Palladium-catalyzed direct arylation of C-H bond to construct quaternary carbon centers: The synthesis of diarylfluorene

Article abstract of DOI:10.1021/ol4013052

A novel Pd-catalyzed C-H functionalization reaction was developed to construct a quaternary carbon center with high yield. This reaction provides an efficient method for the synthesis of 9,9′-diarylfluorenes by direct arylation of monoarylfluorene.

Full text of DOI:10.1021/ol4013052

ORGANIC
LETTERS
2013
Vol. 15, No. 12
3102–3105
Palladium-Catalyzed Direct Arylation
of CꢀH Bond To Construct Quaternary
Carbon Centers: The Synthesis
of Diarylfluorene
Xiao Cao,† Weidong Yang,† Chao Liu,‡ Fuliang Wei,† Kun Wu,‡ Wei Sun,†
Juan Song,*,† Linghai Xie,*,† and Wei Huang*,†
Key Laboratory for Organic Electronics and Information Display and Institute of
Advanced Materials, Nanjing University of Posts and Telecommunications,
Nanjing 210046, People’s Republic of China, College of Chemistry and Molecular
Sciences, Wuhan University, Wuhan, 430072, People’s Republic of China
iamjsong@njupt.edu.cn; iamwhuang@njupt.edu.cn; iamlhxie@njupt.edu.cn
Received May 10, 2013
ABSTRACT
A novel Pd-catalyzed CꢀH functionalization reaction was developed to construct a quaternary carbon center with high yield. This reaction
provides an efficient method for the synthesis of 9,90-diarylfluorenes by direct arylation of monoarylfluorene.
Palladium-catalyzed cross-coupling reactions have be-
come a powerful tool in organic synthesis.1 Numerous
cross-coupling systems have been applied in the prepara-
tionof pharmaceuticals, agrochemicals, and alsoadvanced
materials on both laboratory and industrial scales.2
In those applications, CꢀC, CꢀS, CꢀO, and CꢀN bonds
have been easily constructed with the help of palladium
catalysts.3 However, the construction of quaternary carbon
centers via palladium catalysis has been rarely reported up
to now.4 Recently, a Pd-catalyzed construction of quatern-
ary carbon centers from diazocompounds and carbonyl
compounds has been demonstrated.5 The conjugate addi-
tion of arylboronic acids to β-substituted cyclic enones to
construct stereocenters was also reported by Lu and Stoltz
respectively.4b,6 The Stoltz group reported the formation of
quaternary and tertiary stereocenters via the alkylation of
enolates.7 However, there is no report of the construc-
tion of tetraaryl quaternary carbon centers based on Pd-
catalyzed cross-coupling of aryl halides with triarylmethane
todate(eq 1). Herein, we demonstrateaPd-catalyzed cross-
coupling of triarylmethyl CꢀH bonds with aryl halides for
the direct synthesis of unsymmetric diarylfluorenes.
† Nanjing University of Posts and Telecommunications.
‡ Wuhan University.
(1) Wu, X. F.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1.
(2) Seechurn, C. C. C. J.; Kitching, M. O.; Colacot, T. J.; Snieckus, V.
Angew. Chem., Int. Ed. 2012, 51, 5062.
Diarylfluorenes are widely used in semiconductors, in-
cluding OLEDs, PLEDs, solar cells, fuel cells, memories, and
so on.8 Therefore, efficient preparation of 9,9-diarylfluorenes
(3) (a) Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura, S. J. Am.
Chem. Soc. 2003, 125, 8862. (b) Beccalli, E. M.; Broggini, G.; Martinelli,
M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318. (c) Beletskaya, I. P.;
Cheprakov, A. V. Organometallics 2012, 31, 7753. (d) Cho, S. H.; Kim,
J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068.
(4) (a) Sato, K.; Takiguchi, Y.; Yoshizawa, Y.; Iwase, K.; Shimizu,
Y.; Tarui, A.; Omote, M.; Kumadaki, I.; Ando, A. Chem. Pharm. Bull.
2007, 55, 1593. (b) Lin, S.; Lu, X. Org. Lett. 2010, 12, 2536. (c) Jiang, H.;
Fu, W.; Chen, H. Chem.;Eur. J. 2012, 18, 11884. (d) Fournier, J.;
Lozano, O.; Menozzi, C.; Arseniyadis, S.; Cossy, J. Angew. Chem., Int.
Ed. 2013, 52, 1257.
(5) Chen, Z.-S.; Duan, X.-H.; Zhou, P.-X.; Ali, S.; Luo, J.-Y.; Liang,
Y.-M. Angew. Chem., Int. Ed. 2012, 51, 1370.
(6) Kikushima, K.; Holder, J. C.; Gatti, M.; Stoltz, B. M. J. Am.
Chem. Soc. 2011, 133, 6902.
(7) Streuff, J.; White, D. E.; Virgil, S. C.; Stoltz, B. M. Nat. Chem.
2010, 2, 192.
r
10.1021/ol4013052
Published on Web 06/12/2013
2013 American Chemical Society

is important for both synthetic chemistry and material
sciences. Diarylfluorenes with the same two aryl groups were
mainly applied in OLEDs, PLEDs, and fuel cells.8a,d In
recent years, more and more unsymmetric diarylfluorenes
were utilized based on newly developed synthetic methods.9
However, the developed methods were mainly based on
FriedelꢀCrafts type reactions, which have many limitations
on substrate scope, such as fluorenes containing electronic-
poor aryl and meta-substituted aryl groups.9b,10 These lim-
ited the further applications of diarylfluorenes in material
sciences. Therefore, there is still high demand for novel
and efficient synthetic methods for the access of this type
of compounds.
We started our research by using compounds 1 and 2a as
the standard substrates with Pd as the catalyst to optimize
the reaction conditions. First, several phosphorus ligands
were investigated by using KOtBu as the base and toluene
as the solvent at 100 °C (Table 1 entries 1ꢀ6). A rigid
bidentate ligand dppf afforded a trace amount of the
coupling product. When dppe was applied as the ligand,
it also afforded a trace amount of the coupling product.
However, when more labile bidentate ligand dppb was
utilized, 42% of 3a was obtained. It seemed that the more
labile the bidentate ligand, the higher the yield. Therefore,
2 equivof themonodendate ligandPPh3 wasthenscreened,
which indeed turned out to be the most suitable ligand for
this transformation and afforded the coupling product in
a 95% yield. Moreover, nitrogen ligand phenanthroline
gave a 64% yield of 3a and no extra ligand provided 13%
of the coupling product. Then, we tried to use a weaker base
to replace KOtBu. However, the results exhibited that the
weaker the base, the lower the yield (NaOtBu, 37%;
NaOH, 22%; K3PO4, trace). We also tried to optimize
the reaction temperature. However, when the reaction
temperaturewasloweredtortor60°C, onlyatraceamount
of 3a was observed. A temperature higher than 80 °C
afforded the coupling product in an 84% yield. Solvent
testing showed that other solvents could also afford the
coupling product, but toluene was still the best choice for
this transformation. Therefore, based on these condition
screenings, the final optimized conditions included 5 mol %
of [Pd(dba)2], 10 mol % of PPh3, 1.2 equiv of aryl bromide,
1.2 equiv of KOtBu in toluene at 100 °C for 8ꢀ10 h.
Table 1. Palladium Catalyzed Arylation of Monoarylfluorenea
temp
yield
(%)b
entry
ligand
base
solvent
(°C)
1
dppf
dppe
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
NaOtBu
NaOH
K3PO4
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
THF
100
100
100
100
100
100
100
100
100
rt
trace
trace
42
2
3
dppb
4
PPh3
phenanthroline
ꢀ
95
5
64
6c
7
13
PPh3
37
8
PPh3
22
9
PPh3
trace
trace
trace
84
10
11
12
13
14
15
16
PPh3
PPh3
60
PPh3
80
PPh3
100
100
100
100
34
PPh3
83
PPh3
DMF
54
PPh3
DMSO
44
a Reaction conditions: 1 (121 mg, 0.5 mmol), 2a (102 mg, 0.6 mmol),
5 mol % Pd(dba)2, 10 mol % ligand, base (0.6 mmol, 1.2 equiv). b Yields
were determined by GC. c No ligand.
With the optimized reaction conditions in hand, a
variety of substrates were tested. Most of the employed
aryl bromides reacted smoothly with 1 under the standard
conditions to afford the corresponding products in good to
excellent yields (Scheme 1). CꢀF or CꢀCl bonds were well
tolerated, and thecoupling products wereobtainedingood
yields (3b, 3c, 3j, 3k) . It was worth noting that one of the
two CꢀBr bonds of 1,4-dibromobenzene could be well
preserved by carefully controlling the ratio of the starting
materials to be 1:5, which offered the opportunity for
further functionalizations (3d). However, when the ratio
was changed to 2.5:1, a good yield was easily obtained for
3h which has been shown to be a wide-energy-gap host
material for OLEDs.11 It was shown that steric hindrance
has a certain influence on the coupling reaction, and a
relativelylow yield wasobtained (3i). Wealsoextended our
reaction to some bromo-heterocycles. To our delight, N-
methyl-3-bromocarbazole gave the coupling product 3l in
74% yield. 3-Bromopyridine was also proved to be a
compatible substrate under our standard conditions,
which afforded product 3e in 65% yield. In the case of
2-bromothiophene and 3-bromothiophene, low yields
were obtained (39% for 3g and 54% for 3f). Electron-rich
aryl bromides also worked well and afforded the coupling
products in good yields (3l, 3n, 3o, 3p). β-Naphthalene
bromide and its derivative were readily converted to the
corresponding products (3q, 3r) in 91% and 84% yields,
(8) (a) Beaupre, S.; Boudreault, P.-L. T.; Leclerc, M. Adv. Mater.
2010, 22, E6. (b) Koyama, Y.; Nakazono, K.; Hayashi, H.; Tataka, T.
Chem. Lett. 2010, 39, 2. (c) Abbel, R.; Schenning, A. P. H. J.; Meijer,
E. W. J. Polym. Sci., Polym. Chem. 2009, 47, 4215. (d) Miyatake, K.;
Bae, B.; Watanabe, M. Polym. Chem. 2011, 2, 1919. (e) Xie, L.-H.; Yin,
C.-R.; Lai, W.-Y.; Fan, Q.-L.; Huang, W. Prog. Polym. Sci. 2012, 37,
1192.
(9) (a) Chen, R.-T.; Chen, S.-H.; Hsieh, B.-Y.; Chen, Y. J. Polym.
Sci., Polym. Chem. 2009, 47, 2821. (b) Xie, L.-H.; Hou, X.-Y.; Hua,
Y.-R.; Tang, C.; Liu, F.; Fan, Q.-L.; Huang, W. Org. Lett. 2006, 8, 3701.
(c) Ren, B.-Y.; Ou, C.-J.; Zhang, C.; Chang, Y.-Z.; Yi, M.-D.; Liu, J.-Q.;
Xie, L.-H.; Zhang, G.-W.; Deng, X.-Y.; Li, S.-B.; Wei, W.; Huang, W.
J. Phys. Chem. C 2012, 116, 8881. (d) Xie, L.-H.; Ling, Q.-D.; Hou,
X.-Y.; Huang, W. J. Am. Chem. Soc. 2008, 130, 2120.
(10) (a) Ego, C.; Grimsdale, A. C.; Uckert, F.; Yu, G.; Srdanov, G.;
€
Mullen, K. Adv. Mater. 2002, 14, 809. (b) Wu, C. C.; Liu, T. L.; Hung,
W. Y.; Lin, Y. T.; Wong, K. T.; Chen, R. T.; Chen, Y. M.; Chien, Y. Y.
J. Am. Chem. Soc. 2003, 125, 3710. (c) Kawasaki, S.; Yamada, M.;
Kobori, K.; Jin, F. Z.; Kondo, Y.; Hayashi, H.; Suzuki, Y.; Takata, T.
Macromolecules 2007, 40, 5284.
(11) Ye, S. H.; Liu, Y. Q.; Di, C. A.; Xi, H. X.; Wu, W. P.; Wen, Y. G.;
Lu, K.; Du, C. Y.; Liu, Y.; Yu, G. Chem. Mater. 2009, 21, 1333.
Org. Lett., Vol. 15, No. 12, 2013
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repectively. However, R-naphthalene afforded the corre-
sponding product 3s in a moderate yield. It was note-
worthy that the difunctionalization of aryl dibromides
could afford more interesting molecules in good yields
which might have high potentials on host materials for
OLEDs (3t, 3u) .11
It has been reported that triarylmethane could be ob-
tained via palladium catalyzed cross-coupling of diaryl-
methane with aryl halides.12 Therefore, diarylfluorene
could be synthesized by the one-pot reaction of fluorene
with an excess amount of aryl halides in the presence of
a palladium catalyst.12a Then, we tried the direct synthesis
of diarylfluorene from fluorene with 2.4 equiv of aryl
bromides. To our delight, various “symmetrical” diaryl-
fluorenes were obtained in good to excellent yields under
the standard conditions. Various functional groups, such
as F, Cl, and OMe, could be well tolerated (see Scheme 2
and the Supporting Information). Multifunctionalized
aryl bromides could also afford the corresponding cou-
pling products in good yields (6f, 6i). Furthermore, the
present diarylation reaction was also applicable to a
β-naphthalene bromide system, such as 5d, whichgenerated
6d in 95% yield. However, negligible diarylfluorenes were
observed when 2-bromotoluene, 1-bromonaphthalene,
and heterocycles were employed as substrates under our
standard conditions.
Scheme 1. Arylation of Monoarylfluorene by Different Aryl
Bromidesa
Scheme 2. Diarylation of Fluorenea
a Reaction conditions: 4 (0.5 mmol), 5 (1.2 mmol), 5 mol % Pd(dba)2,
b
10 mol % PPh3, KOtBu (0.6 mmol, 1.2 equiv). Isolated yield. The
ligand is tert-butyldiphenylphosphine.
Insummary, we have developedan efficient Pd-catalyzed
cross-coupling of triarylmethyl CꢀH bonds with aryl
halides for the direct synthesis of unsymmetric diarylfluor-
enes, in which a quaternary carbon center was easily
built. And fluorene was also directly diarylated. A series
of diarylfluorenes, which played an important role in
a Reaction conditions: 1 (0.5 mmol), 2aꢀh (1.2 mmol), 5 mol %
b
Pd(dba)2, 10 mol % PPh3, KOtBu (0.6 mmol). Isolated yield. The
(12) (a) Chen, J.-J.; Onogi, S.; Hsieh, Y.-C.; Hsiao, C.-C.;
Higashibayashi, S.; Sakurai, H.; Wu, Y.-T. Adv. Synth. Catal. 2012,
354, 1551. (b) Zhang, J.; Bellomo, A.; Creamer, A. D.; Dreher, S. D.;
Walsh, P. J. J. Am. Chem. Soc. 2012, 134, 13765.
ligand is tert-butyldiphenylphosphine. c 1,4-Dibromobenzene (2.5 mmol)
is used. d Dibromoarenes (0.2 mmol) are used.
3104
Org. Lett., Vol. 15, No. 12, 2013

semiconductors, were smoothly obtained. Further investi-
gation on the application of this chemistry is currently
underway in our laboratory.
Key Project of the Ministry of Education of China
(707032,208050), Natural Science Foundation of Jiangsu
Province, China (SBK201122680, BK2011761, BK2008053,
SJ209003), and NJUPT (NY210030 and NY211022).
Acknowledgment. The project was supported by the
National Key Basic Research Program of China (973)
(2009CB930600), the National Natural Science Founda-
tion of China (21274064, 21144004, 60876010,61177029,
20774043, 20704023, 20974046), The Program for New
Century Excellent Talents in University (NCET-11-0992),
Supporting Information Available. Experimental pro-
cedures, structural proofs, and spectral data for all new
compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 12, 2013
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