One-pot synthesis and asymmetric oxidation of 2-nitro-4-(trifluoromethyl) benzene containing sulfides

Article abstract of DOI:10.1080/10426507.2010.547893

An efficient one-pot method for the preparation of 2-nitro-4- (trifluoromethyl)benzene containing sulfides from 1,1'-disulfanediylbis[2-nitro- 4-(trifluoromethyl)benzene] is proposed. The corresponding enantiomerically enriched sulfoxides with up to 78% enantiomeric excess are prepared by the asymmetric oxidation of sulfides using a modified Sharpless method. The yield of sulfoxides is shown to decrease with an increase in the bulk of the aliphatic group and with a decrease of the inductive effect of the hydrocarbonic moiety on the sulfur atom. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.547893

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One-Pot Synthesis and Asymmetric
Oxidation of 2-Nitro-4-
(Trifluoromethyl)Benzene Containing
Sulfides
Konstantin S. Rodygin a , Svetlana A. Rubtsova a , Alexander V.
Kutchin a & Pavel A. Slepukhin a
a Institute of Chemistry of Komi Scientific Centre, Ural Branch of
Russian Academy of Sciences, Syktyvkar, Russia
b Institute of Organic Synthesis, Ural Branch of Russian Academy of
Sciences, Ekaterinburg, Russia
Published online: 24 Aug 2011.
To cite this article: Konstantin S. Rodygin , Svetlana A. Rubtsova , Alexander V. Kutchin & Pavel A.
Slepukhin (2011) One-Pot Synthesis and Asymmetric Oxidation of 2-Nitro-4-(Trifluoromethyl)Benzene
Containing Sulfides, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:9, 1885-1894, DOI:
10.1080/10426507.2010.547893
To link to this article: http://dx.doi.org/10.1080/10426507.2010.547893
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Phosphorus, Sulfur, and Silicon, 186:1885–1894, 2011
Copyright ꢀC 2011 Komi Scientific Centre
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.547893
ONE-POT SYNTHESIS AND ASYMMETRIC OXIDATION
OF 2-NITRO-4-(TRIFLUOROMETHYL)BENZENE
CONTAINING SULFIDES
Konstantin S. Rodygin,1 Svetlana A. Rubtsova,1
Alexander V. Kutchin,1 and Pavel A. Slepukhin1
1Institute of Chemistry of Komi Scientific Centre, Ural Branch of Russian Academy
of Sciences, Syktyvkar, Russia
2Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences,
Ekaterinburg, Russia
GRAPHICAL ABSTRACT
Abstract An efficient one-pot method for the preparation of 2-nitro-4-(trifluoromethyl)benzene
containing sulfides from 1,1ꢁ-disulfanediylbis[2-nitro-4-(trifluoromethyl)benzene] is proposed.
The corresponding enantiomerically enriched sulfoxides with up to 78% enantiomeric excess
are prepared by the asymmetric oxidation of sulfides using a modified Sharpless method. The
yield of sulfoxides is shown to decrease with an increase in the bulk of the aliphatic group and
with a decrease of the inductive effect of the hydrocarbonic moiety on the sulfur atom.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Fluorinated sulfides; fluorinated sulfoxides; asymmetric sulfoxidation; Sharpless
method
INTRODUCTION
The interest in chiral sulfoxides is due to their employment in asymmetric synthesis1
and enantioselective catalysis as ligands.2 The increasing use of chiral sulfur ligands in
asymmetric catalysis has been published in recent reviews.3 Nonracemic sulfoxides are
also employed in enantioselective organocatalysis.4 The next aspect of enantiomerically
enriched sulfoxides employment is related to their high biological activity.5 It should be
Received 28 September 2010; accepted 9 December 2010.
This work was supported by the RFBR (the project 10-03-00969) and programs of basic researches BGTC-
01 (the project 09-Т-3-1015). The authors wish to thank V. Polukeev (CJSC «Vekton») for the generous loan of
the corresponding disulfide.
Address correspondence Konstantin S. Rodygin, Institute of Chemistry of Komi Scientific Centre,
Ural Branch of Russian Academy of Sciences, Pervomaiskaja 48, 167982, Syktyvkar, Russia. E-mail:
konstantinrs@rambler.ru
1885

1886
K. S. RODYGIN ET AL.
noted that in the last years, nonracemic compounds are widely used in pharmaceutical
industry,6 among them are sulfinyl derivatives, that play an essential role.7
Fluorinated sulfoxides are of special interest. The introduction of a trifluoromethyl
group allows one not only to retain high pharmacological activity of sulfoxides but also
to increase considerably the solubility in nonpolar solvents and lipids, which obviously
increases the speed of absorption and plays a key role in the compound’s transportation in
vivo.8 Fluoro-containing sulfoxides remain an insufficiently explored class of compounds
inspite of the shown interest of the researchers9 and the fact that some fluorinated sub-
strates have already been employed as insecticides,10 gastric acid secretion inhibitors,11
and antileishmanial preparations.12 Among the methods for preparation of enantiomeri-
cally enriched sulfoxides (separation of a racemic mixture,13 transformation of a reagent
from the chiral pool,14 enzymatic systems,15 or the use of chiral catalyst for enantios-
elective synthesis16), there is a simple and universal method of approach, based on the
enantioselective oxidation of the corresponding prochiral sulfides with the use of catalytic
systems.
According to the literature data,17 the Sharpless method modified by Kagan allows
one to carry out the enantioselective oxidation of alkyl aryl sulfides in good yields and high
enantiomeric excess (ee).
Preparation of thioethers (the initial substrates for oxidation) is also an important
problem of modern organic chemistry. It is related not only to the fact that sulfides are the
main intermediates in the synthesis of sulfoxides, but also to the role in bio-organic and
medicinal chemistry.18 There are a number of methods for the preparation of sulfides19 but
a general one is the condensation of a metal alkyl or aryl thiolate with an alkyl halide in the
presence of a strong base.20 Among the shortcomings of this method, a special attention
should be focused on the heat of the reaction mixture, as in the case of thiol, instability can
result in the formation of undesirable products such as disulfides and resins. The instability
of the initial thiol also causes complications in its use in synthesis.
In the present work, we have compared a general method of approach to the synthesis
of 2-nitro-4-(trifluoromethyl)benzene containing sulfides by the use of thiol and our one-pot
method based on the reduction of the corresponding disulfide. As an available and selective
reducing agent, we have chosen glucose, the use of which has been published earlier in
analogous reactions.21 In addition, here we report the asymmetric oxidation of the sulfides
in the presence of a modified Sharpless system.
RESULTS AND DISCUSSION
The synthesis of 2-nitro-4-(trifluoromethyl)benzenethiol (2) began with the addition
of an alcoholic solution of KOH to an alcoholic suspension of the initial commercially
available and convenient in use disulfide 1 and glucose at room temperature (Scheme 1).
Under these conditions, thiol 2 was obtained in 34% yield. The selection of glucose
as a reducing agent is related to its availability and the selectivity of the reduction (under
these conditions a nitro group is not reduced to an amino group). It should be noted that
a temperature increase leads to a considerable decrease of the conversion of disulfide and
thiol yield. Earlier it has been proposed to use aqueous alcoholic solutions in the analogous
reactions.21 However, it leads to complications in thiol extraction, and therefore, it is useful
to apply anhydrous ethanol as a solvent.

SYNTHESIS AND OXIDATION OF FLUORO-CONTAINING SULFIDES
1887
CF3
NO2
NO2
NO2
SH
R-I, 40 oC
SR
D-glucose, KOH, 20oC
S
-
45 oC
C2H5OH
S
C2H5OH
yield 34%
NO2
F3C
F3C
F3C
1
2
3a: R=Me, yield 49%
3b: R=Et, yield 45%
3c: R=Pr, yield 39%
3d: R=Bu, yield 35%
3e: R=Bn, yield 60%
Scheme 1
Then, following the general procedure, to an alcoholic solution of 2 in the presence
of a strong base (KOH) alkyl iodide was added. The yield and conversion were insufficient
at room temperature, but on heating up to 40 ◦С–45 ◦С, we succeeded to obtain sulfides in
35%–60% yield.
A one-pot method is shorter and more efficient by omitting the stage of thiol extrac-
tion, the work with which is difficult enough (air oxidation by oxygen already occurred
upon gentle heating, and instability was observed under the conditions of column chro-
matography). Glucose and the products of its oxidation do not prevent the main reaction
(presumably, the oxidized product is a lactone, it has not isolated). Th◦e only required con-
◦
dition for good yields is an accurate adjustment of temperature (40 С–45 С), because
on heating above 55 ◦С–60 ◦С the sulfides are unstable. In addition, the conduction of the
reaction in one stage allowed a reduction in the time of the synthesis to only 15–20 min. All
sulfides were isolated by column chromatography. Sulfide 3d was crystallized from diethyl
ether/hexane and unambiguously characterized by means of X-ray experiments (see Figure
S1; supplemental materials).
The corresponding sulfoxides 4a–e in yields 40%–85% and ее 11%–78%
(Scheme 2) were obtained by asymmetric oxidation. The Sharpless method modified by
Kagan was chosen as the catalytic system.
O
NO2
NO2
S
S
R
Ti(O-iPr)4 (1eq.), DET (2 eq.), H2O (1eq.)
R
CH2Cl2, CHP
CF3
CF3
3a: R=Me,
3b: R=Et,
3c: R=Pr,
3d: R=Bu,
3e: R=Bn,
4a: R=Me, yield 60%, ee 20%;
4b: R=Et, yield 52%, ee 68%;
4c: R=Pr, yield 47%, ee 62%;
4d: R=Bu, yield 40%, ee 11%;
4e: R=Bn, yield 85%, ee 78%.
Scheme 2
Oxidation proceeded at room temperature for 1–2 h in anhydrous dichloromethane
in the presence of Sharpless modified reagent.17 At low temperatures, reaction did not
proceed. The oxidizer was a solution of cumene hydroperoxide (CHP) in cumene. The
yield of sulfoxides increased with transition from a C4H9-moiety at sulfur atom to a CH3-
group one and further to a benzene-moiety. Sulfoxide with the benzene-moiety (4e) is

1888
K. S. RODYGIN ET AL.
Table 1 Crystal data and data collection parameters
Compound
3d
C11H12F3NO2S
279.28
130(2)
4a
4d
Empirical formula
Formula weight
Temperature (K)
Crystal system
Space group
a(Å)
C8H6F3NO3S
253.20
295(2)
Monoclinic
P21/n
5.6927(4)
5.6294(6)
30.660(3)
90
92.994(7)
90
981.19(16)
4
C11H12F3NO3S
295.28
136(2)
Triclinic
P-1
Monoclinic
P21/n
14.8786(17)
5.3901(6)
16.5318(19)
90
96.722(9)
90
1316.7(3)
4
12.0506(6)
13.6622(11)
15.7467(13)
80.205(7)
74.194(6)
84.277(5)
2454.2(3)
8
b(Å)
c(Å)
α (◦)
β (◦)
ꢀ (◦)
Volume (Å3)
Z
Calculated density (g/cm3)
Absorption coefficient (mm−1
F (000)
1.512
0.295
1152
1.714
0.367
512
1.490
0.285
608
)
Crystal size (mm)
Crystal color/shape
θ Range for data collection (◦)
Completeness (%)
0.41 × 0.18 × 0.08
Yellow prism
2.63–28.28
96.2
0.46 × 0.25 × 0.07 0.46 × 0.19 × 0.02
Yellow plate
2.66–26.37
97.5
Yellow plate
3.49–26.38
98.4
Reflections collected
24155
4624
6540
Independent reflections (Rint
Observed reflections [I > 2σ(I)] 6082
Refinement method
Data/restrains/parameters
Goodness of fit on F2
R1 (all data)
)
11698 (0.0361)
1940 (0.0573)
954
2650 (0.0657)
1199
Full-matrix least-squares on F2
11698/72/706
1.004
1940/0/145
1.000
0.1507
2650/0/172
0.961
0.1157
0.0973
wR2 (all data)
0.0583
0.1153
0.0630
R1 [I > [2σ(I)]
0.0387
0.0605
0.0440
wR2 [I > [2σ(I)]
Largest peak and hole (eÅ−3
0.0542
0.339 and –0.346
0.1003
0.210 and –0.263
0.0581
0.302 and –0.313
)
obtained in the most yield and enantiomeric excess. A total dependence of enantiomeric
excess on the length of hydrocarbonic group was not observed that is typical for analogous
reactions. All sulfoxides were isolated by column chromatography; sulfoxides 4a,d were
crystallized from diethyl ether/hexane and unambiguously characterized by means of X-ray
experiments (see Figures S2 and S3, supplemental information; Table 1). Bond lengths and
Table 2 Selected X-ray determined bond lengths (in Å) and angles (in ◦)
Compound
S–CAr
S–CAlk
S–O
CAlk–S–CAr
CAr–S–O
3d
1
1.7496 (19)
1.7530 (18)
1.7470 (18)
1.7521 (18)
1.818 (4)
1.8147 (18)
1.8064 (18)
1.8083 (18)
1.8130 (18)
1.782 (4)
—
—
—
103.33 (8)
103.18 (8)
103.17 (9)
103.18 (9)
96.38 (19)
95.17 (12)
—
—
—
2
3
4
—
—
4a
4d
1.484 (3)
1.4948 (18)
104.20 (18)
105.16 (11)
1.815 (2)
1.809 (2)

SYNTHESIS AND OXIDATION OF FLUORO-CONTAINING SULFIDES
1889
angles for S-contained moieties of 3d, 4a, and 4d (Table 2) are typical for these classes of
compounds.22
CONCLUSION
In conclusion, the efficient one-pot synthesis of 2-nitro-4-(trifluoromethyl)benzene
containing sulfides has been achieved starting from the corresponding disulfide. We
have proposed to use disulfide in the synthesis of sulfides as initial substrate. As a re-
sult of the enantioselective Sharpless oxidation, the enantiomerically enriched 2-nitro-4-
(trifluoromethyl)benzene containing sulfoxides have been obtained. The yield of sulfoxides
is shown to decreases with an increase in the bulk of aliphatic moiety and with a decrease
of the inductive effect of the hydrocarbonic group on the sulfur atom.
EXPERIMENTAL
General Experimental Procedures
All reactions were performed with magnetic stirring using freshly distilled solvents
unless otherwise indicated. All reactions of oxidation (with Ti(O-iPr)4) were performed
under an atmosphere of argon. Dichloromethane and ethanol were distilled from calcium
hydride. All other commercially available reagents were used as received unless otherwise
specified. All reactions were monitored by thin layer chromatography (TLC) using MERCK
precoated silica gel 60 F254 and diethyl ether/hexane mixtures as eluents; the TLC spots
were visualized with KMnO4/H2SO4 solution. Column chromatography was carried out
using Merck type 9385 silica gel and diethyl ether/hexane mixtures as eluents.
Proton magnetic resonance spectra were recorded on a Bruker Avance 300 spectrom-
eter. Chemical shifts (δ) are reported in parts per million (ppm) and are referenced to the
residual nondeuterated solvent peak (7.26 ppm for CHCl3 of CDCl3). Coupling constants
(J) are reported in hertz. Data are reported as follows: s, singlet; d, doublet; t, triplet; m,
multiplet; and dd, double doublet. Carbon magnetic resonance spectra were recorded on
a Bruker Avance 300 spectrometer operating at 75 MHz. Chemical shifts (δ) are reported
in ppm and are referenced to the deuterated solvent peak (77.0 ppm for 13C of CDCl3).
Fluorine magnetic resonance spectra were recorded on a Bruker Avance 300 spectrometer
operating at 282 MHz. Chemical shifts (δ) are reported (trifluoroacetic acid as the internal
standard). Melting points were determined using a Gallenkamp-Sanyo apparatus. Optical
rotations were measured using a Kruss P3002RS polarimeter with a 10 cm cell and are
◦
reported as follows: [α]tDC (concentration in g/10 mL, solvent). Elemental analyses were
performed using an automatic analyzer ЕА 1110 CHNS-O. All the ee of sulfoxides were
measured by chiral high-performance liquid chromatography analysis: Chiralcel OD-H and
Chiralcel OJ-H columns using a Surveyor LC with a UV detector.
X-Ray Structure Data Collection and Refinement
X-ray intensity data were collected with an Xcalibur 3 diffractometer with a CCD
detector using Mo-Kα (λ = 0.71069 Å) radiation. Crystal data and data collection param-
eters are summarized in Table 1 (supplemental materials). The unit cell parameters were
refined using all collected spots after the integration process. The data were not corrected
for absorption. The structures were solved by direct methods using SHELX97.23 All the

1890
K. S. RODYGIN ET AL.
structures were refined by full-matrix least-squares on F2 using SHELX97. All the non-
hydrogen atoms were refined with anisotropic temperature factors. The hydrogen atoms
were calculated with AFIX and were included in the refinement with a common isotropic
temperature factor. Crystallographic data for the structure of compounds 3d, 4a, and 4d
have been deposited with the Cambridge Crystallographic Data Centre (CCDC) as supple-
mentary publication numbers CCDC 803705, 803707, and 803706. Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK (E-mail deposit@ccdc.cam.ac.uk).
2-Nitro-4-(Trifluoromethyl)Benzenethiol (2)
To a solution of 1 (444 mg, 1 mmol) in EtOH (10 mL) a solution of α-d-glucose
(540 mg in EtOH, 5 mL, 3 mmol) was added at 55 ◦◦С. The mixture was stirred at 55 ◦С for
10 min, the temperature was then adjusted to 20 C, and a solution of KOH (168 mg in
EtOH, 7 mL, 3 mmol) was added. After 10 min at 20 ◦C, the conversion of disulfide was
92%. The solvent was removed in vacuo and the product was puri◦fied on silica. Purification
◦
1
afforded 2 as a yellowish solid (152 mg, 34%). mp 35 С–36 С; H NMR (300 MHz,
CDCl3) δ 4.26 (s, 1H, SH), 7.61 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 8.56 (s,
1H); 13C NMR (75 MHz, CDCl3) δ 121.9 (dd, JС,F = 272.1 Hz), 123.7 (dd, JС,F = 4.9 Hz),
126.9 (dd, JС,F = 103.54 Hz), 129.7 (dd, JС,F = 4.9 Hz), 132.8 (d, JС,F = 4.9 Hz), 144.1,
146.8; 19F NMR (282 MHz, CDCl3) δ −62.9 (s). Anal. Calcd. for C7H4F3NO2S: С, 37.67;
Н, 1.81; N, 6.28; О, 14.34; S, 14.37. Found: С, 37.59; Н, 1.97; N, 6.10; О, 14.22; S, 14.30.
General Procedure for Synthesis of Sulfides (Two Step)
To a solution of 2 (223 mg, 1 mmol) in EtOH (5 mL) a solution of KOH (56 mg in
EtOH, 3 mL, 1 mmol) was added at 20 ◦С. The mixture was stirred at 20 ◦С for 10 min,
the temperature was then adjusted to 40 ◦C–45 ◦C, and a solution of alkyl iodide (1 mmol
◦
◦
in EtOH, 5 mL) was added. After 20 min at 40 C–45 C, the solvent was removed in
vacuo and the products were purified on silica using 50:1 hexane/diethyl ether. Purification
afforded sulfides. The yields of all sulfides are shown in Scheme 1.
General Procedure for Synthesis of Sulfides (One Pot)
To a solution of 1 (444 mg, 1 mmol) in EtOH (10 mL) a solution of α-D-glucose
(540 mg in EtOH, 5 mL, 3 mmol) was added at 55 ◦С. The mixture was stirred at 55 ◦С
for 10 min, the temperature was then adjusted to 20 ◦C and a solution of KOH (168 mg in
EtOH, 7 mL, 3 mmol) was added. Then a solution of◦alkyl iodide (2 mmol in EtOH,◦5 mL)
◦
was added and the temperature was adjusted to 40 C–45 C. After 10 min at 40 C–45
◦C the solvent was removed in vacuo and the products were purified on silica using 50:1
hexane/diethyl ether. Purification afforded sulfides.
1-(Methylsulfanyl)-2-Nitro-4-(Trifluoromethyl)Benzene
3a. Yellowish
solid24: mp 85 ◦С–86 ◦С; 1H NMR (300 MHz, CDCl3) δ 2.59 (s, 3H), 7.54 (d, J = 7.8 Hz,
1H), 7.84 (d, J = 7.8 Hz, 1H), 8.56 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 16.1, 122.9
(dd, JС,F = 272.1 Hz), 123.5 (dd, JС,F = 3.6 Hz), 126.4 (d, JС,F = 3.6 Hz), 127.1 (dd,
JС,F = 103.55 Hz), 129.7 (dd, JС,F = 3.6 Hz), 142.8, 144.8; 19F NMR (282 MHz, CDCl3)

SYNTHESIS AND OXIDATION OF FLUORO-CONTAINING SULFIDES
1891
δ −62.6 (s). Anal. Calcd. for C8H6F3NO2S: С, 40.51; Н, 2.55; N, 5.90; О, 13.49; S, 13.52.
Found: С, 40.60; Н, 2.66; N, 5.78; О, 13.28; S, 13.40.
1-(Ethylsulfanyl)-2-Nitro-4-(Trifluoromethyl)Benzene 3b. Yellowish solid:
◦
◦
1
mp 69 С–70 С; H NMR (300 MHz, CDCl3) δ 1.48 (t, J = 7.4 Hz, 3H), 3.08 (dd,
J = 7.4 Hz, 2H), 7.57 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.3 Hz, 1H), 8.53 (s, 1H); 13C NMR
(75 MHz, CDCl3) δ 12.6, 26.5, 122.9 (dd, JС,F = 272.2 Hz), 123.5 (dd, JС,F = 3.6 Hz),
126.9 (d, JС,F = 3.6 Hz), 127.1 (dd, JС,F = 103.7 Hz), 129.5 (dd, JС,F = 3.6 Hz), 142.7,
144.88; 19F NMR (282 MHz, CDCl3) δ –62.5 (s). Anal. Calcd. for C9H8F3NO2S: С, 43.03;
Н, 3.21; N, 5.58; О, 12.74; S, 12.76. Found: С, 42.90; Н, 3.20; N, 5.67; О, 12.68; S, 12.85.
2-Nitro-1-(Propylsulfanyl)-4-(Trifluoromethyl)Benzene 3c. Yellowish solid:
mp 69 ◦С–70 ◦С; 1H NMR (300 MHz, CDCl3) δ 1.16 (t, J = 7.1 Hz, 3H), 1.85 (sextet, J =
7.1 Hz, 2H), 3.02 (t, J = 7.1 Hz, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 8.7 Hz, 1H),
8.52 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 13.7, 21.3, 34.4, 123.0 (dd, JС,F = 272.5 Hz),
123.5 (dd, JС,F = 4.9 Hz), 127.0 (d, JС,F = 4.9 Hz), 127.2 (dd, JС,F = 103.72 Hz), 129.4
(dd, JС,F = 4.9 Hz), 142.7, 144.9; 19F NMR (282 MHz, CDCl3) δ –62.5 (s). Anal. Calcd.
for C10H10F3NO2S: С, 45.28; Н, 3.80; N, 5.28; О, 12.06; S, 12.09. Found: С, 45.18; Н,
3.88; N, 5.38; О, 12.16; S, 12.92.
1-(Butylsulfanyl)-2-Nitro-4-(Trifluoromethyl)Benzene 3d. Yellowish solid:
◦
◦
1
mp 56 С–57 С; H NMR (300 MHz, CDCl3) δ 1.02 (t, J = 7.3 Hz, 3H), 1.58–1.60
(m, 2H), 1.80–1.82 (m, 2H), 3.04 (t, J = 7.3 Hz, 2H), 7.56 (d, J = 8.5 Hz, 1H), 7.79 (d,
J = 8.5 Hz, 1H), 8.52 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 13.7, 22.3, 29.7, 32.1, 122.9
(dd, JС,F = 274.1 Hz), 123.5 (dd, JС,F = 3.4 Hz), 127.0 (d, JС,F = 3.4 Hz), 127.1 (dd,
JС,F = 103.74 Hz), 129.4 (dd, JС,F = 3.4 Hz), 142.8, 144.9; 19F NMR (282 MHz, CDCl3) δ
–62.6 (s). Anal. Calcd. for C11H12F3NO2S: С, 47.31; Н, 4.33; N, 5.02; О, 11.46; S, 11.48.
Found: С, 47.22; Н, 4.40; N, 5.21; О, 11.52; S, 11.58.
1-(Benzylsulfanyl)-2-Nitro-4-(Trifluoromethyl)Benzene 3e. Yellowish solid:
mp 132 ◦С–133 ◦С; 1H NMR (300 MHz, CDCl3) δ 4.29 (s, 2H), 7.33–7.51 (m, 5H), 7.62
(d, J = 8.7 Hz, 1H), 7.77 (d, J = 8.7 Hz, 1H), 8.54 (s, 1H); 13C NMR (75 MHz, CDCl3)
δ 37.6, 123.5 (dd, JС,F = 3.5 Hz), 122.9 (dd, JС,F = 272.1 Hz), 127.1 (dd, JС,F = 103.74
Hz), 127.3 (d, JС,F = 3.5 Hz), 128.1, 129.0, 129.0, 129.6 (dd, JС,F = 3.5 Hz), 134.1, 143.0,
145.2; 19F NMR (282 MHz, CDCl3) δ –62.6 (s). Anal. Calcd. for C14H10F3NO2S: С, 53.67;
Н, 3.22; N, 4.47; О, 10.21; S, 10.23. Found: C, 53.78; Н, 3.18; N, 4.58; О, 10.36; S, 10.15.
General Procedure for Synthesis of Sulfoxides
(–)-Diethyl-D-tartrate (1 mmol), titanium tetraisopropoxide (2 mmol), and water (1
mmol) were added to a solution of sulfide (1 mmol) in dichloromethane (10 mL) at room
temperature. The mixture was stirred for 30 min and CHP (84% in cumene, 1 mmol) was
added. After 6 h, the solvent was removed in vacuo and the products were purified on
silica using 50:5 hexane/diethyl ether. Purification afforded sulfoxides. The yields of all
sulfoxides are shown in Scheme 2.
1-(Methylsulfinyl)-2-Nitro-4-(Trifluoromethyl)Benzene 4a. Yellowish solid:
mp 109 ◦С–110 ◦С; [α]D25 = +37.5 (c 0.45, n-hexane); 1H NMR (300 MHz, CDCl3) δ 3.00
(s, 3H), 8.26 (d, J = 8.2 Hz, 1H), 8.55–8.63 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 43.8,
122.3 (dd, JС,F = 273.5), 122.4 (d, JС,F = 3.4 Hz), 127.6, 132.1 (d, JС,F = 3.4 Hz), 133.4
(dd, JС,F = 35.1 Hz), 145.1, 146.5; 19F NMR (282 MHz, CDCl3) δ –62.9 (s). Anal. Calcd.
for C8H6F3NO3S: С, 37.95; Н, 2.39; N, 5.53; О, 18.96; S, 12.66. Found: С, 37.84; Н, 2.45;

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K. S. RODYGIN ET AL.
N, 5.50; О, 18.88; S, 12.78. Chiralcel OD-H column at λ 254 nm, n-hexane/2-propanol
(85:15) as eluent, and a flow rate of 1.0 mL/min: tmaj = 20.58, tmin = 12.56 min, ee = 20%.
1-(Ethylsulfinyl)-2-Nitro-4-(Trifluoromethyl)Benzene 4b. Yellowish solid:
mp 55 ◦С–56 ◦С; [α]D25 = +152.9 (c 0.35, n-hexane); 1H NMR (300 MHz, CDCl3) δ 1.39
(t, J = 6.9 Hz, 3H), 2.84–2.98 (m, 1H), 3.25–3.41 (m, 1H), 8.22 (d, J = 8.2 Hz, 1H),
8.48 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 6.9, 49.7, 122.0
(dd, JС,F = 272.8), 122.6 (d, JС,F = 4.9 Hz), 128.6, 131.5 (d, JС,F = 4.9 Hz), 133.3 (dd,
JС,F = 35.3 Hz), 145.0, 146.3; 19F NMR (282 MHz, CDCl3) δ –62.9 (s). Anal. Calcd. for
C9H8F3NO3S: С, 40.45; Н, 3.02; N, 5.24; О, 17.96; S, 12.00. Found: С, 40.53; Н, 3.12;
N, 5.18; О, 17.99; S, 12.11. Chiralcel OD-H column at λ 254 nm, n-hexane/2-propanol
(85:15) as eluent, and a flow rate of 1.0 mL/min: tmaj = 18.59, tmin = 10.10 min, ee = 68%.
2-Nitro-1-(Propylsulfinyl)-4-(Trifluoromethyl)Benzene 4c. Yellowish solid:
mp 63 ◦С–64 ◦С; [α]D25 = +53.3 (c 0.35, n-hexane); 1H NMR (300 MHz, CDCl3) δ 1.17
(t, J = 7.7 Hz, 3H), 1.74–1.91 (m, 1H), 2.03–2.20 (m, 1H), 2.77–2.89 (m, 1H), 3.16–3.28
(m, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.52 (d, J = 9.0 Hz, 1H), 8.61 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 13.7, 21.3, 34.4, 121.9 (dd, JС,F = 272.3), 123.5 (d, JС,F = 4.9 Hz), 127.0,
129.4 (d, JС,F = 4.9 Hz), 133.2 (dd, JС,F = 35.0 Hz), 145.0, 145.5; 19F NMR (282 MHz,
CDCl3) δ –62.9 (s). Anal. Calcd. for C10H10F3NO3S: С, 42.70; Н, 3.58; N, 4.98; О, 17.07;
S, 11.40. Found: С, 42.81; Н, 3.68; N, 4.89; О, 17.00; S, 11.49. Chiralcel OJ-H column
at λ 254 nm, n-hexane/2-propanol (85:15) as eluent, and a flow rate of 1.0 mL/min: tmaj
12.19, tmin = 9.26 min, ee = 62%.
=
1-(Butylsulfinyl)-2-Nitro-4-(Trifluoromethyl)Benzene 4d. Yellowish solid:
mp 73 ◦С–74 ◦С; [α]D25 = +20.0 (c 0.3, n-hexane); 1H NMR (300 MHz, CDCl3) δ 1.01 (t,
J = 7.8 Hz, 3H), 1.41–1.64 (m, 2H), 1.66–1.82 (m, 1H), 1.97–2.16 (m, 1H), 2.76–2.90 (m,
1H), 3.19–3.33 (m, 1H), 8.23 (d, J = 9.7 Hz, 1H), 8.52 (d, J = 9.7 Hz, 1H), 8.61 (s, 1H);
13C NMR (75 MHz, CDCl3) δ 13.7, 21.7, 25.1, 56.9, 122.3 (dd, JС,F = 273.8), 122.7 (d,
JС,F = 3.7 Hz), 128.2, 131.7 (d, JС,F = 3.7 Hz), 133.9 (dd, JС,F = 35.1 Hz), 145.0, 146.6;
19F NMR (282 MHz, CDCl3) δ –62.9 (s). Anal. Calcd. for C11H12F3NO3S: С, 44.74; Н,
4.10; N, 4.74; О, 16.26; S, 10.86. Found: С, 44.68; Н, 4.15; N, 4.66; О, 16.34; S, 10.95.
Chiralcel OD-H column at λ 254 nm, n-hexane/2-propanol (85:15) as eluent, and a flow
rate of 1.0 mL/min: tmaj = 16.06, tmin = 8.40 min, ee = 11%.
1-(Benzylsulfinyl)-2-Nitro-4-(Trifluoromethyl)Benzene 4e. Yellowish solid:
mp 125 ◦С–126 ◦С; [α]D25 = +222.3 (c 0.3, EtOH); 1H NMR (300 MHz, CDCl3) δ 4.32 (d,
J = 12.8 Hz, 2H), 7.10–7.17 (m, 2H), 7.25–7.38 (m, 3H), 7.95–8.02 (m, 2H), 8.58 (s, 1H);
13C NMR (75 MHz, CDCl3) δ 61.9, 122.1 (dd, JС,F = 3.8 Hz), 122.4 (dd, JС,F = 273.1),
128.5, 128.8, 128.9, 129.4, 130.4, 131.2 (dd, JС,F = 3.8 Hz), 134.0 (dd, JС,F = 35.0 Hz),
145.1, 146.8; 19F NMR (282 MHz, CDCl3) δ –62.9 (s). Anal. Calcd. for C14H10F3NO3S:
С, 51.06; Н, 3.06; N, 4.25; О, 14.58; S, 9.74. Found: С, 51.12; Н, 3.15; N, 4.20; О, 14.62;
S, 9.78. Chiralcel OD-H column at λ 254 nm, n-hexane/2-propanol (85:15) as eluent, and
a flow rate of 1.0 mL/min: tmaj = 30.13, tmin = 15.46 min, ee = 78%.
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