New chiral hosts derived from dimeric tartaric acid: Efficient optical resolution of aliphatic alcohols by inclusion complexation

Article abstract of DOI:10.1002/1099-0690(200009)2000:18<3171::AID-EJOC3171>3.0.CO;2-T

The novel, chiral, host compounds 8 and 9 were derived from tartaric acid. Inclusion complexation with these host compounds permitted highly efficient resolution of some aliphatic alcohols (10-13). The symmetrical dimer host compound 8 is effective for optical resolution of alcohols 10, 12, and 13 by a combination of enantioselective inclusion complexation and distillation techniques. The unsymmetrical dimer host compound 9 is effective for optical resolution of cyanohydrin 11. The crystal structures of the inclusion complexes were analyzed by X-ray diffraction methods in order to elucidate the mechanism of the efficient chiral recognition in the inclusion crystals.

Full text of DOI:10.1002/1099-0690(200009)2000:18<3171::AID-EJOC3171>3.0.CO;2-T

FULL PAPER
New Chiral Hosts Derived from Dimeric Tartaric Acid: Efficient Optical
Resolution of Aliphatic Alcohols by Inclusion Complexation
Koichi Tanaka,*[a] Shinji Honke,[a] Zofia Urbanczyk-Lipkowska,[b] and Fumio Toda[c]
Keywords: Chiral resolution / Host-guest chemistry / Supramolecular chemistry / X-ray structure
The novel, chiral, host compounds 8 and 9 were derived from
plexation and distillation techniques. The unsymmetrical
tartaric acid. Inclusion complexation with these host com- dimer host compound 9 is effective for optical resolution of
pounds permitted highly efficient resolution of some ali-
cyanohydrin 11. The crystal structures of the inclusion com-
phatic alcohols (10−13). The symmetrical dimer host com-
plexes were analyzed by X-ray diffraction methods in order
pound 8 is effective for optical resolution of alcohols 10, 12, to elucidate the mechanism of the efficient chiral recognition
and 13 by a combination of enantioselective inclusion com-
in the inclusion crystals.
Introduction
The design of new lattice inclusion systems has been of
interest in recent years because of their potential applica-
tions in analytical, synthetic, and material sciences.[1] Of the
various kinds of chiral host compounds which we have de-
signed to date {for example: (S,S)-(Ϫ)-1,6-bis(o-chloro-
phenyl)-1,6-diphenylhexa-2,4-diyne-1,6-diol (1),[2] (S,S)-
(Ϫ)-trans-1,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenyl-
prop-1-ynyl]-1,4-dihydroxycyclohexa-2,5-diene
(2),[3]
(S,S,S,S,S,S)-(Ϫ)-hexakis[3-(o-chlorophenyl)-3-hydroxy-3-
phenylprop-1-ynyl]benzene (3),[4] (S,S)-2,2Ј-dihydroxy-
1,1Ј-binaphthyl (4),[5] and (R,R)-(Ϫ)-trans-2,3-bis(hydroxydi-
phenylmethyl)-1,4-dioxaspiro[4,5]decane (5),[6] Scheme 1}, tar-
taric acid derivatives such as 5 are very useful hosts for the
optical resolution of racemic guests[7] and for the enantiose-
lective reaction of prochiral guests.[8] In some cases, how-
ever, 5 does not form an inclusion complex with relatively
voluminous guest molecules. This is probably due to the
molecular size of 5: the void space created by the relatively
small host molecule is too small to include relatively large
guest molecules. In order to solve this problem, dimeric de-
rivatives of tartaric acid were designed to act as hosts which
should be able to accommodate guests of large molecular
size.
Results and Discussion
Heating a solution of (ϩ)-diethyl tartrate and 0.5 molar
equivalents of cyclohexane-1,4-dione in toluene at reflux
[a]
Department of Applied Chemistry, Faculty of Engineering,
Ehime University,
Matsuyama, Ehime 790Ϫ8577, Japan
Fax: (internat.) ϩ 81-89/927-9923
E-mail: tanaka@en3.ehime-u.ac.jp
[b]
containing a catalytic amount of TsOH gave tetraester 6 in
92% yield. Reaction of 6 with PhMgBr in THF gave crude
crystals of (Ϫ)-trans,trans-2,3,10,11-tetrakis(hydroxydi-
phenylmethyl)-1,4,9,12-tetraoxadispiro[4.2.4.2]tetradecane
Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01Ϫ224 Warsaw, Poland
[c]
Department of Chemistry, Faculty of Science, Okayama
University of Science,
1Ϫ1 Ridaicho, Okayama 700Ϫ0005, Japan
Eur. J. Org. Chem. 2000, 3171Ϫ3176
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0918Ϫ3171 $ 17.50ϩ.50/0
3171

K. Tanaka, S. Honke, Z. Urbanczyk-Lipkowska, F. Toda
FULL PAPER
(8). Recrystallization of 8 from EtOH gave the 1:2 inclusion
The unsymmetrical dimeric host 9 also displays interest-
complex of 8 with EtOH as colorless prisms, which, upon ing chiral recognition properties. Compound 9 incorporates
heating, gave pure 8 as the free host compound. By the rac-cyanohydrin 11 in a 1:2 ratio in the absence of toluene,
same method, the unsymmetrical dimer host compound but, in the presence of toluene, takes up (ϩ)-11 together
(Ϫ)-trans,trans-2,3,9,10-tetrakis(hydroxydiphenylmethyl)- with a toluene molecule. For example, when a solution of a
1,4,8,11-tetraoxadispiro[4.1.4.3]tetradecane (9) was pre- 1:2 mixture of 9 and (Ϯ)-11 in toluene (20 mL) was kept at
pared from 7, which in turn was obtained by the condensa- room temperature for 8 h, 1:1:1 inclusion crystals of 9, (ϩ)-
tion reaction of (ϩ)-diethyl tartrate with cyclohexane-1,3- 11, and toluene were formed as colorless prisms in 72%
dione. The dimeric host compounds 8 and 9 showed a yield. One recrystallization of these crystals from toluene
higher inclusion ability for some typical guest compounds gave pure inclusion crystals, which upon heating in vacuo
than the monomeric host compound 5. In particular, the gave (ϩ)-11 (100% ee) in 24% yield as a distillate. On the
symmetrical dimer host 8 took up all guest compounds other hand, when a neat solution of 9 in (Ϯ)-11 was kept
tested (Table 1).
at room temperature for 3 h, a 1:2 inclusion complex of 9
and (Ϯ)-11 was formed as colorless prisms, which upon
heating in vacuo gave (Ϯ)-11 as a distillate.
The role of multiple recognition sites and their topology
in the performance in the chiral discrimination process of
these newly designed host molecules was studied in the solid
state by X-ray diffraction methods. The host molecules 8
and 9 both consist of two terminal hydrophilic 1,4-diol un-
its and two voluminous hydrophobic areas, flanked by
phenyl rings located above and below the cyclohexane ring.
Table 1. Host-guest ratios in the inclusion complexes of 5, 8, and
9 with typical guest compounds
Guest
5
8
9
MeOH
Acetone
1:1
2:1
2:1
Ϫ[a]
1:1
1:1
1:1
2:1
Ϫ[a]
Ϫ[a]
1:2
1:2
1:1
1:1
1:2
1:2
1:2
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
2:1
1:1
1:1
1:1
Ϫ[a]
Cyclopentanone
Ethyl acetate
γ-Butyrolactone
THF
DMF
DMSO
Toluene
Cyclohexane
[a]
No complexation occurred.
The chiral discrimination ability of 8 and 9 was studied;
both showed extremely high chiral recognition ability to-
wards relatively small chiral alcohols which could not be
resolved efficiently by the monomeric host compound 5.
For example, when a mixture of 8 and rac-but-3-yn-2-ol
(10) was ground together with a mortar and pestle for a few
minutes and kept at room temperature for one day, it gave
a 1:1 inclusion complex of 8 and (ϩ)-10. During the reac-
tion, the opposite enantiomer, which was not incorporated
into the host-guest complex, evaporated due to its low boil-
ing point. Heating the inclusion complex in vacuo gave (ϩ)-
10 (59% ee) in 77% yield. When the complexation was re-
peated, (ϩ)-10 (99% ee) was obtained in 28% yield. The
optical purity of (ϩ)-10 was determined by GC, using a
Chiral-DEX CB capillary column.[9] By similar com-
plexation with 8, rac-2-hexanol (12) and rac-2-methyl-1-bu-
tanol (13) were also resolved efficiently, and gave optically
pure (ϩ)-12 and (Ϫ)-13 in 34 and 5% yields, respectively.
The resolution of 10, 12, and 13 by this simple distillation
method[10] is a valuable tool for chiral resolution because
the preparative methods reported to date for optically active
aliphatic alcohols are not efficient. For example, optically
active 10 (70% ee) has been prepared by enzymatic transes-
terification in 31% yield.[11]
The optical resolution of carbonyl compounds by com-
plexation with 8 was less efficient. For example, when a neat
solution of 8 in (Ϯ)-14 was kept at room temperature for
24 h, a 1:1 inclusion complex of 8 and (Ϫ)-14 was formed
as colorless prisms, which upon heating in vacuo gave (Ϫ)-
14 (15% ee) as a distillate.
Figure 1. ORTEP drawing of the 1:1 complex of (R,R,R,R)-(Ϫ)8
and (R)-(Ϫ)-14, showing both hydrogen bonding and incorporation
of the guest molecule as a clathrate
3172
Eur. J. Org. Chem. 2000, 3171Ϫ3176

New Chiral Hosts Derived from Dimeric Tartaric Acid
FULL PAPER
Recently, solid state studies of (R,R)-(Ϫ)-trans-2,3-bis[hyd-
roxy(diphenyl)methyl]-1,4-dioxaspiro[5,4]decane (5), con-
taining one such unit, and its molecular complexes, ex-
plained its universal complexation properties. It appears
that one hydroxy group of the diol moiety forms an intram-
olecular OϪH···O hydrogen bond, whereas the other,
sterically hindered, one is either unbound in the free com-
pound or acts as a hydrogen bond donor or acceptor during
the molecular recognition process.[12] Inspection of the
packing diagrams of several complexes formed in the solid
state by 8 and 9 allows some interesting rationalization for
their differing recognition properties. The molecular struc-
ture of the 1:1 complex between (R,R,R,R)-(Ϫ)-8 and (R)-
(Ϫ)-14 is shown in Figure 1. The diol moieties form a pair
of strong intramolecular hydrogen bonds (O···O separations
˚
of 2.66Ϫ2.67 A), leaving two OH groups available for inter-
actions. One of these (O16d in Figure 1) forms a hydrogen
bond with carbonyl O65a of the host. The second generates
chains made up of host molecules. Two nonparallel sets of
chains found in the crystal permit location of the cyclopen-
tanone ring in the hydrophobic cavity of the neighboring
host molecule. Most interesting is the molecular structure
of the 1:2 complex of (Ϫ)-8 and (Ϫ)-13, shown in Figure 2.
One alcohol hydroxy group (O70Ј) donates an H atom to
the O30 oxygen of the host, forming an intermolecular hy-
drogen bond. A second guest molecule of the same chirality
acts both as hydrogen bond donor and acceptor, forming
an extended hydrogen-bonded network of host molecules:
HOSTϪOH···O(70)ϪH···OϪHOST. These chains are held
together by noncovalent forces other than hydrogen bond-
ing. The hydrogen atom from the sterically hindered O15
hydroxy moiety remains unbound.
Figure 3. ORTEP drawing of the 1:1:1 complex of (R,R,R,R)-(Ϫ)-
9, (ϩ)-11, and toluene
The molecular structure of the 1:1:1 complex of
(R,R,R,R)-(Ϫ)-9 with (ϩ)-(11) and toluene is shown in Fig-
ure 3, and the molecular structure of the 1:2 complex of
(R,R,R,R)-(Ϫ)-9 and (Ϯ)-(11) is shown in Figure 4. As can
be clearly seen, the O16 hydroxy groups provide an enanti-
oselective binding site; i.e. the same enantiomer of cyanohy-
Figure 4. ORTEP drawing of the 1:2 complex of (R,R,R,R)-(Ϫ)-9
and (Ϯ)-11
drin is hydrogen bonded, regardless of whether the complex
is formed from the single enantiomer or from (Ϯ)-11. The
two remaining hydroxy groups form host-to-host hydrogen-
bonded chains. The recognition process is solvent-depend-
ent; the hydrophobic cavities formed by the isomeric host 9
are of different size and shape than those formed by host
8. Their shape is that of an open jaw and could be easily
adjustable by conformational rearrangement of the five-
membered rings. The torsion angles in the central ring are
almost the same in the three crystal structures, and describe
conformations of slightly flattened chairs (a regular chair
in the case of 8), whereas those in the outer five-membered
rings vary. Small differences in conformation in the latter
can cause large differences in the location of the terminal
phenyl rings. The cavities can discriminate between the to-
Figure 2. ORTEP drawing of the 1:2 complex of (R,R,R,R)-(Ϫ)-8
and (Ϫ)-13
Eur. J. Org. Chem. 2000, 3171Ϫ3176
3173

K. Tanaka, S. Honke, Z. Urbanczyk-Lipkowska, F. Toda
FULL PAPER
Figure 7. Packing pattern of the 1:2 complex of (R,R,R,R)-(Ϫ)-
9 and (Ϯ)-11; host molecules (solid lines) form hydrogen-bonded
networks; between them, hydrogen-bonded (Ϫ)-11 and (Ϫ)-11
taken up as a clathrate are shown (open lines)
Figure 5. ORTEP drawing of the 1:1 complex of (R,R,R,R)-(Ϫ)-9
and toluene
pologies of cyanohydrin and toluene molecules. In the ab-
sence of toluene, one molecule of (Ϫ)-11 is incorporated
into the crystal as a clathrate (see Figure 4). When cyanohy-
drin complexation is performed in toluene, a disordered
solvent molecule is included in the cavity (0.7:0.3 occu-
pancy), expelling a molecule of (Ϫ)-11. When no cyanohyd-
rin is present, the cavity is occupied by a disordered toluene
molecule (0.5:0.5 occupancy) and the 1:1 complex of (Ϫ)-9
and toluene shown in Figure 5 is formed. The packing pat-
terns of the 1:1:1 complex of (Ϫ)-9 with (ϩ)-11 and toluene,
and of the 1:2 complex with (Ϯ)-11, are shown in Figure 6
and Figure 7, respectively. The cavities located between hy-
drogen-bonded chains of the host matrix take up toluene
or cyanohydrin in approximately the same space. Interest-
ingly, the latter does not participate in any hydrogen bond-
ing.
Conclusion
In summary, the basic factors playing an important role
in the chiral recognition process in the new hosts (Ϫ)-8 and
(Ϫ)-9 are: the number of 1,4-diol units, their chiral environ-
ment, and the topology of the hydrophobic cavities avail-
able for take-up of the guests as clathrates. Although the
new hosts contain two 1,4-diol units, one of these is mostly
involved in the formation of the host-to-host networks. The
only exception, the 1:2 complex of (Ϫ)-8 and (Ϫ)-13, is a
case in which the second guest molecule is included in the
polar network. The dimeric 1,4-diol units in the host 8 have
the best topology for selective binding of two guest molec-
ules of the same chirality. The large void space created be-
tween the recognition centers of (Ϫ)-9 can be occupied by
neutral solvent molecules, by hydrophobic parts of the guest
molecules, or by nonspecifically attached molecules of the
second enantiomer.
Experimental Section
General Remarks: NMR spectra were recorded on a Jeol Lambda
300 instrument. Ϫ IR spectra were recorded with a Jasco FT-IR
200 spectrometer. Optical rotations were determined with a Jasco
DIP 1000 polarimeter.
(R,R,R,R)-(؊)-trans,trans-2,3,10,11-Tetrakis(hydroxydiphen-
ylmethyl)-1,4,9,12-tetraoxadispiro[4.2.4.2]tetradecane (8): A solu-
tion of (ϩ)-diethyl tartrate (275 g, 1.33 mol) and cyclohexane-1,4-
dione (74 g, 0.66 mol) in toluene (500 mL) containing a catalytic
amount of TsOH was heated under reflux for 120 h. The tetraester
6 was obtained in 92% yield after recrystallization from toluene
(297 g, colorless prisms), m.p. 73Ϫ75 °C. Ϫ [α]D ϭ Ϫ21.6 (c ϭ 1.0,
CHCl3). A solution of 6 (21.4 g, 0.044 mol) in dry THF (50 mL)
Figure 6. Packing pattern of the 1:1:1 complex of (R,R,R,R)-(Ϫ)-
9, (ϩ)-11, and toluene; host molecules (solid lines) form hydrogen-
bonded networks; between them, hydrogen-bonded (ϩ)-11 and dis-
ordered toluene molecules (70% population) are shown (open lines)
3174
Eur. J. Org. Chem. 2000, 3171Ϫ3176

New Chiral Hosts Derived from Dimeric Tartaric Acid
was added with stirring to a solution of PhMgBr in THF (500 mL), ground in a mortar and pestle for a few minutes and kept at room
FULL PAPER
prepared from Mg (15.8 g, 0.65 mol) and bromobenzene (100 g,
0.64 mol), and the mixture was stirred for 6 h. Conventional
temperature for 1 day. A 1:2 inclusion complex of 8 and (Ϫ)-13
was obtained. Heating of the inclusion complex at 180 °C/30 Torr
workup gave crude crystals of (R,R,R,R)-(Ϫ)-trans,trans-2,3,10,11- gave (Ϫ)-13 (27% ee, 4.9 g, 91% yield) as a distillate. When the
tetrakis(hydroxydiphenylmethyl)-1,4,9,12-tetraoxadispiro[4.2.4.2]-
tetradecane (8). Recrystallization of the crude crystals from EtOH
gave the 1:2 inclusion complex of 8 with EtOH as colorless prisms,
which, upon heating, gave pure 8 as a white powder in 35% yield,
m.p. 267Ϫ270 °C. Ϫ [α]D ϭ Ϫ28.0 (c ϭ 1.0, CHCl3 ).
complexation was repeated three times, (Ϫ)-13 (0.27 g, 5% yield) of
100% ee was obtained, with [α]D ϭ Ϫ6.9 (c ϭ 0.41, heptane). The
optical purity of (ϩ)-10 was determined by GC, using a Chiral-
DEX CB capillary column.[9]
Optical Resolution of 2-Methylcyclopentanone (14): A solution of
8 (2.1 g, 2.3 mmol) in (Ϯ)-14 (10 g, 100 mmol) was kept at room
temperature for 24 h. A 1:1 inclusion complex of 8 and (Ϫ)-14 was
formed as colorless prisms (2.2 g, 97% yield, no sharp m.p.), which
upon heating in vacuo gave (Ϫ)-14 (0.15 g, 68% yield) of 15% ee,
with [α]D ϭ Ϫ16.2 (c ϭ 1.0, MeOH), as a distillate. The optical
purity of (Ϫ)-14 was determined by comparison of the measured
[α]D with the literature value.[12] Crystals suitable for X-ray analysis
of the pure 1:1 complex of 8 and (Ϫ)-14 were prepared by com-
plexation of 8 with (Ϫ)-14 of 100% ee, which was obtained by com-
plexation with the host compound 2.[3]
1
8: IR (nujol): ν˜ ϭ 3448 cmϪ1, 3237 (OH). Ϫ H NMR (300 MHz,
CDCl3): δ ϭ 1.06Ϫ1.25 (m, 8 H, CH2), 3.91 (s, 4 H, OH), 4.53 (s,
4 H, CH),7.23Ϫ7.46 (m, 40 H, Ph). Ϫ 13C NMR (300 MHz,
CDCl3): δ ϭ 33.4, 78.2, 80.4, 109.1, 127.2, 127.6, 128.2, 128.5,
142.4,145.9. Ϫ C62H56O8 (929.1164): calcd. C 80.15, H 6.08; found
C 80.03, H 6.25.
(R,R,R,R)-(؊)-trans,trans-2,3,9,10-Tetrakis(hydroxydiphenyl-
methyl)-1,4,8,11-tetraoxadispiro[4.1.4.3]tetradecane (9): A solution
of (ϩ)-diethyl tartrate (110 g, 0.53 mol) and cyclohexane-1,3-dione
(25 g, 0.22 mol) in toluene (300 mL) containing a catalytic amount
of TsOH was heated under reflux for 120 h. The tetraester 7 was
obtained in 43% yield after recrystallization from toluene (46 g,
colorless prisms), m.p. 63Ϫ65 °C. Ϫ [α]D ϭ Ϫ38.3 (c ϭ 1.0,
CHCl3). A solution of 7 (11.6 g, 0.024 mol) in dry THF (30 mL)
was added with stirring to a solution of PhMgBr in THF (300 mL),
prepared from Mg (7.0 g, 0.29 mol) and bromobenzene (46 g, 0.29
mol), and the mixture was stirred for 6 h. Conventional workup
gave crude crystals of (Ϫ)-trans,trans-2,3,9,10-tetrakis(hydroxydi-
phenylmethyl)-1,4,8,11-tetraoxadispiro[4.1.4.3]tetradecane (9).
Recrystallization of 9 from MeOH gave the 1:2 inclusion complex
of 9 with MeOH as colorless prisms, which, upon heating, gave
pure 9 as a white powder in 24% yield,m.p. 259Ϫ261 °C. Ϫ [α]D
ϭ Ϫ140 (c ϭ 1.0, CHCl3).
Optical Resolution of 2-Hydroxypropionitrile (11) in the Presence
of Toluene: A solution of 9 (2.1 g, 2.3 mmol) and (Ϯ)-11 (0.33 g,
4.6 mmol) in toluene (20 mL) was kept at room temperature for
8 h, forming 1:1:1 inclusion crystals of 9, (ϩ)-11, and toluene as
colorless prisms (1.8 g, 72% yield). One recrystallization of the crys-
tals from toluene gave pure inclusion crystals (0.83 g, 28% yield),
m.p. 134Ϫ136 °C), which upon heating in vacuo gave (ϩ)-11
(0.04 g, 24% yield) of 100% ee, with [α]D ϭ ϩ28.4 (c ϭ 0.51,
MeOH), as a distillate.
Optical Resolution of 2-Hydroxypropionitrile (11) in the Absence of
Toluene: A solution of 9 (1 g, 1.1 mmol) in (Ϯ)-11 (2 g, 28 mmol)
was kept at room temperature for 3 h, forming a 1:2 inclusion com-
plex of 9 and (Ϯ)-11 as colorless prisms (1.2 g, 100% yield), m.p.
133Ϫ135 °C.
1
9: IR (nujol): ν˜ ϭ 3369, 3313 (OH) cmϪ1. Ϫ H NMR (300 MHz,
CDCl3): δ ϭ 0.70, 0.89,1.47 (each m, 2 H, CH2), 1.50 (s, 2 H, CH2),
3.51, 4.48 (each s, 2 H, OH), 4.52, 4.58 (each d, J ϭ 7.7 Hz, 2 H,
CH), 6.9 Ϫ7.6 (m, 40 H, Ph). Ϫ 13C NMR (300 MHz, CDCl3):
δ ϭ 19.7, 35.2, 46.3, 77.6, 78.4, 80.8, 81.0, 110.1, 127.0, 127.1,
127.2, 127.3, 127.4, 127.5, 128.0, 128.2, 128.7, 129.0, 142.2, 143.1,
146.0,146.1. Ϫ C62H56O8 (929.1164): calcd. C 80.15, H 6.08; found
C 80.10, H 6.02.
X-ray Crystallographic Study: Crystal data for the 1:1 complex of
(R,R,R,R)-(Ϫ)-8 and (Ϫ)-14, C68H67O9, M ϭ 1028.22, monoclinic
space group P21, (No. 4), a ϭ 10.6546(6), b ϭ 20.393(1), c ϭ
3
˚
˚
13.859(1) A, β ϭ 111.388(5)°, V ϭ 2803.9(3) A , Z ϭ 2, Dcalcd.
ϭ
1.218 Mg mϪ3, µ(Cu-Kα) ϭ 0.634 mmϪ1, F(000) ϭ 1094. An air-
stable crystal of size 0.11 ϫ 0.17 ϫ 0.27 mm was used for data
collection on the Nonius MACH3 diffractometer. A total of 4511
reflections were collected, 3561 unique reflections (Rint ϭ 0.0193)
were used for structure solution and refinement against F2 using
the SHELXS86[14] and SHELXL97[15] programs. Final R indices
are: for I Ͼ 2σ (I): R1 ϭ 0.0458, wR2 ϭ 0.1254. All non-hydroxy
H-atoms were placed geometrically and refined with a riding model
with the Uiso constrained to be 1.2 times that of Ueq of the carrier
atom. Positions for hydroxy group H-atoms were found from differ-
ence mapping and refined with isotropic temperature factors. The
configuration of the guest molecule was set relative to the known
configuration of the host molecule.
Optical Resolution of But-3-yn-2-ol (10): A mixture of 8 (5.5 g,
5.9 mmol) and (Ϯ)-but-3-yn-2-ol (10, 0.9 g, 13 mmol) was ground
in a mortar and pestle for a few minutes and kept at room temper-
ature for 1 day. A 1:1 inclusion complex of 8 and (ϩ)-10 was ob-
tained. Heating of the inclusion complex at 200 °C/30 Torr gave
(ϩ)-10 (59% ee, 0.32 g, 77% yield) as a distillate. When this com-
plexation was repeated, (ϩ)-10 (0.12 g, 28% yield) of 99% ee was
obtained, with [α]D ϭ ϩ50.6 (c ϭ 0.33, dioxane). The optical purity
of (ϩ)-10 was determined by GC, using a Chiral-DEX CB capil-
lary column.[9]
Optical Resolution of 2-Hexanol (12): A mixture of 8 (3.0 g,
3.3 mmol) and (Ϯ)-2-hexanol (12, 0.66 g, 6.5 mmol) was ground in
a mortar and pestle for a few minutes and kept at room temper-
ature for 1 day. A 1:1 inclusion complex of 8 and (ϩ)-12 was ob-
tained. Heating of the inclusion complex at 180 °C/30 Torr gave
(ϩ)-12 (65% ee, 0.32 g, 97% yield) as a distillate. When the com-
plexation was repeated, (ϩ)-12 (0.11 g, 34% yield) of 100% ee was
obtained, with [α]D ϭ ϩ12.0 (c ϭ 0.2, CHCl3),. The optical purity
of (ϩ)-10 was determined by GC, using a Chiral-DEX CB capil-
lary column.[9]
Crystal Data for the 1:2 Complex of (R,R,R,R)-(؊)-8 and (؊)-13:
C72H80O10, M ϭ 1105.36, space group P1, a ϭ 9.3706(5), b ϭ
˚
13.7210(7), c ϭ 14.1083(9) A, α ϭ 64.525(5), β ϭ 72.913(5) γ ϭ
3
˚
84.741(5) deg., V ϭ 1564.04(15) A , Z ϭ 1, Dcalcd. ϭ 1.174
Mg·mϪ3, µ(Cu-Kα) ϭ 0.612 mmϪ1, F(000) ϭ 592. A colorless crys-
tal of size 0.34 ϫ 0.14 ϫ 0.14 mm, sealed by epoxy glue, was used
for data collection (ca. 5.4% decomposition during time of experi-
ment). A total of 6844 reflections were collected on the Nonius
MACH3 diffractometer; 3823 unique with [I Ͼ 2σ (I)] were used
for structure solution and refinement using the SHELXS86[13] and
Optical Resolution of 2-Methyl-1-butanol (13): A mixture of 8 (29 g,
31 mmol) and (Ϯ)-2-methyl-1-butanol (13, 11 g, 123 mmol) was SHELXL97[14] programs. Final R indices are: for [I Ͼ 2σ (I)]: R1 ϭ
Eur. J. Org. Chem. 2000, 3171Ϫ3176
3175

K. Tanaka, S. Honke, Z. Urbanczyk-Lipkowska, F. Toda
0.0412, wR2 ϭ 0.1051. All but non-hydroxy H-atoms were placed of 3119 reflections were collected on Nonius MACH3 diffracto-
FULL PAPER
geometrically and refined with a riding model, with the Uiso con-
strained to be 1.2 times that of Ueq of the carrier atom. Positions
for hydroxy group H-atoms were found from difference mapping
and refined with isotropic temperature factors. The configuration
of the guest molecule was set relative to the known configuration
of the host molecule.
meter using a crystal protected by epoxy glue (4.3% decomposition
during experiment). 2619 unique reflections were used in structure
analysis and refinement using the SHELXS86[14] and SHELXL97[15]
program systems. Final R1 and wR2 factors calculated for 2223 F
Ͼ 4δF are 0.0574 and 0.1532, respectively. All non-hydroxy H-
atoms were placed geometrically and refined with a riding model
with the Uiso constrained to be 1.2 times that of Ueq of the carrier
atom. The disordered toluene molecule was fitted to the regular
hexagon geometry and refined isotropically.
Crystal Data for the 1:1:1 Complex of (R,R,R,R)-(؊)-9, (؉)-11 and
Toluene: C71H67NO10, Mw ϭ 1094.26, orthorhombic space group
P212121 (No. 19), a ϭ 14.3400(2), b ϭ 15.1880(3), c ϭ 27.6300(6)
3
A, V ϭ 6017.7(2) A , Z ϭ 4, Dcalcd. ϭ 1.208 Mg·mϪ3, µ(Mo-Kα) ϭ
0.080 cmϪ1, F(000) ϭ 2320. A total of 10584 unique reflections
were collected on an Nonius Kappa CCD system, with 6309
reflections used in the structure analysis and refinement using the
SHELXS86[14] and SHELXL97[15] programs. Final R1 and wR2
factors are 0.0528 and 0.1283, respectively. The disordered toluene
molecule was fitted to the regular hexagon geometry and refined
isotropically. All non-hydroxy H-atoms were placed geometrically
and refined with a riding model with the Uiso constrained to be 1.2
times that of Ueq of the carrier atom. Positions for hydroxy group
H-atoms were found from difference mapping and refined with iso-
tropic temperature factors.
˚
˚
[1]
‘‘Solid-State Supramolecular Chemistry: Crystal Engineering’’,
in Comprehensive Supramolecular Chemistry, vol. 6 (Eds.: J. L.
Atwood, J. E. D. Davies, D. D. Macnicol, F. Vögtle), Perga-
mon, 1996; E. Weber, T. Hens, T. Brehmer, I. Csoregh, J. Chem.
Soc., Perkin Trans 2 2000, 235Ϫ241.
[2]
F. Toda, K. Tanaka, T. Omata, K. Nakamura, T. Oshima, J.
Am. Chem. Soc. 1983, 105, 5151Ϫ5152.
[3]
F. Toda, T. Shinyama, J. Chem. Soc., Perkin Trans. 1 1997,
1759Ϫ1761.
[4]
S. A. Bourne, M. Sakamoto, F. Toda, J. Chem. Cryst. 1995,
25, 755Ϫ757.
[5]
F. Toda, K. Tanaka, S. Nagamatsu, Tetrahedron Lett. 1984, 25,
4929Ϫ4932; F. Toda, K. Tanaka, T. C. W. Mak, Chem. Lett.
1984, 2085Ϫ2088; I. Goldberg, K. Mori, F. Toda, J. Org. Chem.
1988, 53, 308Ϫ312.
Crystal Data for the 1:2 Complex of (R,R,R,R)-(؊)-9 and (؎)-11:
C68H66N2O10, Mw ϭ 1071.23. Colorless crystals (sealed by epoxy
glue, ca. 6% decomposition), crystallized in orthorhombic space
[6]
F. Toda, K. Tanaka, Tetrahedron Lett. 1988, 29, 551Ϫ554; D.
Seebach, A. K. Beck, R. Imwinkelried, S. Roggo, A. Wonnac-
group P212121 (No. 19), a ϭ 14.1920(6), b ϭ 14.9610(6), c ϭ
ott, Helv. Chim. Acta 1987, 70, 954Ϫ959.
3
[7]
˚
˚
27.725(3) A, V ϭ 5886.8(7) A , Z ϭ 4, Dcalcd. ϭ 1.209, F(000) ϭ
2272, µ(Cu-Kα) ϭ 0.648 cm Ϫ1. A total of 6723 reflections were
collected on Nonius MACH3 diffractometer, and 3119 unique
reflections were used in structure analysis and refinement using the
SHELXS86[14] and SHELXL97[15] program systems. Final R1 and
wR2 factors are 0.0584 and 0.1507, respectively. All non-hydroxy
H-atoms were placed geometrically and refined with a riding model
with the Uiso constrained to be 1.2 times that of Ueq of the carrier
atom. The configurations of the two enantiomeric molecules of 9
were set relative to the known configuration of the host molecule.
Advances in Supramolecular Chemistry, (Ed.: G. W. Gokel), JAI
Press Inc., 1995, vol. 2, pp. 141Ϫ191.
[8]
F. Toda, Top. Curr. Chem. 1988, 149, 211Ϫ238; F. Toda, Synlett
1993, 303Ϫ312; F. Toda, Acc. Chem. Res. 1995, 28, 480Ϫ486.
[9]
Chiral-DEX CB is available from Chrompack, Middelburg,
The Netherlands.
[10]
F. Toda, H. Takumi, Enantiomer 1996, 1, 29Ϫ33.
[11]
M. Schudok, G. Kretzschmar, Tetrahedron Lett. 1997, 38,
387Ϫ388.
[12]
F. Toda, K. Tanaka, H. Miyamoto, H. Koshima, I. Miyahara,
K. Hirotsu, J. Chem. Soc., Perkin Trans. 2 1997, 1877Ϫ1885.
J. J. Partridge, N. K. Chadra, M. R. Uskokovic, J. Am. Chem.
Soc. 1973, 95, 532Ϫ540.
G. M. Sheldrick, Acta Crystallogr., Sect. A 1990, 46, 467Ϫ473.
G. M. Sheldrick, SHELXL97, Program for Crystal Structures
[13]
Crystal Data for the 1:1 Complex of (R,R,R,R)-(؊)-9 and Toluene:
C69H64O8, Mw ϭ 1021.2. Colorless crystals, crystallized in mono-
[14]
[15]
clinic P21 space group (No. 4), a ϭ 10.649(1), b ϭ 22.180(2), c ϭ
Refinement 1997, Univ. of Göttingen, Germany.
Received December 27, 1999
[O99704]
3
˚
˚
12.0333(8) A, β ϭ 101.42(1)°, V ϭ 2785.9(4) A , F(000) ϭ 1084,
µ(Cu-Kα) ϭ 0.623 cmϪ1, Z ϭ 2, Dcalcd. ϭ 1.217 Mg cmϪ1. A total
3176
Eur. J. Org. Chem. 2000, 3171Ϫ3176