Use of 1-pentafluorosulfanyl-phenylacetylenes for the preparation of SF5-substituted five-membered ring heterocycles through 1,3-dipolar cycloadditions. Isoxazoles and isoxazolines

Article abstract of DOI:10.1016/j.jfluchem.2015.06.006

Abstract A synthetic methodology utilizing 1,3-dipolar cycloadditions was developed for the preparation of pentafluorosulfanyl-substituted heterocycles using SF₅-substituted arylacetylenes as key building block dipolarophiles. A group of 4-SF

Full text of DOI:10.1016/j.jfluchem.2015.06.006

Accepted Manuscript
Title: Use of 1-pentafluorosulfanyl-phenylacetylenes for the
preparation of SF5-substituted five-membered ring
heterocycles through 1,3-dipolar cycloadditions. Isoxazoles
and isoxazolines
Author: Simon E. Lopez Akira Mitani Priscila Pena Ion
Ghiviriga William R. Dolbier Jr.
PII:
S0022-1139(15)00159-1
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2015.06.006
FLUOR 8579
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Received date:
Revised date:
Accepted date:
17-4-2015
2-6-2015
4-6-2015
Please cite this article as: S.E. Lopez, A. Mitani, P. Pena, I. Ghiviriga, W.R.
Dolbier Jr., Use of 1-pentafluorosulfanyl-phenylacetylenes for the preparation
of SF5-substituted five-membered ring heterocycles through 1,3-dipolar
cycloadditions. Isoxazoles and isoxazolines, Journal of Fluorine Chemistry (2015),
http://dx.doi.org/10.1016/j.jfluchem.2015.06.006
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*Graphical Abstract - Pictogram
Page 1 of 18

*Graphical Abstract - Synopsis
1,3-Dipolar cycloadditions of nitrile oxides and nitrones with SF5-substituted alkynes
Page 2 of 18

*Highlights (for review)
Highlights for Review
1. 1,3-dipolar cycloadditions of nitrile oxides and nitrones are reported.
2. SF5-substituted alkynes are used in 1,3-dipolar cycloaddition reactions.
3. Preparations of SF5-substituted isoxazoles and isoxazolines are reported.
Page 3 of 18

*Manuscript
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Use of 1-pentafluorosulfanyl-phenylacetylenes for the preparation of SF5-substituted five-membered
ring heterocycles through 1,3-dipolar cycloadditions. Isoxazoles and isoxazolines
Simon E. Lopez,¥£ Akira Mitani,¥ Priscila Pena,¥ Ion Ghiviriga,¥ William R. Dolbier Jr.* ¥
¥Department of Chemistry, University of Florida, Gainesville, FL 32 611-72000, United States
£Departamento de Quimica, Universidad SimonBolivar, Valle de Sartenejas, Baruta, Caracas 1080A, Venezuela
*Corresponding author email: wrd@chem.ufl.edu
Page 4 of 18

Abstract
A synthetic methodology utilizing 1,3-dipolar cycloadditions was developed for the preparation of
pentafluorosulfanyl-substituted heterocycles using SF5-substituted arylacetylenes as key building block
dipolarophiles. A group of 4-SF5-isoxazoles were prepared in moderate yields using in situ generated
nitrile oxides, and 4-SF5-substituted isoxazolines were obtained when nitrones were used as the 1,3-dipole.
Keywords: 1,3-dipolar cycloaddition, pentafluorosulfanyl, aryl SF5-acetylenes, isoxazole, isoxazoline
1. Introduction
Fluorine substitution can have a high impact on the physicochemical properties of organic
molecules, due to the high electronegativity, low polarizability, and small size of the fluorine atom [1].
Fluorinated substituents are often found to be advantageous in biological active compounds, such as
pharmaceuticals [2] and agrochemicals [3]. Among such fluorine-containing substituents, the
pentafluorosulfanyl group (SF5) has emerged as a possible alternative to the trifluoromethyl group (CF3)
[4-11], a very commonly encountered substituent in biological active compounds, because the two groups
share many typical characteristics, such as high electronegativity, steric size, chemical stability, and
lipophilicity [12,13]. The SF5 group has often been referred to as a “supertrifluoromethyl group” [1g]. The
synthesis and utilization of pentafluorosulfanyl-containing compounds has been recently reviewed [14].
Isoxazoles and isoxazolines are important classes of five membered ring, nitrogen-containing
heterocycles that are present in many biologically active compounds and natural products (Figure 1) [15].
The incorporation of the pentafluorosulfanyl group into such heterocycles through 1,3-dipolar
cycloadditions is a subject that should be of interest to both academic and industrial research communities
because of the potential applications of such compounds.
Page 5 of 18

Figure 1. Examples of isoxazoles and isoxazolines with biological activity [16]
2. Results and discussion
A variety of synthetic methodologies have been developed for the preparation of isoxazoles and
isoxazolines, but 1,3-dipolar cycloadditions of nitrile oxides and nitrones to alkynes are among the most
convenient routes [17]. The utility of SF5-alkynes as building blocks has been clearly demonstrated in
recent studies of preparations of pentafluorosulfanyl-substituted pyrroles, thiophenes, pyrazoles and
triazoles (Scheme 1) [18]. The employment of SF5-alkynes as dipolarophile building blocks for the
Scheme 1. Use of 1,3-dipolar cycloadditions to prepare SF5-substituted heterocyclics
Page 6 of 18

preparation of pentafluorosulfanyl substituted isoxazoles and isoxazolines was therefore deemed to be a
likely effective route to such compounds.
Thus, arylacetylenes 1a-c were allowed to react with SF5Cl at -40 oC, employing triethylborane as
low temperature radical initiator to give the corresponding alkenyl chlorides 2a-c in acceptable yields
(Scheme 2) [19]. This reaction appears to be dependent upon the electronic character of the substituent
that is on the aryl ring, with better yields observed for electron-donating groups (2b and 2c). The obtained
alkenyl chlorides were then dehydrohalogenated by treatment with lithium hydroxide in dimethylsulfoxide
to form the required SF5-substituted alkynes 3a-c in good yields.
Phenylnitrile oxide 5a, was generated in situ from benzohydroxyiminoyl chloride 4a (Scheme 3),
and it underwent 1,3-dipolar cycloaddition with phenyl-SF5-acetylene 3a to obtain the SF5-substituted
isoxazole, 6a. Because of the known competitive dimerization of the in situ generated nitrile oxide
intermediate [20], the number of equivalents of benzohydroxyiminoyl chloride and triethylamine was
Scheme 2. Preparation of SF5-arylacetylenes
increased in order to maximize the yield of the desired SF5-isoxazole. Initial attempts that employed only
one or two equivalents of triethylamine and benzohydroxyiminoyl chloride produced low yields of the
desired isoxazole along with considerable amounts of the dimerization product (Table 1, entries 1-2), as
was revealed by examination of proton NMR spectra of the crude product mixtures [21]. Since the rate of
nitrile oxide dimerization appeared to be greater than that of the desired 1,3-dipolar cycloaddition, it was
necessary to use a larger excess of both triethylamine and benzohydroxyiminoyl chloride, as well as to
extend the reaction time. The best yields were obtained by using 5.5 equivalents of nitrile oxide precursor,
which was added in portions over a period of 36 hours (Table 1, entry 5).
Page 7 of 18

Scheme 3. 1,3-Dipolar cycloaddition reaction of SF5-phenylacetylene 3a with an in situ-generated nitrile
oxide intermediate 5a.
Table 1. Optimization conditions for the synthesis of SF5-isoxazole 6a
Entry
4a (equiv.)
Et3N (equiv.)
Time (h)
Yield (%)
1
2
3
4
5
1.0
2.0
3.0
3.0
5.5
1.0
2.0
3.0
3.0
5.5
16
16
24
36
36
5
14
24
35
50
By varying the p-substituents of both the aryl SF5-acetylenes and the nitrile oxides, these
optimized conditions were employed to prepare seven aryl SF5-isoxazoles in moderate yields (Table 2).
Table 2. Preparation of aryl SF5-isoxazoles 6a-g via 1,3-dipolar cycloaddition reactions
Page 8 of 18

Compd. No.
R
H
H
Me
Me
Me
OMe
OMe
R1
H
OMe
H
Yield (%)
50
53
55
59
50
58
51
6a
6b
6c
6d
6e
6f
F
Me
OMe
F
6g
It was also possible to prepare SF5-isoxazolines 7a-c, via the 1,3-dipolar cycloaddition reactions of
nitrones with aryl SF5-acetylenes (Scheme 4). Thus, moderate to good yields were obtained from the
reaction of nitrones 6a-c with alkynes 3a or b in THF at room temperature for 20 hours.
Scheme 4. Preparation of aryl SF5-isoxazolines 8a-c via 1,3-dipolar cycloadditions
The structures of all products were fully characterized by proton, fluorine and carbon NMR
spectroscopy and either HRMS or elemental analysis. Only one regioisomeric product was obtained for
each of the reactions, and the regiochemistry exhibited by the products was assigned on the basis of a
detailed NMR spectroscopic examination of oxazole 6f and oxazoline 8c.
Cross-peaks in the gHMBC spectrum of 6f allow for the assignment of the 1H and 13chemical shifts
in the p-methoxyphenyl moieties and of the oxazole carbons to which they are attached, at 169.4 and
Page 9 of 18

160.0 ppm. The chemical shifts of these carbons were used to assign the methoxyphenyl substituents as
alpha to O and N, and they also clearly demonstrate that the structure of the product is 6f and not its
1
Figure 2. H, 13C and 19F NMR assignments for products 6f and 8c
alternative regioisomer, in which one of these two chemical shifts would be expected to be much
smaller, ca. 110 ppm. Cross-peaks in the HOESY spectrum of 6f, between the equatorial fluorines in the
SF5 group at 77.5 ppm and both of the protons ortho to the oxazole substituent, at 7.64 and 7.45 ppm,
agree with structure 6f and not with the structure of its alternative regioisomer. Similar chemical shifts
and nOes demonstrate that the structure of 8c is as drawn, rather than its alternative regioisomer. The
assigned proton, carbon and fluorine chemical shifts derived from these analyses are provided in Figure
1.
3. Conclusions
A 1,3-dipolar cycloaddition based methodology was utilized for the synthesis of a series of
pentafluorosulfanyl-substituted isoxazoles and isoxazolines using aryl SF5-acetylenes as key building
blocks. Aryl SF5-isoxazoles were obtained in moderate yields from reactions of in situ-generated nitrile
oxides with aryl SF5-acetylenes, and good yields of isoxazolines were obtained from the cycloadditions of
these alkynes with nitrones.
Page 10 of 18

4. Experimental
4.1.General information
1
13
NMR spectra were obtained in CDCl3 using TMS as the internal standard for H (300 MHz) and C
NMR (75 MHz) and CFCl3 for 19F NMR (282 MHz), unless otherwise noted. All reagents were purchased
at commercial quality and were used without further purification. Melting points were determined using a
Thomas-Hoover capillary melting point apparatus and are uncorrected. High resolution mass spectrometric
measurements were performed by the University of Florida Department of Chemistry Mass Spectrometry
Services, using either an Agilent 6220 ESI-TOF instrument or a Thermo Scientific Trace DSQ GC-MS.
Elemental analyses (% C,H,N) of compound 8a was performed using a EA1108 CHNS-O instrument
(Fisons Instruments). Starting materials (E)-1-chloro-2-pentafluorosulfanyl-1-phenylethene (2a) and
1-pentafluorosulfanyl-2-phenylacetylene (3a) were prepared according to our previous reported procedures
[17]. Benzohydroxyiminoyl chlorides (4a-d) [22] and N-benzylideneaniline N-oxides (7a-c) [23] were
prepared according to the literature.
4.2. Preparation of 1-chloro-2-pentafluorosulfanyl-1-arylethenes (2b-c)
Into a three-necked flask equipped with a dry-ice reflux condenser and a nitrogen inlet were added at -40
°C 15 mL of anhydrous hexane, arylacetylene (3 mmol), and SF5Cl (1.2 equiv). The solution was stirred at
this temperature for 5 min, and then Et3B (0.1 equiv, 1 M in hexane) was added slowly using a syringe.
The solution was vigorously stirred for 1 h at -30 °C, and then the mixture was allowed to warm to room
temperature. The mixture was hydrolyzed with aqueous NaHCO3 (10%), and the organic layer was dried
over anhydrous MgSO4. The solvent was removed, and the crude product was passed through a column of
silica gel, eluting with hexanes. Removal of solvent provided the products as colorless oils.
4.2.1. (E)-1-Chloro-2-pentafluorosulfanyl-1-(4-methylphenyl)ethane (2b)
Page 11 of 18

1
19
0.42 g (50%); H NMR,  7.25 (d, J = 6.0 Hz, 2H), 7.23 (d, J = 6.0 Hz, 2H), 6.92 (m, 1H); F NMR, 
81.1 (p, 2JFF = 152 Hz, 1F), 68.9 (d, 2JFF = 152 Hz, 4F); 13C NMR,  143.2, 140.2, 137.6 (p), 132.7, 128.9,
127.5, 21.4; HRMS (GC-CI): m/z Calcd.for C9H8ClF5S: 277.9955. Found: 277.9956.
4.2.2. (E)-1-Chloro-2-pentafluorosulfanyl-1-(4-methoxyphenyl)ethene (2c)
0.60 g (68%); 1H NMR,  7.33 (d, J = 9.0 Hz, 2H), 6.91 (m, 3H), 3.84 (s, 3H); 19F NMR,  81.4 (p, 2JFF =
150 Hz, 1F), 68.9 (d, 2JFF = 150 Hz, 4F); 13C NMR,  160.8, 131.5 (m), 129.3, 127.5, 113.7, 55.3; HRMS
(+ESI-DART): m/z Calcd. for [C9H9ClF5OS]+: 294.9983. Found: 294.9978.
4.3. Preparation of 1-pentafluorosulfanyl-2-(substitutedphenyl)acetylenes (3b-c)
To a solution of the corresponding alkene 2b-c (5.67 mmol) in DMSO (5 mL) was added LiOH x H2O (1.2
g, 28.6 mmol, 5 equiv) at room temperature. The mixture was stirred for 2 hours at room temperature. The
resultant mixture was poured into ice-water, neutralized with 2 M HCl, and extracted twice with diethyl
ether (2 x 25 mL). The organic layers were combined, washed with brine, and then dried over anhydrous
MgSO4. The solvent was removed under reduced pressure. The residue was purified by silica gel column
chromatography (elution with hexanes), to obtain the products as colorless oils.
4.3.1. 1-Pentafluorosulfanyl-2-(4-methylphenyl)acetylene (3b)
1
13
1.21 g (88%); H NMR,  7.46 (d, J = 6 Hz, 2H), 7.21 (d, J = 6 Hz, 2H,), 2.40 (s, 3H, Me); C NMR, 
141.6, 132.5, 129.4, 114.2, 21.6 (C≡C carbons not seen); 19F NMR,  77.6 (p, 1F, 2JFF = 168 Hz), 83.8 (d,
4F, 2JFF = 168 Hz); HRMS (+ESI-DART): m/z Calcd. for [C9H7F5S]+: 242.0189. Found: 242.0198.
4.3.2. 1-Pentafluorosulfanyl-2-(4-methoxyphenyl)acetylene (3c)
1.24 g (85%); 1H NMR,  7.54 (d, J = 6 Hz, 2H), 6.94 (d, 2H, J = 6 Hz), 3.88 (s, 3H, OMe); 13C NMR, 
19
161.8, 134.4, 114.4, 109.0, 55.4 (C≡C carbons not seen); F NMR,  77.4 (p, 1F, 2JFF = 170 Hz), 83.3 (d,
4F, 2JFF = 170 Hz);HRMS (+ESI-DART): m/z Calcd for [C9H8F5OS + NH4]+: 276.0476. Found: 276.0480.
Page 12 of 18

4.4. General procedure for the preparation of 3,5-diarylsubstituted-4-pentafluorosulfanylisoxazoles (6a-g)
To a solution of the SF5-alkyne (1.1 mmol) in THF (3 mL) was added the benzohydroxyiminoyl chloride
(2.2 mmol, 2 equiv). A solution of triethylamine (0.22 g, 2.2 mmol, 2 equiv) in 3 mL of THF was added
dropwise to the mixture at room temperature over 30 minutes. After stirring for 16 hours at room
temperature, a second portion of the SF5-alkyne (3.85 mmol, 3.5 equiv) in THF (9 mL) and triethylamine
(0.78 g, 7.7 mmol) were added dropwise. The reaction mixture was stirred for 20 hours at room
temperature. The resultant mixture was poured into water and extracted twice with ethyl acetate (2 x 20
mL). The organic layers were combined, washed with brine, and then dried over anhydrous MgSO4. The
solvent was removed under reduced pressure. The crude products were purified by silica gel column
chromatography (elution with hexanes-CHCl3; 65:35), to obtain the corresponding SF5-isoxazoles 6 as
white solids.
4.4.1. 3,5-diphenyl-4-(pentafluorosulfanyl)isoxazole (6a) [24]
o
1
0.19 g (50%); mp = 149-150 C; H NMR,  7.66-7.69 (m, 2H), 7.49-7.68 (m, 8H); 19F NMR,  81.9
(p, 2JFF = 162 Hz, 1F), 77.2 (d, 2JFF = 162 Hz, 4F); HRMS (+ESI-DART): m/z Calcd. for [C15H11F5NOS]+:
348.0476. Found: 348.0465.
4.4.2. 3-(4-methoxyphenyl)-5-phenyl-4-(pentafluorosulfanyl)isoxazole (6b)
o
0.22 g (53%); mp = 116-118 C; 1H NMR,  7.66 (d, J = 9.0 Hz, 2H), 7.52 (m, 5H), 7.01 (d, J = 9.0 Hz),
19
2
2
13
3.87 (s, 3H, OCH3); F NMR,  82.2 (p, JFF = 144 Hz, 1F), 77.16 (d, JFF = 144 Hz, 4F); C NMR, 
158.4, 157.5, 157.4, 128.8, 128.3, 126.5, 126.0, 124.3, 117.7, 111.3, 52.8 (SF5-C not observed); HRMS
(+ESI-DART): m/z Calcd. for [C16H13F5NO2S]+: 378.0582. Found: 378.0592.
4.4.3. 3-phenyl-5-(4-methylphenyl)-4-(pentafluorosulfanyl)isoxazole (6c)
0.22 g (55%); mp = 157-159 oC; 1H NMR,  7.70 (m, 2H), 7.62 (m, 1H), 7.57 (m, 2H), 7.46 (d, J = 6 Hz,
2H), 7.33 (d, J = 6 Hz, 2H), 2.47 (s, 3H, CH3); 19F NMR,  82.6 (p, 2JFF = 144 Hz, 1F), 77.7 (d, 2JFF = 144
Page 13 of 18

Hz, 4F); 13C NMR,  169.5, 160.2, 140.0, 131.3, 129.3, 129.2, 128.9, 128.5, 126.9, 125.3, 21.4 (SF5-C not
observed); HRMS (+ESI-DART): m/z Calcd. for [C16H13F5NOS]+: 362.0633. Found: 362.0639.
4.4.4. 3-(4-fluorophenyl)-5-(4-methylphenyl)-4-(pentafluorosulfanyl)isoxazole (6d)
0.25 g (59%); mp = 108-109 oC; 1H NMR,  7.60 (d, J = 9.0 Hz, 2H), 7.55 (m, 2H), 7.38 (d, J = 9 Hz, 2H),
2
7.21 (t, J = 6 Hz, 2H), 2.49 (s, 3H, CH3); 19F NMR,  82.6 (p, 2JFF = 163 Hz, 1F), 77.6 (d, JFF = 163 Hz,
13
4F); C NMR,  169.9, 163.8 (d, JFC = 155 Hz), 159.3, 142.0, 131.5, 129.3, 129.0, 124.4, 123.7, 115.4,
21.6 (SF5-C not observed); HRMS (+ESI-DART): m/z Calcd. for [C16H12F6NOS]+: 380.0538. Found:
380.0535.
4.4.5. 3-(4-methylphenyl)-5-(4-methylphenyl)-4-(pentafluorosulfanyl)isoxazole (6e)
0.21 g (50%); mp = 134-136 oC; 1H NMR,  7.57 (d, J = 9.0 Hz, 2H), 7.42 (d, J = 9.0 Hz, 2H), 7.35 (d, J =
13
9.0 Hz, 2H), 7.29 (d, J = 9.0 Hz, 2H), 2.45 (s, 3H, CH3), 2.43 (s, 3H); C NMR,  141.8, 140.0, 129.3,
19
129.2, 129.0, 128.9, 21.5, 21.4 (quaternary aromatic carbons and C-SF5` not seen); F NMR,  82.3 (p,
2
2JFF = 160 Hz, 1F), 77.2 (d, JFF = 160 Hz, 4F); HRMS (+ESI-DART): m/z Calcd. for [C17H15F5NOS]+:
376.0789. Found: 376.0803.
4.4.6. 3-(4-methoxyphenyl)-5-(4-methoxyphenyl)-4-(pentafluorosulfanyl)isoxazole (6f)
0.26 g (58%); mp = 124-126 oC; 1H NMR (500 MHz),  7.64 (d, J = 6.0 Hz, 2H), 7.45 (d, J = 6 Hz, 2H),
19
7.03 (d, J = 6 Hz, 2H), 7.00 (d, J = 6 Hz, 2H), 3.89 (s, 3H, OCH3), 3.87 (s, 3H, OCH3); F NMR (470
2
13
MHz),  83.2 (p, JFF = 160 Hz, 1F), 77.5 (d, 2JFF = 160 Hz, 4F); C NMR (125.8 MHz),  169.4, 161.4,
160.8, 160.0 130.8, 130.7 120.5, 118.9, 114.0, 113.7, 55.4, 55.3 (SF5-C not seen); HRMS (+ESI-DART):
m/z Calcd. for [C15H15F5NO3S]+: 408.0687. Found: 408.0696.
4.4.7. 3-(4-fluorophenyl)-5-(4-methoxyphenyl)-4-(pentafluorosulfanyl)isoxazole (6g)
0.22 g (51%); mp = 112-114 oC; 1H NMR,  7.85 (d, J = 9.0 Hz, 2H), 7.50 (m, 2H), 7.15 (m, 2H), 7.03 (d,
13
J= 9.0 Hz, 2H), 3.90 (s, 3H, OCH3); C NMR,  169.9, 164.9, 161.0 (d, JFC = 202 Hz), 131.8, 131.1,
Page 14 of 18

124.7, 118.9, 115.8 (d, 2JFC = 14 Hz), 114.4, 114.3, 55.8 (C-SF5 not seen); 19F NMR,  82.4 (p, 2JFF = 160
Hz, 1F), 77.1 (d, 2JFF = 160 Hz, 4F), -111.2 (s, 1F); HRMS (+ESI-DART): m/z Calcd. for [C16H12F6NOS]+:
396.0487. Found: 396.0485.
4.5. General procedure for preparation of 4-pentafluorosulfanyl-2,3,5-triarylsubstituted-4-isoxazolines
(8a-c).
To a solution of the SF5-acetylene (0.785 mmol) in THF (4 mL) was added the corresponding
N-benzylidineaniline N-oxide (1.57 mmol, 2 equiv). The reaction mixture was stirred for 20 hours at room
temperature. The solvent was removed under reduced pressure to give a residue which was then purified
by silica gel column chromatography (elution with hexanes-CHCl3; 65:35), obtaining the corresponding
SF5-isoxazolidines as light yellow solids.
4.5.1. 4-Pentafluorosulfanyl-2,3,5-triphenyl-4-isoxazoline (8a). [24]
0.30 g (90%); mp = 100-101 oC; 1H NMR,  7.78 (d, J = 7.6 Hz, 2H), 7.59 (d, J = 8.5 Hz, 3H), 7.55 (t, J =
7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.42 (t, J = 8.2 Hz, 3H), 7.27 (d, J = 8.6 Hz, 2H), 7.19 (t, J = 7.3 Hz,
1H), 5.84 (s, 1H); 19F NMR,  85.1 (p, 2JFF = 161 Hz, 1F), 74.8 (d, 2JFF = 161 Hz, 4F); 13C NMR,  157.2,
151.2, 140.4, 131.7, 129.8, 129.6, 129.4, 129.1, 128.9, 127.7, 127.2, 125.0, 116.3, 78.5 (SF5-C not
observed); Anal.Calcd. for C21H16F5NOS: C, 59.29; H, 3.79; N, 3.29. Found: C, 58.97; H, 3.59; N, 3.17.
4.5.2. 4-Pentafluorosulfanyl-2-(4-methylphenyl)-3-(4-methoxyphenyl)-5-phenyl-4-isoxazoline (8b).
0.24 g (65%); mp = 96-97 oC; 1H NMR,  7.75 (dd, J = 7.5, 2.0 Hz, 2H), 7.35-7.60 (m, 10H), 7.24 (d, J =
7.3 Hz, 2H), 7.21 (t, J = 7.2 Hz, 2H), 5.80 (s, 1H); 19F NMR,  85.1 (p, 2JFF = 161 Hz, 1F), 74.8 (d, 2JFF =
161 Hz, 4F); 13C NMR,  160.2, 157.0, 151.0, 141.8, 132.4, 129.5, 129.3, 128.7, 124.6, 124.0, 116.1,
114.5, 55.4, 21.7 (SF5-C not observed, isoxazoline C-H obscured by CDCl3 signal, one Ar-C signal not
observed); HRMS (+ESI-DART): m/z Calcd. For [C23H21F5NO2S]+: 470.1208. Found: 470.1231.
4.5.3. 4-Pentafluorosulfanyl-2-phenyl-3-(4-fluorophenyl)-5-phenyl-4-isoxazoline (8c).
Page 15 of 18

o
1
0.21 g (60%); mp = 98-100 C; H NMR (500 MHz),  7.76 (d, J = 6.0 Hz, 2H), 7.58 (m, 1H), 7.55 (m,
19
2H), 7.54 (m, 2H) 7.41 (m, 2H), 7.24 (m, 2H), 7.19 (m, 1H), 7.16 (m, 2H), 5.83 (s, 1H); F NMR (470
MHz),  85.6 (p, 2JFF = 155 Hz, 1F), 75.4 (d, 2JFF = 155 Hz, 4F), -113.1 (s, 1F); 13C NMR (125.8 MHz), 
162.9, 157.0, 150.6, 136.0, 131.4 129.4, 129.3, 129.2, 128.6, 126.7, 126.7, 124.8, 116.1, 116.0, 77.4
(isoxazoline CH); HRMS (+ESI-DART): m/z Calcd. f.6, or [C21H16F6NOS]+: 444.0851, Found: 444.0859.
Acknowledgments
SL thanks Department of Chemistry (Universidad Simon Bolivar, Caracas, Venezuela) for a sabbatical
leave license and Reese Gallagher for his help with the melting points.
References
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