Angewandte
Chemie
DOI: 10.1002/anie.201304295
C–H Carbonylation
Synthesis of Dibenzopyranones through Palladium-Catalyzed Directed
C–H Activation/Carbonylation of 2-Arylphenols**
Shuang Luo, Fei-Xian Luo, Xi-Sha Zhang, and Zhang-Jie Shi*
The dibenzopyranone scaffold is found in many natural
products and biologically active molecules, and was consid-
ered as a privileged structure, which is of great importance as
intermediate for the synthesis of various pharmaceutically
of prefunctionalization. From the point of view of atom- and
process-economical chemistry, to develop an efficient and
general synthetic route with less waste is highly desirable. In
view of recent advances in CÀH bond carbonylation, we
[1]
interesting compounds. Traditionally, major methods for the
synthesis of dibenzopyranone derivatives include: 1) Baeyer–
envisaged that the dibenzopyranone scaffold might be easily
constructed from 2-phenylphenol through palladium-cata-
lyzed C–H activation/carbonylation.
[2]
Villiger oxidation of fluorenone (Scheme 1, path a); 2) lac-
[3]
tonization of 2-halobiarylcarboxylic acid derivatives;
Indeed, C–H functionalization is the most sustainable and
straightforward method to construct complicated molecules
and has received significant attention during the past
[6]
decades. On the other hand, transition-metal-catalyzed
carbonylation of organic halides with CO in the presence of
various nucleophiles has been demonstrated to be a powerful
[
7]
approach to carbonyl compounds. With the combination of
these two important transformations, direct carbonylation of
CÀH bonds is an ideal strategy to introduce carbonyl group
into molecules. For the numerous C–H carbonylation reac-
tions reported to date, directing groups are usually required to
achieve selectivity of these transformations. Various func-
[
8]
[9]
tional groups, such as N-containing heterocycles, amides,
[
10]
[11]
[12]
amidines, aliphatic amines, carboxylic acids, hydroxy
groups,
[
13]
[14]
and free amines,
have been used as directing
groups. However, a C–H carbonylation reaction using a phe-
nolic hydroxy group as a directing group to prepare lactones
has never been approached. The main challenge of this
transformation is the incompatibility of phenols with the
oxidative reaction conditions. Herein, we reported the first
successful and efficient protocol for the synthesis of dibenzo-
pyranones through Pd-catalyzed phenol-directed C–H acti-
vation/carbonylation of 2-phenylphenol derivatives in the
presence of CO.
Scheme 1. Synthesis of dibenzopyranone.
3
) cross-coupling from 2-halobenzaldehydes and o-hydroxy-
[4]
arylboronic acids, followed by lactonization (path c);
4
) intramolecular CÀC bond formation of aryl 2-haloben-
[5]
zoate (path d). Although these present methods exhibited
their individual advantages, they generally involved multistep
procedures, sometimes harsh reaction conditions, starting
materials that are not readily available, and the requirement
Our evaluation started with the reaction of 2-phenyl-
phenol (1a) in the presence of the Pd(OAc) catalyst and
2
K CO as a base under an atmospheric pressure of CO in
2
3
mesitylene at 1208C (Table 1). Different weak oxidants were
tested first, and the desired product dibenzopyranone (2a)
[
*] Dr. S. Luo, Dr. F.-X. Luo, X.-S. Zhang, Prof. Dr. Z.-J. Shi
Beijing National Laboratory of Molecular Sciences (BNLMS)
PKU Green Chemistry Centre and Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education
College of Chemistry
was obtained in a low yield when either AgOAc, Cu(OAc)2,
or air were used as oxidant. The product 2a was produced in
16% yield when the reaction proceeded in the presence of
a catalytic amount of Cu(OAc) (10 mol%) without inert-gas
2
Peking University, Beijing 100871 (China)
[15]
protection. Further studies indicated that the addition of
Prof. Dr. Z.-J. Shi
pivalates improved the reaction slightly, while PivOH was the
most effective one. Further optimization was conducted with
different bases. Na CO provided the best result, and 2a could
State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences
Shanghai 200032 (China)
2
3
be isolated in 91% yield. When the loading of Pd(OAc) was
2
E-mail: zshi@pku.edu.cn
lowered to 5 mol%, the reaction did not lose efficiency. No
product was formed in the absence of Pd(OAc)2.
[
**] Support of this work by NSFC (No. 20925207, 21072010, 20821062)
and the “973” Project from the MOST of China (2009CB825300) is
gratefully acknowledged.
With the optimized conditions in hand, we further
examined the scope of the phenol-directed C–H activation/
carbonylation/lactonization (Figure 1). A variety of 2-aryl
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
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