Kolbe carbon-carbon coupling electrosynthesis using solid-supported bases

Article abstract of DOI:10.1021/jo801016f

(Chemical Equation Presented) We have developed a novel electrolytic system for Kolbe carbon-carbon coupling electrosynthesis based on the acid-base reaction between carboxylic acids as a substrate and solid-supported bases. On the basis of the electrolytic system, Kolbe electrolysis of various carboxylic acids was successfully carried out to provide the corresponding homocoupling products in moderate to excellent yields.

Full text of DOI:10.1021/jo801016f

Kolbe Carbon-Carbon Coupling Electrosynthesis
Using Solid-Supported Bases
Hitoshi Kurihara,† Toshio Fuchigami,† and Toshiki Tajima*,‡
Kolbe electrolysis is the oldest electroorganic reaction4 and
is useful for the synthesis of higher alkanes5 and 1,n-diesters5a,6
because of its specificity and versatility.7 In fact, it cannot be
achieved by other chemical reactions. Kolbe electrolysis is
defined as the electrochemical one-electron oxidation of car-
boxylate ions with decarboxylation that leads to radicals that
dimerize to homocoupling products (Scheme 1). Solid-supported
bases may be applied to the Kolbe electrolysis to form
carboxylate ions by the acid-base reaction with carboxylic acids
as a substrate (eq 1). Furthermore, the conjugate acid-base pair
would play the role of supporting electrolytes. Therefore, it
should enable us to remove the need for supporting electrolytes
in Kolbe electrolysis. We herein report Kolbe carbon-carbon
coupling electrosynthesis using solid-supported bases.
Department of Electronic Chemistry and Global Edge
Institute, Tokyo Institute of Technology,
Yokohama 226-8502, Japan
tajima.t.ac@m.titech.ac.jp
ReceiVed May 15, 2008
First, we measured the cyclic voltammogram of 4,4,4-
trifluoro-3,3-dimethoxybutyric acid (1) in 0.1 M silica gel
supported piperidine (Si-piperidine)/MeOH in order to confirm
the acid-base reaction between 1 and Si-piperidine. As shown
in Figure 1(a), the background cyclic voltammogram was
recorded before the addition of 1. After the addition of 1, the
oxidation current for MeOH was decreased because of the
adsorption of the carboxylate ion derived from 1 on the platinum
electrode surface,8 while the reduction current for H+ was
remarkably increased as shown in Figure 1(b). This electro-
chemical result is consistent with our previous report.3c It should
be emphasized that sufficient ionic conductivity was observed
without any additional supporting electrolytes. These findings
indicate that the acid-base reaction between 1 and Si-piperidine
preferentially occurs in MeOH (eq 1), and the conjugate
acid-base pair seems to play the role of supporting electrolytes.
Next, we investigated Kolbe electrolysis of 19 as a model
reaction using solid-supported bases. It is well-known that
the uses of a platinum anode and high current density
conditions are favored for Kolbe electrolysis, because they
lead to a high concentration of radicals at the platinum anode
surface to afford homocoupling products preferentially.7 With
these facts in mind, Kolbe electrolysis of 1 was examined
under various conditions to optimize the best reaction
conditions as shown in Table 1. The overall experimental
We have developed a novel electrolytic system for Kolbe
carbon-carbon coupling electrosynthesis based on the
acid-base reaction between carboxylic acids as a substrate
and solid-supported bases. On the basis of the electrolytic
system, Kolbe electrolysis of various carboxylic acids was
successfully carried out to provide the corresponding ho-
mocoupling products in moderate to excellent yields.
Organic electrosynthesis has recently attracted much attention
as one of the most environmentally friendly methods in organic
synthesis, because it is based on the mass-free electron transfer
between electrodes and substrates.1 It can avoid not only the
use of conventional redox reagents but also their separation and
waste. However, it requires large amounts of supporting
electrolytes to provide sufficient ionic conductivity to the
solvents for electrolysis.2 In order to remove the need for
supporting electrolytes, we have recently developed a novel
electrolytic system for organic electrosynthesis using solid-
supported bases.3 The system is based on the acid-base
reactions between protic solvents or carboxylic acid substrates
and solid-supported bases, and the conjugate acid-base pairs
act as supporting electrolytes (eq 1). With the use of solid-
supported bases, it is possible to do electrosynthesis without
any additional supporting electrolytes.
(4) Kolbe, H. Ann. Chem. Pharm. 1849, 69, 257–294.
(5) (a) Weedon, B. C. L. In AdVances in Organic Chemistry Methods and
Results; Raphael, R. A., Taylor, E. C., Wynberg, H., Eds.;Interscience Publishers:
New York, 1960; Vol. 1, pp 1-34. (b) Rabjohn, N.; Flasch, G. W. J. Org. Chem.
1981, 46, 4082–4083.
(6) (a) Linstead, R. P.; Lunt, J. C.; Weedon, B. C. L. J. Chem. Soc. 1950,
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117–118.
(7) (a) Vijh, A. K.; Conway, B. E. Chem. ReV. 1967, 67, 623–664. (b) Torii,
S.; Tanaka, H. In Organic Electrochemistry, 4th ed.; Lund, H., Hammerich, O.
Eds.; Marcel Dekker: New York, 2001; pp 499-543. (c) Matsumura, Y. In
Organic Electrochemistry; Scha¨fer,H. J., Ed; Wiley-VCH Weinheim, 2004; Vol.
8, pp 171-197.
(8) (a) Vassiliev, Y. B.; Grinberg, V. A. J. Electroanal. Chem. 1990, 283,
359–378. (b) Vassiliev, Y. B.; Grinberg, V. A. J. Electroanal. Chem. 1991, 308,
1–16. (c) Vassiliev, Y. B.; Grinberg, V. A. J. Electroanal. Chem. 1992, 336,
281–307.
† Department of Electronic Chemistry.
‡ Global Edge Institute.
(1) (a) Organic Electrochemistry, 4th ed.; Lund, H., Hammerich, O., Eds.;
Marcel Dekker: New York, 2001. (b) Organic Electrochemistry; Scha¨fer, H. J.,
Ed.; Wiley-VCH: Weinheim, 2004; Vol. 8 .
(2) Jo¨rissen, J. In Organic Electrochemistry; Scha¨fer, H. J., Ed.; Wiley-VCH:
Weinheim, 2004; Vol. 8, pp 48-49.
(3) (a) Tajima, T.; Fuchigami, T. J. Am. Chem. Soc. 2005, 127, 2848–2849.
(b) Tajima, T.; Fuchigami, T. Angew. Chem., Int. Ed. 2005, 44, 4760–4763. (c)
Tajima, T; Kurihara, H.; Fuchigami, T. J. Am. Chem. Soc. 2007, 129, 6680–
6681.
(9) Kubota, T.; Ishii, T.; Minamikawa, H.; Yamaguchi, S.; Tanaka, T. Chem.
Lett. 1988, 1987–1990.
6888 J. Org. Chem. 2008, 73, 6888–6890
10.1021/jo801016f CCC: $40.75 2008 American Chemical Society
Published on Web 07/25/2008

TABLE 1. Kolbe Electrolysis of 1 Using Solid-Supported Bases
SCHEME 1. Reaction Mechanism of Kolbe Electrolysis
procedure is illustrated in Figure 2. The reactions were run
in an undivided cell and the cathodic reaction involved the
reduction of H+. The use of polystyrene-supported piperidine
(PS-piperidine) and Si-piperidine gave the almost same yields
of the corresponding homocoupling product 2 (entries 1 and
2). However, the cell voltage in entry 1 was extremely high
(more than 100 V) because PS-piperidine did not swell in
MeOH. This means that the piperidine group, which is inside
the polystyrene particle, does not interact with 1 and hence
inhibits the acid-base reaction (eq 1), thereby affording a
low concentration of the conjugate acid-base pair. Therefore,
it results in greater cell resistance and the need for the higher
cell voltage. In contrast, Si-piperidine has high solvent
compatibility,10 because the piperidine group is covalently
immobilized on the porous silica gel surface. Therefore,
Kolbe electrolysis of 1 using Si-piperidine was smoothly
conducted with a lower cell voltage (60-70 V) in entry 2.
Next, MeCN was used as a cosolvent in order to suppress
the oxidation of MeOH (entry 3). As expected, the current
efficiency of 2 in entry 3 was remarkably increased about
twice compared to that in entry 2. As shown in entries 3-7,
Kolbe electrolysis of 1 was carried out using several silica
gel supported bases. When silica gel supported pyridine was
used, the cell voltage was too high to conduct the constant
current electrolysis (entry 4). Although 2 was obtained in
high to excellent yields by using silica gel supported
imidazole and morpholine in entries 5 and 6, the cell voltages
were higher than that in entry 3. These results (entries 4-6)
indicate that the concentrations of the conjugate acid-base
pairs in eq 1 are insufficient for the constant current
electrolysis owing to the low basicities of pyridine, imidazole,
and morpholine. When silica gel supported 1,5,7-tria-
zabicyclo[4.4.0]dec-5-ene (Si-TBD) was used, a large amount
of 1 was recovered (entry 7). In this case, the methoxide ion
(MeO-) derived from the acid-base reaction between MeOH
as a solvent and Si-TBD seems to be mainly oxidized at the
anode, because Si-TBD is a strong base. From entries 3-7,
we selected Si-piperidine as the most suitable solid-supported
base for Kolbe electrolysis. To compare it with a conventional
method,7 we next used NaOMe (1 equiv to 1) as a supporting
electrolyte (entry 8). However, 60% of 1 was recovered. In
this case, MeO- should be mainly oxidized at the anode.
MeOH/MeCN
entry
solid
PSb
SiO2
SiO2
SiO2
SiO2
SiO2
SiO2
base (0.1 M)
piperidine (11.2)c
piperidine
(v/v%)
yielda (%)
50 [25]d
47 [24]
85 [43]
1
2
3
4
5
6
7
8
9h
100/0
e
100/0
50/50
50/50
50/50
50/50
50/50
100/0
50/50
piperidine
pyridine (5.2)
imidazole (7.2)
morpholine (9.0)
TBD (14.5)
NaOMe
96 [48]
83 [42]
44f [22]
34g [17]
93i
SiO2
piperidine
a
19F NMR yield based on the CF3 group using monofluorobenzene as
an internal standard. b Polystyrene. c pKa value of the conjugate acid in
parantheses. d Current efficiency in brackets. e Silica gel. f A large
amount of 1 was recovered. g 60% of 1 was recovered. h 3 faraday
mol-1 was passed. i Isolated yield.
FIGURE 2. Experimental procedure.
According to the comparison, it is clear that the use of Si-
piperidine (entry 3) is superior to the conventional method
in Kolbe electrolysis of 1. Finally, Kolbe electrolysis of 1
using Si-piperidine was carried out until the complete
consumption of 1 (3 faraday mol-1) to provide 2 in excellent
yield (entry 9). It is notable that Si-piperidine was simply
separated by only filtration after the electrolysis and the pure
product 2 was readily isolated by concentration of the filtrate
(Figure 2).
We next examined the reusability of Si-piperidine in Kolbe
electrolysis of 1. Kolbe electrolysis of 1 was carried out 10 times
under the conditions of entry 3 (6 faraday mol-1) in Table 1 by
the reuse of Si-piperidine as shown in Figure 2. As shown in
Figure 3, the yield of 2 was always more than 90% and did not
decrease at all. This clearly suggests that Si-piperidine is
electrochemically stable to even high current consumption and
thus reusable for many times.
To demonstrate the scope of the reactions, we carried out
Kolbe electrolysis of various carboxylic acids using Si-piperidine
as shown in Table 2. The higher alkanes 4 and 6 were
synthesized from open-chain carboxylic acids 3 and 5 in
excellent yields, respectively (entries 1 and 2). In the same
manner, 1,4- and 1,8-diesters 8 and 10 were obtained in high
to excellent yields (entries 3 and 4). Furthermore, Kolbe
FIGURE 1. Cyclic voltammograms of (a) 0.1 M Si-piperidine/MeOH
and (b) 1 (0.1 M) in 0.1 M Si-piperidine/MeOH, recorded at a Pt disk
(10) Nicewonger, R.; Ditto, L.; Varady, L. Tetrahedron Lett. 2000, 41, 2323–
2326.
electrode (φ ) 0.8 mm). The scan rate was 100 mV s-1
.
J. Org. Chem. Vol. 73, No. 17, 2008 6889

the filtrates. On the other hand, Kolbe electrolysis of phenyl
acetic acid (13) and its derivative 15 gave the corresponding
homocoupling products 14 and 16 in only moderate yields,
respectively (entries 6 and 7). In these cases, the benzylic
methoxylated products (non-Kolbe products) were also formed,
because the two-electron oxidation of 13 and 15 with decar-
boxylation generates their corresponding stable benzyl cations,
which react with MeOH as a solvent. This reaction selectivity
is similar to that of the conventional method.7 These results
indicate that the electrolytic system based on the acid-base
reaction between carboxylic acids as a substrate and solid-
supported bases is available for the wide range of Kolbe
carbon-carbon coupling electrosynthesis, especially the syn-
thesis of higher alkanes and 1,n-diesters.
In summary, we have developed a novel electrolytic system
for Kolbe carbon-carbon coupling electrosynthesis based on
the acid-base reaction between carboxylic acids as a substrate
and solid-supported bases. On the basis of the electrolytic
system, Kolbe electrolysis of various carboxylic acids was
successfully carried out to provide the corresponding homo-
coupling products in moderate to excellent yields. This system
has some practical advantages: (a) no need for any additional
supporting electrolytes, (b) simple separation of solid-supported
bases by only filtration, and (c) reusability of solid-supported
bases. It is expected that this system will make a significant
contribution to green chemistry and open a new aspect of
organic electrosynthesis.
FIGURE 3. Yield of 2 in the reuse of Si-piperidine.
TABLE 2. Kolbe Electrolysis of Various Carboxylic Acids Using
Si-Piperidine
Experimental Section
General Procedure for Kolbe Electrolysis of 4,4,4-Trifluoro-
3,3-dimethoxybutyric Acid (1). Kolbe electrolysis of 1 (202 mg,
1 mmol) was carried out with platinum plate electrodes (2 × 2
cm2; distance between electrodes, 1 mm) in 0.1 M Si-piperidine/
MeOH/MeCN (10 mL; MeOH/MeCN ) 50/50 v/v%) using an
undivided cell. Constant current electrolysis (75 mA cm-2) was
conducted with magnetic stirring in an ice bath. The conversion of
1 was monitored by TLC. After the electricity was passed until the
complete consumption of 1, the electrolytic solution was passed
through a glass filter (pore size, 40-60 µm) to remove Si-piperidine.
The filtrate was concentrated to provide the corresponding homo-
coupling product 2. The yield of 2 was calculated by means of 19
F
NMR by using a known amount of monofluorobenzene (96 mg, 1
mmol) as an internal standard. The product 2 was identified by
comparison with the literature values9 using 1H and 19F NMR and
mass spectroscopy.
1,1,1,6,6,6-Hexafluoro-2,2,4,4-tetramethoxyhexane (2). 1H NMR
(270 MHz, CDCl3) δ 1.96 (s, 4H), 3.36 (s, 12H); 19F NMR (254
MHz, CDCl3) δ 1.06 (s); MS (EI, m/z) 314 (M+), 283 (M+-OMe),
251, 231, 213.
Acknowledgment. This work was financially supported by
Grant-in-Aids for Young Scientists (B) (No. 17750144) and
Young Scientists (A) (No. 19685014) from The Ministry of
Education, Culture, Sports, Science and Technology, Japan. Prof.
M. Atobe is acknowledged for fruitful discussions.
a Isolated yield. b The benzylic methoxylated product (non-Kolbe
product) was also formed.
electrolysis of a ꢀ-branched carboxylic acid 11 also proceeded
smoothly to provide the corresponding homocoupling product
12 in excellent yield (entry 5). In entries 1-5, Si-piperidine
was simply separated by filtration after the electrolysis and the
desired pure products were readily isolated by concentration of
Supporting Information Available: Electrochemical cell and
experimental procedures. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO801016F
6890 J. Org. Chem. Vol. 73, No. 17, 2008