Synthesis, optical resolution and enantiomeric recognition ability of novel, inherently chiral calix[4]arenes: Trial application to asymmetric reactions as organocatalysts

Article abstract of DOI:10.1002/ejoc.200800850

Newly designed, inherently chiral calix[4]arenes containing amino phenol structures have been synthesized and resolved to optically pure forms. The enantiomeric recognition ability of one chiral calix[4]arene was examined with mandelic acid by ¹

Full text of DOI:10.1002/ejoc.200800850

FULL PAPER
DOI: 10.1002/ejoc.200800850
Synthesis, Optical Resolution and Enantiomeric Recognition Ability of Novel,
Inherently Chiral Calix[4]arenes: Trial Application to Asymmetric Reactions as
Organocatalysts
Seiji Shirakawa,[a] Akihiro Moriyama,[a] and Shoichi Shimizu*[a]
Keywords: Calixarenes / Chiral resolution / Host–guest systems / Asymmetric catalysis / Michael addition / Organocatalysis
Newly designed, inherently chiral calix[4]arenes containing
amino phenol structures have been synthesized and resolved
to optically pure forms. The enantiomeric recognition ability
of one chiral calix[4]arene was examined with mandelic acid
by 1H NMR spectroscopy, and we found that the inherently
chiral calix[4]arene could be used as a chiral NMR solvating
agent to determine the enantiopurity of mandelic acid at am-
bient temperature. In addition, the chiral calix[4]arenes were
used as organocatalysts in asymmetric Michael-type addition
reactions of thiophenols, and high catalytic efficiency with
low enantioselectivity was observed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Results and Discussion
The chemistry of chiral calixarenes has received increas-
ing interest in recent years because it relates to the develop-
ment of new chiral receptors for asymmetric recognition
and provides potent tools for the stereochemical under-
standing of biochemical systems.[1] Hence, many chiral ca-
lixarenes containing chiral residues at either the wide or the
narrow rim have been prepared as chiral receptors[2] and
catalysts.[3] A more challenging and attractive approach to
introduce chirality is to make the calixarene “inherently”
chiral by creating an asymmetric structure.[4] Over the past
two decades, many inherently chiral calixarenes have been
prepared, and some of them have been resolved into indi-
vidual enantiomers either by chiral preparative HPLC[5] or
by the formation of diastereomers with a chiral auxiliary
linked through covalent bonds.[6,7] In spite of these efforts,
only a few examples of enantiomeric recognition with in-
herently chiral calixarenes have been reported.[5f,5j,6a,6c,6j]
This paper describes the design, synthesis and optical reso-
lution of functionalized inherently chiral calixarenes and
their chiral recognition ability. The enantiomeric recogni-
tion ability of a novel, inherently chiral calix[4]arene was
Synthesis and Optical Resolution
The novel, inherently chiral calix[4]arenes synthesised in
this work are shown in Figure 1. The chiral calix[4]arenes 1
possess amino and hydroxy groups, which are involved in
molecular recognition, at proximal positions on the wide
rim. Such amino phenol (alcohol) structures are often pres-
ent in useful chiral building blocks, such as cinchonidine,
ephedrine and prolinol. Also, the conformations of the chi-
ral calix[4]arenes 1 are fixed in the cone conformation,
which provides a rigid chiral environment.
1
examined through H NMR and UV/Vis titration experi-
ments with mandelic acid. In addition, the chiral calix[4]-
arenes were used in asymmetric Michael-type addition reac-
tions as organocatalysts.[8]
Figure 1. Functionalized inherently chiral calix[4]arenes 1.
The requisite chiral calix[4]arenes 1a–d, which contain
different alkyl substituents on the nitrogen atom, can be
prepared in a similar manner from the already reported
proximally p-dibrominated calix[4]arene 2[9] in a four-step
sequence, as outlined in Scheme 1. Thus, p-dibromocalix[4]-
arene 2 was transformed into the monoformylated com-
pound 3 by treatment with 1.0 equiv. of nBuLi and subse-
[a] Department of Applied Molecular Chemistry, College of Indus-
trial Technology, Nihon University,
Narashino, Chiba 275-8575, Japan
Fax: +81-47-474-2579
E-mail: s5simizu@cit.nihon-u.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
Eur. J. Org. Chem. 2008, 5957–5964
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S. Shirakawa, A. Moriyama, S. Shimizu
FULL PAPER
quent addition of N,N-dimethylformamide. The reductive Lithiation of 5a–d and trapping of the resulting anion with
amination of the formyl group of 3 with primary amines B(OMe)3 gave the corresponding boronates. The boronates
gave the corresponding secondary amines 4a–d in 82–96% were oxidized by H2O2 using a one-pot method to give the
yields. Compounds 4a–d were transformed with n-butyl or target calix[4]arenes 1a–d as racemates in 48–70% yields.
ethyl bromide to the tertiary amines 5a–d in 72–95% yields.
Efficient optical resolution of the racemic calix[4]arene
1a was achieved by recrystallization after complexation
with chiral mandelic acid (Scheme 2). The optical purity of
the chiral calix[4]arene 1a was confirmed by means of chiral
HPLC analysis.[10] To the best of our knowledge, this is the
first example of the optical resolution of an inherently chi-
ral calix[4]arene by diastereomeric complexation without
covalent bonding between chiral molecules.[11] The other ra-
Scheme 2. Optical resolution of the inherently chiral calix[4]arenes
1a–d.
Scheme 1. Synthesis of inherently chiral calix[4]arenes 1a–d.
Figure 2. CD spectra of enantiomers of calix[4]arenes 1a–d in hexane.
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Novel, Inherently Chiral Calix[4]arenes as Organocatalysts
cemic calix[4]arenes 1b–d were resolved in optically pure
forms by preparative chiral HPLC using a SUMICHIRAL
OA-4800 column (2.0ϫ25 cm). The circular dichroism
(CD) spectra of the separated enantiomers of 1a–d showed
perfect mirror images (Figure 2).[12]
Enantiomeric Recognition Ability of 1a for Mandelic Acid
With an efficient synthetic scheme for the synthesis of
inherently chiral calix[4]arenes in hand, the ability of the
chiral calix[4]arene 1a to recognize enantiomers was investi-
gated. 1H NMR studies of the chiral calix[4]arene (+)295-1a
were performed with equimolar amounts of racemic man-
delic acid.[13] As a result of diastereomeric complexation,
clear signal splitting (δ = 4.93 and 4.96 ppm; Figure 3b)
with an upfield shift of the signal of the benzylic proton of
racemic mandelic acid (δ =5.26 ppm; Figure 3a) was ob-
served. In addition, different proportions of both enantio-
mers of mandelic acid were treated with (+)295-1a, and dif-
ferent signal intensities for both (R)- and (S)-mandelic acid
were observed depending on the proportions (Figure 4).
These results clearly indicate that inherently chiral calix[4]-
arene 1a could be used as a chiral NMR solvating agent to
determine the enantiopurity of mandelic acid at ambient
1
temperature. Furthermore, H NMR studies of the chiral
calix[4]arene (+)295-1a with different molar ratios of (R)- or
(S)-mandelic acid were examined (Figure 5). Even in the
Figure 4. 1H NMR spectra of various enantiomeric ratios mandelic
acid in the presence of (+)295-1a in CDCl3 at 27 °C [mandelic acid/
presence of a less than stoichiometric amount of (+)295-1a, (+)295-1a = 1:1].
different chemical shifts of the benzylic proton of (R)- and
(S)-mandelic acid were observed. Interestingly, the degree
of signal separation of (R)- and (S)-mandelic acid (∆∆δ ≈
0.03 ppm) did not depend on the molar ratio of 1a/man-
delic acid, although many chiral solvating agents depend
greatly on the molar ratio of the chiral agent.[13] Also the
magnitude of the upfield shifts of the signals of the benzylic
proton gradually increased with an increase in the molar
ratio of (+)295-1a. However, the addition of more than an
equimolar amount of (+)295-1a showed no further change
in the chemical shifts of the mandelic acids. These results
indicate that inherently chiral calix[4]arene 1a and mandelic
acid form a 1:1 complex.
Figure 5. 1H NMR chemical shift of the signal of the benzylic pro-
ton of mandelic acid with various molar ratios of (+)295-1a/(R)- or
(S)-mandelic acid in CDCl3 at 27 °C.
Next, the association constants of (+)295-1a with (R)- or
(S)-mandelic acid were measured by titration experiments
using UV/Vis spectral measurements (Figure 6). From the
changes in absorption intensity at 279 nm along with the
concentration of mandelic acid, the association constants,
Ka, were calculated by the non-linear least-squares method.
The association constant, Ka, for (+)295-1a with (S)-man-
delic acid (3.5ϫ105 dm–3 mol–1) was 2.2 times larger than
that with (R)-mandelic acid (1.6ϫ105 dm–3 mol–1). Al-
though the mechanism of enantiomeric recognition by chi-
ral calix[4]arene 1a is not yet clear at this stage, one can
speculate that not only the amino and hydroxy groups of
1a, but also the cavity of the calixarene, cooperate in chiral
molecular recognition.
Figure 3. 1H NMR spectra of racemic mandelic acid in the absence
and presence of (+)295-1a in CDCl3 at 27 °C [mandelic acid/(+)295
-
1a = 1:1].
Eur. J. Org. Chem. 2008, 5957–5964
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Table 1. Asymmetric Michael-type addition reactions of thiophenol
catalysed by (+)- or (–)-1.
Entry
Catalyst
Yield[a]
ee (config.)[b]
1
2
(+)295-1a
(–)295-1a
(–)295-1a
(+)294-1b
(–)294-1b
(–)294-1c
(–)294-1d
91%
93%
95%
65%
62%
67%
45%
15% (S)
15% (R)
16% (R)
3% (S)
3% (R)
3% (R)
3% (R)
3[c]
4
5
6
7
[a] Isolated yield. [b] Determined by a previously reported pro-
cedure, see ref.[15a] [c] Reaction temp. –40 °C.
Scheme 3. Asymmetric Michael-type addition reactions catalysed
by (–)295-1a.
Figure 6. Absorption spectra of the chiral calix[4]arene (+)295-1a in
the presence of (R)- or (S)-mandelic acid in CHCl3 at 25 °C.
Conclusions
Asymmetric Michael-Type Addition Reactions Catalysed by
Inherently Chiral Calix[4]arenes 1
In this study, novel, inherently chiral calix[4]arenes were
developed for the recognition of chiral molecules. The in-
herently chiral calix[4]arene 1a could be used as a chiral
NMR solvating agent to determine the enantiopurity of
mandelic acid at ambient temperature. In addition, the chi-
ral calix[4]arenes were used as organocatalysts in asymmet-
ric Michael-type addition reactions of thiophenols. Further
improvements in the structures of the chiral calix[4]arenes
to allow more efficient asymmetric catalysis are now in pro-
gress in our laboratory.
The application of an inherently chiral calix[4]arene 1 as
a chiral organocatalyst[14] is a challenge in organic synthe-
sis. In a preliminary trial, an asymmetric Michael-type ad-
dition reaction of thiophenol, which is known to be cata-
lysed by chiral amino alcohols, was selected as a model re-
action (Table 1).[15] Both enantiomers, (+)295-1a and (–)295
-
1a, promoted the reaction efficiently and gave a Michael
addition product 6a in excellent yields. The chiral induction
of the product was observed to be 15% ee, and the configu-
ration of the major enantiomer was (S) with (+)295-1a, (R)
with (–)295-1a (Entries 1 and 2). Although the observed
enantioselectivity of the product was poor, a certain
Experimental Section
General: 1H and 13C NMR spectra were recorded with a Bruker
amount of chiral induction was observed. Note that this is Avance 400 spectrometer in CDCl3. Tetramethylsilane (TMS)
1
served as the internal standard (δ = 0 ppm) for H and 13C NMR
the first example of an inherently chiral calixarene with no
chiral residue being applied to asymmetric catalysis.[16] Re-
spectroscopy. IR spectra were measured with a Bio-Rad FTS-60A
spectrometer. Circular dichroism (CD) spectra were measured by
action at a lower temperature led to a slight increase in
using a Jasco J-820 spectrometer. UV/Vis spectra were measured
the enantioselectivity with no loss of reactivity (Entry 3).
with a Shimadzu UV-2400PC spectrophotometer. High-perform-
Compounds 1b–d were also examined as catalysts in the
ance liquid chromatography (HPLC) was carried out with a Hitachi
reaction, but gave poor selectivity regardless of the elec-
tronic properties of the benzyl substituent in the tertiary
655 liquid chromatograph instrument and a SUMICHIRAL OA-
4800 column (0.46ϫ25 cm). Optical rotations were measured with
amine on the catalyst (Entries 4–7). Other substrates were
also subjected to the Michael-type addition reactions, and
selected examples are shown in Scheme 3.
a Jasco DIP-1000 digital polarimeter. MS data were measured with
a JEOL JMS-AX500 mass spectrometer (EI, 70 eV) coupled to a
GC. Preparative gel-permeation chromatography (GPC) and pre-
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Novel, Inherently Chiral Calix[4]arenes as Organocatalysts
1
parative HPLC were performed by using a Jai model 908 liquid
chromatograph with JAIGEL 1-H and 2-H columns and with a
SUMICHIRAL OA-4800 column (2.0ϫ25 cm), respectively. Ana-
lytical thin-layer chromatography (TLC) and column chromatog-
raphy were carried out on precoated silica gel 60 F254 plastic sheets
tylamine (96% yield). H NMR (400 MHz, CDCl3): δ = 7.20–7.36
(m, 5 H), 6.47–6.73 (m, 10 H), 4.43 (d, J = 13.4 Hz, 1 H + 1 H),
4.39 (d, J = 13.6 Hz, 1 H + 1 H), 3.76–3.89 (m, 8 H), 3.68 (s, 2 H),
3.57 (s, 2 H), 3.15 (d, J = 13.4 Hz, 1 H + 1 H), 3.07 (d, J = 13.5 Hz,
1 H + 1 H), 1.85–1.93 (m, 8 H), 0.92–1.03 (m, 12 H) ppm. 13C
(E. Merck) and with silica gel 60 (spherical 0.040–0.100 mm, NMR (100 MHz, CDCl3): δ = 156.86, 156.15, 155.91, 155.43,
Kanto), respectively. Tetrahydrofuran (THF) was freshly distilled
from sodium/benzophenone.
140.39, 137.05, 137.02, 135.70, 135.55, 134.66, 134.59, 134.56,
134.53, 133.54, 130.54, 130.49, 128.67, 128.46, 128.34, 128.27,
128.13, 127.93, 127.89, 126.83, 122.16, 121.89, 114.65, 76.75, 76.69,
76.65, 52.94, 52.64, 30.97, 30.85, 23.29, 23.18, 23.14, 10.45, 10.39,
5-Bromo-11-formyl-25,26,27,28-tetrapropoxycalix[4]arene [(؎)-3]:
nBuLi (8.0 mmol, 1.5  in hexane) was added to a solution of 5,11-
dibromo-25,26,27,28-tetrapropoxycalix[4]arene (2)[9] (8.0 mmol) in
THF (120 mL) at –78 °C under argon, and the mixture was stirred
at this temperature for 30 min. Dry N,N-dimethylformamide
(12 mmol) was then added, and the mixture was stirred at –78 °C
for 15 min. The reaction was quenched with aq. 0.2  HCl (60 mL),
and organic materials were extracted with CHCl3 (50 mLϫ2). The
organic extracts were washed with water and dried with MgSO4.
Evaporation of the solvents and purification of the residue by col-
umn chromatography on silica gel (CHCl3/hexane = 3:2 as eluent)
10.19, 10.17 ppm. IR: ν = 2963, 2923, 2876, 1456, 1213, 1196, 1006,
˜
966, 766 cm–1. C48H56BrNO4·0.1CHCl3 (790.87·0.1CHCl3): calcd.
C 71.97, H 7.03, N 1.74; found C 72.08, H 7.08, N 1.66.
5-Bromo-11-{[(4-methoxybenzyl)amino]methyl}-25,26,27,28-tetra-
propoxycalix[4]arene [(؎)-4c]: Calix[4]arene 4c was prepared in a
manner similar to that described for 4a by using (4-methoxybenzyl)-
amine instead of n-butylamine (93% yield). 1H NMR (400 MHz,
CDCl3): δ = 7.20 (d, J = 8.6 Hz, 2 H), 6.89 (d, J = 8.6 Hz, 2 H),
6.48–6.74 (m, 10 H), 4.44 (d, J = 13.3 Hz, 1 H), 4.43 (d, J =
13.4 Hz, 1 H), 4.39 (d, J = 13.5 Hz, 1 H), 4.38 (d, J = 13.4 Hz, 1
H), 3.77–3.87 (m, 8 H), 3.80 (s, 3 H), 3.61 (s, 2 H), 3.56 (s, 2 H),
1
afforded 3a in 79% yield (4.42 g). H NMR (400 MHz, CDCl3): δ
= 9.72 (s, 1 H), 7.21–7.25 (m, 2 H), 6.48–6.73 (m, 8 H), 4.49 (d, J
= 13.7 Hz, 1 H), 4.43 (d, J = 13.7 Hz, 1 H + 1 H), 4.39 (d, J = 3.152 (d, J = 13.4 Hz, 1 H), 3.148 (d, J = 13.4 Hz, 1 H), 3.08 (d, J
13.6 Hz, 1 H), 3.73–4.01 (m, 8 H), 3.26 (d, J = 13.8 Hz, 1 H), 3.19
(d, J = 13.8 Hz, 1 H), 3.17 (d, J = 13.5 Hz, 1 H), 3.10 (d, J =
= 13.4 Hz, 1 H + 1 H), 1.86–1.95 (m, 8 H), 0.93–1.03 (m, 12 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.54, 156.88, 156.16,
13.6 Hz, 1 H), 1.83–1.94 (m, 8 H), 0.94–1.03 (m, 12 H) ppm. 13C 155.92, 155.45, 137.07, 137.04, 135.72, 135.57, 134.69, 134.60,
NMR (100 MHz, CDCl3): δ = 191.70, 162.68, 156.77, 156.20, 134.57, 134.54, 133.56, 132.51, 130.54, 130.49, 129.47, 128.69,
155.49, 137.38, 136.81, 136.14, 135.84, 135.64, 134.95, 134.62,
133.72, 131.08, 130.89, 130.63, 130.47, 130.01, 128.69, 128.46,
128.47, 128.15, 127.91, 122.15, 121.93, 114.64, 113.72, 76.77, 76.71,
76.67, 55.26, 52.50, 52.28, 30.98, 30.86, 23.30, 23.19, 23.15, 10.45,
128.16, 127.91, 122.45, 122.13, 114.88, 76.93, 76.86, 76.77, 76.71, 10.39, 10.19, 10.17 ppm. IR: ν = 2963, 2934, 2876, 1513, 1457,
˜
31.00, 30.97, 30.86, 30.83, 23.30, 23.19, 23.18, 23.12, 10.41, 10.35,
1247, 1212, 1196, 1038, 1006, 966, 766 cm–1. C49H58BrNO5
10.21, 10.17 ppm. IR: ν = 2963, 2932, 2875, 1692, 1456, 1297, 1206, (820.89): calcd. C 71.69, H 7.12, N 1.71; found C 71.74, H 7.10, N
˜
1004, 766 cm–1. C41H47BrO5 (699.71): calcd. C 70.38, H 6.77; found
C 69.93, H 6.72.
1.76.
5-Bromo-11-({[4-(trifluoromethyl)benzyl]amino}methyl)-25,26,27,28-
5-Bromo-11-[(butylamino)methyl]-25,26,27,28-tetrapropoxycalix[4]- tetrapropoxycalix[4]arene [(؎)-4d]: Calix[4]arene 4d was prepared
arene [(؎)-4a]: n-Butylamine (20 mmol) was added to a solution of
3 (4.0 mmol) in THF (40 mL)/ethanol (40 mL) at room tempera-
ture, and the mixture was stirred for 24 h. NaBH4 (4.0 mmol) was
then added, and the mixture was stirred for 30 min. The reaction
was quenched with aq. satd. NH4Cl, and organic materials were
extracted with CHCl3 (50 mL ϫ 2). The organic extracts were
washed with water and dried with MgSO4. Evaporation of the sol-
vents and purification of the residue by column chromatography
on silica gel (CHCl3/AcOEt = 1:3 as eluent) afforded 4a in 82%
yield (2.48 g). 1H NMR (400 MHz, CDCl3): δ = 6.68–6.82 (m, 5
H), 6.59 (t, J = 7.6 Hz, 1 H), 6.39–6.49 (m, 4 H), 4.44 (d, J =
13.5 Hz, 1 H), 4.42 (d, J = 13.4 Hz, 1 H), 4.39 (d, J = 13.4 Hz, 1
in a manner similar to that described for 4a by using [4-(trifluoro-
methyl)benzyl]amine instead of n-butylamine (93 % yield). 1H
NMR (400 MHz, CDCl3): δ = 7.59 (d, J = 8.0 Hz, 2 H), 7.39 (d,
J = 8.0 Hz, 2 H), 6.60–6.69 (m, 7 H), 6.54–6.56 (m, 2 H), 6.48 (t,
J = 7.5 Hz, 1 H), 4.45 (d, J = 13.4 Hz, 1 H + 1 H), 4.40 (d, J =
13.5 Hz, 1 H + 1 H), 3.77–3.88 (m, 8 H), 3.67 (s, 2 H), 3.53 (s, 2
H), 3.15 (d, J = 13.4 Hz, 1 H + 1 H), 3.08 (d, J = 13.2 Hz, 1 H +
1 H), 1.86–1.95 (m, 8 H), 0.94–1.03 (m, 12 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 156.78, 156.33, 155.92, 155.61, 144.61,
137.31, 137.20, 135.55, 135.50, 134.86, 134.75, 134.51, 134.46,
133.24, 130.61, 129.24, 128.92, 128.60, 128.46, 128.39, 128.06,
128.04, 128.00, 127.84, 125.70, 125.30, 125.27, 125.23, 125.19,
H), 4.37 (d, J = 13.5 Hz, 1 H), 4.13 (br. s, 1 H), 3.73–3.91 (m, 8 122.99, 122.15, 121.85, 120.29, 114.62, 76.81, 76.75, 76.69, 52.56,
H), 3.59 (s, 2 H), 3.16 (d, J = 13.5 Hz, 1 H), 3.14 (d, J = 13.5 Hz,
1 H), 3.08 (d, J = 13.5 Hz, 1 H), 3.07 (d, J = 13.5 Hz, 1 H), 2.58
(t, J = 7.3 Hz, 2 H), 1.84–1.92 (m, 8 H), 1.47–1.52 (m, 2 H), 1.34–
52.23, 31.00, 30.99, 30.88, 30.86, 23.29, 23.21, 23.19, 10.40, 10.34,
10.25, 10.23 ppm. IR: ν = 2966, 2935, 2877, 1457, 1326, 1213, 1197,
˜
1164, 1126, 1067, 1006, 966, 766 cm–1. C49H55BrF3NO4 (858.86):
1.38 (m, 2 H), 0.90–1.04 (m, 15 H) ppm. 13C NMR (100 MHz, calcd. C 68.52, H 6.45, N 1.63; found C 68.40, H 6.45, N 1.55.
CDCl3): δ = 157.10, 156.59, 155.95, 155.23, 136.79, 136.62, 136.11,
5-Bromo-11-[(dibutylamino)methyl]-25,26,27,28-tetrapropoxycalix[4]-
136.04, 135.10, 135.01, 134.31, 134.13, 131.07, 130.47, 130.43,
129.16, 128.80, 128.54, 128.24, 127.81, 122.20, 121.86, 114.72,
76.80, 76.69, 76.62, 52.69, 48.02, 31.11, 30.97, 30.95, 30.83, 23.34,
arene [(؎)-5a]: n-Butyl bromide (3.6 mmol) was added to a mixture
of 4a (3.0 mmol), K2CO3 (7.5 mmol) and CH3CN (100 mL), and
the mixture was heated at reflux for 15 h. The mixture was cooled
to room temperature, and the reaction was quenched with water.
After the removal of CH3CN by evaporation, organic materials
were extracted with CHCl3 (50 mLϫ2), and the organic extracts
were dried with MgSO4. Evaporation of the solvents and purifica-
23.24, 23.11, 20.46, 13.98, 10.53, 10.47, 10.11 ppm. IR: ν = 2961,
˜
2930, 2874, 1586, 1463, 1214, 1007, 758 cm–1. C45H58BrNO4·
0.2CHCl3 (756.85·0.2CHCl3): calcd. C 69.55, H 7.49, N 1.79; found
C 69.63, H 7.50, N 1.72.
5-[(Benzylamino)methyl]-11-bromo-25,26,27,28-tetrapropoxycalix[4]- tion of the residue by column chromatography on silica gel (CHCl3/
arene [(؎)-4b]: Calix[4]arene 4b was prepared in a manner similar
to that described for 4a by using benzylamine instead of n-bu-
AcOEt = 3:1 as eluent) afforded 5a in 72% yield (1.76 g). 1H NMR
(400 MHz, CDCl3): δ = 6.77–6.93 (m, 5 H), 6.53 (t, J = 7.5 Hz, 1
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S. Shirakawa, A. Moriyama, S. Shimizu
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H), 6.28–6.39 (m, 4 H), 4.45 (d, J = 13.4 Hz, 1 H), 4.43 (d, J = 3.08 (d, J = 13.3 Hz, 1 H), 3.07 (d, J = 13.4 Hz, 1 H), 2.33 (q, J =
13.3 Hz, 1 H), 4.39 (d, J = 13.4 Hz, 1 H), 4.37 (d, J = 13.3 Hz, 1
6.9 Hz, 2 H), 1.87–1.97 (m, 8 H), 0.92–1.08 (m, 15 H) ppm. 13C
H), 3.86–3.95 (m, 4 H), 3.70–3.77 (m, 4 H), 3.43 (s, 2 H), 3.16 (d, NMR (100 MHz, CDCl3): δ = 156.67, 156.25, 155.73, 155.54,
J = 13.4 Hz, 1 H), 3.14 (d, J = 13.4 Hz, 1 H), 3.08 (d, J = 13.5 Hz, 144.64, 137.27, 137.24, 135.47, 135.12, 134.82, 134.77, 134.42,
1 H), 3.07 (d, J = 13.4 Hz, 1 H), 2.37 (t, J = 7.4 Hz, 4 H), 1.84– 134.10, 132.32, 130.63, 130.50, 128.97, 128.84, 128.66, 128.53,
1.93 (m, 8 H), 1.43–1.50 (m, 4 H), 1.28–1.36 (m, 4 H), 1.02–1.07
128.43, 128.34, 128.02, 127.97, 127.93, 125.76, 125.06, 125.02,
(m, 6 H), 0.90–0.93 (m, 12 H) ppm. 13C NMR (100 MHz, CDCl3): 123.06, 122.14, 121.93, 120.35, 114.59, 76.87, 76.76, 76.65, 57.03,
δ = 157.38, 156.23, 155.66, 154.94, 136.53, 136.46, 136.43, 135.85, 56.97, 47.17, 30.97, 30.84, 23.26, 23.24, 23.17, 12.05, 10.39, 10.34,
135.42, 134.85, 134.02, 133.92, 132.73, 130.38, 130.20, 129.73, 10.26, 10.22 ppm. IR: ν = 2966, 2935, 2877, 1458, 1326, 1213, 1163,
˜
129.11, 128.98, 128.41, 127.59, 127.54, 122.21, 121.93, 114.78, 1125, 1067, 1006, 765 cm–1. C51H59BrF3NO4 (886.92): calcd. C
76.82, 76.70, 76.62, 76.58, 57.95, 53.46, 31.00, 30.95, 30.88, 30.84,
29.19, 23.41, 23.30, 23.07, 20.77, 14.22, 10.64, 10.57, 10.05,
69.06, H 6.71, N 1.58; found C 68.61, H 6.69, N 1.45.
5-[(Dibutylamino)methyl]-11-hydroxy-25,26,27,28-tetrapropoxycalix-
[4]arene [(؎)-1a]: nBuLi (8.0 mmol, 1.5  in hexane) was added to
a solution of 5a (4.0 mmol) in THF (100 mL) at –78 °C under ar-
gon, and the mixture was stirred at this temperature for 30 min.
B(OMe)3 (16 mmol) was added, and the mixture was stirred at
–78 °C for 1 h. Then 30% aq. H2O2 (15 mL) and 3  aq. NaOH
(15 mL) were added to the resulting reaction mixture, which was
warmed to room temperature. After stirring at room temperature
10.00 ppm. IR: ν = 2959, 2931, 2873, 1456, 1212, 1195, 1009,
˜
763 cm–1. C49H66BrNO4 (812.96): calcd. C 72.39, H 8.18, N 1.72;
found C 72.29, H 8.01, N 1.56.
5-{[(Benzyl)(ethyl)amino]methyl}-11-bromo-25,26,27,28-tetraprop-
oxycalix[4]arene [(؎)-5b]: Calix[4]arene 5b was prepared from 4b in
a manner similar to that described for 5a by using ethyl bromide
(3 equiv.) instead of n-butyl bromide (91 % yield). 1H NMR
(400 MHz, CDCl3): δ = 7.16–7.32 (m, 5 H), 6.45–6.76 (m, 10 H), for 1 h, the reaction was quenched with Na2S2O3·5H2O (32 mmol),
4.42 (d, J = 13.4 Hz, 1 H + 1 H), 4.38 (d, J = 13.4 Hz, 1 H + 1 and the mixture was stirred for 30 min. After removal of THF by
H), 3.76–3.88 (m, 8 H), 3.42 (s, 2 H), 3.33 (s, 2 H), 3.14 (d, J = evaporation, organic materials were extracted with CHCl3
13.3 Hz, 1 H), 3.13 (d, J = 13.4 Hz, 1 H), 3.07 (d, J = 13.3 Hz, 1 (50 mL ϫ 2). The organic extracts were washed with water and
H), 3.06 (d, J = 13.3 Hz, 1 H), 2.36 (q, J = 6.9 Hz, 2 H), 1.85–1.94 dried with MgSO4. Evaporation of solvents and purification of the
(m, 8 H), 0.92–1.05 (m, 15 H) ppm. 13C NMR (100 MHz, CDCl3): residue by column chromatography on silica gel (CHCl3/AcOEt =
δ = 156.78, 156.06, 155.71, 155.35, 140.05, 137.06, 136.99, 135.64, 1:1 as eluent) afforded 1a in 51 % yield (1.53 g). 1H NMR
135.15, 134.58, 134.52, 134.15, 132.75, 130.60, 130.37, 129.11, (400 MHz, CDCl3): δ = 6.76–6.86 (m, 4 H), 6.72 (t, J = 7.4 Hz, 1
128.80, 128.64, 128.56, 128.11, 128.08, 127.88, 127.81, 126.55, H), 6.45 (t, J = 7.4 Hz, 1 H), 6.36–6.38 (m, 2 H), 5.81 (s, 2 H), 4.45
122.17, 121.98, 114.65, 76.75, 76.72, 76.66, 76.62, 57.43, 57.00,
46.91, 30.95, 30.82, 23.28, 23.18, 23.12, 11.98, 10.45, 10.40, 10.21,
(d, J = 13.3 Hz, 1 H), 4.43 (d, J = 13.7 Hz, 1 H), 4.40 (d, J =
13.7 Hz, 1 H), 4.37 (d, J = 13.2 Hz, 1 H), 3.86–3.92 (m, 4 H), 3.77
(t, J = 7.1 Hz, 2 H), 3.69 (t, J = 7.1 Hz, 2 H), 3.39 (s, 2 H), 3.15
(d, J = 13.3 Hz, 1 H), 3.13 (d, J = 13.3 Hz, 1 H), 3.06 (d, J =
12.8 Hz, 1 H), 3.03 (d, J = 12.8 Hz, 1 H), 2.32 (t, J = 7.5 Hz, 4 H),
1.87–1.93 (m, 8 H), 1.41–1.47 (m, 4 H), 1.25–1.32 (m, 4 H), 1.01–
1.06 (m, 6 H), 0.88–0.94 (m, 12 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 156.87, 156.30, 156.01, 150.79, 149.74, 135.43, 135.38,
135.33, 134.93, 134.87, 134.82, 130.40, 129.56, 129.50, 128.23,
128.22, 128.00, 127.92, 121.86, 121.74, 114.80, 76.74, 76.70, 76.66,
57.30, 52.81, 31.10, 31.07, 31.00, 28.39, 23.27, 23.20, 20.73, 14.15,
10.17 ppm. IR: ν = 2966, 2876, 1458, 1213, 1009, 964, 763,
˜
738 cm–1. C50H60BrNO4·0.1CHCl3 (818.92·0.1CHCl3): calcd. C
72.43, H 7.28, N 1.69; found C 72.18, H 7.28, N 1.63.
5-Bromo-11-{[(ethyl)(4-methoxybenzyl)amino]methyl}-25,26,27,28-
tetrapropoxycalix[4]arene [(؎)-5c]: Calix[4]arene 5c was prepared
from 4c in a manner similar to that described for 5a by using ethyl
bromide (3 equiv.) instead of n-butyl bromide (95 % yield). 1H
NMR (400 MHz, CDCl3): δ = 7.19 (d, J = 8.6 Hz, 2 H), 6.87 (d,
J = 8.6 Hz, 2 H), 6.45–6.75 (m, 10 H), 4.43 (d, J = 13.4 Hz, 1 H),
4.42 (d, J = 13.3 Hz, 1 H), 4.385 (d, J = 13.5 Hz, 1 H), 4.380 (d, J
= 13.3 Hz, 1 H), 3.77–3.87 (m, 8 H), 3.80 (s, 3 H), 3.36 (s, 2 H),
3.33 (s, 2 H), 3.14 (d, J = 13.5 Hz, 1 H + 1 H), 3.08 (d, J = 13.4 Hz,
1 H), 3.07 (d, J = 13.5 Hz, 1 H), 2.35 (q, J = 7.0 Hz, 2 H), 1.85–
1.96 (m, 8 H), 0.99–1.07 (m, 9 H), 0.90–0.97 (m, 6 H) ppm. 13C
10.45, 10.41, 10.28, 10.24 ppm. IR: ν = 3386, 2961, 2932, 2874,
˜
1592, 1466, 1212, 1006, 763 cm–1. C49H67NO5 (750.06): calcd. C
78.46, H 9.00, N 1.87; found C 78.14, H 8.85, N 1.72.
5-{[(Benzyl)(ethyl)amino]methyl}-11-hydroxy-25,26,27,28-tetraprop-
oxycalix[4]arene [(؎)-1b]: Calix[4]arene 1b was prepared from 5b in
NMR (100 MHz, CDCl3): δ = 158.36, 156.81, 156.09, 155.73, a manner similar to that described for 1a (48% yield). 1H NMR
155.37, 137.10, 137.02, 135.67, 135.17, 134.63, 134.61, 134.55, (400 MHz, CDCl3): δ = 7.20–7.33 (m, 5 H), 6.74 (s, 1 H), 6.71 (s,
134.17, 132.80, 131.92, 130.60, 130.38, 129.95, 129.16, 128.66, 1 H), 6.62–6.64 (m, 2 H), 6.51–6.53 (m, 3 H), 6.44 (t, J = 7.4 Hz,
128.58, 128.13, 127.89, 127.82, 122.17, 122.01, 114.64, 113.48, 1 H), 5.91–5.94 (m, 2 H), 4.43 (d, J = 13.2 Hz, 1 H + 1 H), 4.37
76.77, 76.74, 76.69, 76.65, 56.81, 56.66, 55.23, 46.73, 30.96, 30.85,
(d, J = 13.2 Hz, 1 H + 1 H), 3.80–3.84 (m, 6 H), 3.74 (t, J = 7.3 Hz,
2 H), 3.28–3.42 (m, 4 H), 3.13 (d, J = 13.2 Hz, 1 H), 3.12 (d, J =
13.3 Hz, 1 H), 3.03 (d, J = 13.2 Hz, 1 H), 3.02 (d, J = 13.3 Hz, 1
H), 2.32–2.38 (m, 2 H), 1.87–1.95 (m, 8 H), 0.93–1.04 (m, 15 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 156.78, 156.26, 155.80,
150.17, 149.95, 139.89, 135.66, 135.59, 135.38, 135.11, 134.93,
134.78, 134.74, 132.12, 129.00, 128.82, 128.67, 128.23, 128.14,
127.94, 126.66, 121.79, 114.52, 114.47, 76.76, 76.68, 76.65, 57.07,
56.99, 47.08, 31.02, 30.95, 23.25, 23.21, 23.18, 23.16, 11.81, 10.44,
23.29, 23.18, 23.13, 11.94, 10.46, 10.40, 10.21, 10.17 ppm. IR: ν =
˜
2965, 2934, 2876, 1512, 1457, 1248, 1212, 1196, 1039, 1007, 966,
765 cm–1. C51H62BrNO5·0.1CHCl3 (848.95·0.1CHCl3): calcd. C
71.30, H 7.26, N 1.63; found C 71.22, H 7.27, N 1.62.
5-Bromo-11-({(ethyl)[4-(trifluoromethyl)benzyl]amino}methyl)-
25,26,27,28-tetrapropoxycalix[4]arene [(؎)-5d]: Calix[4]arene 5d
was prepared from 4d in a manner similar to that described for 5a
by using ethyl bromide (3 equiv.) instead of n-butyl bromide (80%
yield). 1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.0 Hz, 2 H),
7.39 (d, J = 7.9 Hz, 2 H), 6.51–6.70 (m, 9 H), 6.42 (t, J = 7.4 Hz,
1 H), 4.43 (d, J = 14.0 Hz, 1 H + 1 H), 4.39 (d, J = 13.6 Hz, 1 H),
4.38 (d, J = 13.6 Hz, 1 H), 3.76–3.87 (m, 8 H), 3.41 (s, 2 H), 3.30
(s, 2 H), 3.15 (d, J = 13.3 Hz, 1 H), 3.14 (d, J = 13.4 Hz, 1 H),
10.41, 10.25, 10.21 ppm. IR: ν = 3537, 2964, 2934, 2876, 1457,
˜
1214, 1008, 967, 766 cm–1. C50H61NO5 (756.02): calcd. C 79.43, H
8.13, N 1.85; found C 78.99, H 8.11, N 1.77.
5-{[(Ethyl)(4-methoxybenzyl)amino]methyl}-11-hydroxy-25,26,27,28-
tetrapropoxycalix[4]arene [(؎)-1c]: Calix[4]arene 1c was prepared
5962
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5957–5964

Novel, Inherently Chiral Calix[4]arenes as Organocatalysts
from 5c in a manner similar to that described for 1a (70% yield).
1H NMR (400 MHz, CDCl3): δ = 7.15 (d, J = 8.5 Hz, 2 H), 6.86
(d, J = 8.6 Hz, 2 H), 6.68 (d, J = 7.0 Hz, 2 H), 6.53–6.92 (m, 5 H),
6.42 (t, J = 7.4 Hz, 1 H), 5.98 (s, 2 H), 4.43 (d, J = 13.2 Hz, 1 H
+ 1 H), 4.37 (d, J = 13.1 Hz, 1 H + 1 H), 3.73–3.85 (m, 8 H), 3.78
(s, 3 H), 3.25–3.35 (m, 4 H), 3.13 (d, J = 13.2 Hz, 1 H), 3.12 (d, J
= 13.3 Hz, 1 H), 3.024 (d, J = 13.2 Hz, 1 H), 3.016 (d, J = 13.2 Hz,
1 H), 2.30–2.35 (m, 2 H), 1.86–1.97 (m, 8 H), 0.93–1.02 (m, 15 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.33, 156.70, 156.34,
155.70, 150.19, 150.06, 135.72, 135.25, 135.01, 134.93, 134.88,
134.77, 134.61, 132.11, 131.70, 130.06, 128.90, 128.63, 128.20,
128.09, 128.01, 127.98, 121.82, 121.78, 114.59, 113.50, 76.77, 76.75,
76.71, 76.64, 56.75, 56.39, 55.24, 46.86, 31.03, 30.97, 23.24, 23.22,
SUMICHIRAL OA-4800 column (2.0ϫ25 cm) with CHCl3 as the
eluent. The calix[4]arenes 1b–d (100 mg) were loaded onto the pre-
parative column, and enantiomerically pure calix[4]arene (+)294-1
(10.0–12.5 mg) and (–)294-1 (10.0–12.5 mg) were obtained.
Measurement of the Association Constants of Chiral Calix[4]arene
(+)295-1a with Mandelic Acid: Association constants (Ka) were de-
termined in CHCl3 solution with a UV/Vis spectrophotometer at
25 °C. A solution of (+)295-1a (3 mL, 5.07ϫ10–5  in CHCl3) was
placed in the sample cell, and pure CHCl3 (3 mL) was placed in
the reference cell. A calculated amount of (R)- or (S)-mandelic acid
(1.25ϫ10–2  stock solution in CHCl3) was then added to the sam-
ple and reference cells, and absorption spectra were recorded. Ad-
ditional amounts of mandelic acid solution were added to the two
cells, and spectra were recorded after each addition. The wave-
length selected for maximal intensity changes was 279 nm. From
the absorption intensities at this wavelength and the mandelic acid
concentration, the association constants (Ka) were calculated by
using the non-linear least-squares method of Marquardt.
23.17, 11.77, 10.41, 10.38, 10.28, 10.25 ppm. IR: ν = 3384, 2964,
˜
2935, 2877, 1512, 1459, 1248, 1214, 1040, 1008, 967, 765 cm–1
.
C51H63NO6·0.3CHCl3 (786.05·0.3CHCl3): calcd. C 75.00, H 7.73,
N 1.70; found C 74.90, H 7.79, N 1.74.
5-({(Ethyl)[4-(trifluoromethyl)benzyl]amino}methyl)-11-hydroxy-
25,26,27,28-tetrapropoxycalix[4]arene [(؎)-1d]: Calix[4]arene 1d
was prepared from 5d in a manner similar to that described for 1a
(70% yield). 1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.1 Hz,
2 H), 7.33 (d, J = 8.0 Hz, 2 H), 6.58–6.68 (m, 5 H), 6.46 (d, J =
7.5 Hz, 2 H), 6.28 (t, J = 7.5 Hz, 1 H), 6.10–6.14 (m, 2 H), 4.44 (d,
J = 13.1 Hz, 1 H), 4.43 (d, J = 13.2 Hz, 1 H), 4.38 (d, J = 13.1 Hz,
1 H), 4.37 (d, J = 13.1 Hz, 1 H), 3.88 (t, J = 7.6 Hz, 2 H), 3.75–
3.81 (m, 6 H), 3.30 (s, 2 H), 3.25 (s, 2 H), 3.13 (d, J = 13.2 Hz, 1
H), 3.12 (d, J = 13.3 Hz, 1 H), 3.02 (d, J = 13.2 Hz, 1 H), 3.01 (d,
J = 13.2 Hz, 1 H), 2.26 (q, J = 7.0 Hz, 2 H), 1.85–1.97 (m, 8 H),
0.93–1.05 (m, 15 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
156.65, 156.43, 155.52, 150.45, 150.12, 144.33, 136.15, 136.12,
135.33, 134.86, 134.60, 134.51, 134.29, 131.55, 129.04, 128.99,
128.67, 128.55, 128.37, 128.16, 127.98, 127.85, 125.76, 125.05,
125.01, 124.97, 123.06, 121.80, 121.72, 120.64, 114.74, 76.88, 76.84,
76.72, 76.62, 56.82, 56.75, 47.14, 31.06, 31.01, 30.95, 23.29, 23.25,
Catalytic Asymmetric Michael-Type Addition Reactions Catalysed
by (+)- or (–)-1: 2-Cyclohexen-1-one (1.50 mmol) was added to a
solution of (+)- or (–)-1 (0.0150 mmol) and thiophenol (1.75 mmol)
in toluene (3 mL) under argon at 20 °C, and the mixture was stirred
at this temperature for 12 h. The reaction was quenched with 1 
aq. HCl (3 mL), and organic materials were extracted with CHCl3
(3 mLϫ2). The organic extracts were washed with water (5 mL)
and dried with MgSO4. Evaporation of the solvent and purification
of the residue by preparative GPC afforded a Michael addition
product. The absolute configuration of the product was determined
by comparison of the observed optical rotation with the reported
value, and the ee was determined by a previously reported pro-
cedure.[15a]
3-(Phenylthio)cyclohexanone (6a):[15a] 1H NMR (400 MHz, CDCl3):
δ = 7.40–7.43 (m, 2 H), 7.25–7.33 (m, 3 H), 3.39–3.45 (m, 1 H),
2.65–2.70 (m, 1 H), 2.28–2.40 (m, 3 H), 2.10–2.16 (m, 2 H), 1.66–
1.78 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 208.71,
133.15, 132.96, 129.03, 127.74, 47.69, 46.04, 40.83, 31.15,
23.18, 23.09, 11.86, 10.38, 10.36, 10.29, 10.26 ppm. IR: ν = 2966,
˜
2936, 2877, 1460, 1326, 1215, 1164, 1125, 1067, 1006, 966,
765 cm–1. C51H60F3NO5·0.2CHCl3 (824.02·0.2CHCl3): calcd. C
72.54, H 7.13, N 1.65; found C 72.81, H 7.30, N 1.68.
23.97 ppm. IR: ν = 2946, 1715, 1222, 745, 694 cm–1. MS (EI): m/z
˜
= 206 [M]+, 110, 97.
Optical Resolution of Chiral Calix[4]arene 1a: A racemic mixture
of calix[4]arene 1a (4.0 mmol) and (R)-mandelic acid (8.0 mmol)
was dissolved in Et2O (100 mL), and hexane (15 mL) was then
gradually added to the solution. The solution was placed in a flask
at room temperature for 2–3 d, which led to a white crystalline
calix[4]arene 1a–(R)-mandelic acid complex. The resulting white
crystals were filtered and dried to yield chirally enriched calix[4]-
arene (+)295-1a–(R)-mandelic acid complex. {The chirally enriched
calix[4]arene (–)295-1a–(R)-mandelic acid complex was obtained
from the filtrate.} The white solid was dissolved in CHCl3 (50 mL),
and satd. aq. NaHCO3 (50 mL) was added to the solution. After
stirring at room temperature for 30 min, the organic layer was sepa-
rated and washed with water (50 mLϫ5). The organic solution was
dried with MgSO4, and the solvent was evaporated to give chirally
enriched calix[4]arene (+)295-1a (65–93% ee, 40–25% yield). Chi-
rally enriched calix[4]arene (+)295-1a was treated again with (R)-
mandelic acid in the same manner as described above. After repeat-
ing this procedure 2–3 times, enantiomerically pure calix[4]arene
(+)295-1a was obtained. The optical purity of the chiral calix[4]-
arene 1a was determined by chiral HPLC analysis [SUMICHIRAL
OA-4800 column (0.46ϫ25 cm) with hexane/iPrOH/MeOH/TFA =
90:5:5:0.3 as eluent].
3-(4-tert-Butylphenylthio)cyclohexanone
(6b):[15a]
1H
NMR
(400 MHz, CDCl3): δ = 7.27–7.37 (m, 4 H), 3.33–3.39 (m, 1 H),
2.64–2.69 (m, 1 H), 2.25–2.39 (m, 3 H), 2.09–2.19 (m, 2 H), 1.66–
1.77 (m, 2 H), 1.30 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 208.85, 151.13, 133.42, 129.26, 126.07, 47.83, 46.29, 40.84, 34.55,
31.22, 24.05 ppm. IR: ν = 2963, 1716, 734 cm–1. MS (EI): m/z =
˜
262 [M]+, 166, 97.
4,4-Dimethyl-3-(phenylthio)cyclohexanone (6c):[17] 1H NMR
(400 MHz, CDCl3): δ = 7.38–7.41 (m, 2 H), 7.21–7.30 (m, 3 H),
3.15–3.19 (m, 1 H), 2.41–2.64 (m, 3 H), 2.27–2.32 (m, 1 H), 1.86–
1.92 (m, 1 H), 1.60–1.67 (m, 1 H), 1.27 (s, 3 H), 1.21 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 208.93, 134.60, 132.66, 129.08,
127.39, 57.59, 45.38, 38.59, 37.84, 34.62, 29.02, 21.03 ppm. IR: ν =
˜
2959, 1707, 737, 688 cm–1. MS (EI): m/z = 234 [M]+, 125, 110.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of all new compounds as well as
the HPLC charts of 1a–d.
Acknowledgments
Optical Resolution of Chiral Calix[4]arenes 1b–d: Optical resolution
of (Ϯ)-1b–d was carried out by preparative HPLC using a
We thank Takako Okazaki and Eiji Asano for their assistance in
this study.
Eur. J. Org. Chem. 2008, 5957–5964
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5963

S. Shirakawa, A. Moriyama, S. Shimizu
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Received: September 4, 2008
Published Online: November 4, 2008
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