Synthesis of trifluoromethyl-/cyclopropyl-substituted 2-isoxazolines by DBU-promoted domino reaction

Article abstract of DOI:10.1016/j.cclet.2017.03.031

NTrifluoromethyl and cyclopropyl substituted 2-isoxazolines were synthesized via a DBU-promoted domino reaction of β-trifluoromethyl-/β-cyclopropyl-substituted enones with hydroxylamine. The domino reaction consists of a Michael addition and the followed cyclization. A wide range of 3-substituted 5-cyclopropyl-5- trifluoromethyl-2-isoxazolines were obtained in good to excellent yields under mild reaction conditions. The method could also apply to other trifluoromethyl-substituted enones.

Full text of DOI:10.1016/j.cclet.2017.03.031

Accepted Manuscript
Title: Synthesis of trifluoromethyl-/cyclopropyl-substituted
2-isoxazolines by DBU-promoted domino reaction
Author: Xiao-Dong Liu Hai-Yan Ma Chun-Hui Xing Long Lu
PII:
S1001-8417(17)30109-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2017.03.031
CCLET 4026
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
6-1-2017
20-3-2017
22-3-2017
Please cite this article as: X.-D. Liu, H.-Y. Ma, C.-H. Xing, L. Lu,
Synthesis of trifluoromethyl-/cyclopropyl-substituted 2-isoxazolines by
DBU-promoted domino reaction, Chinese Chemical Letters (2017),
http://dx.doi.org/10.1016/j.cclet.2017.03.031
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Graphical Abstract
Synthesis of trifluoromethylꢀ/cyclopropylꢀsubstituted 2ꢀisoxazolines by DBUꢀpromoted domino reaction
XiaoꢀDong Liua, HaiꢀYan Maa,∗, ChunꢀHui Xingb, *, Long Lub
a School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237,
China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
R
O
NH2OH(50 wt% aq.)
ꢀH2O
O
F3C
R
CF3
N
DBU, ClCH2CH2Cl, r.t.
O
R
CF3
O
NH2
2
3
Trifluoromethyl and cyclopropyl substituted 2ꢀisoxazolines were synthesized via a DBUꢀpromoted domino reaction of
βꢀtrifluoromethylꢀ/βꢀcyclopropylꢀsubstituted enones with hydroxylamine. A wide range of 3ꢀsubstituted 5ꢀcyclopropylꢀ5ꢀ
trifluoromethylꢀ2ꢀisoxazolines were obtained in good to excellent yields under mild reaction conditions.
∗ Corresponding authors.
Eꢀmail addresses: haiyanma@ecust.edu.cn; xingch@sioc.ac.cn
1
Page 1 of 7

Original article
Synthesis of trifluoromethylꢀ/cyclopropylꢀsubstituted 2ꢀisoxazolines by
DBUꢀpromoted domino reaction
XiaoꢀDong Liua, HaiꢀYan Maa,∗, ChunꢀHui Xingb, *, Long Lub
a School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai
200032, China
ARTICLE INFO
ABSTRACT
Article history:
Trifluoromethyl and cyclopropyl substituted 2ꢀisoxazolines were synthesized via a
DBUꢀpromoted domino reaction of βꢀtrifluoromethylꢀ/βꢀcyclopropylꢀsubstituted enones
with hydroxylamine. The domino reaction consists of a Michael addition and the
Received 8 January 2017
Received in revised form 14 March 2017
Accepted 16 March 2017
Available online
followed cyclization.
A
wide range of 3ꢀsubstituted 5ꢀcyclopropylꢀ5ꢀ
trifluoromethylꢀ2ꢀisoxazolines were obtained in good to excellent yields under mild
reaction conditions. The method could also apply to other trifluoromethylꢀsubstituted
enones.
Keywords:
Isoxazoline
Enone
Michael addition
Cyclization
Domino reaction
1. Introduction
2ꢀIsoxazolines are important heterocycle structures in agricultural and medicinal chemistry [1]. Their derivatives exhibit
multiple bioactivities such as antiꢀinflammation, antiꢀthrombus, and antibacterial activity [2]. Therefore, the synthesis of
2ꢀisoxazolines has attracted more attentions [3ꢀ5]. Construction of these compounds generally involves 1, 3ꢀdipolar cycloaddition
of nitrile oxides with alkenes or intramolecular cyclization of oxime derivatives [4,5]. Recently, 5ꢀtrifluoromethylꢀ2ꢀisoxazolines
were emerged as a class of antiparasitic compounds and drew certain interests [6]. For preparation of these fluorinated
2ꢀisoxazolines, a more efficient method was developed through the domino reaction of Michael addition/cyclization of
trifluoromethylꢀsubstituted enone and hydroxylamine [7].
As is wellꢀknown, organofluorine chemicals are vital to pharmaceutical, agrochemical and material sciences. The employment
of fluorine or fluorineꢀcontaining substituents especially the trifluoromethyl group into organic molecules, might lead to the
enhancement of their bioactivities [8, 9]. On the other hand, cyclopropanes are also crucial synthons in organic synthesis and
significant structural units in many natural products [10]. We are recently focusing on exploring the applications of cyclopropyl
trifluoromethyl ketone (1) in constructing complex compounds. As a novel fluorinated building blocks, 1 combines
trifluoromethyl group with cyclopropyl unit. Both important functional groups would be installed into various molecules through
the transformation of the synthon 1.
We have already investigated bisindolylation reaction of 1 catalyzed by trifluoromethanesulfonic acid [11]. As the continuing
study, we prepared trifluoromethylꢀ/cyclopropylꢀsubstituted enone 2 from 1, and explored the domino reaction of Michael
addition/cyclization of 2 with hydroxylamine (Scheme 1). It provides an efficient method for the syntheses of
5ꢀcyclopropylꢀ5ꢀtrifluoromethylꢀ2ꢀisoxazoline derivatives 3 with broad substrate generality. Herein, we report the results.
O
R
O
O
Ph3P
CH2Cl2, reflux
NH2OH
ꢀH2O
O
R
F3C
R
CF3
CF3
N
O
R
CF3
O
H2N
1
2
3
Scheme 1. General route for the syntheses of 5ꢀcyclopropylꢀ5ꢀtrifluoromethylꢀ2ꢀisoxazolines.
2. Results and discussion
∗ Corresponding authors.
Eꢀmail addresses: haiyanma@ecust.edu.cn; xingch@sioc.ac.cn
2
Page 2 of 7

The initial study began with the examination of the reaction of trifluoromethyl and cyclopropyl substituted enone 2a with
hydroxylamine. No reaction took place in the absence of base at room temperature. Carbonates were tested at first and could not
trigger the reaction (Table 1, entries 1~3). Neither could other weaker inorganic bases (Table 1, entries 9, 10). With the aid of
TBAB (tetrabutylammonium bromide), NaOH, KOH and CsOH may promote 2a to react with hydroxylamine, and afford the
desired 2ꢀisoxazoline product 3a in 27%, 51% and 87% yields, respectively, after being stirred at room temperature for 3 h (Table
1, entries 5~7). A few organic bases were examined as well. The reaction did not happen with Et3N as base (Table 1, entry 12).
Low yield was detected in the existence of TMG (tetramethylguanidine) (Table 1, entry 11). To our pleased, DBU displayed
excellent activation ability, and 99% yield of 2ꢀisoxazoline was obtained (Table 1, entry 13).
Table 1
Screening of bases for the reaction of 2a with NH2OH a
NH2OH (50 wt% aq)
TBAB (10 mol%)
Ph
O
F3C
N
Base, CHCl3, r.t., 3 h
Ph
CF3
O
2a
3a
Entry
1
2
3
4
Base
Na2CO3
K2CO3
Cs2CO3
LiOH
Yield (%)b
n.r.
n.r.
n.r.
n.r.
27
5
6
NaOH
KOH
51
7
8
9
10
11
12
13
CsOH
K3PO4
LiOAc
NaOAc
TMG
87
5
n.r.
n.r.
11
n.r.
99
Et3N
DBU
a Reaction conditions: 2a (0.1 mmol), NH2OH (50 wt% aq., 0.3 mmol), TBAB (0.01 mmol, 10 mol%), and base (0.3 mmol) in CHCl3 (1
mL), stirred at room temperature in a Schlenk tube for 3 h.
b Yields were determined by 19F NMR using 1ꢀfluoronaphehalene as an internal standard.
Then, a brief screening of solvents was performed with DBU as base. The results listed in Table 2 showed that the reaction
proceeded smoothly in all kinds of solvents. 1, 2ꢀDichloroethane was chosen as the optimal solvent since the highest yield was
obtained in it (Table 2, entry 2). Actually, phase transfer catalyst TBAB had few effects on this DBUꢀpromoted reaction. The
reaction still worked well and gave the comparable yield without it (Table 2, entry 3).
Table 2
Screening of solvents for the reaction of 2a with NH2OH a
NH2OH (50 wt% aq)
Ph
O
TBAB (10 mol%)
F3C
N
DBU, Solvent, r.t.
Ph
CF3
O
3a
2a
Entry
1
Solvent
CH2Cl2
ClCH2CH2Cl
ClCH2CH2Cl
CHCl3
CH3CN
THF
1,4ꢀDioxane
MeOH
EtOH
DMSO
DMF
Toluene
Time (h)
Yield (%)b
2
2
2
2
4
4
4
4
4
4
4
4
81
88
84
40
78
47
31
72
77
49
66
65
2
3c
4
5
6
7
8
9
10
11
12
a Reaction conditions: 2a (0.1 mmol), NH2OH (50 wt% aq., 0.15 mmol), TBAB (0.01 mmol, 10 mol%), and base (0.2 mmol) in solvent
(1 mL), stirred at room temperature in a Schlenk tube.
b Yields were determined by 19F NMR using 1ꢀfluoronaphehalene as an internal standard.
c The reaction was performed without TBAB.
With the optimal conditions established, the scope of substrates enones 2 was then explored. As listed in Table 3, a wide range
of substituents including electronꢀdonating and electronꢀwithdrawing groups on the aromatic ring of trifluoromethyl substituted
enones 2 are tolerated, and good to excellent yields of the corresponding tirfluoromethyl and cyclopropyl substituted 2ꢀ
3
Page 3 of 7

isoxazoline 3 were obtained (Table 3, 3aꢀ3l). In addition, tirfluoromethylꢀsubstituted heteroaryl enones 2m was applied to this
reaction, nearly quantitative yield of 3ꢀ(thiophenꢀ2ꢀyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole was isolated (Table 3, 3m).
Besides, alkylꢀsubstituted enones also reacted with hydroxylamine smoothly and afforded the corresponding products in satisfied
yields (Table 3, 3n & 3o).
Table 3
Scope of βꢀcyclopropylꢀ/βꢀtrifluoromethylꢀsubstituted enones 2 for the domino reaction with NH2OH. a,
R
O
NH2OH (50 wt% aq.)
F3C
N
DBU, ClCH2CH2Cl, r.t., 4 h
R
CF3
O
2
3
Yield (%)b
Entry
1
2
3
4
5
6
7
8
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
R
C6H5
Product
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
82
95
88
88
95
94
95
87
89
82
80
80
94
85
80
4ꢀMeOC6H5
2ꢀMeC6H5
3ꢀMeC6H5
4ꢀMeC6H5
4ꢀFC6H5
4ꢀClC6H5
4ꢀBrC6H5
4ꢀCF3C6H5
4ꢀCNC6H5
4ꢀNO2C6H5
2ꢀNaphthyl
Thiophenꢀ2ꢀyl
nꢀButyl
9
10
11
12
13
14
15
C6H5CH2CH2
a
Reaction conditions: 2 (1.0 mmol), NH2OH (50 wt% aq., 1.5 mmol), and DBU (2.0 mmol) in ClCH2CH2Cl (10 mL), stirred at room
temperature in a Schlenk tube for 4 h.
b Isolated yield.
Furthermore, under the same conditions, the method was applied to other enones derived from aryl or heteroaryl
trifluoromethyl ketones and the corresponding products were isolated in moderate to excellent yields (Fig. 1, 3p-3v).
Ar
3p C6H5
Yield (%)
95
Ph
F3C
Ar
3q 4ꢀMeOC6H5 94
N
3r 4ꢀFC6H5
3s 4ꢀClC6H5
3t 4ꢀBrC6H5
92
87
88
O
3
3u Thiophenꢀ2ꢀyl 96
3v Pyridinꢀ2ꢀyl 50
Fig. 1. The products and yields of reactions between enones derivatives under the same conditions.
3. Conclusion
In summary, we have demonstrated a DBUꢀmediated Michael addition/cyclization domino reaction of trifluoromethyl and
cyclopropyl substituted enones with hydroxylamine. The mild conditions and convenient manipulation made this protocol a
practical method to synthesis various 5ꢀcyclopropylꢀ5ꢀtrifluoromethylꢀ2ꢀisoxazoline derivatives efficiently. This method may also
apply to other enones derived from aryl or heteroaryl trifluoromethyl ketones.
4. Experimental
1H NMR and 19F NMR spectra were obtained with an Agilent AMꢀ400 instrument with TMS as the internal standard and CFCl3
as the external standard, respectively. 13C NMR spectra were recorded on an Agilent AMꢀ400 or AMꢀ500 instrument with TMS as
the internal standard. Chemical shifts (δ) are reported in ppm, and coupling constants (J) are in Hertz (Hz). FTꢀIR spectra were
obtained with a Nicolet AVꢀ360 spectrophotometer. Mass spectra were obtained on an Agilent 5973 Network or a Waters
Micromass GCT Premier instrument. All melting points were determined on a Büchi Bꢀ545 melting point apparatus and are
uncorrected. All commercially available reagents were purchased from commercial sources and used directly. All reactions were
monitored by TLC, 19F NMR or 1H NMR. Flash column chromatograph was carried out using 300ꢀ400 mesh silica gel at medium
pressure.
General procedure for the syntheses of cyclopropylꢀ/trifluoromethylꢀsubstituted 2ꢀisoxazolines: Enone 2 (1.0 mmol, 1.0 equiv.),
NH2OH (50 wt% aq., 1.5 mmol, 1.5 equiv.), DBU (2.0 mmol, 2.0 equiv.) and DCE (10 mL) were added to a Schlenk tube
4
Page 4 of 7

equipped with a stir bar. The reaction mixture was stirred at room temperature for appropriate time. The completion of the
reaction was monitored by 19F NMR. When the reaction was completed, DCE was evaporated and the residue was purified by
column chromatography on silica gel to afford 2ꢀisoxazoline 3 as the desired product.
Spectral data of representative products were listed below. Others and general method for the preparation of enones 2 are
provided in Supporting information .
5ꢀCyclopropylꢀ3ꢀphenylꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3a): White solid. Mp: 72ꢀ73 oC. 1H NMR (400 MHz,
CDCl3): δ 7.67ꢀ7.60 (m, 2H), 7.48ꢀ7.38 (m, 3H), 3.67 (d, 1H, J = 17.2 Hz), 3.35 (d, 1H, J = 17.3 Hz), 1.36ꢀ1.29 (m, 1H),
0.88ꢀ0.81 (m, 1H), 0.68ꢀ0.60 (m, 1H), 0.59ꢀ0.51 (m, 1H), 0.47ꢀ0.41 (m, 1H). 19F NMR (376 MHz, CDCl3): δ ꢀ80.61 (s, 3F). 13C
NMR (101 MHz, CDCl3): δ 156.32, 130.70, 128.84, 128.33, 126.77, 125.04 (q, J = 284.3 Hz), 85.81 (q, J = 29.1 Hz), 41.86,
13.27 (d, J = 0.9 Hz), 1.74, ꢀ0.48. IR (KBr, cmꢀ1): 3095, 3017, 2961, 2942, 1604, 1572, 1497, 1447, 1438, 1366, 1328, 1221, 1189,
1163, 1154, 1140, 1032, 983, 920, 779. MS (EI): m/z (%) 255 (M+, 54.50), 69 (100), 77, 186, 41, 119, 51, 91. HRMS (EI): Mass
calculated for C13H12NOF3: 255.0871; Found: 255.0867.
o
1
5ꢀCyclopropylꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3b): White solid. Mp: 73ꢀ75 C. H NMR (400
MHz, CDCl3): δ 7.57 (d, 2H, J = 8.7 Hz), 6.93 (d, 2H, J = 8.8 Hz), 3.85 (s, 3H), 3.64 (d, 1H, J = 17.2 Hz), 3.32 (d, 1H, J = 17.4
Hz), 1.39ꢀ1.26 (m, 1H), 0.90ꢀ0.79 (m, 1H), 0.69ꢀ0.59 (m, 1H), 0.59ꢀ0.50 (m, 1H), 0.49ꢀ0.38 (m, 1H). 19F NMR (376 MHz,
CDCl3): δ ꢀ80.59 (s, 3F). 13C NMR (101 MHz, CDCl3): δ 161.45, 155.81, 128.32, 125.06 (q, J = 284.2 Hz), 120.75, 114.20, 85.42
(q, J = 29.1 Hz), 55.38, 42.10, 13.24 (d, J = 1.1 Hz), 1.74, ꢀ0.50. IR (KBr, cmꢀ1): 3097, 3017, 2962, 2937, 2909, 2840, 1610, 1520,
1438, 1421, 1365, 1327, 1256, 1186, 1162, 1141, 1127, 1034, 985, 919, 832. MS (EI): m/z (%) 285 (M+, 82.08), 69 (100), 149,
147, 135, 133, 77, 41. HRMS (EI): Mass calculated for C14H14NO2F3: 285.0977; Found: 285.0975.
o
1
5ꢀCyclopropylꢀ3ꢀ(oꢀtolyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3c): White solid. Mp: 51ꢀ52 C. H NMR (400 MHz,
CDCl3): δ 7.36ꢀ7.22 (m, 4H), 3.71 (d, 1H, J = 17.3 Hz), 3.42 (d, 1H, J = 17.3 Hz), 2.54 (s, 3H), 1.38ꢀ1.29 (m, 1H), 0.91ꢀ0.83 (m,
1H), 0.69ꢀ0.62 (m, 1H), 0.60ꢀ0.53 (m, 1H), 0.50ꢀ0.43 (m, 1H). 19F NMR (376 MHz, CDCl3): δ ꢀ80.57 (s, 3F). 13C NMR (101
MHz, CDCl3): δ 157.22, 138.20, 131.71, 129.90, 128.78, 127.33, 125.88, 125.08 (q, J = 284.4 Hz), 84.56 (q, J = 29.1 Hz), 44.39,
22.89, 13.21, 1.80, ꢀ0.49. IR (KBr, cmꢀ1): 3102, 3075, 3023, 2971, 2936, 1603, 1593, 1560, 1495, 1460, 1441, 1386, 1348, 1326,
1287, 1189, 1166, 1125, 1038, 899, 866, 828, 759. MS (EI): m/z (%) 269 (M+, 32.85), 200 (100), 69, 130, 91, 65, 41, 132. HRMS
(EI): Mass calculated for C14H14NOF3: 269.1027; Found: 269.1032.
5ꢀCyclopropylꢀ3ꢀ(4ꢀfluorophenyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3f): Yellow liquid. 1H NMR (400 MHz, CDCl3): δ
7.73ꢀ7.52 (m, 2H), 7.11 (t, 2H, J = 8.7 Hz), 3.64 (d, 1H, J = 17.3 Hz), 3.34 (d, 1H, J = 17.3 Hz), 1.37ꢀ1.29 (m, 1H), 0.88ꢀ0.80 (m,
1H), 0.68ꢀ0.61 (m, 1H), 0.59ꢀ0.52 (m, 1H), 0.47ꢀ0.40 (m, 1H). 19F NMR (376 MHz, CDCl3): δ ꢀ80.66 (s, 3F), ꢀ108.73ꢀꢀ108.83 (m,
1F). 13C NMR (101 MHz, CDCl3): δ 164.02 (d, J = 251.8 Hz), 155.39 (d, J = 0.8 Hz), 128.76 (d, J = 8.6 Hz), 124.95 (q, J = 284.3
Hz), 124.51 (d, J = 3.4 Hz), 115.99 (d, J = 22.1 Hz), 85.90 (q, J = 29.2 Hz), 41.85 (d, J = 0.6 Hz), 13.17 (d, J = 1.3 Hz), 1.72,
ꢀ0.52. IR (KBr, cmꢀ1): 3095, 3020, 1604, 1516, 1437, 1414, 1362, 1325, 1204, 1237, 1204, 1165, 1127, 1040, 917, 836. MS (EI):
m/z (%) 273 (M+, 0.83), 69 (100), 41, 300, 231, 76, 67, 89, 162. HRMS (EI): Mass calculated for C13H11NOF4: 273.0777; Found:
273.0781.
o
1
5ꢀCyclopropylꢀ3ꢀ(thiophenꢀ2ꢀyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3m): White solid. Mp: 62ꢀ64 C. H NMR (400
MHz, CDCl3): δ 7.43 (dd, 1H, J = 5.1, 1.1 Hz), 7.22 (dd, 1H, J = 3.6, 1.0 Hz), 7.08 (dd, 1H, J = 5.1, 3.7 Hz), 3.67 (d, 1H, J = 17.1
Hz), 3.36 (d, 1H, J = 17.1 Hz), 1.36ꢀ1.28 (m, 1H), 0.89ꢀ0.79 (m, 1H), 0.70ꢀ0.60 (m, 1H), 0.60ꢀ0.51 (m, 1H), 0.49ꢀ0.40 (m, 1H).
19F NMR (376 MHz, CDCl3): δ ꢀ80.55 (s, 3F). 13C NMR (101 MHz, CDCl3): δ 152.04, 130.50, 129.03, 129.01, 127.40, 124.90 (q,
J = 284.2 Hz), 85.98 (q, J = 29.3 Hz), 42.57, 13.20, 1.78 (s), ꢀ0.44. IR (KBr, cmꢀ1): 3108, 3027, 2922, 2852, 1598, 1438, 1366,
1325, 1161, 1179, 1145, 1120, 1039, 897, 727. MS (EI): m/z (%) 261 (M+, 56.77), 69 (100), 125, 123, 109, 70, 192, 97. HRMS
(EI): Mass calculated for C11H10NOF3S: 261.0435; Found: 261.0439.
3ꢀButylꢀ5ꢀcyclopropylꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3n): Colorless liquid. 1H NMR (400 MHz, CDCl3): δ 3.22 (d,
1H, J = 17.6 Hz), 2.91 (dd, 1H, J = 17.6, 0.7 Hz), 2.32 (t, 2H, J = 7.6 Hz), 1.58ꢀ1.47 (m, 2H), 1.42ꢀ1.29 (m, 2H), 1.26ꢀ1.14 (m,
1H), 0.93 (t, 3H, J = 7.3 Hz), 0.81ꢀ0.71 (m, 1H), 0.62ꢀ0.54 (m, 1H), 0.54ꢀ0.45 (m, 1H), 0.40ꢀ0.33 (m, 1H). 19F NMR (376 MHz,
CDCl3): δ ꢀ80.83 (s, 3F). 13C NMR (101 MHz, CDCl3): δ 158.83, 125.12 (q, J = 284.3 Hz), 84.37 (q, J = 29.1 Hz), 43.88, 28.29,
26.86, 22.12, 13.63, 13.12, 1.66, ꢀ0.68. IR (KBr, cmꢀ1): 3095, 3019, 2961, 2935, 2875, 1635, 1469, 1435, 1327, 1163, 1124, 1035,
1009. MS (EI): m/z (%) 235 (M+, 1.06), 193 (100), 69, 57, 166, 67, 98, 110, 206. HRMS (EI): Mass calculated for C11H16NOF3S:
235.1184; Found: 235.1191.
o
1
3ꢀPhenylꢀ5ꢀ(pyridinꢀ2ꢀyl)ꢀ5ꢀ(trifluoromethyl)ꢀ4,5ꢀdihydroisoxazole (3v): White solid. Mp: 97ꢀ99 C. H NMR (400 MHz,
CDCl3): δ 8.65 (dd, 1H, J = 4.8, 0.6 Hz), 7.88 (d, 1H, J = 7.9 Hz), 7.81 (td, 1H, J = 7.8, 1.7 Hz), 7.74ꢀ7.66 (m, 2H), 7.49ꢀ7.39 (m,
3H), 7.35 (ddd, 1H, J = 7.4, 4.8, 1.1 Hz), 4.47 (d, 1H, J = 17.8 Hz), 4.00 (d, J = 17.8 Hz, 1H). 19F NMR (376 MHz, CDCl3): δ
ꢀ78.78 (s, 3F). 13C NMR (101 MHz, CDCl3): δ 156.77, 154.11, 148.95, 137.02, 130.82, 128.84, 128.09, 126.96, 124.32, 124.01 (q,
J = 284.4 Hz), 122.96, 88.82 (q, J = 29.7 Hz), 41.87. IR (KBr, cmꢀ1): 3070, 2978, 1589, 1574, 1473, 1438, 1361, 1308, 1289, 1170,
1091, 1005, 986, 889, 759. MS (EI): m/z (%) 292 (M+, 7.03), 223 (100), 261, 262, 78, 106, 193, 79, 51. HRMS (EI): Mass
calculated for C15H11N2OF3: 292.0823; Found: 292.0818.
5
Page 5 of 7

Acknowledgment
Supports from the National Natural Science Foundation of China (Nos. 21272257, 21274041 and 21474028) are gratefully
acknowledged.
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