Continuous electrochemical synthetic system using a multiphase electrolyte solution

Article abstract of DOI:10.1016/j.electacta.2010.02.085

A continuous electrochemical synthetic system has been developed using a cyclohexane-based multiphase electrolyte solution composed of lithium perchlorate and nitromethane. The upper cyclohexane phase functioned as both substrate supply and product assembly phases, whereas the electrochemical reactions took place in the lower electrolyte solution phase, achieving spatial separation of the electrolyte solution phase.

Full text of DOI:10.1016/j.electacta.2010.02.085

Electrochimica Acta 55 (2010) 4112–4119
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Electrochimica Acta
journal homepage: www.elsevier.com/locate/electacta
Continuous electrochemical synthetic system using a multiphase
electrolyte solution
Yohei Okada, Kazuhiro Chiba∗
Laboratory of Bio-organic Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A continuous electrochemical synthetic system has been developed using a cyclohexane-based multi-
phase electrolyte solution composed of lithium perchlorate and nitromethane. The upper cyclohexane
phase functioned as both substrate supply and product assembly phases, whereas the electrochemical
reactions took place in the lower electrolyte solution phase, achieving spatial separation of the electrolyte
solution phase.
Received 21 January 2010
Received in revised form 21 February 2010
Accepted 26 February 2010
Available online 4 March 2010
© 2010 Elsevier Ltd. All rights reserved.
Keywords:
Continuous electrochemical synthetic
system
Cyclohexane-based multiphase electrolyte
solution
Anodic oxidation
[2+2] Cycloaddition reactions
Liquid–liquid extraction
1. Introduction
ductivity of the reaction, decreasing the “green” possibilities of
electrochemical reactions. Several elegant approaches, e.g., elec-
Radical ion-based cyclizations have widely been investigated
to give several ring skeletons [1–9]. In this respect, transition
metals have extensively employed as catalysts to generate rad-
ical ions that established a large number of elegant synthetic
approaches [10–14]. In this context, electrochemical processes
have also proven to be effective for generating both nucleophilic
and electrophilic carbons, and provide a unique way to construct
several carbon skeletons [15–22]. In particular, there are many
reports on intra- and intermolecular cyclization reactions that
produce a wide variety of ring products, including natural prod-
uct frameworks possessing several biological activities [23–28]. In
these processes, electrodes function as both oxidizing and reducing
reagents and the consumption of additional reagents is avoidable,
thus, they are promising methodologies from an environmen-
tal viewpoint. However, in these reactions, the use of a large
amount of electrolyte solution composed of polar organic sol-
vent and supporting electrolytes is generally necessary, usually
requiring further separation and/or purification procedures. One
of the common procedures employed to remove these support-
ing electrolytes is liquid–liquid extraction containing water. This
procedure quenches the electrolyte solution and lowers the pro-
trolytic systems using solid-supported reagents [29–30], thin layer
flow cells [31], and ionic liquids [32–33], have been reported to
solve these problems. In this context, an electrochemical synthetic
system where the electrolyte solution phase is spatially separated
is expected to improve the “green” nature of electrochemical reac-
tions (Scheme 1).
Previously, we reported an oxidative carbon–carbon bond
formation system using a cyclohexane-based thermomorphic mul-
tiphase electrolyte solution composed of lithium perchlorate
(LPC) and nitromethane (NM) [34]. In this system, a thermo-
morphic middle phase formed between the upper cyclohexane
phase and the lower LPC/NM electrolyte solution phase, which
provided an effective reaction field for the [3+2] cycloaddition
reactions. The electrochemical reaction took place in the lower
LPC/NM electrolyte solution phase and the desired products were
assembled in the upper cyclohexane phase, enabling the sep-
aration of the desired products from the LPC/NM electrolyte
solution via simple liquid–liquid extraction with cyclohexane
(Scheme 2).
We envisioned that this system could be applied to establish a
novel electrochemical synthetic system where the electrolyte solu-
tion phase was spatially separated to improve the “green” nature
of electrochemical reactions. Here, we report a continuous electro-
chemical synthetic system using a cyclohexane-based multiphase
electrolyte solution composed of LPC and NM.
∗
Corresponding author. Tel.: +81 42 367 5667; fax: +81 42 360 7167.
E-mail address: chiba@cc.tuat.ac.jp (K. Chiba).
0013-4686/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.electacta.2010.02.085

Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
4113
2.2.1. 1-(2-Butyl-4-methylcyclobutoxy)-4-propylbenzene 3a (all
cis, minor)
1H NMR (CDCl3, 600 MHz) ı 7.04 (2H, d, J = 8.1 Hz), 6.76 (2H, d,
J = 8.1 Hz), 4.71 (1H, t, J = 7.3 Hz), 2.67 (1H, sept, J = 7.3 Hz), 2.50 (3H,
t, J = 7.3 Hz), 2.22–2.16 (1H, m) 1.70–1.63 (1H, m), 1.60 (2H, sext,
J = 7.3 Hz), 1.52–1.43 (1H, m) 1.43–1.36 (1H, m), 1.33–1.11 (4H, m),
1.05 (3H, d, J = 7.3 Hz), 0.92 (3H, t, J = 7.3 Hz), 0.86 (3H, t, J = 7.3 Hz).
13C NMR (CDCl3, 150 MHz) ı 157.5, 134.2, 129.1, 114.7, 75.7, 38.6,
37.2, 33.4, 31.6, 29.8, 29.5, 24.8, 22.7, 15.7, 14.1, 13.8 IR (NaCl, cm−1
)
2958, 2929, 1611, 1510, 1456, 1242, 1173, 825 MS (rel. int.) m/z 260
(M+, 17), 218 (30), 176 (51), 154 (100), 136 (74), 107 (47) HRMS calc.
for C18H28O 260.2140, found 260.2142.
2.2.2. 1-(2-Butyl-4-methylcyclobutoxy)-4-propylbenzene 3b (all
trans, major)
1H NMR (CDCl3, 600 MHz) ı 7.06 (2H, d, J = 8.8 Hz), 6.82 (2H,
d, J = 8.8 Hz), 3.86 (1H, t, J = 7.3 Hz), 2.51 (2H, t, J = 7.3 Hz), 2.25–2.13
(2H, m), 2.10 (1H, q, J = 9.5 Hz), 1.65–1.55 (3H, m), 1.43–1.33 (1H, m),
1.33–1.18 (4H, m) 1.16 (3H, d, J = 7.3 Hz), 0.93 (3H, t, J = 7.3 Hz), 0.86
(3H, t, J = 7.3 Hz), 0.80 (1H, q, J = 9.5 Hz). 13C NMR (CDCl3, 150 MHz)
ı 156.4, 134.9, 129.2, 115.8, 84.1, 41.1, 37.2, 36.2, 34.4, 29.5, 27.1,
24.7, 22.7, 19.7, 14.1, 13.8 IR (NaCl, cm−1) 2957, 2927, 1609, 1510,
1456, 1242, 1065, 831 MS (rel. int.) m/z 260 (M+, 30), 218 (16), 176
(20), 154 (100), 136 (85), 107 (32) HRMS calc. for C18H28O 260.2140,
found 260.2143.
Scheme 1. The electrochemical synthetic system where the electrolyte solution
phase is spatially separated.
2. Experimental
2.1. General
1H and 13C NMR spectra were recorded in CDCl3 with TMS
as the initial standard (600 MHz and 150 MHz, respectively). The
following abbreviations were used to explain multiplicities: s, sin-
glet; d, doublet; t, triplet; q, quartet; quint, quintet; sext, sextet;
sept, septet; m, multiplet. TLC analysis was carried out with the
plates containing the fluorescent indicator, detection of compounds
was achieved by UV absorption (254 nm) and by charring after
spraying with 12 molybdo (VI) phosphoric acid n-hydrate in 95%
ethanol. Column chromatography was performed with silica gel
(0.04–0.063 mm).
2.2.3. 1-(2-Butyl-4-methylcyclobutoxy)-4-propylbenzene 3c–d
(diastereomixture)
1H NMR (CDCl3, 600 MHz) ı 7.05 (2H, d, J = 8.8 Hz), 6.75 (2H, d,
J = 8.8 Hz), 4.19 (1H, t, J = 7.3 Hz), 2.76–2.65 (1H, m), 2.65–2.56 (1H,
m), 2.51 (2H, t, J = 7.3 Hz), 1.69–1.55 (4H, m), 1.53–1.45 (1H, m),
1.45–1.35 (1H, m) 1.35–1.20 (4H, m), 1.03 (3H, d, J = 7.3 Hz), 0.93
(3H, t, J = 7.3 Hz), 0.88 (3H, t, J = 7.3 Hz). 13C NMR (CDCl3, 150 MHz)
ı 156.6, 134.5, 129.2, 114.5, 78.2, 40.8, 38.3, 37.2, 36.1, 29.5, 27.5,
24.8, 22.7, 19.1, 14.1, 13.8 IR (NaCl, cm−1) 2959, 2927, 1613, 1510,
1456, 1240, 1075, 829 MS (rel. int.) m/z 260 (M+, 25), 218 (28), 176
(35), 154 (100), 136 (87), 69 (50) HRMS calc. for C18H28O 260.2140,
found 260.2142.
2.2. General procedure of anodic oxidation
Aliphatic olefins (4.0 mmol) and prop-1-enyloxybenzenes
(0.20 mmol) were added to 1.0 M LiClO4–CH3NO2 (20 mL). The
undivided reaction cell used was capped with a septum equipped
with the both carbon felt (CF) anode and cathode (20 mm × 20 mm),
and the Ag/AgCl reference electrode. The electrolysis was then per-
formed at 1.2 V (vs. Ag/AgCl). After the reaction was completed, the
desired products were extracted by cyclohexane and concentrated.
The configurations of the products were confirmed by nuclear Over-
hauser effect spectroscopy (NOE). All percentage values including
the yields and purities of the products and the partition ratios in the
multiphase electrolyte solution were determined by NMR, based on
internal standards.
1H NMR (CDCl3, 600 MHz) ı 7.05 (2H, d, J = 8.8 Hz), 6.75 (2H, d,
J = 8.8 Hz), 4.17 (1H, t, J = 7.3 Hz), 2.76–2.65 (1H, m), 2.65–2.56 (1H,
m), 2.51 (2H, t, J = 7.3 Hz), 1.82–1.69 (1H, m), 1.69–1.55 (3H, m),
1.53–1.45 (1H, m), 1.45–1.35 (1H, m) 1.35–1.20 (4H, m), 1.15 (3H,
d, J = 7.3 Hz), 0.93 (3H, t, J = 7.3 Hz), 0.84 (3H, t, J = 7.3 Hz). 13C NMR
(CDCl3, 150 MHz) ı 156.8, 134.5, 129.2, 114.5, 79.5, 38.3, 36.1, 34.2,
32.6, 29.5, 27.7, 27.3, 22.8, 19.1, 14.1, 13.8.
2.2.4. 1-(2,2-Diethyl-4-methylcyclobutoxy)-4-propylbenzene 7a
(cis)
1H NMR (CDCl3, 600 MHz) ı 7.04 (2H, d, J = 8.8 Hz), 6.75 (2H,
d, J = 8.8 Hz), 4.32 (1H, d, J = 7.3 Hz), 2.73–2.64 (1H, m), 2.50 (2H,
t, J = 7.3 Hz), 1.80–1.72 (2H, m), 1.66–1.56 (3H, m), 1.50 (2H, q,
J = 7.3 Hz), 1.40 (1H, q, J = 5.8 Hz) 1.02 (3H, d, J = 7.3 Hz), 0.92 (3H,
t, J = 7.3 Hz), 0.81 (3H, t, J = 7.3 Hz), 0.80 (3H, t, J = 7.3 Hz). 13C NMR
(CDCl3, 150 MHz) ı 157.4, 134.3, 129.1, 114.8, 79.5, 45.1, 37.2, 35.5,
30.0, 29.9, 24.8, 24.7, 15.7, 13.8, 8.2, 7.7 IR (NaCl, cm−1) 2961, 2929,
1612, 1510, 1458, 1240, 1102, 825 MS (rel. int.) m/z 260 (M+, 8), 218
(7), 176 (100), 154 (48), 136 (31), 69 (25) HRMS calc. for C18H28
260.2140, found 260.2142.
O
2.2.5. 1-(2,2-Diethyl-4-methylcyclobutoxy)-4-propylbenzene 7b
(trans)
1H NMR (CDCl3, 600 MHz) ı 7.04 (2H, d, J = 8.8 Hz), 6.79 (2H, d,
J = 8.8 Hz), 3.97 (1H, d, J = 7.3 Hz), 2.51 (2H, t, J = 7.3 Hz), 2.42–2.32
(1H, m), 1.79 (1H, t, J = 10.3 Hz), 1.73 (1H, sext, J = 7.3 Hz), 1.64–1.55
(3H, m), 1.55–1.43 (2H, m) 1.16 (3H, d, J = 6.6 Hz), 0.99–0.92 (1H, m),
0.92 (3H, t, J = 7.3 Hz), 0.83 (3H, t, J = 7.3 Hz), 0.80 (3H, t, J = 7.3 Hz).
Scheme 2. Oxidative carbon–carbon bond formation system using a cyclohexane-
based thermomorphic multiphase electrolyte solution composed of LPC and NM.

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Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
13C NMR (CDCl3, 150 MHz) ı 157.0, 134.8, 129.2, 115.7, 85.2, 45.3,
37.2, 33.7, 31.7, 30.9, 24.8, 24.0, 19.9, 13.8, 8.4, 8.3 IR (NaCl, cm−1
2.2.10. 1-(2,2-Diethyl-4-methylcyclobutoxy)-2-propylbenzene
11a (cis)
)
1H NMR (CDCl3, 600 MHz) ı 7.17–7.04 (2H, m), 6.82 (1H, t,
J = 7.3 Hz), 6.65 (1H, d, J = 8.1 Hz), 4.38 (1H, d, J = 7.3 Hz), 2.72 (1H,
sept, J = 7.3 Hz), 2.70–2.50 (2H, m), 1.88–1.72 (2H, m), 1.72–1.57
(3H, m), 1.57–1.47 (3H, m), 1.42 (1H, q, J = 5.9 Hz) 1.00 (3H, d,
J = 7.3 Hz), 0.96 (3H, t, J = 7.3 Hz), 0.83 (3H, t, J = 7.3 Hz), 0.82 (3H, t,
J = 7.3 Hz). 13C NMR (CDCl3, 150 MHz) ı 156.7, 131.0, 129.9, 126.6,
119.6, 115.5, 78.8, 45.2, 35.5, 32.9, 30.1, 29.9, 24.8, 23.2, 15.8, 14.2,
8.1, 7.7 IR (NaCl, cm−1) 2961, 2931, 1600, 1490, 1454, 1237, 1126,
748 MS (rel. int.) m/z 260 (M+, 4), 218 (4), 176 (49), 154 (100), 136
(59), 69 (25) HRMS calc. for C18H28O 260.2140, found 260.2122.
2960, 2931, 1610, 1510, 1457, 1240, 1059, 822 MS (rel. int.) m/z 260
(M+, 22), 218 (6), 176 (100), 154 (100), 136 (73), 125 (51) HRMS calc.
for C18H28O 260.2140, found 260.2142.
2.2.6. 2-Methyl-1-(4-propylphenoxy)spiro[3.5]nonane 8a (cis)
1H NMR (CDCl3, 600 MHz) ı 7.04 (2H, d, J = 8.8 Hz), 6.75 (2H, d,
J = 8.8 Hz), 4.27 (1H, d, J = 7.3 Hz), 2.70 (1H, m), 2.51 (2H, t, J = 7.7 Hz),
1.81 (1H, ddd, J = 11.4 Hz, 9.2 Hz, 1.1 Hz), 1.71–1.64 (2H, m), 1.60
(2H, sext, J = 7.3 Hz), 1.55–1.51 (2H, m), 1.51–1.41 (2H, m), 1.45 (1H,
dd, J = 11.4 Hz, 5.9 Hz), 1.40–1.30 (2H, m), 1.29–1.20 (2H, m), 1.04
(3H, d, J = 7.3 Hz), 0.92 (3H, t, J = 7.3 Hz). 13C NMR (CDCl3, 600 MHz)
ı 157.2, 134.0, 128.9, 114.5, 80.3, 42.6, 38.5, 37.1, 36.1, 32.9, 29.9,
26.1, 24.8, 23.0, 22.2, 15.7, 13.8 IR (NaCl, cm−1) 2954, 2925, 2852,
1610, 1508, 1240, 1060, 821 MS (rel. int.) m/z 272 (M+, 3), 230
2.2.11. 1-(2,2-Diethyl-4-methylcyclobutoxy)-2-propylbenzene
11b (trans)
1H NMR (CDCl3, 600 MHz) ı 7.12–7.06 (2H, m), 6.83 (1H, t,
J = 7.3 Hz), 6.79 (1H, d, J = 8.1 Hz), 4.03 (1H, d, J = 7.3 Hz), 2.58 (2H,
t, J = 7.3 Hz), 2.40–2.29 (1H, m), 1.84 (1H, t, J = 10.3 Hz), 1.79 (1H,
sept, J = 7.3 Hz), 1.56–1.47 (2H, m), 1.19 (3H, d, J = 7.3 Hz) 1.00–0.95
(1H, m), 0.94 (3H, t, J = 7.3 Hz), 0.86 (3H, t, J = 7.3 Hz), 0.82 (3H, t,
J = 7.3 Hz). 13C NMR (CDCl3, 150 MHz) ı 156.4, 131.6, 129.9, 126.6,
120.0, 112.7, 84.3, 45.0, 34.0, 32.7, 32.1, 31.0, 23.8, 23.2, 20.2, 14.1,
8.3, 8.2 IR (NaCl, cm−1) 2961, 2932, 1601, 1490, 1454, 1239, 1126,
749 MS (rel. int.) m/z 260 (M+, 8), 218 (5), 176 (62), 154 (100), 136
(62), 69 (39) HRMS calc. for C18H28O 260.2140, found 260.2142.
(25), 176 (100), 147 (76), 107 (96), 81 (80) HRMS calc. for C19H28
272.2140, found 272.2144.
O
2.2.7. 2-Methyl-1-(4-propylphenoxy)spiro[3.5]nonane 8b (trans)
1H NMR (CDCl3, 600 MHz) ı 7.05 (2H, d, J = 8.8 Hz), 6.82 (2H, d,
J = 8.8 Hz), 3.90 (1H, d, J = 7.0 Hz), 2.51 (2H, t, J = 7.7 Hz), 2.38 (1H, m),
1.96 (1H, t, J = 10.3 Hz), 1.72–1.66 (1H, m), 1.60 (2H, sext, J = 7.3 Hz),
1.54–1.33 (7H, m), 1.28-1.19 (1H, m), 1.18–1.08 (1H, m), 1.16 (3H,
d, J = 7.0 Hz), 0.95 (1H, m), 0.93 (3H, t, J = 7.3 Hz). 13C NMR (CDCl3,
150 MHz) ı 157.0, 134.6, 129.1, 115.3, 85.5, 43.0, 39.6, 37.2, 33.5,
32.8, 30.1, 26.2, 24.7, 23.1, 22.1, 19.8, 13.8 IR (NaCl, cm−1) 2954,
2925, 2852, 1612, 1508, 1238, 1020, 823 MS (rel. int.) m/z 272 (M+,
3), 176 (73), 147 (59), 136 (30), 107 (95), 81 (100) HRMS calc. for
3. Results and discussion
Our present study began with the investigation of a model reac-
tion that could realize a desirable synthetic system. Initially, anodic
oxidation of prop-1-enyloxy-4-propylbenzene 1a–b (0.20 mmol),
which was prepared using the previously reported method [35],
in the presence of an excess amount (4.0 mmol, 20 mol equiv.)
of 1-hexene 2 in the LPC/NM electrolyte solution was attempted,
affording the corresponding [2+2] cycloadducts 3a–d in high yield
(Scheme 3) [36].
A plausible reaction mechanism is depicted below. 1a–b was
anodically oxidized to generate the corresponding radical cation,
which was trapped by 2 to give 3a–d (Scheme 4). In this reaction,
an excess amount of 2 was essential for the effective trapping of the
radical cation of 1a–b, possibly due to its short lifetime [37–39].
The yields of 3a–d were dramatically decreased as amounts of 2
decreased (Scheme 5). The configuration of 3a–d was not derived
from 1a–b, suggesting that some sort of stepwise process was
involved in the reaction. We then attempted to incorporate the
second phase, cyclohexane, to the reaction system to form a mul-
tiphase electrolyte solution composed of LPC and NM. Since both
substrates 1a–b and 2 are soluble in cyclohexane, they could be
introduced into this system as a cyclohexane solution. The reaction
was carried out in the cyclohexane-based multiphase electrolyte
solution composed of LPC and NM to give 3a–d in excellent yield.
The amounts of 1a–b and 2 were the same as in Scheme 5, Entry
1. In this system, 5 mL of cyclohexane and 20 mL of LPC/NM elec-
trolyte solution were used, and 79% (0.158 mmol) of 1a–b and 63%
(2.52 mmol) of 2 were partitioned in the upper cyclohexane phase,
C19H28O 272.2140, found 272.2150.
2.2.8. 1-Propyl-4-(2,2,4-trimethylcyclobutoxy)benzene 9a (cis)
1H NMR (CDCl3, 600 MHz) ı 7.04 (2H, d, J = 8.4 Hz), 6.74 (2H, d,
J = 8.4 Hz), 4.30 (1H, d, J = 7.8 Hz), 2.71 (1H, tsept, 7.2 Hz, J = 1.5 Hz),
2.51 (2H, t, J = 7.7 Hz), 1.84 (1H, ddd, J = 11.4 Hz, 8.8 Hz, 1.5 Hz), 1.60
(2H, quint, J = 7.3 Hz), 1.44 (1H, dd, J = 12.0 Hz, 6.0 Hz), 1.20 (3H, s),
1.16 (3H, s), 1.08 (3H, d, J = 7.2 Hz), 0.92 (3H, t, J = 7.3 Hz). 13C NMR
(CDCl3, 600 MHz) ı 157.2, 134.3, 129.1, 114.7, 80.1, 38.6, 38.3, 37.1,
29.7, 29.4, 24.8, 24.0, 15.4, 13.8 IR (NaCl, cm−1) 2956, 2927, 2869,
1612, 1510, 1240, 1097, 827 MS (rel. int.) m/z 232 (M+, 8), 190 (22),
176 (82), 161 (36), 147 (78), 107 (100) HRMS calc. for C16H24
232.1827 found 232.1836.
O
2.2.9. 1-Propyl-4-(2,2,4-trimethylcyclobutoxy)benzene 9b
(trans)
1H NMR (CDCl3, 600 MHz) ı 7.05 (2H, d, J = 8.4 Hz), 6.80 (2H, d,
J = 8.4 Hz), 3.91 (1H, d, J = 7.8 Hz), 2.51 (2H, t, J = 7.7 Hz), 2.41 (1H,
tsept, J = 6.6 Hz, 2.6 Hz), 1.77 (1H, t, J = 10.2 Hz), 1.60 (2H, quint,
J = 7.5 Hz), 1.20 (3H, s), 1.15 (3H, d, J = 6.6 Hz), 1.1 (3H, s), 1.05 (1H,
t, J = 10.2 Hz), 0.92 (3H, t, J = 7.3 Hz). 13C NMR (CDCl3, 600 MHz) ı
156.8, 134.67, 129.2, 115.3, 85.3, 38.5, 37.2, 35.7, 33.3, 29.5, 24.7,
21.7, 19.52, 13.8 IR (NaCl, cm−1) 2956, 2929, 2865, 1610, 1510,
1240, 1062, 829 MS (rel. int.) m/z 232 (M+, 9), 190 (12), 176 (59), 161
(21), 147 (62), 107 (100) HRMS calc. for C16H24O 232.1827, found
232.1834.
Scheme 3. The anodic oxidation of 1a–b in the presence of an excess amount of 2 in the LPC/NM electrolyte solution.

Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
4115
Scheme 4. Plausible reaction mechanism.
Scheme 5. The effects of concentration on 2.
while 21% of (0.042 mmol) of 1a–b and 37% (1.48 mmol) of 2, i.e.,
“35 mol equiv.” for 1a–b, were partitioned in the lower LPC/NM
electrolyte solution phase (Scheme 6).
It was noteworthy that only a moderate yield (65%) of 3a–d was
obtained through anodic oxidation of 1a–b (0.042 mmol) without
cyclohexane even in the presence of an excess amount (1.48 mmol,
35 mol equiv.) of 2 in the LPC/NM electrolyte solution. These results
suggested that a continuous supply of 1a–b from the upper cyclo-
hexane phase to the lower LPC/NM electrolyte solution phase was
crucial for the reaction and that the amount of 1a–b was also cor-
related to the reaction progress (Scheme 8).
This was strongly supported by the fact that excellent yields
of 3a–d were obtained using the condition depicted below
(Scheme 9). In this case, 15 mL of cyclohexane and 10 mL of LPC/NM
electrolyte solution were used, while the concentrations of both
1a–b and 2 in the lower LPC/NM electrolyte solution phase were
intended to be comparable to those of Scheme 6, with a continu-
ous supply of 1a–b from the upper cyclohexane phase to reduce
the amount of the LPC/NM electrolyte solution. The productivity of
It can be explained reasonably that because 1a–b is more
hydrophobic than 2 due to their respective molecular weights,
a larger ratio of 1a–b was portioned in the upper cyclohexane
phase. At the end of the reaction, 3a–d could be completely
separated from the lower LPC/NM electrolyte solution phase via
simple liquid-liquid extraction with cyclohexane to give 3a–d
with high chemoselectivity (Fig. 1). Thus, in this system, cyclo-
hexane plays dual roles as the substrate supply and the product
assembly phases. There is no conductivity in the upper cyclo-
hexane phase, clearly suggesting that activation of 1a–b takes
place in the lower LPC/NM electrolyte solution phase. Namely,
the lower LPC/NM electrolyte solution phase is spatially separated
(Scheme 7).
Scheme 6. The anodic oxidation of 1a–b in the presence of an excess amount of 2 in the cyclohexane-based multiphase electrolyte solution composed of LPC and NM (5 mL
of cyclohexane and 20 mL of LPC/NM were used, respectively).

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Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
Fig. 1. The 1H NMR spectra of 3a–d separated via simple liquid–liquid extraction with cyclohexane.
Scheme 7. The concept of the cyclohexane-based multiphase electrolyte solution composed of LPC and NM.
the LPC/NM electrolyte solution was clearly improved through this
system.
and was continuously supplied to the lower LPC/NM electrolyte
solution phase, whereas a larger ratio of 2 was partitioned in the
lower LPC/NM electrolyte solution such that the amount of 2 in the
lower LPC/NM electrolyte solution phase was relatively high com-
pared to that in LPC/NM electrolyte solution without cyclohexane
(Scheme 10). It could be concluded that a continuous supply of 1a–b
from the upper cyclohexane phase to the lower LPC/NM electrolyte
solution phase was critical for the reaction.
It was also noteworthy that the anodic oxidation of 1a–b
(0.20 mmol) in the presence of 2 (1.0 mmol, 5 mol equiv.) in
cyclohexane-based multiphase electrolyte solution composed of
LPC and NM with 5 mL of cyclohexane and 20 mL of LPC/NM elec-
trolyte solution afforded 3a–d in moderate yield (63%), in sharp
contrast to that in LPC/NM electrolyte solution without cyclohex-
ane (46%, see Scheme 5, Entry 2). These results also suggested that
1a–b was preferentially partitioned in the upper cyclohexane phase
We next examined the reusability of the LPC/NM electrolyte
solution in this system. After extraction of 3a–d, additional
Scheme 8. Plausible reaction mechanism.

Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
4117
Scheme 9. The anodic oxidation of 1a–b in the presence of an excess amount of 2 in the cyclohexane-based multiphase electrolyte solution composed of LPC and NM (15 mL
of cyclohexane and 10 mL of LPC/NM electrolyte solution were used, respectively).
Scheme 10. The anodic oxidation of 1a–b in the presence of an excess amount of 2 in the cyclohexane-based multiphase electrolyte solution composed of LPC and NM (5 mL
of cyclohexane and 20 mL of LPC/NM electrolyte solution were used, respectively).
Scheme 11. Reusability of the LPC/NM electrolyte solution.
amounts of 1a–b and 2 in a cyclohexane solution were introduced
to the residual LPC/NM electrolyte solution. In this case, 5 mL of
cyclohexane and 20 mL of LPC/NM electrolyte solution were used.
The yields of 3a–d were excellent for at least five cycles, indicating
the reusability of the LPC/NM electrolyte solution (Scheme 11). The
amount of the LPC/M electrolyte solution necessary for the reaction
was reduced significantly through this system.
rated from the LPC/NM electrolyte solution via simple liquid–liquid
extraction with cyclohexane to give the cycloadducts with high
chemoselectivity. Prop-1-enyloxy-2-propylbenzene 10a–b could
also be introduced into this system to give the corresponding [2+2]
cycloadducts 11a–b in excellent yield. It should be emphasized that
In order to demonstrate the generality of this system, the anodic
oxidation of 1a–b in the presence of an excess amount (20 mol
equiv.) of several olefins 4–6 was attempted in the cyclohexane-
based multiphase electrolyte solution composed of LPC and NM.
In this case, 5 mL of cyclohexane and 20 mL of LPC/NM electrolyte
solution were used (Table 1). After extraction of the corresponding
[2+2] cycloadducts at the end of the reaction, the residual LPC/NM
electrolyte solution was then reused for the next reaction. The over-
all experimental procedures are illustrated below (Scheme 12).
Surprisingly, several [2+2] cycloadducts 7a–b, 8a–b, 9a–b were
obtained in excellent yields, which could be completely sepa-
Scheme 12. Overall experimental procedures.

4118
Y. Okada, K. Chiba / Electrochimica Acta 55 (2010) 4112–4119
Table 1
Anodic oxidation of 1a–b in the presence of an excess amount of 2, 4–6 in the cyclohexane-based multiphase electrolyte solution composed of LPC and NM
(5 mL of cyclohexane and 20 mL of LPC/NM electrolyte solution were used, respectively).
.
Entry
1
Olefin
Products
Yield (%)a
95 dr 2:1:1:1
2
3
96 dr 1:1
79b dr 1:1
4
>99 dr 1:1
5c
96 dr 1:1
a
Determined by NMR.
Non-cyclized product was obtained in 20% yield (see Ref. [36]).
Prop-1-enyloxy-2-propylbenzene 10a–b was used.
b
c
since all reactions were conducted in the residual LPC/NM elec-
trolyte solution, the amount of the LPC/NM electrolyte solution
used was effectively decreased, thus improving the productivity
of the LPC/NM electrolyte solution significantly.
cycloadducts with high chemoselectivity. A continuous supply of
the substrates from the upper cyclohexane phase to the lower
LPC/NM electrolyte solution phase played a key role in establishing
this system.
4. Conclusion
Acknowledgement
In conclusion, we constructed a continuous electrochemical
synthetic system using a cyclohexane-based multiphase electrolyte
solution composed of LPC and NM. In this system, the upper cyclo-
hexane phase functioned as both the substrate supply and the
product assembly phases, whereas the electrochemical reaction
took place in the lower LPC/NM electrolyte solution phase, achiev-
ing spatial isolation of the electrolyte solution phase. Thus, the
amount of the LPC/NM electrolyte solution used was decreased
significantly, improving the productivity of the LPC/NM electrolyte
solution. In this system, electrochemical [2+2] cycloaddition reac-
tions proceeded effectively, and the products could be separated
from the LPC/NM electrolyte solution via simple liquid–liquid
extraction with cyclohexane to give the corresponding [2+2]
This work was partially supported by a Grant-in-Aid for Sci-
entific Research from the Ministry of Education, Culture, Sports,
Science and Technology.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.electacta.2010.02.085.
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