Direct meta-selective alkylation of perylene bisimides via palladium-catalyzed C - H functionalization

Article abstract of DOI:10.1021/ol9023198

"Chemical Equation Presented" A facile palladium-catalyzed procedure for meta-selective alkylation of perylene bisimides with alkyl halides has been achieved by direct C - H functionalizatlon.

Full text of DOI:10.1021/ol9023198

ORGANIC
LETTERS
2009
Vol. 11, No. 23
5430-5433
Direct Meta-Selective Alkylation of
Perylene Bisimides via
Palladium-Catalyzed C-H
Functionalization
Wan Yue,†,‡ Yan Li,†,‡ Wei Jiang,†,‡ Yonggang Zhen,†,‡ and Zhaohui Wang*,†
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic
Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China,
and Graduate School of the Chinese Academy of Sciences, Beijing 100190, China
wangzhaohui@iccas.ac.cn
Received October 7, 2009
ABSTRACT
A facile palladium-catalyzed procedure for meta-selective alkylation of perylene bisimides with alkyl halides has been achieved by direct C-H
functionalization.
Selective direct C-H functionalization/C-C bond formation
catalyzed by transition metal has been extensively studied
recently.1 This synthetic strategy provides a viable alternative
to a traditional cross-coupling reaction. Approaches for direct
functionalization of an unreactive C-H bond represent a
powerful and relatively straightforward protocol to avoid the
preactivation of the substrates and make the synthetic routine
shorter and more efficient in organic synthesis. To date, great
elegant progress has been achieved for electron-rich arenes
and heterocycles with a directing group which can be ortho-
functionalized by aryl or alkyl halides, boronates, and olefins
under palladium,2 ruthenium,3 or rhodium4 catalysis. How-
ever, direct meta-selective C-H bond transformation of
unreactive arenes is still a challenge. Consequently, develop-
ing a catalytic procedure for the functionalization of a highly
electron-deficient aromatic C-H bond to selectively generate
the meta-substituted products is very significant.5
(2) (a) Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M J. Am. Chem. Soc.
2002, 124, 5286. (b) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172. (c)
Zaitsev, V. G.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 4156. (d) Cai, G.;
Fu, Y.; Li, Y.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 7666.
(3) (a) Kakiuchi, F.; Matsuura, Y.; Kan, S.; Chatani, N. J. Am. Chem.
Soc. 2005, 127, 5936. (b) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002,
35, 826. (c) Ackermann, L.; Nova´k, P.; Vicente, R.; Hofmann, N. Angew.
Chem., Int. Ed. 2009, 48, 6045. (d) Nakazono, S.; Imazaki, Y.; Yoo, H.;
Yang, J.; Sasamori, T.; Tokitoh, N.; Ce´dric, T.; Kageyama, H.; Kim, D.;
Shinokubo, H.; Osuka, A Chem.sEur. J. 2009, 15, 7530. (e) Kakiuchi, F.;
Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2003, 125, 1698.
(4) Oi, S.; Watanabe, S.; Fukita, S.; Inoue, Y. Tetrahedron Lett. 2003,
44, 8665.
† Institute of Chemistry, Chinese Academy of Sciences.
‡ Graduate School of the Chinese Academy of Sciences.
(1) (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879. (b)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (c) Alberico,
D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107, 174. (d) Hassan, J.;
Se´vignon, M.; Gozzi, C.; Schuluz, E.; Lemaire, M. Chem. ReV. 2002, 102,
1359.
(5) (a) Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593. (b) Zhang,
Y.; Shi, B.; Yu, J. Q. J. Am. Chem. Soc. 2009, 131, 5072. (c) Li, Y.; Li, B.;
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10.1021/ol9023198 CCC: $40.75
Published on Web 11/02/2009
 2009 American Chemical Society

Due to the remarkable electro-optical properties,6
perylene-3,4:9,10-tetracarboxylic acid bisimides (PBIs)
have attracted exclusive attention in a wide range of
applications including organic field effect transistors,7
light-emitting diodes,8 solar cells,9 photovoltaic devices,10
etc. Photophysical and redox properties of PBIs can be
conveniently modified through substitution at the bay
(meta) position.11 Substitutions at the bay positions and
expansion of the PBI core are usually carried out starting
from the halogenated derivatives, such as chlorinated or
brominated PBIs.12 However, the preparation of these
halogenated PBIs needs poisonous chlorine, bromine, and
iodine with harsh conditions (concentrated H2SO4 or oleum
upon heating). Thus, an economical and ecological method
to construct the C-C bond would be the direct function-
alization of C-H bonds of PBIs. Very recently, Shinokubo
reported success with Ru-catalyzed ortho-alkylation of
PBIs directed by the carbonyl carbons;3d however, direct
alkylation of unactivated arene with alkyl halide which
selectively occurs at the meta position has not been
achieved to date.
Table 1. Pd-Catalyzed Alkylation of PBIs with Alkyl Halides
entry
halide (Alkyl-X)
n-C6H13Br
n-C8H17Br
n-C12H25Br
CF3CF2C2H4I
n-C4H9(OCH2CH2)3Br
yield (%)a b
product
,
1
2
3
4
5
6
7
41(62)
45(63)
51(72)
22(50)
28(48)
55(68)
40(64)
1a
1b
1c
1d
1e
1a
2a
n-C6H13
I
n-C6H13Br
a Yields are isolated yields. b Yields are based on recovery of starting
materials.
Herein, we present the first example of a palladium-
catalyzed meta-selective alkylation process of highly
electron-deficient PBIs with cheap and readily available
alkyl halides. These facile reactions offer good functional
group compatibility.
Under the optimized catalytic system above, the sub-
strate scope was also explored (Table 1). A variety of alkyl
bromides with different lengths of alkyl chains can be
direct alkylated regioselectively (Table 1, entries 1-3),
while an alkyl iodide also leads to a good yield (Table 1,
entry 6), which is slightly higher than those of alkyl
bromides. The corresponding alkyl chloride turned out to
be a great challenge due to its low reactivity. Notably,
our catalytic system was not limited to the use of simple
alkyl halides but also enabled the transformation of the
alkylhalide bearing fluorocarbon chain and oligo(ethylene
glycol) chain (Table 1, entries 4 and 5). Incorporation of
the hydrophilic and hydrophobic chains into the PBI
skeletons is known to have a strong influence not only on
their self-assemble structures but also on their electro-
optical properties.13
Surprisingly, this condition produces the meta products
with exquisite selectivity as evidenced by COSY and HMBC
experiments. The assignments of Ha, Hb, Hf, Hg, Hc, Hd, and
He were determined with the aid of COSY data (see the
Supporting Information). The HMBC experiment revealed
the correlation between Ha (Hf), Hg, Hf (Ha), and Hb and
four corresponding carbonyl carbons Ch, Ci, Cj, and Ck (δ
162, δ 163) (Figure 1), which have proved the alkylation
occurs at the meta position.
Various ligands, the reaction temperature, and the
amount of catalyst were examined to optimize the reaction
conditions. The best results were obtained under the
system of Pd(OAc)2 as the catalyst, PPh3 as the ligand,
and Cs2CO3 as the base in o-xylene (Table 1). This
particular reaction takes place in the presence of an excess
of cesium carbonate, whereas stronger base t-BuOK leads
to unchanged starting materials. PBI derivatives with two
alkyl groups were also detected by MALDI-TOF; how-
ever, dialkylated PBIs have possible isomers, and the
separation is very difficult.
(6) (a) Zollinger, H. Color Chemistry, 3rd ed.; VCH: Weinheim, 2003.
(b) Wu¨rthner, F. Chem. Commun. 2004, 14, 1564.
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T. J.; Wasielewski, M. R. Angew. Chem., Int. Ed. 2004, 43, 6363. (b)
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2003, 125, 437.
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Friend, R. H.; Mackenzie, J. D. Science 2001, 293, 1119.
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Chem., Int. Ed. 2005, 44, 250. (b) Rohr, U.; Schlichting, P.; Bo¨hm, A.;
Gross, M.; Meerholz, K.; Bra¨uchle, C.; Mu¨llen, K. Angew. Chem. 1998,
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Wang, Z.; Zhu, D. Chem. Commun. 2006, 4587. (d) Li, Y.; Wang, Z.; Qian,
H.; Shi, Y.; Hu, W. Org. Lett. 2008, 10, 529.
Recent studies have found that direct arylation of
electron-deficient arenes at the meta position could be
attributed to higher reactivity of the meta C-H bond.5b,14
(12) See recent examples: (a) Qian, H.; Wang, Z.; Yue, W.; Zhu, D.
J. Am. Chem. Soc. 2007, 129, 10664. (b) Qian, H.; Negri, F.; Wang, C.;
Wang, Z. J. Am. Chem. Soc. 2008, 130, 17970. (c) Shi, Y.; Qian, H.; Li,
Y.; Yue, W.; Wang, Z. Org. Lett. 2008, 10, 2337. (d) Qian, H.; Yue, W.;
Zhen, Y.; Motta, S. D.; Donato, E. D.; Negri, F.; Qu, J.; Xu, W.; Zhu, D.;
Wang, Z. J. Org. Chem. 2009, 74, 6275. (e) Rajasingh, P.; Cohen, R.;
Shirman, E.; Shimon, L. J. W.; Rybtchinski, B. J. Org. Chem. 2007, 72,
5973.
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I.; Rybtchinski, B. Angew. Chem., Int. Ed. 2008, 48, 926. (b) Che, Y.; Datar,
A.; Balakrishman, K.; Zang, L. J. Am. Chem. Soc. 2007, 129, 7234. (c)
Zang, L.; Che, Y.; Moore, J. S. Acc. Chem. Res. 2008, 41, 1596. (d) Zhang,
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Org. Lett., Vol. 11, No. 23, 2009
5431

Scheme 1
Figure 1. HMBC correlations of 1a.
Thus, we propose that the diret meta-selective C-H alky-
lation of highly electron-deficient PBIs is via a proton
abstraction mechanism.
The catalytic cycle was hypothesized as shown in
Scheme 1. In this concerted metalation and proton
abstraction catalytic cycle,15 the alkylpalladium(II) inter-
mediate 3 is formed through an oxidative addition of a
Pd(0) complex with an alkyl halide. However, intermediate
3 may easily undergo ꢀ-hydrogen elimination to form
alkene. Therefore, excessive alkyl halides are needed to
make this transformation proceed smoothly. As we have
mentioned, the excess of carbonate is critical for this
transformation. Carbonate ligand exchanges with the X
ligand of 3 to form intermediate 4, which attacks the meta
position of the PBIs to give the key transition state 5.
Deprotonation of the latter forms alkyl-palladium(II)
intermediate 6, which upon reductive elimination gives
product and regenerates the palladium(0) catalyst.
The UV-vis absorption (Figure 2) and fluorescence
spectra (see the Supporting Information) have not been
changed significantly compared with compound 1.16 The
absorption spectra show well-defined vibronic fine struc-
ture of the S0-S1 transition (Figure 2) and display two
major bands near 490 and 524 nm arising from the PBI
core. However, the molar extinction coefficients of the
lowest-energy absorption band are somewhat reduced with
the introduction of the alkyl chains, especially electron-
withdrawing fluorocarbon chains (Table 2).
and one quasireversible reduction wave, and the reduction
potential of 1d is less negative than the other PBIs, which
can also be attributed to the electron affinity of fluorine
atoms (Table 2).
Cyclic voltammograms (see the Supporting Information)
of these compounds exhibit one reversible reduction wave
(14) (a) Garcia-Cuadrado, D.; Braga, A. A. C.; Maseras, F.; Echavarren,
A. M. J. Am. Chem. Soc. 2006, 128, 1066. (b) Lapointe, D.; Fagnou, K.
Org. Lett. 2009, 11, 4160. (c) Zhang, Y. H.; Shi, B. F.; Yu, J. Q. Angew.
Chem., Int. Ed. 2009, 48, 6097.
(15) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K J. Am. Chem.
Soc. 2006, 128, 8754.
Figure 2. UV-vis absorption spectra of PBI 1 (orange line), 1a
(black line), 1b (red line), 1c (blue line), 1d (violet line), 1e (pink
line), and 2a (olive line) in CH2Cl2 (1 × 10-5 M) at room
temperature.
(16) (a) Weissman, H.; Shirman, E.; Ben-Moshe, T.; Cohen, R.; Leitus,
G.; Shimon, L. J. W.; Rybtchinski, B. Inorg. Chem. 2007, 46, 4790. (b)
Facchetti, A.; Yoon, M. H.; Stern, C. L.; Katz, H. E.; Marks, T. J. Angew.
Chem., Int. Ed. 2003, 42, 3900.
5432
Org. Lett., Vol. 11, No. 23, 2009

range of substrates, especially alkanes with fluorocarbon
chains and hydrophilic oligo(ethylene glycol) chains. The
generality and unique properties of perylene bisimides may
expand the scope of this reaction to more academic and
industrial applications.
Table 2. Electro-Optical Properties of Alkylated PBIs
PBI
ε [m-1, cm-1
]
λmax [nm]
λem [nm]
Ea
Ea
2r
1r
1a
1b
1c
1d
1e
2a
6.91 × 104
7.06 × 104
6.60 × 104
4.05 × 104
5.30 × 104
6.35 × 104
526
526
526
522
524
524
542
542
542
539
539
540
-0.65
-0.65
-0.65
-0.60
-0.64
-0.73
-0.89
-0.85
-0.87
-0.85
-0.86
-0.94
Acknowledgment. For financial support of this research,
we thank the National Natural Science Foundation of China
(Grant 20772131), 973 Program (Grant 2006CB932101,
2006CB806200), Chinese Academy of Sciences, and BASF
SE.
a Half wave redox potential (in V vs Ag/AgCl) measured in CH2Cl2
with a scan rate of 100 mV/s.
Supporting Information Available: Experimental pro-
cedure and characterization of new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
In conclusion, a palladium-catalyzed meta-selective
alkylation process of highly electron-deficient PBIs with
cheap and readily available alkyl halides has been
achieved. This synthetic route can be applied to a wide
OL9023198
Org. Lett., Vol. 11, No. 23, 2009
5433