An aqueous silica gel disperse electrolysis system. N-Oxyl-mediated electrooxidation of alcohols

Article abstract of DOI:10.1016/S0040-4039(00)01979-1

N-Oxyl-mediated electrooxidation of alcohols was performed in an aqueous silica gel disperse system. The newly devised electrolysis system offers an organic solvent-free and operationally simple procedure for oxidation of alcohols and could be successfully applied to kinetic resolution of sec-alcohol as well as enantioselective oxidation of meso-1,4-diol affording optically active γ-lactone.

Full text of DOI:10.1016/S0040-4039(00)01979-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 445–448
An aqueous silica gel disperse electrolysis system.
N-Oxyl-mediated electrooxidation of alcohols
Hideo Tanaka,* Yusuke Kawakami, Kentaro Goto and Manabu Kuroboshi
Department of Applied Chemistry, Faculty of Engineering, Okayama University Tsushima-naka 3-1-1, Okayama,
Okayama 700-8530, Japan
Received 13 October 2000; accepted 2 November 2000
Abstract—N-Oxyl-mediated electrooxidation of alcohols was performed in an aqueous silica gel disperse system. The newly
devised electrolysis system offers an organic solvent-free and operationally simple procedure for oxidation of alcohols and could
be successfully applied to kinetic resolution of sec-alcohol as well as enantioselective oxidation of meso-1,4-diol affording optically
active g-lactone. © 2001 Elsevier Science Ltd. All rights reserved.
N-Oxyl-mediated electrooxidation of alcohols has been
trolytes were inevitably used to achieve significant cur-
rent density. Recently, we have reported N-oxyl/
bromide salt double redox-mediated electrooxidation of
intensively investigated and many successful applica-
1
tions have been reported. The electrooxidation was
2
mainly carried out in a divided cell under a regulated
potential condition and hence polar organic solvents
involving a high concentration of the supporting elec-
alcohols in an H O/CH Cl two-phase system. The
2
2
2
two-phase electrolysis could be performed by use of a
simple beaker-type undivided cell under a constant
OH
R2
Br-
N+
O
2
Anode
R1
1
PhCOO
N O•
N O•
2e
O
+
[
Br ]
2
N O•
R1
R2
3
(S)-4
2
aqueous phase
silica gel
Scheme 1. N-Oxyl/bromide salt-mediated electrooxidation of alcohols.
Table 1. Electrooxidation of a-phenylethanol 1a in an undivided cell under a constant current
a
Entry
Electrolysis system
Yield, %b
2
a
1a
1
2
3
4
5
NaBr-NaHCO ; H O (5 ml); silica gel (500 mg)
88
74
48
4
–
3
2
NaBr-NaHCO ; H O/CH Cl (4 ml/4 ml)
19
49
76
89
3
2
2
2
NaBr-NaHCO ; H O/MeCN (4 ml/4 ml)
3
2
Lutidine (21 mmol); LiClO4 (0.2 mmol); CH Cl /MeCN (3 ml/2 ml)
2
2
Lutidine (2 mmol); NaClO4 (0.5 mmol); H O/MeCN (1 ml/4 ml)
3
2
a
2
Carried out in an undivided cell fitted with two platinum electrodes (1.5×2 cm ) under a constant current (30 mA, 2.2 F/mol) at room
temperature.
b
Isolated yields.
Keywords: electrochemistry; oxidation; alcohols; enantioselective.
*
Corresponding author. Tel.: +81-86-251-8074; fax: +81-86-251-8079; e-mail: tanaka95@cc.okayama-u.ac.jp
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01979-1

4
46
H. Tanaka et al. / Tetrahedron Letters 42 (2001) 445–448
current condition, thereby offering a more beneficial
procedure for practical use. The N-oxyl-mediated
electrooxidation processes reported so far are, how-
ever, not necessarily satisfactory in terms of opera-
tional simplicity, manufacturing cost, and/or environ-
mental stress arising from the use of organic solvents.
In our continuing studies on the N-oxyl/bromide
salt-mediated electrooxidation, we found that an
aqueous silica gel disperse system could be used suc-
cessfully for the electrooxidation of alcohols with-
out the use of any organic solvent (Scheme 1). Herein,
we describe the first example of an aqueous silica
gel disperse electrolysis system for the oxidation of
alcohols 1.
Table 2. Electrooxidation of alcohols in an aqueous silica gel disperse system
Entry
1
Alcohol
F/mol
2.2
Product (Yield, %)a
O
OH
(88)
(82)
(82)
(42)b
(86)
(84)
(92)
(91)
(72)
( – )c
2a
1
a
OH
OH
OH
O
2
3
4
5
6
7
8
9
2.5
2.5
2.5
2.5
4.5
4.5
4.5
4.5
4.5
Cl
Cl
2b
1b
O
2c
1
c
O
MeO
MeO
2d
1
d
e
OH
O
1
2e
OH
HO
O
O
1f
2f
OH
OH
O
O
1g
2g
OH
O
OH
1h
2h
O
HO
OH
O
O
O
1
i
j
2
i
10
OH
HO
O
1
2j
a
b
Isolated yields after column chromatography.
m-Bromo-p-methoxyacetophenone
c
was obtained in 11% yield. Considerable amounts of dimeric esters were obtained.

H. Tanaka et al. / Tetrahedron Letters 42 (2001) 445–448
Chiral N-Oxyl (S)-4 (1 mol%)
447
OH
O
OH
aq. 20 w% NaBr/sat. NaHCO – Silica Gel
3
+
o
Cl
(R)-1b (43%)
Cl
3
0 mA, 1.5 F/mol, -15 C
Cl
2
b (52%)
1b
75%ee, S = 12
Scheme 2. Oxidative kinetic resolution of sec-alcohol 1b.
Chiral N-Oxyl (S)-4 (1 mol%)
aq. 20 w% NaBr/sat. NaHCO – Silica Gel
OH
OH
3
O
(
89%)
o
74%ee
[α] = +36.1o
3
0 mA, 4.5 F/mol, -15 C
O
25
meso-1g
2g
D
Scheme 3. Enantioselective oxidation of meso-diol 1g.
The electrolysis was carried out in a disperse system
with silica gel (Merck Kieselgel 60, 230–400 mesh) as
the disperse phase and aqueous 20 w% NaBr saturated
moiety to afford a mixture of the ketone 2d and its
m-bromo-substituted product (Entry 4). 1,4-Diols and
1,5-diols were selectively converted to g-lactones and
−
1
with NaHCO as the disperse media. The silica gel (500
d-lactone, respectively, after passage of 4.5 F/mol of
electricity (Entries 6–9). Under similar conditions, 1,5-
diol 1j afforded no detectable amount of the corre-
sponding lactone 2j, yielding a mixture of esters
3
mg) was dispersed in an acetone solution of a-
1
2
phenylethanol 1a (R ꢀPh, R ꢀCH ; 1 mmol) and N-
3
oxyl 3 (0.01 mmol) and most of the solvent was
evaporated under reduced pressure. The residual solids
3
resulting from intermolecular reactions (Entry 7).
and aqueous 20 w% NaBr saturated with NaHCO (5
3
ml) were placed in a beaker-type undivided cell fitted
Kinetic resolution of secondary alcohol 1b with chiral
2
with two platinum foil electrodes (1.5×2 cm ). A regu-
4
N-oxyl (S)-4 was carried out in a similar silica gel
−
1
lated dc current (30 mA, 2.2 F/mol ) was supplied
disperse electrolysis system (Scheme 2). Passage of 1.5 F/
(
Table 1, Entry 1). The work-up process is quite simple;
−1
mol of electricity at −15°C afforded the correspond-
thus, the disperse phase (silica gel) was freed from the
aqueous phase by filtration and rinsed with acetone.
The organic filtrate was concentrated in vacuo and the
residue was passed through a short column (SiO2,
hexane/AcOEt: 5/1) to afford acetophenone 2a in 88%
yield. Use of NaCl or NaI in place of NaBr could not
effectively promote the oxidation, affording only 33%
and 11% yields of 2a, respectively.
ing ketone 2b in 52% yield and recovered alcohol 1b in
5
4
3% yield, 75% ee (S=12). Enantioselective oxidation
of meso-1,4-diol 1g was achieved in a similar manner,
6
5
affording bicyclic lactone 2g in 89% yield, 74% ee
Scheme 3).
(
The characteristic features of the silica gel-disperse
electrolysis system are summarized as follows:
1
2
3
. Electrolysis can be performed in an undivided cell
under a constant current condition (self-controlled
potential) without the use of organic solvents.
. The work-up process is exceptionally simple; just
filtration, extraction of silica gel with acetone, evap-
oration, and short column chromatography.
. High current efficiency and good to excellent yields
of products can be achieved.
When the N-oxyl/NaBr-mediated electrooxidation of
1
a was carried out in a two-phase system comprising
2
CH Cl and aqueous NaBr/NaHCO (Entry 2) or in a
2
2
3
homogeneous system (aqueous acetonitrile) (Entry 3), a
silimar reaction occurred but less effectively, affording
74 and 48% yields of 2a, respectively. The presence of a
bromide salt (NaBr) is indispensable for the electrooxi-
dation of 1a in an undivided cell, since no appreciable
reaction occurred in the absence of the bromide salt; see
for example entries 4 and 5. Notably, both electrolysis
systems have been frequently used for N-oxyl-mediated
electrooxidation of alcohols in a divided cell, affording
good to excellent yields of the corresponding carbonyl
References
1
a
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The newly devised silica gel disperse electrolysis system
was successfully applied to the electrooxidation of vari-
ous alcohols. The representative results are summarized
in Table 2. Oxidation of sec-alcohols 1 proceeded
smoothly to afford the corresponding ketones 2 (En-
tries 1–3, and 5), while a-(p-methoxyphenyl)ethanol 1d
partially suffered bromination on the p-methoxypheny
.

4
48
H. Tanaka et al. / Tetrahedron Letters 42 (2001) 445–448
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