Synthesis of oligophenylene-substituted calix[4]crown-4s and their silver(I) ion-induced nanocones formation

Article abstract of DOI:10.1021/jo051896z

A novel series of oligophenylene OPP(n)-substituted calix[4]crown-4s bearing up to three phenylene units, 1a-d, has been efficiently synthesized by means of either microwave-assisted or silver(I) ion-assisted Pd-catalyzed Suzuki cross-coupling of tetraiodocalix[4]crown-4 and the corresponding oligophenylboronic acids. Complexation of OPP(n)-substituted calix[4]crown-4s with silver (I) ion was substantiated by ¹H NMR spectroscopic and high-resolution ESI- or MALDI-TOF- MS studies. The weak binding affinities of OPP(n)-substituted calix[4]crown-4s for silver (I) ion, which were estimated from ¹H NMR titrations with binding association in the range of 30-90 M^-1, allows reversible disassembling in the presence of KI at ambient temperature. Remarkably, the single-crystal X-ray structures of OPP(n)-calix[4]crown-4-Ag⁺ complexes indicate the atypical silver (I) ion-crown ether binding mode resulting in the formation of rigid nanocones with volume created up to ～1500 A³. Our results suggested that despite the weak binding affinity of crown ether ligands for silver (I) ion, this weak interaction is still be useful as a tool to construct supramolecular architectures.

Full text of DOI:10.1021/jo051896z

Synthesis of Oligophenylene-Substituted Calix[4]crown-4s and Their
Silver(I) Ion-Induced Nanocones Formation
Man Shing Wong,*,† Ping Fang Xia,† Pik Kwan Lo,† Xiao Hua Sun,†
Wai Yeung Wong,† and Shaomin Shuang*,‡
Department of Chemistry, Hong Kong Baptist UniVersity, Kowloon Tong, Hong Kong SAR, China, and
School of Chemistry and Chemical Engineering, Institute of AdVanced Chemistry, Shanxi UniVersity,
Taiyuan 030006, China
mswong@hkbu.edu.hk; smshuang@sxu.edu.cn
ReceiVed September 9, 2005
A novel series of oligophenylene OPP(n)-substituted calix[4]crown-4s bearing up to three phenylene
units, 1a-d, has been efficiently synthesized by means of either microwave-assisted or silver(I) ion-
assisted Pd-catalyzed Suzuki cross-coupling of tetraiodocalix[4]crown-4 and the corresponding oligo-
phenylboronic acids. Complexation of OPP(n)-substituted calix[4]crown-4s with silver (I) ion was
1
substantiated by H NMR spectroscopic and high-resolution ESI- or MALDI-TOF- MS studies. The
weak binding affinities of OPP(n)-substituted calix[4]crown-4s for silver (I) ion, which were estimated
1
from H NMR titrations with binding association in the range of 30-90 M-1, allows reversible
disassembling in the presence of KI at ambient temperature. Remarkably, the single-crystal X-ray structures
of OPP(n)-calix[4]crown-4‚Ag+ complexes indicate the atypical silver (I) ion-crown ether binding mode
resulting in the formation of rigid nanocones with volume created up to ∼1500 Å3. Our results suggested
that despite the weak binding affinity of crown ether ligands for silver (I) ion, this weak interaction is
still be useful as a tool to construct supramolecular architectures.
Introduction
can be reliably used to predict and control the formation and
structure of supramolecular architectures are fundamentally
important, since they are essential toward a rational design and
There has been tremendous interest in the design and synthesis
of novel nanoscale supramolecular architectures based on
various noncovalent interactions including metal chelation,
hydrogen bonding, and charge-transfer interactions in the past
two decades as some of these assemblies show great potential
for nanotechnological applications.1 Knowledge and tools that
(1) For recent reviews: (a) Lehn, J. M. Supramolecular Chemistry;
VCH: Weinhein, Germany, 1995. (b) Steed, J. W., Atwood, J. L.
Supramolecular Chemistry; VCH: Weinhein, Germany, 2000. (c) Leininger,
S.; Olenyuk, B.; Stang, P. J. Chem. ReV. 2000, 100, 853-908. (d) Holliday,
B. J.; Mirkin, C. A. Angew. Chem., Int. Ed. 2001, 40, 2022-2043. (e) Prins,
L. J.; Reinhoudt, D. N.; Timmerman, P. Angew. Chem., Int. Ed. 2001, 40,
2382-2426.
† Hong Kong Baptist University.
‡ Shanxi University.
10.1021/jo051896z CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/07/2006
940
J. Org. Chem. 2006, 71, 940-946

Oligophenylene-Substituted Calix[4]crown-4s
an optimization of the functional assemblies. Design of comple-
mentary structural components that can self-assemble into
supramolecular architectures requires building in relatively
strong and directional adhesive forces, as they are important
for the stability of the desirable structure. As a result, the weak
affinity of hard base for soft acid is not often considered to be
useful as a tool to construct supramolecular architectures.
Calix[4]tubes based on bis-calix[4]arene ethers2 and calix-
[4]-bis-crowns3 have been explored and studied by several
groups; however, there are no rigid calix[4]tubes or calix[4]-
cones with extended hydrophobic cavity reported so far. One
of the logical approaches to construct an elongated hollow
structure is to extend the bowl-shaped curvature of the calix-
[4]arene in the cone conformation. Recently, syntheses of several
extended oligophenylenevinyl (OPV)- and oligophenylene
(OPP)-substituted calix[4]arenes end-capped with either alkyl-
sulfanyl or alkylsulfonyl groups have been successfully achieved.4
Nevertheless, simply extending the skeleton with arylenevinyl
or arylene units on the upper rim of calix[4]arene does not create
an enlarged cavity as the conformationally mobile tetraalkylated
calix[4]arene interconverts between two C2V “pinched or flat-
tened” cone conformers in solution at room temperature and
also adopts a pinched cone conformation such as in the solid
state.5
To create a calix[4]arene-derived hollow cavity, our strategy
is first to suppress the mobility of the cone conformer followed
by an opening up of the flattened cavity induced by metal
complexation. To stabilize the cone conformation and introduce
binding sites for metal chelation at the lower rim of calix[4]-
arene, one of the approaches is to introduce a polyether bridge
at the lower rim linked between two distal phenolic rings.6 We
herein describe the efficient protocols for the synthesis of
oligophenylene-substituted 25,27-dipropoxy-calix[4]crown-4s
1a-d and an investigation of silver(I) ion-induced assembling
the soft acid, silver(I) ion, can be useful as a tool to construct
supramolecular architectures: rigid nanocones. The merit of
using such weak binding interaction is that it allows the
reversibility of this assembling process, which can be easily
switched on or off even though this crown ether ligand can
interact with other metal ions such as sodium or lithium ions.
Results and Discussion
Facile syntheses of OPP(n)-substituted 25,27-dipropoxycalix-
[4]arene-crown ethers are summarized in Scheme 1. Chemo-
selective 1,3-dipropylation of calix[4]arene7 was carried out with
an excess of 1-bromopropane and K2CO3 in refluxing CH3CN
affording 2 in 82% yield. Subsequent reaction of 2 with
triethylene glycol ditosylate with an excess of NaH as a base
in DMF afforded 1a in an excellent yield (90%). To extend the
skeleton of calix[4]arene with phenylene units, previously
established palladium-catalyzed Suzuki cross-coupling protocol
was employed.4b,c Iodination of 1a with CF3COO-Ag+/I2 in
refluxing chloroform8 afforded tetraiodocalix[4]arene 3. Cross-
coupling of 3 with various arylboronic acids including 4-me-
thylphenylboronic acid, 4-fluorophenylboronic acid, 4-(tri-
methylsilyl)phenylboronic, phenylboronic acid, and biphenyl-
boronic acid in the presence of a catalytic amount of Pd(PPh3)4
complex heating at 80 °C9 afforded the corresponding arylene-
substituted calix[4]crown-4s 4-6, 1b, or 1c, respectively, in
poor to good yields (Scheme 1). On the other hand, direct
coupling of 3 and terphenylboronic acid under the same
conditions gave no desired product in which only trisubstituted
product was isolated. The reason for unsatisfactory or incomplete
conversion with the conventional protocol is that in contrast to
the conformationally mobile tetraalkoxycalix[4]arenes, the im-
mobility of calix[4]crown-4 skeleton with a pinched cone
conformation further aggravated the steric crowdedness between
partially arylene-substituted calix[4]crown-4s and bulky aryl-
boronic acid particularly for the construction of the fourth OPP
arm. As the preparation of 4-(trimethylsilyl)phenyl-substituted
calix[4]crown-4 afforded very low yield, the previously estab-
lished synthetic approach,4c which required such TMS-
compound as an intermediate, was not explored for the synthesis
OPP(n)-calix[4]crown-4s.
Alternatively, a microwave-assisted coupling protocol10 was
explored. Among various conditions examined, temperature
gradient mode, in which the reaction mixture was first irradiated
at 80 °C for 10 min followed by irradiation at 130 °C for 20-
30 min, was found to have the most efficient conditions for the
cross-coupling. Microwave-assisted Suzuki cross-coupling of
tetraiodocalix[4]arene with terphenylboronic acid in THF af-
forded the desired product 1d in 68% isolated yield. Under the
microwave heating conditions, syntheses of 1b and 1c were
greatly improved with isolated yields of 90% and 75%,
respectively. All the newly synthesized calix[4]crown-4s were
of rigid nanocones. The current work shows for the first time
that the weak affinity of the hard base, crown ether ligand, for
(2) (a) Ikeda, A.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 3102-3110.
(b) Matthews, S. E.; Schmitt, P.; Felix, V.; Drew, M. G. B.; Beer, P. D. J.
Am. Chem. Soc. 2002, 124, 1341-1353.
(3) (a) Thue´ry, P.; Nierlich, M.; Lamare, E.; Dozol, J. F.; Asfari, Z.;
Vicens, J. J. Incl. Phenom. 2000, 36, 375-408. (b) Kim, J. S.; Lee, W. K.;
Kim, J. G.; Suh, I. H.; Yoon, J. Y.; Lee, J. H. J. Org. Chem. 2000, 65,
7215-7218. (c) Kim, S. K.; Sim, W.; Vicens, J.; Kim, J. S. Tetrahedron
Lett. 2003, 44, 805-809. (d) Kim, S. K.; Vicens, J.; Park, K. M.; Lee, S.
S.; Kim, J. S. Tetrahedron Lett. 2003, 44, 993-997. (e) Kim, S. K.; Lee,
J. K.; Lee, S. H.; Lim, M. S.; Lee, S. W.; Sim, W.; Kim, J. S. J. Org.
Chem. 2004, 69, 2877-2880.
(4) (a) Wong, M. S.; Chan, W. H.; Chan, W. Y.; Li, J.; Dan, X.
Tetrahedron Lett. 2000, 41, 9293-9297. (b) Wong, M. S.; Zhang, X. L.;
Chen, D. Z.; Cheung, W. H. Chem. Commun. 2003, 138-139. (c) Wong,
M. S.; Xia, P. F.; Zhang, X. L.; Lo, P. K.; Cheng, Y.-K.; Yeung, K.-T.;
Guo, X.; Shuang, S. M. J. Org. Chem. 2005, 70, 2816-2819.
(5) Ikeda, A.; Tsuzuki, H.; Shinkai, S. J. Chem. Soc., Perkin Trans. 2
1994, 2073-2080.
(6) Arduini, A.; Fabbi, M.; Mantovani, M.; Mirone, L.; Pochini, A.;
Secchi, A.; Ungaro, R. J. Org. Chem. 1995, 60, 1454-1457.
(7) van Loon, J. D.; Arduini, A.; Coppi, L.; Verboom, W.; Pochini, A.;
Ungaro, R.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1990, 55, 5639-
5646.
(8) Timmerman, P.; Verboom, W.; Reinhoudt, D. N.; Arduini, A.; Sicuri,
A. R.; Pochini, A.; Ungaro, R. Synthesis 1994, 185-189.
(9) Suzuki, A. J. Organomet. Chem. 1999, 576, 147-168.
(10) For a recent review: Kappe, C. O. Angew. Chem., Int. Ed. 2004,
43, 6250-6284.
J. Org. Chem, Vol. 71, No. 3, 2006 941

Wong et al.
SCHEME 1. Synthesis of Oligophenylene-Substituted 25,27-Dipropoxycalix[4]arene-Crown Ethersa
a Reagents and conditions: (i) K2CO3, CHCN, reflux, overnight; (ii) NaH, DMF, 80 °C, overnight; (iii) CF3COOAg, CHCl3, reflux, 2 h; (iv) Pd(PPh3)4,
2 M K2CO3, Tol-CH3OH, 80 °C, overnight; (v) Pd(PPh3)4, 2 M K2CO3, Tol-CH3OH or THF, microwave heat: 80 °C, 10 min and then 130 °C, 20-30 min;
(vi) CF3COOAg, Pd(PPh3)4, 2 M K2CO3, THF, 80 °C, 1-2 h.
fully characterized with 1H NMR, 13C NMR, and high-resolution
ESI-MS or MALDI-TOF and found to be in good agreement
with the structures.
As predicted by the MM2 molecular calculations11 and
1
revealed by H NMR studies, 25,27-dipropoxy-calix[4]arene-
crown-4, 1a, and its extended analogues, 1b-d, preferentially
adopt a pinched cone conformation stabilized by π-π interac-
tions with a limited cavity, in which the propoxy-substituted
aryl rings, characterized by the upfield shift of aromatic protons
1
in the H NMR spectrum, are parallel to one another. The
1
variable-temperature H NMR studies further confirmed the
mobility-restricted conformation of these calix[4]crown-4s.
Indeed, the single-crystal X-ray structure of 1a shows a pinched
cone structure with the bridged phenyl rings leaning outward
(Figure 1).
Silver(I) ion has been shown to interact with the π-electron
cloud of cone-conformed tetraalkoxycalix[4]arene resulting in
a cation-π complex.5 However, 1H NMR spectroscopic studies
FIGURE 1. ORTEP drawings of 1a (25% probability). All hydrogen
atoms are omitted for clarity.
showed that there are no observable interactions between
arylene-substituted tetraalkoxycalix[4]arenes and the Ag+ ion.
1a-d as shown in Figure 2 suggesting that they all adopt the
On the other hand, upon an addition of AgCF3COO, there are
same binding mode. In particular, large downfield shifts of
dramatic shifts of proton resonances of calix[4]crown-4s in the
protons upon complexation come from two parallel distal
propoxy-substituted aryl rings of calix[4]crown-4s (i.e., 1a: ∆δ
for m-Ar-H and p-Ar-H ) 0.91 and 0.58 ppm, respectively, in
CDCl3) implying a change in the conformation of the cone
structure. Complexation of calix[4]crown-4s with Ag+ ion was
further confirmed by high-resolution ESI-MS or MALDI-TOF-
1H NMR spectra indicating the presence of interaction between
calix[4]crown-4s and Ag+ ion. The patterns or trends of Ag+-
induced chemical shifts are consistent for all calix[4]crown-4s
(11) MM2 molecular calculations were performed by CS Chem 3D Pro,
Version 5.0.
942 J. Org. Chem., Vol. 71, No. 3, 2006

Oligophenylene-Substituted Calix[4]crown-4s
FIGURE 2. 1H NMR spectra of calix[4]crown-4s 1a-d and the corresponding spectra upon addition of 10 equiv of AgCF3COO in CDCl3 and
CD3COCD3 (10:1).
MS measurements in which the spectra of the solution mixture
of the calix[4]crown-4s and CF3COO-Ag+ shows either a base
peak or peak at m/z 729.2318, 1035.3631, 1339.4852, and
1643.6117 with expected isotopic distribution patterns which
correspond to [1a + Ag]+, [1b + Ag]+, [1c + Ag]+, and [1d
+ Ag]+, respectively (see the Supporting Information).
to be 91, 91, 47, and 30 M-1, respectively, which were
determined by the nonlinear curve fitting analysis12 with data
obtained from H NMR titrations in CDCl3:CD3COCD3 (10:
1
1), indicating that the binding interaction is not very strong.
Even though potassium ion does not form a complex with calix-
[4]crown-4 as revealed from the 1H NMR titration study,
reversibility of this assembling process can easily be achieved
by stirring the complex with KI at ambient temperature in which
To probe the influence of the upper rim functionality on the
binding mode or site, we also prepared a series of para-
substituted phenyl-calix[4]crown-4s, 4-6, bearing either methyl
or fluoro or trimethylsilyl substituent. Consistently, the microwave-
assisted cross-coupling protocol was found to be superior to
the conventional procedure (Scheme 1). An investigation of 1H
NMR spectroscopic studies revealed that complexation, which
is essentially not affected by the electronic and steric properties
of aryl rings substituted at the upper rim, was observed in all
cases (Figure 3). In addition, complexation of 4-6 with the
Ag+ ion was again confirmed by high-resolution ESI-MS or
MALDI-TOF measurements with a base peak or peak at m/z
1091.4313, 1107.3245, and 1323.5214 corresponding to [4 +
Ag]+, [5 + Ag]+, and [6 + Ag]+, respectively. These results
further suggested that the Ag+ ion is bound to the ether ligands
at the lower rim of calix[4]crown-4s. Although the high-
resolution ESI-MS measurements indicate a 1:1 binding stoi-
chiometry in all cases, we were unable to confirm the 1:1
binding stoichiometry of 1a‚AgCF3COO and 1b‚AgCF3COO
complexes in solution by the Job plots based on the change of
1
the complexation-induced chemical shifts disappear in the H
NMR spectrum upon addition of KI.
Consistent to the relatively small cavity size of these calix-
[4]crown-4s, only small cations could bind to them, which was
1
confirmed by H NMR titrations and MALDI-TOF measure-
1
ments. To evaluate their binding affinities and selectivity, H
NMR titrations in CDCl3:CD3COCD3 (10:1) were again used
with various triflate salts. The results are tabulated in Table 1.
In contrast to the silver complexes, the binding of lithium and
sodium ions to the calix[4]crown-4s was kinetically slow relative
to the NMR time scale under the experimental conditions (see
the Supporting Information). Lithium ion shows similar binding
affinity toward the calix[4]crown-4s but sodium ion exhibits
about an order of magnitude stronger binding affinity, which is
attributed to the better cavity size matching of sodium ion. In
addition, these calix[4]crown-4s show excellent Na+
/K+ ion
selectivity as potassium ion does not form a complex with calix-
[4]crown-4s.
1
Remarkably, the single-crystal X-ray structure of the 1a‚Ag+
complex grown from chloroform unambiguously shows the
atypical silver(I) ion-crown ether binding mode, in which the
Ag+ ion is directionally chelated by six ether-type ligands with
bond lengths in the range of 2.31-2.49 Å at the lower rim of
chemical shift of H NMR data, which show an asymmetric
graph deviating from a 1:1 binding stoichiometry (see the
Supporting Information). The discrepancy could arise from the
change in chemical shift induced by conformational change of
calix[4]crown-4s upon Ag+ ion binding, in addition to com-
plexation-induced chemical shift. The binding constants of 1a‚
Ag+, 1b‚Ag+, 1c‚Ag+, and 1d‚Ag+ complexes were estimated
(12) Macomber, R. S. J. Chem. Educ. 1992, 69, 375-378.
J. Org. Chem, Vol. 71, No. 3, 2006 943

Wong et al.
FIGURE 3. 1H NMR spectra of calix[4]crown-4s 4-6 and the corresponding spectra upon addition of 10 equiv of AgCF3COO in CDCl3 and
CD3COCD3 (10:1).
TABLE 1. Binding Constant (M-1)a of Calix[4]crowns-4s with
alleviate the steric crowdedness of the coupling reaction site
and thus could promote the cross-coupling reaction. Indeed, with
Metal Triflates
compd
Ag+
Li+
Na+
K+
an addition of 4 equiv of CF3COO-Ag+ or CH3COO-Ag+, the
cross-coupling reaction of tetraiodocalix[4]crown-4, 3, and
various arylboronic acids proceeded effectively and efficiently
under conventional conditions (see Scheme 1). As anticipated,
such Ag(I) ion-assisted enhancement was not apparent for the
cross-coupling of conformationally mobile tetrakisiodotetra-
alkoxycalix[4]arene, indicating the importance of the immobility
of the calix[4]arene structure. Complexation of tetraiodocalix-
[4]crown-4 with silver(I) ion was evidenced by the high-
resolution MALDI-TOF-MS measurement and 1H NMR studies,
in which the shifts of proton resonances in the 1H NMR spectra
upon addition of CF3COO-Ag+ were very similar to those of
OPP-calix[4]crown-4s studies shown above, suggesting that the
enhancement is related to silver(I) ion-calix[4]crown ether
binding. On the other hand, neither lithium nor sodium ion
exhibit the enhancement effect for the cross-coupling. As a
result, the Ag(I) ion-assisted enhancement could also be
contributed to a certain extent by an increase in the rate of
oxidative insertion of tetraiodocalix[4]crown-4.14
1a
1b
1c
1d
91
91
47
30
74
57
38
b
1181
643
419
141
no
no
no
no
a Determined by 1H NMR titrations in CDCl3:CD3COCD3 (10:1).
b Precipitation of complex.
calix[4]crown-4s (Figure 4). This is clearly different from the
previously reported binding mode of Ag+-calix[4]arene crown
ether complexes in which the Ag+ ion is generally bonded by
three crown ether ligands.13 Strikingly, the four aryl rings are
pseudo-C4V symmetrically conformed creating a rigid hollow
cavity. Both intra- and intermolecular interactions such as π-π
interactions appear insignificant in stabilizing this complex
structure in contrast to the structure of calix[4]crown-4 itself.
Furthermore, the 1b‚Ag+ complex adopts the same binding
mode resulting in the formation of a more extended rigid
hydrophobic cavity with a minor twisting of the phenyl-aryl
rings as revealed from the single-crystal X-ray structure. Such
a rigid nanocone could further be extended with an increase in
phenylene unit. The preliminary X-ray structural results of 1c‚
Ag+ and 1d‚Ag+ complexes consistently indicate the anticipated
silver(I) ion-crown ether binding mode and rigid nanocone
supramolecular structures with a more elongated cavity. The
estimated nanocone volume created in the 1d‚Ag+ complex is
∼1500 Å3.
Conclusions
In summary, we have developed facile and efficient microwave-
assisted as well as silver(I) ion-assisted Pd-catalyzed Suzuki
cross-coupling protocols for the synthesis of oligophenylene-
substituted calix[4]crown-4s. We have also shown that despite
the weak binding affinity of crown ether ligands for the silver-
(I) ion, this weak interaction is useful as a tool to construct
supramolecular architectures, rigid nanocones with volume
created up to ∼1500 Å3 based on silver(I) ion-induced assembly
of oligophenylene-substituted 25,27-dipropoxy-calix[4]crown-
4s.
It was thought that complexation of the Ag(I) ion with calix-
[4]crown-4 leading to the opening up of the pinched cone could
(13) (a) Thue´ry, P.; Nierlich, M.; Arnaud-Neu, F.; Souley, B.; Asfari,
Z.; Vicens, J. Supramol. Chem. 1999, 11, 143-150. (b) Jeunesse, C.;
Dieleman, C.; Steyer, S.; Matt, D. J. Chem. Soc., Dalton Trans. 2001, 881-
892.
(14) Malm, J.; Bjo¨rk, P.; Gronowritz, S.; Ho¨rnfeldt, A.-B. Tetrahedron
Lett. 1992, 33, 2199-2202.
944 J. Org. Chem., Vol. 71, No. 3, 2006

Oligophenylene-Substituted Calix[4]crown-4s
FIGURE 4. ORTEP drawings of (a) 1a‚Ag+ and (b) 1b‚Ag+ (25% probability). All hydrogen atoms are omitted for clarity.
× 10 mL). The combined organic layer was dried with anhydrous
Experimental Section
Na2SO4 and evaporated to dryness. The crude product was purified
by flash chromatography on basic aluminum oxide, using dichlo-
romethane and ethyl acetate for gradient elution. The final product,
1c, was recrystallized from dichloromethane:methanol as colorless
crystals (0.55 g, 75% yield). 1H NMR (400 MHz, CDCl3, 25 °C):
δ 7.75-7.79 (m, 4H), 7.65-7.71 (m, 8H), 7.43-7.48 (m, 8H), 7.36
(t, J ) 7.6 Hz, 2H), 7.00-7.17 (m, 14H), 6.72 (d, J ) 8.4 Hz,
4H), 6.56 (s, 4H), 4.58 (d, J ) 12.8 Hz, 4H), 4.29 (m, 8H), 3.87
(s, 4H), 3.78 (t, J ) 7.2 Hz, 4H), 3.36 (d, J ) 13.2 Hz, 4 H), 2.05
(m, 4H), 1.18 (t, J ) 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3, 25
°C): δ 157.8, 154.5, 140.8, 140.4, 140.2, 139.9, 139.6, 138.4, 136.8,
135.8, 134.9, 132.9, 128.8, 128.4, 127.7, 127.5, 127.4, 127.3, 127.1,
127.0, 126.9, 126.6, 126.5, 77.7, 74.1, 71.8, 70.4, 30.8, 23.7, 11.0.
HRMS (MALD-TOF): calcd for C88H78O6Na 1253.5696; found
1253.5673 (M + Na+). Calcd for C88H78O6Ag 1337.4870; found
1337.44852 (M + Ag+). Mp 298-300 °C.
General Procedure for Silver(I) Ion-Assisted Suzuki Cross-
Coupling. A mixture of tetraiodocalix[4]arene 3 (68 mg, 0.06
mmol) and CF3COO-Ag+ (54 mg, 0.24 mmol) in 14 mL of THF
was stirred for 5 min under nitrogen at room temperature. After
adding 4-terphenylboronic acid (98.7 mg, 0.36 mmol), tetrakis-
(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol), and 2 M
K2CO3 (1 mL), the solution mixture was heated to 80 °C and kept
at that temperature for 1-2 h. After cooling, the product mixture
was poured into water (5 mL) and extracted with dichloromethane
(3 × 20 mL). The combined organic layer was dried with anhydrous
Na2SO4 and evaporated to dryness. The crude product was purified
by flash chromatography on basic aluminum oxide, using dichlo-
romethane and ethyl acetate for gradient elution. The final product,
1d, was recrystallized from dichloromethane:methanol as colorless
crystals (65 mg, 70% yield). 1H NMR (400 MHz, CDCl3, 25 °C):
δ 7.58-7.74 (m, 20H), 7.47 (d, J ) 4.8 Hz, 4H), 7.40 (t, J ) 7.6
Hz, 4H), 7.13-7.30 (m, 20H), 7.04 (d, J ) 8.0 Hz, 4H), 6.67 (d,
J ) 8.4 Hz, 4H), 6.51 (s, 4H), 4.53 (d, J ) 13.2 Hz, 4H), 4.23 (br
s, 8H), 3.81(br s, 4H), 3.72 (t, J ) 6.8 Hz, 4H), 3.32 (d, J ) 13.6
Hz, 4H), 1.99 (m, 4H), 1.13 (t, J ) 7.2 Hz, 6H). 13C NMR (100
MHz, CDCl3, 25 °C): δ 157.9, 154.6, 140.7, 140.3, 140.1, 140.0,
139.6, 139.4, 139.1, 139.1, 137.8, 136.9, 135.0, 134.9, 133.0, 128.8,
128.7, 127.7, 127.6, 127.5, 127.4, 127.4, 127.0, 127.0, 126.9, 126.9,
126.7, 126.5, 126.5, 77.7, 74.1, 71.9, 70.4, 30.9, 23.7, 11.0. HRMS
(MALD-TOF): calcd for C112H94O6Na 1558.6981; found 1558.6971
(M + Na+). Calcd for C112H94O6Ag 1643.613; found 1643.6117
(M + Ag+). Mp 336-338 °C.
2: To a suspension of calix[4]arene (4.25 g, 10 mmol) in CH3-
CN (300 mL) were added 1-iodopropane (18.2 mL, 200 mmol)
and K2CO3 (6.9 g, 50 mmol). After the reaction mixture was heated
at 90 °C with stirring under N2 for 30 h, the solvent was evaporated
to dryness. The residue was dissolved in dichloromethane (150 mL)
and suspension was neutralized by 10% HCl. The organic layer
was concentrated and precipitated with methanol affording a pure
compound 2 as a white solid (4.15 g, 82%). 1H NMR (CDCl3, 270
MHz, 25 °C): δ 8.30 (s, 2H), 7.03 (d, J ) 7.3 Hz, 4H), 6.91 (d, J
) 7.6 Hz, 4H), 6.73 (t, J ) 7.4 Hz, 2H), 6.62 (t, J ) 7.4 Hz, 2H),
4.30 (d, J ) 13.2 Hz, 4H), 3.96(t, J ) 6.2 Hz, 4 H), 3.36 (d, J )
13.0 Hz, 4H), 2.06 (m, 4H), 1.30 (t, J ) 7.3 Hz, 6H). 13C NMR
(CDCl3, 66.5 MHz, 25 °C): δ 153.2, 151.8, 133.4 128.8, 128.3,
128.1, 125.2, 118.9, 78.3, 31.5, 23.6, 11.0. Mp 275-276 °C.
1a: To a solution of 2 (2.04 g, 4.0 mmol) in dry DMF (400 mL)
was added NaH (60% in oil, 288 mg, 12 mmol), which was washed
twice with petroleum ether before use. The mixture was heated at
70 °C and was added with triethylene glycol ditosylate (2 g, 4.37
mmol) in 10 mL of DMF. The reaction mixture was stirred at room
temperature overnight and then heated at 80 °C under N2 for 15 h.
The solvent was evaporated to dryness. The residue was taken up
with HCl (10%) and extracted with ethyl acetate. The organic layer
was dried over Na2SO4, filtered, and evaporated. The residue was
dissolved in dichloromethane and precipitated with ethanol to obtain
a pure white powder of 1a (1.60 g, 67% yield). The filtrate was
evaporated to dryness and then purified by silica gel column
chromatography, using petroleum ether and ethyl acetate (v/v 3:1)
1
as eluent affording another batch of 1a (0.55 g, 23% yield). H
NMR (400 MHz, CDCl3, 25 °C): δ 7.14 (d, J ) 7.2 Hz, 4H), 6.94
(t, J ) 7.6 Hz, 2H), 6.19 (dd, J ) 6.8, 8.4 Hz, 2H), 6.09 (d, J )
7.6 Hz, 4H), 4.40 (d, J ) 13.2 Hz, 4H), 4.12 (m, 8H), 3.77 (s,
4H), 3.66 (t, 4H, J ) 6.8 Hz), 3.16 (d, J ) 13.2 Hz, 4H), 1.93 (m,
4H), 1.12 (t, J ) 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3, 25
°C): δ 158.2, 154.7, 136.8, 133.0, 129.1, 127.4, 122.2, 122.0, 77.1,
73.7, 71.8, 70.4, 30.4, 23.6, 10.9. FAB (MS) m/z 645 (M + Na+).
HRMS (MALD-TOF): calcd for C40H46O6Na 645.3192; found
645.3176 (M + Na+). HRMS (ESI): calcd for C40H46O6Ag
729.2345; found 729.2318 (M + Ag+). Mp 163-165 °C.
General Procedure for Microwave-Assisted Suzuki Cross-
Coupling. A mixture of tetraiodocalix[4]arene 3 (67.6 mg, 0.06
mmol), (1,1′-biphenyl-4-yl)boronic acid (71.3 mg, 0.36 mmol),
tetrakis(triphenylphosphine)palladium(0) (7 mg, 10 mol %), THF
(3 mL), and 2 M K2CO3 (0.8 mL) in a sealed vial was stirred and
irradiated with standard mode for 10 min holding at 80 °C (10-50
W, 100 psi) and then for another 20-30 min holding at 130 °C
(100-300 W, 100 psi). After cooling, the product mixture was
poured into water (5 mL) and extracted with dichloromethane (3
X-ray crystallography: Preliminary examination and intensity
data collection were carried out at 293 K on a CCD area-detector
diffractometer, using graphite-monochromated Mo KR radiation
(λ ) 0.71073 Å). The collected frames were processed with the
J. Org. Chem, Vol. 71, No. 3, 2006 945

Wong et al.
software SAINT.15 The data were corrected for absorption with
the program SADABS.16 The structures were solved by direct
methods and refined by full-matrix least-squares on F2, using the
SHELXTL software package.17 Unless stated otherwise, non-
hydrogen atoms were refined with anisotropic displacement pa-
rameters. Hydrogen atoms were generated in their idealized
positions and allowed to ride on the respective carbon atoms.
Crystal data for 1a: C43H53O6, Mw ) 665.85, crystal size )
0.32 × 0.24 × 0.20 mm3, orthorhombic, space group Pnn2, a )
18.6014(8) Å, b ) 19.2511(9) Å, c ) 10.3718(5) Å, V ) 3714.1-
(3) Å3, Z ) 4, µ(Mo KR) ) 0.078 mm-1. Intensity data were
measured on a Bruker-AXS CCD area-detector diffractometer with
graphite monochromated Mo KR (λ ) 0.71073 Å) radiation, 17807
reflections were measured, 5583 unique, R(int) ) 0.0192. Final R
) 0.0627 and Rw ) 0.1724 for 4647 observed reflections with I >
2σ(I) and GOF ) 1.022.
Å) radiation, 48242 reflections were measured, 16980 unique, R(int)
) 0.0498. Final R1 ) 0.0538 and wR2 ) 0.1377 for 9335 observed
reflections with I > 2σ(I) and GOF ) 1.018.
Crystal data for 1b + Ag: C79H63Ag7Cl3F21O20, Mw ) 2592.73,
crystal size ) 0.24 × 0.16 × 0.10 mm3, triclinic, space group P1h,
a ) 12.5115(11) Å, b ) 14.6376(12) Å, c ) 24.260(2) Å, R )
89.413(2)°, â ) 80.832(2)°, γ ) 87.561(2)°, V ) 4382.1(6) Å3, Z
) 2, µ(Mo KR) ) 1.736 mm-1. Intensity data were measured on
a Bruker-AXS CCD area-detector diffractometer with graphite
monochromated Mo KR (λ ) 0.71073 Å) radiation, 21473
reflections were measured, 14813 unique, R(int) ) 0.0446. Final
R1 ) 0.0616 and wR2 ) 0.1345 for 6419 observed reflections with
I > 2σ(I) and GOF ) 0.915.
Acknowledgment. This work was supported by a Faculty
Research Grant (FRG/03-04/II-58) and a Hong Kong Baptist
University and Earmarked Research Grant (HKBU2019/02P)
from the Research Grants Council, Hong Kong SAR, China.
Crystal data for 1a + Ag: C92H92Ag6F18O24, Mw ) 2570.88,
crystal size ) 0.28 × 0.20 × 0.15 mm3, monoclinic, space group
P21/n, a ) 19.450(6) Å, b ) 25.180(8) Å, c ) 20.114(6) Å, â )
Supporting Information Available: General experimental
details, 1H NMR, 13C NMR, and MS data for 1b and 3-6, results
of 1H NMR titration and Job plots for 1a‚AgCF3COO and
100.102(7)°, V ) 9698(5) Å3, Z ) 4, µ(Mo KR) ) 1.294 mm-1
.
Intensity data were measured on a Bruker-AXS CCD area-detector
1
diffractometer with graphite monochromated Mo KR (λ ) 0.71073
1b‚AgCF3COO complexes, results of H NMR titrations for 1a-
c‚LiCF3COO and 1a-d‚NaCF3COO complexes, 1H NMR and 13
C
NMR spectra of all the newly synthesized calix[4]crown-4s,
and high-resolution MS spectra of the 1a-d‚Ag complexes.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Bruker SMART and SAINT+, Version 6.02a; Siemens Analytical
X-ray Instruments Inc.: Madison, WI, 1998.
(16) Sheldrick, G. M. SADABS; University of Go¨ttingen: Go¨ttingen,
Germany, 1997.
(17) Sheldrick, G. M. SHELXTL-Plus V5.1; Software Reference Manual;
Brucker AXC Inc.: Madison, WI, 1997.
JO051896Z
946 J. Org. Chem., Vol. 71, No. 3, 2006