Absolute configuration and racemization mechanism of arenechalcogenic acids: Resolution of tellurinic acid

Article abstract of DOI:10.1016/j.tetasy.2004.10.018

An optically active arenetellurinic acid (+)-1d was obtained by means of liquid chromatography on a chiral column. The absolute configuration of the optically active tellurinic acid was assigned by comparing its circular dichroism spectrum with that of an

Full text of DOI:10.1016/j.tetasy.2004.10.018

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3791–3797
Absolute configuration and racemization mechanism of
arenechalcogenic acids: resolution of tellurinic acid
Yusuke Nakashima,a Toshio Shimizu,a,* Kazunori Hirabayashi,a Masanori Yasui,b
Masaki Nakazato,b Fujiko Iwasakib and Nobumasa Kamigataa,*
aDepartment of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-ohsawa, Hachioji,
Tokyo 192-0397, Japan
bDepartment of Applied Physics and Chemistry, The University of Electro-Communications, Chofu, Tokyo 182-8585, Japan
Received 21 September 2004; accepted 4 October 2004
Abstract—An optically active arenetellurinic acid (+)-1d was obtained by means of liquid chromatography on a chiral column. The
absolute configuration of the optically active tellurinic acid was assigned by comparing its circular dichroism spectrum with that
of an optically active sulfinic acid, the absolute configuration of which was determined by X-ray crystallographic analysis. The
absolute configurations of areneseleninic acids, which were previously obtained by chromatographic resolution, were assigned also
on the basis of their circular dichroism spectra. The optically active tellurinic acid (S)-(+)-1d was stable toward racemization in hex-
ane, although the racemization occurred in hexane/2-propanol. Kinetic studies on the racemization, the oxygen exchange reaction
using H218O, and theoretical studies revealed that a pathway involving an achiral tellurane formed by the addition of water to tel-
lurinic acid exists for the racemization. The racemization mechanism of the optically active seleninic acid involving a seleninate
anion, which was proposed previously, was confirmed by experiments using H218O. The racemization mechanism of the optically
active sulfinic acid in solution was concluded to be the same as that of the optically active seleninic acid. The difference in
the racemization mechanism among the optically active chalcogenic acids is due to their ability to form hypervalent hydrate
structures.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
during concentration of the eluates under reduced pres-
sure. Recently, we also reported the isolation of opti-
cally active methaneseleninic acid as a stable solid by
chiral crystallization.4 To the best of our knowledge,
there is no study concerning optically active tellurinic
acids, which are analogues of seleninic acids. Moreover,
there are few reports on the preparation of racemic tel-
lurinicacids so far. 5 The scarcity seems to be due to that
the tellurinic acids have polymeric structures and are
insoluble in common organic solvents.
Recently, many chiral tricoordinated selenium and tellu-
rium compounds, such as oxides, onium salts, ylides,
and imides, have been isolated, and their characteristics
clarified.1 Chalcogenic acids are also tricoordinated
chalcogen compounds and have pyramidal structures.
Therefore, chalcogenic acids have stereogenic centers
on the chalcogen atoms. Previously, we have reported
the resolution of areneseleninicacids by means of liquid
chromatography on an optically active column, and
found that the optically active areneseleninic acids race-
mize in solution.2,3 It was also found that the racemiza-
tion of areneseleninicacids is suppressed to some extent
by the bulky substituents at the ortho position of the
benzene ring, although no single enantiomers could be
isolated as stable solids due to complete racemization
We examined the resolution of arenetellurinicacids by
means of liquid chromatography on optically active
columns and succeeded in obtaining an optically active
tellurinic acid for the first time, the absolute configura-
tion of which was assigned. The racemization mecha-
nism of the optically active tellurinic acid was
clarified. Herein, we report the resolution of tellurinic
acid, together with the absolute configurations and
the racemization mechanisms of the optically active
chalcogenic acids.6
*
Corresponding authors. Tel.: +81 426 77 2556; fax: +81 426 77
2525; e-mail: kamigata-nobumasa@c.metro-u.ac.jp
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.10.018

3792
Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
2. Results and discussion
2.1. Preparation of arenetellurinic acids
Arenetellurinicacids having bulky substituents of vari-
ous sizes 1a–d were prepared from corresponding diaryl
ditellurides by oxidation with ozone and subsequent
hydrolysis in yields of 24%, 63%, 61%, and 32%, respec-
tively. Tellurinicaicds
both the aromaticand aliphaticregions of their
1a–d showed broad signals in
1H
NMR spectra in CDCl3, which may be because that
the arenetellurinicaicds are very polar moleucles and
associate in nonpolar solvent. The IR spectra of 1a–d
in the solid state (KBr) showed broad bands centering
on 3360–3400 (OH) cmꢀ1 as well as broad bands in
the range of 500–800cmꢀ1, which were assigned to m
(Te@O). The breadth of the bands of m (Te@O)
appeared to be due to intermolecular interactions in
Figure 1. Circular dichroism spectrum of (+)-1d in hexane.
the solid state. Arenetellurinicaicds
1a and 1b were
the optically active tellurinic acid took place during
the concentration of the eluate. To the best of our
knowledge, this is the first report of the isolation of an
optically active tellurinic acid, although the enantio-
meric excess could not be determined.
insoluble in organicsolvents without hcloroform and
dichloromethane. On the other hand, arenetellurinic
acids 1c and 1d were soluble not only in halogenated sol-
vents, but also in hexane and alcohol, which were used
as the eluents for HPLC on optically active columns.
2.3. Absolute configurations of optically active arenetel-
lurinic acid (+)-1d and optically active areneseleninic
acids
O
1) O3
ArTeTeAr
Ar Te OH
As far as we know, there is no report of the relationship
between the absolute configurations and the chiroptical
properties of the optically active arenechalcogenic acids.
On the other hand, there are many reports concerning
the crystal structures of sulfinic acids, and some crystals
of sulfinic acids belonging to chiral space groups.7,8 For
example, the crystal structure of arenesulfinic acid 2 with
a crown-ether ring has been reported, and it was clari-
fied that the crystal belongs to the chiral space group
P212121 although the chirality of 2 is not mentioned in
the paper.7 If the relationship between the chiroptical
properties and the absolute configuration of an enantio-
mer of 2 could be determined, the absolute configura-
tions of the arenechalcogenic acids would be clarified
on the basis of the chiroptical properties. Therefore, are-
nesulfinicacid 2 was prepared and its chiral crystals ob-
tained by recrystallization from ether according to the
literature.7 One of the single crystals showed a positive
Cotton effect at around 240nm in the solid state (KBr
disk), while another one showed a negative Cotton effect
in the same region (Fig. 2), whereas acetonitrile and
ether solutions of the crystals showed no Cotton effect
even within 5s after dissolution. These results indicate
that the optically active sulfinic acid 2 racemizes very
rapidly in solution. The absolute configuration of 2,
which showed a negative Cotton effect at around
240nm, was determined to be S by X-ray crystallo-
graphicanalysis ( Fig. 3). The two oxygen atoms of the
OH and S@O groups could be discriminated on the
basis of the bond distances between the sulfur atom
and the oxygen atoms, while the hydrogen atom of the
OH group was found on the D-map. Thus, on the basis
of the similarity of their circular dichroism spectra, the
absolute configuration of optically active tellurinic
acid (+)-1d, which showed a negative Cotton effect
2) H2O
1a: Ar = Ph
1b: Ar = 2,4,6-Me3C6H2
1c: Ar = 2,4,6-Et3C6H2
1d: Ar = 2,4,6-i-Pr3C6H2
2.2. Resolution of arenetellurinic acids 1c and 1d by means
of HPLC
Arenetellurinicacids 1c and 1d were subjected to chro-
matography on two types of chiral column
(4.6 · 250mm), one packed with amylose carbamate
derivative-silica gel (Daicel Chiralpak AS) and the other
packed with cellulose carbamate derivative-silica gel
(Daicel Chiralcel OD), using hexane/2-propanol as the
eluent. Their chromatograms showed only one peak in
both cases. However, the ratio of the enantiomers was
considered to differ between the former portion and
the latter portion of the peak. When 1d was subjected
to chromatography on a larger column (10 · 250mm),
which was packed with cellulose carbamate derivative-
silica gel using hexane as the eluent, the fraction corre-
sponding to the first half of the peak showed a positive
28
435
specific rotation {½aŠ ¼ þ2:5 ꢁ 103 (c 1.2 · 10ꢀ3, hex-
ane)} and a negative Cotton effect at 238nm on the cir-
cular dichroism spectrum (Fig. 1), whereas the following
fractions showed no Cotton effect. On the other hand,
arenetellurinicaicd 1c could not be optically resolved
under the same conditions. In the case of the optically
active seleninic acids, concentration of the eluates
caused complete racemization.2,3 By contrast, the molar
ellipticity of (+)-1d was not reduced by concentration of
the hexane solution, indicating that no racemization of

Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
3793
O
Ar Se OH
Ar = 2,4,6-Me C H
2
3a:
3b:
3c:
3d:
3
6
Ar = 2,4,6-Et C H
3
6
2
Ar = 2,4,6-i-Pr C H
3
6
2
Ar = 2,4,6-t-Bu C H
3
6
2
2.4. Racemization of optically active chalcogenic acids
The stability toward the racemization of optically active
tellurinicacid ( S)-(+)-1d was examined in solution. The
change of the circular dichroism spectrum of (S)-(+)-1d
in various solvents (ca. 2 · 10ꢀ5 M) was monitored at
room temperature. No change in the ellipticity at
270nm was observed on the circular dichroism spectrum
of (S)-(+)-1d in hexane even after 3days, indicating that
no racemization occurred under the given conditions.
However, the ellipticity in the same region was de-
creased with time in hexane/2-propanol (99/1), and
showed a good linear relationship in the first-order rate
plots. The kinetics for the racemization of (S)-(+)-1d
was examined in order to clarify the mechanism. The
first-order rate constants and half-lives for the racemiza-
tion of (S)-(+)-1d are summarized in Table 1. The rate
constant in 2-propanol/H2O (4/1) (2.16 · 10ꢀ3 sꢀ1) was
much larger than that in hexane/2-propanol (99/1)
(1.18 · 10ꢀ4 sꢀ1), indicating that a small volume of resi-
dual water in the distilled 2-propanol may cause the
racemization of the optically active tellurinic acid. Two
mechanisms involving water for the racemization are
proposed. One is the formation of an achiral tellurane
by the addition of water to tellurinicacid, and the other
is the formation of a tellurinate anion by the deprotona-
tion of tellurinic acid with water. The oxygen exchange
reaction of tellurinic acid was examined using H218O
to check whether the tellurane is involved in the mecha-
nism. When racemic tellurinic acid 1d was dissolved in 2-
propanol/H218O (4/1, 95 atom% 18O) and allowed to
stand for 2h, the ratio of 2,4,6-i-Pr3C6H2Te16O2H:
2,4,6-i-Pr3C6H2Te16O18OH:2,4,6-i-Pr3C6H2Te18O2H
was 5:3:5 based on the peak intensities on the MS spec-
trum, meaning that the oxygen atoms of tellurinicacid
were indeed exchanged via an achiral tellurane formed
by the addition of water. However, the rate of the
reaction for tellurane formation is distinctly lower than
the rate of the racemization. Comparing the rate
constants of the racemization of (S)-(+)-1d, the rate
constant in 2-propanol/H2O (4/1) is approximately
three times as large as that in 2-propanol/D2O (4/1),
showing that there is a primary kineticisotope effect in
Figure 2. Circular dichroism spectra of the enantiomers of sulfinic acid
2 in the solid state (KBr disk).
˚
Figure 3. X-ray structure of (S)-2. Selected bond lengths (A) and bond
angles (ꢁ): S1–O1 1.4734(11), S1–O2 1.6231(10), S1–C2 1.8052(12),
O1–S1–O2 110.56(7), O1–S1–C2 103.92(6), O2–S1–C2, 100.61(5).
at 238nm, was determined to be S. The absolute
configurations of optically active seleninic acids 3a–d
obtained by chromatographic resolution2,3 have not
been determined so far. In the same manner, the abso-
lute configurations of the enantiomers of 3, which
showed negative Cotton effects at around 230–250nm,
were determined to be S while those of the enantiomers
that showed positive Cotton effects in the same region
were determined to be R.
Table 1. First-order rate constants and half-lives for racemization of
(S)-(+)-1da
k1 · 104 (sꢀ1
No racemization (after 3days)
1.18 98.2
21.6 5.34
7.87 14.5
)
t1/2 (min)
O
O
O
Solvent
Hexane
O
SO2H
O
Hexane/2-propanol (99/1)
2-Propanol/H2O (4/1)
2-Propanol/D2O (4/1)
a In ca. 2 · 10ꢀ5 M solution at 25 1ꢁC.
2

3794
Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
the optically active seleninic acid, that is, it proceeds
O
OH
OH
Te
H2O/-OH-
-H+
via a sulfinate anion with the extrusion of a proton,
although intermolecular proton transfer may participate
in the racemization.
-H+
H2O/-OH-
+
:
Ar
:
:
Ar
Te
Te
OH
OH
O
Ar
A
OH-
Vertex inversion and edge inversion, which are known
to be the racemization mechanisms of some tricoordi-
nated optically active chalcogen compounds,10 and
intramolecular proton transfer between the two oxygen
atoms of the chalcogenic acids (Scheme 3) are also pos-
sible racemization mechanisms of the chalcogenic acids.
The barriers for vertex inversion, edge inversion and
intramolecular proton transfer of benzenechalcogenic
acid were estimated by MO calculations (MP2/
LANL2DZ) (Table 2). The activation energies of the
inversions and intramolecular proton-transfer are higher
than 23kcalmolꢀ1, and are too high for rapid racemiza-
tion to occur at room temperature.
-H2O
-H2O
OH
:
Te OH
OH
Ar
Scheme 1.
the racemization. Thus, the rate-controlling step of the
racemization is the proton transfer from water to
tellurinicaicd, and the equilibrium between tellurinic
acid and an achiral diol cation A probably participates
in the racemization (Scheme 1).
O
Ch
Previously, we proposed that the racemization of the
optically active areneseleninic acid proceeds via the cor-
responding seleninate anion with the extrusion of a pro-
ton under dilute conditions (Scheme 2).3 However, the
pathway involving an achiral selenurane, which is
formed by the addition of water to seleninicacid, might
exist in the racemization of areneseleninic acid. There-
fore, a further investigation was carried out in order
to confirm the racemization mechanism of areneseleni-
nicaidc. A hexane/2-propanol (99/1) solution of
enantiomerically pure (R)-3c was stirred in the presence
of excess H218O (97 atom% 18O) for 30min at room
temperature. However, no ion peak corresponding to
seleninic acid containing 18O was observed in the MS
spectrum despite racemization taking place. This result
indicates that the formation of selenurane by the addi-
tion of water does not occur under the given conditions.
Therefore, the racemization of the optically active arene-
seleninic acids in solution was confirmed to proceed via
a seleninate anion with the extrusion of a proton
(Scheme 2).
O
H
H
O
Ch
:
:
Ar
O
Ar
Scheme 3.
Table 2. Activation energies of vertex inversion, edge inversion, and
intramolecular proton transfer of benzenechalcogenic acids
(kcalmolꢀ1
)
Vertex
inversion
Edge
inversion
Intramolecular
proton transfer
PhSO2H
PhSeO2H
PhTeO2H
59.6a
71.8a
81.8a
Ab
23.8c
25.0c
27.0c
31.6a
25.8a
a Uncorrected values.
b The transition state was not found.
c The values were corrected for zero-point vibrational energies using a
scaling factor of 0.9434 at the standard state (298.15K, 1atm).
The difference in the racemization mechanisms among
the optically active chalcogenic acids can be explained
by the ability to form hypervalent hydrate structures
(sulfurane, selenurane, and tellurane) of the chalcogenic
acids. The energy gaps of the hydrogen-bonding forms
and the hydrate forms of the arenechalcogenic acids
(Scheme 4) were estimated by MO calculations (MP2/
LANL2DZ), and as a result, energy changes from the
hydrogen-bonding forms to the hydrate forms of benz-
enesulfinic acid, benzeneseleninic acid, and benzenetellu-
O
O
OH
Se
H3O+
- H+
- H+
-
Se
Se
:
:
H3O+
:
OH
R
O
O
R
R
Scheme 2.
As stated above, optically active sulfinic acid 2 race-
mized very rapidly in solution. Therefore, the racemiza-
tion mechanism of optically active sulfinic acid 2 was
also examined. When a 2-propanol solution of sulfinic
acid 2 was stirred in the presence of excess H218O (95
atom% 18O) for 2h at room temperature, no ion peak
corresponding to sulfinic acid containing 18O was ob-
served in the MS spectrum, indicating that addition of
water to sulfinic acid does not occur under the given
rinicaicd
1a were 17.8, 14.0, and ꢀ4.85kcalmolꢀ1
,
respectively, meaning that tellurinic acid forms tellurane
more readily than either sulfinic acid or seleninic acid
OH
O
H
OH
:
O H
Ar Ch
Ch
Ar
conditions. In general, arenesulfinic acids are more
9
O H
OH
acidicthan areneseleninicacids.
Therefore, the racemi-
hydrogen-bonding form
hydrate form
zation of the optically active sulfinic acid in solution is
concluded to proceed in the same manner as that of
Scheme 4.

Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
3795
does. However, the results also show that tellurinicacid
1a mainly exists in the hydrate form in the presence of
water. In the case of a model molecule of tellurinic acid
4 with bulky substituents, the energy change from the
hydrogen-bonding form to the hydrate form is almost
nil (ꢀ1.00kcalmolꢀ1), indicating that bulky substituents
are effective for suppressing the formation of achiral tel-
lurane (hydrate form).
component which remained in the aqueous layer ex-
tracted with dichloromethane (50mL · 2). The com-
bined organiclayer was dried over anhydrous
magnesium sulfate. The solution was concentrated to
small volume (ca. 5mL) under reduced pressure, at
which point methanol (50mL) was added. The fine pre-
cipitates formed were washed with methanol and dried
in vacuo.
4.3. Benzenetellurinic acid 1a5h
1
O
Yield 24%; mp 270ꢁC (colorless powder; decomp.); H
NMR (500MHz, CDCl3): d 2.55 (1H, br), 6.76 (5H,
br); MS (EI, 30eV) m/z 207, 205, 154, 77; MS (FAB)
m/z 239 (M+ꢀH, 130Te), 237 (M+ꢀH, 128Te); IR (KBr)
3394 (br, OH), 3053, 1477, 1436, 1062, 735, 630 (br,
Te
OH
4
Te@O)cmꢀ1
.
4.4. 2,4,6-Trimethylbenzenetellurinic acid 1b
3. Conclusion
1
Yield 63%; mp 226ꢁC (colorless powder; decomp.); H
NMR (500MHz, CDCl3): d 1.62 (3H, br), 2.17 (6H,
br), 2.62 (1H, br), 6.68 (2H, br); MS (EI, 30eV) m/z
248, 246, 119, 105, 91; MS (FAB) m/z 281 (M+ꢀH,
130Te), 279 (M+ꢀH, 128Te); IR (KBr) 3367 (br, OH),
2963, 2932, 2874, 2360, 1592, 1559, 1457, 1037, 1020,
The resolution of arenetellurinic acid was accomplished
by means of liquid chromatography on a chiral column.
The relationship between the absolute configurations
and the circular dichroism spectra of the optically active
arenechalcogenic acids was clarified on the basis of X-
ray crystallographic analysis of an arenesulfinic acid.
Kineticstudies on the racemization, the oxygen exchange
reaction using H218O, and theoretical studies revealed
that a pathway involving an achiral tellurane exists for
the racemization of the optically active arenetellurinic
acid in solution, and the racemization of the optically
active areneseleninic acid proceeds via a seleninate
anion.
871, 667 (br, Te@O)cmꢀ1
.
4.5. 2,4,6-Triethylbenzenetellurinic acid 1c
1
Yield 61%; mp 201ꢁC (colorless powder; decomp.); H
NMR (500MHz, CDCl3): d 0.75 (3H, br), 1.17 (6H,
br), 1.70 (1H, br), 2.54 (4H, br), 3.00 (2H, br), 6.82
(2H, br); MS (EI, 30eV) m/z 290, 288, 160, 133; MS
(FAB) m/z 323 (M+ꢀH, 130Te), 321 (M+ꢀH, 128Te);
IR (KBr) 3384 (br, OH), 2922, 2360, 2341, 1457, 1100,
4. Experimental
4.1. General
1031, 846, 630 (br, Te@O), 542cmꢀ1
.
4.6. 2,4,6-Triisopropylbenzenetellurinic acid 1d
Dichloromethane, hexane and 2-propanol were distilled
from CaH2 before use. Melting points were determined
on a Yamato MP-21 melting point apparatus. UV–vis
spectra were measured on a UV-3100PC UV-VIS-NIR
scanning spectrometer. IR spectra were measured on a
Yield 32%; mp 209ꢁC (colorless powder from methanol;
1
decomp.); H NMR (500MHz, CDCl3): d ꢀ0.3 to 2.0
(18H, br), 2.81 (3H, br), 4.14 (1H, br), 7.03 (2H, br);
MS (EI, 30eV) m/z 332, 330, 203, 189, 91; MS (FAB)
m/z 365 (130Te, M+ꢀH), 363 (128Te, M+ꢀH); IR (KBr)
3393 (br, OH), 2960, 2867, 2360, 1595, 1463, 1103,
878, 647 (br, Te@O)cmꢀ1; UV (hexane) kmax 279 (sh, e
3.30 · 103), 249 (sh, e 1.08 · 104), 197 (e 6.70 · 104)nm.
1
Perkin–Elmer spectrum GX FT-IR system. H and 13C
NMR spectra were recorded on a JEOL JNM-EX-500
FT NMR System. Mass spectra (MS) were determined
on a JEOL JMS-LX1000 and a JEOL JMS-GCMATE
system. Circular dichroism spectra were measured on a
JASCO J-725 spectropolarimeter. Optical rotations
were measured on a JASCO DIP-140 digital polarimeter
4.7. Resolution of 1d
A racemic sample of 1d (30mg) in hexane (0.5mL) was
charged to a chiral column packed with cellulose carba-
mate derivative-silica gel (Daicel Chiralcel OD;
10 · 250mm) and eluted with hexane at a flow rate of
1.0mLminꢀ1. Arenetellurinic acid (1mg) was collected
from the first half of the peak. The chemical structure
was confirmed by 1H NMR spectra after concentration.
and are given in 10ꢀ1 degcm2 gꢀ1
.
4.2. General procedure for the preparation of arenetellu-
rinic acids 1
Diaryl ditelluride (5mmol) was dissolved in dichloro-
methane (100mL) and ozone bubbled into the solution
at ꢀ40ꢁC. After disappearance of color for the ditellu-
ride, water (100mL) was added to the solution, and
the mixture stirred vigorously for 4h at room tempera-
ture. The organiclayer was separated and the organic
4.8. (S)-(+)-1d
28
435
Mp 208ꢁC (colorless powder; decomp.); ½aŠ
¼
þ2:5 ꢁ 103 (c 1.2 · 10ꢀ3, hexane); CD (hexane) 270 ([h]

3796
Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
1.27 · 104), 238 ([h] ꢀ2.18 · 104)nm. Enantiomericex-
Cambridge CrystallographicData Centre as supplemen-
tary publication numbers CCDC 250403.
1
cess could not be determined by HPLC or H NMR
using Eu(hfc)3.
4.12. Kinetic studies on racemization of (S)-(+)-1d
4.9. 2-Sulfino-1,3-xylyl-18-crown-5 27
Kineticstudies of ( S)-(+)-1d were examined in solutions
(ca. 2 · 10ꢀ5 M) at 25 1ꢁC. The rates of racemization
were calculated on the basis of their circular dichroism
spectra and plotted to the first-order rate equation.
To the THF (10mL) solution of 2-bromo-1,3-xylyl-18-
crown-5 (1.12g, 3.00mmol) was added dropwise BuLi
(3.12mmol) at ꢀ78ꢁC. The solution was stirred for
2h, and sulfur dioxide bubbled into the solution for
10min. The reaction mixture was slowly warmed to
room temperature and concentrated under reduced pres-
sure. The residue was dissolved into chloroform (15mL)
and extracted with 10% aqueous sodium hydroxide solu-
tion (15mL · 2) and with water (20mL · 2). The com-
bined aqueous layer was concentrated to 20mL under
reduced pressure, acidified with 4M hydrochloric acid
(50mL), extracted with chloroform (20mL · 5). The
solution was dried over anhydrous magnesium sulfate
and concentrated under reduced pressure. Recrystalliza-
tion of the residue from ether afforded 2 (282mg, 26%):
mp 97–99ꢁC (from ether, lit. 101–104ꢁC); 1H NMR
(500MHz, CDCl3): d 3.56–3.74 (16H, m), 4.75 (4H,
br), 7.30 (2H, d, J = 7.35Hz), 7.35 (1H, t, J = 7.35Hz),
9.70 (1H, br); 13C NMR (125MHz, CDCl3): d 68.6,
69.5, 70.1, 70.2, 70.6, 130.4, 131.4, 137.1, 147.6; UV
(MeCN) kmax 270 (e 2.98 · 103), 222 (e 1.39 · 104), 197
(e 6.53 · 104)nm.
4.13. Theoretical study
Geometries were optimized using the MP211 method
with the LANL2DZ12 basis set. All calculations were
performed by using the GAUSSIAN 9813 program on an
IBM p690-681 (RegattaH) computer. Vibrational fre-
quency analysis of each geometry of transition states
of vertex inversion, edge inversion, and intramolecular
proton-transfer of chalcogenic acids showed one imagi-
nary frequency which corresponds to the vertex inver-
sion or edge inversion mode, clearly indicating the real
saddle-point in the reaction pathway. Differences in
the zero-points energies between the saddle-points of
inversions and the ground states are within
0.75kcalmolꢀ1 in each chalcogenic acid, and thus the
energies are uncorrected.
References
4.10. Procedure for the measurement of circular dichroism
spectrum of 2 in solid state
1. For reviews, see: (a) Shimizu, T.; Kamigata, N. Rev.
Heteroat. Chem. 1998, 18, 11; (b) Shimizu, T.; Kamigata,
N. Org. Prep. Proced. Int. 1997, 29, 603.
2. Shimizu, T.; Watanabe, I.; Kamigata, N. Angew. Chem.,
Int. Ed. 2001, 40, 2460.
3. Shimizu, T.; Nakashima, Y.; Watanabe, I.; Hirabayashi,
K.; Kamigata, N. J. Chem. Soc., Perkin Trans. 1 2002,
2151.
4. Nakashima, Y.; Shimizu, T.; Hirabayashi, K.; Kamigata,
N.; Yasui, M.; Nakazato, M.; Iwasaki, F. Tetrahedron
Lett. 2004, 45, 2301.
5. (a) Piette, J. L.; Renson, M. Bull. Soc. Chim. Belg. 1970,
79, 353; (b) Thavornyutikarn, W. R.; McWhinnie, W. R.
J. Organomet. Chem. 1973, 50, 135; (c) Bergman, J.; Siden,
J.; Maartmann-Moe, K. Tetrahedron 1984, 40, 1607; (d)
Reichel, L.; Kirschbaum, E. Justus Liebigs Ann. Chem.
1936, 523, 211; (e) Schulz, P.; Klar, G. Z. Naturforsch.,
Teil B 1975, 30, 43; (f) Balfe, M. B.; Chaplin, C. A.;
Phillips, H. J. Chem. Soc. 1938, 341; (g) Balfe, M. B.;
Nandi, K. N. J. Chem. Soc. 1941, 70; (h) Lederer, K. Ber.
Dtsch. Chem. Ges. 1915, 48, 1345; (i) Bill, W. F. J. Org.
Chem. 1986, 51, 1150.
6. Some of our preliminary results in this area have been
communicated previously; Nakashima, Y.; Shimizu, T.;
Hirabayashi, K.; Kamigata, N. Org. Lett. 2004, 6, 2575.
7. Ptasinska, M. S.; Aarts, V. M. L. J.; Egberink, R. J. M.;
Eerden, J.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem.
1988, 53, 5484.
A mixture of a single crystal of 2 (ca. 1mg) and 70mg of
KBr was ground and formed into disk with a radius of
6.5mm and the KBr disk was used for measurement of
circular dichroism spectrum.
4.11. X-ray crystallographic analysis of 2
Crystal data of
C16H24O7S, Mr = 360.41; orthorhombic, space group
P212121, a = 9.3667(11), b = 12.5180(11), c =
2 with negative Cotton effect:
3
˚
˚
14.8160(13)A, V = 1737.2(3)A , Z = 4, T = 100K,
Dc = 1.378gcmꢀ3, l = 0.221mmꢀ1, (MoKa 0.71073A).
˚
A
prismatircycstal with dimensions of 0.50
·
0.49 · 0.38mm3 was used for the data collection. A total
of 4544 reflections were measured of which 3982 reflec-
tions (Rint = 0.0098) including Bijvoet pairs were inde-
pendent and 3857 reflections with I > 2r(I). Lorentz
and polarization corrections were made. Absorption
correction was applied using a W scan method with
Tmin = 0.968, Tmax = 0.997. The H-atom of the sulfino
group was located on the D-map and refined with an
isotropicthermal parameter. Final refinement with 264
parameters against 3982 reflections gave R = 0.0263,
ꢀ3
˚
wR = 0.0613, and Dqmin = ꢀ0.17, Dqmax = 0.17eA
.
8. Seff, K.; Heidner, E. G.; Meyers, M.; Trueblood, K. N.
Acta Crystallogr. 1969, B25, 350.
9. Filippo, D. D.; Momicchioli, F. Tetrahedron 1969, 25,
5733.
10. (a) Andersen, K. K.; Folly, J. W.; Perkins, T. I.; Gaffield,
W.; Papanikolau, N. E. J. Am. Chem. Soc. 1964, 86, 5637;
(b) Mislow, K.; Green, M. M.; Laur, P.; Melillo, J. T.;
Absolute structure parameter was 0.00(5). The sulfino
group was found to be disordered into two atomicposi-
tions with the site occupancy factors of 0.783(2) [(S)-
form] and 0.217(2) (incomplete structure). Crystallo-
graphic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the

Y. Nakashima et al. / Tetrahedron: Asymmetry 15 (2004) 3791–3797
3797
Simmons, T.; Ternary, A. L., Jr. J. Am. Chem. Soc. 1965,
87, 1958; (c) Zhao, S.; Samuel, O.; Kagan, H. B.
Tetrahedron 1987, 43, 5135; (d) Darwish, D.; Tomilson,
R. L. J. Am. Chem. Soc. 1968, 90, 5938; (e) Campbell, S.
J.; Darwish, D. Can. J. Chem. 1974, 52, 2953; (f)
Moriyama, M.; Oae, S.; Numata, T.; Furukawa, N.
Chem. Ind. 1976, 163; (g) Andersen, K. K.; Caret, R. L.;
Ladd, D. L. J. Org. Chem. 1976, 41, 3096; (h) The
Chemistry of the Sulphonium Group; Stirling, C. J., Patai,
S., Eds.; Wiley: New York, 1981; (i) Day, J.; Cram, D. J. J.
Am. Chem. Soc. 1965, 87, 4398; (j) Moriyama, M.;
Yoshimura, T.; Furukawa, N.; Numata, T.; Oae, S.
Tetrahedron 1976, 32, 3003; (k) Kamigata, N.; Taka, H.;
Matsuhisa, A.; Matsuyama, H.; Shimizu, T. J. Chem.
Soc., Perkin Trans. 1 1994, 2257; (l) Kamigata, N.; Taka,
H.; Matsuhisa, A.; Shimizu, T. J. Phys. Org. Chem. 1995,
8, 139; (m) Shimizu, T.; Seki, N.; Taka, H.; Kamigata, N.
J. Org. Chem. 1996, 61, 6013; (n) Shimizu, T.; Matsuhisa,
A.; Kamigata, N.; Ikuta, S. J. Chem. Soc., Perkin Trans. 1
1995, 1805; (o) Shimizu, T.; Kamigata, N. Rev. Heteroat.
Chem. 1998, 18, 11; (p) Shimizu, T.; Kamigata, N.; Ikuta,
S. J. Chem. Soc., Perkin Trans. 2 1999, 1469.
11. (a) Moeller, C.; Plesset, M. S. Phys. Rev. 1934, 46, 618;
(b) Hehre, W. J.; Radom, L.; Schleyer, P. V. R.; Pople,
J. A. Ab initio Molecular Orbital Theory; Wiley: New
York, 1986, Chapter 2.9.3.
12. (a) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284;
(b) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270.
13. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G.
E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millan, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.;
Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.;
Cui, Q.; Morokuma, K.; Malich, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko,
A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R.
L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Gonzales, C.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andreas, J.
L.; Head-Gordon, M.; Reploge, E. S.; Pople, J. A.
Gaussian 98; Gaussian Inc.: Pittsburgh, PA, 1998.