ORGANIC
LETTERS
2012
Vol. 14, No. 24
6186–6189
Pd-Catalyzed β‑Selective Direct CÀH
Bond Arylation of Thiophenes with
Aryltrimethylsilanes
Kenji Funaki,† Tetsuo Sato,†,‡ and Shuichi Oi*,†,‡
Department of Applied Chemistry, Graduate School of Engineering and Environment
Conservation Research Institute, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku,
Sendai 980-8579, Japan
Received October 22, 2012
ABSTRACT
Direct arylation of thiophenes and benzothiophenes with aryltrimethylsilanes was effectively catalyzed by PdCl2(MeCN)2 in the presence of CuCl2
as an oxidant. The reaction preferentially occurred at the β-position of both thiophenes and benzothiophenes.
The transition metal catalyzed cross-coupling reac-
tion of aromatic compounds has emerged as a promising
strategy for the construction of various fine chemicals,
such as organic electronic materials, pharmaceuticals,
and agrochemicals.1 Most recently, the direct arylation
of aromatic CÀH bonds has attracted considerable atten-
tion because of the synthetic and atom efficient nature of
the reaction. In particular, many different catalyst systems
have been reported for direct CÀH arylation of five-
membered heteroarenes.2À6 However, it is difficult to achieve
the direct CÀH bond arylation at a desired position of the
five-membered heteroarene rings because several CÀH
bonds with different reactivities exist in these rings. An ex-
ample of a switch in regioselectivity was reported for azoles,
in which the regioselectivity of Pd- catalyzed arylation of
imidazole and thiazole was switched from C-2 to C-5 when
a Cu salt was added to the catalytic systems.3 In contrast to
this, it has been a challenge to achieve the β-selective arylation
of thiophenes. The reaction of thiophenes and benzothio-
phenes with aryl halides or arylmetal reagents produces
R-arylated products under a majority of the reaction condi-
tions previously reported (eq 1).4 Fagnou et al. reported a
sequential method for the synthesis of β-arylbenzothiophenes
by using R-chlorobenzothiophene as a substrate, which
forced arylation at the β-position followed by reductive
dechlorination to afford β-arylbenzothiophenes (eq 2).5
Bach et al. reported the β-selective oxidative coupling
† Department of Applied Chemistry.
‡ Environment Conservation Research Institute.
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r
10.1021/ol3029109
Published on Web 12/05/2012
2012 American Chemical Society