Pd-catalyzed oxidative cross-coupling of perfluoroarenes with aromatic heterocycles

Article abstract of DOI:10.1021/ja106046p

A straightforward and practical method for direct Pd(OAc) ₂-catalyzed oxidative cross-coupling of electron-deficient perfluoroarenes with aromatic heterocycles has been developed. Because of its low catalyst loading (2.5 mol %), high reaction efficiency, good chemo-and regioselectivity, and excellent functional-group compatibility, this protocol provides a useful and operationally simple access to perfluoroarene-thiophene structures of interest in functional materials for electronic devices.

Full text of DOI:10.1021/ja106046p

Published on Web 08/30/2010
Pd-Catalyzed Oxidative Cross-Coupling of Perfluoroarenes with Aromatic
Heterocycles
Chun-Yang He, Shilu Fan, and Xingang Zhang*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Received July 8, 2010; E-mail: xgzhang@mail.sioc.ac.cn
Scheme 1. Direct Pd-Catalyzed Oxidative Cross-Coupling of
Abstract: A straightforward and practical method for direct
Pd(OAc)2-catalyzed oxidative cross-coupling of electron-deficient
perfluoroarenes with aromatic heterocycles has been developed.
Because of its low catalyst loading (2.5 mol %), high reaction
efficiency, good chemo- and regioselectivity, and excellent
functional-group compatibility, this protocol provides a useful and
operationally simple access to perfluoroarene-thiophene struc-
tures of interest in functional materials for electronic devices.
Perfluoroarenes with Aromatic Heterocycles
range of perfluoroarene-thiophene structures with high efficiency
and regioselectivity.
We began this study by choosing electron-deficient pentafluo-
robenzene (1a) and 1-(thiophen-2-yl)ethanone (2a) as model
substrates (eq 1):
Perfluorinated aromatic rings are a prominent structural motif
found in numerous functional materials of importance in various
application fields.1 In particular, because of the strong electron-
withdrawing effect of perfluorinated aryl groups, which induces a
significant lowering of the HOMO and LUMO energy levels with
respect to the nonfluorinated counterparts,1d,2 molecules containing
the perfluoroarene-thiophene structure play a primary role as active
materials in electronic devices, such as organic light-emitting diodes
(OLEDs) and field-effect transistors (FETs). Generally, such a
structural moiety is achieved by cross-coupling of organometallic
aryls (boronic acids or stannanes) with aryl halides (ArX).2d,3
However, this “prefunctionalization” process suffers from the
tedious procedures for the preparation of the organometallic
reagents, the incompatibility of important functional groups, and
the use of toxic substrates (stannanes). In this context, direct
transition-metal-catalyzed C-H bond functionalization of perfluo-
roarenes with ArX, which represents a better reaction efficiency,
has recently been reported.4 From the point of view of synthetic
simplicity, the carbon-carbon bond formation obtained via twofold
C-H functionalization (i.e., the oxidative cross-coupling approach)
would be more straightforward. Although important progress in this
field has been made,5-7 selective oxidative cross-coupling methods
are still restricted to limited substrates, and direct transition-metal-
catalyzed oxidative cross-coupling of perfluoroarenes with het-
eroarenes has not been reported to date; this still poses a great
synthesis challenge because of the difficulties in controlling the
selectivity of the two C-H activation steps and in suppressing
undesired homocouplings.8 Hence, new methods to overcome these
daunting limitations for widespread synthetic applications are highly
desirable.
Initially, on the basis of our previous research work,9 the reaction
was carried out with 1a (2.0 equiv), 2a (1.0 equiv), Ag2CO3 (1.5
equiv), and Pd(OAc)2 (10 mol %) in DMF + DMSO (5%) at 120
°C and provided a good yield (72% NMR yield) of 3a with
perfluoroaryl located only at the R position of the thiophene ring.
Encouraged by this preliminary result, we further investigated the
reaction parameters (see Table S1 in the Supporting Information)
and found that DMSO is critical for the reaction efficiency. The
absence of DMSO or use of other solvents (DMF, NMP, dioxane,
HOAc) led to a lower yield or even no formation of 3a.10 We
supposed that DMSO might function as a ligand to activate the Pd
catalyst and prevent the formation of palladium black.11 In addition,
silver salts are also essential to the reaction efficiency, and a 1/1
Ag2CO3/AgOAc mixture afforded a better yield (73% isolated yield)
than the sole use of either of the silver salts. Probably, one of them
serves as a base and the other as a promoter and an oxidant for the
Pd(0)/Pd(II) catalytic cycle,8a since no reaction was observed in
the absence of the silver salts. However, the roles of these silver
salts remain elusive and will be addressed in the future. Further
studies showed that instead of Ag2CO3/AgOAc, using 1.5 equiv of
Ag2CO3 in conjunction with 1.0 equiv of HOAc provided a slightly
higher isolated yield (77%). Other oxidants [Cu(OAc)2, oxone, BQ,
and PhI(OAc)2] were ineffective. To our delight, further reducing
the Pd(OAc)2 loading to 2.5 mol % with utilization of 3.0 equiv of
1a gave the best isolated yield (86%).
Very recently, we developed a straightforward protocol for direct
olefination of perfluoroarenes that uses a Pd catalyst, which
represents one of the rare examples of catalytic direct olefination
of electron-deficient arenes.9 Inspired by this preliminary study,
herein we describe the first example of direct Pd(OAc)2-catalyzed
oxidative cross-coupling of electron-deficient perfluoroarenes with
heteroarenes via twofold C-H functionalization (Scheme 1). With
a low loading of Pd catalyst (2.5 mol %) and good functional-
group compatibility, this straightforward protocol provides a wide
Under the optimum reaction conditions, a variety of penta-
fluorophenyl-thiophene structures were obtained with high ef-
ficiency (Table 1). Versatile functional groups such as methyl
ketone, ester, aldehyde, amide, and chloride are compatible with
the catalytic system (entries 3a-e and 3j), and these groups can
easily be further functionalized utilizing traditional techniques. In
particular, for compound 3e, which is a useful building block for
the synthesis of n-type organic semiconductors, a good yield was
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10.1021/ja106046p  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Oxidative Cross-Coupling of Pentafluorobenzene with
Table 2. Oxidative Cross-Coupling of Fluoroarenes with Various
Various Heteroarenesa
Heteroarenesa
a Reaction conditions (unless otherwise specified): 1a (3.0 equiv) and
2 (0.6 mmol) in DMF (2 mL) + DMSO (100 µL). All reported reaction
yields are isolated yields. b Reaction run at 140 °C. c With isolation of
13% homocoupling of 3g (see the Supporting Information). d Using 4.0
equiv of 1a and 3.0 equiv of Ag2CO3 at 140 °C. e Using DMSO as the
solvent.
a Reaction conditions (unless otherwise specified): Fluoroarene
(2.0-3.0 equiv) and 2 (0.6 mmol) in DMF (2 mL) + DMSO (100 µL).
All reported reaction yields are isolated yields. b Reaction run at 140 °C.
c Using 3.0-5.0 equiv of 1 and 5 mol % Pd(OAc)2 at 140 °C. d Using
DMSO as the solvent. e Using 2.0 equiv of 1 at 140 °C. f Using 1.0
equiv of 1 and 2.0 equiv of 2.
obtained, although a small amount of homocoupling of 2-chlo-
rothiophene was observed (entry 3e). For 3-methylthiophene, good
regioselectivity was still observed at the R-positon of the thiophene
ring (entry 3g). It is noteworthy that a symmetrical 2,5-bis(per-
fluorophenyl)thiophene can easily be prepared from unfunctional-
ized thiophene in good yield (76%) via only one step (entry 3h),
thus providing a new strategy for the efficient synthesis of this
family of compounds.2,3 Furthermore, the heteroarenes are not
limited to simple thiophenes, as benzo[b]thiophene and other
aromatic heterocycles such as furans and indole are also suitable
substrates for the reaction (entries 3i-m).
Scheme 2. Syntheses of n-Type Organic Semiconductors 6 and 7
To further ascertain the scope of this methodology, a variety of
fluoroarenes were investigated (Table 2). Although substrates
bearing three or four fluorines contain more than one reaction site,
reasonable yields of monothiophene- or -indole-substituted products
were still observed, again with a useful functional-group tolerance
(entries 3n-p and 3x). The low reactivity of 1,3,5-trifluorobenzene
is probably due to the low acidity of the C-H bond to be activated
(entry 3x).4a,12 In addition, the successful formation of 3s, 3u, and
3v in good yields with intact chloride and bromide provided a good
opportunity for further formation of carbon-carbon or carbon-
heteroatom bonds by transition-metal-catalyzed coupling and other
reactions. A large conjugated system can also be constructed using
this protocol, thus allowing for the facile synthesis of a highly
functionalized perfluoroarene-thiophene structure in a simple
manner (entry 3w). To demonstrate the synthetic application of this
methodology, n-type organic semiconductors 6 and 72d were easily
prepared in only one step without the prerequirement of preparation
of aryl halides or organometallic reagents, providing even higher
yields than the traditional techniques2d,3a (Scheme 2).
(2.5 mol %), high reaction efficiency, good chemo- and regiose-
lectivity, and excellent functional-group compatibility, this protocol
provides a useful and operationally simple access to perfluoro-
arene-thiophene structures of interest in functional materials for
electronic devices. Further studies to expand the substrate scope
and their applications as well as investigations of the reaction
mechanism are now in progress.
Acknowledgment. The NSFC (20902100, 20832008), the
Shanghai Rising-Star Program (09QA1406900), and SIOC are
greatly acknowledged for funding of this work. The authors thank
Prof. Qilong Shen for proofreading and helpful discussions.
Supporting Information Available: Detailed experimental proce-
dures and characterization data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
In conclusion, we have developed a straightforward and practical
method for direct Pd(OAc)2-catalyzed oxidative cross-coupling of
electron-deficient perfluoroarenes with aromatic heterocycles via
twofold C-H functionalization. Because of its low catalyst loading
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