An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C?H Bond Activations

Article abstract of DOI:10.1002/anie.201700405

C?H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C?H arylation of unactivated benzene derivatives. A Pd₂(dibenzylideneacetone)₃ catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.

Full text of DOI:10.1002/anie.201700405

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201700405
German Edition: DOI: 10.1002/ange.201700405
Annulation Chemistry
An Annulative Synthetic Strategy for Building Triphenylene
À
Frameworks by Multiple C H Bond Activations
Bijoy P. Mathew+, Hyun Ji Yang+, Joohee Kim, Jae Bin Lee, Yun-Tae Kim, Sungmin Lee,
Chang Young Lee, Wonyoung Choe, Kyungjae Myung, Jang-Ung Park,* and Sung You Hong*
Dedicated to Professor Peter H. Seeberger on the occasion of his 50th birthday
À
À
Abstract: C H activation is a versatile tool for appending aryl synthesis, and C H activation, are logical choices to access
groups to aromatic systems. However, heavy demands on atomically precise graphene segments—also known as poly-
multiple catalytic cycle operations and site-selectivity have cyclic aromatic hydrocarbons (PAHs).[1,5–11]
limited its use for graphene segment synthesis. A Pd-catal-
Among the 35 parent structural units of PAHs, tripheny-
yzed one-step synthesis of functionalized triphenylene lene belongs to a branched all-benzoid category.[12] Pd-
frameworks is disclosed, which proceeds by 2- or 4-fold catalyzed annulation approaches to triphenylene moieties
are based on aryne chemistry.[13–17] For example, Pꢀrez et al.
À
C H arylation of unactivated benzene derivatives.
A
Pd2(dibenzylideneacetone)3 catalytic system, using cyclic dia- have reported [2+2+2] cyclotrimerization of benzynes (Sche-
ryliodonium salts as p-extending agents, leads to site-selective me 1a).[16] The Larock group introduced annulation of arynes
inter- and intramolecular tandem arylation sequences. More- using 2-halobiaryls.[17] Alternatively, Nishihara et al. have
over, N-substituted triphenylenes are applied to a field-effect reported a non-benzyne route using o-bromobenzyl alcohol
transistor sensor for rapid, sensitive, and reversible alcohol as an annulating agent (route A, Scheme 1b).[18] Yorimitsu
vapor detection.
et al. developed a multi-step transformation approach from
dibenzothiophenes (route B, Scheme 1b).[19] Shimizu and
G
raphene is a fundamentally and industrially important coworkers introduced [4+2]-type aromatic annulation
synthetic carbon allotrope that has been applied to a vast between 9-stannafluorenes and di-/tetra-halogenated com-
array of applications since its isolation by Geim and pounds (route C, Scheme 1b).[20] However, these methods for
Novoselov in 2004.[1–4] The development of synthetic methods
for accessing (functionalized) graphene and its molecular
segment has been a recent theme for synthetic chemists in
pursuit of two-dimensional nanostructures with finely tuned
properties.[1] Although top-down synthetic routes are well-
established for producing large-scale graphene materials,
bottom-up synthetic approaches, including the Diels–Alder
reaction, cross-coupling reactions, surface-mediated
[*] Dr. B. P. Mathew,[+] H. J. Yang,[+] J. B. Lee, Y.-T. Kim, Prof. Dr. C. Y. Lee,
Prof. Dr. S. Y. Hong
School of Energy and Chemical Engineering
Ulsan National Institute of Science and Technology (UNIST)
50 UNIST-gil, Ulsan 44919 (Republic of Korea)
E-mail: syhong@unist.ac.kr
Dr. B. P. Mathew,[+] Prof. Dr. K. Myung, Prof. Dr. S. Y. Hong
Center for Genomic Integrity (CGI), Institute for Basic Science (IBS)
School of Life Science
UNIST, 50 UNIST-gil, Ulsan 44919 (Republic of Korea)
J. Kim, Prof. Dr. J.-U. Park
School of Materials Science and Engineering, UNIST
50 UNIST-gil, Ulsan 44919 (Republic of Korea)
E-mail: jangung@unist.ac.kr
S. Lee, Prof. Dr. W. Choe
Department of Chemistry, UNIST
50 UNIST-gil, Ulsan 44919 (Republic of Korea)
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201700405.
Scheme 1. Synthesis of triphenylene frameworks.
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[a]
À
Table 1: Optimization of 2-fold C H arylation.
tailored triphenylene synthesis typically require laborious
prefunctionalization steps. Therefore, the development of
concise synthetic strategies to provide triphenylene frame-
works from unactivated substrates is an important synthetic
goal in graphene chemistry.
Herein, we show that unactivated and readily available
arene substrates can undergo Pd-catalyzed 2- or even 4-fold
Entry
Deviations from standard conditions
Yield [%][b]
À
C H arylation to afford substituted triphenylenes 3 or
phenanthro[9,10-b]triphenylenes 4, respectively (Scheme 1c).
To our knowledge, this is the first example of a straightforward
p-extension strategy utilized to provide triphenylene frame-
works from acetanilides and benzamides. The N-substituted
triphenylenes obtained are incorporated into an alcohol field-
effect transistor (FET) sensor, which exhibits a rapid and
reversible response.
1
2
3
4
5
6
7
8
none
no Pd2(dba)3
85
0
52
39
55
0
trace
0
Pd2(dba)3 (1.5 mol%)
Pd(PPh3)4 (instead of Pd2(dba)3)
Pd(OAc)2 (instead of Pd2(dba)3)
no NaOAc
NaOAc (1.0 instead of 5.0 equiv)
AgOAc (instead of NaOAc)
KOAc (instead of NaOAc)
K2S2O8 (1.0 equiv) added
air
BHT (1.0 equiv) added
TEMPO (1.0 equiv) added
toluene (instead of ODCB)
DMF (instead of ODCB)
ODCB (2 instead of 4 mL)
2a (1.5 instead of 3.0 equiv)
1008C
9
trace
64
31
Over the last few decades, direct arylation methods have
emerged aided by bench-stable hypervalent iodine com-
pounds.[21,22] It was anticipated that 2, with cyclic geometry,
10
11
12
13
14
15
16
17
18
27
À
has the potential for 2-fold C H arylation of 1 toward
9[c]
trace
0
aromatic annulation (Figure 1). Simple amide moieties were
chosen as the directing groups (DGs) owing to 1) their wide
prevalence in natural products and functional organic materi-
52
als, 2) the effective facilitation of sp2 C H activation,
À
51
8[c]
[a] Reaction conditions: 1a (0.228 mmol), 2a (3.0 equiv), Pd2(dba)3
(5 mol%), NaOAc (5.0 equiv), ODCB (4 mL), 1508C, 24 h under N2
atmosphere; ODCB=1,2-dichlorobenzene, dba=dibenzylidene-
acetone. [b] Isolated yields. [c] Yield determined by GC using n-dodecane
as an internal standard.
reduced yields (entries 10 and 11). The presence of radical
scavengers (butylated hydroxytoluene (BHT) and 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO)) affected the reac-
tion yields drastically (entries 12 and 13), indicating the
potential involvement of a radical pathway. A probable
thermal reduction of Pd(OAc)2 to Pd0 may account for
a moderate yield (55%, entry 5).[23] However, an alternative
mechanistic pathway involving a PdII/PdIV manifold cannot be
ruled out completely.[22,24] When other solvents were used,
such as toluene or N,N-dimethylformamide (DMF), the
reaction did not progress (entries 14 and 15). Reduction of
the reaction volume (2 mL) only caused a moderate drop in
yield (52%, entry 16). Finally, decreasing the concentration of
2a (1.5 equiv, entry 17) and reducing the reaction temper-
ature (1008C, entry 18) led to moderate and poor yields,
respectively.
With the optimized conditions in hand, our subsequent
goal was to investigate the reaction scope. Arenes with ortho-
alkyl groups, including iPr (1a), methyl (1b), and ethyl (1c),
gave good yields of the corresponding triphenylenes. Func-
tional groups with p-electron donors, such as ortho-phenyl
(1d), ortho-fluoro (1e), and ortho-OMe (1 f) were tolerated,
furnishing the annulated products in moderate to good yields.
However, electron-withdrawing trifluoromethyl, cyano, and
nitro groups resulted in poorer reactivity (3ha, 30%; 3ia and
3ja, no product). Pivanilide (1g) with no ortho-substituent
gave a poor yield (3ga, 25%). Subsequently, the 2-fold
arylation was attempted with meta-substituted substrates with
methyl and cyano groups (data not shown), but no product
À
Figure 1. Proposed 2-fold C H arylation mechanism.
and 3) increased processability for FET applications.
In cycle I, cyclic diaryliodonium salt 2 undergoes successive
single-electron reductions by Pd0 to form X-PdII-aryl com-
plex A, as previously suggested by the Glorius group.[23]
Subsequently, cyclopalladation of arene 1 would afford C,
which can undergo reductive elimination to give aryl iodide
D. In cycle II, oxidative addition, concerted metalation–
deprotonation, and subsequent reductive elimination, regen-
erate Pd0 and afford the desired product 3.
To examine the feasibility of this strategy, various reaction
parameters were surveyed. The optimized conditions pro-
vided annulated product 3aa in 85% yield (Table 1). In the
absence of catalyst (entry 2), there was no reactivity. Changes
in the palladium source or catalyst loading caused diminished
yields (entries 3–5). A control reaction without NaOAc
showed no reactivity (entry 6). Other weak bases, such as
AgOAc and KOAc, were ineffective (entries 8 and 9).
Addition of external oxidants, such as K2S2O8 or air, led to
2
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formation was observed. The para-substituted substrate 1k
changes, the yield of the bis-annulated product improved
was subjected to the reaction conditions, but a poor isolated
yield was obtained (26%). Additionally, the compatibility of
this method with other simple but electron-deficient benza-
mide substrates was examined. Benzamide-based tripheny-
lene derivatives (3na, 3oa, and 3pa) were obtained in
moderate yields (56%, 40%, and 51%, respectively) with
incomplete conversion of the corresponding substrates. Cyclic
diaryliodonium salts 2b and 2c bearing difluoro and dimethyl
groups provided good yields to afford 3ab and 3ac, respec-
tively. Given the difficulties in constructing a diverse array of
tailored triphenylenes, arising from the planar and (un)sym-
metrical structures,[15,19] the reaction scope of this approach is
comparable to that of previously reported methods.[16–20]
Overall, the electronic nature of the substrates bearing
amide DGs (and substituents) significantly affects the effi-
ciency of the annulation.
moderately to 40%. However, we still observed mono-
annulation with the reduced amount (18%). We performed
additional reactions with 2b and 2c, and observed
With the aim of using alternative DGs, we reacted
1-phenylpyrrolidin-2-one (1l) with 2a. Particularly note-
worthy is the formation of phenanthro[9,10-b]triphenylene
À
product 4la arising from 4-fold C H arylation in 10%
isolated yield along with product 3la (35% yield, Table 2).
Scheme 2. Synthesis of phenanthro[9,10-b]triphenylene 4 frameworks.
À
To enhance the yield of the bis-annulated (or 4-fold C H
arylated) product, we doubled the number of equivalents of
2a (6.0 equiv) and reduced the volume of 1,2-dichloro-
benzene (ODCB; 2 mL), as shown in Scheme 2. With these
phenanthro[9,10-b]triphenylene derivative formation in
33% and 40% yields, respectively. Single-crystal X-ray
diffraction analysis unambiguously confirmed the structure
of 4lb.[25] Interestingly, chlorinated substrate 1q gave bis-
annulated product 4qa, albeit with a poor isolated yield
(25%). The photophysical properties of compounds 4 were
also studied (Supporting Information).
Table 2: Reaction scope.[a]
To highlight the applicability of substituted triphenylenes,
readily soluble and processable 3aa was incorporated into
graphene-based FETs for application as a chemical gas sensor
as part of our ongoing research on the functionalization of
nanostructured carbons.[26–28] Graphene FETs were fabricated
on a Si wafer as a bottom gate structure (gate: doped Si;
dielectric layer: 300 nm-thick SiO2), and then 3aa was non-
covalently immobilized on the graphene channel with p–p
interactions, as shown in Figure 2a.[26,29] Figure 2b presents
the transfer curves of graphene FETs before and after 3aa
coating (Supporting Information, Figure S60). The pristine
FET showed ambipolar behavior consistent with the expected
semimetallic characteristics of graphene,[30–32] with a positive
charge neutrality point of approximately 38 V (black curve in
Figure 2b). The hole (electron) mobility of the graphene FET
was 2940 cm2 VÀ1 sÀ1 (2520 cm2 VÀ1 sÀ1) for a channel length of
70 mm and width of 5 mm. After 3aa coating, the graphene
FET showed a leftward VDirac shift because of its negative
charge transfer effect, with negligible change in mobility. The
similar slopes (trans-conductance (gm)) of the two curves in
Figure 2b indicate that graphene segment structured 3aa can
induce charge transfer without causing additional scatterings
on the graphene channel. Figure 2c reveals that the response
of the 3aa-functionalized sensor to ethanol vapor at 1000 ppm
is fast and completely reversible. The sensitivity was main-
tained upon multiple exposures. Hydrogen bonding with the
amide functionality of 3aa may give rise to ethanol binding on
[a] Standard conditions; isolated yields. [b] Reaction conditions: 1h
(0.228 mmol), 2a (3.0 + 2.0 equiv), Pd2(dba)3 (5 + 2.5 mol%), NaOAc
(5.0 equiv), ODCB (4 mL), 1508C, 48 h under N2 atmosphere.
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program
of
MOTIE/KEIT
(10046306). B.P.M. is a recipient of
the IBS fellowship (IBS-R022-D1-
2017). We are grateful to Prof. R.
Tenne at Weizmann Institute of
Science and Prof. J.-M. Kee at
UNIST for their helpful comments.
Conflict of interest
The authors declare no conflict of
interest.
À
Keywords: arylation · C
H activation · diaryliodonium salt ·
palladium · triphenylene
Figure 2. a) Interaction of 3aa with the graphene surface. b) Transfer characteristics (VD =0.1 V).
c) Real-time response. d) Sensor sensitivities.
the 3aa-functionalized graphene channel, which effectively
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Experimental Section
General procedure for annulation: An oven-dried Schlenk tube
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(5.0 equiv), and Pd2(dba)3 (5 mol%). The tube was evacuated and
purged with N2 repeatedly five times. To this mixture was added
ODCB and the system stirred at 1508C for 24 h. Upon completion of
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Acknowledgements
This work was supported by the National Research Founda-
tion of Korea (NRF-2016R1A2B4015497) and the IT R&D
4
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Final Article published: && &&, &&&&
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Annulation Chemistry
Closing the circle: Palladium-catalyzed 2-
À
or 4-fold C H arylation of unactivated
arenes was developed to access substi-
tuted triphenylene frameworks.
B. P. Mathew, H. J. Yang, J. Kim, J. B. Lee,
Y.-T. Kim, S. Lee, C. Y. Lee, W. Choe,
K. Myung, J.-U. Park,*
S. Y. Hong*
&&&& — &&&&
An Annulative Synthetic Strategy for
Building Triphenylene Frameworks by
À
Multiple C H Bond Activations
6
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