Preparation of optically active ortho-chloro- and ortho-bromophenyl sulfoxides

Article abstract of DOI:10.1016/S0957-4166(99)00078-6

The preparation of the diastereomerically pure menthyl (S)-2-chloro- and (S)-2-bromophenyl sulfinates by esterification of the corresponding sulfinic acids with (1R,2S,5R)-(-)-menthol and recrystallization/epimerization is reported. The two sulfinates have been converted into enantiomerically pure aryl, vinyl and alkyl sulfoxides by reaction with organomagnesium reagents. These sulfoxides are useful chiral auxiliaries to control the stereochemical outcome of radical reactions.

Full text of DOI:10.1016/S0957-4166(99)00078-6

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1051–1060
Preparation of optically active ortho-chloro- and
ortho-bromophenyl sulfoxides
Christoph Imboden and Philippe Renaud ∗
Université de Fribourg, Institut de Chimie Organique, Pérolles, CH-1700 Fribourg, Switzerland
Received 20 January 1999; accepted 3 March 1999
Abstract
The preparation of the diastereomerically pure menthyl (S)-2-chloro- and (S)-2-bromophenyl sulfinates by
esterification of the corresponding sulfinic acids with (1R,2S,5R)-(−)-menthol and recrystallization/epimerization
is reported. The two sulfinates have been converted into enantiomerically pure aryl, vinyl and alkyl sulfoxides by
reaction with organomagnesium reagents. These sulfoxides are useful chiral auxiliaries to control the stereochem-
ical outcome of radical reactions. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
The use of sulfoxides as chiral templates has been intensively investigated in carbanion alkylations,
Michael additions and cycloadditions.1 They have been found to have wide applications in the synthesis
of biologically active compounds.2 In our recent work, we found that good stereochemical control
could be achieved in radical alkylation and cyclization of simple sulfinylated alkyl radicals by using
either ortho-chloro- or ortho-bromophenyl sulfoxides.3 Moreover, we have very recently used ortho-
bromophenyl sulfoxides to run efficient hydrogen abstraction–fragmentation cascades leading to enan-
tiomerically enriched alkenes.4 In this article, we report an efficient method for the preparation of
enantiomerically pure ortho-chloro- and ortho-bromophenyl sulfoxides.
2. Results and discussion
Different attempts to prepare optically active ortho-chloro- and ortho-bromophenyl methyl sulfoxides
by enantioselective oxidation of the corresponding methyl sulfides (‘sulfoxidation’) have been reported.
However, only low to moderate enantioselectivities have been achieved.5,6
∗
Corresponding author. E-mail: philippe.renaud@unifr.ch
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00078-6

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2.1. Enantioselective sulfoxidation approach
Our first attempt to prepare the ortho-chlorophenyl methyl sulfoxides 2 was based on the Kagan
procedure using Ti(Oi-Pr)4/(R,R)-(+)-diethyl tartrate/H2O.7 Oxidation of the methyl sulfide 1 gave the
desired methyl sulfoxides 2 with low to moderate enantioselectivities depending on the oxidant (cumene
hydroperoxide: 27% ee, 91% yield; tert-butyl hydroperoxide: 88% ee, 91% yield) (Eq. 1). With this
last oxidant, the best enantioselectivity (88% ee) was not reproducible and enantioselectivities as low
as 40% ee were obtained in some runs. Moreover, sulfoxide 2 was not crystalline and it was therefore
impossible to use recrystallization to enhance its enantiomeric excess. As a consequence, this approach
was abandoned for a more convenient preparation procedure.
(1)
2.2. The Andersen approach
The preparation of enantiomerically pure sulfoxides by nucleophilic substitution at the sulfur center
is very well documented since the pioneering work of Andersen with menthyl sulfinate.8 Many different
types of sulfinic acid derivatives have been developed9 but the original Andersen procedure using menthyl
sulfinates is still highly attractive for the preparation of aryl sulfoxides because of its efficiency and
low cost. The crucial step of this approach is the preparation of diastereomerically pure sulfinates
followed by nucleophilic displacement of the alkoxy moiety with organomagnesium compounds. We
decided to investigate the preparation of the menthyl sulfinates 7 and 8 and to study the separation
of the diastereomers. Starting from the commercially available ortho-chloro- and ortho-bromoanilines
3 and 4, we prepared the sulfinic acids 5 and 6 according to a literature procedure by diazonation and
reaction with SO2 (Scheme 1).10 The crude sulfinic acids were directly esterified by treatment with oxalyl
chloride followed by reaction with (1R,2S,5R)-(−)-menthol. Menthyl sulfinates 7 and 8 were isolated
as white solids (1:1 mixture of diastereomers) in 80 and 92% yield from the corresponding aniline,
respectively. Several cycles of crystallization (Et2O/hexane)–epimerization of the mother liquor (conc.
HCl, acetone11,12) afforded the diastereomerically pure sulfinates (S)-7 and (S)-8 in 72% and 81% yield
from the sulfinic acids 5 and 6, respectively.
The absolute (S) configurations at sulfur of the sulfinate esters 7 and 8 were determined by chemical
correlation according to Eqs. 2 and 3. The para-tolyl sulfoxides (R)-(+)-9 and (R)-(+)-1013 were
synthesized from diastereomerically pure 7 and 8 by reaction with para-tolylmagnesium iodide in 80%
and 65% yield, respectively (Eq. 2). The enantiomeric excess of these two sulfoxides was found to be
over 99% by HPLC analysis with a chiral column (Daicel Chiralcel OB-H). The (S)-(−)-enantiomers of 9
and 10 have been prepared by Furukawa from the menthyl sulfinate (S)-11 by reaction with ortho-chloro-
and ortho-bromophenylmagnesium bromide (Eq. 3).13c Since the nucleophilic substitution at the sulfur
atom of the sulfinate is known to occur with inversion of configuration,14 it was possible to assign the (S)
configuration for the sulfinates 7 and 8.

C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
1053
Scheme 1.
(2)
(3)
Methyl ((R)-12, (R)-13) and vinyl ((R)-14, (R)-15) sulfoxides were synthesized from the diastereomer-
ically pure sulfinate (S)-7 and (S)-8 in good yields and excellent enantiomeric excess (Eq. 4, Table 1).
For analytical reasons, the racemic sulfoxides were synthesized by oxidation of the corresponding sulfide
with m-CPBA.
(4)
3. Conclusion
We have shown that the Andersen method is efficient for the preparation of enantiomerically pure
ortho-chloro- and ortho-bromophenyl sulfoxides. The key menthyl sulfinates (S)-7 and (S)-8 were
synthesized in good yields from the corresponding ortho-chloro- and ortho-bromoaniline. The absolute
configuration of the sulfinates has been proved by chemical correlation via preparation of the known
ortho-chloro- and ortho-bromophenyl para-tolyl sulfoxides. These sulfoxides are actually being applied

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C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
Table 1
Preparation of methyl and vinyl sulfoxides (R)-12–15 from (S)-7 and (S)-8 according to Eq. 4
for the control of the relative and absolute stereochemistry of radical cyclization and fragmentation
reactions.
4. Experimental
4.1. General
THF was freshly distilled from potassium under N2, CH2Cl2, pyridine and benzene from CaH2, Et2O
from sodium/benzophenone. Flash column chromatography (FC) and filtration: silica gel Merck or Baker
(60 870–230 mesh); elution with EtOAc and hexane or petroleum ether (p.e.); m.p.: not corrected;
Büchi–Tottoli apparatus and Reichert Thermovar Kofler hot stage. FT-IR: Mattson–Unicam 5020. NMR:
Varian Gemini 200 (1H=200 MHz, 13C=50.3 MHz); Bruker AM-360 (1H=360.13 MHz); Bruker Avance
DRX-500 (1H=500 MHz, 13C=125.77 MHz); unless otherwise indicated, spectra were recorded in CDCl3
solns; for 1H chemical shifts δ in ppm relative to CHCl3 (=7.27 ppm); for 13C chemical shifts δ in ppm
relative to CHCl3 (=77.0 ppm); MS: Finnigan 1020; Nermag R10-10C; vacuum generators micromass
E70/70 and Hewlett–Packard 5988A; CI, chemical ionization with NH3 or CH4; EI, electron ionization
at 70 eV; FAB, fast atom bombardment, matrix 3-nitrobenzyl alcohol (NBA), Xe-bombardment (8 kV, 1
mA); microanalyses: Ciba, Mikrolabor, CH-1700 Fribourg–Marly, Switzerland. HPLC: Daicel Chiralcel
OB-H (0.46 cm diameter, 25 cm length), flow rate 0.5 ml/min.
4.2. General procedure 1. Preparation of sulfinic acids10
4.2.1. Preparation of copper catalyst15
A cold saturated soln of CuSO4 (500 g, 3.13 mol) in H2O (1.4 l) was placed in a beaker and stirred as
Zn dust (200 g, 3.06 mol) was added very slowly. Too rapid addition makes the copper go lumpy. The
addition was discontinued before complete decoloration of the CuSO4 soln took place. The temperature
reached 80°C at the end of the addition. The aqueous layer was removed and the copper stayed at the
bottom of the beaker as a heavy dark red layer that was washed twice with cold H2O. Traces of Zn were
removed by covering the copper with twice its volume of H2O and addition of 1 N HCl until hydrogen
formation stopped. The copper took an intensive red color and was washed with H2O until the H2O
stayed neutral. The catalyst was highly air sensitive and was stored as a wet paste.

C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
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4.2.2. Preparation of the sulfinic acids
2-Haloaniline (0.24 mol) was dissolved in H2O (640 ml) and conc. H2SO4 (97%, 176 ml) was added.
On cooling to 0°C, the 2-haloaniline sulfate crystallized as a white solid. At 0°C, a soln of NaNO2 (0.28
mol) in H2O (110 ml) was added dropwise to the white suspension. The solid disappeared and a cooled
soln (0°C) of conc. H2SO4 (95–97%, 88 ml) in H2O (60 ml) was added. The flask and its contents were
weighed and SO2 was passed through the soln at −25°C until the weight ceased to increase (200 g). It
is important to keep the soln at −25°C in order to increase the absorption of SO2 and the yield, since
both the diazo compound and the sulfinic acid are unstable. The SO2 absorption was finished within 1 h.
The mixture was transferred to an ice cooled 3 l beaker and a catalytic amount of copper was added in
portions with constant stirring until the violent gas evolution was finished. During the addition of copper,
a slow stream of SO2 was passed through the soln. The sulfinic acid precipitated and was isolated by
filtration and washed with H2O. The solid was treated with 10% Na2CO3 (1000 ml). The copper stayed
in the filter and the clear aq. soln was acidified with cold 50% H2SO4. The white precipitate was extracted
with Et2O (2000 ml). Drying (Na2SO4) and evaporation gave the sulfinic acid as a white solid, which was
used without further purification for the next step. The sulfinic acids can be stored at −25°C for several
days.
4.3. General procedure 2. Preparation of sulfinate esters12
Freshly prepared sulfinic acid (0.144 mol) was added at rt in small portions to a soln of SOCl2 (0.722
mol, 85.9 g, 52.5 ml) in benzene (250 ml). The mixture was stirred until all the solid was dissolved and
no more gas evolution was observed. The excess of SOCl2 was removed by azeotropic distillation with
benzene (3×200 ml). The mixture was concentrated to 50 ml and the residue was diluted with anhydrous
Et2O (250 ml). A soln of (1R,2S,5R)-(−)-menthol (0.155 mol, 24.2 g) in anhydrous pyridine (25 ml)
was added dropwise at 0°C. The mixture was stirred for 1 h at rt and then hydrolyzed with H2O (100
ml). The organic layer was washed with 10% HCl (100 ml) and brine (50 ml). The organic layer was
dried (Na2SO4), filtered and evaporated to give the sulfinate ester as a white solid (1:1 mixture of two
diastereoisomers).
4.4. General procedure 3. Preparation of the sulfoxides12
A 1 M soln of the Grignard reagent was prepared from Mg (0.121 g, 5 mmol) and halide (5.5 mmol) in
Et2O (5 ml). Part of this soln (1.5 ml, 1.5 mmol) was added dropwise at 0–10°C to a soln of sulfinate ester
(1 mmol) in benzene (2 ml). The soln was stirred at rt for 2–3 h and the reaction mixture was hydrolyzed
with sat. NH4Cl (2 ml) and extracted with Et2O (5 ml). The collected organic layers were washed with
brine (5 ml), dried (Na2SO4), filtered and evaporated to give the crude sulfoxide.
4.5. 2-Chloro-1-benzenesulfinic acid 5
From compound 3 (30 g, 0.235 mol) and NaNO2 (19.47 g, 0.282 mol) according to general procedure
1, crude 5 (36.5 g, 90%) was obtained and used without further purification for the next step. White solid,
1
m.p.: 120°C. H NMR (200 MHz, DMSO): 7.90–7.80 (m, 1 arom. H); 7.70–7.41 (m, 3 arom. H). 13C
NMR (50.3 MHz, DMSO): 145.53 (s), 132.92 (d), 130.87 (s), 129.88 (d), 127.65 (d), 124.77 (d). IR
(KBr): 3081, 1572, 1283, 1244. MS (FAB): 221 (78), [M+Na]+, 187 (50), 175 (10), 159 (15), 153 (33),
137 (100), 127 (15), 115 (55), 110 (33).

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4.6. 2-Bromo-1-benzenesulfinic acid 6
From compound 4 (40 g, 0.233 mol) and NaNO2 (19.47 g, 0.282 mol) according to general procedure
1, crude 6 (44.8 g, 87%) was obtained and used without further purification for the next step. White solid,
m.p.: 130°C. 1H NMR (200 MHz, DMSO): 7.90–7.35 (m, 4 arom. H). 13C NMR (50.3 MHz, DMSO):
147.19 (s), 133.08 (d), 132.97 (d), 128.13 (d), 125.03 (d), 119.72 (s). IR (KBr): 2879, 2461, 2112, 1830,
1633, 1444, 1332, 1282. MS (FAB): 267 (40, [M+Na]+), 187 (15), 175 (45), 153 (80), 137 (100), 125
(25), 115 (25), 79 (35), 63 (85).
4.7. (SS,1R,2S,5R)-(−)-1-(2-Chlorophenylsulfinyloxy)-2-isopropyl-5-methylcyclohexane (S)-7
From compound 5 (25 g, 0.142 mol) and (1R,2S,5R)-(−)-menthol (23.9 g, 0.153 mol) according to ge-
neral procedure 2, crude 7 (35.8 g, 80%) was obtained as a 1:1 mixture of diastereomers. Recrystallization
procedure for compound 7 (10 g, 1:1 mixture of diastereomers): the white solid was dissolved in acetone
and conc. HCl (3 drops) was added. The colorless soln was stirred for 10 min at rt After evaporation, the
resulting crystals were dissolved in Et2O (21.5 ml). The slightly yellowish soln was diluted with hexane
(215 ml) and the colorless soln was allowed to crystallize at −24°C for 16 h. The resulting white solid (6.4
g of a 1:12 mixture of diastereoisomers) was removed by filtration. The filtrate was concentrated and the
remaining solid (3.6 g, 1:1 mixture of diastereomers) was dissolved in Et2O (7.8 ml) and hexane (78 ml).
One drop of conc. HCl was added and the clear soln was allowed to crystallize at −24°C for 16 h. This
procedure was repeated 7 times. The collected solid was recrystallized in Et2O:hexane (1:10) at −24°C to
give diastereomerically pure (S)-7 (32.2 g, 72%) as white crystals, m.p.: 99–100°C. [α]D25=−277 (c=1,
1
acetone). H NMR (500 MHz): 8.05–7.97 (m, 1 arom. H); 7.50–7.42 (m, 2 arom. H); 7.42–7.36 (m,
1 arom. H); 4.12 (dt, J=4.5, 10.7, CHOSO); 2.40–2.33 (m, CHHCHOSO); 2.18–2.07 (m, CH(CH3)2);
1.72–1.62 (m, CHHCHCH3); CHHCHCH(CH3)2); 1.53–1.40 (m, CHCH3); 1.38–1.30 (m, CHCHOSO);
1.27–1.17 (m, CHHCHOSO); 1.09–0.98 (m, CHHCHCH(CH3)2); 0.95 (d, J=6.5, CH3); 0.91–0.80 (dm,
4H, J=7.07, CHHCHCH3, isopropyl CH3); 0.67 (d, J=6.9, isopropyl CH3). 13C NMR (125 MHz): 143.44
(s), 133.01 (d), 132.03 (s), 130.04 (d), 127.38 (d), 125.70 (d), 80.44 (d), 47.83 (d), 42.51 (t), 33.94 (t),
31.72 (d), 25.11 (d), 23.16 (t), 22.04 (q), 20.81 (q), 15.37 (q). IR (KBr): 3065, 2930, 2890, 1576, 1451,
1387, 1372, 1245, 1181, 1097. MS (EI): 315 (56, [M+1]+), 205 (10), 177 (100), 139 (31), 97 (3), 83 (22).
Anal. calcd for C16H23ClO2S (314.87): C 61.03, H 7.36; found C 60.93, H 7.38.
4.8. (SS,1R,2S,5R)-(−)-1-(2-Bromophenylsulfinyloxy)-2-isopropyl-5-methylcyclohexane (S)-8
From compound 6 (40 g, 0.181 mol) and (1R,2S,5R)-(−)-menthol (30.4 g, 0.195 mol) according to
general procedure 2, crude 8 (59.8 g, 92%) was obtained as a 1:1 mixture of diastereomers. Recrystalli-
zation procedure for compound 8 (10 g, 1:1 mixture of diastereomers): the white solid was dissolved
in acetone (56 ml) and conc. HCl (3 drops) was added. The colorless soln was stirred for 10 min
at rt. After evaporation, the resulting crystals were dissolved in Et2O (26 ml). The slightly yellowish
soln was diluted with hexane (260 ml) and the resulting colorless soln was allowed to crystallize at
−24°C for 16 h. The resulting white solid (6.5 g of a 1:10 mixture of diastereoisomers) was removed by
filtration. The filtrate was concentrated and the resulting oily solid (3.5 g, 1:1 mixture of diastereomers)
was dissolved in Et2O (11 ml) and hexane (110 ml). One drop of conc. HCl was added and the clear
soln was allowed to crystallize at −24°C for 16 h. This procedure was repeated 6 times. The collected
crystals were then recrystallized in Et2O:hexane (1:10) at −24°C to give diastereomerically pure (S)-
1
8 (52.7 g, 81%) as white crystals, m.p.: 108.7–109.2°C. [α]D25=−221 (c=1, acetone). H NMR (500

C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
1057
MHz): 8.01–7.99 (m, 1 arom. H); 7.60–7.51 (m, 2 arom. H); 7.42–7.39 (m, 1 arom. H); 4.12 (td, J=10.7,
4.5, CHOSO); 2.46–2.35 (m, CHHCHOSO); 2.19–2.06 (m, CH(CH3)2); 1.72–1.63 (m, CHHCHCH3,
CHHCHCH(CH3)2); 1.54–1.43 (m, CHCH3); 1.40–1.31 (m, CHCHOSO); 1.29–1.19 (tm, J=12.22,
CHHCHOSO); 1.08–0.98 (m, CHHCHCH(CH3)2); 0.96 (d, J=6.5, CH3); 0.92–0.80 (dm, 4H, J=7.07,
CHHCHCH3, isopropyl CH3); 0.67 (d, J=6.9, isopropyl CH3). 13C NMR (125 MHz): 145.23 (s), 133.27
(d), 133.21 (d), 128.03 (d), 126.12 (d), 120.49 (s), 80.18 (d), 47.86 (d), 42.58 (t), 33.98 (t), 31.76 (d),
25.19 (d), 23.22 (t), 22.06 (q), 20.82 (q), 15.40 (q). IR (KBr): 3443, 2950, 2912, 2890, 1571, 1447, 1386,
1372, 1243, 1131. MS (EI): 360 (30, [M+1]+), 223 (100), 204 (15), 139 (66), 97 (14), 83 (83), 69 (30),
57 (31), 55 (47). Anal. calcd for C16H23BrO2S (359.32): C 53.48, H 6.45; found C 53.41, H 6.54.
4.9. (R)-(+)-2-Chlorophenyl 4-methylphenyl sulfoxide 9
From Mg (122 mg, 5 mmol), 4-iodotoluene (1.2 g, 5.5 mmol) and (S)-7 (314 mg, 1 mmol) according
to general procedure 3, the title compound was obtained. The resulting yellow oil was purified by FC
(EtOAc:hexane 1:10) to give compound 9 (176 mg, 70%) as a white solid, m.p.: 90–91°C. [α]D25=+162
(c=1, acetone). R:S >99.5:0.5 (HPLC, i-PrOH:hexane 5:95, tr(R)=40 min, tr(S)=44 min). 1H NMR (360
MHz): 8.10–8.04 (m, 1 arom. H); 7.65–7.58 (m, 2 arom. H); 7.54–7.47 (m, 1 arom. H); 7.42–7.30 (m, 2
arom. H); 7.27–7.21 (m, 2 arom. H); 2.36 (s, CH3). 13C NMR (50 MHz): 143.61 (s), 142.02 (s), 141.36
(s), 131.79 (d), 131.10 (s), 129.92 (d), 127.87 (d), 126.07 (d), 125.71 (d), 21.41 (q). IR (KBr): 3443,
3053, 2922, 2361, 1928, 1813, 1593. MS (EI): 250 ([M]+, 57), 233 (27), 202 (30), 184 (31), 167 (12),
139 (21), 111 (33), 91 (92), 77 (100). Anal. calcd for C13H11ClOS (250.74): C 62.27, H 4.42; found C
62.3, H 4.46.
4.10. (R)-(+)-2-Bromophenyl 4-methylphenyl sulfoxide 10
From Mg (122 mg, 5 mmol), 4-iodotoluene (1.2 g, 5.5 mmol) and (S)-8 (359 mg, 1 mmol) according
to general procedure 3, the title compound was obtained. The resulting yellow oil was purified by FC
(EtOAc:hexane 1:10) to give compound 10 (192 mg, 65%) as a white solid, m.p.: 88–89°C. [α]D25=+147
1
(c=1, THF). R:S >99.5:0.5 (HPLC, i-PrOH:hexane 5:95, tr(R)=48 min, tr(S)=42 min). H NMR (360
MHz): 8.11–8.05 (m, 1 arom. H); 7.69–7.49 (m, 4 arom. H); 7.37–7.30 (m, 1 arom. H); 7.29–7.20 (m, 2
arom. H); 2.37 (s, CH3). 13C NMR (50.3 MHz): 145.23 (s), 142.02 (s), 141.43 (s), 133.06 (d), 132.07
(d), 129.90 (d), 128.44 (d), 126.33 (d), 119.96 (s), 21.42 (q). IR (KBr): 3437, 3050, 2921, 1592, 1492,
1445, 1402, 1310, 1092, 1081. MS (EI): 296 (100, [M+1]+), 279 (61), 247 (15), 215 (60), 199 (22), 184
(14), 139 (42), 123 (31), 107 (91), 91 (43). Anal. calcd for C13H11BrOS (295.20): C 52.9, H 3.76; found
C 52.83, H 3.80.
4.11. (R)-(+)-2-Chlorophenyl methyl sulfoxide 12
From Mg (122 mg, 5 mmol), iodomethane (5.5 mmol, 781 mg, 0.34 ml) and (S)-7 (314 mg, 1 mmol)
in benzene (2 ml) according to general procedure 3, the title compound was obtained. FC (EtOAc:hexane
1:4) gave compound 12 (131 mg, 75%), pale yellow oil. [α]D25=+139 (c=1, THF). R:S >99:1 (HPLC,
1
i-PrOH:hexane 10:90, tr(R)=58 min, tr(S)=28 min). H NMR (360 MHz): 7.99–7.91 (m, 1 arom. H);
7.58–7.49 (m, 1 arom. H); 7.49–7.35 (m, 2 arom. H); 2.81 (s, CH3). 13C NMR (50 MHz): 143.72 (s),
131.80 (d), 129.68 (s), 129.63 (d), 128.01 (d), 125.22 (d), 41.63 (q). IR (film): 3485, 3059, 2997, 2914,
1566, 1446, 1290, 1093, 1014, 950. MS (EI): 174 (83, [M]+), 159 (100), 131 (66), 111 (25), 99 (9), 75
(35), 63 (9). Anal. calcd for C7H7ClOS (174.65): C 48.14, H 4.04; found C 48.15, H 4.11.

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4.12. (R)-(+)-2-Bromophenyl methyl sulfoxide 13
From Mg (122 mg, 5 mmol), iodomethane (781 mg, 5.5 mmol, 0.34 ml) and (S)-8 (359 mg, 1 mmol)
in benzene (2 ml) according to general procedure 3, the title compound was obtained. FC (EtOAc:hexane
1:4) gave compound 13 (170 mg, 80%) as a pale yellow oil. [α]D25=+251 (c=1, THF). R:S >99.5:0.5
(HPLC, i-PrOH:hexane 5:95, tr(R)=33 min, tr(S)=52 min). 1H NMR (360 MHz): 7.97–7.93 (m, 1 arom.
H); 7.62–7.54 (m, 2 arom. H); 7.42–7.34 (m, 1 arom. H); 2.83 (s, CH3). 13C NMR (50 MHz): 145.56 (s),
132.85 (d), 132.14 (d), 128.65 (d), 125.66 (d), 118.37 (s), 41.93 (q). IR (film): 3495, 3065, 3001, 2916,
1574, 1450, 1292, 1246, 1060, 1029, 950. MS (EI): 219 (95, [M]+), 204 (100), 177 (38), 155 (16), 139
(57), 124 (11), 108 (29), 96 (93), 75 (62). Anal. calcd for C7H7BrSO (219.10): C 38.37, H 3.22; found C
38.36, H 3.46.
4.13. (R)-(+)-2-Chlorophenyl vinyl sulfoxide 14
From a 1 M soln of vinylmagnesium bromide in THF (13 ml, 13 mmol) and (S)-7 (4.0 g, 12.7 mmol)
according to general procedure 3, in THF (50 ml) instead of benzene, the title compound was obtained.
FC (EtOAc:hexane 1:4) gave compound 14 (1.4 g, 60%) as a colorless oil. [α]D25=+207 (c=1, THF). R:S
1
>99.5:0.5 (HPLC, i-PrOH:hexane 10:90, tr(R)=21 min, tr(S)=36 min). H NMR (360 MHz): 7.81–7.75
(m, 1 arom. H); 7.52–7.33 (m, 3 arom. H); 6.83 (dd, J=16.3, 9.7, CHSO); 6.17 (d, J=16.3, CHH_C); 5.87
(d, J=9.7, CHH_C). 13C NMR (50.3 MHz): 141.53 (s), 140.30 (d), 131.75 (d), 130.17 (s), 129.63 (d),
128.06 (d), 125.00 (d), 120.73 (t). IR (film): 3535, 3061, 3005, 1547, 1450, 1367, 1246. MS (CI): 187
(100, [M+1]+), 170 (6), 159 (2), 138 (13), 135 (2), 75 (2). Anal. calcd for C8H7ClOS (186.66): C 51.48,
H 3.78; found: C 51.49, H 3.86.
4.14. (R)-(+)-2-Bromophenyl vinyl sulfoxide 15
From a 1 M soln of vinylmagnesium bromide in THF (10.4 ml, 10.4 mmol) and (S)-8 (2.5 g, 6.9 mmol)
according to general procedure 3, in THF (28 ml) instead of benzene, the title compound was obtained.
FC (EtOAc:hexane 1:4) gave compound 15 (1.2 g, 75%) as a colorless oil. [α]D25=+305 (c=1, THF). R:S
1
>99.5:0.5 (HPLC, i-PrOH:hexane 10:90, tr(R)=23 min, tr(S)=45 min). H NMR (360 MHz): 7.82–7.77
(m, 1 arom. H); 7.59–7.50 (m, 2 arom. H); 7.39–7.32 (m, 1 arom. H); 6.88 (dd, J=16.4, 9.4, CHSO); 6.24
(d, J=16.4, CHH_C); 5.98 (d, J=9.4, CHH_C). 13C NMR (50 MHz): 143.49 (s), 140.59 (d), 132.84 (d),
132.06 (d), 128.69 (d), 125.59 (d), 120.81 (t), 118.90 (s). IR (film): 3425, 2955, 1724, 1568, 1446, 1367,
1178, 1068, 1014. MS (EI): 232 (9, [M+1]+), 202 (2), 182 (10), 157 (3), 141 (4), 108 (7), 87 (20), 71
(100). Anal. calcd for C8H7BrOS (231.11): C 41.58, H 3.05; found C 41.92, H 3.37.
4.15. Syntheses of racemic diaryl sulfoxides16
4.15.1. (ꢀ)-2-Chlorophenyl 4-methylphenyl sulfoxide (ꢀ)-9
To a soln of 2-chloroaniline (1.3 g, 10 mmol) in H2O (25 ml) was added at 80°C conc. HCl (5 ml).
On cooling to 0°C, the hydrochloride precipitated as a white solid. At 0°C, a soln of NaNO2 (691 mg, 10
mmol) in H2O (5 ml) was added dropwise to the white suspension. The soln was neutralized with cold
sat. NaOAc. The yellow precipitate was filtered and the filtrate was added dropwise at 80°C to a soln of
NaOH (480 mg, 12 mmol) and p-thiocresol (1.5 g, 12 mmol) in H2O (10 ml). The reaction mixture was
heated at 95°C for 1 h. The mixture was cooled to rt and extracted with Et2O (100 ml). The organic layer
was washed with brine (50 ml), dried (Na2SO4), filtered and evaporated to give the crude sulfide. Bulb to

C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
1059
bulb distillation gave pure 2-chlorophenyl 4-methylphenyl sulfide (1.7 g, 74%) as a colorless oil which
crystallized to a white solid. B.p.: 160°C/1.3 mbar, m.p: 29°C).
2-Chlorophenyl 4-methylphenyl sulfide (235 mg, 1 mmol) was dissolved in CH2Cl2 (20 ml) and treated
at −10°C with a dried (MgSO4) soln of m-CPBA (172 mg, 1 mmol) in CH2Cl2 (10 ml) over a period of
30 min. The soln was stirred for 1 h at −10°C before warming to rt. KF (174 mg, 3 mmol) was added
and the resulting suspension was stirred overnight at rt and then filtered through Celite. After removing
the solvent, the residue was purified by FC (EtOAc:hexane 1:5) to give (ꢀ)-9 (237 mg, 95%) as a white
solid, m.p.: 81.5–82°C. The analytical data was identical to the enantiomerically pure products.
4.15.2. (ꢀ)-2-Bromophenyl 4-methylphenyl sulfoxide (ꢀ)-10
According to the procedure for the synthesis of (ꢀ)-9 from 2-bromoaniline (1.5 g, 8.7 mmol), NaNO2
(600 mg, 8.7 mmol), p-thiocresol (1.3 g, 10.4 mmol) and m-CPBA (1.3 g, 8 mmol) the title compound
was obtained. FC (EtOAc:hexane 1:5) gave (ꢀ)-10 (2.1 g, 90%) as a white solid, m.p.: 95.5–96°C. The
analytical data was identical to the enantiomerically pure products.
4.15.3. (ꢀ)-2-Chlorophenyl methyl sulfoxide (ꢀ)-12
A soln of CH3I (1.7 g, 12 mmol) in benzene (10 ml) was added to a soln of 2-chlorothiophenol (1.7 g,
12 mmol), NaOH (680 mg, 17 mmol) and Bu4NI (111 mg, 0.3 mmol) in H2O (10 ml). The mixture was
vigorously stirred for 24 h at rt. After extraction with Et2O (3×100 ml), the collected organic layers were
washed with brine (3×100 ml), dried (Na2SO4), filtered and evaporated to give 2-chlorophenyl methyl
sulfide (1.7 g, 89%) as a pale yellow oil which was used without further purification. 2-Chlorophenyl
methyl sulfide (159 mg, 1 mmol) was dissolved in CH2Cl2 (20 ml) and treated at −10°C with a dried
(MgSO4) soln of m-CPBA (172 mg, 1 mmol) in CH2Cl2 (10 ml) over a period of 30 min. The soln
was stirred for 1 h at −10°C before warming to rt. KF (174 mg, 3 mmol) was added and the resulting
suspension was stirred overnight and then filtered through Celite. After removing the solvent, the residue
was purified by FC (EtOAc:hexane 1:4) to give (ꢀ)-12 (162 mg, 93%) as a pale yellow oil. The analytical
data was identical to the enantiomerically pure products.
4.15.4. (ꢀ)-2-Bromophenyl methyl sulfoxide (ꢀ)-13
According to the procedure for the synthesis of (ꢀ)-12 from CH3I (1.7 g, 12 mmol), bromothiophenol
(2.3 g, 12 mmol) and m-CPBA (2.1 g, 12 mmol) the title compound was obtained. FC (EtOAc:hexane 1:4)
gave (ꢀ)-13 (2.3 g, 89%) as a pale yellow oil. The analytical data was identical to the enantiomerically
pure products.
4.15.5. (ꢀ)-2-Chlorophenyl vinyl sulfoxide (ꢀ)-14
From a 1 M soln of vinylmagnesium bromide in THF (3 ml, 3 mmol) and compound 7 (850 mg, 2.7
mmol) according to general procedure 3, in THF (15 ml) instead of benzene, the title compound was
obtained. FC (EtOAc:hexane 1:4) gave (ꢀ)-14 (327 mg, 65%) as a colorless oil. The analytical data was
identical to the enantiomerically pure products.
4.15.6. (ꢀ)-2-Bromophenyl vinyl sulfoxide (ꢀ)-15
From a 1 M soln of vinylmagnesium bromide in THF (4.2 ml, 4.2 mmol) and compound 8 (1.43 g,
4 mmol) according to general procedure 3, in THF (10 ml) instead of benzene, the title compound was
obtained. FC (EtOAc:hexane 1:4) gave (ꢀ)-15 (674 mg, 73%) as a colorless oil. The analytical data was
identical to the enantiomerically pure products.

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C. Imboden, P. Renaud / Tetrahedron: Asymmetry 10 (1999) 1051–1060
Acknowledgements
We thank the Fonds National Suisse de la Recherche Scientifique for financial support and Thierry
Bourquard as well as Anne Giraud for performing preliminary asymmetric sulfoxidation experiments.
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