Anodic oxidation on a boron-doped diamond electrode mediated by methoxy radicals

Article abstract of DOI:10.1002/anie.201200878

Direct evidence: The existence of methoxy radical species formed during an anodic oxidation in MeOH on a boron-doped diamond (BDD) electrode was confirmed by ESR spectroscopy. Effective production of a neolignan, licarinA, was accomplished by the BDD-medi

Full text of DOI:10.1002/anie.201200878

Angewandte
Chemie
DOI: 10.1002/anie.201200878
Electrosynthesis
Anodic Oxidation on a Boron-Doped Diamond Electrode Mediated by
Methoxy Radicals**
Takenori Sumi, Tsuyoshi Saitoh, Keisuke Natsui, Takashi Yamamoto, Mahito Atobe,
Yasuaki Einaga,* and Shigeru Nishiyama*
Table 1: Synthesis of (ꢁ)-parasitenone (4) using anodic oxidation and
electrochemical synthesis of bisketal 2.
The boron-doped diamond (BDD) electrode[1a,b] is known to
possess a wide range of applications for the direct generation
of hydroxyl radicals and resulting inorganic peroxides such as
persulfate,[1c] perphosphate,[1d] and hypochlorite.[1e] In con-
trast to the extensive use of the BDD electrode in biological
and inorganic chemistry, only a few examples exist in which
electrochemically generated hydroxyl or alkoxy radicals have
been employed to promote reactions of highly functionalized
organic substances. The known applications include reactions
Entry
Anode/Oxidant
Potential
Yield (Product) [%][b]
(V vs. SCE)
1[a]
2[a]
3[a]
4
5
6
Pt net
1.15
1.05
1.25
–
–
–
100 (2)
50 (3)
100 (2)
100 (3)
50 (3)
GC beaker
BDD plate
DDQ[c]
of relatively simple substrates, such as acetal production by
[2]
ꢀ
oxidative C C bond cleavage, and BDD-mediated oxida-
tive couplings to construct diaryl linkages.[3] In general, alkoxy
radicals,[4] formed by anodic oxidation of the corresponding
alcohols, function as mediators in reaction pathways that are
different from those occurring under standard electrolysis
conditions using carbon or platinum electrodes.
[d]
PhI(OAc)2
CAN[e]
70 (3)
[a] 40 mm solution of 1 in 5% KOH MeOH solution, Pt wire cathode.
[b] Isolated yield. [c] 2,3-Dichloro-5,6-dicyano-p-benzoquinone, solvent:
MeOH/CH2Cl2. [d] Solvent: MeOH. [e] Ammonium hexanitratocerate
(IV), solvent: MeOH.
Dolson and Swenton have termed reactions that proceed
by the generation of methoxy radicals, formed by anodic
oxidation of MeOH followed by chemical reaction of the
derived radical and ionic species, as EECrCp processes.[5] In
a previous effort focusing on the synthesis of (ꢁ)-para-
sitenone (4) (Table 1),[6] we have used an oxidative quantita-
tive dimethoxy-acetalization reaction (1!2), occurring in
a basic MeOH solution at a Pt electrode,[5] as the key step
(entry 1). A similarly efficient reaction takes place when the
BDD electrode is employed (entry 3), while the correspond-
ing aldehyde 3[6] is produced from 1 in the oxidative reaction
occurring on a glassy carbon (GC) electrode (entry 2). The
process taking place in a basic MeOH solution (entry 1) might
involve the intermediacy of methoxy radicals in the manner
described by Swenton. Similarly, reaction at the BDD
electrode (entry 3) is anticipated to produce the same radical
species. These observations indicated that the acetalization
reaction (1!2) at Pt or BDD electrodes proceeds through the
EECrCp pathway in which the initially formed arene cation
radical intermediate A is converted to a cation B that
undergoes addition of methoxide, while the ECEC mecha-
nism proceeds through radical C (Scheme 1). Also, the lack of
production of methoxy radicals at the GC electrode enables
the initially formed cation radical A to undergo proton loss
(to D) in the route for formation of aldehyde 3. Despite the
plausibility of the mechanistic pathways suggested for the
conversion of 1 to either 2 or 3, no studies exist providing
direct proof for the involvement of radical species in
processes of this type. In the current study, we have carried
out ESR experiments to determine if radical intermediates
are generated in electrochemical oxidation reactions of
methanol using BDD, Pt, and GC electrodes. In addition,
we have probed electrochemical oxidation reactions of
isoeugenol (5)[5] as part of the biomimetic preparation of
the neolignan, licarin A (6).
[*] T. Sumi, Dr. T. Saitoh, K. Natsui, Dr. T. Yamamoto,
Prof. Dr. S. Nishiyama
Department of Chemistry, Faculty of Science
and Technology, Keio University
Hiyoshi 3-14-1, Kohoku-ku, 223-8522 Yokohama (Japan)
E-mail: nisiyama@chem.keio.ac.jp
Prof. Dr. M. Atobe
Department of Advanced Materials Chemistry
Graduate School of Engineering
Yokohama National University
Tokiwadai 79-5, Hodogaya-ku, 240-8501 Yokohama (Japan)
Prof. Dr. Y. Einaga
Department of Chemistry, Faculty of Science and Technology
Keio University, Hiyoshi 3-14-1
Kohoku-ku, 223-8522 Yokohama (Japan)
and
JST, CREST, Hiyoshi 3-14-1, 223-8522 Yokohama (Japan)
E-mail: einaga@chem.keio.ac.jp
To gain information about whether or not radical species
are involved in electrochemical oxidation reactions con-
ducted in MeOH, we have carried out an ESR study using the
radical trapping agent 5,5-dimethyl-1-pyrroline-N-oxide
(DMPO) (Scheme 2). Anodic oxidations of methanolic
solutions of DMPO were performed employing constant
[**] Supported by a grant from the Science Research Promotion Fund
from the Promotion and Mutual Aid Corporation for Private Schools
of Japan from MEXT.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201200878.
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anode used in the order BDD > Pt > GC. Thus, the
ESR spectroscopic data suggested that methoxy
radicals are generated in electrochemical oxidation
reactions of MeOH and that they are produced with
greater efficiency when the BDD anode is used.
We have probed an application of anodic
oxidation using the BDD electrode in the context
of the preparation of the benzofuran-type neo-
lignan,[8] (ꢁ)-licarin A (6). In nature, neolignans are
known to be biosynthesized by enzymatic oxidation
of corresponding phenol precursors.[9] Several bio-
mimetic syntheses of 6, starting with isoeugenol (5)
and employing a variety of oxidants, have been
described previously.[10] Included in these
approaches was one that employed an electrochem-
ical protocol,[11] in which electrolysis using a Pt
electrode was reported to provide 6 in 29%. In
contrast to that occurring at a Pt anode, anodic
oxidation of 5 in MeOH solution employing the
BDD electrode was anticipated to involve or be
accompanied by the formation of methoxy radicals. To probe
the consequences of this factor, we have investigated product
distributions of reactions of 5 promoted using BDD, Pt, and
GC anodes. The reactions were conducted under CPE
conditions and the used potentials were larger than the
oxidation potential of 5 (from linear sweep voltammetry, LSV,
measurments). The results of these experiments, displayed in
Table 2, showed that licarin A (6) is produced in 10–25%
yield (entries 1–4), along with substantial amounts of recov-
Scheme 1.
Anodic oxidation pathway for construction of bisdimethyl acetal (2).
Scheme 2. Trap reaction of the methoxy radical by DMPO.
potential electrolysis (CPE) conditions (1.06 V vs. the satu-
rated calomel electrode, SCE, 0.1m LiClO4 as supporting salt)
with BDD, Pt, and GC electrodes as anodes, and Pt wire as the
cathode. ESR of the product mixtures led to signals, displayed
in Figure 1, which occur at the magnetic field value antici-
pated for nitroxyl radicals generated by reaction of DMPO
with methoxy and not hydroxymethyl radicals.[7] The inten-
sities of the ESR signal for the formed radical varied with the
Table 2: Electrochemical synthesis of licarin A (6).
Entry
Anode
Solvent
Potential
Yields [%][b]
[V vs. SCE]
6
7
8
1
2
Pt plate
MeOH
MeOH
MeOH
0.80[c]
0.90[d]
0.69[c]
0.92[d]
0.74[c]
1.06[d]
1.27[d]
1.19[d]
20
25
17
10
21
40
–
9
–
–
–
–
–
16
–
19
16
17
6
18
–
3[e]
4
GC plate
5
6
BDD on Si plate
7[f]
8[f]
MeCN
MeNO2
–
–
–
[a] 10 mm solution of 5 in 0.1m LiClO4 solution, Pt wire cathode,
1.0 Fmolꢀ1. [b] Isolated yield. [c] The first oxidation potential. [d] The
second oxidation potential. [e] 0.5 Fmolꢀ1. [f] 0.1 Fmolꢀ1
.
ered 5, when Pt and GC electrodes were used. The highest
yield (40%) of 6 is obtained (entry 6) when the oxidation is
performed using the BDD anode. In this case, the vicinal
substituted products[12] 7 and 8[13] were also produced, likely
through a pathway involving 1) the formation of radical
intermediate 9 through sequential electron transfer and
deprotonation, 2) self-coupling of 9 to form 7 and coupling
Figure 1. ESR spectra obtained for the methoxy radical on several
electrode materials. Standard condition: 10 mm solution of 5,5’-
dimethyl-1-pyrroline N-oxide (DMPO) in 0.1m LiClO4/MeOH, Pt-wire
cathode (Applied potential: 1.06 V vs. SCE), AN (hyperfine coupling
constant of N) value: 13.37 G (cf. 13.58 G), AH (hyperfine coupling
constant of H) value: 7.98 G (cf. 7.61 G).
2
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of 9 with a methoxy radical to form 8, and 3) MeOH
addition.[14] Additional observations made in this effort
suggested that methoxy radicals participated in the mecha-
nism for the formation of 6. For example, 6 is not formed in
electrochemical oxidation reactions occurring in non-alco-
holic solvents like MeCN and MeNO2 (entries 7–8). In
addition, when alcohols other than MeOH were employed
as solvents for this process, 6–8 were generated in decreased
yields. Finally, in contrast to phenol oxidation reactions in
hexafluoroisopropyl alcohol, which have been reported to
take place in higher yields,[2b–d] the reaction of 5 promoted by
a BDD electrode in trifluoroethanol (TFE) is not efficient.
In the next stage of this study, we explored electro-
chemical oxidation reactions of 5 using the BDD electrode in
a flow cell system (Figure 2).[15] We anticipated that the use of
this type of system would lead to improved current efficien-
cies and avoidance of secondary oxidation reactions of the
deprotonation reacts rapidly with methoxy radicals formed
in high concentration at the surface of the electrode in the
pathway for generation of 8 (Table 3). Because the diffusion
layer of the flow-type cell system is thinner than in the batch-
type cell system,[15] it might be associated with a high
probability of the reaction between radical 9 and methoxy
radicals.
Table 3: Electrochemical flow reaction of 5 by means of the BDD
electrode.[a]
Entry
j
Flow rate
[mLminꢀ1
Yields [%][b]
[mAcmꢀ2
]
]
6
7
8
sm
1
2
3
4
5
6
0.5
1.0
1.5
2.0
1.0
0.1
7
7
8
8
3
4
7
12
8
9
9
9
3
3
9
12
30
68
67
66
60
90
40
24
43
7
9
10
1
1
0.025
0.05
0.15
–
7
42
32
8[c]
1.0
[a] 10 mm solution of 5 in 0.1m LiClO4 MeOH solution, BDD anode, Pt-
plate cathode, 1.0 Fmolꢀ1. [b] Isolated yield. [c] Batch-type cell (potential:
>5.55 vs. Pt wire).
We have demonstrated that methoxy radicals were
generated by electrochemical oxidation of MeOH using
a BDD anode. In addition, the results showed that the
electrooxidative reaction of isoeugenol (5) using the BDD
electrode produced (ꢁ)-licarin A (6) in higher yields than
related processes employing Pt and GC electrodes. Finally,
electrooxidation of 5 in a BDD-electrode-based flow system
formed the coupling product 8 highly efficiently, and the
coupling reaction was facilitated by high concentrations of
methoxy radicals formed at the anode. Further studies on the
applicability of electrochemical oxidation reactions taking
place at the BDD electrode and in particular those reactions
that lead to the formation of biologically important low-
molecular-weight substances are in progress.
Figure 2. The flow cell system by means of BDD electrode.
formed products. Although when conducted using the batch
electrochemical system, 6 is produced in higher yields when
the BDD electrode is employed as the anode in contrast to
the Pt and GC electrodes. However, long reaction times (13 h
for a 1 mmol scale) were required to generate 1 Fmolꢀ1 of
electricity. As a result, the prolonged exposure of the products
to the oxidation conditions causes over-oxidation leading to
formation of undesired polymerization and/or decomposition
products. Use of a flow cell system would circumvent this
problem. Moreover, it was expected to generate high
concentrations of methoxy radicals at the anode, which
would facilitate highly efficient one-electron oxidation pro-
cesses.
Received: February 1, 2012
Published online: && &&, &&&&
Keywords: boron-doped diamond electrode · electrochemistry ·
.
electrosynthesis · radicals
To determine if these expectations were correct and to
explore more generally the scope and limitations of electro-
chemical oxidation reactions mediated by the BDD electrode,
methanolic solutions of 5 were submitted to electrochemical
oxidation reactions in the flow cell system. Studies, in which
the current density and flow rate were varied, established
optimized conditions (current density 1.0 mAcmꢀ2, flow rate
0.05 mLminꢀ1, entry 6) for the conversion of 5 to 8 as the
major product. Interestingly, product distributions from
reactions in the flow system are different from those obtained
using the batch system discussed above (see Table 2). This
observation suggests that the radical intermediate 9, pro-
duced from 5 by sequential one-electron oxidation and
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4
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Electrosynthesis
T. Sumi, T. Saitoh, K. Natsui,
T. Yamamoto, M. Atobe, Y. Einaga,*
S. Nishiyama*
&&&& — &&&&
Anodic Oxidation on a Boron-Doped
Diamond Electrode Mediated by Methoxy
Radicals
Direct evidence: The existence of
confirmed by ESR spectroscopy. Effective
methoxy radical species formed during an
anodic oxidation in MeOH on a boron-
doped diamond (BDD) electrode was
production of a neolignan, licarin A, was
accomplished by the BDD-mediated
anodic oxidation protocol (see picture).
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!