A mild and highly efficient conversion of arylboronic acids into phenols by oxidation with MCPBA

Article abstract of DOI:10.1055/s-0032-1318197

A mild and highly efficient synthesis of phenols from arylboronic acids in a H₂O-EtOH (1:2) solution was achieved by using MCPBA as the oxidant at room temperature. Isotopical labeling studies had shown that the hydroxyl oxygen atom of the phenol might originate from the MCPBA. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1318197

LETTER
▌499
lAetteMr ild and Highly Efficient Conversion of Arylboronic Acids into Phenols by
Oxidation with MCPBA
Conversion of Arylboronic Acids into Phenols
Dong-Song Chen, Jing-Mei Huang*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong 510640, P. R. of China
Fax +86(20)87110622; E-mail: chehjm@scut.edu.cn
Received: 05.12.2012; Accepted after revision: 17.01.2013
idants were employed, such as K2S2O8, O2, and tert-butyl
Abstract: A mild and highly efficient synthesis of phenols from ar-
hydroperoxide (TBHP, Table 1, entries 9–11), phenylbo-
ronic acid was not consumed completely, and only 5–15%
ylboronic acids in a H2O–EtOH (1:2) solution was achieved by us-
ing MCPBA as the oxidant at room temperature. Isotopical labeling
yield of the desired product was obtained within six hours.
Phenol was obtained in moderate yield by using H2O2
(30%) as oxidant (Table 1, entries 12 and 13). Hence, the
best conditions are shown in entry 2 (Table 1).
studies had shown that the hydroxyl oxygen atom of the phenol
might originate from the MCPBA.
Key words: arylboronic acids, efficiency, MCPBA, oxidation,
phenols
Table 1 Optimization of the Reaction Conditions for the Hydroxyl-
ation of Phenylboronic Acida
Phenols are widely used as versatile intermediates and
employed in the synthesis of natural products, materials,
and biological and pharmaceutical compounds.1 Phenols
are usually prepared from aryl halides through a nucleo-
philic substitution or by metal-catalyzed hydroxylation,
and copper-catalyzed transformations of diazoarenes are
also applied in the laboratory.2 In recent years, several
methods have been established to convert arylboronic ac-
ids into phenols with or without metal catalysis.3 Aqueous
hydrogen peroxide,3h–j oxone,3k molecular oxygen (or
air),3d,l and sodium perborate3m,n had been applied as oxi-
dants for the hydroxylation of arylboronic acids. These
transformations were often carried out under basic (alkali
base) or neutral conditions.
OH
B(OH)2
oxidant, solvent
r.t.
2a
1a
Entry
Oxidant
Solvent
Yield of 2a (%)b
1
2
MCPBA
MCPBA
MCPBA
MCPBA
MCPBA
MCPBA
MCPBA
MCPBA
K2S2O8
O2
H2O–EtOH (1:1)
H2O–EtOH (1:2)
H2O–EtOH (1:4)
H2O
84
98
86
70
82
86
88
89
5
3
4
5
EtOH
MCPBA (m-chloroperbenzoic acid) is widely used as an
electrophilic reagent capable of reacting with many func-
tional groups, and it can deliver oxygen to alkenes, sul-
fides, selenides, and amines.4 Herein, we report the first
use of MCPBA as an oxidant to convert arylboronic acids
into phenols efficiently at room temperature without any
alkali base, metal catalyst, or ligand.
6
H2O–THF (1:2)
H2O–MeCN (1:2)
H2O–MeOH (1:2)
H2O–EtOH (1:2)
H2O–EtOH (1:2)
H2O–EtOH (1:2)
H2O
7
8
9
10
11
12
13
5
Studies were initiated in a H2O–EtOH (1:1) solution using
MCPBA as the oxidant at room temperature. The result
was promising, and the yield of phenol increased to 84%
(Table 1, entry 1). Increasing the amount of ethanol in the
H2O–EtOH solution resulted in a higher yield of product
(98%, Table 1, entry 2). However, a further increase of
ethanol (Table 1, entry 3) or using pure water (Table 1, en-
try 4) or pure ethanol (Table 1, entry 5) separately resulted
in a decreased yield of phenol. This indicated that the con-
centration of ethanol had a significant effect on the reac-
tion efficiency. Studies on the effect of other solvents
(Table 1, entries 6–8) showed that using THF, MeCN, and
MeOH resulted in a lower yield of phenol. When other ox-
TBHP
15
63
69
H2O2
H2O2
H2O–EtOH (1:2)
a Reaction conditions: phenylboronic acid (0.5 mmol) and oxidant
(0.5 mmol) in solvent (2 mL)5 at r.t., 6 h, air.
b Yield determined by 1H NMR spectroscopy.
Subsequently, a variety of boronic acids were examined to
generate the hydroxylation products under the optimized
conditions. The results are summarized in Table 2. The
substituted aromatic boronic acids bearing electron-defi-
cient or electron-rich groups were converted into the cor-
responding phenols smoothly in good to excellent yields.
p-Cyanophenol, m-nitrophenol, p-chlorophenol, p-tert-
buylphenol, and 1-naphthol were obtained in yields of
above 95%. The functional groups which are easily oxi-
SYNLETT 2013, 24, 0499–0501
Advanced online publication: 06.02.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1318197; Art ID: ST-2012-W1028-L
© Georg Thieme Verlag Stuttgart · New York

500
D.-S. Chen, J.-M. Huang
LETTER
dized,3l including methylthio and aldehyde, were tolerated
in these mild processes. More importantly, the electron-
rich phenols such as p-methoxyphenol, 2,6- dimethylphe-
nol, and p-tert-buylphenol, which are difficult to obtain
from the traditional nucleophilic substitution of aryl ha-
lides, could be easily generated using this method. The
substrate scope of this methodology had been extended to
the phenylboronic pinacol ester 1k and cyclohexylboronic
acid 1l. And the desired products 2a and 2l were obtained
in 96% and 60% yield after six hours, respectively
(Scheme 1). However, the heteroarylboronic acids, for ex-
ample, 4-pyridinylboronic acid, 2-furanylboronic acid,
and 3-thiopheneboronic acid, were not suitable for this
reaction.
Table 2 Hydroxylation of Arylboronic Acids in Aqueous Ethanol
Solutiona,b (continued)
B(OH)2
OH
MCPBA, H2O–EtOH (1:2)
6 h, r.t.
R
R
1
2
Entry
9
Product
Yield (%)
OH
80
MeS
2i
OH
10
quant.
Table 2 Hydroxylation of Arylboronic Acids in Aqueous Ethanol
Solutiona,b
2j
B(OH)2
OH
MCPBA, H2O–EtOH (1:2)
6 h, r.t.
a Reaction conditions: boronic acids (0.5 mmol), MCPBA (0.5 mmol)
with H2O–EtOH (1:2; 2 mL), 6 h, r.t.
b Isolated yield.
R
R
1
2
Entry
1
Product
Yield (%)
B(OH)2
16OH
MCPBA, H218O–EtOH (1:2)
6 h, r.t.
OH
97
1a
2a 98% yield
Scheme 2
2a
OH
2
3
4
96
97
85
NC
O
OH
2b
B
O
O2N
OH
OH
2a 96% yield
1k
MCPBA, H2O–EtOH (1:2)
6 h, r.t.
2c
OH
B
OH
OH
2l 60% yield
OHC
1l
2d
OH
Scheme 1
5
6
95
91
Cl
In the interest of elucidating the reaction process, we first
considered the source of phenolic oxygen, so a prelimi-
nary mechanistic study with isotope-labeled water
(H218O) was performed (Scheme 2). When the reaction of
phenylboronic acid was carried out employing H218O
(H218O content: >40%) as a solvent under the optimal re-
action conditions, incorporation of 18O into the phenol
was not observed by HRMS analysis, which implied that
the oxygen source for the phenol formation was not wa-
ter.6 The same yield was obtained when the control reac-
tion was carried out under an N2 atmosphere (Scheme 3),
suggesting that molecular oxygen was not crucial for the
process and the oxygen source for the phenol formation
was not O2.
2e
OH
MeO
2f
OH
7
94
2g
OH
8
quant.
t-Bu
Hence, based on the above observation, the source of phe-
nolic oxygen might be from MCPBA. The mechanism of
2h
Synlett 2013, 24, 499–501
© Georg Thieme Verlag Stuttgart · New York

LETTER
Conversion of Arylboronic Acids into Phenols
501
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B(OH)2
OH
MCPBA, H2O–EtOH (1:2)
N2, 6 h, r.t.
2a 98% yield
1a
Scheme 3
the oxidative hydroxylation of phenylboronic acid was
hypothesized (Scheme 4), as suggested by the recently re-
ported work on the mechanism studies of the aerobic oxi-
dative hydroxylation of arylboronic acids through
photoredox catalysis.3d Firstly, 1a reacted with MCPBA
to generate the intermediate 3a, then rearrangement of 3a
afforded a phenolic species 4a. Finally, the hydroxylated
product 2a was obtained by hydrolysis of 4a.
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HO
OH
B
MCPBA
B(OH)2
O
O
Cl
H
O
1a
3a
OH
OB(OH)2
H3O+
2a
4a
Scheme 4 The proposed mechanism of the reaction
In conclusion, a highly efficient synthesis of phenols7
from arylboronic acids has been developed by using
MCPBA as an oxidant. The process employed a mixture
of water and ethanol as the reaction medium. It is a mild
and simple reaction under metal-, ligand-, and base-free
conditions. Further investigations to determine the mech-
anism of the reaction and to expand their scope are under
way in our laboratory.
(o) Patcharin, K.; Ekasith, S.; Raghu, N. D.; Hidehiro, S.
Tetrahedron Lett. 2012, 53, 6104. (p) Naveen, M.; Ismail;
Kottur, M. K.; Rajesh, K. R.; Bhaskar, K.; Pallavi, R.;
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(4) (a) Swern, D. Organic Peroxides; Wiley: New York, 1971.
(b) Plesnicar, B. Organic Chemistry; Academic Press: New
York, 1978.
(5) Tap water was applied. The same results were obtained from
ultrapure water.
Acknowledgment
We are grateful for financial support from the National Natural Sci-
ence Foundation of China (Grant 20972055, 21172080) and the
Fundamental Research Funds for the Central Universities (Grant
2011ZZ0005).
(6) (a) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett.
1998, 39, 2937. (b) Lam, P. Y. S.; Bonne, D.; Vincent, G.;
Clark, C. G.; Combs, A. P. Tetrahedron Lett. 2003, 44, 1691.
(7) General Procedure for the Hydroxylation of
Phenylboronic Acid
To the mixture of phenylboronic acid (0.5 mmol) in a H2O–
EtOH (1:2) solution (2 mL) in a round-bottom flask was
added MCPBA (0.5 mmol) at r.t. When phenylboronic acid
was completely consumed (monitored by TLC, 6 h), 0.1 M
aq NaHCO3 (5 mL) was added to the mixture. Then the
reaction mixture was extracted with EtOAc (2 × 15 mL).
The combined organic layer was washed with H2O (10 mL)
and brine (5 mL), dried over anhyd MgSO4, filtered, and
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel (PE–EtOAc = 4:1),
and the corresponding phenol was obtained as a colorless
solid (2a, 46 mg, 97%).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SuppInigfor
m
o
ti
References and Notes
(1) (a) Rappoport, Z. The Chemistry of Phenols; Wiley-VCH:
Weinheim, 2003. (b) Tyman, J. H. P. Synthetic and Natural
Phenols; Elsevier: New York, 1996.
(2) (a) Hoarau, C.; Pettus, T. R. R. Synlett 2003, 127.
(b) Hanson, P.; Jones, J. R.; Taylor, A. B.; Walton, P. H.;
Timms, A. W. J. Chem. Soc., Perkin Trans. 2 2002, 1135.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 499–501

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