Nickel(0)-catalyzed dimerization of ethyl cyclopropylideneacetates

Article abstract of DOI:10.1021/jo0255678

The dimerization of ethyl cyclopropylideneacetates proceeded in the presence of Ni(0) catalysts, and cyclic compounds or linear compounds were formed in selective manners. The structures of products were highly dependent on the structure of the substrate

Full text of DOI:10.1021/jo0255678

Nick el(0)-Ca ta lyzed Dim er iza tion of Eth yl
Cyclop r op ylid en ea ceta tes
Taishi Kawasaki,† Shinichi Saito,*,‡ and Yoshinori Yamamoto*,†
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, J apan, and
Institute for Chemical Reaction Science, Tohoku University, Sendai 980-8578, J apan
ssaito@ch.kagu.tus.ac.jp
Received J anuary 30, 2002
The dimerization of ethyl cyclopropylideneacetates proceeded in the presence of Ni(0) catalysts,
and cyclic compounds or linear compounds were formed in selective manners. The structures of
products were highly dependent on the structure of the substrate and the ligands bound to the
catalyst. The mechanism of the reactions was discussed in detail.
In tr od u ction
Compared to that of the unsubstituted methylenecy-
clopropane, the reactivity of substituted methylenecyclo-
propanes is lower. Though a large number of the codimer-
izations of substituted methylenecyclopropanes with
olefins have been reported in the literature,1 fewer
examples of homodimerization reactions have been re-
ported.1,5
Alkylidenecyclopropanes are strained reactive mol-
ecules, and many transition-metal catalyzed reactions
have been reported.1 For example, unsubstituted meth-
ylenecyclopropane cyclodimerized in the presence of Ni
or Pd catalyst and the formation of cyclobutane and
cyclopentane derivatives have been reported (eq 1).2 In
We have recently examined the reactivities of unsatur-
ated hydrocarbons such as conjugated enynes6 and al-
lenes7 in the presence of nickel(0) catalysts and discov-
ered that the reactivities of these compounds changed
dramatically by the introduction of an electron-with-
drawing group to the hydrocarbons. These studies led us
to examine the reactivities of electron-deficient alky-
lidenecyclopropanes in the presence of nickel catalysts.
In this paper, we report the dimerization reactions of
ethyl cyclopropylideneacetates in the presence of nickel
catalysts.
the presence of similar catalysts, methylenecyclopropane
also reacted with unsaturated hydrocarbons and cyclo-
pentane derivatives were isolated (eq 2).3 The cleavage
Resu lts
Ethyl cyclopropylideneacetate (1) dimerized in the
presence of Ni(0) catalysts at room temperature. The
distribution of the products was highly dependent on the
ligand bound to the Ni catalyst, and the results were
summarized in Table 1. Thus, the formation of cyclopen-
tane derivatives such as 2 and 3 was observed when the
reaction was carried out in the presence of Ni-PPh3
complexes, which were prepared in situ from Ni(cod)2 and
PPh3 (entries 1-2). Higher selectivity was observed when
the reaction was carried out at 80 °C (entry 3). On the
other hand, the formation of cyclohexane derivatives (4
and 5) was observed when the reaction was carried out
in the presence of Ni(cod)2 alone or in the presence of
the Ni-P(o-tol)3 complex (entries 4-5).
of the distal bond and proximal bond was observed,
depending on various factors such as the reaction condi-
tion and the structure of the substrate.4
† Department of Chemistry, Tohoku University.
‡ Institute for Chemical Reaction Science, Tohoku University.
Current address: Department of Chemistry, Faculty of Science, Tokyo
University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601,
J apan.
(1) Reviews: (a) Binger, P.; Bu¨ch, H. M. Top. Curr. Chem. 1987,
135, 77-151. (b) Dzhemilev, U. M.; Khusnutdinov, R. I.; Tolstikov, G.
A. J . Organomet. Chem. 1991, 409, 15-65. (c) Binger, P.; Schmidt, T.
Metal-Catalyzed Cycloadditions of Methylenecyclopropanes. In Car-
bocyclic Three- and Four-Membered Ring Compounds; Houben-Weyl,
de Meijere, A., Eds.; Thieme: Stuttgart, 1997; Vol. E 17b, pp 2217-
2294.
(2) Binger, P. Angew. Chem., Int. Ed. Engl. 1972, 11, 309-310.
(3) Noyori, R.; Odagi, T.; Furukawa, J . J . Am. Chem. Soc. 1970, 92,
5780-5781.
(4) Binger, P.; Wedemann, P. Tetrahedron Lett. 1985, 26, 1045-
1048.
(5) Binger, P.; Germer, A. Chem. Ber. 1981, 114, 3325-3335.
(6) (a) Saito, S.; Tanaka, T.; Koizumi, T.; Tsuboya, N.; Itagaki, H.;
Kawasaki, T.; Endo, S.; Yamamoto, Y. J . Am. Chem. Soc. 2000, 122,
1810-1811. (b) Saito, S.; Kawasaki, T.; Tsuboya, N.; Yamamoto, Y. J .
Org. Chem. 2001, 66, 796-802.
(7) Saito, S.; Hirayama, K.; Kabuto, C.; Yamamoto, Y. J . Am. Chem.
Soc. 2000, 122, 10776-10780.
10.1021/jo0255678 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/06/2002
J . Org. Chem. 2002, 67, 4911-4915
4911

Kawasaki et al.
TABLE 1. Nick el-Ca ta lyzed Dim er iza tion of Eth yl
Cyclop r op ylid en ea ceta te (1)
room temperature. However, the formation of a dimerized
product 11 was observed after prolonged heating at 50
°C (eq 5). The reaction of 12 also proceeded at 50 °C, but
the product turned out to be a complex mixture of
dimerized compounds (eq 6).8
yield (%)
entry
ligand (mol %)
timea (h)
2
3
4
5
1
2
PPh3 (40)
PPh3 (20)
PPh3 (20)
4
2
39
52
0
2
8
22
28
74
6
3
1b
4c
5c
42
0.25
21
20
2
9
Finally, we examined the [3 + 2] cycloaddition reac-
tions of 1 and 6 with methyl fumarate 13 to compare the
reactivities of the compounds. Unlike the results pro-
duced by dimerization reactions, similar products were
isolated in these reactions. Thus, cyclopentane deriva-
tives 14 and 15 were isolated respectively in the reactions
of 1 and 6 with 13 in the presence of the Ni-PPh3
complex (eqs 7 and 8). In both reactions, the cleavage of
P(o-tol)3 (20)
32
a
The progress of the reaction was monitored by TLC until
compound 1 disappeared. The reaction was carried out at 80 °C.
A similar result was obtained when the reaction was carried out
b
at 100 °C. c NMR yields (%).
We next examined the reaction of ethyl cyclopropy-
lidenepropanoate (6) in the presence of Ni catalysts.
Though the rate of the reaction of 6 was very slow at
room temperature and at 50 °C, the formation of a linear
dimer 7 was observed when the reaction was carried out
at 80 °C in the presence of the Ni-PPh3 complex (eq 3).
When the catalyst was switched to the Ni-P(o-tol)3
complex, a drastic change was observed and cyclopentane
derivatives 8 and 9 were isolated as the products at room
temperature (eq 4). On the other hand, the formation of
the distal bond was observed. It is noteworthy that these
reactions did not proceed at room temparature.
Discu ssion
Though it has been reported that unsubstituted me-
thylenecyclpropane cyclodimerized in the presence of
nickel catalyst, the homodimerization reactions of sub-
stituted methylenecyclopropanes have been scarcely
reported. To the best of our knowledge, the reactions of
a few methylenecyclopropanes such as 1-methylene-2-
vinylcyclopropane,5 2-methyl-1-methylenecyclopropane,
and 2,2-dimethyl-1-methylenecyclopropane1 are the only
transition metal-catalyzed cyclodimerization reactions
reported to date. We have shown that the dimerization
of some electron-deficient ethoxycarbonyl methylenecy-
clopropanes proceeded under mild conditions, while the
reactivity of alkyl- or arylmethylenecyclopropanes is
considerably lower. Since the Ni-catalyzed reaction of
alkylmethylenecyclopropanes with olefins proceeded
a complex mixture was observed when 6 was treated with
Ni(cod)2 (result not shown). It is noteworthy that the
products observed in the reaction of 6 were quite different
from those observed in the reaction of 1.
Though the reactivity of unsubstituted methylenecy-
clopropane is comparable to the reactivities of 1 and 6
and many examples for the codimerization of the sub-
stituted methylenecyclopropanes with olefins have been
reported, the reactivity of substituted methylenecyclo-
propanes in the homodimerization reactions has been
scarcely reported in the literature.1,5 We carried out the
reactions of non-electron-deficient methylenecyclopro-
panes such as 10 and 12 and compared the reactivities
of 10 and 12 with those of 1 and 6 (eqs 5 and 6). The
reactivity of 10 was lower, and no reaction took place at
(8) Similar results were obtained when the reactions were carried
out at 80 °C and/or in the presence of a smaller amount (20 mol %) of
PPh3. The result of the reaction which gave the best isolated yield was
shown.
4912 J . Org. Chem., Vol. 67, No. 14, 2002

Dimerization of Ethyl Cyclopropylideneacetates
SCHEME 1
condition. In the presence of P(o-tol)3 or in the absence
of the ligand, however, another rearrangement might
take place, and a nickelacycloheptane 20 (or 21) might
be formed (path d). Cyclohexane 4 (or 5) would be formed
by the reductive elimination of the Ni complex. In the
reactions of 1, the cleavage of the proximal bond of the
cyclopropane ring always took place.
On the other hand, the cleavage of the distal bond of
the cyclopropane ring took place in the reactions of 6,
and the proposed mechanisms of the reactions were
summarized in Scheme 2. In contrast to the reactions of
1, the cleavage of the proximal bond would be suppressed
by the strong steric hindrance of the substituents, and
the less sterically hindered nickelacyclobutane 22 or the
isomers such as 23 and 24 would be formed by the
cleavage of the distal bond. These complexes will further
react with the double bond of 6 to yield a π-allyl
intermediate 25 (or 26). In the presence of the P(o-tol)3
ligand, the formation of the nickelacyclohexane 27 and
the reductive elimination of the nickel catalyst will follow,
and the cyclopentane 8 (or 9) would be formed (path a).
However, in the presence of Ni-PPh3 catalyst, a more
sterically hindered nickelacyclohexane 29 would be gen-
erated because the ligand (PPh3) bound to the Ni atom
is less bulky (path b). The â-elimination of the nickel
hydride would follow, and the linear dimer 7 would be
isolated as the product.
While the reaction of 6 with methyl fumarate (13)
proceeded as we expected and the formation of the
cyclopentane 15 was observed by the cleavage of the
distal bond, the result of the reaction of 1 with 13 was
unexpected. In this reaction, the distal bond was cleaved,
and the cyclopentane derivative 14 was isolated. This
result is in sharp contrast to the result of the cyclodimer-
ization of 1, where the cleavage of the proximal bond was
observed (Table 1). Since the coordination ability of 13
is very strong12 and an excess of 13 was present in the
reaction mixture, it is likely that 13 strongly interacts
with the Ni catalyst and the formation of 16 was
suppressed (Scheme 3). Instead, the generated fumarate
complex 31 would further react with 1 and complex 34
would be generated. The cleavage of the distal bond
would occur probably because of the steric and/or elec-
tronic effect of 13 bound to the Ni atom. A similar result
has been reported by Binger and Wedemann in the
reaction of unsubstituted methylenecyclopropane with
acrylates and fumarates. While the cleavage of the
proximal bond occurred in the reactions of acrylates with
methylenecyclopropane, the cleavage of the distal bond
was observed in the reactions of fumarates.4
under milder conditions when an electron-withdrawing
group was introduced to the olefin,1,9 the enhanced
reactivities of electron-deficient methylenecyclopropanes
could be explained in terms of the enhanced reactivity
of the carbon-carbon double bond of the methylenecy-
clopropane. The reactivity of this bond was further
enhanced by the strain induced by the cyclopropyl ring.
It is noteworthy that the structures of products in the
dimerization reactions of 1 and 6 were quite different,
depending on several factors such as the structure of the
starting material and the ligand. In the reaction of 1,
cyclopentane derivatives 2 and 3 were isolated when the
Ni-catalyzed reaction was carried out in the presence of
PPh3, while cyclohexanes 4 and 5 were also isolated in
the presence of P(o-tol)3 or in the absence of the phos-
phine ligand. The formation of these products could be
explained by proposing Scheme 1 as the mechanism of
this reaction. Thus, compound 1 was activated by the
coordination of Ni catalyst, and a nickelacyclobutane 16
(path a) or a nickelacyclopentane 17 (path b) would be
generated. The nickelacyclohexane 18 would be formed
by the addition of nickelacyclobutane 16 to 1 or by the
cyclopropenyl-butenyl rearrangement10 of 17.11 The
reductive elimination of the nickel catalyst will follow,
and the cyclopentane derivative 2 (3) will be formed in
the presence of PPh3 ligand (path c). Though we did not
confirm that the isomerization of 2 to 3 took place under
the reaction condition, the observed high selectivity of
this reaction at high temperature strongly indicates that
the isomerization of 2 proceeds under the reaction
Con clu sion
We examined the Ni-catalyzed dimerization of ethyl
cyclopropylideneacetates for the first time and found that
the [3 + 2] cyclodimerizations and linear dimerizations
proceeded in the presence of Ni catalysts under mild
(9) Other examples: (a) Binger, P. Synthesis 1973, 427-428. (b)
Noyori, R.; Odagi, T.; Furukawa, J . J . Am. Chem. Soc. 1972, 94, 4018-
4020. (c) Binger, P.; Brinkmann, A.; Wedemann, P. Chem. Ber. 1983,
116, 2920-2930.
(10) The structures of some intermediates proposed in Scheme 1
have been isolated or characterized spectroscopically. The cycloprope-
nyl-butenyl rearrangement has also been observed. See: Binger, P.;
Doyle, M. J .; Benn, R. Chem. Ber. 1983, 116, 1-10.
(11) A reviewer has pointed out the possibility of the formation of a
nickelaspiroheptane as an intermediate, which might be generated by
the oxidative addition of 16 to 1.
(12) Closely related Ni, Pd, and Pt species formed more stable
π-complexes with olefins having substituents of greater electron-
withdrawing abilities. See: Chatt, J .; Rowe, G. A.; Williams, A. A. Proc.
Chem. Soc. 1957, 208. Greaves, E. O.; Lock, C. J . L.; Maitlis, P. M.
Can. J . Chem. 1968, 46, 3879-3891. Takahashi, S.; Hagihara, N.
Nippon Kagaku Zasshi 1967, 88, 1306-1310. Yamamoto, T.; Yama-
moto, A.; Ikeda, S. J . Am. Chem. Soc. 1971, 93, 3360-3364.
J . Org. Chem, Vol. 67, No. 14, 2002 4913

Kawasaki et al.
SCHEME 2
SCHEME 3
Exp er im en ta l Section
Methylenecyclopropanes 1,4,14 6,15 10,16,17 and 1217,18 were
prepared as reported. Other reagents were commercially
available and used without further purification. The nickel-
catalyzed reactions were carried out under Ar. The structures
of 2, 3, 7, 8, and 9 were further confirmed by carrying out NOE
experiments (see Supporting Information).
Nick el(0)-Ca ta lyzed Rea ction of Electr on -Deficien t
Meth ylen ecyclop r op a n es. A Rep r esen ta tive P r oced u r e.
To a dark red mixture of Ni(cod)2 (13.8 mg, 0.05 mmol) and
PPh3 (27 mg, 0.1 mmol) in dry toluene (0.25 mL) was added a
solution of 1 (63 mg, 0.5 mmol) in dry toluene (0.25 mL) at
room temperature. The progress of the reaction was monitored
by TLC, and the mixture was stirred until the starting
material disappeared (2 h). The mixture was passed through
a short silica gel column (hexane and ether) and evaporated.
The residue was further purified by MPLC (hexane/AcOEt 15:
1) to give 2 (33 mg, 52%) and 3 (18 mg, 28%). Other reactions
were carried out under the same conditions except for the time
and temperature, which have already been described (vide
supra).
conditions. The reactivities of the methylenecyclopro-
panes were enhanced by the introduction of an electron-
withdrawing ethoxycarbonyl group. The mode of the
reactions was significantly affected by the structure of
substrates and the ligand bound to the Ni catalyst, and
the mechanisms of the reactions were proposed. This
study provided a new synthetic method for the prepara-
tion of functionalized spiro compounds containing cyclo-
propyl rings, some of which are known as antitumor
agents.13
(Z)-4-E t h oxyca r b on yl-7-(et h oxyca r b on ylm et h ylen e)-
sp ir o[2.4]h ep ta n e (2): colorless oil; 1H NMR (300 MHz,
CDCl3) 5.62 (dd, J ) 1.8, 1.8 Hz, 1H), 4.14-4.00 (m, 4H), 3.01-
2.90 (m, 1H), 2.65-2.55 (m, 2H), 2.18-1.92 (m, 3H), 1.85-
(14) Miller, S. A.; Gadwood, R. C. Organic Syntheses; Wiley &
Sons: New York, 1993; Collect. Vol. VIII, pp 556-562.
(15) Kortmann, I.; Westermann, B. Synthesis 1995, 931-933.
(16) Schweizer, E. E.; Berninger, C. J .; Thompson, J . G. J . Org.
Chem. 1968, 33, 336-339.
(17) Utimoto, K.; Tamura, M.; Sisido, K. Tetrahedron 1973, 29,
1169-1171.
(18) Nemoto, H.; Miyata, J .; Hakamata, H.; Nagamochi, M.; Fuku-
moto, K. Tetrahedron 1995, 51, 5511-5522.
(13) McMorris, T. C. Bioorg. Med. Chem. 1999, 7, 881-886.
4914 J . Org. Chem., Vol. 67, No. 14, 2002

Dimerization of Ethyl Cyclopropylideneacetates
1.77 (m, 1H), 1.23 (dd, J ) 7.2, 7.2 Hz, 3H), 1.21 (dd, J ) 7.1,
7.1 Hz, 3H), 1.01-0.92 (m, 2H); 13C NMR (75 MHz, CDCl3)
174.2, 168.4, 165.2, 108.9, 60.4, 59.5, 54.6, 38.3, 29.3, 27.3, 20.1,
14.4, 14.3, 14.2; IR (neat) 2980, 2905, 1736, 1719, 1639, 1560,
(Z)-4-E t h oxyca r b on y-6-(1-et h oxyca r b on yl-1-m et h yl-
m eth ylen e)sp ir o[2.4]h ep ta n e (9): colorless oil; 1H NMR (300
MHz, CDCl3) 4.16 (ddd, J ) 7.1, 7.1, 7.1 Hz, 2H), 4.07 (ddd, J
) 7.1, 7.1, 7.1 Hz, 2H), 3.52 (ddd, J ) 18.7, 2.0, 2.0 Hz, 1H),
2.77 (ddd, J ) 18.7, 2.2, 2.2 Hz, 1H), 2.61 (d, J ) 17.9 Hz,
1H), 2.38 (d, J ) 18.4 Hz, 1H), 1.78 (s, 3H), 1.28 (dd, J ) 7.2,
7.2 Hz, 3H), 1.20 (dd, J ) 7.1, 7.1 Hz, 3H), 1.04 (s, 3H), 0.80-
0.73 (m, 1H), 0.57-0.46 (m, 2H), 0.35-0.28 (m, 1H); 13C NMR
(75 MHz, CDCl3) 175.8, 168.1, 155.7, 119.1, 60.3, 59.9, 50.6,
45.7, 43.3, 27.4, 20.3, 15.7, 14.4, 14.2, 9.5, 9.1; IR (neat) 3078,
2982, 2936, 2905, 2827, 1726, 1708, 1647, 1462, 1421, 1366,
1460, 1448, 1425, 1383, 1346, 1269, 1180, 1096, 1040 cm-1
.
HRMS Calcd for C14H20O4: 252.1360. Found: 252.1368. Anal.
Calcd for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.71; H, 7.99.
(E)-4-E t h oxyca r b on yl-7-(et h oxyca r b on ylm et h ylen e)-
sp ir o[2.4]h ep ta n e (3): colorless oil; 1H NMR (300 MHz,
CDCl3) 5.11 (dd, J ) 2.4, 2.4 Hz, 1H), 4.15-4.04 (m, 4H), 3.21-
3.01 (m, 2H), 2.65 (dd, J ) 7.2, 5.2 Hz, 1H), 2.22-2.00 (m,
2H), 1.24 (dd, J ) 7.2, 7.2 Hz, 3H), 1.22 (dd, J ) 7.1, 7.1 Hz,
3H), 1.11-1.05 (m, 2H), 0.97-0.84 (m, 2H); 13C NMR (75 MHz,
CDCl3) 173.9, 172.1, 167.0, 105.1, 60.4, 59.5, 50.4, 32.8, 30.5,
27.8, 21.3, 15.6, 14.3, 14.2; IR (neat) 3078, 2980, 2937, 2907,
2874, 1736, 1713, 1647, 1458, 1448, 1369, 1348, 1327, 1261,
1319, 1283, 1240, 1204, 1173, 1153, 1096, 1057, 1024 cm-1
.
HRMS Calcd for C16H24O4: 280.1673. Found: 280.1661. Anal.
Calcd for C16H24O4: C, 68.54; H, 8.63. Found: C, 68.46; H, 8.72.
(Z)-5-Ben zyl-3-ph en ylm eth ylen e-1,5-h exadien e (11): col-
orless oil; 1H NMR (300 MHz, CDCl3) 7.35-7.18 (m, 10H), 6.79
(ddd, J ) 17.5, 11.1, 0.9 Hz, 1H), 6.41 (s, 1H), 5.26 (d, J )
17.6 Hz, 1H), 5.11 (ddd, J ) 11.0, 1.5, 1.5 Hz, 1H), 4.95 (s,
1H), 4.88 (s, 1H), 3.38 (s, 2H), 3.03 (s, 2H); 13C NMR (75 MHz,
CDCl3) 147.0, 139.6, 137.3, 136.1, 133.9, 131.5, 129.4, 129.1,
128.3, 128.1, 126.7, 126.1, 115.9, 113.4, 42.8, 40.3; IR (neat)
3082, 3061, 3026, 2905, 1749, 1734, 1717, 1699, 1684, 1670,
1647, 1601, 1576, 1558, 1541, 1522, 1508, 1493, 1474, 1456,
1437, 1394, 1339, 1074, 1030, 1003 cm-1. HRMS Calcd for
1177, 1161, 1096, 1078, 1040 cm-1
14H20O4: 252.1360. Found: 252.1350. Anal. Calcd for
. HRMS Calcd for
C
C14H20O4: C, 66.65; H, 7.99. Found: C, 66.60; H, 8.16.
(1E,2Z)-Di(eth oxyca r bon ylm eth ylen e)cycloh exa n e (4):
1
colorless oil; H NMR (300 MHz, CDCl3) 5.64 (s, 1H), 5.59 (s,
1H), 4.13 (ddd, J ) 7.2, 7.2, 7.2 Hz, 2H), 4.10 (ddd, J ) 7.1,
7.1, 7.1 Hz, 2H), 3.01-3.00 (m, 2H), 2.33-2.31 (m, 2H), 1.75
(dd, J ) 3.2, 3.1 Hz, 4H), 1.25 (dd, J ) 7.3, 7.3 Hz, 3H), 1.20
(dd, J ) 7.2, 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) 166.2,
165.9, 158.1, 157.9, 115.2, 114.6, 60.1, 59.8, 39.1, 30.9, 28.0,
27.5, 14.2, 14.0; IR (neat) 2982, 2937, 2860, 1715, 1639, 1445,
1371, 1304, 1269, 1225, 1190, 1161, 1134, 1096, 1061, 1036
cm-1. HRMS Calcd for C14H20O4: 252.1360. Found: 252.1333.
Anal. Calcd for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.80;
H, 8.15.
C
20H20: 260.1564. Found: 260.1562.
Nick el(0)-Ca ta lyzed Cou p lin g Rea ction betw een Me-
th ylen ecyclop r op a n es a n d F u m a r a te. A Rep r esen ta tive
P r oced u r e. To a dark red mixture of Ni(cod)2 (13.8 mg, 0.05
mmol), PPh3 (27 mg, 0.1 mmol), and dimethyl fumarate (360
mg, 2.5 mmol) in dry toluene (0.25 mL) was added a solution
of 1 (63 mg, 0.5 mmol) in dry toluene (0.25 mL) at room
temperature. The mixture was stirred at 100 °C, and the
progress of the reaction was monitored by TLC until the
starting material disappeared (26 h). The mixture was passed
through a short silica gel column (hexane and ether) and
evaporated. The residue was further purified by silica gel
column chromatography (hexane/AcOEt 10:1) to give 14 (96
mg, 71%). Other reactions were carried out under the same
conditions except for the time and temperature, which have
already been described.
(1E,2E)-Di(eth oxyca r bon ylm eth ylen e)cycloh exa n e (5).
The charactarization of this compound was based on the
spectral data of (1E,2E)-di(methoxycarbonylmethylene)cyc-
1
lohexane.19 5: colorless oil; H NMR (300 MHz, CDCl3) 5.81
(dd, J ) 1.4, 1.4 Hz, 2H), 4.15 (ddd, J ) 7.1, 7.1, 7.1 Hz, 4H),
2.96-2.95 (m, 4H), 1.71 (dddd, J ) 3.3, 3.3, 3.3, 3.3 Hz, 4H),
1.26 (dd, J ) 7.2, 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) 166.3,
160.3, 115.0, 60.0, 30.0, 25.7, 14.2; IR (neat) 2980, 2937, 2860,
1715, 1634, 1445, 1371, 1329, 1286, 1236, 1177, 1134, 1096,
1074, 1036 cm-1. HRMS Calcd for C14H20O4: 252.1360.
Found: 252.1366.
Eth yl 4-[1-(1-Eth oxycar bon ylvin yl)cyclopr opyl]-2-m eth -
yl-3-m eth ylen ebu ta n oa te (7): colorless oil; 1H NMR (300
MHz, CDCl3) 6.14 (d, J ) 1.3 Hz, 1H), 5.50 (d, J ) 1.5 Hz,
1H), 4.90 (s, 1H), 4.88 (d, J ) 0.9 Hz, 1H), 4.19 (ddd, J ) 7.1,
7.1, 7.1 Hz, 2H), 4.09 (ddd, J ) 7.1, 7.1, 7.1 Hz, 2H), 3.17 (ddd,
J ) 7.3, 7.3, 7.3 Hz, 1H), 2.47 (d, J ) 15.4 Hz, 1H), 2.16 (d, J
) 15.2 Hz, 1H), 1.29 (dd, J ) 7.1, 7.1 Hz, 3H), 1.211 (dd, J )
7.2, 7.2 Hz, 3H), 1.206 (d, J ) 7.0 Hz, 3H), 0.77-0.57 (m, 4H);
13C NMR (75 MHz, CDCl3) 174.5, 166.7, 146.1, 143.3, 126.1,
112.9, 60.4, 44.5, 42.6, 22.1, 15.9, 14.2, 14.1, 12.8, 12.5; IR
(neat) 3082, 2982, 2939, 2907, 2876, 1720, 1645, 1626, 1553,
1447, 1425, 1371, 1339, 1302, 1273, 1246, 1184, 1121, 1096,
1028 cm-1. HRMS Calcd for C16H24O4: 280.1673. Found:
280.1690. Anal. Calcd for C16H24O4: C, 68.54; H, 8.63. Found:
C, 68.41; H, 8.82.
(E)-4-E t h oxyca r b on yl-6-(1-et h oxyca r b on yl-1-m et h yl-
m eth ylen e)sp ir o[2.4]h ep ta n e (8): colorless oil; 1H NMR (300
MHz, CDCl3) 4.17-4.04 (m, 4H), 3.20 (d, J ) 18.2 Hz, 1H),
2.85 (dd, J ) 21.6, 21.6 Hz, 2 H), 2.40 (d, J ) 18.0 Hz, 1H),
1.85 (s, 3H), 1.25 (dd, J ) 7.2, 7.2 Hz, 3 H), 1.21 (dd, J ) 7.1,
7.1 Hz, 3H), 1.09 (s, 3H), 0.77-0.70 (m, 1H), 0.52-0.42 (m,
2H), 0.37-0.31 (m, 1H); 13C NMR (75 MHz, CDCl3) 175.5,
168.0, 155.9, 119.1, 60.5, 59.9, 49.5, 45.3, 43.2, 28.9, 20.6, 15.6,
14.4, 14.2, 9.9, 8.5; IR (neat) 3078, 2982, 2936, 2905, 1726,
1709, 1647, 1460, 1418, 1366, 1308, 1283, 1259, 1196, 1157,
1109, 1057, 1022 cm-1. HRMS Calcd for C16H24O4: 280.1673.
Found: 280.1678. Anal. Calcd for C16H24O4: C, 68.54; H, 8.63.
Found: C, 68.35; H, 8.84.
tr a n s-1-(1-Eth oxyca r bon ylm eth ylen e)-3,4-d im eth oxy-
ca r bon ylcyclop en ta n e (14): colorless oil; 1H NMR (300 MHz,
CDCl3) 5.79 (dddd, J ) 2.2, 2.2, 2.2, 2.2 Hz, 1H), 4.13 (ddd, J
) 7.1, 7.1, 7.1 Hz, 2H), 3.70 (s, 3H), 3.69 (s, 3H), 3.47-3.33
(m, 1H), 3.26-3.12 (m, 2H), 2.98-2.84 (m, 2H), 2.78-2.69 (m,
1H), 1.25 (dd, J ) 7.2, 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
173.7, 173.5, 166.1, 161.3, 113.6, 59.7, 52.11, 52.06, 46.8, 45.7,
38.1, 35.6, 14.2; IR (neat) 2982, 2955, 2907, 2845, 1738, 1713,
1661, 1437, 1373, 1348, 1269, 1209, 1128, 1096, 1034 cm-1
.
Anal. Calcd for C13H18O6: C, 57.77; H, 6.71. Found: C, 57.72;
H, 6.82.
tr a n s-1-(1-E t h oxyca r b on yl-1-m et h ylm et h ylen e)-3,4-
d im eth oxyca r bon ylcyclop en ta n e (15): colorless oil; 1H
NMR (300 MHz, CDCl3) 4.16 (ddd, J ) 7.1, 7.1, 7.1 Hz, 2H),
3.70 (s, 3H), 3.69 (s, 3H), 3.38-3.29 (m, 1H), 3.20-3.13 (m,
2H), 2.90-2.83 (m, 2H), 2.66-2.57 (m, 1H), 1.83 (s, 3H), 1.27
(dd, J ) 7.2, 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) 174.0,
173.9, 167.6, 152.8, 120.8, 60.2, 52.2, 52.1, 47.4, 45.8, 37.2, 36.7,
15.9, 14.3; IR (neat) 2984, 2955, 2907, 2851, 1738, 1735, 1705,
1647, 1437, 1367, 1340, 1312, 1285, 1267, 1200, 1101, 1026
cm-1. Anal. Calcd for C14H20O6: C, 59.14; H, 7.09. Found: C,
59.09; H, 7.26.
Ack n ow led gm en t. We thank Ihara Chemical In-
dustry (J apan) for the gift of 1-ethoxy-1-(trimethylsily-
loxy)cyclopropane.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 2-5, 7-9, 11, 14, and 15 and the
summary of the NOE experiments (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
(19) Piers, E.; McEachern, E. J .; Romero, M. A. J . Org. Chem. 1997,
62, 6034-6040.
J O0255678
J . Org. Chem, Vol. 67, No. 14, 2002 4915