Selective oxidative hydroxylation of arylboronic acids by colloidal nanogold catalyzed in situ generation of H2O2 from alcohols under aerobic conditions

Article abstract of DOI:10.1246/BCSJ.20190265

Selective hydroxylation of arylboronic acids was achieved through PVP (polyvinylpyrrolidone)-stabilized nanogold catalyzed in situ generated H₂O₂ formed by the oxidation of an alcoholic solvent under aerobic conditions. The synthetic application of in situ generated H₂O₂ was investigated through aerobic epoxidation of (E)-chalcone.

Full text of DOI:10.1246/BCSJ.20190265

Advance Publication Cover Page
Selective Oxidative Hydroxylation of Arylboronic Acids by Colloidal Nanogold Catalyzed in
Situ Generation of H2O2 from Alcohols Under Aerobic Conditions
Vinsen, Yuta Uetake, and Hidehiro Sakurai*
Advance Publication on the web December 18, 2019
doi:10.1246/bcsj.20190265
© 2019 The Chemical Society of Japan
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Selective Oxidative Hydroxylation of
Arylboronic Acids by Colloidal
Nanogold Catalyzed in Situ Generation
of H2O2 from Alcohols Under Aerobic
Conditions
Scheme 1. Aerobic Au:PVP catalyzed reaction of phenylboronic
acid (1a)
Vinsen, Yuta Uetake, Hidehiro Sakurai*
To confirm whether alcohol plays a role in determining the
selectivity of hydroxylation, EtOH and water at various ratios
were employed as solvent (Table 1, entries 1–5). In all cases,
quantitative conversion was observed at 27 °C after 15 h, and
higher EtOH ratios resulted in higher selectivity towards
hydroxylation. When the reaction was carried out without oxygen,
no reaction occurred, which was consistent with our previous
results4 that oxygen is indispensable (entry 6). After revealing the
effect of EtOH in promoting selective hydroxylation, we tested
various alcohols in hope to achieve higher selectivity (entries
7–12). Primary and secondary alcohols were found to be suitable
solvents to achieve selective hydroxylation. 2-PrOH provided the
highest selectivity, with nearly quantitative hydroxylation (entry
10). The use of MeOH (entry 7) and the highly acidic
trifluoroethanol (entry 12) resulted in product yields close to that
in water. t-BuOH resulted in poor conversion and selectivity
(entry 11). These results indicate that the reducing ability of the
solvent plays a significant role in the reaction mechanism.
Division of Applied Chemistry, Graduate School of Applied
Chemistry, Osaka University, 2-1 Yamadaoka, Suita, Osaka
565-0871, Japan
Received Month Date, Year;
E-mail: hsakurai@chem.eng.osaka-u.ac.jp
Selective hydroxylation of arylboronic acids were achieved
through
PVP (polyvinylpyrrolidone)-stabilized
nanogold
catalyzed in situ generated H2O2 formed by the oxidation of an
alcoholic solvent under aerobic conditions. The synthetic
application of in situ generated H2O2 was investigated through
aerobic epoxidation of (E)-chalcone.
Since the seminal work by Haruta et al.1 on the oxidation of
CO by nano-sized gold, interest in nanogold as catalysts has
exponentially increased over the past few decades. Amongst the
myriad of nanogold catalyzed reactions, oxidation reactions
remain as a central theme. Previously, we have reported PVP
(polyvinylpyrrolidone)-stabilized gold nanoclusters (Au:PVP)
catalyzed reactions.2–6 In all of these cases, nanogold-catalyzed
Table 1. Optimization of solvent
oxidations play
a key role. In the Au:PVP catalyzed
homocoupling of arylboronic acids, hydroxylation into phenols
cannot be avoided under basic conditions.4 Therefore, several
approaches to achieve selective homocoupling were developed,
such as employment of chitosan as a stabilizing agent7 or HAP as
a solid support.8 Selective hydroxylation of arylboronic acids3 by
the Au-catalytic system has also been thoroughly investigated.
However, these examples utilize an additional reductant9–11,
electrolytic,12 or photoredox catalysis.13,14 In many cases, in situ
generation of H2O2 through the reduction of O2 by reductant (e.g.
H2,15 NH4HCO29) is involved in the mechanism. We envisioned
that as alcohols are readily oxidized by Au:PVP,5,6 it could act as
both solvent and reductant. Here, we report a more selective and
simpler alternative to achieve selective hydroxylation through in
situ generation of H2O2 from oxidation of an alcoholic solvent by
the Au:PVP catalytic system.
We started our investigation by switching the solvent of
Au:PVP catalyzed homocoupling of phenylboronic acid (1a) from
water to EtOH using K2CO3 as a base (Scheme 1). However, this
resulted in mediocre conversion with poor selectivity. When the
base was changed to KOH, the reaction was completed to afford a
phenol (2a) and a biphenyl (3a) in 89% and 11% yields,
respectively.
Recovery and Yield (%)a
Entry
Solvent
1a
0
0
0
0
0
>99
0
0
0
2a
31
58
65
73
89
0
25
91
90
99
0
3a
69
42
35
27
11
trace
75
9
10
1
2
3
4
5
6b
7
8
H2O
H2O/EtOH (3:1)
H2O/EtOH (1:1)
H2O/EtOH (1:3)
EtOH
EtOH
MeOH
1-PrOH
1-BuOH
2-PrOH
t-BuOH
CF3CH2OH
9
10
11
12
0
88
0
trace
12
76
24
aDetermined by 1H NMR analysis using mesitylene as an internal
standard. bCarried out under vacuum.
Next, the effect of the base was investigated using EtOH as
a solvent (Table 2). We first confirmed that base was necessary
for the reaction (entry 1). Inorganic hydroxides provided

2
consistent quantitative conversions, with stronger inorganic
hydroxides yielding higher selectivity towards hydroxylation
(entries 2–6). In contrast, organic bases were not suitable as it
provides very low to zero conversions due to the coordination to
the surface of gold nanoclusters, decreasing the catalytic activity
(entries 7–9). These results indicate that selective hydroxylation is
linked with the strength of base.
inhibitors for gold-based nanocluster catalysts.16 However, low
conversion of para-iodophenylboronic acid was obtained when
EtOH was used as a solvent (entry 8). In the case of
para-formylphenylboronic acid (1i), the desired hydroxylated
compound 2i was obtained in 54% yield along with a significant
amount of 4-hydroxybenzylidenacetone, derived through aldol
condensation reaction with in situ generated acetone (entry 9).
This result clearly indicated that 2-PrOH was oxidized under the
reaction conditions to afford acetone. Noted that the
corresponding isopropyl ester or carboxylic acid, through the
oxidation of the formyl group was not observed.5
Table 2. Optimization of base using EtOH as solvent
The catalytic mechanism for the homocoupling of
arylboronic acids has been thoroughly studied.7,17 It is also well
established that oxygen is readily adsorbed on nano-sized gold
surfaces.18,19 This results in the formation of superoxo-like
species,20 which generates Lewis acidic sites on the gold surface21
to facilitate adsorption of substrates such as arylborates4,17 and
alcohols.22,23 Under the basic aqueous conditions, formation of
HOO– reduced from O2 is unavoidable,17 which is then
responsible for arylboronic acid hydroxylation. As alcohols are
readily adsorbed18,19 and oxidized by nano-sized gold surfaces,5,6
oxygen-promoted oxidation of alcohols on the gold surface could
directly form H2O2. First, oxygen is adsorbed on the gold surface,
followed by adsorption of alkoxide more predominant than that of
arylboronate. At the same time, hydrogen atom expelled during
alkoxide formation and oxygen could interact to form a peroxide.
Subsequent β-hydride elimination then results in the formation of
either an aldehyde or ketone and H2O2. This proposed mechanism
is supported by the fact that 1) oxygen is necessary, 2)
non-reducing alcohols does not promote selective hydroxylation,
and 3) stronger bases promote higher selectivity, probably due to
the formation of highly nucleophilic peroxide anion under the
reaction conditions. The drastic change of chemoselectivity
would attribute to the preferential adsorption of the solvent
alcohols, which undergo the degradative production of H2O2
under the reaction conditions. It is also assumed that the
generation of transmetallation-active borate intermediate may be
suppressed in alcoholic solvents, impeding the homocoupling
catalytic cycle. MeOH did not promote selective hydroxylation as
it is less readily oxidized compared to EtOH and 2-PrOH.24 In
fact, we have previously demonstrated that Au:PVP catalyzed
oxidation of MeOH occurs only at elevated temperatures.25 When
non-reducing alcohols are utilized, only dissolved residual water
participates in the reaction.
Recovery and Yield (%)a
Entry
Base
1a
83
0
0
0
2a
6
3a
11
46
15
11
trace
22
12
0
1
2
3
4
5
6
7
8
9
None
LiOH
NaOH
KOH
CsOH
K2CO3
Et3N
54
85
89
98
21
0
0
57
88
100
100
DBU
DMAP
0
0
0
aDetermined by 1H NMR analysis using mesitylene as an internal
standard.
Table 3. Substrate scope
Recovery and Yield (%)a
Entry
R
1
0
0
2
1
2
3
4
5
6
7
8b
9
p-OMe (1b)
p-F (1c)
98
96
99
53
54
89
99
16
54
p-Cl (1d)
m-Cl (1e)
o-Cl (1f)
p-Br (1g)
p-I (1h)
0
46
46
11
0
84
0
Since in situ formation of H2O2 is likely to occur under the
aerobic Au:PVP catalyzed, alcoholic, and basic system, we sought
to apply this catalytic system into other oxidation reactions. We
chose (E)-chalcone (4) as our model substrate. The corresponding
epoxide product (5) was obtained in 51% isolated yield and total
conversion of the starting material when the reaction was carried
out in EtOH at 27 °C under air in the presence of 3 atom% of
Au:PVP with a stoichiometric amount of KOH (Scheme 3).26 This
highlights the potential to apply the in situ generated H2O2 by the
Au:PVP catalytic system to other oxidation reactions.
p-I (1h)
p-CHO (1i)
aDetermined by 1H NMR analysis using mesitylene as an internal
standard. bPerformed under EtOH as solvent.
Substrate scope was screened using 2-PrOH as a solvent and
KOH as a base (Table 3) because KOH is easier to handle and
cheaper than CsOH. We found that para-substituted arylboronic
acids (1b–d, 1g, 1h) undergo excellent conversions and
hydroxylation selectivity. Although selectivity for hydroxylations
were excellent, mediocre conversions were obtained with meta-
and ortho-substituted arylboronic acids (entries
4 and 5).
Surprisingly, para-iodophenylboronic acid (1h) proceeded
through the reaction normally. This is in contrary to our
expectation, as we previously reported that aryl iodides are strong
Scheme 2. Aerobic epoxidation of (E)-chalcone (4) catalyzed by

Au:PVP.
In summary, by utilizing an alcoholic solvent and Au:PVP
as catalyst, we were able to generate H2O2 in situ, which could be
utilized for selective hydroxylation of arylboronic acids and
aerobic oxidations. We have successfully demonstrated one
example by achieving aerobic epoxidation of (E)-chalcone.
Chem. Soc 2013, 135, 13286.
15. B. Puértolas, A. K. Hill, T. García, B. Solsona, L.
Torrente-Murciano, Catal. Today 2015, 248, 115.
16. R. N. Dhital, C. Kamonsatikul, E. Somsook, Y. Sato, H.
Sakurai, Chem. Commun. 2013, 49, 2542.
17. S. Karanjit, M. Ehara, H. Sakurai, Chem. Asian J. 2015, 10,
2397.
18. A. Henglein, Langmuir 1999, 15, 6738.
2. Experimental
19. B. E. Salisbury, W. T. Wallace, R. L. Whetten, Chem. Phys.
2000, 262, 131.
Preparation of Au:PVP. The preparation of Au:PVP(K-30) was
carried out following our previously reported method.4
20. H. Nakatsuji, Z.-M. Hu, H. Nakai, K. Ikeda, Surf. Sci. 1997,
387, 328.
General procedure for hydroxylation of arylboronic acids.26
To a 15 mL test tube was added 0.200 mmol of arylboronic acid,
33.7 mg KOH, and 2 atom% of Au:PVP catalyst before addition
of 5 mL solvent. The reaction mixture was stirred at 27 °C for 15
h under air, then quenched by ca. 1 mL of 1 M HCl solution. The
products were extracted with EtOAc (ca. 20 mL × 3) and the
combined organic layer was dried over Na2SO4 and evaporated in
vacuo. The mixture was then analyzed by 1H NMR.
Aerobic Epoxidation of (E)-chalcone. To a 15 mL test tube was
added 0.200 mmol of (E)-chalcone, 11.2 mg KOH, and 3 atom%
of Au:PVP catalyst before addition of 5 mL EtOH. The reaction
mixture was stirred at 27 °C for 15 h under air, then quenched by
ca. 1 mL of 1 M HCl solution. The products were extracted with
EtOAc (ca. 20 mL × 3) and the combined organic layer was dried
over Na2SO4 and evaporated in vacuo. The product was purified
using preparative TLC with an eluent system consisting 1:1:6
ratio of EtOAc, CH2Cl2, and n-hexane, respectively.
21. M. Boronat, A. Corma, J. Catal. 2011, 284, 138.
22. K. Bobuatong, S. Karanjit, R. Fukuda, M. Ehara, H. Sakurai,
Phys. Chem. Chem. Phys. 2012, 14, 3103.
23. S. Karanjit, K. Bobuatong, R. Fukuda, M. Ehara, H. Sakurai,
Int. J. Quant. Chem. 2013, 113, 428.
24. D. Wang, J. Liu, Z. Wu, J. Zhang, Y. Su, Z. Liu, C. Xu, Int.
J. Electrochem. Sci. 2009, 4, 1672.
25. P. Preedasuriyachai, H. Kitahara, W. Chavasiri, H. Sakurai,
Chem. Lett. 2010, 39, 1174.
26. Since the H2O2 generated in situ was consumed by reacting
with Au:PVP catalyst itself (this phenomenon was also
explained in ref. 5), it is intrinsically difficult to keep the
generated H2O2 untouched during the H2O2 generation step.
Therefore, the reaction is necessary to be conducted through
the in-situ generation of H2O2 in the presence of the
substrates such as arylboronic acids and chalcone. We
appreciate one of the reviewers for the helpful discussion.
Acknowledgement
This work is supported by JST-ACT-C project and JST-Mirai
Program (JPMJMI18E3).
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