Highly efficient and recyclable chiral Pt nanoparticle catalyst for enantioselective hydrogenation of activated ketones

Article abstract of DOI:10.1016/j.catcom.2018.03.012

Thermoregulated phase-separable chiral Pt nanoparticle catalyst exhibited excellent ee (>99%) in the enantioselective hydrogenation of activated ketones for preparing chiral α-hydroxy acetals and chiral 1,2-diols. More importantly, the chiral catalyst could be easily separated by phase separation and directly reused in the next cycle without any loss in catalytic activity and enantioselectivity, even in the gram-scale reaction. The leaching of Pt was under the detection limit of the instrument.

Full text of DOI:10.1016/j.catcom.2018.03.012

Catalysis Communications 110 (2018) 55–58
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short communication
Highly efficient and recyclable chiral Pt nanoparticle catalyst for
enantioselective hydrogenation of activated ketones
⁎
Xiuru Xue, Pu Chen, Peng Xu, Yanhua Wang
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Thermoregulated phase-separable chiral Pt nanoparticle catalyst exhibited excellent ee (> 99%) in the en-
antioselective hydrogenation of activated ketones for preparing chiral α-hydroxy acetals and chiral 1,2-diols.
More importantly, the chiral catalyst could be easily separated by phase separation and directly reused in the
next cycle without any loss in catalytic activity and enantioselectivity, even in the gram-scale reaction. The
leaching of Pt was under the detection limit of the instrument.
Enantioselective hydrogenation
Activated ketones
Pt
Nanoparticle
Recyclable
1. Introduction
turns into homogeneous phase in which the reaction runs efficiently.
After reaction, with temperature decreasing the system becomes two-
Chiral secondary alcohols are very important intermediates and
phase again. Therefore, the chiral Pt nanoparticle catalyst can be easily
separated from products by simple phase separation and directly reused
in the next cycle. Namely, the system is characterized by the homo-
geneous reaction coupled with biphase separation.
Encouraged by these results, we herein applied the thermoregulated
phase-separable chiral Pt nanoparticle catalyst to enantioselective hy-
drogenation of various activated ketones for synthesizing chiral α-hy-
droxy acetals and chiral 1,2-diols with the aim to achieve excellent
enantioselectivity and to realize the recyclability of the catalyst (Fig. 1).
auxiliaries in the asymmetric synthesis chemistry. For example, chiral
α-hydroxy acetals not only can be converted to chiral 1,2-diols, chiral
β-amino alcohols and chiral aldol derivatives [1–3], but also are ne-
cessary chiral building blocks for synthesis of lipoxine A [4], rhodinose
5], rocellaric acid [6], grayanotoxins [7] and amino sugars [8].
Meanwhile, chiral 1,2-diols are crucial components for synthesis of
[
insect pheromones [9], δ-lactones [10], β-lactone esterase inhibitors
11], especially for anti-HIV pharmaceutical tenofovir [12] and many
[
other biologically active substances [13]. Due to their great importance,
much attention has been paid to exploring high-efficiency methods to
obtain chiral α-hydroxy acetals [14–16] and chiral 1,2-diols [17–19].
Among them, the enantioselective hydrogenation of activated ketones
is one of the most effective and atom economic methods for preparation
of chiral α-hydroxy acetals and chiral 1,2-diols. In the past few decades,
great progress with high enantioselectivity has been made in this re-
action [20–26], however, studies about the recyclable chiral catalyst for
enantioselective hydrogenation to obtain chiral α-hydroxy acetals and
chiral 1,2-diols with excellent enantioselectivity has not been reported.
Based on our previous studies, the thermoregulated phase-separable
chiral Pt nanoparticle catalyst was developed and successfully applied
in asymmetric hydrogenation of a series of α-ketoesters with high cat-
alytic activity, enantioselectivity, recyclability and general applicability
2. Experimental
2.1. Materials and analyses
Unless otherwise noted, all chemicals were purchased from com-
mercial sources without further purification. PtCl (57.6% of Pt) was
4
purchased from Japan. 1,1-Dimethoxyacetone 1a (97%), cyclobutyl
methyl ketone (97%) and 2-hexanone (98%) were from Alfa Aesar. 2,2-
Diethoxyacetophenone 1h (96%) was purchased from Acros.
Acetophenone (99%) was from Aladdin. 1-Hydroxybutan-2-one 1j
(98%), (1-hydroxycyclohexyl)(phenyl)methanone 1m (98%) and 2-
hydroxy-1-phenylethanone 1l (97%) were from Ark. 3,3-
Dimethoxybutan-2-one 1i (97%), 3-hydroxy-2-butanone 1k (97%) and
4-hydroxy-2-butanone (95%) were from Adamas. Pyruvic aldehyde
[
27]. The working principle can be simply described as follows: before
reaction, the system consists of two phases, one is the upper organic
phase and another is the chiral Pt nanoparticle catalyst phase. When the
temperature rises above the critical solution temperature, the system
2
(30 wt% in H O) was from Accela. 1,3-Propanediol (98%) and 4,4-di-
methoxy-2-butanone (92%) were from Innochem. Ethyl alcohol, pro-
panol, isopropanol, n-butanol, t-butyl alcohol, toluene, glacial acetic
⁎
Corresponding author.
E-mail address: yhuawang@dlut.edu.cn (Y. Wang).
https://doi.org/10.1016/j.catcom.2018.03.012
Received 31 January 2018; Received in revised form 8 March 2018; Accepted 10 March 2018
Available online 12 March 2018
1566-7367/ © 2018 Elsevier B.V. All rights reserved.

X. Xue et al.
Catalysis Communications 110 (2018) 55–58
Table 1
Enantioselective hydrogenation of 1,1-dimethoxyacetone 1a catalyzed by the thermo-
a
regulated phase-separable chiral Pt nanoparticles.
Entry CILPEG-CD/Pt
mol/mol)
T (°C)
P
H2 (MPa) t (h) Conv.b (%) eeb (%)
(
Fig. 1. Enantioselective hydrogenation of activated ketones catalyzed by the thermo-
regulated phase-separable chiral Pt nanoparticles.
1
2
3
4
5
6
7
8
9
10
11
1
1
1
4
30
30
30
30
25
35
40
30
30
30
30
30
30
30
5
5
5
5
5
5
5
5
3
4
6
5
5
5
3
3
3
3
3
3
3
3
3
3
3
1
2
2.5
49
80
92
> 99
37
86
60
> 99
29
80
89
5
7
8
8
8
8
8
8
8
8
8
8
8
> 99
> 99
> 99
> 99
> 99
95
> 99
83
94
> 99
> 99
> 99
> 99
acid, n-heptane and cyclohexane were all analytical reagents and pur-
chased from Kermel. 1-(1,3-Dioxan-2-yl)ethanone 1b, 1,1-diethoxy-2-
propanone 1c, 1,1-dipropoxy-2-propanone 1d, 1,1-dibutoxy-2-propa-
none 1e, 1,1-diisopropoxy-2-propanone 1f and 1,1-ditertbutoxy-2-pro-
panone 1g were synthesized as reported [28,29]. H NMR was recorded
on a Varian (400 MHz). Chemical shifts (δ) are denoted in ppm using
residual solvent peaks as internal standard (CDCl
c
1
3
, δ = 7.26 ppm).
> 99
20
40
2
3
4
Chiral GC analyses were carried out on Fuli 9790 GC instrument
equipped with an Agilent CP-Chirasil-Dex (25 m × 0.25 mm
72
×
0.25 μm) and an FID detector (N
sion electron microscopic) images were carried out by using a Tecnai G
0 S-TWIN (200 kV) instrument. ICP-AES (Inductively coupled plasma
atomic emission spectrometer) analyses were performed on Optima
2
as a carrier gas). TEM (Transmis2-
a
Reaction conditions: 3.56 × 10−3 mmol of Pt, the corresponding amount of CILPEG-
2
CD, toluene (1.0 g), n-heptane (0.3 g), glacial acetic acid (1.6 g), 1a/Pt = 100 (mol/mol),
cyclohexane (50 mg).
b
Determined by chiral GC analysis.
nd cycle of entry 7 at 30 °C.
2000 DV (detection limit is 10 ppm).
c
2
2.2. Preparation of the chiral Pt nanoparticle catalyst
was added. The reactor was flushed three times with 2.0 MPa H
2
and
stirred under 5.0 MPa H at 30 °C for 3 h. After reaction, the autoclave
2
As a− typical example,
a
mixture of PtCl
4
(1.20 mg,
was cooled in an ice-water bath and then depressurized. The lower
chiral Pt nanoparticle catalyst phase was easily separated by simple
phase separation and directly reused in next catalytic cycle. The upper
phase was directly analyzed by chiral GC.
3
−2
3
.56 × 10 mmol) and CILPEG-CD (32 mg, 2.85 × 10 mmol) was
added to a 75 mL stainless-steel autoclave. The autoclave was flushed
for three times with 2.0 MPa H and then inflated to 4.0 MPa with H
2
2
.
After being stirred at 80 °C for 8 h, the reactor was cooled to room
temperature and depressurized. The color of the mixture changed from
claret to black, indicating the formation of the chiral Pt nanoparticle
catalyst. The preparation of other chiral Pt nanoparticle catalysts with
different ratios of CILPEG-CD to Pt was carried out according to the same
procedure.
3
. Results and discussion
Our studies began by using 1,1-dimethoxyacetone 1a as model
substrate for enantioselective hydrogenation to screen the optimal re-
action conditions. Firstly, a series of chiral Pt nanoparticle catalysts
with different molar ratios of CILPEG-CD to Pt were prepared and tested
in the reaction (Table 1, entries 1–4). The results showed that the
conversion greatly increased from 49% to > 99% with increasing the
molar ratio from 4 to 8, while the > 99% ee was obtained and remained
when the molar ratio was in the range of 5 to 8. Subsequently, the effect
of reaction temperature was explored in the range of 25–40 °C. As
shown in Table 1, when the temperature was increased from 25 to
2.3. Enantioselective hydrogenation experiments
The enantioselective hydrogenation of 1,1-dimethoxyacetone 1a
was used as a representative: The autoclave was charged with the
above-prepared chiral Pt nanoparticle catalyst (32 mg, containing
−3
3
.56 × 10 mmol of Pt), CILPEG-CD (12 mg), glacial acetic acid (1.6 g),
toluene (1.0 g), n-heptane (0.3 g) and cyclohexane (50 mg, internal
standard). The mixture was stirred for 30 min at 30 °C, and then 1,1-
dimethoxyacetone 1a (42 mg, 1a/Pt = 100:1) was added. The reactor
3
4
0 °C, the conversion rapidly increased from 37% to > 99% (entry 5 vs.
). This can be explained by the fact that the reaction system changes
from two-phase to homogeneous phase at 30 °C. Meanwhile, the > 99%
ee remained unchanged. However, once the temperature exceeded
2
was flushed three times with 2.0 MPa H and stirred under required
hydrogen pressure at an appointed temperature for a designated time.
After reaction, the autoclave was cooled in an ice-water bath and then
depressurized. The lower chiral Pt nanoparticle catalyst phase was ea-
sily separated from the upper organic phase containing products by
simple phase separation and directly reused in next catalytic cycle. The
3
6
0 °C, the decrease in the conversion or the ee was observed (entries
–7 vs. 4). According to the reported literatures [20,30], it's most likely
that the chiral modifier is either desorbed from the metal catalyst sur-
face or hydrogenated at higher temperature. However, in our experi-
ment no hydrogenation product of the chiral ionic liquid CILPEG-CD was
1
upper phase was directly analyzed by chiral GC and H NMR.
1
detected by H NMR. To further illustrate this phenomenon, the catalyst
of entry 7 was reused at 30 °C and the results indicated that the decrease
was probably the result of desorption of CILPEG-CD from Pt nanoparticle
catalyst (entry 8 vs. 7). In addition, the dependence of the conversion
and the ee on hydrogen pressure was investigated between 3 and 6 MPa
(entries 4 and 9–11). The data showed that both the conversion and the
ee increased with increasing hydrogen pressure until the > 99% con-
version and ee were achieved at 5 MPa. With a further increase in the
hydrogen pressure to 6 MPa, the conversion and the ee remained
2
.4. Gram-scale reaction
The autoclave was charged with chiral Pt nanoparticle catalyst
−2
(
0.80 g, containing 8.90 × 10 mmol of Pt), CILPEG-CD (0.30 g), glacial
acetic acid (40.0 g), toluene (25.0 g), n-heptane (7.50 g) and cyclo-
hexane (1.25 g, internal standard). The mixture was stirred for 30 min
at 30 °C, and then 1,1-dimethoxyacetone 1a (1.05 g, 1a/Pt = 100:1)
56

X. Xue et al.
Catalysis Communications 110 (2018) 55–58
Table 2
Enantioselective hydrogenation of activated ketones catalyzed by the thermoregulated
a
phase-separable chiral Pt nanoparticles.
Fig. 2. Recycling efficiency of the thermoregulated phase-separable chiral Pt nanoparticle
catalyst for enantioselective hydrogenation of 1,1-dimethoxyacetone 1a.
unchanged. It was also clearly to see that prolonging reaction time led
to an increase from 20% to > 99% in the conversion (entries 4 and
12–14). Therefore, the optimal reaction conditions for enantioselective
hydrogenation of 1,1-dimethoxyacetone 1a were established and
shown in Table 1 (entry 4) with the conversion of > 99% as well as
excellent enantioselectivity of > 99%.
With the optimized reaction conditions in hand, we evaluated the
recycling efficiency of the thermoregulated phase-separable chiral Pt
nanoparticle catalyst in the enantioselective hydrogenation of 1,1-di-
methoxyacetone 1a. After reaction, the lower chiral Pt nanoparticle
catalyst phase was easily separated from the upper organic phase by
simple phase separation and then directly reused in the next reaction
run. As shown in Fig. 2, the > 99% conversion and ee remained un-
changed even after four catalytic cycles. TEM images revealed that after
four cycles the size of Pt nanoparticles changed within the margin of
error from 2.0 to 2.2 nm (Fig. 3). In addition, we studied the leaching of
Pt in the upper organic phase by ICP-AES and the results indicated that
the leaching was under the detection limit of the instrument. These
results further confirmed that the thermoregulated phase-separable
chiral Pt nanoparticle catalyst is stable, enantioselective and recyclable
for enantioselective hydrogenation of activated ketones.
of chiral α-hydroxy acetals and chiral 1,2-diols by employing various
activated ketones as substrates (Table 2). The results showed that a
series of chiral α-hydroxy acetals and chiral 1,2-diols bearing different
substituent groups (2b–d and 2h–m) were obtained with up to > 99%
ee while substrates with bulky group of X(Y) gave relatively low ee
resulting from the steric hindrance (2e–g).
As a further demonstration of the practical applicability of this
study, a gram-scale reaction was performed with 1,1-dimethoxyacetone
1a (1.05 g, 8.90 mmol) as test substrate under the optimized reaction
In further experiments, we turned our attention to exploring the
generality of the thermoregulated phase-separable chiral Pt nano-
particle catalyst in the enantioselective hydrogenation for preparation
conditions. We pleased to find that the desired product 2a was obtained
with 96% ee at > 99% substrate conversion. More importantly, the
chiral Pt nanoparticle catalyst could be reused three times without any
loss in catalytic activity and enantioselectivity. These results further
suggested that our chiral catalyst is highly efficient and recyclable for
preparation of chiral α-hydroxy acetals and chiral 1,2-diols.
To gain further insight into the above-mentioned reaction, we made
an attempt to the chiral Pt nanoparticles-catalyzed hydrogenation of
simple ketones, such as 2-hexanone, cyclobutyl methyl ketone and
acetophenone. However, no products were found in this process. Then
the hydrogenation of 4,4-dimethoxy-2-butanone (β-keto acetal) and 4-
hydroxy-2-butanone (β-hydroxy ketone) was explored, similarly, no
products were achieved. In comparison to the hydrogenation of α-keto
acetals and α-hydroxy ketones, it seems that ketones with electron-
withdrawing groups in the α-position are more easily hydrogenated,
which is in agreement with previous literatures [31,32]. Meanwhile, we
found the hydrogenation rate of α-keto acetals was faster than α-hy-
droxy ketones, which is also consistent with the inductive effect of
electron-withdrawing groups (eOR > eOH). Namely, the above re-
sults probably suggest the effect of the electron-withdrawing groups in
α-position to the ketone seems very indispensable.
4. Conclusion
In summary, a highly efficient and recyclable thermoregulated
phase-separable chiral Pt nanoparticle catalyst was firstly reported
for enantioselective hydrogenation of activated ketones. Excellent
Fig. 3. TEM images and size distribution histograms of the chiral Pt nanoparticle catalyst
freshly prepared (a) and after four cycles (b) (200 particles).
57

X. Xue et al.
Catalysis Communications 110 (2018) 55–58
enantioselectivity reached up to > 99%. More importantly, the catalyst
could be easily separated from products by simple phase separation and
directly reused in the next catalytic cycle without any loss in activity
and enantioselectivity. The leaching of Pt was under the detection limit
of the instrument. In addition, the gram-scale reaction was also
achieved with > 99% conversion and 96% ee, even after three cycles.
These inspiring results indicated that the thermoregulated phase-se-
parable chiral Pt nanoparticle catalyst was highly enantioselective and
recyclable for preparation of chiral α-hydroxy acetals and chiral 1,2-
diols. Till now, studies on the mechanism aspects are still open [33–35]
which need more detailed investigations and this will be the focus of
our future work.
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