Pd(OAc)2/o-chloranil/M(OTf)n: A catalyst for the direct C-H arylation of polycyclic aromatic hydrocarbons with boryl-, silyl-, and unfunctionalized arenes

Article abstract of DOI:10.1021/ol203235w

Pd(OAc)₂/o-chloranil/M(OTf)_n can effectively promote the C-H arylation of fluoranthene with arylboron compounds or arylsilanes. The reaction takes place with high regioselectivity at the C3 position of fluoranthene. Moreover, the new

Full text of DOI:10.1021/ol203235w

ORGANIC
LETTERS
2012
Vol. 14, No. 1
418–421
Pd(OAc)2/o-Chloranil/M(OTf)n: A Catalyst
for the Direct CÀH Arylation of Polycyclic
Aromatic Hydrocarbons with Boryl-, Silyl-,
and Unfunctionalized Arenes
Katsuaki Kawasumi, Kenji Mochida, Tomonori Kajino, Yasutomo Segawa, and
Kenichiro Itami*
Department of Chemistry, Graduate School of Science, Nagoya University,
Nagoya 464-8602, Japan
itami.kenichiro@a.mbox.nagoya-u.ac.jp
Received December 5, 2011
ABSTRACT
Pd(OAc)2/o-chloranil/M(OTf)n can effectively promote the CÀH arylation of fluoranthene with arylboron compounds or arylsilanes. The reaction
takes place with high regioselectivity at the C3 position of fluoranthene. Moreover, the new catalytic system allows the use of unfunctionalized
arenes as coupling partners in the arylation of polycyclic aromatic hydrocarbons.
The arylation of polycyclic aromatic hydrocarbons
(PAHs) is a fundamental reaction in the synthesis of
π-extended PAHs useful in the field of materials science
and nanocarbon chemistry.1 Typically arylation of
PAHs has been executed by a two-step sequence con-
sisting of either (i) halogenation of PAHs followed by
Pd-catalyzed cross-coupling reactions,2 or (ii) Ir-cata-
lyzed CÀH borylation of PAHs followed by Pd-cata-
lyzed cross-coupling with aryl halides.3 Very recently,
we discovered that the combination of Pd(OAc)2/o-
chloranil catalyzes the direct CÀH arylation at the
‘armchair’ edge of PAHs, such as pyrene, with arylbor-
on compounds (Figure 1).4À6 We also demonstrated
that the sequence of Pd-catalyzed direct arylation of
pyrene with o-biphenylboroxin followed by FeCl3-
mediated cyclodehydrogenation rapidly extends a
(4) Mochida, K.; Kawasumi, K.; Segawa, Y.; Itami, K. J. Am. Chem.
Soc. 2011, 133, 10716.
(5) For excellent reviews on CÀH arylation of aromatic compounds,
see: (a) Ackermann, L.; Vincente, R.; Kapdi, A. R. Angew. Chem., Int.
Ed. 2009, 48, 9792. (b) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q.
Angew. Chem., Int. Ed. 2009, 48, 5094. (c) Sun, C.-L.; Li, B.-J.; Shi, Z.-J.
Chem. Commun. 2010, 46, 677. (d) Liu, C.; Zhang, H.; Shi, W.; Lei, A.
Chem. Rev. 2011, 111, 1780.
(6) For our selected contributions in the field, see: (a) Yanagisawa, S.;
Sudo, T.; Noyori, R.; Itami, K. J. Am. Chem. Soc. 2006, 128, 11748.
(b) Ban, I.; Sudo, T.; Taniguchi, T.; Itami, K. Org. Lett. 2008, 10, 3607.
(c) Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org. Lett. 2009, 11,
1733. (d) Join, B.; Yamamoto, T.; Itami, K. Angew. Chem., Int. Ed. 2009,
48, 3644. (e) Yanagisawa, S.; Ueda, K.; Sekizawa, H.; Itami, K. J. Am.
Chem. Soc. 2009, 131, 14622. (f) Ueda, K.; Yanagisawa, S.; Yamaguchi,
J.; Itami, K. Angew. Chem., Int. Ed. 2010, 49, 8946. (g) Kirchberg, S.;
Tani, S.; Ueda, K.; Yamaguchi, J.; Studer, A.; Itami, K. Angew. Chem.,
Int. Ed. 2011, 50, 2387. (h) Yamaguchi, A. D.; Mandal, D.; Yamaguchi,
J.; Itami, K. Chem. Lett. 2011, 40, 555. (i) Yamamoto, T.; Muto, K.;
Komiyama, M.; Canivet, J.; Yamaguchi, J.; Itami, K. Chem.;Eur. J.
2011, 17, 10113. (j) Mandal, D.; Yamaguchi, A. D.; Yamaguchi, J.;
Itami, K. J. Am. Chem. Soc. 2011, 133, 19660.
(1) (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons, Wiley-VCH:
€
New York, 1997; pp 43À128. (b) Feng, X.; Pisula, W.; Mullen, K. Pure
Appl. Chem. 2009, 81, 2203.
(2) For representative examples, see: (a) Jackson, E. A.; Steinberg,
B. D.; Bancu, M.; Wakamiya, A.; Scott, L. T. J. Am. Chem. Soc. 2007,
129, 484. (b) Figueira-Duarte, T. M.; Simon, S. C.; Wagner, M.;
€
Druzhinin, S. I.; Zachariasse, K. A.; Mullen, K. Angew. Chem., Int.
Ed. 2008, 47, 10175. (c) Tao, S. L.; Peng, Z. K.; Zhang, X. H.; Wang,
P. F.; Lee, C. S.; Lee, S. T. Adv. Funct. Mater. 2005, 15, 1716. (d) Oh,
H.-Y.; Lee, C.; Lee, S. Org. Electron. 2009, 10, 163. (e) Zao, Z.; Chen, S.;
Lam, J. W. Y.; Lu, P.; Zhong, Y.; Wong, K. S.; Kwok, H. S.; Tang, B. Z.
Chem. Commun. 2010, 46, 2221. (f) Yang, C.-H.; Guo, T.-F.; Sun, I.-W.
J. Luminesc. 2007, 124, 93.
(3) (a) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard,
J. A. K.; Marder, T. B.; Perutz, R. N. Chem. Commun. 2005, 2172.
(b) Kimoto, T.; Tanaka, K.; Sakai, Y.; Ohno, A.; Yoza, K.; Kobayashi,
K. Org. Lett. 2009, 11, 3658. (c) Chen, H.; Hu, X.; Ng, S.-C. J. Polym.
Sci., Part A: Polym. Chem. 2010, 48, 5562. (d) Qiao, Y.; Zhang, J.; Xu,
W.; Zhu, D. Tetrahedron 2011, 67, 3395.
r
10.1021/ol203235w
Published on Web 12/21/2011
2011 American Chemical Society

pyrene π-system with high directionality along the
synthesize all other possible isomers selectively (1-, 2-, 7-,
and 8-phenylfluoranthenes). During these studies, we
also found that trimethylphenylsilane could also be used
for the CÀH phenylation of fluoranthene (entry 2).8
Although high regioselectivity was secured, the low re-
activity was the bane of the original Pd(OAc)2/o-chloranil
system.
armchair edge.4
Table 1. Discovery of Pd(OAc)2/o-Chloranil/M(OTf)n as Cat-
alytic System for the C3-Selective CÀH Arylation of Fluor-
anthene with Arylboron Compounds or Arylsilanesa
Figure 1. Direct CÀH arylation of polycyclic aromatic
hydrocarbons.
entry
2
additive
none
3a (%)b
selectivityc (%)
1
PhB(OH)2
PhSiMe3
PhB(OH)2
PhB(OH)2
PhB(OH)2
PhSiMe3
PhB(neo)d
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
28
92
85
91
94
92
89
90
88
89
89
87
87
2
none
32
Although these studies established the viability of the
direct PAH arylation process, there still exist several
challenges (Figure 1). For example, new catalysts and/
or reaction conditions that allow effective π-extension at
the ‘zigzag’ edge of PAHs must be established for future
applications to a controlled synthesis of graphene nano-
ribbons. In addition, it is extremely important to investi-
gate whether unfunctionalized arenes, the ideal atom-
economical arylating agents, undergo a catalyzed CÀH
coupling with PAHs (CÀH/CÀH cross-coupling). Herein
we report our finding that a new catalytic system, Pd-
(OAc)2/o-chloranil/M(OTf)n, can effectively promote the
CÀH arylation of fluoranthene at the zigzag edge with
arylboron compounds7 or arylsilanes.8 Moreover, we
have found that the new system allows the use of unfunc-
tionalized arenes as coupling partners in PAH arylation.
We began our study by examining various arylboron
compounds and additives in the Pd(OAc)2/o-chloranil-
catalyzed CÀH arylation of fluoranthene (1) (Table 1).
When the reaction was conducted with PhB(OH)2, C3-
phenylation product 3a was obtained only in 28% yield
(entry 1).9 The structure of 3a was unambiguously deter-
mined by an X-ray diffraction study (see the Supporting
Information for details). The presence of one minor
regioisomer was indicated from GC analysis, but it was
extremely difficult to identify the structure of the isomer
unambiguously since there exists no reliable method to
3
AgBF4
AgOCOCF3
AgOTf
AgOTf
AgOTf
AgOTf
Y(OTf)3
Sc(OTf)3
LiOTf
23
4
18
5
36
6
52 (41)
50
7
8
55 (50)
55 (42)
54 (38)
47 (43)
39
9
10
11
12
HOTf
a Conditions: 1 (0.20 mmol, 1.0 equiv), 2 (0.40 mmol for boronic acid,
neopentyl glycol ester, and silane, 0.13 mmol for boroxin) Pd(OAc)2
(10 μmol, 5 mol %), o-chloranil (0.20 mmol, 1.0 equiv), additive
(20 μmol, 10 mol %), 1,2-dichloroethane (1 mL), 80 °C, 2À16 h. b Yield
of 3a was determined by GC analysis using n-dodecane as an internal
standard. The number in the parentheses is the yield of 3a after silica gel
chromatography. c Regioselectivity of reaction determined by GC ana-
lysis (calibration curve of 3a was tentatively used for that of minor
regioisomer). d PhB(neo) = phenylboronic acid neopentyl glycol ester.
Expecting that silver salts might activate an arylboron
compound,10 arylsilanes,11 or an assumed arylpalladium
intermediate,4 we added various silver salts to the Pd-
(OAc)2/o-chloranil system. While most of the examined
silver salts, such as AgBF4 and AgOCOCF3, only had a
negative effect, it was found that silver triflate (AgOTf)
did improve the efficiency of the reaction (Table 1, entries
5 and 6). Though arylboron compounds were not as
efficient as arylsilanes at this point, we elected to focus
(7) For examples of CÀH/CÀB biaryl coupling, see refs 4 and 6g, and
references therein.
(10) (a) Furuya, T.; Ritter, T. Org. Lett. 2009, 11, 2860. (b) Seiple,
I. B.; Su, S.; Rodriguez, R. A.; Gianatassio, R.; Fujiwara, Y.; Sobel,
A. L.; Baran, P. S. J. Am. Chem. Soc. 2010, 132, 13194. (c) Wisniewska,
H. M.; Jarvo, E. R. Chem. Sci 2011, 2, 807.
(11) (a) Yanagisawa, A.; Kageyama, H.; Nakatsuka, Y.; Asakawa,
K.; Matsumoto, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38,
3701. (b) Hirabayashi, K.; Kawashima, J.; Nishihara, Y.; Mori, A.;
Hiyama, T. Org. Lett. 1999, 1, 299. (c) Itami, K.; Mineno, M.; Yoshida,
J. Org. Lett. 2002, 4, 3635. (d) Itami, K.; Kamei, T.; Mineno, M.;
Yoshida, J. Chem. Lett. 2002, 31, 1984. (e) Nokami, T.; Tomida, Y.;
Kamei, T.; Itami, K.; Yoshida, J. Org. Lett. 2006, 8, 729.
(8) For examples of CÀH/CÀSi biaryl coupling, see: (a) Yang, S.; Li,
B.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 6066. (b) Hachiya, H.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2010, 49, 2202.
(c) Liang, Z.; Yao, B.; Zhang, Y. Org. Lett. 2010, 12, 3185. (d) Han, W.;
Mayer, P.; Ofial, A. R. Chem.;Eur. J. 2011, 17, 6904.
(9) CÀH/CÀSn and CÀH/CÀSi coupling of fluoranthene catalyzed
by PdÀCu system was reported by Oi and co-workers. (a) Kawai, H.;
Kobayashi, Y.; Oi, S.; Inoue, Y. Chem. Commun. 2008, 1464. (b) Funaki,
K.; Kawai, H.; Sato, T.; Oi, S. Chem. Lett. 2011, 40, 1050.
Org. Lett., Vol. 14, No. 1, 2012
419

on arylboron compounds given their ease of preparation
and widespread commercial availability. Gratifyingly,
the use of phenylboronic acid neopentyl glycol ester or
phenylboroxin provided 3a in 50% and 55% yield, re-
spectively (entries 7 and 8). It was also found that some
other metal triflates such as Y(OTf)3, Sc(OTf)3, and
LiOTf also promoted the reaction of 1 and phenylboroxin
(entries 9À11), whereas triflic acid (HOTf) did not func-
tion as a promoter (entry 12). In view of efficiency, cost,
and availability, we selected AgOTf as our first choice
additive for the coupling.
regioselectivity. Except for ortho substituted products,
the major C3-arylated fluoranthenes 3 could be isolated
in a pure form by simple recrystallization from hexane/
CH2Cl2. Notably, halogen-containing arylboroxins un-
derwent cross-coupling, leaving carbonÀhalogen bonds
intact (3h and 3i). The tolerance of the reaction for
carbonÀhalogen bonds makes it attractive for the rapid
and selective assembly of arene units in combination with
carbonÀhalogen bond cross-couplings such as the SuzukiÀ
Miyaura reaction.
Scheme 1. Discovery of CÀH/CÀH Cross-Coupling Reaction
of Polycyclic Aromatic Hydrocarbons and Unfunctionalized
Arenes
Table 2. Scope of C3-Selective CÀH Arylation of Fluoranthene
with Arylboroxins Catalyzed by Pd(OAc)2/o-Chloranil/AgOTf.a
In addition to CÀH/CÀB and CÀH/CÀSi couplings,
we found that the oxidative CÀH/CÀH cross-coupl-
ing5d,12,13 of PAHs and unfunctionalized aromatic com-
pounds is also possible with our newly developed catalytic
conditions. Representative results are shown in Scheme 1.
For example, fluoranthene (1.0 equiv) was reacted with
mesitylene (36 equiv) at 50 °C under the influence of
Pd(OAc)2/o-chloranil/AgOTf to afford 3-mesitylfluor-
anthene (3c) in 74% yield with virtually complete regios-
electivity. Furthermore, it was found that pyrene and 2,7-
di-tert-butylpyrene also react with mesitylene to furnish
the corresponding C4-mesitylated pyrenes (4a and 4b) in
44% and 57% yield, respectively (Scheme 1). In both
cases, arylation occurred exclusively at the C4-position of
a Conditions: 1 (0.20 mmol, 1.0 equiv), 2 (0.13 mmol, 0.67 equiv),
Pd(OAc)2 (10 μmol, 5 mol %), o-chloranil (0.20 mmol, 1.0 equiv),
AgOTf (20 μmol, 10 mol %), 1,2-dichloroethane (1 mL), 80 °C, 2 h.
Yields after silica gel chromatography are given below the structures and
the number in the parentheses is the regioselectivity of reaction.
(12) For reports of CÀH/CÀH biaryl coupling of naphthalene and
benzene derivatives, see: (a) Li, R.; Li, J.; Lu, W. Organometallics 2006,
25, 5973. (b) Dohi, T.; Ito, M.; Morimoto, K.; Iwata, M.; Kita, Y.
Angew. Chem., Int. Ed. 2008, 47, 1301. (c) Kita, Y.; Morimoto, K.; Ito,
M.; Ogawa, C.; Goto, A.; Dohi, T. J. Am. Chem. Soc. 2009, 131, 1668.
(13) For selected examples of CÀH/CÀH biaryl coupling using
simple substrates, see: (a) Stuart, D. R.; Fagnou, K. Science 2007, 316,
1172. (b) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008,
130, 9254. (c) Deprez, N. R.; Sanford, M. J. Am. Chem. Soc. 2009, 131,
11234. (d) Li, Y.; Wang, W.-H.; Yang, S.-D.; Li, B.-J.; Feng, C.; Shi,
Z.-J. Chem. Commun. 2010, 46, 4553. (e) Potavathri, S.; Pereira, K. C.;
Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J. Am. Chem. Soc.
2010, 132, 14676. (f) Xi, P.; Yang, F.; Qin, S.; Zhao, D.; Lan, J.; Gao, G.;
Hu, C.; You, J. J. Am. Chem. Soc. 2010, 132, 1822. (g) Zhao, X.; Yeung,
C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837. (h) Han, W.;
Mayer, P.; Ofial, A. R. Angew. Chem., Int. Ed. 2011, 50, 2178.
(i) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Am.
Chem. Soc. 2011, 133, 2160. (j) Reference 6h. (k) Reference 6j.
Under the optimized reaction conditions (Table 1, en-
try 8), the scope with respect to arylboroxins 2 was
investigated. As shown in Table 2, various arylboroxins
2 react with fluoranthene (1) to give the corresponding
C3-arylated fluoranthenes 3. Both electron-rich (3bÀ3e)
and electron-deficient (3fÀ3i) aryl groups could be in-
stalled onto the fluoranthene ring with high C3-regios-
electivity. It was found that phenylboroxins with ortho
substitution (3bÀ3d, 3f, and 3h) showed higher regios-
electivity. As a striking example, 3-mesitylfluoranthene
(3c) was obtained in 71% yield with virtually complete
420
Org. Lett., Vol. 14, No. 1, 2012

the pyrene ring, which is consistent with our previous
CÀH/CÀB coupling.4
Scheme 2. ‘Zigzag’ Extension at ‘Zigzag’ Edge
A more challenging CÀH/CÀH cross-coupling be-
tween two different PAHs is also possible. For example,
fluoranthene (1.0 equiv) reacts with naphthalene (20
equiv) in the presence of Pd(OAc)2 (10 mol %), o-chlor-
anil (1.0 equiv), and AgOTf (20 mol %) in 1,2-dichlor-
oethane at 80 °C to furnish 3-(1-naphthyl)fluoranthene
(3j) in 10% yield (Scheme 2). Though low yielding, the
reaction takes place with complete regioselectivity for
both coupling partners (C3 position for fluoranthene
and C1 position for naphthalene). The regiochemistry
of 3j was unambiguously confirmed by X-ray crystal
structure analysis (see the Supporting Information for
details). However, it is clear that catalytic activity needs to
be increased before the CÀH/CÀH cross-coupling be-
tween two PAHs becomes synthetically useful. When
1-naphthylboroxin was used as an arylating agent, 3j
was produced in 20% yield (Scheme 2). Thus, under the
present catalytic conditions, the CÀH/CÀB cross-cou-
pling is still better for such a challenging coupling in terms
of reaction efficiency.
Apart from low efficiency, the successful installation of
a 1-naphthyl group to the ‘zigzag’ edge of fluoranthene
ring is encouraging. The application of a cyclodehydro-
genation method14 to close the resultant ‘fjord’ region of
3j would set the stage for controlled π-growth in the
‘zigzag’ direction through the sequential integration of
CÀH arylation and cyclodehydrogenation. It was found
that the anionic cyclodehydrogenation developed by the
group of Scott15 is suitable for such a purpose. When a
THF solution of 3j (1.0 equiv) and potassium naphthale-
nide (25 equiv) was heated at 90 °C for 1 h under
microwave irradiation, the desired indeno[1,2,3-cd]pery-
lene (5) was obtained in 17% yield.16 We believe that such
a sequence would be complementary to our previous
methods for a controlled π-extension in the ‘armchair’
direction using pyrene or phenanthrene as a template.4
In summary, a new Pd(OAc)2/o-chloranil/M(OTf)n
catalytic system has been developed for the CÀH aryla-
tion of fluoranthene with arylboron compounds or arylsi-
lanes. The reaction takes place with high regioselectivity at
the C3 position of the fluoranthene ring. More interest-
ingly, we have discovered that the oxidative CÀH/CÀH
cross-coupling of PAHs and unfunctionalized aromatic
compounds is also possible with the Pd(OAc)2/o-chlora-
nil/AgOTf catalyst. We believe that this ‘ideal’ arene-
assembling reaction will find use in the atom- and step-
economical synthesis of π-extended PAHs for various
applications. The application of Pd(OAc)2/o-chloranil/
AgOTf catalysis to various planar and geodesic PAHs
and the development of a third-generation catalyst
with much higher activity are currently ongoing in our
laboratory.
Acknowledgment. This work was supported by the
Funding Program for Next Generation World-Leading
Researchers from JSPS (220GR049 to K.I.). Prof. Lawrence
T. Scott (Boston College, USA) is greatly acknowledged for
his valuable comments and disccusion. We thank Dr. Jean
Bouffard (University of California, Riverside, USA) for
critical comments.
€
€
(14) (a) Bohnen, A.; Koch, K.-H.; Luttke, W.; Mullen, K. Angew.
Chem., Int. Ed. Engl. 1990, 29, 525. (b) Pschirer, N. G.; Kohl, C.; Nolde,
€
F.; Qu, J.; Mullen, K. Angew. Chem., Int. Ed. 2006, 45, 1401. For a
review, see: (c) Sarhan, A. A. O.; Bolm, C. Chem. Soc. Rev. 2009, 38,
2730.
Supporting Information Available. Experimental pro-
cedures and characterization data for all new compounds;
CIF files of 3a and 3j. This material is available free of
charge via the Internet at http://pubs.acs.org.
(15) Rickhaus, M.; Belanger, A. P.; Wegner, H. A.; Scott, L. T.
J. Org. Chem. 2010, 75, 7358.
(16) The microwave-assisted anionic cyclodehydrogenation of a
range of PAHs including 3j was already established by the group of
Scott. Belanger, A. P., Ph.D. Thesis, Boston College, December 2008.
Org. Lett., Vol. 14, No. 1, 2012
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