A mild conversion of arylboronic acids and their pinacolyl boronate esters into phenols using hydroxylamine

Article abstract of DOI:10.1016/j.tetlet.2007.02.069

Hydroxylamine was found to be a mild reagent for conversion of arylboronic acids and their pinacolyl boronate esters into phenols. This procedure works on most arylboronic acids at room temperature, yielding phenols in moderate to good yields, and efficiently on arylboronates also yielding phenols in good yields.

Full text of DOI:10.1016/j.tetlet.2007.02.069

Tetrahedron Letters 48 (2007) 2713–2715
A mild conversion of arylboronic acids and their pinacolyl
boronate esters into phenols using hydroxylamine
Ebrahim Kianmehr,* Maryam Yahyaee and Katayoun Tabatabai
School of Chemistry, University College of Science, University of Tehran, Tehran 14155-6455, Iran
Received 5 November 2006; revised 7 February 2007; accepted 14 February 2007
Available online 17 February 2007
Abstract—Hydroxylamine was found to be a mild reagent for conversion of arylboronic acids and their pinacolyl boronate esters
into phenols. This procedure works on most arylboronic acids at room temperature, yielding phenols in moderate to good yields,
and efficiently on arylboronates also yielding phenols in good yields.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
as oxone7 and sodium perborate8 can also be employed
for the oxidation of boronic acid derivatives. However,
a new general, mild and easy to handle reagent for con-
version of arylboronic acids and esters to phenols is still
required.
Phenols serve as synthetic building blocks and interme-
diates for the construction of important molecules rang-
ing from polymers to pharmaceuticals1 and due to the
importance of their derivatives, much attention has been
focused on their synthesis.2 One of the key features of
organoboranes is that they can be prepared containing
a wide variety of functional substituents. Boronic acids
and esters are mild organic Lewis acids and their reactiv-
ity profile, coupled with their stability and ease of han-
dling, make them a particularly attractive class of
synthetic intermediates.3 Although the oxidation of aryl-
boronic acids is not a popular or economical approach
for preparing phenols, it gives access to phenols that
might be difficult to obtain by other means. It was re-
cently reported that a one-pot C–H borylation/oxida-
tion sequence gives access to meta-substituted phenols
that would be difficult to obtain by other methods.4
To the best of our knowledge there are only a few meth-
ods described in the literature for the conversion of aryl-
boronic acids into phenols. Treatment of arylboronic
acids and esters with alkaline hydrogen peroxide was
first reported by Ainley and Challenger5 and later mod-
ified by Petasis and co-workers6 but when sensitive sub-
stituents are present, alkaline hydrogen peroxide can
lead to undesirable side reactions. Milder oxidants such
We were aware of a variety of different ipso-substitution
reactions of arylboronic acids.9 Considering the mecha-
nism proposed by Kuivila,10 Scheme 1, we were inter-
ested in using a substitute for hydrogen peroxide with
similar structure but different oxidative properties.
Hydroxylamine is cheap and easy to handle as its hydro-
chloride salt so we considered the reactions of arylbo-
ronic acids with hydroxylamine, produced in situ from
hydroxylammonium chloride and sodium hydroxide.
The results are summarized in Table 1 (entries 12–21).
As can be seen from the Table, the corresponding phe-
nols were typically obtained in moderate to good yields.
However, in the case of arylboronic acids having
strongly electron-withdrawing groups, the yields were
lower. Ethanol or water could be used as the solvent.
Boronic acids are often best handled as ester derivatives,
in which the two hydroxyl groups are masked, and
hence are less polar and easier to handle, using boronate
esters instead of boronic acids may also influence the
efficiency of the reaction.11 This Letter also describes
our efforts to use boronate esters in this reaction and
the results are summarized in Table 1 (entries 1–11).
As can be seen from the Table, in most cases the prod-
ucts were obtained in good to excellent yields. The best
results were obtained with those involving derivatives
containing electron-donating groups.
Keywords: Arylboronic acid; Arylboronate ester; Phenol;
Hydroxylamine.
*
Corresponding author. Tel.: +98 21 61112726; fax: +98 21
66495291; e-mail: kianmehr@khayam.ut.ac.ir
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.02.069

2714
E. Kianmehr et al. / Tetrahedron Letters 48 (2007) 2713–2715
-
-
OH
OH
HOO
-
-
OB(OH)2
OH
B(OH)2
B
OH
OH
O
Scheme 1.
Table 1. Conversion of arylboronic acids and esters into phenols using NH2OHÆHCl:NaOH (1.1 equiv:1.5 equiv and 1.5 equiv:2.0 equiv,
respectively) in ethanol at room temperaturea
O
O
OH
Ar B
OH
Ar B
Ar OH
Ar OH
1
2
Entry
Ar, 1
Time (h)
Yield (%)
Entry
Ar, 2
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Phenyl, 1a
23
18
18
18
25
48
48
48
23
48
48
57
81
94
92
67
63
71
52
69
86
—
12
13
14
15
16
17
18
19
20
21
Phenyl, 2a
26
24
25
23
48
26
48
26
27
24
68
53
82
86
48
46
Trace
32
91
4-Bromophenyl, 1b
3,5-Dimethylphenyl, 1c
3-Methylphenyl, 1d
3-Fluorophenyl, 1e
4-Chlorophenyl, 1f
2-Naphthyl, 1g
3-Nitrophenyl, 1h
2,4-Dichlorophenyl, 1i
4-Methoxyphenyl, 1j
4-Acetylphenyl, 1k
4-Bromophenyl, 2b
3,5-Dimethylphenyl, 2c
3-Methylphenyl, 2d
4-Chlorophenyl, 2e
2-Naphthyl, 2f
3-Nitrophenyl, 2g
4-Fluorophenyl, 2h
4-Methoxyphenyl, 2i
4-Acetylphenyl, 2j
10
11
—
a All the products and starting arylboronic esters are known compounds apart from 1e and 1i. These were characterized by physical and spectral
analysis (see Supplementary data).
To investigate the reaction mechanism, we first consid-
ered the source of phenolic oxygen. For this reason,
the reactions were conducted in the absence of oxygen,
under a nitrogen atmosphere, and in degassed solvent.
Under the above mentioned conditions no difference
was observed in the yields and times of the reactions.
To make sure that only the hydroxylamine oxygen was
the source for phenolic oxygen, the reactions were
repeated using hydrazinium hydroxide. Under these
conditions no phenolic compound was observed. Also,
addition of NaOH was necessary and the reactions
failed to proceed with hydroxylammonium chloride
alone. A mechanistic rationalization is provided in
Scheme 2, following the mechanism proposed by Kuiv-
ila.10 Another possibility is that the products arise from
addition of the nitrogen of hydroxylamine to boron (A
in Scheme 2) followed by phenyl migration to the oxy-
gen of hydroxylamine through a four membered TS.
This was explored using H2NOCH3 in place of hydrox-
ylamine, however, with this reagent the reaction failed to
proceed and the expected anisole derivatives were not
observed.
In summary, we have successfully carried out the con-
version of arylboronic acids and esters into phenols in
good yields using hydroxylamine hydrochloride and
sodium hydroxide, which is an easy to handle reagent
system, under very mild reaction conditions.
2. Typical procedure
To a solution of arylboronic acid (1.0 equiv) or arylbo-
ronic ester (1.0 equiv) in ethanol, hydroxylammonium
chloride (1.1 equiv or 1.5 equiv) and sodium hydroxide
(1.5 equiv or 2.0 equiv) were added and the mixture was
stirred at room temperature for 18–48 h. The reaction
progress was monitored by TLC. Work-up of the reaction
involved evaporating the solvent under reduced pressure,
then extraction with dichloromethane. The solvent was
removed under vacuum and the product was purified by
column chromatography (silica gel, Merck 230–400
mesh) using hexane–ethyl acetate (9:1) as eluent. Forma-
tion of the required pinacolyl esters was easily achieved by
reaction of the boronic acids with pinacol in ether.12
OH
OH
OH
-
NH2OH
NH2OH
-
-
B
OH
B(OH)2
B
+
OH
NH2
B
OH
H
O
NH3
O
N
+
+
H
HO
H
-
NH3
A
OH
OB(OH)2
Scheme 2.

E. Kianmehr et al. / Tetrahedron Letters 48 (2007) 2713–2715
2715
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Acknowledgements
Financial support by the research council of the Univer-
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Supplementary data
Characterization data of 1i and 1e. Supplementary data
associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2007.02.069.
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