Synthesis of Triphenylenes Starting from 2-Iodobiphenyls and Iodobenzenes via Palladium-Catalyzed Dual C-H Activation and Double C-C Bond Formation

Article abstract of DOI:10.1021/acs.orglett.6b02071

A novel and facile approach for the synthesis of triphenylenes has been developed via palladium-catalyzed coupling of 2-iodobiphenyls and iodobenzenes. The reaction involves dual palladium-catalyzed C-H activations and double palladium-catalyzed C-C bond formations. A range of unsymmetrically functionalized triphenylenes can be synthesized with the reaction. The approach features readily available starting materials, high atom- and step-economy, and access to various unsymmetrically functionalized triphenylenes.

Full text of DOI:10.1021/acs.orglett.6b02071

Letter
pubs.acs.org/OrgLett
Synthesis of Triphenylenes Starting from 2‑Iodobiphenyls and
Iodobenzenes via Palladium-Catalyzed Dual C−H Activation and
Double C−C Bond Formation
Shulei Pan, Hang Jiang, Yu Zhang, Dushen Chen, and Yanghui Zhang*
School of Chemical Science and Engineering, Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University,
1239 Siping Road, Shanghai 200092, China
S
* Supporting Information
ABSTRACT: A novel and facile approach for the synthesis of triphenylenes has been developed via palladium-catalyzed
coupling of 2-iodobiphenyls and iodobenzenes. The reaction involves dual palladium-catalyzed C−H activations and double
palladium-catalyzed C−C bond formations. A range of unsymmetrically functionalized triphenylenes can be synthesized with the
reaction. The approach features readily available starting materials, high atom- and step-economy, and access to various
unsymmetrically functionalized triphenylenes.
olycyclic aromatic hydrocarbons (PAHs) are one of the
most important classes of organic molecules due to their
group realized the coupling of arynes with 1-(2-bromophenyl)-
1H-indole.12 Nishihara and co-workers reported the annulation
of o-iodobiphenyls with o-bromobenzyl alcohols under
palladium catalysis, providing an efficient method for the
synthesis of highly substituted triphenylenes.4d,13 Other
palladium-catalyzed examples include double cross-coupling
of 9-stannafluorenes with 1,2-dibromoarenes,14 double cross-
coupling of 1,2-bis(pinacolatoboryl)arenes with 2,2′-dibromo-
biaryls,15 and the intramolecular cyclization of terarylsulfonium
salts obtained from dibenzothiophenes.16 Although these
reactions offer versatile methods for the synthesis of
triphenylenes, it is still desirable to develop general and facile
methods starting from readily available substrates for the
synthesis of triphenylenes, particularly substituted ones, which
play important roles in materials chemistry.3a−c
Recently, our group disclosed that dibenzopalladacyclopen-
tadienes have intriguing reactivities and have been exploited to
develop facile and practical synthetic methods.17 During the
research on the synthesis of tetraphenylenes, we isolated a small
amount of triphenylene when iodobenzene was added.17a
Unfortunately, in spite of our great efforts, we failed to improve
the yield of triphenylene. Dibenzopalladacyclopentadienes can
also be generated from 2-iodobiphenyls under basic con-
ditions,17b,c so we envisioned that triphenylenes could be
formed by the coupling of 2-iodobiphenyl with iodobenzene
under the basic conditions. Herein, we report a new method for
the synthesis of triphenylenes starting from readily available
P
widespread applications in various fields.1 Among these,
triphenylenes are particularly interesting. As the smallest
example of all-benzenoid polycyclic aromatic hydrocarbons,
triphenylene has the same fundamental skeleton as many other
PAHs and can act as a precursor to synthesize these PAHs.2
More importantly, triphenylenes have great application
potentials in supramolecular and materials chemistry.3
Triphenylenes have been employed to make functional organic
materials such as discotic liquid crystals and organic light-
emitting diodes.4
Over the past decades, interest in the chemistry of
triphenylenes has increased continuously, and the synthesis of
triphenylenes has attracted considerable attention.5 To date, a
variety of synthetic strategies for triphenylenes have been
developed. One of the common strategies involves the
cyclization of o-terphenyls.6 A second popular approach for
the synthesis of triphenylenes is the trimerization of arynes.7
This approach is primarily limited to the synthesis of
symmetrical triphenylenes. Furthermore, a variety of other
interesting synthetic means are available.8 More recently,
palladium catalysis based methods have gained great attention
as they offer facile and efficient strategies for the synthesis of
triphenylenes. Miura and co-workers found that o-dibromo-
benzenes could undergo Pd-catalyzed coupling reaction with o-
phenybenzyl alcohols to form triphenylenes.9 The Larock
group disclosed a novel method for the synthesis of substituted
triphenylenes via the palladium-catalyzed annulation of o-
iodobiphenyls with arynes.10 The Cheng group developed the
carbocyclization of arynes with aryl iodides,11 and the Zhang
Received: July 15, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02071
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Letter
substrates 2-iodobiphneyls and iodobenzenes under palladium
catalysis.
We initiated our research by investigating the coupling
reaction of 2-iodobiphenyl and iodobenzene. After extensive
screening, we obtained the desired triphenylene in 38% yield
when the reaction was carried out in DMF in the presence of
Pd(OAc)2, K2CO3, and KOAc under N2 atmosphere (Table 1,
small amount of triphenylene was observed for the reactions in
t-BuOH or THF (entries 13−16). In addition, the reaction in 2
mL of DMF was less effective (entry 17), and the yields
decreased when the reaction was carried out at a higher or
lower temperature (entries 18 and 19). Finally, the use of 1 or 2
equiv of PhI resulted in lower yields (entries 20 and 21).
Having developed an efficient procedure for the synthesis of
triphenylene, we next investigated the substrate scope of this
transformation. We first examined the performance of a range
of 2-iodobiphenyls under the optimized reaction conditions.
Therefore, as shown in Table 2, 2-iodobiphenyls bearing a
methoxy group at the 3′ or 4′ position coupled with
iodobenzene (entries 1 and 2). It is noted that the reaction
selectively occurred at the less hindered position for 1c, so the
reactions of 1b and 1c formed the same product 3ba. The
substrate bearing 2′-methoxy group was also suitable, albeit in a
lower yield (entry 3). The substrates bearing a methyl or
phenyl group were also reactive (entries 4−6). A range of
electron-withdrawing substituents were then examined. The
trifluoromethyl group was well-tolerated, and triphenylenes
were formed in good or excellent yields (entries 7 and 8).
However, other electron-withdrawing groups including ester,
carbonyl, and nitro gave much lower yields (entries 9−11). In
these reactions, a portion of 2-iodobiphenyls was recovered.
The reason could be that it is difficult to cleave the C−H bonds
of the electron-deficient benzene. Both fluoro and chloro
groups, on the iodo-containing benzene ring or the other
phenyl group, were well-tolerated under the standard
conditions (entries 12−15). 2-Iodobiphenyl bearing two
methyl groups was also reactive (entry 16). Furthermore,
symmetrically substituted substrates, containing phenyl of
trifluoromethyl groups, underwent the double coupling
reaction, albeit in lower yields (entries 17 and 18). It is
noted that unsymmetrically substituted 2-iodobiphenyls were
suitable, affording unsymmetrically functionalized triphenylenes
(entries 19 and 20).
Next, the iodobenzene scope was examined. The methoxy
groups at the para and meta positions were compatible, and the
reactions afforded methoxylated triphenylene in 91% or 74%
yield (entries 21 and 22). It should be mentioned that the
reaction for 2c took place at the less hindered position, forming
the same product as that for 2b. In a similar way, iodobenzenes
containing a m- or p-methyl group formed the same product
3ea (entries 23 and 24). The chloro and fluoro groups were
tolerated in the reaction (entries 25−27), and the reactions of
2g and 2h formed the same product 3pa. 4-Iodobiphenyl and
1-(difluoromethoxy)-4-iodobenzene were also suitable (entries
28 and 29). The reactions of iodobenzenes bearing electron-
withdrawing groups such as trifluoromethyl and ester were low
yielding (entries 30 and 31). The major reason was that these
electron-deficient iodobenzenes tended to undergo homocou-
pling to form biphenyl byproducts. Bromobenzene was also
reactive, albeit in a low yield (entry 32). To obtain multiple
substituted triphenylene derivatives, we also examined the
reaction of substituted iodobenzenes and 2-iodobiphenyls.
4-Iodoanisole reacted with symmetrically substituted 2-
iodobiphenyls to afford multiply substituted triphenylenes in
moderate yields (entries 33−35). When unsymmetrically
substituted 2-iodobiphenyls were used, two regioisomers were
formed (entry 36).
Table 1. Optimization of Reaction Conditions for the Pd-
Catalyzed Formation of Triphenylene from 2-Iodobiphenyl
and Iodobenzene
base 1
(2 equiv)
base 2
(3 equiv)
ligand
(mol %)
solvent
(4 mL)
a
entry
yield (%)
b
1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
NaOAc
CsOAc
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
DMSO
t-BuOH
THF
38
41
48
46
49
60
63
63
45
b
2
PPh3 (20)
L1 (10)
L2 (10)
L3 (10)
dppf (10)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
dppf (5)
b
3
b
4
b
5
b
6
7
8
9
c
10
11
12
13
14
15
16
17
18
19
20
21
71 (70)
43
35
50
41
4
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
6
d
DMF
55
e
DMF
DMF
DMF
DMF
10
f
52
g
47
h
64
a
The yields were determined by 1H NMR analysis of the crude
reaction mixtures using CHCl2CHCl2 as the internal standard.
b
c
d
e
f
Pd(OAc)2 (10 mol %). Isolated yield. 2 mL. 100 °C. 140 °C.
g
h
1 equiv of PhI. 2 equiv of PhI. L1: PPh2CH2PPh2. L2:
PPh2(CH2)4PPh2. L3: bis(dicyclohexylphosphino)ferrocene. dppf: 1,
1′-bis(diphenylphosphino)ferrocene.
entry 1). However, further efforts failed to improve the yield, so
we sought the aid of ligands. While PPh3 gave a similar yield
(entry 2), the use of a bidentate phosphine ligand led to a slight
increase in yield (entries 3−5). The yield was improved to 60%
when dppf was employed (entry 6). Notably, the yield
remained almost unchanged when the loadings of Pd(OAc)2
and the ligand were reduced to 5 mol % (entry 7). Next, we
examined the impact of bases on the reaction. We found that
replacing K2CO3 with Na2CO3 resulted in an identical yield
(entry 8). However, while a combination of Na2CO3 and
NaOAc gave a lower yield (entry 9), a 71% yield was obtained
in the presence of Na2CO3 and CsOAc (entry 10).
Furthermore, the absence of Na2CO3 or CsOAc led to a
much lower yield (entries 11 and 12). The reason remains to be
investigated. The effect of solvents was also examined. The
reactions in NMP or DMSO were lower yielding, and only a
While the detailed mechanism of the reaction remains to be
investigated and other reaction pathways cannot be ruled out,
based on our previous works, a tentative mechanism can be
B
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Letter
Table 2. Substrate Scope with Respect to 2-Iodobiphenyls
a
b
Yields are those of purified and isolated products. The ratio of the two isomers is 1:2.44.
proposed as shown in Scheme 1. Therefore, the catalytic cycle
should begin with the oxidative addition of 2-iodobiphenyl to
Pd(0) to form complex A. Intramolecular C−H activation
yields palladacycle B. Next, B undergo oxidative addition with
iodobenzene to give Pd(IV) complex C. The subsequent
reductive elimination generates Pd(II) complex E. At this stage,
an alternative pathway for the formation of E from B cannot be
ruled out. Complex B could undergo transmetalation-type
exchange of aryl ligands with the phenylpalladium(II) species,
which is formed by the oxidative addition of iodobenzene to
Pd(0) to afford dinuclear arylpalladium complex D.18 The
reductive elimination of complex D leads to complex E.
In conclusion, a novel and facile approach for the synthesis of
triphenylenes has been developed. The starting materials 2-
iodobiphenyls and iodobenzenes are readily available. The
reaction involves two palladium-catalyzed C−H activations and
two palladium-catalyzed C−C bond formation steps, which
makes the reaction atom- and step-economic. A range of
unsymmetrically functionalized triphenylenes can be synthe-
sized with this method. Therefore, the approach features readily
C
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Letter
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available starting materials, atom- and step-economy, and
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b02071.
Detailed experimental procedures, spectroscopic data,
and characterization of products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: zhangyanghui@tongji.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́
21, 5254. (d) Cardenas, D. J.; Martín-Matute, B.; Echavarren, A. M. J.
Am. Chem. Soc. 2006, 128, 5033.
This work was supported by the National Natural Science
Foundation of China (21372176), Tongji University 985 Phase
III funds, the Program for Prof. of Special Appointment
(Eastern Scholar) at Shanghai Institutions of Higher Learning,
and the Shanghai Science and Technology Commission
(14DZ2261100).
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