Stereoselective cyclopropanation of α-bromochalcone with diethyl malonate promoted by K2CO3

Article abstract of DOI:10.1016/j.tet.2013.02.011

A new Michael-initiated cyclopropanation reaction using α-bromochalcones as Michael acceptor was developed. Compared to previous works using arylidenemalonates as Michael acceptor, this novel protocol could improve the synthesis of trans-isomers of diethyl 2-benzoyl-3-phenyl- cyclopropane-1,1-dicarboxylates. More importantly, this method also provided the first access to the cis-isomers of these densely substituted cyclopropanes with the Michael-initiated ring closure (MIRC) strategy, albeit with a poor diastereoselectivity.

Full text of DOI:10.1016/j.tet.2013.02.011

Tetrahedron xxx (2013) 1e7
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Stereoselective cyclopropanation of a-bromochalcone with diethyl
malonate promoted by K2CO3
*
*
Yongxian Sun, Gaosheng Yang , Yue Shen, Zan Hua, Zhuo Chai
Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials, Institute of Organic Chemistry,
School of Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new Michael-initiated cyclopropanation reaction using
a-bromochalcones as Michael acceptor was
Received 19 August 2012
Received in revised form 26 November 2012
Accepted 1 February 2013
Available online xxx
developed. Compared to previous works using arylidenemalonates as Michael acceptor, this novel pro-
tocol could improve the synthesis of trans-isomers of diethyl 2-benzoyl-3-phenyl-cyclopropane-1,1-
dicarboxylates. More importantly, this method also provided the first access to the cis-isomers of
these densely substituted cyclopropanes with the Michael-initiated ring closure (MIRC) strategy, albeit
with a poor diastereoselectivity.
Keywords:
Stereoselective cyclopropanation
Cyclopropane-1,1-dicarboxylates
Ó 2013 Published by Elsevier Ltd.
a
-Bromochalcone
Malonate
Michael addition
1. Introduction
stereoselective synthesis of polyfunctional tetrahydrofurans via
AlCl3-promoted [3þ2] annulation with aromatic aldehydes.9b Some
Cyclopropane-1,1-dicarboxylates, known as a type of the acti-
vated DonoreAcceptor (DeA) cyclopropanes, are very useful
building blocks in organic synthesis.1 Especially, as a result of recent
intense researches, this type of DeA cyclopropanes have been
successfully utilized in many cycloadditions to construct a number
of carbocyclic skeletons2 and heterocyclic compounds3 with high
atom-economy and stereoselectivity. Consequently, the synthesis
of this type of highly useful building blocks has received much
interest among organic chemists, and numerous methods have
been reported.4e8 In this field, the Michael-initiated ring closure
(MIRC) strategy is one of the most convenient ways, for that it
usually required only cheap and readily available reagents and mild
reaction conditions. Reported reaction systems with this strategy
include the cyclopropanation reaction of sulfur,4a,b phosphorus4a,b
interesting reactivities of trans 2,3-disubstituted DeA cyclopro-
panes were found in the [3þ2]-annulation with regard to stereo-
selectivity. For example, the use of electron-rich or electron-
deficient aldehydes led to different stereoisomers of the resulting
pentasubstituted polyfunctional tetrahydrofuran products as the
major products. However, from a synthetic viewpoint, the [3þ2]-
annulation of DeA cyclopropanes would be more useful if all the
diastereomers of these polysubstituted tetrahydrofuran products
are accessible through this methodology. On this point, we pre-
sumed that the employment of cis cyclopropanes might produce
products with diastereoselectivity complementary to those ob-
tained with the trans ones, which would also provide information
useful to related systems. Moreover, the mechanism, especially the
stereochemical process of this kind of reactions remained unclear.9b
It’s believed that a study on the relationship between the structures
of the starting cyclopropane and the tetrahydrofuran products
would be conducive to a deeper understanding of the reaction
mechanism. However, the application of cis cyclopropanes in Lewis
acid-catalyzed [3þ2]-annulations is less studied probably due to the
lack of efficient methods for the synthesis of this type of cyclopro-
panes. Notably, most previous MIRC methods reported in this realm
used the alkenes derived from malonate like 4 as Michael accept-
or,4,9a which was not applicable to the synthesis of cis-3.9a Herein,
we present a new MIRC strategy for the synthesis of these cyclo-
or arsonium4c ylides with
b-substituted methylidenemalonates,
and the organocatalyzed asymmetric cyclopropanation of
a,b-un-
saturated aldehydes5 or nitroalkenes6 with halomalonates.
Our group have developed a cyclopropanation reaction of
chloroacetophenones with diethyl benzylidenemalonates to afford
2,3-disubstituted diethyl trans-2-benzoyl-3-phenylcyclopropane-
1,1-dicarboxylates 3 with high stereoselectivity (Scheme 1).9a We
have also demonstrated the utility of these trans-3 products in the
* Corresponding authors. Tel.: þ86 553 3869310; fax: þ86 553 3883517; e-mail
propanes, utilizing a domino Michael addition/a-alkylation process
addresses: gshyang@mail.ahnu.edu.cn (G. Yang), chaizhuo@live.cn (Z. Chai).
0040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.02.011
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2
Y. Sun et al. / Tetrahedron xxx (2013) 1e7
of diethyl malonate with
a
-bromochalcones in the presence of
With the optimized reaction conditions in hand, the scope of the
K2CO3. Compared to previous works, this new protocol allowed for
the synthesis of trans-3 in much improved yields, and more im-
portantly, rendered the much less common cis-3 available.
present reaction, as to the selective preparation of trans-3, was
firstly probed with a variety of different a-bromochalcones 1 and
diethyl malonate 2 (Table 2). Compared to our previous report,9a
the yields of the desired products were generally significantly im-
proved here, especially for those bearing electron-donating groups
on the phenyl ring (Ar1 and Ar2). For substrates bearing electron-
withdrawing groups, the reaction needed to be carried out at
a much lower temperature (20 ꢀC) to obtain good yields, while very
complicated systems were observed at 80 ꢀC (Table 2, entries 6, 7,
and 12).10 Moreover, the result of substrate 1l could be greatly
improved by performing the reaction at 20 ꢀC with reduced amount
of K2CO3 (Table 3, entry 12). Of note, the diastereoselectivity of
these reactions was invariably high (>95:5).
Scheme 1. Two MIRC methods for the synthesis of cyclopropane-1,1-dicarboxylates 3.
Table 2
Preparation of trans-3a
2. Results and discussion
Initially, the reaction of a-bromochalcone 1a with diethyl mal-
onate 2 was used as a model reaction to screen the reaction con-
ditions. Table 1 summarizes the results. A dramatic solvent effect on
the yield was observed, and DMSO was found to be the solvent of
choice, giving the desired product 3a in 82% yield and 52:48 dia-
stereoselectivity at 20 ꢀC (Table 1, entry 5). Despite the low dr
values, the cis-isomer could be conveniently isolated in pure form
by flash chromatography. The employment of the more basic NaOH
or an organic base Et3N failed to improve the results (Table 1, en-
tries 6 and 7). In addition, other conditions including the reaction
temperature, the loading of K2CO3, and the ratio of diethyl malo-
nate 2 were screened (Table 1, entries 8e17). For the selective
formation of trans-3a, a high temperature (80 ꢀC) and a large excess
of K2CO3 (3 equiv) were identified as the optimal reactions condi-
tions, giving the desired product in 88% yield and excellent dia-
stereoselectivity (97:3 dr, Table 1, entry 14). To obtain as much as of
cis-3a, a low temperature (20 ꢀC) and a high molar ratio of diethyl
malonate (3 equiv) were beneficial, giving a total yield of 83% yield
and the highest cis/trans selectivity (49:51, Table 1, entry 13).
Entry
Substrate (Ar1, Ar2)
Yieldb (%)
1
2
3
4
Ph, Ph (1a)
trans-3a/85
trans-3b/71
trans-3c/71
trans-3d/73
trans-3e/75
trans-3f/87
trans-3g/77
trans-3h/70
trans-3i/38
trans-3j/41
trans-3k/46
trans-3l/31
4-MeC6H4, Ph (1b)
4-MeOC6H4, Ph (1c)
3,4-(MeO)2C6H3, Ph (1d)
4-ClC6H4, Ph (1e)
2,4-Cl2C6H3, Ph (1f)
4-NO2C6H4, Ph (1g)
Ph, 4-MeC6H4 (1h)
Ph, 4-MeOC6H4 (1i)
Ph, 4-ClC6H4 (1j)
5
6c
7c
8
9
10
11
12c
Ph, 4-BrC6H4 (1k)
Ph, 4-NO2C6H4 (1l)
a
The reaction was conducted with 0.5 mmol of 1 and 0.6 mmol of 2 in the
presence of 1.5 mmol of K2CO3 in 5.0 mL of DMSO at 80 ꢀC.
b
Isolated yields of the pure products. The dr values are >95:5 as estimated by 1
H
NMR.
c
The reaction was carried out at 20 ꢀC.
Table 1
Screening of reaction conditionsa
Table 3
Preparation of trans and cis-3a
Entry Base (equiv) Solv.
Temp (ꢀC) Time (h) Yieldb (%) trans/cisc
1
2
3
4
5
6
7
8
K2CO3 (0.6)
K2CO3 (0.6)
K2CO3 (0.6)
K2CO3 (0.6)
K2CO3 (0.6)
NaOH (0.6)
Et3N (0.6)
K2CO3 (0.6)
K2CO3 (0.6)
K2CO3 (0.6)
K2CO3 (1.2)
K2CO3 (3.0)
K2CO3 (0.6)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
Toluene
CH2Cl2
THF
20
20
20
20
20
20
20
50
80
110
20
20
20
80
80
80
80
78
78
78
78
78
78
78
49
25
25
78
78
60
13
13
13
13
28
18
38
68
82
55
9
74
86
46
81
83
83
88
56
49
51
7:26
81:19
51:49
70:30
52:48
55:45
53:47
77:23
93:7
Entry
Substrate (Ar1, Ar2)
Yieldb (%)
1
2
3
4
5
6
7
8
Ph, Ph (1a)
4-MeC6H4, Ph (1b)
trans-3a/42
trans-3b/49
trans-3c/45
trans-3d/46
trans-3e/46
trans-3f/44
trans-3g/45
trans-3h/41
trans-3i/45
trans-3j/44
trans-3k/43
trans-3l/66
trans-3m/40
trans-3n/28
trans-3o/32
trans-3g/47
trans-3g/45
cis-3a/41
cis-3b/40
cis-3c/46
cis-3d/45
cis-3e/46
cis-3f/53
cis-3g/53
cis-3h/47
cis-3i/42
cis-3j/46
cis-3k/46
cis-3l/0
cis-3m/36
cis-3n/40
cis-3o/0
cis-3g/51
cis-3g/51
EtOH
4-MeOC6H4, Ph (1c)
3,4-(MeO)2C6H3, Ph (1d)
4-ClC6H4, Ph (1e)
2,4-Cl2C6H3, Ph (1f)
4-NO2C6H4, Ph (1g)
Ph, 4-MeC6H4 (1h)
Ph, 4-MeOC6H4 (1i)
Ph, 4-ClC6H4 (1j)
Ph, 4-BrC6H4 (1k)
Ph, 4-NO2C6H4 (1l)
4-MeOC6H4, 4-MeOC6H4 (1m)
4-MeOC6H4, 4-BrC6H4 (1n)
4-MeOC6H4, 4-NO2C6H4 (1o)
4-NO2C6H4, Ph ((Z)-1g)
4-NO2C6H4, Ph ((E)-1g)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
EtOH
9
10
11
12
13d
14
15d
16
17
93:7
9
53:47
89:11
51:49
97:3
96:4
88:12
88:12
10
11
12
13
14
15
16
17
a
The reaction was conducted on 0.5 mmol scale (1a) in the presence of a base and
1.2 equiv of 2 in 5.0 mL of solvent.
a
b
The reaction was conducted with 0.5 mmol of 1 and 1.5 mmol of 2 in the
Isolated combined yields of the two diastereomers of 3a.
presence of 0.3 mmol of K2CO3 in 5.0 mL of DMSO at 20 ꢀC.
c
Determined by 1H NMR.
b
d
Isolated yields of the pure products.
3.0 equiv of 2 was used.
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Y. Sun et al. / Tetrahedron xxx (2013) 1e7
3
Next, the reaction scope was examined with the conditions
leading to the formation of the both diastereomers of 3 (Table 3). In
general, the desired products 3 were obtained in good to high
combined yields and with similarly poor diastereoselectivity (about
1:1 dr). Interestingly, the presence of strong electron-withdrawing
groups on the Ar2 of 1 gave the trans-isomers exclusively (Table 3,
entries 12 and 15), while their presence on the Ar1 brought in little
effect on the results (Table 3, entries 6 and 7). Noteworthy, the
amount of the base K2CO3 was found to have a remarkable effect on
the diastereoselectivity (compare entries 6e7 in Tables 2 and 3).
The two diastereomers of 3 were easily separated by column
chromatography, and the structure of cis-3e was unambiguously
confirmed by X-ray crystallographic analysis (Fig. 1). It should be
noted that the configuration of the Michael acceptor 1 did not in-
fluence the results of the reaction: both the pure (Z)-1g and (E)-1g
(X-ray, see Supplementary data) were subjected to the same re-
action conditions to give the almost identical result (Table 3, entries
16 and 17).
when strong electron-withdrawing groups were present on the
Ar2 or a large excess of the base K2CO3 was used, the formation of
intermediate 5 would be facilitated. Therefore, the thermody-
namically favored equilibrium with 6 might predominate in the
reaction leading to the selective formation of trans-3. Similarly,
high reaction temperature (Table 1) would allow for fast in-
terconversions between 5, 6, and 7, and the thermodynamically
favored way to the trans-3 through 6 might again be preferred. On
the contrary, a low reaction temperature and/or reduced amount
of base would render the kinetically favored way to cis-3 through
7 more competitive.
3. Conclusion
In conclusion, we have developed a novel K2CO3-promoted
domino Michael addition/
of diethyl 2-benzoyl-3-phenyl-cyclopropane-1,1-dicarboxylates.
This new and simple protocol features the use of -bromochalcones
a-alkylation process for the preparation
a
as the Michael acceptor, which enables the first synthesis of the cis-
isomers of the desired cyclopropanes via the MIRC strategy, despite
the poor diastereoselectivity. The application of the resultant cis-
isomers in related reactions like cycloadditions and the de-
velopment of an asymmetric version11 are currently under in-
vestigation in our laboratories.
4. Experimental section
4.1. General remarks
All the a-bromochalcones used were synthesized according to
references.12 All the other reagents and solvents were purchased
from commercial suppliers and purified by standard techniques.
Cyclopropanation reactions were performed in oven-dried glass-
ware. Flash column chromatography was performed using silica gel
(200e400 mesh). For thin-layer chromatography (TLC), silica gel
plates (HSGF 254) were used and compounds were visualized by
irradiation with UV light. 1H NMR spectra (300 MHz) and 13C NMR
spectra (75 MHz) were recorded on a Bruker Avance 300 spec-
Fig. 1. ORTEP for cis-3e (CCDC 895789).
trometer in CDCl3. All chemical shifts (d) are given in parts per
Based on the above experimental results and previous stud-
ies,4,9a the formation of cyclopropanes 3 was tentatively explained
as follows (Scheme 2). Initial Michael addition of diethyl malonate
million. Data are reported as follows: chemical shift, multiplicity,
coupling constants (Hertz) and integration. Melting points were
determined on an SGW X-4 apparatus and uncorrected. Infrared
spectra were recorded on a Shimadzu IRPrestige-21 spectropho-
tometer. Mass spectral analysis was performed on an Agilent 6220
Time-of-Flight LC/MS system (Applied Agilent Co. Ltd). Single
crystal X-ray diffraction data were collected on a Bruker Smart
APEX 2 X-ray diffractometer equipped with a normal focus Mo-
target X-ray tube.
2 to
a-bromochalcone 1 would generate intermediate 5, which
might be in equilibriums with 6 and 7 through proton transfer
processes. Intermediates 6 and 7 would then underwent cycliza-
tion through a relatively slower intramolecular SN2 reaction to
give trans-3 and cis-3, respectively. Intermediate 6 might be
slightly more stable than 7 due to sterical reasons. In Table 3,
4.2. General procedure for preparation of compound 3 (Table 3)
To a solution of 0.5 mmol of a-bromochalcones and 1.5 mmol of
diethyl malonate in 5.0 mL of DMSO was added 0.3 mmol of K2CO3.
Stirring was continued for 60e78 h at 20 ꢀC (monitored by TLC).
Upon completion, the reaction mixture was diluted with 5 mL of
H2O and extracted with ethyl ether (3ꢁ10 mL). The combined ether
solution was washed twice with water, dried with anhydrous so-
dium sulfate, and concentrated under reduced pressure to yield
a crude product. The crude product was purified by column
chromatography.
4.2.1. Diethyl trans-2-benzoyl-3-phenylcyclopropane-1,1-dicarboxy-
late (trans-3a).9a Yellow oil (eluting with PE:EA¼25:1); 1H NMR
(300 MHz, CDCl3) d 8.15e8.07 (m, 2H, ArH), 7.66e7.57 (m, 1H, ArH),
7.55e7.46 (m, 2H, ArH), 7.34e7.22 (m, 5H, ArH), 4.14 (q, J¼7.2 Hz,
Scheme 2. Proposed mechanism for the formation of trans-3 and cis-3.
2H, OCH2), 4.13 (d, J¼7.7 Hz, 1H, CH), 4.01 (q, J¼7.2 Hz, 2H, OCH2),
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4
Y. Sun et al. / Tetrahedron xxx (2013) 1e7
3.89 (d, J¼7.7 Hz, 1H, CH), 1.11 (t, J¼7.2 Hz, 3H, CH3), 0.98
721, 686 cmꢂ1; HRMS (ESI) calcd for C23H25O6 ([MþH]þ) 397.1651,
(t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d
193.6,165.9,165.7,
found 397.1651.
136.7, 133.6, 133.4, 128.7, 128.6, 128.5, 128.3, 127.6, 62.0, 61.9, 46.0,
35.8, 34.9, 13.81, 13.76; IR (neat): nmax (cmꢂ1)¼1732, 1682, 1597,
1582, 1497, 745, 698; HRMS (ESI) calcd for C22H23O5 ([MþH]þ):
367.1545. Found 367.1538.
4.2.7. Diethyl
trans-2-benzoyl-3-(3,4-dimethoxyphenyl)cyclo-pro-
pane-1,1-dicarboxylate (trans-3d).9a Yellow oil (eluting with PE:
CH2Cl2¼1.7:1); 1H NMR (300 MHz, CDCl3)
d: 8.15e8.08 (m, 2H,
ArH), 7.66e7.58 (m, 1H, ArH), 7.56e7.46 (m, 2H, ArH), 6.87e6.75
(m, 3H, ArH), 4.18e3.98 (m, 5H, 2OCH2, CH), 3.87 (s, 3H, OCH3),
3.86 (s, 3H, OCH3), 3.84 (d, J¼7.8 Hz, 1H, CH), 1.09 (t, J¼7.2 Hz, 3H,
4.2.2. Diethyl cis-2-benzoyl-3-phenylcyclopropane-1,1-dicarboxylate
(cis-3a). White solid (eluting with PE:EA¼25:1), mp 54e55 ꢀC;
1H NMR (300 MHz, CDCl3)
d
: 8.04 (d, J¼7.6 Hz, 2H, ArH), 7.63e7.45
CH3), 1.05 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d:
(m, 3H, ArH), 7.37e7.28 (m, 2H, ArH), 7.25e7.17 (m, 3H, ArH),
4.42e4.23 (m, 2H, OCH2), 4.22e4.03 (m, 2H, OCH2), 3.86 (d,
J¼9.9 Hz, 1H, CH), 3.46 (d, J¼9.9 Hz, 1H, CH), 1.34 (t, J¼7.1 Hz, 3H,
193.5, 166.0, 165.8, 148.7, 148.6, 136.7, 133.7, 128.8, 128.6, 125.9,
120.6, 111.9, 110.8, 62.0, 61.9, 55.94, 55.86, 46.1, 35.51, 35.46, 14.0,
13.8; IR (neat) n: 1732, 1681, 1595, 1519, 1450, 1026, 858, 763,
CH3), 1.11 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 193.1,
692 cmꢂ1; HRMS (ESI) calcd for C24H27O7 ([MþH]þ) 427.1757,
169.8, 165.0, 138.0, 133.4, 131.5, 130.8, 128.8, 128.2, 127.7, 127.2, 62.7,
found 427.1747.
61.3, 41.5, 38.9, 34.6, 14.1, 13.7; IR (KBr) n: 1728, 1682, 1595, 1579,
1498, 1448, 1095, 1026, 1006, 763, 719, 694 cmꢂ1; HRMS (ESI) calcd
4.2.8. Diethyl cis-2-benzoyl-3-(3,4-dimethoxyphenyl)cyclo-propane-
for C22H23O5 ([MþH]þ) 367.1545, found 367.1540.
1,1-dicarboxylate (cis-3d). Yellow oil (eluting with PE:CH2Cl2¼
1.7:1); 1H NMR (300 MHz, CDCl3)
d
: 8.04 (d, J¼7.3 Hz, 2H, ArH), 7.60
4.2.3. Diethyl
1,1-dicarboxylate (trans-3b). Yellow oil (eluting with PE:EA¼25:1);
1H NMR (300 MHz, CDCl3)
: 8.14e8.07 (m, 2H, ArH), 7.65e7.57 (m,
trans-2-benzoyl-3-(4-methylphenyl)cyclopro-pane-
(t, J¼7.2 Hz, 1H, ArH), 7.50 (m, 2H, ArH), 6.96 (s, 1H, ArH), 6.82 (d,
J¼8.4 Hz, 1H, ArH), 6.70 (d, J¼8.4 Hz, 1H, ArH), 4.43e4.05 (m, 4H,
2OCH2), 3.83 (d, J¼9.9 Hz, 1H, CH), 3.81 (s, 3H, OCH3), 3.74 (s, 3H,
OCH3), 3.43 (d, J¼9.9 Hz, 1H, CH), 1.35 (t, J¼7.2 Hz, 3H, CH3), 1.14 (t,
d
1H, ArH), 7.54e7.46 (m, 2H, ArH), 7.19 (d, J¼7.8 Hz, 2H, ArH), 7.10 (d,
J¼7.8 Hz, 2H, ArH), 4.18e3.97 (m, 5H, 2OCH2, CH), 3.84 (d, J¼7.7 Hz,
1H, CH), 2.32 (s, 3H, CH3),1.11 (t, J¼7.2 Hz, 3H, CH3), 1.02 (t, J¼7.2 Hz,
J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 193.0, 169.8, 165.1,
148.1, 148.0, 138.2, 133.3, 128.7, 128.2, 124.0, 123.0, 114.4, 110.5, 62.6,
3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 193.7, 166.0, 165.8, 137.3,
61.2, 55.72, 55.70, 41.4, 38.7, 35.0, 14.1, 13.8; IR (neat) n: 1728, 1680,
136.8, 133.6, 130.4, 129.0, 128.7, 128.6, 128.5, 61.9, 61.8, 46.1, 35.7,
1517, 1448, 854, 806, 765, 719, 688 cmꢂ1; HRMS (ESI) calcd for
35.1, 21.1, 13.8; IR (neat)
n
: 1732, 1681, 1597, 1519, 1448, 1020, 858,
C
24H27O7 ([MþH]þ) 427.1757, found 427.1756.
812, 767 cmꢂ1; HRMS (ESI) calcd for C23H25O5 ([MþH]þ) 381.1702,
found 381.1702.
4.2.9. Diethyl trans-2-benzoyl-3-(4-chlorophenyl)cyclopro-pane-1,1-
dicarboxylate (trans-3e).9a Yellow oil (eluting with PE:EA¼25:1);
4.2.4. Diethyl cis-2-benzoyl-3-(4-methylphenyl)cyclopropane-1,1-
1H NMR (300 MHz, CDCl3)
d: 8.12e8.05 (m, 2H, ArH), 7.66e7.57 (m,
dicarboxylate (cis-3b). White solid (eluting with PE:EA¼25:1),
1H, ArH), 7.55e7.47 (m, 2H, ArH), 7.31e7.21 (m, 4H, ArH), 4.17e3.98
(m, 5H, 2OCH2, CH), 3.84 (d, J¼7.7 Hz, 1H, CH), 1.10 (t, J¼7.2 Hz, 3H,
mp 73e74 ꢀC; 1H NMR (300 MHz, CDCl3)
d
: 8.03 (d, J¼7.7 Hz, 2H,
ArH), 7.64e7.45 (m, 3H, ArH), 7.19 (d, J¼7.8 Hz, 2H, ArH), 7.02 (d,
J¼7.8 Hz, 2H, ArH), 4.41e4.23 (m, 2H, OCH2), 4.21e4.05 (m, 2H,
OCH2), 3.83 (d, J¼9.9 Hz, 1H, CH), 3.41 (d, J¼9.9 Hz, 1H, CH), 2.27 (s,
CH3), 1.05 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 193.3,
165.7, 165.5, 136.7, 133.7, 133.6, 132.1, 130.0, 128.8, 128.6, 128.5, 62.2,
62.0, 46.1, 35.0, 13.9, 13.8; IR (neat) n: 1732, 1682, 1597, 1582, 1493,
3H, CH3), 1.34 (t, J¼6.9 Hz, 3H, CH3), 1.12 (t, J¼6.9 Hz, 3H, CH3); 13
C
849, 760, 698 cmꢂ1; HRMS (ESI) calcd for C22H22ClO5 ([MþH]þ)
NMR (75 MHz, CDCl3)
d
: 193.1, 169.8, 165.0, 138.2, 136.8, 133.2,
401.1155, found 401.1150.
130.6, 128.7, 128.4, 128.2, 62.5, 61.2, 41.5, 38.7, 34.7, 21.1, 14.1, 13.7;
IR (KBr)
n
: 1745, 1728, 1668, 1595, 1450, 1091, 1037, 1002, 810, 717,
4.2.10. Diethyl cis-2-benzoyl-3-(4-chlorophenyl)cyclopro-pane-1,1-
688 cmꢂ1; HRMS (ESI) calcd for C23H25O5 ([MþH]þ) 381.1702,
dicarboxylate (cis-3e). White solid (eluting with PE:EA¼25:1), mp
found 381.1702.
105e106 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.06e7.99 (m, 2H, ArH),
7.66e7.57 (m, 1H, ArH), 7.54e7.46 (m, 2H, ArH), 7.29e7.15 (m, 4H,
ArH), 4.40e4.05 (m, 4H, 2OCH2), 3.84 (d, J¼9.9 Hz, 1H, CH), 3.39 (d,
J¼9.9 Hz, 1H, CH), 1.34 (t, J¼7.2 Hz, 3H, CH3), 1.12 (t, J¼7.2 Hz, 3H,
4.2.5. Diethyl trans-2-(4-anisyl)-3-benzoylcyclopropane-1,1-dicar-
boxylate (trans-3c).9a Yellow oil (eluting with PE:EA¼20:1); 1H
NMR (300 MHz, CDCl3)
d: 8.13e8.08 (m, 2H, ArH), 7.65e7.57 (m, 1H,
CH3); 13C NMR (75 MHz, CDCl3)
d: 193.0, 169.5, 164.8, 138.0, 133.5,
ArH), 7.55e7.47 (m, 2H, ArH), 7.23 (d, J¼8.7 Hz, 2H, ArH), 6.83 (d,
J¼8.7 Hz, 2H, ArH), 4.18e3.98 (m, 5H, 2OCH2, CH), 3.82 (d, J¼7.7 Hz,
1H, CH), 3.79 (s, 3H, OCH3), 1.11 (t, J¼7.2 Hz, 3H, CH3), 1.04 (t,
133.2, 132.2, 130.1, 128.8, 128.2, 127.8, 62.7, 61.4, 41.6, 38.0, 34.4,
14.0, 13.7; IR (KBr) n: 1747, 1730, 1670, 1593, 1579, 1494, 1448, 1035,
825, 715, 688 cmꢂ1; HRMS (ESI) calcd for C22H22ClO5 ([MþH]þ)
J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d
: 193.7, 166.1, 165.8,
401.1155, found 401.1148.
159.1, 136.8, 133.6, 129.7, 128.7, 128.6, 125.4, 113.7, 62.0, 61.9, 55.2,
46.1, 35.4, 35.3,13.90,13.87; IR (neat)
n
: 1734, 1683, 1610, 1517, 1448,
4.2.11. Diethyl
trans-2-benzoyl-3-(2,4-dichlorophenyl)cyclo-pro-
1026, 839, 767, 692 cmꢂ1; HRMS (ESI) calcd for C23H25O6 ([MþH]þ)
pane-1,1-dicarboxylate (trans-3f).9a White solid (eluting with PE:
397.1651, found 397.1642.
EA¼18:1), mp 95e96 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.09 (d,
J¼7.3 Hz, 2H, ArH), 7.62 (t, J¼7.0 Hz, 1H, ArH), 7.52 (t, J¼7.0 Hz, 2H,
ArH), 7.41 (s, 1H, ArH), 7.20 (d, J¼8.4 Hz, 1H, ArH), 7.14 (d, J¼8.3 Hz,
1H, ArH), 4.19e4.03 (m, 5H, 2OCH2, CH), 3.88 (d, J¼7.4 Hz, 1H, CH),
4.2.6. Diethyl cis-2-(4-anisyl)-3-benzoylcyclopropane-1,1-di-carbox-
ylate (cis-3c). White solid (eluting with PE:EA¼20:1), mp
78e79 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.07e8.00 (m, 2H, ArH),
1.16e1.05 (m, 6H, 2CH3); 13C NMR (75 MHz, CDCl3)
d: 193.1, 165.8,
7.64e7.56 (m, 1H, ArH), 7.54e7.46 (m, 2H, ArH), 7.23 (d, J¼8.2 Hz,
2H, ArH), 6.75 (d, J¼8.7 Hz, 2H, ArH), 4.13e4.06 (m, 4H, 2OCH2),
3.83 (d, J¼9.9 Hz, 1H, CH), 3.75 (s, 3H, OCH3), 3.40 (d, J¼9.9 Hz, 1H,
CH), 1.34 (t, J¼7.2 Hz, 3H, CH3), 1.13 (t, J¼7.2 Hz, 3H, CH3); 13C NMR
165.3, 136.74, 136.69, 134.3, 133.8, 130.7, 130.6, 129.4, 128.8, 128.6,
126.8, 62.3, 61.9, 45.5, 35.3, 34.0, 13.8; IR (KBr) n: 1730, 1681, 1595,
1556, 1473, 1450, 1055, 852, 810, 771, 742, 705 cmꢂ1; HRMS (ESI)
calcd for C22H21Cl2O5 ([MþH]þ) 435.0766, found 435.0760.
(75 MHz, CDCl3) d: 193.1, 169.8, 165.0, 158.6, 138.2, 133.3, 131.9,
128.7,128.2,123.4,113.1, 62.6, 61.2, 55.1, 41.5, 38.5, 34.8,14.1,13.8; IR
(KBr) : 1751,1724,1683,1610,1595,1516,1463,1450,1031, 837, 802,
4.2.12. Diethyl cis-2-benzoyl-3-(2,4-dichlorophenyl)cyclopro-pane-
1,1-dicarboxylate (cis-3f). Pale solid (eluting with PE:EA¼18:1), mp
n
Please cite this article in press as: Sun, Y.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.011

Y. Sun et al. / Tetrahedron xxx (2013) 1e7
5
92e93 ꢀC; 1H NMR (300 MHz, CDCl3)
d
: 8.03 (d, J¼7.7 Hz, 2H, ArH),
61.8, 55.5, 45.8, 35.7, 34.9, 13.9, 13.8; IR (neat)
n
: 1728, 1670, 1600,
7.66e7.57 (m, 1H, ArH), 7.56e7.46 (m, 3H, ArH), 7.33 (d, J¼1.2 Hz,
1H, ArH), 7.13 (dd, J¼8.4, 1.2 Hz, 1H, ArH), 4.39e4.27 (m, 2H, OCH2),
4.18e4.04 (m, 2H, OCH2), 3.99 (d, J¼9.6 Hz, 1H, CH), 3.25 (d,
J¼9.6 Hz, 1H, CH), 1.34 (t, J¼7.1 Hz, 3H, CH3), 1.08 (t, J¼7.1 Hz, 3H,
1577, 1510, 1458, 850, 746, 698 cmꢂ1; HRMS (ESI) calcd for C23H25O6
([MþH]þ) 397.1651, found 397.1641.
4.2.18. Diethyl
1,1-dicarboxylate (cis-3i). Primrose solid (eluting with PE:EA¼
20:1), mp 95e96 ꢀC; 1H NMR (300 MHz, CDCl3)
cis-2-(4-methoxybenzoyl)-3-phenylcyclopro-pane-
CH3); 13C NMR (75 MHz, CDCl3)
d: 193.1, 169.3, 164.6, 137.7, 136.7,
133.7, 133.5, 132.4, 129.3, 128.80, 128.77, 128.3, 126.5, 62.8, 61.4,
42.0, 36.6, 34.4, 14.1, 13.6; IR (KBr) : 1735, 1672, 1593, 1479, 1446,
d
: 8.03 (d, J¼8.7 Hz,
n
2H, ArH), 7.35e7.15 (m, 5H, ArH), 6.97 (d, J¼8.4 Hz, 2H, ArH),
4.41e4.23 (m, 2H, OCH2), 4.21e4.03 (m, 2H, OCH2), 3.89 (s, 3H,
OCH3), 3.82 (d, J¼9.9 Hz, 1H, CH), 3.40 (d, J¼9.9 Hz, 1H, CH), 1.34 (t,
J¼7.2 Hz, 3H, CH3), 1.10 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (75 MHz,
1029, 856, 806, 773, 721, 692 cmꢂ1; HRMS (ESI) calcd for
C
22H21Cl2O5 ([MþH]þ) 435.0766, found 435.0767.
4.2.13. Diethyl trans-2-benzoyl-3-(4-nitrophenyl)cyclopro-pane-1,1-
CDCl3) d: 191.3, 169.9, 165.1, 163.7, 131.8, 131.3, 130.7, 130.6, 127.6,
dicarboxylate (trans-3g).9a Primrose solid (eluting with PE:EA¼
127.1, 113.9, 62.5, 61.2, 55.5, 41.2, 38.6, 34.4, 14.1, 13.7; IR (KBr) n:
15:1), mp 94e95 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.19 (d, J¼8.6 Hz,
1728, 1666, 1600, 1575, 1510, 842, 758, 694 cmꢂ1; HRMS (ESI) calcd
2H, ArH), 8.10 (d, J¼7.3 Hz, 2H, ArH), 7.70e7.61 (m, 1H, ArH),
7.58e7.46 (m, 4H, ArH), 4.20e3.99 (m, 5H, 2OCH2, CH), 3.95 (d,
J¼7.4 Hz, 1H, CH), 1.14e1.02 (m, 6H, 2CH3); 13C NMR (75 MHz,
for C23H25O6 ([MþH]þ) 397.1651, found 397.1651.
4.2.19. Diethyl
1,1-dicarboxylate (trans-3j). Yellow oil (eluting with PE:EA¼27:1);
1H NMR (300 MHz, CDCl3)
: 8.09e8.01 (m, 2H, ArH), 7.52e7.45 (m,
trans-2-(4-chlorobenzoyl)-3-phenylcyclopro-pane-
CDCl3) d: 192.8, 165.3, 165.2, 147.5, 141.2, 136.5, 134.0, 129.7, 128.9,
128.6, 123.6, 62.5, 62.2, 46.3, 35.1, 34.9, 13.9, 13.8; IR (KBr)
n
: 1732,
d
1668, 1521, 1448, 1037, 856, 740, 698 cmꢂ1; HRMS (ESI) calcd for
2H, ArH), 7.35e7.27 (m, 5H, ArH), 4.14 (q, J¼7.2 Hz, 2H, OCH2),
4.08e3.97 (m, 3H, OCH2, CH), 3.88 (d, J¼7.7 Hz, 1H, CH), 1.12 (t,
J¼7.2 Hz, 3H, CH3), 0.91 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (75 MHz,
C
22H22NO7 ([MþH]þ) 412.1396, found 412.1391.
4.2.14. Diethyl cis-2-benzoyl-3-(4-nitrophenyl)cyclopropane-1,1-
CDCl3) d: 192.4, 165.8, 165.6, 140.2, 135.1, 133.2, 130.0, 129.1, 128.6,
dicarboxylate (cis-3g). Yellow oil (eluting with PE:EA¼15:1); 1H
128.4, 127.8, 62.1, 62.0, 46.1, 35.8, 34.9, 13.9, 13.8; IR (neat) n: 1728,
NMR (300 MHz, CDCl3)
d: 8.13e8.07 (m, 2H, ArH), 8.06e8.00 (m,
1683, 1589, 1570, 854, 744, 698 cmꢂ1; HRMS (ESI) calcd for
2H, ArH), 7.68e7.61 (m, 1H, ArH), 7.57e7.49 (m, 4H, ArH),
4.44e4.27 (m, 2H, OCH2), 4.20e4.05 (m, 2H, OCH2), 3.92 (d,
J¼9.6 Hz, 1H, CH), 3.47 (d, J¼9.6 Hz, 1H, CH), 1.36 (t, J¼6.9 Hz, 3H,
C
22H22ClO5 ([MþH]þ) 401.1155, found 401.1155.
4.2.20. Diethyl cis-2-(4-chlorobenzoyl)-3-phenylcyclopro-pane-1,1-
CH3), 1.12 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 192.9,
dicarboxylate (cis-3j). Primrose solid (eluting with PE:EA¼27:1),
169.1, 164.5, 147.0, 139.4, 137.7, 133.8, 131.8, 128.9, 128.2, 122.8, 63.0,
mp 57e58 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.01e7.95 (m, 2H, ArH),
61.6, 41.9, 37.6, 34.1, 14.0, 13.7; IR (neat)
n
: 1734, 1676, 1597, 1517,
7.50e7.45 (m, 2H, ArH), 7.33e7.27 (m, 2H, ArH), 7.25e7.18 (m, 3H,
ArH), 4.42e4.24 (m, 2H, OCH2), 4.19e4.04 (m, 2H, OCH2), 3.76 (d,
J¼9.9 Hz, 1H, CH), 3.45 (d, J¼9.9 Hz, 1H, CH), 1.35 (t, J¼7.1 Hz, 3H,
1448, 1095, 854, 727, 692 cmꢂ1; HRMS (ESI) calcd for C22H22NO7
([MþH]þ) 412.1396, found 412.1396.
CH3), 1.10 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 191.8,
4.2.15. Diethyl trans-2-(4-methylbenzoyl)-3-phenylcyclopro-pane-
169.6, 164.8, 139.9, 136.4, 131.4, 130.7, 129.6, 129.1, 127.7, 127.3, 62.7,
1,1-dicarboxylate (trans-3h).9a Yellow oil (eluting with PE:EA¼
61.3, 41.6, 38.8, 34.5, 14.0, 13.7; IR (KBr) n: 1732, 1668, 1587, 1446,
27:1); 1H NMR (300 MHz, CDCl3)
d
: 8.01 (d, J¼8.1 Hz, 2H, ArH),
850, 761, 698 cmꢂ1; HRMS (ESI) calcd for C22H22ClO5 ([MþH]þ)
7.35e7.26 (m, 7H, ArH), 4.14 (q, J¼7.1 Hz, 2H, OCH2), 4.10 (d,
J¼7.7 Hz, 1H, CH), 4.00 (q, J¼7.1 Hz, 2H, OCH2), 3.87 (d, J¼7.7 Hz, 1H,
CH), 2.44 (s, 3H, CH3), 1.12 (t, J¼7.0 Hz, 3H, CH3), 0.99 (t, J¼7.1 Hz,
401.1155, found 401.1154.
4.2.21. Diethyl trans-2-(4-bromobenzoyl)-3-phenylcyclopro-pane-
3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 193.2, 166.0, 165.8, 144.6,
1,1-dicarboxylate (trans-3k).9a Saffron oil (eluting with PE:
134.3, 133.6, 129.4, 128.7, 128.6, 128.3, 127.6, 62.0, 61.9, 46.0, 35.9,
EA¼27:1); 1H NMR (300 MHz, CDCl3)
d: 8.02e7.93 (m, 2H, ArH),
34.9, 21.8, 13.9, 13.8; IR (neat)
n
: 1732, 1676, 1606, 1446, 850, 742,
7.70e7.61 (m, 2H, ArH), 7.36e7.27 (m, 5H, ArH), 4.23e4.09 (m, 2H,
OCH2), 4.07e3.96 (m, 3H, OCH2, CH), 3.88 (d, J¼7.7 Hz, 1H, CH), 1.12
(t, J¼7.2 Hz, 3H, CH3), 0.99 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz,
698 cmꢂ1; HRMS (ESI) calcd for C23H25O5 ([MþH]þ) 381.1702,
found 381.1694.
CDCl3) d: 192.6, 165.8, 165.6, 135.5, 133.2, 132.1, 130.1, 129.0, 128.6,
4.2.16. Diethyl cis-2-(4-methylbenzoyl)-3-phenylcyclopro-pane-1,1-
128.4, 127.8, 62.1, 62.0, 46.2, 35.8, 34.9, 13.9, 13.8; IR (neat) n: 1734,
dicarboxylate (cis-3h). Yellow oil (eluting with PE:EA¼27:1); 1H
1683, 1585, 852, 744, 698 cmꢂ1; HRMS (ESI) calcd for C22H22BrO5
NMR (300 MHz, CDCl3)
d
: 7.94 (d, J¼7.8 Hz, 2H, ArH), 7.35e7.16
([MþH]þ) 445.0650, found 445.0643.
(m, 7H, ArH), 4.41e4.24 (m, 2H, OCH2), 4.21e4.04 (m, 2H, OCH2),
3.83 (d, J¼9.9 Hz, 1H, CH), 3.42 (d, J¼9.9 Hz, 1H, CH), 2.43 (s, 3H,
CH3), 1.34 (t, J¼7.2 Hz, 3H, CH3), 1.10 (t, J¼7.2 Hz, 3H, CH3); 13C
4.2.22. Diethyl cis-2-(4-bromobenzoyl)-3-phenylcyclopro-pane-1,1-
dicarboxylate (cis-3k). Pale solid (eluting with PE:EA¼27:1), mp
NMR (75 MHz, CDCl3)
d
: 192.6, 169.9, 165.1, 144.2, 135.7, 131.7,
82e83 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 7.94e7.86 (m, 2H, ArH),
130.7, 129.4, 128.4, 127.6, 127.1, 62.6, 61.2, 41.3, 38.8, 34.6, 21.7,
7.68e7.61 (m, 2H, ArH), 7.34e7.27 (m, 2H, ArH), 7.25e7.17 (m, 3H,
ArH), 4.42e4.25 (m, 2H, OCH2), 4.20e4.01 (m, 2H, OCH2), 3.75 (d,
J¼9.9 Hz, 1H, CH), 3.46 (d, J¼9.9 Hz, 1H, CH), 1.35 (t, J¼7.2 Hz, 3H,
14.1, 13.7; IR (neat) n: 1728, 1676, 1606, 1498, 1446, 848, 765,
696 cmꢂ1; HRMS (ESI) calcd for C23H25O5 ([MþH]þ) 381.1702,
found 381.1701.
CH3), 1.10 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 192.0,
169.6, 164.8, 136.8, 132.1, 131.4, 130.7, 129.7, 128.6, 127.7, 127.3, 62.7,
4.2.17. Diethyl trans-2-(4-methoxybenzoyl)-3-phenylcyclo-propane-
61.4, 41.6, 38.8, 34.5, 14.1, 13.7; IR (KBr) n: 1732, 1670, 1585, 1444,
1,1-dicarboxylate (trans-3i).9a Yellow oil (eluting with PE:EA¼
840, 759, 696 cmꢂ1; HRMS (ESI) calcd for C22H22BrO5 ([MþH]þ)
20:1); 1H NMR (300 MHz, CDCl3)
d
: 8.10 (d, J¼8.8 Hz, 2H, ArH),
445.0650, found 445.0649.
7.34e7.22 (m, 5H, ArH), 6.98 (d, J¼8.8 Hz, 2H, ArH), 4.14 (q, J¼7.1 Hz,
2H, OCH2), 4.08 (d, J¼7.7 Hz, 1H, CH), 4.00 (q, J¼7.1 Hz, 2H, OCH2),
3.89 (s, 3H, OCH3), 3.87 (d, J¼7.7 Hz, 1H, CH), 1.12 (t, J¼7.1 Hz, 3H,
4.2.23. Diethyl trans-2-(4-nitrobenzoyl)-3-phenylcyclopro-pane-1,1-
dicarboxylate (trans-3l). Primrose solid (eluting with PE:EA¼
CH3), 0.98 (t, J¼7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d
: 191.8,
15:1), mp 119e120 ꢀC; 1H NMR (300 MHz, CDCl3)
d: 8.41e8.34 (m,
166.1, 165.9, 164.0, 133.7, 131.0, 129.9, 128.6, 128.3, 127.6, 113.9, 61.9,
2H, ArH), 8.30e8.23 (m, 2H, ArH), 7.35e7.27 (m, 5H, ArH),
Please cite this article in press as: Sun, Y.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.011

6
Y. Sun et al. / Tetrahedron xxx (2013) 1e7
4.20e3.98 (m, 5H, 2OCH2, CH), 3.92 (d, J¼7.6 Hz, 1H, CH), 1.12 (t,
J¼7.2 Hz, 3H, CH3), 1.00 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz,
HRMS (ESI) calcd for
442.1501.
C
23H24NO8 ([MþH]þ) 442.1502, found
CDCl3) d: 192.4, 165.7, 165.4, 150.7, 141.1, 132.9, 129.6, 128.5, 128.0,
124.0, 62.3, 62.2, 46.6, 36.0, 35.3, 13.9, 13.8; IR (KBr) n: 1722, 1689,
Acknowledgements
1602, 1525, 1463, 854, 746, 698 cmꢂ1; HRMS (ESI) calcd for
C
22H22NO7 ([MþH]þ) 412.1396, found 412.1396.
We thank the National Natural Science Foundation of China
(21172002, 20972001) for generous financial support. We are also
grateful to Professors Shuangliu Zhou, Xiaolong Mu and Yun Wei
for assistance in obtaining crystallographic data.
4.2.24. Diethyl trans-2-(4-anisyl)-3-(4-methoxybenzoyl)cy-clopro-
pane-1,1-dicarboxylate (trans-3m). Yellow oil (eluting with PE:
EA¼10:1); 1H NMR (300 MHz, CDCl3)
: 8.09 (d, J¼8.7 Hz, 2H, ArH),
d
7.22 (d, J¼8.2 Hz, 2H, ArH), 6.97 (d, J¼8.7 Hz, 2H, ArH), 6.83 (d,
J¼8.4 Hz, 2H, ArH), 4.13 (q, J¼7.1 Hz, 2H, OCH2), 4.07e3.96 (m, 3H,
OCH2, CH), 3.89 (s, 3H, OCH3), 3.83 (d, J¼7.7 Hz, 1H, CH), 3.82 (s,
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.02.011.
3H, OCH3), 1.11 (t, J¼7.1 Hz, 3H, CH3), 1.03 (t, J¼7.1 Hz, 3H, CH3); 13
C
NMR (75 MHz, CDCl3) d: 191.9, 166.2, 166.0, 164.0, 159.1, 131.0,
130.0, 129.7, 125.6, 113.9, 113.7, 61.9, 61.8, 55.5, 55.3, 45.8, 35.2, 35.1,
References and notes
13.9; IR (neat) n: 1730, 1672, 1600, 1575, 1517, 1463, 1440, 850,
819 cmꢂ1; HRMS (ESI) calcd for C24H27O7 ([MþH]þ) 427.1757,
1. Recent reviews: (a) Reissig, H. U.; Zimmer, R. Chem. Rev. 2003, 103, 1151e1196;
(b) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321e347; (c) Rubin, M.;
Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117e3179; (d) Simone, F. D.;
Waser, J. Synthesis 2009, 3353e3374; (e) Carson, C. A.; Kerr, M. A. Chem. Soc. Rev.
2009, 38, 3051e3060; (f) Lebold, T. P.; Kerr, M. A. Pure Appl. Chem. 2010, 82,
1797e1812.
2. For selected recent examples, see: (a) Chagarovskiy, A. O.; Budynina, E. M.;
Ivanova, O. A.; Grishin, Y. K.; Trushkov, I. V.; Verteletskii, P. V. Tetrahedron 2009,
65, 5385e5392; (b) Qu, J.-P.; Deng, C.; Zhou, J.; Sun, X.-L.; Tang, Y. J. Org. Chem.
2009, 74, 7684e7689; (c) Trost, B. M.; Morris, P. J. Angew. Chem., Int. Ed. 2011, 50,
6167e6170; (d) Grover, H. K.; Lebold, T. P.; Kerr, M. A. Org. Lett. 2011, 13,
220e223; (e) Sapeta, K.; Kerr, M. A. Org. Lett. 2009, 11, 2081e2084; (f) Ivanova,
O. A.; Budynina, E. M.; Chagarovskiy, A. O.; Kaplun, A. E.; Trushkov, I. V.;
Melnikova, M. Y. Adv. Synth. Catal. 2011, 353, 1125e1134; (g) Ivanova, O. A.;
Budynina, E. M.; Grishin, Y. K.; Trushkov, I. V.; Verteletskii, P. V. Angew. Chem.,
Int. Ed. 2008, 47, 1107e1110.
3. For selected recent examples, see: (a) Parsons, A. T.; Smith, A. G.; Neel, A. J.;
Johnson, J. S. J. Am. Chem. Soc. 2010, 132, 9688e9692; (b) Lebold, T. P.; Kerr, M. A.
Org. Lett. 2009, 11, 4354e4357; (c) Tomilov, Y. V.; Novikov, R. A.; Nefedov, O. M.
Tetrahedron 2010, 66, 9151e9158; (d) Xing, S.; Pan, W.; Liu, C.; Ren, J.; Wang, Z.
Angew. Chem., Int. Ed. 2010, 49, 3215e3218; (e) Campbell, M. J.; Johnson, J. S.;
Parsons, A. T.; Pohlhaus, P. D.; Sanders, S. D. J. Org. Chem. 2010, 75, 6317e6325;
(f) Smith, A. G.; Slade, M. C.; Johnson, J. S. Org. Lett. 2011, 13, 1996e1999; (g)
Dias, D. A.; Kerr, M. A. Org. Lett. 2009, 11, 3694e3697; (h) Karadeolian, A.; Kerr,
M. A. J. Org. Chem. 2010, 75, 6830e6841.
4. (a) Krief, A.; Provins, L.; Froidbise, A. Tetrahedron Lett. 1998, 39, 1437e1440; (b)
Appel, R.; Hartmann, N.; Mayr, H. J. Am. Chem. Soc. 2010, 132, 17894e17900; (c)
Jiang, H.; Deng, X.; Sun, X.; Tang, Y.; Dai, L.-X. J. Org. Chem. 2005, 70,
10202e10205.
found 427.1756.
4.2.25. Diethyl cis-2-(4-anisyl)-3-(4-methoxybenzoyl)cyclo-propane-
1,1-dicarboxylate (cis-3m). Yellow oil (eluting with PE:EA¼10:1);
1H NMR (300 MHz, CDCl3)
d
: 8.02 (d, J¼8.7 Hz, 2H, ArH), 7.22 (d,
J¼8.1 Hz, 2H, ArH), 6.96 (d, J¼8.7 Hz, 2H, ArH), 6.74 (d, J¼8.7 Hz, 2H,
ArH), 4.41e3.98 (m, 4H, 2OCH2), 3.89 (s, 3H, OCH3), 3.79 (d,
J¼10.4 Hz, 1H, CH), 3.74 (s, 3H, OCH3), 3.34 (d, J¼10.4 Hz, 1H, CH),
1.34 (t, J¼7.2 Hz, 3H, CH3), 1.13 (t, J¼7.2 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) d: 191.3, 170.0, 165.2, 163.7, 158.6, 131.8, 131.3,
130.5, 123.7, 113.9, 113.1, 62.5, 61.1, 55.5, 55.1, 41.2, 38.2, 34.6, 14.1,
13.8; IR (neat) n: 1726, 1670, 1598, 1575, 1516, 1458, 842, 761,
700 cmꢂ1; HRMS (ESI) calcd for C24H27O7 ([MþH]þ) 427.1757, found
427.1755.
4.2.26. Diethyl
trans-2-(4-anisyl)-3-(4-bromobenzoyl)cyclo-pro-
pane-1,1-dicarboxylate (trans-3n).9a Yellow oil (eluting with
PE:EA¼15:1); 1H NMR (300 MHz, CDCl3)
: 7.96 (d, J¼8.4 Hz, 2H,
d
ArH), 7.65 (d, J¼8.4 Hz, 2H, ArH), 7.21 (d, J¼8.4 Hz, 2H, ArH), 6.83 (d,
J¼8.4 Hz, 2H, ArH), 4.19e4.08 (m, 2H, OCH2), 4.07e3.95 (m, 3H,
OCH2, CH), 3.81 (d, J¼7.7 Hz, 1H, CH), 3.79 (s, 3H, OCH3), 1.13 (t,
J¼7.2 Hz, 3H, CH3), 1.03 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz,
5. (a) Xie, H.; Zu, L.; Li, H.; Wang, J.; Wang, W. J. Am. Chem. Soc. 2007, 129,
ꢀ
10886e10894; (b) Ibrahem, I.; Zhao, G.-L.; Rios, R.; Vesely, J.; Sunden, H.; Dziedzic,
CDCl3) d: 192.7, 165.9, 165.7, 159.2, 135.5, 132.1, 130.1, 129.7, 128.9,
ꢀ
P.; Cordova, A. Chem.dEur. J. 2008, 14, 7867e7879; (c) Uria, U.; Vicario, J. L.;
125.2, 113.8, 62.1, 61.9, 55.3, 46.2, 35.3, 35.2, 13.9; IR (neat) n: 1728,
Badía, D.; Carrillo, L.; Reyes, E.; Pesquera, A. Synthesis 2010, 701e713; (d)
1676, 1585, 1516, 848, 815 cmꢂ1; HRMS (ESI) calcd for C23H24BrO6
ꢀ
ꢀ
Companyo, X.; Alba, A.-N.; Cardenas, F.; Moyano, A.; Rios, R. Eur. J. Org. Chem.
2009, 3075e3080; (e) Terrasson, V.; Van der Lee, A.; De Figueiredo, R. M.; Cam-
pagne, J. M. Chem.dEur. J. 2010, 16, 7875e7880.
([MþH]þ) 475.0756, found 475.0746.
6. (a) Fan, R.; Ye, Y.; Li, W.; Wang, L. Adv. Synth. Catal. 2008, 350, 2488e2492; (b)
Xuan, Y.; Nie, S.; Dong, L.; Zhang, J.; Yan, M. Org. Lett. 2009, 11, 1583e1586; (c)
Russo, A.; Lattanzi, A. Tetrahedron: Asymmetry 2010, 21, 1155e1157.
7. Rh/Cu-catalyzed cyclopropanation of alkenes with diazomalonate: (a) Chelucci,
4.2.27. Diethyl cis-2-(4-anisyl)-3-(4-bromobenzoyl)cyclopro-pane-
1,1-dicarboxylate (cis-3n). Yellow oil (eluting with PE:EA¼15:1); 1H
NMR (300 MHz, CDCl3)
d
: 7.90 (d, J¼8.4 Hz, 2H, ArH), 7.64 (d,
ꢀ
G.; Saba, A. Tetrahedron Lett. 1995, 36, 4673e4676; (b) Gonzalez-Bobes, F.;
J¼8.4 Hz, 2H, ArH), 7.21 (d, J¼8.4 Hz, 2H, ArH), 6.76 (d, J¼8.7 Hz, 2H,
ArH), 4.39e4.06 (m, 4H, 2OCH2), 3.75 (s, 3H, OCH3), 3.74 (d,
J¼9.9 Hz, 1H, CH), 3.40 (d, J¼9.9 Hz, 1H, CH), 1.34 (t, J¼7.2 Hz, 3H,
Fenster, M. D. B.; Kiau, S.; Kolla, L.; Kolotuchin, S.; Soumeillant, M. Adv. Synth.
Catal. 2008, 350, 813e816; (c) Nishimura, T.; Maeda, Y.; Hayashi, T. Angew.
Chem., Int. Ed. 2010, 49, 7324e7327 with phenyliodium yield of malonates; (d)
Goudreau, S. R.; Marcoux, D.; Charette, A. B. J. Org. Chem. 2009, 74, 470e473.
8. (a) Krief, A.; Provins, L.; Froidbise, A. Synlett 1999, 1936e1938; (b) Matsumoto,
M.; Mizuno, T.; Watanabe, N. Tetrahedron Lett. 2004, 45, 3779e3782; (c) Adamo,
M. F. A.; Suresh, S.; Piras, L. Tetrahedron 2009, 65, 5402e5408; (d) Elinson, M.
N.; Feducovich, S. K.; Starikova, Z. A.; Olessova, O. S.; Vereshchagin, A. N.;
Nikishin, G. I. Tetrahedron Lett. 2000, 41, 4937e4941; (e) Elinson, M. N.;
Feducovich, S. K.; Starikova, Z. A.; Vereshchagin, A. N.; Belyakova, P. A.; Nikishin,
G. I. Tetrahedron 2006, 62, 3989e3996; (f) Crane, Z. D.; Nichols, P. J.; Sammakia,
T.; Stengel, P. J. J. Org. Chem. 2011, 76, 277e280.
CH3), 1.13 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3)
d: 192.1,
169.6, 164.9, 158.7, 136.8, 132.1, 131.8, 129.7, 128.6, 123.2, 113.2, 62.6,
61.3, 55.1, 41.6, 38.4, 34.6, 14.1, 13.8; IR (neat) n: 1734, 1683, 1676,
1585, 1500, 850, 808 cmꢂ1; HRMS (ESI) calcd for C23H24BrO6
([MþH]þ) 475.0756, found 475.0756.
4.2.28. Diethyl trans-2-(4-anisyl)-3-(4-nitrobenzoyl)cyclopro-pane-
9. (a) Yang, G.; Hua, Y.; Shen, Y. Chin. J. Chem. 2009, 27, 1811e1819; (b) Yang, G.;
Shen, Y.; Li, K.; Sun, Y.; Hua, Y. J. Org. Chem. 2011, 76, 229e233.
1,1-dicarboxylate (trans-3o). Yellow oil (eluting with PE:EA¼10:1);
1H NMR (300 MHz, CDCl3)
d
: 8.36 (d, J¼8.4 Hz, 2H, ArH), 8.26 (d,
10. In
a control experiment, product trans-3f was subjected to a reaction
condition similar to that of entry 6, Table 2 (3 equiv of K2CO3 in DMSO at
80 ꢀC for 17 h) and remarkable decomposition was observed. The major
decomposed product is also the major component observed in the crude
reaction mixture of the cyclopropanation at 80 ꢀC, as determined by 1H NMR
analysis.
J¼8.7 Hz, 2H, ArH), 7.21 (d, J¼8.7 Hz, 2H, ArH), 6.85 (d, J¼8.4 Hz, 2H,
ArH), 4.19e3.99 (m, 5H, 2OCH2, CH), 3.86 (d, J¼7.5 Hz, 1H, CH), 3.80
(s, 3H, OCH3), 1.12 (t, J¼7.0 Hz, 3H, CH3), 0.86 (t, J¼7.2 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3)
d: 192.4, 165.7, 165.5, 159.3, 150.7, 141.1,
11. Preliminary studies using the reaction conditions in entries 7, 16 and 17 in Table
3 and (ꢂ)-N-benzylcinchonidinium chloride (20 mol %) as the catalysts in
DMSO led to racemic cis/trans products. For substrate 1l, the use of toluene as
129.64, 129.61, 124.8, 124.0, 113.9, 62.3, 62.1, 55.3, 46.6, 35.5, 13.9; IR
(neat)
n
: 1730, 1685, 1604, 1527, 1517, 1463, 848, 744, 709 cmꢂ1
;
Please cite this article in press as: Sun, Y.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.011

Y. Sun et al. / Tetrahedron xxx (2013) 1e7
7
solvent (84 h at 20 ꢀC, 45% conversion) gave the highest ee value of 23% ee for
the minor cis-3l (6% yield) and 16% ee for the major trans-3l (26% yield). Further
studies toward the optimization of the present system using other chiral phase
transfer catalysts are still underway.
12. (a) Cromwell, N. H.; Cram, D. J.; Harris, C. E. Org. Synth. 1947, 27, 9e10; (b)
Ducki, S.; Mackenzie, G.; Greedy, B.; Armitage, S.; Chabert, J. F.; Bennett, E.;
Nettles, J.; Snyder, J. P.; Lawrence, N. J. Bioorg. Med. Chem. 2009, 17,
7711e7722.
Please cite this article in press as: Sun, Y.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.02.011