A practical method for preparation of phenols from arylboronic acids catalyzed by iodopovidone in aqueous medium

Article abstract of DOI:10.1016/j.tetlet.2019.06.018

A novel and efficient strategy for the ipso-hydroxylation of arylboronic acids to phenols has been developed using inexpensive, readily available, air-stable water-soluble povidone iodine as catalyst and aqueous hydrogen peroxide as oxidizing agent. The reactions were performed at room temperature under metal-, ligand- and base-free condition in a short reaction time. The corresponding substituted phenols were obtained in moderate to good yields by oxidative hydroxylation of arylboronic acids in aqueous medium.

Full text of DOI:10.1016/j.tetlet.2019.06.018

Accepted Manuscript
A Practical Method for Preparation of Phenols from Arylboronic Acids Cata-
lyzed by Iodopovidone in Aqueous Medium
Guangying Lu, Yaoyao Ren, Bin Dong, Bin Zhou, Jiangmeng Ren, Yanxiong
Ke, Bu-Bing Zeng
PII:
S0040-4039(19)30557-X
https://doi.org/10.1016/j.tetlet.2019.06.018
TETL 50859
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
9 April 2019
24 May 2019
10 June 2019
Please cite this article as: Lu, G., Ren, Y., Dong, B., Zhou, B., Ren, J., Ke, Y., Zeng, B-B., A Practical Method for
Preparation of Phenols from Arylboronic Acids Catalyzed by Iodopovidone in Aqueous Medium, Tetrahedron
Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.06.018
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A Practical Method for Preparation of
Phenols from Arylboronic Acids Catalyzed
by Iodopovidone in Aqueous Medium
Leave this area blank for abstract info.
a
a
a
a
a
b
a
Guangying Lu , Yaoyao Ren , Bin Dong , Bin Zhou , Jiangmeng Ren , Yanxiong Ke , and Bubing Zeng
OH Povidone Iodine (0.03 eq.)
R
R
B
OH
H O (30% aq), r.t.
OH
2
2
Yields up to 99%
EDGs and EWGs were well toleranted

1
Tetrahedron Letters
journal homepage: www.elsevier.com
A Practical Method for Preparation of Phenols from Arylboronic Acids Catalyzed by
Iodopovidone in Aqueous Medium
a
a
a
a
a
b,
Guangying Lu , Yaoyao Ren , Bin Dong , Bin Zhou , Jiangmeng Ren , Yanxiong Ke , and Bu-Bing
Zeng 
a,
a
School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. of China
Engineering Research Centre of Pharmaceutical Process Chemistry, School of Pharmacy, East China University of Science and Technology, 130 Meilong
b
Road, Shanghai 200237, P. R. of China
—
——
ARTICLE INFO
ABSTRACT


Corresponding author. Tel.: 021-64253689; e-mail: zengbb@ecust.edu.cn
Corresponding author. Tel.: 021-64250622; e-mail: key@ecust.edu.cn
Article history:
Received
A novel and efficient strategy for the ipso-hydroxylation of arylboronic acids to phenols has
been developed using inexpensive, readily available, air-stable water-soluble povidone iodine as
catalyst and aqueous hydrogen peroxide as oxidizing agent. The reactions were performed at
room temperature under metal-, ligand- and base-free condition in a short reaction time. The
corresponding substituted phenols were obtained in moderate to good yields by oxidative
hydroxylation of arylboronic acids in aqueous medium.
Received in revised form
Accepted
Available online
Keywords:
Arylboronic acid
Oxidation
2
009 Elsevier Ltd. All rights reserved.
ipso-hydroxylation
Povidone iodine
Phenols are important synthetic intermediates and are widely used in the synthesis of pharmaceuticals, polymers, and natural
products. Many biologically active compounds, ranging from natural products to pharmaceuticals were reported to possess phenols in
monomeric or polymeric forms.1,2 The synthesis of phenols therefore continues to attract the attention of organic chemists, and various
methods for their preparation have been developed in which the preparation of phenols from arylboronic acids is more acceptable as
compared to the conventional transformations using aryl halides or aryl diazonium salts as substrates. Since the oxidation of arylboronic
acid and its derivatives to phenols was firstly reported by Ainley and Challenger using alkaline hydrogen peroxide and was further
3
-5
modified by Kuivila and Olah, a number of methods for the transformation of arylboronic acids to phenols have been reported in
6
7
recent time using either metal-catalyzed systems, such as magnetic CuFe
amphiphilic surfactant catalytic system, Cu-II--Cyclodextrin complex nano-catalyst, CuSO
2
O
4
nanoparticles, Cu
2
O/NH
3
,
CuCl
2
/Brij S-100/O
2
10
8
9
4
/ 1,10-phenanthroline catalytic system,
1
1
12
13
CuSO
irradiation,
Pd(Ligang)Cl
4
•5H
2
1
O/Ellagic acid catalytic system, clay entrapped Cu(OH)
x
,
2 3
Cu complex/visible light/air, -Fe O /visible light
4
15
16
17
nano-Ag/mont K-10/H
2
O
2
20
,
Ag/zeolite nanocomposite/H
2
O
2
,
[Ru(bpy)
3
Cl
2
2
]·6H O/visible light irradiation,
1
8
,19 Zr-MOF, or metal-free catalytic oxidative systems such as MeNHNH
21
2
,
acidic Al
2
O
3
2
/air, methylene blue/light
,2 N(Et)
2
/ UV-visible light irradiation/O
,
23
Flavinium catalyst/N
H
·H
2
O/CF
CH
OH-CH
OH/O
,
24
PhI/NaIO
25
irradiation/O
PhI(OAc) /Et
and NaClO
polymer-supported oxidative systems have also been developed, such as AuNPs/PVP/air,
2
3
2
2
4
34
3
2
3
2
4
,
N,26-28 NH
HCO
/H
2
O
,
29
O
,
30
I
-H
2
O
,
31
32
33
® 35-37
amine oxide , benzoquinone,
38
39
2
3
4
3
2
3
2
2
2
NH OH, TBHP, m-CPBA, Oxone ,
4
0
2
.
Besides these known metal and metal-free catalyzed protocols, the ipso-hydroxylation of arylboronic acids using
4
1
42
2 4 2 2
N H /PEG-400/air, H O Amberlite IR-
4
3
44
1
20, PVD-H
2 2
O complex [PVP = poly(N-vinyl-2-pyrrolidone)].
The continuous concern with this conversion is necessary, as a supplement for the conversion of arylboronic acids to phenols. The
development of catalytic systems that are readily accessible, air and moisture stable, high yield, inexpensive, environmentally
acceptable, and that can promote these reactions under mild reaction conditions are still attractive. As a stoichiometric, environmentally
friendly and commercial available oxidant, aqueous hydrogen peroxide shows an advantage of high efficiency in certain oxidative
4
5
reactions. Olah et. al. developed a convenient and efficient reagent system for the ipso-hydroxylation of arylboronic acids to the
4
4,3
corresponding phenols using hydrogen peroxide and a solid PVD-H
2
O
2
complex in 2001 and 2009, respectively.
Polyvinylpyrrolidone (PVP, povidone) is a water-soluble polymer made from the monomer of N-vinylpyrrolidone, that is used as a
dispersing and suspending agent and can be easily recovered and recycled. Povidone iodine (PVP-I, Iodopovidone) is widely used in
clinical as antiseptic agent for the treatment of skin disinfection before and after surgery.
To the best of our knowledge, no iodopovidone catalyzed hydroxylation of aryl/alkylboronic compounds has been reported so far.
Herein, we would like to report the efficient, environmentally friendly protocol for iodopovidone catalyzed hydroxylation of
arylboronic acids using hydrogen peroxide as oxidant.

2
Tetrahedron
Table 1Optimization of the reaction conditions
OH
Povidone Iodine
B
OH
H O (30% aq), r.t.
2
2
OH
1a
2a
Cat.
eq.)
T
Yield
(h) (%)
Entry
Oxidant
-
Solvent
Base
b
(
1
2
3
4
5
6
7
8
9
H
H
H
H
H
2
2
2
2
2
O
O
O
O
O
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
0.03
-
1
1
1
1
1
1
1
1
1
1
1
0
H
H
2
O
O
2
73
93
73
Trace
14
23
68
59
37
2
2
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.01
0.05
0.03
0.03
0.03
TBHP
m-CPBA
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
THF
MeCN
EtOH
i-PrOH
DMF
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
c
i-PrOH
67
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
O
O
O
O
O
O
O
O
0.5 87
1.5 91
2
1
1
1
1
1
90
85
92
94
46
81
KOH
Cs
K
2 3
CO
2
CO
3
a
2 2
O
(30% aq, 1 mL), solvent (2 mL), ca 30 °C. b Isolated yields, c i-
Reagents and conditions: phenylboronic acid (5 mmol), H
PrOH/H O = 1:1 (v/v).
2
As shown in Table 1, phenylboronic acid was chosen as the model substrate at room temperature to optimize the reaction conditions
including the amount of catalyst, oxidants, solvents, and bases. An initial screening revealed that iodopovidone catalyzed hydroxylation
did not proceeded in the absence of hydrogen peroxide(Table 1, entry 1), and phenylboronic acid was oxidized into phenol with the
yield of 73% using hydrogen peroxide in the absence of iodopovidone (Table 1, entry 2). Interestingly, the yield of phenol increased
dramatically to 93% within 1 h when the reaction was catalyzed by iodopovidone in the presence of aqueous hydrogen peroxide (Table
1
, entry 3), the yields were not obviously improved when the same reaction was carried out using TBHP or m-CPBA in the replacement
of aqueous hydrogen peroxide (Table 1, entries 4 and 5), the possible reason is that m-CPBA is insoluble in water. The use of other
solvents including THF, MeCN, EtOH, iso-propanol, DMF and 1:1 aqueous iso-propanol were examined and found to be ineffective
(Table 1, entries 6-11). In addition, the yields were ranged from 87% to 91% under the same condition when the reaction time was
shortened to 30 min or extended to 1.5 h or 2 h (Table 1, entries 12-14). Several trials were carried out using different loading amounts
of iodopovidone and hydrogen peroxide to further establish the optimal amount of catalyst/oxidant required for this transformation. It
was observed that 0.03 equiv. of iodopovidone was sufficient for smooth transformation of phenylboronic acid to phenol (Table 1,
2 3 2 3
entries 3, 15 and 16). The addition of different bases such as KOH, Cs CO and K CO in the reaction resulted in a dramatic fluctuation
in the reaction outcomes. Therefore, the use of base was ignored in this study with the consideration of hydroxylation products and
work-up operation. Thus, the optimal reaction condition was determined as follows: 1a (5 mmol, 1.0 equiv.), iodopovidone (0.03 equiv.
of effective iodine), aqueous hydrogen peroxide (1.0 mL) and room temperature， in comparing with the optimal condition reported by
3
1
Bora,
In order to evaluate the scopes and limitations of current procedure, the investigations were extended to additional substrates with the
multiple functional groups for the exploration of the substrate, and the results were summarized in Table 2. The successful of the
iodoprovdone catalyzed hydroxylation of various arylboronic acids demonstrated the excellent functional group tolerance of the
protocol developed in the present study. It was noteworthy that the biphenylboronic acid and 2-naphthylboronic acid proceed well to
give corresponding products with excellent yield up to 97.7% yield (Table 2, entries 2 and 3). Phenyl ring bearing electron donating
group (Table 2, entries 4-9) and electron withdrawing group (Table 2, entries 10-16) had less effect on the production yields suggesting
that electron density is not the main influencing factor for this oxidative transformation. Halide-substituted arylboronic acid could also
give the desired product in good yield (Table 2, entry 17). It was interesting that some arylboronic acids with sensitive substituents also
give the product in excellent yield under the current reaction condition (Table 2, entries 18 and 19). Arylboronic acids with ortho-fluoro
substituted gave lower yield of around 75% (Table 2, entries 20 and 21), while the production yields were excellent when fluorine
attached on meta- or para-position of the arylboronic acids (Table 2, entries 22 and 23).
Table 2 Synthesis of Phenols Catalyzed by Povidone Iodine
OH
R
R
Povidone Iodine
B
OH
H O (30% aq), r.t.
OH
2
2
1
2
Yield (%)b, c
Entry
1
Product
3
6
44
31
19
40
11
9
3 (86 , 97 , 93 , 92 , 98 , 92 )
OH
2a

3
1
0
17
12
9
9
4 (95 , 94 , 88 )
2
3
OH 2b
3
2
18
7
43
38
17
40
7.7 (46 , 82 , 80 , 86 , 94 , 87 , 91 , 89)
2c
HO
HO
NHAc
9
8
3
4
5
6
2d
2e
5
O
OH
HO
2f
86.4
OBn
9
9
2
7
8
HO
HO
OCF3
2
g
3
8
19
7.3 (97 , 98 )
CMe3
CH3
2h
3
1
9
9 (82 )
9
HO
HO
2i
CH3
CF3
2j
98.6
1
0
CF3
NO2
1
8
33
19
40
34
9
9
0 (70 , 95 , 87 , 87 , 97 )
1
1
1
2
2
k
HO
HO
HO
1
0
18
12
19
2(84 , 75 , 82 , 94 )
NO2
2l
2
m
7
3.4
1.5
1
3
CN
9
9
9
1
1
1
4
5
6
HO
SO CH 2n
2
3
O
3
3
44
8
31
40
7 (63 , 80 , 64 , 91 , 90 )
HO
HO
2o
8
40
5 (67 , 90 )
CO Et 2p
2
Br
Br
4
6
9
8
5.2 (87 )
1
1
7
8
HO
2q
O
8
2r
N
OH
H

4
Tetrahedron
2
s
95
1
2
9
0
S
OH
F
F
7
7
8
4
HO
HO
2t
OMe
2
2
1
2u
F
F
F
4
0
9
9
3.5 (85 )
2
3
HO
HO
F
F
2
v
2w
0
2
CH3
a
Reagents and conditions: ArB(OH)
2
2 2 2
(5 mmol), PVP-I (0.03 equiv. of effective iodine), H O (30% aq, 1 mL), H O (2 mL), ca 30
b
c
°
C. Yield of isolated product. Numbers in parentheses are the literature values.
The catalytic mechanism of reaction is similar to that of depicted by Bora.31 What needs to be pointed out is that the current optimal
condition is more efficient than that of Bora’s condition, (more substrates loading amount and less effective iodine and hydrogen
peroxide usage). The reasonable explanation is that povidone (PVD) can form complexes with hydrogen peroxide and iodine
simultaneously, and it reduces the decomposition of hydrogen peroxide and loss of iodine in catalytic cycles.
In conclusion, a mild and efficient catalytic oxidative ipso-hydroxylation of arylboronic acids to the corresponding phenol catalyzed
by povidone iodine has been developed using hydrogen peroxide in aqueous medium. This transformation proceeded smoothly with
wide substrate scope, simple work-up procedure, ambient-pressure, short reaction time and room temperature conditions. Further
exploration of this new catalyst system in other types of reactions is underway in our laboratory.
Acknowledgments
This work was financially supported by Science and Technology Commission of Shanghai Municipality (14DZ1900102) and the
Fundamental Research Funds for the Central University (WY1113007).
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Graphical Abstract
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A Practical Method for Preparation of
Phenols from Arylboronic Acids Catalyzed
by Iodopovidone in Aqueous Medium
Leave this area blank for abstract info.
a
a
a
a
a
b
a
Guangying Lu , Yaoyao Ren , Bin Dong , Bin Zhou , Jiangmeng Ren , Yanxiong Ke , and Bubing Zeng
OH Povidone Iodine (0.03 eq.)
R
R
B
OH
H O (30% aq), r.t.
OH
2
2
Yields up to 99%
EDGs and EWGs were well toleranted
Highlight
ipso-Hydroxylation of arylboronic acids were catalyzed by PVP-I in aqueous H O
2
2
Sensitive substrates were well tolerated under PVP-I and H O condition
2
2
Mild condition and simple work-up procedure benefit this oxidative transformation