Successful application of indirect electrooxidation for the transformation of biaryl methanols to the corresponding biaryl ketones

Article abstract of DOI:10.1080/00397911.2010.517369

Various biaryl methanols were electrooxidized into the corresponding biaryl ketones in good yields and under very mild reaction conditions. Because of the relatively high oxidation potential, bulky structure, and somewhat poor solubility, biaryl methanols do not readily undergo direct electrooxidative transformations as a synthetic step toward the corresponding biaryl ketones. Herein, we report the successful indirect electrooxidation of secondary biaryl methanols featuring the use of a slight excess amount of KI (1.2 equivalents, relative to the substrate) in MeOH. Copyright

Full text of DOI:10.1080/00397911.2010.517369

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Successful Application of Indirect
Electrooxidation for the Transformation
of Biaryl Methanols to the Corresponding
Biaryl Ketones
Mitsuhiro Okimoto a , Takashi Yoshida a , Masayuki Hoshi a , Tomohito
Chiba a & Kei Maeo a
a Department of Biotechnology and Environmental Chemistry ,
Kitami Institute of Technology , Kitami , Hokkaido , Japan
Published online: 27 Jul 2011.
To cite this article: Mitsuhiro Okimoto , Takashi Yoshida , Masayuki Hoshi , Tomohito Chiba & Kei
Maeo (2011) Successful Application of Indirect Electrooxidation for the Transformation of Biaryl
Methanols to the Corresponding Biaryl Ketones, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:21, 3134-3139, DOI:
10.1080/00397911.2010.517369
To link to this article: http://dx.doi.org/10.1080/00397911.2010.517369
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Synthetic Communications1, 41: 3134–3139, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517369
SUCCESSFUL APPLICATION OF INDIRECT
ELECTROOXIDATION FOR THE TRANSFORMATION OF
BIARYL METHANOLS TO THE CORRESPONDING
BIARYL KETONES
Mitsuhiro Okimoto, Takashi Yoshida, Masayuki Hoshi,
Tomohito Chiba, and Kei Maeo
Department of Biotechnology and Environmental Chemistry, Kitami Institute
of Technology, Kitami, Hokkaido, Japan
GRAPHICAL ABSTRACT
Abstract Various biaryl methanols were electrooxidized into the corresponding biaryl
ketones in good yields and under very mild reaction conditions. Because of the relatively
high oxidation potential, bulky structure, and somewhat poor solubility, biaryl methanols
do not readily undergo direct electrooxidative transformations as a synthetic step toward
the corresponding biaryl ketones. Herein, we report the successful indirect electrooxidation
of secondary biaryl methanols featuring the use of a slight excess amount of KI (1.2 equiva-
lents, relative to the substrate) in MeOH.
Keywords Biaryl ketones; biaryl methanols; electron transfer; iodine ion; oxidation
INTRODUCTION
The oxidation of secondary alcohols into the corresponding ketones has served
as an important, fundamental, and practical transformation in organic synthesis.
Accordingly, there has been numerous reports of such oxidations via indirect electro-
oxidative methods that involve various mediators as the electron carrier.[1–16] To the
best of our knowledge, however, the indirect electrooxidation of widespread biaryl
methanols (1) to the corresponding biaryl ketones (2) has yet to be reported. Shono
and coworkers have carried out pioneering studies on the indirect electrooxidation of
secondary aliphatic alcohols to the corresponding ketones in aqueous solutions, with
tert-butanol or tert-butanol=n-hexane as the cosolvent, and in the presence of a
Received December 6, 2009.
Address correspondence to Mitsuhiro Okimoto, Department of Biotechnology and Environmental
Chemistry, Kitami Institute of Technology, Koen-cho 165, Kitami, Hokkaido 990-8507, Japan. E-mail:
okimotmt@mail.kitami-it.ac.jp
3134

INDIRECT ELECTROOXIDATION OF BIARYL METHANOLS
3135
catalytic amount of iodide ions (0.10–0.25 equivalents, relative to the substrate) as
the mediator.[17] Their studies, however, did not include the electrooxidation of steri-
cally hindered secondary aromatic alcohols such as biaryl methanols 1. In fact, their
similar reaction conditions, the oxidation of diphenyl methanol (1a) resulted in a
poor yield (less than 60%) of diphenyl ketone (2a). On the other hand, because
ketones that possess an a-hydrogen immediately undergo electrooxidation to give
a-hydroxydimethylacetals or their derivatives, the corresponding aliphatic and alkyl
aromatic ketones could not be obtained by the indirect electrooxidation of secondary
aliphatic and a-alkyl benzyl alcohols in MeOH using iodide ion as mediator.[18,19]
During the course of our studies on the preparative-scale indirect electrooxidation
of several organic compounds in the presence of iodide ions,[20–26] we discovered that
our methodology can be successfully applied toward the electrooxidation of a wide
range of biaryl methanols 1 to the corresponding biaryl ketones 2 in good to
excellent yields. The reactions were carried out in MeOH and involved the use of
excess amounts (versus catalytic amounts) of the iodide ion source (KI) as the
mediator. Initially, the optimal reaction conditions for the indirect electrooxidation
were examined using diphenyl methanol (1a) as the model substrate. The types of the
supporting electrolytes along with the corresponding yields of the resulting diphenyl
ketone (2a) are listed in Table 1. Remarkably, the use of merely 1.2 equivalents of KI
(relative to 1a) was effective in the formation of 2a in a reasonable yield of 79%
(entry 11), which was improved to nearly 90% by the addition of NaOMe (2.0
equivalents, entry 5).
In contrast, the use of a catalytic amount of KI (0.6 equivalent, relative to 1a)
actually decreased the yield of 2a (entry 4). Substitution of KI (entry 5) with KBr
Table 1. Influence of supporting electrolytesa
Yield (%)
Entry
Supporting electrolytes (mmol)
2ab
Unreacted 1ab
1
2
p-TsON(Et)4 (10)ꢀKI (6)
NaOAc (10)ꢀKI (6)
NaOH (10)ꢀKI (6)
NaOMe (10)ꢀKI (3)
NaOMe (10)ꢀKI (6)
NaOMe (10)ꢀKI (9)
t-BuOK (10)ꢀKI (6)
NaOMe (10)ꢀKBr (6)
NaOMe (10)ꢀKCl (6)
NaOMe (10)ꢀnone
NoneꢀKI (6)
63
77
82
45
89
89
82
17
28
26
79
36
22
15
53
10
10
17
80
68
69
20
3
4
5
6
7
8
9
10
11
a1a, 5 mmol; MeOH, 40 mL; constant current, 0.3 A; current passed,
13.4 Fmolꢀ1; rt ca. 20 ꢁC.
bYields were determined by GC analysis.

3136
M. OKIMOTO ET AL.
(entry 8) or KCl (entry 9) resulted in lower yields of 2a (17% and 28%, respectively).
The use of a stronger base (t-BuOK instead of NaOMe) did not increase the yield
(entry 7). These results indicate that the relative amount of KI strongly affects the
yield of 2a (entries 4–6). Contrary to the typical role as a catalyst for indirect electro-
oxidations, the use of iodide ions in substantial amounts (relative to substrate 1a) was
essential in increasing the yields of ketone 2a. Immediately upon the start of the elec-
trooxidation reaction, the yield of 2a was proportional to the amount of current
passed—specifically, 28% after 3.0 Fmolꢀ1, then 57% after 6.0 Fmolꢀ1. However, as
the reaction proceeded, current efficiency gradually decreased—specifically, 86% after
12.0 Fmolꢀ1, then 89% after 15 Fmolꢀ1. Accordingly, sufficient amounts of current
are required to consume most of 1a. As a note, significant differences were not
observed by varying the amount of NaOMe [from 5 mmol (81%) to 25 mmol
(84%)] nor by adjusting the reaction temperature [from 5 ꢁC (83%) to 45 ꢁC (71%)].
Based on these results, the optimal reaction conditions were applied to the electroox-
idation reaction of a wide variety of biaryl methanols (1a–m), as listed in Table 2.
In most cases, the reactions involve the passage of 13.4 Fmolꢀ1 with a constant
current of 0.3 A (6.0 h). In the cases of 1e, 1k, and 1m, however, the consumption of
the substrates required only about half of the electricity (7.2 Fmolꢀ1); the reason
remains unclear. Unexpectedly, substituent effects were not observed (for example,
1e versus 1h). The electrooxidation was also applied to a fluorene-type 1m, in which
two aromatic rings are combined via two carbon-carbon bonds. In the cases of 1e,
1h, and 1i, the resulting products (2e, 2h, and 2i, respectively) precipitated from
the reaction mixture during the latter half of the electrooxidation reaction because
of their low solubilities in MeOH. For this electrooxidation system, although the
Table 2. Indirect electrooxidation of biaryl methanolsa
Current passed
(Fmolꢀ1
Yield of
2 (%)b
Substrates
R1
R2
)
Mp or bp (ꢁC)
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
13.4
13.4
13.4
13.4
7.2
83
90
88
92
95
82
95
95
77
81
96
73
93
47–49
43–45
3,4-di-Me-C6H3
4-t-Bu-C6H4
4-MeO-C6H4
4-MeO-C6H4
2-CO2Me-C6H4
4-F-C6H4
151–153=1 mmg
58–61
4-MeO-C6H4
Ph
141–143
49–52
46–48
13.4
13.4
13.4
13.4
13.4
7.2
1g
1h
1i
Ph
4-Cl-C6H4
Ph
4-Cl-C6H4
142–144
130–132
68–70
4-NO2-C6H4
4-MeO-C6H4
2-Thionyl
1j
3-F-C6H4
Ph
Ph
1k
1l
56–57
69–72
79–81
4-Pyridil
13.4
7.2
1m
Fluorenol
a1, 5 mmol; KI, 6 mmol; NaOMe, 10 mmol; MeOH, 40 mL; constant current, 0.3 A; rt ca. 20 ꢁC.
bIsolated yields based on the substrates.

INDIRECT ELECTROOXIDATION OF BIARYL METHANOLS
3137
reaction pathway remains to be further investigated, it is clear that iodide ions play
an important role as electron carriers. Because catalytic amounts of the iodide ion
were not enough to fully enhance the oxidation process of biaryl methanols, our
reaction mechanism may differ from that proposed by Shono’s group.[17] The results
of this study represent the first known examples of indirect electrooxidations of mul-
tiple biaryl methanols to the corresponding ketones in good yields. In conclusion,
our method involves the use of a slight excess of iodide ions as the mediators and
allows for the preparation of biaryl ketones without any effects of the construction
and=or property of substituent of the substrate. Moreover, the advantages of our
method include (1) very mild reaction conditions, (2) absence of harsh toxic reagents,
such as metal oxidants or special reagents, and (3) a simple one-pot procedure.
EXPERIMENTAL
Preparative-scale electrooxidations were carried out in a tall 50-mL beaker
equipped with a fine frit cup as the cathode compartment with a nickel coil cathode,
along with a cylindrical platinum net anode. The typical procedure was as follows: A
solution of diaryl methanol 1 (5 mmol) in MeOH (40 mL) containing KI (6 mmol)
and NaOMe (10 mmol) was electrooxidized under a constant current (0.3 A). During
the course of the electrooxidation, the anolyte was magnetically stirred at ca. 20 ꢁC.
Upon passage of the electrolytic current (7.2 or 13.4 Fmolꢀ1), the reaction mixture
was concentrated in vacuo (ca. 10 mL) at approximately 50 ꢁC. The resulting oily
residue was treated with water (ca. 30 mL), extracted with ethyl ether or chloroform
(3 ꢂ 40 mL), and dried over magnesium sulfate. After removal of the solvent in
vacuo, the desired biaryl ketones 2 were isolated by silica-gel column chromato-
graphy using ether=hexane (1:3) as the eluent. During the electrooxidation, the com-
position of the reaction mixture was monitored by gas chromaography (GC) or
thin-layer chromatography (TLC). Electric current was passed until almost all of
the substrate was consumed. Melting points and Infrared (IR) spectra of all products
were in good agreement with those of authentic samples.
ACKNOWLEDGMENT
We are thankful for the financial support of the President’s Discretionary
Finance Council of Kitami Institute of Technology (2008–2009).
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