368
Published on the web March 2, 2011
Practical Synthesis of Diethyl Phenylsuccinate
by Mg-promoted Carboxylation of Ethyl Cinnamate
Hirofumi Maekawa,* Taro Murakami, Takeshi Miyazaki, and Ikuzo Nishiguchi*
Department of Materials Science and Technology, Nagaoka University of Technology,
1603-1 Kamitomioka-cho, Nagaoka, Niigata 940-2188
(Received January 5, 2011; CL-110004; E-mail: maekawa@vos.nagaokaut.ac.jp)
Mg-promoted reduction of ethyl cinnamate (1a) in the
COOMe
Ph
COOMe
COOMe
COOMe
presence of carbon dioxide gave a mixture of ¢-carboxylated
compound 2a and ¡,¢-dicarboxylated compound 3a. Similar
reductive carboxylation of 1a followed by acidic decarboxylation
of one of the two geminal carboxyl groups of the generated 3a and
esterification afforded selective formation of diethyl phenyl-
succinate (2a) in good yield.
COOMe
1) + e / MeCN /
CO2
+
Ph
Ph
COOMe
Ph
Ph
2) esterification
COOMe
COOMe
+
TotalYield : 62~79%
Scheme 1.
+ e or Mg / ECl / DMF
E
COOEt
Effective utilization of carbon dioxide has been an
important theme for a long time because of concern about
global warming gasses and securing carbon resources against
exhaustion of petroleum and coal. Many studies on reactions of
carbon dioxide have been reported and most of them are related
to synthesis of carbonate.1,2 Transition-metal-catalyzed carbon
fixation, with the exception of nickel3-7 has generally treated not
carbon dioxide8 but carbon monoxide. Electrophilic attack of
anionic species like Grignard reagents9 may be one of the most
promising synthetic routes to make use of carbon dioxide.
Tokuda and Senboku revealed electrochemical fixation of
carbon dioxide in the presence of halogenated compounds, vinyl
triflate, and alkenes and the application to synthesis of organic
fine-chemicals and pharmaceuticals.10-12 Electrochemical car-
boxylation of benzylideneacetone,13 acetophenone,14 sty-
rene,15,16 and phenylacetylene17 has been also reported to give
selective formation of ¡-carboxylated or ¡,¢-dicarboxylated
compounds in high yields. Lamy,18 Inesi,19 and Lu20,21 reported
electrochemical carboxylation of cinnamic acid derivatives,
however their methods are not practical because of few reaction
examples, considerable recovery of starting material, or for-
mation of three different products as shown in Scheme 1.20
We have already reported generation and reactions of radical
anion species by electron transfer, especially electrochemical
and Mg-promoted reduction of aromatic carbonyl compounds
and their selective cross-coupling reactions.22,23 In our previous
work, Mg-promoted acylation or electrochemical silylation of
ethyl cinnamate in N,N-dimethylformamide22,23 brought about
selective formation of ¢-acylated or ¢-silylated compound
shown in Scheme 2 in high yield, however this carboxylation
gave different products from the reported acylation, silylation,
and electrochemical carboxylation due to the difference of
electrophilicity or reaction conditions.18-20,22,23
COOEt
ECl :
MeCOCl : Yield 71%
TMSCl : Yield 79%
Ph
1a
Scheme 2.
Table 1. Mg-promoted carboxylation of ethyl cinnamate derivativesa
Mg / TMSCl /
CO2 / DMF
COOEt
1)
COOEt
COOEt
+
COOEt
Ar
COOEt
1a~i
Ar
3a~i
Ar
EtI / NaHCO3
2)
COOEt
2a~i
GC yield/%
Entry
Ar
2
3
Total
1
2
3
4
5
6
1a
1d
1f
1g
1h
1i
C6H5
2-ClC6H4
4-MeOC6H4
4-CF3C6H4
2-Furyl
32
54
9
33
30
44
38
27
36
39
18
14
70
81
45
72
48
58
2-Thienyl
aReaction conditions: 1) Substrate (2 mmol), Mg (3 mol equiv), TMSCl
(2 mol equiv), DMF (10 mL), ¹15 °C, CO2 bubbling; 2) Etl (9.5
mol equiv), NaHCO3 (4.5 mol equiv), 50 °C.
hydrogen carbonate as shown in Table 1. The products, ¡,¢-
dicarboxylated compounds, are expected to result in selective
decarboxylation under heating to afford ¢-carboxylated com-
pounds, while ¢-carboxylated compounds formed in this Mg-
promoted reduction may be still alive under the same conditions.
The results of Mg-promoted carboxylation followed by
decarboxylation and esterification are summarized in Table 2.
In all the examples, phenylsuccinic acid derivatives 2 were
obtained in good yield and no remarkable electron-withdrawing
effect was observed (Table 2, Entries 2-4 and 7) although yield
of the products with a methoxy or methyl group at the 4-position
might decrease because of the electron-donating effect to make
generated anionic species unstable (Table 2, Entries 5 and 6).
Derivatives with naphthalene or heteroaromatic rings such
as furan and thiophene instead of phenyl rings can be trans-
formed to give the corresponding carboxylated compounds
(Table 2, Entries 8-10). Benzylideneacetone (4a) and cinnamo-
nitrile (4b) were also applicable to this reaction to give the
corresponding ethyl 4-oxo-2-phenylpentanoate (5a) and ethyl 3-
In this study, Mg-promoted reduction of ethyl cinnamate in
the presence of carbon dioxide followed by esterification gave a
mixture of ¢-carboxylated compound 2 and ¡,¢-dicarboxylated
compound 3, which were easily transformed to diethyl phenyl-
succinate after decarboxylation and esterification.
Ethyl cinnamate and its derivatives were also carboxylated
to give a mixture of 2 and 3, which were directly transformed
into the corresponding esters by ethyl iodide and sodium
Chem. Lett. 2011, 40, 368-369
© 2011 The Chemical Society of Japan
Maekawa, Hirofumi
