Synthesis of Octaaryl Naphthalenes and Anthracenes with Different Substituents

Article abstract of DOI:10.1002/anie.201709332

A synthesis of multiply arylated naphthalenes and anthracenes with eight different substituents has been accomplished. The key intermediates are tetraarylthiophene S-oxides, which are synthesized through a method involving sequential C?H arylation and cross-coupling from 3-methoxythiophene, followed by oxidation of the sulfur atom. The resulting tetraarylthiophene S-oxides can be converted into a tetraaryl benzynes or naphthalynes and then merged through [4+2] cycloaddition reaction with another tetraarylthiophene S-oxide, thereby resulting in the programmed synthesis of octaarylnaphthalenes and octaarylanthracenes.

Full text of DOI:10.1002/anie.201709332

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Accepted Article
Title: Synthesis of Octaaryl Naphthalenes and Anthracenes with
Different Substituents
Authors: Shin Suzuki, Kenichiro Itami, and Junichiro Yamaguchi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201709332
Angew. Chem. 10.1002/ange.201709332
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http://dx.doi.org/10.1002/ange.201709332

10.1002/anie.201709332
Angewandte Chemie International Edition
Synthesis of Octaaryl Naphthalenes and Anthracenes with
Different Substituents
Shin Suzuki,[1] Kenichiro Itami,* [1,2] and Junichiro Yamaguchi*[3]
Abstract: A synthesis of multiply arylated naphthalenes and
a) Previous Work: Synthesis of HABs
anthracenes with eight different substituents has been
accomplished. The key intermediate is a tetraarylthiophene S-
H
OMe
H
oxides, which is synthesized by a protocol involving sequential
C–H arylation and cross-coupling from 3-methoxythiophene,
followed by oxidation of the sulfur atom. The resulting
H
[4+2] cycloaddition
S
S
O
HABs (hexaarybenzenes)
tetraarylthiophene S-oxide can be converted to
a tetraaryl
b) Synthesis of OANs and OAAs: This Work
benzynes or naphthalynes, then merged via a [4+2] cycloaddition
reaction with another tetraarylthiophene S-oxide, resulting in the
programmed
synthesis
of
octaarylnaphthalene
and
S
octaarylanthracene.
O
Multiply arylated acenes such as arylated naphthalenes
and anthracenes are intriguing structural motifs that are
frequently utilized in optoelectronic organic materials,
especially as organic light-emitting diodes and organic
transistor materials.1 Despite these promising applications,
the synthesis of multiply arylated acenes still remains a
significant challenge in chemistry. Although several synthetic
methods have been reported thus far, they are best suited for
the synthesis of symmetrically arylated acenes but not
unsymmetrical acenes.2 Therefore, the development of a
general synthetic method that can introduce different aryl
groups onto an acene framework at will is in high demand.
Moreover, an efficient method would enable rapid
modification of these privileged structures, allowing expedited
evaluation of their structure-function relationship.
with
“tetraarylbenzyne”
“tetraarylnaphthalyne”
[4+2] cycloaddition
[4+2] cycloaddition
S
O
OAN (1)
(octaarylnaphthalene)
8 different aryls
OAA (2)
(octaarylanthracene)
8 different aryls
Figure 1. a) Our previous synthesis of hexaarylbenzenes (HABs). b) A
general synthetic plan toward multiply arylated naphthalenes and
anthracenes.
Our group and others have developed general methods to
access multiply arylated alkenes and heteroaromatics with
different substituents in
a predictable and programmed
manner.3,4 In 2015, we achieved the synthesis of
hexaarylbenzenes (HABs) using a [4+2] cycloaddition of
tetraarylthiophene S-oxides with diarylethynes (Figure 1A).5
The synthesis of tetraarylthiophenes was carried out by a
sequential regioselective C–H arylation and cross-coupling of
In view of the significance of linearly π-extended benzenoid
molecules in materials science, we decided to undertake the
programmed synthesis of multiply arylated acenes. Based on
our synthesis of HABs, we hypothesized that multiply arylated
naphthalenes and anthracenes could be synthesized by a
[4+2] cycloaddition of tetraarylthiophenes S-oxides with
multiply arylated benzynes or naphthalynes, which can be
prepared from another tetraarylthiophene S-oxide (Figure 1B).
Herein, we report the synthesis of acenes with eight different
aryls, octaarylnaphthalene (1: OAN) and octaarylanthracene
(2: OAA).
3-methoxythiophene.3h
Subsequently,
these
tetraarylthiophenes were oxidized to the corresponding
thiophene S-oxides, followed by [4+2] cycloaddition with
symmetrical/unsymmetrical diarylethynes to produce HABs
with five or six different aryl groups.
In 1996, Pascal and coworkers reported the synthesis of
octaphenylnaphthalenes using a [4+2] cycloaddition reaction
of tetraphenylcyclopentadienone with tetraphenylbenzyne.6
Inspired by their synthesis, we envisioned that
octaarylnaphthalene (1: OAN) could be synthesized by [4+2]
cycloaddition of tetraarylthiophene S-oxide 3B with
tetraarylbenzyne 4 (Figure 2). As a precursor of 4, we
selected tetraarylanthranilic acid 5, which could in turn be
generated by [4+2] cycloaddition of 3A with maleimide,
followed by Hoffmann rearrangement.
[1]
S. Suzuki, Prof. Dr. K. Itami
Institute of Transformative Bio-Molecules (WPI-ITbM) and Graduate
School of Science, Nagoya University, Chikusa, Nagoya 464-8602,
Japan
E-mail: itami@chem.nagoya-u.ac.jp (KI)
Prof. Dr. K. Itami
JST-ERATO, Itami Molecular Nanocarbon Project, Nagoya
University, Chikusa, Nagoya 464-8602, Japan
Prof. Dr. J. Yamaguchi
Department of Applied Chemistry, Waseda University, 3-4-1
Ohkubo, Shinjuku, Tokyo 169-8555, Japan.
E-mail: junyamaguchi@waseda.jp (JY)
Supporting information for this article is given via a link at the end of
the document.
[2]
[3]
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10.1002/anie.201709332
Angewandte Chemie International Edition
OMe
a.
O
O
N
H
+
3B
PhNO2
[85%]
S
[4+2]
cycloaddition
F3C
OMe
t-Bu
O
tetraarylbenzyne
4
tetraarylthiophene S-oxide 3a
1
sequential
[4+2] cycloaddition
F3C
OMe
O
O
O
O
N
H
N
H
6
3A
b. NaClO, NaOH
; KOH
[91%]
(5a/5b = 3:2 or 2:3)
S
O
S
O
F3C
(i) [4+2]
H2N
CO2H
cycloaddition
(ii) Hoffmann
rearrangement
R1
R2
3A
3B
anthranilic acid
5
5a: R1 = NH2,
5b: R1 = COOH, R2 = NH2
R2 = COOH
Figure 2. Synthetic strategy toward OAN 1.
c.
t-BuONO
(–N2 and CO2)
The synthesis of OAN 1 commenced with the [4+2]
cycloaddition of 3a with maleimide at 210 ºC to afford the
corresponding phthalimide 6 in 85% yield (Scheme 1).
Although the cycloaddition proceeded at room temperature,
aromatization (which involves dehydrogenation) required
OMe
OMe
Me
OMe
+
Me
S
F3C
Cl
O
these
high
temperatures.
Subsequent
Hoffmann
“tetraarylbenzyne” 4
tetraarylthiophene S-oxide 3b
rearrangement of 6, followed by hydrolysis under basic
conditions, provided tetraarylanthranilic acid 5 as a mixture of
regioisomers (5a/5b = 3:2 or 2:3) in 91% combined yield
(over 2 steps). Then in situ generation of tetraarylbenzyne 4
using tert-butyl nitrite, followed by reaction with another
tetraarylthiophene S-oxide 3b, produced OAN 1 as a mixture
of regioisomers (1a/1b = 1:2) in 22% combined yield. These
isomers can be easily separated by preparative thin-layer
chromatography. The structure of 1a was unambiguously
determined by X-ray crystallographic analysis (Figure 3a).
The X-ray crystal structure of 1a showed an end-to-end twist
of the central naphthalene core with an angle of 29.2° (Figure
3b,c), which is similar to the reported data for
octaphenylnaphthalenes.6 The photophysical properties of 1
were similar to octaphenylnaphthalenes as well (Figure S2).7
It should be emphasized that the present report represents
the first synthesis and characterization of an OAN with the
aryl substituents being all different.
–SO
Cl
Me
OMe
MeO
MeO
Me
OMe
+
OMe
Me
OMe
[22%]
(1a/1b = 1:2)
separable
Me
1a
1b
CF3 Cl
CF3
Scheme 1. Synthesis of OANs (1). Reaction conditions: a) maleimide (3.0
equiv), PhNO2, RT to 210 °C, 48 h, 85%; b) NaClO aq. (1.5 equiv), NaOH
aq. (5.0 equiv), MeOH, reflux, 10 min; KOH (36 equiv), i-PrOH, reflux, 16 h,
91% (5a/5b = 3:2 or 2:3, 2 steps); c) 3b (2.0 equiv), t-BuONO (1.5 equiv),
DCE, 80 °C,
2 h, 22% (1a/1b = 1:2) For the preparation of
tetraarylthiophenes 3a and 3b, see the Supporting Information.
Next, the synthesis of octaarylanthracenes (2: OAAs) was
undertaken. We envisaged that OAAs 2 could be synthesized
by [4+2] cycloaddition of tetraarylthiophene S-oxide 3B with
tetraarylnaphthalyne 8 (Figure 4). 8 was then thought to arise
from a [4+2] cycloaddition of 3A with benzyne from a novel
“double benzyne precursor” 7, which would enable the
sequential generation of two benzyne moieties. Although
double benzyne precursors8-17 have been reported, these
required controlled reaction conditions to prevent an over-
generation of benzyne moieties or the use of a strong base
for the generation of arynes.
Our design of 7 involves an unsymmetrical composition of a
hydroxy group and a triflate group ortho to two trimethylsilyl
groups. A trimethylsilyl group next to a hydroxy group is inert
toward the fluoride-based conditions that are usually used to
generate benzyne moieties, whereas the opposite triflate side
can generate the reactive benzyne moiety. Therefore, 7
would sequentially generate benzyne moieties and react with
3A then with 3B.
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10.1002/anie.201709332
Angewandte Chemie International Edition
a)
in 96% combined yield. Finally, treatment of 9 with TBAF and
another thiophene S-oxide 4b produced OAAs 2 as a mixture
of regioisomers (2a/2b = 1:1) in 46% yield. These isomers
can also be separated by preparative thin-layer
chromatography, from which 2a was crystallized and
characterized by X-ray crystallographic analysis (Figure
5).18,19
y
+
S
x
[4+2]
cycloaddition
O
c)
b)
2
3B
8
b
c
a
[4+2]
cycloaddition
double benzyne precursor (7)
e
f
d
TfO
TMS
OH
inert toward
fluoride conditions
z
twist angles benzene unit
(29.2°) (15.0°, 14.1°)
+
TMS
7
x
sequential generation
of benzyne
S
O
active toward
fluoride conditions
Figure 3. [a] X-ray crystal structure of 1a. In the ORTEP drawing of 1a,
hydrogen atoms are omitted for clarity and thermal ellipsoid are drawn at
50% probabilities. [b] The structure of 1a viewed from the y axis. Four aryl
groups in the y axis are omitted for clarity. [c] Selected carbons (pale red)
and centroids (blue) for the estimation of end-to-end twist angles (C(a)–
C(d)–C(f)–C(c)) and twist angles per benzene unit (C(a)–C(d)–C(e)–C(b)
and C(b)–C(e)–C(f)–C(c)).
3A
Figure 4. Synthetic strategy toward OANs 2 and design of a “double
benzyne precursor” 7.
Although the regioselectivity of the [4+2] cycloaddition still
has room for improvement, this method allows access to all
possible OANs and OAAs by installing aryl substituents at the
desired positions of a thiophene core. Additionally, the
potential functions and aesthetic appearance, as well as the
structural diversity of OANs/OAAs are extremely high. The
number of possible OANs or OAAs with all different
The synthesis of OAA 2 is depicted in Scheme 2. Precursor
7 was prepared from 2,5-dibromohydroquinone in 4 steps
(see the Supporting Information for details). [4+2]
cycloaddition of 7 with 3a smoothly proceeded in the
presence of tetrabutylammonium fluoride (TBAF) to afford the
corresponding hydroxynaphthalene in 84% yield. Triflation of
the resulting hydroxy group provided tetraarylnaphthalyne
precursor 9 as a mixture of regioisomers (9a/9b = 5:4 or 4:5)
substituents
(N)
from
eight
different
substituents
mathematically reaches 10080.20
OMe
OMe
a. TBAF, 3a
[84%]
HO
Br
Br
TfO
TMS
OH
+
F3C
b. Tf2O, i-Pr2NEt
[96%]
S
OH
TMS
4 steps
F3C
t-Bu
O
double benzyne precursor 7
tetraarylthiophene S-oxide 3a
via
TMS
OH
R1
R2
9a: R1 = TMS, R2 = OTf
9b: R1 = OTf, R2 = TMS
Cl
c. TBAF
OMe
Me
Me
OMe
OMe
MeO
MeO
Me
OMe
Me
OMe
+
S
F3C
Cl
OMe
O
tetraarylthiophene S-oxide 3b
Me
OMe
Me
8
[46%]
(2a/2b = 1:1)
separable
CF3
Cl
CF3
2a
2b
Scheme 2. Synthesis of OAAs (2). Reaction conditions: a) 7 (3.0 equiv), TBAF (6.0 equiv), THF, RT, 24 h, 84%; b) Tf2O (3.0 equiv), i-PrNEt2 (3.0 equiv), DMAP
(20 mol%), CH2Cl2, 0 °C to RT, 12 h, 96% (9a:9b=5:4 or 4:5); c) 3b (2.0 equiv), TBAF (2.0 equiv), THF, RT, 24 h, 46% (2a/2b = 1:1).
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10.1002/anie.201709332
Angewandte Chemie International Edition
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Figure 5. X-ray crystal structure of 2a. In the ORTEP drawing of 2a, hydrogen
atoms are omitted for clarity and thermal ellipsoid are drawn at 50%
probabilities.
In summary, we have developed a novel synthetic method
for octaarylnaphthalenes (OAN) and octaarylanthracenes (OAA)
using [4+2] cycloaddition of tetraarylthiophene S-oxides with
multiply arylated arynes. The present study also shows the
versatility of tetraarylthiophene S-oxides in [4+2] cycloadditions,
now allowing the synthesis of multiply arylated benzenes,
pyridines, naphthalenes, and anthracenes in a predictable and
programmed manner. Along with this development of a new
method for previously unattainable molecular structures, the
discovery of new functional materials can be expected.
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Acknowledgements
This work was supported by JSPS KAKENHI Grant Number
JP16H01011, JP16H01140, JP16H04148 (to J. Y.), the ERATO
program from JST (to K. I.), and a JSPS research fellowship for
young scientists (to S. S.). We also thanks Dr. Yasutomo
Segawa and Kenta Kato for assistance with X-ray crystal
structure analysis and computational studies. We thank Dr.
Yoshihiro Ishihara (Vertex Pharmaceuticals) for fruitful
discussion and critical comments. ITbM is supported by the
World Premier International Research Center (WPI) Initiative,
Japan.
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Keywords: arenes • polycycles • cycloaddition • arynes •
molecular diversity
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2 into the corresponding 9,10-endoperoxides was
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[3]
[20] Based on the concept of permutation, the number of OANs or OAAs
with eight different substituents (N) can be calculated by the formula N
= 2 x7!.
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Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Shin Suzuki, Kenichiro Itami,* and
Junichiro Yamaguchi*
Page No. – Page No.
Synthesis of Octaaryl Naphthalenes
and Anthracenes with Different
Substituents
A novel synthetic method for octaarylnaphthalenes (OAN) and octaarylanthracenes
(OAA) with eight different substituents has been demonstrated using [4+2]
cycloaddition of tetraarylthiophene S-oxides with multiply arylated arynes.
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