Synthesis of Doubly Annulated m-Terphenyl-Based Molecular Tweezers and Their Charge-Transfer Complexes with DDQ as a Guest

Article abstract of DOI:10.1002/chem.201803137

The synthesis of a doubly-annulated m-terphenyl-based tweezer platform has been developed, which affords ready incorporation of various pincer units from monobenzenoid to polybenzenoid electron donors. The complexation study with 2,3-dichloro-5,6-dicyano-

Full text of DOI:10.1002/chem.201803137

A Journal of
Accepted Article
Title: A synthesis of doubly-annulated m-terphenyl based molecular
tweezers and their charge-transfer complexes with DDQ as a
guest
Authors: Khushabu Thakur, Denan Wang, Sergey V Lindeman, and
Rajendra Rathore
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A synthesis of doubly-annulated m-terphenyl based molecular
tweezers and their charge-transfer complexes with DDQ as a
guest
Khushabu Thakur,[a] Denan Wang,*[a] Sergey V. Lindeman[a] and Rajendra Rathore‡[a]
In memory of Rajendra Rathore
Abstract:
A synthesis of doubly-annulated m-terphenyl-based
Such
a doubly-annulated m-terphenyl (TP) platform holds a number of
tweezer plateform has been developed, which affords ready
incorporation of various pincer units from monobenzenoid to
polybenzenoid electron donors. The complexation study with DDQ as
guest has been carried out, and the crystal structure of T-Py∩DDQ
reveals the sandwich-type binding mode in the solid state.
advantages when compared to the platform utilized for the preparation of
Zimmerman’s tweezers (Figure 1). First, this platform can be readily
transformed to a variety of tweezers with different pincers in one synthetic step,
as we will demonstrate. Second, the conformation flexibility of the annulating
bridges in TP-based tweezers is expected to promote the binding with guests of
varied size and shape. Third, unlike the ZT platform, which requires the
installation of a solubilizing group (see Figure 1), the annulating bridges in TP-
based tweezers inherently serve as solubilizing groups towards organic
solvents. Finally, the platform itself is oxidized at a relatively high potential (~1.7
V vs SCE), and the electronic coupling between the pincers and the platform is
minimized due to meta connections.[18]
Molecular tweezers are a class of structures with open
cavities that can bind guest molecules, and thus have attracted
considerable interest in the recognition/sensing of a variety of
guests, including explosives such as trinitrotoluene.[1-6] Due to the
potential applications of tweezers for the detection of various
synthetic, as well as biological, guest molecules, tremendous
synthetic effort has been devoted toward the preparation of
diverse tweezer platforms.[5-14] Zimmerman’s tweezer (ZT, Figure
1 (left)) is the most recognized tweezer scaffold. The structural
features of ZT include a doubly annulated m-terphenyl framework,
in which the pincers are connected at the 2- and 12-terphenyl
positions, and thus are held at a distance of ~7 Å. The ~7 Å
separation between cofacially-arrayed pincers allows efficient π-
π interactions with a sandwiched guest molecule. Despite the
effectiveness of the ZT platform,[5-6, 15-16] the syntheses are rather
tedious, and the platform holding the pincers is highly electro-
active. Moreover, as the pincers are attached in the beginning
steps of the synthesis, ready attachment of different pincers is
laborious. Furthermore, the synthetic scheme for ZTs has a
number of steps that are rather time consuming and give low
product yield.[5-6, 15-16]
Figure 1. Comparison of Zimmerman’s tweezer platform (left)[5-6, 15-16] with our
proposed doubly-annulated m-terphenyl (TP) platform (right). Due to the
conformation flexibility of the annulated bridges center-to-center distance
between pincers in TP platform may vary.
Accordingly, here we describe the successful preparation of a
doubly-annulated m-terphenyl (TP) platform, containing
trifluoromethane-sulfonate (or triflate, -OTf) groups at the 2- and
12-positions for ready installation of various pincers via a facile
and high-yielding Suzuki coupling reaction.[18-20] We demonstrate
the successful preparation of a number of tweezers based on a
TP-platform with different pincers varying from monobenzenoid to
polybenzenoid electron donors (such as tetramethylbenzene,
naphthalene, pyrene). The complexation study with DDQ as guest
has been carried out, and complexation product, T-Py∩DDQ, has
been characterized by X-ray crystallography.
In this work, we seek to improve upon the ZT platform by
exploring the preparation of a common doubly-annulated m-
terphenyl platform, with appropriate functional groups, that would
afford a ready attachment of pincers in one synthetic step.
A
recent report by Rathore and coworkers has described a versatile
synthesis for the efficient preparation of doubly annulated p-
terphenyls.[17] It can be readily seen (Figure 1) that if a similar
double annulation is performed onto an m-terphenyl derivative,
the resulting doubly-annulated derivative with appropriate
substitutions at the 2- and 12-positions could serve as a versatile
platform for the ready construction of a variety of tweezers with
different pincers.
As shown in Scheme 1, synthesis of the doubly-annulated m-
terphenyl platform (TP or 1g) begins with commercially available
1,5-dibromo-2,4-diiodobenzene 1a, which can also be
synthesized in excellent yields at a 50-100 gram scale by
iodination of m-dibromobenzene in concentrated sulfuric acid.
Accordingly, an efficient palladium-catalyzed reaction[21] of an
inexpensive commercially available 2-methyl-3-butyn-2-ol with 1a
leads to a quantitative formation of 1b, where the more reactive
iodo substituents are selectively substituted by acetylenic
[a]
Dr. K. Thakur, Dr. D. Wang, Dr. S. V. Lindeman, Prof. R. Rathore
Department of Chemistry, Marquette University
Milwaukee, WI 53201-1881 (USA)
E-mail: denan.wang@marquette.edu
[‡]
Deceased February 16, 2018
Supporting information for this article is given via a link at the end of
the document.
alcohols.
A
standard Suzuki coupling of 1b with 3-
methoxybenzeneboronic acid in the presence of Pd(PPh3)4 as a
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catalyst afforded the desired terphenyl 1c in good overall yield.
The resulting diacetylenic-m-terphenyl 1c was subjected to
catalytic hydrogenation in ethyl acetate in the presence of 10%
palladium on activated carbon as the catalyst. The resulting
reduced terphenyl 1d was sufficiently pure, and thus, was treated
directly with methanesulfonic acid in dichloromethane at room
temperature to afford the doubly-bridged m-terphenyl 1e via two
facile intramolecular Friedel-Crafts cyclizations[17] (Scheme 1).
Conversion of the 2,12- methoxy substituents of 1e to the
corresponding trifluoromethanesulfonates (i.e. 1e to 1g) was
accomplished in excellent yield by a demethylation reaction[22]
using BBr3 followed by a reaction[23] with triflic anhydride in a
mixture of pyridine and dichloromethane.
0.06 kcal/mol. Yet, X-ray crystallographic analysis of the
doubly annulated m-terphenyl 1e showed that in the solid
state it exists only in the anti-conformation, due to
stabilization by packing forces (Figure 2A).
Synthesis of various tweezers (see structures below)
containing duryl (T-Dur), naphthyl (T-Nap) and pyrenyl (T-Py)
groups as pincers was readily accomplished by a standard Suzuki
coupling of the doubly-annulated m-terphenyl-ditriflate 1g with
various boronic acids (i.e. durylboronic acid or 2-naphthylboronic
acid or 2-pyrenylboronic acid) in the presence of Pd(PPh3)4 as a
catalyst in toluene as a solvent (Scheme 2). All three molecular
1
tweezers are fully characterized with H/13C NMR and MALDI-
TOF mass spectra (Figure S1).
The proposed doubly annulated framework may exist in two
nearly isoenergetic conformations with varied orientation of the
annulated bridge with respect to the plane of the central aromatic
moiety (syn or anti). Indeed, the structural flexibility of the new TP
1
platform led to a broad feature between 0.8-1.5 ppm on the H-
NMR spectra at 20 ˚C, which corresponded to the methyl groups
in the annulated region. In the case of representative doubly-
bridged m-terphenyl 1e, variable- temperature 1H NMR
spectroscopy in CDCl3 over a temperature range of +20 to -60 °C
(Figure S2) showed that the interchange between the two
conformers can be frozen at ∼ -60 °C, and the estimated
activation energy for the interchange between syn and anti-
conformers was found to be 11.5 kcal•mol-1.
Scheme 2. Synthesis of various tweezers: T-Dur, T-Nap and T-Py.
In the context of application of a TP platform in molecular
recognition, a syn conformation is preferred, as its relative
arrangement of the pincers would favor the trapping of the guest
molecule. Indeed, according to the DFT calculations of T-Dur, T-
Nap and T-Py, the syn configuration is the preferred conformation,
lower by 0.4-1.3 kcal/mol lower than the anti conformation. This
difference due to the geometrical architecture of the TP-
framework, which leads to more favorable CH-π interactions in
the syn conformation (Figure S11 in the Supporting Information).
As the result, the relative orientation of the pincers is non-parallel,
with interplanar angles in a wide 6-74° range. In the solid state,
T-Dur exists in a syn-conformation with a disordered chloroform
solvent molecule positioned in the cleft between two terminal
durene moieties that have an interplanar angle of 74° (Figure 2B).
However, in the presence of the guest molecule, the relative
energetics of the syn/anti conformations of the tweezer will
change depending on the nature of host/guest interactions.
Scheme 1. Synthesis of the doubly-annulated m-terphenyl platform for the
preparation of various tweezers.
To probe whether the TP-based tweezers can effectively host
a guest molecule, we next studied their binding affinity with
DDQ—a powerful electron acceptor (Ered = 0.56 V vs SCE).[24]
Mixing of DDQ with T-Dur, T-Nap and T-Py in CH2Cl2 resulted in
the appearance of a characteristic charge-transfer band in their
UV-vis absorption spectra (Figures S4-S6 in the Supporting
Information), suggesting formation of electron donor-acceptor
(EDA) complexes. Interestingly, analysis of the Benesi-
Hildebrand plots showed that as the size of the aromatic pincer
increases, the binding constant (K) also increases, from 26 M-1 in
T-Dur, to 196 M-1 in T-Nap, to 415 M-1 in T-Py.
Figure 2. An ORTEP diagram of the molecular structure of A, the doubly
annulated m-terphenyl 1e; B. T-Dur with disordered chloroform solvent.
(Thermal ellipsoids drawn at 50% probability, solvent molecules and hydrogen
atoms removed for clarity).
DFT calculations at M06-2X/6-31G(d) with an implicit
treatment of CH2Cl2 as a solvent predict that the energetic
difference between syn and anti is indeed small, i.e., only
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It is well known that the formation constant of EDA
complexes is highly dependent on the free energy of the electron
transfer (i.e., ΔGET = Eox[donor] – Ered[acceptor]);[25] and the
oxidation potentials of polycyclic aromatic hydrocarbons generally
decrease with an increasing number of aromatic rings.[26] Indeed,
a plot of K against ΔGET shows a strong dependence that is well
described by the linear plot in the range of ΔGET = 1.2 to 0.7 V
(Figure S7 in the Supporting Information).[25]
moiety (Figure 3). A smaller contact area of the Dur- and Nap-
based pincers may prevent efficient stacking with DDQ leading to
diminished values of the binding constant.
In conclusion, we have successfully developed an efficient
method to synthesize a doubly-annulated m-terphenyl tweezer
platform, containing trifluoromethane-sulfonate groups at the 2-
and 12-positions for ready installation of various pincers. In
comparison with the Zimmerman tweezers, this new platform has
a higher oxidation potential and more structural flexibility to bind
with guest molecules, and the synthetic strategy affords
incorporation of pincers late in the synthesis. Thus, the
successful preparation of a number of tweezers based on a TP-
platform with different pincers varying from monobenzenoid to
polybenzenoid electron donors as pincers has been described,
and their binding affinity has been examined with DDQ as the
guest molecule. Among investigated tweezers, the pyrene-based
tweezer (T-Py) shows the strongest association with DDQ, with a
binding constant of 415 M-1 in a dichloromethane solution, and the
crystal structure reveals the sandwich-type complexation in the
solid state. Thus, the binding constants are of the same order of
magnitude as original Zimmerman tweezers,[6] and therefore this
novel framework holds potential in recognition/sensing of a variety
of guests. Future studies may involve introduction of the pincers
with large graphitic cores such as HBC. More applications of
molecular tweezers exploiting the reported novel framework are
under investigation.
Figure 3. Showing the side and top views (A/B) and
a space-filling
representation (C) of the X-ray structures of 1:1 EDA complex of T-Py∩DDQ
together with a solvent molecule (i.e. CH2Cl2). (Thermal ellipsoids drawn at 50%
probability).
Acknowledgements
We thank the NSF (CHE-1508677) for financial support,
Professor Scott A. Reid (Marquette University) for helpful
discussions and Dr. Maxim V. Ivanov (Marquette University) for
calculations and helpful discussions. The calculations were
performed on the high-performance computing cluster Père at
Marquette University and XSEDE.
Fortunately, we have obtained crystals of the charge-transfer
complex of T-Py and DDQ (i.e., T-Py∩DDQ) suitable for X-ray
crystallography. Dark-colored crystals of the 1:1 complex were
isolated from an equimolar solution of T-Py and DDQ in a mixture
of dichloromethane and acetonitrile, by a very slow evaporation of
the solution at ambient temperatures. X-ray crystallographic
analysis of the T-Py∩DDQ charge-transfer complex revealed that
DDQ is bound in a sandwich configuration between a pair of
pyrenyl donors, Figure 3. In addition, the entire complex contains
a local symmetry plane, and the m-terphenyl platform of the T-Py
tweezer adopts an achiral syn conformation (Figure 3). The
pyrene pincers are oriented almost parallel to each other with a
dihedral angle of 13.2°, and DDQ is located between the two
pyrenyl with equivalent interplanar distances of 3.2 Å. The
remaining empty space near the central benzene ring of the m-
terphenyl platform in the T-Py∩DDQ complex is filled by a solvent
Conflict of interest
The authors declare no conflict of interest.
Keywords: molecular tweezers • self-assembly •
supramolecular chemistry • charge transfer • DDQ
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Entry for the Table of Contents
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Khushabu Thakur,[a] Denan Wang,*[a]
Sergey V. Lindeman[a] and Rajendra
Rathore‡[a]
Page 1. – Page 4.
A synthesis of doubly-annulated m-
terphenyl based molecular tweezers
and their charge-transfer complexes
with DDQ as a guest
A synthesis of m-terphenyl-based tweezer plateform has been developed, which
affords ready incorporation of various pincer units as electron donors.
This article is protected by copyright. All rights reserved.