Synthesis and structural features of sulfur-substituted calix[4]pyrrole for a bottom-up control of the substrate-directed self-assembly of supramolecular structures

Article abstract of DOI:10.1016/j.tet.2011.07.082

The synthesis of six new calix[4]pyrroles, containing sulfur-substituted phenylene units is reported. Halogen-anions and organic aromatic mono- and bis-anions have been selected to explore the formation of host-guest complexes and the possible self-assembly of multi-component structures with the six calixpyrroles. The type of aryl substitution modulates the strength of binding and the selectivity towards different anions and, in some cases, the combination of receptors and bis-anionic precursors, offers a way to build systems in which capsular assemblies are observed.

Full text of DOI:10.1016/j.tet.2011.07.082

Tetrahedron 67 (2011) 7548e7556
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and structural features of sulfur-substituted calix[4]pyrrole for
a bottom-up control of the substrate-directed self-assembly of supramolecular
structures
*
Anna Barattucci, Paola Bonaccorsi, Grazia Cafeo , Franz H. Kohnke, Teresa Papalia
ꢀ
Dipartimento di Chimica Organica e Biologica, Universita di Messina, Viale F. Stagno D’Alcontres 31, 98166 Messina, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of six new calix[4]pyrroles, containing sulfur-substituted phenylene units is reported.
Halogen-anions and organic aromatic mono- and bis-anions have been selected to explore the formation
of hosteguest complexes and the possible self-assembly of multi-component structures with the six
calixpyrroles. The type of aryl substitution modulates the strength of binding and the selectivity towards
different anions and, in some cases, the combination of receptors and bis-anionic precursors, offers a way
to build systems in which capsular assemblies are observed.
Received 24 January 2011
Received in revised form 8 July 2011
Accepted 26 July 2011
Available online 31 July 2011
Keywords:
Calixpyrrole
Ó 2011 Elsevier Ltd. All rights reserved.
Sulfur
Self-assembly
Supramolecular chemistry
1. Introduction
medium.13 Calixpyrrole 2 was also found to form capsular 2:1
complexes with several bis-anions. Recently the capsular self-
Molecular recognition phenomena have been extensively in-
vestigated and exploited for the self assembly of supramolecular
structures.1e3 The possibility of controlling molecular motion
within supramolecular systems lies some steps beyond simple
molecular recognition, and has the attractive goal of constructing
molecular machines.4 Numerous examples have been described in
which molecular motion is controlled by means of changing a given
property of one (or more) of the components of a supramolecular
structure, e.g., the oxidation state of dipyridinium dications in
catenanes and rotaxanes5 or changes in the pH of the medium.6 The
supramolecular chemistry of anions has been comparatively less
investigated in this area as a means to build molecular switches and
machines.7e9 Over the last decade calixpyrroles, calix[4]pyrrole 1
being the simplest example, have emerged as very interesting
molecular receptors that can bind anions.10,11 They also have the
potential to act as ditopic receptors in which, while the anion is
bound by hydrogen bonding interactions with the NH units, the
calix adopts a cone conformation that is capable of hosting cations
(e.g., Csþ).12 Recently we described the first examples of pH-driven
molecular switches based on complexes of calixpyrrole 2 with ar-
omatic bis-anions. In these supramolecular systems different an-
ionic centres could be generated as a function of the pH of the
assembly of calixpyrrole derivatives containing ureido units and
encapsulating pyridine N-oxide derivatives has also been
reported.14e17
As a development of our previous work using receptor 2,13,18 and
taking into account the above, we decided to explore whether
molecular switches and capsules could be assembled using ana-
logues of 2 having different phenylene units as meso-substituents.
In particular, we decided to design and realize the synthesis of
sulfur-substituted calix[4]pyrroles; indeed, sulfur is one of the most
versatile elements in organic synthesis since it can easily be in-
troduced in different substrates as a nucleophile or electrophile
substituent and due to its ability to change oxidation state.19 We
considered it significant that the new receptors contain sulfur-
substituted phenylene units in which the electron density could
be easily ‘adjusted’ without major changes in the proximity of the
NH array, which is responsible for hydrogen-bonding to the anions.
In fact, aromatic substituents at the meso positions may modulate
the complexation strength of calixpyrroles towards anions by
* Corresponding author. Tel.: þ39 090 6765171; fax: þ39 090 393895; e-mail
address: gcafeo@unime.it (G. Cafeo).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.082

A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
7549
providing
either
additional
CH-anion20
or
anione
p
-
derivatives
- and
different electron-densities. The
obtained in equal amounts, and single isomers were isolated by
a combination of flash chromatography and crystallization (overall
yield ca. 39%). Condensation with acetone of either compounds 6 or
a
,
a
- and
a
,
b
-(8e10) shown in Scheme 1, including the
interactions.21,22
a,
a
a,
b-9 derivatives in which the two phenylene rings have
We also considered it important that the meso substituents
contain functional groups that could be exploited to use the cal-
ixpyrroles in the synthesis of linear polymers23 and/or for their
anchoring onto surfaces (e.g., gold),24 the ultimate target being the
potential use of these molecules for the construction of materials
that would produce a mechanical response in the presence of
specific guests.25 Here we report our initial findings on the
hosteguest chemistry with halogen anions and several aromatic
mono and bis-anions for a number of sulfur-substituted cal-
ixpyrrole derivatives that fulfil the characteristics outlined above.
a,
a-
and -isomers were
a,b
7, severally led to the formation of calixes (
a
,a
-þ
a,b-) 8 and 10 in 25
and 40% yields, respectively. The alternative route to 9 by oxidation
of the sulfide units in calixpyrroles 8 gave complex mixtures of
decomposition products.
The stereochemistries of calixes 8 and 10 were attributed on the
basis of their 1H NMR spectra and by comparison with previously
synthesized calixpyrrole derivatives that show structural analo-
2. Results and discussion
gies.13 Assignment of the stereochemistry of
a,a- and a,b-9 was
complicated by the different groups (SR and SO2R) that these two
2.1. Synthesis of the receptors
calixpyrroles exhibit at the two aryl meso-substituents. However,
even in this case, discrimination between
a,
a-9 and
a
,b
-9 was
-9,
The calixpyrroles
a
,
a- and
a,
b-(8e10) were synthesized as
possible on the basis of 1H NMR. Thus, the methyl protons of
a,a
shown in Scheme 1. We selected the thiophenol 3 as the starting
material.26 It was reacted with methyl acrylate in the presence of
a catalytic amount of trimethylbenzylammonium hydroxide (TRI-
TON B) to obtain sulfide 4 in 80% yield.27 The ester function was
considered useful for potential chemical modifications, while the
sulfide moiety could be oxidized, thus modulating the electron-
density of the phenylene unit. Sulfone 5 was easily prepared by
the oxidation of 4 with m-chloroperbenzoic acid (m-CPBA) at room
temperature. We did not stop the oxidation at the sulfoxide stage in
order to avoid stereochemical complications in subsequent steps.
Although the sulfoxide units provide a means to obtain interesting
chiral calixpyrroles, we did not explore this issue in the current
work. The reaction of 4 or 5 with excess pyrrole gave dipyrro-
methanes 6 and 7, respectively, in good yields.
which are directly linked to the aryl-substituted carbon atom of the
macroring, resonate as two singlets at 1.80 and 1.89 ppm, while the
other four methyls appear as two singlets at 1.60 and 1.50 ppm
(1:1:2:2 ratio for the four signals). Two signals at 1.88 and 1.83 ppm
are also observed for the methyl groups on the meso-aryl-
substituted carbon atoms of
a,b-9, while the other four meso-
methyl groups resonate as a singlet at 1.60 ppm (overall intensity
ratio 1:1:4, respectively). The isochrony of the meso-methyl groups
at 1.60 ppm in
rocycle being more similar than in
compound the a,b stereochemistry shown in Scheme 1. These as-
a,
b-9 is consistent with the two faces of the mac-
a,a
-9, hence, we assigned to this
signments were found to be consistent with the 1H NMR data
recorded for the interactions of each isomer with the various an-
ionic and bis-anionic guests (vide infra).
We were aware that the 1:1 condensation with acetone of 6 and
7 would allow the one-pot formation of the six calixpyrrole
The six receptors shown in Scheme 1 constitute a toolbox suited
to explore several issues concerning the molecular recognition of
Scheme 1.

7550
A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
anions. These include the facial selectivity of binding both as
a function of the configuration of the substituents ( - vs -) and
observation of just one NH resonance in the complexes of
-10, and two sets of NH units in -9 is consistent with total
facial selectivity (Fig. 1 and Fig. S7eS9). A competition experiment
for the binding of p-MeOC6H4Oꢁ was conducted between
-8 and
-10. In the presence of 1 equiv of salt the corresponding com-
a,a-8 and
a
,a
a
,b
a
,
a
a,a
as a function of their relative electronic densities (possible anion-
p
interactions).12 Therefore, we selected halogeneanions and organic
aromatic mono- and bis-anions to explore the formation of
hosteguest complexes and the possible self-assembly of multi-
component structures similar to those previously observed with
calixpyrrole derivative 2.13
a,a
a,a
plexes with
a
,a
-8 and
a
,a
-10 were present in 3:7 ratio, indicating
that Ka
tests of a,b-8 and a,b
¼ꢁ5.4 Ka -8 for this anion (Fig.1). In the complexation
a
,a
-10
a,a
-10 with C6H5Oꢁ and p-MeOC6H4Oꢁ, the broad
signal for the two NH units in each of the two free receptors became
two rather sharp low-field signals in each of the two complexes
(Figs. S10b,c and S11b,c). This is consistent with a slow binding on
the NMR time-scale. In fact, at room temperature there is only one
NH resonance in the free receptors since the NH units flip within
2.2. Hosteguest chemistry
The hosteguest chemistry of 8e10 with anions was investigated
by means of 1H NMR titrations using the complexation induced
shifts (CISs). Typically, the interaction between the calixpyroles and
the calixpyrrole cavity and give a time-averaged signal;
a,b-8 and
a,b
-10 have 2 equiv faces when they are not complexed. Upon
the anions produces a downfield shift (higher
resonances. Upon binding, the protons of the organic anions are
shifted to lower values, this effect being larger when the guest is
d values) of the NH
complexation with the anions, a cone conformation of the calix is
stabilized by the NH/Oꢁ bonds, with the anion sitting on one face
of the macrocycle. This situation creates two different sets of NH
units, and in fact two NH signals are observed at low fields for the
d
sandwiched between the meso-aryl substituents in the
a,a-
receptors.
complexes of
treated with p-NO2C6H4Oꢁ only one NH signal is observed in the
complexes ( 11.2 and 11.1, Fig. S10c and S11c, respectively). This is
consistent with a fast exchange of this anion between the two faces
of either of the macrocycles. In these complexes the resonances of
the anionic guests were all shifted up-field.
a,b-8 and a,b-10. However, when a,b-8 or a,b-10 are
2.2.1. Mono-anions. Table 1 shows the mono-anions that were
chosen to study the binding ability of receptors 8e10. Halide anions
(entries 1 and 2) were used as their n-Bu4Nþ salts and spectra were
recorded in CD2Cl2 in order to obtain data that would be compa-
rable with previous studies conducted on calix[4]pyrrole 2.13 All of
the other mono-anions were used as their Csþ salts, generated in
situ with Cs2CO3 in CD3CN (entries 3e5).
d
Receptor
a,b-9 has two configurationally different faces with
respect to the calixpyrrole moiety mean plane. One face contains
Table 1
Mono-anions and receptors used in the complexation tests
a
,
a
-8
a,
b
-8
a
,a
-9
a
,
b-9
a
,
a
-10
a,b-10
1a
2a
3b
4b
5b
Fꢁ
NT
NT
Fꢁ
NT
NT
Fꢁ
NT
NT
Clꢁ
Clꢁ
Clꢁ
PhOꢁ
PhOꢁ
PhOꢁ
PhOꢁ
PhOꢁ
PhOꢁ
p-MeOC6H4Oꢁ
p-NO2C6 H4Oꢁ
p-MeOC6H4Oꢁ
p-NO2C6 H4Oꢁ
NT
p-MeOC6H4Oꢁ
p-NO2C6 H4Oꢁ
NT
p-MeOC6H4Oꢁ
p-NO2C6 H4Oꢁ
p-NO2C6 H4Oꢁ
p-NO2C6 H4Oꢁ
NT: not tested.
a
As n-butylammonium salts in CD2Cl2.
As caesium salt in CD3CN.
b
The binding of fluoride with
a,
a-(8e10) was too strong for NMR
a phenylene unit, that is, more electron-rich (the sulfide side) than
titration. The presence of a coupling constant between fluoride and
the pyrrole NH signal at low field, which appeared as doublets
(Fig. S1eS3), indicated very strong and kinetically slow complexa-
tions on the NMR time scale. The corresponding complexes with
chloride were kinetically fast (Fig. S4eS6) and 1H NMR titration
data could be fitted for the 1:1 models28 to give Ka values of
the other (the sulfone side), therefore, an anionic guest might ex-
hibit facial selectivity. The spectrum of the free a,b-9 showed two
different NH resonances (two pyrrole rings adjacent to the meso-
phenylenesulfone and two pyrrole rings adjacent to the meso-
phenylenesulfide unit, respectively). In the spectra of the com-
plexes of
resonances at low fields that were of equal intensities. Therefore
these anions bind to either faces (sulfide or the sulfone side) of
a,b
-9 and PhOꢁ or p-OMePhOꢁ we observed four NH
74ꢀ7 Mꢁ1, 316ꢀ14 Mꢁ1, 2200ꢀ320 Mꢁ1, for
a,a-8, a,a-9 and a,a-10,
respectively. These values are consistent with an increasingly
electron deficient character of the meso-phenylene unit in these
receptors. A competition experiment for the binding of Fꢁ was
a,b-
9 without face selectivity, forming 1:1 complexes that are kineti-
cally slow on the NMR time-scale (Fig. 2b and c). In the complex of
conducted between
a
,a
-9 and
a,
a
-10 in which an equimolar solu-
a,b
-9 with p-NO2C6H4Oꢁ two low-field NH resonances with a 1:1
tion of these two receptors was titrated with Fꢁ. In the mixture, the
NH resonances of the two complexes were detectable as separate
intensity were observed (Fig. 2d). This originates from a fast ex-
change between the two faces of the receptor, resembling the sit-
doublets. The complexation of
quantitative complexation of
a
,
a
-10.
-9 was observed only after almost
uation already observed for a,b-8 and a,b-10. Therefore, none of
these complexation experiments provided conclusive evidence for
the preferential binding of the tested anions onto either face of
a,
a
The organic mono-anions, shown in Table 1 (entries 3e5), were
chosen because they have a varied charge density at the phenolic
oxygen as well as different charge distributions and electron den-
sities over their aromatic rings. Equimolar solutions of the re-
ceptors and the phenols led to the quantitative formation of 1:1
complexes only upon addition of the base, whilst no interaction
(CISs) was detected with the protonated phenols.
a,b-9.
2.2.2. Bis-anions. The formation of pH-controlled switchable as-
semblies and molecular capsules was investigated using only the
a,a-receptors with the bis-anions listed in Table 2. This choice was
based on a similar study conducted using receptor 2.13 The different
regiochemistries of the hydroxybenzoic acids appeared useful for
studying the steric requirements of capsular assembly. In particular,
The up-field shifts of phenolates in all of the complexes with
a
,a
-(8e10) indicated that binding was occurring on the face con-
taining the aromatic meso-substituents.13 Moreover, the
receptor
a,a-9 with two different groups at the aryl meso-

Fig. 1. Partial 1H NMR spectra (500 MHz, CD3CN) for the competitive binding of p-MeOC6H4OꢁCsþ by receptors
a,a-8 and a,a-10. Black and white squares mark resonances for the
anion included in either receptor
a,
a-8 or receptor
a,
a-10, respectively; (a)
a,
a-8; (b)
a
,a
-8þp-MeOC6H4OꢁCsþ (1:0.85); (c)
a,
a-8þ
a
,
a
-10þp-MeOC6H4OꢁCsþ (1:1:1); (d)
a,a-10. At
20 ꢂC the intensities of the ‘black and white’ H2,6 resonances have a 3:7 ratio.
Fig. 2. Partial 1H NMR spectra (300 MHz, CD3CN, 20 ꢂC) for the binding of PhOꢁCsþ, p-MeOC6H4OꢁCsþ and p-NO2C6H4OꢁCsþ by receptor
a,b-9. Black circles and squares mark the
resonances for the receptor and the anion in each trace, respectively; (a)
b and c the intensities of the four NH resonances are equivalent within experimental error, hence no preference of the anions for either of the two different faces a,b-9 can be detected.
a
,
b
-9; (b)
a
,
b
-9þPhOꢁCsþ (1:1); (c)
a
,
b
-9þp-MeOC6H4OꢁCsþ (1:1); (d)
a
,
a
-9þp-NO2C6H4OꢁCsþ (1:1). In traces

7552
A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
Table 2
The addition to Cs2CO3 in a 1:1 solution of
a,a-10 and p-
Bis-anions (as cesium salts) and receptors used in the complexation tests conducted
in CD3CN
OHeC6H4eCOOH acid in CD3CN induced the formation of a pre-
cipitate, thus preventing solution studies. The same experiment
using DBU generated the carboxylate-bound complex that cleanly
evolved to the phenolate-bound complex with the addition of
a second equivalent of DBU (Fig. S13). We could not detect the
formation of any capsular 2:1 complex. Addition of one more
a
,
a
-8
a
,
a
-9
a,a-10
1
2
m-ꢁOeC6H4eCOOꢁ
p-ꢁOeC6H4eCOOꢁ
m-ꢁOeC6H4eCOOꢁ
p-ꢁOeC6H4eCOOꢁ
m-ꢁOeC6H4eCOOꢁ
p-ꢁOeC6H4eCOOꢁ
equivalent of
a,
a-10 still did not produce the capsule.
The 1:1 solution of
a,a
-9 and m-OHeC6H4eCOOH, in CD3CN, in
substituents of the receptor could lead to interesting stereochem-
ical outcomes (chiral species) as consequence of capsule formation
by a process analogous to that described by Rebek.29
the presence of Cs2CO3 showed the initial formation of the
carboxylate-bound complex (deprotonation of the carboxyl unit is
fast) that cleanly evolved to the phenolate-bound complex (after
sonication). However, even after the addition of one more equiva-
When Cs2CO3 was added to a 2:1 solution of
a,a-10 and m-
OHeC6H4eCOOH in CD3CN, the formation of a kinetically slow
carboxylate-bound complex was observed. Immediately after son-
ication of the sample, two new signals for the pyrrolic NH reso-
nance were detected with a 1:1: ratio, respectively (Fig. 3). The
spectrum is consistent with the formation of a capsular assembly
involving two units of calix and one of the bis-anion. The two
chemical shifts observed for the NH units of the two receptors are
consistent with one being involved in binding the carboxylate unit
and the other binding the phenolate anionic sites, respectively.
Similar results were observed using DBU as the base (13 equiv for
total deprotonation of the acidic sites, Fig. S12). In a solution
(2.5ꢃ10ꢁ3 M) that contained the bis-anion and the calix in a 1:1
stoichiometry there was no evidence for the presence in of any of
the two (carboxylate or phenolate-bound) 1:1 complexes that can
be formed. This observation is consistent with a remarkable syn-
ergic effect of the initial 1:1 calix/bis-anion binding event(s) that
favours the formation of the capsular assembly.
lent of
present in solution (Fig. S14). Hence, no capsular assembly could be
detected for -9 with the bis-anion of the m-OHeC6H4eCOOH.
When Cs2CO3 was added to a 1:1 solution of -9 and p-
OHeC6H4eCOOH in CD3CN, of the carboxylate-bound complex was
initially observed, but the species in solution evolved to give
a complicated mixture of carboxylate-bound and phenolate-bound
complexes and as well as capsular complex. The addition of 1 equiv
a,a-9 the phenolate-bound complex was the only species
a,a
a,a
of
a
,
a
-9 led to the unique presence of capsules in solution (Fig. 4).
The proton resonances of the guest clearly indicate that it fits
inside two receptors (two molecules of -9), that assemble each
a,a
others as two interlocking horseshoes having two different ends
(sulfide and sulfone groups). The interlocked calix units produce
a chiral structure.29 However, the different possible orientations of
the anionic guest (e.g., the direction of the phenolateecarboxylate
vector within the capsule and the different ‘Y’ modes of binding of
the carboxylate with the NH units of one of the calyxes30,31) can
Fig. 3. Partial 1H NMR (300 MHz, CD3CN, 20 ꢂC) spectra of: (a)
addition of the base; (c) same as (b), but after several minutes of sonication. Since each macrocycle in the capsule interacts with either a phenolate or a carboxylate unit, the two
receptors appear as distinguishable units. The NH units which in each macrocycle are hydrogen-bonded to either of the two anionic centres of the guest are assigned. Black circles
mark the resonances for the receptor(s), black squares mark the resonances of m-HOeC6H4eCOOH (a) or of the complexed anion (b and c).
a
,a
-10þm-HO-C6H4eCOOH (2:1); (b)
a
,a
-10þm-HOeC6H4eCOOH (2:1)þCs2CO3 (in excess as a solid) shortly after the

A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
7553
Fig. 4. Partial 1H NMR (500 MHz, CD3CN, 20 ꢂC) spectra of: (a)
addition of the base; (c) same as (b), but after several minutes of sonication; (d)
rocycle in the capsule interacts with either a phenolate or a carboxylate unit, the two receptors appear as distinguishable units. Black circles mark the resonances for the free
receptor in (a) or of the receptor in its 1:1 complex in traces (b) and (c). The white circles mark resonances of the NH units in the capsules (c) and (d). Black squares mark the
resonances of p-OHeC6H4eCOOH (a), or of the anion in its 1:1 complex (b) and (c). The white squares mark the resonance for the encapsulated bis-anion (c and d).
a,
a
-9þp-OHeC6H4eCOOH (1:1); (b)
a
,
a
-9þp-OHeC6H4eCOOH (1:1)þCs2CO3 (in excess as a solid) shortly after the
a
,
a
-9þp-OHeC6H4eCOOH (2:1)þCs2CO3 (in excess as a solid) after sonication. Since each mac-
produce different sets of diastereomeric three-component-
assemblies. The diastereomeric sets of capsules are not distin-
guishable in the 1H NMR spectrum at 500 MHz, and the NH reso-
nances are rather broad and partially overlapping. However,
conclusive evidence for the formation of capsules is provided by the
signals of the aromatic benzo-protons of the calyxes which all ap-
pear at different chemical shifts (diastereotopic) in the racemic
mixtures of ‘supramolecules’. The spectrum is consistent with an
NMR time-averaged structure in which the bis-anion is spinning
around its OeCO2 axis (Fig. 5).
presence of 2 equiv of receptor. This dominant formation of the
three-component ‘supramolecule’ indicates that there is a positive
synergism between the two binding events.
All of the solutions used in the NMR study on the capsules were
also examined by ESI-MS (negative mode). However, none of the
recorded spectra show signals that can be assigned to the presence
of capsules. Indeed, the solutions used in these experiments were
considerably (100 times) more diluted than those used in the NMR
study, and we speculate that the dissociation induced by the high
dilution accounts for this result.
When the m-ꢁOeC6H4eCOOꢁ was used as guest for receptor
a
,a
-8, we always observed two types of NH resonances, typical for
3. Conclusions
phenolate-bound and carboxylate-bound 1:1 complexes. Thus, it
appears that the combination of steric requirements and relative
strengths of interaction of the anionic centres with the NH units
results in a lack of significant selectivity between the two nega-
tively charged sites. No capsular assemblies were detected.
This work demonstrates that the previously studied self as-
sembly of capsular structures from calixpyrrole 2 and selected ar-
omatic bis-anions can be extended to novel derivatives in which the
aryl substituents have different functional groups. The type of aryl
substitution modulates the strength of binding and the selectivity
towards different anions. Moreover, appropriate combinations of
receptors and bis-anionic precursors provides a means to construct
systems in which, under increasing basic conditions, there is
a switch in the mode of binding of the anionic guest or alternatively
capsular assemblies are formed.
Macrocycle
2:1 complexes in the presence of the p-ꢁOeC6H4eCOOꢁ (S15).
When the relative stoichiometry was 1.5:1 ( -8/bis-anion), the
a,a-8 was observed to produce both the 1:1 and the
a,a
phenolate-bound complex and the capsular assembly were ob-
served in a 6:4 ratio, respectively. This proportion was shifted to-
wards the nearly quantitative formation of the capsule in the

7554
A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
Fig. 5. The possible stereoisomers that can be formed by the three-component capsular assemblies made up by two molecules of a,a
-9 and one unit of the bis-anion p-ꢁOH-
C6H4eCOOꢁ assuming that this is spinning along its OeCO2 axis within the capsules as indicated by circular arrows. This spinning is consistent with 1H NMR spectrum of the
mixture at room temperature. The shaded shape within the capsule represents the bis-anion. The rectangular elements represent mirror planes by which the capsules on the same
row are related trough reflection.
4. Experimental section
between the salt and macrocycle were also re-determined from the
intensities of the resonance of the pyrrole protons of the host versus
those of the n-tetrabutylammonium cation. Quantitative 1H NMR
integrations were obtained by the use of appropriate pulse delays in
all cases. Processing the data with the WinEQNMR program28 pro-
duced the reported Ka values for the 1:1 complexation model. For the
complexation experiments, receptor was dissolved in CD3CN to
a concentration of 2.5ꢃ10ꢁ3 M and 1 M equivalent of the neutral
putative guest was added. No cis could be detected that would
suggestinteractionsbetween neutral compoundsand receptors. The
mixtures were treated with a base, namely, Cs2CO3 or DBU. Because
Cs2CO3 is only sparingly soluble in CD3CN, it had to be added as
a solid and was always used in excess. DBU could be added in known
amounts from stock solutions of suitable concentrations, which
provided a practical means of adjusting the concentration of the
base in the mixtures to achieve the stepwise deprotonation of the
carboxylic and phenolic units in the guests.
4.1. General methods and instrumentation
Acetone was distilled from dry CaCO3. Pyrrole was distilled be-
fore use. All other chemicals were of standard reagent grade and
were used without further purification. All air-sensitive and/or
moisture-sensitive reactions were conducted under a dry argon at-
mosphere. Thin layer chromatography (TLC) was conducted on
Merck SiO2 60 F254 plastic plates. Compounds were visualized with
vanillin or by examination under UV light. Column chromatography
was conducted on Aldrich Silica gel 230e400 mesh, 60 A. H and 13C
NMR spectra were recorded on a Varian Gemini-300 at 300 and
75 MHz, respectively, and a Varian 500 spectrometer at 500 and
125 MHz, respectively, using the residual proton resonances of the
solvents (CDCl3, CD2Cl2 and CD3CN) as
were determined on a Kofler hot stage apparatus, and are not
1
ꢁ
d reference. Melting points
corrected.
4.1.2. 3-[(4-Acetylphenyl)thio]-propanoic
acid,
methyl
ester
4.1.1. 1H NMR titrations. The n-tetrabutylammonium salts were
dried in a vacuum oven for at least 24 h. For measurements in CD2Cl2
this was stored on dry alumina and care was taken to minimize
exposure to the atmosphere during sample preparation and titra-
tion. The anions were added as measured volumes of solutions (ca.
0.031 M) in CD2Cl2 to the solution of the macrocycle under in-
vestigation (0.0025 M) in the same solvent (0.7 mL). The sample
volume was kept constant by evaporating the excess solvent with
a flow of dry nitrogen. After each addition the stoichiometric ratios
(4)27. Triton B (40% w/w solution in MeOH, 377 mg, 0.1 mmol) was
added to a solution of thiol 3 (1 g, 6.6 mmol) in dry THF (12 mL) at
ꢁ78 ꢂC and after 50 methyl acrylate (0.570 g, 6.6 mmol) was added.
The mixture was stirred under argon atmosphere at room tem-
perature until complete disappearance of the starting material,
then it was quenched with water and extracted with Et2O. The
organic phase was extracted with aqueous NaCl (saturated solu-
tion), dried (MgSO4) and concentrated to give 3-[(4-acetylphenyl)
thio]-propanoic acid, methyl ester (4) (95%) as a white solid, mp

A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
7555
88 ꢂC; dH (300 MHz, CDCl3); 7.87 and 7.35 (AA0BB0 system, 2ꢃ2H,
fractional crystallization from toluene to separate
from -macrocycles.
a
,
a
-macrocycles
AreH), 3.71 (s, 3H, OCH3), 3.27 (t, J¼7.4 Hz, 2H, CH2eS), 2.70 (t,
J¼7.4 Hz, 2H, CH2eCOOMe), 2.58 (s, 3H, CH3); dC (75 MHz, CDCl3)
197.0 (COOCH3), 171.8 (CO), 142.9, 134.3 (Cq), 128.8, 127.0 (CH), 51.9
(COOCH3), 33.6 (CH2eS), 27.1 (CH2eCOOMe), 26.4 (CH3).
a,b
4.3.1. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-
10
a
,20
a
-bis-[4-(2-methoxycarbonylethyl-1-thio)phenyl]-calix[4]pyr-
-8). 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexam-
,20 -bis-[4-(2-methoxycarbonylethyl-1-thio)phenyl]-ca-
lix[4]pyrrole (
role
(a,a
4.1.3. 3-[(4-Acetylphenyl)sulfonyl]-propanoic acid, methyl ester
(5). m-CPBA in CH2Cl2 (80%, 10 mL/m-CPBA mmol, 3 equiv) was
added to a solution of 3-[(4-acetylphenyl)thio]-propanoic acid,
methyl ester 4 (1 equiv) in CH2Cl2 (10 mL) at ꢁ78 ꢂC. After 1 h the
reaction was quenched by addition of an Na2S2O3 solution (10%,
10 mL). The organic phase was extracted with aqueous NaHCO3
(saturated solution), dried (MgSO4) and concentrated to give 3-[(4-
acetylphenyl)sulfonyl]-propanoic acid, methyl ester (5) (96%) as white
solid, mp 105 ꢂC; dH (300 MHz, CDCl3); 8.15 and 8.05 (AA0BB0 system,
2ꢃ2H, AreH), 3.66 (s, 3H, OCH3), 3.47 (t, J¼7.4 Hz, 2H, CH2eSO2), 2.78
(t, J¼7.4 Hz, 2H, CH2eCOOMe), 2.68 (s, 3H, CH3); dC (75 MHz, CDCl3)
196.5 (COOCH3), 170.2 (CO), 142.2, 141.0 (Cq), 129.0, 128.6 (CH), 52.3
(COOCH3), 51.4 (CH2eSO2), 27.4 (CH2eCOOMe), 26.9 (CH3).
ethyl-10
a
a
a,a-8) was obtained from toluene as a white solid
(Rf: 0.5, 7%), mp 197 ꢂC; dH (300 MHz, CDCl3) 7.28 and 7.05 (AA0BB0
system, 2ꢃ4H, AreH), 7.15 (br s, 4H, NH), 5.92 and 5.76 (2ꢃm,
2ꢃ4H, pyrrole
b
-CH), 3.69 (s, 6H, OCH3), 3.15 (t, J¼7.1 Hz, 4H,
CH2eS), 2.63 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.88, 1.62 and 1.56
(3ꢃs, 3ꢃ6H, CH3); dH (300 MHz, CD2Cl2) 7.30 (br s, 4H, NH), 7.21
and 6.89 (AA0BB0 system, 2ꢃ4H, AreH), 5.92 and 5.64 (2ꢃm,
2ꢃ4H, pyrrole
b-CH), 3.64 (s, 6H, OCH3), 3.12 (t, J¼7.3 Hz, 4H,
CH2eS), 2.60 (t, J¼7.3 Hz, 4H, CH2eCOOMe), 1.86, 1.62 and 1.52
(3ꢃs, 3ꢃ6H, CH3); dH (300 MHz, CD3CN) 7.82 (br s, 4H, NH), 7.18
and 6.84 (AA0BB0 system, 2ꢃ4H, AreH), 5.84 and 5.63 (2ꢃm,
2ꢃ4H, pyrrole
b
-CH), 3.60 (s, 6H, OCH3), 3.12 (t, J¼7.1 Hz, 4H,
CH2eS), 2.58 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.83, 1.63 and 1.48
(3ꢃs, 3ꢃ6H, CH3); dC (75 MHz, CDCl3) 172.1 (COOCH3), 146.8, 138.8,
136.5, 133.1 (Cq), 129.6, 128.3, 106.1, 103.4 (CH), 52.0 (COOCH3),
44.6, 35.3 (Cq), 34.5 (CH2eS), 30.3 (CH3), 29.2 (CH2eCOOCH3), 28.1,
27.9 (CH3); m/z (ESI-MS) calcd for C46H52N4O4S2 M¼788.3, found
[MþH]þ 789.4.
4.2. Dipyrromethane derivatives (6) and (7). General
procedure
TFA (1.5 equiv) was added to a solution of the propanoic acid
methyl ester 4 or 5 (1 equiv) inpyrrole(15 equiv), at 0 ꢂC. Themixture
was stirred under argon atmosphere at room temperature for 1.5 h,
then neutralized (NaOH 1 M) and extracted (CH2Cl2). The organic
phase was dried (MgSO4) and concentrated to fractionally remove
CH2Cl2 and excess pyrrole under reduced pressure. The crude brown
oil was subjected to column chromatography (SiO2, CH2Cl2/EtOAc in
polarity gradient) to give the dipyrromethane derivative.
4.3.2. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-
10
role
ethyl-10
lix[4]pyrrole (a,b-8) was obtained from toluene as a white solid (Rf:
a
,20
b
-bis-[4-(2-methoxycarbonylethyl-1-thio)phenyl]-calix[4]pyr-
-8). 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexam-
,20 -bis-[4-(2-methoxycarbonylethyl-1-thio)phenyl]-ca-
(a,b
a
b
0.48, 6%), mp 187 ꢂC; dH (300 MHz, CDCl3) 7.23 and 7.04 (AA0BB0
system, 2ꢃ4H, AreH), 7.12 (br s, 4H, NH), 5.92 and 5.74 (2ꢃm,
4.2.1. 5-Methyl-5-[4-(2-methoxycarbonylethyl-1-thio)phenyl]dipyrro-
methane (6). After column chromatography (Rf 0.4), 5-methyl-5-[4-
(2-methoxycarbonylethyl-1-thio)phenyl]dipyrromethane (6) (50%)
was obtained as a white solid, mp 102 ꢂC; dH (300 MHz, CDCl3) 7.80
(br s, 2H, NH), 7.25 and 7.04 (AA0BB0 system, 2ꢃ2H, AreH), 6.68 (m,
2ꢃ4H, pyrrole
b
-CH), 3.68 (s, 6H, OCH3), 3.14 (t, J¼7.1 Hz, 4H,
CH2eS), 2.62 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.87 (s, 6H, CH3), 1.52
(s,12H, CH3); dH (300 MHz, CD3CN) 8.00 (br s, 4H, NH), 7.19 and 6.95
(AA0BB0 system, 2ꢃ4H, AreH), 5.83 and 5.75 (2ꢃm, 2ꢃ4H, pyrrole
b-CH), 3.60 (s, 6H, OCH3), 3.12 (t, J¼7.1 Hz, 4H, CH2eS), 2.58 (t,
2H, pyrrole
a
-CH), 6.17 and 5.96 (2ꢃm, 2ꢃ2H, pyrrole
b-CH), 3.67 (s,
J¼7.1 Hz, 4H, CH2eCOOMe), 1.83 (s, 6H, CH3), 1.51 (s, 12H, CH3); dC
(75 MHz, CDCl3) 172.1 (COOCH3), 145.5, 138.6, 136.0, 133.0 (Cq),
129.5, 128.0, 105.7, 103.2 (CH), 51.8 (COOCH3), 44.3, 35.2 (Cq), 34.2
(CH2eS), 29.0 (CH2eCOOCH3), 29.2, 28.9 (CH3); m/z (ESI-MS) calcd
for C46H52N4O4S2 M¼788.3, found [MþH]þ 789.4.
3H, OCH3), 3.14 (t, J¼7.4 Hz, 2H, CH2eS), 2.63 (t, J¼7.4 Hz, 2H,
CH2eCOOMe), 2.03 (s, 3H, CH3); dC (75 MHz, CDCl3) 172.1 (COOCH3),
145.9, 137.0, 133.3 (Cq), 129.7, 128.1, 117.0, 108.3, 106.3 (CH), 51.8
(COOCH3), 44.4 (Cq), 34.2, 28.9 (CH2), 28.7 (CH3).
4.2.2. 5-Methyl-5-[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]di-
pyrromethane (7). After column chromatography (Rf 0.5), 5-methyl-
5-[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]dipyrromethane
(7) (65%) as white solid, mp 135 ꢂC; dH (300 MHz, CDCl3) 7.87 (br s,
2H, NH), 7.80 and 7.32 (AA0BB0 system, 2ꢃ2H, AreH), 6.73 (m, 2H,
4.3.3. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-10
(2-methoxycarbonylethyl-1-sulfonyl)phenyl]-20 -[4-(2-
-9). 5,10,15,
-[4-(2-methoxy
a-[4-
a
methoxycarbonylethyl-1-thio)phenyl]-calix[4]pyrrole
20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-10
(a,a
a
carbonylethyl-1-sulfonyl)phenyl]-20a-[4-(2-methoxycarbonylethyl-
pyrrole
a
-CH), 6.19 and 5.96 (2ꢃm, 2ꢃ2H, pyrrole
b-CH), 3.64 (s, 3H,
1-thio)phenyl]-calix[4]pyrrole (
a,a-9) was obtained as a white solid
OCH3) 3.42 (t, J¼7.4 Hz, 2H, CH2eSO2), 2.77 (t, J¼7.4 Hz, 2H,
CH2eCOOMe), 2.08 (s, 3H, CH3); dC (75 MHz, CDCl3) 170.4 (COOCH3),
154.3, 136.6, 135.8 (Cq), 128.5, 127.9, 117.7, 108.5, 106.8 (CH), 52.3
(COOCH3), 51.4 (CH2eSO2), 45.0 (Cq), 28.5 (CH3), 27.6 (CH2eCO).
(Rf: 0.60, 6%) from toluene, mp 124 ꢂC; dH (300 MHz, CDCl3) 7.76 and
7.19 (AA0BB0 system, 2ꢃ2H, AreH), 7.39 and 7.35 (2ꢃbr s, 2ꢃH, NH),
7.22 and 6.89 (AA0BB0 system, 2ꢃ2H, AreH), 5.93, 5.62 and 5.59
(4ꢃm, 4ꢃ2H, pyrrole -CH), 3.67 and 3.65 (2ꢃs, 2ꢃ3H, OCH3), 3.41
b
(t, J¼7.1 Hz, 2H, CH2eSO2), 3.13 (t, J¼7.1 Hz, 2H, CH2eS), 2.76 and
2.62 (2ꢃt, J¼7.1 Hz, 2ꢃ2H, CH2eCOOMe), 1.90 and 1.87 (2ꢃs, 2ꢃ3H,
CH3), 1.62 and 1.56 (2ꢃs, 2ꢃ6H, CH3); dH (300 MHz, CD2Cl2) 7.72 and
7.19 (AA0BB0 system, 2ꢃ2H, AreH), 7.32 and 7.29 (2ꢃbr s, 2ꢃH, NH),
7.21 and 6.90 (AA0BB0 system, 2ꢃ2H, AreH), 5.94 and 5.63 (4ꢃm,
4.3. Macrocycles
procedure
a,a-(8e10) and a,b-(8e10). General
TFA (5 equiv) was added to a solution of dipyrromethane 6
(1 equiv) and dipyrromethane 7 (1 equiv) in dry acetone (0.14 M), at
0 ꢂC. The mixture was stirred under argon atmosphere at room
temperature for 1 h, then it was neutralized (NaOH 1 M) and
extracted (CH2Cl2). The organic phase was dried (MgSO4), concen-
trated and the brown oil was subjected to column chromatography
4ꢃ2H, pyrrole
b
-CH), 3.65 and 3.62 (2ꢃs, 2ꢃ3H, OCH3), 3.40 (t,
J¼7.2 Hz, 2H, CH2eSO2), 3.12 (t, J¼7.2 Hz, 2H, CH2eS), 2.71 and 2.61
(2ꢃt, J¼7.2 Hz, 2ꢃ2H, CH2eCOOMe),1.91 and 1.86 (2ꢃs, 2ꢃ3H, CH3),
1.63 and 1.53 (2ꢃs, 2ꢃ6H, CH3); dH (300 MHz, CD3CN) 7.90 and 7.88
(2ꢃbr s, 2ꢃH, NH), 7.71 and 7.14 (AA0BB0 system, 2ꢃ2H, AreH), 7.19
and 6.85 (AA0BB0 system, 2ꢃ2H, AreH), 5.87 and 5.64 (4ꢃm, 4ꢃ2H,
(SiO2, CH2Cl2/EtOAc, 95:5) to give the mixture of the
a-a and the a-
b
isomers of each macrocycle. This mixture was then subjected to
pyrrole
b-CH), 3.59 and 3.54 (2ꢃs, 2ꢃ3H, OCH3), 3.41 (t, J¼7.1 Hz, 2H,

7556
A. Barattucci et al. / Tetrahedron 67 (2011) 7548e7556
CH2eSO2), 3.12 (t, J¼7.1 Hz, 2H, CH2eS), 2.63 and 2.58 (2ꢃt, J¼7.1 Hz,
2ꢃ2H, CH2eCOOMe), 1.89 and 1.83 (2ꢃs, 2ꢃ3H, CH3), 1.64 and 1.51
(2ꢃs, 2ꢃ6H, CH3), dC (75 MHz, CDCl3) 172.1, 170.9 (COOCH3), 154.1,
145.5, 139.5, 138.7, 136.7, 136.4, 135.2, 133.4 (Cq), 129.6, 128.7, 128.4,
128.0, 106.5, 105.9, 103.7, 103.5 (CH), 52.7, 52.6 (COOCH3), 51.7
(CH2eSO2), 45.2, 44.6, 44.6, 35.5 (Cq), 34.3 (CH2eS), 29.6, 29.4, 29.2
(CH3), 29.1, 28.0 (CH2eCOOCH3), 28.0 (CH3); m/z (ESI-MS) calcd for
C46H52N4O6S2 M¼821.06, found [MþH]þ 821.5.
2.77 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.92 (s, 6H, CH3), 1.56 (s, 12H,
CH3); dH (300 MHz, CD3CN) 8.00 (br s, 4H, NH), 7.72 and 7.20 (AA0BB0
system, 2ꢃ4H, AreH), 5.87 and 5.82 (2ꢃm, 2ꢃ4H, pyrrole
b-CH), 3.53
(s, 6H, OCH3), 3.41 (t, J¼7.1 Hz, 4H, CH2eSO2), 2.62 (t, J¼7.1 Hz, 4H,
CH2eCOOMe),1.88 (s, 6H, CH3),1.53 (s,12H, CH3); dC (75 MHz, CDCl3)
170.4 (COOCH3), 153.6, 139.1, 136.5, 135.0 (Cq), 128.4, 127.8, 106.2,
103.5 (CH), 52.3 (COOCH3), 51.4 (CH2eSO2), 45.0, 35.3 (Cq), 30.2
(CH2eCOOCH3), 29.2, 27.6 (CH3); m/z (ESI-MS) calcd for
C46H52N4O8S2 M¼852.3, found [MþH]þ 853.2.
4.3.4. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-10
[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]-20 -[4-(2-
methoxycarbonylethyl-1-thio)phenyl]-calix[4]pyrrole ( -9). 5,10,15,
20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-10 -[4-(2-methoxy-
carbonylethyl-1-sulfonyl)phenyl]-20 -[4-(2-methoxycarbonylethyl-
1-thio)phenyl]-calix[4]pyrrole ( -9) was obtained as a white solid
a-
b
Acknowledgements
a,b
a
This work was funded by Messina University.
b
a,b
Supplementary data
(Rf: 0.60, 5%) from toluene, mp 190 ꢂC; dH (300 MHz, CDCl3) 7.77 and
7.24 (AA0BB0 system, 2ꢃ2H, AreH), 7.27 and 7.26 (2ꢃbr s, 2ꢃH, NH),
7.28 and 7.04 (AA0BB0 system, 2ꢃ2H, AreH), 5.93, 5.78 and 5.73
Supplementary material contains the figures for the partial 1H
NMR spectra cited in the main text as S1eS15. Supplementary data
associated with this article can be found, in the online version, at
doi:10.1016/j.tet.2011.07.082.
(4ꢃm, 4ꢃ2H, pyrrole -CH), 3.68 and 3.64 (2ꢃs, 2ꢃ3H, OCH3), 3.42
b
(t, J¼7.1 Hz, 2H, CH2eSO2), 3.15 (t, J¼7.1 Hz, 2H, CH2eS), 2.76 and
2.63 (2ꢃt, J¼7.1 Hz, 2ꢃ2H, CH2eCOOMe), 1.91 and 1.87 (2ꢃs, 2ꢃ3H,
CH3), 1.54 (s, 12H, CH3); dH (300 MHz, CD3CN) 7.99 and 7.90 (2ꢃbr s,
2ꢃH, NH), 7.71 and 7.19 (AA0BB0 system, 2ꢃ2H, AreH), 7.19 and 6.94
References and notes
(AA0BB0 system, 2ꢃ2H, AreH), 5.86 and 5.79 (4ꢃm, 4ꢃ2H, pyrrole
b-
1. Jin, P.; Dalgarno, S. J.; Atwood, J. L. Coord. Chem. Rev. 2010, 254, 1760e1768.
2. Dalgarno, S. J. Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2009, 105, 190e205 and
references therein.
3. Meyer, C. D.; Joiner, C. S.; Stoddart, J. F. Chem. Soc. Rev. 2007, 36, 1705e1723.
4. Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72e191.
5. Loeb, S. J. Chem. Soc. Rev. 2007, 36, 226e235.
CH), 3.60 and 3.53 (2ꢃs, 2ꢃ3H, OCH3), 3.41 (t, J¼7.1 Hz, 2H,
CH2eSO2), 3.12 (t, J¼7.1 Hz, 2H, CH2eS), 2.62 and 2.58 (2ꢃt, J¼7.1 Hz,
2ꢃ2H, CH2eCOOMe), 1.88 and 1.83 (2ꢃs, 2ꢃ3H, CH3), 1.52 (s, 12H,
CH3); dC (75 MHz, CDCl3) 172.3, 171.4 (COOCH3), 154.1, 145.6, 139.5,
138.7, 136.7, 136.5, 135.2, 133.4 (Cq), 129.8, 128.7, 128.3, 128.0, 106.5,
105.9, 103.7, 103.5 (CH), 52.6, 52.5 (COOCH3), 51.7 (CH2eSO2), 45.2,
44.6, 35.5, 34.5 (Cq), 29.6, 29.4, 29.3 (CH3), 29.3, 27.9 (CH2eCOOCH3);
m/z (ESI-MS) calcd for C46H52N4O6S2 M¼821.06, found [MþH]þ
821.5.
6. Leung, KC.-F.; Chak, C.-P.; Lo, C.-M.; Wong, W.-Y.; Xuan, S.; Cheng, C. H. K. Chem.
dAsian J. 2009, 4, 364e381.
7. Nielsen, K. A.; Cho, W.-S.; Sarova, G. H.; Petersen, B. M.; Bond, A. D.; Becher, J.;
Jensen, F.; Guldi, D. M.; Sessler, J. L.; Jeppesen, J. O. Angew. Chem., Int. Ed. 2006,
45, 6848e6853.
8. Nielsen, K. A.; Sarova, G. H.; Martin-Gomis, L.; Fernandez-Lazaro, F.; Stein, P. C.;
Sanguinet, L.; Levillain, E.; Sessler, J. L.; Guldi, D. M.; Sastre-Santos, A.; Jeppesen,
J. O. J. Am. Chem. Soc. 2008, 130, 460e462.
9. Huang, Y. L.; Hung, W.-C.; Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Angew.
Chem., Int. Ed. 2007, 46, 6629e6633.
10. Gale, P. A.; Sessler, J. L.; Kral, V. Chem. Commun. 1998, 1e8 and references
therein.
4.3.5. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-
10
pyrrole (
methyl-10
nyl]-calix[4]pyrrole (a,a-10) was obtained as a white solid (Rf:
a
,20
a
-bis[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]-calix[4]
-10). 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexa-
,20 -bis[4-(2-methoxycarbonylethyl-1-sulfonyl)phe-
a,a
a
a
11. Gale, P. A.; Anzenbacher, P., Jr.; Sessler, J. L. Coord. Chem. Rev. 2001, 222, 57e102.
12. Wintergerst, M. P.; Levitskaia, T. G.; Moyer, B. A.; Sessler, J. L.; Delmau, L. H. J.
Am. Chem. Soc. 2008, 130, 4129e4139.
0.40, 8%) from toluene, mp 160 ꢂC. dH (300 MHz, CDCl3) 7.76 and
7.18 (AA0BB0 system, 2ꢃ4H, AreH), 7.27 (br s, 4H, NH), 5.96 and
13. Cafeo, G.; Kohnke, F. H.; Valenti, L.; White, A. J. P. Chem.dEur. J. 2008, 14,
11593e11600.
5.61 (2ꢃm, 2ꢃ4H, pyrrole
b-CH), 3.66 (s, 6H, OCH3), 3.42 (t,
ꢂ
14. Chas, M.; Gil-Ramírez, G.; Escudero-Adan, E. C.; Benet-Buchholz, J.; Ballester, P.
Org. Lett. 2010, 12, 1740e1743.
J¼7.1 Hz, 4H, CH2eSO2), 2.77 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.91,
1.64 and 1.56 (3ꢃs, 3ꢃ6H, CH3); dH (300 MHz, CD2Cl2) 7.73 and
7.18 (AA0BB0 system, 2ꢃ4H, AreH), 7.35 (br s, 4H, NH), 5.95 and
15. Gil-Ramírez, G.; Chas, M.; Ballester, P. J. Am. Chem. Soc. 2010, 132, 2520e2521.
16. Verdejo, B.; Gil-Ramírez, G.; Ballester, P. J. Am. Chem. Soc. 2009, 131, 3178e3179.
17. Ballester, P.; Gil-Ramírez, G. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10455e10459.
18. Bruno, G.; Cafeo, G.; Kohnke, F. H.; Nicolo, F. Tetrahedron 2007, 63,
10003e10010.
19. Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-O.; Noyori, R. Tetrahedron 2001, 57,
2469e2476.
20. Berryman, O. B.; Bryantsev, V. S.; Stay, D. P.; Johnson, D. W.; Hay, B. P. J. Am.
Chem. Soc. 2007, 129, 48e58.
21. Gil-Ramirez, G.; Escudero-Adan, E. C.; Benet-Buchholz, J.; Ballester, P. Angew.
Chem., Int. Ed. 2008, 47, 4114e4118.
22. Yaroslav, S.; Rosokha, S. V.; Lindeman, S. V.; Rosokha, Kochi, J. K. Angew. Chem.,
Int. Ed. 2004, 43, 4650e4652.
23. Aydogan, A.; Coady, D. J.; Kim, S. K.; Akar, A.; Bielawski, C. W.; Marquez, M.;
Sessler, J. L. Angew. Chem., Int. Ed. 2008, 47, 9648e9652.
24. Jensen, L. G.; Nielsen, K. A.; Breton, T.; Sessler, J. L.; Jeppesen, J. O.; Levillain, E.;
Sanguinet, L. Chem.dEur. J. 2009, 15, 8128e8133.
5.63 (2ꢃm, 2ꢃ4H, pyrrole
b-CH), 3.62 (s, 6H, OCH3), 3.39 (t,
J¼7.1 Hz, 4H, CH2eSO2), 2.71 (t, J¼7.1 Hz, 4H, CH2eCOOMe), 1.91,
1.64 and 1.54 (3ꢃs, 3ꢃ6H, CH3); dH (300 MHz, CD3CN) 7.86 (br s,
4H, NH), 7.71 and 7.14 (AA0BB0 system, 2ꢃ4H, AreH), 5.88 and
5.64 (2ꢃm, 2ꢃ4H, pyrrole
b-CH), 3.54 (s, 6H, OCH3), 3.41 (t,
J¼7.3 Hz, 4H, CH2eSO2), 2.63 (t, J¼7.3 Hz, 4H, CH2eCOOMe), 1.89,
1.65 and 1.49 (3ꢃs, 3ꢃ6H, CH3); dC (75 MHz, CDCl3) 170.4
(COOCH3), 154.7, 138.9, 136.4, 135.2 (Cq), 128.5, 127.5, 106.3, 103.4
(CH), 52.3 (COOCH3), 51.3 (CH2eSO2), 44.9, 35.1 (Cq), 30.0 (CH3),
27.6 (CH2eCOOCH3), 27.4, 27.4 (CH3); m/z (ESI-MS) calcd for
C46H52N4O8S2 M¼852.3, found [MþH]þ 853.2.
25. Tipple, C. A.; Lavrik, N. V.; Culha, M.; Headrick, J.; Datskos, P.; Sepaniak, M. J.
Anal. Chem. 2002, 74, 3118e3126.
4.3.6. 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexamethyl-
26. De Collo, T. V.; Lees, W. J. J. Org. Chem. 2001, 66, 4244e4249.
27. Baskin, J. M.; Wang, Z. Tetrahedron Lett. 2002, 43, 8479e8483.
28. Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311e312.
10
pyrrole (
methyl-10
calix[4]pyrrole (a,b-10) was obtained as a white solid (Rf: 0.40, 7%)
a
,20
b
-bis[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]-calix[4]
-10). 5,10,15,20,22,24-Hexahydro-5,5,10,15,15,20-hexa-
,20 -bis[4-(2-methoxycarbonylethyl-1-sulfonyl)phenyl]-
a,b
a
ꢀ
29. See for example: Rivera, J. M.; Martõn, T.; Rebek, J., Jr. J. Am. Chem. Soc. 2001,
b
123, 5213e5220 for an intriguing example of chiral capsules self assembled
from calixpyrrole derivatives see also Ref. 14.
30. Sessler, J. L.; An, D.; Cho, W.-S.; Lynch, V.; Yoon, D.-W.; Hong, S.-J.; Lee, C.-H. J.
Org. Chem. 2005, 70, 1511e1517.
31. Cafeo, G.; Kohnke, F. H.; White, A. J. P.; Garozzo, D.; Messina, A. Chem.dEur. J.
2007, 13, 649e656.
from toluene, mp 220 ꢂC. dH (300 MHz, CDCl3) 7.80 and 7.33 (AA0BB0
system, 2ꢃ4H, AreH), 7.26 (br s, 4H, NH), 5.96 and 5.76 (2ꢃm, 2ꢃ4H,
pyrrole
b-CH), 3.65 (s, 6H, OCH3), 3.43 (t, J¼7.1 Hz, 4H, CH2eSO2),