Angewandte
Chemie
DOI: 10.1002/anie.201106451
Homogeneous Catalysis
À
Palladium-Catalyzed Decarboxylative C H Bond Arylation of
Thiophenes**
Peng Hu, Min Zhang, Xiaoming Jie, and Weiping Su*
2-Arylthiophene is an ubiquitous structural motif in natural
products,[1] pharmaceuticals,[2] and functional organic materi-
als,[3] as exemplified by the three 2-arylthiophene-containing
molecules depicted in Scheme 1.
Rh,[5h] and Cu[5i] catalysts; thus thiophenes were directly used
to replace expensive thienyl organometallic reagents in
traditional cross-coupling reactions. As a highly efficient
approach to 2-arylthiophenes, the oxidative cross-coupling of
two unfunctionalized arenes has been realized in the palla-
À
dium-catalyzed reactions of thiophenes with C H acidic
polyfluoroarenes[6a] and nitrogen-containing heteroarenes.[6b]
Moreover, metal-free oxidative cross-couplings of thiophenes
with electron-rich arenes has also been reported.[6c] Although
these transformations represent substantial progress toward
the syntheses of 2-arylthiophenes in an atom-economical and
environmentally benign way, there is significant room for
improvement with respect to the generality and functional-
group tolerance of these state-of-the-art methods.
On the other hand, the use of carboxylic acids as cross-
coupling components by a metal-promoted decarboxylation
process is a rapidly growing area of research because of their
low cost, diversity, and ready availability.[7–12] Recently,
decarboxylative cross-coupling reactions have been expanded
[11]
À
to decarboxylative C H bond functionalization, including
intramolecular reactions for the syntheses of dibenzofur-
ans,[11b] intermolecular reactions for the selective arylation of
indoles,[11c,d] ortho acylation of acetanilides,[11g,h] the construc-
tion of azole–azole linkages,[11i] and the direct arylation of C
À
Scheme 1. Three examples illustrating the importance of compounds
containing a 2-arylthiophene moiety: A natural product (A);[1a] Evista
(B), a medicine used to prevent and treat osteoporosis;[2b] ITPEEPT
(C), an electrochromic device.[3b]
H acidic polyfluorobenzenes.[11f,j] A decarboxylative C H
À
bond functionalization that combines two newly emerging
À
approaches, that is, decarboxylation and direct C H bond
functionalization, offers a new synthetic strategy in synthesis.
However, the challenges posed by this promising process
Conventionally, 2-arylthiophenes are synthesized by
cross-coupling reactions of (hetero)aryl halides with (heter-
o)aryl organometallic reagents.[4] Owing to the wide applica-
tions of this family of compounds, the development of new
methods for the synthesis of valuable 2-arylthiophenes from
simple and readily available starting materials by concise
steps continues to be a target of intense interest.[4–6] In this
À
remain. For example, many of the decarboxylative C H bond
functionalization reactions were restricted to a narrow range
of arene carboxylic acids because the reactivity of the arene
carboxylic acids toward decarboxylation is very sensitive to
the substitutents on benzene rings. Herein, we report the
À
decarboxylative C H bond arylation of thiophenes catalyzed
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context, the direct C H arylation of thiophenes with aryl
by a Pd(OAc)2/Ag2CO3 system; electron-rich, electron-defi-
cient, and heterocyclic benzoic acids can all be used as aryl
sources in this reaction and a broad spectrum of functional
groups can be tolerated.
As generally proposed for similar processes, the Pd/Ag-
catalyzed decarboxylative C H arylation of thiophenes may
iodides and bromides has been achieved by using Pd,[5a–f] Ir,[5g]
[*] Dr. P. Hu, M. Zhang, X. Jie, Prof. W. Su
State Key Laboratory of Structural Chemistry
Fujian Institute of Research on the Structure of Matter
Chinese Academy of Sciences
À
À
involve a Pd-promoted C H cleavage to form a palladium
Yangqiao West Road 155, Fuzhou, Fujian 350002 (China)
E-mail: wpsu@fjirsm.ac.cn
intermediate, a Ag-promoted decarboxylation to generate an
aryl silver species, a subsequent aryl transfer from Ag to Pd,
and reductive elimination (Scheme 2). In light of this
proposal, we envisioned that the major problems impeding
the execution of the target process would result from the
following side reactions: 1) the unstable aryl silver inter-
mediate is liable to protodecarboxylation[12] and decarbox-
ylative homocoupling[10j] if the desired cross-coupling reaction
[**] Financial support from the 973 Program (2011CB932404,
2011CBA00501), NSFC (20821061, 20925102), “The Distinguished
Oversea Scholar Project”, the “One Hundred Talent Project”, the
Knowledge Innovation Program of CAS, and the Key Project from
CAS is greatly appreciated.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 227 –231
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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