Direct arylation of polycyclic aromatic hydrocarbons through palladium catalysis

Article abstract of DOI:10.1021/ja202975w

We have discovered that the combination of Pd(OAc)₂/o-chloranil can catalyze the direct C-H bond arylation of polycyclic aromatic hydrocarbons (PAHs) with arylboroxins that occurs selectively at the K-region. The sequential integration of Pd-catalyzed direct arylation of PAHs and FeCl ₃-mediated cyclodehydrogenation is effective in rapidly extending a parent PAH π-system with high directionality.

Full text of DOI:10.1021/ja202975w

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pubs.acs.org/JACS
Direct Arylation of Polycyclic Aromatic Hydrocarbons through
Palladium Catalysis
Kenji Mochida,† Katsuaki Kawasumi,† Yasutomo Segawa, and Kenichiro Itami*
Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
S Supporting Information
b
Scheme 1. Direct Arylation of Small PAHs as a Possible
Initial Step toward Controlled Synthesis of Graphenes
ABSTRACT: We have discovered that the combination of
Pd(OAc)2/o-chloranil can catalyze the direct CꢀH bond
arylation of polycyclic aromatic hydrocarbons (PAHs) with
arylboroxins that occurs selectively at the K-region. The
sequential integration of Pd-catalyzed direct arylation of
PAHs and FeCl3-mediated cyclodehydrogenation is effec-
tive in rapidly extending a parent PAH π-system with high
directionality.
raphenes, two-dimensional sheets of sp2-hydridized carbon,
G
have received tremendous amounts of interests from almost
all areas of science and technology.1 As the shape, width, and
edge periphery (topology) determine the properties of gra-
phenes, a bottom-up synthesis of structurally uniform graphenes
is recognized as one of the greatest challenges of primary impor-
tance in this research field.1,2 Among various potential strategies,
a two-step approach through (i) controlled organic synthesis of
relatively large polycyclic aromatic hydrocarbons (PAHs) with
various topologies,3 followed by (ii) the surface-assisted coupling
of these PAHs4 or (ii0) the amplification sheet-growth using
these PAHs as a seed,5 holds promise for a controlled synthesis of
graphenes. As a possible first step toward this end, we herein
report the regioselective direct arylation of PAHs with arylbor-
oxins catalyzed by Pd(OAc)2/o-chloranil system (Scheme 1).
We also demonstrate that the sequential integration of Pd-
catalyzed direct arylation of PAHs and FeCl3-mediated cyclode-
hydrogenation is particularly effective in extending a parent PAH
π-system with high directionality.
Scheme 2. Pd-Catalyzed Direct CꢀH Arylation of Pyrene
with Phenylboroxin (1a)a
During the last two decades, significant progress has been
made in the synthesis of various types of extended PAHs as
exemplified by M€ullen’s giant molecular graphenes and nano-
ribbons.3 Typically, these extended PAHs have been fabri-
cated by (i) unit assembly using DielsꢀAlder reaction6 or
SuzukiꢀMiyaura coupling7 followed by (ii) cyclization using
cyclodehydrogenation,8 flash-vacuum pyrolysis,9 benzannula-
tion,10 photocyclization,11 and ring-closing metathesis.12 In
addition to these valuable routes, we envisioned that a
direct CꢀH bond arylation of commercially available small
PAHs occurring in a regioselective and predictable fashion
should find significant utility in the synthesis of extended
PAHs.13,14
a Reaction conditions: pyrene (0.20 mmol), 1a (0.13 mmol), Pd(OAc)2
(5.0 μmol), oxidant (0.20 mmol), DCE (2 mL), 80 °C, 2 h. Yields of 2a
were determined by GC analysis using n-dodecane as an internal standard.
We began our study by examining various arylating reagents,
catalysts, and additives in the CꢀH bond arylation of pyrene, a
model substrate for commercially available PAH. After extensive
screening, we identified that the combination of Pd(OAc)2
(catalyst), o-chloranil (oxidant), and arylboroxins (arylating reagents)
as providing the best system (Scheme 2). For example, pyrene
(1.0 equiv) could be effectively phenylated with phenylboroxin
Received: April 11, 2011
Published: June 23, 2011
r
2011 American Chemical Society
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|

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Table 1. CꢀH Arylation of Pyrene with Arylboroxins 1a
Scheme 3. Arylation of Substituted Pyrene and
Phenanthrene
a Conditions: 2,7-di-tert-butylpyrene (1.0 equiv), arylboroxin (0.67 equiv),
Pd(OAc)2 (2.5 mol %), o-chloranil (1.0 equiv), DCE, 80 °C, 2 h.
b Conditions: 2,7-di-tert-butylpyrene (1.0 equiv), arylboroxin (1.0 equiv),
Pd(OAc)2 (5 mol %), o-chloranil (2.0 equiv), DCE, 80 °C, 12 h.
c Conditions: phenanthrene (1.0 equiv), arylboroxin (0.67 equiv),
Pd(OAc)2 (5 mol %), o-chloranil (1.5 equiv), DCE, 80 °C, 12 h.
a Conditions: pyrene (0.20 mmol), 1 (0.13 mmol), Pd(OAc)2 (5.0
μmol), o-chloranil (0.20 mmol), DCE (2 mL), 80 °C, 2 h. b Isolated
yields. The numbers in the parentheses are the yields of diarylation
products. c Structures were confirmed by X-ray crystal structure analysis.
Having developed an efficient Pd(OAc)2/o-chloranil catalytic
system, we then examined the scope of applicable arylboroxins 1
(Table 1). Under the optimized conditions shown in Scheme 2,
various electronically and structurally diverse arylboroxins were
found to react with pyrene to give the corresponding 4-arylpyrenes
2 in moderate to good isolated yields. Some of the structures of 2
were unambiguously confirmed by X-ray crystallography (entries
1 and 8). Although diarylation also took place, pyrene was mainly
converted to the arylation products; combined yields of mono-
and diarylation products based on reacted pyrene were good to
excellent. Sterically demanding groups such as ortho-substituted
phenyl groups, the mesityl group, and the 1-naphtyl group were
effectively transferred to the pyrene ring (entries 5ꢀ9).
(1a: 0.67 equiv) in 1,2-dichloroethane (DCE) at 80 °C under the
action of Pd(OAc)2/o-chloranil to furnish 4-phenylpyrene (2a)
in 50% yield after 2 h. Under these conditions, biphenyl
(homocoupling product of 1a) was formed only in 3% yield.
Other phenylboron compounds such as phenylboronic acid and
the corresponding boronate esters can also be used, albeit in
somewhat lower efficiency (see the Supporting Information for
details). Very interestingly, the CꢀH/CꢀB cross-coupling15
took place exclusively at the C4 position of the pyrene ring.16ꢀ18
The use of o-chloranil as an oxidant is critically important for
the present reaction to occur. As shown in Scheme 2, other
frequently used oxidants such as DDQ, p-chloranil, p-benzoqui-
none, CuCl2, and K2S2O8 were ineffective. 3,5-Di-tert-butyl-1,
2-benzoquinone was the only oxidant other than o-chloranil that
displayed any reactivity. It became clear from these studies that
the high reactivity of o-chloranil stems not only from its high
oxidation aptitude,19 but also from the o-quinone structure.
Although further investigations are needed, Pd species bound
with two oxygen atoms of o-chloranil (o-quinone, o-semiquinone,
or catecholate form)20 might be responsible for the unique
reactivity in CꢀH/CꢀB coupling.
On the basis of these findings, we further investigated the
range of PAHs that could be employed. In this study, we report
the reactions of PAHs having K-regions (Scheme 3).21 The
reaction of 2,7-di-tert-butylpyrene with phenyl-, 2-chlorophenyl-,
and mesitylboroxin proceeded smoothly to give the correspond-
ing 4-arylated pyrenes (3a, 3e, and 3h) in good yields. When 2,
7-di-tert-butylpyrene was treated with an excess of arylboroxins
(1a, 1e, and 1h), the double CꢀH arylation took place to afford
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Scheme 4. Possible Mechanisms for C4-Selective Arylation
of Pyrene
Scheme 5. Synthesis of Extended PAHs through Sequential
CꢀH Arylation with o-Biphenylboroxin and FeCl3 Oxidationa
a Conditions: (a) PAH (1.0equiv), 6(0.6equivfor 7and 8, 1.0 equivfor9),
Pd(OAc)2 (5 mol %), o-chloranil (1.2 equiv for 7 and 8, 2.2 equiv for 9),
DCE, 80 °C. (b) FeCl3 (5.0 equiv for 7 and 8, 7.5 equiv for 9), DCM/
MeNO2, 0 °C to rt.
the corresponding diaryled pyrenes (4a, 4e, and 4h) in good to
high yields. It was also found that there is almost no regiocontrol
over the second arylation (C9/C10 = 1.1:1ꢀ1:1.5), although we
observed a small aryl group dependence on regioselectivity. The
CꢀH arylation of phenanthrene also occurred efficiently with
various arylboroxins to afford the corresponding 9-arylphenan-
threnes (5a, 5e, and 5f) in good to excellent yields.14 As in the
case of pyrene, phenanthrene reacted exclusively at the K-region.
Apart from achieving the efficient π-extension of PAHs
through Pd catalysis, the unique regioselectivity (e.g., C4-selec-
tivity for pyrene) is particularly interesting as it might provide
insight into the mechanism. Although the precise details are
unclear at present, several mechanisms could explain the C4-
selectivity of pyrene arylation (Scheme 4). One possible me-
chanism is based on electrophilic palladation followed by palla-
dium migration. Similar to typical SEAr reactions,16 electrophilic
palladation of pyrene with arylpalladium species (generated from 1)
might occur at the most nucleophilic C1 position of pyrene
ring. This initially formed cationic intermediate A can isomerize
into the formal C4-attacked intermediate C through σꢀπꢀσ
isomerization of allylic palladium species B. From a consideration
of resonance effects, C is likely to be thermodynamically more
stable than the other possible intermediates as it has two intact
benzene rings within the pyrene framework. Deprotonation of C
followed by reductive elimination from D produces 4-arylpyrenes 2.
Another possible mechanism is based on pyreneꢀpalladium
complexation. As indicated in other works,22 the π-complexation
of palladium might occur selectively at the C4ꢀC5 double bond of
pyrene (K-region). Electrophilic palladation triggered by this
complexation (E) would directly furnish the cationic intermediate
C. Alternatively, Heck-like carbopalladation (insertion) of arylpal-
ladium species might occur from E to give F. This is reminiscence
of the C4-regioselectivity observed in the addition of methyl-
lithium to pyrene.23 The thus-formed F can be transformed to
4-arylpyrenes 2 either by β-hydrogen elimination or by proto-
depalladation/oxidation sequence. Further detailed study for the
elucidation of the reaction mechanism coupled with the accelera-
tion effect of o-chloranil is currently underway.
Finally, we examined the synthesis of more extended PAHs by
the sequential integration of Pd-catalyzed CꢀH bond arylation
and cyclodehydrogenation (Scholl reaction).8a Shown in Scheme 5
are the representative examples using o-biphenylboroxin (6) as
an arylating agent.24 For example, phenanthrene cross-coupled
with 6 under the action of Pd(OAc)2/o-chloranil to afford
9-biphenylated phenanthrene. The follow-up treatment with
FeCl3 in CH2Cl2/MeNO2 at room temperature successfully
closed the “fjord region” of the initial coupling product to furnish
dibenzochrysene (7) in 60% overall yield. Similarly, the two-step
reaction of benzo[a]anthracene resulted in the formation of
tribenzotetraphene (8) in 12% yield. The low isolated yield of 8 is
partly due to the solubility issues. Two-directional π-extension of
PAHs is even more interesting. For example, a double CꢀH
bond arylation of 2,7-di-tert-butylpyrene with 6, followed by
cyclodehydrogenation, gave hexabenzotetracene 9 in 60% yield.
It is noteworthy that the reaction can be conducted on a gram scale.
In summary, we have demonstrated that the newly developed
Pd(OAc)2/o-chloranil system is an effective catalyst for the
oxidative direct arylation of PAHs with arylboroxins. The un-
expected emergence of unique C4-regioselecivity for pyrene
arylation is particularly interesting not only because it provides
information about the mechanism, but also because it can be
utilized complementarily with the other π-extendable reactions
such as bromination (C1)16 and Ir-catalyzed CꢀH borylation
(C2).17 We also demonstrate that the sequential integration of
Pd-catalyzed direct arylation of PAHs and FeCl3-mediated cyclo-
dehydrogenation is particularly effective in rapidly extending a
parent PAH π-system with high directionality. Elucidation of the
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COMMUNICATION
mechanism of Pd(OAc)2/o-chloranil-mediated CꢀH bond ar-
ylation, synthesis of a whole range of extended PAHs, and the
controlled synthesis of graphenes such as graphene nanoribbons
are currently ongoing in our laboratory.
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threne and fluoranthene): Kawai, H.; Kobayashi, Y.; Oi, S.; Inoue, Y.
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’ ASSOCIATED CONTENT
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bromination are known to occur preferentially at the C1 position of
pyrene ring: Vollmann, H.; Becker, H.; Corell, M.; Streeck, H.;
Langbein, G. Liebigs Ann. Chem. 1937, 531, 1.
(17) Ir-catalyzedCꢀH borylation is known to occur at the C2 position
of pyrene ring: Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard,
J. A. K.; Marder, T. B.; Perutz, R. N. Chem. Commun. 2005, 2172.
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pyrene ring: (a) Moriarty, R. M.; Dansette, P.; Jerina, D. M. Tetrahedron
Lett. 1975, 16, 2557. (b) Pryor, K. E.; Shipp, G. W., Jr.; Skyler, D. A.;
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S
Supporting Information. Experimental procedures, charac-
b
terization data of new compounds, and CIF file of 2a, 2h, and
8. This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
itami.kenichiro@a.mbox.nagoya-u.ac.jp
Author Contributions
†These authors contributed equally.
’ ACKNOWLEDGMENT
This work was supported by a Grant-in-Aid for Scientific
Research from MEXT. K.M. thanks the Nagoya University
Global COE program of Elucidation and Design of Materials
and Molecular Functions for postdoctoral fellowship.
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