A facile preparation of trans-1,2-cyclopropanes containing p-trifluoromethylphenyl group and its application to the construction of pyrazole and cyclopropane ring fused pyridazinone derivatives

Article abstract of DOI:10.1016/j.tet.2008.05.016

A facile methodology for the preparation of highly functionalized trans-1,2-cyclopropanes containing p-trifluoromethylphenyl group 3 is described. Arsonium bromides 1 reacted with electron-deficient olefins 2 in the presence of K₂CO₃ to provide 3 stereoselectively in moderate to good yields. This process has been successfully applied to the construction of cyclopropane ring fused pyridazinone derivatives 4 or pyrazole derivatives 5.

Full text of DOI:10.1016/j.tet.2008.05.016

Tetrahedron 64 (2008) 6670–6674
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A facile preparation of trans-1,2-cyclopropanes containing p-
trifluoromethylphenyl group and its application to the construction
of pyrazole and cyclopropane ring fused pyridazinone derivatives
,
b,
c
,
a,
a
d
d
a
a
a
Weiguo Cao a
, Hui Zhang , Jie Chen , Hongmei Deng , Min Shao , Lu Lei , Jiaxian Qian , Yuan Zhu
*
*
a Department of Chemistry, Shanghai University, Shanghai 200444, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
c Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
d Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile methodology for the preparation of highly functionalized trans-1,2-cyclopropanes containing p-
trifluoromethylphenyl group 3 is described. Arsonium bromides 1 reacted with electron-deficient olefins
2 in the presence of K2CO3 to provide 3 stereoselectively in moderate to good yields. This process has
been successfully applied to the construction of cyclopropane ring fused pyridazinone derivatives 4 or
pyrazole derivatives 5.
Received 5 January 2008
Received in revised form 29 April 2008
Accepted 5 May 2008
Available online 9 May 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
trifluoromethylphenyl group, which can further be transformed
into pyrazole and cyclopropane ring fused pyridazinone derivatives
The synthesis and application of multisubstituted cyclopro-
panes have been a subject of great interest due to their roles as the
basic structural elements in a wide range of biologically active
compounds and important intermediates in organic synthesis.1
On the other hand, it is well accepted that selective introduction
of fluorine-containing functionality to organic compounds often
causes marked effects on their physical and chemical properties,2
and these effects can make them suitable for diverse applications in
synthetic, agricultural, and medicinal chemistry as well as in ma-
terial science.3 It is therefore still of importance to develop simple
and effective methods for the synthesis of cyclopropanes with
fluorine-containing group.4
The tandem Michael addition–elimination of ylides to electron-
deficient alkenes provides easy access to functionalized cyclopro-
panes.5 Among the ylides reported, arsonium ylides are known for
their high reactivity and high diastereoselectivity in alkene, epox-
ide, and cyclopropane formation.6 They have similar reactivity to
the telluronium ylides, and in general exhibit higher diaster-
eoselectivities than the latter. Moreover, the stability of triphenyl
arsine in air may facilitate the experimental operations. Continuing
our efforts toward the stereoselective synthesis and application
of cyclopropanes,7 we focused on an arsonium ylide-based
stereoselective synthesis of trans-cyclopropanes with p-
with potential biological activities.8,9
2. Results and discussion
In the presence of K2CO3, arsonium bromides 1 reacted with
electron-deficient olefins 2 in chloroform at room temperature for
the time indicated in Table 1 to give cyclopropanes 3 in moderate to
good yields (Scheme 1).
In the beginning, the stereochemistry of compounds 3a–h was
deduced from their 19F and 1H NMR spectra. For example, the 19F
NMR spectrum of 3a showed a peak at ꢀ63.1 ppm (s, –CF3), in-
dicating one sole product with p-trifluoromethylphenyl group was
obtained. In addition, the 1H NMR spectrum of compound 3a
showed two doublets at 3.16 ppm (J¼8.0 Hz, 1H) and 3.76 ppm
(J¼8.0 Hz, 1H) assigned to be the two cyclopropyl protons. The 19F
Table 1
Preparation of cis-1,2-cyclopropanes with arsonium bromide 1 and olefin 2
Entry
R1
R2
Product 3
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
–CN
–C(O)Ph
–CN
–CN
–CN
–CN
–C(O)OCH3
–C(O)OCH3
–C(O)OCH3
–C(O)OCH3
3a
3b
3c
3d
3e
3f
12
10
7
5
6
6
6
6
50
67
77
80
78
81
90
67
–C(O)(furan-2-yl)
–C(O)(thiophen-2-yl)
–C(O)Ph
–C(O)(furan-2-yl)
–C(O)(thiophen-2-yl)
–Ph
3g
3h
* Corresponding authors. Fax: þ86 21 6613 4856.
E-mail addresses: wgcao@staff.shu.edu.cn (W. Cao), yehao7171@shu.edu.cn
(H. Zhang).
a
Isolated yield.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.016

W. Cao et al. / Tetrahedron 64 (2008) 6670–6674
6671
F3C
R2
CN
H
CN
K2CO3
CF3
+
Ph3AsCH2R1 Br
H
R2
R1
1
2
3
Scheme 1.
and 1H NMR spectra of compounds 3b–h manifested themselves in
a similar manner. In all of compounds 3a–h, the coupling constant
of the two vicinal cyclopropyl protons (J¼8.0–9.0 Hz) indicated
a trans configuration.10 Furthermore, we treated the supposed
trans-1,2-cyclopropanes 3e–g with hydrazine monohydrate in DME
by refluxing to prepare 4a–c (Scheme 2, Table 2), and confirmed the
stereochemistry of compound 4a by X-ray diffraction analysis
(Fig. 1 11). This fact led to a mechanism for the stereoselective for-
mation of cyclopropane ring fused pyridazinone derivatives
outlined in Scheme 3. The hydrazone A was formed by the con-
densation of carbonyl group on the cyclopropane 3 with hydrazine,
and then the intramolecular nucleophilic addition–elimination
between the ester group and the free amino group of hydrazone
generated 4. Thus, to form 4a, PhCO and CO2Me in 3e would only
be cis, which at last established the trans relationship of the
p-trifluoromethylphenyl and PhCO groups. Therefore, we found
a facile method to synthesize trans-1,2-cyclopropanes 3. Addi-
tionally, this method provides a quick and efficient entry to
functionalized pyrazole derivatives of biological interest due to
the well known fact that the reactivity of the cyclopropanes with
Figure 1. X-ray structure of compound 4a.
condensation of carbonyl group on the cyclopropane with hydra-
zine providing hydrazone C. The intramolecular nucleophilic ad-
dition between the cyclopropane ring and the free amino group of
hydrazone was involved in the second step to generate the pyr-
azoline D, followed by the easy transformation of pyrazoline D into
pyrazoline E. The aromatization of pyrazoline E to pyrazoline F in
the last step was achieved by the elimination of malononitrile in
the presence of hydrazine as the base.
carbonyl group is similar to that of
a,b-unsaturated carbonyl
compounds.12 1,2-trans-Cyclopropanes 3b–d reacted with hydra-
zine monohydrate by refluxing in DME to afford 3-aryl-5-p-
trifluoromethylphenylpyrazoles 5a–c in good to excellent yields
(Scheme 2, Table 2). The structure of 5a was confirmed by its X-ray
diffraction analysis (Fig. 2 11). The mechanism was also proposed as
shown in Scheme 4. In this reaction, the first step was the
The packing diagrams of compounds 4a (Fig. 3 11) and 5a
(Fig. 4 11) showed that there were intermolecular hydrogen bonds
existing in each molecule with bond lengths of 3.037 Å and 2.905 Å,
respectively. It also showed
p–p stacking in compound 5a with
molecular layer distance of 3.5923 Å, which indicated the good co-
planar feature of compound 5a.
F3C
F3C
3. Conclusions
CN
NH
CN
CO2CH3
H
DME
DME
H
.
+
NH2NH2 H2O
O
In summary, highly functionalized 1,2-trans-cyclopropanes
containing trifluoromethyl group were stereoselectively synthe-
sized under mild conditions in good yields. These versatile cy-
clopropane building blocks were successfully applied to the
synthesis of pyrazole and cyclopropane ring fused pyridazinone
derivatives.
H
H
R1
N
R3
3e_g
4a-c
F3C
R3
CN
CN
H
N
.
+
NH2NH2 H2O
N
F3C
F3C
H
H
F3C
R1
3b_d
CN
CN
5a-c
H
H
DME
reflux
+ NH2NH2 . H2O
Scheme 2.
H
H
CO2CH3
CO2CH3
R1
R3
NNH2
3e_g
Table 2
A
F3C
Preparation of pyrazole and pyridazinone derivatives
F3C
Entry
3
R1
R3
Product
Yielda (%)
CN
NH
CN
1
2
3
4
5
6
3e
3f
3g
3b
3c
3d
–C(O)Ph
–Ph
–(Furan-2-yl)
–(Thiophen-2-yl)
–Ph
–(Furan-2-yl)
–(Thiophen-2-yl)
4a
4b
4c
5a
5b
5c
88
82
74
90
80
78
H
-CH3OH
H
O
–C(O)(furan-2-yl)
–C(O)(thiophen-2-yl)
–C(O)Ph
–C(O)(furan-2-yl)
–C(O)(thiophen-2-yl)
O
C
H
H
OCH3
NH
N
R3
R3
N
4a-c
B
a
Scheme 3.
Isolated yield.

6672
W. Cao et al. / Tetrahedron 64 (2008) 6670–6674
Figure 2. X-ray structure of compound 5a.
F3C
F3C
F3C
CN
CN
CN
CN
CN
H
H
H
DME
+ NH2NH2 . H2O
H
H2N
reflux
H
H
CN
R3
R1
3b_d
R3
H2NN
N
C
D
F3C
R3
CN
H
.
proton
exchange
NH2NH2
NH2NH2 H2O
N
+
NC
CN
H
HN
N
H
CN
R3
F3C
N
5a-c
F
Scheme 4.
4. Experimental
4.1. General information
All reagents and solvents were obtained from commercial
sources and used without further purification. All melting points
were uncorrected. Melting points were determined on a WRS-1
digital melting point apparatus made by Shanghai physical in-
strument factory (SPOIF), China. IR spectra were measured on
Figure 3. Packing diagram of compound 4a.
Figure 4. Packing diagram of compound 5a.

W. Cao et al. / Tetrahedron 64 (2008) 6670–6674
6673
a AVATAR370 FT spectrometer and expressed in cmꢀ1 (KBr disc). All
1H, 13C, and 19F NMR spectra were recorded on a Bruker AM-500,
using CDCl3 as solvent. Mass spectra were recorded on an HP5989A
mass spectrometer. HRMS spectra were run on a Waters Micromass
GCT instrument. Elemental analyses were measured on the ele-
mentar vario EL III. X-ray crystal data were collected with a Bruker
Smart Apex2 CCD. Flash chromatography was performed on col-
126.1 (3JC–F¼3.8 Hz), 125.0, 124.0 (1JC–F¼271.5 Hz), 114.9, 54.1, 34.6,
14.2; IR (film) n
: 2242, 1739, 1683, 1326 cmꢀ1; MS m/z (EI): 374.2
[(Mþ1)]þ; HRMS (EI): calcd for C20H14O3NF3 (Mþ) 373.0926, found
373.0923.
4.2.6. Compound 3f
Yellow oil; 1H NMR (CDCl3)
d
: 3.71 (d, J¼8.5 Hz, 1H, CH), 3.79 (s,
umns of silica gel (20–30
mm).
3H, OCH3), 3.97 (d, J¼8.5 Hz,1H, CH), 6.63 (d, J¼1.5 Hz,1H, furan-H),
7.37 (d, J¼3.5 Hz, 1H, furan-H), 7.52–7.68 (m, 4H, ArH), 7.70 (dd,
4.2. General procedure for preparation of compound 3
J¼1.5, 3.5 Hz, 1H, furan-H); 19F NMR (CDCl3)
d
: ꢀ62.72 (s, CF3); 13
C
NMR (CDCl3)
d
: 177.9,163.9,151.8,147.9,135.9,131.1 (2JC–F¼32.8 Hz),
Olefin 2 was prepared from malononitrile or methyl 2-cyano-
acetate (1.1 mmol) and p-trifuoromethylbenzaldehyde (1.0 mmol)
in methanol (5.0 mL) in the presence of piperidine (0.05 mL) fol-
lowed by gentle heating at 50 ꢁC until the aldehyde was consumed.
A mixture of olefin 2 (1 mmol), arsonium salt 1 (1.2 mmol), and
K2CO3 (3 mmol) was stirred at room temperature in CHCl3 (5 mL).
The completion of the reaction was monitored by TLC. The solid was
filtered off and the solvent was removed under reduced pressure.
The residue was chromatographed on silica gel (eluent: petroleum
ether 60–90 ꢁC–ethyl acetate) to give the desired product 3.
129.6, 128.9, 126.0 (3JC–F¼3.8 Hz), 123.4 (1JC–F¼271.5 Hz), 119.4,
113.2, 54.1, 28.6, 34.4, 14.2; IR (film) n ;
: 2247, 1746, 1676, 1326 cmꢀ1
MS m/z (EI): 364.2 [(Mþ1)]þ; HRMS (EI): calcd for C18H13 O4NF3
[(MþH)]þ 364.0797, found 364.0725.
4.2.7. Compound 3g
Yellow oil; 1H NMR (CDCl3)
d
: 3.67 (d, J¼8.5 Hz, 1H, CH), 3.78 (s,
3H, OCH3), 3.91 (d, J¼8.5 Hz, 1H, CH), 7.21 (dd, J¼3.0, 5.0 Hz, 1H,
thiophene-H), 7.52–7.71 (m, 4H, ArH), 7.78 (d, J¼5.0 Hz, 1H, thio-
phene-H), 7.85 (d, J¼3.0 Hz, 1H, thiophene-H); 19F NMR (CDCl3)
d:
ꢀ62.74 (s, CF3); 13C NMR (CDCl3)
d: 181.6, 163.8, 142.2, 135.8, 131.2
4.2.1. Compound 3a
(2JC–F¼32.8 Hz),129.5,128.9,128.8,128.7,126.1 (3JC–F¼3.6 Hz), 124.0
Yellow oil; 1H NMR (CDCl3)
d
: 3.16 (d, J¼8.0 Hz, 1H, CH), 3.76 (d,
(1JC–F¼271.0 Hz), 114.8, 54.2, 39.9, 35.7, 14.2; IR (film)
n: 2247, 1746,
J¼8.0 Hz, 1H, CH), 7.45–7.76 (m, 4H, ArH); 19F NMR (CDCl3)
d
: ꢀ63.1
1666, 1326, 848 cmꢀ1; MS m/z (EI): 380.0 [(Mþ1)]þ; HRMS (EI):
calcd for C18H13O3NF3S [(MþH)]þ 380.0568, found 380.0467.
(s, CF3); 13C NMR (CDCl3)
d
: 135.2, 132.9 (2JC–F¼32.7 Hz), 131.1, 126.8
(3JC–F¼3.7 Hz), 124.2 (1JC–F¼271.5 Hz), 112.5, 110.7, 109.5, 38.2, 20.1,
14.2; IR (film)
n
: 2256, 1731, 843, 760, 734 cmꢀ1; MS m/z (EI): 261.0
4.2.8. Compound 3h
(Mþ); HRMS (EI): calcd for C13H6N3F3 (Mþ) 261.0514, found
261.0520.
Yellow oil; 1H NMR (CDCl3)
d: 3.65 (s, 3H, OCH3), 3.73 (d,
J¼9.0 Hz,1H, CH), 3.91 (d, J¼9.0 Hz,1H, CH), 7.36–7.70 (m, 9H, ArH);
19F NMR (CDCl3)
d
: ꢀ62.67 (s, CF3); 13C NMR (CDCl3)
d: 171.2, 167.9,
4.2.2. Compound 3b
164.0, 130.5, 130.2 (2JC–F¼32.8 Hz), 129.1, 128.9, 128.8, 125.9 (3JC–F
¼
Yellow oil; 1H NMR (CDCl3)
d
: 3.97 (d, J¼8.0 Hz, 1H, CH), 4.10 (d,
3.6 Hz), 124.9 (1JC–F¼271.3 Hz), 116.2, 53.7, 40.8, 35.8, 14.2; IR (film)
J¼8.0 Hz, 1H, CH), 7.52–8.12 (m, 9H, ArH); 19F NMR (CDCl3)
d
: ꢀ62.9
n
: 2243, 1742, 1325, 842, 759, 698 cmꢀ1; MS m/z (EI): 346.2
(s, CF3); 13C NMR (CDCl3)
d
: 188.4, 138.1, 135.4, 133.5, 132.0 (2JC–F
¼
¼
[(Mþ1)]þ; HRMS (EI): calcd for C19H14O2NF3 (Mþ) 345.0977, found
32.9 Hz), 139.5, 129.1, 129.0, 126.4 (3JC–F¼3.6 Hz), 124.5 (1JC–F
345.0978.
271.0 Hz), 111.9, 111.2, 35.6, 32.2, 15.2; IR (film)
n
: 2250, 1680, 846,
734, 708 cmꢀ1; MS m/z (EI): 340.0 (Mþ); HRMS (EI): calcd for
19H11ON2F3 (Mþ) 340.0823, found 340.0812.
C
4.3. General procedure for preparation of compound 4 or 5
4.2.3. Compound 3c
The mixture of compound 3 (1.0 mmol) and hydrazine mono-
hydrate (85%, 1.2 mmol) was refluxed in DME (5 mL) until TLC
showed the completion of the reaction. After cooling, DME was
removed in vacuo and the product was purified by flash chroma-
tography on silica gel (eluent: petroleum ether 60–90 ꢁC–ethyl
acetate).
Yellow oil; 1H NMR (CDCl3)
d
: 3.91 (d, J¼8.0 Hz, 1H, CH), 4.11 (d,
J¼8.0 Hz, 1H, CH), 6.75 (dd, J¼1.0, 1.1 Hz, 1H, furan-H), 7.53–7.73 (m,
4H, ArH), 7.54 (d, J¼1.1 Hz,1H, furan-H), 7.80 (d, J¼1.0 Hz,1H, furan-
H); 19F NMR (CDCl3)
d
: ꢀ62.9 (s, CF3); 13C NMR (CDCl3)
d: 176.6,
151.7, 148.7, 133.4, 131.0 (2JC–F¼32.9 Hz), 126.3 (3JC–F¼4 Hz), 125.0,
124.7, 124.5 (1JC–F¼272.0 Hz), 114.0, 111.8, 111.0, 37.2, 35.2, 15.1; IR
(film)
n
: 2251, 1671, 847 cmꢀ1; MS m/z (EI): 331.1 [(Mþ1)]þ; HRMS
4.3.1. Compound 4a
(EI): calcd for C17H10 O2N2F3 [(MþH)]þ 331.0694, found 331.0695.
Yellow solid, mp: 217.6–218.9 ꢁC; 1H NMR (CDCl3)
d: 3.15 (d,
J¼6.5 Hz, 1H, CH), 3.66 (d, J¼7 Hz, 1H, CH), 7.46–7.76 (m, 9H, ArH),
4.2.4. Compound 3d
9.16 (s, 1H, NH); 19F NMR (CDCl3)
d
d
: ꢀ62.8 (s, CF3); 13C NMR (CDCl3)
Yellow oil; 1H NMR (CDCl3)
d
: 3.95 (d, J¼8.0 Hz, 1H, CH), 4.97 (d,
: 131.7 (2JC–F¼32.5 Hz), 131.1, 129.2, 128.6, 126.5 (3JC–F¼3.7 Hz),
J¼8.0 Hz, 1H, CH), 7.30 (dd, J¼4.0, 5.0 Hz, 1H, thiophene-H), 7.52–
126.4, 123.8 (1JC–F¼271.3 Hz), 115.1, 113.5, 32.1, 31.7, 29.8, 26.8, 22.8,
7.73 (m, 4H, ArH), 7.90 (d, J¼5.0 Hz, 1H, thiophene-H), 8.05 (d,
14.3; IR (film) n: 3452, 3071, 2924, 2249, 1682, 1327, 1125, 845,
J¼4.0 Hz, 1H, thiophene-H); 19F NMR (CDCl3)
d
: ꢀ62.9 (s, CF3); 13C
690 cmꢀ1; MS m/z (EI): 355.2 (Mþ). Anal. Calcd for C19H12O N3F3: C,
NMR (CDCl3)
d
: 180.4, 142.2, 137.5, 135.2, 134.4, 133.4, 132.0 (2JC–F
¼
64.23; H, 3.40; N, 11.83. Found: C, 64.20; H, 3.73; N, 11.19.
32.9 Hz), 129.0, 126.4 (3JC–F¼3.6 Hz), 124.6 (1JC–F¼270.2 Hz),
111.8, 111.1, 37.5, 36.3, 15.1; IR (film)
n
: 2249, 1656, 850 cmꢀ1; MS
4.3.2. Compound 4b
m/z (EI): 347.0 (Mþ); HRMS (EI): calcd for C17H10ON2F3S [(MþH)]þ
Yellow solid, mp: 199.2–202.2 ꢁC; 1H NMR (CDCl3)
d: 3.14 (d,
347.0466, found 347.0467.
J¼6.5 Hz, 1H, CH), 3.69 (d, J¼6.5 Hz, 1H, CH), 6.59 (m, 1H, furan-H),
6.94 (d, J¼3.5 Hz, 1H, furan-H), 7.62 (m, 1H, furan-H), 7.65 (m, 4H,
4.2.5. Compound 3e
ArH), 8.86 (s, 1H, NH); 19F NMR (CDCl3)
d
: ꢀ62.8 (s, CF3); 13C NMR
Yellow oil; 1H NMR (CDCl3)
d: 3.73 (s, 3H, OCH3), 3.74 (d,
((CD3)2CO)
d
: 158.7, 150.4, 145.8, 137.8, 137.5, 130.9 (2JC–F¼31.9 Hz),
J¼8.5 Hz, 1H, CH), 3.89 (d, J¼8.5 Hz, 1H, CH), 7.52–8.02 (m, 9H,
130.2, 126.5 (3JC–F¼3.4 Hz), 125.2 (1JC–F¼270.0 Hz), 115.0, 113.0,
ArH); 19F NMR (CDCl3)
d
: ꢀ62.72 (s, CF3); 13C NMR (CDCl3)
d: 189.1,
112.3, 32.2, 31.0, 27.6, 23.3, 14.4; IR (film) n: 3456, 2923, 2854, 2251,
164.0, 135.8, 135.2, 134.6, 131.2 (2JC–F¼32.8 Hz), 129.2, 128.8, 128.5,
1670, 1132, 1069, 765 cmꢀ1; MS m/z (EI): 345.2 (Mþ). Anal. Calcd for

6674
W. Cao et al. / Tetrahedron 64 (2008) 6670–6674
2000, 56, 3635; (f) Ramachandran, P. V. Asymmetric Fluoroorganic Chemistry:
Synthesis, Applications, and Future Directions; American Chemical Society:
Washington, DC, 1999; (g) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992,
48, 6555.
C17H10O2N3F3: C, 59.14; H, 2.92; N, 12.17. Found: C, 59.17; H, 3.08; N,
11.88.
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Gaunt, M. J. Angew. Chem., Int. Ed. 2004, 43, 4641; (d) Papageorgiou, C. D.; Ley,
S. V.; Gaunt, M. J. Angew. Chem., Int. Ed. 2003, 42, 828; (e) Kimber, M. C.; Taylor,
D. K. J. Org. Chem. 2002, 67, 3142; (f) Avery, T. D.; Fallon, G.; Greatrex, B. W.;
Pyke, S. M.; Taylor, D. K.; Tiekink, E. R. T. J. Org. Chem. 2001, 66, 7955; (g)
Aggarwal, V. K.; Alonso, E.; Fang, G. Y.; Ferrara, M.; Hynd, G.; Porcelloni, M.
Angew. Chem., Int. Ed. 2001, 40, 1433; (h) Aggarwal, V. K.; Smith, H. W.; Hynd,
G.; Jones, R. V. H.; Fieldhouse, R.; Spey, S. E. J. Chem. Soc., Perkin Trans. 1 2000,
3267; (i) Solladie-Cavallo, A.; Diep-Vohuule, A.; Isarno, T. Angew. Chem., Int. Ed.
1998, 37, 1689.
6. For reviews on arsonium ylides, see: (a) Lloyd, D.; Gosney, I.; Ormiston, R. A.
Chem. Soc. Rev. 1987, 16, 45; (b) Johnson, A. W. Ylide Chemistry; Academic: New
York, NY, 1966; (c) Song He, H.; Wan Ying Chung, C.; Yuen Sze But, T.; Toy, P. H.
Tetrahedron 2005, 61, 1385; (d) Huang, Y.; Shen, Y. Adv. Organomet. Chem. 1982,
20, 113.
7. (a) Ren, Z.; Cao, W.; Chen, J.; Wang, Y.; Ding, W. J. Heterocycl. Chem. 2006, 43,
495; (b) Ren, Z.; Cao, W.; Ding, W.; Wang, Y. Synthesis 2005, 2718; (c) Ren, Z.;
Cao, W.; Tong, W.; Zhu, J. Synth. Commun. 2005, 35, 2509; (d) Ren, Z.; Cao, W.;
Chen, J.; Wang, Y.; Ding, W. Synth. Commun. 2005, 35, 3099; (e) Ren, Z.; Cao, W.;
Ding, W.; Shi, W. Synth. Commun. 2004, 34, 4395; (f) Cao, W.; Ding, W.; Chen, J.;
Chen, Y.; Zang, Q.; Chen, G. Synth. Commun. 2004, 34, 1599; (g) Ren, Z.; Cao, W.;
Ding, W.; Wang, Y.; Wang, L. Synth. Commun. 2004, 34, 3785.
4.3.3. Compound 4c
Yellow solid, mp: 218.8–220.1 ꢁC; 1H NMR (CDCl3)
d: 3.16 (d,
J¼6.5 Hz,1H, CH), 3.65 (d, J¼6.5 Hz, 1H, CH), 7.13 (m, 1H, thiophene-
H), 7.42 (m, 1H, thiophene-H), 7.50 (m, 1H, thiophene-H), 7.65 (m,
4H, ArH), 8.63 (m, 1H, NH); 19F NMR (CDCl3)
d
: ꢀ66.1 (s, CF3); 13C
NMR ((CD3)2CO)
d
: 158.8, 141.6, 140.7, 137.8, 130.9 (2JC–F¼31.8 Hz),
130.2, 130.0, 129.4, 128.7, 126.5 (3JC–F¼3.8 Hz), 125.2 (1JC–F¼270 Hz),
115.0, 32.5, 31.4, 27.9, 23.3, 14.1; IR (film) n: 3443, 2923, 2853, 2249,
1679, 1326, 1123, 845, 710 cmꢀ1; MS m/z (EI): 361.1 (Mþ). Anal.
Calcd for C17H10ON3F3S: C, 56.51; H, 2.79; N, 11.63. Found: C, 56.48;
H, 2.92; N, 11.55.
4.3.4. Compound 5a
White solid, mp: 142–144 ꢁC; 1H NMR (CDCl3)
d
: 6.91 (s, 1H, CH),
: ꢀ62.53 (s, CF3); IR
: 3140, 760, 680 cmꢀ1; MS m/z (EI): 288.0 (Mþ). Anal. Calcd
7.40–7.90 (m, 9H, Ph–H); 19F NMR (CDCl3)
(film)
d
n
for C16H11N2F3: C, 66.66; H, 3.85; N, 9.72. Found: C, 66.28; H, 4.06;
N, 9.32.
4.3.5. Compound 5b
White solid, mp: 152–154 ꢁC; 1H NMR (CDCl3)
d: 6.52 (m, 1H,
J¼1.5, 3.0 Hz, furan-H), 6.68 (d, 1H, J¼3.0 Hz, furan-H), 6.83 (s, 1H,
CH), 7.49 (d, 1H, J¼1.5 Hz, furan-H), 7.68–7.90 (m, 4H, ArH); 19F
NMR (CDCl3)
d
: ꢀ62.55 (s, CF3); IR (film)
n
: 3205, 751, 687 cmꢀ1; MS
m/z (EI): 278.0 (Mþ). Anal. Calcd for C14H9ON2F3: C, 60.44; H, 3.26;
N, 10.07. Found: C, 60.28; H, 3.47; N, 9.65.
8. (a) Michel, J.; Verdonk, M. L.; Essex, J. W. J. Med. Chem. 2006, 49, 7427; (b)
Alloza, I.; Baxter, A.; Chen, Q.; Rune Matthiesen, R.; Vandenbroeck, K. Mol.
Pharmacol. 2006, 69, 1579; (c) Wesolowski, S. S.; Jorgensen, W. L. Bioorg. Med.
Chem. Lett. 2002, 12, 267; (d) Plount Price, M. L.; Jorgensen, W. L. J. Am. Chem.
Soc. 2000, 122, 9455; (e) Jeremy, L.; Jenkins, J. L.; Glick, M.; Davies, J. W. J. Med.
Chem. 2004, 47, 6144; (f) Chanteau, F.; Plantier-Royon, R.; Portella, C. Synlett
2004, 512; (g) Sloop, J. C.; Bumgardner, C. L.; Loehle, W. D. J. Fluorine Chem.
2002, 118, 135; (h) Volle, J.-N.; Schlosser, M. Eur. J. Org. Chem. 2000, 823; (i)
Hanamoto, T.; Suetake, T.; Koga, Y.; Kawanami, T.; Furunob, H.; Inanaga, J.
Tetrahedron 2007, 63, 5062; (j) Peat, A. J.; Townsend, C.; McKay, M. C.; Garrido,
D.; Terry, C. M.; R. Wilson, J. L. R.; Thomson, S. A. Bioorg. Med. Chem. Lett. 2004,
14, 813; (k) Bourrain, S.; Ridgill, M.; Collins, I. Synlett 2004, 795.
4.3.6. Compound 5c
White solid, mp: 168–169 ꢁC; 1H NMR (CDCl3)
d
: 6.82 (s, 1H, CH),
7.11 (m, 1H, thiophene-H), 7.34 (m, 2H, thiophene-H), 7.69–7.85 (m,
4H, ArH); 19F NMR (CDCl3)
d
: ꢀ62.58 (s, CF3); IR (film)
n: 3158, 829,
757 cmꢀ1; MS m/z (EI): 294.0 (Mþ). Anal. Calcd for C14H9N2F3S: C,
57.14; H, 3.08; N, 9.52. Found: C, 57.35; H, 3.42; N, 9.34.
Acknowledgements
9. (a) Brule, C.; Bouillon, J. P.; Nicolai, E.; Portella, C. Synthesis 2006, 103; (b)
Dinoiu, V.; Tinant, B.; Nuzillard, J. M.; Bouillon, J. P. J. Fluorine Chem. 2006, 127,
101; (c) Cachet, X.; Deguin, B.; Tillequin, F.; Koch, M.; Chiaroni, A. Heterocycles
2002, 57, 523; (d) Horino, H.; Mimura, T.; Kobayashi, S.; Ohta, M.; Kubo, H.; Ito,
K.; Tsumura, M.; Kitagawa, M. Chem. Pharm. Bull. 2000, 48, 490; (e) Cignarella,
G.; Barlocco, D.; Rossi, G.; Rossi, E. Synthesis 1990, 160; (f) Stimac, A.; Stanovnik,
B.; Tisler, M.; Golic, L. Tetrahedron 1990, 46, 6915; (g) Horino, H.; Mimura, T.;
Ohta, M.; Kubo, H.; Kitagawa, M. Bioorg. Med. Chem. Lett. 1997, 7, 437; (h)
Stimac, A.; Stanovnik, B.; Tisler, M. J. Heterocycl. Chem. 1991, 28, 417; (i) Koenig,
J. J.; Wermuth, C. G. Tetrahedron 1974, 30, 501.
This project was supported by the National Natural Science
Foundation of China and the Foundations of Education Commission
of Shanghai Municipality (nos. J50102 and 08ZZ44).
References and notes
1. For reviews on the synthesis and application of cyclopropanes, see: (a) Lebel,
H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977; (b)
Pietruszka, J. Chem. Rev. 2003, 103, 1051; (c) Reissig, H. U.; Zimmer, R. Chem. Rev.
2003, 103, 1151; (d) Wessjohann, L. A.; Brandt, W. Chem. Rev. 2003, 103, 1625; (e)
Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J. Tetrahedron 2003, 59, 5623; (f) Li, A.
H.; Dai, L. X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341.
2. (a) Hiyama, T. Organofluorine Compounds. Chemistry and Applications; Springer:
New York, NY, 2000; (b) O’Hagan, D.; Harper, D. B. J. Fluorine Chem. 1999, 100,
127; (c) Eswarakrishnan, S. Fluorine in Bioorganic Chemistry; Welch, J. T., Ed.;
Wiley: New York, NY, 1991; (d) Welch, J. T. Selective Fluorination in Organic and
Bioorganic Chemistry; American Chemical Society: Washington, DC, 1991.
3. (a) Chambers, R. D. Fluorine in Organic Chemistry, 2nd ed.; Blackwell: London,
2004; (b) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214; (c) Smart,
B. E. J. Fluorine Chem. 2001, 109, 3; (d) Park, B. K.; Kitteringham, N. R.; O’Niel,
P. M. Annu. Rev. Pharmacol. Toxicol. 2001, 41, 443; (e) Lin, P.; Jiang, J. Tetrahedron
10. (a) Pretsch, E.; Bu¨hlmann, P.; Affolter, C. Structure Determination of Organic
Compounds Tables of Spectral Data; Springer: Zurich, Switzerland, 2000; (b)
Zhang, H.; Cao, W.; Ren, Z.; Chen, J.; Sun, R.; Hu, J.; Qian, J.; Deng, H. Chin. J.
Chem. 2007, 25, 1187.
11. CCDC-651125 (4a) and CCDC-651124 (5a) contain all crystallographic details of
this publication and are available free of charge at www.ccdc.cam.ac.uk/consts/
retrieving.html or can be ordered from the following address: Cambridge
Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; fax: þ44
1223 336 033; or deposit@ccdc.cam.ac.uk. Unit cell parameters (4a): a¼11.
5304 Å, b¼11.3696 Å, c¼13.3334 Å;
b
¼100.007; space group: P2(1)/c0. Unit cell
parameters (5a): a¼14.7249 Å, b¼5.8139 Å, c¼15.6286 Å;
b
¼99.054; space
group: P2(1)/n0.
12. Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.; Tanko, J.; Hudlicky, T. Chem. Rev.
1989, 89, 165.