Electroreductive hydrogenation of activated olefins using the concept of site isolation

Article abstract of DOI:10.1016/j.elecom.2016.10.015

Electroreductive hydrogenation of activated olefins was investigated using the concept of site isolation. It was shown by electrochemical measurements as well as preparative electrolyses that the use of silica gel-supported sulfonic acid (Si-SO₃H) promotes the protonation step in electroreductive hydrogenation of activated olefins without electroreductive destruction at the cathode. On the basis of the concept of site isolation, electroreductive hydrogenation of several activated olefins was successfully carried out to provide the corresponding hydrogenation products in high yields.

Full text of DOI:10.1016/j.elecom.2016.10.015

Electroreductive hydrogenation of activated olefins using the concept of site
isolation
Shinsuke Tomida, Ryohei Tsuda, Shiho Furukawa, Marie Saito, Toshiki
Tajima
PII:
DOI:
Reference:
S1388-2481(16)30261-2
doi:10.1016/j.elecom.2016.10.015
ELECOM 5811
To appear in:
Electrochemistry Communications
Received date:
Revised date:
Accepted date:
17 October 2016
27 October 2016
27 October 2016
Please cite this article as: Shinsuke Tomida, Ryohei Tsuda, Shiho Furukawa, Marie Saito,
Toshiki Tajima, Electroreductive hydrogenation of activated olefins using the concept of
site isolation, Electrochemistry Communications (2016), doi:10.1016/j.elecom.2016.10.015
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ACCEPTED MANUSCRIPT
Electroreductive hydrogenation of activated olefins using the
concept of site isolation
*
Shinsuke Tomida, Ryohei Tsuda, Shiho Furukawa, Marie Saito, Toshiki Tajima
Department of Applied Chemistry, Shibaura Institute of Technology, 3-7-5
Toyosu, Koto-ku, Tokyo 135-8548, Japan
E-mail: t-tajima@sic.shibaura-it.ac.jp
Corresponding Author: Toshiki Tajima
Department of Applied Chemistry, Shibaura Institute of Technology
3
-7-5 Toyosu, Koto-ku, Tokyo 135-8548, Japan
Tel.: +81-3-5859-8155, Fax: +81-3-5859-8101, E-mail: t-tajima@sic.shibaura-it.ac.jp

ACCEPTED MANUSCRIPT
ABSTRACT
Electroreductive hydrogenation of activated olefins was investigated using the
concept of site isolation. It was shown by electrochemical measurements as well as
preparative electrolyses that the use of silica gel-supported sulfonic acid (Si-SO H)
3
promotes the protonation step in electroreductive hydrogenation of activated olefins
without electroreductive destruction at the cathode. On the basis of the concept of site
isolation, electroreductive hydrogenation of several activated olefins was successfully
carried out to provide the corresponding hydrogenation products in high yields.
Keywords:
Site isolation; electroreductive hydrogenation; activated olefin; solid-supported acid;
cation exchange

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1
. Introduction
In principle, opposing reagents such as an acid and a base cannot be put in a
single reactor without their mutual destruction. On the other hand, immobilization
of the opposing reagents onto respective solid materials suppresses their mutual
destruction to allow the simultaneous use in a single reactor [1–2]. This is
well-known as the concept of site isolation, which is based on the spatial isolation
of opposing active sites. On the basis of the concept of site isolation, one-pot
multistep reactions have been demonstrated using a variety of solid-supported
catalysts [3–8]. However, its application to electrochemistry has been limited to
electrochemical measurements of site-isolated electroactive sites [9–10].
Electrodes in electrochemical reactions are inherently site-isolated
heterogeneous redox reagents. Therefore, an anode and a cathode can be put in a
single reactor without their mutual destruction. On the other hand, we found that
solid-supported bases are not oxidized at anodes [11–12]. It can be regarded as
site isolation in electrochemical reactions. Solid-supported reagents, which
cannot diffuse into electric double layer, are not subject to electrochemical
destruction at electrodes.

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On the basis of the concept of site isolation in electrochemical reactions, we
demonstrated promotion of the deprotonation step in anodic methoxylation of
sulfides using solid-supported bases [13]. In the reaction, solid-supported bases
acted as electrochemically inactive bases at the anode. On the other hand,
solid-supported acids could also play a role of electrochemically inactive acids at
cathodes. This prompted us to apply solid-supported acids to electrochemical
reactions for promoting the protonation step without electroreductive destruction
at cathodes. We herein demonstrate electroreductive hydrogenation of activated
olefins [14] using the concept of site isolation.
2
. Materials and methods
2
.1. Materials
Silica gel-supported sulfonic acid (Si-SO H, size: 40–63 m, loading: 0.68 mmol
3
-1
g ) was purchased from SiliCycle. All other reagents were purchased from commercial
suppliers and used without further purification.

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2
.2. Electrochemical measurements
Electrochemical measurements were carried out with a three-electrode system using
a glassy carbon (GC) disk working electrode (= 1 mm), a Pt wire counter electrode,
+
and an Ag|Ag electrode as a reference electrode.
2
.3. General procedure for electroreductive hydrogenation of an activated olefin using
Si-SO H
3
Electroreductive hydrogenation of an activated olefin (1 mmol) was carried out with
2
2
a Pt plate anode (2 × 2 cm ) and a GC plate cathode (2 × 2 cm ) in 0.1 M
Bu NBF /MeCN (10 ml) in the presence of Si-SO H (1 mmol based on the SO H
4
4
3
3
-2
group) using an undivided cell. Constant current electrolysis (10 mA cm ) was
conducted with magnetic stirring at room temperature. After the electrolysis, the
electrolytic solution was passed through a glass filter (pore size: 5–10m) to remove
Si-SO H. The filtrate was concentrated under reduced pressure and the residue was
3
passed through a short column of silica gel eluting with CHCl . The eluent was
3
concentrated under reduced pressure and the hydrogenation product in the residue was
1
identified by comparison with an authentic sample using H NMR and mass

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1
spectroscopy. The yield of the product was calculated by means of H NMR using a
known amount of toluene or nitromethane (1 mmol) as an internal standard.
3
. Results and discussion
3
.1. Linear sweep voltammetry of MeSO H and Si-SO H
3
3
In order to verify site isolation between a solid-supported acid and a cathode,
we measured the linear sweep voltammograms of methanesulfonic acid
MeSO H) and Si-SO H, respectively. A GC disk electrode was employed for the
(
3
3
+
measurements. As shown in Fig. 1(a), the reduction current for H was clearly
observed in the presence of MeSO H (the onset potential was ca. -0.9 V vs.
3
+
Ag|Ag ). In contrast, no reduction current was observed in the presence of
Si-SO H as shown in Fig. 1(b). These results indicate that site isolation between
3
Si-SO H and the cathode is achieved.
3
<
Fig. 1 >

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3.2. Cyclic voltammetry of dimethyl maleate in the absence and presence of
Si-SO H
3
It has been reported that electroreduction of activated olefins in aprotic
organic solvents leads to the corresponding hydrogenation, coupling, and
polymeric products depending on the reaction conditions as shown in Scheme 1
[
15]. The hydrogenation product is preferentially formed under acidic conditions
via 2-electron-2-proton reduction (Scheme 1, path A), while the coupling and/or
polymeric products are predominantly formed under neutral and basic conditions
via 1-electron reduction or less (Scheme 1, paths B and C). With these facts in
mind, we measured the cyclic voltammograms of dimethyl maleate (1) in the
absence and presence of Si-SO H. As shown in Fig. 2(a), the reduction wave for
3
+
1
was observed at ca. -2.05 V vs. Ag|Ag in the absence of Si-SO H. On the other
3
hand, the reduction wave became larger in the presence of Si-SO H as shown in
3
Fig. 2(b). In addition, the reduction current was slightly observed from ca. -1.25
+
V vs. Ag|Ag in the presence of Si-SO H, which seems to correspond to the
3
reduction of HBF derived from the cation exchange reaction between Si-SO H
4
3
and Bu NBF as a supporting electrolyte (Eq. (1)). These results suggest that the
4
4

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use of Si-SO H promotes the protonation of the radical anion intermediate of
1
3
without electroreductive destruction.
<
Scheme 1 >
<
Fig. 2 >
(
1)
3.3. Electroreductive hydrogenation of dimethyl maleate in the absence and
presence of acids
We investigated the electroreductive hydrogenation of
1 in the absence and
presence of acids as shown in Table 1. In the absence of acids, the corresponding
hydrogenation product
only a small amount of
2
was generated in low yield (entry 1). On the other hand,
was formed and a certain amount of was recovered in
2
1
the presence of MeSO H (entry 2). In this case, MeSO H seems to be mainly
3
3
reduced at the cathode. In contrast, the yield of
2
increased up to 81% with
increasing the amount of Si-SO H (entries 3-5). These results indicate that
3

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Si-SO H promotes the protonation step without electroreductive destruction at the
3
cathode. However, the yield decreased using a larger amount of Si-SO H (entry
3
6). In this case, electroreduction of
1 might compete with that of HBF derived
4
from the cation exchange reaction between Si-SO H and Bu NBF (Eq. (1)). We
3
4
4
next focused on the cathode materials. Pb and Pt, which respectively have high
and low hydrogen overvoltages, were selected as cathodes. In spite of their
hydrogen overvoltages, the use of Si-SO H was effective for electroreductive
3
hydrogenation of
1 (entries 7-10). In particular, it is notable that the use of
Si-SO H gave in good yield even when a Pt cathode was used (entry 10). From
2
3
these results, it is clear that Si-SO H acts as an electrochemically inactive acid
3
regardless of the cathode materials.
<
Table 1 >
3
.4. Influence of the cation exchange ability and selectivity of Si-SO H on
3
electroreductive hydrogenation of dimethyl maleate
It is well-known that solid-supported acids have cation exchange ability and
selectivity [16]. We then focused on the influence of the cation exchange ability

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and selectivity of Si-SO H on electroreductive hydrogenation of
1
. As shown in
3
Table 2, the yield of
2 increased with increasing the concentration of Bu NBF4
4
(
entries 1-3). On the other hand, the yield decreased with decreasing the cation
size of supporting electrolytes (entries 3-6). In these cases, cation exchange
reaction between Si-SO H and supporting electrolytes (R NBF ) should occur to
3
4
4
generate HBF as an electrochemically active acid (Eq. (2)). Therefore, HBF4
4
might be reduced at the cathode. In order to verify the hypothesis, the equilibrium
concentration of HBF in each electrolytic solution was determined by an
4
acid-base titration before the electrolyses. As shown in Table 2, the equilibrium
concentration seems to depend not only on the concentration of supporting
electrolytes but also on the cation size. Furthermore, the equilibrium
concentration of HBF is closely related to both the yield of
2
and the recovery of
4
1
. This relationship suggests that HBF acts as both a promotor of the
4
deprotonation step and a competitor of the electroreduction of
1. In other words,
HBF seems to play a role of an electrochemically active acid in electroreductive
4
hydrogenation of 1.

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(
2)
<
Table 2 >
3.5. Electroreductive hydrogenation of activated olefins in the absence and
presence of acids
We next carried out the electroreductive hydrogenation of several activated
olefins in the absence and presence of acids as shown in Table 3. In all cases, the
corresponding hydrogenation products were generated in moderate yields in the
absence of acids (entries 1, 4, 7, and 10). On the other hand, the desired products
were obtained in high yields in the presence of Si-SO H (entries 3, 6, 9, and 12),
3
while only small amounts of them were formed and certain amounts of substrates
were recovered in the presence of MeSO H (entries 2, 5, 8, and 11). From these
3
results, it is clear that the use of Si-SO H is effective for the promotion of the
3
deprotonation step in electroreductive hydrogenation of activated olefins.
<
Table 3 >

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4
. Conclusions
In conclusion, we have successfully demonstrated the effective electroreductive
hydrogenation of activated olefins using the concept of site isolation. It was found that
the use of Si-SO H promotes the protonation step in electroreductive hydrogenation of
3
activated olefins and thus minimizes and even eliminates the competing coupling of the
radical anion intermediate and its polymerization. It is expected that the concept of site
isolation can be applied to a variety of electrochemical reactions as well as one-pot
multistep reactions including electrochemical reactions. The mechanistic aspects and
further applications are now under investigation.
Acknowledgements
This work was supported by a Grant-in-Aid for Young Scientists (A) (No.
2
3685036) from The Ministry of Education, Culture, Sports, Science and Technology,
Japan.

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References
[
1] B.J. Cohen, M.A. Kraus, A. Patchornik, Organic synthesis involving multipolymer
reactions. Polymeric trityllithium, J. Am. Chem. Soc. 99 (1977) 4165–4167.
[
2] B.J. Cohen, M.A. Kraus, A. Patchornik, "Wolf and Lamb" reactions equilibrium and
kinetic effects in multipolymer systems, J. Am. Chem. Soc. 103 (1981) 7620–7629.
[
3] F. Gelman, J. Blum, D. Avnir, One-pot sequences of reactions with sol-gel
entrapped opposing reagents:ꢀ An enzyme and metal-complex catalysts, J. Am. Chem.
Soc. 124 (2002) 14460–14463.
[
4] K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, An acidic
layered clay is combined with a basic layered clay for one-pot sequential reactions, J.
Am. Chem. Soc. 127 (2005) 9674–9675.
[
5] V. Rodionov, H. Gao, S. Scroggins, D.A. Unruh, A.-J. Avestro, J.M.J. Fréchet, Easy
access to a family of polymer catalysts from modular star polymers, J. Am. Chem. Soc.
32 (2010) 2570–2572.
1

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[
6] Y. Yang, X. Liu, X. Li, J. Zhao, S. Bai, J. Liu, Q. Yang, A yolk–shell nanoreactor
with a basic core and an acidic shell for cascade reactions, Angew. Chem. Int. Ed. 51
(2012) 9164 –9168.
[
7] H. Yang, L. Fu, L. Wei, J. Liang, B.P. Binks, Compartmentalization of incompatible
reagents within pickering emulsion droplets for one-pot cascade reactions, J. Am.
Chem. Soc. 137 (2015) 1362–1371.
[
8] L.-C. Lee, J. Lu, M. Weck, C.W. Jones, Acid–base bifunctional shell cross-linked
micelle nanoreactor for one-pot tandem reaction, ACS Catal. 6 (2016) 784–787.
[
9] K.W. Pollak, J.W. Leon, J.M.J. Fréchet, M. Maskus, H.D. Abruña, Effects of
dendrimer generation on site isolation of core moieties:ꢀ Electrochemical and
fluorescence quenching studies with metalloporphyrin core dendrimers, Chem. Mater.
1
0 (1998) 30–38.
[
10] T.H. Galow, F. Ilhan, G. Cooke, V.M. Rotello, Recognition and encapsulation of
an electroactive guest within a dynamically folded polymer, J. Am. Chem. Soc. 122
2000) 3595–3598.
(

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[
11] T. Tajima, T. Fuchigami, Development of an electrolytic system using
solid-supported bases for in situ generation of a supporting electrolyte from methanol as
a solvent, J. Am. Chem. Soc. 127 (2005) 2848–2849.
[
12] T. Tajima, T. Fuchigami, An electrolytic system that uses solid-supported bases for
in situ generation of a supporting electrolyte from acetic acid solvent, Angew. Chem.
Int. Ed. 44 (2005) 4760–4763.
[
13] T. Tajima, H. Kurihara, Deprotonation in anodic methoxylation of fluoroethyl
phenyl sulfides using site-isolated heterogeneous bases, Chem. Commun. (2008)
167–5169.
14] Y. Miura, H. Tateno, T. Tajima, An electrolytic system based on the acid-base
reaction between solid-supported acids and water, Electrochemistry 81 (2013) 371–373.
15] M.F. Nielsen, J.H.P. Utley, Reductive coupling, in: H. Lund, O. Hammerich (Eds.),
Organic Electrochemistry, Marcel Dekker, New York, 2001, pp. 795–882.
5
[
[
[
16] E. M. Thurman, M. S. Mills, Solid-Phase Extraction, Wiley-Interscience, New
York, 1998.

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0
0.2
0.4
0.6
0.8
-
-
-
-
(a)
-1
(b)
-
1.2
1.4
background
0 0.5
-
-
3
-2.5
-2
-1.5
-1
-0.5
Potential / V vs. Ag|Ag+
Fig. 1. Linear sweep voltammograms of (a) MeSO H (1 mmol) and (b) Si-SO H (1
3
3
mmol based on the SO H group) in 0.1 M Bu NBF /MeCN under mechanical stirring,
3
4
4
-1
recorded at a GC disk electrode ( = 1 mm). The sweep rate was 10 mV s .

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0.05
0
-
-
-
-
0.05
-
0.1
0.15
0.2
0.25
0.3
0.35
-
(
a)
(b)
background
-
-3
-2.5
-2
-1.5
-1
-0.5
0 0.5
Potential / V vs. Ag|Ag+
Fig. 2. Cyclic voltammograms of 1 (1 mmol) in the (a) absence and (b) presence of
Si-SO H (1 mmol based on the SO H group) in 0.1 M Bu NBF /MeCN, recorded at a
3
3
4
4
-1
GC disk electrode ( = 1 mm). The sweep rate was 100 mV s .

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Scheme 1. Reaction mechanism of electroreduction of activated olefins.

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Table 1. Electroreductive hydrogenation of 1 in the absence and presence of acids
a 1
H NMR yield.
b
Recovery of 1 in parentheses.

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Table 2. Electroreductive hydrogenation of 1 using various supporting electrolytes
a
Determined by an acid-base titration with 0.05 M Bu NOH/MeOH using thymol blue
4
as a pH indicator after Si-SO H was filtrated.
3
b 1
H NMR yield.
c
Electrolysis was conducted in a water bath.
d
Recovery of 1 in parentheses.
e
Dimethyl fumarate was also recovered.

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Table 3. Electroreductive hydrogenation of activated olefins in the absence and presence
of acids
a 1
H NMR yield.
b
Recovery of 1 in parentheses.

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Graphical abstract

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Highlights
•
•
•
The concept of site isolation in electrochemical reactions
Site isolation between a solid-supported acid and a cathode
A solid-supported acid promotes electroreductive hydrogenation of activated olefins