An iodine-promoted, mild and efficient method for the synthesis of phenols from arylboronic acids

Article abstract of DOI:10.1055/s-0031-1290654

A mild and efficient methodology for the ipso-hydroxylation of arylboronic acids to phenols has been developed using aqueous hydrogen peroxide as oxidizing agent and molecular iodine as catalyst. The reactions were performed at room temperature in short reaction time under metal-, ligand- and base-free conditions. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290654

LETTER
1079
An Iodine-Promoted, Mild and Efficient Method for the Synthesis of Phenols
from Arylboronic Acids
S
ynthesis of Pheno
n
ls from Aryl
k
boronic
A
cid
u
s
r Gogoi, Utpal Bora*
Department of Chemistry, Dibrugarh University, Dibrugarh 786004, Assam, India
Fax +91(373)2370323; E-mail: utbora@yahoo.co.in
Received 6 January 2012
such as long reaction times,9,11 the use of ligand/base,7 and
Abstract: A mild and efficient methodology for the ipso-hydroxy-
lation of arylboronic acids to phenols has been developed using
aqueous hydrogen peroxide as oxidizing agent and molecular iodine
as catalyst. The reactions were performed at room temperature in
short reaction time under metal-, ligand- and base-free conditions.
the need for toxic chlorinated organic solvents.8 Thus, the
development of catalytic systems that are readily accessi-
ble, air and moisture stable, inexpensive, environmentally
acceptable, and that can promote these reactions under
mild reaction conditions are still desirable. Aqueous hy-
drogen peroxide is well-known as a stoichiometric, envi-
ronmentally friendly oxidant that shows a high efficiency
per weight of oxidant.12 Moreover, for a long time, iodine
has been recognised as a good catalyst and reagent in or-
ganic chemistry.13 In the present study, we wish to report
the use of iodine as an extremely powerful promoter for
oxidative ipso-hydroxylation of arylboronic acids at room
temperature under metal-, ligand- and base-free condi-
tions.
Key words: arylboronic acid, phenol, hydroxylation, hydrogen
peroxide, iodine
Phenol compounds and derivatives have been found in nu-
merous natural products and are well-known precursors
for the synthesis of pharmaceuticals, polymers, and natu-
rally occurring compounds.1 Consequently, the synthesis
of phenols continues to attract the attention of organic
chemists and a wide variety of methods have been devel-
oped their synthesis over the years. Among the approach-
es, nucleophilic aromatic substitution of aryl halides,
copper-catalyzed transformation of diazoarenes, and ben-
zyne protocols are dominant.2 However, these methods
can suffer from disadvantages such as harsh reaction con-
ditions, and diazotization requires conversion of the ami-
no groups into diazoarenes, which is often not compatible
with many other functional groups. There are some re-
ports on the conversion of aryl bromides and chlorides
into phenols in the presence of palladium-based catalysts
and phosphine ligands.3 Moreover, aryl iodides have been
converted into the corresponding phenols in the presence
of a copper catalyst using non-phosphine ligands4 at ele-
vated temperature. In recent years, arylboronic acid deriv-
atives have immerged as one of the most powerful
synthons in organic chemistry.5 Interestingly, although
phenols have been found as by-products in many metal-
catalyzed reactions of arylboronic acids,6 there are very
few reports available that deal with methodologies for hy-
droxylation of arylboronic acids. The innocuous nature of
arylboronic acids, which are generally non-toxic, stable to
heat, air, and moisture, and are availability in a wide range
of phenylboronic acid derivatives, make them an interest-
ing and valuable potential precursor of phenols. There are
some reports in which CuSO4-phenanthrolin,7 H2O2-
poly(N-vinylpyrrolidone),8 NH2OH,9 potassium peroxy-
monosulfate,10 or aqueous hydrogen peroxide11 have been
effectively utilized for the hydroxylation of arylboronic
acid. These strategies, however, have some disadvantages
To investigate the effectiveness of hydrogen peroxide
(30% aqueous) in the hydroxylation reaction, phenylbo-
ronic acid (1a; 1 mmol) was chosen as a model substrate
and the reactions were performed under aerobic condi-
tions at room temperature; the results are summarized in
Table 1. When a mixture of 1a (1 mmol) and aqueous hy-
drogen peroxide (2 mL) was stirred at room temperature
for 1 h, only a trace amount of phenol (2a) was obtained
(Table 1, entry 1). The insolubility in water of most of the
reagents and substrates restricts their use in water as a sol-
vent. Therefore, we carried out the reaction in acetonitrile
and the yield of phenol 2a was slightly increased (Table 1,
entry 2). Interestingly, the yield of 2a was elevated to 85%
within 1 h in the presence of iodine (20 mol%; Table 1,
entry 3). We carried out the reaction between phenylbo-
ronic acid and aqueous hydrogen peroxide in the presence
of various solvents by using iodine as reaction promoter.
The reaction was found to proceed in both protic and apro-
tic solvents, although variations in yields were observed
(Table 1, entries 3–9). Similarly, 50% aqueous tetrahy-
drofuran (THF), aqueous acetonitrile, and aqueous meth-
anol gave comparable results (Table 1, entries 7–9) under
the same reaction conditions. However, the use of dichlo-
romethane as solvent provided reduced yields (Table 1,
entry 6). We obtained the best result by using iodine and
aqueous hydrogen peroxide without using any solvent
(Table 1, entry 10). Several test reactions were carried out
using different amounts of iodine and hydrogen peroxide
to establish the optimal amount of catalyst required for
this transformation. It was observed that 5 mol% iodine
was sufficient for smooth oxidation of 1.0 mmol of the
substrate (Table 1, entries 10–15). The reaction did not
proceed in the absence of hydrogen peroxide (Table 1, en-
SYNLETT 2012, 23, 1079–1081
x
x
.
x
x
.
2
0
1
2
Advanced online publication: 28.03.2012
DOI: 10.1055/s-0031-1290654; Art ID: B01112ST
© Georg Thieme Verlag Stuttgart · New York

1080
A. Gogoi, U. Bora
LETTER
try 16). However, the reaction gave phenol (2a) in good Kuivila15 and Kianmehr.9 It is reported that the reaction
yield in the absence of iodine when the reaction time was between hydrogen peroxide and iodine in neutral medium
extended to 36 h (Table 1, entry 17).
leads to the formation of hypoiodous acid (HOI).16 Hy-
poiodous acid could then react with phenylboronic acid to
form adduct A. Removal of HI and subsequent phenyl mi-
gration to the oxygen generates adduct B. Finally, hydrol-
ysis of adduct B leads to the formation of phenol. Excess
hydrogen peroxide in the reaction medium facilitates the
regeneration of iodine from hydroiodic acid.
Table 1 Optimization of Reaction Conditions for Iodine-Mediated
ipos-Hydroxylationa
OH
I2/H2O2 (30% aq)
OH
B
r.t.
OH
1a
2a
Entry Oxidant Solvent
Catalyst
Time Yield
(min) (%)b
H2O2 + I2
2HOI
– HI
OH
–B OH
+O
OH
B(OH)2
1
2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O2
H2O
–
–
–
60
60
04
O
I
MeCN
MeCN
MeOH
THF
07
B
H
A
3
I2 (20 mol%) 50
I2 (20 mol%) 50
I2 (20 mol%) 50
I2 (20 mol%) 70
I2 (20 mol%) 50
85
Scheme 1
4
82
Table 2 Iodine-Catalyzed Synthesis of Phenolsa
5
81
OH
I2/H2O2 (30% aq)
6
CH2Cl2
75
B
OH
r.t.
R
R
OH
7
THF–H2O (1:1)
85
Entry
1
R
Time (min)
Yield (%)b,c
8
MeCN–H2O (1:1) I2 (20 mol%) 50
MeOH–H2O (1:1) I2 (20 mol%) 50
80
H
45
45
30
45
30
30
50
60
35
50
60
50
93
91
90
91
92
92
90
91
87
88
85
84
80
9
82
2
p-OMe
o-OMe
m-OMe
o-Me
10
11
12
13
14
15
16
17
–
–
–
–
–
–
–
–
I2 (20 mol%) 45
I2 (15 mol%) 45
I2 (10 mol%) 45
92
3
90
4
90
5
I2 (5 mol%)
I2 (3 mol%)
I2 (5 mol%)
45
60
60
93
6
p-Me
85
7
p-Cl
80c,d
trace
80c
8
p-COMe
o-NO2
p-CHO
p-NH2
p-OH
I2 (20 mol%) 60
– 36 h
9
H2O2
10
11
12
13
a Reagents and conditions: phenylboronic acid (1 mmol), H2O2 (30%
aq, 2 mL), solvent (2 mL), ca 28 °C.
b Isolated yields.
c The reaction did not reach completion.
d H2O2 (1 mL) was used
thiophene-2-boronic acid 120
a Reagents and conditions: ArB(OH)2 (1 mmol), I2 (5 mol%), H2O2
(30% aq, 2 mL), ca 28 °C.
To evaluate the scope and limitations of the current proce-
dure, the reactions of a wide array of electronically di-
verse arylboronic acids were examined using iodine as
catalyst (Table 2).14 In general, arylboronic acids with ei-
ther electron-withdrawing or electron-donating substitu-
ents such as OMe, Me, Cl, COMe, NO2, CHO, NH2, OH
(Table 2, entries 2–12) underwent the ipso-hydroxylation
reaction in good yields (80–93%). It was observed that a
variety of substituents were tolerated on the aromatic sub-
strate. The reaction was also compatible with heteroaryl-
boronic acid (Table 2, entry 13).
b Yield of isolated product.
c All compounds were characterized by 1H NMR, 13C NMR, FT-IR
and MS.
In conclusion, we have developed a mild and efficient
methodology for the ipso-hydroxylation of arylboronic
acids to the corresponding phenol using aqueous hydro-
gen peroxide as oxidizing agent and molecular iodine as
catalyst. Advantages of the protocol are that it operates at
room temperature under mild reaction conditions in short
reaction time without requiring metal, ligand or base.
A mechanistic path for the reaction is proposed in
Scheme 1, following the mechanism proposed by
Synlett 2012, 23, 1079–1081
© Thieme Stuttgart · New York

LETTER
Synthesis of Phenols from Arylboronic Acids
1081
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Acknowledgment
We wish to thank the Department of Science and Technology, New
Delhi for financial support (NO. SR/FTICS-0098/2009). A.G.
thanks the Department of Science and Technology, New Delhi for
an INSPIRE research fellowship.
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Procedure: A 50 mL round-bottom flask was charged with
arylboronic acid (1 mmol), 30% aqueous H2O2 (2 mL) and
iodine (5 mol%) and the reaction mixture was stirred at room
temperature. After completion of the reaction (TLC) the
reaction mixture was diluted with water (20 mL) and
extracted with diethyl ether (3 × 15 mL). The ether extract
was washed with sodium thiosulfate solution (10 mL). The
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