3.44 =d, Jˆ7.2 Hz, 2H), 3.99 =d, Jˆ7.2 Hz,
2H), 7.40 =m, 10H); 13C NMR =50 MHz, DMSO): d
35.33, 37.81, 51.37, 128.39, 128.51, 129.39, 131.57,
191.99; IR =KBr): 3400, 3050, 3000, 1695, 1595,
1445 cm21. Anal. Calcd for C20H14O2Cl2: C, 60.32; H,
3.95. Found: C, 60.29; H, 3.88.
3.3.3. 1,5-Dichloro-4,8-dipropyltricyclo[5.1.0.03,5]octane-
2,6-dione 11c). Method =a) was used. n-BuLi =12.1 mL of
1.6 M in hexane, 19.3 mmol), THF =50 mL), CH2Cl2
=2.09 g, 24 mmol) and ethyl =2E)-hexenoate =2.87 g,
20 mmol) were employed to give 1c: 0.91 g =33%) as a
1
white solid: mp 108±1098C; H NMR =200 MHz, CDCl3)
d 0.96 =t, Jˆ7.2 Hz, 6H), 1.15±1.60 =m, 4H), 1.67±1.77 =m,
4H), 1.84 =dt, Jˆ6.2, 6.0 Hz, 2H), 2.23 =d, Jˆ6.2 Hz, 2H);
13C NMR =50 MHz, CDCl3) d 13.53, 21.50, 30.55, 32.53,
39.80, 50.19, 192.6; IR =KBr): 3060, 2974, 2964, 1702,
1294, 1145, 874, 681 cm21. Anal. Calcd for C14H18O2Cl2:
C, 58.14; H, 6.27. Found: C, 57.92; H, 6.02.
3.3.9.
1,5-Dichloro-4,8-di1 p-chlorophenyl)tricyclo-
3.3.4. 1,5-Dichloro-4,8-dibutyltricyclo[5.1.0.03,5]octane-
2,6-dione 11d). Method =a) was used. n-BuLi =5 mL of
1.6 M in hexane, 7.2 mmol), THF =15 mL), CH2Cl2
=0.75 g, 8.9 mmol), and ethyl =2E)-heptenoate =1.15 g,
7.0 mmol) were employed to give 1d: 0.338g =31%) as a
white solid: mp 1058C; 1H NMR =200 MHz, CDCl3) d 0.91
=t, Jˆ7.2 Hz, 6H), 1.30±1.53 =m, 8H), 1.68±1.90 =m, 6H),
2.22 =d, Jˆ6.0 Hz, 2H); 13C NMR =50 MHz, CDCl3) d
13.84, 21.18, 22.18, 28.41, 30.92, 32.74, 39.86, 50.27,
192.7; IR =KBr): 3360, 3025, 2962, 2825, 1700, 1466,
[5.1.0.03,5]octane-2,6-dione 11i). Method =b) was used.
n-BuLi =6.25 mL of 1.6 M in hexane, 10 mmol), THF
=25 mL), CH2Cl2 =0.958g, 11.4 mmol), and ethyl = E)-p-
chlorocinnamate in 4 mL of THF =2.42 g, 11 mmol) were
employed to give 1i: 1.420 g =67%) as a white solid: mp
2258C =decomposition); 1H NMR =200 MHz, DMSO-D6) d
3.48=d, Jˆ7.4 Hz, 2H), 4.04 =d, Jˆ7.2 Hz, 2H), 7.45 =m,
8H); 13C NMR =50 MHz, DMSO-D6): d 34.70, 37.79, 51.26,
128.53, 130.75, 131.31, 133.20, 191.66; IR =neat): 3350,
3040, 3000, 1695, 1590, 1485 cm21. Anal. Calcd for
C20H12O2Cl4: C, 56.37; H, 2.84. Found: C, 56.46; H, 2.85.
1299, 1280, 1145, 874 cm21
.
Anal. Calcd for
C16H22O2Cl2: C, 60.53; H, 6.99. Found: C, 60.74; H, 7.12.
3.3.10.
1,5-Dichloro-4,8-di1 p-methylphenyl)tricyclo-
3.3.5. 1,5-Dichloro-4,8-dipentyltricyclo[5.1.0.03,5]octane-
2,6-dione 11e). Method =a) was used. n-BuLi =7.10 mL of
1.6 M in hexane, 11 mmol), THF =20 mL), CH2Cl2 =1.02 g,
12 mmol), and ethyl =2E)-octenoate =1.70 g, 10 mmol) were
employed to give 1e: 0.545 g =32%) as a white solid: mp
[5.1.0.03,5]octane-2,6-dione 11j). Method =b) was used.
n-BuLi =4.5 mL of 1.6 M in hexane, 7.2 mmol), THF
=15 mL), CH2Cl2 =0.685 g, 8.1 mmol), and ethyl =E)-p-
methylcinnamate =1.33 g, 7.0 mmol) were employed to
give 1j: 0.565 g =42%) of the product as a white solid: mp
1928C =decomposition); 1H NMR =200 MHz, CDCl3) d 2.37
=s, 6H), 3.05 =d, Jˆ6.8Hz, 2H), 3.28=d, Jˆ6.9 Hz, 2H),
7.15±7.26 =m, 8H); 13C NMR =50 MHz, CDCl3) d 21.19,
36.05, 38.51, 50.41, 127.01, 129.10, 129.42, 138.82, 191.62;
IR =KBr): 3400, 3052, 1709, 1515, 1445, 1243, 1098, 812,
517 cm21. Anal. Calcd for C22H18O2Cl2: C, 68.58; H, 4.71.
Found: C, 68.52; H, 4.94.
1
1018C; H NMR =200 MHz, CDCl3) d 0.88 =t, Jˆ5.8Hz,
6H), 1.36±1.86 =m, 18H), 2.23 =d, Jˆ6.16 Hz, 2H); 13C
NMR =50 MHz, CDCl3): d 13.89, 22.36, 27.83, 28.67,
31.18, 32.71, 39.79, 50.22, 192.7. Anal. Calcd for
C18H26O2Cl2: C, 62.96; H, 7.63. Found: C, 61.19; H, 7.82.
3.3.6. 1,5-Dichloro-4,8-diisobutyltricyclo[5.1.0.03,5]octane-
2,6-dione 11f). Method =a) was used. n-BuLi =2.5 mL of
1.6 M in hexane, 4.0 mmol), THF =10 mL), CH2Cl2
=0.418g, 4.9 mmol), and ethyl = E)-5-methyl-2-hexenoate
=0.703 g, 4.5 mmol) were employed to give 1f: 0.20 g
3.3.11.
1,5-Dichloro-4,8-di1o-chlorophenyl)tricyclo-
[5.1.0.03,5]octane-2,6-dione 11k). Method =b) was used.
n-BuLi =9.3 mL of 1.6 M in hexane, 14.8mmol), THF
=25 mL), CH2Cl2 =1.31 g, 15.6 mmol), and ethyl =E)-o-
chlorocinnamate =2.908g, 13.8mmol) were employed to
1
=32%) as a white solid: mp 2208C =decomposition); H
NMR =200 MHz, CDCl3) d 0.97 =dd, Jˆ7.0, 7.0 Hz, 12H),
1.58 =m, 4H), 1.82 =m, 2H), 1.87 =m, 2H), 2.23 =d, Jˆ6.5 Hz,
2H); 13C NMR =50 MHz, CDCl3) d 22.16, 22.32, 27.91,
31.57, 37.17, 39.90, 50.13, 192.58; IR =KBr): 3038, 2958,
2930, 1700, 1294, 1102, 876, 586. Anal. Calcd for
C16H22O2Cl2: C, 60.57; H, 6.99. Found: C, 60.19; H, 7.23.
1
give 1k: 0.716 g =24.4%) as a solid: mp 2478C; H NMR
=500 MHz, DMSO-D6) d 3.60 =d, Jˆ7.0 Hz, 2H), 3.94 =d,
Jˆ7.5 Hz, 2H), 7.38±7.44 =m, 4H), 7.51 =dd, Jˆ1.5, 6.5 Hz,
2H), 7.55 =dd, Jˆ2.0, 7.5 Hz, 2H); 13C NMR =50 MHz,
DMSO-D6): d 34.72, 37.43, 50.59, 127.50, 129.49,

S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
3041
130.29, 130.80, 132.04, 135.21 191.28; IR =KBr): 3400,
3050, 1695, 1595, 1445 cm21
Anal. Calcd for
C20H12O2Cl4: C, 56.32; H, 2.84. Found: C, 56.43; H, 2.91.
1685, 1420, 1370, 1280, 1130, 1010, 870 cm21. Anal.
Calcd for C14H18O2Br2: C, 44.47; H, 4.80. Found: C,
44.66; H, 4.96.
.
3.3.12. 1,5-Dibromo-4,8-dimethyltricyclo[5.1.0.03,5]octane-
2,6-dione 11l). To a solution of diisopropylamine =0.094 g,
0.93 mmol) in 3 mL of THF was added n-BuLi =0.67 mL of
1.61 M in hexane, 1 mmol) at 08C. The solution was stirred
at this temperature for 20 min. Then to the solution was
added slowly 0.261 g =1.5 mmol) of dibromomethane at
2958C. The mixture was stirred for 30 min at this tempera-
ture. Then 0.114 g =1.0 mmol) of ethyl crotonate was added
to the ¯ask. The solution was stirred for 15 min at 2958C,
and then 10 mL of water was added to the ¯ask. The cooling
bath was removed. After the reaction mixture was allowed
to warm up to room temperature, 10% HCl solution was
added to acidify the solution. The solvent was concentrated
in vacuo. The solid was washed with diethyl ether to give
3.3.15. 1,5-Dibromo-4,8-diphenyltricyclo[5.1.0.03,5]octane-
2,6-dione 11o). To a solution of HMDS =0.775 g, 5.0 mmol)
in 5 mL of THF was added n-BuLi =2.71 mL of 1.62 M in
hexane, 4.4 mmol) at 08C. The solution was stirred at the
same temperature for 20 min. Then to the solution was
added slowly 0.765 g =4.4 mmol) of dibromomethane at
2958C. The mixture was stirred for 20 min at the same
temperature. Then 0.352 g =2.0 mmol) of ethyl =E)-cinna-
mate was added to the ¯ask. The solution was stirred for
15 min. 5 mL of water was added to the ¯ask. The cooling
bath was removed. After the mixture was allowed to warm
up to room temperature, 10% HCl solution was added to
acidify the solution. The solvent was removed in vacuo.
The solid was washed with diethyl ether to give 0.27 g
=60.8%) of 1o as a solid: mpˆ2248C =decomposition);
1H NMR =200 MHz, CDCl3) d 3.14 =d, Jˆ7.1 Hz, 2H),
3.20 =d, Jˆ7.0 Hz, 2H), 7.26±7.42 =m, 10H); IR =KBr):
3400, 3050, 3000, 1695, 1595, 1445 cm21. Anal. Calcd
for C20H14O2Br2: C, 53.84; H, 3.16. Found: C, 53.77; H,
3.27.
1
the 0.02 g =13%) of 1l: mpˆ1928C; H NMR =200 MHz,
CDCl3) d 1.49 =d, Jˆ6.1 Hz, 6H), 1.76±3.20 =m, 2H),
2.28=d, Jˆ6.3 Hz, 2H); 13C NMR =50 MHz, CDCl3) d
15.74, 27.39, 40.51, 41.06, 192.7; IR =KBr): 1675, 1420,
1370, 1270, 1121, 995 cm21
. Anal. Calcd for
C10H10O2Br2: C, 37.30; H, 3.13. Found: C, 37.11; H, 3.33.
3.3.13. 1,5-Dibromo-4,8-diethyltricyclo[5.1.0.03,5]octane-
2,6-dione 11m). To a solution of diisopropylamine =0.094 g,
0.93 mmol) in 3 mL of THF was added n-BuLi =0.67 mL of
1.6 M in hexane, 1 mmol) at 08C. The solution was stirred at
this temperature for 20 min. Then to the solution was added
slowly 0.261 g =1.5 mmol) of dibromomethane at 2958C.
The mixture was stirred for 20 min at this temperature. Then
0.128g =1.0 mmol) of ethyl E-2-pentenoate was added to
the ¯ask. The solution was stirred for 15 min. 5 mL of water
was added to the reaction bottle. The cooling bath was
removed. After the reaction mixture was allowed to warm
up to room temperature, 10% HCl solution was added to
acidify the solution. The solvent was removed in vacuo. The
solid was washed with diethyl ether to give 0.017 g
3.3.16.
1,5-Dibromo-4,8-di1 p-chlorophenyl)tricyclo-
[5.1.0.03,5]octane-2,6-dione 11p). To a solution of diiso-
propylamine =0.094 g, 0.93 mmol) in 3 mL of THF was
added n-BuLi =0.67 mL of 1.6 M in hexane, 1 mmol) at
08C. The solution was stirred at this temperature for
20 min. Then to the solution was added slowly 0.261 g
=1.5 mmol) of dibromomethane at 2958C. The mixture
was stirred for 20 min at the same temperature. Then
0.210 g =1.0 mmol) of ethyl =E)-4-chloro cinnamate was
added to the ¯ask. The solution was stirred for 15 min,
and then 5 mL of water was added to the ¯ask. The cooling
bath was removed. After the mixture was warmed up to
room temperature, 10% hydrochloric acid solution was
added to acidify the solution. The solvent was removed in
vacuo. The solid was washed with diethyl ether to give
0.092 g =35.7%) of 1p as a solid: mpˆ1838C =decomposi-
tion); 1H NMR =200 MHz, CDCl3) d 3.08=d, Jˆ6.7 Hz, 2H),
3.15 =d, Jˆ6.7 Hz, 2H), 7.21±7.41 =m, 8H); IR =KBr): 3050,
1
=10.4%)of 1m as a solid: mpˆ1638C; H NMR =200 MHz,
CDCl3) d 1.11 =t, Jˆ7.1 Hz, 6H), 1.58±1.91 =m, 6H), 2.32
=d, Jˆ6.1 Hz, 2H); 13C NMR =50 MHz, CDCl3) d 12.53,
24.63, 33.66, 39.70, 40.60, 192; IR =KBr): 1700, 1420,
1370, 1280, 1130, 1010, 870 cm21. Anal. Calcd for
C12H14O2Br2: C, 41.17; H, 4.03. Found: C, 41.03; H, 4.27.
2950, 1680, 1480, 1470, 1300, 1270, 1240, 1200 cm21
.
Anal. Calcd for C20H12O2Br2Cl2: C, 46.63; H, 2.34.
Found: C, 44.87; H, 2.50.
3.3.14. 1,5-Dibromo-4,8-dipropyltricyclo[5.1.0.03,5]octane-
2,6-dione 11n). To
a
solution of diisopropylamine
3.3.17.
1,5-Dibromo-4,8-di1 p-methylphenyl)tricyclo-
=0.094 g, 0.93 mmol) in 3 mL of THF was added n-BuLi
=0.67 mL of 1.6 M in hexane, 1 mmol) at 08C. The solution
was stirred at the same temperature for 20 min. Then to the
solution was added slowly 0.261 g =1.5 mmol) of dibromo-
methane at 2958C. The mixture was stirred for 20 min at
the same temperature. Then 0.142 g =1.0 mmol) of ethyl
=2E)-hexenoate was added to the ¯ask. The solution was
stirred for 15 min, and then 5 mL of water was added to
the ¯ask. The cooling bath was removed. After the mixture
was warmed up to room temperature, 10% HCl solution was
added to acidify the solution. The solvent was removed in
vacuo. The solid was washed with diethyl ether to give
0.01 g =5.3%) of 1n as a solid: mpˆ1138C =decomposition);
1H NMR =200 MHz, CDCl3) d 0.98=t, Jˆ7.1 Hz, 6H),
1.58±1.91 =m, 10H), 2.32 =d, Jˆ6.1 Hz, 2H); IR =KBr):
[5.1.0.03,5]octane-2,6-dione 11q). To a solution of diiso-
propylamine =0.094 g, 0.93 mmol) in 3 mL of THF was
added n-BuLi =0.67 mL of 1.6 M in hexane, 1 mmol) at
08C. The solution was stirred at the same temperature for
20 min. Then to the solution was added slowly 0.261 g
=1.5 mmol) of dibromomethane at 2958C. The mixture
was stirred for 20 min at this temperature. Then 0.190 g
=1.0 mmol) of ethyl =E)-4-methylcinnamate was added to
the ¯ask. The solution was stirred for 15 min and then
5 mL of water was added to the ¯ask. The cooling bath
was removed. After the mixture was allowed to warm up
to room temperature, 10% hydrochloric acid solution was
added to acidify the solution. The solvent was removed in
vacuo. The solid was washed with diethyl ether to give
0.042 g =19%) of 1q as a solid: mpˆ2158C =decomposition)

3042
S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
1H NMR =200 MHz, CDCl3) d 2.35 =s, 6H), 3.10 =d,
Jˆ6.7 Hz, 2H), 3.16 =d, Jˆ6.7 Hz, 2H), 7.14±7.24 =m,
8H); 13C NMR =50 MHz, CDCl3) d 21.22, 35.70, 38.21,
40.93, 128.3, 129.0, 129.6, 138.8, 191.6; IR =KBr) 3000,
2608C. The solution was stirred for 11 h at the same
temperature. Then the mixture was warmed up to 08C and
was stirred for 16 h. The reaction mixture was quenched
with ice-water, neutralized with 10% HCl, and extracted
with diethyl ether =10 mL£3). The combined organic
phase was washed with saturated sodium chloride, and
dried over anhydrous magnesium sulfate to give 0.232 g
1700, 1510, 1280, 1255, 1220, 1150, 1120, 1100 cm21
.
Anal. Calcd for C22H18O2Br2: C, 55.72; H, 3.28. Found:
C, 55.66; H, 3.79.
1
=53%) of 1s as a solid: mpˆ1058C =decomposition); H
3.3.18. Preparation of 1,5-dichloro-4,8-dimethyltri-
cyclo[5.1.0.03,5]octane-2,6-dione 11a) with 13E)-1,1-
dichloropenten-2-one. To a solution of 0.446 g =3 mmol)
of =3E)-1,1-dichloropenten-2-one in 10 mL of diethyl ether
was added sodium ethoxide =0.204 g, 3 mmol) at 278to
2608C. The solution was stirred for 7 h at the same
temperature. Then the mixture was warmed up to 08C and
was stirred for 37 h. The reaction mixture was quenched
with ice-water, neutralized with 10% HCl, and extracted
with diethyl ether =10 mL£3). The combined organic
phase was washed with saturated sodium chloride, and
dried over anhydrous magnesium sulfate. The solvent was
removed in vacuo to give 0.185 g =53%) of 1a.
NMR =200 MHz, CDCl3) d 0.88 =t, Jˆ6.84 Hz, 6H),
1.28±1.79 =m, 20H), 1.84 =q, Jˆ6.87 Hz, 2H), 2.23 =d,
Jˆ6.06 Hz, 2H); 13C NMR =50 MHz, CDCl3) d 13.99,
22.46, 28.13, 28.72, 31.49, 32.75, 39.84, 50.25, 192.67; IR
=KBr): 3400, 2940, 1695, 1295, 1100, 940, 870, 680, 970,
860 cm21. Anal. Calcd for C20H30Cl2O2: C, 64.34; H, 8.10.
Found: C, 64.67; H, 7.85.
3.3.22. Preparation of 1,5-dichloro-4,8-diphenyltricy-
clo[5.1.0.03,5]octane-2,6-dione 11h) with 1E)-1,1-di-
chloro-4-phenyl-3-butene-2-one in the presence of
sodium ethoxide. To a solution of 0.444 g =2.03 mmol) of
=3E)-1,1-dichloro-4-phenylbutene-2-one in 15 mL of
diethyl ether was added sodium ethoxide =0.139 g,
2.03 mmol) at 278to 2608C. The solution was stirred for
10 h at the same temperature. Then the mixture was warmed
up to 08C and was stirred for 13 h. The reaction mixture was
quenched with ice-water, neutralized with 10% HCl. The
residue was washed with ethyl acetate to give 0.182 g =70%)
of 1h.
3.3.19. Preparation of 1,5-dichloro-4,8-dipropyltri-
cyclo[5.1.0.03,5]octane-2,6-dione 11c) with 13E)-1,1-di-
chlorohepten-2-one. To a solution of 0.412 g =2.3 mmol)
of =3E)-1,1-dichlorohepten-2-one in 10 mL of diethyl ether
was added sodium ethoxide =0.155 g, 2.3 mmol) at 278to
2608C. The solution was stirred for 4 h at the same
temperature. Then the mixture was warmed up to 08C and
was stirred for 6 h. The reaction mixture was quenched with
ice-water, neutralized with 10% HCl, and extracted with
diethyl ether =10 mL£3). The combined organic phase
was washed with saturated sodium chloride, and dried
over anhydrous magnesium sulfate. The solvent was
removed in vacuo to give 0.188 g =57%) of 1c.
3.3.23. Preparation of 1,5-dichloro-4,8-diphenyltricy-
clo[5.1.0.03,5]octane-2,6-dione 11h) with 1E)-1,1-di-
chloro-4-phenyl-3-buten-2-one in the presence of
lithium hydroxide. To a solution of 0.197 g =0.92 mmol)
of =E)-1,1-dichloro-4-phenyl-3-buten-2-one in 1 mL of THF
was added a solution of 0.022 g =0.92 mmol) of lithium
hydroxide in 0.7 mL of water at 2958C. The solution was
stirred for 14 min, and 2 mL of water was added to the
reaction bottle at 2958C. The cooling bath was removed.
After the reaction mixture was warmed up room tempera-
ture, and 2 M hydrochloric acid solution was added to acid-
ify the solution. The solvent was removed in vacuo and the
precipitate was ®ltered and washed with ether to give
0.110 g =94%) of 1h.
3.3.20. Preparation of 1,5-dichloro-4,8-di110-propenyl)-
tricyclo[5.1.0.03,5]octane-2,6-dione 11r) with 13E, 5E)-
1,1-dichloroheptadien-2-one. To a solution of 0.539 g
=3 mmol) of =3E, 5E)-1,1-dichloroheptadien-2-one in
10 mL of diethyl ether was added sodium ethoxide
=0.222 g, 3 mmol) at 278to 2608C. The solution was stir-
red for 7 h at the same temperature. Then the mixture was
warmed up to 08C and was stirred for 88 h. The reaction
mixture was quenched with ice-water, neutralized with 10%
HCl, and extracted with diethyl ether =10 mL£3). The
combined organic phase was washed with saturated
sodium chloride, and dried over anhydrous magnesium sul-
fate to give 0.204 g =48%) of 1r as a solid: mpˆ1538C
=decomposition); 1H NMR =200 MHz, CDCl3) d 1.74±
1.79 =dd, Jˆ1.85, 6.62 Hz, 6H), 2.47±2.60 =m, 4H), 5.20±
5.33 =dq, Jˆ7.74, 1.68Hz, 2H), 5.83±5.97 =m, 2H); 13C
NMR =50 MHz, CDCl3) d 18.22, 34.65, 39.93, 49.71
122.21, 134.59, 190.84; IR =KBr): 3050, 1700, 1290,
1235, 1155, 1045, 970, 860, 795, 665 cm21. Anal. Calcd
for C14H14Cl2O2: C, 58.97; H, 4.95. Found: C, 58.74; H,
4.98.
3.3.24. Preparation of 1,5-dichloro-4,8-di13,4-methylene-
dioxa)phenyltricyclo[5.1.0.03,5]octane-2,6-dione 11t) with
13E)-1,1-dichloro-4-13,4-methylenedioxa)phenylbuten-2-
one. To a solution of 0.154 g =0.6 mmol) of =3E)-1,1-
dichloro-4-=3,4-methylenedioxa)phenylbuten-2-one in 5 mL
of diethyl ether was added sodium ethoxide =0.041 g,
0.6 mmol) at 278to 2608C. The solution was stirred for
8h at the same temperature. Then the mixture was warmed
up to 08C and was stirred for 16 h. The reaction mixture was
quenched with ice-water, neutralized with 10% HCl, and
extracted with diethyl ether =10 mL£3). The combined
organic phase was washed with saturated sodium chloride,
and dried over anhydrous magnesium sulfate to give 0.081 g
=71%) of 1t as a solid: mp: 1718C =decomposition); 1H NMR
=200 MHz, CDCl3) d 2.97 =d, Jˆ6.84 Hz, 2H), 3.22 =d,
Jˆ6.84 Hz, 2H), 6.00 =s, 4H), 6.74±6.83 =m, 3H); IR
=KBr): 2900, 1695, 1490, 1445, 1350, 1295, 845, 800,
710, 670 cm21. Anal. Calcd for C22H14Cl2O2: C, 59.35; H,
3.17. Found: C, 59.30; H, 3.13.
3.3.21. Preparation of 1,5-dichloro-4,8-dihexyltricyclo-
[5.1.0.03,5]octane-2,6-dione 11s) with 1E)-1,1-dichloro-3-
decen-2-one. To a solution of 0.52 g =2.33 mmol) of =E)-
1,1-dichloro-3-decen-2-one in 15 mL of diethyl ether was
added sodium ethoxide =0.16 g, 2.3 mmol) at 278to

S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
3043
3.3.25. 1E)-1,1-Dichloro-3-penten-2-one 13a). Step 1: To a
solution of 2.40 g =30 mmol) of dried dichloromethane in
40 mL of THF was added 18mL =30 mmol) BuLi =1.6 M in
hexane) at 2958C in 30 min, and then 2.10 g =30 mmol) of
=2E)-butenal was added. The mixture was stirred for 2.5 h at
the same temperature. The reaction was quenched with ice-
water, neutralized with 10% HCl, extracted with ethyl
acetate =20 mL£3). The organic phases were combined,
washed with saturated NaCl solution, and dried over
anhydrous magnesium sulfate. The solvent was removed
and the crude product was puri®ed on silica gel chromato-
graphy =hexane/ethyl acetate 30:1) to give 4.05 g =87%) of
=E)-1,1-dichloro-3-penten-2-ol. Step 2: To a solution of
30.7 g =350 mmol) of manganese dioxide in 35 mL of
dried hexane was added 2.72 g =17.5 mmol) of =E)-1,1-
dichloro-3-penten-2-ol, and stirred for 20 h at room
temperature. The excess of MnO2 was ®ltrated out and the
solvent was removed in vacuo and the residue was puri®ed
on silica gel chromatography to give 1.89 g =71%) of 3a: 1H
NMR =60 MHz, CCl4) d 2.01 =d, Jˆ6.0 Hz, 3H), 5.72 =s,
1H), 6.22±7.14 =m, 2H); IR =neat): 2950, 1700, 1625, 1440,
3.3.28. 13E, 5E)-1,1-Dichloroheptadien-2-one 13r). Step
1: To a solution of 0.8g =10 mmol) of dried dichloro-
methane in 30 mL of THF was added 6.2 mL of BuLi
=1.6 M in hexane, 10 mmol) at 2958C in 30 min, and then
0.96 g =10 mmol) of =2E, 4E)-1,1-dichloro-hexadienal was
added. The mixture was stirred for 2.5 h at the same
temperature. The reaction was quenched with ice-water,
neutralized with 10% HCl, extracted with ethyl acetate
=20 mL£3). The organic phases were combined, washed
with saturated NaCl solution, and dried over anhydrous
magnesium sulfate. The solvent was removed and the
crude product was puri®ed on silica gel chromatography
=hexane/ethyl acetate 30:1) to give 1.27 g =71%) of =3E,
5E)-1,1-dichloroheptadien-2-ol. Step 2: To a solution of
13.2 g =160 mmol) of manganese dioxide in 30 mL of
dried hexane was added 1.32 g =7.9 mmol) of =3E, 5E)-
1,1-dichloro-heptadien-2-ol, and stirred for 42 h at room
temperature. The excess of MnO2 was ®ltrated out and the
solvent was removed in vacuo and the residue was puri®ed
on silica gel chromatography =hexane/ethyl acetate 30:1) to
give 0.838 g =59.7%) of 3r: 1H NMR =60 MHz, CCl4) d 2.60
=d, Jˆ5.0 Hz, 3H), 5.75 =s, 1H), 6.15±7.51 =m, 4H); IR
=neat): 2980, 1690, 1630, 1590, 1440, 1375, 1330, 1240,
1130, 1060, 1000, 810, 760 cm21. Anal. Calcd for
C7H8Cl2O2: C, 46.96; H, 4.50. Found: C, 47.02; H, 4.47.
1290, 765, 710 cm21
.
3.3.26. 1E)-1,1-Dichloro-3-hepten-2-one 13c). Step 1: To a
solution of 2.40 g =30 mmol) of dried dichloromethane in
30 mL of THF was added 18mL =30 mmol) BuLi =1.6 M in
hexane) at 2958C in 30 min, and then 2.99 g =30 mmol) of
=2E)-hexenal was added. The mixture was stirred for 2.5 h at
the same temperature. The reaction was quenched with ice-
water, neutralized with 10% HCl, extracted with ethyl
acetate =20 mL£3). The organic phases were combined,
washed with saturated NaCl solution, and dried over
anhydrous magnesium sulfate. The solvent was removed
and the crude product was puri®ed on silica gel chromato-
graphy =hexane/ethyl acetate 30:1) to give 3.92 g =21 mmol,
71%) of 1,1-dichloro-3-hepten-2-ol. Step 2: To a solution of
7.80 g =89.3 mmol) of manganese dioxide in 30 mL of dried
hexane was added 0.817 g =4.46 mmol) of =E)-1,1-dichloro-
3-hepten-2-ol, and stirred for 23 h at room temperature. The
excess of MnO2 was ®ltrated out and the solvent was
removed in vacuo and the residue was puri®ed on silica
3.3.29. 13E)-1,1-Dichlorodecen-2-one 13s). Step 1: To a
solution of 1.7 g =20 mmol) of dried dichloromethane in
10 mL of THF was added 12.8mL =20 mmol) BuLi
=1.6 M in hexane) at 2958C in 30 min, and then 0.82 g
=5.82 mmol) of =2E)-1,1-dichlorononenal was added. The
mixture was stirred for 2.5 h at the same temperature. The
reaction was quenched with ice-water, neutralized with 10%
HCl, extracted with ethyl acetate =20 mL£3). The organic
phases were combined, washed with saturated NaCl
solution, and dried over anhydrous magnesium sulfate.
The solvent was removed to give 1.25 g of the crude
product of =3E)-1,1-dichloro-nonen-2-ol. Step 2: To a
solution of 10.2 g =117 mmol) of manganese dioxide in
20 mL of dried hexane was added 1.25 g of the crude
product of =3E)-1,1-dichloro-nonen-2-ol, and was stirred
1
gel chromatography to give 0.409 g =51%) of 3c: H NMR
for 4.8days at room temperature. The excess of MnO
2
=60 MHz, CCl4) d 0.96 =t, Jˆ6.2 Hz, 3H), 1.25±1.72 =m,
2H), 2.06±2.35 =m, 2H), 5.76 =s, 1H), 6.22±7.32 =m, 2H); IR
=neat): 2980, 1700, 1620, 1460, 1380, 1300, 1160,
was ®ltrated out and the solvent was removed in vacuo.
The residue was puri®ed on silica gel chromatography =hex-
ane/ethyl acetate 30:1) to give 0.29 g =in two steps yield
44.5%) of 3s: IR =neat): 2925, 1690, 1620, 1460, 1460,
1210, 1150, 960, 790.
980 cm21
.
3.3.27. 1E)-1,1-Dichloro-4-phenyl-3-buten-2-one 13h). To
a solution of 1.59 g =9.0 mmol) of ethyl =E)-cinnamate and
1.01 g =12 mmol) of dichloromethane in 10 mL of THF was
added 8.7 mmol of LDA at 2958C for 15 min. The solution
was stirred for 30 min at the same temperature. Then the
reaction mixture was quenched with 10% HCl at 2958C,
and extracted with diethyl ether =10 mL£3). The combined
organic phase was washed with saturated sodium chloride,
and dried over anhydrous magnesium sulfate. The crude
product was puri®ed on a silica gel chromatography =hex-
3.3.30. 13E)-1,1-Dichloro-4130,40-methylenedioxyphenyl)-
buten-2-one 13t). Step 1: To a solution of 0.252 g
=3 mmol) of dried dichloromethane in 10 mL of THF was
added 1.78mL =3 mmol) BuLi =1.6 M in hexane) at 2958C
in 30 min, and then 0.50 g =2.8mmol) of =3 E)-1,1-dichloro-
4-=30,40-methylenedioxyphenyl)butenal was added. The
mixture was stirred for 2.5 h at the same temperature. The
reaction was quenched with ice-water, neutralized with 10%
HCl, extracted with ethyl acetate =20 mL£3). The organic
phases were combined, washed with saturated NaCl solu-
tion, and dried over anhydrous magnesium sulfate. The
solvent was removed to give 0.799 g of the crude product
of =3E)-1,1-dichloro-4=30,40-methylene-dioxyphenyl)buten-
2-ol. Step 2: To a solution of 5.22 g =60 mmol) of manga-
nese dioxide in 20 mL of dried hexane was added 0.799 g of
1
ane/ethyl acetate 100:1) to give 0.767 g =41%) of 3h. H
NMR =200 MHz, CDCl3) d 5.99 =s, 1H), 7.20 =d,
Jˆ16 Hz, 1H), 7.42±7.46 =m, 3H), 7.62±7.67 =m, 2H),
7.90 =d, Jˆ16 Hz, 1H); 13C NMR =50 MHz, CDCl3) d
69.80, 117.54, 128.87, 129.06, 131.50, 133.80, 147.98,
185.73.

3044
S. Tsuboi et al. / Tetrahedron 57 ,2001) 3035±3044
the crude product of =3E)-1,1-dichloro-4-=30,40-methylene-
dioxyphenyl)buten-2-ol, and stirred for 67 h at room
temperature. The excess of MnO2 was ®ltrated out and the
solvent was removed in vacuo and the residue was puri®ed
on silica gel chromatography =hexane/ethyl acetate 30:1) to
give 0.141 g =in two steps yield 19.8%) of 3t: H NMR
=60 MHz, CCl4) d 5.76 =s, 1H), 5.94 =s, 2H), 6.76 =m,
2H), 7.01 =m, 3H).
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saturated esters 5a±o. To a solution of n-BuLi =1.61 M in
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204 mg =1 mmol), 1h: 76 mg =43.4%); 5o: 204 mg
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Acknowledgements
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We are grateful to SC-NMR Laboratory of Okayama
University for the measurement of NMR spectra. We also
thank Emeritus Professor Masanori Utaka for fruitful
discussion.