A polyaromatic receptor with an ethereal fence that directs K+ for effective cation-π interaction

Article abstract of DOI:10.1021/ja060502y

We have designed and synthesized a HAB-based receptor with six ethereal oxygens on one face of the central benzene ring by a trimerization of a diarylacetylene in which the ethereal oxygens are tied together with a tetramethylene bridge. This unique amphi

Full text of DOI:10.1021/ja060502y

Published on Web 03/30/2006
A Polyaromatic Receptor with an Ethereal Fence that Directs K+ for Effective
Cation-π Interaction
Ruchi Shukla, Sergey V. Lindeman, and Rajendra Rathore*
Department of Chemistry, Marquette UniVersity, P.O. Box 1881, Milwaukee, Wisconsin 53201-1881
Received January 28, 2006; E-mail: rajendra.rathore@marquette.edu
Scheme 1. Synthesis of HAB-based Receptor 5Sa
The hexaphenylbenzene core has gained considerable attention
due to its unique propeller-shaped structure and its usage for the
preparation of modern graphitic materials for the applications in
the emerging area of molecular electronics and nanotechnology.1
Numerous possibilities exist for future development and use of novel
architectures based on hexaarylbenzene (HAB) derivatives in sensor
applications and host-guest chemistry, in general, if a controlled
synthesis can be developed which will allow the positioning of all
the ortho substituents (such as ethereal oxygens on the peripheral
aryl rings) on one face of the central benzene ring. Interestingly,
however, the ortho-substituted HAB derivatives exist as a mixture
of rotamers due to the restricted rotation around the C-C bonds
between the six peripheral aryl rings and the central benzene ring.
For instance, it has been established2 that trimerization of bis(2-
methoxyphenyl)acetylene leads to the formation of only eight
rotamers (i.e., six achiral and one pair of enantiomeric rotamers)
of hexakis(2-methoxyphenyl)benzene out of the possible nine
rotamers. The only missing rotamer from this synthesis is the one
which contains all the ethereal oxygens on one face of the propeller.
Such a symmetrical isomer can be potentially useful for directing
a metal cation to the central benzene ring with the aid of six ethereal
oxygens that are prearranged in a manner akin to an 18-crown-6
geometry.3 Accordingly, in this paper, we now report a new strategy
to access this elusive rotamer containing all the ethereal oxygens
on one face of the HAB and delineate by NMR spectroscopy and
X-ray crystallography that it binds a single potassium cation to the
central benzene ring via a synergistic interaction with the hydro-
philic ethereal fence and the hydrophobic π-cloud of the central
benzene ring4 as follows.
a Conditions: (a) NaOH, EtOH, reflux; (b) TiCl4, Zn, Py, THF, reflux;
(c) Br2, AcOH; (d) KOtBu, THF, 22 °C; (e) Co2(CO)8, dioxane, reflux.
recovered 4. The identity of 5s was readily established by the
1
simplicity of its H/13C NMR spectra in comparison to that of 5u
and was further confirmed by FAB mass spectrometry (see
Supporting Information).
1
The binding of K+ cation to 5s was monitored by H NMR
spectroscopy. Thus, an incremental addition of potassium per-
fluorotetraphenylborate solution (0.08 M) to a solution of 5s in
acetone-d6 (0.02 M) showed the appearance of a new set of signals
in addition to the initial signals due to the uncomplexed 5s. The
1H NMR signals due to the 5s were completely replaced by the
new signals upon addition of 1 equiv of K+, as shown in Figure 1.
It was conceived that preparation of the HAB derivative with
oxygens on one face can be accomplished by a trimerization of a
diarylacetylene in which the ethereal oxygens are tied together with
a polymethylene bridge (see structure 4 in Scheme 1). Unfortu-
nately, the synthesis of such bridged acetylenic derivatives from
existing procedures was possible only in very poor yields.5
Therefore, we first developed a practical route to access the bridged
diarylacetylene 4 in which the ethereal oxygens are tied with a
tetramethylene bridge (see Scheme 1).6 For example, a reaction of
2 equiv of isopropylsalicylaldehyde (1) with 1,4-dibromobutane in
the presence of NaOH in refluxing ethanol afforded dialdehyde 2
in 95% yield. The McMurry coupling under mild dilution produced
a mixture of cis/trans stilbenes 3 in >85% yield on a 20 g scale
reaction, which were readily converted to the corresponding acet-
ylene 4 (in >80% yield) by a simple bromination and dehydro-
bromination reaction sequence (see Supporting Information).
A Co2(CO)8-catalyzed trimerization of 4 in refluxing dioxane
for 12 h produced a mixture which contained roughly 25% trimer
and ∼75% of the starting acetylene 4. A quick chromatographic
separation on silica gel (using hexanes and ethyl acetate mixture
as eluent) afforded pure symmetrical isomer 5s and the unsym-
metrical isomer 5u in ∼1:2 ratio in >95% yield based on the
1
It is noteworthy that the H NMR spectrum remained unchanged
upon further addition of K+ solution (i.e., beyond 1 equiv). Such
a spectral change is readily reconciled as arising from the
complexation of K+ to 5s. Moreover, it is noted that the potassium
cation is held strongly in the [5s, K+] complex because of the fact
that it does not undergo an exchange reaction with the uncomplexed
5s on the NMR time scale (at 22 °C). Unfortunately, an accurate
binding constant for the formation of [5s, K+] could not be
determined by NMR method as it simply showed complete capture
of the K+ and suggested that the binding constant is too large to
be measured by NMR spectroscopy.7
To ascertain the structure of the [5s, K+] complex, we attempted
the crystallization of [5s, K+] -B(C6F5)4 by a slow diffusion of
hexanes in an acetonitrile solution of the complex that resulted in
poor quality crystals. However, by changing the counteranion from
-B(C6F5)4 to -BPh4, the formation of an excellent crop of single
crystals of the [5s, K+] -BPh4 from an acetonitrile-CH2Cl2 mixture
at 22 °C resulted. The structure of the complex [5s, K+ CH3CN]
-BPh4 is shown in Figure 2.
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J. AM. CHEM. SOC. 2006, 128, 5328-5329
10.1021/ja060502y CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Figure 3. Molecular structure of [5s, K+] showing the effective overlap
of the polar ethereal fence with K+ while it rests on the aromatic bottom
via cation-π interactions. The methyls of isopropyl groups and CH3CN
are omitted.
propeller may only occur at the expense of substantial repulsive
interaction among the peripheral aryl rings.9
In summary, we have designed and synthesized a HAB-based
receptor that contains a bipolar receptor site that allows a remarkably
efficient binding of a single potassium cation because it synergisti-
cally interacts with the polar ethereal fence and with the central
benzene ring via cation-π interactionsa phenomenon that is well
established in gas phase10 and in solid state 8 and is known to play
an important role in the stabilization of tertiary structures of various
proteins.11 We believe that the development of this unique receptor
with an amphiphilic binding pocket and the electronically coupled
peripheral aryl groups12 will allow its usage for the development
of practical sensors for various metal ions. We are currently
exploring the selectivity of the binding of various metal cations to
receptor 5s as well as its usage for sensing devices.
Figure 1. Partial 1H NMR spectra obtained upon the incremental addition
of KB(C6F5)4 to 5s in acetonitrile-CH2Cl2 at 22 °C.
Acknowledgment. We thank the National Science Foundation
(Career Award) and Marquette University for financial support. This
paper is dedicated to Prof. S. Chandrasekaran (I. I. Sc., Bangalore,
India) on the occasion of his 60th birthday.
Figure 2. Structure of [5s, K+] -BPh4 with a single CH3CN molecule
complexed to K+. The hydrogens and the anion are omitted.
Supporting Information Available: Preparation, spectral data for
1-5, and the X-ray data. This material is available free of charge via
the Internet at http://pubs.acs.org.
The X-ray structure in Figure 2 reveals that a single potassium
cation sits in a shallow cavity with an (hydrophobic) aromatic
bottom (i.e., the central benzene ring) while effectively interacting
with the (hydrophilic) polar fence formed by six ethereal oxygens.
The depth (i.e., the distance between the mean planes of the central
benzene ring carbons and the ethereal fence) and the radius of the
cavity are 2.22 and 2.97 Å, respectively. Such a bipolar nature of
the cavity in 5s allows a tight van der Waals fit for a single K+
cation as discussed below.
References
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Bloor, D., Eds.; Oxford University Press: New York, 1995. (b) Watson,
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(3) Compare: Trueblood, K. N.; Knobler, C. B.; Maverick, E.; Helgeson, R.
The most striking feature of the structure in Figure 2 is the
symmetrical η6-coordination of the K+ by the central benzene ring
of 5s. The distance between the mean plane of the benzene ring
and the K+ is 2.742 Å, a distance that is much shorter than the
sum of van der Waals/ionic radii of carbon and K+ (i.e., 3.22 Å)
and surpasses any of the previous experimental observations of the
cation-arene contacts.8 One of the main factors favoring such a
close K+‚‚‚Ar coordination is the synergistic coordination of
potassium cation by the all six ethereal oxygens prearranged in a
geometry similar to that of the 18-crown-6. Another feature of the
structure is that the K+ sits slightly (i.e., ∼0.52 Å) above the
coordination plane of the ethereal fence, as pictured below in Figure
3. A simple geometrical consideration showed that the possible
perpendicular orientation of the peripheral aryl rings in 5s could
provide a more coplanar coordination of potassium cation with the
ethereal fence with an almost normal K+‚‚‚O separation of ∼2.84
Å (as opposed to the observed K+‚‚‚O separation of 2.83-3.21 Å
or av. 3.02 Å). However, such a structural alteration of the HAB
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5, 3951 and references therein.
(6) Complete synthetic details for the preparation of various bridged diaryl-
acetylenes will be presented separately.
(7) Competition experiments indicated that 5s and 18-crown-6 have a
comparable affinity for K+.
(8) (a) Atwood, J. L.; Crissinger, K. D.; Rogers, R. D. J. Organomet. Chem.
1978, 155, 1. (b) King, B. T.; Noll, B. C.; Michl, J. Collect. Czech. Chem.
Commun. 1999, 64, 1001. (c) Compare: Hu, J.; Barbour, Gokel, G. W.
Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5121 and references therein.
(9) Note that dihedral angles between peripheral aryl rings and central benzene
ring vary between 55 and 70°; see CCD Database.
(10) Guo, B. C.; Purnell, J. W.; Castlman, A. W., Jr. Chem. Phys. Lett. 1990,
168, 155 and references therein.
(11) (a) Burley, S. K.; Petsko, G. A. FEBS Lett. 1986, 203, 139. (b) Sakurai,
Y.; Mizuno, T.; Hiroaki, H.; Gohda, K.; Oku, J.; Tanaka, T. Angew. Chem.,
Int. Ed. 2005, 44, 6180 and references therein.
(12) Rathore, R.; Burns, C. L.; Abdelwahed, S. H. Org. Lett. 2004, 6, 1689.
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