Synthesis of tetrafunctionalized pentiptycenequinones for construction of cyclic dimers with a cylindrical shape by boronate ester formation

Article abstract of DOI:10.1016/j.tetlet.2015.06.070

Abstract New tetrasubstituted pentiptycenequinone derivatives 1 and 2 having two sets of diol moieties in a syn orientation were synthesized from the corresponding 2,3-disubstituted anthracene derivatives. The semicircular scaffold of these molecules is expected to be useful to create a belt-like structure having an aromatic π-wall. Indeed, the reaction of 1 with 1,4-phenylenediboronic acid or 4,4′-biphenyldiboronic acid quantitatively gave a 2:2 macrocyclic product via boronate ester formation. The efficient formation of these cyclic structures can be explained by favorable intramolecular cyclization at the final step.

Full text of DOI:10.1016/j.tetlet.2015.06.070

Accepted Manuscript
Synthesis of tetrafunctionalized pentiptycenequinones for construction of cyclic
dimers with a cylindrical shape by boronate ester formation
Shigehisa Akine, Daisuke Kusama, Yuri Takatsuki, Tatsuya Nabeshima
PII:
S0040-4039(15)01089-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.06.070
TETL 46462
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
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13 June 2015
24 June 2015
Please cite this article as: Akine, S., Kusama, D., Takatsuki, Y., Nabeshima, T., Synthesis of tetrafunctionalized
pentiptycenequinones for construction of cyclic dimers with a cylindrical shape by boronate ester formation,
Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.06.070
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Synthesis of tetrafunctionalized
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boronate ester formation
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Shigehisa Akine, Daisuke Kusama, Yuri Takatsuki and Tatsuya Nabeshima

1
Tetrahedron Letters
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Synthesis of tetrafunctionalized pentiptycenequinones for construction of cyclic
dimers with a cylindrical shape by boronate ester formation
Shigehisa Akinea,∗ Daisuke Kusamab, Yuri Takatsukia,b and Tatsuya Nabeshimab*
a Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
b Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
New tetrasubstituted pentiptycenequinone derivatives 1 and 2 having two sets of diol moieties in
a syn orientation were synthesized from the corresponding 2,3-disubstituted anthracene
derivatives. The semicircular scaffold of these molecules is expected to be useful to create a
belt-like structure having an aromatic π-wall. Indeed, the reaction with 1 with 1,4-
phenylenediboronic acid or 4,4'-biphenyldiboronic acid quantitatively gave a 2:2 macrocyclic
product via boronate ester formation. The efficient formation of these cyclic structures can be
explained by favorable intramolecular cyclization at the final step.
Available online
Keywords:
Iptycene
Boronate
2009 Elsevier Ltd. All rights reserved.
Macrocycle
Belt-like structure
Quinone
Triptycene is a paddle-wheel-like molecule that has three
fused benzene rings around [2.2.2]bicyclooctatriene framework.
The very rigid molecular framework is useful for constructing
various kinds of functional molecules1 such as molecular gears,2
non-stacking emissive polymers,3 porous materials,4 etc. The
triptycene and its homologues are known as iptycenes.
Representative members of the iptycene families are
pentiptycene (Scheme 1a) with five benzene rings and
heptiptycene with seven benzene rings, in which the benzene
rings are connected by two and three bicyclic cores, respectively.
One of the most important structural motifs of the iptycene
derivatives is the non-coplanar arrangement of the benzene rings
strictly fixed at an angle of about 120 deg by the rigid
framework. This arrangement of the benzene rings is suitable for
making a bent π-wall, and the resulting concave surface could
nicely emulate the partial structure of an aromatic π-belt.5,6
Indeed, there have been a number of reports on macrocyclic
molecules in which two or more triptycene units are connected
belt-like structures is important to create a new type of molecular
receptors, porous materials, organic–inorganic hybrid nanotubes,
etc.
by suitable linkers.7,8
If larger-sized iptycenes such as
pentiptycene and heptiptycene are used, we would obtain a more
rigid belt-like cylindrical structure that has a well-defined and
Scheme 1.
Tetrasubstituted pentiptycenequinones 1 and 2. (c) Formation of
macrocyclic structure from semicircular molecules and
(a) Triptycene and pentiptycene.
(b)
a
shape-persistent
cavity.
For
example,
bifunctional molecules.
cyclododeciptycenequinone is a macrocyclic compound that is
completely composed of iptycene scaffold.9 The rigid framework
of this molecule could particularly be useful to make a well-
defined belt-like structure10 in which flipping motions of the
aromatic rings are completely suppressed. In this context,
development of versatile precursors for a wide variety of such
———
Thus, we focused on tetrasubstituted pentiptycene derivatives
(Scheme 1b) as one-half of a macrocyclic structure, which are
expected to give a series of belt-like structures by the reaction
with other suitable bifunctional building blocks (Scheme 1c).
∗ Corresponding authors. Tel.: +81 76 264 5701; fax: +81 76 264 5742 (S.A.); tel./fax: +81 29 853 4507 (T.N.). E-mail addresses:
akine@se.kanazawa-u.ac.jp (S. Akine), nabesima@chem.tsukuba.ac.jp (T. Nabeshima).

2
Tetrahedron
Among the reported synthetic protocols to suitably
assigned to the syn isomer. This syn isomer of the tetraester 10
was hydrolyzed using potassium carbonate in aqueous
methanol/THF mixed solvent to yield tetrahydroxy derivative 2.
functionalized pentiptycene derivatives,11 the reaction of 1,4-
benzoquinone with 2 equiv of anthracene in the presence of
chloranil is advantageous.12
Various functionalized
pentiptycenequinones can be obtained from simple precursors via
facile one-pot procedure based on this protocol. In order to
obtain tetrasubstituted pentiptycene derivatives that could be
used as a building block of a belt-like structure, two pairs of
substituents have to be introduced in a syn orientation. We chose
hydroxy and hydroxymethyl groups as the substituents so that the
two diol moieties can be utilized to link the two semicircular
units together by the reaction with a suitable bifunctional unit.
Herein, we report the synthesis of
tetrahydroxy
pentiptycenequinone derivatives 1 and 2. We found that the
reactions of the tetrahydroxy derivative 1 with some diboronic
acids quantitatively gave a macrocyclic compound.
The tetrahydroxy derivative
1 was synthesized from
tetramethoxypentiptycenequinone (5),13 which was prepared from
2,3-dimethoxyanthracene (3)14 and 1,4-benzoquinone (4)
(Scheme 2). The pentiptycenequinone 5 was obtained as a
mixture of syn and anti isomers, which were separated by silica
gel chromatography according to literature to yield the anti
isomer with the higher Rf value and the syn isomer with the
lower Rf value. The demethylation of the syn isomer of 5 with
boron tribromide afforded tetrahydroxy derivative 1. For the
synthesis of the hydroxymethyl derivative 2, we used 2,3-
Scheme
2.
Synthesis
of
tetrasubstituted
bis(acetoxymethyl)anthracene (9) as
a
precursor.
2,3-
pentiptycenequinones. Reagents and conditions, a) chloranil,
AcOH, yield 33% (anti isomer 24%); b) BBr3, dichloromethane,
yield 61%; c) NaBH4, LiCl, 2-propanol, yield 83%; d) NBS,
AIBN, CCl4, yield 67%; e) KOAc, DMF, yield 92%; f) chloranil,
AcOH, yield 31% (anti isomer 45%); g) K2CO3,
H2O/methanol/THF, yield 100%.
Bis(bromomethyl)anthracene (8) was synthesized by the
reduction of 2,3-dimethylanthraquinone (6)15 with sodium
borohydride followed by bromination with N-bromosuccinimide.
This dibromide 8 was converted to the diacetate 9 by the reaction
with potassium acetate. The tetraacetoxypentiptycenequinone
(10) was synthesized by the reaction of this diacetate 9 with 1,4-
benzoquionone (4) in acetic acid in the presence of chloranil.
The syn and anti isomers of this pentiptycenequinone derivative
10 were separated by silica gel chromatography in a manner
similar to that for the methoxy derivative 5, and the anti isomer
(the higher Rf value) and the syn isomer (the lower Rf value)
were isolated. The complete separation was confirmed by the 1H
NMR spectra in benzene-d6, while the two isomers were
observed at very similar chemical shifts in other solvents. The
stereoconfiguration of the anti isomer of 10 was confirmed by X-
ray crystallographic analysis16 and the other was unambiguously
In recent years, there are
a number of reports on
macrocyclization utilizing boronate ester formation.17 Since the
tetrahydroxy compounds 1 and 2 have two sets of diol moieties
fixed in a syn orientation, these compounds are expected to form
a
macrocycle with an appropriate diboronic acid.
We
investigated the macrocyclization of 1 with diboronic acid A in
CDCl3. At the initial stage, no signal of diboronic acid A was
observed due to its low solubility in CDCl3. After 2 days,
Figure 1. 1H NMR spectra of 1 (400 MHz, 1.0 mM) before and after the reaction with boronic acids A–D. (a) In CDCl3 and (b) in
CDCl3/CD3CN (9:1). Asterisks denote the solvent signal.

3
1
however, a yellow clear solution was obtained. In the H NMR
more complicated equilibria. The macrocyclization proceeds
spectrum, the protons of bridgehead methyne (Ha) and catechol
(Hb) were observed at 5.77 and 7.33 ppm respectively, which
appeared at lower field than the corresponding protons of the
hydroxy derivative 1 (Figure 1a, i and ii). The signal of 1,4-
phenylenediboronate moiety (Hc) was observed at 8.04 ppm.
Since each of these signals was observed as one singlet,
via at least six equilibrium steps involving four intermediates a–d
(Scheme 5). To simplify the analysis, we assumed that all the
boronate ester formation steps have the same equilibrium
constant (= K') except for the final intramolecular cyclization step
(K6). Based on this assumption, the five equilibrium constants
K1–K5 satisfy the conditions K1 = 4K', K2 = K3 = K', and K4 = K5 =
2K', given the statistical correlation. We determined these
equilibrium constants as K' ~ 1×104 M–1 and K6 ~ 50
formation of
a macrocyclic compound having an n:n
stoichiometry was suggested. The mass spectrum (MALDI-TOF
MS; anthracene matrix with silver triflate as an additive) showed
a peak at m/z = 1344.3 for [M + Ag]+, attributed to the 2:2
macrocycle. Thus, the reaction of pentiptycenequinone 1 and
diboronic acid A afforded a macrocyclic compound formulated
as 1A (Scheme 3). The macrocycle 1A readily dissociated into
its constituents in polar solvents such as CDCl3/CD3OD (9:1),
CDCl3/DMSO-d6 (9:1), and CDCl3/DMF-d7 (9:1), while it
remained intact in CDCl3/CD3CN (9:1) (Figure 1b, ii) and
CDCl3/acetone-d6 (9:1).
(dimensionless) by 1H NMR spectroscopy.
This large
equilibrium constant at the final step (K6 ~ 50), which is defined
as [1A]/[d], means that the macrocycle 1A is about 50 times
more favorable than the acyclic species d. On the basis of this
estimation, we can conclude that this favorable cyclization at the
final step significantly contributes to the efficient macrocycle
formation of 1A, compared to the formation of the non-cyclic
analog 1B2. Thus, the stability of 1A can be explained by
favorable intramolecular cyclization at the final step.
Scheme 5.
Proposed equilibria for the formation of
macrocyclic boronate ester 1A. Excess water is assumed to be
present in the solution.
Scheme 3. Formation of macrocyclic boronate 1A from
pentiptycenequinone 1 and diboronic acid A.
We also investigated the macrocyclization using diboronic
1
acids with different structures. The H NMR spectrum of the
The corresponding non-cyclic compound 1B2 was also
prepared quantitatively by the condensation of tetrahydroxy
derivative 1 with 2 equiv of phenylboronic acid (B) in CDCl3
(Figure 1a, iii). However, compared to the macrocycle 1A, this
non-cyclic compound 1B2 was found to be less stable in
CDCl3/CD3CN (9:1) and CDCl3/acetone-d6 (9:1). The diboronate
ester 1B2 was readily hydrolyzed to give a mixture containing
monoboronate ester 1B1 and the tetrahydroxy derivative 1 in
these solvents. The equilibrium constants for the boronate ester
formation in CDCl3/CD3CN (9:1) (Figure 1b, iii) were
determined to be K1 = 3.5×103 M–1 and K2 = 7.4×102 M–1
(Scheme 4). The K2/K1 ratio was approximately 0.25, which
nicely agrees with the ideal independent binding model of a two-
site receptor.18 This indicates that the boronate ester formation at
one catechol moiety does not affect the boronate formation at the
other side. From the values of K1 and K2, we estimated the
equilibrium constants for the condensation of one catechol
moiety and one boronic acid moiety as K' = 1.6×103 M–1 (~ 1/2K1
~ 2K2).
reaction mixture of 1 with 1,3-phenylenediboronic acid (C)
showed several signals assignable to the bridgehead methyne
protons and broad aromatic signals (Figure 1a, iv). This indicates
that several oligomers with different chain lengths were formed
instead of a macrocyclic compound with a discrete structure. On
the other hand, the reaction of 1 with 4,4'-biphenyldiboronic acid
(D) yielded a single macrocyclic compound, which showed a
simple 1H NMR signal pattern similar to that of 1A (Figure 1a, v).
The chemical shifts of the bridgehead methyne proton Ha and
catechol proton Hb were similar to those of 1A, indicating that a
similar high symmetrical macrocycle 1D was quantitatively
formed. The 2:2 macrocyclic structure was confirmed by
MALDI-MS measurement (m/z = 1496.5 for [M + Ag]+). It is
interesting to note that the reaction of hydroxymethyl analog 2
with 1,4-phenylenediboronic acid A did not form a single
macrocyclic product. This inefficient macrocyclization can be
explained by the seven-membered ring formation, which should
be less advantageous than the formation of a five-membered ring
with a more planar structure.
In
conclusion,
we
have
newly
synthesized
pentiptycenequinone derivatives 1 and 2 that have two diol
groups in a syn arrangement. The reaction of 1 with diboronic
acids such as 1,4-phenylenediboronic acid (A) and 4,4'-
biphenyldiboronic acid (D) gave a 2:2 macrocyclic compound in
a quantitative yield.
In this macrocyclization, the linear
arrangement of the two boronic acid moieties in the diboronic
acids is crucial for the efficient macrocyclization. Thus,
tetrahydroxypentiptycenequinone 1 was a useful building block
for belt-like macrocyclic boronate compounds. The rigid
macrocycles based on a pentiptycene skeleton generally have a
shape-persistent cavity, which would be useful as porous
materials for adsorption of larger organic molecules.
Scheme 4. Equilibria for the formation of diboronate ester
1B2.
In contrast to the non-cyclic derivative 1B2, the formation of
1A from two molecules of 1 and two molecules of A involves

4
Tetrahedron
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class of pentiptycene derivatives is now in progress.
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Acknowledgments
We thank Dr. Takashi Nirasawa (Bruker Daltonics K.K.) for
the MALDI-TOF MS measurement of compound 1D. This work
was supported in part by Grant for Basic Science Research
Projects from The Sumitomo Foundation (S.A.), Kanazawa
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Supplementary Material
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16. X-ray crystallographic analysis of the anti isomer of 10•2CH2Cl2
‒
Supplementary data associated with this article can be found
in the online version, at http://dx.doi.org/10.1016/j.tetlet.####.
(C48H40Cl4O10 = 918.60): triclinic P1, a = 8.7047(8), b =
11.5288(11), c = 11.6509(11) Å, α = 96.427(3), β = 110.015(3), γ
= 96.690(3) deg, V = 1076.59(18) Å3, Z = 1, T = 140 K, R1 =
0.0628 (I > 2σ(I)), wR2 = 0.1694 (all data). The ORTEP drawing
(50% probability) is shown below.
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