G Model
CCLET 5578 No. of Pages 4
Chinese Chemical Letters
Communication
Palladium-catalyzed oxidative homocoupling of 2-arylquinazolinones
a,b,
a
a
a
a
a
Yadong Feng *, Zhengping Wu , Ting Chen , Qi Fu , Qihua You , Jinhai Shen ,
b,
Xiuling Cui *
College of Environment and Public Health, Xiamen Huaxia University, Xiamen 361024, China
a
b
Research Center of Molecular Medicine, Ministry of Education, Key Laboratory of Fujian Molecular Medicine, Key Laboratory of Precision Medicine and
Molecular Diagnosis of Fujian Universities, Key Laboratory of Xiamen Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University, Xiamen
3
61021, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Pd-catalyzed oxidative homocoupling of 2-arylquinazolinones was successfully developed for the direct
construction of biaryls via C ꢀꢀ H bond activation. New well-defined structure that possessed two
quinazolinone units was obtained with high efficiency and atomic economy. The protocols offer an
efficient approach to the synthetically useful and functionalized biaryls in good yields using
quinazolinone as a directing group.
Received 8 March 2020
Received in revised form 20 March 2020
Accepted 31 March 2020
Available online xxx
©
2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
2
-Arylquinazolinones
Homocoupling
Palladium-catalyzed
C ꢀꢀ H bond activation
Biaryls have attracted considerable attention in the fields of
electrochemistry, photochemistry and biochemistry, because they
are privileged p-conjugated cores in biologically active molecules,
isoxazoles via direct C ꢀꢀ H bond activation using benzoisoxazole as
a new directing group reported by Ji group simultaneously [7].
As well-known, quinazolinone has become increasingly valu-
able framework because of its biological activities, such as
antibacterial, antifungal, antimalarial, anticancer, antihyperten-
sive, antitubercular, and anticonvulsant [8]. Logically, biaryls with
two quinazolinone units could be potentially used for the
development of new drugs or advanced functional materials. For
example, compounds I and II (Fig. 1) show activity against Gram-
positive and Gram-negative bacteria and yeasts [9].
advanced functional materials, ligands, and synthetic intermedi-
ates [1]. Over the last decade, metal-catalyzed direct dehydrogen-
ative coupling reactions via dual C–H bond activation have been
developed as the most attractive and powerful approaches to
biaryls, since the starting materials could be used directly without
prior functionalization, and the sole byproduct would only be 2
+
equiv. of H [2]. In 1965, van Helden and Verberg disclosed the first
oxidative C ꢀꢀ H/C ꢀꢀ H coupling of aromatic compounds in the
Recently, our group has developed a series of easy methods for
modification of arene via C–H bond activation, in which
quinazolinones act as directing groups since there are two N
atoms in the molecule [10]. However, to the best of our knowledge,
no example was reported on the direct construction of biaryls with
two 2-arylquinazolinone units. In our continuing effort to build
new molecules through C–H bond activation [11], herein, we
present a Pd-catalyzed oxidative homocoupling of 2-arylquinazo-
2
presence of stoichiometric amounts of PdCl to synthesize biaryls
[
3]. Subsequently, in 2006, Lu and co-workers disclosed an
intermolecular cross-coupling of simple arenes via C ꢀꢀ H activation
for synthesis of biaryls employing Pd(OAc) /TFA/K as the
2
2 2 8
S O
catalytic system [4]. After that, the regioselective palladium-
catalyzed homocoupling of indolizines was also demonstrated by
You and co-workers in 2009 [5]. Recently, Zhou and Wang reported
an efficient oxidative homocoupling of benzene to synthesize
2
linones with O as an oxidant using quinazolinone as a directing
biaryls by using O
loading (Pd(OAc) , 0.07 mol%) was required [6]. Also noteworthy is
a palladium-catalyzed oxidative homocoupling of 3-arylbenzo[d]
2
as the sole oxidant, in which low catalyst
group (Scheme 1). New well-defined structure possessed two 2-
arylquinazolinone units was obtained with high efficiency and
atomic economy. This protocol features simple operation, easily
available starting materials, high efficiency, environmental friend-
liness, and tolerance of a wide range of substrates.
2
Initially, 2-phenylquinazolin-4(3H)-one (1a) was chosen as
a model substrate to examine the impact of various parameters
on the reaction (Table 1). The results revealed that
*
Corresponding authors at: College of Environment and Public Health, Xiamen
0
0
0
2,2 -([1,1 -biphenyl]-2,2 -diyl)bis(quinazolin-4(3H)-one) (2a) was
1001-8417/© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Feng, Yadong
