The preparation of aliphatic fluorinated sulfoximines

Article abstract of DOI:10.1055/s-2003-37651

This work describes the preparation of an aliphatic series of the N-trifluoromethanesulfonyl-S-trifluoromethyl-S-sulfoximine group. The key step of the synthesis is the imination of fluorinated sulfoxides under experimental conditions, which avoid cleavage of the alkyl group. The formation of sulfoximines 6 and 15 allows the preparation of various fluorinated sulfoximines having strong electron withdrawing properties.

Full text of DOI:10.1055/s-2003-37651

PAPER
565
The Preparation of Aliphatic Fluorinated Sulfoximines
T
E
he Preparation
m
of
A
liphatic Fluori
m
nated
S
ulfoximinesanuel Magnier, Claude Wakselman*
SIRCOB-CNRS, Bâtiment Lavoisier, Université de Versailles-Saint-Quentin, 45 avenue des Etats-Unis, 78035 Versailles, France
Fax +33(1)39254452; E-mail: wakselma@chimie.uvsq.fr
Received 22 October 2002; revised 19 December 2002
(
Figure 1, compounds 2). Preparation of aliphatic com-
Abstract: This work describes the preparation of an aliphatic series
of the N-trifluoromethanesulfonyl-S-trifluoromethyl-S-sulfoximine
group. The key step of the synthesis is the imination of fluorinated
sulfoxides under experimental conditions, which avoid cleavage of
pounds substituted by this powerful electron withdrawing
group would be useful for the study of the stabilization of
an adjacent carbanion and for the synthesis of highly acti-
the alkyl group. The formation of sulfoximines 6 and 15 allows the vated dienophiles.
preparation of various fluorinated sulfoximines having strong elec-
tron withdrawing properties.
Our synthetic plan was close to the one reported by
Yagulpol’skii et al. in the aromatic series but experimen-
tal conditions had to be adapted, especially the imination
step, in order to be compatible with an aliphatic chain
5
Keywords: fluorine, sulfur, arylations, sulfoximines, imination of
sulfoxides
(
Scheme 1).
Since their discovery in 1950 by Bentley and Whitehead,1
Octyl trifluoromethylsulfide (4) was obtained from oc-
tanethiol (3) and bromotrifluoromethane in the presence
of Rongalite (sodium hydroxymethanesulfinate) and so-
sulfoximines have been widely studied. Two main reasons
can explain the increasing popularity of this function: the
unusual chemical versatility of sulfoximines which have
®
dium phosphate according to our previously described
7
2
method. Derivative 4 was not isolated (it was obtained as
made them widely used in synthesis and the great interest
an inseparable mixture with the dioctyl disulfide) and the
crude residue was directly oxidized with MCPBA to give
rise to the sulfoxide 5 with an acceptable overall yield
from the thiol 3 (28% for the two steps). Subsequent imi-
nation of the sulfoxide 5 was crucial and required careful
examination of the experimental conditions. The most
widely used preparation for the construction of ‘free sul-
foximines’ remains the original hydrazoic acid method
of the potential anti-cancer agent, the methionine sulfox-
imine (MSO). More recently, easy preparations of opti-
3
cally active forms of sulfoximines have made them very
4
efficient chiral ligands in asymmetric catalysis. Despite
the interest in sulfoximines, only a few methods for their
synthesis are at the disposal of the organic chemist.
Yagupol’skii et al. in 1986, published the preparation of
highly fluorinated sulfoximines, N-trifluoromethane-
8
developed by Whitehead and Bentley, where sulfuric
acid is added to a suspension of sodium azide in chloro-
form containing the precursor sulfoxide. It has been sug-
sulfonyl-S-trifluoromethyl-S-arylsulfoximines
Figure 1). To the best of our knowledge, the synthesis of
1a–c5
(
this type of sulfoximines has been described only in the
aromatic series. By chemical analogy, the skeleton of
these compounds is close to the structure of triflones,
gested that the reaction involves nucleophilic attack by the9
sulfur atom on a protonated hydrazoic acid intermediate.
Unfortunately, these conditions are not suited to trifluo-
romethylsulfoxides, which are not iminated by sodium
where one of the oxygens is replaced by the N–SO CF3
2
group. These particular fluorinated sulfoximines are re-
ported to possess electron-withdrawing effects greater
than that of the corresponding triflones.6
10
11
azide in sulfuric acid. Yagupol’skii et al. have found
that imination of aryltrifluoromethylsulfoxides occurs if
the sulfuric acid is replaced by oleum and the reaction
We describe here the extension of the range of known per- heated at 70 °C. This last method however seemed to us to
fluoroalkylated sulfoximines in the aliphatic series be too drastic for our substrate 5. Under the strongly acid-
ic conditions of this reaction, heterolysis of the carbon–
sulfur bond can occur, alkyl groups tend to be lost when a
O
O
N-R
R'
CF3
positive charge is built up on sulfur by protonation in the
S
S
CF3SO2N
9
RF
reaction medium. We thus decided to combine the two
1
2
described methods. Treatment of a suspension of sulfox-
ide 5 and sodium azide by oleum in dichloromethane at
room temperature gave rise to the desired sulfoximine 6 in
good yield. Lastly, the latter was transformed into its de-
rivative 7 by treatment with pyridine and trifluo-
2
R = H, Ar, TMS, SO2RF, NO2
R' = CH3, C8H17
1
a–c R = Cl, F, NO2
R
RF = CF3, C8F17
Figure 1
13
romethanesulfonic anhydride. This reaction sequence
allowed us to introduce the N-trifluoromethanesulfonyl-S-
trifluoromethyl-sulfoximine on an alkyl chain with an ac-
ceptable 18% overall yield, starting from the commercial
thiol.
Synthesis 2003, No. 4, Print: 18 03 2003.
Art Id.1437-210X,E;2003,0,04,0565,0569,ftx,en;P05702SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
©

5
66
E. Magnier, C. Wakselman
PAPER
Scheme 1
O
N-SO2C4F9
BSTFA, MeCN
8 h, reflux, 74%
O
N-TMS
C8H17
NaH, C4F9SO2F
S
6
S
CF3
C8H17
THF, 24 h, reflux, 75%
CF3
9
8
Scheme 2
The relatively easy preparation of the versatile ‘free sul-
foximine’ 6 allowed us to develop the synthesis of various
fluorinated sulfoximines possessing electron withdrawing
properties.
Compound 6 was thus converted into its trimethylsilyl de-
rivative 8 by treatment with bis(trimethylsilyl)trifluoroac-
etamide (BSTFA), in good yield. Utilization of
1
4
bis(trimethylsilyl)acetamide (BSA) gave a much lower
yield. Sulfoximine 8 is also a convenient intermediate for
the preparation of other funtionalized sulfoximines. Fur-
thermore, treatment of 6 with base and perfluorobutane-
sulfonyl fluoride gave rise to the sulfoximine 9 in a good Scheme 4
yield (Scheme 2).
Another means to increase the electron withdrawing pow-
The methodology described in Scheme 1 has also been
applied to the synthesis of the new sulfoximine 16 as pre-
sented in Scheme 5. Dimethyl disulfide was perfluorooc-
tylated following our method and the resulting thioether
was oxidized with MCPBA to give rise to the sulfoxide
er of our sulfoximine was to introduce a nitro group on the
nitrogen. For this purpose, we used a method already de-
1
5
scribed for non-fluorinated sulfoximines. Treatment of
the sulfoxide 6, first with nitric acid to protonate 6, then
with acetic anhydride (Scheme 3) and catalytic sulfuric
acid gave rise to the compound 10.
17
1
4. Imination was then carried out in good yield. Howev-
er, introduction of the triflyl group proved difficult due to
1
6
Bolm et al. have published an efficient method to intro- the low solubility of the free sulfoximine 15. Sulfoximine
duce aromatic rings on to the nitrogen of sulfoximines. 16 was thus obtained in four steps starting from the com-
The authors described the N-arylation of non-fluorinated mercial dimethyl disulfide 12.
In conclusion, we have described an efficient methodolo-
gy suitable for the synthesis of new fluorinated sulfox-
imines, with high electron withdrawing power, in the
aliphatic series. Further applications of these new com-
pounds in organic chemistry are currently under investi-
gation in our laboratory.
1
) HNO3, CH2Cl2, 10 min, RT
) Ac2O, H2SO4, 1 h, 0 °C to r.t.
O
N-NO2
C8H17
6
S
2
CF3
51%
10
Scheme 3
Melting points were determined on a Mettler FP61 apparatus. NMR
spectra were recorded in CDCl solutions, on a Bruker AC-300
spectrometer. Reported coupling constants and chemicals shifts
were based on a first-order analysis. Internal reference was the re-
3
sulfoximines by coupling with various aryl bromides, in
the presence of palladium acetate and BINAP as an elec-
tron rich ligand. To our delight, this procedure was effi-
1
sidual peak of CHCl (7.27 ppm) for H (300 MHz) NMR spectra,
3
1
3
ciently applied to our sulfoximines. Under the described central peak of CDCl (77 ppm) for C (75 MHz) NMR spectra, in-
3
1
9
conditions, benzonitrile and 2,4-dinitrobenzene were in- ternal CFCl (0 ppm) for F (282 MHz) NMR spectra. Chemical
3
shifts are reported in parts per million (ppm) and constants J in
Hertz (Hz). The peaks are characterized by s (singlet), d (doublet),
t (triplet). Mass spectra were carried out at the Ecole Normale
troduced on the nitrogen of the sulfoximine 6 to afford re-
spectively 11a and 11b in reasonable yield (Scheme 4).
Synthesis 2003, No. 4, 565–569 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Preparation of Aliphatic Fluorinated Sulfoximines
567
Scheme 5
–
1
Supérieure (Paris). IR spectra were recorded on a Nicolet 400SD
spectrometer. Elemental analyses were determined by the Microan-
alytical laboratory of the CNRS (Gif sur Yvette). Column chroma-
tography was performed with Merck silica gel (70–230 mesh) using
various solvents. Reagents were obtained from various commercial
sources and used as received. All solvents were distilled prior to use
and all reactions were carried out under argon.
IR (neat): 3149 (br), 2960, 2929, 2847, 1193 cm .
1
H NMR (300 MHz, CDCl ): δ = 3.17 (m, 2 H, CH S), 1.95 (m, 2
H, CH ), 1.47 (m, 2 H, CH ), 1.27 (m, 8 H, 4 CH ), 0.88 (t, 3 H,
3
2
2
2
2
J = 8.1 Hz, CH3).
1
3
C NMR (77 MHz, CDCl ): δ = 120.7 (q, CF , J = 340.8 Hz), 49.1
CH S), 31.6, 28.9, 28.8, 28.4, 22.4, 20.7, 13.8 (CH ).
3
3
(
2
3
1
9
F NMR (282 MHz, CDCl ): δ = –79.7 (s, CF ).
3
3
Octyl Trifluoromethylsulfoxide (5)
A mixture of octanethiol (20 g, 0.14 mol) and sodium phosphate (27
g, 0.16 mol) in DMF (270 mL) was stirred for 15 min in a heavy
+
MS (CI, NH ): m/z = 246 [MH ].
3
HRMS: m/z calcd for C
H F ONS: 246.1139; found, 246.1145.
19 3
9
walled glass flask (Parr apparatus). H O (13 mL) and Rongalite
2
Anal. Calcd for C H F NOS: C, 44.07; H, 7.40; N, 5.71. Found: C,
9
18 3
(
63.3 g, 0.41 mol) were then quickly introduced. The flask was im-
4
4.03; H, 7.38; N, 5.83.
mediately evacuated (5 mm Hg) before being connected to a bro-
motrifluoromethane pressure cylinder. The pressure was
maintained at 4.5 bar, with constant shaking, during the absorption
process which takes ca. 8 h. The apparatus was vented, then the su-
S-Perfluorooctyl-S-methyl-sulfoximine (15)
White powder; yield: 91% (2.83 g).
Mp 123.8 °C
pernatant liquor was removed and diluted with H O (500 mL). The
2
–
1
remaining salts were taken up in Et O (100 mL), filtered on celite,
IR (nujol): 3144 (br), 2955, 2924, 2852, 1465, 1260, 1198 cm .
2
and washed with Et O (100 mL). The aq phase was extracted with
2
1
H NMR (300 MHz, CDCl ): δ = 3.16 (s, 3 H).
3
Et O (5 × 300 mL). The combined organic layers were washed with
2
13C NMR (77 MHz, CDCl
): δ = 37.6 (CH ).
NaHCO (5 × 300 mL), brine, then dried over MgSO and concen-
3
3
3
4
trated under reduced pressure. The crude mixture was diluted in
CH Cl (680 mL), then MCPBA 70% (84.3 g, 0.48 mol) was added
at 0 °C. The reaction was stirred for 2 d at this temperature, then fil-
19
F NMR (282 MHz, CD OD): δ = –81.2 (s, CF ), –111.9 (d, AB
3
3
2
2
system, SCF F ), –117.1 (d, AB system, SCF F ), –120.5 (d, CF ),
1 2 1 2 2
–
121.9 (s, 3 CF ), –123.1 (s, CF ), –126.6 (s, CF ).
2 2 2
tered on celite. The organic layer was washed with H O (2 × 200
2
MS (CI, NH ): m/z = 515 [M + 18].
mL), NaHCO (5 × 300 mL), brine (200 mL), dried over MgSO ,
3
3
4
concentrated under reduced pressure and the residue was purified
HRMS: m/z calcd for C H F NOS: 497.9820; found, 497.9821.
9 4 17
by column chromatography (pentane–Et O, 98:2). Compound 5
2
was isolated as a colorless oil in 28% (8.9 g) yield.
N-Trifluoromethanesulfonyl-S-trifluoromethyl-S-octyl-sulfox-
imine (7)
–
1
IR (neat): 2962, 2930, 2853, 1205 cm .
A mixture of the sulfoximine 6 (0.3 g, 1.22 mmol) and pyridine (0.3
g, 3.66 mmol) in CH Cl (14 mL) was cooled to 0 °C. Triflic anhy-
1
H NMR (300 MHz, CDCl ): δ = 3.08 (m, 1 H, CH H S), 2.87 (m,
3
1
2
2
2
1
H, CH H S), 1.90 (m, 2 H, CH ), 1.51 (m, 2 H, CH ), 1.32 (m, 8
1 2 2 2
dride (0.5 g, 1.83 mmol) was added dropwise at this temperature,
then the reaction was stirred for 4 h at r.t. CH Cl (30 mL) was add-
H, 4 CH ), 0.88 (t, 3 H, J = 8.1 Hz, CH ).
2
3
2
2
1
3
C NMR (77 MHz, CDCl ): δ = 125.3 (q, CF , J = 340.2 Hz), 48.4
ed and the organic layer was washed with H
(3 × 20 mL), H O (20 mL), dried over MgSO , concentrated under
4
2
O (30 mL), HCl 2 N
3
3
(
q, CH S, J = 2.8 Hz), 31.5, 28.9, 28.8, 28.5, 22.4, 21.6, 13.9 (CH ).
2
2
3
reduced pressure and the residue was purified by column chroma-
1
9
F NMR (282 MHz, CDCl ): δ = –74.3 (s, CF ).
3
3
tography (pentane–Et O, 9:1). Compound 7 was isolated as a color-
2
MS (EI, 70 eV): m/z (%) = 161 (5) [M – CF ], 112 (20), 83 (75), 69
less oil in 95% (0.44 g) yield.
3
(
100).
–
1
IR (neat): 2965, 2924, 2858, 1465, 1383, 1234 cm .
Anal. Calcd for C H F OS: C, 46.94; H, 7.44. Found: C, 47.19; H,
9
17
3
1
H NMR (300 MHz, CDCl ): δ = 3.59 (m, 2 H, CH S), 2.03 (m, 2
3
2
7
.66.
H, CH ), 1.54 (m, 2 H, CH ), 1.32 (m, 8 H, 4 CH ), 0.89 (t, 3 H,
2
2
2
J = 8.1 Hz, CH3).
13C NMR (77 MHz, CDCl
S-Trifluoromethyl-S-octyl-sulfoximine (6)
A mixture of sulfoxide 5 (5 g, 21.7 mmol) and NaN (2.8 g, 43.5
): δ = 119.9 (q, CF , J = 331.3 Hz), 118.9
3
3
3
mmol) in CH Cl (31 mL) was cooled to 0 °C. Oleum 30–33% (10
(q, CF , J = 320.5 Hz), 52.0 (CH S), 31.5, 28.7, 28.6, 27.8, 22.4,
20.7, 13.8 (CH ).
3
3
2
2
2
mL) was added dropwise at this temperature, then the reaction was
stirred for 16 h at r.t. under a slight pressure of argon and then
poured onto ice. The phases were separated and the aq phase was
extracted with CH Cl (3 × 50 mL). The organic layers were mixed,
19
F NMR (282 MHz, CDCl ): δ = –73.7 (s, CF ), –78.8 (s, CF ).
3
3
3
MS (CI, NH ): m/z = 395 [M + 18].
3
2
2
+
dried over MgSO and concentrated under reduced pressure. Purifi-
MS (EI, 70 eV): m/z (%) = 377 (2%), [M ], 196 (40), 69 (100).
HRMS: m/z calcd for C H F NO S : 378.0632; found, 378.0636.
4
cation by distillation under vacuum (90 °C, 1 mm Hg) afforded the
desired sulfoximine 6 as a colorless liquid in 70% (3.8 g) yield.
1
0
17
6
3 2
Synthesis 2003, No. 4, 565–569 ISSN 0039-7881 © Thieme Stuttgart · New York

5
68
E. Magnier, C. Wakselman
PAPER
1
3
Anal. Calcd for C H F NO S : C, 31.83; H, 4.54; N, 3.71. Found:
C NMR (77 MHz, CDCl ): δ = 120.9 (q, CF , J = 341.9 Hz), 48.3
10
18
6
3
2
3
3
C, 32.17; H, 4.61; N, 3.74.
(CH S), 31.5, 28.7, 28.6, 28.1, 22.4, 21.6, 13.9 (CH ).
2
3
1
9
F NMR (282 MHz, CDCl ): δ = –66.3 (s, CF ).
3
3
N-Trimethylsilyl-S-trifluoromethyl-S-octyl-sulfoximine (8)
A soln of the sulfoximine 6 (0.5 g, 2.04 mmol) and bis(trimethylsi-
+
MS (CI, NH ): m/z = 291 [MH ], 308 [M + 18].
3
lyl)trifluoroacetamide BSTFA (0.68 g, 2.65 mmol) in CH CN (5
mL) was refluxed for 8 h. The reaction mixture was concentrated
under reduced pressure and the residue was purified by column
3
HRMS: m/z calcd for C H F N O S: 291.0990; found, 291.0988.
9 18 3 2 3
Anal. Calcd for C H F N O S: C, 37.24; H, 5.90; N, 9.65. Found:
9
17
3
2
3
C, 37.45; H, 5.92; N, 9.54.
chromatography (pentane–Et O, 9:1). Compound 8 was isolated as
2
a colorless oil in 74% (0.5 g) yield.
N-(2-Cyanophenyl)-S-trifluoromethyl-S-octyl-sulfoximine
11a)
A soln of the sulfoximine 6 (0.16 g, 0.65 mmol) in toluene (6.5 mL)
–
1
IR (neat): 2960, 2924, 2858, 1475, 1280, 1183 cm .
(
1
H NMR (300 MHz, CDCl ): δ = 3.04 (m, 2 H, CH S), 1.84 (m, 2
3
2
was transferred via canula to a Schlenk tube charged with Pd(OAc)2
H, CH ), 1.43 (m, 2 H, CH ), 1.29 (m, 8 H, 4 CH ), 0.89 (t, 3 H,
2
2
2
(0.0073 g, 0.0325 mmol) and BINAP (0.0305 mg, 0.049 mmol). 2-
J = 8.1 Hz, CH ), 0.20 (s, 9 H, SiMe ).
3
3
bromobenzonitrile (0.12 g, 0.65 mmol) and cesium carbonate (0.3
g, 0.91 mmol) were added, the reaction was heated at reflux for 2 h
then concentrated under reduced pressure. The residue was purified
1
3
C NMR (77 MHz, CDCl ): δ = 120.5 (q, CF , J = 341.3 Hz), 52.6
3
3
(
CH S), 31.6, 28.9, 28.8, 28.3, 22.5, 20.7, 13.9 (CH ), 1.6 (s,
2
3
SiMe3).
by column chromatography (pentane–Et O, 9:1). Compound 11a
2
1
9
F NMR (282 MHz, CDCl ): δ = –80.2 (s, CF ).
was isolated as a colorless oil in 43% (0.12 g) yield.
3
3
MS (CI, NH ): m/z = 246 [(M – SiMe ) + 1].
IR (neat): 2960, 2924, 2858, 2228, 1598, 1480, 1449, 1332, 1198
cm .
3
3
–
1
HRMS: m/z calcd for C H F NOSSi: 318.1535; found, 318.1528.
1
2
27 3
1
H NMR (300 MHz, CDCl ): δ = 7.57 (dd, 1 H, CH Ar, J = 7.9
H6–H5
3
6
N-Perfluorobutylsulfonyl-S-trifluoromethyl-S-octyl-sulfox-
imine (9)
Hz, JH6–H4 = 1.6 Hz), 7.44 (ddd, 1 H, CH Ar, J
= 8.2 Hz,
5
H5–H4
JH5–H3 = 1.6 Hz), 7.34 (dd, 1 H, CH Ar, J
= 7.5 Hz), 7.11 (ddd,
3
H3–H4
A soln of the sulfoximine 6 (1.8 g, 7.34 mmol) in THF (35 mL) was
cooled to 0 °C. NaH 60% in mineral oil (0.6 g, 14.7 mmol) was add-
ed portionwise under argon and the reaction stirred for 2 h at r.t. Per-
fluorobutanesulfonyl fluoride (6.73 g, 22.1 mmol) was added and
the reaction was stirred for 6 h at r.t. and 16 h at reflux. The reaction
1 H, CH Ar), 3.47 (m, 1 H, CH H S), 3.34 (m, 1 H, CH H S), 2.10
4 1 2 1 2
(m, 2 H, CH ), 1.54 (m, 2 H, CH ), 1.30 (m, 8 H, 4 CH ), 0.89 (t, 3
2
2
2
H, J = 8.1 Hz, CH3).
13
C NMR (77 MHz, CDCl ): δ = 145.1 (C–N), 133.4 (CH), 133.3
3
(
(
CH), 123.6 (CH), 123.2 (CH), 121.2 (q, CF , J = 340.2 Hz), 117.2
3
mixture was poured into H O (40 mL). The aq layer was extracted
2
C–CN), 108.7 (CN), 51.2 (CH S), 31.6, 28.8, 28.7, 28.2, 22.5,
2
with CH Cl (3 × 50 mL), dried over MgSO , concentrated under
2
2
4
2
1.0, 13.9 (CH3).
reduced pressure and the residue was purified by column chroma-
1
9
F NMR (282 MHz, CDCl ): δ = –73.0 (s, CF ).
tography (pentane–Et O, 9:1). Compound 9 was isolated as a color-
3
3
2
less oil in a 75% (2.9 g) yield.
MS (CI, NH ): m/z = 364 [M + 18].
3
–
1
IR (neat): 2960, 2934, 2857, 1475, 1388, 1234, 1183 cm .
HRMS: m/z calcd for C H F N OS: 347.1405; found, 347.1404.
1
6
22
3
2
1
H NMR (300 MHz, CDCl ): δ = 3.62 (m, 2 H, CH S), 2.08 (m, 2
3
2
Anal. Calcd for C H F N OS: C, 55.48; H, 6.11; N, 8.09. Found:
16 21 3 2
C, 55.86; H, 6.25; N, 7.84.
H, CH ), 1.55 (m, 2 H, CH ), 1.37 (m, 8 H, 4 CH ), 0.90 (t, 3 H,
2
2
2
J = 8.1 Hz, CH3).
1
3
N-(2,4-Dinitrophenyl)-S-trifluoromethyl-S-octyl-sulfoximine
11b)
Colorless oil; yield: 67% (0.22 g).
C NMR (77 MHz, CDCl ): δ = 52.2 (CH S), 31.4, 28.5, 28.4, 27.7,
3
2
(
2
1
2.3, 20.8, 13.5 (CH3).
9
F NMR (282 MHz, CDCl ): δ = –73.9 (s, CF ), –81.3 (s, CF ),
3
3
3
–
1
IR (neat): 2955, 2934, 2858, 1608, 1536, 1480, 1342, 1198 cm .
–
112.3 (s, CF ), –121.5 (s, CF ), –126.5 (s, CF ).
2 2 2
1
H NMR (300 MHz, CDCl ): δ = 8.62 (d, 1 H, CH Ar, J
= 2.6
MS (CI, NH ): m/z = 545 [M + 18].
3
3
H3–H5
3
Hz), 8.28 (dd, 1 H, CH Ar, J
= 8.9 Hz), 7.59 (d, 1 H, CH Ar),
5
H5–H6
6
HRMS: m/z calcd for C H F NO S : 528.0537; found, 528.0532.
1
3
18 12
3 2
3
.42 (m, 2 H, CH S), 2.05 (m, 2 H, CH ), 1.53 (m, 2 H, CH ), 1.30
2 2 2
Anal. Calcd for C H F NO S : C, 29.61; H, 3.25; N, 2.66. Found:
(m, 8 H, 4 CH ), 0.89 (t, 3 H, J = 8.1 Hz, CH ).
1
3
17 12
3
2
2
3
C, 29.57; H, 3.27; N, 2.76.
13
C NMR (77 MHz, CDCl ): δ = 144.2 (C–N), 142.3 (C–NO ),
3
2
1
42.0 (C–NO ), 127.2 (CH), 124.9 (CH), 121.0 (q, CF , J = 345.0
2
3
N-Nitro-S-trifluoromethyl-S-octyl-sulfoximine (10)
Hz), 120.6 (CH), 51.4 (CH S), 31.5, 28.8, 28.7, 28.0, 22.5, 20.7,
1
2
HNO 100% (0.088 mL) was added dropwise to a soln of the sul-
3
3.9 (CH3).
foximine 6 (0.5 g, 2.04 mmol) in CH Cl (4 mL). The reaction mix-
2
2
1
9
F NMR (282 MHz, CDCl ): – 73.3 (s, CF ).
ture was stirred for 10 min and cooled to 0 °C. Acetic anhydride (4
mL), H SO (1 drop) were added and the reaction mixture was
3
3
2
4
MS (CI, NH ): m/z = 429 [M + 18].
3
stirred for 15 min at 0 °C, then for 1 h at ambient temperature.
CH Cl was added and the organic phase was washed with H O (10
HRMS: m/z calcd for C H F N O S: 412.1154; found, 412.1149.
1
5
21
3
3
5
2
2
2
mL), NaHCO (3 × 30 mL), H O (20 mL), dried over MgSO , con-
Anal. Calcd for C15
H
20
F
3
N
2
O
5
S: C, 43.79; H, 4.90; N, 10.21.
3
2
4
centrated under reduced pressure and the residue purified by col-
Found: C, 44.03; H, 5.09; N, 10.51.
umn chromatography (pentane–Et O, 95:5). Compound 10 was
isolated as a colorless oil in 51% (0.31 g) yield.
2
Perfluorooctyl Methylsulfide (13)
Dimethyl disulfide (5 g, 53 mmol) was dissolved in DMF (65 mL)
IR (neat): 2955, 2919, 2852, 2253, 1541, 1465, 1301, 1260, 1132
cm .
–
1
under argon. Perfluorooctyl iodide C
8
F17I (60.82 g, 111.4 mmol),
pre-washed with a 10% aq soln of Na S O , was added followed by
2
2
5
1
H NMR (300 MHz, CDCl ): δ = 3.47 (m, 2 H, CH S), 2.01 (m, 2
3
2
H O (4 mL). Lastly, sodium hydroxymethanesulfinate (24.5 g,
2
H, CH ), 1.51 (m, 2 H, CH ), 1.32 (m, 8 H, 4 CH ), 0.89 (t, 3 H,
2
2
2
159.2 mmol) was added in portions over 6 h. The soln was stirred
J = 8.1 Hz, CH3).
Synthesis 2003, No. 4, 565–569 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Preparation of Aliphatic Fluorinated Sulfoximines
569
at r.t. for 20 h and diluted with H O (300 mL). The mixture was ex-
SCF F ), –119.1 (d, CF ), –121.6 (s, CF ), –122.0 (s, CF ), –122.3
2
1
2
2
2
2
tracted with Et O (3 × 100 mL) and the organic layer washed with
(s, CF ), –123.1 (s, CF ), –126.5 (s, CF ).
2 2 2
2
NaHCO (5% in H O, 3 × 100 mL) and H O (200 mL), then dried
3
2
2
MS (CI, NH ): m/z = 647 [M + 18].
3
over MgSO , and concentrated under reduced pressure. Purification
4
HRMS: m/z calcd for C H F NO S : 629.9313; found, 629.9307.
by distillation under vacuum (60 °C, 15 mm Hg) afforded the de-
10
3
20
3 2
sired sulfide 13 as a colorless liquid in 40% (20 g) yield.
1
H NMR (300 MHz, CDCl ): δ = 2.41 (s, 3 H).
3
Acknowledgments
1
1
3
C NMR (77 MHz, CDCl ): δ = 40.2 (CH ).
3
3
This work was supported by the Centre National de la Recherche
Scientifique. We thank Atofina for the generous gift of the perfluo-
roalkyl halides, Dr. M. Popkin and Dr. K. Wright for improvement
of the English manuscript.
9
F NMR (282 MHz, CDCl ): δ = –81.6 (s, CF ), –91.2 (s, CF ),
3
3
2
–
–
120.6 (CF ), –122.0 (s, CF ), –122.6 (s, 2 CF ), –123.5 (s, CF ),
2
2
2
2
126.9 (s, CF2).
Perfluorooctyl Methylsulfoxide (14)
Compound 13 (6.00 g, 12.8 mmol) was diluted in CH Cl (65 mL) References and Notes
2
2
and mCPBA 70% (3.17 g, 12.8 mmol) was added at 0 °C. The reac-
tion was stirred for 1 d at this temperature, then filtered over celite.
The organic layer was washed with H O (2 × 200 mL), NaHCO
(
1) Bentley, H. R.; Whitehead, J. K. J. Chem. Soc. (D) 1950,
081.
2
2
3
(2) (a) Johnson, C. R. In Comprehensive Organic Chemistry,
(
5 × 300 mL), brine (200 mL), dried over MgSO then concentrated
4
Vol 3; Barton, D.; Ollis, W. D., Eds.; Pergamon: Oxford,
under reduced pressure. Compound 14 was isolated without further
purification as a white powder in 90% (5.60 g) yield; mp 85.2 °C.
1979, 223–232. (b) Johnson, C. R. Aldrichimica Acta 1985,
18, 3. (c) Reggelin, M.; Zur, C. Synthesis 2000, 1.
–
1
IR (nujol): 2929, 2960, 2858, 1460, 1372 cm .
(3) Bailey, H. H. Chem. Biol. Interact. 1998, 111, 239.
(4) Bolm, C.; Simi , O. J. Am. Chem. Soc. 2001, 123, 2081; and
references therein.
(5) (a) Kondratenko, N. V.; Popov, V. I.; Radchenko, O. A.;
Ignatev, N. V.; Yagupol’skii, L. M. Zh. Org. Khim. 1986, 22,
1716. (b) Yagupol’skii, L. M. J. Fluorine Chem. 1987, 36, 1.
(6) (a) Boiko, V. N.; Kirii, N. V.; Yagupol’skii, L. M. J.
Fluorine. Chem. 1994, 67, 119. (b) Bzhezovsky, V.;
Penkovsky, V. Phosphorous, Sulfur Silicon Relat. Elem.
1994, 95, 413.
1
H NMR (300 MHz, CDCl ): δ = 2.87 (s, 3 H).
3
1
3
C NMR (77 MHz, CDCl ): δ = 34.1 (CH ).
3
3
1
9
F NMR (282 MHz, CDCl ): δ = –81.1 (s, CF ), –116.7 (d, AB sys-
3
3
tem, SCF F ), –121.1 (s, CF ), –122.3 (s, 3 CF ), –123.2 (s, CF ),
1
2
2
2
2
–
124.1 (d, AB system, SCF F ), –126.6 (s, CF ).
1 2 2
MS (CI, NH ): m/z = 500 [M + 18].
3
HRMS: m/z calcd for C H F OS: 482.9711; found, 482.9716.
9
3 17
(
7) Anselmi, A.; Blazejewski, J.-C.; Tordeux, M.; Wakselman,
C. J. Fluorine. Chem. 2000, 105, 41.
8) Bentley, H. R.; Whitehead, J. K. J. Chem. Soc. 1952, 1572.
N-Trifluoromethanesulfonyl-S-perfluorooctyl-S-methyl-sul-
foximine (16)
(
To a soln of the sulfoximine 15 (0.75 g, 1.52 mmol) in CH Cl (15
(9) Johnson, C. R.; Janiga, E. R. J. Am. Chem. Soc. 1973, 95,
7692.
10) We assume that the lack of reactivity is due to the poor
nucleophilicity of the sulfur because of the presence of the
trifluoromethyl group.
(11) Kondratenko, N. V.; Radchenko, O. A.; Yagupol’skii, L. M.
Zh. Org. Khim. 1984, 20, 2250.
(12) Attempts at imination of sulfoxide 5 under Yagupol’skii’s
conditions gave rise to a complex mixture of products in a
low yield. In Bentley and Whitehead’s conditions no
transformation of the fluorinated sulfoxide 5 was observed.
2
2
mL), NaH 60% dispersion in mineral oil (0.1 g, 2.43 mmol) was
added in portions at 0 °C. The reaction mixture was refluxed for 30
min and cooled again to 0 °C. Triflic anhydride (0.86 g, 3.03 mmol)
was then added dropwise, then the reaction mixture was refluxed for
(
8
h and poured into ice. The phases were separated and the aq phase
was extracted with CH Cl (3 × 50 mL). The organic layers were
2
2
combined, dried over MgSO and concentrated under reduced pres-
4
sure. The residue was purified by column chromatography (pen-
tane–Et O, 9:1). Compound 16 was isolated as colorless oil in a
2
4
0% (0.54 g) yield.
(
(
(
13) Craig, D.; Geach, N. J. Synlett 1993, 481.
14) Hwang, K. J. J. Org. Chem. 1986, 51, 99.
15) Mutti, R.; Winternitz, P. Synthesis 1986, 426.
Mp 127 °C.
–
1
IR (nujol): 2950, 2924, 2847, 1470, 1383, 1219, 1152 cm .
1
H NMR (300 MHz, CDCl ): δ = 3.69 (s, 3 H).
(16) Bolm, C.; Hildebrand, J. P. J. Org. Chem. 2000, 65, 169.
(17) (a) Wakselman, C.; Tordeux, M.; Clavel, J.-L.; Langlois, B.
J. Chem. Soc., Chem. Commun. 1991, 993. (b)Clavel, J.-L.;
Langlois, B.; Nantermet, R.; Tordeux, M.; Wakselman, C. J.
Chem. Soc., Perkin Trans. 1 1992, 3371.
3
1
3
C NMR (77 MHz, CDCl ): δ = 40.1 (CH ).
3
3
1
9
F NMR (282 MHz, CDCl ): δ = –78.9 (s, NSO CF ), –81.2 (s,
3
2
3
CF ), –108.2 (d, AB system, SCF F ), –111.3 (d, AB system,
3
1 2
Synthesis 2003, No. 4, 565–569 ISSN 0039-7881 © Thieme Stuttgart · New York