Donor-acceptor molecular figures-of-eight

Article abstract of DOI:10.1039/c1cc15333a

The intermolecular template-directed synthesis, separation and characterisation of two constitutional isomers that are self-complexing donor-acceptor [1]rotaxanes has been achieved by click chemistry, starting from a π-electron deficient tetracationic cyc

Full text of DOI:10.1039/c1cc15333a

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COMMUNICATION
Donor–acceptor molecular figures-of-eightw
Megan M. Boyle,a Ross S. Forgan,a Douglas C. Friedman,a Jeremiah J. Gassensmith,a
Ronald A. Smaldone,a J. Fraser Stoddart*ab and Jean-Pierre Sauvage*ac
Received 27th August 2011, Accepted 16th September 2011
DOI: 10.1039/c1cc15333a
The intermolecular template-directed synthesis, separation and
characterisation of two constitutional isomers that are self-
complexing donor–acceptor [1]rotaxanes has been achieved by
click chemistry, starting from a p-electron deficient tetracationic
cyclophane containing two azide functions and a p-electron rich
1,5-dioxynaphthalene-containing polyether chain terminated by
propargyl groups.
orientations resemble the transition state which is passed
through between the out-out and in-in forms.
Access to the molecular Fo8s, employing donor–acceptor
interactions as the source of their templation, necessitates that
we identify bisfunctional CBPQT4+ derivatives which would
not have their binding affinities impaired—either sterically or
electronically—by the substituents, yet also be highly reactive.
With these requirements in mind, we chose the electronically
benign11 and sterically small azide function12 to achieve
bisfunctionality of the CBPQT4+ ring. Starting from commercially
available 2-bromo-1,4-dimethylbenzene, the template-directed
synthesis13 (see ESI) of 14+ was achieved in four steps. The
bisfunctionalisation of the CBPQT4+ ring results in the
formation, in an approximately 1 : 1 ratio, of two regioisomers,
namely cis-14+ and trans-14+ in which the azide functions are,
respectively, (i) pointing towards the same bipyridinium
(BIPY2+) unit and (ii) pointing towards the two different
BIPY2+ units. Although the cis and trans isomers of 14+
could not be separated and identified unambiguously by 1H NMR
spectroscopy, a doubling up of peaks (Fig. S4 in ESI), shifted
from each other by 0.5 ppm in the 13C NMR spectrum,
provided evidence for a ca. 1 : 1 mixture of isomers. X-Ray
crystallography, performed on a single crystal grown by slow
evaporation of EtOH into a solution of 1ꢀ4PF6 in DMF,
revealed (Fig. S5 in SI) the presence of disorder associated
with the constitutional locations—cis and trans—of the two
azide functions on the CBPQT4+ ring. All attempts to
separate cis-1ꢀ4PF6 from trans-1ꢀ4PF6 have so far been in
vain. The mixture of isomers was employed in the template-
directed synthesis of molecular Fo8 compounds which, in the
event, we have been able to separate by high performance
liquid chromatography (HPLC) as their cis and trans isomers.
Molecular modelling was used to identify the bispropargyl
ether 2 of the 1,5-dioxynaphthalene (DNP) unit, carrying two
hexaethyleneglycol chains, as a suitable guest for the 14+
isomers while also making it possible for two successive
CuAAC reactions to take place (Scheme 1a) in DMF and so
produce the molecular Fo8s 34+ as a mixture of regioisomers,
cis-34+ and trans-34+, in 12% yield. Iterative HPLC with
recycling through an XBridge Prep C-18 OBC 19 ꢁ 100 mm
column, using a gradient of aqueous acetonitrile as the eluent,
was used in order to separate the regioisomers as their 4TFAꢂ
Self-complexing compounds,1 as well as pretzelanes,2 that
exhibit both chirality3 and bistability4 have been synthesised
using intramolecular template-directed protocols starting from
precursors of the tetracationic cyclophane, cyclobis(paraquat-
p-phenylene)5
(CBPQT4+
)
which
ends
up
being
monofunctionalised on one of its p-xylylene linkers. Here, we
describe how isomeric ‘‘Molecular 8’’ compounds,6 which we
refer to as Figure-of-Eight (Fo8) molecules, can be synthesised
(Scheme 1a) using an intermolecular template-directed strategy.
Thus, isomeric CBPQT4+ derivatives 14+, functionalised with
azides on both p-xylylene linkers, act as the recognition sites for
the binding of a 1,5-dioxynaphthalene-containing polyether
chain 2 terminated by propargyl ethers, which react subsequently
under Cu-mediated azide-alkyne cycloaddition (CuAAC)
conditions7 to give a mixture of cis and trans isomers of the
molecular Fo8 34+. This architecture has been realised
previously by Vogtle et al.6 who preformed a [2]rotaxane
and then inserted a couple of covalent linkers into the
mechanically interlocked molecule (MIM) to produce a self-
threaded ‘‘Molecular 8’’ which is topologically trivial,8 unlike
the Figure-Eight knot or the Figure-Eight catenane.9 The
‘‘Molecular 8’’, however, resembles the rose Figure-Eight in
appearance and leads logically to our naming the [1]rotaxanes
reported here as molecular Fo8s. Furthermore, the topology is
similar to that found in macrobicyclic compounds10 with
protonated bridgehead nitrogen atoms when their relative
a Department of Chemistry, Northwestern University, 2145 Sheridan
Road, Evanston, IL 60208, USA.
E-mail: stoddart@northwestern.edu, j-sauvage@northwestern.edu
b Graduate School of EEWS (WCU), Korea Advanced Institute of
Science and Technology (KAIST), 373-1, Guseong Dong, Yuseong
Gu, Daejeon 305-701, Republic of Korea
´
University of Strasbourg, ISIS, 8 allee Gaspard Monge, F-67000
Strasbourg, France. E-mail: jpsauvage@unistra.fr
c
1
salts. The H NMR spectra of the faster and slower moving
ꢂ
w Electronic supplementary information (ESI) available: Syntheses
and 1H NMR characterisation of compounds, crystal structure of
1ꢀ4PF6. See DOI: 10.1039/c1cc15333a
isomers, after conversion to their 4PF6 salts, are shown in
Fig. 1a and b, respectively. Careful scrutiny of the
c
11870 Chem. Commun., 2011, 47, 11870–11872
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Scheme 1 Synthesis (a) of the Molecular Fo8s 34+ from the bisfunctionalised 14+. Electron-deficient CBPQT4+ bisfunctionalised with azides 14+
is ‘‘clicked’’ to the electron-rich bisalkyne 2 to form two regioisomers (cis and trans) of the molecular Fo8s 34+. Note that the azides can be
oriented such that they are pointing towards opposite BIPY2+ units (trans) or towards the same BIPY2+ unit (cis). Furthermore, these
orientations are implicated in the regioisomers of the Fo8. The trans isomer (b) of 34+ shows the molecule is reminiscent of a fused ring system with
an element of self-complexation. The molecular mechanics minimisation (MMFF94) was accomplished using Spartan 2010.
through-bond (COSY, Fig. 2) and through-space (NOESY,
Fig. 3) correlations found in the 2D spectra of each isomer
heterotopic with respect to each other. The outcome is that we
expect to observe four resonances for protons a to the nitrogens
and also four resonances for the protons b to the nitrogens. This
expectation is realised in the 1H NMR spectrum (Fig. 1b) of the
cis isomer.
1
allowed the full H NMR spectroscopic characterisation and
assignment of trans-34+ and cis-34+, respectively. Although
the 1H NMR spectra of the two regioisomers reveal significant
differences, they display the same number of resonances.
(The labelling of the protons on the structural formulae of
trans-34+ and cis-34+ in Scheme 1a corresponds to the assign-
ment of the resonances in Fig. 1a and b, respectively.) These
observations are not unexpected based on an analysis of the
molecular symmetries and topic relationships14 of trans-34+
and cis-34+. The trans isomer has Ci symmetry which means
that the eight heterotopic protons on one BIPY2+ unit are
related enantiotopically in pairs to the eight heterotopic
protons on the other BIPY2+ unit. The outcome is that we
expect to observe four resonances for protons a to the nitrogens
and also four resonances for the protons b to the nitrogens. This
expectation is realised in the 1H NMR spectrum (Fig. 1a) of the
trans isomer. By contrast, the cis isomer has C2 symmetry which
means that the eight protons in each BIPY2+ unit are related
homotopically in pairs while the two sets of BIPY2+ units are
Not only did an analysis of the 2D NMR spectra allow us to
1
assign the 1D H NMR spectra in Fig. 1a and b to the trans
and cis isomers, respectively, but it also assisted us in identifying
the conformation shown in Scheme 1b as the major onez for
trans-34+— and the analogous one in relation to the relative
orientation of the DNP unit inside the CBPQT4+ ring of the
cis-34+ as well. Finally, the minor peaks observed in the
1H NMR spectra (Fig. 1) are not impurities: they are lower
symmetry minor conformations which are in slow equilibrium
on the 1H NMR time-scale with their corresponding major
conformations as evidenced by the exchange peaks present in
the NOESY spectra (Fig. 3 and ESI). These dynamic processes
are currently under investigation.
It is half a century since Wasserman and Frisch15 published
their seminal paper on chemical topology in 1961. In the rapidly
expanding real estate being claimed by MIMs,16 topological
1
Fig. 1 Partial H NMR spectra (500 MHz, CD3CN, 298 K) of the constitutional isomers of 3ꢀ4PF6. Both (a) cis–3ꢀ4PF6 and (b) trans–3ꢀ4PF6
contain the same count of heterotopic protons on account of their molecular symmetries and the same number of resonances are observed in their
respective 1H NMR spectra. The small baseline resonances represent as yet unidentified conformations, which are in slow equilibrium on the
1H NMR time-scale with the major conformations of 3ꢀ4PF6 (ca. 10 : 1 ratio), as verified by exchange peaks present in the NOESY spectrum
illustrated in Fig. 3. See also the ESI.
c
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collaboration supported in the US by the National Science
Foundation under grant CHE-0924620. We also acknowledge
support from the World Class University (WCU) Program
(R-31-2008-000-10055-0) in Korea.
Notes and references
z The local C2h symmetry of a 1,5-dioxynaphthalene unit can commute
as two different conformations19 with both the cis and trans isomers of
3
4+. In the case of the latter, the conformation shown in Scheme 1b is
predicted by quantum mechanical calculations to be the most stable.
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Fig. 2 1H–1H gDQF COSY (600 MHz, CD3CN, 298 K) spectrum of
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Fig. 3 A region of the NOESY (600 MHz, CD3CN, 298 K) spectrum
of cis–3ꢀ4PF6. Note that the black peaks are phased positive which
correspond to chemical exchange peaks with the uncomplexed species
and the red peaks are phased negative which correspond to positive
nOe’s of the Fo8. This region of the spectrum shows the through-space
correlations of the featured BIPY2+ protons a to the nitrogen and the
p-xylylene protons. These key correlations allow for the assignment of
the protons in this region. Furthermore, the chemical exchange peaks
that are boxed in green are a selection of the peaks which indicate that
the major species is in exchange with a minor one.
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chemistry9,17 is going to assume more and more importance in
the design and synthesis of compounds, such as Fo8s, which are
beyond just simple catenanes, rotaxanes, and knots.18
The research reported in this communication is based upon
the work supported under the auspices of an international
19 S. A. Vignon and J. F. Stoddart, Collect. Czech. Chem. Commun.,
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c
11872 Chem. Commun., 2011, 47, 11870–11872
This journal is The Royal Society of Chemistry 2011