Efficient electrochemical dicarboxylation of phenyl-substituted alkenes: Synthesis of 1-phenylalkane-1,2-dicarboxylic acids

Article abstract of DOI:10.1055/s-2001-11417

Electrochemical dicarboxylation of phenyl-substituted alkenes in the presence of atmospheric pressure of carbon dioxide with a platinum plate cathode and a magnesium rod anode readily took place efficiently in a DMF solution containing 0.1 M Et₄NClO₄ to give the corresponding 1,2-dicarboxylic acids in high yields.

Full text of DOI:10.1055/s-2001-11417

418
LETTER
Efficient Electrochemical Dicarboxylation of Phenyl-substituted Alkenes:
Synthesis of 1-Phenylalkane-1,2-dicarboxylic Acids
Hisanori Senboku,* Hirokazu Komatsu, Yusuke Fujimura, Masao Tokuda*
Laboratory of Organic Synthesis, Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-
8628, Japan
Fax +81-11-706-6598; E-mail: tokuda@org-mc.eng.hokudai.ac.jp
Received 29 December 2000
R1
Ph R1
Abstract: Electrochemical dicarboxylation of phenyl-substituted
alkenes in the presence of atmospheric pressure of carbon dioxide
with a platinum plate cathode and a magnesium rod anode readily
took place efficiently in a DMF solution containing 0.1 M Et4NClO4
to give the corresponding 1,2-dicarboxylic acids in high yields.
CO2
R2
Pt
Mg
COOH
Ph
HOOC
R3
R3 R2
0.1M Et4NClO4 - DMF
3 F/mol, 25 mA/cm2
1
2
-10 °C
Key words: carboxylic acids, magnesium, phenyl-substituted alk-
enes, electrochemical carboxylation, electrochemistry
Scheme 1
Table 1 Electrochemical Dicarboxylation of Phenyl-substituted
One of useful methods for preparation of carboxylic acids
is one carbon elongation reaction of organic halides or
alkenes using a cyanide ion of KCN or NaCN, carbon
monoxide, and carbon dioxide. 2-Phenylsuccinic acids,
useful compounds as synthetic intermediates or as antitu-
mor agents,1 have been prepared by several methods: i.e.,
addition of NaCN to ethyl -cyano- -phenylacrylate,2a
addition of HCN to -phenylcinnamonitrile,2b addition of
1,1-diaminoethene to -nitrostyrene,2c reductive addition
of arenediazonium salts to maleic or fumaric acid,2d con-
densation of benzaldehyde, phenylacetonitrile, and
NaCN,2b and oxidative coupling of carboxylic acid dian-
ions.2e,2f In these preparations, however, there are several
drawbacks: the use of hazardous or complex reagents, the
requirement of a long reaction time, and limitation to a
preparation of symmetrical dicarboxylic acids in the case
of oxidative coupling. Carboxylic acids can also be pre-
pared by chemical fixation of carbon dioxide to alkenes,
but severe reaction conditions are required in these reac-
tions.3 On the other hand, an electrochemical fixation of
carbon dioxide to organic halides or carbonyl compounds
can be readily carried out efficiently even in an atmo-
spheric pressure of CO2 under neutral and mild conditions
to give carboxylic acids in high yields.4,5 We have already
reported that electrochemical carboxylation of allylic ha-
lides,6 propargylic bromides,7 1,4-dibromo-2-bromome-
thylbut-2-ene,8 vinyl bromides,9 and vinyl triflates10
proceeds efficiently by using magnesium as a reactive-
metal anode to give the corresponding carboxylic acids in
high yields. As one of our continuing studies on electro-
chemical carboxylation, we recently succeeded in an effi-
cient electrochemical fixation of two CO2 molecules to
the C=C bond of phenyl-substituted alkenes to give the
corresponding 2-phenylsuccinic acids in moderate to high
yields. In this paper, we report such a convenient and ef-
ficient method for synthesizing various 2-phenylsuccinic
acids by electrochemical dicarboxylation. Although elec-
trochemical carboxylation of phenyl-substituted alkenes
Alkenesa
Conversion
(%)
Yieldb
(%)
Alkene
R1
R2
R3
Entry
1c
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
H
Me
H
H
Ph
H
H
H
Me
H
H
Ph
H
H
H
H
Me
H
H
73
98
98
98
93
84
84
66 (90)
68 (69)
77 (79)d
70 (71)d
91 (98)
84 (>99)e
84 (92)e
1g
H
Ph
a Alkene 1 (3.5 mmol) in DMF (20 ml) containing 0.1 M Et4NClO4
was electrolyzed in the presence of an atmospheric pressure of CO2
using a one-compartment cell equipped with a Pt plate cathode (2
3 cm2) and an Mg rod anode ( 3 mm).
b Isolated yields. The yields based on a reacted starting alkene 1 are
shown in parentheses.
c Electrolysis was carried out in the presence of 4-methoxyphenol
(3 mg).
d Isomer ratio (threo:erythro); 2.7:1 (entry 3), 2.5:1 (entry 4).
e Isomer ratio (dl:meso); 1.8:1 (entry 6), 1.9:1 (entry 7).
has been reported by several workers, a mixture of mono-
and dicarboxylated acids has been obtained,11,12 and dicar-
boxylic acids have only been formed in low conversions
by using an Ni(II) catalyst.12
A general procedure of the present electrochemical dicar-
boxylation is as follows: Alkene (3.5 mmol) in 20 mL of
DMF containing 0.1 M Et4NClO4 was electrolyzed at -10
°C with a constant current (25 mA/cm2) under an atmo-
spheric pressure of carbon dioxide. A one-compartment
cell equipped with a platinum plate cathode (2 3 cm2)
and a magnesium rod anode ( 3 mm was used for elec-
trolysis. The electricity passed was 3 F/mol. After elec-
trolysis, the electrolyzed solution was acidified with 2N
HCl and extracted with diethyl ether. The ethereal solu-
tion was washed successively with H2O and saturated
Synlett 2001, No. 3, 418–420 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Efficient Electrochemical Dicarboxylation of Phenyl-substituted Alkenes
419
Table 2 Reduction Peak Potentials of Phenyl-substituted Alkenes 1
NaHCO3. The aqueous solution was again acidified with
2N HCl, and the resulting carboxylic acid was extracted
with ether. The combined ethereal solution was washed
with saturated brine and dried over MgSO4. Evaporation
of the solvent gave an almost pure 1,2-dicarboxylic acid.
Alkene
R3
R1
R2
Ered (V vs Ag/Ag+)a
1a
1b
1c
1d
1e
1f
H
Me
H
H
Ph
H
H
H
Me
H
H
Ph
H
H
H
H
Me
H
H
-2.91
< -3.0
< -3.0
< -3.0
-2.58
The results of the electrochemical dicarboxylation are
summarized in Table 1. Electrochemical dicarboxylation
of phenyl-substituted alkenes proceeded in high conver-
sions (73-98%) to give the corresponding 1,2-dicarboxyl-
ic acids in high yields. For instance, electrochemical
dicarboxylation of styrene (1a) gave 2-phenylsuccinic
acid in 66% isolated yield (entry 1). The conversion of
styrene was 73% and the yield based on the converted 1a
was 90%. Electrochemical dicarboxylation of other sub-
stituted styrenes using our method was also found to occur
-2.44
-2.50
1g
H
Ph
a Reduction peak potentials were determined with a gold disk elec-
trode at the scan rate of 0.1 Vs-1 and are shown in V vs Ag/Ag+.
At Cathode
CO2 (Ered = -2.53 V vs Ag/Ag+)
efficiently. Thus, electrochemical dicarboxylation of
-
path a
+e
CO2
methylstyrene (1b) and 1,1-diphenylethylene (1e) gave
the corresponding 2,2-disubstituted succinic acids 2b and
2e in 68% and 91% yields, respectively (entries 2 and 5).
When (E)- (1c) and (Z)- -methylstyrenes (1d) were sub-
jected to the present dicarboxylation, a mixture of threo-
and erythro-2-methyl-3-phenylsuccinic acids13 was ob-
tained in 77% and 70% yields, respectively (entries 3 and
4). Isomer ratios of threo- and erythro-2-methyl-3-phe-
COO
R
•
1) +e
COO
COO
Ph
Ph
Ph
2) CO2
R
A
D
R = H
R = Ph
B R = H
E
R = Ph
path b
CO2
1
nylsuccinic acids, determined by H NMR, were 2.7:1
+e
Ph
Ph
Ph
Ph
(entry 3) and 2.5:1 (entry 4), respectively, and the threo-
isomer was preferentially obtained in each case. Further-
more, similar electrochemical carboxylations of (E)- (1f)
and (Z)-stilbenes (1g) gave 2,3-diphenylsuccinic acid,2f
both in 84% yields, which contains a dl-isomer as a major
product (dl:meso = 1.8:1 in entry 6, 1.9:1 in entry 7). The
present dicarboxylation also took place efficiently when
cycloalkenes were used as substrates. Thus, a similar elec-
trochemical carboxylation of 1,2-dihydronaphthalene (3)
gave naphthalene-1,2-dicarboxylic acid (4) in 73% isolat-
ed yield. A similar electrochemical reaction of 1-phenyl-
cyclohexene (5) gave 1-phenylcyclohexane-1,2-dicarbox-
ylic acid (6) in 65% yield (Scheme 2). This dicarboxylic
acid 6 was not produced in the nickel catalyzed electro-
chemical carboxylation.12
C
At Anode
Mg
Mg2+
2e
+
O
O
Ph
H+
O
B or E
+
Mg2+
2
Mg
O
R
Scheme 3
From these results and the reduction potential of CO2
(-2.53 V vs Ag/Ag+), two possible reaction pathways
shown in Scheme 3 may be considered.11b One is the path-
way a, in which alkenes 1 have more negative reduction
potentials than that of CO2 (entries 1, 2, 3, and 4 in Table
1). In these cases, a one-electron reduction of carbon di-
oxide preferentially occurs to generate its anion radical,
since the reduction potentials of alkenes 1 are more nega-
tive than that of carbon dioxide. The addition of CO2 an-
ion radical to alkenes 1 would result in the formation of an
intermediate A. Further one-electron reduction followed
by reaction with CO2 gives rise to dicarboxylate ion B
(path a). On the other hand, in the reaction of alkenes 1
whose reduction potentials are almost the same or slightly
more positive than that of CO2 (entries 5, 6, and 7 in Table
1), a direct or CO2-mediated one-electron reduction of
COOH
CO2
COOH
Pt
Mg
0.1M Et4NClO4 - DMF
3 F/mol, 25 mA/cm2
73%
trans / cis = 7
3
4
-10 °C
Ph
COOH
Ph
CO2
COOH
Pt
Mg
0.1M Et4NClO4 - DMF
3 F/mol, 25 mA/cm2
65%
5
6
-10 °C
Scheme 2
Cyclic voltammetry of phenyl-substituted alkenes 1 was alkenes 1 takes place to generate their anion radicals C.
carried out, and the observed reduction peak potentials Reaction of C with CO2 gives monocarboxylated interme-
(Ered) are summarized in Table 2.
diate D. Further one-electron reduction followed by reac-
Synlett 2001, No. 3, 418–420 ISSN 0936-5214 © Thieme Stuttgart · New York

420
H. Senboku et al.
LETTER
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tion with CO2 leads to the formation of dicarboxylate ion
E (path b). At an anode, on the other hand, a dissolution
of magnesium metal takes place to give magnesium ion in
both of the electrochemical pathways described above.
The magnesium ion readily captures carboxylate ions B or
E to form stable magnesium carboxylates, which upon an
acid treatment give dicarboxylic acids 2.
Acknowledgement
This work was supported by a Grant-in-Aid for Scientific Research
(B) (No. 10555314) from the Ministry of Education, Science,
Sports and Culture, and by a Grant-in-Aid for Encouragement of
Young Scientists (No. 12750753) from the Japan Society for the
Promotion of Science.
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Article Identifier:
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Synlett 2001, No. 3, 418–420 ISSN 0936-5214 © Thieme Stuttgart · New York