EC-backward-E electrochemistry supported by an alkoxyphenyl group

Article abstract of DOI:10.1016/j.tetlet.2009.07.049

EC-backward-E electrochemistry through electrocatalytic formal [2+2] cycloaddition reaction between anodically activated aliphatic enol ethers and unactivated olefins possessing an alkoxyphenyl group was clearly described by using cyclic voltammetric stud

Full text of DOI:10.1016/j.tetlet.2009.07.049

Tetrahedron Letters 50 (2009) 5413–5416
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Tetrahedron Letters
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EC-backward-E electrochemistry supported by an alkoxyphenyl group
Yohei Okada a, Ryoichi Akaba b, Kazuhiro Chiba a,
*
a Laboratory of Bio-organic Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509 Tokyo, Japan
b Department of Chemistry, Gunma College of Technology, 580 Toba-machi, Maebashi, 371-8530 Gunma, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
EC-backward-E electrochemistry through electrocatalytic formal [2+2] cycloaddition reaction between
anodically activated aliphatic enol ethers and unactivated olefins possessing an alkoxyphenyl group
was clearly described by using cyclic voltammetric studies and spin density observation with B3LYP/6-
31G(d) calculations. The alkoxyphenyl group was found to regulate the electron transfer, which operates
as an electron donor during the formation of the cyclobutane ring and as an electron acceptor from the
anode to give the final product (EC-backward-E).
Received 23 June 2009
Accepted 10 July 2009
Available online 14 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Electrochemical reactions have proven to be an effective way of
generating radical anions or cations and causing both inter- and
intramolecular cyclization reactions.1 Anodic oxidation of elec-
tron-rich olefins provides radical cations, which can be used in car-
bon–carbon bond formation reactions to build up varied carbon
frameworks. For electrocatalytic reactions in particular, targeted
organic reactions proceed with very low energy consumption.2 In
addition, the progress of these chemical reactions can be externally
regulated simply by controlling the application of potential. These
electrochemical reactions offer new and efficient pathways for the
production of organic compounds. Furthermore, electrochemical
reactions provide a platform in which mechanistic studies would
be carried out on reaction intermediates, including ions, radicals,
and radical ions, which support to optimize reaction conditions.3
We previously reported electrocatalytic formal [2+2] cycloaddi-
tion reactions between anodically activated enol ethers possessing
an alkoxyphenyl group and unactivated aliphatic olefins.4 For
example, anodic oxidation of 1-methoxy-4-(4-methoxybut-3-
enyl)benzene in the presence of unactivated aliphatic olefins in
lithium perchlorate/nitromethane electrolyte solution gave the
corresponding [2+2] cycloadducts in moderate to high yield
(Scheme 1). However, anodic oxidation of enol ethers without an
alkoxyphenyl group did not give the corresponding [2+2] cycload-
duct, with anodically induced olefin metathesis taking place in-
stead (Scheme 2).5 These results indicated that the alkoxyphenyl
group played an important role in the formation of the cyclobutane
ring. On the basis of these hypotheses, we also reported electrocat-
alytic formal [2+2] cycloaddition reactions between anodically
activated aliphatic enol ethers and unactivated olefins possessing
an alkoxyphenyl group.6 For example, anodic oxidation of 1-eth-
oxyprop-1-ene 1 in the presence of 4-allylanisole 2 in lithium per-
chlorate/nitromethane electrolyte solution gave the corresponding
[2+2] cycloadduct 3a–c in high yield (Scheme 3).
MeO
OMe
MeO
(+)CF-CF(-)
OMe
1.2 V(vs. Ag/AgCl)
+
1.0 M LiClO4/CH3NO2
R
61-88%
R
Scheme 1. Electrocatalytic formal [2+2] cycloaddition reactions between anodi-
cally activated enol ethers possessing an alkoxyphenyl group and unactivated
aliphatic olefins.
OMe
(+)CF-CF(-)
1.2 V(vs. Ag/AgCl)
+
1.0 M LiClO4/CH3NO2
50-78%
R
Scheme 2. Anodically induced olefin metathesis.
MeO
MeO
(+)CF-CF(-)
1.2 V(vs. Ag/AgCl)
1
+
O
0.3 F/mol
3a-c
1.0 M LiClO4/CH3NO2
81%
dr 2:1:1
O
2
Scheme 3. Electrocatalytic formal [2+2] cycloaddition reaction between anodically
activated aliphatic enol ethers and unactivated olefins possessing an alkoxyphenyl
group.
* Corresponding author. Tel.: +81 42 367 5667; fax: +81 42 360 7167.
E-mail address: chiba@cc.tuat.ac.jp (K. Chiba).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.049

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Y. Okada et al. / Tetrahedron Letters 50 (2009) 5413–5416
A radical cation generated from the enol ether is trapped by the
olefin to give the corresponding cyclobutyl radical cation interme-
diate, followed by intramolecular electron transfer from the alk-
oxyphenyl group. As the oxidation potential of the alkoxyphenyl
group is higher than that of the enol ether, intermolecular electron
transfer occurs between the starting enol ether and the alkoxyphe-
nyl radical cation, which completes the formation of [2+2] cycload-
duct with a catalytic amount of electric input.
In these sequential reactions, anodic backward discharge is also
possible, which reduces alkoxyphenyl radical cation at the anode
to complete the overall electrocatalytic pathway of the electro-
chemical reactions (Fig. 1). The electron transfer from the anode
is a key process in the EC-backward-E electrochemistry, which
consists of the initial electron transfer from 1 to anode, oxidation
of 1, its reaction with 2, and then the electron transfer from anode
to alkoxyphenyl radical cation, reduction of alkoxyphenyl radical
cation, to give 3a–c (vide infra).
Herein we wish to report that the EC-backward-E electrochem-
istry is actually observed, which supports the observed electrocat-
alytic results. We also provide pieces of evidence from molecular
orbital calculations that uncovers the role of the alkoxyphenyl
group that regulates the electron transfers required for the forma-
tion of cyclobutane ring.
Figure 2. The cyclic voltammograms of 1-ethoxyprop-1-ene (8 mM) and of 1-
ethoxyprop-1-ene (8 mM) in the presence of 4-allyanisole (160 mM) in 0.1 M
lithium perchlorate/nitromethane.
bon working electrode, a platinum counter electrode, and an Ag/
AgCl reference electrode.
The oxidation peak of 1, at around 1.18 V versus Ag/AgCl, was
hardly visible in the presence of 2. In sharp contrast, in the pres-
ence of allylbenzene, which did not give a cycloadduct in the ano-
First, we measured the oxidation potential of the substrates. 1
showed peak oxidation potential at 1.18 V (vs Ag/AgCl), while the
oxidation potential of 2 and 3a–c was 1.57 V and 1.52 V (vs Ag/
AgCl), respectively. These potentials show that 1 is preferentially
oxidized on the anode to generate the corresponding radical cation
1+Å, even in the presence of nucleophiles. 1+Å is then trapped by 2 to
form a cyclobutyl radical cation intermediate 3a–c+Å. To complete
the formation of the cyclobutane ring, intramolecular electron
transfer must take place from the alkoxyphenyl group to the cyclo-
butyl moiety. As the oxidation potential of 3a–c is relatively high
compared to that of 1, the intermediate ring-closed radical cation
can repeatedly oxidize other starting enol ether molecules. How-
ever, if the intermolecular carbon–carbon bond formation and
the subsequent electron transfer from the alkoxyphenyl group to
the cyclobutyl moiety take place, it should also be possible that
the radical cation intermediate—which corresponds to the one-
electron oxidized species of the desired cycloadduct, with an oxi-
dation potential of 1.52 V (vs Ag/AgCl)—is directly reduced on the
anode by backward electron transfer.
dic oxidation of
1 in lithium perchlorate/nitromethane, the
oxidation peak of 1 was clearly observed, as shown in Figure 3.
These results indicate that intermolecular carbon–carbon bond for-
mation between anodically activated aliphatic enol ethers and
unactivated olefins possessing an alkoxyphenyl group was based
on EC-backward-E electrochemistry on the anode. Furthermore,
in these cyclic voltammograms for 1 and 2, an increase in the oxi-
dation current was observed at the potential where 3a–c is oxi-
dized. This oxidation peak enhancement is consistent with in-
situ generation of 3a–c via the EC-backward-E process on the an-
ode. Intermolecular electron transfer between 3a–c+Å and another
1 can also take place in a bulk solution.
We propose the following mechanism consistent with the ob-
served EC-backward-E electrochemistry (Scheme 4). 1+Å reacts with
2 to give a ring-opened radical cation A+Å which is rapidly con-
verted to a ring-closed radical cation B+Å. B+Å thus formed is rapidly
We then monitored the electrochemical process by cyclic vol-
tammetry (CV). Figure 2 shows the cyclic voltammograms of 1
(8 mM) and of 1 in the presence of 2 (160 mM) in 0.1 M lithium
perchlorate/nitromethane electrolyte solution using a glassy car-
MeO
MeO
Intramolecular
Electron Transfer
O
MeO
O
O
Electrode
Process
Electrode
Process
MeO
O
O
Figure 1. The cyclic voltammograms of 1-ethoxyprop-1-ene (8 mM) and of 1-
ethoxyprop-1-ene (8 mM) in the presence of 4-allyanisole (160 mM) in 0.1 M
lithium perchlorate/nitromethane.
Figure 3. The cyclic voltammograms of 1-ethoxyprop-1-ene (8 mM) in the
presence of allybenzene (160 mM) in 0.1 M lithium perchlorate/nitromethane.

Y. Okada et al. / Tetrahedron Letters 50 (2009) 5413–5416
5415
-e-
cate that the alkoxyphenyl group acts as an electron donor to give
the ring-closed radical cation B+Å which is then reduced at the
anode.
1
1+.
A+.
1+. + 2
A+.
It is of interest to note that the ring-closed B+Å would have a life-
time long enough to be reduced at the anode and to oxidize 1. Life-
time of cyclobutyl radical cations reported so far seems to be very
short, and could not be detected even by the nanosecond time-re-
solved laser flash photolysis studies.10
B+.
+e-
B+.
3a-c
In conclusion, we described EC-backward-E electrochemistry
through electrocatalytic formal [2+2] cycloaddition reactions be-
tween anodically activated aliphatic enol ethers and unactivated
olefins possessing an alkoxyphenyl group by cyclic voltammetric
and computational studies. The results demonstrated the role of
the alkoxyphenyl group that regulates the electron transfer, which
operates as an electron donor during the formation of the cyclobu-
tane ring and as an electron acceptor from the anode to give the fi-
nal product. The first intramolecular electron transfer from the
alkoxyphenyl group is thought to be triggered by the formation
of the cyclobutyl radical cation via intermolecular carbon–carbon
bond formation. The unique intermolecular reaction that generates
the unstable cyclobutyl radical cation intermediate is assisted by a
lithium perchlorate/nitromethane electrolyte solution, which
effectively stabilizes the cationic intermediates and promotes
intermolecular carbon–carbon bond formation. This type of elec-
trocatalytic reaction is expected to open the door to more efficient
electro-organic reactions. It is also emphasized that EC-backward-
E electrochemistry should be more frequently observed and may
conveniently be utilized as a diagnostic tool to find electrocatalytic
reactions in general. Further efforts in the development of electro-
catalytic reactions are underway in our laboratory.
B+. + 1
3a-c + 1+.
O
O
C1 C2
A+.
O
O
C1C2
B+.
Scheme 4. Summarization of the EC-backward-E reactions.
reduced at the anode to give 3a–c since the electron transfer from
the anode to a substrate radical cation can only be possible when
its neutral form has an oxidation potential that is relatively high
compared to that of anode. In this case, the oxidation potential of
3a–c is 1.52 V (vs Ag/AgCl), which can be reduced at the anode un-
der these reaction conditions (vide supra). The EC-backward-E
electrochemistry seems to be rare, but Feldberg and Jeftic de-
scribed it fully, both theoretically and experimentally.7 Our case
is the first one in which electrochemical oxidation triggers the
[2+2] cycloaddition reaction between olefins to give a cyclobutane
ring though such electrochemical behavior has been reported for
the oxygenations of olefin radical cations.8
Acknowledgment
This work was partially supported by a Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology.
References and notes
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0.84 during the ring closure of A+Å to B+Å. These results clearly indi-
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