α-Hydroxylation of 1,3-dicarbonyl compounds catalyzed by polymer-incarcerated gold nanoclusters with molecular oxygen

Article abstract of DOI:10.1246/cl.2012.976

α-Hydroxylation of 1,3-dicarbonyl compounds was successfully catalyzed by carbon-stabilized polymer-incarcerated gold nanoclusters (PI/CB-Au). The reaction proceeded under mild conditions using molecular oxygen as oxidant with wide substrate scopes and the catalyst could be recovered and reused by a simple operation. The control experiments and the reaction monitoring revealed that α-peroxide compounds were reaction intermediates, and PI/CB-Au also catalyzed isomerization.

Full text of DOI:10.1246/cl.2012.976

doi:10.1246/cl.2012.976
976
Published on the web September 8, 2012
¡-Hydroxylation of 1,3-Dicarbonyl Compounds Catalyzed
by Polymer-incarcerated Gold Nanoclusters with Molecular Oxygen
Hiroyuki Miyamura and Shū Kobayashi*
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033
(Received May 31, 2012; CL-120468; E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp)
¡-Hydroxylation of 1,3-dicarbonyl compounds was success-
Table 1. Optimization of reaction conditions
fully catalyzed by carbon-stabilized polymer-incarcerated gold
nanoclusters (PI/CB-Au). The reaction proceeded under mild
conditions using molecular oxygen as oxidant with wide
substrate scopes and the catalyst could be recovered and reused
by a simple operation. The control experiments and the reaction
monitoring revealed that ¡-peroxide compounds were reaction
intermediates, and PI/CB-Au also catalyzed isomerization.
Yield/%a
Entry Catalyst
Base
Solvent
1b 1c 1d
1
2
3
4
5
6
7
8
9
None
PI/CB-Au None
PI/CB-B None
PI-Au
PI/CB-Au None
PI/CB-Au None
K2CO3 MeCN/H2O = 9/1
7
nd nd
MeCN
MeCN
MeCN/H2O = 9/1
MeCN/H2O = 9/1
BTF/H2O = 9/1
62 16 nd
nd nd nd
nd nd 14
59 12 nd
54 nd nd
69 nd Trace
71 nd Trace
None
We have recently developed highly active gold nanocluster
catalysts, which were immobilized on polystyrene-based poly-
mer with a crosslinking moiety, namely polymer-incarcerated
gold (PI-Au).1-3 The catalysts have been used for various
aerobic oxidations in organic synthesis, such as alcohols to
aldehydes and ketones,1,4 aldehydes to carboxylic acids,5
alcohols to esters,6,7 alcohols to amides,8 hydroquinones to
quinones,9 and amines to imines.10 This method has also been
applied to the preparation of various metal nanocluster catalysts
including bimetallic alloyed clusters and multifunctional cata-
lysts.11-17 In addition, we have demonstrated that incorporation
of spherical hollow carbon black (ketjen black) during the
catalyst preparation enhances the activity of the catalysts and the
stability of metal nanoclusters by increasing the specific surface
area to afford carbon-stabilized polymer-incarcerated metal
nanoclusters (PI/CB-M).18 Features of these catalysts are ease
of use in liquid-phase organic transformations because of the
high accessibility of organic molecules to the inside of
amphiphilic polymer supports, availability in various types of
oxidation reactions with molecular oxygen under ambient
conditions (at room temperature under atmospheric conditions),
reusability without metal leaching and loss of activity, and
applicability for reaction integration19 such as tandem reac-
tions6-8,16 and flow systems.20,21
Since Haruta and co-workers discovered gold nanocluster
catalysts for carbon monoxide oxidation,22-24 gold nanocluster
catalysis has also been applied to various oxidative organic
transformations, including synthesis of complex molecules.25-32
However, only dehydrogenation reactions are possible with
these catalysts under mild conditions and there are few examples
of oxygenation reactions. Recently, Sakurai et al. demonstrated
an oxygenation of benzyl ketones using Au:PVP as a homoge-
neous catalyst via a peroxo intermediate.33
The 1,3-dicarbonyl-2-hydroxy moiety is observed in various
natural compounds, pharmaceutical compounds, and bioactive
compounds, and ¡-hydroxylation of 1,3-dicarbonyl compounds,
which is the most direct method to construct this motif, is a quite
important transformation.34 Many methods using molecular
oxygen as an oxidant with Ce,35-37 Cs,38 Mn,39,40 Pd,41,42 and
Fe43 as homogeneous catalysts and photooxidation with sensi-
tizers44,45 have been developed. However, methods using
PI/CB-Au KHCO3 MeCN
PI/CB-Au KHCO3 BTF/H2O = 9/1
PI/CB-Au KHCO3 MeCN/MeOH = 9/1 80 nd nd
10 PI/CB-Au K2CO3 MeOH
aIsolated yield.
11 nd 56
reusable heterogeneous catalysts and gold catalysts have not
been reported. Here, we show reusable heterogeneous gold-
catalyzed ¡-hydroxylation of 1,3-dicarbonyl compounds using
molecular oxygen as an oxidant under very mild conditions as
one of the greenest methods for this transformation.
First, we chose ketoester 1a as a model substrate for
optimization of the reaction conditions (Table 1). The ¡-
hydroxylation reaction hardly proceeded under basic conditions
in the absence of any catalysts (Entry 1). When the PI-Au
catalyst was used in the acetonitrile (MeCN)-water cosolvent
system, only naphthol derivative 1d, which was produced by a
dehydrogenation reaction, was obtained (Entry 4). In contrast,
when PI/CB-Au was used as a catalyst in MeCN-water, MeCN,
or benzotrifluoride (BTF (=trifluoromethylbenzene))-water, a
mixture of ¡-hydroxylated compound 1b and peroxide com-
pound 1c was obtained in good yields (Entries 2, 5, and 6).
Addition of potassium hydrogencarbonate (KHCO3) improved
the selectivity of 1b (Entries 7-9) and the desired compound was
obtained in 80% yield in the MeCN-MeOH cosolvent system
(Entry 9). Interestingly, in the presence of K2CO3 in MeOH, 1d
was obtained as the major product (Entry 10).
To gain insight into the reaction pathway, we performed
several control experiments. First, it was confirmed that carbon-
stabilized polymer-incarcerated boron (PI-CB/B), prepared from
sodium borohydride and a polymer,16 could not mediate this
oxidation reaction at all, either with or without base (Entry 3).
Therefore, background reactions catalyzed by either carbon
black or remaining boron species in the polymer can be rejected.
Second, peroxide compound 1c was quite stable in the solid state
in air at room temperature (no decomposition occurred over two
weeks); however, it was slowly converted to hydroxylated
Chem. Lett. 2012, 41, 976-978
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

977
Table 2. Substrate scope
Entry Product
x
y
Solvent
Yield/%a
1
2
3
4
5
6
7
8
9
2b
3b
4b
5b
6b
7b
8b
9b
10b
3
3
2
4
5
5
3
3
4
5
4
0.5 MeCN/H2O = 10/1
79
1
1
2
2
2
1
MeCN/MeOH = 10/1 75
BTF/H2O = 10/1
MeCN/H2O = 10/1
MeCN/H2O = 10/1
MeCN/H2O = 10/1
MeCN/H2O = 10/1
49
46
48
69
72
71
62
40 (6)b
Scheme 1. Proposed reaction pathway.
0.5 MeCN/H2O = 10/1
0.2 MeCN/H2O = 10/1
compound 1b in MeCN at room temperature (12% after 12 h).
Peroxide 1c could be transformed to 1b smoothly in the presence
of the PI/CB-Au catalyst (50% after 12 h) and much smoother
conversion was seen in the presence of both PI/CB-Au and the
base (>95% after 12 h). In contrast, no transformation from
either 1b or 1c to 1d was observed in the presence of the base
and/or PI/CB-Au.
10 11b (11e)
11 12b (12e)
aIsolated yield. Yield of compound e. Compounds e and b
cannot be separated and the ratio of b and e was determined by
1H NMR analysis. 20 mol % of NaB(OMe)4 was used. BTF:
2
MeCN/H2O = 10/1
1.5 MeCN/H2O = 10/1c 44 (31)b
b
c
benzotrifluoride.
Taking account of these control experiments, we propose the
reaction pathway shown in Scheme 1. Keto form 1a and enol
form 1a¤ of the substrate are held in equilibrium under the
reaction conditions. When a weak base is used, the oxygenation
reaction proceeds to afford peroxide 1c in the presence of
PI/CB-Au and molecular oxygen, followed by isomerization
catalyzed by PI/CB-Au to give hydroxylated product 1b. On the
other hand, the dehydrogenative oxidation proceeds to afford
naphthol 1d in the presence of a strong base and PI/CB-Au.
Compound 1d cannot be obtained from 1c or 1b under any
conditions.
We then examined the substrate scope using the PI/CB-Au
catalyst under atmospheric oxygen. It was found that the best
conditions of solvent systems and amount of base generally
depended on the substrate, while MeCN-water and MeCN-
MeOH cosolvent systems were similar (Table 2). Cyclic
ketoesters could be converted to the desired hydroxylated
products 2b and 3b (Chart 1) in good yields (Entries 1 and 2).
Acyclic ketoesters were also oxidized to the corresponding
hydroxylated compounds 4b-6b in moderate yields (Entries
3-5). A ketoamide was oxidized to hydroxylated product 7b
with retention of the ratio of the diastereomers (Entry 6).
Malonic ester derivatives also were oxidized smoothly to the
corresponding hydroxylated compounds 8b-10b (Entries 7-9).
When reactive groups with a peroxy moiety were included in the
starting materials, 1,2-dioxane intermediates 11e and 12e were
also obtained (Entries 10 and 11).46-48 A mixture of compounds
12b and 12e was converted to just 12b in 71% yield by
treatment with 1 equiv of triphenylphosphine.
Chart 1. Structures of products.
The reaction profile in the oxidation of malonic ester 8a
using PI/CB-Au is shown in Figure 1. Initially, the fraction
of peroxo intermediate 8c increased, and 8c was converted
gradually to hydroxylated product 8b. Judging from this result,
the reaction speeds of the first and second steps are similar.
Recovery and reuse of the catalyst was examined using
malonic ester 8a as the substrate (Table 3). The PI/CB-Au
catalyst could be recovered by simple filtration. In the second
and third runs, conversion of 8a was complete, but peroxo
Figure 1. Reaction profile of the oxidation reaction using
PI/CB-Au.
intermediate 8c remained. These results indicate that the
recovered catalyst retains activity for the first step; however,
activity for the second step decreased a little during recycling. In
other words, the metal nanocluster catalyst is important for both
Chem. Lett. 2012, 41, 976-978
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

978
Table 3. Recovery and reuse of the catalyst
2011, 133, 3095.
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Run
8b/%
8c/%
1
2
3
72
55
62
0
11
9
the first and second steps. The deactivation of the PI/CB-Au
catalyst is presumably caused by adsorption of small amounts of
solvents or organic compounds on the nanocluster surface. We
tried to regenerate the recovered catalyst by heating; however,
this treatment was not effective in this case.1,8,12
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In conclusion, we have demonstrated that PI/CB-Au
catalyzed ¡-hydroxylation of 1,3-dicarbonyl compounds. The
reaction proceeded under mild conditions using molecular
oxygen as oxidant, and the catalyst could be recovered by a
simple operation. The control experiments and reaction mon-
itoring revealed that ¡-peroxide compounds were intermediates
and that the polymer-incarcerated gold nanocluster also cata-
lyzed isomerization to the hydroxylated compounds. This
catalytic system satisfies criteria for green sustainable chemistry,
and a new class of heterogeneous gold nanocluster catalyzed
oxygenation reaction has been developed.
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© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/