A new approach to α-(trifluoromethyl)benzyl substituted oxaziridines

Article abstract of DOI:10.1016/j.jfluchem.2013.03.018

The synthesis of N-substituted oxaziridines bearing an α- (trifluoromethyl)benzyl substituent at C(3) was achieved by m-CPBA oxidation of the corresponding 3-imino-1,1,1-trifluoro-2-arylpropan-2-ols and their trimethylsilyl protected derivatives, respectively. In all cases, mixtures of diastereoisomers were formed. The prepared oxaziridine derivatives were shown to be able to oxidize thioanisole to thioanisole S-oxide in the presence of methanesulfonic acid.

Full text of DOI:10.1016/j.jfluchem.2013.03.018

Journal of Fluorine Chemistry 151 (2013) 7–11
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A new approach to
a
-(trifluoromethyl)benzyl substituted oxaziridines
a,
Emilia Obijalska a, , Grzegorz Mloston , Greta Utecht a,1, Heinz Heimgartner b
*
*
´
a
´
´
´
Department of Organic and Applied Chemistry, University of Ło´dz, Tamka 12, PL-91-403 Łodz, Poland
b Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
A R T I C L E I N F O
A B S T R A C T
Article history:
The synthesis of N-substituted oxaziridines bearing an
a-(trifluoromethyl)benzyl substituent at C(3)
Received 1 March 2013
was achieved by m-CPBA oxidation of the corresponding 3-imino-1,1,1-trifluoro-2-arylpropan-2-ols and
their trimethylsilyl protected derivatives, respectively. In all cases, mixtures of diastereoisomers were
formed. The prepared oxaziridine derivatives were shown to be able to oxidize thioanisole to thioanisole
S-oxide in the presence of methanesulfonic acid.
Received in revised form 19 March 2013
Accepted 21 March 2013
Available online 6 April 2013
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
(Trifluoromethyl)trimethylsilane
Fluorinated heterocycles
Oxaziridines
b-Imino alcohols
1. Introduction
In continuation of our studies on nucleophilic trifluoromethy-
lation of
a
-imino ketones, reactions of arylglyoxalimines 5 were
-trifluoromethylated O-
Oxaziridines are under extensive study as attractive oxidizing
agents, and the so-called ‘Davies oxaziridine’ is the best known
example [1]. In a recent paper, the first enantioselective oxidation
of N-tosylated aryl and alkyl aldimines using meta-chloroperben-
zoic acid (m-CPBA) was described [2]. On the other hand,
fluorinated heterocycles are of special interest, as the introduction
of a fluorinated fragment results in substantial change of physico-
chemical properties, reactivity and biological activites [3].
However, fluorinated oxaziridines are less well known, and the
reported examples mainly originate from perfluorinated starting
materials [4]. Recently, oxaziridines derived from fluoral N-alkyl
imines were reported [5]. Starting with enantiopure substrates, the
corresponding products were obtained in a highly diastereoselec-
tive manner.
In our hands, camphorquinone monoimines 1 were reacted
with (trifluoromethyl)trimethylsilane (Ruppert-Prakash reagent
[6]) yielding trifluoromethylated hydroxyimines 2 chemo- and
diastereoselectively [7]. Unexpectedly, the attempted oxidation of
products 2 with m-CPBA led to nitrones 3 instead of the expected
oxaziridines 4 [8] (Scheme 1). However, in one case, an oxaziridine
derivative was obtained by photolysis of an isolated nitrone 3 as a
mixture of the endo and exo-isomers.
shown to yield the corresponding
a
silylated hydroxyimine derivatives 6 [9] (Scheme 2).
The goal of the present study was the synthesis of new
a-
(trifluoromethyl)benzyl-substituted oxaziridines starting with
compounds 6 or the corresponding imino alcohols 7. In addition,
the oxidizing properties of this type of oxaziridines should be
compared with known models of fluorine containing oxaziridines.
2. Results and discussion
Initial experiments on the oxidation of a C55N group were
performed starting with the O-protected imino alcohols 6 [9],
which after treatment with m-CPBA in dichloromethane at 0 8C
were converted into mixtures of diastereoisomeric oxaziridines 8
in good yields (Scheme 3, Method A). The ratio of diastereoisomers
(dr) was determined by 19F-NMR spectroscopy and ranked
between 9:1 and 6:4 (Table 1). Only in the case of 8e isolation
of the major isomer in pure from was successfully performed by
fractional crystallization. In all other cases, neither crystallization
nor chromatography allowed to separate the isomers. In order to
obtain the non-protected oxaziridinyl alcohols 9, the initially
obtained products 8 were treated with tetrabutylammonium
fluoride (TBAF) in THF at 0 8C. Under these conditions, in the series
of the N-tert-butyl derivatives, desilylation occurred smoothly
with no decomposition of the oxaziridine ring. In contrast, the N-
isopropyl analogs led to complex mixtures of unidentified
products.
* Corresponding author. Tel.: +48 42 635 57 61; fax: +48 42 665 51 62.
E-mail addresses: emiliaobijalska@gmail.com (E. Obijalska),
gmloston@uni.lodz.pl (G. Mloston´ ).
An alternative pathway (Method B) for the synthesis of
oxaziridines 9 started with deprotection of 6 under standard
1
Part of the Bachelor Thesis of G. Utecht, University of Ło´ dz´, 2012.
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.03.018

8
E. Obijalska et al. / Journal of Fluorine Chemistry 151 (2013) 7–11
R
R
R
N
CF3SiMe3
N
N
m-CPBA
O
OH
OH
O
CF3
CF3
1
2
3
R = Me
hv
Me
N
O
N
O
+
Me
OH
CF3
2-exo,3-endo-4
OH
CF3
2-exo,3-endo-4
Scheme 1. Oxidation of
a-imino trifluoromethyl alcohols derived from norbornane leading to nitrones.
Table 2
CF3SiMe3
Ar
HO CF3
Me3SiO CF3
desilylation
Oxidation of thioanisole with oxaziridines 8 and 9e.
NR
NR
NR
Ar
O
Ar
Oxaziridine
Acid
Yield (%)
7
6
5
8d
9e
8a
8b
8d
8e
9e
No acid
No acid
MeSO3H
MeSO3H
MeSO3H
MeSO3H
MeSO3H
No reaction
No reaction
Scheme 2. Trifluoromethylation of monoimines derived from arylglyoxals.
70
76
83
72
80
Me3SiO CF3
Ar
m-CPBA
TBAF
THF, 0 oC, 2 h
R
CH2Cl2, 0 oC, 1 h
N
Method A
O
8
HO CF3
Ar
The major diastereoisomers of 9d and 9e were isolated as pure
compounds after fractional crystallization of the crude mixtures.
The spectroscopic data confirm the structure of oxaziridines 9. For
example, the 13C-NMR spectrum of 9d showed the signal of C(3) of
the oxaziridine ring at 73.4 ppm as a quartet (3JC,F = 1.5 Hz). The
CF3 group absorbed at 124.3 ppm (1JC,F = 285.3 Hz) and the
benzylic C-atom appeared at 74.1 ppm (2JC,F = 28.7 Hz). Further-
more, the 19F-NMR spectrum showed the signal of the CF3 group at
ꢀ76.6 ppm.
Me3SiO CF3
R
NR
N
O
Ar
6
9
HO CF3
Method B
m-CPBA
CH2Cl2, 0 oC, 1 h
TBAF
THF, 0 oC, 2 h
NR
Ar
7
Scheme 3. Oxidation of
a-imino trifluoromethyl alcohols and their O-silylated
Unfortunately, attempts to grow crystals suitable for X-ray
crystallography with the aim of determining the absolute
configuration in both cases, 9d and 9e, were unsuccessful.
It is worth mentioning that oxaziridines 9 are stable compounds
and don’t undergo decomposition during storage in the refrigera-
tor neither as solid materials nor in solution.
The application of oxaziridines for oxidations of sulfides and N-
heterocycles is well documented [1,4,10,11]. In general, oxazir-
idines bearing perfluorinated alkyl residues at the C-atom, are
more powerful oxidizing agents in comparison with the non-
fluorinated analogous [5,11].
analogs derived from arylglyoxals.
conditions, and the obtained imino alcohols 7 were oxidized
(Scheme 3). Using this method, both N-tert-butyl and N-isopropyl
derivatives were obtained in good yields with comparable ratios of
diastereoisomers. Again, the highest dr value was observed in the
case of the N-tert-butyl 4-nitrobenzyl derivative 9d.
Table 1
Synthesis of oxaziridines 8 and 9.
In order to check the oxidizing properties of oxaziridines 8 and
9, the conversion of thioanisole (10) into (methyl)(phenyl)sulf-
oxide (11) was examined as a model reaction (Scheme 4). The first
experiments were performed using 8d or 9e and 10 in a 1:1 ratio.
When CHCl3 was used as a solvent at room temperature, no
reaction was observed even after 24 h (Table 2). However, after
addition of three mol-equivalents of methanesulfonic acid, the TLC
control evidenced complete conversion of 10 to 11 as the sole
Ar
Ph
R
7
a
Yield
(%)
8
a
Yield dra
9
a
Yield dra
Methodb
(%)
(%)
i-Pr
–
80
–
70
–
6:4
–
–
84
–
–
A
B
A
A
B
A
B
A
B
9:1
4-MeOC6H4
4-NO2C6H4
i-Pr
i-Pr
b
c
84
81
–
6:4
8:2
–
–
c
–
c
–
–
42
–
82
80
87
79
68
>20:1e
9:1
4-NO2C6H4
t-Bu
d
e
d
e
85
–
9:1
–
d
d
e
e
63
9:1
d
Benzofuran-2-yl t-Bu
–
c
70
–
8:2
–
9:1
O
S
a
8a-b,d-e; 9e
Ratio of diastereoisomers.
S
b
Method A: oxidation-desilylation (via 8); Method B: desilylation-oxidation
(via 7).
Ph
Me
Ph
Me
CHCl3, r.t.
c
10
11
Not isolated.
d
e
Desilylation of major isomer of 8e.
The minor isomer was not detected using 19F NMR.
Scheme 4. Oxidation of thioanisole with oxaziridines 8 and 9.

E. Obijalska et al. / Journal of Fluorine Chemistry 151 (2013) 7–11
9
product after 1 h at room temperature. Analogous results were
observed when oxaziridines 8a,b,e were used instead of 8d. These
experiments showed that oxaziridines 8 and 9 are only moderately
active oxidizing reagents, and the oxygen transfer requires
activation by a strong Brønsted acid. A similar influence of strong
acids in oxidation reactions with oxaziridines has already been
reported [12].
combined and dried over anhydrous Na2SO4. After filtration, the
solvents were evaporated and the crude, oily products 6 were used
for further reactions without purification.
4.4. Syntheses of (trifluoromethyl)oxaziridines 8 and 9
Method A – general procedures. Oxidation of 6: m-CPBA (70%,
250 mg, 1.1 mmol) was added in small portions to the magneti-
cally stirred solution of the corresponding silyl ether 6 in CH2Cl2
(2 ml), cooled in an ice-bath. Next, the solution was stirred for ca.
2 h, and a saturated solution of K2CO3 was added. The mixture was
extracted three times with CH2Cl2. The organic layers were
combined and dried over anhydrous Na2SO4. After filtration, the
solvent was evaporated and the crude oily products 8 were purified
by column chromatography (SiO2, hexane/CH2Cl2 7:3).
Desilylation of 8: The flask containing a solution of compound 8
in THF (2 ml) was placed in an ice bath. Next, TBAF dissolved in THF
(1 M, 1.5 ml, 1.5 mmol) was added dropwise and the mixture was
stirred for ca. 3 h. Then, a portion of water was added and the
mixture was extracted three times with CH2Cl2. The organic layers
were combined and dried over anhydrous Na2SO4. After filtration,
the solvents were evaporated, and the crude oily products 9 were
purified by column chromatography (SiO2, hexane/CH2Cl2 7:3).
After additional crystallization from an appropriate solvent,
products 9d and 9e were obtained as pure diastereoisomers.
Method B – general procedures. Desilylation of 6: To a flask placed
in ice-bath and containing the corresponding silyl ether 6 in THF
(2 ml), a solution of TBAF in THF (1 M, 1.5 ml, 1.5 mmol) was added
and the mixture was magnetically stirred for ca. 3 h. Then, a
portion of water was added and the mixture was extracted three
times with CH2Cl2. The organic layers were combined and dried
over anhydrous Na2SO4. After filtration, the solvents were
3. Conclusions
The present study showed that the O-silylated imino alcohols 6,
obtained easily from glyoxal monoimines 5 via nucleophilic
trifluoromethylation with Ruppert-Prakhash reagent, can be
oxidized under standard conditions to give oxaziridines 8 as a
mixture of diastereoisomers. After desilylation, oxaziridines 9
were obtained. Alternatively, compounds 9 can be prepared from 6
via the desilylation/oxidation sequence. These results demon-
strate, that the earlier observed transformation of
a-trifluoro-
methyl -hydroxy imines 2, derived from camphorquinone, into
a
nitrones 3 (and not to the expected oxaziridines), upon the
treatment with m-CPBA, results from the steric hindrance and not
from the presence of the strongly electron-withdrawing CF3
substituent.
In contrast to other fluorinated oxaziridines, derivatives 8 are
less useful oxidizing reagents, which require the presence of a
strong Brønsted acid to convert sulfides into sulfoxides. Similar
behavior was also observed in the case of the O-deprotected
oxaziridine 9e.
4. Experimental part
4.1. General experimental procedures
evaporated, and the products
7 were purified by column
Melting points were determined on a Melt-Temp. II apparatus
(Aldrich) in capillary and they are uncorrected. The 1H, 13C{1H} and
19F NMR spectra were recorded using Bruker Avance III 600
spectrometer using solvent signal as reference. Assignments of
signals in 13C NMR spectra were made on the basis of HMQC
experiments. The IR spectra were measured using an NEXUS FT-IR
spectrophotometer. The MS spectra (ESI, ESI-HRMS) were obtained
using Varian 500-MS or Bruker maXis spectrometers. The EI-HRMS
spectra were recorded on the Finnigan MAT 95 double focusing (BE
geometry) mass spectrometer.
chromatography (SiO2, hexane/CH2Cl2 7:3).
Oxidation of 7: A flask containing compound 7 dissolved in
CH2Cl2 (2 ml) was placed in an ice bath, and m-CPBA (70%, 250 mg,
1.1 mmol) was added. The mixture was stirred for ca. 2 h. Next, a
saturated solution of K2CO3 was added, and the resulting mixture
was extracted three times with CH2Cl2. The organic layers were
combined and dried over anhydrous Na2SO4. After filtration, the
solvent was evaporated to dryness, and the crude products 9 were
obtained as viscous oils and purified by column chromatography
(SiO2, hexane/CH2Cl2 7:3).
4.2. Materials
4.4.1. 3-Imino-1,1,1-trifluoro-2-arylpropan-2-ols 7
3-(Isopropyl)imino-1,1,1-trifluoro-2-phenylpropan-2-ol
(7a).
A commercial solution of tetrabutylammonium fluoride (TBAF,
1 M in THF), m-chloroperbenzoic acid (m-CPBA), and thioanisole
were purchased from Sigma–Aldrich and (trifluoromethyl)tri-
Yield: 196 mg (80%). Colorless, viscous oil. 1H NMR (600 MHz):
d
3
1.16, 1.24 (2d, JH,H = 6.6 Hz, 6H, CH(CH3)2), 3.70–3.75 (m, 1H,
CH(CH3)2), 5.75 (s, 1H, OH), 7.38–7.44 (m, 3 arom. CH), 7.67–7.68
methylsilane from Fluorochem.
a
-Iminoketones (5a–5e) were
(m, 2 arom. CH), 8.10 (s, 1H, HC55N) ppm. 13C NMR (150 MHz):
d
prepared according to the known protocol [9]. Dimethoxyethane
(DME) was dried over sodium in the presence of benzophenone
and freshly distilled prior to the use. Tetrahydrofuran (THF) was
used as commercial solvent without drying.
23.4, 23.6 (CH(CH3)2), 58.6 (CH(CH3)2), 75.7 (q, 2JC,F = 28.5 Hz, Cq),
1
124.2 (q, JC,F = 285.0 Hz, CF3), 126.4, 128.6, 128.9 (5 arom. CH),
135.3 (1 arom. C), 155.2 (C55N) ppm. 19F NMR (565 MHz):
d
ꢀ77.10
(s, 3F, CF3) ppm. IR (film):
v 3327br.m (OH), 3065w, 2974 m,
2933 m, 2874 m, 1668 m (C55N), 1452 m, 1386 m, 1265s, 1194s,
1166s, 1017 m, 978 m cmꢀ1. ESI-MS: m/z 204 (12), 246 (100
[M+1]+), 247 (12). EI-HRMS: Calcd. for C12H14F3NO+ (M+): m/z
245.10223; found: m/z 245.10275.
4.3. Reactions of
a-imino ketones 5 with
(trifluoromethyl)trimethylsilane
A solution of the corresponding
a
-imino ketone 5 (1.0 mmol) in
3-(Isopropyl)imino-1,1,1-trifluoro-2-(4-nitrophenyl)propan-2-ol
anhydrous DME (ꢁ1.5 ml), was placed in a dry, two-necked flask,
equipped with septum and a tube filled with anhydrous CaCl2.
Next, a catalytic amount of freshly dried CsF and (trifluoromethyl)-
trimethylsilane (0.17 ml, 157 mg, 1.1 mmol) were added. The
mixture was stirred at room temperature for ca. 1 h and
subsequently quenched with water (5 ml). The solution was
extracted three times with CH2Cl2. The organic layers were
(7c). Yield: 122 mg (42%). Colorless crystals, m.p. 70–72 8C (Et2O/
3
hexane). 1H NMR (600 MHz):
d
1.17, 1.25 (2d, JH,H = 6.6 Hz, 6H,
CH(CH3)2), 3.74–3.78 (m, 1H, CH(CH3)2), 5.86 (s, 1H, OH), 7.87–
7.88 (m, 2 arom. CH), 8.08 (s, 1H, HC55N), 8.27–8.29 (m, 2 arom. CH)
ppm. 13C NMR (150 MHz):
76.1 (q, JC,F = 30.2 Hz, Cq), 123.9, 127.8 (4 arom. CH), 124.0 (q,
1JC,F = 286.8 Hz, CF3), 142.4, 148.6 (2 arom. C), 154.0 (C55N) ppm.
d
23.6, 23.7 (CH(CH3)2), 58.9 (CH(CH3)2),
2

10
E. Obijalska et al. / Journal of Fluorine Chemistry 151 (2013) 7–11
3
19F NMR (565 MHz):
(OH), 3166w, 2981 m, 2879w, 1667 m, 1516s (C55N), 1534s, 1266s,
1197s, 1161s, 1017 m cmꢀ1. ESI-MS: m/z 291 (100, [M+1]+), 292
(10). EI-HRMS: Calcd. for C12H13F3N2O3 (M+): m/z 290.08796;
d
ꢀ76.87 (s, 3F, CF3) ppm. IR (KBr):
v
3343br.m
(s, 9H, Si(CH3)3), 1.14 (d, JH,H = 6.6 Hz, 3H, CH(CH3)2), 1.25
3
(d, JH,H = 6.0 Hz, 3H, CH(CH3)2), 4.34 (s, 1H, OCHN), 8.23–8.26
(m, 2 arom. CH); minor diastereomer: 0.26 (s, 9H, Si(CH3)3),
1.06 (d, 3JH,H = 6.6 Hz, 3H, CH(CH3)2), 1.21 (d, 3J H,H = 6.0 Hz, 3H,
CH(CH3)2), 4.34 (s, 1H, OCHN), 8.20–8.22 (m, 2 arom. CH); both
diastereomers: 2.26–2.34 (m, 1H, CH(CH3)2), 7.77–7.81 (m, 2
arom. CH) ppm. 13C NMR (150 MHz):
(Si(CH3)3), 62.6 (CH(CH3)2), 78.5 (q, JC,F = 27.2 Hz, Cq), 81.0
(OCHN), 124.1 (q, JC,F = 288.3 Hz, CF3), 148.6 (1 arom. C);
minor diastereomer: 2.2 (Si(CH3)3), 62.7 (CH(CH3)2), 80.5
(OCHN), 78.9 (q, JC,F = 28.5 Hz, Cq), 148.5 (1 arom. C); both
+
found: m/z 290.08783.
3-(tert-Butyl)imino-1,1,1-trifluoro-2-(4-nitrophenyl)propan-2-ol
(7d). Yield: 192 mg (63%). Colorless crystals, m.p. 97–99 8C
d major diastereomer: 2.3
(CH2Cl2/hexane). 1H NMR (600 MHz):
d
1.25 (s, 9H, C(CH3)3),
2
1
7.87–7.89, 8.27–8.28 (2 m, 4 arom. CH), 7.98 (s, 1H, HC55N) ppm.
13C NMR (150 MHz):
d
29.2 (C(CH3)3), 58.0 (C(CH3)3), 74.1 (q,
2JC,F = 30.1 Hz, Cq), 123.8 (q, JC,F = 285.3 Hz, CF3), 123.7, 127.6 (4
1
2
arom. CH), 142.4, 148.3 (2 arom. C), 150.8 (C55N) ppm. 19F NMR
diastereomers: 18.6, 18.8, 21.3 (CH(CH3)2), 113.5, 113.8,
128.74, 128.77, 128.8 (5 arom. CH), 126.9, 128.0 (1 arom. C)
ppm. The CF3 signal for the minor product could not be found.
(565 MHz, CDCl3):
d
ꢀ76.79 (s, 3F, CF3) ppm. IR (KBr):
v 3312br.m
(OH), 2972 m, 2944w, 2877w, 1668w, 1600w, 1518vs (C55N),
1418w, 1352s, 1264s, 1191vs, 1152vs, 1111 m, 1012 m,
970 m cmꢀ1. ESI-HRMS: Calcd. for C13H15F3N2O3Na+ ([M+23]+):
m/z 327.09270; found: m/z 327.09279. Calcd. for C13H16F3N2O3
([M+1]+): m/z 305.11075; found: m/z 305.11078.
19F NMR (565 MHz):
d
major diastereomer: ꢀ74.9 (s, 3F, CF3);
3085w,
minor diastereomer: ꢀ75.7 (s, 3F, CF3) ppm. IR (film):
v
+
2977 m, 2900 m, 2459w, 1941w, 1771w, 1609s, 1351s, 1254s,
1174s, 1119w cmꢀ1. ESI-MS: m/z 306 (18), 352 (12), 379 (100,
[M+1]+), 382 (18). EI-HRMS: Calcd. for C15H22F3N2O4Si+
([M+1]+): m/z 379.13013; found: m/z 379.13010.
4.4.2. (Trifluoromethyl)(trimethylsilyloxy)oxaziridines 8
N-Isopropyl-3-[2,2,2-trifluoro-1-phenyl-1-(trimethylsilyloxy)
ethyl]oxaziridine (8a). Yield: 233 mg (70%). Colorless, viscous oil.
Compound isolated as a mixture of diastereomers (6:4). 1H NMR
N-(tert-Butyl)-3-[2,2,2-trifluoro-1-(4-nitrophenyl)-1-(trimethyl-
silyloxy)ethyl]oxaziridine (8d). Yield: 333 mg (85%); isolated as a
mixture of diastereomers (9:1). Colorless oil. 1H NMR (600 MHz):
d
(600 MHz):
d
major diastereomer: 0.13 (s, 9H, Si(CH3)3), 1.14, 1.28
major diastereomer: 0.24 (s, 9H, Si(CH3)3), 1.14 (s, 9H, C(CH3)3),
4.52 (s, 1H, OCHN), 7.80–7.82, 8.26–8.29 (2 m, 4 arom. CH); minor
diasteromer: 0.29 (s, 9H, Si(CH3)3), 1.22 (s, 9H, C(CH3)3), 4.55 (s, 1H,
OCHN), 7.83–7.85, 8.31–8.33 (2 m, 4 arom. CH) ppm. 13C NMR
3
(2d, JH,H = 6.6 Hz, 6H, CH(CH3)2), 4.39 (s, 1H, OCHN); minor
diastereomer: 0.19 (s, 9H, Si(CH3)3), 0.96 (d, JC,H = 6.6 Hz, 3H,
CH(CH3)2), 1.21 (d, JH,H = 6.2 Hz, 3H, CH(CH3)2), 4.38 (s, 1H,
3
3
OCHN); both diastereomers: 2.23–2.32 (m, 1H, CH(CH3)2), 7.37–
(150 MHz): d major diastereomer: 2.4 (Si(CH3)3), 25.3 (C(CH3)3),
2
7.42 (m, 3 arom. CH), 7.59–7.61 (m, 2 arom. CH) ppm. 13C NMR
59.0 (C(CH3)3), 74.8 (OCHN), 78.7 (q, JC,F = 28.7 Hz, Cq), 124.2 (q,
1JC,F = 288.3 Hz, CF3), 123.3, 128.6 (4 arom. CH), 142.7, 148.5 (2
arom. C). Due to low intensities, absorption signals of the minor
diastereomer could not be determined. 19F NMR (565 MHz):
d
(150 MHz): d major diastereomer: 2.31 (Si(CH3)3), 62.7 (CH(CH3)2),
2
1
78.2 (q, JC,F = 34.7 Hz, Cq), 81.6 (OCHN) 124.6 (q, JC,F = 288.3 Hz,
CF3), 136.1 (1 arom. C); minor diastereomer: 2.37 (Si(CH3)3), 62.5
2
(CH(CH3)2), 78.4 (q, JC,F = 28.7 Hz, Cq), 81.3 (OCHN) 124.7 (q,
major diastereomer: ꢀ74.9 (s, CF3); minor diastereomer: ꢀ75.9 (s,
CF3) ppm. IR (KBr): 2980 m, 2904w, 1525s, 1351vs, 1303s, 1292s,
1252s, 1178vs, 1045 m, 1015 m, 850 m cmꢀ1. ESI-HRMS: Calcd. for
16H23F3NO4SiNa+ ([M+23]+): m/z 415.12714; found: m/z
415.12729.
N-(tert-Butyl)-3-[1-(benzofuran-2-yl)-2,2,2-trifluoro-1-(tri-
1JC,F = 286.8 Hz, CF3), 135.1 (1 arom. C); both diastereomers: 18.70,
18.73, 21.43, 21.48 (CH(CH3)2), 127.4, 128.2, 128.5, 129.1, 129.3 (5
v
arom. CH) ppm. 19F NMR (565 MHz):
d
major diastereomer: ꢀ75.7
C
(s, 3F, CF3); minor diastereomer: ꢀ76.2 (s, 3F, CF3) ppm. IR (film):
v
3065w, 2977 m, 2899w, 1498w, 1451 m, 1253 m, 1170 m, 1027 m,
847 m cmꢀ1. ESI-MS: m/z 330 (25), 331 (65), 332 (100, [Mꢀ1]+),
352 (65), 352 (67), 353 (90).
methylsilyloxy)ethyl]oxaziridine (8e). Yield: 0.271 g (70%). Colorless
crystals, m.p. 65–67 8C (hexane). The product was isolated as a
single diastereomer after fractional crystallization. 1H NMR
N-Isopropyl-3-[2,2,2-trifluoro-1-(4-methoxyphenyl)-1-(tri-
methylsilyloxy)ethyl]oxaziridine (8b). Yield: 305 mg (84%). Color-
less, viscous oil. Compound isolated as a mixture of diastereomers
(600 MHz):
1H, OCHN), 6.95 (s, 1H, 1 arom. CH), 7.26–7.28, 7.33–7.36, 7.52–
7.54, 7.60–7.61 (4 m, 4 arom. CH) ppm. 13C NMR (150 MHz):
1.7
d 0.11 (s, 9H, Si(CH3)3), 1.15 (s, 9H, C(CH3)3), 4.65 (s,
(6:4). 1H NMR (600 MHz):
d
major diastereomer: 0.11 (s, 9H,
d
Si(CH3)3), 1,14, 1.27 (2d, 3JH,H = 6.6 Hz, 6H, CH(CH3)2), 3.83 (s, 3H,
CH3O), 4.35 (s, 1H, OCHN); minor diastereomer: 0.19 (s, 9H,
Si(CH3)3), 1.00, 1.22 (2d, 3JH,H = 6.6 Hz, 6H, CH(CH3)2), 3.82 (s, 3H,
CH3O), 4.34 (s, 1H, OCHN); both diastereomers: 2.24–2.31 (m, 1H,
CH(CH3)2), 6.88–6.93, 7.47–7.52 (2 m, 4 arom. CH) ppm. 13C NMR
(Si(CH3)3), 25.3 (C(CH3)3), 58.8 (C(CH3)3), 74.4 (OCHN), 75.9 (q,
2JC,F = 28.7 Hz, Cq), 107.8, 111.8, 121.9, 123.5, 125.4 (5 arom. CH),
123.8 (q, 1JC,F = 288.3 Hz, CF3), 127.7, 150.8, 154.9 (3 arom. C) ppm.
19F NMR (565 MHz):
d
ꢀ76.5 (s, CF3) ppm. IR (KBr):
2962 m, 1454w, 1365w, 1294s, 1251s, 1204vs, 1155vs, 1142vs,
990 m cmꢀ1
1045 m, 1024 m, ESI-HRMS: Calcd. for
C
18H24F3NO3Na+ ([M+23]+): m/z 410.13698; found: m/z 410.13714.
v 2982 m,
(150 MHz):
d
major diastereomer: 2.28 (Si(CH3)3), 55.42 (OCH3),
.
2
62.64 (CH(CH3)2), 77.9 (q, JC,F = 27.2 Hz, Cq), 81.6 (OCHN), 124.6
1
(q, JC,F = 288.3 Hz, CF3), 160.3 (1 arom. C); minor diastereomer:
2.34 (Si(CH3)3), 55.37 (OCH3), 62.55 (CH(CH3)2), 78.2 (q,
4.4.3. (Trifluoromethyl)(hydroxy)oxaziridines 9
N-Isopropyl-3-(2,2,2-trifluoro-1-phenyl-1-hydroxyethyl)oxaziri-
1
2JC,F = 27.2 Hz, Cq), 81.3 (OCHN), 124.7 (q, JC,F = 286.8 Hz, CF3),
160.2 (1 arom. C); both diastereomers: 18.7, 18.8, 21.4, 21.5
(CH(CH3)2), 113.5, 113.8, 128.74, 128.77, 128.8 (5 arom. CH), 126.9,
dine (9a). Yield: 0.219 g (84%); isolated as a mixture of
diastereomers (9:1). Colorless, viscous oil. 1H NMR (600 MHz,
128.0 (1 arom. C) ppm. 19F NMR (565 MHz):
d
major diastereomer:
ꢀ75.9 (s, 3F, CF3); minor diastereomer: ꢀ76.5 (s, 3F, CF3) ppm. IR
(film): 3047w, 2976 m, 2901 m, 2841w, 1771w, 1613 m, 1515 m,
CDCl3):
d
major diastereomer: 1.14, (d, JH,H = 6.6 Hz, 3H,
3
CH(CH3)2), 2.38–2.45 (m, 1H, CH(CH3)2), 3.55 (s, 1H, OH), 4.48
3
v
(s, 1H, OCHN); minor diastereomer: 1.11 (d, JH,H = 6.6 Hz, 3H,
1466 m, 1254s, 1166s, 1032 m cmꢀ1. ESI-MS: m/z 364 (100,
[M+1]+), 386 (70, [M+23]+). EI-HRMS Calcd. for C16H24F3NO3Si+
(M+): m/z 363.14658; found: m/z 363.14776.
CH(CH3)2), 2.17–2.23 (m, 1H, CH(CH3)2), 3.18 (s, 1H, OH), 4.43 (s,
1H, OCHN); both diastereomers: 1.19–1.22 (m, 6H, CH(CH3)2),
7.30–7.37, 7.55–7.59 (2 m, 5 arom., CH) ppm. 13C NMR (150 MHz):
N-Isopropyl-3-[2,2,2-trifluoro-1-(4-nitrophenyl)-1-(trimethyl-
silyloxy)ethyl]oxaziridine (8c). Yield: 306 mg (81%). Yellow,
viscous oil. Compound isolated as a mixture of diastereomers
d major diastereomer: 18.3, 21.2 (CH(CH3)2), 61.2 (CH(CH3)2), 73.7
(q, 2JC,F = 28.7 Hz, Cq), 79.2 (OCHN), 124.6 (q, 1JC,F = 268.7 Hz, CF3),
133.4 (1 arom. C); minor diastereomer: 18.1, 21.0 (CH(CH3)2), 61.7
1
(8:2). 1H NMR (600 MHz):
d
major diastereomer: 0.21
(CH(CH3)2), 79.8 (OCHN), 126.9 (q, JC,F = 286.8 Hz, CF3), 133.7 (1

E. Obijalska et al. / Journal of Fluorine Chemistry 151 (2013) 7–11
11
arom. C); both diastereomers: 126.4, 128.6, 129.2 (5 arom. CH)
ppm. Due to low intensity, the signal for C(20) could not be found.
19F NMR (565 MHz, CDCl3):
major diastereomer: ꢀ76.94 (3F,
3473
br.m (OH), 3066w, 2979 m, 2933 m, 1454 m, 1373 m, 1292 m,
1201s, 1164s, 1007 m cmꢀ1. ESI-MS: m/z 262 (50, [M+1]+), 284
(100, [M+23]+).
4.5. Oxidation of thioanisole with (trifluoromethyl)oxaziridines –
general procedure
d
CF3); minor diastereomer: ꢀ76.93 (3F, CF3) ppm. IR (film):
v
The corresponding (trifluoromethyl)oxaziridine
8
or
9
(1.05 mmol) was dissolved in CHCl3 and, subsequently, thioanisole
(1.0 mmol) and methanesulfonic acid (3.0 mmol) were added to
this solution at room temperature. The progress of the reaction was
monitored by TLC, and when the reaction was finished (1–2 h), an
aqueous solution of K2CO3 was added. The resulting mixture was
extracted with CH2Cl2, the separated organic layers were
combined, dried over Na2SO4, filtered, and concentrated in vacuo.
The obtained thioanisole S-oxide was purified by column
chromatography (SiO2, 9:1 hexane/ethyl acetate). Yield: 98–
N-Isopropyl-3-[2,2,2-trifluoro-1-(4-nitrophenyl)-1-hydroxyethyl]
oxaziridine (9c). Yield: 0.251 g (82%); obtained as
a single
diastereomer. Yellowish, viscous oil. 1H NMR (600 MHz, CDCl3):
3
3
d
1.16 (d, JH,H = 6.6 Hz, 3H, CH(CH3)2), 1.22 (d, JH,H = 6.0 Hz, 3H,
CH(CH3)2), 2.43–2.49 (m, 1H, CH(CH3)2), 3.74 (s, 1H, OH), 4.50 (s,
1H, OCHN), 7.76–7.78, 8.20–8.22 (2 m, 4 arom. CH) ppm. 13C NMR
(150 MHz):
d
18.3, 21.1 (CH(CH3)2), 61.2 (CH(CH3)2), 73.9 (q,
116 mg (70–83%), yellowish oil. 1H NMR (600 MHz):
d 2.72 (s,
3H, CH3), 7.50–7.55 (m, 3 arom. H), 7.62–7.67 (m, 2 arom. H) ppm
(lit. [13]).
1
2JC,F = 28.7 Hz, Cq), 78.6 (OCHN), 124.1 (q, JC,F = 288.3 Hz, CF3),
123.6, 127.8 (4 arom. CH), 140.2, 148.6 (2 arom. C) ppm. 19F NMR
(565 MHz, CDCl3):
d
ꢀ76.7 (s, 3F, CF3) ppm. IR (KBr):
v 3385 br.m,
(OH), 3118w, 1610 m, 1526s, 1353s, 1173s, 1058 m cmꢀ1
.
Acknowledgement
N-(tert-Butyl)-3-[2,2,2-trifluoro-1-(4-nitrophenyl)-1-hydroxy
ethyl]oxaziridine (9d). Yields: 0.256 g (80%, method A), 0.262 g
(82%, method B); isolated as a single diastereomer after additional
crystallization. Colorless crystals, m.p. 116–119 8C (hexane/Et2O).
E.O. acknowledges the National Science Center (Poland) for
financial support (Grant ‘SONATA’ # DEC-2011/03/D/ST5/05231)
and the authors thank PD Dr. L. Bigler, University of Zurich, for ESI-
¨
1H NMR (600 MHz):
d 1.18 (s, 9H, C(CH3)3), 4.08 (s, 1H, OH), 4.69 (s,
HRMS.
1H, OCHN), 7.84–7.86, 8.28–8.29 (2 m, 4 arom. CH) ppm. 13C NMR
3
(150 MHz):
d
25.4 (C(CH3)3), 59.0 (C(CH3)3), 73.4 (q, JC,F = 1.5 Hz,
2
1
OCHN), 74.1 (q, JC,F = 28.7 Hz, Cq), 124.3 (q, JC,F = 285.3 Hz, CF3),
123.9, 128.0 (4 arom. CH), 140.7, 148.8 (2 arom. C) ppm. 19F NMR
References
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[2] L. Lykke, C. Rodriguez-Escrich, K.A. Jorgensen, J. Am. Chem. Soc. 133 (2011)
14932–14935.
[3] (a) V.A. Petrov (Ed.), Fluorinated Heterocyclic Compounds: Synthesis, Chemistry,
and Applications, John Wiley & Sons, Inc., Hoboken, New Jersey, 2009;
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(565 MHz):
d
ꢀ76.6 (s, CF3) ppm. IR (KBr):
v3437br.m (OH), 2982w,
1611 m, 1528vs, 1352s, 1274 m, 1200s, 1169vs, 1166s, 854 m cmꢀ1
.
ESI-HRMS: Calcd. for C13H15F3N2O4Na+ ([M+23]+): m/z 343.08761;
found: m/z 343.08728.
N-(tert-Butyl)-3-[1-(benzofuran-2-yl)-2,2,2-trifluoro-1-hydroxy
ethyl]oxaziridine (9e). Yields: 0.214 g (68%, method B), 0.249 g
(79%, method A); isolated as a single diastereomer after fractional
crystallization. Colorless crystals, m.p. 70–72 8C (hexane). 1H NMR
(600 MHz):
d 1.20 (s, 9H, C(CH3)3), 3.87 (s, 1H, OH), 4.85 (s, 1H,
OCHN), 7.03 (s, 1H, 1 arom. CH), 7.26–7.28, 7.33–7.36, 7.54–7.55,
7.61–7.62 (4 m, 4 arom. CH) ppm. 13C NMR (150 MHz):
[8] G. Mloston´ , E. Obijalska, A. Linden, H. Heimgartner, J. Fluorine Chem. 131 (2010)
578–583.
d 25.4
3
(C(CH3)3), 59.0 (C(CH3)3), 72.3 (q, JC,F = 1.5 Hz, OCHN), 72.8 (q,
2JC,F = 29.7 Hz, Cq), 107.7, 111.8, 121.9, 123.3, 125.3 (5 arom. CH),
123.8 (q, 1JC,F = 287.2 Hz, CF3), 127.5, 149.7, 155.7 (3 arom. C) ppm.
´
[9] G. Mloston, E. Obijalska, A. Tafelska-Kaczmarek, M. Zaidlewicz, J. Fluorine Chem.
131 (2010) 1289–1296.
`
´
[10] C. Boudou, M. Berges, C. Sagnes, J. Sopkova-de Oliveira Santos, S. Perrio, P.
Metzner, J. Org. Chem. 72 (2007) 5403–5406.
19F NMR (565 MHz):
d
ꢀ77.0 (s, CF3) ppm. IR (KBr):
(OH), 2983 m, 2971w, 1455w, 1370 m, 1281 m, 1194s, 1160vs,
1136 m, 999 m cmꢀ1 ESI-HRMS: Calcd. for C15H16F3NO3Na+
([M+23]+): m/z 338.09745; found: m/z 338.09757.
v 3481br.m
[11] C. Balsarini, B. Novo, G. Resnati, J. Fluorine Chem. 80 (1996) 31–34.
[12] L. Bohe´, M. Lusinchi, X. Luisinchi, Tetrahedron 55 (1999) 155–166.
[13] J.N. Moorthy, K. Senapati, K.N. Parida, J. Org. Chem. 75 (2010) 8416–8421.
.