Synthesis of Functionalized Triphenylenes via a Traceless Directing Group Strategy

Article abstract of DOI:10.1021/acs.orglett.8b00071

A novel ligand-free Pd-catalyzed cascade reaction between o-chlorobenzoic acids and cyclic diaryliodonium salts is reported. This one-pot procedure involves a carboxylic acid directed o-arylation followed by intramolecular decarboxylative annulation affording various valuable triphenylenes, which can be further transformed into diversified building blocks for material chemistry. For the first time, it was shown that an aromatic halide can react with diaryliodonium salts under the direction of carboxylic acid functionality. It was also demonstrated that the carboxylic acid could be employed as both a traceless directing group and functional handle for the atom- and step-economical one-pot double cross-coupling annulation reaction with cyclic diaryliodonium salts as the π-extending agents.

Full text of DOI:10.1021/acs.orglett.8b00071

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis of Functionalized Triphenylenes via a Traceless Directing
Group Strategy
Shuai Yang,† Feng Wang,† Yanqi Wu,‡ Wenkai Hua,† and Fengzhi Zhang*,†
†College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, P. R. China
‡Institute of Information Resource, Zhejiang University of Technology, Hangzhou, 310014, P. R. China
S
* Supporting Information
ABSTRACT: A novel ligand-free Pd-catalyzed cascade
reaction between o-chlorobenzoic acids and cyclic diary-
liodonium salts is reported. This one-pot procedure involves
a carboxylic acid directed o-arylation followed by intra-
molecular decarboxylative annulation affording various val-
uable triphenylenes, which can be further transformed into
diversified building blocks for material chemistry. For the first
time, it was shown that an aromatic halide can react with diaryliodonium salts under the direction of carboxylic acid functionality.
It was also demonstrated that the carboxylic acid could be employed as both a traceless directing group and functional handle for
the atom- and step-economical one-pot double cross-coupling annulation reaction with cyclic diaryliodonium salts as the π-
extending agents.
Scheme 1. O-Arylation of Arenes via Directing Group
Strategy
he use of abundant and diversified carboxylic acids for
Ttransition-metal catalyzed reactions is a fast growing area
of research.1 Pioneering work has well established the fact that
the carboxylic acid functionality could be employed as either a
functional handle to undergo ipso-decarboxylative cross-
coupling reactions2 or a removable/traceless directing group
for ortho arene functionalization,3 which requires no significant
prefunctionalization and proceeds under catalytic conditions
leading to dramatically streamlined syntheses of functionalized
poly(hetero)aromatic compounds. Even though the possibil-
ities encompassed by the traceless carboxylic acid directing
group strategy are immense,4 only a few classes of trans-
formations on a small range of substrates have been explored to
date.5 Furthermore, in those examples, the carboxylic acid
functionalities were simply removed via protodecarboxylation
in situ or by another extra step,5 and had not been employed as
functional handles for further decarboxylative cross-coupling
reactions (Scheme 1, eq 1).
Polycyclic aromatic hydrocarbons (PAHs), regarded as
segments of infinite two-dimensional graphene, have been
extensively exploited as potential candidates for optoelectronic
devices and π-conjugated functional materials.6 Among these,
triphenylenes are the most often synthesized, by either aryne-
based7 or nonaryne-based8 approaches, which however still
suffer from different drawbacks, such as harsh conditions or
limited substrate scopes, etc. Recently, Park and Hong reported
a novel triphenylene synthesis by multiple C−H bond
activations.9 In this example, the amide functionality was
employed as the directing group and remained in the
triphenylenes after the reaction, thus limiting the structural
diversity of the final products (Scheme 1, eq 2). Although the
amide directing group can be removed, it does require extra
steps and resources. This limitation can be overcome by
employing traceless directing groups such as carboxylic acid
functionality, which can be easily detached from the products in
situ.5
In continuation of our research interest in decarboxylative
cross-coupling reactions10 and cyclic diaryliodonium salt
chemistry,11−13 we would like to develop a novel and efficient
method for the synthesis of various asymmetrical triphenylenes
and their N-incorporated derivatives in an atom- and step-
economical way14 by employing the carboxylic acids as both
traceless directing groups and functional handles, together with
Received: January 8, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00071
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the cyclic diaryliodonium salts as the 1,4-dimetal equivalents for
the double cross-coupling reactions (Scheme 1, eq 3).
However, there are some problems to be solved. First, to our
knowledge there is no report on the cross-coupling between the
aromatic halides and diaryliodonium salts. Second, the
carboxylic acid functionality might react with the cyclic
diaryliodonium salt straightway via either o-arylation13d,15 or
decarboxylative arylation.16 Third, even if the first carboxylic
acid directed o-arylation step takes place successfully, the in situ
protodecarboxylation5 might occur to give the acyclic coupling
compound as the final product, without the desired
triphenylene product being formed from the intramolecular
decarboxylative annulation.
With the optimum conditions in hand, we next examined the
scope of this novel acid directed ortho-arylation/decarboxylative
annulation sequence using a range of commercially available o-
chloro(hetero)aromatic acid derivatives (Table 2). Yields were
Table 2. Acid Substrate Scope
We initiated the investigation by performing the reaction of
the commercially available o-chloro benzoic acid 1a with cyclic
diaryliodonium salt 2a under transition metal (TM) catalyzed
conditions (Table 1).
a
Table 1. Reaction Optimization
b
c
entry
Pd(OAc)2 (mol %)
base
solvent
yield (%)
generally moderate to good for benzoic acids with simple alkyl
substituents (3b−c). For the substrates with more than one
chloro substituent on the aromatic ring, only one of the
chlorines ortho to the carboxylic acid was reacted (3d−f),
which demonstrated the essential directing effect of the acid
functionality. The substrates with either electron-donating or
-withdrawing groups were effective for the reaction (3g−k).
Except in the case of the phenyl chloride, the 1-bomo-2-
naphthoic acid also reacted well to give the benzo[g]chrysene
3l in 67% yield. However, the 3-chlorobenzothiophene-2-
carboxylic acid only afforded the benzo[b]phenanthro[9,10-
d]thiophene 3m in 35% yield probably due to catalyst
poisoning by sulfur.
To fully establish the scopes of this one-pot annulation
process, a range of substituted cyclic diaryliodonium salts were
prepared according to Olofsson’s method and subjected to the
optimized reaction protocol with ortho-chloro benzoic acid
derivatives (Table 3).17 Initially we tested the reactions of
symmetrical cyclic diaryliodonium salts with 2-chlorobenzoic
acid or 2-chloro-5-substitutedbenzoic acids (4a−f), which
afforded the corresponding products in moderate to good
yields. Next, a series of unsymmetrical cyclic diaryliodonium
salts were examined (3d, 4g−k). It was found that both
electron-donating and -withdrawing substituents on diary-
liodonium salts were tolerated, although the yield was
decreased when the unsymmetrical diaryliodonium salt with a
strong electron-rich substituent was employed (4j).
d
1
10
10
10
10
10
NaHCO3
K3PO4
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMA
30
46
57
66
67
d
2
d
3
d
4
5
6
−
̵
−̵
58
7
10
10
10
10
10
10
10
5
8
DMSO
iPrOH
DCE
58
9
−̵
−̵
74
68
69
74
81
10
11
NMP
NMP
NMP
NMP
NMP
e
12
f
13
14
15
2.5
b
K2CO3
a
c
d
0.5 mmol scale. Anhydrous solvent. Isolated yields. PPh3 (20 mol
%) was added. Salt 2a (0.8 equiv). Salt 2a (1.5 or 2.0 equiv).
e
f
After intensive screening of the catalytic systems (see
Supporting Information), we are pleased to find the desired
triphenylene 3a could be obtained in 30% yield with Pd(OAc)2
(10 mol %) as the catalyst, PPh3 (20 mol %) as the ligand, and
NaHCO3 (2.2 equiv) as the base in DMF at 110 °C for 17 h
(Table 1, entry 1). Next a base screening was carried out to
optimize the yield (Table 1, entries 1−4), and it was found that
the yield could be improved to 66% with K2CO3 as the base
(Table 1, entry 4). The blank experiment showed that the
reaction was still equally effective without the ligand (Table 1,
entry 5). However, the control experiment run in the absence
of the Pd catalyst was negative (Table 1, entry 6). The impact
of the solvent was then investigated (Table 1, entries 7−11),
and the product was isolated in 74% yield when NMP was used
as the solvent (Table 1, entries 11). Fine tuning of the salt-to-
acid ratio (Table 1, entries 12−13) and amount of the catalyst
(Table 1, entries 14−15) provided the optimized product yield
of 81% (Table, entry 15).
In order to gain insight into this novel annulation process, we
carried out the following control experiments (Scheme 2).
First, when the ortho-chloro benzoic acid 1a was reacted under
the optimum conditions alone without the presence of cyclic
diaryliodonium salts, the triphenylene product 3a did not form
at all. Furthermore, no cyclized product 5 was obtained by
reacting the ortho-chloro benzoic acid 1a with 2-methylfuran
(Scheme 2, eq 4), which showed that a benzyne mechanism as
described by Larock for the synthesis of triphenylene did not
involve our annulation reaction.7b Except in the case of the o-
B
DOI: 10.1021/acs.orglett.8b00071
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Letter
decarboxylative arylation/cyclization pathway might operate in
our annulation reaction (Scheme 3). First, a five-membered
Table 3. Cyclic Diaryliodonium Salt Scope
Scheme 3. Proposed Reaction Pathway
Pd(II) complex I might be formed from the ortho-
chlorobenzoic acid 1a, which then attacks the cyclic diary-
liodonium salt 2a to give the Pd (IV) complex II. A reductive
elimination followed by decarboxylation affords the Pd
coordinated polyphenyl iodide IV which can be cyclized to
give the seven-membered Pd(IV) complex V. Finally, a
reductive elimination releases the triphenylene product 3a
and Pd(OTf)I, which could be reduced under the reaction
conditions to give the Pd(0) catalyst for the next catalytic
cycle.19
Scheme 2. Control Experiments
Compared with their all-hydrocarbon analogues, N-incorpo-
rated triphenylenes which exhibit unprecedented chemical and
physical properties have been far less studied because of their
limited accessibility.20 By reacting 5-amino-2-chlorobenzoic
acid 10 with cyclic diaryliodonium salt 2a under optimum
conditions at 110 °C, interestingly the carbazolyl substituted
triphenylene 11 was obtained in 33% yield, which can be used
as an organic electronic device.21 By conducting the reaction at
145 °C in the presence of 2.5 equiv amounts of diaryliodoniym
salt 2a, the yield of compound 11 could be improved to 81%
(Scheme 4, eq 8). However, if 6-amino-2-chlorobenzoic acid 12
was treated with cyclic diaryliodonium salt 2a under the
optimum conditions at 110 °C, the 1-amino triphenylene 13
was obtained in 46% yield along with 10% N-arylated
triphenylene 14 (Scheme 4, eq 9), which did not cyclize to
form the carbazole probably due to the nearby steric hindrance.
By conducting the reaction at 145 °C in the presence of 2.5
equiv amounts of diaryliodoniym salt 2a, the yield of
compound 13 could be improved to 65%. To demonstrate
the applicability of our novel triphenylene synthetic method, we
managed to convert the substituted triphenylene 13 to different
N-incorporated PAHs successfully. After a simple protection,
the N-substituted triphenylene 15 was obtained which could be
applied to a field-effect transistor sensor for rapid, sensitive, and
reversible alcohol vapor detection (Scheme 4, eq 9).9 The N-
substituted triphenylene 15 could be cyclized to give the
polycyclic product 16, with possibly improved physicochemical
properties for applications as organic electronics.20 Treated
chlorobenzoic acid 1a, the o-bromobenzoic acid 6 also reacted
well giving the triphenylene 3a in 65% yield (Scheme 2, eq 5).
However, under the above optimum conditions the o-
iodobenzoic acid 6b only afforded the desired product 3a in
poor yield (unoptimized). By reacting the 2,6-dimethylbenzoic
acid 7 with the cyclic diaryliodonium salt 2a under the
optimum conditions (Scheme 2, eq 6), the decarboxylative
arylated product 8 was not obtained, which indicated that our
reaction requires a synergistic effect of both carboxylic acid and
ortho-chlorine. Finally, it was found that no reaction took place
between chlorobenzene 9 and diaryliodonium salt 2a under the
optimum conditions (Scheme 2, eq 7), which demonstrates the
essential directing effect of carboxylic acid.
Based on the above experiments and previous literature,8d,18
an acid directed ortho-arylation followed by an intramolecular
C
DOI: 10.1021/acs.orglett.8b00071
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Organic Letters
Letter
under Grant No. LR15H300001. We also thank the Zhejiang
Provincial Thousand-Talent Program and Zhejiang University
of Technology for financial support.
Scheme 4. Synthesis of Amino Substituted Triphenylenes
and Further Transformations into N-Incorporated PAHs
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ASSOCIATED CONTENT
* Supporting Information
■
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: zhangfengzhi@zjut.edu.cn.
ORCID
Fengzhi Zhang: 0000-0001-9542-6634
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
This research was supported by the Zhejiang Provincial Natural
Science Foundation of China for Distinguished Young Scholars
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