Enantioselective inclusion of chiral alkyl aryl sulfoxides in a supramolecular helical channel consisting of an enantiopure 1,2-amino alcohol and an achiral carboxylic acid

Article abstract of DOI:10.1016/j.tetasy.2007.11.041

The enantioselective clathrate formation of alkyl aryl sulfoxides 4 was achieved with dissymmetric one-dimensional helical channels created in two-component hosts consisting of (1R,2S)-2-amino-1,2-diphenylethanol 1 and an achiral carboxylic acid, p-tert-butylbenzoic acid 2, or 2-anthraquinonecarboxylic acid 3. X-ray crystallographic analyses showed that the host framework (1R,2S)-1·3 in the single crystal of a clathrate with methyl p-methylphenyl sulfoxide 4n [(1R,2S)-1·3·4n (single)] maintained a supramolecular helical array as those of the solvent-included single crystals (1R,2S)-1·3·EtOH(single) and (1R,2S)-1·3·H₂O·THF(single), while the guest 4n molecules were highly disordered. Moreover, the X-ray powder diffraction pattern of (1R,2S)-1·3·4n(clathrate) obtained through the clathrate formation demonstrated that the molecular arrangements of (1R,2S)-1, 3, and 4n were not the same as those which appeared in (1R,2S)-1·3·4n(single); the channel was enlarged. These results are consistently explained by assuming the dynamic motion of the framework (1R,2S)-1·3 to achieve widely applicable clathrate formation.

Full text of DOI:10.1016/j.tetasy.2007.11.041

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 295–301
Enantioselective inclusion of chiral alkyl aryl sulfoxides in a
supramolecular helical channel consisting of an enantiopure
1,2-amino alcohol and an achiral carboxylic acid
Yuka Kobayashi, Soetrisno, Koichi Kodama and Kazuhiko Saigo*
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received 6 November 2007; accepted 28 November 2007
Abstract—The enantioselective clathrate formation of alkyl aryl sulfoxides 4 was achieved with dissymmetric one-dimensional helical
channels created in two-component hosts consisting of (1R,2S)-2-amino-1,2-diphenylethanol 1 and an achiral carboxylic acid, p-tert-
butylbenzoic acid 2, or 2-anthraquinonecarboxylic acid 3. X-ray crystallographic analyses showed that the host framework (1R,2S)-
1ꢀ3 in the single crystal of a clathrate with methyl p-methylphenyl sulfoxide 4n [(1R,2S)-1ꢀ3ꢀ4n (single)] maintained a supramolecular
helical array as those of the solvent-included single crystals (1R,2S)-1ꢀ3ꢀEtOH(single) and (1R,2S)-1ꢀ3ꢀH2OꢀTHF(single), while the guest
4n molecules were highly disordered. Moreover, the X-ray powder diffraction pattern of (1R,2S)-1ꢀ3ꢀ4n(clathrate) obtained through the
clathrate formation demonstrated that the molecular arrangements of (1R,2S)-1, 3, and 4n were not the same as those which appeared in
(1R,2S)-1ꢀ3ꢀ4n(single); the channel was enlarged. These results are consistently explained by assuming the dynamic motion of the frame-
work (1R,2S)-1ꢀ3 to achieve widely applicable clathrate formation.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
From the middle of the 1970s to the middle of the 1980s,
chirality-recognition through clathrate formation has been
reported by some pioneering groups.10 The enantiomeric
excesses of guests included in the clathrate crystals were,
however, not so high due to their zero-dimensional cavities.
In the second stage of chirality-recognition through clath-
rate formation, higher-dimensional host frameworks have
been developed, such as two-dimensional sheets11 and
three-dimensional hydrogen-bonding networks,12 which
offered cavities fit for the functional group and molecular
shape of the guests. This strategy has been successfully ap-
plied to the design of tailor-made hosts for racemic targets.
Such a precisely designed host can realize extremely high
chirality-recognition for a particular racemic guest. At
the same time, however, its chirality-recognition ability
dramatically deteriorates, even when racemic guests, which
have a chemical structure only slightly different from that
of the particular guest, are targeted. The singular chiral-
ity-recognition of a certain racemic guest by a host in clath-
rate formation is attributable to the inevitability that the
host is designed to have only one (or a very few) global
minimum with a large thermodynamical advantage on
the potential surface for the clathrate formation with a
Chirality-recognition has attracted much attention because
it is a fundamental phenomenon in various chiral technol-
ogies, such as chromatographic analyses (high-perfor-
mance liquid chromatography,1 liquid chromatography,2
gas chromatography,3 capillary electrophoresis,4 etc.), dia-
stereomeric crystallization,5 asymmetric synthesis,6 host–
guest complexation,7 membrane separation,8 enzymatic
separation,9 and so on. To understand such chirality-recog-
nition phenomena and to develop new selectors/resolving
agents/chiral auxiliaries/hosts, the elucidation of chirality-
recognition processes is indispensable; it is very important
to detect differences in thermodynamic and/or kinetic
properties between stereoisomers (diastereomers and enan-
tiomers) in chirality-recognition processes.
*
Corresponding author. Tel.: +81 3 5841 7266; fax: +81 3 5802 3348;
e-mail: saigo@chiral.t.u-tokyo.ac.jp
Present address: Waseda Institute for Advanced Study (WIAS), Waseda
University, Nishiwaseda, Shinjuku-ku, Tokyo 169-8050, Japan.
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.041

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Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 295–301
single kind of enantiomer of the guest, owing to the intri-
cate intermolecular interaction system of the host. Thus,
clathrate formation has serious limitation in wide
applicability.13
The preparation of the helical architectures and the inclu-
sion of the guests were very easy. A solution of equimolar
amounts of amino alcohol (1R,2S)-1 and carboxylic acid 2
or 3 in methanol or ethanol was refluxed for 30 min, and
then the solvent was evaporated to dryness to give the cor-
responding salt (host) as a crystalline powder. The host
(1R,2S)-1ꢀ2 or (1R,2S)-1ꢀ3, which was finely powdered,
was suspended in hexane containing 4 equiv of guest 4
for 4 h with stirring to afford the (1R,2S)-1ꢀ2ꢀ4/(1R,2S)-
1ꢀ3ꢀ4 clathrate, which was collected by filtration and
washed with hexane or toluene. The molar ratio of the
included guest (the inclusion ratio) was estimated on the
basis of the amount of the host by an NMR measurement
of the clathrate. The enantiomeric excess (ee) of the guest,
isolated from the clathrate by preparative thin layer chro-
matography, was determined by high-performance liquid
chromatography (HPLC) on a chiral column.
Recently, we developed a supramolecular host system, con-
sisting of an enantiopure amine and an achiral carboxylic
acid (the two-component salt strategy).14 In the supra-
molecular assemblies, there exists a one-dimensional helical
channel with a twofold screw axis in the center, originating
from the topology of a hydrogen-bonding network created
from ammonium cations and carboxylate anions. Through
a study on the chirality-recognition of racemic 1-arylalka-
nols by the supramolecular host system, the supramolecu-
lar architectures have been demonstrated to be promising
frameworks for enantioselective clathrate formation;14 the
helical channels offer dissymmetric cavities interactive with
guest molecules. Herein, we report the application of
supramolecular architectures with a one-dimensional heli-
cal channel to the enantioselective inclusion of racemic
alkyl aryl sulfoxides and the behavior of the host and guest
molecules in the channel, examined by X-ray crystallo-
graphic and powder diffraction analyses.
The inclusion was performed for 17 types of sulfoxides 4 by
using (1R,2S)-1ꢀ2 and (1R,2S)-1ꢀ3 salts as hosts. The results
are summarized in Table 1. Most of sulfoxides 4 examined
were included in the (1R,2S)-1ꢀ2 and/or (1R,2S)-1ꢀ3 host
Table 1. Chirality-recognition of 4 with (1R,2S)-1ꢀ2 and (1R,2S)-1ꢀ3
2. Results and discussion
O
COOH
COOH
2.1. Enantioselective inclusion of alkyl aryl sulfoxides with
supramolecular hosts
tBu
H2N
OH
O
The combinations of enantiopure/achiral primary amines
and achiral/enantiopure carboxylic acids generally afford
a helical architecture with a twofold screw axis in their salt
crystals. Among candidates of chiral primary amine com-
ponents, enantiopure erythro-2-amino-1,2-diphenylethanol
1 was found to be fascinating for the construction of effec-
tive supramolecular hosts, because the two phenyl groups
of 1 tend to have a gauche conformation in salt crystals
to afford small voids, which were sometimes occupied by
solvent molecules.15 The molecular arrangement strongly
indicates that the size and shape of the voids in salt crystals
can be controlled by properly selecting the achiral carbox-
ylic acid component. Moreover, in a helical architecture,
there is a hydrogen-accepting site in each amine/carboxylic
acid pair, and the hydroxy group of 1 offers hydrogen-
donating and -accepting sites. This means that a helical
architecture consisting of 1 and an achiral carboxylic acid
would be able to include guests with a hydrogen-donating
and/or -accepting group. In this study, we selected racemic
alkyl aryl sulfoxides 4, of which the oxygen atom has a
hydrogen-accepting ability, as target guests. Since the hy-
droxy hydrogen atom of 1 is located a little way from the
twofold screw axis of a helical architecture of 1 and an
achiral carboxylic acid, large cavities are required to cap-
ture target 4 by intermolecular interaction between the
hydroxy hydrogen atom of 1 and the oxygen atom of 4.
Therefore, we used p-tert-butylbenzoic acid 2 and 2-anthra-
quinonecarboxylic acid 3 as the achiral carboxylic acid
components with an expectation that the bulky substituent
in 2 and the large and planar aryl group in 3 would afford
relatively large cavities in their helical architectures with 1,
respectively.
1
2
3
O
*
S
R1
R2
4
Guest R1
R2
(1R,2S)-1ꢀ2 salt
(1R,2S)-1ꢀ3 salt
Inclusion eeb (%) Inclusion eeb (%)
ratioa
ratioa
4a
4b
4c
4d
4e
4f
Me
H
H
H
H
H
0.88
0.68
0.45
0.25
0.41
0.75
0.25
0.32
99 (R)
64 (S)
84 (S)
5 (S)
92 (R)
98 (S)
97 (S)
21 (R)
—
—
—
25 (S)
—
4 (S)
—
0.92
0.44
1.00
0.87
12 (R)
12 (R)
96 (R)
91 (R)
—
96 (S)
92 (S)
62 (S)
—
30 (R)
82 (R)
38 (R)
75 (R)
96 (R)
72 (S)
90 (R)
88 (R)
Et
iPr
iBu
tBu
Me o-Me
iPr o-Me
Me o-OMe
iPr o-OMe
Me m-Me
iPr m-Me
c
—
0.88
0.61
0.78
4g
4h
4i
c
c
—
—
—
—
c
4j
0.66
0.66
0.75
0.32
1.00
0.93
0.50
0.88
c
4k
4l
Me m-OMe 0.23
c
4m
4n
4o
4p
4q
iPr
Me p-Me
iPr p-Me
Me p-OMe
iPr p-OMe
m-OMe
—
0.46
c
—
0.49
0.27
3 (R)
74 (R)
a The inclusion ratio (the guest/the host) was calculated on the basis of the
1H NMR analysis of the clathrate crystal.
b The enantiomeric excess was determined by a HPLC analysis. The
absolute configuration of the major enantiomer was shown in the
parenthesis.
c Not included.

Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 295–301
297
Table 2. Crystal data and details of the final refinement calculations for
(1R,2S)-1ꢀ3ꢀEtOH(single) (A), (1R,2S)-1ꢀ3ꢀH2OꢀTHF(single) (B), and
(1R,2S)-1ꢀ3ꢀ(R)-4n(single) (C)
with moderate to excellent enantioselectivity, although the
inclusion ratios were not necessarily 1.00, probably due to
the insufficient intermolecular interaction between (1R,2S)-
1ꢀ2/(1R,2S)-1ꢀ3 host and guests 4, resulting in the incom-
plete inclusion of 4 with (1R,2S)-1ꢀ2/(1R,2S)-1ꢀ3 and/or
in the volatilization of 4 during the isolation and handling
of the (1R,2S)-1ꢀ2ꢀ4/(1R,2S)-1ꢀ3ꢀ4 clathrates, as was ob-
served for the inclusion of 1-arylalkanols in a similar heli-
cal architecture.14 As can be seen from Table 1, the
(1R,2S)-1ꢀ3 host showed a superior chirality-recognition
ability for sulfoxides 4, compared with the (1R,2S)-1ꢀ2
host. However, it is noteworthy that the (1R,2S)-1ꢀ2 and
(1R,2S)-1ꢀ3 hosts could complementarily recognize the chi-
rality of the sulfoxides 4; the (1R,2S)-1ꢀ2 salt showed a chi-
rality-recognition ability for 4a, 4b, and 4e with a relatively
short molecular length better than did the (1R,2S)-1ꢀ3 host.
The results strongly indicate that the chirality-recognition
ability of the present supramolecular system for alkyl aryl
sulfoxides can be tuned upon properly selecting the achiral
carboxylic acid component. Thus, it was clearly demon-
strated that the present host system consisting of 1 and
an achiral carboxylic acid could be successfully applied to
the enantioselective inclusion of sulfoxides via clathrate
formation.
A
B
C
Chemical formula
Crystal system
Space group
Z
C31H29NO6 C33H33NO7 C99H84N3O16.5S1.5
Monoclinic Monoclinic Monoclinic
P21
P21
P21
2
2
2
˚
a (A)
13.863(3)
5.764(2)
17.341(6)
90
12.945(12)
5.877(5)
17.988(17)
90
13.273(5)
17.478(6)
17.503(5)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
94.060(9)
90
94.345(4)
90
94.976(4)
90
3
˚
V (A )
1382.2(6)
1.229
296
1365.0(2)
1.352
103
4045(3)
1.334
100
Density (g cmꢁ3
)
Temperature (K)
Reflections collected 2747
8644
4637
16,764
10,915
Reflections used in
refinement
2705
LS parameters
GOF
345
0.81
0.0607
0.1406
371
1036
1.001
0.0847
0.2209
0.884
0.1086
0.3029
Ra (F) [I > 2s(I)]
wRb (all F2)
P
P
a R = jFo ꢁ Fcj/ Fo.
h
i
1=2
P
P
2
b wR ¼
wðF o ꢁ F cÞ = wF 2o
.
2.2. Structure of the (1R,2S)-1ꢀ3 framework in the clathrates
To clarify the structure of clathrates (1R,2S)-1ꢀ3ꢀ4, X-ray
crystallographic analyses were carried out. Although we
could prepare two single crystals, (1R,2S)-1ꢀ3ꢀEtOH(single)
and (1R,2S)-1ꢀ3ꢀH2OꢀTHF(single), of which EtOH and
H2O/THF originated from the solvent(s) used for the
recrystallization of the (1R,2S)-1ꢀ3 salt, respectively, as ref-
erences for the clathrates, only one kind of single crystal,
(1R,2S)-1ꢀ3ꢀ(R)-4n(single), was obtained among the clath-
rates upon recrystallization from MeOH; disappointingly,
we could only determine the structure of the framework
consisting of (1R,2S)-1 and 3 in (1R,2S)-1ꢀ3ꢀ(R)-4n(single)
due to the significant disorder of the guest (R)-4n molecules
even at ꢁ173 °C. Moreover, the positions of guests also
could not be determined for the other clathrates (1R,2S)-
1ꢀ3ꢀ4, despite much effort, which resulted in only
incomplete X-ray crystallographic analyses. The crystal
data of (1R,2S)-1ꢀ3ꢀEtOH(single), (1R,2S)-1ꢀ3ꢀH2Oꢀ
THF(single), and (1R,2S)-1ꢀ3ꢀ(R)-4n(single) are listed in
Table 2.
The crystal structures of (1R,2S)-1ꢀ3ꢀEtOH(single) and
(1R,2S)-1ꢀ3ꢀH2OꢀTHF(single) are very similar to each
other, as shown in Figure 1. In both single crystals, a
columnar hydrogen-bonding network with a twofold screw
axis in the center is formed from the ammonium cations of
(1R,2S)-1 and the carboxylate anions of 3. However, a rel-
atively large one-dimensional channel is constructed from
(1R,2S)-1 and 3 molecules, compared with those in the pre-
viously reported hosts.14 The cross section of the one-
dimensional channels formed in the single crystals is about
Figure 1. One-dimensional channels created in (a) (1R,2S)-1ꢀ3ꢀEtOH(sin-
gle) and (b) (1R,2S)-1ꢀ3ꢀH2OꢀTHF(single).
˚
12 ꢂ 6 A. In the channel, the space created by two anthra-
quinonyl groups is almost symmetrical, while the space
around 1 is dissymmetrical owing to the two asymmetric
centers in (1R,2S)-1. The hydrogen-bonding site for a guest
molecule arising from the hydroxy group of (1R,2S)-1 is
located near the dissymmetrical space in the channel. The
channel is filled with disordered EtOH and H2O/THF mol-
ecules, respectively.

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Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 295–301
In contrast, the b-axis (the column axis) of (1R,2S)-1ꢀ3ꢀ
(R)-4n(single) is about three times longer than those of
(1R,2S)-1ꢀ3ꢀEtOH(single) and (1R,2S)-1ꢀ3ꢀH2OꢀTHF-
(single), although the other unit cell parameters are similar
to the others; the hydrogen-bonding network composed of
(1R,2S)-1ꢀ3 and the cross section of the one-dimensional
channel in the network of (1R,2S)-1ꢀ3ꢀ(R)-4n(single) are
very similar to those of (1R,2S)-1ꢀ3ꢀEtOH(single) and
(1R,2S)-1ꢀ3ꢀH2OꢀTHF(single). This fact implies that the
framework of the (1R,2S)-1ꢀ3 host in (1R,2S)-1ꢀ3ꢀ(R)-
4n(single) is similarly constructed independent of the guest
molecules, although the positions of three molecules of the
guest (R)-4n in the asymmetric unit are highly disordered.
The crystal structure of (1R,2S)-1ꢀ3ꢀ(R)-4n(single) is shown
in Figure 2. It is noteworthy that the positions of the sulfur
and oxygen atoms in the three molecules of the sulfoxide
(R)-4n are almost ordered owing to the fixation of (R)-4n
by hydrogen-bonding interaction between the oxygen atom
of (R)-4n and the hydroxy hydrogen atom of (1R,2S)-1; the
Oꢀ ꢀ ꢀO distances are close to each other and are in the range
ratio of 1.00 was achieved in the clathrate formation. These
results strongly suggest that the structure of (1R,2S)-
1ꢀ3ꢀ(R)-4n(single) solved by the X-ray analysis does not re-
flect that of the actual crystal (1R,2S)-1ꢀ3ꢀ(R)-4n(clathrate)
obtained through the clathrate formation; the actual crys-
tal should shrink during single crystal formation to result
in the short contacts and the forcing-out of the guest
molecules.
In the next stage, we investigated the X-ray powder diffrac-
tion (XRPD) patterns of the clathrates. As shown in Figure
3, the XRPD pattern of (1R,2S)-1ꢀ3ꢀ(R)-4n(single) is largely
different from that of the powdery crystal (1R,2S)-1ꢀ3ꢀ(R)-
4n(clathrate), meaning that the molecular arrangements in
(1R,2S)-1ꢀ3ꢀ(R)-4n(single) and (1R,2S)-1ꢀ3ꢀ(R)-4n(clath-
rate) are different from each other. Then, we tried to esti-
mate the unit cell of (1R,2S)-1ꢀ3ꢀ(R)-4n(clathrate) from its
XRPD pattern using DICVOL in the DASH program pack-
age.16 As a result, the calculation gave unit cell parameters
2
˚
˚
with reasonable v values; 14.145 A for the a-axis, 6.002 A
˚
˚
of 2.62–2.68 A. However, some short contacts are observed
for the b-axis, 19.242 A for the c-axis, and 92.13° for b. The
between the disordered guest molecules. Moreover, the
occupancy of the guest molecule is 0.50 for one host frame-
work in the crystal in contrast to the fact that an inclusion
a and b axes are slightly longer than those of (1R,2S)-
1ꢀ3ꢀ(R)-4n(single), while the c-axis is obviously longer by
˚
ca. 2 A. This result would imply that the framework
(1R,2S)-1ꢀ3 can flexibly change its size depending on the
shape of a guest to possess several local minima on the
potential surfaces for the clathrate formation, including a
minimum observed for the frameworks in (1R,2S)-1ꢀ3ꢀ
EtOH(single), (1R,2S)-1ꢀ3ꢀH2OꢀTHF(single), and (1R,2S)-
1ꢀ3ꢀ(R)-4n(single), upon sliding the anthraquinonyl groups
facing each other.
Most likely owing to the high flexibility of the (1R,2S)-1ꢀ3
framework, the ‘dynamic inclusion’ of guests was realized
to make the (1R,2S)-1ꢀ3 host applicable to a wide variety
of sulfoxides 4 regardless of the substituent on the phenyl
group and the a-alkyl group as shown in Table 1. The chi-
rality-recognition by the dynamic host (1R,2S)-1ꢀ3 is rather
similar to that by chiral stationary phases for HPLC, which
achieve dynamic chirality-recognition owing to their mod-
erately controlled structures with mobility.17
3. Conclusions
We designed a large dissymmetric one-dimensional channel
in supramolecular two-component hosts by using (1R,2S)-
2-amino-1,2-diphenylethanol 1 and an achiral carboxylic
acid, such as p-tert-butylbenzoic acid 2 and 2-anthraqui-
nonecarboxylic acid 3, and found that various kinds of
alkyl aryl sulfoxides 4 were included in the (1R,2S)-1ꢀ2/
(1R,2S)-1ꢀ3 hosts with moderate/excellent enantioselectivi-
ties to give the corresponding clathrates. The X-ray crystal-
lographic analyses of one of the clathrates [(1R,2S)-1ꢀ3ꢀ
(R)-4n(single)], as well as (1R,2S)-1ꢀ3ꢀEtOH(single) and
(1R,2S)-1ꢀ3ꢀH2OꢀTHF(single) including solvent(s) for the
recrystallization of the (1R,2S)-1ꢀ3 salt revealed that a
supramolecular helical hydrogen-bonding network was
commonly constructed by (1R,2S)-1 and 3. Although the
molecular arrangement (1R,2S)-1ꢀ3ꢀ(R)-4n could not be di-
rectly determined by X-ray crystallographic analysis due to
the transformation of the crystal structure during single
Figure 2. Crystal structure of (1R,2S)-1ꢀ3ꢀ(R)-4n(single). (a) Top view and
(b) side view. The occupancy of the disordered guest is 0.5. Dotted line
shows the predicted positions of the guest.

Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 295–301
299
Figure 3. XRPD patterns of (a) (1R,2S)-1ꢀ3ꢀ(R)-4n(clathrate) afforded through the clathrate formation and (b) (1R,2S)-1ꢀ3ꢀ(R)-4n(single) obtained by
recrystallization from MeOH.
crystal formation, the prediction of a possible unit cell for
(1R,2S)-1ꢀ3ꢀ(R)-4n(clathrate) on the basis of its XRPD pat-
tern indicated that the unit cell was enlarged in the inclu-
sion process, suggesting dynamic inclusion behavior.
4, isolated from the clathrate by preparative thin layer
chromatography, was determined by HPLC on a chiral col-
umn. The column used as well as the conditions is listed in
Table 3.
4.2. Single crystal X-ray crystallographic analysis
4. Experimental
The X-ray intensities were collected with a Rigaku MER-
CURY CCD system or a Bruker APEX II CCD area
detector by using Mo Ka radiation (k = 0.71073 A). The
4.1. General procedure for the inclusion of 4 with (1R,2S)-
1ꢀ2/(1R,2S)-1ꢀ3
˚
crystal structures were solved by the direct method with
the SHELXL-97 program18 and refined by the full-matrix
least-squares procedure for all non-hydrogen atoms aniso-
tropically. All hydrogen atoms were generated geometri-
cally. The absolute configuration of the included
sulfoxide 4n was determined on the basis of the known
absolute configuration of 1. CCDC 657007–657009 contain
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
Finely powdered (1R,2S)-1ꢀ2 or (1R,2S)-1ꢀ3 (0.2 mmol)
was suspended in hexane (1 mL) containing 4 equiv of 4
for 4 h with stirring to afford the corresponding (1R,2S)-
1ꢀ2ꢀ4/(1R,2S)-1ꢀ3ꢀ4 clathrate, which was collected by filtra-
tion and washed with a small amount of hexane or toluene.
The molar ratio of the included guest 4 was estimated on
the basis of the amount of (1R,2S)-1ꢀ2ꢀ4/(1R,2S)-1ꢀ3ꢀ4 by
an NMR measurement of the clathrate. The ee of the guest

300
Y. Kobayashi et al. / Tetrahedron: Asymmetry 19 (2008) 295–301
Table 3. Conditions for the HPLC analyses
V. J. Chromatogr., A 1997, 774, 143–175; (e) Eiceman, G. A.;
Guest Columna Solventb Flow rate Retention time (min)
Hill, H. H.; Gardea-Torresdey, J. Anal. Chem. 1998, 70, 321–
339; (f) Bicchi, C.; D’Amato, A.; Rubiolo, P. J. Chromatogr.,
A 1999, 843, 99–121.
(v/v)
(mL/min)
4a
4b
4c
4d
4e
4f
OB-H
OB-H
OB-H
OB-H
AS-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
OB-H
8:2
8:2
8:2
8:2
8:2
8:2
8:2
8:2
8:2
8:2
8:2
8:2
9:1
8:2
8:2
8:2
8:2
1.0
1.0
1.0
0.8
0.7
1.0
1.0
1.0
1.0
1.0
0.8
0.8
0.8
1.0
1.0
1.0
0.8
t1(S) = 10.3, t2(R) = 17.9
t1(S) = 8.5, t2(R) = 18.0
t1(S) = 6.4, t2(R) = 9.9
t1(S) = 7.8, t2(R) = 11.3
t1(S) = 11.6, t2(R) = 17.5
t1(S) = 8.6, t2(R) = 21.9
t1(S) = 7.2, t2(R) = 14.6
t1(S) = 9.1, t2(R) = 17.7
t1(S) = 5.5, t2(R) = 9.7
t1(S) = 7.5, t2(R) = 11.0
t1(S) = 6.6, t2(R) = 8.0
t1(S) = 15.0, t2(R) = 23.7
t1(S) = 11.8, t2(R) = 14.1
t1(S) = 8.0, t2(R) = 18.0
t1(S) = 6.7, t2(R) = 12.6
t1(S) = 15.1, t2(R) = 33.7
t1(S) = 9.3, t2(R) = 16.3
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4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
a Daicel Chiralcel.
b A mixture of hexane/2-propanol.
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
4.3. X-ray powder diffraction (XRPD)
X-ray powder diffractions were collected with a Rigaku
RINT2000 diffractometer with a Cu Ka X-ray tube, oper-
ated at 40 kV and 100 mA at room temperature, between
5° and 40° in a 2h/h-scan mode with a step of 0.01° in
2h. Samples were not rotated during the data collection.
Acknowledgments
Financial supports from the Ministry of Education, Cul-
ture, Sports, Science and Technology, Japan (Grand-
in-Aid for Scientific Research (B) 19350064) for K.S. and
from Ito Science Foundation for Y.K. are gratefully
acknowledged. We deeply thank Dr. Kenji Yoza at Bluker
AXS Co. Ltd. for his great effort in the X-ray crystallo-
graphic analysis of (1R,2S)-1ꢀ3ꢀ4n(single).
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Pickering, P. J.; Chaudhuri, J. B. Chirality 1997, 9, 261–267;
(c) Brice, L. J.; Pirkle, W. H. Chiral Separations 1997, 309–
334.
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