Lewis acid promoted reactions of γ,γ-dialkoxyallylic zirconium species with various carbonyl compounds

Article abstract of DOI:10.1016/j.tet.2005.09.009

The reactions of γ,γ-dialkoxyallylic zirconium species with carbonyl compounds in the presence of Lewis acid are reported. The reactivity of γ,γ-dialkoxyallylic zirconium species and reaction pathway were strongly dependent on the structure and electrostatic nature of the carbonyl compounds.

Full text of DOI:10.1016/j.tet.2005.09.009

Tetrahedron 61 (2005) 10868–10879
Lewis acid promoted reactions of g,g-dialkoxyallylic zirconium
species with various carbonyl compounds
Hisanaka Ito,a Azusa Satob and Takeo Taguchia,
*
aTokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
bTokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
Received 3 August 2005; accepted 3 September 2005
Available online 22 September 2005
Abstract—The reactions of g,g-dialkoxyallylic zirconium species with carbonyl compounds in the presence of Lewis acid are reported. The
reactivity of g,g-dialkoxyallylic zirconium species and reaction pathway were strongly dependent on the structure and electrostatic nature of
the carbonyl compounds.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
(3) A variety type of substrates can be used as a precursor
(acrolein acetal and acrylic acid ortho ester etc.). Along with
this line, we have reported the preparative method for the
allylic zirconium,2 alkoxyallylic zirconium,3 and dialkoxy-
allylic zirconium species4,5 from the corresponding allylic
ethers (Scheme 1).
Although many kinds of allylic organometallics have been
reported during the last three decades, development of novel
preparative methods and their useful reactions is an
important subject due to the importance of the carbon–
carbon bond formation in the organic synthesis.1 We have
developed the preparative method for the allylic and related
zirconium species from allyl ether derivatives with
zirconocene–butene complex through b-elimination of
alkoxyl group.2–5 Our method for the generation of allylic
zirconiums has some characteristic features: (1) zirconium
species attack initially to the double bond of the allyl ether
and the subsequent elimination of alkoxyl group provides
the allylic zirconium.6,7 Mechanism of this process is
different from that of the reaction of low valent metal with
allyl halide involving the direct oxidative insertion of metal
to carbon–halogen bond. (2) Relatively stable allylic ether
can be used as a precursor for the allylic organometallics.
Among the reactions of allylic zirconium species with
carbonyl compounds, we found interesting reactivities of g,
g-dialkoxyallylic zirconium species and the detail of the
reaction as a,b-unsaturated acyl anion equivalent have been
reported.4 g,g-Dialkoxyallylic zirconium species 1 react
with aldehyde at the g-position of zirconium in the absence
or presence of 0.2–0.3 equiv of Lewis acid (Eq. 1 in
Scheme 2). Therefore, this zirconium species 1 work as
acryloyl anion equivalent.10 On the other hand, in the
presence of more than a stoichiometric amount of Lewis
acid, gem-dialkoxycyclopropane derivatives 3 are formed in
the reaction of 1 with aldehyde, in which 1 serves as
Scheme 1.
Keywords: Lewis acid; Zirconium species; Cyclopropane derivatives.
*
Corresponding author. Tel./fax: C81 426 76 3257; e-mail: taguchi@ps.toyaku.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.009

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10869
Using TMSOTf, the reaction of 1 with other carbonyl
compounds was examined (Table 2). The zirconium species
1 reacted with not only aliphatic aldehydes but also aromatic
aldehydes to give the cyclopropane derivatives (3b, 3c, and
3d) in good yields (entries 1–3). Ketones also reacted with 1
to afford the adducts (3e, 3f). Although the isolation yield
was satisfactoly in the case of ketone, small amount of
elimination product was obtained because of the adducts
were relatively unstable due to the facile elimination of the
hydroxyl group during silica gel column chromatography
(entries 4, 5).
Table 2. TMSOTf-promoted reaction of 1 with carbonyl compounds
Scheme 2.
dialkoxycyclopropyl anion equivalent (Eq. 2 in Scheme 2).
We report here the detail of the Lewis acid promoted
reactions of g,g-dialkoxyallylic zirconium species with
carbonyl compounds.5
Entry
Carbonyl compound
Product
Yield
(%)a,b
1
2
87
75
3b
3c
2. Results and discussions
2.1. Reaction of g,g-diethoxyallylic zirconium species 1
with carbonyl compounds (1,2-addition)
g,g-Dialkoxyallylic zirconium species 1 can be prepared
from triethyl orthoacrylate8 with zirconocene–butene
complex9 by our reported procedure as shown in Scheme 2.
Examination of Lewis acid for the preparation of gem-
dialkoxycyclopropane derivatives by the reaction of the
zirconium species 1 with aldehyde is summarized in
Table 1. In the presence of stoichiometric amount of
Lewis acid, the zirconium species 1 smoothly reacted with
aldehydes to give the gem-diethoxycyclopropane deriva-
tives 3 as a diastereomeric mixture. Regarding the Lewis
acid, when BF3$OEt2 or TiCl4 was employed, the reaction
of 1 with 3-phenylpropionaldehyde gave 3a in 75 and 57%
yield, respectively, along with a small amount of uncyclized
product 4a11 (entries 1 and 2). This result may support the
following discussion for the mechanism of this reaction
(vide infra). Trimethylsilyl trifluoromethanesulfonate
(TMSOTf) smoothly promoted the reaction of 1 to give
3a in 88% yield without the formation of 4a (entry 3).
3
4
5
81
83
76
3d
3e
3f
a Isolated yield. Yield was based on 1.
b Diastereomeric mixture (1:1–2:1).
The reaction of g,g-diethoxyallylic zirconium species 1
with glyoxylate derivatives12 was examined. Under the
reaction conditions using TMSOTf (see Table 2), the
desired product could not be obtained (Table 3, entry 1).
In toluene, Cu(OTf)2 or Zn(OTf)2 which can be coordinated
by two carbonyl groups also did not work well resulting in a
complex mixture along with a significant amount of starting
glyoxylate (entries 2 and 3). We found that the reaction
proceeded smoothly in dichloromethane solvent. Thus, after
the generation of 1 in toluene, the solvent was changed to
dichloromethane for the reaction with glyoxylate and the
best result was obtained in the case of Cu(OTf)2 (entry 5).
Table 1. Examination of Lewis acid for the reaction of 1
The reaction of the zirconium species 1 with imine
derivatives was also examined (Scheme 3). Although 1
reacted with benzylideneaniline to give cyclopropane
adduct 6 in 94% yield, unfortunately with other structurally
similar imine derivatives such as naphthylideneaniline or
benzylidene-p-methoxyaniline, clean reaction was not
realized.
Entry
Lewis acid
Yield of 3a (%)a,b
1
2
3
BF3$OEt2
TiCl4
TMSOTf
75
57
88
a Isolated yield. Yield was based on 1.
b Diastereomeric mixture (1:1–2:1).

10870
H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
Table 3. Reaction of 1 with glyoxylate in the presence of Lewis acid
in the formation of the oxetane derivative, which after
hydrolysis gave uncyclized product 4 as a by-product. The
formation of cyclopropane derivatives in the reaction of
alkoxyallylic tin derivatives with carbonyl compounds has
also been reported.13
2.2. Reaction of g,g-diethoxyallylic zirconium species 1
with unsaturated carbonyl compounds
Entry
R1
Lewis
acid
Solvent
Product
Yield
(%)a,b
c
c
c
1
2
3
4
5
6
7
8
9
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Me
Et
TMSOTf Toluene
Cu(OTf)2 Toluene
Zn(OTf)2 Toluene
TMSOTf CH2Cl2
Cu(OTf)2 CH2Cl2
Zn(OTf)2 CH2Cl2
Cu(OTf)2 CH2Cl2
Cu(OTf)2 CH2Cl2
Cu(OTf)2 CH2Cl2
—
—
—
The reaction of g,g-diethoxyallylic zirconium species 1
with a,b-unsaturated ketone derivatives was examined.
Under the TMSOTf-promoted conditions, with acyclic vinyl
ketone, 5-phenylpent-1-en-3-one, the 1,4-addition reaction
at the b-position of 1 proceeded predominantly to afford the
cyclopropane 8a in good yield (Scheme 5). With cyclo-
alkenones, 1,4-adduct 8b and 8c were selectively obtained.
5a
5a
5a
5b
5c
5d
52
85
55
60
78
60
Bn
a Isolated yield. Yield was based on 1.
b Diastereomeric mixture (1:1–2:1).
TMSOTf promoted reaction of 1 with benzyl acrylate as a
typical model substrate of a,b-unsaturated ester was
conducted (Scheme 6). Two products, diethoxycyclo-
propane 11 and diethoxycyclobutane 12 were obtained,
although the yield was not good as a synthetic reaction. The
reaction pathway to these products is possibly explained by
considering the intermediate 10 derived through the 1,4-
addition of the b-position of the zirconium species 1. In the
intermediate 10, both nucleophilic centers competitively
react to the carbenium ion site, that is, attack by ketene silyl
acetal moiety provides the cyclobutane 12 (path B),14
c Complex mixture along with the recovery of glyoxylate.
Scheme 3.
Scheme 4.
The reaction mechanism for the 1,2-addition of g,g-
diethoxyallylic zirconium species 1 to the carbonyl
compound is shown in Scheme 4. When less than a
stoichiometric amount of Lewis acid is employed, the
zirconium species 1 react at the g-position with carbonyl
compound through six-membered transition state, in which
the activation of carbonyl group can be achieved by the
coordination to the zirconium.4 However, two geminal
g-ethoxy substituents of the zirconium species 1 makes the
g-position sterically hindered site and due to the ketene
acetal structure the b-position should be electron rich site
compared with allylic and g-alkoxyallylic zirconium
species. Therefore, in the presence of stoichiometric amount
of Lewis acid, this zirconium species 1 react with activated
carbonyl compound at the b-position as a ketene diethyl
acetal leading to the formation of intermediate 7.
Subsequently, in the case of TMSOTf as Lewis acid,
alkylzirconium part attacks to oxocarbenium ion moiety
intramolecularly to give cyclopropane derivative 3 (path B).
In the case of BF3$OEt2, competitive attack of the alkoxyl
group in the intermediate 7 to the oxocarbenium ion resulted
while the cyclopropane 11 is formed by the attack of
alkylzirconium moiety (path A). To control the reaction
pathway and to improve the product yield further reactions
were conducted using various a,b-unsaturated carbonyl
compounds such as lactone, amide, and N-acyloxazolidi-
none derivatives as described below.
Scheme 5.

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10871
electron density of the ketene acetal moiety in the
intermediate 10 by replacing one oxygen atom with
electron-donating nitrogen atom would make path B
favorable (Scheme 6). Therefore, as the substrate we
adopted the acryl amide instead of ester for the selective
construction of cyclobutane derivatives.
Results of the reaction of 1 with acryl amide derivatives 16
in the presence of TMSOTf are shown in Table 4. As
expected, the reaction of 1 with N,N-dimethyl acrylamide
smoothly proceeded to give cyclobutane derivative 17
exclusively (entry 1). In this reaction, the cis isomer was
predominantly obtained. Improvement of the diastereo-
selectivity could be achieved by employing a more bulky
substituent on the nitrogen atom (R1ZR2ZBn or i-Pr,
entries 2,3). The ratio of cyclobutane 17 and cyclopropane
18 was found to be affected by the electron density on the
nitrogen atom. That is, when the electron density of the
nitrogen atom was lowered by connecting to an aromatic
ring, as in the case of N,N-diphenyl acrylamide, cyclo-
propane derivative 18 was obtained as a major product
(entry 5). Under these conditions, the reaction did not
proceed by introducing a substituent on the acryloyl moiety
(crotonamide and methacrylamide) under these conditions.
Scheme 6.
With a,b-unsaturated lactone derivatives the reaction
proceeded smoothly. In the reaction of the zirconium
species 1 with five-membered ring lactone, a mixture of the
cyclopropane 13a and the cyclobutane 14 were obtained in
16 and 48% yield, respectively. On the other hand,
cyclopropane derivative 13b was selectively obtained in
the case of six-membered ring lactone. These results should
be explained as follows. In both cases, 1,4-addition reaction
at the b-position of the zirconium species 1 to the a,b-
unsaturated lactone afforded the intermediate (15a or 15b)
having oxonium ion and silyl enol ether parts in the same
molecule. In the case of six-membered ring lactone, it
should be difficult to form the cyclobutane ring, because the
oxonium ion and silyl enol ether are not close enough to
react due to the equatorial oriented oxonium ion part on the
pseudo chair like conformation of six-membered ring silyl
enol ether (Scheme 7).
Table 4. Reaction of 1 with acrylamie derivatives
Entry
Amide
Yield
(%)a
17/18b
17: cis/
transb
1
2
3
4
5
R1ZR2ZMe
16a
16b
16c
16d
16e
54
83
56
85
61
O95:5
O95:5
O95:5
O95:5
25:75
82:18
O95:5
O95:5
83:17
85:15
R1ZR2ZBn
R1ZR2Zi-Pr
R1ZMe, R2ZPh
R1ZR2ZPh 16e
a Isolated yield. Yield was based on 1.
b Ration was determined by crude 1H NMR.
The reaction of the zirconium species 1 with N,N-dibenzyl
propiolamide (19) also proceeded to give the cyclobutene
derivative 20 in 51% yield (Scheme 8).
Scheme 8.
The selective construction of cyclopropane derivatives
through path A in Scheme 6 was surveyed. To suppress
the formation of cyclobutane derivatives through path B,
a,b-unsaturated N-acyloxazolidinone derivatives 21, which
have oxazolidinone instead of dialkyl amine as the amide
moiety, was used with the expectation of lowered
nucleophilicity of ketene acetal moiety in the intermediate
Scheme 7.
For the development of a highly selective method for the
preparation of either cyclopropane or cyclobutane deriva-
tives, we paid attention to the electron density of the ketene
acetal moiety in the intermediate. Thus, an increase in the

10872
H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
due to the decrease in the electron density as compared with
N,N-dialkylamide. The results are summarized in Table 5.
For the reaction to proceed, choice of solvent and Lewis
acid was crucial. That is, since the 1,4-addition of 1 did not
occur in toluene in which 1 was prepared, it was needed to
change the solvent to dichloromethane before 1 was reacted
with N-acyloxazolidinones. As a Lewis acid, diethyl-
aluminum chloride worked nicely as compared with other
Lewis acid such as trimethylsilyl triflate or titanium
chloride. Thus, in the presence of 1.5 equiv of diethyl-
aluminum chloride in dichloromethane, reaction of 1 with
N-acryloyloxazolidinone 21a gave the cyclopropane deriva-
tive 22a as a sole product (entry 1). Under the similar
conditions, 21b or 21c, which has substitent on the a,b-
unsaturated carbonyl moiety, also reacted with 1 to give the
cyclopropane 22 selectively in good yield, but the
diastereoselectivity was low (entries 2 and 3). Surprisingly,
sterically demanding b,b-disubstituted compound 21d also
reacted with 1 under these conditions to afford cyclopropane
derivative 22d in moderate yield.
Table 5. The reaction of 1 with acryloyl oxazolidinone derivatives
Entry
Substrate
Product
Yield
(%)a,b
1
83
21a
21b
21c
21d
22a
22b
22c
22d
2
3
4
90 (1:1)
72 (7:3)
39
The asymmetric reaction of 1 with chiral substrate 23 was
also examined, but any chiral induction was not observed
(Scheme 9).
The high selectivity for the formation of cyclopropane
derivative 22 should be explained by the relatively lower
electron density of the N,O-acetal moiety in the intermediate
27 as compared with that of the acrylamide which produced
cyclobutane derivatives 17. Thus, by changing the
electronic nature of the residual group of the enoyl
compound, selective formation of the gem-dialkoxycyclo-
propane 22 or cyclobutane 17 can be controlled through the
1,4-addition of 1 to an a,b-unsaturated carboxylic acid
derivative (Scheme 10).
a Isolated yield. Yield was based on 1.
b Ration was determined by crude 1H NMR.
3. Conclusion
The addition reactions of g,g-dialkoxyallylic zirconium
species 1 with various carbonyl compounds in the presence
of Lewis acid were described. In the case of the reaction
with aldehyde and ketones, 1,2-addition of the zirconium
species 1 proceeded as dialkoxycyclopropyl anion equivalent.
On the other hand, the reaction of 1 with a,b-unsaturated ester
and amide derivatives gave cyclopropane and cyclobutane
derivatives through 1,4-addition reaction. These compounds
Scheme 9.
Scheme 10.

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10873
could be obtained selectively by the appropriate choice of the
substrate and reaction conditions.
2.45 (1H, br s), 1.99–1.91 (2H, m), 1.36 (1H, ddd, JZ9.9,
8.2, 6.5 Hz), 1.23 (6H, t, JZ7.1 Hz), 1.10 (1H, dd, JZ9.9,
5.8 Hz), 0.81 (1H, dd, JZ6.5, 5.8 Hz). 13C NMR (100 MHz,
CDCl3) d 142.2, 128.3, 128.2, 125.7, 91.3, 72.1, 62.4, 61.9,
38.2, 32.1, 30.9, 17.3, 15.4, 15.3. Anal. Calcd for C16H24O3:
C, 72.69; H, 9.15. Found: C, 72.54; H, 9.02.
4. Experimental
Zirconocene dichloride was purchased from Tokyo Kasei
Kogyo. All reactions were conducted under an argon
Compound 3a-more polar. Colorless oil; IR (neat) 3443
n cmK1. 1H NMR (500 MHz, CDCl3) d 7.32–7.20 (5H, m),
3.82–3.71 (3H, m), 3.60 (1H, dq, JZ9.5, 7.0 Hz), 3.54 (1H,
dq, JZ9.3, 7.0 Hz), 2.87 (1H, ddd, JZ14.1, 7.5, 7.5 Hz),
2.75 (1H, ddd, JZ14.1, 8.4, 8.4 Hz), 2.35 (1H, br s), 1.94–
1.88 (2H, m), 1.34 (1H, ddd, JZ10.0, 6.8, 5.8 Hz), 1.22
(3H, t, JZ7.0 Hz), 1.20 (3H, t, JZ7.0 Hz), 1.04 (1H, dd,
JZ10.0, 5.8 Hz), 1.00 (1H, dd, JZ6.8, 5.8 Hz). 13C NMR
(125.7 MHz, CDCl3) d 142.2, 128.5, 128.3, 125.7, 91.3,
68.6, 62.2, 61.8, 38.8, 31.7, 30.5, 15.3, 15.2, 14.6. Anal.
Calcd for C16H24O3: C, 72.69; H, 9.15. Found: C, 72.47; H,
9.22.
1
atmosphere. H and 13C NMR spectra were recorded in
CDCl3, and the chemical shifts are given in ppm using
CHCl3 (7.26 ppm) in CDCl3 for 1H NMR and CDCl3
(77.01 ppm) for 13C NMR as an internal standard,
respectively. Mass spectra and HRMS were recorded by
electron impact ionization at 70 eV. Column chromato-
graphy was performed on neutral silica gel (75–150 mm).
Medium-pressure liquid chromatography (MPLC) was
performed on a 30!2.2 cm i.d. prepacked column (silica
gel, 10 mm) with a UV or RI detector.
4.1. General procedure for generation of 1 and its
reaction with aldehyde (ketone) or a,b-unsaturated
carbonyl compounds in the presence of Lewis acid
4.1.3. Cyclohexyl(2,2-diethoxycyclopropyl)methanol
(3b). Compound 3b-less polar. Colorless oil; IR (neat)
3476 n cmK1. 1H NMR (500 MHz, CDCl3) d 3.87 (1H, dq,
JZ9.5, 7.1 Hz), 3.78 (1H, dq, JZ9.3, 7.1 Hz), 3.62–3.53
(2H, m), 3.06 (1H, br t, JZ7.8 Hz), 2.35 (1H, br s), 1.97
(1H, br d, JZ12.8 Hz), 1.84–1.72 (3H, m), 1.67 (1H, br d,
JZ11.0 Hz), 1.54–1.46 (1H, m), 1.34 (1H, ddd, JZ9.6, 9.0,
6.4 Hz), 1.30–1.00 (5H, m), 1.22 (3H, t, JZ7.2 Hz), 1.21
(3H, t, JZ7.1 Hz), 1.10 (1H, dd, JZ9.6, 5.7 Hz), 0.77 (1H,
dd, JZ6.4, 5.7 Hz). 13C NMR (125.7 MHz, CDCl3) d 91.1,
77.4, 62.4, 61.8, 43.7, 29.3, 29.2, 29.1, 26.6, 26.2, 26.1,
18.3, 15.4, 15.3. Anal. Calcd for C14H26O3: C, 69.38; H,
10.81. Found: C, 69.38; H, 10.97.
Under argon atmosphere, to a solution of zirconocene
dichloride (1.05 g, 3.6 mmol) in toluene (18 mL) was added
n-butyllithium (1.46 M in hexane, 4.9 mL, 7.2 mmol) at
K78 8C and the mixture was stirred at the same temperature
for 1 h. A solution of triethyl orthoacrylate (522 mg,
3 mmol) in toluene (5 mL) was added to the reaction
mixture at K78 8C and then the temperature was raised to
ambient temperature. After being stirred for 3 h, were
successively added a solution of carbonyl compound
(3.6 mmol) in toluene (3 mL) at K78 8C and trimethylsilyl
trifluoromethanesulfonate (0.6 mL, 3.3 mmol), and the
whole was stirred at the same temperature for 10 min. The
reaction temperature was raised to ambient temperature and
the stirring was continued for 4.5 h. After addition of
saturated aqueous ammonium chloride, the reaction mixture
was extracted with ether for three times. Organic layer was
washed with brine, dried with magnesium sulfate, and
concentrated under vacuum. The residue was purified by
neutral silica gel column chromatography to afford product.
If the trimethylsilyl group could not be completely cleaved
under the above mentioned procedure, the organic layer was
washed several times with 1 N HCl. Although compound 3
is relatively stable under acid treatment in workup stage, it is
labile during the purification by acidic silica gel column
chromatography.
Compound 3b-more polar. Colorless oil; IR (neat) 3443
1
n cmK1. H NMR (500 MHz, CDCl3) d 3.81 (1H, dq, JZ
9.5, 7.1 Hz), 3.77 (1H, dq, JZ9.3, 7.1 Hz), 3.64–3.52 (3H,
m), 1.89 (1H, br d, JZ12.7 Hz), 1.81–1.72 (4H, m), 1.68
(1H, br d, JZ12.0 Hz), 1.51–1.44 (1H, m), 1.37 (1H, ddd,
JZ9.6, 7.7, 5.0 Hz), 1.30–1.08 (5H, m), 1.22 (3H, t, JZ
7.1 Hz), 1.21 (3H, t, JZ7.1 Hz), 1.02–0.98 (2H, m). 13C
NMR (125.7 MHz, CDCl3) d 91.3, 72.6, 62.3, 61.6, 44.0,
29.1, 29.0, 28.0, 26.6, 26.4, 26.3, 15.4, 15.3, 14.2. Anal.
Calcd for C14H26O3: C, 69.38; H, 10.81. Found: C, 69.10; H,
10.90.
4.1.4. 1-(2,2-Diethoxycyclopropyl)-1-octanol (3c). Com-
pound 3c-less polar. Colorless oil; IR (neat) 3471 n cmK1
.
1H NMR (500 MHz, CDCl3) d 3.83 (1H, dq, JZ9.5,
7.1 Hz), 3.77 (1H, dq, JZ9.3, 7.1 Hz), 3.61–3.49 (2H, m),
3.31 (1H, m), 2.30 (1H, br s), 1.70–1.23 (13H, m), 1.21 (3H,
t, JZ7.1 Hz), 1.19 (3H, t, JZ7.1 Hz), 1.06 (1H, dd, JZ
10.0, 5.7 Hz), 0.87 (3H, t, JZ7.1 Hz), 0.76 (1H, dd, JZ6.1,
6.0 Hz). 13C NMR (125.7 MHz, CDCl3) d 91.4, 72.9, 62.4,
61.9, 36.5, 31.8, 31.1, 29.7, 29.3, 25.8, 22.7, 17.5, 15.4,
15.3, 14.1. Anal. Calcd for C15H30O3: C, 69.72; H, 11.70.
Found: C, 69.87; H, 11.98.
4.1.1. g,g-Diethoxyallylic zirconium species (1). 1H NMR
(300 MHz, benzene-d6) d 6.00–5.92 (10H, m), 4.50 (1H, t,
JZ8.7 Hz), 4.04 (2H, q, JZ7.2 Hz), 3.91 (2H, q, JZ
7.0 Hz), 3.80 (2H, q, JZ6.9 Hz), 1.97 (2H, d, JZ8.7 Hz),
1.33 (3H, t, JZ7.2 Hz), 1.25 (3H, t, JZ6.9 Hz), 1.08 (3H, t,
JZ7.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 152.6, 110.7,
93.9, 68.8, 64.2, 64.0, 34.3, 20.1, 15.6, 15.1.
4.1.2. 1-(2,2-Diethoxycyclopropyl)-3-phenyl-1-propanol
(3a). Compound 3a-less polar. Colorless oil; IR (neat)
3468 n cmK1. 1H NMR (400 MHz, CDCl3) d 7.33–7.19 (5H,
m), 3.88 (1H, dq, JZ9.5, 7.1 Hz), 3.81 (1H, dq, JZ9.3,
7.1 Hz), 3.64–3.54 (2H, m), 3.42 (1H, m), 2.86 (1H, ddd,
JZ14.2, 9.7, 6.3 Hz), 2.74 (1H, ddd, JZ14.2, 9.5, 7.0 Hz),
Compound 3c-more polar. Colorless oil; IR (neat) 3435
n cmK1. 1H NMR (500 MHz, CDCl3) d 3.82–3.65 (3H, m),
3.58 (1H, dq, JZ9.5, 7.1 Hz), 3.52 (1H, dq, JZ9.3, 7.1 Hz),
2.25 (1H, br s), 1.60–1.23 (13H, m), 1.20 (6H, t, JZ7.1 Hz),
1.01–0.93 (2H, m), 0.87 (3H, t, JZ7.1 Hz). 13C NMR

10874
H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
(125.7 MHz, CDCl3) d 91.4, 69.2, 62.2, 61.7, 37.2, 31.8,
30.5, 29.6, 29.3, 25.4, 22.7, 15.4, 15.3, 14.5, 14.1. Anal.
Calcd for C15H30O3: C, 69.72; H, 11.70. Found: C, 69.45; H,
11.84.
69.8, 62.5, 62.1, 46.0, 33.6, 30.5, 25.9, 15.4, 15.3, 13.5.
Anal. Calcd for C17H26O3: C, 73.35; H, 9.41. Found: C,
73.21; H, 9.47.
4.1.8. Isopropyl 2-(2,2-diethoxycyclopropyl)-2-hydroxy-
acetate (5a). Compound 5a-less polar. Colorless oil; IR
(neat) ncmK1; 3478, 2979, 2934, 1731, 1452, 1376, 1255,
1195, 1108, 1054, 953. 1H NMR (400 MHz, CDCl3) d 5.09
(1H, dq, JZ6.0, 6.0 Hz), 3.89–3.80 (2H, m), 3.72 (1H, dq,
JZ9.2, 6.8 Hz), 3.63 (1H, dq, JZ9.2, 7.2 Hz), 3.57 (1H, dq,
JZ9.2, 7.2 Hz), 2.97 (1H, d, JZ6.8 Hz), 1.43 (1H, ddd, JZ
10.0, 8.4, 6.4 Hz), 1.26 (3H, d, JZ6.0 Hz), 1.25 (3H, d, JZ
6.0 Hz), 1.22 (3H, t, JZ7.2 Hz), 1.18 (3H, t, JZ7.2 Hz),
1.10 (1H, dd, JZ10.0, 6.4 Hz), 1.02 (1H, t, JZ6.4 Hz). 13C
NMR (100.6 MHz, CDCl3) d 173.8, 90.5, 70.1, 69.2, 62.4,
62.1, 28.5, 21.8, 21.7, 16.1, 15.4, 15.2. ESI-MS m/z: 247
(MCC1). HRMS Calcd for C12H23O5: 247.1545 (MCC1),
found: 247.1556.
4.1.5. (2,2-Diethoxycyclopropyl)-phenylmethanol (3d).
Compound 3d-less polar. Colorless oil; IR (neat) 3420
n cmK1. 1H NMR (500 MHz, CDCl3) d 7.47–7.28 (5H, m),
4.45 (1H, dd, JZ8.3, 1.2 Hz), 3.95 (1H, dq, JZ9.5, 7.1 Hz),
3.82 (1H, dq, JZ9.5, 7.1 Hz), 3.70 (1H, dq, JZ9.5, 7.1 Hz),
3.59 (1H, dq, JZ9.5, 7.1 Hz), 2.76 (1H, br s), 1.63 (1H, ddd,
JZ9.9, 8.5, 6.5 Hz), 1.31 (3H, t, JZ7.1 Hz), 1.23 (3H, t,
JZ7.1 Hz), 1.16 (1H, dd, JZ9.9, 5.9 Hz), 0.98 (1H, dd, JZ
6.5, 5.9 Hz). 13C NMR (125.7 MHz, CDCl3) d 143.3, 128.4,
127.4, 125.9, 91.7, 74.5, 62.6, 62.1, 32.5, 17.8, 15.5, 15.3.
Anal. Calcd for C14H20O3: C, 71.16; H, 8.53. Found: C,
70.99; H, 8.55.
Compound 3d-more polar. White crystal; mp 40–41 8C. IR
1
(KBr) 3235 ncmK1. H NMR (500 MHz, CDCl3) d 7.49–
Compound 5a-more polar. Colorless oil; IR (neat) ncmK1
;
7.28 (5H, m), 4.76 (1H, d, JZ6.7 Hz), 3.83 (1H, dq, JZ9.5,
7.1 Hz), 3.71–3.62 (2H, m), 3.37 (1H, dq, JZ9.5, 7.1 Hz),
2.65 (1H, br s), 1.57 (1H, ddd, JZ9.9, 6.8, 6.8 Hz), 1.28
(3H, t, JZ7.1 Hz), 1.19–1.12 (2H, m), 1.14 (3H, t, JZ
7.1 Hz). 13C NMR (125.7 MHz, CDCl3) d 143.9, 128.2,
127.3, 125.8, 91.4, 71.6, 62.3, 61.8, 32.5, 15.7, 15.3, 15.2.
Anal. Calcd for C14H20O3: C, 71.16; H, 8.53. Found: C,
71.04; H, 8.46.
3466, 2979, 2934, 1736, 1455, 1376, 1261, 1200, 1108,
1057, 959. 1H NMR (400 MHz, CDCl3) d 5.09 (1H, dq, JZ
6.0, 6.0 Hz), 4.07 (1H, dd, JZ7.6, 4.0 Hz), 3.80 (1H, dq,
JZ9.6, 7.2 Hz), 3.76 (1H, dq, JZ9.2, 7.2 Hz), 3.58 (1H, dq,
JZ9.2, 7.2 Hz), 3.56 (1H, dq, JZ9.6, 7.2 Hz), 3.00 (1H, d,
JZ4.0 Hz), 1.50 (1H, ddd, JZ10.0, 7.6, 6.4 Hz), 1.27 (6H,
d, JZ6.0 Hz), 1.19 (3H, t, JZ7.2 Hz), 1.17 (3H, t, JZ
7.2 Hz), 1.11 (1H, dd, JZ10.0, 6.4 Hz), 1.04 (1H, t, JZ
6.4 Hz). 13C NMR (100.6 MHz, CDCl3) d 173.3, 90.9, 69.4,
68.9, 62.3, 61.8, 28.2, 21.8, 21.7, 16.0, 15.3. ESI-MS m/z:
247 (MCC1). HRMS Calcd for C12H23O5: 247.1545
(MCC1), found: 247.1561. Anal. Calcd for C12H22O5: C,
58.52; H, 9.00. Found: C, 58.29; H, 8.60.
4.1.6. 1-(2,2-Diethoxycyclopropyl)cyclohexanol (3e).
1
Colorless oil; IR (neat) 3438 n cmK1. H NMR (500 MHz,
CDCl3) d 3.87 (1H, dq, JZ9.5, 7.1 Hz), 3.81 (1H, dq, JZ
9.5, 7.1 Hz), 3.59 (1H, dq, JZ9.5, 7.1 Hz), 3.49 (1H, dq,
JZ9.5, 7.1 Hz), 2.98 (1H, s), 1.76–1.45 (8H, m), 1.41–1.25
(2H, m), 1.27 (1H, dd, JZ10.4, 7.3 Hz), 1.23 (3H, t, JZ
7.1 Hz), 1.22 (3H, t, JZ7.1 Hz), 1.17 (1H, dd, JZ7.3,
5.7 Hz), 0.94 (1H, dd, JZ10.4, 5.7 Hz). 13C NMR
(125.7 MHz, CDCl3) d 92.0, 68.4, 62.4, 62.2, 39.7, 37.1,
33.1, 25.8, 22.2, 21.9, 15.4, 15.3, 13.2. Anal. Calcd for
C13H24O3: C, 68.38; H, 10.59. Found: C, 68.22; H, 10.81.
4.1.9. Methyl 2-(2,2-diethoxyxyclopropyl)-2-hydroxy-
acetate (5b). Compound 5b-less polar. Colorless oil; IR
(neat) ncmK1; 3478, 2978, 1741, 1443, 1256, 1197, 1093,
1054, 940. 1H NMR (400 MHz, CDCl3) d 3.93 (1H, dd, JZ
8.4, 5.2 Hz), 3.86–3.68 (2H, m), 3.77 (3H, s), 3.61 (1H, dq,
JZ9.2, 7.2 Hz), 3.55 (1H, dq, JZ9.2, 7.2 Hz), 3.00 (1H, d,
JZ5.2 Hz), 1.46 (1H, ddd, JZ10.4, 8.4, 6.4 Hz), 1.21 (3H,
t, JZ7.2 Hz), 1.18 (3H, t, JZ7.2 Hz), 1.12 (1H, dd, JZ
10.4, 6.4 Hz), 1.01 (1H, t, JZ6.4 Hz). 13C NMR
(100.6 MHz, CDCl3) d 174.5, 90.6, 70.2, 62.5, 62.1, 52.3,
28.3, 16.2, 15.3, 15.2. ESI-MS m/z: 219 (MCC1). HRMS
Calcd for C10H19O5: 219.1232 (MCC1), found: 219.1235.
4.1.7. 2-(2,2-Diethoxycyclopropyl)-4-phenyl-2-butanol
(3f). Compound 3f-less polar. Colorless oil; IR (neat)
3518 n cmK1. 1H NMR (500 MHz, CDCl3) d 7.30–7.17 (5H,
m), 3.89 (1H, dq, JZ9.5, 7.1 Hz), 3.83 (1H, dq, JZ9.5,
7.1 Hz), 3.61 (1H, dq, JZ9.5, 7.1 Hz), 3.51 (1H, dq, JZ9.5,
7.1 Hz), 3.16 (1H, br s), 2.80–2.70 (2H, m), 1.90–1.76 (2H,
m), 1.41 (3H, s), 1.29–1.20 (2H, m), 1.25 (3H, t, JZ7.1 Hz),
1.23 (3H, t, JZ7.1 Hz), 1.01 (1H, dd, JZ10.2, 5.6 Hz). 13C
NMR (125.7 MHz, CDCl3) d 143.0, 128.4, 128.3, 125.6,
91.1, 69.2, 62.4, 62.2, 44.4, 33.0, 30.3, 29.3, 15.4, 15.3,
14.0. Anal. Calcd for C17H26O3: C, 73.35; H, 9.41. Found:
C, 73.26; H, 9.52.
Compound 5b-more polar. Colorless oil; IR (neat) ncmK1
;
3460, 2977, 1742, 1445, 1380, 1255, 1200, 1056, 979, 939.
1H NMR (400 MHz, CDCl3) d 4.15 (1H, d, JZ7.6 Hz),
3.82–3.69 (2H, m), 3.78 (3H, s), 3.57 (1H, dq, JZ9.6,
7.2 Hz), 3.53 (1H, dq, JZ9.6, 7.2 Hz), 3.07 (1H, br s), 1.53
(1H, ddd, JZ11.2, 7.6, 6.0 Hz), 1.18 (3H, t, JZ7.2 Hz),
1.16 (3H, t, JZ7.2 Hz), 1.10 (1H, dd, JZ11.2, 6.0 Hz), 1.05
(1H, t, JZ6.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 174.3,
91.1, 69.1, 62.7, 62.1, 52.6, 28.4, 16.1, 15.5, 15.4. ESI-MS
m/z: 219 (MCC1). HRMS Calcd for C10H19O5: 219.1232
(MCC1), found: 219.1237. Anal. Calcd for C10H18O5: C,
55.03; H, 8.31. Found: C, 54.61; H, 8.11.
Compound 3f-more polar. Colorless oil; IR (neat) 3509
n cmK1. 1H NMR (500 MHz, CDCl3) d 7.32–7.17 (5H, m),
3.88 (1H, dq, JZ9.5, 7.1 Hz), 3.82 (1H, dq, JZ9.5, 7.1 Hz),
3.61 (1H, dq, JZ9.5, 7.1 Hz), 3.49 (1H, dq, JZ9.5, 7.1 Hz),
3.14 (1H, br s), 2.90–2.69 (2H, m), 1.97–1.87 (2H, m), 1.31
(1H, dd, JZ10.5, 7.3 Hz), 1.26 (3H, s), 1.24 (3H, t, JZ
7.1 Hz), 1.21 (3H, t, JZ7.1 Hz), 1.18 (1H, dd, JZ7.3,
5.6 Hz), 0.99 (1H, dd, JZ10.5, 5.6 Hz). 13C NMR
(125.7 MHz, CDCl3) d 142.9, 128.3, 128.3, 125.6, 92.1,
4.1.10. Ethyl 2-(2,2-diethoxycyclopropyl)-2-hydroxy-
acetate (5c). Compound 5c-less polar. Colorless oil; IR
(neat) ncmK1; 3480, 2978, 1937, 1738, 1449, 1369, 1255,

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10875
1195, 1093, 1053, 945. 1H NMR (400 MHz, CDCl3) d 4.25
(2H, q, JZ7.2 Hz), 3.93 (1H, dd, JZ8.4, 7.2 Hz), 3.85 (1H,
dq, JZ9.2, 7.2 Hz), 3.73 (1H, dq, JZ9.6, 7.2 Hz), 3.64 (1H,
dq, JZ9.2, 7.2 Hz), 3.57 (1H, dq, JZ9.6, 7.2 Hz), 2.93 (1H,
d, JZ7.2 Hz), 1.46 (1H, ddd, JZ10.4, 8.4, 6.4 Hz), 1.30
(3H, t, JZ7.2 Hz), 1.24 (3H, t, JZ7.2 Hz), 1.19 (3H, t, JZ
7.2 Hz), 1.13 (1H, dd, JZ10.4, 6.4 Hz), 1.04 (1H, t, JZ
6.4 Hz). 13C NMR (100.6 MHz, CDCl3) d 174.2, 90.6, 70.1,
62.5, 62.1, 61.5, 28.4, 16.2, 15.4, 15.2, 14.2. ESI-MS m/z:
233 (MCC1). HRMS Calcd for C11H21O5: 233.1389
(MCC1), found: 233.1389.
5.9 Hz), 0.92 (1H, dd, JZ6.7, 5.9 Hz). 13C NMR
(125.7 MHz, CDCl3) d 147.8, 143.8, 129.0, 128.4, 126.7,
126.3, 117.2, 113.4, 91.5, 62.4, 61.8, 57.1, 34.0, 18.0, 15.4,
15.1. EI-MS m/z: 311 (MC), 266 (MCKOEt). Anal. Calcd
for C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C, 76.99;
H, 8.11; N, 4.46.
Compound 6-more polar. Colorless oil; IR (neat) ncmK1
;
1
3382, 2882, 1603, 1513, 1296, 1121, 1052, 747. H NMR
(500 MHz, CDCl3) d 7.56–7.23 (5H, m), 7.10 (2H, t, JZ
7.5 Hz), 6.66 (1H, t, JZ7.5 Hz), 6.51 (2H, d, JZ7.5 Hz),
4.35 (1H, br s), 4.17 (1H, d, JZ9.7 Hz), 3.90 (1H, dq, JZ
9.4, 7.1 Hz), 3.65–3.58 (2H, m), 3.11 (1H, dq, JZ9.4,
7.1 Hz), 1.52 (1H, ddd, JZ9.7, 9.7, 6.7 Hz), 1.32 (3H, t, JZ
7.1 Hz), 1.20 (1H, dd, JZ9.7, 5.6 Hz), 1.08 (3H, t, JZ
7.1 Hz), 0.96 (1H, dd, JZ6.7, 5.9 Hz). 13C NMR
(125.7 MHz, CDCl3) d 147.8, 143.8, 129.0, 128.4, 126.7,
126.3, 117.2, 113.4, 91.5, 62.4, 61.8, 57.1, 34.0, 18.0, 15.4,
15.1. EI-MS m/z: 311 (MC), 266 (MCKOEt). Anal. Calcd
for C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C, 76.99;
H, 8.11; N, 4.46.
Compound 5c-more polar. Colorless oil; IR (neat) ncmK1
;
3464, 2978, 2930, 1738, 1449, 1370, 1255, 1200, 1056, 944.
1H NMR (400 MHz, CDCl3) d 4.32–4.21 (2H, m), 4.15 (1H,
dd, JZ7.6, 2.0 Hz), 3.86–3.72 (2H, m), 3.64–3.52 (2H, m),
1.58–1.51 (1H, m), 2.96 (1H, br s), 1.30 (3H, td, JZ7.2,
2.0 Hz), 1.20 (3H, td, JZ7.2, 2.0 Hz), 1.19 (3H, td, JZ7.2,
2.0 Hz), 1.13 (1H, ddd, JZ10.4, 6.4, 2.0 Hz), 1.07 (1H, td,
JZ6.4, 2.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 173.7,
90.9, 68.8, 62.4, 61.9, 61.6, 28.2, 16.0, 15.3, 15.2, 14.2. ESI-
MS m/z: 233 (MCC1). HRMS Calcd for C11H21O5:
233.1389 (MCC1), found: 233.1381.
4.1.13. 4-(2,2-Diethoxycyclopropyl)-1-phenyl-2-buta-
1
none (8a). Colorless oil; IR (neat) 1715 ncmK1. H NMR
4.1.11. Benzyl 2-(2,2-diethoxycyclopropyl)-2-hydroxy-
acetate (5d). Compound 5d-less polar. Colorless oil; IR
(neat) ncmK1; 3465, 2977, 2930, 1739, 1455, 1376, 1256,
1196, 1092, 1054, 993. 1H NMR (400 MHz, CDCl3) d 7.40–
7.31 (5H, m), 5.26 (1H, d, JZ12.4 Hz), 5.21 (1H, d, JZ
12.4 Hz), 4.02 (1H, dd, JZ8.0, 7.2 Hz), 3.84 (1H, dq, JZ
9.6, 7.2 Hz), 3.67 (1H, dq, JZ9.6, 7.2 Hz), 3.62 (1H, dq,
JZ9.6, 7.2 Hz), 3.48 (1H, dq, JZ9.6, 7.2 Hz), 2.97 (1H, d,
JZ7.2 Hz), 1.48 (1H, ddd, JZ10.4, 8.0, 6.0 Hz), 1.22 (3H,
t, JZ7.2 Hz), 1.15 (3H, t, JZ7.2 Hz), 1.12 (1H, dd, JZ
10.4, 6.0 Hz), 1.06 (1H, t, JZ6.0 Hz). 13C NMR
(100.6 MHz, CDCl3) d 174.0, 135.4, 128.6, 128.4, 128.3,
90.5, 70.1, 67.1, 62.5, 62.1, 28.2, 16.2, 15.4, 15.2. ESI-MS
m/z: 295 (MCC1). HRMS Calcd for C16H22O5Na:
317.1365 (MCCNa), found: 317.1396.
(400 MHz, CDCl3) d 7.30–7.16 (5H, m), 3.73–3.48 (4H, m),
2.90 (2H, t, JZ7.8 Hz), 2.74 (2H, t, JZ7.8 Hz), 2.55–2.41
(2H, m), 1.77–1.54 (2H, m), 1.20 (3H, t, JZ7.1 Hz), 1.18
(3H, t, JZ7.1 Hz), 1.11 (1H, dq, JZ10.0, 7.0 Hz), 0.94 (1H,
dd, JZ10.0, 5.4 Hz), 0.43 (1H, dd, JZ7.0, 5.4 Hz). 13C
NMR (100.6 MHz, CDCl3) d 209.9, 141.1, 128.5, 128.3,
126.0, 91.9, 62.2, 61.4, 44.2, 42.7, 29.8, 24.7, 22.7, 18.0,
15.4, 15.3. Anal. Calcd for C18H26O3: C, 74.45; H, 9.02.
Found: C, 74.40; H, 9.08.
4.1.14. 3-(2,2-Diethoxycyclopropyl)-5-phenyl-1-penten-
3-ol (9). Compound 9-less polar. Colorless oil; IR (neat)
3496 ncmK1. 1H NMR (400 MHz, CDCl3) d 7.31–7.16 (5H,
m), 5.83 (1H, dd, JZ17.3, 10.7 Hz), 5.31 (1H, dd, JZ17.3,
1.7 Hz), 5.15 (1H, dd, JZ10.7, 1.7 Hz), 3.88 (1H, dq, JZ
9.5, 7.1 Hz), 3.82 (1H, dq, JZ9.5, 7.1 Hz), 3.62 (1H, dq,
JZ9.5, 7.1 Hz), 3.50 (1H, dq, JZ9.5, 7.1 Hz), 3.35 (1H, s),
2.81 (1H, ddd, JZ13.8, 9.9, 7.5 Hz), 2.66 (1H, ddd, JZ
13.8, 9.6, 7.8 Hz), 2.02–1.93 (2H, m), 1.37 (1H, dd,
JZ10.5, 7.3 Hz), 1.25 (3H, t, JZ7.1 Hz), 1.20 (3H, t, JZ
7.1 Hz), 1.14 (1H, dd, JZ7.3, 5.9 Hz), 0.95 (1H, dd, JZ
10.5, 5.9 Hz). 13C NMR (100.6 MHz, CDCl3) d 142.9,
141.9, 128.4, 128.3, 125.6, 113.0, 92.2, 72.3, 62.6, 62.2,
44.8, 32.4, 30.2, 15.4, 15.3, 13.8. Anal. Calcd for C18H26O3:
C, 74.45; H, 9.02. Found: C, 74.38; H, 9.09.
Compound 5d-more polar. Colorless oil; IR (neat) ncmK1
3455, 2976, 2930, 1742, 1455, 1379, 1258, 1201, 1120,
;
1
1056, 981. H NMR (400 MHz, CDCl3) d 7.41–7.29 (5H,
m), 5.27 (1H, d, JZ12.0 Hz), 5.20 (1H, d, JZ12.0 Hz), 4.20
(1H, dd, JZ8.0, 4.0 Hz), 3.79 (1H, dq, JZ10.0, 7.2 Hz),
3.62 (1H, dq, JZ9.6, 7.2 Hz), 3.56 (1H, dq, JZ9.6, 7.2 Hz),
3.37 (1H, dq, JZ10.0, 7.2 Hz), 2.98 (1H, d, JZ4.8 Hz),
1.53 (1H, ddd, JZ10.4, 8.0, 6.8 Hz), 1.19 (3H, t, JZ
7.2 Hz), 1.13 (1H, dd, JZ10.4, 6.8 Hz), 1.08 (3H, t, JZ
7.2 Hz), 1.06 (1H, t, JZ6.8 Hz). 13C NMR (100.6 MHz,
CDCl3) d 173.6, 135.2, 128.6, 128.5, 128.4, 90.8, 69.1, 67.2,
62.3, 61.8, 28.2, 16.2, 15.3, 15.2. ESI-MS m/z: 295 (MCC
1). HRMS Calcd for C16H22O5Na: 317.1365 (MCCNa),
found: 317.1381.
Compound 9-more polar. Colorless oil; IR (neat) 3494
1
ncmK1. H NMR (400 MHz, CDCl3) d 7.29–7.15 (5H, m),
6.05 (1H, dd, JZ17.3, 10.7 Hz), 5.34 (1H, dd, JZ17.3,
1.3 Hz), 5.16 (1H, dd, JZ10.7, 1.3 Hz), 3.86 (1H, dq, JZ
9.5, 7.1 Hz), 3.76 (1H, dq, JZ9.5, 7.1 Hz), 3.60 (1H, dq,
JZ9.5, 7.1 Hz), 3.48 (1H, dq, JZ9.5, 7.1 Hz), 3.45 (1H, br
s), 2.74 (1H, ddd, JZ13.6, 12.4, 5.2 Hz), 2.66 (1H, ddd, JZ
13.6, 12.1, 4.9 Hz), 1.97 (1H, ddd, JZ13.6, 12.1, 5.2 Hz),
1.80 (1H, ddd, JZ13.6, 12.4, 4.9 Hz), 1.36 (1H, dd, JZ
10.4, 7.4 Hz), 1.24 (3H, t, JZ7.1 Hz), 1.25–1.21 (1H, m),
1.20 (3H, t, JZ7.1 Hz), 1.02 (1H, dd, JZ10.4, 5.8 Hz). 13C
NMR (100.6 MHz, CDCl3) d 144.5, 142.9, 128.4, 128.3,
125.6, 112.2, 91.2, 72.1, 62.5, 62.3, 42.7, 32.4, 29.8, 15.3,
4.1.12. N-[(2,2-Diethoxycyclopropyl)(phenyl)methyl]-
aniline (6). Compound 6-less polar. Colorless oil; IR
(neat) ncmK1; 3402, 2975, 1707, 1603, 1507, 1264, 1054,
750. 1H NMR (500 MHz, CDCl3) d 7.43–7.22 (5H, m), 7.06
(2H, t, JZ7.5 Hz), 6.63 (1H, t, JZ7.5 Hz), 6.52 (2H, d, JZ
7.5 Hz), 4.49 (1H, br s), 4.11 (1H, d, JZ8.6 Hz), 3.86–3.53
(4H, m), 1.57 (1H, ddd, JZ10.3, 8.6, 6.7 Hz), 1.22 (3H, t,
JZ7.1 Hz), 1.20 (3H, t, JZ7.1 Hz), 1.07 (1H, dd, JZ10.3,

10876
H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
15.2, 13.6. Anal. Calcd for C18H26O3: C, 74.45; H, 9.02.
Found: C, 74.50; H, 9.12.
128.3, 127.9, 127.8, 102.3, 66.0, 56.8, 56.1, 40.7, 37.8, 22.9,
15.2, 15.1. EI-MS m/z: 292 (MC). Anal. Calcd for
C17H24O4: C, 69.84; H, 8.27. Found: C, 69.78; H, 8.24.
4.1.15. 3-(2,2-Diethoxycyclopropyl)cyclopentanone (8b).
Compound cis-12. Colorless oil; IR (neat) ncmK1; 2977,
1737, 1455, 1197, 1054, 975. 1H NMR (400 MHz, CDCl3) d
7.40–7.28 (5H, m), 5.20 (1H, d, JZ12.5 Hz), 5.10 (1H, d,
JZ12.5 Hz), 3.61 (2H, dq, JZ9.7, 7.1 Hz), 3.52–3.43 (2H,
m), 3.38 (1H, dq, JZ9.7, 7.0 Hz), 3.21 (1H, t, JZ8.8 Hz),
2.53–2.43 (1H, m), 1.97 (1H, dt, JZ11.3, 8.8 Hz), 1.79 (1H,
dt, JZ11.3, 8.8 Hz), 1.19 (3H, t, JZ7.1 Hz), 1.11 (3H, t,
JZ7.0 Hz), 1.07 (3H, d, JZ7.0 Hz). 13C NMR (100.6 MHz,
CDCl3) d 171.0, 136.3, 128.4, 128.1, 127.9, 103.9, 66.2,
57.7, 57.6, 47.5, 39.9, 22.3, 15.2, 15.1, 15.0. EI-MS m/z: 292
(MC). Anal. Calcd for C17H24O4: C, 69.84; H, 8.27. Found:
C, 69.78; H, 8.24.
1
Colorless oil; IR (neat) 1742 n cmK1. H NMR (500 MHz,
CDCl3) d 3.70–3.37 (4H, m), 2.40–1.99 (4H, m), 1.97–1.81
(2H, m), 1.68–1.56 (1H, m), 1.13–1.06 (6H, m), 1.04–0.90
(2H, m), 0.51 (0.5H, t, JZ5.7 Hz), 0.47 (0.5H, t, JZ
5.7 Hz). 13C NMR (125.7 MHz, CDCl3) d 219.11, 219.00,
91.47, 91.35, 61.92, 61.86, 61.38, 61.30, 45.12, 44.09,
38.18, 38.01, 36.13, 29.70, 29.66, 29.59, 28.68, 17.24,
17.05, 15.24, 15.20, 15.11, 15.08. Anal. Calcd for
C13H22O3: C, 68.99; H, 9.80. Found: C, 68.81; H, 9.89.
4.1.16. 3-(2,2-Diethoxycyclopropyl)cyclohexanone (8c).
Compound 8c-less polar. Colorless oil; IR (neat) 1714
n cmK1. 1H NMR (500 MHz, CDCl3) d 3.76–3.66 (2H, m),
3.73 (1H, dq, JZ9.5, 7.1 Hz), 3.69 (1H, dq, JZ9.5, 7.1 Hz),
2.58 (1H, br d, JZ14.0 Hz), 2.34 (1H, br d, JZ14.3 Hz),
2.25 (1H, ddd, JZ14.2, 11.5, 6.0 Hz), 2.16 (1H, dd, JZ
14.0, 10.5 Hz), 2.06–2.00 (1H, m), 1.93–1.88 (1H, m), 1.71–
1.43 (3H, m), 1.17 (3H, t, JZ7.1 Hz), 1.16 (3H, t, JZ
7.1 Hz), 1.02–0.95 (2H, m), 0.54–0.48 (1H, m). 13C NMR
(125.7 MHz, CDCl3) d 211.5, 91.5, 62.1, 61.6, 48.2, 41.3,
38.3, 30.5, 30.3, 24.9, 17.3, 15.4, 15.3. Anal. Calcd for
C13H22O3: C, 68.99; H, 9.80. Found: C, 68.81; H, 9.89.
4.1.19. 7,7-Diethoxy-6-methyl-4-oxabicyclo[3.2.0]hep-
tan-2-one (14a). Compound 14a-less polar. Colorless
crystals; mp 60.5–62.0 8C. IR (KBr) ncmK1; 2980, 1779,
1
1732, 1457, 1373, 1189, 1097, 1012. H NMR (500 MHz,
CDCl3) d 4.40 (1H, dd, JZ9.9, 2.2 Hz), 4.26 (1H, dd, JZ
9.9, 7.7 Hz), 3.74 (1H, dq, JZ9.4, 7.0 Hz), 3.51–3.42 (3H, m),
3.36 (1H, dd, JZ7.7, 2.3 Hz), 2.96 (1H, qd, JZ7.7, 2.2 Hz),
2.86–2.78 (1H, m), 1.21 (3H, t, JZ7.0 Hz), 1.15 (3H, t, JZ
7.0 Hz), 1.10 (3H, d, JZ7.5 Hz). 13C NMR (100.6 MHz,
CDCl3) d 175.32, 100.8, 67.6, 58.3, 56.8, 49.5, 41.3, 30.1,
15.0, 14.9, 10.0. EI-MS m/z: 214 (MC). Anal. Calcd for
C11H18O4: C, 61.66; H, 8.47. Found: C, 61.85; H, 8.34.
Compound 8c-more polar. Colorless oil; IR (neat) 1716
n cmK1. 1H NMR (500 MHz, CDCl3) d 3.78–3.69 (2H, m),
3.53 (1H, dq, JZ9.5, 7.1 Hz), 3.48 (1H, dq, JZ9.5, 7.1 Hz),
2.42 (1H, br d, JZ13.1 Hz), 2.34 (1H, br d, JZ14.2 Hz),
2.26 (1H, ddd, JZ13.8, 12.1, 5.6 Hz), 2.17–2.11 (1H, m),
2.07–2.00 (2H, m), 1.70–1.45 (3H, m), 1.18 (3H, t, JZ
7.1 Hz), 1.17 (3H, t, JZ7.1 Hz), 1.01 (1H, ddd, JZ9.8, 9.8,
6.2 Hz), 0.97 (1H, dd, JZ9.8, 5.1 Hz), 0.48 (1H, dd, JZ6.2,
5.1 Hz). 13C NMR (125.7 MHz, CDCl3) d 211.7, 91.7, 62.3,
61.6, 47.3, 41.4, 38.6, 31.7, 30.7, 25.2, 17.1, 15.4, 15.3.
Anal. Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C,
68.71; H, 9.83.
Compound 14a-more polar. Colorless oil; IR (neat) ncmK1
;
1
2977, 2930, 1775, 1455, 1371, 1259, 1164, 1052, 928. H
NMR (400 MHz, CDCl3) d 4.37 (1H, dd, JZ9.4, 7.1 Hz),
4.22 (1H, dd, JZ9.4, 2.1 Hz), 3.58 (1H, dq, JZ9.8, 7.1 Hz),
3.54–3.41 (2H, m), 3.37 (1H, dq, JZ9.4, 7.1 Hz), 3.28 (1H,
d, JZ8.1 Hz), 2.51–2.36 (2H, m), 1.19 (3H, t, JZ7.1 Hz),
1.16 (3H, t, JZ7.1 Hz), 1.15 (3H, d, JZ7.1 Hz). 13C NMR
(100.6 MHz, CDCl3) d 174.7, 99.4, 73.3, 57.2, 56.7, 45.9,
46.1, 34.5, 15.0, 14.9, 14.2. EI-MS m/z: 214 (MC). HRMS
Calcd for C11H18O4: 214.1205 (MC), found: 214.1206.
4.1.17. Benzyl 3-(2,2-diethoxycyclopropyl)propanoate
(11). Colorless oil; IR (neat) ncmK1; 2975, 1737, 1455,
1263, 1166, 1054, 697. 1H NMR (400 MHz, CDCl3) d 7.41–
7.28 (5H, m), 5.12 (2H, s), 3.74–3.49 (4H, m), 2.46 (2H, td,
JZ7.2, 4.3 Hz), 1.82 (1H, sext, JZ7.2 Hz), 1.66 (1H, sext,
JZ7.2 Hz), 1.21–1.11 (1H, m), 1.20 (3H, t, JZ7.1 Hz),
1.17 (3H, t, JZ7.1 Hz), 0.97 (1H, dd, JZ10.0, 5.5 Hz), 0.47
(1H, t, JZ5.5 Hz). 13C NMR (100.6 MHz, CDCl3) d 173.3,
136.1, 128.5, 128.2, 91.8, 66.1, 62.2, 61.4, 34.1, 24.6, 23.9,
18.0, 15.4, 15.3. EI-MS m/z: 292 (MC), 263 (MCKEt), 247
(MCKOEt), 201 (MCKBn). Anal. Calcd for C17H24O4: C,
69.84; H, 8.27. Found: C, 69.64; H, 8.41.
4.1.20. 4-(2,2-Diethoxycyclopropyl)dihydro-2(3H)-fura-
none (13a). IR (neat) ncmK1; 2977, 1779, 1458, 1372, 1267,
1166, 1054, 1018. 1H NMR (400 MHz, CDCl3) d 4.39 (1H,
dd, JZ8.8, 7.0 Hz), 4.09 (1H, dd, JZ8.8, 6.7 Hz), 3.76–
3.66 (2H, m), 3.58 (1H, dq, JZ9.5, 7.1 Hz), 3.15 (1H, dq,
JZ9.3, 7.1 Hz), 2.71 (1H, dd, JZ19.6, 10.7 Hz), 2.41–2.30
(2H, m), 1.23–1.16 (1H, m), 1.20 (3H, t, JZ7.1 Hz), 1.19
(3H, t, JZ7.1 Hz), 1.07 (1H, dd, JZ9.9, 6.0 Hz), 0.61 (1H,
t, JZ6.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 177.0, 90.7,
72.7, 62.3, 61.8, 35.3, 35.0, 27.4, 17.1, 15.3, 15.2. EI-MS
m/z: 215 (MCC1), 169 (MCKOEt). Anal. Calcd for
C11H18O4: C, 61.66; H, 8.47. Found: C, 61.64; H, 8.30.
4.1.18. Benzyl 2,2-diethoxy-3-methylcyclobutanecar-
boxylate (12). Compound trans-12. Colorless oil; IR
(neat) ncmK1; 2975, 1738, 1455, 1329, 1226, 1188, 1132,
4.1.21. 4-(2,2-Diethoxycyclopropyl)tetrahydro-2H-
pyran-2-one (13b). Compound 13b-less polar. Colorless
oil; IR (neat) ncmK1; 2976, 1739, 1446, 1399, 1285, 1252,
1221, 1196, 1060. 1H NMR (500 MHz, CDCl3) d 4.44 (1H,
dt, JZ11.3, 4.1 Hz), 4.25 (1H, td, JZ11.3, 4.1 Hz), 3.75
(1H, dq, JZ9.4, 7.1 Hz), 3.72 (1H, dq, JZ9.4, 7.1 Hz), 3.53
(1H, dq, JZ9.4, 7.1 Hz), 3.44 (1H, dq, JZ9.4, 7.1 Hz), 2.84
(1H, dd, JZ17.5, 5.9 Hz), 2.31 (1H, dd, JZ17.5, 9.4 Hz),
1.99–1.93 (1H, m), 1.76–1.65 (2H, m), 1.19 (3H, t, JZ
1
1051, 697. H NMR (400 MHz, CDCl3) d 7.41–7.27 (5H,
m), 5.25 (1H, d, JZ12.6 Hz), 5.09 (1H, d, JZ12.6 Hz),
3.64–3.50 (2H, m), 3.37 (2H, q, JZ7.1 Hz), 3.30 (1H, dd,
JZ9.2, 5.3 Hz), 2.73–2.62 (1H, m), 2.32 (1H, ddd, JZ11.2,
10.0, 5.3 Hz), 1.41 (1H, ddd, JZ11.2, 9.2, 7.3 Hz), 1.18
(3H, t, JZ7.1 Hz), 1.10 (3H, t, JZ7.1 Hz), 1.07 (3H, d, JZ
5.8 Hz). 13C NMR (100.6 MHz, CDCl3) d 171.4, 136.6,

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10877
7.1 Hz), 1.18 (3H, t, JZ7.1 Hz), 1.05 (1H, dd, JZ9.8,
5.5 Hz), 1.00 (1H, td, JZ9.8, 5.5 Hz), 0.57 (1H, t, JZ
5.5 Hz). 13C NMR (125.7 MHz, CDCl3) d 171.0, 91.2, 68.6,
62.2, 61.8, 36.7, 31.6, 30.0, 28.2, 17.3, 15.4, 15.3. HRMS
Calcd for C12H20O4: 228.1362 (MC), found: 228.1340.
2970, 1643, 1442, 1374, 1291, 1191, 1134, 1058. 1H NMR
(400 MHz, CDCl3) d 4.57–4.46 (1H, m), 3.50–3.39 (4H, m),
3.42–3.31 (1H, m), 3.14 (1H, dd, JZ10.0, 8.5 Hz), 2.35–
2.24 (1H, m), 1.92 (1H, q, JZ10.0 Hz), 1.75 (1H, dt, JZ
10.0, 8.5 Hz), 1.38 (3H, d, JZ6.7 Hz), 1.36 (3H, d, JZ
6.8 Hz), 1.19 (3H, d, JZ6.5 Hz), 1.17 (3H, t, JZ7.0 Hz),
1.12 (3H, t, JZ7.0 Hz), 1.12 (3H, d, JZ6.4 Hz), 1.05 (3H,
d, JZ6.8 Hz). 13C NMR (125.7 MHz, CDCl3) d 169.2,
103.9, 57.1, 56.9, 47.9, 47.8, 45.5, 38.0, 23.3, 20.9, 20.0,
19.5, 15.3, 15.2, 14.3. EI-MS m/z: 285 (MC). Anal. Calcd
for C16H31NO3: C, 67.33; H, 10.95; N, 4.91. Found: C,
67.13; H, 10.87; N, 4.89.
Compound 13b-more polar. Colorless oil; IR (neat) ncmK1
;
2976, 1741, 1454, 1398, 1307, 1254, 1223, 1196, 1063. 1H
NMR (400 MHz, CDCl3) d 4.42 (1H, dt, JZ11.4, 4.2 Hz),
4.25 (1H, ddd, JZ11.4, 10.1, 4.0 Hz), 3.80–3.68 (2H, m),
3.56 (1H, dq, JZ9.5, 7.0 Hz), 3.47 (1H, dq, JZ9.5, 7.0 Hz),
2.69 (1H, ddd, JZ17.2, 7.1, 1.2 Hz), 2.31 (1H, dd, JZ17.2,
9.9 Hz), 2.11–2.04 (1H, m), 1.80–1.65 (2H, m), 1.20 (3H, t,
JZ7.0 Hz), 1.19 (3H, t, JZ7.0 Hz), 1.08–0.98 (2H, m),
0.60–0.52 (1H, m). 13C NMR (100.6 MHz, CDCl3) d 171.3,
91.3, 68.6, 62.3, 61.8, 35.7, 31.3, 30.2, 29.3, 17.1, 15.4,
15.3. EI-MS m/z: 229 (MCC1), 183 (MCKOEt). HRMS
Calcd for C12H20O4: 228.1362 (MC), found: 228.1368.
4.1.25.
2,2-Diethoxy-N,3-dimethyl-N-phenylcyclo-
butanecarboxamide (17d). Compound cis-17d. Colorless
oil; IR (neat) ncmK1; 2975, 1657, 1496, 1387, 1190, 1054,
699. 1H NMR (400 MHz, CDCl3) d 7.37 (2H, t, JZ7.2 Hz),
7.32–7.22 (3H, m), 3.53–3.41 (2H, m), 3.27 (3H, s), 3.13–
3.04 (2H, m), 3.01–2.93 (1H, m), 2.29–2.19 (1H, m), 1.92–
1.85 (1H, m), 1.79–1.69 (1H, m), 1.20 (3H, t, JZ7.0 Hz),
1.09 (3H, d, JZ6.9 Hz), 1.00 (3H, t, JZ6.8 Hz). 13C NMR
(100.6 MHz, CDCl3) d 170.6, 144.0, 129.2, 128.0, 127.3,
103.6, 57.1, 56.3, 45.4, 38.8, 37.9, 23.5, 15.4, 15.0, 14.4.
EI-MS m/z: 292 (MCC1), 262 (MCKEt). Anal. Calcd for
C17H25NO3: C, 70.07; H, 8.65; N, 4.81. Found: C, 69.78; H,
8.67; N, 4.75.
4.1.22. N,N-Dimethyl-2,2-diethoxy-3-methylcyclobutane-
carboxamide (17a). Compound 17a-less polar. Colorless
oil; IR (neat) ncmK1; 2977, 1650, 1398, 1263, 1192, 1054,
968, 659. 1H NMR (500 MHz, CDCl3) d 3.46–3.42 (3H, m),
3.27–3.20 (2H, m), 3.10 (3H, s), 2.87 (3H, s), 2.32 (1H, ddq,
JZ9.8, 8.8, 6.8 Hz), 1.90 (1H, q, JZ10.2 Hz), 1.75 (1H, dt,
JZ10.2, 8.8 Hz), 1.14 (3H, t, JZ7.1 Hz), 1.07 (3H, t, JZ
7.0 Hz), 1.02 (3H, d, JZ6.8 Hz). 13C NMR (125.7 MHz,
CDCl3) d 170.5, 104.2, 56.9, 56.2, 46.6, 38.1, 36.9, 35.4,
22.9, 15.4, 15.2, 14.3. EI-MS m/z: 229 (MC), 200 (MCK
Et), 184 (MCKOEt). HRMS Calcd for C12H23NO3:
229.1678 (MC), found: 229.1674.
Compound trans-17d. Colorless oil; IR (neat) ncmK1; 2974,
1657, 1496, 1380, 1053, 701. 1H NMR (400 MHz, CDCl3) d
7.35 (2H, t, JZ7.2 Hz), 7.29–7.21 (3H, m), 3.38–3.29 (2H,
m), 3.28 (3H, s), 3.22 (1H, d, JZ8.0 Hz), 2.83–2.72 (2H,
m), 2.29–2.14 (2H, m), 1.26–1.25 (1H, m), 1.15 (3H, t, JZ
7.0 Hz), 0.95 (3H, d, JZ6.9 Hz), 0.83 (3H, t, JZ6.9 Hz).
13C NMR (125.7 MHz, CDCl3) d 171.2, 144.2, 129.2, 128.8,
127.4, 102.3, 56.4, 55.7, 44.3, 39.5, 38.0, 24.8, 15.2, 15.1,
14.3. EI-MS m/z: 292 (MCC1), 262 (MCKEt), 246 (MCK
OEt). Anal. Calcd for C17H25NO3: C, 70.07; H, 8.65; N,
4.81. Found: C, 70.17; H, 8.68; N, 4.77.
Compound 17a-more polar. Colorless oil; IR (neat) ncmK1
;
2975, 1649, 1393, 1226, 1134, 1060, 985. 1H NMR
(500 MHz, CDCl3) d 3.59–3.48 (2H, m), 3.39 (1H, dd,
JZ8.3, 3.3 Hz), 3.34 (2H, q, JZ7.1 Hz), 3.02 (3H, s), 2.93
(3H, s), 2.68–2.59 (1H, m), 2.33 (1H, ddd, JZ10.0, 9.4,
3.3 Hz), 1.27 (1H, dt, JZ10.0, 8.3 Hz), 1.21 (3H, t, JZ
7.1 Hz), 1.06 (3H, t, JZ7.1 Hz), 1.02 (3H, d, JZ5.9 Hz).
13C NMR (125.7 MHz, CDCl3) d 171.2, 102.8, 56.6, 56.4,
44.4, 39.3, 37.3, 35.9, 24.2, 15.2, 15.1 14.5. EI-MS m/z: 229
(MC), 184 (MCKOEt). HRMS Calcd for C12H23NO3:
229.1678 (MC), found: 229.1664.
4.1.26. 2,2-Diethoxy-3-methyl-N,N-diphenylcyclo-
butanecarboxamide (17e). White crystal; mp 87.5–
88.4 8C. IR (KBr) ncmK1; 2972, 1660, 1479, 1365, 1134,
1055, 982. H NMR (400 MHz, CDCl3) d 7.39–7.13 (10H,
1
m), 3.53–3.33 (3H, m), 2.93–2.82 (2H, m), 2.33 (1H, td, JZ
9.8, 1.8 Hz), 2.25 (1H, dq, JZ2.8, 7.0 Hz), 1.29–1.21 (1H,
m), 1.25 (3H, t, JZ7.0 Hz), 0.99 (3H, d, JZ6.8 Hz), 0.87
(3H, t, JZ7.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 171.5,
143.2, 129.9, 128.8, 126.9, 125.8 103.0, 56.4, 55.9, 45.1,
39.4, 24.3, 15.3, 15.11, 14.4. EI-MS m/z: 353 (MC). Anal.
Calcd for C22H27NO3: C, 74.76; H, 7.70; N, 3.96. Found: C,
74.78; H, 7.46; N, 4.15.
4.1.23. N,N-Dibenzyl-2,2-diethoxy-3-methylcyclobutane-
carboxamide (17b). Colorless oil; IR (neat) ncmK1; 2977,
1650, 1443, 1424, 1218, 1198, 1064, 702. 1H NMR
(500 MHz, CDCl3) d 7.37 (2H, t, JZ7.6 Hz), 7.32–7.22
(6H, m), 7.18 (2H, d, JZ7.4 Hz), 5.41 (1H, d, JZ14.1 Hz),
5.26 (1H, d, JZ17.3 Hz), 5.15 (1H, d, JZ17.3 Hz), 4.65
(1H, d, JZ14.1 Hz), 3.39–3.32 (2H, m), 3.30–3.20 (2H, m),
3.11 (1H, dq, JZ9.2, 7.0 Hz), 2.36–2.26 (1H, m), 2.03 (1H,
dt, JZ13.2, 10.2 Hz), 1.84 (1H, dt, JZ10.2, 8.6 Hz), 1.09
(3H, t, JZ7.1 Hz), 1.07 (3H, d, JZ6.9 Hz), 1.01 (3H, t, JZ
7.0 Hz). 13C NMR (125.7 MHz, CDCl3) d 171.0, 137.1,
137.0, 129.4, 128.9, 128.3, 127.4, 127.3, 126.5, 104.2, 57.1,
57.0, 48.8, 48.4, 46.9, 38.1, 23.3, 15.2, 14.4. EI-MS m/z: 381
(MC), 336 (MCKOEt), 290 (MCKBn). Anal. Calcd for
C24H31NO3: C, 75.56; H, 8.19; N, 3.67. Found: C, 75.37; H,
8.10; N, 3.75.
4.1.27. 3-(2,2-Diethoxycyclopropyl)-N,N-diphenylpro-
panamide (18e). Colorless oil; IR (neat) ncmK1; 2975,
1732, 1675, 1593, 1492, 1369, 1273, 1054. 1H NMR
(400 MHz, CDCl3) d 7.40–7.22 (10H, m), 3.68–3.48 (4H,
m), 2.39–2.32 (2H, m), 1.96–1.83 (1H, m), 1.68–1.57 (1H,
m), 1.18 (3H, t, JZ7.1 Hz), 1.16 (3H, t, JZ7.1 Hz), 1.16–
1.08 (1H, m), 0.91 (1H, dd, JZ9.9, 5.4 Hz), 0.38 (1H, t, JZ
5.4 Hz). 13C NMR (100.6 MHz, CDCl3) d 172.9, 142.9,
130.0–125.0 (aromatic), 92.0, 62.1, 61.4, 35.0, 25.0, 24.3,
17.9, 15.4, 15.3. EI-MS m/z: 353 (MC), 324 (MCKEt).
4.1.24. 2,2-Diethoxy-N,N-diisopropyl-3-methylcyclo-
;
butanecarboxamide (17c). Colorless oil; IR (neat) ncmK1

10878
H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
Anal. Calcd for C22H27NO3: C, 74.76; H, 7.70; N, 3.96.
Found: C, 74.43; H, 7.69; N, 4.07.
2976, 1781, 1698, 1453, 1388, 1262, 1199, 1054, 1001, 954.
1H NMR (400 MHz, CDCl3) d 4.40 (2H, t, JZ8.1 Hz), 4.02
(2H, t, JZ8.1 Hz), 3.84 (1H, sext, JZ6.9 Hz), 3.74–3.54
(4H, m), 2.09 (1H, ddd, JZ13.9, 6.9, 4.9 Hz), 1.32 (1H,
ddd, JZ13.6, 9.4, 6.9 Hz), 1.22 (3H, d, JZ6.9 Hz), 1.20
(3H, t, JZ7.1 Hz), 1.18 (3H, t, JZ7.1 Hz), 1.18–1.10 (1H,
m), 0.99 (1H, dd, JZ9.9, 5.5 Hz), 0.48 (1H, t, JZ5.5 Hz).
13C NMR (100.6 MHz, CDCl3) d 177.1, 153.1, 91.3, 62.1,
61.8, 61.4, 42.8, 37.4, 31.9, 23.3, 18.4, 17.3, 15.4, 15.3. EI-
MS m/z: 285 (MC), 256 (MCKEt), 240 (MCKOEt).
HRMS Calcd for C14H23NO5: 285.1576 (MC), found:
285.1561.
4.1.28. N,N-Dibenzyl-4,4-diethoxy-3-methyl-1-cyclo-
butene-1-carboxamide (20). Colorless oil; IR (neat)
ncmK1; 2975, 1639, 1611, 1421, 1219, 1188, 1048, 979.
1H NMR (400 MHz, CDCl3) d 7.39–7.17 (10H, m), 6.44
(1H, s), 4.67 (1H, s), 4.65 (1H, s), 4.63 (1H, d, JZ14.6 Hz),
4.50 (1H, d, JZ14.6 Hz), 3.74 (1H, dq, JZ9.4, 7.1 Hz),
3.72–3.64 (2H, m), 3.56 (1H, dq, JZ9.4, 7.1 Hz), 2.98 (1H,
q, JZ7.0 Hz), 1.18 (6H, t, JZ7.1 Hz), 1.12 (3H, d, JZ
7.0 Hz). 13C NMR (100.6 MHz, CDCl3) d 165.5, 143.7,
142.3, 137.0, 136.9, 128.8, 128.7, 128.5, 128.4, 127.4,
127.3, 127.1, 105.0, 59.4, 59.3, 50.3, 47.9, 46.8, 15.4, 15.3,
13.8. EI-MS m/z: 379 (MC). HRMS Calcd for C24H29NO3:
379.2147 (MC), found: 379.2134.
4.2.3. 3-[3-(2,2-Diethoxycyclopropyl)butanoyl]-1,3-oxa-
zolidin-2-one (22c). Compound 22c-less polar. Colorless
oil; IR (neat) ncmK1; 2976, 1782, 1699, 1388, 1295, 1220,
1060. 1H NMR (400 MHz, CDCl3) d 4.38 (2H, t, JZ
8.0 Hz), 4.02 (2H, td, JZ8.0, 3.4 Hz), 3.80–3.64 (2H, m),
3.55–3.40 (2H, m), 3.16 (1H, dd, JZ15.5, 7.6 Hz), 2.75
(1H, dd, JZ15.5, 6.2 Hz), 1.87–1.74 (1H, m), 1.17 (3H, t,
JZ7.1 Hz), 1.16 (3H, t, JZ7.1 Hz), 1.07 (1H, td, JZ10.0,
6.4 Hz), 1.06 (3H, d, JZ6.9 Hz), 0.98 (1H, dd, JZ10.0,
6.3 Hz), 0.48 (1H, t, JZ6.3 Hz). 13C NMR (125.7 MHz,
CDCl3) d 172.3, 153.5, 92.3, 62.6, 61.4, 42.5, 42.4, 31.4,
30.1, 19.8, 17.8, 15.4. EI-MS m/z: 285 (MC). Anal. Calcd
for C14H23NO5: C, 58.93; H, 8.13; N, 4.91. Found: C, 58.66;
H, 8.14; N, 4.91.
4.2. General procedure for the reaction of 1 with acryloyl
oxazolidinone derivatives in the presence of Lewis acid
A solution of triethyl orthoacrylate (174 mg, 1 mmol) in
toluene (2 mL) was added to a solution of ‘Cp2Zr’
(1.2 mmol), prepared from Cp2ZrCl2 with n-BuLi at
K78 8C. After being stirred for 3 h at room temperature,
the solvent was removed in vacuo and CH2Cl2 (8 mL) was
added to the residue. A solution of acryloyl oxazolidinone
derivative (1.2 mmol) shown in Table 4 in CH2Cl2 (2 mL)
and diethylaluminum chloride (1.0 M n-hexane solution,
1.5 mL, 1.5 mmol) were added to the mixture at K78 8C
and then the mixture was stirred at room temperature for
3 h. The reaction mixture was extracted with diethyl ether
after addition of NH4Cl aq and the extract was washed with
brine, dried over MgSO4. Purification of the residue,
obtained by evaporation of the solvent, by neutral silica
gel column chromatography (hexane–AcOEt) gave the
product 22 shown in Table 5.
Compound 22c-more polar. Colorless oil; IR (neat) ncmK1
;
2975, 1782, 1700, 1388, 1222, 1059, 761. 1H NMR
(400 MHz, CDCl3) d 4.40 (2H, t, JZ8.1 Hz), 4.01 (2H,
td, JZ8.1, 2.4 Hz), 3.82–3.68 (2H, m), 3.58–3.42 (2H, m),
3.11 (1H, dd, JZ15.4, 5.3 Hz), 2.83 (1H, dd, JZ15.4,
8.7 Hz), 1.87–1.75 (1H, m), 1.19 (3H, t, JZ7.1 Hz), 1.18
(3H, t, JZ7.1 Hz), 1.10 (3H, d, JZ6.6 Hz), 1.04 (1H, td,
JZ10.0, 6.5 Hz), 0.94 (1H, dd, JZ9.9, 6.5 Hz), 0.57 (1H, t,
JZ6.5 Hz). 13C NMR (125.7 MHz, CDCl3) d 172.8, 153.5,
91.9, 62.6, 61.9, 61.5, 42.6, 41.3, 31.6, 30.4, 20.5, 17.7,
15.5, 15.3. EI-MS m/z: 285 (MC). Anal. Calcd for
C14H23NO5: C, 58.93; H, 8.13; N, 4.91. Found: C, 58.63;
H, 8.10; N, 4.88.
4.2.1. 3-[3-(2,2-Diethoxycyclopropyl)propanoyl]-1,3-
oxazolidin-2-one (22a). Colorless oil; IR (neat) ncmK1
;
2976, 1782, 1700, 1389, 1212, 1053, 761. 1H NMR
(400 MHz, CDCl3) d 4.40 (2H, t, JZ8.1 Hz), 4.01 (2H, t,
JZ8.1 Hz), 3.74–3.53 (4H, m), 3.09–2.94 (2H, m), 1.93–
1.82 (1H, m), 1.70–1.59 (1H, m), 1.27–1.20 (1H, m), 1.19
(3H, t, JZ7.0 Hz), 1.18 (3H, t, JZ7.0 Hz), 0.97 (1H, dd,
JZ9.9, 5.6 Hz), 0.48 (1H, t, JZ5.6 Hz). 13C NMR
(100.6 MHz, CDCl3) d 173.2, 153.5, 91.9, 62.1, 62.0,
61.4, 42.5, 34.9, 24.6, 23.1, 18.0, 15.4, 15.3. EI-MS m/z: 271
(MC). Anal. Calcd for C13H21NO5: C, 57.55; H, 7.80; N,
5.16. Found: C, 57.44; H, 7.83; N, 5.19.
4.2.4. 3-[3-(2,2-Diethoxycyclopropyl)-3-methylbuta-
noyl]-1,3-oxazolidin-2-one (22d). Colorless oil; IR (neat)
ncmK1; 2976, 1780, 1698, 1391, 1361, 1219, 1052, 761. 1H
NMR (400 MHz, CDCl3) d 4.37 (2H, t, JZ7.1 Hz), 4.07–
3.98 (2H, m), 3.76 (1H, dq, JZ9.5, 7.1 Hz), 3.74 (1H, dq,
JZ9.5, 7.1 Hz), 3.52–3.44 (2H, m), 3.16 (1H, d, JZ
15.3 Hz), 2.92 (1H, d, JZ15.3 Hz), 1.28 (1H, dd, JZ10.3,
8.0 Hz), 1.18 (3H, t, JZ7.1 Hz), 1.17 (3H, t, JZ7.1 Hz),
1.11 (3H, s), 1.07 (3H, s), 0.88–0.83 (2H, m). 13C NMR
(100.6 MHz, CDCl3) d 172.1, 153.6, 91.5, 62.2, 61.6, 61.3,
45.3, 42.7, 35.0, 33.0, 26.6, 25.4, 15.5, 15.4, 14.3. EI-MS
m/z: 299 (MC), 270 (MCKEt), 254 (MCKOEt). Anal.
Calcd for C15H25NO5: C, 60.18; H, 8.42; N, 4.68. Found: C,
59.98; H, 8.31; N, 4.66.
4.2.2. 3-[3-(2,2-Diethoxycyclopropyl)-2-methylpro-
panoyl]-1,3-oxazolidin-2-one (22b). Compound 22b-less
polar. Colorless oil; IR (neat) ncmK1; 2976, 1780, 1699,
1
1388, 1267, 1200, 1055. H NMR (400 MHz, CDCl3) d
4.42–4.36 (2H, m), 4.08–3.95 (2H, m), 3.82 (1H, tq, JZ6.7,
6.7 Hz), 3.74–3.49 (4H, m), 1.79–1.61 (2H, m), 1.24–1.14
(10H, m), 0.95 (1H, dd, JZ9.9, 5.4 Hz), 0.54 (1H, t, JZ
5.4 Hz). 13C NMR (125.7 MHz, CDCl3) d 177.1, 153.1,
91.8, 62.6, 61.8, 61.3, 42.8, 37.2, 32.0, 22.9, 17.9, 16.5,
15.4. EI-MS m/z: 285 (MC). Anal. Calcd for C14H23NO5: C,
58.93; H, 8.13; N, 4.91. Found: C, 58.85; H, 8.17; N, 4.93.
4.2.5. (4S)-4-benzyl-3-[3-(2,2-diethoxycyclopropyl)pro-
panoyl]-1,3-oxazolidin-2-one (24). Colorless oil; IR
(neat) ncmK1; 2975, 1784, 1700, 1388, 1269, 1211, 1054,
703. 1H NMR (500 MHz, CDCl3) d 7.33 (2H, t, JZ7.1 Hz),
7.27 (1H, t, JZ7.1 Hz), 7.21 (2H, d, JZ7.6 Hz), 4.70–4.64
(1H, m), 4.20 (1H, dd, JZ8.9, 7.7 Hz), 4.16 (1H, dd, JZ8.9,
Compound 22b-more polar. Colorless oil; IR (neat) ncmK1
;

H. Ito et al. / Tetrahedron 61 (2005) 10868–10879
10879
3. Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
7873.
3.0 Hz), 3.80–3.51 (4H, m), 3.31 (1H, dt, JZ13.4, 2.4 Hz),
3.11–2.95 (2H, m), 2.77 (1H, dt, JZ13.4, 9.0 Hz), 1.97–
1.88 (1H, m), 1.72–1.63 (1H, m), 1.30–1.24 (1H, m), 1.22
(3H, t, JZ7.1 Hz), 1.19 (3H, t, JZ7.0 Hz), 1.01 (1H, dd,
JZ9.9, 5.4 Hz), {0.53 (t, JZ5.4 Hz), 0.51 (t, JZ5.4 Hz)
1H}. 13C NMR (125.7 MHz, CDCl3) d 173.0, 153.4, 135.3,
129.4, 128.9, 127.3, 92.0, 66.2, 62.2, 61.5, 55.2, 37.9, 35.4,
24.7, 23.1, 18.0, 15.4, 15.3. EI-MS m/z: 361 (MC), 316
(MCKOEt). Anal. Calcd for C20H27NO5: C, 66.46; H, 7.53;
N, 3.88. Found: C, 66.21; H, 7.37; N, 3.89.
4. (a) Ito, H.; Taguchi, T. Tetrahedron Lett. 1997, 38, 5829. (b)
Sato, A.; Ito, H.; Taguchi, T. J. Org. Chem. 2000, 65, 918. (c)
Sato, A.; Ito, H.; Yamaguchi, Y.; Taguchi, T. Tetrahedron
Lett. 2000, 41, 10239.
5. (a) Ito, H.; Kuroi, H.; Ding, H.; Taguchi, T. J. Am. Chem. Soc.
1998, 120, 6623. (b) Ito, H.; Sato, A.; Taguchi, T. Tetrahedron
Lett. 1999, 40, 3217. (c) Ito, H.; Sato, A.; Kusanagi, T.;
Taguchi, T. Tetrahedron Lett. 1999, 40, 3397.
6. Titanium and Zirconium in Organic Synthesis; Marek, I., Ed.;
Wiley-VCH: Weinheim, Germany, 2002; See also Ref. 1f.
7. Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835.
8. Stetter, H.; Uerdingen, W. Synthesis 1973, 207.
4.3. 3-(2,2-Diethoxycyclopropyl)-propionic acid benzyl
ester (25). Under an argon atmosphere, to a solution of
benzyl alcohol (19.1 mg, 0.18 mmol) in THF (1.5 mL) was
added n-butyllithium (1.46 M in hexane, 0.09 mL,
0.13 mmol) at K78 8C and the mixture was stirred at 0 8C
for 15 min. A solution of 24 (32 mg, 0.09 mmol) in THF
(1 mL) was added to the reaction mixture at K78 8C and
then the temperature was raised to ambient temperature.
After being stirred for 1 h, saturated aqueous ammonium
chloride was added to the mixture and the reaction mixture
was extracted with ether for three times. Organic layer was
washed with brine, dried over magnesium sulfate, and
concentrated under vacuum. The residue was purified by
neutral silica gel column chromatography to afford product
25 (25 mg, 0.084 mmol, 95%). Spectral data of 25 was
identified with those of compound 11.
9. Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1986, 27, 2829.
10. Reviews of a,b-unsaturated acyl anion equivalent based on the
heteroatom stabilized allylic and allenic anions; (a)
Yamamoto, Y. In Trost, B. M., Fleming, I., Eds.; Compre-
hensive Organic Synthesis; Pergamon: Oxford, 1991; Vol. 2.
(b) Yamamoto, H. In Trost, B. M., Fleming, I., Eds.;
Comprehensive organic synthesis; Pergamon: Oxford, 1991;
Vol. 2. Addition of a,b-unsaturated acyl zirconiums as
unmasked acyl anions with aldehyde and ketone; (c) Harada,
S.; Taguchi, T.; Tabuchi, N.; Narita, K.; Hanzawa, Y. Angew.
Chem., Int. Ed. Engl. 1998, 37, 1696 and references cited. See
also; (d) Hanzawa, Y.; Tabuchi, N.; Taguchi, T. Tetrahedron
Lett. 1998, 39, 8141. (e) Hanzawa, Y. In Titanium and
Zirconium in Organic Synthesis; Marek, I., Ed.; Wiley-VCH:
Weinheim, 2002.
11. Hena, M. A.; Terauchi, S.; Kim, C.; Horiike, M.; Kiyooka, S.
Tetrahedron: Asymmetry 1998, 9, 1883.
References and notes
12. (a) Schuda, P. F.; Ebner, C. B.; Potlock, S. J. Synthesis 1987,
12, 1055. (b) Trova, M. P.; Gauuan, P. J. F.; Pechulis, A. D.;
Bubb, S. M.; Bocckino, S. B.; Crapoc, J. D.; Dayc, B. J.
Bioorg. Med. Chem. 2003, 11, 2695.
1. For reviews on preparation and reactions of allylic organo-
metallic reagents, see: (a) Yamamoto, Y.; Maruyama, K.
Heterocycles 1982, 18, 357. (b) Hoffmann, R. W. Angew.
Chem., Int. Ed. Engl. 1982, 21, 555. (c) Yamamoto, Y. Acc.
Chem. Res. 1987, 20, 243. (d) Roush, W. R. In Trost, B. M.,
Fleming, I., Eds.; Comprehensive Organic Synthesis;
Pergamon: Oxford, 1991; Vol. 2. (e) Yamamoto, Y. In Trost,
B. M., Fleming, I., Eds.; Comprehensive Organic Synthesis;
Pergamon: Oxford, 1991; Vol. 2. (f) Yamamoto, Y.; Asao, N.
Chem. Rev. 1993, 93, 2207.
13. Examples for the cyclopropanation reaction of monoalkoxy-
allylic metals with carbonyl compounds. (a) Hoffmann, R. W.;
Metternich, R. Liebigs Ann. Chem. 1985, 2390. (b) Barrett,
A. G. M.; Seefeld, M. A. Tetrahedron 1993, 49, 7857. (c)
Marshall, J. A.; Luke, G. P. J. Org. Chem. 1991, 56, 483. (d)
Marshall, J. A.; Jablonowski, J. A.; Luke, G. P. J. Org. Chem.
1994, 59, 7825.
2. (a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992,
33, 1295. (b) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y.
Tetrahedron 1995, 51, 4507. (c) Ito, H.; Motoki, Y.; Taguchi,
T.; Hanzawa, Y. J. Am. Chem. Soc. 1993, 115, 8835. (d) Ito,
H.; Ikeuchi, Y.; Taguchi, T.; Hanzawa, Y.; Shiro, M. J. Am.
Chem. Soc. 1994, 116, 5469. (e) Ito, H.; Hanzawa, Y.;
Taguchi, T. J. Synth. Org. Chem. Jpn. 1994, 52, 217. (f) Ito, H.
Chemistry and Chemical Industry 1995, 48, 155. (g) Hanzawa,
Y.; Ito, H.; Taguchi, T. Synlett 1995, 299–305.
14. For reviews on the [2C2]-cycloaddition of ketene acetal with
a,b-unsaturated carbonyl compound, see: (a) Carbocyclic
four-membered ring compounds; de Meijere, A., Ed.; Houben-
Weyl Methods of Organic Chemistry; Thieme: Stuttgart, 1997;
Vol. 17e/f. (b) Lee-Ruff, E.; Mladenova, G. Chem. Rev. 2003,
103, 1449. (c) Fruhauf, H.-W. Chem. Rev. 1997, 97, 523. (d)
Crimmins, M. T.; Reinhold, T. L. Org. React. 1993, 44, 297.
(e) Brannock, K. C.; Burpitt, R. D.; Thweatt, J. G. J. Org.
Chem. 1964, 29, 940.