An efficient and highly stereoselective synthesis of novel trifluoromethylated trans-dihydrofuro[2,3-c]pyrazoles using arsonium ylides

Article abstract of DOI:10.1016/j.tet.2012.01.030

An efficient approach of highly stereoselective synthesis of novel trifluoromethylated trans-4,5-dihydrofuro[2,3-c]pyrazoles has been described. Arsonium bromides 1 reacted smoothly with the electron-deficient alkenes (Z)-4-aryl-1-phenyl-3-(trifluoromethy

Full text of DOI:10.1016/j.tet.2012.01.030

Tetrahedron 68 (2012) 2121e2127
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient and highly stereoselective synthesis of novel trifluoromethylated
trans-dihydrofuro[2,3-c]pyrazoles using arsonium ylides
,
Jiaping Zhang a, Shuxin Yang a, Kai Zhang a, Jie Chen a, Hongmei Deng d, Min Shao d, Hui Zhang a
,
*
,b,c,
Weiguo Cao a
*
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 of 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:
An efficient approach of highly stereoselective synthesis of novel trifluoromethylated trans-4,5-
dihydrofuro[2,3-c]pyrazoles has been described. Arsonium bromides 1 reacted smoothly with the
Received 5 December 2011
Received in revised form 31 December 2011
Accepted 13 January 2012
electron-deficient alkenes (Z)-4-aryl-1-phenyl-3-(trifluoromethyl)-1H-pyrozol-5(4H)-ones
2 to give
products trans-dihydrofuro[2,3-c]pyrazoles 3 with high stereoselectivity and in good to excellent yields,
using CH2Cl2 as solvent and K2CO3 as base.
Available online 20 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Dihydrofuro[2,3-c]pyrazoles
Arsonium ylides
Trifluoromethylated
Electron-deficient alkenes
Stereoselective synthesis
1. Introduction
In the course of investigations concerning the exploitation of
novel bioactive molecules, the usual design was to combine the
Pyrazoles, including their fluorinated derivatives, have
demonstrated a broad spectrum of biological activities and
represented an important structural class in pharmaceuticals
and agrochemicals.1e4 Much work has been done on the design
and the synthesis of complex pyrazoles, giving particular rele-
vance to the functionalization of the scaffold in different re-
gions5 and in particular, to the synthesis of ring-condensed
structures.6 Indeed, the preparation of pyrazole-fused ring de-
rivatives is very important and challenging from the synthetic
point of view.
Dihydrofurans belong to an important class of compounds,
which show a wide range of biological activities and form the core
structure of many natural products.7 Among them, 2,3-
dihydrofurans have gained importance as structural features of
natural products, such as aflatoxins,8 natural germination inhibitor
(þ)-erigeronic acid A,9 monomers for the synthesis of biodegrad-
able polymers (e.g., naturally occurring polyethers),10 and other
useful synthetic intermediates.7c
known pharmacophore into a single molecule as a central scaf-
fold.3,6 Therefore, the integration of a pyrazole ring with CF3-group
and a substituted dihydrofuran ring in one molecule could lead to
the novel trifluoromethylated dihydrofuropyrazoles, which may
show a modified biological activity. The literature survey showed
that there are no reports of CF3-substituted dihydrofuro[2,3-c]
pyrazoles and their stereoselective synthesis. Furthermore, arso-
nium ylides are known to show their high reactivity and high
diastereoselectivity in heterocycle and carbocycle synthesis in the
reactions with the electron-deficient alkenes.11 Thus, in our con-
tinuing efforts of synthesizing new fluorinated compounds with
promising biological properties,12 herein, we reported an efficient
synthetic method for the synthesis of novel trifluoromethylated
trans-4,5-dihydrofuro[2,3-c]pyrazoles 3 via the high stereoselective
reaction of arsonium bromides 1 and the electron-deficient alkenes
(Z)-4-aryl-1-phenyl-3-(trifluoromethyl)-1H-pyrozol-5(4H)-ones
2 in CH2Cl2 under reflux, using K2CO3 as base (Scheme 1).
2. Results and discussion
Choosing an appropriate solvent is of crucial importance for the
successful organic reactions. To search the optimal solvent, the
* Corresponding authors. Fax: þ86 21 66134856; e-mail addresses: wgcao@
staff.shu.edu.cn, yehao7171@shu.edu.cn (W. Cao).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.030

2122
J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
CF3
CF3
H
N
N
N
Ha
R
K2CO3
R2
R1
N
+ Ph3As
Ph3As-CH2RBr
R2
+
O
O
CH2Cl2, reflux
Hb
R1
1
2
3
R1 = Me,
R1 = H,
R1 = Cl,
R2 = H 2a
R2 = H 2b
R2 = H 2c
R = CO2Me, 1A
1B
R = COPh, 1C
1D
R = COMe,
2d
2e
R
R
R
1 = Br,
1 = F,
1 = H,
R2 = H
R2 = H
R = furoyl,
R2 = Cl 2f
Scheme 1. Synthesis of trifluoromethylated trans-4,5-dihydrofuro[2,3-c]pyrazoles 3.
reaction of arsonium bromide 1A with (Z)-4-benzylidene-1-
phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one 2b was exam-
ined using 1,2-dimethoxyethane (DME), acetonitrile, tetrahydro-
furan (THF), chloroform, and dichloromethane (DCM) as solvents,
respectively, at room temperature to synthesize 3Ab. The results
were summarized in Table 1 and the reaction in DCM resulted in the
product with a higher yield (entry 5).
was found to be the best base among those tested (entries 5e11). And
the optimal result was obtained when the reaction was performed in
DCM under reflux, whereby the yield of 3Ab reached 82% (entry 11).
Having established the optimized conditions for the CF3-
substituted ring-fused dihydrofuropyrazoles synthesis, we inten-
ded to determine its scope with respect to arsonium bromides 1
and the fluorinated electron-deficient alkenes 2. A series of tri-
fluoromethylated trans-4,5-dihydrofuro[2,3-c]pyrazoles
3 were
Table 1
synthesized under the identical conditions. All the reactions pro-
ceeded smoothly to afford the products in good to excellent yields
(Table 2). Still, it was observed that the reaction was significantly
affected by electronic effects of the substituents on pyrazole sub-
strates. The alkenes 2 with electronically poor aryl group at the
Optimization for the synthesis of 3Ab
Entry
Solvent
Base
Ratio
(2b/1A/base)
Temp
(ꢀ C)
Time (h)
Isolated
yield (%)
1
2
3
4
5
6
7
8
CH3CN
CHCl3
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
KF$2H2O
K2CO3
K2CO3
K2CO3
K2CO3
1:1.2:2
1:1.2:2
1:1.2:2
1:1.2:2
1:1.2:2
1:1.2:2
1:1.2:2
1:1.8:2
1:1.2:3
1:1.8:3
1:1.8:2
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
40
48
48
48
48
48
48
48
12
12
12
36
30
32
16
24
58
43
20
64
48
50
82
a
position to olefinic bond of pyrazole substrates showed higher
activity than those bearing electronically neutral substituents. For
example, the reactions of compounds 2 with R1 substituents as
halogen completed faster than those reactions of compounds 2
with R1 substituent as methyl group or hydrogen atom (Table 2,
entries 1, 2 vs 3e6). Moreover, steric effects have been found to play
an important role in this reaction. It was noted that arsonium
bromides 1 with R group as methyl or methoxy rendered the re-
action faster and gave better yields than those with the aryl or
heteroaryl groups (entries 1, 7 vs 8, 9).
DME
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
10
11
Bold value represents optimized reaction conditions.
The structures of the products were identified by 1H NMR, 13
C
NMR, 19F NMR, MS, and IR. It was found that their 1H NMR spectra
were all in the similar manner. The coupling constant between Ha
and Hb on the fused dihydrofuran was 5.5e6.5 Hz, which confirmed
the trans configuration of compounds 3.13 An X-ray diffraction
Other reaction conditions, including reaction temperature, base
and the molar ratio of 2b to 1A and base, were then investigated. A
series of experiments revealed that 1.0 equivof 2b,1.8 equivof 1A, and
2.0 equiv of base were sufficient for the synthesis of 3Ab and K2CO3
Table 2
Synthesis of trifluoromethylated trans-4,5-dihydrofuro[2,3-c]pyrazoles 3a
Entry
R
Arsonium
bromides 1
R1
R2
The fluorinated
electron-deficient
alkenes 2
Time (h)
Product 3
Isolated yield (%)
1
2
3
4
5
6
7
8
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
COMe
COPh
Furoyl
COMe
COPh
Furoyl
COMe
COMe
COMe
COPh
1A
1A
1A
1A
1A
1A
1B
1C
1D
1B
1C
1D
1B
1B
1C
1C
1C
1C
CH3
H
Cl
Br
F
H
CH3
CH3
CH3
Cl
Cl
Cl
Br
F
H
H
Br
H
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
H
H
H
Cl
2a
2b
2c
2d
2e
2f
2a
2a
2a
2c
2c
2c
2d
2e
2b
2b
2d
2f
24
36
10
6
3Aa
3Ab
3Ac
3Ad
3Ae
3Af
3Ba
3Ca
3Da
3Bc
3Cc
3Dc
3Bd
3Be
3Bb
3Cb
3Cd
3Cf
78
82
81
85
84
80
80
73
70
82
76
82
89
85
83
75
80
73
15
20
20
28
36
11
19
27
10
12
16
21
20
20
9
10
11
12
13
14
15
16
17
18
COPh
COPh
a
Conditions: fluorinated electron-deficient alkenes 2 1.0 mmol, arsonium bromide 1 1.8 equiv, K2CO3 2.0 equiv, CH2Cl2 5 mL, reflux.

J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
2123
method was used to further elucidate the structures of 3. It was
4. Experimental
proved that the 3D perspective view of the crystal structure of 3Ac
was unequivocally the trans-isomer by X-ray crystallographic
analysis (Fig. 1).14
4.1. General information
All reagents and solvents were purchased from commercial
sources and used without further purification, except that arso-
nium bromides 113c and (Z)-1-phenyl-3-(trifluoromethyl)-1H-
pyrozol-5(4H)-one derivatives 217 were prepared according to the
known literature. Melting points were recorded on a WRS-1 in-
strument and uncorrected. 1H, 19F, and 13C NMR spectra were
recorded on a Bruker DRX-500 MHz spectrometer. All chemical
shifts are reported in parts per million downfield (positive) of the
standard: C6F6 for 19F, TMS for 1H and 13C NMR spectra. IR spectra
were obtained on an AVATAR370 FT-IR spectrometer. Elemental
analysis was performed on an Elementar Vario EL-III instrument.
LRMS was run on an Agilent LC/MSD SL mass spectrometer. HRMS
was run on an APEXIII 7.0 TESLA FTMS mass spectrometer. X-ray
analysis was performed on a Bruker Smart Apex2 CCD spectrom-
eter. Compounds previously described in the literature were char-
acterized by comparing their 1H NMR spectra to the published data.
All yields reported in this publication refer to isolated ones of
compounds and their purity was determined by 1H NMR.
4.2. General procedure for preparation of compound 2
Fig. 1. X-ray structure of compound 3Ac.
Ethyl 4,4,4-trifluoroacetoacetate 9.20 g (0.05 mol) and phenyl-
hydrazine 5.40 g (0.05 mol) were mixed andrefluxed in AcOH (30 mL)
for 6 h. Then the mixture was cooled to room temperature. After fil-
tration, the residue was recrystallized from ethanol to give the pure 1-
phenyl-3-trifluoromethyl-2-pyrazolin-5-one 10.23 g, yield 90%.
Aromatic aldehyde (0.012 mol) and 1-phenyl-3-(tri-
fluoromethyl)-2-pyrazolin-5-one 2.28 g (0.010 mol) were heated in
an oil-bath at 160e170 ꢀC for 4e6 h. The reaction mixture was
cooled, triturated in ethyl ether (20 mL) and filtered off. The colored
filter cake was recrystallized to afford the corresponding (Z)-4-aryl-
1-phenyl-3-(trifluoromethyl)-1H-pyrozol-5(4H)-ones 2 as colored
crystals. The Z configuration of compound 2 was confirmed by
single-crystal X-ray diffraction analysis.14
Based on the published results,15,16 a plausible mechanism of
this reaction was hypothesized as shown in Scheme 2. Firstly, the
Michael addition of arsonium ylide 4, derived from arsonium salt 1
with K2CO3 as base, to compound 2, can potentially lead to two
possible intermediates 5 or 6. Due to the steric repulsion between
two bulky groups (R and Ar) in the intermediate of 5, the in-
termediate 6 should be more stable and favored. However, the size
of R group could still influence the stability of the intermediate 6.
The bigger size of R group could lead to the more intense repulsion
between R and CF3-group in the conformation of 6. As a result,
arsonium bromide 1 with small R group as methyl or methoxy gave
the higher yield in shorter time as shown in Table 2. The intra-
molecular ring closure of the intermediate 6 provided transient
trans-cyclopropane 7 as a typical donoreacceptor cyclopropane.15
The donor group Ar served to stabilize the partial positive charge
on zwitterion 8 that was created as the C1eC2 bond cleavage of 7.
Subsequently, the oxygen anion in intermediate 9, formed through
enolation of 8, attacked the carbon cation stereoselectively to give
the final cyclized product trans-isomer 3. cis-Isomer was not ob-
tained due to the repulsion interaction between R and Ar groups,
which are both situated on the same side of the dihydrofuran ring
in the structure of 11. Furthermore, the reason that compound 2
more readily underwent reaction when R1 or R2 was the electron-
withdrawing group was attributed to that the carbon cation in
zwitterion 8 was more electrophilic and thus showed higher ac-
tivity owing to the electron-withdrawing effect.
4.2.1. (Z)-4-(4-Methylbenzylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one (2a). Red solid; yield: 67%; mp:
156.3e157.8 ꢀC; 1H NMR (500 MHz, CDCl3)
d: 2.47 (s, 3H), 7.27e7.29
(m, 1H), 7.35 (d, J¼8.0 Hz, 2H), 7.44e7.47 (m, 2H), 7.73 (s, 1H), 7.91
(d, J¼8.0 Hz, 2H), 8.46 (d, J¼8.0 Hz, 2H) ppm; 19F NMR (470 MHz,
CDCl3)
d
: ꢁ63.37 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3)
d: 161.2,
2
150.2, 146.6, 140.8 (q, JCeF¼37.5 Hz), 137.6, 135.0, 130.2, 129.9,
1
129.0, 126.1, 120.4, 119.9 (q, JCeF¼270.0 Hz), 119.8, 22.1 ppm; IR
(KBr):
n 3042, 1693, 1589, 1547, 1497, 1432, 1334, 1317, 1178, 1128,
1113, 959, 817, 754 cmꢁ1; MS (EI) m/z (%): 331 (Mþ); Anal. Calcd for
C18H13F3N2O: C 65.45; H 3.97; found: C 65.50; H 3.90.
4.2.2. (Z)-4-Benzylidene-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-
5(4H)-one (2b). Red solid; yield: 59%; mp: 132.1e133.9 ꢀC; 1H NMR
(500 MHz, CDCl3):
d 7.26e7.30 (m, 1H), 7.44e7.47 (m, 2H),
7.54e7.57 (m, 2H), 7.62e7.65 (m, 1H), 7.77 (s, 1H), 7.91 (d, J¼7.5 Hz,
3. Conclusion
2H), 8.53 (d, J¼7.5 Hz, 2H) ppm; 19F NMR (470 MHz, CDCl3)
d:
ꢁ63.45 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3)
d: 161.1, 150.7,
In summary, an efficient method for the stereoselective syn-
thesis of new CF3-substituted trans-dihydrofuro[2,3-c]pyrazoles
was first developed. This protocol provided a new avenue for de-
veloping pyrazole-fused derivatives. The best result was obtained
with arsonium bromides, (Z)-4-aryl-1-phenyl-3-(trifluoromethyl)-
1H-pyrozol-5(4H)-ones, K2CO3 base, and DCM solvent under reflux.
A possible reaction pathway is proposed, which proceeds through
a tandem Michael addition, cyclopropanation, the opening of three-
membered ring, and stereoselective cyclization.
140.8 (q, 2JCeF¼37.5 Hz), 137.5, 134.6, 132.5, 129.0, 127.9, 126.3, 123.1,
121.5, 120.0 (q, 1JCeF¼262.5 Hz), 119.9 ppm; IR (KBr):
n 1699, 1608,
1596, 1499, 1433, 1319, 1176, 1149, 1118, 959, 753, 688 cmꢁ1; MS (EI)
m/z (%): 317 (Mþ); Anal. Calcd for C17H11F3N2O: C, 54.56; H, 3.51;
found: C 54.61; H 3.57.
4.2.3. (Z)-4-(4-Chlorobenzylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one (2c). Red solid; yield: 78%; mp:
1
166.8e167.9 ꢀC (lit.17: 166.0e167.0 ꢀC); H NMR (500 MHz, CDCl3):

2124
J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
Scheme 2. Proposed mechanism for the formation of product 3.
d
7.27e7.30 (m,1H), 7.44e7.51 (m, 4H), 7.69 (s,1H), 7.89 (d, J¼7.5 Hz,
1JCeF¼275.0 Hz), 119.8, 118.7, 116.4 (d, 2JCeF¼21.2 Hz) ppm; IR (KBr):
2H), 8.49 (d, J¼8.5 Hz, 2H) ppm.
n 1698, 1596, 1556, 1498, 1434, 1322, 1245, 1174, 1162, 1137, 1119,
1096, 961, 850, 753 cmꢁ1; MS (EI) m/z (%): 334 (Mþ); Anal. Calcd for
4.2.4. (Z)-4-(4-Bromobenzylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one (2d). Red solid; yield: 80%; mp:
177.7e179.0 ꢀC (lit.17: 157.0e159.0 ꢀC); 1H NMR (500 MHz, CDCl3):
C17H10F4N2O: C 61.08; H 3.02; found: C 61.10; H 3.05.
4.2.6. (Z)-4-(3-Chlorobenzylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one (2f). Red solid; yield: 43%; mp:
d
7.27e7.30 (m, 1H), 7.44e7.47 (m, 2H), 7.66e7.68 (m, 3H), 7.88 (d,
J¼7.5 Hz, 2H), 8.40 (d, J¼8.5 Hz, 2H) ppm.
163.3e164.9 ꢀC; 1H NMR (500 MHz, CDCl3):
d 7.24e7.28 (m, 1H),
7.42e7.49 (m, 4H), 7.66 (s, 1H), 7.86e7.88 (m, 2H), 8.46e8.78 (m,
4.2.5. (Z)-4-(4-Fluorobenzylidene)-1-phenyl-3-(trifluoromethyl)-1H-
pyrazol-5(4H)-one (2e). Red solid; yield: 48%; mp: 112.4e113.7 ꢀC;
2H) ppm 19F NMR (470 MHz, CDCl3)
NMR (125 MHz, CDCl3)
d
: ꢁ63.58 (s, CF3) ppm; 13C
2
d
: 161.0, 148.8, 140.5 (q, JCeF¼37.5 Hz),
1H NMR (500 MHz, CDCl3):
d
7.21 (m, 2H), 7.28 (m,1H), 7.46 (m, 2H),
137.3, 135.7, 132.3, 131.2, 130.1, 129.0, 126.4, 121.9, 120.0 (q,
7.69 (s, 1H), 7.90 (d, J¼8.0 Hz, 2H), 8.60e8.62 (m, 2H) ppm; 19F NMR
1JCeF¼275.0 Hz),119.9,118.6 ppm; IR (KBr):
n 1700,1610,1590,1570,
(470 MHz, CDCl3)
NMR (125 MHz, CDCl3)
d
: ꢁ63.46 (s, CF3), ꢁ100.09 (m, AreF) ppm; 13C
1489, 1431, 1305, 1252, 1200, 1149, 1004, 965, 876, 754 cmꢁ1; MS
(EI) m/z (%): 350 (Mþ); Anal. Calcd for C17H10ClF3N2O: C 58.22; H
2.87; found: C 58.24; H 2.88.
1
d
: 166.3 (d, JCeF¼250.0 Hz), 161.1, 148.9,
2
140.4 (q, JCeF¼37.5 Hz), 137.6, 137.4, 129.0, 126.3, 121.4 (q,

J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
2125
4.3. General procedure for preparation of compound 3
13C NMR (125 MHz, CDCl3):
d
170.4, 163.2 (d, 1JCeF¼247.5 Hz), 159.5,
2
137.3, 136.2 (q, JCeF¼38.8 Hz), 134.2, 129.5, 127.4, 127.0, 120.6 (q,
To 5 mL DCM, arsonium bromide 1 (1.8 mmol), (Z)-4-aryl-1-
phenyl-3-(trifluoromethyl)-1H-pyrozol-5(4H)-one derivative
1JCeF¼267.5 Hz), 118.7, 116.0, 99.2, 53.0, 51.0 ppm; IR (KBr):
n 2964,
2
1727, 1601, 1545, 1512, 1485, 1456, 1408, 1253, 1223, 1180, 1130, 1039,
950, 840, 756 cmꢁ1; MS (EI) m/z (%): 406 (Mþ); HRMS (ESI) m/z calcd
for C20H14F4N2O3 [(MþNa)þ]: 429.0825; found: 429.0833.
(1.0 mmol), and K2CO3 (2.0 mmol) were added. The mixture was
stirred under reflux. After the completion of the reaction (moni-
tored by TLC), the solid was filtered off and the filtrate was con-
centrated by a rotary evaporator. The residue was purified by
column chromatography on silica gel, using petroleum ether
(60e90 ꢀC)/ethyl acetate as eluent to give the desired product 3.
4.3.6. trans-Methyl 5-(3-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-
4,5-dihydro-1H-furo[2,3-c]pyrazole-4-carboxylate (3Af). White solid;
yield: 80%; mp: 94.5e95.6 ꢀC; 1H NMR (500 MHz, CDCl3):
d 3.85 (s,
3H), 4.27 (d, J¼6.5 Hz, 1H), 6.77 (d, J¼6.5 Hz, 1H), 7.29e7.47 (m, 7H),
4.3.1. trans-Methyl 1-phenyl-5-p-tolyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazole-4-carboxylate (3Aa). White solid;
7.80 (d, J¼7.5 Hz, 2H) ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ62.84 (s,
CF3) ppm; 13C NMR (125 MHz, CDCl3):
d 170.3, 159.5, 140.2, 137.2,
yield: 78%; mp: 76.3e77.9 ꢀC; 1H NMR (500 MHz, CDCl3):
d
2.38 (s,
136.2 (q, 2JCeF¼38.8 Hz), 135.1, 130.5, 129.5, 127.1, 125.8, 123.8, 120.6
3H), 3.82 (s, 3H), 4.31 (d, J¼6.5 Hz, 1H), 6.76 (d, J¼6.5 Hz, 1H),
(q, 1JCeF¼267.5 Hz),118.8, 98.6, 53.0, 51.0 ppm; IR (KBr):
n 2955,1742,
7.23e7.45 (m, 7H), 7.80 (d, J¼8.0 Hz, 2H) ppm; 19F NMR (470 MHz,
1600, 1542, 1486, 1457, 1408, 1261, 1209, 1178, 1132, 1042, 950, 788,
759 cmꢁ1; MS (EI) m/z (%): 422 (Mþ); HRMS (ESI) m/z calcd for
C20H14ClF3N2O3 [(MþNa)þ]: 445.0551; found: 445.0547.
CDCl3):
d
ꢁ62.80 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3):
d 170.7,
2
160.0, 140.0, 137.4, 136.2 (q, JCeF¼38.8 Hz), 135.2, 130.0, 126.1,
129.4, 127.0, 125.9, 122.7 (q, 1JCeF¼267.5 Hz), 119.6, 100.1, 52.9, 51.0,
21.3 ppm; IR (KBr):
n
2950, 2938, 1734, 1601, 1543, 1523, 1485, 1457,
4.3.7. (trans-1-Phenyl-5-p-tolyl-3-(trifluoromethyl)-4,5-dihydro-1H-
furo[2,3-c]pyrazol-4-yl)ethanone (3Ba). White solid; yield: 80%;
1407, 1250, 1220, 1176, 1127, 943, 805, 754 cmꢁ1; MS (EI) m/z (%):
402 (Mþ); HRMS (ESI) m/z calcd for C21H17F3N2O3 [(MþNa)þ]:
425.1099; found: 425.1084.
mp: 95.9e96.5 ꢀC; 1H NMR (500 MHz, CDCl3):
d 2.36 (s, 3H, CH3),
2.37 (s, 3H), 4.32 (d, J¼5.5 Hz, 1H), 6.77 (d, J¼5.5 Hz, 1H), 7.21e7.30
(m, 5H), 7.42e7.45 (m, 2H), 7.80 (d, J¼7.5 Hz, 2H) ppm; 19F NMR
4.3.2. trans-Methyl
1H-furo[2,3-c]pyrazole-4-carboxylate (3Ab). White solid; yield:
82%; mp: 70.1e70.7 ꢀC; 1H NMR (500 MHz, CDCl3):
3.84 (s, 3H),
1,5-diphenyl-3-(trifluoromethyl)-4,5-dihydro-
(470 MHz, CDCl3):
CDCl3):
d
ꢁ61.78 (s, CF3) ppm; 13C NMR (125 MHz,
2
d
203.8, 160.0, 139.6. 137.3, 135.7 (q, JCeF¼40.0 Hz), 135.5,
d
129.8, 129.4, 127.0, 125.8, 120.8 (q, 1JCeF¼267.5 Hz), 118.8, 99.3, 58.5,
4.33 (d, J¼6.0 Hz, 1H), 6.82 (d, J¼6.0 Hz, 1H), 7.28e7.31 (m, 1H),
28.8, 21.3 ppm; IR (KBr): n 2937, 2922, 1709, 1601, 1540, 1484, 1457,
7.47e7.46 (m, 7H), 7.81e7.83 (m, 2H) ppm; 19F NMR (470 MHz,
1407, 1273, 1179, 1113, 1040, 950, 810, 754 cmꢁ1; MS (EI) m/z (%):
386 (Mþ); HRMS (ESI) m/z calcd for C21H17F3N2O2 [(MþNa)þ]:
409.1123; found: 409.1135.
CDCl3):
d
ꢁ62.80 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3):
d 170.6,
2
160.0, 138.3, 137.3, 136.2 (q, JCeF¼38.8 Hz), 129.5, 129.2, 127.0,
1
125.8, 121.3 (q, JCeF¼267.5 Hz), 119.6, 100.0, 52.9, 51.0 ppm; IR
(KBr):
n
2958, 2941, 1730, 1601, 1545, 1486, 1459, 1408, 1253, 1180,
4.3.8. (trans-1,5-Diphenyl-3-(trifluoromethyl)-4,5-dihydro-1H-furo
[2,3-c]pyrazol-4-yl)ethanone (3Bb). White solid; yield: 83%; mp:
1126, 948, 832, 753 cmꢁ1; MS (EI) m/z (%): 388 (Mþ); HRMS (ESI) m/
z calcd for C20H15F3N2O3 [(MþNa)þ]: 411.0944; found: 411.0927.
97.2e97.7 ꢀC; 1H NMR (500 MHz, CDCl3):
d 2.39 (s, 3H), 4.34 (d,
J¼5.5 Hz, 1H), 6.84 (d, J¼5.5 Hz, 1H), 7.29e7.31 (m, 1H), 7.39e7.46
4.3.3. trans-Methyl 5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-
4,5-dihydro-1H-furo[2,3-c]pyrazole-4-carboxylate (3Ac). White solid;
(m, 7H), 7.82 (d, J¼8.5 Hz, 2H) ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ61.71 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3):
d 203.7, 160.0,
yield: 81%; mp: 93.7e94.4 ꢀC; 1H NMR (500 MHz, CDCl3):
d
3.86 (s,
138.5. 137.3, 135.7 (q, 2JCeF¼38.8 Hz), 129.5, 129.2, 127.1, 125.6, 120.8
1
3H), 4.28 (d, J¼6.5 Hz, 1H), 6.80 (d, J¼6.5 Hz, 1H), 7.31e7.49 (m, 7H),
(q, JCeF¼267.5 Hz), 118.8, 99.0, 58.6, 28.8 ppm; IR (KBr):
n 2910,
7.81 (d, J¼7.5 Hz, 2H) ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ62.85 (s,
1718, 1598, 1552, 1488, 1453, 1400, 1271, 1186, 1125, 1041, 947, 765,
699 cmꢁ1; MS (EI) m/z (%): 372 (Mþ); HRMS (ESI) m/z calcd for
C20H15F3N2O2 [(MþNa)þ]: 395.0972; found: 395.0978.
CF3) ppm; 13C NMR (125 MHz, CDCl3):
d 170.4, 160.0, 137.2, 136.8,
136.2 (q, 2JCeF¼38.8 Hz), 129.5, 127.2, 120.6 (q, 1JCeF¼267.5 Hz), 118.8,
98.9, 53.2, 51.0 ppm; IR (KBr):
n 2956, 1724, 1603, 1543, 1489, 1459,
1409, 1251, 1178, 1137, 1126, 1091, 951, 809, 756 cmꢁ1; MS (EI) m/z
(%): 422 (Mþ); HRMS (ESI) m/z calcd for C20H14ClF3N2O3 [(MþNa)þ]:
445.0551; found: 445.0547.
4.3.9. (trans-5-(4-Chlorophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)ethanone (3Bc). White solid;
yield: 82%; mp: 111.0e113.0 ꢀC; 1H NMR (500 MHz, CDCl3):
d 2.39
(s, 3H), 4.27 (d, J¼5.5 Hz, 1H), 6.82 (d, J¼5.5 Hz, 1H), 7.29e7.32 (m,
4.3.4. trans-Methyl 5-(4-bromophenyl)-1-phenyl-3-(trifluoromethyl)-
4,5-dihydro-1H-furo[2,3-c]pyrazole-4-carboxylate (3Ad). White solid;
3H), 7.38 (d, J¼8.0 Hz, 2H), 7.43e7.46 (m, 2H), 7.80 (d, J¼8.0 Hz, 2H)
ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ61.68 (s, CF3) ppm; 13C NMR
yield: 85%; mp: 96.5e97.0 ꢀC; 1H NMR (500 MHz, CDCl3):
d
3.83 (s,
(125 MHz, CDCl3): d 203.4, 160.0, 137.2. 137.0, 135.7 (q,
3H), 4.25 (d, J¼6.5 Hz, 1H), 6.75 (d, J¼6.5 Hz, 1H), 7.26e7.32 (m, 3H),
2JCeF¼38.8 Hz), 135.3, 129.5, 129.4 127.2, 127.1, 120.7 (q,
7.43e7.46 (m, 2H), 7.56 (d, J¼8.5 Hz, 2H), 7.78 (d, J¼7.5 Hz, 2H) ppm;
1JCeF¼267.5 Hz), 118.8, 98.0, 58.6, 28.7 ppm; IR (KBr):
n 2931, 1714,
19FNMR (470 MHz, CDCl3):
d
ꢁ62.84 (s, CF3) ppm;13C NMR (125 MHz,
1600, 1543, 1492, 1458, 1405, 1273, 1185, 1116, 1089, 961, 819,
758 cmꢁ1; MS (EI) m/z (%): 406 (Mþ); HRMS (ESI) m/z calcd for
C20H14ClF3N2O2 [(MþNa)þ]: 429.0591; found: 429.0588.
2
CDCl3):
d
170.4, 159.5, 137.2, 136.2 (q, JCeF¼38.8 Hz), 132.3, 129.5,
127.4, 127.1, 123.7, 120.4 (q, 1JCeF¼267.5 Hz), 98.9, 53.0, 50.9 ppm; IR
(KBr): n 2956, 1725, 1602, 1543, 1488, 1459, 1250, 1178, 1138, 1126, 1111,
950, 834, 757 cmꢁ1; MS (EI) m/z (%): 466 (Mþ); HRMS (ESI) m/z calcd
for C20H14BrF3N2O2 [(MþNa)þ]: 489.0015; found: 489.0032.
4.3.10. (trans-5-(4-Bromophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)ethanone (3Bd). White solid;
yield: 89%; mp: 112.7e113.1 ꢀC; 1H NMR (500 MHz, CDCl3):
d 2.41
4.3.5. trans-Methyl 5-(4-fluorophenyl)-1-phenyl-3-(trifluoromethyl)-
4,5-dihydro-1H-furo[2,3-c]pyrazole-4-carboxylate (3Ae). White solid;
(s, 3H), 4.27 (d, J¼5.5 Hz, 1H), 6.83 (d, J¼5.5 Hz, 1H), 7.26e7.35 (m,
3H), 7.46e7.49 (m, 2H), 7.57 (d, J¼8.0 Hz, 2H), 7.82 (d, J¼8.0 Hz, 2H)
yield: 84%; mp: 93.0e94.3 ꢀC; 1H NMR (500 MHz, CDCl3):
d
3.83 (s,
ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ61.68 (s, CF3) ppm; 13C NMR
3H), 4.31 (d, J¼6.5 Hz, 1H), 6.80 (d, J¼6.5 Hz, 1H), 7.15 (m, 2H),
(125 MHz, CDCl3): d 203.4, 160.0, 137.5, 137.2, 135.7 (q,
7.30e7.36 (m, 1H), 7.44e7.48 (m, 4H), 7.81e7.83 (m, 2H) ppm; 19F
2JCeF¼38.8 Hz), 132.4, 129.5, 127.3, 127.2, 123.5, 120.7 (q,
NMR (470 MHz, CDCl3):
d
ꢁ62.84 (s, CF3), ꢁ111.43 (m, AreF) ppm;
1JCeF¼267.5 Hz), 118.8, 98.0, 58.5, 28.8 ppm; IR (KBr):
n 2921, 1707,

2126
J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
1600, 1540, 1487, 1458, 1406, 1269, 1242, 1193, 1125, 1040, 960, 805,
755 cmꢁ1; MS (EI) m/z (%): 450 (Mþ); HRMS (ESI) m/z calcd for
C20H14BrF3N2O2 [(MþNa)þ]: 473.0078; found: 473.0083.
757 cmꢁ1; MS (EI) m/z (%): 512 (Mþ); HRMS (ESI) m/z calcd for
C25H16BrF3N2O2 [(MþNa)þ]: 535.0245; found: 535.0238.
4.3.16. (trans-5-(3-Chlorophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)(phenyl)methanone (3Cf). Yel-
4.3.11. (trans-5-(4-Fluorophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)ethanone (3Be). White solid;
low oil; yield: 73%; 1H NMR (500 MHz, CDCl3):
d
5.27 (d, J¼6.5 Hz,
yield: 85%; mp: 117.1e119.3 ꢀC; 1H NMR (500 MHz, CDCl3):
d
2.38 (s,
1H), 6.84 (d, J¼6.5 Hz, 1H), 7.24e7.51 (m, 9H), 7.63e7.65 (m, 1H),
3H), 4.28 (d, J¼5.5 Hz, 1H), 6.81 (d, J¼5.5 Hz, 1H), 7.08e7.12 (m, 2H),
7.81 (d, J¼7.8 Hz, 2H), 7.94 (d, J¼7.4 Hz, 2H) ppm; 19F NMR
7.29e7.46 (m, 5H), 7.79 (d, J¼7.5 Hz, 2H) ppm; 19F NMR (470 MHz,
(470 MHz, CDCl3):
CDCl3):
d
ꢁ62.17 (s, CF3) ppm; 13C NMR (125 MHz,
2
CDCl3):
(125 MHz, CDCl3):
d
ꢁ61.68 (s, CF3), ꢁ111.43 (m, AreF) ppm; 13C NMR
d
196.0, 160.0, 143.3, 138.0, 137.2, 136.3 (q, JCeF¼38.8 Hz),
1
d
203.5, 163.2 (d, JCeF¼247.5 Hz), 159.8, 137.2,
135.6, 135.4, 134.3, 133.4, 133.0, 129.6, 129.3, 128.7, 128.5, 127.4,
2
135.7 (q, JCeF¼38.8 Hz), 134.4, 129.5, 127.7, 127.2, 120.0 (q,
122.4, 120.4 (q, CF3, 1JCeF¼267.5 Hz), 118.8, 99.8, 53.1 ppm; IR (KBr):
1JCeF¼267.5 Hz), 118.8, 116.3, 98.3, 58.6, 28.8 ppm; IR (KBr):
n
2922,
n 1697, 1598, 1541, 1484, 1456, 1384, 1230, 1180, 1121, 1040, 950, 904,
1714, 1602, 1536, 1512,1483, 1456, 1408, 1271, 1244,1181, 1133,1109,
1039, 960, 835, 757 cmꢁ1; MS (EI) m/z (%): 390 (Mþ); HRMS (ESI) m/
z calcd for C20H14F4N2O2 [(MþNa)þ]: 413.0877; found: 413.0884.
757 cmꢁ1; MS (EI) m/z (%): 468 (Mþ); HRMS (ESI) m/z calcd for
C25H16ClF3N2O2 [(MþNa)þ]: 491.0751; found: 491.0747.
4.3.17. trans-(Furan-2-yl)(5-(p-tolyl)-1-phenyl-3-(trifluoromethyl)-
4,5-dihydro-1H-furo[2,3-c]pyrazol-4-yl)methanone (3Da). Colorless
4.3.12. (trans-1-Phenyl-5-p-tolyl-3-(trifluoromethyl)-4,5-dihydro-
1H-furo[2,3-c]pyrazol-4-yl)(phenyl)methanone (3Ca). Yellow oil;
oil; yield: 70%; 1H NMR (500 MHz, CDCl3):
d 2.38 (s, 3H), 5.11 (d,
yield: 73%; 1H NMR (500 MHz, CDCl3):
d
2.41 (s, 3H), 5.32 (d,
J¼6.0 Hz, 1H), 6.58e6.59 (m, 1H), 6.82 (d, J¼6.0 Hz, 1H), 7.22e7.32
(m, 6H), 7.43 (m, 2H), 7.64 (m, 1H), 7.80 (d, J¼8.0 Hz, 2H) ppm; 19F
NMR (470 MHz, CDCl3): ꢁ62.83 (s, CF3) ppm; 13C NMR (125 MHz,
CDCl3): 184.4, 160.2, 151.5, 147.8, 139.7, 137.4, 135.7 (q,
2JCeF¼38.8 Hz), 135.4, 129.8, 129.3, 126.9, 126.1, 120.5 (q,
J¼6.0 Hz, 1H), 6.78 (d, J¼6.0 Hz, 1H), 7.26e7.34 (m, 5H), 7.44e7.51
(m, 4H), 7.65 (m, 1H), 7.83 (d, J¼7.5 Hz, 2H), 7.93 (d, J¼7.5 Hz, 2H)
ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ61.75 (s, CF3) ppm; 13C NMR
2
(125 MHz, CDCl3):
d
193.8, 150.4, 138.2 (q, JCeF¼38.8 Hz), 137.5,
137.2,135.4,134.1,133.1,132.2, 129.4,129.1, 129.0, 128.8, 128.3, 127.3,
1JCeF¼267.5 Hz), 119.4, 118.9, 113.0, 100.2, 53.5, 21.3 ppm; IR (KBr):
n
1
121.5, 121.1 (q, JCeF¼267.5 Hz), 96.2, 53.2, 20.9 ppm; IR (KBr):
n
2923, 1679, 1600, 1568, 1542, 1489, 1461, 1406, 1269, 1183, 1123,
1041, 1022, 814, 758 cmꢁ1; MS (EI) m/z (%): 438 (Mþ); HRMS (ESI)
m/z calcd for C24H17F3N2O3 [(MþNa)þ]: 461.1089; found: 461.1077.
2923, 1702, 1682, 1597, 1513, 1480, 1456, 1449, 1218, 1135, 1019, 974,
808, 761 cmꢁ1; MS (EI) m/z (%): 448 (Mþ); HRMS (ESI) m/z calcd for
C26H19F3N2O2 [(MþNa)þ]: 471.1298; found: 471.1278.
4.3.18. trans-(Furan-2-yl)(5-(4-chlorophenyl)-1-phenyl-3-(tri-
4.3.13. (trans-1,5-Diphenyl-3-(trifluoromethyl)-4,5-dihydro-1H-furo
[2,3-c]pyrazol-4-yl)(phenyl)methanone (3Cb). Yellow oil; yield:
fluoromethyl)-4,5-dihydro-1H-furo[2,3-c]pyrazol-4-yl)methanone
(3Dc). Yellow oil; yield: 82%; 1H NMR (500 MHz, CDCl3):
d 5.07 (d,
75%; 1H NMR (500 MHz, CDCl3):
d
5.34 (d, J¼6.0 Hz, 1H), 6.86 (d,
J¼6.5 Hz, 1H), 6.80 (d, J¼6.5 Hz, 1H), 7.14e7.16 (m, 1H), 7.28e7.46
J¼6.0 Hz, 1H), 7.30e7.34 (m, 1H), 7.44e7.52 (m, 9H), 7.66 (m, 1H),
(m, 7H), 7.66e7.67 (m, 1H), 7.76e7.81 (m, 3H) ppm; 19F NMR
7.85 (m, 2H), 7.95 (m, 2H) ppm; 19F NMR (470 MHz, CDCl3):
(470 MHz, CDCl3):
d
ꢁ62.25 (s, CF3) ppm; 13C NMR (125 MHz,
d
ꢁ62.16 (s, CF3) ppm; 13C NMR (125 MHz, CDCl3):
d
196.2, 160.3,
CDCl3): d 188.5, 160.2, 142.5, 137.3, 136.8, 136.4, 135.8 (q,
2
138.4, 137.4, 135.8 (q, JCeF¼38.8 Hz), 135.5, 134.2, 129.7, 129.4,
2JCeF¼38.8 Hz),135.6,133.8,129.5,128.7,127.5,127.2,123.7,120.5 (q,
1
129.3, 129.0, 128.9, 127.0, 126.0, 120.5 (q, JCeF¼267.5 Hz), 118.9,
1JCeF¼267.5 Hz), 118.9, 100, 54.6 ppm; IR (KBr):
n 1661, 1600, 1542,
100.8, 53.2 ppm; MS (EI) m/z (%): 434 (Mþ); IR (KBr):
n
1685, 1598,
1486, 1457, 1411, 1268, 1218, 1192, 1123, 1041, 969, 861, 762 cmꢁ1
;
1579, 1541, 1524, 1454, 1407, 1272, 1219, 1172, 1136, 1041, 1007,
760 cmꢁ1; HRMS (ESI) m/z calcd for C25H17F3N2O2 [(MþNa)þ]:
457.1134; found: 457.1134.
MS (EI) m/z (%): 458 (Mþ); HRMS (ESI) m/z calcd for C23H14ClF3N2O3
[(MþNa)þ]: 481.0527; found: 481.0537.
Acknowledgements
4.3.14. (trans-5-(4-Chlorophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)(phenyl)methanone (3Cc). Yel-
The authors are grateful to the National Natural Science Foun-
dation of China (Grant Nos. 21072126, 20872088) and Leading Ac-
ademic Discipline Projects of Shanghai Municipal Education
Commission (Grant No. J50102) for their financial support.
low oil; yield: 76%; 1H NMR (500 MHz, CDCl3):
d
5.28 (d, J¼6.0 Hz,
1H), 6.84 (d, J¼6.0 Hz, 1H), 7.31e7.38 (m, 3H), 7.43e7.53 (m, 6H),
7.67 (m, 1H), 7.82 (d, J¼7.8 Hz, 2H), 7.94 (d, J¼7.8 Hz, 2H) ppm; 19F
NMR (470 MHz, CDCl3):
CDCl3):
d
ꢁ62.17 (s, CF3) ppm; 13C NMR (125 MHz,
2
d
195.9, 160.0, 143.3, 138.0, 137.2 (q, JCeF¼38.8 Hz), 136.4,
Supplementary data
135.5, 135.4, 134.4, 133.4, 133.0, 129.6, 129.3, 128.7, 128.5, 127.4,
1
122.4, 120.4 (q, JCeF¼267.5 Hz), 118.8, 99.8, 53.1 ppm; IR (KBr):
n
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2012.01.030. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
1685, 1671, 1597, 1481, 1456, 1448, 1215, 1133, 1013, 965, 824,
757 cmꢁ1; MS (EI) m/z (%): 468 (Mþ); HRMS (ESI) m/z calcd for
C25H16ClF3N2O2 [(MþNa)þ]: 491.0751; found: 491.0747.
4.3.15. (trans-5-(4-Bromophenyl)-1-phenyl-3-(trifluoromethyl)-4,5-
dihydro-1H-furo[2,3-c]pyrazol-4-yl)(phenyl)methanone (3Cd). Yel-
References and notes
low oil; yield: 80%; 1H NMR (500 MHz, CDCl3):
d
5.28 (d, J¼6.5 Hz,
1. Eicher, T.; Hauptmann, S. A Speicher in the Chemistry of Heterocycles, 2nd ed.;
Wiley: New York, NY, 2004; 179e184.
1H), 6.84 (d, J¼6.5 Hz, 1H), 7.29e7.34 (m, 3H), 7.46e7.53 (m, 5H),
7.58e7.60 (m, 1H), 7.65e7.68 (m, 1H), 7.83 (d, J¼7.5 Hz, 2H), 7.94 (d,
2. (a) Banks, R. E. Preparation, Properties and Industrial Applications of Organo
Fluorine Compounds; Ellis Horwood Ltd: Chichester, UK, 1982; (b) Elguero, J.
Pyrazoles and Their Benzoderivatives In. Comprehensive Heterocyclic Chemistry;
Potts, K. T., Ed.; Pergamon: Oxford, 1984; Vol. 1, pp 167e343; (c) Elguero, J.
Pyrazoles In. Comprehensive Heterocyclic Chemistry; Potts, K. T., Ed.; Pergamon:
Oxford, 1996; Vol. 2, pp 1e75; (d) Touzot, A.; Soufyaneb, M.; Berber, H.; Toupet,
L.; Mirand, C. J. Fluorine Chem. 2004, 125, 1299.
J¼7.5 Hz, 2H) ppm; 19F NMR (470 MHz, CDCl3):
d
ꢁ62.15 (s, CF3)
ppm; 13C NMR (125 MHz, CDCl3):
d 195.9, 160.0, 137.4, 137.3, 135.6,
135.2 (q, 2JCeF¼38.8 Hz),134.4, 132.4,129.5,129.0,127.6,127.1,123.7,
1
120.3 (q, JCeF¼267.5 Hz), 118.9, 99.8, 53.1 ppm; IR (KBr):
n 1681,
1658, 1605, 1542, 1485, 1457, 1446, 1265, 1219, 1120, 1009, 979, 819,

J. Zhang et al. / Tetrahedron 68 (2012) 2121e2127
2127
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Koami, T.; Shiozawa, F.; Oka, Y.; Takaoka, A.; Yamaguchi, A.; Endo, M.; Sato, M.
Bioorg. Med. Chem. Lett. 2010, 20, 112; (d) Magedov, I. V.; Manpadi, M.; Van
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ꢀ
ꢀ
ꢀ
a
cell parameters (3Ac): a: 7.935(2) A; b: 15.050(4) A; c: 16.356(4) A;
: 103.254(3); : 90.000; space group: P2(1)/c. Unit cell parameters (2a): a: 21.
: 90.000;
b
g
ꢀ
ꢀ
ꢀ
a
66(3) A; b: 9.463(15) A; c: 17.19(3) A;
space group: C2/c.
: 90.000; b: 116.564(19); g: 90.000;
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