Silver-Catalyzed Hydrogenation of Ketones under Mild Conditions

Article abstract of DOI:10.1002/adsc.201801523

The silver-catalyzed hydrogenation of ketones using H₂ as hydrogen source is reported. Silver nanoparticles are generated from simple silver (I) salts and operate at 25 °C under 20 bar of hydrogen pressure. Various aliphatic and aromatic ketones, including natural products were reduced into the corresponding alcohols in high yields. This silver catalyst allows for the selective hydrogenation of ketones in the presence of other functional groups. (Figure presented.).

Full text of DOI:10.1002/adsc.201801523

Title: Silver-Catalyzed Hydrogenation of Ketones under Mild Conditions
Authors: Shengdong Wang, Haiyun Huang, Svetlana Tsareva,
Christian Bruneau, and Cedric Fischmeister
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Silver-Catalyzed Hydrogenation of Ketones under Mild
Conditions
a,‡
a,‡
b
a
Shengdong Wang, Haiyun Huang, Svetlana Tsareva, Christian Bruneau, and
a*
Cédric Fischmeister
a
S. Wang, H. Huang, Dr. C. Bruneau, Dr. C. Fischmeister
Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) – UMR 6226
F-35042 Rennes, France.E-mail: cedric.fischmeister@univ-rennes1.fr
ORCID C. Fischmeister 0000-0002-9490-8145
b
S. Tsareva, Univ Rennes, CNRS, ScanMat - UMS 2001, F-35000 Rennes, France.
‡
These two authors contributed equally to this work.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The silver-catalyzed hydrogenation of ketones This silver catalyst allows for the selective hydrogenation
using H
are generated from simple silver (I) salts and operate at
5 °C under 20 bar of hydrogen pressure. Various aliphatic Keywords: Catalysis; Hydrogenation; Ketones;
2
as hydrogen source is reported. Silver nanoparticles of ketones in the presence of other functional groups.
2
and aromatic ketones, including natural products were Nanoparticles; Silver
reduced into the corresponding alcohols in high yields.
that an acetyl group was not hydrogenated by Ag-
Introduction
NPs supported on alumina when the reaction was
conducted at 160 °C under 30 bar of hydrogen
Reduction processes play a crucial role in numerous
industrial processes and for this reason they have
been a topic of continuous intense researches in
academia and industry. This situation will very likely
persist owing to the growing demand for biosourced
[5a]
pressure.
reported the hydrogenation of two benzylic ketones
using magnetic Ag-F nanoparticles supported on
In another example, Moores and Li
3
O
4
carboxymethyl cellulose. The corresponding alcohols
were obtained in moderate to high yield at 100 °C
compounds
yet
requiring
reduction
and
[7]
and 40 bar of hydrogen pressure in water. In 2009,
De Vos reported polymer stabilized Ag-NPs that
reduced a number of unsaturated ketones with
moderate to high selectivity at 60 °C and 40 bar of
[1]
hydrogenation protocols. Industrial hydrogenation
processes are essentially employing heterogeneous
catalysis
excepted
when
highly
selective
transformations are necessary albeit a number of
heterogeneous catalyst display this property. Metal
nanoparticles are at the frontier between
homogeneous and heterogeneous catalysis as they
display in general high activity and selectivity and
can be recycled. For these reasons, metal
nanoparticles (NPs) have been attracting a strong
[8]
hydrogen pressure.
More recently, Moores
described the use of plasmonic silver nanocubes for
the hydrogenation of ketones and aldehydes. Four
ketones were hydrogenated at 80 °C and 1 bar of
[
9]
hydrogen pressure under irradiation at 450 nm.
In our ongoing efforts to produce the biosourced γ–
valerolactone by reduction of levulinic acid with
[2]
interest over the past 20 years in catalysis. Among
metal-NPs, silver-NPs (Ag-NPs) are receiving
attention as an alternative to expensive metal-NPs
based on gold, platinum or other noble transition
metals.[ The efficient and selective reduction of
aldehydes was extensively studied by Claus since the
[10]
iridium complexes, we became interested in using
less expensive metals for hydrogenation reactions.
Initially inspired by the work of Li[ on the
homogeneous hydrogenation of aldehydes, we
focused our attention on the silver-catalyzed
hydrogenation of ketones (Scheme 1).
11]
3]
mid-nineties using Ag-NPs supported on SiO
2
or
[
4]
TiO .
2
Ag-NPs have also been reported for the
hydrogenation of nitro-aromatics into aniline
derivatives[ and for the selective hydrogenation of
5]
[6]
amides into alcohols and amines.
The
hydrogenation of keto-derivatives with Ag-NPs turns
to be more difficult and only a few recent results are
published. As an illustration, we could mention that
during his investigations on the scope of the Ag-NPs
hydrogenation of nitroaromatics, Shimizu reported
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
Table 1. Ag-catalyzed hydrogenation of acetophenone[a]
Entry
Catalyst
AgOTf
AgOTf
AgOTf
AgOTf
Base
Solvent
Pentane
Toluene
THF
CPME
1,4-
Dioxane
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Yield (%)b
1
2
3
4
KHMDS
KHMDS
KHMDS
KHMDS
85
92
73
62
Scheme 1. Silver-catalyzed hydrogenation of carbonyl
derivatives
5
AgOTf
AgCl
KHMDS
82
6
7
8
9
10
11
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
(10)
KHMDS (5) Toluene
KHMDS
Toluene
(10)
KHMDS
Toluene
(10)
<5
10
33
83
89
Results and Discussion
Ag
2
O
Ag
2
CO
3
Acetophenone was initially selected as a model
substrate. Several experimental parameters were
screened and optimized. As depicted in Table 1, we
first investigated the hydrogenation catalyzed by
silver triflate at 25 °C with KHMDS as the base in
apolar solvents, in which very good yields were
obtained (Table 1, entries1-2). More polar ether
solvent resulted in lower yields of 1-phenylethanol
AgPF
6
AgSbF
6
e
AgClO
4
4
4
4
99
e
f
1
4
AgClO
AgClO
AgClO
Toluene
99 (99)
90
15
c
1
1
6
78
(
Table 1, entries 3-5). Following this first screening,
7d
AgClO
52
4
various silver salts were evaluated emphasizing the
superiority of silver perchlorate (Table 1, entries 3-
18
19
20
AgClO
AgClO
AgClO
4
4
4
LDA(10)
NaOEt(10)
Cs CO (10)
2 3
HCOONa
(10)
tBuOK(10)
NaOH(10)
2 3
K CO (10)
KHMDS(5)
-
Toluene
Toluene
Toluene
<5
<5
<5
1
1). Further optimization reactions were then pursued
with this catalyst. Interestingly, it was possible to
decrease the amount of base to 10 mol% but
decreasing the catalyst loading or the hydrogen
pressure led to lower yields of alcohol (Table 1,
entries 16-17). Various bases were also evaluated
2
1
AgClO
4
Toluene
<5
22
23
24
25
26
[a]
AgClO
AgClO
AgClO
-
4
4
4
Toluene
Toluene
Toluene
Toluene
Toluene
11
<5
<5
0
(
Table 1, entries 18-24) but none of them led to the
results obtained with KHMDS. In fact, all those bases
led to very poor results indicating a very peculiar role
of KHMDS. Finally, experiments conducted in the
AgClO
4
0
Reaction conditions: acetophenone (0.5 mmol), [Ag] (6
absence of AgClO or KHMDS were found totally
4
2
mol%), Base (20 mol% unless other value mentioned), H = 20
bar, Solvent (2mL), 25 C (oil bath),17 h.
HNMR.
ineffective hence demonstrating the necessity of both
components (Table 1, entries 25-26).
°
[b]
Determined by 1
NMR signals of
[c]
[d]
[e]
3 mol%.
H
2
= 10 bar.
1
With these optimized conditions in hand, we
performed the hydrogenation of a number of
commercially available ketones to highlight the
efficacy of the catalytic system. Selected aromatic
and aliphatic ketones featuring various steric and
electronic demands were thus subjected to the
catalytic system at 25 °C. However, in some
examples it was necessary to warm the reactions to
[f ]
acetophenone not detected by H NMR. isolated yield.
Of note, the fully hydrogenated product 2o’ could be
obtained upon heating the reaction at 60 °C. Aliphatic
ketones including the naturally occurring and
sterically hindered camphor 1r were also
hydrogenated in very good yields (Table 2, entries
1
6-18). Similarly, heterocyclic keto-compounds were
6
0 °C in order to reach good yields. In several cases,
reduced to the corresponding alcohols in high yields.
In the case of 3-acetyl-1-methylpyrrole 1u and 2-
benzofuranyl methyl ketone 1v, a slight heating at
full conversions were obtained leading to very clean
reaction mixtures. In those cases, the products were
isolated by a simple filtration on a short plug of silica.
As shown in Table 2, sterically hindered ketones and
both electron-withdrawing as well as electron-
donating substituted aromatic ketones were
hydrogenated in high yields (entries 1-14). Under the
standard reaction conditions, p-acetyl-acetophenone
60 °C was necessary to ensure good yields (Table 2,
entries 21-22). Finally, the chemoselectivity of the
catalytic system was evaluated using a series of
bifunctional keto-derivatives. Aldehydes were also
introduced in this study in order to demonstrate the
applicability of the catalytic system to the
hydrogenation of aldehydes. In all cases, the selective
reduction of the ketone or aldehyde functional group
took place delivering the alcohols in good to high
yields (Table 2, entries 23-26). One limitation was
1
o was partially hydrogenated furnishing the mono-
reduced ketone 2o in 92% yield (Table 2, entry 15).
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
nevertheless observed with the challenging
benzylidene acetone 1aa which delivered a mixture
99[e]
[11]
of alcohol 2aa and ketone 2aa’in a 30/70 ratio.
2
o’
Finally, in order to highlight the general applicability
of this catalytic system and draw some lines for
further developments, we have attempted and
succeeded with the selective hydrogenation of
benzonitrile1ab. If the reaction of nitrile was not
observed at room temperature (Table 2, entry 24),
raising the temperature to 80 °C and the hydrogen
pressure to 40 bar enabled the reduction of
benzonitrile 1ab into benzylamine 2ab in 83%
isolated yield (Table 2, entry 28).
>99[c]
1
1
6
7
1p
2p
78
1
q
2q
1
1
8
9
80
2
r
1
r
79
1
s
2s
Table 2. Silver-catalyzed hydrogenation of ketones:
Substrate scope[
a]
[c]
[d]
20
>99 (99)
1
t
2t
Entry Substrate
Product
Isolated yield
b
(%)
2
1
88[e]
>99c
1u
2u
1
1
a
2a
97[e]
2
2
2
3
1
v
2v
2
3
71
87
88(99)[d]
1
w
1
1
b
c
2b
2
2
4
5
93
1
x
2x
2y
2c
[
c]
[d]
4
5
6
>99 (73)
[c]
[d]
>99 (83)
1
d
2d
1
y
>99[c] (99)d
1
e
2e
2
6
75
61e
1z
2z
1
f
2f
3
7
0[f]
7
>99[c] (85)d
2
aa
2
g
2
2
7
1
g
1
aa
0[f]
8
9
>99 [c]
90
2
aa’
1
h
2h
8[g]
83
1
ab
2
ab
1
i
2i
[
a]
Reaction conditions: substrate (0.5 mmol), AgClO
4
(6
1
0
>99[c]
°
mol%), KHMDS (10 mol%), H = 20 bar, toluene (2 mL), 25 C
2
[
b]
[c]
(
oil bath), 17 h. isolated by coloumn Product isolated by
1
j
2j
[
d]
simple filtration on a silica plug. Results in parenthesis
e
[f]1
95[e]
obtained with AgOTf as catalyst, 24 h. 60 °C (oil bath).
NMR ratio. AgOTf (6 mol%), KHMDS (20 mol%), 80 °C, 17
h.
H
1
1
1
2
[
g]
1
k
2k
>99[c,d]
1
l
2l
If the use of silver perchlorate in catalytic amounts
and small scale syntheses should not present
important safety issues, the situation may be different
on larger scale syntheses. Considering this potential
hazard, we have duplicated some reactions with silver
triflate. These reactions performed over an extended
reaction time of 24 h led in general to similarly good
yields (Table 2, entries 4, 5, 7, 13, 20, 23, 25). It is
worth mentioning that the repeatability and
reproducibility of the reaction was checked with
several substrates.
99 (99)[d]
1
1
3
4
1
m
2m
>99[c,e]
1
n
2
n
9
2
1
5
2
o
1
o
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
Following our investigations on the efficiency and
scope of the reaction, we turned our attention to the
nature of the catalyst. Although we did not employ
any nanoparticle stabilizer or support, the
involvement of Ag-NPs was considered seeing the
heterogeneous nature of the reaction media at the end
of the catalytic transformations. As explained in a
review by Finke,[ there is not a single test leading to
unambiguous distinction between homogeneous or
metal-NPs catalysis. Hence, we have conducted a
series of experiments in order to identify the nature of
the catalyst. We have first considered the mercury
poisoning test with both silver precursors in the
reduction of 1a (Hg/Ag = 300). However, due to
experimental constraint (high pressure reactor),
mercury was added at the onset of the reaction. In
both cases we observed complete inhibition of the
reaction. Next, the reusability of the catalyst was
evaluated. Two different procedures were used and in
both cases very good yields were obtained in a
formation of nanoparticles with disperse size
distribution due to agglomeration. In all cases EDS
analyses on several particles for each samples
evidenced the formation of silver nanoparticles (see
SI for details). The observation of Ag-NPs after only
15 minutes of reaction is in agreement with fast
initiation observed in kinetic studies. The
unambiguous formation of nanoparticles raises the
issue of stabilizers in general necessary to prevent
extensive agregation of nanoparticles. Considering
that hydrogenation reactions promoted by metal-
12]
[5, 7-9, 13]
nanoparticles do not require a base,
we believe
that the bulky potassium hexamethyldisilazide
initially introduced as a base necessary for hydrogen
activation in an homogeneous catalytic reaction may
play the role of stabilizing agent via electrostatic
and/or electrosteric effects which are known
[14]
processes for metal nanoparticle stabilization.
second run (see SI for details). The kinetic profile of Conclusion
the reaction was also investigated with AgOTf
precursor. It was found that the reaction proceeded
without induction period hence suggesting a
homogeneous catalytic process or fast generation of
Ag-NPs (see SI for details).
In summary, the unprecedented hydrogenation of
ketones with a silver catalyst is reported. These in
situ generated silver nanoparticles operate at 25 °C
and low hydrogen pressure. High efficacy and
selectivity have been achieved in a number of cases
involving various ketones. These important
characteristics make this process interesting for the
synthesis of a broad range of chemicals. Further
studies will be carried out to elucidate the non-
common formation of nanoparticles and to extend the
applicability of these catalysts.
Experimental Section
(
a)
(b)
General procedure for the catalytic hydrogenation of
ketones: In an argon-filled glove box, a high pressure
reactor was charged sequentially with base (5-20 mol%),
silver salt (6 mol%), ketone (0.5 mmol) and 2 mL of dry
2
toluene. The reactor was then charged with H (20 bar) and
stirred at the appropriate temperature for 17 h. The reactor
was carefully depressurized and the reaction mixture was
filtrated through a short plug of silica. The solvent was
1
evaporated and the crude product was analyzed by H
NMR. This crude product was then purified by flash
column chromatography on silica gel using a mixture of
heptane and ethyl acetate as the eluent.
(
c)
(d)
Acknowledgements
Figure 1: TEM images of reaction mixtures with AgOTf
as precursor; (a) and (b) after 15 minutes; (c) and (d) after
The authors acknowledge the China Scholarship Council for a
grant to SW. We also acknowledge M. Julien Hervochon for
checking the reproducibility of the catalytic process.
1
7 h.
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aliquot of the supernatant liquid of each reaction was
taken and deposited onto a TEM copper grid. As
depicted in Figure 1, TEM images revealed the
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
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Advanced Synthesis & Catalysis
10.1002/adsc.201801523
FULL PAPER
Silver-Catalyzed Hydrogenation of Ketones
under Mild Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
a,‡
a,‡
Shengdong Wang, Haiyun Huang, Svetlana
b
a
Tsareva, Christian Bruneau, and Cédric
a*
Fischmeister
6
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