Synthesis and optical resolution of a series of inherently chiral calix[4]crowns with cone and partial cone conformations

Article abstract of DOI:10.1002/chem.200500272

A series of inherently chiral calix[4]arenes with cone and partial cone conformations and with crown ether moieties of variable size have been readily synthesized. By taking advantage of the carboxy appendage on the lower rim, these were condensed with th

Full text of DOI:10.1002/chem.200500272

FULL PAPER
DOI: 10.1002/chem.200500272
Synthesis and Optical Resolution of a Series of Inherently Chiral
Calix[4]crowns with Cone and Partial Cone Conformations
Jun Luo, Qi-Yu Zheng, Chuan-Feng Chen,* and Zhi-Tang Huang*[a]
Abstract: A series of inherently chiral
calix[4]arenes with cone and partial
cone conformations and with crown
ether moieties of variable size have
been readily synthesized. By taking ad-
vantage of the carboxy appendage on
the lower rim, these were condensed
with the chiral auxiliary (S)-BINOL to
form diastereomers which, in most
cases, could be separated by prepara-
tive TLC, or more desirably, by column
chromatography on silica gel (diaster-
eomeric excess >99% based on HPLC
analysis). Seven enantiopure antipodes
of inherently chiral calix[4]crowns were
obtained after hydrolysis. It has been
found that both the size of the crown
moiety and alkylation of the last phe-
nolic hydroxy group (accompanied
with or without a change in the confor-
mation) affect the separation of the di-
astereomers.
Keywords: calixarenes · chirality ·
crown compounds · optical resolu-
tion · synthesis
Introduction
this reason, until now, only one report each on the chiral dis-
crimination and asymmetric catalysis of inherently chiral
calix[4]arenes has been published.[2h,4a]
Inherently chiral calixarenes, whose chirality originates from
the unsymmetrical array of achiral functionalities on the
cavity-shaped calixarene skeletons (upper rim and/or lower
rim, as well as other positions), have enriched the variety of
chiral molecules and attracted increasing attention in recent
years owing to their potential use in chiral discrimination
and asymmetric catalysis.[1] Compared with chiral calix[4]ar-
enes with chiral functionalities attached directly to the calix-
arene skeleton, the synthesis of calix[4]arenes with inherent
chirality tends to be more challenging as there are always
regio- and stereoselective problems involved in their synthe-
sis. Moreover, optical resolution of the racemates usually re-
quires the use of HPLC methods (chiral columns for race-
mates[2] and nonchiral columns for diastereomers of inher-
ently chiral calix[4]arenes[2e,3]), which is inappropriate for
scale-up. In only two cases has optical resolution been real-
ized by conventional column chromatography on silica gel.[4]
Clearly, the difficult access to optically pure, inherently
chiral calix[4]arenes has impeded the research into their
chiral discrimination and asymmetric catalytic abilities. For
In a preliminary paper[5] we reported a convenient ap-
proach to enantiopure antipodes of AABH-type inherently
chiral calix[4]crown-4 molecules through the reaction of rac-
emic calix[4]crown derivatives
1
with (S)-BINOL, followed by the
separation of the diastereomers
formed by preparative TLC and
subsequent cleavage of the (S)-
BINOL auxiliary. Their successful
synthesis and resolution encouraged
us to investigate the generality of
these methods. In addition we may
have gained some insight into the
relationship between the structure
of these calix[4]crown-4 molecules
and their optical resolution. There are two ways to modify
the structure of compound 1: 1) by changing the size of the
crown ether moiety and 2) by alkylating or esterifying the
phenolic hydroxy group with or without changing the con-
formation. The carboxy group is retained for further con-
densation with the chiral auxiliary. Herein we report the
synthesis of a series of inherently chiral calix[4]crowns with
cone or partial cone conformations and their optical resolu-
tion by separation of the diastereomers derived from (S)-
BINOL by preparative TLC or column chromatography on
silica gel and the subsequent hydrolysis of the chiral auxili-
ary.
[a]Dr. J. Luo, Dr. Q.-Y. Zheng, Prof. C.-F. Chen, Prof. Z.-T. Huang
Center for Molecular Science, Institute of Chemistry
Chinese Academy of Sciences, Beijing 100080 (China)
Fax : (+86)10-625-64723
E-mail: cchen@iccas.ac.cn
huangzt@public.bta.net.cn
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5917

Results and Discussion
in the presence of N,N’-dicyclohexylcarbodiimide (DCC)
and 4-dimethylaminopyridine (DMAP) in CH2Cl2 at room
temperature to furnish 5a and 5b as pairs of diastereomers.
We successfully separated the diastereomeric mixture of
crown-5 5a (ca. 1:1 ratio) to yield 5a-1 and 5a-2 (diastereo-
meric excess, de>99% by HPLC analysis) by preparative
TLC. In fact, among other chiral auxiliaries such as l-men-
thol, l-cinchonidine, and several l-amino acid esters, (S)-
BINOL proved to be the most efficient. So it seems that the
close proximity of the rigid structure of the axial chiral
BINOL moiety to the inherently chiral calixarene backbone
can favor the separation of the diastereomers. The separa-
tion of the diastereomeric mixture of crown-6 5b, on the
other hand, failed. The diastereomers of compound 5b ap-
peared as two overlapping spots on TLC sheets even after
several rounds of development.
Changing the crown-4 moiety to crown-5, crown-6 or open
chain analogues: 1,2-Calix[4]crown-5 (2a) and 1,2-calix[4]-
crown-6 (2b) were synthesized according to literature proce-
dures.[6] As indicated in Scheme 1, reaction of 2a or 2b with
1.1 equivalents of ethyl bromoacetate in the presence of one
equivalent of Cs2CO3 in dry DMF at 60–708C furnished the
tri-O-alkylated compound 3a or 3b as racemates in good
yields. Their complicated NMR spectra suggested the ab-
sence of symmetry. Signals arising from the ArCH2Ar
carbon atoms appeared at around d=31 ppm, indicating
that they all adopted the cone conformation.[7] Similar to
the behavior observed by Pappalardo and co-workers,[2f] the
outcome of this reaction is determined by the ability of the
cone conformation of the phenolate intermediate to be sta-
bilized by strong hydrogen bonding rather than by metal
template effects. Thus, the tri-O-alkylated cone conformer
can be obtained regardless of the size of the 1,2-crown ether
moiety. Compounds 3a and 3b were efficiently resolved by
HPLC using Chiralpak AD column (n-hexane/2-propanol
9:1, 0.5 mLminÀ1, 258C). The retention times for the enan-
tiomers of the crown-5 derivative 3a are 7.8 and 31.9 min
(enantiomeric ratio 49:51), yet for the crown-6 derivative 3b
the retention times are 9.7 and 12.9 min (enantiomeric ratio
50:50).
The 1H NMR spectra of 5a-1 and 5a-2 are shown in
Figure 1 (tBu groups are not included). In general, the sig-
nals arising from the calix[4]arene skeleton and the (S)-
Although the enantiomers of 3a and 3b can be resolved
by HPLC, it is more attractive to convert them to diaster-
eomers and to separate these. Thus, compounds 3a and 3b
were directly hydrolyzed to furnish the carboxylic acid de-
rivatives 4a and 4b whose structures were confirmed by
their spectroscopic data. Compounds 4a and 4b, which pos-
sess a carboxylic group, were then treated with (S)-BINOL
1
Figure 1. Partial H NMR spectra of diastereomers 5a-1 and 5a-2.
Scheme 1.
5918
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928

Synthesis and Optical Resolution of Chiral Calix[4]crowns
FULL PAPER
BINOL moiety of 5a-1 resemble the corresponding signals
of 5a-2. This indicates that the introduction of the outer
chiral moiety distorts the skeletons of the calixarene enan-
tiomers similarly. Combined with the results reported previ-
ously, the fact that the diastereomers of calix[4]crown-4 and
-crown-5 could be separated by TLC while those of calix[4]-
crown-6 could not implies that increasing the size or the
flexibility of the crown ether moiety has a detrimental effect
on the separation of the diastereomers. To confirm this, an
open-chain calix[4]arene analog 4g was also synthesized
(Scheme 2). The diastereomers derived from this compound
produced only one spot on TLC analysis.
Figure 2. CD spectra (CH2Cl2, 258C) of the enantiomers 4a-1 (solid line)
and 4a-2 (dotted line).
action of 4c–4 f with (S)-BINOL is slower than those of 4a
and 4b. This may be a result of steric hindrance at the lower
rim caused by the introduction of the alkyl group. Accord-
ing to previous reports,[2f,g,8] the alkylation of the last hy-
droxy group of racemates of inherently chiral calix[4]crown
ethers is detrimental to their resolution by HPLC. However,
we found that the diastereomeric crown-5 derivatives 5c
and 5d, and even the crown-6 derivatives 5e and 5 f could,
with sufficient care, be separated by column chromatogra-
phy on silica gel (de>99% by HPLC analysis).
Scheme 2.
The isolated diastereomers 5a-1 and 5a-2 were hydro-
lyzed under alkaline conditions to give optically pure 4a-1
and 4a-2, respectively. Their CD spectra (Figure 2) are
mirror images. The [a]2D5 values of the enantiomers 4a-1 and
4a-2 are À16 and +16 (c=0.5 in chloroform), respectively,
which shows their enantiomeric nature and high ee values.
By comparing the 1H NMR spectra of 5c-1 and 5c-2
(Figure 3), we can see that there are more discernible differ-
ences than between 5a-1 and 5a-2. The proton signals aris-
ing from the binaphthyl moiety appear in the region of d=
8.00–7.00 ppm and have slightly different chemical shifts and
splitting patterns. The signals below d=7.00 ppm are attrib-
uted to the calixarene moiety. The signals arising from the
aromatic rings of 5c-1 exhibit a single peak at d=6.91 ppm,
a pair of doublets at approximately d=6.90 ppm (partly
buried in the former), and a singlet at d=6.59 ppm. Yet for
5c-2, there is a single peak at d=6.81 ppm and three pairs
Alkylation of the remaining phenolic OH; retention of the
cone conformation: Besides changing the size of the crown
ether moiety, we also alkylated the last phenolic hydroxy
group of compounds 3a and 3b. The reactions of 3a and 3b
with alkylating agents nPrI and BnBr (2.0 equiv) in the pres-
ence of NaH (5.0 equiv) in dry
DMF and subsequent hydroly-
sis with water provided the
tetra-O-alkylated derivatives
4c–4 f in 66–88% yields
(Scheme 3).
In general, the clear splitting
pattern of four pairs of dou-
blets due to the methylene
protons of the ArCH2Ar moi-
eties in the 1H NMR spectra of
compounds 4c–4 f and the cor-
responding carbon resonances
at around d=31 ppm in their
13C NMR spectra corroborate
their molecular asymmetry and
cone conformations. They
were then treated with (S)-
BINOL. We found that the re-
Scheme 3.
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5919

C.-F. Chen, Z.-T. Huang et al.
spectra of the diastereomers of 5d–5 f also show significant
differences (refer to the corresponding spectroscopic data)
in most regions. As a result of the significant differences in
1
the H NMR spectra of each pair of tetra-O-alkylated dia-
stereomers and improvements in their separation compared
with the tri-O-alkylated diastereomers, we speculate that al-
kylation of the last hydroxy group increases the steric hin-
drance at the lower rim, so that under the influence of the
bulky outer chiral moiety (S)-BINOL, the calix skeletons of
the tetra-O-alkylated diastereomers may suffer distortion to
quite different degrees. It is reasonable to suggest that the
differences in the structures of these diastereomers facilitate
their separation.
1
Figure 3. Partial H NMR spectra of diastereomers 5c-1 and 5c-2.
After hydrolysis of 5c–5 f, four pairs of enantiomers were
obtained. Their CD spectra all show symmetrical images
(Figure 4) and their specific rotations have the same magni-
tudes with opposite signs.
of doublets at approximately d=6.76, 6.69, and 65 ppm
(partly overlapping). The hydroxy signal of 5c-1 appears at
d=6.36 ppm, whilst that of 5c-2 is at d=5.95 ppm. For the
signals of the OCH2CO2 methylene protons, 5c-1 exhibits a
pair of doublets at d=4.85 and 4.63 ppm, whereas 5c-2 ex-
hibits a pseudosinglet at d=4.58 ppm, which indicates that
the OCH2CO2 group of the latter can rotate more freely
than the former. The protons of the ArCH2Ar moieties ex-
hibit four pairs of doublets for both diastereomers, with
those of 5c-1 at d=4.55, 4.42, 4.40, 4.34, 3.11, 3.09, 3.06, and
3.05 ppm and those of 5c-2 at d=4.40, 4.36, 4.33, 4.11, 3.09,
3.07, 2.95, and 2.93 ppm. It is interesting that the chemical
shifts of the bridging methylene protons of 5c-2 are at lower
Alkylation of the free phenolic OH; changing to partial
cone conformations: The successful separation of the tetra-
O-alkylated diastereomeric cone conformers 5c–5 f prompt-
ed us to investigate the possibility of synthesizing and opti-
cally resolving partial cone conformers. So far tetra-O-alky-
lated inherently chiral calix[4]arenes with partial cone con-
formations have been synthesized by reacting 1,2-di-O-sub-
stituted calix[4]arenes with suitable alkylating agents using
Cs2CO3 as the base.[2d,f,4b,9] It has been proven that the first
alkylation reaction occurs on the same side as the di-O-sub-
1
fields than the corresponding shifts of 5c-1. The H NMR
Figure 4. CD spectra (CH2Cl2, 258C) of the enantiomers of 4c–4 f (the solid lines and the dotted lines denote 4–1 and 4–2, respectively).
5920
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928

Synthesis and Optical Resolution of Chiral Calix[4]crowns
FULL PAPER
stituted moieties to yield a tri-
O-alkylated cone conformer
intermediate. However, under
the template effect of the Cs+
cation, the second alkylation
reaction has to occur on the
opposite side to avoid steric
hindrance, giving tetra-O-alky-
lated products with partial
cone conformations. We treat-
ed compounds 3a and 3b with
nPrI (10 equiv) in DMF in the
presence of Cs2CO3 (10 equiv)
at 708C for two days. As ex-
pected, compounds 3d and 3e
with partial cone conforma-
tions were obtained in moder-
ate yields (Scheme 4). The
NMR spectra of 3d and 3e re-
semble each other. The reso-
nances arising from the bridg-
ing methylene carbon atoms
are observed at d=37.92,
Scheme 4.
37.62, 31.63, and 31.05 ppm for
3d and at d=38.11, 37.81,
31.32, and 30.74 ppm for 3e,
respectively. Because only the unsubstituted aromatic ring
of 3a and 3b can rotate as the other three are immobilized
by the substituents, we can deduce that 3d and 3e adopt
partial cone conformations. Indeed, because of the diamag-
netic shielding effect, the methyl and methylene protons of
the inverted O-propyl groups in 3d and 3e appear at a
higher field than those of 4c and 4e cone conformers bear-
ing a propyl group. Hydrolysis of 3d and 3e afforded the
carboxylic acid derivatives 4h and 4i, respectively. Com-
pared with those of 3d and 3e, all the signals arising from
the methyl and methylene protons in the inverted O-propyl
group of 4h and 4i are positioned at remarkably high fields.
This phenomenon indicates that the inverted propyl group is
deeply buried in the hydrophobic cavity generated by the
three remaining phenol units in a sort of “self-inclusion”
complex. It is still not clear why this simple hydrolysis reac-
tion can cause such significant conformational adjustment.
Compounds 4h and 4i were then treated with (S)-BINOL
to furnish 5h and 5i, respectively, each as a pair of diaster-
eomers. Similarly, both the tetra-O-alkylated diastereomeric
crown-5 and crown-6 partial cone conformers 5h and 5I, re-
spectively, can readily be separated by preparative TLC
(CHCl3:AcOEt=4:1, de>99%). After hydrolysis, two pairs
of enantiomers were obtained. Their CD spectra show sym-
metrical images (Figure 5) and their specific rotations have
the same magnitudes with opposite signs.
With a method for the synthesis of calix[4]arenes with
partial cone conformations in hand, we synthesized a confor-
mational isomer of 4h that also adopts a partial cone confor-
mation, the only difference being that it has a different in-
verted aromatic ring (Scheme 5). 1,2-Calix[4]crown-5 2a was
Figure 5. CD spectra (CH2Cl2, 258C) of the enantiomers of 4h and 4i
(the solid lines and the dotted lines denote 4–1 and 4–2, respectively).
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5921

C.-F. Chen, Z.-T. Huang et al.
hydroxy group with or without changing the conformation
has a beneficial effect upon the separation of the diaster-
eomers; 3) for our resolution method, it is necessary for the
carboxylic group to be on the same side of the calixarene as
the crown moiety at the lower rim. Enantiomers 4 possess
crown moieties and carboxylic groups that may serve as rec-
ognition sites. We believe the reactions described in this
work provide a convenient access to optically pure inherent-
ly chiral calix[4]crowns on a large scale and will facilitate
the research into their chiral discrimination and asymmetric
catalytic abilities which is now under investigation in our
laboratory.
Experimental Section
General remarks: Melting points were determined on an electrothermal
melting point apparatus and are uncorrected. 1H and 13C NMR spectra
were obtained at 300.13 and 75 MHz on a Bruker DMX300 NMR spec-
trometer (CDCl3 and TMS as internal standard), respectively. MALDI-
TOF MS were recorded with a Bruker BIFLEXIII spectrometer with
CCA (2-cyano-4’-hydroxycinnamic acid) as the matrix. CD spectra were
recorded with a JASCO J-810 spectrometer. NaH (80% in oil, Merck)
was washed twice with petroleum ether (30–608C) and stored in a desic-
cator. All other chemicals were reagent grade and were used without fur-
ther purification. Self-made preparative TLC plates were prepared using
silica gel HF254 (10–40 mm) and carboxymethylcellulose (CMC) as adhe-
sive. Column chromatography was performed on silica gel (200–
300 mesh). Petroleum ether used for column chromatography refers to of
the 60–908C fraction.
Scheme 5.
treated with nPrI under the same reaction conditions as
used for the alkylation of compounds 3a and 3b to yield in-
herently chiral racemate 6 with a cone conformation. Com-
pound 6 was then subjected to the same reaction conditions
as used to esterify 2a to yield 7 with a partial cone confor-
mation, which was confirmed by its spectroscopic data.
Compound 7, with the inverted aromatic ring bearing the
ethoxycarbonylmethyl group, was then hydrolyzed to give
carboxylic acid derivative 8. Compound 8 was then treated
with (S)-BINOL to yield a diastereomeric mixture. Howev-
er, TLC analysis of compound 8 showed only one spot with
various developing solvents and attempts to separate it
failed. So it seems that in our system, it is essential that the
carboxylic group is syn to the crown moiety if the diastereo-
meric mixture is to be separated by conventional chroma-
tography methods.
5,11,17,23-Tetra-tert-butyl-25,26-bis[(ethoxyethyl)oxy]-27,28-dihydroxyca-
lix[4]arene (2c): NaH (0.924 g, 5.0 equiv) was added to a suspension of
p-tert-butylcalix[4]arene (5 g, 7.7 mmol) in DMF (500 mL) and the reac-
tion mixture was stirred at room temperature for 1 h. Then bromoethyl
ethyl ether (2.83 g, 2.2 equiv) was added and the mixture was stirred at
608C for 24 h. Methanol (40 mL) was added dropwise to remove excess
NaH. After removal of the solvent under reduced pressure, the residue
was partitioned between 10% HCl (300 mL) and CH2Cl2 (2”300 mL).
The organic layer was dried over Na2SO4 and evaporated. The residue
was purified by column chromatography (SiO2, petroleum ether/AcOEt
9:1) to give 2c as a white solid. Yield 56%; m.p. 205–2078C (CH2Cl2/
1
CH3OH); H NMR: d=8.53 (s, 2H; OH), 6.97–6.87 (m, 8H), 4.57 (d, J=
12.6 Hz, 1H; ArCH2Ar), 4.39 (d, J=13.2 Hz, 2H; ArCH2Ar), 4.28 (d, J=
14.3 Hz, 1H; ArCH2Ar), 4.11–3.61 (m, 12H; CH2CH2OCH2CH3), 3.28
(d, J=12.7 Hz, 4H; ArCH2Ar), 1.29 (t, J=6.9 Hz, 6H; OCH2CH3), 1.18
(s, 18H), 1.06 ppm (s, 18H); 13C NMR: d=151.81, 148.91, 146.01, 141.91,
133.79, 133.65, 128.48, 127.69, 125.78, 125.73, 125.08, 125.05, 74.36, 69.68,
66.70, 33.96, 33.82, 32.44, 31.73, 31.13, 31.55, 31.29, 15.23 ppm; IR (KBr):
n˜ =3366, 1484, 1200, 1122 cmÀ1; MALDI-TOF MS: m/z: 792.2 [M]+,
815.2 [M+Na]+, 831.2 [M+K]+; elemental analysis calcd (%) for
C52H72O6: C, 78.75; H, 9.15; found: C, 78.67; H, 9.20.
Conclusions
In conclusion, we have demonstrated a facile way to synthe-
size a series of tri- and tetra-O-alkylated inherently chiral
calix[4]crowns with cone and partial cone conformations. By
taking advantage of the carboxylic group appended on the
lower rim of 4, diastereomers 5a–5i were formed by con-
densation with chiral auxiliary (S)-BINOL. Chemical resolu-
tion was effected by preparative TLC for compounds 5a,
5h, and 5i, and by conventional column chromatography on
silica gel for 5c–5 f. After hydrolysis, the (S)-BINOL unit
was removed and seven pairs of optically pure enantiomers
of 4 were obtained. Structural modification has a profound
effect upon the separation of the diastereomers. It seems
that 1) increasing the size or the flexibility of the crown
ether moiety has a detrimental effect upon the separation of
diastereomers; 2) in contrast, alkylation of the last phenolic
Reaction of 2a–2c with ethyl bromoacetate: General procedure for the
preparation of cone conformers 3a–3c: A stirred mixture of 2a–2c
(3.7 mmol), ethyl bromoacetate (0.68 g, 1.1 equiv), and Cs2CO3 (1.21 g,
1.0 equiv) in DMF (250 mL) was heated at 608C for 6 h. Then 10% HCl
(4 mL) was added to quench the reaction. After removal of the solvent
under reduced pressure, the residue was partitioned between water and
CH2Cl2. The organic layer was dried with Na2SO4 and the solvent evapo-
rated. The residue was purified by column chromatography to give 3a–3c
as white solids.
3-{[(Ethoxycarbonyl)methyl]oxy}-p-tert-butylcalix[4]arene-(1,2)-crown-5,
cone conformer (3a): Column chromatography (SiO2, petroleum ether/
AcOEt 4:1). Yield 77%; m.p. 154–1558C (CH2Cl2/CH3OH); 1H NMR:
d=7.11 (s, 2H), 7.06 and 7.02 (2d, J=2.1 Hz, 1H each), 6.66 (s, 2H),
6.45 (s, 1H), 6.44 (s, 1H), 4.56 (d, J=15.7 Hz, 1H; CH2CO2), 4.52–3.66
5922
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928

Synthesis and Optical Resolution of Chiral Calix[4]crowns
FULL PAPER
(m, 21H), 3.26 (d, J=14.1 Hz, 1H; ArCH2Ar), 3.23 (d, J=11.3 Hz, 1H;
ArCH2Ar), 3.21(d, J=13.5 Hz, 1H; ArCH2Ar), 3.19 (d, J=11.8 Hz, 1H;
ArCH2Ar), 1.33 (t, J=7.2 Hz, 3H; CH2CH3), 1.32 (s, 18H), 0.93 (s, 9H),
0.77 ppm (s, 9H); 13C NMR: d=169.8, 153.6, 152.5, 150.7, 146.1, 145.8,
145.2, 141.0, 135.9, 135.4, 132.9, 132.0, 132.01, 131.7, 129.3, 128.1, 125.8,
125.6, 125.4, 125.2, 125.1, 125.0, 124.8, 124.74, 76.22, 72.42, 72.28, 72.06,
70.99, 70.37, 69.88, 69.61, 68.41, 60.88, 34.15, 33.84, 33.61, 31.79, 31.68,
31.07, 31.34, 30.98, 30.80, 14.3 ppm; IR (KBr): n˜ =3480, 1755, 1482, 1202,
1123 cmÀ1; MALDI-TOF MS: m/z: 915.8 [M+Na]+, 931.8 [M+K]+; ele-
mental analysis calcd (%) for C56H76O9: C, 75.30; H, 8.58; found: C,
75.32; H, 8.58.
146.03, 142.51, 134.24, 134.01, 133.95, 133.40, 132.21, 132.14, 129.04,
128.20, 126.08, 125.80, 125.78, 125.68, 125.65, 125.45, 125.41, 125.07, 75.82,
74.37, 72.15, 71.28, 70.91, 70.69, 70.22, 70.15, 69.74, 34.02, 34.01, 33.89,
33.86, 31.54, 31.35, 31.20, 31.16, 32.24, 32.08, 31.27, 30.48 ppm; IR (KBr):
n˜ =3446, 1760, 1482, 1248, 1201, 1123 cmÀ1; MALDI-TOF MS: m/z: 887.2
[M+Na]+, 903.2 [M+K]+; elemental analysis calcd (%) for C54H72O9: C
74.97, H 8.39; found: C 74.99, H 8.32.
3-[(Carboxymethyl)oxy]-p-tert-butylcalix[4]arene-(1,2)-crown-6,
cone
conformer (4b): Yield 83%; m.p. 125–1278C (CH2Cl2/CH3OH); 1H
NMR: d=7.75 (s, 1H; OH), 7.02–6.85 (m, 8H), 4.91 and 4.45 (2d, J=
16.0 Hz, 1H each; CH2CO2), 4.50 (d, J=14.1 Hz, 1H; ArCH2Ar), 4.34
(d, J=12.6 Hz, 1H; ArCH2Ar), 4.26 (d, J=13.5 Hz, 1H; ArCH2Ar), 4.24
(d, J=12.9 Hz, 1H; ArCH2Ar), 4.53–3.67 (m, 20H), 3.34 (d, J=13.9 Hz,
1H; ArCH2Ar), 3.29 (d, J=12.6 Hz, 1H; ArCH2Ar), 3.27 (d, J=12.9 Hz,
2H; ArCH2Ar), 1.17, 1.15, 1.10, and 1.05 ppm (4s, 9H each); 13C NMR:
d=171.32, 152.05, 151.71, 151.09, 148.75, 146.81, 146.63, 145.84, 142.41,
134.16, 133.82, 133.54, 132.99, 132.70, 128.74, 128.00, 126.26, 125.85,
125.66, 125.64, 125.60, 125.55, 125.41, 125.32, 125.00, 75.40, 74.26, 72.06,
71.22, 70.70, 70.57, 70.40, 70.32, 70.26, 69.77, 34.04, 33.97, 33.90, 33.78,
32.30, 32.25, 30.97, 31.43, 31.29, 31.24 ppm; IR (KBr): n˜ =3422, 1748,
1482, 1201, 1124 cmÀ1; MALDI-TOF MS: m/z: 931.2 [M+Na]+, 947.5
[M+K]+; elemental analysis calcd (%) for C56H76O10: C 73.98, H 8.43;
found: C 73.53, H 8.30.
3-{[(Ethoxycarbonyl)methyl]oxy}-p-tert-butylcalix[4]arene-(1,2)-crown-6,
cone conformer (3b): Column chromatography (SiO2, petroleum ether/
acetone 8:1). Yield 82%; m.p. 152–1548C (CH2Cl2/CH3OH); 1H NMR:
d=7.11 (s, 2H), 7.05 and 7.02 (2d, J=2.1 Hz, 1H each), 6.62 (s, 2H),
6.48 (s, 2H), 5.82 (s, 1H; OH), 4.53 (s, 2H; CH2CO2), 4.48 (d, J=
11.7 Hz, 1H; ArCH2Ar), 4.42 (d, J=13.2 Hz, 1H; ArCH2Ar), 4.29–3.61
(m, 24H), 3.28 (d, J=12.5 Hz, 1H; ArCH2Ar), 3.24 (d, J=11.6 Hz, 1H;
ArCH2Ar), 3.20 (d, J=12.1 Hz, 1H; ArCH2Ar), 3.17 (d, J=12.7 Hz, 1H;
ArCH2Ar), 1.32 (t, J=7.3 Hz, 3H; CH2CH3), 1.31 (s, 18H), 0.88 (s, 9H),
0.78 ppm (s, 9H); 13C NMR: d=169.64, 153.61, 152.18, 150.81, 150.53,
145.86, 145.74, 145.38, 141.32, 135.86, 135.56, 132.88, 131.88, 131.81,
131.76, 129.33, 128.34, 125.67, 125.61, 125.23, 125.17, 125.08, 124.94,
124.84, 124.79, 74.92, 72.31, 71.85, 71.14, 70.76, 70.62, 69.69, 69.58, 60.92,
34.12, 33.82, 33.75, 33.62, 31.74, 31.65, 31.04, 31.00, 31.52, 31.33, 30.87,
14.24 ppm; IR (KBr): n˜ =3467, 1737, 1482, 1202, 1124 cmÀ1; MALDI-
TOF MS: m/z: 958.8 [M+Na]+, 975.8 [M+K]+; elemental analysis calcd
(%) for C58H80O10: C, 74.33; H, 8.60; found: C, 74.31; H, 8.63.
5,11,17,23-Tetra-tert-butyl-25,26-bis[(ethoxyethyl)oxy]-27-[(carboxyme-
thyl)oxy]-28-hydroxycalix[4]arene, cone conformer (4g): Yield 62%;
m.p. 162–1648C (CH2Cl2/CH3OH); 1H NMR: d=11.9 (s, 1H; COOH),
7.75 (s, 1H; OH), 7.09 and 7.02 (2d, J=2.0 Hz, 1H each), 7.03 and 7.00
(2d, J=2.2 Hz, 1H each), 6.86 and 6.80 (2d, J=2.0 Hz, 1H each), 6.75
and 6.74 (2s, 1H each), 4.76 and 4.61 (2d, J=15.7 Hz, 1H each,
CH2CO2), 4.49 (d, J=12.7 Hz, 1H; ArCH2Ar), 4.41 (d, J=12.5 Hz, 1H;
ArCH2Ar), 4.38 (d, J=13.4 Hz, 1H; ArCH2Ar), 4.31 (d, J=12.9 Hz, 1H;
ArCH2Ar), 4.68–3.54 (m, 12H; CH2CH2OCH2CH3), 3.29 (d, J=13.5 Hz,
1H; ArCH2Ar), 3.27 (d, J=12.3 Hz, 2H; ArCH2Ar), 3.23 (d, J=12.6 Hz,
1H; ArCH2Ar), 1.29 (t, J=6.9 Hz, 6H; CH2CH3), 1.23, 1.21, 1.11, and
0.96 ppm (4s, 9H each); 13C NMR: d=170.88, 151.76, 151.49, 151.09,
148.60, 146.96, 146.82, 145.93, 141.95, 134.48, 134.32, 134.24, 133.83,
133.28, 133.11, 128.39, 127.81, 126.31, 126.06, 125.64, 125.62, 125.41,
125.39, 125.16, 124.84, 75.16, 74.79, 71.47, 69.26, 68.88, 66.73, 66.58, 34.10,
33.86, 33.70, 32.14, 31.92, 31.28, 30.67, 31.44, 31.40, 31.37, 31.13, 15.19,
5,11,17,23-Tetra-tert-butyl-25,26-bis[(ethoxyethyl)oxy]-27-{[(ethoxycarbo-
nyl)methyl]oxy}-28-hydroxycalix[4]arene, cone conformer (3c): Column
chromatography (SiO2, petroleum ether/AcOEt 9:1). Yield 62%; m.p.
117–1208C; 1H NMR: d=7.07 (s, 2H), 7.02 (d, J=2.3 Hz, 1H), 7.00 (d,
J=2.3 Hz, 1H), 6.64 (s, 1H), 6.63 (s, 1H), 6.52 (s, 2H), 5.98 (s, 1H; OH),
4.63 and 4.53 (2d, J=15.8 Hz, 1H each, CH2CO2), 4.56 (d, J=12.8 Hz,
1H; ArCH2Ar), 4.44 (d, J=12.9 Hz, 2H; ArCH2Ar), 4.34 (d, J=13.3 Hz,
1H; ArCH2Ar), 4.30–3.79 (m, 10H), 3.62 (q, J=7.2 Hz, 2H; CH2CH3),
3.59 (q, J=7.2 Hz, 2H; CH2CH3), 3.24 (d, J=13.5 Hz, 1H; ArCH2Ar),
3.23 (d, J=11.4 Hz, 1H; ArCH2Ar), 3.20 (d, J=12.8 Hz, 1H; ArCH2Ar),
3.17 (d, J=12.6 Hz, 1H; ArCH2Ar), 1.33 (t, J=7.1 Hz, 3H;
CO2CH2CH3), 1.24 (t, J=7.2 Hz, 3H; OCH2CH3), 1.23 (t, J=7.2 Hz, 3H;
OCH2CH3), 1.29, 1.28, 0.90 and 0.82 ppm (4s, 9H each); 13C NMR: d=
169.89, 153.51, 152.38, 151.02, 150.49, 145.73, 145.60, 145.38, 141.16,
135.63, 135.38, 132.87, 132.12, 132.06, 132.01, 129.10, 128.43, 125.64,
125.58, 125.18, 125.12, 125.03, 124.95, 124.93, 124.81, 74.72, 72.31, 71.95,
69.34, 69.26, 66.60, 66.33, 60.94, 34.10, 33.82, 33.78, 33.67, 31.74, 31.65,
31.10, 31.07, 31.39, 30.99, 15.50, 15.30, 14.24 ppm; IR (KBr): n˜ =3538,
1759, 1481, 1203 cmÀ1; MALDI-TOF MS: m/z: 901.1 [M+Na]+; elemen-
tal analysis calcd (%) for C56H78O8: C, 76.50; H, 8.94; found: C, 76.28; H,
8.94.
15.07 ppm; IR (KBr): n˜ =3309, 1766, 1482, 1246, 1200, 1123 cmÀ1
;
MALDI-TOF MS: m/z: 873.5 [M+Na]+, 889.5 [M+K]+; elemental anal-
ysis calcd (%) for C54H74O8: C 76.20, H 8.76; found: C 76.10, H 8.75.
Alkylation of the last phenolic OH group: general procedure for the
preparation of cone conformers 4c–4 f: Compound 3a or 3b (1.5 mmol)
and NaH (0.18 g, 5.0 equiv) in DMF (100 mL) were stirred at room tem-
perature for 1 h. Then alkylating agent was added and the temperature
was kept at 708C overnight. Water (15 mL) was added and the mixture
was stirred for another 3 h. After removal of the solvent under reduced
pressure, 10% HCl (50 mL) was added. The aqueous solution was ex-
tracted with CH2Cl2 (2”50 mL). The organic layer was dried with
Na2SO4 and the solvent evaporated. The residue was purified by column
chromatography (SiO2, petroleum ether/AcOEt 1:1) to give 4c–4 f as
white solids.
Hydrolysis of compounds 3a–3c: General procedure for the preparation
of 4a, 4b, and 4g: Compounds 3a–3c (1.8 mmol) in THF (100 mL) were
refluxed with aqueous 10% tetramethylammonium hydroxide solution
(8.18 mL, 5 equiv) for 12 h. After removal of the solvent, 10% HCl
(40 mL) was added. The aqueous solution was extracted with CH2Cl2 (2”
40 mL). The organic layer was dried with Na2SO4 and the solvent evapo-
rated. The residue was crystallized from CH2Cl2/CH3OH to give the
products 4a, 4b, and 4g as white solids.
3-[(Carboxymethyl)oxy]-4-propoxy-p-tert-butylcalix[4]arene-(1,2)-crown-
5, cone conformer (4c): Yield 88%; m.p. 186–1888C (CH2Cl2/CH3OH);
1H NMR: d=11.28 (s, 1H; COOH), 7.18 (s, 2H), 7.15 (s, 2H), 6.62 (s,
2H), 6.53 (s, 2H), 4.89 and 4.55 (2d, J=15.7 Hz, 1H each, CH2CO2), 4.61
(d, J=12.5 Hz, 1H; ArCH2Ar), 4.39 (d, J=12.6 Hz, 1H; ArCH2Ar), 4.26
(d, J=13.0 Hz, 1H; ArCH2Ar), 4.20 (d, J=13.8 Hz, 1H; ArCH2Ar),
4.47–3.73 (m, 18H), 3.27 (d, J=12.9 Hz, 1H; ArCH2Ar), 3.26 (d, J=
13.5 Hz, 1H; ArCH2Ar), 3.21 (d, J=12.5 Hz, 1H; ArCH2Ar), 3.17 (d, J=
12.0 Hz, 1H; ArCH2Ar), 1.63–1.59 (m, 2H; CH2CH2CH3), 1.37 and 0.85
(2s, 18H each), 1.00 ppm (t, J=7.4 Hz, 3H; CH2CH2CH3); 13C NMR: d=
170.83, 154.07, 152.01, 150.84, 150.82, 147.11, 145.33, 145.15, 145.00,
135.69, 135.00, 134.91, 134.87, 132.98, 132.55, 131.59, 131.35, 126.06,
125.87, 125.48, 125.34, 125.23, 125.19, 124.76, 124.57, 78.44, 75.41, 73.55,
71.49, 71.04, 70.67, 70.53, 70.45, 69.11, 34.21, 34.08, 33.66, 31.73, 31.60,
31.03, 31.19, 31.12, 30.89, 30.47, 23.02, 10.25 ppm; IR (KBr): n˜ =3235,
3-[(Carboxymethyl)oxy]-p-tert-butylcalix[4]arene-(1,2)-crown-5,
cone
conformer (4a): Yield 80%; m.p. 128–1308C (CH2Cl2/CH3OH); 1H
NMR: d=7.03 and 6.97 (2d, J=2.4 Hz, 1H each, ArH), 6.95 (s, 3H;
ArH), 6.85 (d, J=2.3 Hz, 1H; ArH), 6.82 and 6.77 (2d, J=2.4 Hz, 1H
each, ArH), 4.84 and 4.37 (2d, J=16.0 Hz, 1H each, CH2CO2), 4.44 (d,
J=12.5 Hz, 1H; ArCH2Ar), 4.30 (d, J=12.4 Hz, 1H; ArCH2Ar), 4.26 (d,
J=13.5 Hz, 1H; ArCH2Ar), 4.21 (d, J=12.9 Hz, 1H; ArCH2Ar), 4.33–
3.66 (m, 16H), 3.36 (d, J=13.6 Hz, 1H; ArCH2Ar), 3.28 (d, J=12.6 Hz,
1H; ArCH2Ar), 3.27 (d, J=13.3 Hz, 1H; ArCH2Ar), 3.26 (d, J=12.5 Hz,
1H; ArCH2Ar), 1.23, 1.13, 1.08, and 1.01 ppm (4s, 9H each, C(CH3)3);
13C NMR: d=171.13, 152.38, 151.35, 150.33, 149.26, 147.07, 146.53,
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5923

C.-F. Chen, Z.-T. Huang et al.
1762, 1481, 1200 cmÀ1; MALDI-TOF MS: m/z: 929.9 [M+Na]+; elemen-
tal analysis calcd (%) for C57H78O9: C 75.46, H 8.67; found: C 75.56, H
8.65.
3-{[(Ethoxycarbonyl)methyl]oxy}-4-propoxy-p-tert-butylcalix[4]arene-
(1,2)-crown-5, partial cone conformer (3d): Column chromatography
(SiO2, petroleum ether/AcOEt 6:1). Yield 42%; m.p. 251–2538C
(CH2Cl2/CH3OH); 1H NMR: d=7.36 and 7.23 (2d, J=2.4 Hz, 1H each),
7.05 (s, 2H), 6.87 and 6.86 (2d, J=2.7 Hz, 1H each), 6.64 and 6.62 (2d,
J=2.4 Hz, 1H each), 4.50 and 4.36 (2d, J=15.2 Hz, 1H each, CH2CO2),
4.33 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.29 (d, J=12.3 Hz, 1H; ArCH2Ar),
4.25–3.51 (m, 22H), 3.19 (t, J=7.8 Hz, 2H; CH2CH2CH3), 3.11 (d, J=
13.0 Hz, 1H; ArCH2Ar), 3.05 (d, J=12.8 Hz, 1H; ArCH2Ar), 1.63–1.50
(m, 2H), 1.43 and 1.31 (2 s, 9H each), 1.29 (t, J=7.2 Hz, 3H;
CO2CH2CH3), 1.05 (s, 18H), 0.70 ppm (t, J=7.2 Hz, 3H; CH2CH2CH3);
13C NMR: d=169.74, 155.06, 153.81, 153.58, 153.49, 144.88, 144.33,
143.91, 143.21, 135.74, 134.91, 132.94, 132.69, 132.64, 132.04, 132.02,
132.00, 127.91, 127.63, 126.14, 126.04, 125.75, 125.56, 125.51, 125.44, 74.02,
73.00, 71.59, 71.36, 71.27, 70.83, 70.78, 70.58, 70.24, 69.34, 60.78, 37.92,
37.62, 31.63, 31.05, 34.04, 34.03, 33.75, 31.78, 31.68, 31.43, 31.37, 23.82,
14.20, 10.31 ppm; IR (KBr): n˜ =1760, 1479, 1201, 1122 cmÀ1; MALDI-
TOF MS: m/z: 957.6 [M+Na]+, 973.5 [M+K]+; elemental analysis calcd
(%) for C59H82O9: C 75.77, H 8.84; found: C 75.96, H 8.84.
3-[(Carboxymethyl)oxy]-4-benzyloxy-p-tert-butylcalix[4]arene-(1,2)-
crown-5, cone conformer (4d): Yield 66%; m.p. 128–1308C (CH2Cl2/
1
CH3OH); H NMR: d=7.38–7.34 (m, 5H; OCH2Ph), 7.13–7.08 (m, 4H),
6.62 and 6.57 (2d, J=1.7 Hz, 1H each), 6.48 (s, 2H), 4.97 and 4.83 (2d,
J=11.1 Hz, 1H each, OCH2Ph), 4.85 and 4.42 (2d, J=15.8 Hz, 1H each,
CH2CO2), 4.58 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.26 (d, J=12.4 Hz, 1H;
ArCH2Ar), 4.17 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.31–3.69 (m, 17H), 3.23
(d, J=12.8 Hz, 1H; ArCH2Ar), 3.14 (d, J=12.6 Hz, 1H; ArCH2Ar), 3.05
(d, J=12.6 Hz, 1H; ArCH2Ar), 2.88 (d, J=13.0 Hz, 1H; ArCH2Ar),
1.34, 1.33, 0.86, and 0.82 ppm (4s, 9H each); 13C NMR: d=170.77,
154.13, 152.10, 150.87, 149.96, 147.00, 145.36, 145.27, 145.10, 136.41,
135.65, 134.87, 134.81, 134.77, 132.94, 132.74, 132.11, 131.30, 130.06,
128.42, 128.40, 126.02, 125.73, 125.40, 125.33, 125.24, 125.21, 124.75,
124.45, 78.50, 75.38, 73.50, 71.28, 71.07, 70.56, 70.49, 70.45, 69.06, 34.17,
34.06, 33.70, 33.64, 31.72, 31.57, 31.02, 31.16, 31.08, 30.53 ppm; IR (KBr):
n˜ =3246, 1761, 1480, 1199 cmÀ1; MALDI-TOF MS: m/z: 977.1 [M+Na]+;
elemental analysis calcd (%) for C61H78O9: C 76.70, H 8.23; found: C
76.43, H 8.26.
3-{[(Ethoxycarbonyl)methyl]oxy}-4-propoxy-p-tert-butylcalix[4]arene-
(1,2)-crown-6, partial cone conformer (3e): Column chromatography
(SiO2, petroleum ether/AcOEt 5:1). Yield 55%; m.p. 193–1958C
(CH2Cl2/CH3OH); 1H NMR: d=7.35 and 7.22 (2d, J=2.4 Hz, 1H each),
7.07 (s, 2H), 6.89 and 6.87 (2d, J=2.4 Hz, 1H each), 6.68 and 6.67 (2d,
J=2.5 Hz, 1H each), 4.50 and 4.37 (2d, J=15.3 Hz, 1H each, CH2CO2),
4.35 (d, J=11.9 Hz, 1H; ArCH2Ar), 4.31 (d, J=12.2 Hz, 1H; ArCH2Ar),
4.28–4.18 (m, 2H; CO2CH2CH3), 4.17–3.46 (m, 24H), 3.10 (d, J=13.5 Hz,
1H; ArCH2Ar), 3.05 (d, J=13.7 Hz, 1H; ArCH2Ar), 2.93 and 2.90 (2d,
J=7.2 Hz, 1H each, CH2CH2CH3), 1.55–1.39 (m, 2H; CH2CH2CH3),
1.42, 1.32, 1.07, and 1.05 (4s, 9H each), 1.30 (t, J=6.9 Hz, 3H;
CO2CH2CH3), 0.53 ppm (t, J=7.2 Hz, 3H; CH2CH2CH3); 13C NMR: d=
169.75, 155.03, 155.80, 153.50, 152.98, 145.14, 144.29, 144.01, 143.33,
135.49, 135.42, 133.11, 132.92, 132.90, 132.36, 132.07, 132.05, 127.74,
127.45, 126.21, 126.19, 125.80, 125.56, 125.29, 125.25, 73.80, 72.11, 71.07,
70.83, 70.72, 70.45, 70.42, 70.30, 70.25, 69.82, 69.19, 60.77, 38.11, 37.81,
31.32, 30.74, 34.06, 34.00, 33.75, 33.74, 31.75, 31.66, 31.36, 31.30,
23.59 ppm; IR (KBr): n˜ =1762, 1479, 1201 cmÀ1; MALDI-TOF MS: m/z:
1001.5 [M+Na]+, 1017.5 [M+K]+; elemental analysis calcd (%) for
C61H86O10·0.5H2O: C 74.13, H 8.87; found: C 74.08, H 8.71.
3-[(Carboxymethyl)oxy]-4-propoxy-p-tert-butylcalix[4]arene-(1,2)-crown-
6, cone conformer (4e): Yield 67%; m.p. 152–1548C (CH2Cl2/CH3OH);
1H NMR: d=7.15 (s, 2H), 7.14 and 7.12 (2d, J=1.7 Hz, 1H each), 6.58
(s, 2H), 6.51 and 6.49 (2d, J=2.5 Hz, 1H each), 4.78 and 4.53 (2d, J=
15.7 Hz, 1H each, CH2CO2), 4.58 (d, J=13.0 Hz, 1H; ArCH2Ar), 4.39 (d,
J=12.4 Hz, 1H; ArCH2Ar), 4.22 (d, J=12.7 Hz, 1H; ArCH2Ar), 4.19 (d,
J=12.7 Hz, 1H; ArCH2Ar), 4.05–3.60 (m, 22H), 3.23 (d, J=12.8 Hz, 2H;
ArCH2Ar), 3.16 (d, J=12.5 Hz, 1H; ArCH2Ar), 3.14 (d, J=12.5 Hz, 1H;
ArCH2Ar), 2.00–1.83 (m, 2H; CH2CH2CH3), 1.34 (s, 18H each, C-
(CH3)3), 0.98 (t, J=7.5 Hz, 3H; CH2CH2CH3), 0.83 and 0.82 ppm (2s, 9H
each); 13C NMR: d=170.61, 154.27, 151.88, 150.83, 150.79, 147.14, 145.27,
145.16, 145.00, 135.50, 135.03, 135.01, 134.88, 132.96, 132.55, 131.59,
131.44, 126.07, 125.85, 125.50, 125.25, 125.18, 125.16, 124.76, 124.57, 78.38,
75.20, 73.17, 71.25, 70.92, 70.85, 70.73, 70.57, 70.27, 69.04, 34.21, 34.08,
33.66, 31.73, 31.60, 31.03, 31.19, 30.82, 30.73, 23.00, 10.29 ppm; IR (KBr):
n˜ =3230, 1762, 1481, 1200, 1123 cmÀ1; MALDI-TOF MS: m/z: 973.8
[M+Na]+, 989.8 [M+K]+; elemental analysis calcd (%) for C59H82O10: C
74.49, H 8.69; found: C 74.48, H 8.64.
3-[(Carboxymethyl)oxy]-4-propoxy-p-tert-butylcalix[4]arene-(1,2)-crown-
5, partial cone conformer (4h): This compound was synthesized by hy-
drolysis of 3d following the same procedure as used for the hydrolysis of
3-[(Carboxymethyl)oxy]-4-benzyloxy-p-tert-butylcalix[4]arene-(1,2)-
crown-6, cone conformer (4 f): Yield 66%; m.p. 103–1058C (CH2Cl2/
CH3OH); 1H NMR: d=7.36–7.32 (m, 5H; OCH2Ph), 7.12 and 7.08 (2d,
J=2.1 Hz, 1H each), 7.11 and 7.07 (2d, J=2.1 Hz, 1H each), 6.60 and
6.48 (2d, J=1.4 Hz, 1H each), 6.55 and 6.46 (2d, J=1.4 Hz, 1H each),
4.94 and 4.80 (2d, J=11.1 Hz, 1H each, OCH2Ph), 4.73 and 4.45 (2d, J=
15.8 Hz, 1H each, CH2CO2), 4.55 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.27 (d,
J=12.4 Hz, 1H; ArCH2Ar), 4.18 (d, J=12.6 Hz, 1H; ArCH2Ar), 4.39–
3.57 (m, 21H), 3.22 (d, J=12.8 Hz, 1H; ArCH2Ar), 3.13 (d, J=12.6 Hz,
1H; ArCH2Ar), 3.02 (d, J=12.5 Hz, 1H; ArCH2Ar), 2.87 (d, J=12.9 Hz,
1H; ArCH2Ar), 1.32, 1.31, 0.84, and 0.81 ppm (4s, 9H each); 13C NMR:
d=170.53, 154.35, 152.00, 150.83, 150.02, 147.01, 145.34, 145.24, 145.14,
136.48, 135.44, 134.98, 134.87, 134.75, 132.90, 132.73, 132.07, 131.40,
130.00, 128.46, 128.44, 128.40, 126.00, 125.76, 125.54, 125.24, 125.07,
124.78, 124.46, 78.45, 75.19, 73.13, 71.23, 70.99, 70.83, 70.72, 70.57, 70.53,
70.23, 68.95, 34.17, 34.06, 33.70, 33.64, 31.72, 31.57, 31.02, 31.23, 30.95,
30.83 ppm; IR (KBr): n˜ =3230, 1761, 1480, 1199, 1123 cmÀ1; MALDI-
TOF MS: m/z: 1021.0 [M+Na]+, 1037.0 [M+K]+; elemental analysis
calcd (%) for C63H82O10: C 75.72, H 8.27; found: C 75.73, H 8.34.
1
4a, 4b, and 4g. Yield 99%; m.p. 209–2118C (CH2Cl2/CH3OH); H NMR:
d=9.49 (s, 1H; CO2H), 7.22 (s, 2H), 7.20 (d, J=2.2 Hz, 1H), 7.07 (d, J=
2.3 Hz, 1H), 7.01 (d, J=2.3 Hz, 1H), 6.96 (d, J=2.1 Hz, 2H), 6.90 (d, J=
2.3 Hz, 1H), 4.64 (d, J=12.1 Hz, 1H; ArCH2Ar), 4.24 and 4.17 (2d, J=
15.5 Hz, 1H each, OCH2CO2), 4.06 (d, J=12.0 Hz, 1H; ArCH2Ar), 3.98
(d, J=17.7 Hz, 1H; ArCH2Ar), 4.13–3.52 (m, 19H), 3.28 (d, J=12.2 Hz,
1H; ArCH2Ar), 3.26 (d, J=12.1 Hz, 1H; ArCH2Ar), 2.24–2.19 (m, 1H),
1.93–1.86 (m, 1H), 1.37, 1.27, 1.26, and 1.11 (4s, 9H each), 0.27–0.07 (m,
2H), À0.31 ppm (t, J=7.5 Hz, 3H; CH2CH2CH3); 13C NMR: d=169.41,
154.12, 153.55, 150.96, 150.31, 147.38, 145.68, 145.46, 145.28, 136.01,
135.60, 134.48, 133.49, 132.80, 132.69, 132.09, 132.07, 127.86, 126.38,
126.01, 125.30, 125.27, 125.19, 125.15, 124.82, 75.58, 72.16, 71.25, 70.71,
70.62, 70.01, 69.23, 68.91, 39.62, 38.29, 30.94, 30.14, 34.19, 34.00, 31.56,
31.44, 31.35, 31.30, 22.29, 9.77 ppm; IR (KBr): n˜ =3396, 1761, 1480, 1201,
1124 cmÀ1; MALDI-TOF MS: m/z: 929.4 [M+Na]+, 945.4 [M+K]+; ele-
mental analysis calcd (%) for C57H78O9: C 75.46, H 8.67; found: C 75.31,
H 8.71.
Alkylation of the last phenolic OH group: general procedure for the
preparation of partial cone conformers 3d and 3e: Compound 3a or 3b
(1.8 mmol), nPrI (3.06 g, 10 equiv), and Cs2CO3 (5.84 g, 10 equiv) in
DMF (100 mL) were stirred at 708C for 2 d. Then 10% HCl (15 mL) was
added to quench the reaction. After removal of the solvent under re-
duced pressure, the residue was partitioned between water (50 mL) and
CH2Cl2 (2”50 mL). The organic layer was dried with Na2SO4 and the sol-
vent evaporated. The residue was purified by column chromatography
and then recrystallized from CH2Cl2/CH3OH to give 3d or 3e as a white
solid.
3-[(Carboxymethyl)oxy]-4-propoxy-p-tert-butylcalix[4]arene-(1,2)-crown-
6, partial cone conformer (4i): This compound was synthesized by hydrol-
ysis of 3e following the same procedure as used for the hydrolysis of 4a,
1
4b, and 4g. Yield 87%; m.p. 142–1448C (CH2Cl2/CH3OH); H NMR: d=
9.55 (s, 1H; CO2H), 7.21 (d, J=2.3 Hz, 2H), 7.19 (d, J=2.3 Hz, 1H),
7.08 (d, J=2.3 Hz, 1H), 7.01 (d, J=2.3 Hz, 1H), 6.95 (s, 2H), 6.91 (d, J=
2.4 Hz, 1H), 4.64 (d, J=12.1 Hz, 1H; ArCH2Ar), 4.22 and 4.16 (2d, J=
15.5 Hz, 1H each, CH2CO2), 4.13 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.13–
3.54 (m, 24H), 3.25 (d, J=12.2 Hz, 2H; ArCH2Ar), 2.29–2.22 (m, 1H),
5924
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928

Synthesis and Optical Resolution of Chiral Calix[4]crowns
FULL PAPER
1.96–1.89 (m, 1H), 1.37, 1.26, 1.25, and 1.12 (4s, 9H each), 0.22–0.16 (m,
2H), À0.34 ppm (t, J=7.2 Hz, 3H; CH2CH2CH3); 13C NMR: d=169.27,
154.07, 153.74, 150.79, 150.31, 147.27, 145.70, 145.38, 145.27, 135.65,
135.55, 134.42, 133.57, 132.89, 132.62, 132.40, 132.11, 127.80, 126.21,
125.93, 125.39, 125.26, 125.20, 125.06, 124.81, 74.91, 72.07, 71.09, 70.93,
70.68, 70.62, 70.57, 70.55, 69.31, 69.25, 69.00, 39.67, 38.25, 30.84, 30.39,
34.17, 33.98, 31.54, 31.42, 31.35, 31.29, 22.21, 9.67 ppm; IR (KBr): n˜ =
Compound 5c-1: Yield 24%; m.p. 129–1318C; 1H NMR: d=8.00 (d, J=
8.9 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 7.84 (d, J=8.7 Hz, 1H), 7.82 (d, J=
6.0 Hz, 1H), 7.36 (d, J=8.9 Hz, 1H), 7.49–7.15 (m, 6H), 6.99 (d, J=
8.3 Hz, 1H), 6.91–6.89 (m, 4H), 6.59 (s, 4H), 6.36 (s, 1H; OH), 4.85 and
4.63 (2d, J=16.8 Hz, 1H each, CH2CO2), 4.55 (d, J=12.9 Hz, 1H;
ArCH2Ar), 4.42 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.40 (d, J=12.8 Hz, 1H;
ArCH2Ar), 4.34 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.22–3.57 (m, 18H), 3.11
(d, J=14.1 Hz, 1H; ArCH2Ar), 3.09 (d, J=12.0 Hz, 1H; ArCH2Ar), 3.06
(d, J=13.4 Hz, 1H; ArCH2Ar), 3.05 (d, J=12.5 Hz, 1H; ArCH2Ar),
1.87–1.64 (m, 2H), 1.23 (s, 9H), 1.19 (s, 9H), 0.94 (s, 18H), 0.87 ppm (t,
J=7.4 Hz, 3H; CH2CH2CH3); 13C NMR: d=169.80, 153.52, 153.16,
153.05, 152.99, 152.31, 147.52, 145.03, 144.88, 144.45, 144.17, 134.97,
134.67, 134.32, 134.30, 133.74, 133.58, 132.95, 132.80, 132.78, 132.69,
131.98, 130.01, 129.78, 128.75, 128.14, 127.92, 126.90, 126.44, 126.12,
125.82, 125.52, 125.45, 125.30, 125.18, 124.96, 124.77, 124.68, 124.60,
124.58, 123.82, 123.14, 121.95, 118.40, 114.14, 77.30, 73.74, 72.47, 71.28,
70.44, 70.30, 70.25, 70.12, 70.04, 33.94, 33.69, 33.67, 31.58, 31.56, 31.29,
31.28, 31.17, 30.76, 23.26, 10.50 ppm; IR (KBr): n˜ =3291, 1784, 1480,
3394, 1760, 1480, 1202, 1121 cmÀ1
; MALDI-TOF MS: m/z: 973.5
[M+Na]+, 989.5 [M+K]+; elemental analysis calcd (%) for C59H82O10: C
74.49, H 8.69; found: C 74.23, H 8.71.
Condensation of 4 with (S)-BINOL: general procedure for the prepara-
tion of diastereomers 5a–5i: Compound
4 (0.55 mmol), (S)-BINOL
(0.173 g, 1.1 equiv), DCC (1.1 equiv for 4a and 4b, 3.0 equiv for 4c–4i),
and DMAP (0.014 g, 0.2 equiv) in CH2Cl2 (50 mL) were stirred at room
temperature for a period of time (1 d for 4a and 4b, 5 d for 4c–4i). After
filtering off the insoluble DCC, CH2Cl2 was evaporated and a small
amount of AcOEt was added. The insoluble DCC was again removed by
filtration and the solvent was evaporated. The residue was purified by
column chromatography and then subjected to preparative TLC (only for
4a, 4b, 4h, and 4i).
1203, 1122 cmÀ1
;
MALDI-TOF MS: m/z: 1197.6 [M+Na]+, 1213.6
[M+K]+; elemental analysis calcd (%) for C77H90O10: C 78.67, H 7.72;
found: C 78.45, H 7.80.
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-p-tert-butylca-
lix[4]arene-(1,2)-crown-5, cone conformer (5a): First the crude product
was purified by column chromatography (SiO2, petroleum ether/AcOEt
4:1) and then the isolated diastereomeric mixture was subjected to prepa-
rative TLC (CHCl3/AcOEt 5:1) to give 5a-1 and 5a-2 as white solids.
Compound 5c-2: Yield 22%; m.p. 130–1328C; 1H NMR: d=7.99 (d, J=
8.9 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 7.84 (d, J=8.8 Hz, 2H), 7.50–7.13
(m, 7H), 7.04 (d, J=8.4 Hz, 1H), 6.81 (s, 2H), 6.77–6.65 (m, 6H), 5.95 (s,
1H; OH), 4.58 (s, 2H; CH2CO2), 4.40 (d, J=13.6 Hz, 1H; ArCH2Ar),
4.36 (d, J=13.4 Hz, 1H; ArCH2Ar), 4.33 (d, J=12.5 Hz, 1H; ArCH2Ar),
4.11 (d, J=13.0 Hz, 1H; ArCH2Ar), 4.10–3.43 (m, 18H), 3.09 (d, J=
12.5 Hz, 1H; ArCH2Ar), 3.07 (d, J=12.5 Hz, 1H; ArCH2Ar), 2.95 (d, J=
12.9 Hz, 1H; ArCH2Ar), 2.93 (d, J=13.0 Hz, 1H; ArCH2Ar), 1.95 (m,
2H), 1.14, 1.11, 1.04, and 1.00 (4s, 9H each), 0.95 ppm (t, J=7.4 Hz, 3H;
CH2CH2CH3); 13C NMR: d=169.31, 153.42, 153.40, 153.15, 152.01,
151.94, 147.69, 145.07, 144.69, 144.56, 144.21, 134.23, 134.12, 133.95,
133.83, 133.63, 133.48, 133.34, 133.27, 133.04, 132.12, 130.26, 130.13,
128.86, 128.16, 127.85, 127.16, 126.59, 126.05, 125.88, 125.33, 125.17,
125.09, 125.07, 124.96, 124.95, 124.86, 124.80, 124.71, 124.69, 123.71,
123.45, 121.87, 118.58, 114.31, 77.15, 73.33, 73.19, 71.11, 70.57, 70.51,
70.40, 70.15, 33.86, 33.78, 33.73, 31.48, 31.37, 31.60, 31.09, 30.62, 23.15,
10.59 ppm; IR (KBr): n˜ =3445, 1785, 1480, 1203, 1121 cmÀ1; MALDI-
TOF MS: m/z: 1197.5 [M+Na]+, 1213.4 [M+K]+; elemental analysis
calcd (%) for C77H90O10: C 78.67, H 7.72; found: C 78.49, H 7.78.
Compound 5a-1: Yield 25%; m.p. 139–1418C; 1H NMR: d=8.09 (d, J=
8.9 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H), 7.86 (d, J=7.7 Hz, 1H), 7.83 (d, J=
8.7 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.53 (d, J=8.9 Hz, 1H), 7.37–7.06
(m, 10H), 6.66 (s, 2H), 6.35 and 6.34 (2s, 1H each), 6.02 (s, 1H; OH),
4.43 (d, J=13.8 Hz, 1H; ArCH2Ar), 4.29 and 4.13 (2d, J=16.3 Hz, 1H
each, CH2CO2), 4.39–3.59 (m, 19H), 3.31 (d, J=13.6 Hz, 1H; ArCH2Ar),
3.19 (d, J=12.6 Hz, 1H; ArCH2Ar), 3.01 (d, J=13.7 Hz, 1H; ArCH2Ar),
2.94 (d, J=13.2 Hz, 1H; ArCH2Ar), 1.39, 1.37, 0.93, and 0.74 ppm (4s,
9H each); 13C NMR: d=168.45, 153.56, 152.23, 151.94, 150.51, 150.38,
147.35, 146.15, 145.75, 145.14, 141.30, 136.10, 135.34, 133.58, 133.53,
132.74, 132.20, 131.64, 131.57, 131.52, 130.42, 130.18, 129.60, 128.82,
128.24, 128.10, 128.02, 127.18, 126.62, 126.10, 126.06, 125.91, 125.49,
125.47, 125.18, 125.06, 125.00, 124.73, 124.65, 124.63, 123.97, 123.35,
121.81, 118.41, 113.94, 76.34, 71.94, 71.69, 71.52, 70.69, 70.28, 70.17, 69.38,
68.29, 34.13, 33.86, 33.78, 33.53, 31.80, 31.67, 31.02, 30.97, 31.48, 30.68,
30.59 ppm; IR (KBr): n˜ =3421, 1784, 1481, 1205, 1122 cmÀ1; MALDI-
TOF MS: m/z: 1155.6 [M+Na]+, 1171.6 [M+K]+; elemental analysis
calcd (%) for C74H84O10: C 78.41, H 7.47; found: C 78.59, H 7.53.
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-benzyloxy-p-
tert-butylcalix[4]arene-(1,2)-crown-5, cone conformer (5d): Column chro-
matography (SiO2, petroleum ether/AcOEt 5:1 then petroleum ether/ace-
tone 10:1).
Compound 5a-2: Yield 23%; m.p. 140–1428C; 1H NMR: d=8.08 (d, J=
8.9 Hz, 1H), 7.98 (d, J=8.2 Hz, 1H), 7.85 (d, J=9.0 Hz, 1H), 7.84 (d, J=
7.8 Hz, 1H), 7.52 (t, J=7.9 Hz, 1H), 7.51 (d, J=8.7 Hz, 1H), 7.39–7.06
(m, 6H), 7.13 and 7.10 (2d, J=2.0 Hz, 1H each), 7.03 and 7.02 (2s, 1H
each), 6.61 and 6.60 (2s, 1H each), 6.33 and 6.31 (2s, 1H each), 6.06 (s,
1H; OH), 4.36 (d, J=13.8 Hz, 1H; ArCH2Ar), 4.35 (d, J=12.5 Hz, 1H;
ArCH2Ar), 4.24 (d, J=12.8 Hz, 1H; ArCH2Ar), 4.26 and 4.02 (2d, J=
16.5 Hz, 1H each, CH2CO2), 4.00 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.18–
3.55 (m, 16H), 3.24 (d, J=13.5 Hz, 1H; ArCH2Ar), 3.17 (d, J=12.6 Hz,
1H; ArCH2Ar), 3.00 (d, J=13.1 Hz, 1H; ArCH2Ar), 2.90 (d, J=13.1 Hz,
1H; ArCH2Ar), 1.36, 1.33, 0.90, and 0.71 ppm (4s, 9H each); 13C NMR:
d=168.25, 153.56, 151.96, 151.67, 150.74, 150.52, 147.45, 146.01, 145.74,
145.21, 140.95, 135.86, 135.53, 133.51, 133.49, 132.69, 132.19, 131.75,
131.72, 131.47, 130.32, 130.30, 129.22, 128.89, 128.25, 127.96, 127.92,
127.26, 126.70, 126.18, 125.98, 125.86, 125.48, 125.41, 125.08, 125.02,
124.95, 124.72, 124.60, 124.58, 123.67, 123.52, 121.80, 118.47, 114.23, 76.21,
72.11, 71.64, 71.34, 70.74, 70.33, 70.10, 69.63, 68.46, 34.15, 33.81, 33.77,
33.54, 31.78, 31.70, 31.03, 30.98, 31.39, 30.83, 30.60 ppm; IR (KBr): n˜ =
Compound 5d-1: Yield 31%; m.p. 133–1358C; 1H NMR: d=8.01 (d, J=
8.9 Hz, 1H), 7.95 (d, J=8.2 Hz, 1H), 7.82 (d, J=8.9 Hz, 1H), 7.81 (d, J=
7.7 Hz, 1H), 7.50–7.02 (m, 13H), 6.91–6.89 (m, 4H), 6.58–6.55 (m, 4H),
6.14 (s, 1H; OH), 4.78 and 4.72 (2d, J=11.0 Hz, 1H each), 4.73 and 4.57
(2d, J=16.9 Hz, 1H each, CH2CO2), 4.42 (d, J=12.9 Hz, 1H; ArCH2Ar),
4.39 (d, J=12.4 Hz, 1H; ArCH2Ar), 4.29 (d, J=13.8 Hz, 1H; ArCH2Ar),
4.25 (d, J=13.0 Hz, 1H; ArCH2Ar), 4.06–3.41 (m, 16H), 3.07 (d, J=
12.7 Hz, 1H; ArCH2Ar), 3.01 (d, J=12.9 Hz, 2H; ArCH2Ar), 2.93 (d, J=
12.9 Hz, 1H; ArCH2Ar), 1.24, 1.19, 0.94, and 0.92 ppm (4s, 9H each); 13C
NMR: d=170.09, 153.63, 152.96, 152.75, 152.36, 152.20, 147.62, 144.99,
144.85, 144.44, 144.42, 137.97, 134.93, 134.66, 134.60, 134.13, 133.73,
133.54, 132.99, 132.87, 132.80, 132.61, 132.00, 130.09, 129.96, 129.70,
129.68, 128.81, 128.13, 128.11, 127.95, 127.63, 127.00, 126.53, 126.00,
125.90, 125.48, 125.36, 125.20, 125.18, 124.90, 124.75, 124.67, 124.60,
123.74, 123.27, 121.87, 118.49, 114.19, 73.76, 72.49, 71.10, 70.35, 70.27,
70.21, 70.15, 70.03, 69.89, 33.94, 33.67, 33.65, 31.67, 31.47, 30.71, 31.60,
31.56, 31.23 ppm; IR (KBr): n˜ =3524, 1783, 1479, 1204, 1121 cmÀ1
;
MALDI-TOF MS: m/z: 1245.2 [M+Na]+; elemental analysis calcd (%)
3502, 1784, 1481, 1205, 1122 cmÀ1
; MALDI-TOF MS: m/z: 1155.7
[M+Na]+, 1171.7 [M+K]+; elemental analysis calcd (%) for C74H84O10
:
for C81H90O10: C 79.51, H 7.41; found: C 79.69, H 7.52.
Compound 5d-2: Yield 33%; m.p. 123–1258C; 1H NMR: d=7.95 (d, J=
8.9 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.83 (d, J=
8.2 Hz, 1H), 7.51–6.92 (m, 13H), 6.89 (s, 2H; ArH), 6.90 and 6.88 (2d,
J=2.4 Hz, 1H each), 6.61 and 6.56 (2d, J=2.3 Hz, 1H each), 6.59 (s,
2H), 4.90 and 4.69 (2d, J=10.8 Hz, 1H each), 4.72 and 4.60 (2d, J=
C 78.41, H 7.47; found: C 78.44, H 7.51.
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-propoxy-p-tert-
butylcalix[4]arene-(1,2)-crown-5, cone conformer (5c): Column chroma-
tography (SiO2, petroleum ether/AcOEt 5:1 then petroleum ether/ace-
tone 9:1).
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5925

C.-F. Chen, Z.-T. Huang et al.
15.7 Hz, 1H each, CH2CO2), 4.40 (d, J=13.7 Hz, 1H; ArCH2Ar), 4.36 (d,
J=13.0 Hz, 1H; ArCH2Ar), 4.23 (d, J=12.4 Hz, 1H; ArCH2Ar), 4.20 (d,
J=13.0 Hz, 1H; ArCH2Ar), 3.98–3.19 (m, 16H), 3.05 (d, J=12.7 Hz, 1H;
ArCH2Ar), 3.00 (d, J=13.5 Hz, 1H; ArCH2Ar), 2.98 (d, J=12.8 Hz, 1H;
ArCH2Ar), 2.95 (d, J=13.7 Hz, 1H; ArCH2Ar), 1.25, 1.17, 0.95, and
0.94 ppm (4s, 9H each); 13C NMR: d=169.80, 153.71, 152.73, 152.36,
152.03, 151.99, 147.74, 145.32, 144.78, 144.48, 138.16, 134.77, 134.65,
134.59, 134.56, 133.64, 133.43, 133.12, 133.05, 132.89, 132.58, 132.11,
130.38, 130.15, 129.96, 129.94, 128.86, 128.23, 128.21, 128.14, 127.85,
127.69, 127.19, 126.68, 126.08, 125.79, 125.37, 125.35, 125.13, 125.11,
124.89, 124.80, 124.70, 124.68, 123.53, 123.51, 121.78, 118.57, 114.33, 73.85,
72.75, 70.72, 70.52, 70.38, 69.91, 69.86, 69.72, 33.99, 33.91, 33.69, 33.68,
31.67, 31.38, 31.05, 30.62, 31.60, 31.54, 31.26 ppm; IR (KBr): n˜ =3420,
1784, 1479, 1203 cmÀ1; MALDI-TOF MS: m/z: 1245.1 [M+Na]+; elemen-
tal analysis calcd (%) for C81H90O10·0.5H2O: C 78.93, H 7.44; found: C
78.98, H 7.57.
OH), 4.75 (ABq, J=11.0 Hz, 2H; OCH2Ph), 4.46 (ABq, J=17.2 Hz, 2H;
OCH2CO2), 4.48 (d, J=14.5 Hz, 1H; ArCH2Ar), 4.40 (d, J=11.1 Hz,
1H; ArCH2Ar), 4.27 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.10 (d, J=12.8 Hz,
1H; ArCH2Ar), 4.15–3.39 (m, 20H), 3.07 (d, J=13.6 Hz, 1H; ArCH2Ar),
3.03 (d, J=13.6 Hz, 1H; ArCH2Ar), 2.96 (d, J=13.1 Hz, 1H; ArCH2Ar),
2.90 (d, J=12.9 Hz, 1H; ArCH2Ar), 1.20, 1.17, 0.96, and 0.95 ppm (4s,
9H each); 13C NMR: d=169.54, 153.51, 152.80, 152.77, 152.38, 152.11,
147.49, 145.00, 144.82, 144.55, 144.45, 137.84, 134.70, 134.50, 134.10,
134.05, 133.68, 133.47, 133.04, 132.98, 132.01, 130.17, 129.92, 129.73,
129.72, 128.75, 128.18, 128.15, 128.13, 127.93, 127.75, 127.03, 126.62,
125.96, 125.94, 125.43, 125.41, 125.17, 125.03, 124.88, 124.84, 124.75,
124.67, 124.56, 123.55, 123.33, 122.03, 118.28, 114.07, 72.96, 72.11, 70.85,
70.63, 70.49, 70.45, 70.27, 70.17, 69.99, 69.80, 33.90, 33.69, 33.68, 31.53,
31.52, 31.26, 31.11, 31.04 ppm; IR (KBr): n˜ =3365, 1784, 1479, 1203 cmÀ1
;
MALDI-TOF MS: m/z: 1289.0 [M+Na]+; elemental analysis calcd (%)
for C83H94O11: C 78.64, H 7.47; found: C 78.81, H 7.62.
Compound 5 f-2: Yield 16%; m.p. 104–1068C; 1H NMR: d=8.03 (d, J=
8.9 Hz, 1H), 7.97 (d, J=8.3 Hz, 1H), 7.85 (d, J=8.6 Hz, 2H), 7.53–7.15
(m, 12H), 7.04 (d, J=8.4 Hz, 1H), 6.87 (s, 3H), 6.82 (d, J=1.7 Hz, 1H),
6.64 and 6.62 (2s, 2H each), 4.83 (ABq, J=11.0 Hz, 2H; OCH2Ph), 4.44
(ABq, J=16.6 Hz, 2H; OCH2CO2), 4.46 (d, J=12.6 Hz, 1H; ArCH2Ar),
4.38 (d, J=12.8 Hz, 1H; ArCH2Ar), 4.22 (d, J=12.9 Hz, 1H; ArCH2Ar),
4.20 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.06–3.36 (m, 20H), 3.08 (d, J=
12.6 Hz, 1H; ArCH2Ar), 3.00 (d, J=12.8 Hz, 1H; ArCH2Ar), 2.99 (d, J=
11.8 Hz, 1H; ArCH2Ar), 2.95 (d, J=12.8 Hz, 1H; ArCH2Ar), 1.20, 1.16,
0.99, and 0.98 ppm (4s, 9H each); 13C NMR: d=169.21, 153.48, 152.81,
152.52, 152.49, 152.16, 147.53, 145.11, 144.76, 144.56, 144.52, 138.07,
134.56, 134.45, 134.08, 133.87, 133.58, 133.44, 133.41, 133.23, 132.96,
132.90, 132.01, 130.25, 129.99, 129.87, 129.85, 128.78, 128.20, 128.14,
128.12, 127.94, 127.69, 127.04, 126.52, 126.02, 125.94, 125.44, 125.38,
125.11, 125.00, 124.88, 124.85, 124.72, 124.67, 123.53, 123.30, 121.95,
118.57, 114.14, 73.02, 72.14, 70.91, 70.73, 70.49, 70.37, 70.26, 69.53, 33.91,
33.89, 33.73, 33.71, 31.53, 31.50, 31.29, 31.02, 30.91, 29.70 ppm; IR (KBr):
n˜ =3284, 1784, 1479, 1203 cmÀ1; MALDI-TOF MS: m/z: 1289.2 [M+Na]+
; elemental analysis calcd (%) for C83H94O11: C 78.64, H 7.47; found: C
78.25, H 7.57.
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-propoxy-p-tert-
butylcalix[4]arene-(1,2)-crown-6, cone conformer (5e): Column chroma-
tography (SiO2, petroleum ether/AcOEt 5:1 then petroleum ether/ace-
tone 10:1).
Compound 5e-1: Yield 26%; m.p. 113–1158C; 1H NMR: d=8.01 (d, J=
8.9 Hz, 1H), 7.95 (d, J=8.3 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.84 (d, J=
5.8 Hz, 1H), 7.47 (t, J=7.2 Hz, 1H), 7.45 (d, J=9.0 Hz, 1H), 7.33–7.29
(m, 4H), 7.18 (t, J=8.0 Hz, 1H), 7.01 (d, J=8.4 Hz, 1H), 6.89–6.61 (m,
8H), 4.58 (ABq, J=16.2 Hz, 2H; CH2CO2), 4.60 (d, J=12.9 Hz, 1H;
ArCH2Ar), 4.43 (d, J=12.5 Hz, 1H; ArCH2Ar), 4.34 (d, J=12.5 Hz, 1H;
ArCH2Ar), 4.26 (d, J=12.8 Hz, 1H; ArCH2Ar), 4.17–3.49 (m, 22H), 3.11
(d, J=12.4 Hz, 1H; ArCH2Ar), 3.09 (d, J=13.7 Hz, 1H; ArCH2Ar), 3.04
(d, J=14.2 Hz, 1H; ArCH2Ar), 3.01 (d, J=12.7 Hz, 1H; ArCH2Ar),
1.84–1.61 (m, 2H), 1.18, 1.16, 0.98, and 0.96 (4s, 9H each), 0.88 ppm (t,
J=7.5 Hz, 3H; CH2CH2CH3); 13C NMR: d=169.27, 153.29, 153.26,
153.05, 152.94, 152.25, 147.46, 145.13, 144.89, 144.47, 144.31, 134.78,
134.54, 134.31, 133.91, 133.77, 133.55, 133.16, 133.14, 132.99, 132.70,
131.99, 130.04, 129.68, 128.73, 128.19, 127.94, 126.92, 126.58, 126.10,
125.87, 125.55, 125.44, 125.19, 125.17, 124.92, 124.84, 124.82, 124.75,
124.62, 123.63, 123.24, 122.18, 118.23, 114.09, 77.32, 77.25, 73.03, 71.79,
70.91, 70.70, 70.60, 70.42, 70.31, 69.97, 69.83, 33.94, 33.74, 33.71, 31.55,
31.33, 31.19, 31.07, 23.39, 10.44 ppm; IR (KBr): n˜ =3292, 1784, 1480,
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-propoxy-p-tert-
butylcalix[4]arene-(1,2)-crown-5, partial cone conformer (5h): First the
crude product was purified by column chromatography (SiO2, petroleum
ether/AcOEt 4:1) and then the diastereomeric mixture was subjected to
preparative TLC (CHCl3/AcOEt 5:1) to give 5h-1 and 5h-2 as white
solids.
1203, 1122 cmÀ1
;
MALDI-TOF MS: m/z: 1241.3 [M+Na]+, 1257.2
[M+K]+; elemental analysis calcd (%) for C79H94O11: C 77.80, H 7.77;
found: C 77.87, H 7.91.
Compound 5e-2: Yield 22%; m.p. 113–1158C; 1H NMR: d=8.05 (d, J=
8.9 Hz, 1H), 7.98 (d, J=8.2 Hz, 1H), 7.87 (d, J=9.1 Hz, 1H), 7.86 (d, J=
6.5 Hz, 1H), 7.54–7.25 (m, 6H), 7.18 (t, J=7.2 Hz, 1H), 7.05 (d, J=
8.4 Hz, 1H), 6.82 and 6.81 (2s, 1H each), 6.76–6.69 (m, 6H), 4.44 (ABq,
J=16.5 Hz, 2H; OCH2CO2), 4.49 (d, J=12.4 Hz, 1H; ArCH2Ar), 4.36
(d, J=12.4 Hz, 1H; ArCH2Ar), 4.33 (d, J=12.7 Hz, 1H; ArCH2Ar), 4.16
(d, J=12.7 Hz, 1H; ArCH2Ar), 4.12–3.59 (m, 22H), 3.11 (d, J=12.6 Hz,
2H; ArCH2Ar), 2.98 (d, J=13.3 Hz, 1H; ArCH2Ar), 2.94 (d, J=13.2 Hz,
1H; ArCH2Ar), 1.90 (m, 2H; CH2CH2CH3), 1.12, 1.11, 1.08, and 1.04 (4s,
9H each), 0.93 ppm (t, J=7.4 Hz, 3H; CH2CH2CH3); 13C NMR: d=
168.9, 153.5, 153.3, 153.2, 152.1, 152.0, 147.5, 145.0, 144.7, 144.6, 144.2,
134.0, 133.9, 133.7, 133.6, 133.5, 133.4, 133.3, 133.2, 132.0, 130.1, 130.0,
128.8, 128.2, 128.1, 127.9, 127.8, 127.1, 126.5, 126.0, 125.9, 125.8, 125.2,
125.1, 125.0, 124.9, 124.8, 124.7, 124.6, 123.9, 123.5, 123.3, 121.8, 118.5,
114.1, 72.73, 72.62, 70.80, 70.74, 70.62, 70.57, 70.49, 70.38, 70.15, 69.87,
33.75, 33.67, 33.50, 31.50, 31.36, 31.31, 31.11, 30.95, 30.86, 23.11,
10.35 ppm; IR (KBr): n˜ =3291, 1785, 1480, 1203, 1121 cmÀ1; MALDI-
TOF MS: m/z: 1241.2 [M+Na]+, 1257.2 [M+K]+; elemental analysis
calcd (%) for C79H94O11: C 77.80, H 7.77; found: C 77.85, H 7.83.
Compound 5h-1: Yield 24%; m.p. 118–1208C; 1H NMR: d=7.99 (d, J=
8.9 Hz, 1H), 7.93 (d, J=8.2 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.86 (d, J=
7.9 Hz, 1H), 7.43 (d, J=8.9 Hz, 1H), 7.47–6.98 (m, 7H), 7.06 (s, 2H),
7.01 (s, 2H), 6.87 (s, 2H), 6.69 and 6.67 (2d, J=2.4 Hz, 1H each), 4.70 (d,
J=13.3 Hz, 1H; ArCH2Ar), 4.34 (2d, J=16.6 Hz, 2H; OCH2CO2), 4.25
(d, J=12.1 Hz, 1H; ArCH2Ar), 4.09–3.59 (m, 20H), 3.06 (d, J=12.5 Hz,
1H; ArCH2Ar), 2.98 (d, J=13.4 Hz, 1H; ArCH2Ar), 2.72 (t, J=7.5 Hz,
2H; CH2CH2CH3), 1.41, 1.30, 1.09, and 1.04 (4s, 9H each), 0.88–0.76 (m,
2H; CH2CH2CH3), 0.41 ppm (t, J=7.5 Hz, 3H; CH2CH2CH3); 13C NMR:
d=169.12, 154.89, 153.81, 153.52, 153.14, 152.46, 146.94, 145.18, 144.53,
144.05, 143.23, 135.38, 135.39, 133.86, 133.60, 133.24, 133.06, 133.03,
132.40, 132.23, 132.08, 131.69, 130.31, 129.54, 128.60, 128.19, 128.17,
127.96, 126.74, 126.72, 126.68, 126.51, 126.35, 126.05, 125.91, 125.88,
125.73, 125.55, 125.17, 125.03, 124.20, 123.12, 122.12, 118.05, 113.79, 73.78,
73.07, 71.61, 70.87, 70.60, 70.50, 70.22, 70.11, 69.38, 69.18, 38.18, 38.16,
31.89, 30.66, 34.04, 33.76, 33.75, 32.10, 31.64, 31.32, 23.46, 9.93 ppm; IR
(KBr): n˜ =3249, 1785, 1479, 1203, 1120 cmÀ1; MALDI-TOF MS: m/z:
1197.2 [M+Na]+, 1213.2 [M+K]+. HRMS [M+NH4]+: calcd. (%) for
C77H94O10N: 1192.6872; found: 1192.6850.
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-benzyloxy-p-
tert-butylcalix[4]arene-(1,2)-crown-6, cone conformer (5 f): Column chro-
matography (SiO2, petroleum ether/AcOEt 5:1 then petroleum ether/ace-
tone 10:1).
Compound 5 f-1: Yield 20%; m.p. 112–1148C; 1H NMR: d=8.03 (d, J=
8.9 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.82 (d, J=
5.8 Hz, 1H), 7.51–7.03 (m, 13H), 6.89 and 6.88 (2s, 1H each), 6.85 (s,
2H), 6.62 and 6.57 (2d, J=2.3 Hz, 1H each), 6.59 (s, 2H), 6.16 (s, 1H;
Compound 5h-2: Yield 24%; m.p. 132–1358C; 1H NMR: d=8.05 (d, J=
8.9 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.76 (d, J=
8.8 Hz, 1H), 7.52 (d, J=8.9 Hz, 1H), 7.50–7.03 (m, 7H), 7.29 and 7.21
(2d, J=2.4 Hz, 1H each), 7.06 and 7.03 (2d, J=2.5 Hz, 1H each), 6.83 (d,
J=2.5 Hz, 1H), 6.79 (d, J=2.5 Hz, 1H), 6.54 (d, J=2.4 Hz, 1H), 6.44 (d,
J=2.4 Hz, 1H), 4.33 and 3.70 (2d, J=15.8 Hz, 1H each, OCH2CO2), 4.24
(d, J=12.6 Hz, 1H; ArCH2Ar), 4.08–3.40 (m, 23H), 3.01 (d, J=12.8 Hz,
5926
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928

Synthesis and Optical Resolution of Chiral Calix[4]crowns
FULL PAPER
1H; ArCH2Ar), 2.63 (d, J=13.3 Hz, 1H; ArCH2Ar), 1.77–1.64 (m, 2H;
CH2CH2CH3), 1.40, 1.38, 1.02, and 1.00 (4s, 9H each), 0.83 ppm (t, J=
7.5 Hz, 3H; CH2CH2CH3); 13C NMR: d=167.37, 154.91, 153.49, 153.16,
152.75, 152.33, 147.33, 144.80, 144.41, 143.76, 143.25, 135.97, 134.79,
133.65, 133.54, 132.76, 132.43, 132.36, 132.02, 131.81, 131.69, 131.67,
130.02, 129.68, 128.71, 128.16, 127.95, 127.92, 127.90, 126.92, 126.51,
126.11, 126.02, 126.00, 125.89, 125.86, 125.61, 125.31, 125.30, 124.58,
124.30, 123.24, 121.89, 118.77, 114.48, 74.24, 72.97, 71.71, 70.57, 70.55,
70.51, 70.47, 70.37, 69.64, 69.56, 37.79, 37.25, 31.26, 31.17, 34.08, 34.05,
33.69, 31.84, 31.75, 31.40, 31.34, 23.97, 10.38 ppm; IR (KBr): n˜ =3238,
1786, 1479, 1202, 1120 cmÀ1; MALDI-TOF MS: m/z: 1197.4 [M+Na]+,
1213.4 [M+K]+. HRMS [M+NH4]+: calcd. (%) for C77H94O10N:
1192.6872; found: 1192.6916.
The relative spectroscopic data were identical to those of the racemates
4.
Compound 4a-1: Yield 0.055 g, 80%; m.p. 127–1298C; [a]2D5 =À16 (c=0.5
in CHCl3). Compound 4a-2: Yield 0.057 g, 82%; m.p. 127–1298C; [a]D25
+16 (c=0.5 in CHCl3).
=
Compound 4c-1: Yield 0.057 g, 78%; m.p. 116–1188C; [a]2D5 =+8 (c=0.5
in CHCl3). Compound 4c-2: Yield 0.052 g, 72%; m.p. 116–1188C; [a]D25
À8 (c=0.5 in CHCl3).
=
Compound 4d-1: Yield 0.059 g, 77%; m.p. 109–1118C; [a]2D5 =À8 (c=0.5
in CHCl3). Compound 4d-2: Yield 0.063 g, 82%; m.p. 109–1118C; [a]D25
+8 (c=0.5 in CHCl3).
=
Compound 4e-1: Yield 0.063 g, 83%; m.p. 93–958C; [a]2D5 =À4 (c=0.5 in
CHCl3). Compound 4e-2: Yield 0.057 g, 75%; m.p. 93–958C; [a]2D5 =+4
(c=0.5 in CHCl3).
Compound 4 f-1: Yield 0.06 g, 75%; m.p. 91–938C; [a]2D5 =À20 (c=0.5 in
CHCl3). Compound 4 f-2: Yield 0.06 g, 75%; m.p. 91–938C; [a]2D5 =+20
(c=0.5 in CHCl3).
3-({[(S)-2’-Hydroxybinaphthyloxycarbonyl]methyl}oxy)-4-propoxy-p-tert-
butylcalix[4]arene-(1,2)-crown-6, partial cone conformer (5i): First the
crude product was purified by column chromatography (SiO2, petroleum
ether/AcOEt 4:1) and then the diastereomeric mixture was subjected to
preparative TLC (CHCl3/AcOEt 5:1) to give 5i-1 and 5i-2 as white
solids.
Compound 4h-1: Yield 0.062 g, 85%; m.p. 122–1248C; [a]2D5 =À32 (c=0.5
in CHCl3). Compound 4h-2: Yield 0.059 g, 81%; m.p. 122–1248C; [a]D25
+32 (c=0.5 in CHCl3).
=
Compound 5i-1: Yield 31%; m.p. 127–1298C; 1H NMR: d=8.01 (d, J=
8.9 Hz, 1H), 7.94 (d, J=8.2 Hz, 1H), 7.87 (d, J=8.9 Hz, 1H), 7.85 (d, J=
7.9 Hz, 1H), 7.49–6.97 (m, 8H), 7.23 and 7.09 (2d, J=2.4 Hz, 1H each),
7.06 and 7.02 (2d, J=2.4 Hz, 1H each), 6.88 and 6.70 (2d, J=2.4 Hz, 1H
each), 6.86 and 6.68 (2d, J=2.4 Hz, 1H each), 4.49 (d, J=12.9 Hz, 1H;
ArCH2Ar), 4.34 (d, J=12.4 Hz, 1H; ArCH2Ar), 4.25 (ABq, J=16.5 Hz,
2H; CH2CO2), 4.19–3.43 (m, 24H), 3.04 (d, J=12.6 Hz, 1H; ArCH2Ar),
2.92 (d, J=13.1 Hz, 1H; ArCH2Ar), 2.58–2.51 (m, 2H; CH2CH2CH3),
1.39, 1.31, 1.07, and 1.06 (4s, 9H each), 0.86–0.79 (m, 2H), 0.31 ppm (t,
J=7.2 Hz, 3H; CH2CH2CH3); 13C NMR: d=168.97, 154.93, 153.69,
153.24, 152.75, 152.19, 147.14, 145.37, 144.58, 144.17, 143.44, 135.65,
135.32, 133.72, 133.58, 133.36, 133.27, 132.77, 132.72, 132.48, 132.14,
131.94, 130.32, 129.89, 128.71, 128.20, 127.99, 127.77, 127.04, 126.96,
126.59, 126.57, 126.28, 126.26, 125.94, 125.88, 125.57, 125.38, 125.31,
124.89, 123.85, 123.25, 121.98, 118.11, 113.73, 73.71, 71.90, 70.68, 70.52,
70.42, 70.34, 70.18, 70.09, 69.81, 69.68, 69.23, 38.32, 38.11, 30.59, 34.07,
34.03, 33.78, 31.99, 31.65, 31.30, 23.36, 9.79 ppm; IR (KBr): n˜ =3274,
1784, 1479, 1203, 1120 cmÀ1; MALDI-TOF MS: m/z: 1241.5 [M+Na]+,
1257.5 [M+K]+; elemental analysis calcd (%) for C79H94O11: C 77.80, H
7.77; found: C 77.69, H 7.90.
Compound 5i-2: Yield 31%; m.p. 128–1308C; 1H NMR: d=8.05 (d, J=
8.9 Hz, 1H), 7.97 (d, J=8.2 Hz, 1H), 7.83 (d, J=5.7 Hz, 1H), 7.80 (d, J=
8.7 Hz, 1H), 7.50 (d, J=8.9 Hz, 1H), 7.53–7.01 (m, 9H), 7.08 and 7.05
(2d, J=2.4 Hz, 1H each), 6.85 and 6.61 (2d, J=2.4 Hz, 1H each), 6.80
and 6.51 (2d, J=2.4 Hz, 1H each), 4.32 (d, 1H; J=14.2 Hz, ArCH2Ar),
4.27 and 3.85 (2d, J=16.2 Hz, 1H each, CH2CO2), 4.15–3.20 (m, 27H),
3.01 (d, J=12.8 Hz, 1H; ArCH2Ar), 2.78 (d, J=12.9 Hz, 1H; ArCH2Ar),
1.69–1.56 (m, 2H), 1.38, 1.36, 1.04, and 1.01 (4s, 9H each), 0.71 ppm (t,
J=7.2 Hz, 3H; CH2CH2CH3); 13C NMR: d=167.98, 155.04, 153.53,
152.93, 152.80, 152.16, 147.42, 145.09, 144.32, 143.91, 143.38, 135.59,
135.42, 133.56, 133.47, 133.01, 132.77, 132.57, 132.13, 132.09, 131.79,
131.75, 130.13, 129.95, 128.77, 128.22, 127.97, 127.95, 127.46, 127.08,
126.57, 126.24, 126.10, 126.08, 126.02, 125.84, 125.50, 125.26, 125.24,
124.58, 123.73, 123.31, 121.95, 118.51, 114.17, 73.98, 71.98, 70.82, 70.62,
70.41, 70.37, 70.32, 70.25, 69.90, 69.55, 38.04, 37.41, 31.08, 30.82, 34.10,
34.02, 33.72, 33.71, 31.84, 31.72, 31.37, 31.32, 23.80, 10.18 ppm; IR (KBr):
n˜ =3275, 1784, 1479, 1203, 1120 cmÀ1; MALDI-TOF MS: m/z: 1241.4
[M+Na]+, 1257.3 [M+K]+; elemental analysis calcd (%) for C79H94O11: C
77.80, H 7.77; found: C 77.86, H 7.79.
Compound 4i-1: Yield 0.061 g, 80%; m.p. 112–1148C; [a]2D5 =À40 (c=0.5
in CHCl3). Compound 4i-2: Yield 0.062 g, 82%; m.p. 112–1148C; [a]D25
+40 (c=0.5 in CHCl3).
=
3-Propoxy-p-tert-butylcalix[4]arene-(1,2)-crown-5, cone conformer (6): A
stirred mixture of 2a (1.7 g, 2.1 mmol), n-propyl iodide (246 mL,
1.2 equiv), and Cs2CO3 (0.822 g, 1.2 equiv) in DMF (80 mL) was heated
at 608C for 6 h. Then 10% HCl (2.5 mL) was added to quench the reac-
tion. After removal of the solvent under reduced pressure, the residue
was partitioned between water and CH2Cl2. The organic layer was dried
with Na2SO4 and the solvent evaporated. The residue was purified by
column chromatography (SiO2, petroleum ether/acetone 20:1) to give 6
as a white solid. Yield 46%; m.p. 236–2388C (CH2Cl2/CH3OH); 1H
NMR: d=7.14 (s, 2H), 7.07 and 7.06 (2d, J=2.3 Hz, 1H each), 6.53 (s,
2H), 6.46 (s, 2H), 5.99 (s, 1H; OH), 4.47 (d, J=13.4 Hz, 1H; ArCH2Ar),
4.47 (d, J=13.4 Hz, 1H; ArCH2Ar), 4.38 (d, J=13.7 Hz, 1H; ArCH2Ar),
4.37 (d, J=13.0 Hz, 1H; ArCH2Ar), 4.34 (d, J=12.7 Hz, 1H; ArCH2Ar),
4.56–3.64 (m, 18H), 3.23 (d, J=14.1 Hz, 2H; ArCH2Ar), 3.18 (d, J=
14.4 Hz, 2H; ArCH2Ar), 2.06–1.85 (m, 2H), 1.34, 1.33, 0.83, and 0.78 (4s,
9H each), 1.12 ppm (t, J=7.2 Hz, 3H; CH2CH2CH3); 13C NMR: d=
153.62, 151.76, 151.24, 150.86, 145.80, 145.49, 144.88, 141.06, 136.01,
135.89, 132.26, 131.93, 131.87, 131.79, 129.02, 128.79, 125.74, 125.58,
125.13, 125.00, 124.98, 124.75, 124.72, 124.61, 77.85, 76.12, 72.08, 71.61,
71.15, 70.52, 69.98, 69.78, 68.38, 34.15, 33.82, 33.68, 33.60, 31.78, 31.68,
31.04, 31.03, 31.05, 30.96, 30.87, 23.44, 11.04 ppm; IR (KBr): n˜ =3546,
1483, 1203, 1120 cmÀ1; MALDI-TOF MS: m/z: 871.4 [M+Na]+, 887.4
[M+K]+; elemental analysis calcd (%) for C55H76O7: C 77.79, H 9.02;
found: C 77.77, H 9.08.
3-Propoxy-4-{[(ethoxycarbonyl)methyl]oxy}-p-tert-butylcalix[4]arene-
(1,2)-crown-5, partial cone conformer (7): Compound
6 (0.671 g,
0.79 mmol), ethyl bromoacetate (879 mL, 10 equiv), and Cs2CO3 (2.58 g,
10 equiv) in DMF (60 mL) were stirred at 708C for 2 d. Then 10% HCl
(6.5 mL) was added to quench the reaction. After removal of the solvent
under reduced pressure, the residue was partitioned between water
(50 mL) and CH2Cl2 (2”50 mL). The organic layer was dried with
Na2SO4 and the solvent evaporated. The residue was purified by column
chromatography (SiO2, petroleum ether/ethyl acetate 10:1) to give 7 as a
1
white solid. Yield 42%; m.p. 238–2408C; H NMR: d=7.25 and 7.22 (2d,
J=2.6 Hz, 1H each), 7.07 and 7.06 (2d, J=2.5 Hz, 1H each), 7.03 and
7.00 (2d, J=2.5 Hz, 1H each), 6.55 (s, 2H), 4.28 (ABq, J=15.0 Hz, 2H;
CH2CO2), 4.30 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.20 (q, J=7.2 Hz, 2H;
CO2CH2CH3), 4.06–3.50 (m, 21H), 4.10 (d, J=12.6 Hz, 1H; ArCH2Ar),
3.98 (d, J=13.2 Hz, 1H; ArCH2Ar), 3.06 (d, J=12.8 Hz, 1H; ArCH2Ar),
3.04 (d, J=12.7 Hz, 1H; ArCH2Ar), 1.90 (m, 2H), 1.44, 1.33, 1.03, and
1.02 (4s, 9H each), 1.29 (t, J=7.2 Hz, 3H; CO2CH2CH3), 0.98 ppm (t, J=
7.5 Hz, 3H; CH2CH2CH3); 13C NMR: d=169.68, 155.08, 153.72, 153.56,
153.40, 144.88, 144.00, 143.70, 143.54, 135.90, 135.21, 132.65, 132.47,
132.33, 132.20, 131.46, 131.44, 128.25, 127.87, 126.07, 125.68, 125.49,
Hydrolysis of compounds 5: general procedure for the preparation of op-
tically pure enantiomers 4: Compound 5–1 or 5–2 (0.08 mmol) in THF
(10 mL) was refluxed with aqueous 10% tetramethylammonium hydrox-
ide solution (5.0 equiv, 0.44 mL) for 12 h. After removal of the solvent,
10% HCl (10 mL) was added. The aqueous solution was extracted with
CH2Cl2 (2”10 mL), And then the organic layer was dried with Na2SO4
and the solvent evaporated. The residue was purified by column chroma-
tography (SiO2, petroleum ether/AcOEt 3:1 to 1:1) to give enantiomeri-
cally pure compound 4–1 or 4–2 as a white solid without recrystallization.
Chem. Eur. J. 2005, 11, 5917 – 5928
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5927

C.-F. Chen, Z.-T. Huang et al.
125.41, 125.39, 125.26, 76.31, 73.22, 71.60, 71.11, 70.94, 70.77, 70.15, 69.94,
69.05, 60.71, 37.40, 37.37, 30.96, 34.04, 33.68, 33.66, 31.76, 31.69, 31.35,
Recogn. 1994, 19, 17–39; b) H. Otsuka, S. Shinkai, Supramol. Sci.
1996, 3, 189–205; c) M. Vysotsky, C. Schmidt, V. Bçhmer, Adv. Su-
pramol. Chem. 2000, 7, 139–233.
23.69, 14.22, 10.55 ppm; IR (KBr): n˜ =1763, 1479, 1201, 1122 cmÀ1
;
MALDI-TOF MS: m/z: 957.5 [M+Na]+, 973.5 [M+K]+; elemental anal-
[2]a) S. Shinkai, T. Arimura, H. Kawabata, H. Murakami, K. Araki, K.
Iwamoto, T. Matsuda, J. Chem. Soc. Chem. Commun. 1990, 1743–
1744; b) K. Iwamoto, A. Yanagi, T. Arimura, T. Matsuda, S. Shinkai,
Chem. Lett. 1990, 1901–1904; c) S. Shinkai, T. Arimura, H. Kawaba-
ta, H. Murakami, K. Iwamoto, J. Chem. Soc. Perkin Trans. 1 1991,
2429–2434; d) S. Pappalardo, S. Caccamese, L. Giunta, Tetrahedron
Lett. 1991, 32, 7747–7750; e) K. Iwamoto, H. Shimizu, K. Araki, S.
Shinkai, J. Am. Chem. Soc. 1993, 115, 3997–4006 (Corrigendum:
1993, 115, 12228); f) G. Ferguson, J. F. Gallagher, L. Giunta, P. Neri,
S. Pappalardo, M. Parisi, J. Org. Chem. 1994, 59, 42–53; g) F.
Arnaud-Neu, S. Caccamese, S. Fuangswasdi, S. Pappalardo, M. F.
Parisi, A. Petringa, G. Principato, J. Org. Chem. 1997, 62, 8041–8048;
h) T. Jin, K. Monde, Chem. Commun. 1998, 1357–1358; i) S. Caccam-
ese, A. Bottino, F. Cunsolo, S. Parlato, P. Neri, Tetrahedron: Asymme-
try 2000, 11, 3103–3112; j) D. Hesek, Y. Inoue, M. G. B. Drew, P. D.
Beer, G. A. Hembury, H. Ishida, F. Aoki, Org. Lett. 2000, 2, 2237–
2240.
[3]a) B. Xu, P. J. Carroll, T. M. Swager, Angew. Chem. 1996, 108, 2238–
2242; Angew. Chem. Int. Ed. Engl. 1996, 35, 2094–2097; b) M. A.
Tairov, M. O. Vysotsky, O. I. Kalchenko, V. V. Pirozhenko, V. I. Kal-
chenko, J. Chem. Soc. Perkin Trans. 1 2002, 1405–1411.
[4]a) C. Dieleman, S. Steyer, C. Jeunesse, D. Matt, J. Chem. Soc. Dalton
Trans. 2001, 2508–2517; b) F. Narumi, W. Yamabuki, T. Hattori, H.
Kameyama, S. Miyano, Chem. Lett. 2003, 32, 320–321.
ysis calcd (%) for C59H82O9: C 75.77, H 8.84; found: C 75.80, H 8.89.
3-Propoxy-4-[(carboxymethyl)oxy]-p-tert-butylcalix[4]arene-(1,2)-crown-
5, partial cone conformer (8): Compound 7 (0.14 g, 0.15 mmol) in THF
(20 mL) was refluxed with aqueous 10% tetramethylammonium hydrox-
ide solution (682 mL, 5 equiv) for 12 h. After removal of the solvent,
10% HCl (20 mL) was added. The aqueous solution was extracted with
CH2Cl2 (2”20 mL) and then the organic layer was dried with Na2SO4
and the solvent evaporated. The residue was crystallized from CH2Cl2/
CH3OH to give 8 as a white solid. Yield 84%; m.p. 143–1458C (CH2Cl2/
CH3OH); 1H NMR: d=7.72 (s, 1H; CO2H), 7.26 (s, 2H), 7.13 and 7.11
(2d, J=2.4 Hz, 1H each), 6.90 and 6.89 (2d, J=2.3 Hz, 1H each), 6.74 (s,
2H), 4.38 (d, J=12.3 Hz, 1H; ArCH2Ar), 4.19 (d, J=12.4 Hz, 1H;
ArCH2Ar), 4.07–3.54 (m, 24H), 3.16 (d, J=12.5 Hz, 1H; ArCH2Ar), 3.14
(d, J=12.4 Hz, 1H; ArCH2Ar), 1.92–1.72 (m, 2H), 1.45 and 1.31 (2s, 9H
each), 1.09 (s, 18H), 0.95 ppm (t, J=7.2 Hz, 3H; CH2CH2CH3); 13C
NMR: d=168.46, 153.59, 153.31, 152.79, 150.83, 145.97, 145.88, 145.44,
145.17, 135.28, 134.82, 134.25, 133.85, 133.11, 132.82, 131.62, 131.55,
127.84, 127.49, 126.92, 126.88, 125.50, 125.37, 124.31, 124.08, 75.98, 72.76,
71.91, 71.40, 70.92, 70.87, 70.29, 70.22, 69.03, 66.25, 38.28, 31.01, 30.58,
34.25, 34.12, 33.84, 33.83, 31.70, 31.58, 31.09, 23.40, 10.48 ppm; IR (KBr):
n˜ =3406, 1759, 1479, 1202, 1122 cmÀ1; MALDI-TOF MS: m/z: 929.4
[M+Na]+, 945.4 [M+K]+; elemental analysis calcd (%) for C57H78O9: C
75.46, H 8.67; found: C 75.25, H 8.55.
[5]Y. D. Cao, J. Luo, Q. Y. Zheng, C. F. Chen, M. X. Wang, Z. T. Huang,
J. Org. Chem. 2004, 69, 206–208.
[6]A. Arduini, A. Casnati, M. Fabbi, P. Minari, A. Pochini, A. R. Sicuri,
R. Ungaro, Supramol. Chem. 1993, 1, 235–246.
[7]C. Jaime, J. de Mendoza, P. Prados, P. M. Nieto, C. Sanchez, J. Org.
Chem. 1991, 56, 3372–3377.
Acknowledgements
We thank the National Natural Science Foundation of China, the Chinese
Academy of Sciences, the Major State Basic Research Development Pro-
gram of China (Grant No. G2000078100) and MOST 2002CCA03100 for
financial support.
[8]S. Caccamese, A. Notti, S. Pappalardo, M. F. Parisi, G. Principato,
Tetrahedron 1999, 55, 5505–5514.
[9]S. Shimizu, A. Moriyama, K. Kito, Y. Sasaki, J. Org. Chem. 2003, 68,
2187–2194.
[1]For reviews on inherently chiral calixarenes and related compounds,
Received: March 10, 2005
see: a) V. Bçhmer, D. Kraft, M. Tabatabai, J. Incl. Phenom. Mol.
Published online: June 23, 2005
5928
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5917 – 5928