Synthesis of substituted cyclopropanone acetals by carbometallation and its oxidative cleavage with manganese(IV) oxide and lead(IV) oxide

Article abstract of DOI:10.1016/S0022-328X(01)00679-9

A variety of substituted cyclopropanone acetals were prepared by the addition of an organozinc reagent or a Grignard reagent to a substituted cyclopropenone acetal. MnO₂- or PbO₂-mediated oxidative ring opening reaction of the substituted cyclopropanone acetals affords β-alkoxyesters and protected β-aminoesters with high efficiency.

Full text of DOI:10.1016/S0022-328X(01)00679-9

Journal of Organometallic Chemistry 624 (2001) 300–306
www.elsevier.nl/locate/jorganchem
Synthesis of substituted cyclopropanone acetals by
carbometallation and its oxidative cleavage with manganese(IV)
oxide and lead(IV) oxide
Masaharu Nakamura, Toshihiro Inoue, Eiichi Nakamura *
Department of Chemistry, The Uni6ersity of Tokyo, Hongo Bunkyo-ku, Tokyo 113-0033, Japan
Received 3 November 2000; accepted 5 January 2001
Dedicated to Prof J.F. Normant on the occasion of his 65th birthday in recognition of his outstanding contribution to organometallic
chemistry
Abstract
A variety of substituted cyclopropanone acetals were prepared by the addition of an organozinc reagent or a Grignard reagent
to a substituted cyclopropenone acetal. MnO2- or PbO2-mediated oxidative ring opening reaction of the substituted cyclo-
propanone acetals affords b-alkoxyesters and protected b-aminoesters with high efficiency. © 2001 Elsevier Science B.V. All rights
reserved.
Keywords: Carbometallation; Cyclopropane; Oxidation; Ring opening; Manganese dioxide; Lead dioxide
substituted cyclopropanes belongs to the least-devel-
oped transformations of the compounds, since it often
1. Introduction
encounters the problem of regioselectivity of the ring
Synthetic transformations of cyclopropane deriva-
opening [2]. Here we report a new synthetic route to
tives have been the subject of numerous investigations
b-alkoxyesters and b-aminoesters 3 by regioselective
and provided a large number of synthetically useful
oxidative cleavage of substituted cyclopropanone ac-
routes to a variety of functionalized organic molecules
etals 2. The latter have been synthesized by carbometal-
[1]. Among these transformations, oxidative cleavage of
lation of readily accessible cyclopropenone acetals
(CPAs) 1 [3] (Scheme 1).
2. Results and discussion
The starting cyclopropanone acetals were prepared
by allylzincation [4] or iron-catalyzed carbomagnesa-
tion [5] reaction of CPAs, which can be synthesized on
a large scale from inexpensive 1,3-dichloroacetone [3,6].
Table 1 summarizes the results of carbometallation and
sequential trapping of the intermediary cyclopropyl
metal species. Addition of phenylmagnesium bromide
to CPA 1a (R1=H) proceeded smoothly at −45°C to
Scheme 1.
afford 2-phenylcyclopropanone acetal 2a in 96% yield
(Table 1, entry 1). Electrophilic trapping of the cyclo-
* Corresponding author.
propylmagnesium species with allyl bromide afforded
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)00679-9

M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
301
Table 1
cerium(IV) ammonium nitrate (CAN) or thallium(III)
nitrate under various conditions gave a mixture of
products, and the reaction with lead tetraacetate gave
none of the desired ring opening product. We finally
found that manganese(IV) dioxide (MnO2) in the pres-
ence of an acid is an effective oxidant for the selective
ring opening reaction.
Carbometallation and successive electrophilic trapping of cyclo-
propenone acetalsa,b
The oxidative ring opening reaction was conducted
by the addition of a slight excess amount of MnO2 to
the solution of 2a in methanol in the presence of
Scheme 2.
Table 2
Oxidative ring opening reaction of 2 with MnO2 and PbO2a
cis-2-allyl-3-phenylcyclopropanone acetal 2b as a single
stereoisomer in 85% yield, indicating cis-stereochem-
istry of the carbomagnesation (Table 1, entry 2). The
addition of a vinyl Grignard reagent took place
smoothly to afford a vinylated cyclopropanone acetal
in good yield, while the addition of a substituted
alkenyl Grignard reagent afforded the carbometallation
product in lower yield (entries 3–5). Chiral cyclo-
propanone acetals bearing a quaternary chiral center
were prepared by enantioselective allylzincation reac-
tion of substituted CPAs 1b (R1=Et) and 1c (R1=Ph)
[4], in order to obtain mechanistic information on the
subsequent oxidative ring opening reactions (vide in-
fra). Addition of a chiral allylzinc reagent bearing an
anionic bis-oxazoline ligand derived from (S)-(+)-2-
phenylglycinol, thus, gave 2,2-disubstituted cyclo-
propanone acetal in excellent yield with high
enantioselectivity (entries 6 and 7).
We first examined the oxidative ring cleavage reac-
tion of 2-phenycyclopropanone acetal 2a (R1=H,
R2=Ph, E=H) under a variety of oxidative condi-
tions. The oxidative ring opening reaction [7] with

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M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
Table 3
3a (R=OAc) was obtained in 84% yield (entry 8). The
ring opening reaction with PbO2 in CH3CN afforded
the b-aminophenylpropionate derivative 4a in 77%
yield as observed in the reaction with MnO2 (entry 9).
A series of substituted cyclopropanes 2 were next
subjected to the oxidative ring opening reaction condi-
tions (Table 3) in order to study selectivity issues. When
an optically active cyclopropanone acetal 2g was sub-
jected to the PbO2-promoted ring opening reaction,
racemic 3-acetoxy-3-phenyl-5-hexenoate ester 3g was
obtained in 67% yield as a sole regioisomer (Table 3,
entry 1). An optically active cyclopropanone acetal
bearing an ethyl group (2f) also gave a racemic product
(Table 3, entry 2). When a cis-disubstituted cyclo-
propanone acetal 2b was treated with PbO2 in MeOH,
2-allyl-3-methoxy-3-phenylpropionate 3b was obtained
as a sole regioisomer in 54% yield (Table 3, entry 3).
Oxidative ring opening reaction of substituted cyclopropanone acetal
2 under various conditionsa
The product, however, was
a
6:4 mixture of
diastereomers, and therefore, it was found that the
stereochemistry of starting material was lost com-
pletely. The rate of the oxidative ring opening reaction
of a cyclopropane substrate without a stabilizing group
(e.g. 2f) was found to be much slower than those of 2a
and 2g bearing a phenyl group (Table 3, entry 2).
The reaction of 2-styrylcyclopropanone acetal 2d
with MnO2 in methanol afforded only one product
owing to the regioselective ring opening and the re-
gioselective addition of methanol (Table 2, entry 2).
However, the oxidative ring opening reaction of iso-bu-
tenyl cyclopropanone acetal (2e) under the same condi-
tions gave a mixture of isomers concerning to the
position of double bond in the product (Table 3, entry
4). It should be noted that the regioselectivity of the
cyclopropane cleavage is highly selective in all cases as
shown in Table 3.
These experimental observations suggest that the re-
action proceeds via a stepwise ring opening mechanism.
Scheme 3 depicts a plausible reaction mechanism. Thus,
one-electron oxidation of the acetal by the metal oxide
and addition of solvent take place sequentially to gener-
ate a radical cation and a neutral radical intermediates
A and B, respectively. The second one-electron oxida-
tion generates the cation C, which is trapped by solvent
to give D. The regioselectivity of the ring opening
depends on the stability of the radical cation intermedi-
ate A; namely, an sp2 carbon substituent, such as
phenyl or alkenyl group, stabilizes the radical in A.
trifluoromethanesulfonic acid (TfOH) at 25°C. The re-
action was complete in 1 h at 25°C to afford b-
methoxypropionate ester 3a in 71% yield (Scheme 2 and
Table 2, entry 1). As shown in entry 2, 2-styrylcyclo-
propanone acetal was also converted to the correspond-
ing b-methoxyester 3d in good yield under the same
conditions. The geometry of the alkenic moiety in the
product was exclusively trans in spite of the fact that
the starting olefin was a mixture of geometrical isomers
(trans/cis=76:24), indicating the involvement of a se-
quential one-electron oxidation mechanism (vide infra).
An amination reaction could also be achieved when the
ring opening reaction of 2a was carried out in acetoni-
trile (entry 3). Consecutive regioselective ring opening
and trapping of the resulting cationic intermediate with
acetonitrile (Ritter-type reaction) accounts for the for-
mation of the b-aminopropionate derivative 4a.
Lead dioxide (PbO2) was also found to promote
selective ring opening reaction of the cyclopropanone
acetals 2.
A stoichiometric amount of PbO2 in
methanol converts 2a to 3a in 80% yield in the presence
of two equivalents of TfOH (entry 4). This reaction was
found to be applicable also to ethanol and isopropanol,
and afforded 3-ethoxy and 3-isopropoxy substituted
ester, respectively (entries 5 and 6). As shown in entry
7, 3-benzyloxy-3-phenylpropionate derivative 3a (R=
OBn) was also synthesized in 78% yield by using benzyl
alcohol as a solvent. When the ring opening reaction of
2a was carried out in acetic acid, b-acetoxypropionate
3. Experimental
3.1. General considerations
All reactions were carried out under inert atmosphere
(Ar or N2) in a pre-dried glassware. Anhydrous tetrahy-
drofuran and diethylether were purchased from Kanto

M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
303
solution was stirred for about 4 h at that temperature.
Allyl bromide (3.63 g, 30 mmol) was added at −45°C
dropwise, and then the reaction mixture was warmed to
25°C. The reaction mixture was diluted with ethyl
acetate and 1.5 N aqueous HCl. Aqueous layer was
extracted with ethyl acetate twice and combined organ-
ics were washed with brine, and then dried over
MgSO4. Evaporation of solvent afforded a pale yellow
oil (2.77 g). Purification by silica gel chromatography
(silica gel; 60 g, eluent hexane–ethyl acetate; 100:0–
95:5) afforded 2.21 g of disubstituted cyclopropanone
acetal 2b (R1=H, R2=Ph, E=CH2CHꢀCH2) (85%
yield).
Compound 2b. IR (neat, cm−1) 3060(s), 2956(m),
2866(s), 1732(m), 1498(s), 1471(m), 1394(s), 1263(m),
1
1105(m), 1022(m), 910(s), 766(s), 702(s); H-NMR (400
MHz, CDCl3) (l) 0.94 (s, 3H), 1.08 (s, 3H), 1.62 (ddd,
J=7.1, 7.3, 11.0 Hz, 1H), 2.08–2.16 (m, 1H), 2.18–
2.25 (m, 1H), 2.38 (d, J=11.0 Hz, 1H), 3.46 (d, J=
10.5 Hz, 1H), 3.57 (d, J=10.5 Hz, 1H), 3.58 (br s, 2H),
4.93 (ddd, J=10.3, 4.2, 1.5 Hz, 1H), 5.02 (ddd, J=
17.1, 3.4, 1.6 Hz, 1H), 5.70–5.82 (m, 1H), 7.10–7.35
(m, 5H); 13C-NMR (100 MHz, CDCl3) (l) 22.3, 22.6,
26.2, 29.1, 30.9, 31.5, 75.5, 76.2, 91.5, 114.9, 125.6,
127.8 (2C), 129.0 (2C), 136.1, 137.0; Anal. Found: C,
79.30; H, 8.60. Calc. for C17H22O2: C, 79.03; H, 8.58%.
2-Phenylcyclopropanone 2,2-dimethyl-1,3-propane-
diyl acetal (2a). IR (CCl4, cm−1) 2958(s), 2856(m),
Scheme 3.
Chemical Co. These ethereal solvents were dried over
molecular sieves in a storage flask. The water content of
the solvent was determined with a Karl–Fischer Mois-
ture Titrator (MKC-210, Kyoto Electronics Company)
to be less than 10 ppm. Unless otherwise noted, materi-
als purchased from Tokyo Kasei Co, Aldrich Inc., and
other commercial suppliers, were distilled or recrystal-
lized before use. Alkyllithium reagents were purchased
from Aldrich Inc. and Kanto Chemical Co, and titrated
prior to use. FeCl3 was purchased from Kanto Chemi-
cal Co. Inc. and thoroughly dehydrated by SOCl2 and
1
1471(m), 1173(s), 1074(s), 1043(m), 908(s), 696(s); H-
NMR (400 MHz, CDCl3) (l) 0.80 (s, 3H), 1.13 (s, 3H),
1.36 (dd, J=6.4, 7.2 Hz, 1H), 1.52 (dd, J=6.4, 10.4
Hz, 1H), 2.37 (dd, J=7.2, 10.4 Hz, 1H), 3.12 (d,
J=10.8 Hz, 1H), 3.32 (d, J=10.8 Hz, 1H), 3.59 (dis-
torted d, J=12.4 Hz, 1H), 3.61 (distorted d, J=12.4
Hz, 1H), 7.1–7.3 (m, 5H); 13C-NMR (100 MHz,
CDCl3) (l) 19.6, 22.1, 22.5, 30.0, 30.5, 75.7, 76.2, 90.5,
125.4, 126.9 (2C), 127.8 (2C), 137.2; Anal. Found: C,
77.00; H, 8.30. Calc. for C14H18O2: C, 77.03; H, 8.31%.
1
dried over P2O5 under reduced pressure. All H-NMR
spectra were taken at 400 MHz and 13C-NMR spectra
at 100 MHz using a JEOL EXcaliber-400 instrument,
are reported in ppm (l). IR spectra recorded on a
JASCO IR-800 are reported in cm−1. GC analysis was
performed on a Shimadzu GC 14A and 14B equipped
with a capillary column, HR-1 (0.25 mm ID×25 m) or
CP-Chirasil-DEX CB (0.25 mm ID×25 m). Elemental
analyses were performed on a Perkin–Elmer 2400CHN
elemental analyzer. Mass spectra were obtained by the
atmospheric chemical ionization (APCI) method with a
Shimadzu LCMS-QP8000.
3.3. Preparation of (2S)-2-allyl-2-phenylcyclopropanone
2,2-dimethyl-1,3-propanediyl acetal (2g)
To a solution of bis-oxazoline (170 mg, 0.56 mmol)
and 2,2%-bipyridyl (ca. 1 mg) in dry THF (0.56 ml) was
added a 1.60 M solution of BuLi in hexane at 0°C until
the clear solution turned into a red-brown suspension.
After the addition of BuLi, the reaction mixture was
stirred for 20 min at room temperature (r.t.) and then
cooled to 0°C at which time a 0.88 M solution of
allylzinc bromide in THF (0.55 ml, 0.48 mmol) was
added to the solution. The clear red solution was
allowed to warm to r.t. for 20 min and then cooled
back to 0°C. A solution of CPA 1c (95.1 mg, 0.44
mmol) in dry THF (1.07 ml) was then added dropwise
to the reaction mixture. The reaction mixture (1.73 ml)
3.2. Representati6e procedure for carbometallation and
successi6e electrophilic trapping reaction of
cyclopropenone acetal; preparation of
2-allyl-3-phenylcyclopropanone
2,2-dimethyl-1,3-propanediyl acetal (2b)
To a solution of phenylmagnesium bromide (12
mmol) and cyclopropenone acetal 1 (1.40 g, 10 mmol)
in dry THF (36 ml) was added a 0.1 M THF solution
of FeCl3 (3 ml, 0.3 mmol) at −45°C. The colorless
reaction mixture turned dark brown and the resulting

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M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
was transferred into an oven-dried Teflon® vessel with a
screw cap under an inert atmosphere. The reaction
vessel was maintained under high pressure (1 GPa) for
13 h at 25°C. The reaction mixture was quenched with
saturated NH4Cl (20 ml), filtered through a pad of
Florisil®, and concentrated in vacuo. Purification of the
residual oil on silica gel afforded the allylation product
as a colorless oil (77 mg, 98% yield). Enantiomeric
excess of 2g was determined as \98% ee by capillary
GLC analysis (CP-Chirasil-DEX-CB, 0.25-mm ID×25
m, 120°C, retention times; 59.24 and 59.92 min,
respectively).
128.0, 128.5 (2C), 140.1, 171.5; Anal. Found: C, 67.37;
H, 8.27. Calc. for C15H22O4: C, 67.65; H, 8.33%.
3-Hydroxy-2,2-dimethylpropyl 3-methoxy-5-phenyl-
4-(E)-pentenoate (3d). IR (neat, cm−1) 3481(br s),
2962(s), 2866(m), 1732(s), 1473(m), 1375(m), 1161(s),
1101(s), 1055(s), 970(m), 910(m), 733(s), 694(m); 1H-
NMR (400 MHz, CDCl3) (l) 0.91 (s, 3H), 0.92 (s, 3H),
2.59 (dd, J=4.8, 14.8 Hz, 1H), 2.72 (dd, J=8.4, 14.8
Hz, 2H), 3.30 (s, 2H), 3.32 (s, 3H), 3.97 (s, 2H),
4.18–4.24 (m, 1H), 6.07 (dd, J=8.0, 16.0 Hz, 1H), 6.63
(d, J=16.0 Hz, 1H); 13C-NMR (100 MHz, CDCl3) (l)
21.7 (2C), 36.4, 41.4, 56.4, 68.1, 69.7, 78.8, 126.4 (2C),
127.7, 127.9, 128.4 (2C), 133.3, 135.9, 171.3; Anal.
Found: C, 69.61; H, 8.08. Calc. for C17H24O4: C, 69.84;
H, 8.27%.
Compound 2g. IR (neat, cm−1) 3073, 2956, 2856,
1639, 1602, 1498, 1471, 1446, 1351, 1292, 1157, 1132,
1
1070, 1043, 910, 700; H-NMR (400 MHz, CDCl3) (l)
0.93 (s, 3H), 1.07 (d, J=5.9 Hz, 1H), 1.07 (s, 3H), 1.37
(dd, J=1.5, 5.9 Hz, 1H), 2.34 (dd with shoulders,
J=7.3, 14.7 Hz, 1H), 2.76 (ddd, J=1.5, 6.4, 14.7 Hz,
1H), 3.30 (d, J=11.0 Hz, 1H), 3.35 (dd, J=0.97, 11.0
Hz, 1H), 3.60 (distorted dd, J=0.97, 10.7 Hz, 1H),
3.62 (distorted d, J=10.7 Hz, 1H), 4.86–4.94 (m, 2H),
5.61–5.73 (m, 1H) 7.15–7.22 (m, 1H) 7.27–7.31 (m,
4H); 13C-NMR (100 MHz, CDCl3) (l) 22.0, 22.1, 22.7,
30.6, 37.4, 38.6, 75.5, 76.4, 92.0, 116.3, 126.2, 127.9
(2C), 129.2 (2C), 135.4, 139.4; [h]2D0=1.02 (c=3.9,
benzene); Anal. Found: C, 79.07; H, 8.83. Calc. for
C17H22O2: C, 79.03; H, 8.59%.
3.5. Oxidati6e ring opening reaction of 2a with MnO2
in CH3CN; preparation of 3-hydroxy-2,2-dimethyl-
propyl 3-(acetylamino)-3-phenylpropanoate (4a)
To a solution of phenylcyclopropanone acetal 2a
(43.2 mg, 0.20 mmol) in 1.0 ml of CH3CN was added
21.3 mg of MnO2 (0.24 mmol). To this reaction mixture
was added CF3SO3H (48.7 ml, 0.55 mmol) at 25°C.
After stirring for 1 h, the reaction was quenched with
H2O (1.0 ml). The suspension was filtered and organic
layer was separated and aqueous layer was extracted
with 1.0 ml of ether (three times). Combined organic
layers were washed with brine, dried over MgSO4,
filtered and concentrated in vacuo to afford a crude
product (61.0 mg). The crude product was purified by
flash column chromatography (silica gel 2.7 g, elution
with 25% and then 70% EtOAc–hexane) to afford 4a
(45 mg, 78%) and the elimination compound (8.9 mg,
11%).
3.4. Oxidati6e ring opening reaction of 2a with MnO2
in MeOH; preparation of 3-hydroxy-2,2-dimethylpropyl
3-methoxy-3-phenylpropanoate (3a) (R=Me)
To a solution of 2-phenylcycropropanone acetal 2a
(64.9 mg, 0.30 mmol) in 1.5 ml of MeOH was added
25.9 mg of MnO2 (0.30 mmol). To this reaction mixture
was added CF3SO3H (52.2 ml, 0.40 mmol) at 25°C.
After stirring for 2 h, the solution was quenched by the
addition of water (1.5 ml). The suspension was filtered
and organic layer was separated and aqueous layer was
extracted with 1.5 ml of ether (three times). Combined
organic layers were washed with brine, dried over
MgSO4, filtered and concentrated in vacuo to afford a
crude product (73.9 mg). The crude product was
purified by flash column chromatography (silica gel 2.3
g, elution with 12.5% and then 20% EtOAc–hexane) to
afford 3a (56.7 mg, 71%) and the elimination com-
pound (3.5 mg, 5%).
Compound 4a. IR (neat, cm−1) 3298(br s), 3065(w),
2963(s), 1732(s), 1652(s), 1548(s), 1375(s), 1259(s),
1
1168(s), 1034(s), 1004(m), 762(m), 701(s), 639(m); H-
NMR (400 MHz, CDCl3) (l) 0.83 (s, 3H), 0.83 (s, 3H),
2.01 (s, 3H), 2.86 (dd, J=6.0, 15.2 Hz, 1H), 2.92 (dd,
J=7.2, 15.2 Hz, 1H), 3.10 (d, J=11.2 Hz, 1H), 3.27
(d, J=11.2 Hz, 1H), 3.84 (dd, J=11.2, 16.4 Hz, 2H),
5.48 (dd, J=6.4, 14.4 Hz, 1H), 6.48 (br d, J=6.0 Hz,
1H), 7.24–7.37 (m, 5H); 13C-NMR (100 MHz, CDCl3)
(l) 21.6 (2C), 23.5, 36.1, 40.6, 49.9, 67.8, 69.8, 126.2
(2C), 127.8, 128.7 (2C), 140.1, 169.3, 171.5; Anal.
Found: C, 64.92; H, 7.92; N, 4.59. Calc. for
C16H23NO4: C, 65.51; H, 7.90; N, 4.77%.
Compound 3a. IR (neat, cm−1) 3481(br s), 2960(s),
2875(w), 1734(s), 1456(m), 1375(m), 1271(m), 1161(s),
3.6. Oxidati6e ring opening reaction of 2a by PbO2 in
MeOH; preparation of 3-hydroxy-2,2-dimethylpropyl
3-methoxy-3-phenylpropanoate (3a) (R=Me)
1
1105(s), 1055(s), 762(m), 702(s), 447(s); H-NMR (400
MHz, CDCl3) (l) 0.89 (s, 3H), 0.90 (s, 3H), 2.62 (dd,
J=4.8, 14.8 Hz, 1H), 2.83 (dd, J=9.2, 15.2 Hz, 1H),
3.21 (s, 3H), 3.25 (dd, J=11.2, 15.2 Hz, 2H), 3.96 (dd,
J=11.2, 16.0 Hz, 2H), 4.62 (dd, J=4.8, 9.2 Hz, 1H),
7.29–7.39 (m, 5H); 13C-NMR (100 MHz, CDCl3) (l)
21.5 (2C), 36.4, 43.6, 55.7, 68.1, 69.6, 80.1, 126.5 (2C),
To a solution of 2-phenyl cyclopropenone acetal 2a
(43.1 mg, 0.20 mmol) in 0.5 ml of MeOH was added
47.8 mg of PbO2 (0.20 mmol). To this reaction mixture
was added CF3SO3H (34.7 ml, 0.40 mmol) at 25°C.

M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
305
After stirring for 1 h, the reaction was quenched with
H2O (0.5 ml). The suspension was filtered and organic
layer was separated. The aqueous layer was extracted
with 0.5 ml of ether (three times). Combined organic
layers were washed with brine, dried over MgSO4,
filtered and concentrated in vacuo to afford a crude
product (51.5 mg). The crude product was purified by
flash column chromatography (silica gel 2.0 g, elution
with 12.5% and then 20% EtOAc–hexane) to afford 3a
(42.2 mg, 80%) and the elimination compound (4.9 mg,
11%).
3-Hydroxy-2,2-dimethylpropyl 3-acetoxy-3-phenyl-
propanoate 3a (R=Ac). IR (neat, cm−1) 3843(br s),
2964(s), 2875(m), 1739(s), 1456(m), 1373(s), 1232(s),
1
1171(s), 1026(s), 733(m); H-NMR (400 MHz, CDCl3)
(l) 0.88 (s, 3H), 0.88 (s, 3H), 2.06 (s, 3H), 2.81 (dd,
J=5.2, 15.6 Hz, 1H), 3.00 (dd, J=9.2, 15.6 Hz, 1H),
3.24 (dd, J=11.6, 15.6 Hz, 2H), 3.93 (dd, J=10.8, 22.4
Hz, 2H), 6.17 (dd, J=4.8, 9.2 Hz, 1H), 7.27–7.39 (m,
5H); 13C-NMR (100 MHz, CDCl3) (l) 21.12, 21.46
(2C), 36.27, 41.54, 67.88, 69.67, 72.19, 126.34 (2C),
128.34, 128.52 (2C), 138.80, 169.70, 170.13; APCI–MS
m/z (%)=295 (8) [M++H], 277 (100) [M+−OH], 235
(18) [M+−OAc], 217 (40) [M+−OAc−H2O].
3-Hydroxy-2,2-dimethylpropyl
3-ethoxy-3-phenyl-
propanoate 3a (R=Et). IR (neat, cm−1) 3468(br s),
2972(s), 2876(s), 1735(s), 1474(m), 1455(m), 1376(s),
1345(m), 1309(m), 1270(s), 1171(s), 1096(s), 1056(s),
3.7. Oxidati6e ring opening reaction of 2g with PbO2
in AcOH; preparation of 3-hydroxy-2,2-dimethylpropyl
3-acetoxy-3-phenyl-5-hexenoate (3g)
1
1003(m), 914(m), 761(m), 734(s), 703(s); H-NMR (400
MHz, CDCl3) (l) 0.90 (s, 3H), 0.93 (s, 3H), 1.15 (t,
J=7.2 Hz, 3H), 2.62 (dd, J=4.8, 14.8 Hz, 1H), 2.83
(dd, J=9.6, 14.8 Hz, 1H), 3.26 (dd, J=9.6, 22.0 Hz,
2H), 3.49 (q, 6.0 Hz, 2H), 3.95 (dd, J=6.8, 17.6 Hz,
2H), 4.74 (dd, J=4.8, 17.6 Hz, 1H), 7.26–7.38 (m, 5H);
13C-NMR (100 MHz, CDCl3) (l) 15.1, 21.4 (2C), 36.4,
43.8, 64.3, 68.0, 69.5, 78.3, 126.5 (2C), 128.0, 128.5 (2C),
141.0, 171.8; APCI–MS m/z (%)=281 (13) [M+−H],
277 (100) [M+−3H], 263 (99) [M+−OH], 235 (17)
[M+−OMe], 217 (21) [M+−OMe−H2O].
To a solution of 2-allyl-2-phenylcyclopropanone ace-
tal (2g) (49.2 mg, 0.19 mmol) in 0.5 ml of dry acetic acid
was added 49.5 mg of PbO2 (0.21 mmol) at 25°C. The
reaction mixture was stirred for 4 h and, then, quenched
with H2O (0.5 ml). The suspension was filtered and
organic layer was separated and aqueous layer was
extracted with 0.5 ml of ether (three times). Combined
organic layers were washed with brine, dried over
MgSO4, filtered and concentrated in vacuo. The crude
product (66.1 mg) was purified by flash column chro-
matography (silica gel 2.0 g, elution with 12.5% and
then 20% EtOAc–hexane) to afford 3g (48.7 mg, 67%)
and the elimination compound (8.9 mg, 14%).
3-Hydroxy-2,2-dimethylpropyl
3-isopropoxy-3-
phenylpropanoate 3a (R=i-Pr). IR (neat, cm−1
)
3462(br s), 2970(s), 2885(w), 1732(s), 1456(m), 1377(m),
1
1269(m), 1167(s), 1051(s), 912(m), 733(m), 702(m); H-
NMR (400 MHz, CDCl3) (l) 0.89 (s, 3H), 0.90 (s, 3H),
1.05 (d, J=6.0 Hz, 3H), 1.11 (d, J=5.6 Hz, 3H), 2.58
(dd, J=4.4, 14.8 Hz, 1H), 2.79 (dd, J=9.6, 14.8 Hz,
1H), 3.20 (d, J=11.6 Hz, 1H), 3.29 (d, J=11.6 Hz,
1H), 3.49 (sep, J=6.0 Hz, 1H), 3.84 (d, J=11.2 Hz,
1H), 4.04 (d, J=10.8, Hz, 1H), 4.86 (dd, J=4.4, 9.6
Hz, 1H), 7.26–7.40 (m, 5H); 13C-NMR (100 MHz,
CDCl3) (l) 21.1, 21.6, 23.4, 36.5, 44.2, 68.1, 69.3, 69.6,
75.5, 126.4 (2C), 127.7, 128.4 (2C), 141.7, 171.7; Anal.
Found: C, 69.07; H, 8.62. Calc. for C17H26O4: C, 69.36;
H, 8.90%.
3-Hydroxy-2,2-dimethylpropyl 3-benzyloxy-3-phenyl-
propanoate 3a (R=CH2Ph). IR (neat, cm−1) 3467(br
s), 3063(m), 3031(m), 2961(s), 2875(w), 1735(s),
1495(m), 1472(m), 1455(m), 1377(m), 1308(m), 1271(m),
1200(m), 1168(s), 1057(s), 1004(m), 912(w), 759(m),
739(m), 701(s); 1H-NMR (400 MHz, CDCl3) (l) 0.85 (s,
6H), 2.67 (dd, J=4.8, 15.2 Hz, 1H), 2.91 (dd, J=9.2,
15.2 Hz, 1H), 3.17 (dd, J=11.2, 28.0 Hz, 2H), 3.88 (d,
J=10.8 Hz, 1H), 3.97 (d, J=10.8, Hz, 1H), 4.30 (d,
J=11.6 Hz, 1H), 4.43 (d, J=11.6, Hz, 1H), 4.86 (dd,
J=4.8, 9.2 Hz, 1H), 7.18–7.43 (m, 10H); 13C-NMR
(100 MHz, CDCl3) (l) 21.4 (2C), 36.4, 43.6, 68.0, 69.5,
70.7, 78.0, 126.7 (2C), 127.6, 127.8 (2C), 128.2, 128.3
(2C), 128.7 (2C), 137.9, 140.5, 171.6; Anal. Found: C,
73.84; H, 7.63. Calc. for C21H26O4: C, 73.66; H, 7.65%.
Compound 3g. IR (neat, cm−1) 3566(br s), 2960(s),
2866(w), 1732(s), 1448(m), 1373(s), 1236(s), 1018(m),
1
920(m), 700(m); H-NMR (400 MHz, CDCl3) (l) 0.75
(s, 3H), 0.78 (s, 3H), 2.11 (s, 3H), 2.96 (dd, J=6.8, 14.0
Hz, 1H), 3.03 (s, 2H), 3.19 (dd, J=8.0, 18.4 Hz, 1H),
3.29 (d, J=14.0 Hz, 1H), 3.51 (d, J=18.4 Hz, 1H),
3.77 (dd, J=10.8, 13.2 Hz, 2H), 5.06 (d, J=9.6 Hz,
1H), 5.08 (d, J=9.2 Hz, 1H), 5.41–5.51 (m, 1H),
7.25–7.29 (m, 1H), 7.33–7.38 (m, 4H); 13C-NMR (100
MHz, CDCl3) (l) 21.4, 21.5, 22.2, 36.1, 41.9, 43.1, 67.8,
69.5, 82.8, 119.4, 124.8 (2C), 127.4, 128.2 (2C), 131.5,
141.7, 170.0; Anal. Found: C, 67.94; H, 7.81. Calc. for
C19H26O5: C, 68.24; H, 7.84%.
3-Hydroxy-2,2-dimethylpropyl 3-methoxy-3-ethyl-5-
hexenoate (3f). IR (neat, cm−1) 3446(br s), 2968(s),
2885(w), 1732(s), 1458(m), 1373(m), 1186(m), 1065(m),
1
918(m); H-NMR (400 MHz, CDCl3) (l) 0.89 (t, J=
7.2 Hz, 3H), 0.93 (s, 6H), 1.62 (dq, J=2.0, 7.6 Hz, 2H),
3.39 (d, J=6.4 Hz, 2H), 2.54 (dd, J=14.0, 17.2 Hz,
2H), 3.24 (s, 3H), 3.33 (s, 2H), 3.94 (s, 2H), 5.13 (d,
J=9.2 Hz, 1H), 5.14 (d, J=17.6 Hz, 1H), 5.76–5.86
(m, 1H); 13C-NMR (100 MHz, CDCl3) (l) 7.5, 21.7,
21.7, 27.3, 36.4, 39.0, 39.7, 49.0, 68.5, 69.9, 78.0, 118.4,
122.2, 171.3; APCI–MS m/z (%)=259 (30) [M++H],
241 (13) [M+−OH], 227 (100) [M+−OMe], 209 (11)
[M+−OMe−H2O].

306
M. Nakamura et al. / Journal of Organometallic Chemistry 624 (2001) 300–306
3-Hydroxy-2,2-dimethylpropyl
2-[acetoxy(phenyl)-
4. Conclusions
methyl]-4-pentenoate (3b) major diastereomer. IR (neat,
cm−1) 3525(br s), 2962(s), 2875(w), 1734(s), 1373(m),
1232(s), 1182(m), 1024(m), 916(m), 733(m), 702(m); H-
In summary, we have demonstrated that carbometal-
lation of a cyclopropenone acetal provides useful syn-
thetic routes to a variety of substituted esters. The
two-step reaction sequence afforded b-alkoxy and b-
aminoesters of some structural varieties. It has been
shown for the first time that metal oxide such as MnO2
and PbO2 can be used for selective ring opening reaction
of substituted cyclopropanes and the reaction affords a
variety of synthetically valuable protected b-hydroxy and
b-aminopropionate esters.
1
NMR (400 MHz, CDCl3) (l) 0.93 (s, 3H), 0.94 (s, 3H),
2.01 (s, 3H), 1.95–2.01 (m, 1H), 2.15–2.23 (m, 1H),
3.01–3.07 (m, 1H), 3.33 (dd, J=11.6, 31.6 Hz, 1H), 3.94
(dd, J=10.8, 12.8 Hz, 2H), 4.97 (dd, J=1.2, 8.0 Hz,
1H), 5.00 (d, J=10.0 Hz, 1H), 5.58–5.68 (m, 1H), 5.86
(d, J=10.4 Hz, 1H); 7.30–7.37 (m, 5H); 13C-NMR (100
MHz, CDCl3) (l) 21.1, 21.6 (2C), 33.3, 35.3, 51.7,
68.0, 69.8, 76.5, 117.6, 127.3 (2C), 128.5 (2C), 128.6,
133.6, 137.4, 169.5, 172.8. Minor diastereo-
mer. IR (neat, cm−1) 3523(br s), 2962(s), 2885(w),
1732(s), 1456(m), 1373(s), 1234(s), 1026(s), 916(s), 734(s),
700(s); 1H-NMR (400 MHz, CDCl3) (l) 0.76 (s, 3H), 0.78
(s, 3H), 2.08 (s, 3H), 2.42–2.54 (m, 2H), 3.01 (dd,
J=11.6, 20.0 Hz, 1H), 3.03–3.08 (m, 1H), 3.65 (d,
J=10.8 Hz, 1H), 3.78 (d, J=11.2 Hz, 1H), 5.04 (dd,
J=1.6, 8.4 Hz, 1H), 5.08 (ddd, J=1.2, 2.4, 16.8 Hz, 1H),
5.70–5.81 (m, 1H), 5.96 (d, J=8.8 Hz, 1H); 7.26–7.47
(m, 5H); 13C-NMR (100 MHz, CDCl3) (l) 21.2, 21.5,
33.0, 36.1, 51.8, 67.7, 69.6, 75.5, 117.2, 127.0 (2C), 128.4
(3C), 134.4, 137.9, 169.7, 172.3; APCI–MS m/z (%)=
335 (35) [M++H], 317 (43) [M+−OH], 275 (100)
[M+−OAc], 257 (33) [M+−OAc−H2O].
Acknowledgements
This research was supported by the Ministry of Edu-
cation, Science, Sports and Culture, Grant-in-Aid for
Scientific Research (B), 12440175, 2000.
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3-Hydroxy-2,2-dimethylpropyl 2-methoxy-5-methyl-
4-hexenoate (3e). IR (neat, cm−1) 3459(br s), 2969(s),
2821(w), 1737(s), 1452(m), 1377(m), 1278(m), 1212(m),
1
1151(m), 1099(m), 1057(m), 1004(m), 838(m); H-NMR
(400 MHz, CDCl3) (l) 0.92 (s, 6H), 1.73 (s, 3H), 1.76 (s,
3H), 2.42 (dd, J=5.6, 14.8 Hz, 2H), 2.60 (dd, J=8.4,
14.8 Hz, 2H), 3.23 (s, 3H), 3.29 (s, 2H), 3.96 (dd, J=10.8,
22.0 Hz, 2H), 4.34 (m, 1H), 5.03 (d, J=8.4 Hz, 1H),
13C-NMR (100 MHz, CDCl3) (l) 18.4, 21.6, 21.6, 25.9,
36.5, 41.3, 55.7, 68.2, 69.6, 74.0, 123.9, 137.7, 171.6; Anal.
Found: C, 63.76; H, 9.65. Calc. for C13H24O4: C, 63.91;
H, 9.90%.
3-Hydroxy-2,2-dimethylpropyl 5-methoxy-5-methyl-
2-hexenoate (3e%). IR (neat, cm−1) 3450(br s), 2977(s),
2826(w), 1737(s), 1473(m), 1376(m), 1254(m), 1170(s),
1062(s), 1006(m), 978(m), 853(w), 754(w); 1H-NMR (400
MHz, CDCl3) (l) 0.92 (s, 6H), 1.27 (s, 6H), 3.13 (d,
J=6.8 Hz, 2H), 3.15 (s, 3H), 3.31 (s, 2H), 3.96 (s, 2H),
5.58 (d, J=16.4 Hz, 1H), 5.69 (dt, J=6.8, 15.6 Hz, 1H),
13C-NMR (100 MHz, CDCl3) (l) 21.5, 25.7, 36.5, 37.9,
50.4, 68.3, 69.6, 74.7, 121.5, 139.5, 172.1; Anal. Found:
C, 63.68; H, 9.62. Calc. for C13H24O4: C, 63.91; H, 9.90%.
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.