Configurational stability of optically active dichloromethyl p-tolyl sulfoxide and its anionic species: Experimental and theoretical study

Article abstract of DOI:10.1002/hc.21074

Racemization of optically active dichloromethyl p-tolyl sulfoxide took place at -78°C in the presence of potassium bis(trimethylsilyl)amide (KHMDS), while the same racemization did not occur under reflux in toluene in the absence of KHMDS. Density functional theory calculations suggested that the pyramidal inversion at the sulfur center was unlikely to be involved in the racemization mechanism. An anionic species of the sulfoxide was found to be gradually converted into chlorobis(p-tolylsulfinyl)methane and dichlorocarbene. We propose a racemization mechanism mediated by achiral potassium p-toluenesulfenate and chloro(p-tolylsulfinyl)methylene. 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:131-137, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21074

Full text of DOI:10.1002/hc.21074

Heteroatom Chemistry
Volume 24, Number 2, 2013
Configurational Stability of Optically Active
Dichloromethyl p-Tolyl Sulfoxide and
Its Anionic Species: Experimental and
Theoretical Study
Tsutomu Kimura,1 Takahiro Tsuru,2 Hitoshi Momochi,2
and Tsuyoshi Satoh1,2
1Department of Chemistry, Faculty of Science, Tokyo University of Science, Tokyo 162-0826, Japan
2Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Tokyo
162-0826, Japan
Received 29 October 2012; revised 21 December 2012
INTRODUCTION
ABSTRACT: Racemization of optically active
dichloromethyl p-tolyl sulfoxide took place at −78◦C
S-Chiral sulfoxides, in which two different organic
in the presence of potassium bis(trimethylsilyl)amide
(KHMDS), while the same racemization did not
occur under reflux in toluene in the absence of
KHMDS. Density functional theory calculations sug-
gested that the pyramidal inversion at the sul-
fur center was unlikely to be involved in the
racemization mechanism. An anionic species of
the sulfoxide was found to be gradually converted
into chlorobis(p-tolylsulfinyl)methane and dichloro-
carbene. We propose a racemization mechanism me-
diated by achiral potassium p-toluenesulfenate and
groups are connected to the stereogenic sulfur atom
of the sulfinyl group, adopt a configurationally sta-
ble trigonal pyramidal molecular geometry. Opti-
cally active S-chiral sulfoxides are often used as chi-
ral auxiliaries in asymmetric synthesis and are also
found in biologically active compounds [1–5]. There-
fore, the knowledge of the stereochemical behavior
of S-chiral sulfoxides is of great importance and
a considerable effort has been directed toward the
elucidation of this behavior for a long time [6–15].
Optically active aryl 1-chloroalkyl sulfoxides are a
class of useful synthetic intermediates because the
carbon atom bearing arylsulfinyl and chloro groups
can act as both a nucleophile and an electrophile,
and various synthetic transformations with the sul-
foxides have been developed [16–18]. On the other
hand, only a limited number of studies have been
reported for optically active aryl dichloromethyl sul-
foxides 1 [19]. Recently, we established an efficient
method for the optical resolution of racemic aryl
dichloromethyl sulfoxides 1 utilizing (–)-menthone
as a resolving agent [20]. In the course of our study
on the synthetic applications of the sulfoxides 1
[21, 22], we encountered the facile racemization of
the sulfoxides 1 under basic reaction conditions [23];
however, in general, the S-chiral sulfoxides do not
ꢀC
chloro(p-tolylsulfinyl)methylene.
2013 Wiley Peri-
odicals, Inc. Heteroatom Chem 24:131–137, 2013;
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hc.21074
Correspondence to: Tsutomu Kimura; e-mail: kimtwo@rs
.tus.ac.jp
Contract grant sponsor: Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Contract grant number: 22590021.
Contract grant sponsor: Tokyo University of Science Grant for
Research Promotion.
Supporting Information is available in the online issue at
wileyonlinelibrary.com.
ꢀC
2013 Wiley Periodicals, Inc.
131

132 Kimura et al.
TABLE 1 Configurational Stability of Optically Active Sulfoxides (R)-1a, (R)-2a, and (S)-3a (Tol = 4-CH3C6H4)
Entry
Sulfoxide
Conditions
ee (%)
1
2
3
4
5
6
7
(R)-1a
(R)-1a
(R)-1a
(R)-2a
(R)-2a
(S)-3a
(S)-3a
Toluene, 110◦C, 24 h
99a
80b
KHMDS (1.2 equiv), THF, −78 ◦C, 40 s
KHMDS (1.2 equiv), THF, −78◦C, 5 min
Toluene, 110◦C, 24 h
4c
>99a
>99a
>99a
>99a
KHMDS (1.2 equiv), THF, −78◦C, 5 min
Toluene, 110◦C, 24 h
KHMDS (3.5 equiv), THF, −78◦C, 5 min
aSulfoxide was recovered quantitatively.
bSulfoxide was recovered in 94% yield.
cSulfoxide was recovered in 40% yield.
readily racemize [7, 8]. Herein, we report an experi-
mental and theoretical study on the configurational
stability and racemization mechanism of optically
active aryl dichloromethyl sulfoxides.
RESULTS AND DISCUSSION
Configurational Stability of Optically Active
S-Chiral Sulfoxides
SCHEME 1 Structures of model compounds and energy
barriers for the pyramidal inversion of S-chiral sulfoxides.
Optically active dichloromethyl p-tolyl sulfoxide
[(R)-1a] and closely related sulfoxides (R)-2a and
(S)-3a were subjected to thermal and basic con-
ditions to evaluate their configurational stabilities
(Table 1). No significant loss of enantiomeric ex-
cess (ee) was observed when enantiopure sulfoxides
(R)-1a, (R)-2a, and (S)-3a were stirred at 110◦C in
toluene for 24 h (entries 1, 4, and 6). These re-
sults indicated that the sulfoxides (R)-1a, (R)-2a, and
(S)-3a were configurationally stable under neutral
conditions. On the other hand, treatment of opti-
cally active sulfoxide (R)-1a with 1.2 equiv of potas-
sium bis(trimethylsilyl)amide (KHMDS) in THF
resulted in a significant loss of ee within 5 min (en-
tries 2 and 3). Chloromethyl p-tolyl sulfoxide (R)-2a
and methyl p-tolyl sulfoxide (S)-3a did not racem-
ize in the presence of KHMDS (entries 5 and 7)
The generation of carbanions from sulfoxides 2a
and 3a was confirmed by the reaction with CH3OD.
α-Deuterated sulfoxides were obtained with 99% D
content.
Energy Barriers for the Pyramidal Inversion at
the Sulfur Atom
As one of the representative racemization pathways
of S-chiral sulfoxides, pyramidal inversion at the sul-
fur atom is of concern. Therefore, energy barriers
for pyramidal inversion of dichloromethyl phenyl
sulfoxide (1b), chloromethyl phenyl sulfoxide (2b),
and methyl phenyl sulfoxide (3b) and their anionic
species (1bꢀ, 2bꢀ, and 3bꢀ) were calculated using the
6-311++G(d,p) basis set at the B3LYP level with
the Gaussian software (Scheme 1) [24]. The anionic
species 1bꢀ, 2bꢀ, and 3bꢀ had a trigonal pyramidal
geometry around the sulfur atom as well as sulfox-
ides 1b, 2b, and 3b in the ground state (see the
Supporting Information) [25, 26]. The energy bar-
riers for the pyramidal inversion of neutral sulfox-
ides 1b, 2b, and 3b were estimated to be 42.9, 39.4,
and 41.1 kcal/mol, respectively. These values were
Heteroatom Chemistry DOI 10.1002/hc

Configurational Stability of Optically Active Dichloromethyl p-Tolyl Sulfoxide and Its Anionic Species 133
Racemization Mechanism
On the basis of the above experimental results, we
propose a plausible racemization mechanism as
follows (Scheme 3). Elimination of potassium chlo-
ride from dichloro(p-tolylsulfinyl)methylpotassium
[(R)-1aꢀ] results in the formation of chloro(p-
tolylsulfinyl)methylene (6). Alternatively, elim-
ination of potassium p-toluenesulfenate from
dichloro(p-tolylsulfinyl)methylpotassium [(R)-1aꢀ]
leads to the formation of dichlorocarbene. When the
resulting potassium p-toluenesulfenate reacts with
chloro(p-tolylsulfinyl)methylene (6), chlorobis(p-
tolylsulfinyl)methane (4) is formed. The elimina-
tion processes are in equilibrium, and achiral
SCHEME 2 Identification of by-products in the reaction of
sulfoxide 1a with KHMDS.
consistent with the experimental and calculated val-
ues of closely associated compounds [7, 11, 12]. The
computational results suggested that the thermal
pyramidal inversion of neutral sulfoxides 1b, 2b,
and 3b hardly takes place. On the other hand, en-
ergy barriers for the pyramidal inversion of anionic
species 1bꢀ, 2bꢀ, and 3bꢀ (1bꢀ: 25.6 kcal/mol, 2bꢀ:
22.6 kcal/mol, 3bꢀ: 24.4 kcal/mol) were smaller than
those of corresponding neutral sulfoxides 1b, 2b,
and 3b by approximately 17 kcal/mol, respectively.
These results indicated that the anionic species are
more likely to racemize in comparison to the neutral
sulfoxides. However, there was no significant differ-
ence between the energy barriers of anionic species
1bꢀ, 2bꢀ, and 3bꢀ. This conflicted with the experimen-
tal results, in which dichloromethyl p-tolyl sulfoxide
(1a) readily racemized in the presence of KHMDS,
while chloromethyl p-tolyl sulfoxide (2a) and methyl
p-tolyl sulfoxide (3a) did not racemize. Therefore,
the pyramidal inversion pathway is unlikely to be
involved in the racemization mechanism.
potassium
p-toluenesulfenate
and
chloro(p-
tolylsulfinyl)methylene (6) mediate the racem-
ization of dichloro(p-tolylsulfinyl)methylpotassium
(1aꢀ). As shown in Fig. 1, the optimized geometry
of chloro(p-tolylsulfinyl)methylene (6) adopted a
planar structure, in which the sum of bond angles
around the sulfur atom was 356.1◦.
Optically active dichloromethyl p-tolyl sulfox-
ides bearing a substituent at the 1-position were ex-
pected not to racemize under basic conditions be-
cause they do not have an acidic hydrogen atom
at the 1-position. Therefore, optically active 1,1-
dichloroethyl p-tolyl sulfoxide (R)-7 was prepared by
methylation of sulfoxide (R)-1a with iodomethane,
and sulfoxide (R)-7 was subjected to basic conditions
(Scheme 4). Indeed, sulfoxide (R)-7 did not racemize
at all.
The difference in the configurational stability
between the anionic species of the sulfoxides (R)-1a,
(R)-2a, and (S)-3a appears to be dependent on
the feasibility of the elimination processes. The
elimination of potassium p-toluenesulfenate from
dichloro(p-tolylsulfinyl)methylpotassium (1aꢀ) gives
dichlorocarbene, whereas the same eliminations
from chloro(p-tolylsulfinyl)methylpotassium and
(p-tolylsulfinyl)methylpotassium give chlorocar-
bene and carbene, respectively. The former is
the more favorable process because the result-
ing dichlorocarbene is more stable than either
chlorocarbene or carbene [28]. The choice of
countercation is also an important factor for the
progress of racemization. As previously reported,
when the sulfoxide (R)-1a was deprotonated
with lithium diisopropylamide, the racemization
proceeded more slowly than that with KHMDS
[23]. Dichloro(p-tolylsulfinyl)methylpotassium hav-
ing an electropositive potassium cation is more
likely to undergo the elimination than dichloro(p-
Identification of By-Products
After careful examination of the remaining
components in the reaction of sulfoxide (R)-
1a with KHMDS, we found that chlorobis(p-
tolylsulfinyl)methane (4) was formed as a by-
product (Scheme 2, Eq. (1)). The formation of
by-product 4 was confirmed by its oxidation
to known chloroditosylmethane [27]. Chlorobis(p-
tolylsulfinyl)methane (4) appeared to be produced
from 2 equiv of dichloro(p-tolylsulfinyl)methyl an-
ion via a C S bond cleavage and a C S bond
formation. In addition, when the sulfoxide 1a was
treated with KHMDS in the presence of styrene,
(2,2-dichlorocyclopropyl)benzene (5) was obtained
in 3% yield (Scheme 2, Eq. (2)), suggesting that
dichlorocarbene was generated during the course of
the reaction. Dichlorocarbene seemed to be gener-
ated from dichloro(p-tolylsulfinyl)methyl anion via
a C S bond cleavage.
tolylsulfinyl)methyllithium.
Therefore,
lithium
amides are suitable for the generation of anionic
Heteroatom Chemistry DOI 10.1002/hc

134 Kimura et al.
SCHEME 3 A plausible mechanism for the racemization of sulfoxide 1a in the presence of KHMDS.
CONCLUSIONS
We investigated the configurational stability of op-
tically active dichloromethyl p-tolyl sulfoxides un-
der thermal and basic conditions. In contrast to
the usual S-chiral sulfoxides, an anionic species
of dichloromethyl p-tolyl sulfoxide was susceptible
to racemization. The experimental and computa-
tional results suggested that the racemization took
place via achiral potassium p-toluenesulfenate and
chloro(p-tolylsulfinyl)methylene rather than pyrami-
dal inversion at the sulfur atom. The stereochemical
findings described here will contribute to the further
development of the chemistry of optically active S-
chiral sulfoxides.
FIGURE 1 Geometry of chloro(phenylsulfinyl)methylene 6
optimized at the B3LYP/6–311++G(d,p) level. Selected bond
˚
˚
˚
lengths and angles: S–O, 1.50 A; S–C1, 1.80 A; S–C2, 1.64 A;
◦
◦
˚
C2–Cl, 1.73 A; O–S–C1, 111.1 ; C1–S–C2, 107.7 ; C2–S–O,
137.3◦; S–C2–Cl, 117.1◦; O–S–C2–Cl, −14.9◦.
EXPERIMENTAL
General
Melting points were measured on a Yanaco MP-S3
apparatus (Yanaco, Kyoto, Japan) and are uncor-
rected. NMR spectra were measured in a CDCl3 so-
lution (Acros Organics, Fair Lawn, NJ) using Jeol
JNM-LA 500 (JEOL, Tokyo, Japan) and Bruker DPX
300 (Bruker Biospin, Billerica, MA) spectrometers.
Assignments in 13C NMR spectra were made us-
ing DEPT 90 and 135 experiments. Mass spectra
(MS) were obtained at 70 eV by direct insertion
with a Hitachi M-80B mass spectrometer (Hitachi
High-Technologies, Tokyo, Japan). IR spectra were
recorded on a Perkin–Elmer Spectrum One FTIR
instrument (Perkin–Elmer, Waltham, MA). Silica
gel 60 N (Kanto Chemical, Tokyo, Japan) contain-
ing 0.5% fluorescence reagent 254 (Merck KGaA,
Darmstadt, Germany) and a quartz column were
used for column chromatography, and the prod-
ucts having UV absorption were detected by UV
SCHEME 4 Synthesis of 1,1-dichloroethyl p-tolyl sulfoxide
(R)-7 and racemization experiment of (R)-7 under basic con-
ditions.
species of aryl dichloromethyl sulfoxides in asym-
metric synthesis [21, 22]. In the previous study, we
proposed a chlorine-assisted pyramidal inversion
mechanism [23]. If the mechanism is operative,
chloromethyl p-tolyl sulfoxide 2a should also
racemize under basic reaction conditions. However,
sulfoxide 2a did not racemize at all in the pres-
ence of KHMDS. Therefore, the chlorine-assisted
pyramidal inversion mechanism is unlikely to be
involved in the racemization mechanism.
Heteroatom Chemistry DOI 10.1002/hc

Configurational Stability of Optically Active Dichloromethyl p-Tolyl Sulfoxide and Its Anionic Species 135
irradiation. Anhydrous THF was purchased from
in toluene (0.91 mL, 0.46 mmol) at −78◦C, and the
mixture was stirred at that temperature for 10 min.
The reaction was quenched with sat. aq. NH4Cl
(1 mL), and the mixture was extracted with CHCl3
(2 × 10 mL). The organic layer was dried over
MgSO4 and concentrated under reduced pressure.
The residue was purified by column chromatogra-
phy on silica gel using hexane-EtOAc (2:1) as the
Kanto Chemical and used as supplied. Toluene
(Kanto Chemical) and diisopropylamine (Kanto
Chemical) was distilled from CaH2 (Nacalai Tesque,
Kyoto, Japan). Iodomethane (Kanto Chemical) was
distilled from desiccant-anhydrous calcium sulfate
(W.A. Hammond, Drierite Co., Xenia, OH). All re-
actions involving air- or water-sensitive compounds
were routinely conducted in glassware, which had
been flame-dried under a positive pressure of ar-
gon. Optically active sulfoxides (R)-1a, (R)-2a, and
(S)-3a were prepared according to the procedure de-
scribed in the literature [20,29]. Enantiomeric excess
of sulfoxides 1–3 were determined by HPLC anal-
ysis [JASCO Gulliver (JASCO, Tokyo, Japan), 10%
i-PrOH/hexane (v/v) (Kanto Chemical), flow rate:
0.50 mL/min] equipped with a Chiralcel OD column
(ϕ 0.46 cm × 25 cm) (Daicel Chemical Industries,
Osaka, Japan) provided by Daicel Chemical. Specific
rotations were measured on a JASCO DIP-1000 Po-
larimeter (JASCO).
*
eluent to give a diastereomeric mixture of (Rs ,
Ss , r*)- and (Rs , Ss , s*)-4 [8.0 mg, 0.025 mmol,
13%, Rf = 0.24 (hexane-EtOAc = 2:1)] as a pale
*
*
*
*
*
orange oil and (Rs , Rs )-4 [21.3 mg, 0.065 mmol,
34%, Rf = 0.19 (hexane-EtOAc = 2:1)] as a colorless
solid.
*
*
*
*
(Rs , Ss , r*)- and (Rs , Ss , s*)-
*
*
Chlorobis(p-tolylsulfinyl)methanes [(Rs , Ss ,
*
*
r*)-4 and (Rs ,Ss ,s*)-4]
A 52:48 mixture of two diastereomers; pale orange
oil; IR (neat) 2922, 1595, 1492, 1450, 1400, 1085,
1
1056, 812, 754 cm−1; H NMR δ 2.44 (s, 6H), 2.46
(s, 6H), 5.03 (s, 1H), 5.46 (s, 1H), 7.33–7.44 (m, 8H),
7.62 (d, J = 8.2 Hz, 4H), 7.75 (d, J = 8.2 Hz, 4H); 13C
NMR δ 21.5 (CH3), 21.6 (CH3), 88.7 (CH), 90.8 (CH),
125.2 (CH), 126.2 (CH), 129.9 (CH), 130.0 (CH),
135.0 (C), 135.5 (C), 143.3 (C), 143.8 (C); MS (FAB+)
m/z (%) 327 ([M + H]+, 100), 171 (58), 139 (65),
123 (20); HRMS (FAB+) calcd for C15H16ClO2S2:
Racemization Experiments under Thermal
Conditions
A solution of (R)-1a (22.3 mg, 0.100 mmol) in toluene
(1.0 mL) was stirred at 110◦C for 24 h. The solu-
tion was concentrated under reduced pressure, and
the residue was purified by column chromatography
on silica gel using hexane-EtOAc (5:1) as the eluent
to give 1a [22.1 mg, 0.0990 mmol, 99%, Rf = 0.43
(hexane-EtOAc = 2:1)] as a colorless solid.
30
327.0280, found: 327.0278; [α]D = −0.45 (c 0.39,
ethanol).
*
*
(Rs , Rs )-Chlorobis(p-tolylsulfinyl)methane
*
*
Racemization Experiments under Basic
Conditions
[(Rs , Rs )-4]
Colorless crystals; mp 162.5–163.5◦C (EtOAc/
hexane); IR (KBr) 2911, 1593, 1494, 1447, 1399,
A solution of (R)-1a (22.3 mg, 0.100 mmol) in THF
(1.0 mL) was added to a 0.50 M solution of KHMDS
in toluene (0.24 mL, 0.12 mmol) at −78◦C, and the
mixture was stirred at that temperature for 40 s. The
reaction was quenched with sat. aq. NH4Cl (1 mL),
and the mixture was extracted with CHCl3 (2 ×
10 mL). The organic layer was dried over MgSO4 and
concentrated under reduced pressure. The residue
was purified by column chromatography on silica
gel using hexane-EtOAc (5:1) as the eluent to give
1a [21.0 mg, 0.094 mmol, 94%, Rf = 0.43 (hexane-
EtOAc = 2:1)] as a colorless solid.
1
1091, 1048, 815, 724 cm−1; H NMR δ 2.41 (s, 3H),
2.43 (s, 3H), 4.80 (s, 1H), 7.34 (d, J = 8.0 Hz, 2H),
7.36 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.3 Hz, 2H),
7.70 (d, J = 8.3 Hz, 2H); 13C NMR δ 21.5 (CH3),
21.6 (CH3), 94.3 (CH), 125.0 (CH), 125.9 (CH), 130.0
(CH), 130.1 (CH), 135.9 (C), 136.9 (C), 143.0 (C),
143.8 (C); MS (FAB+) m/z (%) 327 ([M + H]+, 100),
171 (77), 139 (88), 123 (30); HRMS (FAB+) calcd for
29
C15H16ClO2S2: 327.0280, found: 327.0278; [α]D
−3.8 (c 0.45, ethanol).
=
Oxidation of Chlorobis(p-tolylsulfinyl)methane
(4)
Reaction of Sulfoxide (R)-1a with KHMDS
Leading to the Formation of
Chlorobis(p-tolylsulfinyl)methane 4
m-Chloroperoxybenzoic acid (35.9 mg, 0.156 mmol)
was added to solution of chlorobis(p-
a
A solution of (R)-1a (85.4 mg, 0.383 mmol) in THF
tolylsulfinyl)methane (4, 8.4 mg, 0.026 mmol,
(3.8 mL) was added to a 0.50 M solution of KHMDS
a 58:22:20 mixture of three diastereomers) in CHCl3
Heteroatom Chemistry DOI 10.1002/hc

136 Kimura et al.
(0.52 mL) at 25◦C, and the reaction mixture was
stirred at that temperature for 72 h. The reaction
was quenched with sat. aq. Na2SO3 (0.5 mL), and
the mixture was extracted with CHCl3 (2 × 10 mL).
The organic layer was dried over MgSO4 and
concentrated under reduced pressure. The residue
was purified by column chromatography on silica
gel using hexane-EtOAc (3:1) as the eluent to give
chloroditosylmethane [9.1 mg, 0.025 mmol, 98%,
Rf = 0.16 (hexane-EtOAc = 3:1)] as a colorless solid.
duced pressure. The residue was purified by column
chromatography on silica gel using hexane-EtOAc
(5:1) as the eluent to give (R)-7 [45.4 mg, 0.191 mmol,
16%, Rf = 0.26 (hexane-EtOAc = 5:1)] as a colorless
oil.
1,1-Dichloroethyl p-Tolyl Sulfoxide [(R)-7]
IR (neat) 3057, 2987, 2926, 1597, 1493, 1439, 1371,
1
1098, 1080, 1068, 1053, 812, 740 cm−1; H NMR δ
2.26 (s, 3H), 2.45 (s, 3H), 7.35 (d, J = 8.1 Hz, 2H),
7.72 (d, J = 8.1 Hz, 2H); 13C NMR δ 21.6 (CH3), 30.8
(CH3), 98.0 (C), 127.5 (CH), 129.2 (CH), 135.2 (C),
143.7 (C); MS (FAB+) m/z (%) 237 ([M+H]+, 100),
Chloroditosylmethane
Colorless crystals; mp 167.0–168.0◦C (CHCl3); IR
(KBr) 2923, 1593, 1346, 1200, 1159, 1078, 818, 763,
185 (19), 141 (60), 123 (42); HRMS (FAB+) calcd
1
726 cm−1; H NMR δ 2.49 (s, 6H), 5.51 (s, 1H), 7.41
25
for C9H11Cl2OS: 236.9908, found: 236.9907; [α]D
=
(d, J = 8.3 Hz, 4H), 7.91 (d, J = 8.3 Hz, 4H); 13C
NMR δ 21.8 (CH3), 84.0 (CH), 129.8 (CH), 130.6
(CH), 132.5 (C), 147.0 (C).
−34.1 (c 0.41, ethanol); HPLC: DAICEL CHIRALCEL
OD (ϕ 0.46 cm × 25 cm); 2-propanol/hexane = 1/9;
flow rate = 0.50 mL/min; detection at 254 nm; re-
tention time = 11.5 min (major), 13.2 min (minor);
31% ee.
Treatment of Sulfoxide 1a with KHMDS in the
Presence of Styrene
A solution of 1a (112 mg, 0.500 mmol) in THF
(5.0 mL) was added to a 0.50 M solution of
KHMDS in toluene (1.20 mL, 0.60 mmol) and
styrene (521 mg, 5.00 mmol) at −78◦C, and the mix-
ture was allowed to warm to room temperature. The
reaction mixture was stirred at that temperature
for 20 h. The reaction was quenched with sat. aq.
NH4Cl (3 mL), and the mixture was extracted with
CHCl3 (2 × 20 mL). The organic layer was dried over
MgSO4 and concentrated under reduced pressure.
The residue was purified by column chromatogra-
phy on silica gel using hexane-EtOAc (2:1) as the
eluent to give (2,2-dichlorocyclopropyl)benzene [5,
2.5 mg, 0.0134 mmol, 3%, Rf = 0.65 (hexane)] as
a colorless oil, chlorobis(p-tolylsulfinyl)methane (4,
22.3 mg, 0.0682 mmol, 27%), and dichloromethyl p-
toly sulfoxide (1a, 16.1 mg, 0.0721 mmol, 14%).
Density Functional Theory Calculations
Density functional theory calculations were per-
formed with the Gaussian 03 software [24]. All ge-
ometries employed in this study have been fully
optimized in the gas phase without any symmetry
constraints at the B3LYP/6-311++G(d,p) level. The
QST3 method was used to locate the transition states
[30]. Frequency calculations were carried out at the
same computational level to confirm that the struc-
tures obtained correspond to energetic minima or
transition states (zero or one imaginary frequen-
cies, respectively). The Jmol program was used to
draw the molecular structures [31]. High perfor-
mance computing resources were provided by the
Tokyo University of Science.
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