A Cinchona Alkaloid-Functionalized Mesostructured Silica for Construction of Enriched Chiral β-Trifluoromethyl-β-Hydroxy Ketones over An Epoxidation-Relay Reduction Process

Article abstract of DOI:10.1002/asia.201600640

A cinchona alkaloid-functionalized heterogeneous catalyst is prepared through a thiol-ene click reaction of chiral N-(3,5-ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co-condensation of 1,2-bis(triethoxysilyl)ethane and 3-(triethoxysilyl)propane-1-thiol. Structural analyses and characterizations disclose its well-defined chiral single-site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β-trifluoromethyl-β,β-disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β-trifluoromethyl-β-hydroxy ketones through a sequential epoxidation-relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone, showing an attractive feature in a practical construction of enriched chiral β-CF₃-substituted molecules.

Full text of DOI:10.1002/asia.201600640

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: A Cinchona Alkaloid-Functionalized Mesostructured Silica for Construction
of Enriched Chiral β-Trifluoromethyl-β-Hydroxy Ketones over An Epoxidation-
Relay-Reduction Process
Authors: Guohua Liu; Xiaomin Shu; Liang Li; Gengwei Zhang; Cuibao Li; Tanyu
Cheng; Ronghua Jin
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Chemistry - An Asian Journal
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FULL PAPERS
DOI: 10.1002/asia.200((will be filled in by the editorial staff))
A Cinchona Alkaloid-Functionalized Mesostructured Silica for Construction of
Enriched Chiral β-Trifluoromethyl-β-Hydroxy Ketones over An Epoxidation-Relay-
Reduction Process
Cuibao Li, Xiaomin Shu, Liang Li, Genwei Zhang, Ronghua Jin, Tanyu Cheng, Guohua Liu*
Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai
Normal University, Shanghai 200234, P. R. China
Abstract:
functionalized heterogeneous catalyst is its monodisperse property. As
prepared through thiol-ene click heterogenous catalyst, it enables an enone, showing an attractive feature in
reaction of chiral N-(3,5- efficient asymmetric epoxidation of a practical construction of enriched
ditrifluoromethylbenzyl)quininium achiral β-trifluoromethyl-β,β- chiral β-CF3-substituted molecules.
A
cinchona alkaloid- and electron microscopy images reveal and reused in asymmetric epoxidation
a
of 4,4,4-trifluoro-1,3-diphenylbut-2-
a
bromide and a mesostructured silica disubstituted, where those obtained
obtained by co-condensation of 1,2- chiral products can be converted easily
Keywords: Asymmetric catalysis •
Heterogeneous catalyst •
Immobilization • Silica • Supported
catalysts
bis(triethoxysilyl)ethane
(triethoxysilyl)propane-1-thiol.
Structural analyses
characterizations disclose its well- Furthermore,
and
3- into enriched chiral β-trifluoromethyl-
β-hydroxy ketones through a sequential
and epoxidation-relay-reduction
process.
heterogeneous
this
defined chiral single-site active center, catalyst can be recovered conveniently
enantioselective tandem reduction-isomerition reaction,[4]
asymmetric epoxidation[5] and so on.[6] Among these methods,
asymmetric epoxidation is accepted extensively as a powerful
and reliable organic transformations for construction of these
ketones with CF3-bearing chiral tertiary carbon center, as it is
not only useful to prepare enriched chiral epoxides[5] but also
can be used to convert into various chiral β-trifluoromethyl-
β-hydroxy ketones.[5b,7] Although tremendous efforts have
been made in asymmetric epoxidation,[8] its application in
construction of enriched chiral epoxides from achiral β-
trifluoromethyl-β,β-disubstituted enones is still rare.[5] Only
two successful examples enable asymmetric epoxidation of
achiral β-trifluoromethyl-β,β-disubstituted enones to enriched
Introduction
Construction of enriched chiral β-trifluoromethylated
aromatic ketones with CF3-bearing chiral tertiary carbon
center is highly desirable because these ketones as synthetic
building blocks can be converted easily into various
biologically active organic molecules in fluorine chemistry.[1]
So far, strategy for enantioselective construction of these
ketones with CF3-bearing chiral tertiary carbon center
empolys mainly β-trifluoromethyl-β,β-disubstituted enones as
prochiral substrates, which includes enantioselective
reduction,[2]
enantioselective
aldol
reaction,[3]
chiral epoxides, where Shibata group[5a] reported
a
methylhydrazine-induced asymmetric epoxidation of β-
trifluoromethyl-β,β-disubstituted enones through the use of
chiral cinchona alkaloid as a catalyst while Chen[5b] group
peformed this asymmetric transformation through the
utilization of a pentafluorinated quinidine-based catalyst
under hydrogen peroxide condition. Despite of both highly
catalytic performances, their practical applications are still
hindered greatly due to the inherent drawbacks of expensive
chiral ligands and complicated product isolation. Therefore,
development of an immobilization strategy to overcome these
limitations is an unmet challenge both in fundamental
research and practical application.
[a]
Professor Guohua Liu
Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai
Key Laboratory of Rare Earth Functional Materials, Shanghai Normal
University
Address: No.100 Guilin Rd.
Fax: (+) (0086)2164322511
E-mail: ghliu@shnu.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.200xxxxxx.((Please delete if not
appropriate))
1

Chemistry - An Asian Journal
10.1002/asia.201600640
Mesostructured silica nanoparticles, especially periodic using cetyl-trimethylammonium bromide (CTAB) as a
mesoporous organosilicas as a kind of idea supports, have structure-directing template[12] gave mercapto-functionalized
been well-documented in immobilization of various chiral mesoporous nanoparticles (SH@Et@MNPs (1)) in the form
molecules for asymmetric catalysis,[9] Recently, we also of
a
white powder. Thiol-ene click reaction[13] of
found that ethylene-bridged mesoporous nanoparticles SH@Et@MNPs
(1)
and
N-(3,5-
(MNPs) could be applied successfully to asymmetric ditrifluoromethylbenzyl)quininium bromide (2) then led to
transfer hydrogenation of various ketones, leading to the crude heterogeneous catalyst, Cinchona@Et@MNPs (3).
excellent catalytic and enantioselective performances that Finally, this crude one was Soxhlet extracted strictly,
are benefited from highly hydrophobic nature of ethene- affording its pure catalyst 3 as a light-yellow powder (see SI
bridged organosilicate walls.[10] This significent feature in experimental section and in Figure S1-3).
facilitates an aqueous enantioselective reaction because
Figure 1 showed the 29Si magic angle spinning (MAS)
hydrophobic nature enhances reaction rate in a biphasic NMR spectra of 1 and catalyst 3, where both only produced
reaction medium. Thus, taking consideration of ethylene- one group of T signals that were derived from organosilica.
bridged MNPs as a support, it is reasonable to expect that These exclusive T signals demonstrated that all Si species in
chiral cinchona alkaloid anchored onto such
a
catalyt 3 were bonded to carbon atoms.[14] As compared these
mesostructured silica enables an efficient asymmetric isomer values of Si species with those standard values in the
epoxidation of β-trifluoromethyl-β,β-disubstituted enones.
literature,[14] both T signals around −59.5 and −67.2 ppm in
As an ongoing research aimed at developing heterogeneous catalyst 3 were responded to T2 [RSi(OSi)2(OH)] and T3
catalysts for enantioselective reactions,[11] in this contribution, [RSi(OSi)3] (R = alkyl-linked cinchona alkaloid or ethylene-
we utilize the ethylene-bridged mesoporous nanoparticles to bridged groups) species. These observation expatiated that
anchor N-(3,5-ditrifluoromethylbenzyl)quininium bromide catalyst 3 possessed an organosilicate network with R-
through a thiol-ene click approach, constructing a cinchona Si(OSi)2(OH) and [R-Si(OSi)3] species as its main
alkaloid-functionalized mesoporous organosilica. As
a
orgnaosilicate wall. Furthermore, the absence of signals from
heterogeneous catalyst, it not only displays a highly −90 to −120 ppm means no inorganosilica species for Q-
enantioselective epoxidation of achiral β-trifluoromethyl-β,β- series, indicating that no carbon–silicon bonds cleaved during
disubstituted enones but also converts epoxides into chiral β- the co-condensation process
trifluoromethyl-β-hydroxy ketones through
a sequential
epoxidation-relay-reduction process. As demonstrated in the
study, the superior catalytic performance is attributed to
salient hydrophobicity and confined chiral cinchona alkaloid
catalytic nature. Furthermore, this heterogeneous catalyst can
be recovered conveniently and reused repeatedly for at least
eight times without loss of its catalytic activity in asymmetric
epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone.
Results and Discussion
Synthesis and structural characterization of the
heterogeneous catalyst
Figure 1. Solid-state 29Si CP/MAS NMR spectra of 1 and catalyst 3.
a
c
b
e
f
Catalyst 3
1
d
g
*
*
e
Scheme 1. Preparation of catalysts 3.
300
250
200
150
100
50
0 ppm
Figure 2. Solid-state 13C CP/MAS NMR spectra of 1 and catalyst 3.
Ethylene-bridged chiral cinchona alkaloid-functionalized
mesoporous
Cinchona@Et@MNPs (3), were constructed as outlined in
Scheme 1. Firstly, co-condensation of 1,2-
bis(triethoxysilyl)ethane and 3-(triethoxysilyl)propane-1-thiol
nanoparticles,
abbreviated
as
Anchoring chiral cinchona alkaloid-functionality on the
ethylene-bridged silicate network of 3 could be confirmed by
2

Chemistry - An Asian Journal
10.1002/asia.201600640
solid-state 13C cross-polarization (CP) MAS NMR and the residual CTAB surfactant.[15] After the elimination of
spectroscopy. As shown in Figure 2, both 1 and catalyst 3 the contribution coming from water, the total weight loss of
produced strong carbon signals of -SiCH2 groups at ~6 ppm, the organic moieties was 32.59%. In sharp contrast to the
which ascribed their ethylene-bridged silica embedded in TG/DTA curve of SH@Et@MNPs (1) with 22.07% of the
their silicate networks. In contrast catalyst 3 with its parent 1, total weight loss for the similar organic moieties (see SI in
the characteristic carbon signals between 162 and 112 ppm in Figure S2), the actual loss of cinchona alkaloid was 10.52%,
the spectrum of 3 were assigned to the carbon atoms of the meaning that the loading amount of chiral cinchona alkaloid
aromatic ring while peaks between 75 and 49 ppm ascribed was 105.20 mg (0.166 mmol) per gram catalyst.
the carbon atoms of cyclic alkyl groups in the part of chiral
moiety. These observed chemical shifts of catalyst 3 were
absent in the spectrum of 1, suggesting that the single-site
chiral cinchona alkaloid-functionality had been anchored
successfully onto 1 through this thiol-ene click reaction as
these chemical shifts were same as those of its homogeneous
counterpart.[8a] In addition, the peaks around ~14, ~30 and
~60 ppm for methyl (or methylene) groups without/with
connection to nitrogen atom in CTAB moiety could be
observed clearly that were attributed to the residual CTAB
molecule in catalyst 3.[15]
100
80
100
80
60
60
DTA of 3
TG of 3
40
40
20
20
400
600
800
1000
1200
Temperature/ K
Figure 3. The TG/DTA curves of catalyst 3.
Figure 5. (a) SEM images of 3, (b) TEM images of 3, and (c) TEM image with a
chemical mapping of 3 showing the distribution of Si (white) and S (red).
Its mesostructural morphology of catalyst 3 were further
characterized using nitrogen adsorption–desorption technique,
X-ray diffraction (XRD), scanning electron microscopy
(SEM) and transmission electron microscopy (TEM). As
shown in Figure 4, the heterogeneous catalysts 3 displayed
the type IV nitrogen adsorption-desorption isotherms with the
H2 hysteresis loop while the low-angle XRD pattern (see SI
in Figure S3) exhibited the well resolved peaks at 2θ = 0.8°-
1.0°, indicating the ordered mesoporous structure. The SEM
image (Figure 5a) revealed that catalyst 3 was composed of
the uniformly distributed nanopartiles with a particle size of
Figure 4. Nitrogen adsorption-desorption isotherms of 1 and catalyst 3.
Figure 3 exhibited the TG/DTA curves of catalyst 3. It was
found that an endothermic peak around 356 K with 13.45%
of weight loss was due to the release of physical adsorption
water. Two exothermic peaks around 455 K and 1050 K with
28.21% of the total weight loss could be assigned to the
oxidation of the organic moieties including propyl-linked
thiol, alkyl-linked cinchona alkaloid, ethylene-bridged groups
3

Chemistry - An Asian Journal
10.1002/asia.201600640
sequential epoxidation-relay-reduction process.[5a,5b] The
results showed that this epoxidation-relay-reduction could
afford the reductive products of (S)-4,4,4-trifluoro-3-
hydroxy-1,3-diphenylbutanone in a quantitatively with the
retained 96% ee value (Entry 1, Table 1). This finding
offered an opportunity to test its enantiospecificity (%es)
[%es = 100 (product ee)/(chiral intermediate ee)]. As
observed, this enantioselective epoxidation-relay-reduction
had excellent enantiospecificity (100%), indicating the
superiority of this enantioselective relay reaction.
Having obtained an efficient epoxidation-relay-reduction,
we further investigated its applicability with a series of β-
trifluoromethylated enones. As shown in Table 1, various β-
trifluoromethylated enones could be transformed steadily to
the responding chiral products with high yields and
enantioselectivities as shown in column 8-9 in Table 1. In
order to compare their enantiospecificities, the single-step
enantioselective epoxidation of β-trifluoromethylated enones
to chiral epoxides[5a] catalyzed by 3 was also performed in
column 5-7 in Table 1. As expected, these enantioselective
epoxidation-relay-reduction had excellent enantiospecificities
(more than 99%), confirming the benefit in the practical
construction of enriched chiral β-CF3-substituted compounds.
Also, it was found that the structures and electronic
properties of substituents on the aromatic rings at R1 or R2
groups did not affect their enantiospecificity, where the
asymmetric reactions with various electron-withdrawing and
-donating substituents on the aryl moiety at R1 or R2 were
equally efficient (Entries 2–12).
about 130 nm, while the TEM image (Figure 5b) verified its
mesostructural morphology. It was noteworthy that the
sulphur atoms in catalyst 3 were uniformly distribution
within its organosilicate network observed in a TEM image
with a chemical mapping technique (Figure 5c). This finding
suggested that the uniformly chiral cinchona alkaloid-
functionalities in catalyst 3 play an important role to
dominate its catalytic performance discussed below.
Catalytic performance of the heterogeneous catalyst
Catalytic properties
Cinchona alkaloids are well-known as an efficient chiral
catalyst to catalyze asymmetric epoxidation of various
16]
enones,[5,
As presented in this study, we examined the
enantioselective performance of catalyst 3 in the asymmetric
epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone at
first, where the methylhydrazine-induced epoxidation with
5.0 mol% of 3 as a catalyst under air atmosphere was
investigated according to the reported method.[5a] It was
found that the asymmetric epoxidation of 4,4,4-trifluoro-1,3-
diphenylbut-2-enone catalyzed by 3 gave phenyl((2R,3R)-3-
phenyl-3-(trifluoromethyl)oxiran-2-yl)methanone in a 96%
yield with excellent diastereoselectivity (50:1) and
enantioselectivity of 96% ee (Entry 1, Table 1), which was
comparable to that of its homogeneous counterpart.[5a] Based
on this excellent catalysis, direct transformation of 4,4,4-
trifluoro-1,3-diphenylbut-2-enone to (S)-4,4,4-trifluoro-3-
hydroxy-1,3-diphenylbutanone was performed through a
Table 1. The epoxidation-relay-reduction of β-trifluoromethyl-β,β-disubstituted enones.[a]
6a-6l (R1, R2)
7a-7l[b]
%ee[c]
8a-8l
Entry
6a-6l
%es[e]
R1
R2
Yield
96
dr[d]
Yield
95
%ee[c]
96
1
2
3
4
5
6
7
8
9
10
6a
6b
6c
6d
6e
6f
Ph
Ph
96
94
94
94
96
96
95
92
94
96
50:1
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
p-FPh
p-ClPh
p-BrPh
p-MePh
p-MeOPh
Ph
Ph
95
100:1
50:1
96
94
Ph
95
95
94
Ph
93
50:1
94
95
Ph
97
50:1
93
97
Ph
94
100:1
100:1
100:1
100:1
25:1
94
97
6g
6h
6i
p-FPh
p-ClPh
p-BrPh
p-MePh
95
95
96
Ph
94
95
96
Ph
93
93
97
6j
Ph
96
93
96
4

Chemistry - An Asian Journal
10.1002/asia.201600640
11
6k
6l
Ph
Ph
p-MeOPh
95
92
96
93
100:1
50:1
94
91
96
>99
>99
12
biphenyl
99
[a] Reaction conditions: catalyst 3 (30.12 mg, 5.0 μmol of cinchona alkaloid 5.0%, based on TG analysis), trifluoromethylated enones (0.10 mmol) and Cs2CO3 (39.10 mg, 0.12
mmol, 1.2 equiv) in 5.0 mL (0.017 M) of methyl tert-butyl ether (MTBE) were added hydrazine (6.5 μL, 0.12 mmol, 1.2 equiv) at ambient temperature (25 °C). The mixture was
then stirred at room temperature (25 °C) under air atmosphere for 6-18 h. After that, Zn (13.0 mg, 0.2 mmol, 2 equiv) and NH4Cl (8.0 mg, 0.15 mmol, 1.5 equiv) in 1.0 mL of EtOH
was added, and the mixture was stirred at 40 °C for 2 h. [b] Data were obtained in single-step reactions. [c] The dr values were determined by 1H NMR of the crude products (see SI
in Figure S7). [d] The ee values were determined by chiral HPLC analysis (see SI in Figures S4-5). [e] The es equals (ee of product)/(ee of chiral intermediate).
than that achieved with its inorganosilicate analogue 3' (the
Investigating reaction rate of asymmetric epoxidation
initial TOFs were 4.0 molmol-1h-1 for 3' versus 6.6 molmol-1h-
1 for 3).
Another aim in the design of the heterogeneous catalyst 3
expects to obtain a highly efficient epoxidation through the
overcoming the intrinsic limitation of slow diffusion during
the catalytic process. As observed, the single-step
asymmetric epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-
enone catalyzed by 3 could be completed within 6 h although
its reaction time was longer than 4 h obtained with its
homogeneous counterpart. This result suggested that this
asymmetric epoxidation has a relatively fast reaction rate as a
generally heterogeneous catalyst often needs an obviously
longer reaction time than its corresponding homogeneous
counterpart due to the slow diffusion. This observation
indicated that the hydrophobic benefit of the organosilicate
network in the designed catalyst 3 could promote the single-
step asymmetric epoxidation. In order to confirm the
hydrophobic benefit of catalyst 3, this enantioselective
epoxidation catalyzed a parallel inorganosilicate analogue 3'
was compared, where its analogue 3' could be obtained
through the co-condensation of tetraethoxysilane (instead of
1,2-bis(triethoxysilyl)ethane) and 3-(triethoxysilyl)propane-
1-thiol following the similar synthetic process. Differented
from catalyst 3 with organosilicate ethylene-bridged units as
the silica network, this comparable inorganosilicate analogue
3' had inorganosilicate Si-O-Si-linked units as its silica
network. It was found that the asymmetric epoxidation
catalyzed by 3' was markedly slower than that attained with
catalyst 3 (12 h for 3' versus 6 h for catalyst 3). This
phenomenon demonstrated that the hydrophobic nature of 3
is beneficial to draw 4,4,4-trifluoro-1,3-diphenylbut-2-enone
into the catalytically activity center in nanochannels from
aqueous system, thereby accelerating reaction rates.[10] This
judgment could further be proved by a kinetic investigation
as shown in Figure 6, where the asymmetric epoxidation of
4,4,4-trifluoro-1,3-diphenylbut-2-enone catalyzed by its
homogeneous counterpart, catalyst 3 and its analogue 3' were
performed. The results showed that the enantioselective
reaction catalyzed by 3 resulted in an initial activity higher
100
80
60
40
Homo-counterpart
20
Catalyst 3
Inorganosilicate analog 3'
0
0
1
2
3
4
5
6
7
8
Raction time (h)
Figure 6. Comparison of the enantioselective epoxidation-reduction of 4,4,4-trifluoro-
1,3-diphenylbut-2-enone catalyzed by its homogeneous counterpart (2), catalyst 3 and
its inorganosilicate analogue 3'. Reactions were carried out using 5 mol% of catalysts.
Catalyst recycling and reuse
In addition to the aim for construction of optically pure β-
trifluoromethyl-β-hydroxy
ketones,
an
important
consideration is the ease of separation for the heterogeneous
catalyst 3, and the recycled heterogeneous catalyst 3 can
retain its reactivity and enantioselectivity after multiple
recycling. As observed, the heterogeneous catalyst 3 could be
recovered easily from the reaction system by simple
centrifugation. As shown in Table 2, in eight consecutive
reactions, the recycled heterogeneous catalyst 3 still produced
chiral products with 91% yield and 95% ee in the asymmetric
epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone to
phenyl((2R,3R)-(3-phenyl-3-(trifluoromethyl)oxiran-2-
yl)methanone.
Table 2. Reusability of catalyst 3 for asymmetric epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-en-1-one to phenyl ((2R,3R)-3-phenyl-3-(trifluoromethyl)oxiran-2-yl)methanone.[a,
b]
Run time
% Conversion
% ee
1
2
3
4
5
6
7
8
98
96
96
96
95
96
95
96
95
96
95
96
94
96
91
95
5

Chemistry - An Asian Journal
10.1002/asia.201600640
[a] Reaction conditions: catalyst 3 (301.20 mg, 5.0 μmol of cinchona alkaloid 5.0%, based on TG analysis), trifluoromethylated enones (1.0 mmol) and Cs2CO3 (1.20 mmol, 1.2
equiv) in 20.0 mL (0.017 M) of methyl tert-butyl ether (MTBE) were added hydrazine (1.2 mmol, 1.2 equiv) at ambient temperature (25 °C). The mixture was then stirred at room
temperature (25 °C) under air atmosphere for 6 h. [b] Determined by chiral HPLC analysis (see SI in Figure S6).
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trifluoromethyl-β,β-disubstituted enones to chiral β-
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more than 99% enantiospecificity. As presented in this study,
[2]
[3]
C. Benhaim, L. Bouchard, G. Pelletier, J. Sellstedt, L. Kristofova, S. Daigneault,
hydrophobic periodic mesoporous organosilica, uniformly
distributed active species, and confined cinchona alkaloid
catalytic nature are responsible for its highly catalytic
performance. Furthermore, the heterogeneous catalyst could
also be recovered easily and reused repeatedly eight times
without obvious effect on its reactivity in the enantioselective
epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enonee,
affording a practical approach for construction of valuable
chiral β-CF3-substituted molecules.
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Preparation of the heterogeneous Catalyst 3. In a typical synthesis, a dry 50 mL
round-bottom flask was charged with SH@Et@MNPs (1) (0.50 g), chiral cinchona
alkaloid (2) (309.0 mg, 0.50 mmol), and 2.0 mol% of 2,2-dimethoxy-1,2-
diphenylethanone photoinitiator, backfilled with argon, and irradiated for 27 h with a 15
W blacklight (λmax = 365 nm). The resulting solid was filtered through filter paper and
rinsed with excess methanol and dichloromethane. After Soxlet extraction in
dichloromethane solvent for 12 h to remove any homogeneous and unreacted starting
materials, the solid was dried overnight at 60ºC under vacuum to afford the
heterogeneous catalyst (3) (0.58 g) as a light−yellow powder. IR (KBr) cm−1: 3425.3 (s),
2919.9 (w), 2849.9 (w), 1490.1 (w), 1411.6 (m), 1167.5 (s), 1037.1 (s), 872.7 (m), 767.9
(m), 698.3 (m), 445.5 (m). 13C CP MAS NMR (161.9 MHz): 162.1−112.2 (C of Ar, Ph
and CF3), 73.2−49.0 (C of cyclic alkyl groups in cycling group connected to N atom, of
–CHOH, and of –OCH3, and C of –NCH2 and –NCH3 in CTAB molecule), 46.5-31.2 (C
of –SCH2CH2CH2Si, and of –CH2CH2CH2NCH3), 23.5 (C of –SCH2CH2CH2Si, of –
CH2CH2CH2–, and of cyclic alkyl groups in cycling group without connected to N atom
in CTAB molecule), 13.3 (13.4 (C of −CH2CH3 in CTAB molecule), 5.9 (C of −CH2Si)
ppm. 29Si MAS/NMR (79.4 MHz): T2 (δ = −59.5 ppm), T3 (δ = −67.2 ppm). Elemental
analysis (%): C 18.15, H 2.83, N 0.56, S 0.88.
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General procedure for the enantioselective epoxidation-relay-reduction of β-
trifluoromethyl-β,β-disubstituted enones. A typical procedure was as follows: To a
stirred suspension of catalyst 3 (30.12 mg, 5.0 μmol of cinchona alkaloid 5.0%, based
on TG analysis), trifluoromethylated enones (0.10 mmol) and Cs2CO3 (39.10 mg, 0.12
mmol, 1.2 equiv) in 5.0 mL (0.017 M) of methyl tert-butyl ether (MTBE) were added
hydrazine (6.5 μL, 0.12 mmol, 1.2 equiv) at ambient temperature (25 °C). The mixture
was then stirred at the same temperature under air atmosphere for 6-18 h. During this
period, the reaction was monitored constantly by TLC. When the reaction was
completed, catalyst was separated by centrifugation (10,000 rpm) for the recycling
experiment. Aqueous solution was added Zn (13.0 mg, 0.2 mmol, 2 equiv) and NH4Cl
(8.0 mg, 0.15 mmol, 1.5 equiv) in 1.0 mL of EtOH, and the mixture was stirred at 40 °C
for 2 h. The reaction was then quenched with water. Aqueous layer was extracted with
ethyl ether (3 × 3.0 mL). The combined ethyl ether extracts were washed with NaHCO3
and brine, and then dehydrated with Na2SO4. After evaporation of ethyl ether, the
residue was purified by silica gel flash column chromatography to afford the desired
product. The yields were determined by 1H-NMR, and the ee values were determined by
a HPLC analysis using a UV-Vis detector and a Daicel chiralcel column (Φ 0.46 × 25
cm).
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Acknowledgements
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We are grateful to China National Natural Science Foundation (21402120), Shanghai
Sciences and Technologies Development Fund (13ZR1458700), CSIRT (IRT1269) and
Shanghai Municipal Education Commission (14YZ074) for financial supports.
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6

Chemistry - An Asian Journal
10.1002/asia.201600640
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Received: ((will be filled in by the editorial staff))
Revised: ((will be filled in by the editorial staff))
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7

Chemistry - An Asian Journal
10.1002/asia.201600640
Entry for the Table of Contents (Please choose one layout only)
Layout 2:
Heterogeneous Asymmetric
Catalysis
Cuibao Li, Xiaomin Shu, Liang Li,
Genwei Zhang, Ronghua Jin, Tanyu
Cheng, Guohua Liu* …….… Page
– Page
A cinchona alkaloid-functionalized
mesostructured silica enables an
efficient asymmetric epoxidation of
through a sequential epoxidation-
relay-reduction
superior catalytic performance are
attributed to hydrophobic
process.
The
A
Cinchona
Alkaloid-
achiral
disubstituted, where these chiral
products can be converted
β-trifluoromethyl-β,β-
Functionalized Mesostructured
Silica
Enriched
Trifluoromethyl-β-Hydroxy
Ketones over An Epoxidation-
Relay-Reduction Process
mesoporous organosilica network,
uniformly distributed active species,
and confined cinchona alkaloid
catalytic nature.
for Construction of
Chiral β-
conveniently into enriched chiral β-
trifluoromethyl-β-hydroxy ketones
0