Anodic cyclization of dimethyl 2-(3-Oxo-3-arylpropyl) malonates into the corresponding dimethyl 2-aroylcyclopropane-1,1-dicarboxylates

Article abstract of DOI:10.1055/s-0033-1339198

A variety of dimethyl 2-(3-oxo-3-arylpropyl)malonates were electrooxidized in methanol, in the presence of potassium iodide and a base or a neutral salt, to give the corresponding cyclized dimethyl 2-aroylcyclopropane-1,1- dicarboxylates in moderate to good yields. The reactions were carried out under extremely mild reaction conditions, in which the optimal amount of electrolytic current varied from 2.12-2.41 F·mol^-1 depending on the substrates. The reaction presumably proceeds via a two-electron oxidation process, in which iodide ions play an important role as the electron carrier between the anode and the substrate. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1339198

1568▌
LETTER
lAettner odic Cyclization of Dimethyl 2-(3-Oxo-3-arylpropyl) Malonates into the
Corresponding Dimethyl 2-Aroylcyclopropane-1,1-dicarboxylates
New Anodic Cyclization of Dimethyl Malonate Derivatives
Mitsuhiro Okimoto,* Haruki Yamamori, Kousuke Ohashi, Masayuki Hoshi, Takashi Yoshida
Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan
Fax +81(0157)24-7719; E-mail: okimotmt@mail.kitami-it.ac.jp
Received: 15.04.2013; Accepted after revision: 21.05.2013
diaroyl cyclopropane4 and 1,2-diaroyl cyclopentane5 de-
Abstract: A variety of dimethyl 2-(3-oxo-3-arylpropyl)malonates
rivatives (Scheme 1 and Scheme 2, respectively) via intra-
were electrooxidized in methanol, in the presence of potassium io-
molecular formation of a carbon–carbon bond, with
iodide ions as the electron carrier.
dide and a base or a neutral salt, to give the corresponding cyclized
dimethyl 2-aroylcyclopropane-1,1-dicarboxylates in moderate to
good yields. The reactions were carried out under extremely mild
reaction conditions, in which the optimal amount of electrolytic cur-
rent varied from 2.12–2.41 F·mol–1 depending on the substrates.
The reaction presumably proceeds via a two-electron oxidation pro-
cess, in which iodide ions play an important role as the electron car-
rier between the anode and the substrate.
Unfortunately, however, attempts to form the 1,2-diaroyl
four-, six-, seven-, or eight-membered-ring compounds
using similar electrooxidative methods proved to be un-
successful. In the continuation of our investigations, we
discovered that dimethyl 2-(3-oxo-3-arylpropyl)malo-
nates 1 can be readily converted into the corresponding
cyclized dimethyl 2-aroylcyclopropane-1,1-dicarboxyl-
ates 2 via intramolecular cyclization, as shown in Scheme
3.6
Key words: oxidation, electron transfer, radicals, cyclization, sub-
stituent effects, ring closure, green chemistry, iodine
The formation of carbon–carbon bonds is essential in the
syntheses of organic compounds and typically involves
well-known classical chemical reactions. In certain cases,
however, carbon–carbon bond formation can be effective-
ly achieved via electrooxidation,1–3 which is typically car-
ried out under very mild reaction conditions (room
temperature and atmospheric pressure), and without the
use of special and often harsh reagents. Previously, we re-
ported on the successful electrooxidative synthesis of 1,2-
Although the formation of cyclopropane derivatives via
electrochemical means has been previously described,7
the electrooxidative formation of dimethyl 2-aroylcyclo-
propane-1,1-dicarboxylates 2 starting from dimethyl 2-(3-
oxo-3-arylpropyl)malonates 1, to the best of our knowl-
edge, has yet to be reported. Moreover, we believe that the
present cyclopropanation is significantly different from
our previous studies;4 specifically, the optimal amount of
KI was 2 mmol (0.33 equiv, substrate 6 mmol) for the pre-
O
O
O
O
– 2 e, – 2 H+
2.4–2.8 F⋅mol–1
X
X
X
X
76–89%
X = H, alkyl, OMe, halogen
Scheme 1 Electrooxidative formation of 1,2-diaroylcyclopropanes
O
O
O
O
– 2 e, – 2 H+
2.1–3.2 F⋅mol–1
X
X
X
X
63–77%
X = H, alkyl, OMe, halogen
Scheme 2 Electrooxidative formation of 1,2-diaroylcyclopentanes
– 2 e, – 2 H+
O
O
O
O
X
X
electrooxidation
OMe
OMe
OMe
OMe
X = H, Me, OMe, halogen
O
O
1
2
Scheme 3 Electrooxidative formation of dimethyl 2-aroylcyclopropane-1,1-dicarboxylates
SYNLETT 2013, 24, 1568–1572
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DOI: 10.1055/s-0033-1339198; Art ID: ST-2013-U0341-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
New Anodic Cyclization of Dimethyl Malonate Derivatives
1569
vious study, whereas 5 mmol (1.0 equiv, substrate 5 actions using NaI (82%, Table 1, entry 11) or combina-
mmol) is required for the present electrooxidations. Fur- tions of KI and other neutral salts such as TsON(Et)4 and
thermore, the presence of a base was essential in the pre- NaClO4 (Table 1, 78% for entry 6 and 81% for entry 7, re-
vious study, but not necessary for the reactions described spectively), whereas lower yields were observed using
herein.
KCl (44%, Table 1, entry 12) or KBr (68%, Table 1, entry
13). Good yields were also obtained for the reactions us-
ing KI in combination with either a weak base such as
NaOAc (81%, Table 1, entry 8) or a strong base such as
KOt-Bu (82%, Table 1, entry 10). These results suggest
that the yield of 2a is strongly affected by the presence and
nature of halides, especially iodide ions, but surprisingly
not by the basicity of the electrolyte. Unfortunately, we
have yet to establish the reasoning behind the relationship
between the product yields and the amounts of KI and
NaOMe.
First, the reaction conditions for the anodic cyclizations
were optimized in methanol using dimethyl 2-(3-oxo-3-
phenylpropyl)malonate (1a, X = H) as the model substrate
and with the passage of 2.40 F·mol–1 of electricity. Vari-
ous combinations of the supporting electrolytes (media-
tors, bases, and/or neutral salts) are listed in Table 1, along
with the yields of the resulting cyclized product, dimethyl
2-benzoylcyclopropane-1,1-dicarboxylate (2a, X = H).
Interestingly, although the presence of NaOMe by itself
was ineffective (0%, Table 1, entry 1), and the presence of
KI (1.0 equiv) by itself gave a moderate yield (70%, Table During the early stages of the electrooxidation, under fa-
1, entry 2), the presence of both KI (1.0 equiv) and vorable reaction conditions (Table 1, entry 4), the yield of
NaOMe (0.4 equiv) was effective and provided a good 2a increased proportionally to the amount of current
yield (83%, Table 1, entry 4).
passed – specifically, 32% after 0.66 F·mol–1 (current ef-
ficiency >97%), then 63% after 1.32 F·mol–1 (current effi-
ciency >95%). The maximum yield of 2a (83%) was
attained following the passage of ca. 2.1 F·mol–1 of elec-
trolytic current (current efficiency = 79%). As a note, ex-
cess passage of electric current did not significantly
improve the yield of 2a – for example, after the passage of
4.6 F·mol–1 of current, the yield of 2a was merely 80%.
Table 1 Effects of Mediators and Electrolytes on the Yield of 2aa
O
O
O
O
electrooxidation
– 2 e, – 2 H+
OMe
OMe
OMe
OMe
O
O
1a
2a
In contrast to the results of our previous studies, 2a did not
undergo further oxidation to form a tarlike material.5 Our
results showed that the yield of 2a was not significantly
affected by the amount of KI (5.0–10.0 mmol), the reac-
tion temperature (5–45 °C), nor the constant current (0.2–
0.4 A).
Entry
Mediator (mmol) Electrolyte (mmol) Yield of 2a (%)b
1
2
none
NaOMe (2)
none
0c
70
KI (5)
KI (2)
KI (5)
KI (5)
KI (5)
KI (5)
KI (5)
KI (5)
KI (5)
NaI (5)
KCl (5)
KBr (5)
3
NaOMe (2)
NaOMe (2)
NaOMe (5)
TsON(Et)4 (2)
NaClO4 (2)
NaOAc (2)
NaOH (2)
63
83
31c
78
81
81
78
82
82
44c
68
Subsequently, based on the above-mentioned optimal re-
action conditions, the electrooxidations of dimethyl 2-(3-
oxo-3-arylpropyl)malonates 1b–i were carried out, and
the results are listed in Table 2.8 During the course of the
electrooxidations, the progress of the reaction was moni-
tored by analyzing the composition of the mixture (ano-
lyte) using gas chromatograph (SE-30, 0.5 m) or silica gel
TLC analysis. With the sole exception of 2f (yield of
58%), products 2b–i were obtained in reasonable yields
(69–77%).
4
5
6
7
8
9
10
11
12
13
KOt-Bu (2)
NaOMe (2)
NaOMe (2)
NaOMe (2)
It is interesting to note that the nature of the substituent on
the arylpropyl moiety, whether electron-withdrawing (1g,
1h, and 1i) or electron-donating (1b, 1c, and 1d), did not
significantly affect the reaction. Although the details of
the reaction mechanism remain unclear, our studies indi-
cate that the iodide ion plays an important role as the elec-
tron carrier during this indirect electrooxidation process,
in which substrate 1 loses two electrons and two protons
during the formation of product 2.
a Reaction conditions: substrate 1a (5 mmol), MeOH (40 mL), con-
stant current (0.3 A), current passed (2.40 F·mol–1), ca. 15 °C, anode
(Pt net), cathode (Ni coil).
b Determined using GC analysis.
c Unreacted substrate 1a was detected using GC analysis.
In conclusion, the synthesis of dimethyl 2-aroylcyclopro-
pane -1,1-dicarboxylate 2 via electrooxidative intramo-
lecular ring formation was successfully carried out under
mild reaction conditions at room temperature and in the
absence of any harsh oxidants and/or special reagents. For
these reactions, the halide ions, especially iodide ions,
Decreasing the amount of KI (from 1.0 to 0.4 equiv) while
increasing the amount of NaOMe (from 0.4 to 1.0 equiv)
reduced the yields of 2a (Table 1, 63% for entry 3 and
31% for entry 5, respectively). In regards to the nature of
the mediator, comparable yields were observed for the re-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1568–1572

1570
M. Okimoto et al.
LETTER
J. Tetrahedron Lett. 2001, 42, 2173. (r) Suga, S.; Suzuki, S.;
Yamamoto, A.; Yoshida, J. J. Am. Chem. Soc. 2000, 122,
10244. (s) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.;
Yamamoto, A.; Fujiwara, K. J. Am. Chem. Soc. 1999, 121,
9546. (t) Matsumoto, K.; Fuji, S.; Ueoka, K.; Suga, S.;
Yoshida, J. Angew. Chem. Int. Ed. 2008, 47, 2506.
(u) Nokami, T.; Ohata, K.; Inoue, M.; Tsuyama, H.;
Shibuya, A.; Soga, K.; Okajima, M.; Suga, S.; Yoshida, J.
J. Am. Chem. Soc. 2008, 130, 10864. (v) Kanada, Y.;
Onomura, O.; Maki, T.; Matsumura, Y. Chirality 2003, 15,
89. (w) Libendi, S. S.; Demizu, Y.; Onomura, O. Org.
Biomol. Chem. 2009, 7, 351.
Table 2 Electrooxidative Cylizations of Dimethyl 2-(3-Oxo-3-aryl-
propyl)malonatesa
O
O
O
O
X
electrooxidation
– 2 e, – 2 H+
X
OMe
OMe
OMe
OMe
O
O
1
2
Substrate 1
X
H
Current passed Yield of 2
(F·mol–1)
(%)b
1a
1b
1c
1d
1e
1f
2.12
2.24
2.35
2.25
2.18
2.38
2.13
2.14
2.41
72
72
76
77
71
58
73
69
74
(2) Reports from our laboratory: (a) Chiba, T.; Okimoto, M.
J. Org. Chem. 1992, 57, 1375. (b) Chiba, T.; Okimoto, M.
Chem. Lett. 1993, 22, 521. (c) Chiba, T.; Okimoto, M.;
Nagai, H.; Takata, Y. J. Org. Chem. 1979, 44, 3519.
(d) Okimoto, M.; Chiba, T. J. Org. Chem. 1990, 55, 1070.
(e) Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.;
Komata, M.; Numata, K.; Tomozawa, K. Synlett 2006, 1753.
(f) Okimoto, M.; Takahashi, Y. Synthesis 2002, 2215.
(g) Okimoto, M.; Numata, K.; Takahashi, Y.; Hoshi, M.;
Tomozawa, K.; Shigemoto, T. Synlett 2005, 2507.
(3) As some general references on the review of the
electroorganic chemistry, see: (a) Moeller, K. D.
Tetrahedron 2000, 56, 9527. (b) Lund, H. J. Electrochem.
Soc. 2002, 149, S21. (c) Sperry, J. B.; Wright, D. L. Chem.
Soc. Rev. 2006, 35, 605. (d) Yoshida, J.; Kataoka, K.;
Horcajada, R.; Nagai, A. Chem. Rev. 2008, 108, 2265.
(4) Okimoto, M.; Takahash, Y.; Kakuch, T. Bull. Chem. Soc.
Jpn. 2003, 76, 207.
4-Me
3,4-Me2
4-MeO
2-MeO-5-Me
2-Me-5-Br
4-F
1g
1h
1i
4-Cl
4-Br
a Reaction conditions: substrate 1 (5 mmol), KI (0.83 g, 5 mmol),
NaOMe (2 mmol), MeOH (40 mL), constant current (0.3 A), ca. 15 °C,
anode (Pt net), cathode (Ni coil).
b Isolated yield.
(5) Okimoto, M.; Yamamori, H.; Ohashi, K.; Nishikawa, S.;
Hoshi, M.; Yoshida, T. Synlett 2012, 23, 2544.
(6) (a) Allen, C. F. H.; Cressman, H. W. J. J. Am. Chem. Soc.
1933, 55, 2953. (b) Crossland, I.; Bock, K.; Norrestam, R.
Acta Chem. Scand., Ser. B 1985, 39, 7. (c) Es-Sayed, M.;
Devine, P.; Burgess, L. E.; de Meijere, A.; Meyers, A. I.
J. Chem. Soc., Chem. Commun. 1995, 141.
(7) (a) Matsumura, Y.; Inoue, M.; Nakamura, Y.; Talib, I. L.;
Maki, T.; Onomura, O. Tetrahedron Lett. 2000, 41, 4619.
(b) Elinson, M. N.; Feducovich, S. K.; Bushuev, S. G.;
Zakharenkov, A. A.; Pashchenko, D. V.; Nikishin, G. I.
Mendeleev Commun. 1998, 8, 15. (c) Elinson, M. N.;
Feducovich, S. K.; Starikova, Z. A.; Olessova, O. S.;
Vereshchagin, A. N.; Nikishin, G. I. Tetrahedron Lett. 2000,
41, 4937. (d) Elinson, M. N.; Fedukovich, S. K.;
presumably serve as the electron carrier during the cycli-
zation step. Investigations are currently under way in our
laboratories to expand the scope of our electrooxidative
methodology to include four-, six-, seven-, or eight-
membered-ring compounds. At the same time, we are now
studying the electrochemical intramolecular cyclizations
of analogous substrates that possess β-dicarbonyl com-
pound moieties, such as methyl acetoacetate or acetyl ac-
etone.
Zaimovskaya, T. A.; Vereshchagin, A. N.; Nikishin, G. I.
Russ. Chem. Bull. 2003, 52, 2241. (e) Elinson, M. N.;
Feducovich, S. K.; Lizunova, T. L.; Nikishin, G. I.
Tetrahedron 2000, 56, 3063. (f) Elinson, M. N.; Feducovich,
S. K.; Nikishin, G. I. ARKIVOC 2001, (ix), 31.
References and Notes
(1) For examples, see: (a) Andreades, S.; Zahnow, E. W. J. Am.
Chem. Soc. 1969, 91, 4181. (b) Nilsson, A.; Rolan, A.; Park,
V. D. Tetrahedron Lett. 1975, 1107. (c) Richard, J. A.;
Evans, D. H. J. Electroanal. Chem. 1977, 81, 171.
(8) General Procedures
(d) Nyberg, K. Acta Chem. Scand. 1973, 27, 503.
3-Bromo-1-arylpropan-1-ones were prepared via typical
Friedel–Crafts acylation,9 using commercially available 3-
bromopropionyl chloride and aromatic compounds in the
presence of AlCl3 at <45 °C. Dimethyl 2-(3-oxo-3-
arylpropyl)malonates 1 were prepared by mixing the
corresponding bromo aryl ketone and dimethyl malonate
with a slight excess (1.1 equiv) of NaOMe in MeOH for ca.
40 min at r.t.10 Preparative-scale electrooxidations were
carried out in a tall 50 mL beaker equipped with a fine frit
cup as the cathode compartment with a nickel coil cathode,
along with a cylindrical platinum net anode (height: 35 mm,
diameter: 30 mm, 50 mesh).
(e) Longchamp, M. S.; Caullet, C.; Libert, M. Bull. Soc.
Chim. Fr. 1974, 353. (f) Yoshida, K.; Fueno, T. J. Org.
Chem. 1972, 37, 4145. (g) Nilsson, A.; Palmquist, U.;
Ronlán, A.; Parker, V. D. J. Am. Chem. Soc. 1975, 97, 3540.
(h) Sainsbury, M.; Watt, J. J. Chem. Soc., Perkin Trans. 1
1979, 108. (i) Miyashi, T.; Nishizawa, Y.; Sugiyama, T.;
Mukai, T. J. Am. Chem. Soc. 1977, 99, 6111. (j) Chiba, T.;
Takata, Y. J. Org. Chem. 1977, 42, 2973. (k) Yoshida, K.;
Fueno, T. J. Org. Chem. 1971, 36, 1523. (l) Fry, A. J.;
Porter, J. M.; Fry, P. F. J. Org. Chem. 1996, 61, 3191.
(m) Mizuno, K.; Ichinose, N.; Otsuji, Y. J. Org. Chem. 1992,
57, 1855. (n) Shundo, R.; Nishiguch, I.; Matsubara, Y.;
Hirashima, T. Tetrahedron 1991, 47, 831. (o) Chiba, K.;
Arakawa, T.; Tada, M. Chem. Commun. 1996, 1763.
(p) Chiba, K.; Jinno, M.; Nozaki, A.; Tada, M. Chem.
Commun. 1997, 1403. (q) Suga, S.; Okajima, M.; Yoshida,
Typical Procedures
A solution of dimethyl 2-(3-oxo-3-benzoylpropyl)malonates
1a (1.32 g, 5 mmol) in MeOH (40 mL) containing KI (0.83
g, 5.0 mmol) and NaOMe (2.0 mmol) was electrooxidized
Synlett 2013, 24, 1568–1572
© Georg Thieme Verlag Stuttgart · New York

LETTER
New Anodic Cyclization of Dimethyl Malonate Derivatives
1571
under a constant current (0.3 A) at ca. 15 °C with magnetic
(CO), 194.46 (CO). MS (EI, 70 eV): m/z (%) = 290 [M+]
(33), 259 [M+ – CH3O] (26), 258 (33), 231 [M+ – CO2CH3]
(14), 230 (41), 199 (17), 172 [M+ – 2 × CO2CH3] (8), 134
(24), 133 [(CH3)2C6H3CO] (100), 105 [(CH3)2C6H3] (34).
HRMS: m/z [M+] calcd for C16H18O5: 290.1154; found:
290.1149.
stirring. During the course of the electrooxidation, the
composition of the reaction mixture was monitored using
GC and/or TLC analyses. Passage of the electric current was
maintained until the formation of the product was no longer
detected. The reaction mixture was concentrated in vacuo at
approximately 50 °C to near dryness. The resulting residue
was treated with brine (ca. 30 mL), then extracted with Et2O
(3 × 50 mL). The combined ether solution was washed with
Na2S2O3 aq solution (15 wt%, 30 mL), and dried overnight
over Na2SO4. After removal of the solvent in vacuo, the
crude product was purified using silica gel column
chromatography (height, 300 mm; diameter, 15 mm) with
CH2Cl2 as the eluent to afford product 2a as a viscous oil
(0.96 g, 72%). The electrooxidation products were
characterized using HRMS, IR, 1H NMR, and 13C NMR
spectroscopy.
Dimethyl 2-Benzoylcyclopropane-1,1-dicarboxylate (2a)
Yield 0.94 g (72%); colorless, cubic crystals, mp 25–27 °C
(from MeOH); Rf = 0.58 (silica gel; Et2O–n-hexane, 2:1). IR
(neat): 2955, 1738 (vs), 1732 (vs), 1681 (vs), 1597, 1436,
1336, 1276, 1212, 1132, 704 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.79 (dd, J = 8.5, 4.1 Hz, 1 H, CH), 2.22 (dd, J
= 6.9 4.4 Hz, 1 H, CH), 3.57 (dd, J = 8.0, 7.9 Hz, 1 H, CH),
3.69 (s, 3 H, CH3O), 3.80 (s, 3 H, CH3O), 7.45–7.53 (m, 3 H,
arom.), 7.97–8.30 (m, 2 H, arom.). 13C NMR (100 MHz,
CDCl3): δ = 21.09 (CH2), 31.00 (CH), 39.03 (C), 52.85
(CH3), 53.31 (CH3), 128.40 (CH), 128.71 (CH), 133.60
(CH), 137.00 (C), 166.47 (CO), 169.47 (CO), 194.79 (CO).
MS (EI, 70 eV): m/z (%) = 262 [M+] (2), 231 [M+ – CH3O]
(46), 230 (68), 203 [M+ – CO2CH3] (24), 202 (63), 171 (19),
144 [M+ – 2 × CO2CH3] (9), 106 (19), 105 [C6H5CO] (100),
77 [C6H5] (53). HRMS: m/z [M+] calcd for C14H14O5:
262.0841; found: 262.0802.
Dimethyl 2-(4-Methoxybenzoyl)cyclopropane-1,1-
dicarboxylate (2d)
Yield 1.12 g (77%); colorless, fine cubic crystals, mp 59–61
°C (from MeOH); Rf = 0.46 (silica gel; Et2O–n-hexane, 2:1).
IR (KBr): 2954, 1737 (vs), 1732 (vs), 1667 (vs), 1599 , 1265,
1237 , 1214 , 1171 (vs), 1131, 1025 cm–1. 1H NMR (400
MHz, CDCl3): δ = 1.75 (dd, J = 8.4, 4.1 Hz, 1 H, CH), 2.20
(dd, J = 6.9, 4.1 Hz, 1 H, CH), 3.53 (dd, J = 8.7, 6.8 Hz, 1 H,
CH), 3.69 (s, 3 H, CH3O), 3.80 (s, 3 H, CH3O), 3.87 (s, 3 H,
CH3O), 6.95 (d, J = 8.8 Hz, 2 H, arom.), 7.99 (d, J = 8.8 Hz,
2 H, arom.). 13C NMR (100 MHz, CDCl3): δ = 20.98 (CH2),
30.80 (CH), 38.68 (C), 52.81 (CH3), 53.26 (CH3), 55.53
(CH3), 113.88 (CH), 130.04 (CH), 130.79 (C), 163.97 (C),
166.61 (CO), 169.66 (CO), 192.93 (CO). MS (EI, 70 eV):
m/z (%) = 292 [M+] (36), 261 [M+ – CH3O] (24), 260 (18),
232 (30), 201 (19), 174 [M+ – 2 × CO2CH3] (8), 136 (24),
135 [CH3OC6H4CO] (100), 107 [CH3OC6H4] (19), 92 (20).
HRMS: m/z [M+] calcd for C15H16O6: 292.0947; found:
292.0943.
Dimethyl 2-(2-Methoxy-5-methylbenzoyl)cyclopropane-
1,1-dicarboxylate (2e)
Yield 0.95 g (62%); colorless, fine cubic crystals, mp 89–91
°C (from MeOH); Rf = 0.49 (silica gel; Et2O–n-hexane, 2:1).
IR (KBr): 2952, 1734 (vs), 1668 (vs), 1497 , 1437, 1285
1252 (vs), 1212, 1168, 1131 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.74 (dd, J = 8.7, 4.3 Hz, 1 H, CH), 2.20 (dd, J
= 7.1, 4.2 Hz, 1 H, CH), 2.29 (s, 3 H, CH3), 3.69 (dd, J = 8.5,
7.1 Hz, 1 H, CH), 3.71 (s, 3 H, CH3O), 3.78 (s, 3 H, CH3O),
3.87 (s, 3 H, CH3O), 6.87–6.90 (m, H, arom.), 7.26–7.46 (m,
2 H, arom.). 13C NMR (100 MHz, CDCl3): δ = 20.21 (CH3),
21.23 (CH2), 35.70 (CH), 39.16 (C), 52.78 (CH3), 53.05
(CH3), 55.91 (CH3), 111.8 (CH), 127.67 (C), 130.01(CH),
130.63 (C), 134.78 (CH), 157.19 (C), 166.86 (CO), 169.79
(CO), 196.72 (CO). MS (EI, 70 eV): m/z (%) = 306 [M+]
(19), 275 [M+ – CH3O] (13), 243 (7), 236 (9), 162 (46), 161
(13), 150 (18), 149 [CH3, CH3OC6H3CO] (100), 106
[CH3OC6H3] (9), 91 (21). HRMS: m/z [M+] calcd for
C16H18O6: 306.1103; found: 306.1111.
Dimethyl 2-(4-Methylbenzoyl)cyclopropane-1,1-
dicarboxylate (2b)
Yield 0.99 g (72%); colorless, fine cubic crystals, mp 91–93
°C (from MeOH); Rf = 0.62 (silica gel; Et2O–n-hexane, 2:1).
IR (KBr): 2953, 1746 (vs), 1732 (vs), 1665 (vs), 1294, 1234,
1220, 1199, 1184, 963 cm–1. 1H NMR (400 MHz, CDCl3): δ
= 1.77 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.21 (dd, J = 6.9, 4.4
Hz, 1 H, CH), 2.42 (s, 3 H, CH3), 3.55 (dd, J = 8.7, 6.8 Hz,
1 H, CH), 3.69 (s, 3 H, CH3O), 3.81 (s, 3 H, CH3O), 7.28 (d,
J = 8.3 Hz, 2 H, arom.), 7.90 (d, J = 8.3 Hz, 2 H, arom.). 13
NMR (100 MHz, CDCl3): δ = 21.11 (CH2), 21.72 (CH3),
30.95 (CH), 38.86 (C), 52.85 (CH3), 53.29 (CH3), 128.54
(CH), 129.38 (CH), 134.51 (C), 144.56 (C), 166.56 (CO),
C
Dimethyl 2-(2-methyl-5-bromobenzoyl)cyclopropane-
1,1-dicarboxylate (2f)
Yield 1.03 g (58%); colorless, fine cubic crystals, mp 92–94
°C (from MeOH); Rf = 0.61 (silica gel; Et2O–n-hexane, 2:1).
IR (KBr): 2953, 1744 (vs), 1728 (vs), 1666 (vs), 1436, 1295
(vs), 1220, 1184, 1145, 963 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.77 (dd, J = 8.5, 4.1 Hz, 1 H, CH), 2.22 (dd, J
= 6.8, 4.1 Hz, 1 H, CH), 2.43 (s, 3 H, CH3), 3.55 (dd, J = 8.7,
6.9 Hz, 1 H, CH), 3.69 (s, 3 H, CH3O), 3.80 (s, 3 H, CH3O),
169.61 (CO), 194.29 (CO). MS (EI, 70 eV): m/z (%) = 276
[M+] (16), 245 [M+ – CH3O] (44), 244 (65), 217 [M+ –
CO2CH3] (21), 216 (63), 185 (21), 158 [M+ – 2 × CO2CH3]
(10), 120 (26), 119 [CH3C6H4CO] (100), 91 [CH3C6H4] (68).
HRMS: m/z [M+] calcd for C15H16O5: 276.0998; found:
276.1001.
Dimethyl 2-(3,4-dimethylbenzoyl)cyclopropane-1,1-
dicarboxylate (2c)
7.26–7.31 (m, 1 H, arom.), 7.65–7.93 (m, 2 H, arom.). 13
C
NMR (100 MHz, CDCl3): δ = 21.12 (CH2), 21.72 (CH3),
30.95 (CH), 38.86 (C), 52.85 (CH3), 53.29 (CH3), 127.14
(C), 128.55 (CH), 129.38 (CH), 130.37 (CH), 134.51 (C),
144.56 (C), 166.56 (CO), 169.61 (CO), 194.29 (CO). MS
(EI, 70 eV): m/z (%) = 356 [M+, 81Br] (13), 354 [M+, 79Br]
(13), 325 [M+, 81BrOCH3] (17), 324 (27), 323 [M+,
79BrOCH3] (16), 322 (26), 297 [M+, 81BrCO2CH3] (10), 296
(37), 295 [M+, 79BrCO2CH3] (11), 294 (38), 199
Yield 1.10 g (76%); colorless, fine cubic crystals, mp 65–
67 °C (from MeOH); Rf = 0.60 (silica gel; Et2O–n-hexane,
2:1). IR (KBr): 2954, 1757 (vs), 1741 (vs), 1662 (vs), 1438,
1279, 1245, 1212 (vs), 1166, 1138 cm–1. 1H NMR (400
MHz, CDCl3): δ = 1.76 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.19
(dd, J = 6.9, 4.1 Hz, 1 H, CH), 2.32 (br s, 6 H, 2 × CH3), 3.55
(dd, J = 8.7, 7.1 Hz, 1 H, CH), 3.69 (s, 3 H, CH3O), 3.80 (s,
3 H, CH3O), 7.18–7.30 (m, 1 H, arom.), 7.70–7.82 (m, 2 H,
arom.). 13C NMR (100 MHz, CDCl3): δ = 19.77 (CH3), 20.08
(CH3), 21.17 (CH2), 30.92 (CH), 38.87 (C), 52.81 (CH3),
53.25 (CH3), 126.23 (CH), 129.43 (CH), 129.92 (CH),
134.91 (C), 137.09 (C), 143.31 (C), 166.57 (CO), 169.64
[81BrCH3C6H3CO] (99), 197 [79BrCH3C6H3CO] (100), 171
[81BrCH3C6H3] (24), 169 [79BrCH3C6H3] (22), 90 (21), 89
(17). HRMS: m/z [M+] calcd for C15H1581BrO5: 356.0082;
found: 356.0066. HRMS: m/z [M+] calcd for C15H1579BrO5:
354.0103; found: 354.0085.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1568–1572

1572
M. Okimoto et al.
LETTER
Dimethyl 2-(4-Fluorobenzoyl)cyclopropane-1,1-
dicarboxylate (2g)
238 (32), 237 [M+, 35ClCO2CH3] (27), 236 (67), 207 (8), 205
(23), 180 [M+, 37Cl – 2 × CO2CH3] (5), 178 [M+, 35Cl – 2 ×
CO2CH3] (15), 141 [37ClC6H4CO] (56), 139 [35ClC6H4CO],
(100) 113 [37ClC6H4] (28), 111 [35ClC6H4] (53). HRMS: m/z
[M+] calcd for C14H1337ClO5: 298.0422; found: 298.0409.
HRMS: m/z [M+] calcd for C14H1335ClO5: 296.0452; found:
296.0435.
Yield 1.02 g (73%); viscous oily liquid; Rf = 0.61 (silica gel;
Et2O–n-hexane, 2:1). IR (neat): 2955, 1737 (vs), 1732 (vs),
1678 (vs), 1598, 1508, 1437, 1276, 1216 (vs), 1157, 1131
cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.79 (dd, J = 8.7, 4.4
Hz, 1 H, CH), 2.23 (dd, J = 6.9, 4.4 Hz, 1 H, CH), 3.52 (dd,
J = 8.5, 6.7 Hz, 1 H, CH), 3.69 (s, 3 H, CH3O), 3.81 (s, 3 H,
CH3O), 7.08–7.21 (m, 2 H, arom.), 7.99–8.08 (m, 2 H,
arom.). 13C NMR (100 MHz, CDCl3): δ = 21.03 (CH2), 30.89
Dimethyl 2-(4-Bromobenzoyl)cyclopropane-1,1-
dicarboxylate (2i)
Yield 1.26 g (74%); colorless, fine powder, mp 56–58 °C
(from MeOH); Rf = 0.64 (silica gel; Et2O–n-hexane, 2:1). IR
(neat): 2954, 1733 (vs), 1677 (vs), 1585, 1439, 1334, 1276
(vs), 1215, 1131, 1070 cm–1. 1H NMR (400 MHz, CDCl3): δ
= 1.79 (dd, J = 8.5, 4.4 Hz, 1 H, CH), 2.22 (dd, J = 6.9, 4.4
Hz, 1 H, CH), 3.49 (dd, J = 8.6, 6.9 Hz, 1 H, CH), 3.69 (s, 3
H, CH3O), 3.81 (s, 3 H, CH3O), 7.63 (d, J = 8.7 Hz, 2 H,
arom.), 7.86 (d, J = 8.7 Hz, 2 H, arom.). 13C NMR (100 MHz,
CDCl3): δ = 21.01 (CH2), 30.86 (CH), 39.13 (C), 52.92
(CH3), 53.38 (CH3), 128.90 (C), 129.89 (CH), 131.52 (CH),
135.68 (C), 166.28 (CO), 169.33 (CO), 193.77 (CO). MS
(EI, 70 eV): m/z (%) = 342 [M+, 81Br] (33), 340 [M+, 79Br]
(34), 310 (59), 308 (58), 283 [M+, 81BrCO2CH3] (100), 282
(36), 281 [M+, 79BrCO2CH3] (100), 280 (37), 251 (41), 249
(39), 224 [M+, 81Br – 2 × CO2CH3] (25), 222 [M+, 79Br – 2 ×
CO2CH3] (25), 185 [81BrC6H4CO] (62), 183 [79BrC6H4CO]
(63), 157 [81BrC6H4] (28), 155 [79BrC6H4] (27), 115 (30).
HRMS: m/z [M+] calcd for C14H1381BrO5: 341.9926; found:
341.9978. HRMS: m/z [M+] calcd for C14H1379BrO5:
339.9946; found: 339.9952.
(CH), 39.05 (C), 52.92 (CH3), 53.38 (CH3), 115.90 (d, JC–F
88 Hz, CH), 131.15 (d, JC–F = 38 Hz, CH), 133.43 (d, JC–F
=
=
12 Hz, C), 166.08 (d, JC–F = 255 Hz, C), 166.41 (CO), 169.43
(CO), 193.18 (CO). MS (EI, 70 eV): m/z (%) = 280 [M+] (7),
249 [M+ – CH3O] (38), 248 (59), 221 [M+ – CO2CH3] (28),
220 (65), 189 (28), 162 [M+ – 2 × CO2CH3] (17), 133 (24),
123 [FC6H4CO] (100), 95 [FC6H4] (48). HRMS: m/z [M+]
calcd for C14H13FO5: 280.0747; found: 280.0759.
Dimethyl 2-(4-Chlorobenzoyl)cyclopropane-1,1-
dicarboxylate (2h)
Yield 0.79 g (53%); colorless, fine needle crystals, mp 58–
60 °C (from MeOH); Rf = 0.65 (silica gel; Et2O–n-hexane,
2:1). IR (neat): 2954, 1738 (vs), 1732 (vs), 1678 (vs), 1589,
1436, 1403, 1275, 1214 (vs), 1131, 1091 cm–1. 1H NMR (400
MHz, CDCl3): δ = 1.79 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.23
(dd, J = 6.9, 4.4 Hz, 1 H, CH), 3.50 (dd, J = 8.7, 6.9 Hz, 1 H,
CH), 3.68 (s, 3 H, CH3O), 3.81 (s, 3 H, CH3O), 7.46 (d, J =
8.7 Hz, 2 H, arom.), 7.94 (d, J = 8.7 Hz, 2 H, arom.). 13
C
NMR (100 MHz, CDCl3): δ = 21.00 (CH2), 30.90 (CH),
39.14 (C), 52.92 (CH3), 53.38 (CH3), 129.00 (C), 129.82
(CH), 135.37 (CH), 140.08 (C), 166.33 (CO), 169.39 (CO),
193.61 (CO). MS (EI, 70 eV): m/z (%) = 298 [M+, 37Cl] (4),
296 [M+, 35Cl] (12), 267 [M+, 37ClOCH3 (15)], 266 (31), 265
[M+, 35ClOCH3] (44), 264 (56), 239 [M+, 37ClCO2CH3] (9),
(9) Fuson, R. C.; Walker, J. T. Org. Synth., Coll. Vol. II; John
Wiley and Sons: New York, 1943, 169.
(10) Adams, R.; Kamm, R. M. Org. Synth., Coll. Vol. I; John
Wiley and Sons: New York, 1941, 250.
Synlett 2013, 24, 1568–1572
© Georg Thieme Verlag Stuttgart · New York

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