Electrochemical hydroxylation of organoboron compounds

Article abstract of DOI:10.1039/b914093j

Cathodic hydroxylation of organoboron compounds was successfully performed under an oxygen atmosphere, producing the corresponding phenol derivatives with high selectivity and efficiency.

Full text of DOI:10.1039/b914093j

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Electrochemical hydroxylation of organoboron compoundsw
Kohei Hosoi, Yu Kuriyama, Shinsuke Inagi and Toshio Fuchigami*
Received (in Cambridge, UK) 14th July 2009, Accepted 9th December 2009
First published as an Advance Article on the web 8th January 2010
DOI: 10.1039/b914093j
Cathodic hydroxylation of organoboron compounds was
successfully performed under an oxygen atmosphere, producing
the corresponding phenol derivatives with high selectivity and
efficiency.
p-(methylthio)phenol (2a), was obtained in 38% yield together
with recovery of a large amount of 1a (entry 1). If reduction of
the substrate itself occurred, then hydrogenated or dimerized
products would be formed. Under a nitrogen atmosphere
without oxygen, the cathodic reaction hardly proceeded
(entry 2). However, intensive addition of oxygen by bubbling
Organoboron compounds have been widely used in the fields
of synthetic organic chemistry, materials chemistry and the
1
pharmaceutical sciences. The unique behavior of organo-
7
into the electrolytic solution resulted in the predominant
formation of the phenol derivative 2a in excellent yield
(entry 3). Therefore, it was proposed that oxygen dissolved
in the electrolytic solution is reduced to form a superoxide
boron compounds is mainly due to the Lewis acidity, which
2
arises from the vacant p-orbital on the boron atom. There-
8
fore, the electrochemical reduction behavior of organoboron
compounds has significant interest and calls for investigation.
In a previous report, the cathodic behavior of triarylborane
was investigated and a reversible two step electron transfer
ion, which then reacted with the substrate. The use of an
undivided cell resulted in quantitative recovery of the starting
material (entry 4).
In order to elucidate the reaction mechanism, cyclic
voltammetry (CV) measurements were performed for oxygen
in the presence and absence of boronic acid 1a (Fig. 1). The
voltammogram of oxygen (line a) exhibited a clear reduction
peak at À1.0 V versus SCE, and a corresponding reverse
anodic wave. The presence of thioanisole did not affect the
redox behavior of oxygen (line b). In sharp contrast, the
reverse anodic wave disappeared completely in the presence
of boronic acid 1a (line c), which indicates that the reduced
oxygen species (superoxide ion) is consumed during cyclic
scanning. In this case, the reduction wave of 1a was observed
around À2.7 V (see also Fig. S2w). Even when the cathodic
scan was returned to À1.8 V, the reverse anodic wave was
still diminished. These results suggest that the cathodically
generated superoxide ion reacts with the neutral boronic acid.
CV measurements of oxygen were then carried out in the
3
was observed in the reduction process. On the other hand, the
indirect electrochemical oxidation of arylboronic acid esters
revealed that a complex mixture of brominated, coupled and
4
hydroxylated products was formed.
The electrochemical reduction of boronic acids was studied with
consideration of these results, and it was found that the elimina-
tion of a boryl group led to the formation of the corresponding
phenol derivatives in good yields. We report the highly efficient
electrochemical synthesis of phenol derivatives from boronic acids
5,6
without the need for reagents such as hydrogen peroxide.
Firstly, the cathodic reaction of p-(methylthio)phenyl-
4
boronic acid (1a) was performed in 0.1 M Bu NClO –
4
acetonitrile by constant current electrolysis in a divided
cell (Table 1). Under air conditions, the hydroxylated product,
Table 1 Cathodic hydroxylation of 1a under various atmospheres
a
Yield (%)
Entry
Atmosphere
Air
Product
Recovery
1
2
3
38
2
91
0
30
82
1
N
2
O
O
2
b
4
2
94
a
1
Determined by H NMR. An undivided cell was used.
b
Department of Electronic Chemistry, Tokyo Institute of Technology,
259 Nagatsuta, Midori-ku, Yokohama 226-8502, Japan.
E-mail: fuchi@echem.titech.ac.jp; Fax: (+)81-45-924-5406;
Tel: (+)81-45-924-5406
Fig. 1 Cyclic voltammograms of oxygen in the presence and absence
4
of boronic acid, measured in 0.1 M Bu
4
NClO
4
–acetonitrile with a
À1
glassy carbon (GC) disk working electrode at 100 mV s . (a) O
2
only,
(
b) O
2 2
with thioanisole, and (c) O with p-(methylthio)phenylboronic
w Electronic supplementary information (ESI) available: Experimental
section, Fig. S1 and S2. See DOI: 10.1039/b914093j
acid (1a).
1
284 | Chem. Commun., 2010, 46, 1284–1286
This journal is ꢀc The Royal Society of Chemistry 2010

View Article Online
preceding mechanism where the superoxide ion initiates
the hydroxylation reaction. Furthermore, a conventional
hydroxylation procedure using hydrogen peroxide under basic
conditions was applied to 1a; however, oxidation of the sulfide
9
to sulfone occurred prior to hydroxylation and 2a was not
obtained. The use of superoxide ion, which has a weak
1
0
oxidizing ability, can suppress undesirable reactions of
oxidizable functional groups. Therefore, the electrochemical
reduction process has been found to be superior to con-
ventional hydroxylation with respect to reaction efficiency
and selectivity.
The cathodic hydroxylation of a variety of arylboronic acids
was investigated under oxygen atmosphere conditions, and the
results are summarized in Table 2. All of the boronic acids
afforded the corresponding phenol derivatives in good yields,
regardless of the functional groups at the para- and meta-
positions and their reduction potentials. The vinyl group
remained intact without formation of the corresponding epoxide
red
(entry 3). p-Acetophenylboronic acid 1d (E
SCE) and m-nitrophenylboronic acid 1f (E
p
red
p
= À1.71 V vs.
=À 1.25 V vs.
Scheme 1 Plausible reaction mechanism for the cathodic hydroxylation
SCE) with easily reducible functional groups were also efficiently
converted to the corresponding phenol derivatives without un-
desirable side reactions (entries 4 and 6). Pinacol boryl ester 1e
was also found to undergo a similar cathodic hydroxyl-
ation (entry 5). These examples suggest that the reduction of
oxygen takes place prior to reduction of the functional groups
of the substrate, and the generated superoxide ion attacks
immediately and predominantly the boron atom of the substrate
during the cathodic process.
of arylboronic acid.
presence of 1a with various scan rates ranging from 50 to
À1
1
000 mV s (Fig. S1w). The reverse anodic wave did not
À1
appear, even at a high scan rate of 1000 mV s . The results
indicated that the superoxide ion reacts with boronic acid
immediately after generation at the cathode.
Although the reaction mechanism is currently unclear, we
propose a tentative one as shown in Scheme 1. One electron
reduction of oxygen at the cathode generates the superoxide ion
that then reacts with the boronic acid. Dehydroxylation and
subsequent one electron reduction (from the cathode or
superoxide ion) lead to the formation of intermediate A. The
Finally,
a heterocyclic compound, benzo[b]thiophene-
red
2-boronic acid 3 (Ep = À2.50 V vs. SCE), was subjected
to the reaction system (Scheme 2). Similarly to the cases of the
benzeneboronic acid derivatives, selectively hydroxylated
product 4 was obtained in its keto form in low yield, together
with a major hydrogenated product 5. The latter could be
produced by elimination of the boryl group in a direct or
6
rearrangement of the aryl group then affords a phenolic species.
Finally, the phenol derivative is obtained by acid hydrolysis. The
reaction of the superoxide ion occurs predominantly at the boron
atom without any undesirable side reactions.
indirect reduction process, considering the reduction
red
potentials of 3 and oxygen (Ep
= À1.0 V vs. SCE). To
Chemical treatment of boronic acid 1a with KO
nitrile at room temperature also produced the corresponding
2
in aceto-
clarify the reaction mechanism, further experiments with other
heterocyclic compounds bearing boryl groups are now under
investigation.
phenol 2a in moderate yield (49%), which supports the
Table 2 Cathodic hydroxylation of a variety of arylboronic acids under oxygen atmosphere conditions
1
R
2
R
red
p
a
Entry
Compound
E
(V vs. SCE)
Product
Yield (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
p-CH
H
3
S
(OH)
(OH)
(OH)
(OH)
2
2
2
2
À2.63
À2.83
À2.40
2a
2b
2c
2d
2e
2f
91 (83)
79
77 (70)
84
88
p-CH
p-CH
p-CH
2
QCH
CO
3
À1.71, À2.30
À2.90
3
Pinacol
(OH)
m-NO
2
2
À1.25
(88)
a
1
Determined by H NMR and isolated yields are shown in parentheses.
This journal is ꢀc The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1284–1286 | 1285

View Article Online
M. Yamashita and K. Nozaki, Science, 2006, 314, 113; N. Fujita,
S. Shinkai and T. D. James, Chem.–Asian J., 2008, 3, 1076;
K. Parab, K. Venkatasubbaiah and F. Ja
¨
kle, J. Am. Chem. Soc.,
006, 128, 12879; Y. Nagata and Y. Chujo, Macromolecules, 2008,
1, 3488; R. Baggio, D. Elbaum, Z. F. Kanyo, P. J. Carroll,
2
4
R. C. Cavalli, D. E. Ash and D. W. Christianson, J. Am. Chem.
Soc., 1997, 119, 8107.
N. Matsumi, K. Naka and Y. Chujo, J. Am. Chem. Soc., 1998, 120,
2
Scheme
2
Cathodic reduction of 3 under oxygen atmosphere
5
112; J. Yoshino, N. Kano and T. Kawashima, Tetrahedron, 2008,
conditions.
64, 7774; A. Wakamiya, T. Taniguchi and S. Yamaguchi, Angew.
Chem., Int. Ed., 2006, 45, 3170; S. Yamaguchi, T. Shirasaka,
S. Akiyama and K. Tamao, J. Am. Chem. Soc., 2002, 124, 8816;
In conclusion, cathodic hydroxylation of organoboron
compounds was successfully carried out under an oxygen
atmosphere, producing the corresponding phenol derivatives
with high selectivity and efficiency. Cyclic voltammetric
analysis provided evidence that once the reduced species of
oxygen (superoxide ion) is generated at the cathode, it then
reacts very rapidly with the neutral boron atom. The electro-
chemical reduction process was found to be superior to
conventional methods using hydrogen peroxide, with respect
to both reaction efficiency and selectivity. This method has the
potential for application to the selective synthesis of a variety
of phenol derivatives.
S. Sole
T. Miyahara and K. Kurihara, J. Am. Chem. Soc., 2004, 126, 5684.
3 T. J. Dupont and J. L. Mills, J. Am. Chem. Soc., 1975, 97, 6375.
´
¨
and F. P. Gabbaı, Chem. Commun., 2004, 1284;
4
D.-Q. Shi, A. Gitkis and J. Y. Becker, Electrochim. Acta, 2007, 53,
824.
G. Zweifel and H. C. Brown, Org. React., 1963, 13, 1;
H. C. Brown, C. Snyder, B. C. Subba Rao and G. Zweifel,
Tetrahedron, 1986, 42, 5505; J. Simon, S. Salzbrunn,
G. K. S. Prakash, N. A. Petasis and G. A. J. Olah, J. Org. Chem.,
1
5
2001, 66, 633.
H. G. Kuivila, J. Am. Chem. Soc., 1954, 76, 870.
6
7 Caution: Bubbling oxygen into organic solvents may lead to
explosive mixtures.
J. Simonet and J.-F. Pilard, in Organic Electrochemistry, ed.
H. Lund and M. M. Baizer, Marcel Decker, New York, 4th edn,
001, ch. 29; D. T. Sawyer, Acc. Chem. Res., 1981, 14, 393;
P. S. Singh and D. H. Evans, J. Phys. Chem. B, 2006, 110, 637–644.
The obtained product was a mixture of p-(methylsulfonyl)phenol
and 2,4,6-tris[p-(methylsulfonyl)phenyl]boroxin determined by
8
9
2
Notes and references
1
A. Pelter, K. Smith and H. C. Brown, Borane Reagents, Academic
Press, London, 1988; A. Suzuki, J. Organomet. Chem., 1999, 576,
1
11
H-, B-NMR and MS (see ESIw).
10 Y.-J. Chen and J.-Y. Shen, Tetrahedron Lett., 2005, 46,
4205.
147; E. R. Burkhardt and K. Matos, Chem. Rev., 2006, 106, 2617;
S. Darses and J. P. Genet, Chem. Rev., 2008, 108, 288; Y. Segawa,
1
286 | Chem. Commun., 2010, 46, 1284–1286
This journal is ꢀc The Royal Society of Chemistry 2010