Letter
Palladium-Catalyzed Intermolecular Oxyarylation of Vinylacetates
with Retention of an Alkenyl Moiety
Sheng-Qi Qiu,† Yun-He Xu,*,† and Teck-Peng Loh*,†,‡
†Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
‡Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371
S
* Supporting Information
ABSTRACT: Palladium-catalyzed intermolecular oxyarylation reac-
tion of vinylacetates with retention of the double bond in the final
product is developed. Under the optimized reaction conditions, the
desired products of multisubstituted vinylesters could be obtained in
moderate to high yields.
irect oxidative functionalization of sp2 alkenes via the
oxidative Heck reaction has been shown to be a powerful
the oxyarylated product 4a could be obtained in 53% yield (Table
1, entry 1). However, in the absence of Ag2O, no desired product
could be obtained even though a stoichiometric amount of Pd(0)
catalyst was used (Table 1, entries 2−4). To our delight, a very
high yield could be achieved by using Pd(OAc)2 as catalyst
(Table 1, entry 5). Subsequently, other halobenzenes were tested
in this reaction; only product 4a′ generated from p-xylene
reacting with 1a could be detected after the reaction (Table 1,
entries 6−8). Therefore, benzene was employed as the aryl
source, and compound 4a was isolated in 33% yield (Table 1,
entry 9). Other corresponding oxyarylated products also were
obtained in low yields using p-xylene and mesitylene (Table 1,
entries 10 and 11). Next, it was observed that reducing the
amount of pivalic acid used will lead to a decrease in yield of the
product. Other silver bases and Pd(II) catalysts were also found
to be efficient to afford the desired product (Table 1, entries 13−
16). It was noted that reducing the loading of the palladium
catalyst and Xantphos ligand (Table 1, entry 17) or replacing
Xantphos with PPh3 (Table 1, entry 18) as well as changing the
solvent (Table 1, entries 19 and 20) all led to a slight decrease in
the yield of the product. Control experiments were also carried
out; no desired product was found in the absence of palladium
catalyst, while in the absence of silver oxide, an isolated 21% yield
of product could be observed (Table 1, entries 21 and 22).
After optimization of the reaction conditions, various acids
were screened in this reaction. It was found that the phenylacetic
acid and its derivatives could react well with vinylacetate 1a to
give the desired products in good yields regardless of substituents
present on the acid. Further screening of the acid-containing
heteroatom on the substituted chain will lead to dramatic
decrease in product yields. Only 29 and 52% yields were obtained
when 2-acetoxyacetic acid and 5-acetamidopentanoic acid were
applied, respectively, in this reaction (Chart 1, 4f and 4k). Other
acids such as pentanoic acid and cyclopropanecarboxylic acid
could also smoothly provide the corresponding products in
D
method for olefin functionalization because it avoids the need to
use prefunctionalized alkenes such as alkenylhalides and/or
alkenyl organometallics.1 Inspired by the pioneering work of
Gusevskaya2 and Ishii,3 research groups of Loh,4 Glorious,5 Yu,6
Shi,7 Georg,8 Liu,9 Giuaizeau,10 Iwasawa,11 Backvall,12 and others
̈
have developed transition-metal-catalyzed vinyl C−H bond
direct functionalization methods (Scheme 1, eq 1).13 In
Scheme 1. Functionalization Reactions of Alkenes
connection with our interest in the synthesis of trisubstituted
alkenes,4,14 we are interested in the sequential α- and β-sp2 C−H
bond difunctionalization of simple alkenes.15 This proves to be
more difficult than we anticipated.16 Another approach is to
obtain a difunctionalized vinyl ester via one-pot C−H bond
functionalization followed by an exchange with a nucleophile. As
a proof of concept, we exchanged the acetate group with other
functionalized esters. In this work, we would like to communicate
the results of a palladium-catalyzed intermolecular arylation and
esterification of vinylacetates with retention of the double bond
after reaction (Scheme 1, eq 2). Using different acids allowed us
to introduce a different functional group in the ester functional
group of the product.
Initially, we searched for optimized reaction conditions for the
oxyarylation of vinylacetate 1a with cheap and commercially
available iodobenzene and pivalic acid as the efficient
nucleophile. The results are summarized in Table 1. In the
presence of Pd(PPh3)4, Ag2O, and Xantphos in p-xylene solution,
Received: May 23, 2015
© XXXX American Chemical Society
A
Org. Lett. XXXX, XXX, XXX−XXX
Qiu, Sheng-Qi
