Selective synthesis of two constitutionally isomeric oriented calix[6]arene-based rotaxanes

Article abstract of DOI:10.1002/anie.200461336

Only in apolar media is the calix[6]arene wheel threaded from its upper rim by asymmetric bipyridinium axles. This leads to the formation of oriented pseudorotaxanes. Their stoppering with a different stopper yields rotaxanes characterized by the unequivo

Full text of DOI:10.1002/anie.200461336

Communications
Rotaxane Synthesis
Selective Synthesis of Two Constitutionally
Isomeric Oriented Calix[6]arene-Based
Rotaxanes**
Arturo Arduini,* Flavio Ciesa, Marcello Fragassi,
Andrea Pochini, and Andrea Secchi
Rotaxanes are key compounds for the construction of
synthetic molecular machines.[1,2] In spite of the remarkable
achievements in their synthesis, as well as in the control of the
movement of the wheel along the dumbbell component,[3] the
synthesis of rotaxanes endowed with an unequivocal and
predetermined relative orientation of the wheel/dumbbell
systems still represents a relatively unexplored field.[4] In fact,
the structure of the cyclic component employed is often
related to that of a two-dimensional macrocycle, such as a
crown ether, or three-dimensional symmetrical hosts, such as
cucurbitols,[5] and thus have degenerate properties on the two
sides of the wheel that face the two identical[6] or different[7]
stoppers of the dumbbell. In the cases where the three-
dimensional and nonsymmetrical cyclodextrins are used as
the wheel, an axle can thread the cyclodextrin from both rims,
thus leading to a mixture of orientational pseudorotaxane
isomers[8] in which the orientation of the cyclodextrin along
the axle is virtually unpredictable.[9] It could, however, be
foreseen that a predetermined orientation of the components
within these interlocked systems could endow devices with
new properties.
A relatively new type of wheel that can be used in this
context is the calix[6]arene platform. We have shown that
triphenylureidocalix[6]arene derivatives can act as heterodi-
topic receptors and form remarkably stabile pseudorotaxanes
[10]
with dioctylviologen salts (Ks = 1.3 ꢀ 106 mÀ1
)
as well as a
calixarene-based rotaxane based on this axle/wheel dyad.[11]
The binding properties of triphenylureidocalix[6]arene (1)
were used to address the threading of an asymmetrical
dipyridinium axle that threads the wheel exclusively from the
upper rim in the apolar solvent C6D6 to yield an oriented
pseudorotaxane.[12]
Herein it is demonstrated that the binding features of 1
can be exploited to control the orientation of the pseudo-
rotaxane stoppers by using two different stoppers to yield an
asymmetric [2]rotaxane having an unequivocal orientation of
the wheel with respect to the different stoppers, and that an
[*] Prof. Dr. A. Arduini, F. Ciesa, Dr. M. Fragassi, Prof. Dr. A. Pochini,
Dr. A. Secchi
Dipartimento di Chimica Organica ed Industriale dell’Universitꢀ
Parco Area delle Scienze 17/a, 43100 Parma (Italy)
Fax: (+39)0521-905-472
E-mail: arturo.arduini@unipr.it
[**] This research was partly supported by MIUR (Supramolecular
Devices Project) and FIRB (Manipolazione Molecolare per Mac-
chine Nanometriche). We thank the Centro Interdipartimentale di
Misure “G. Casnati” for NMR measurements.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200461336
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Chemie
axle based on the 4,4’-bipyridyl group can also thread through
the wheel from its lower rim.
The design of the axial component was based on the
observations that the position of the two identical diphenyl-
acetyl stoppers of a calix[6]arene-based rotaxane with respect
to the calixarene rims can be established by NMR techni-
ques.[12]
Axle 5a, in which the 4,4’-bipyridyl unit is functionalized
with two C6 alkyl chains, one of which bears a diphenylacetyl
stopper at one side and the other an alcoholic OH group to be
used for further stoppering, was synthesized from 6-hydroxy-
hexyl tosylate 2 in 12% overall yield according to Scheme 1.
Wheel 1 was added to a solution of 5a in toluene to effect the
threading reaction. An excess of dicyclohexylacetyl chloride
was added to the homogeneous deep red solution thus
obtained to stopper the alcoholic OH group of the pseudo-
rotaxane 7a (Scheme 2). Rotaxane 8 was isolated in 25%
yield after chromatographic separation.
Scheme 1. a) R1Cl, CH2Cl2, reflux, 2 h; b) 4,4’-dipyridine, CH3CN, reflux,
24 h; c) 2, CH3CN, reflux, 48 h (11 and 8% overall yield for 5a and 5b,
respectively); d) 4b, 3a, CH3CN, reflux, 8 h. Cy=cyclohexyl, Ts=tol-
uene-4-sulfonyl.
Dumbbell 6 was also synthesized for comparison and
enable the structure of 8 to be established (Scheme 1). The
1H NMR spectrum of 8 in C6D6 shows that the calixarene
Scheme 2. a) Toluene, reflux; b) Cy2CHCOCl, toluene; c) Ph2CHCOCl, toluene.
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279

Communications
wheel rearranges and assumes a more-stiffened cone struc-
At this point a question came apparent: are these results
sufficient to exclude the threading of some of the axles 5a or
5b from the lower rim, or is this direction of threading
prevented because of the insufficient size of the calix[6]arene
annulus for these guests? Acetonitrile should decrease the
extent of ion pairing of the axle and hence limit the magnitude
of the pivoting role exerted by the ureido groups of the wheel
during threading.
ture. The downfield shift of almost Dd = 2 ppm of the
resonances of the six NH protons indicates their involvement
in hydrogen bonding with the two tosylate anions of 5a, as
also shown by X-ray structural data.[13] The position of the
calixarene along the axle was established by looking at the
variation in the chemical shifts of the protons of the dumbbell
portion between C1 and C1’ relative to those of 6 (see
Scheme 2 for numbering). In particular, the protons from C2
to C6’ in 8 undergo a substantial upfield shift, while those
from C5’ to a’ are downfield shifted to a much smaller extent.
The relative orientation of the dumbbell C6 spacers with
respect to the calixarene rims were established through
ROESY experiments, which showed cross peaks between
protons 4 and 5 of the axle and protons m, n, and o of the
wheel (see Supporting Information).
The lack of ROE cross peaks between the two different
stoppers and the corresponding hexyl chains, or with protons
of the wheel, precluded the existence of equivalent matching
spacer—stopper groups. Nevertheless, the presence of only
one signal for proton a at d = 5.24 ppm in the NMR spectrum
of 8[12] enables it to be assumed that the diphenylacetyl
stopper is positioned at the upper rim of the wheel, while the
dicyclohexyl one points toward the lower rim of the calix-
arene.
Pseudorotaxane formation in CD3CN was thus studied by
1H NMR spectroscopy by equilibrating 1 and 5a in a 1:1
molar ratio. In the spectrum of the solution thus obtained,
most of the signals appeared as broad peaks and this prevents
accurate assignment. However, the presence of three singlets
at d = 5.11, 5.13, and 5.14 ppm (relative ratio 9:59:32) in the
region where the proton a of the diphenylacetyl moiety
resonates suggested that this proton existed in three different
environments. In particular, the signal at d = 5.11 ppm was
easily assigned to the free axle while the other two were
tentatively assigned to the two isomeric pseudorotaxanes 7b
and 7a. A similar distribution of products was also observed
by dissolving the oriented pseudorotaxane 7a that had
formed in C6D6 in CD3CN. This observation shows that the
oriented pseudorotaxane 7a can dissociate into its compo-
nents in acetonitrile and that the threading/dethreading
processes can occur from both calix[6]arene rims, thus
yielding both pseudorotaxanes isomers (see the Supporting
Information). This result clearly indicates that the calix[6]-
arene annulus is also large enough to thread on to the axle
from the lower rim, and that indeed, in acetonitrile, the
control elements governing the exclusive threading from the
upper rim operate—if at all—only to a limited extent. Both
rotaxanes 8 and 10 were obtained in 24% yield as unique
chromatographic fractions by treating 1, axle 5a, and
dicyclohexylacetyl chloride in acetonitrile (Scheme 3). Their
1H NMR spectra in C6D6 correspond exactly to the sum of
rotaxanes 8 and 10, and thus indirectly demonstrate that only
To confirm the structure of 8, and also to exclude the
presence of other rotaxanes in the reaction mixture, the
rotaxane isomer 10 (see Scheme 2) was also synthesized (in
18% yield) by employing the new axle 5b, which is
characterized by the presence of a dicyclohexylacetic stopper
1
(see Scheme 1). As expected, the H NMR spectrum of 10
shows that the conformation of the calix[6]arene is almost
exactly the same as that observed in 8. However, the protons
of the dumbbell portion between C3’ to C6 in 10 are
substantially shifted upfield, while those from C5 to C1 are
shifted downfield. The presence of only one singlet at d =
5.23 ppm strongly suggests that the
diphenylacetyl stopper is in proximity
to the lower rim in 10, while the dicy-
clohexyl stopper is oriented toward the
upper rim of the calixarene (see the
Supporting Information).
These data can be tentatively
explained if it is considered that axles
5a and 5b are present as tight ion pairs
during the initial formation of the pseu-
dorotaxane in toluene and as such can
not fit into the calixarene cavity. These
conditions maximize the hydrogen-
bonding ability of the ureido NH
groups toward the axle counteranion(s)
that thus pivot the cationic portion of the
axles to thread through the wheel exclu-
sively from the upper rim. The high
kinetic stability of the oriented pseudo-
rotaxane that forms favors the stopper-
ing of the OH group that protrudes from
the lower rim of the wheel, without any
detectable axle–wheel isomerization.
Scheme 3. a) CH3CN, reflux; b) Cy2CHCOCl.
280
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Chemie
one of the two constitutionally isomeric rotaxanes had formed
in the apolar toluene (see the Supporting Information).
The study of the unidirectional movement of the wheel
along the axle of the new oriented calix[6]arene-based
rotaxanes under the action of electrochemical stimuli is
under investigation.
Received: July 16, 2004
Keywords: calixarenes · rotaxanes · self-assembly ·
.
solvent effects · supramolecular chemistry
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