Yolk-shell-structured mesoporous silica: A bifunctional catalyst for nitroaldol-Michael one-pot cascade reaction

Article abstract of DOI:10.1039/c6cy00716c

Great interest in heterogeneous asymmetric catalysis has focused on obtaining an enantioselective cascade reaction through a controllable active site-isolated heterogeneous catalyst. Herein, we utilize a yolk-shell-structured mesoporous silica and assemble an active site-isolated bifunctional heterogeneous catalyst, where chiral cinchonine-based squaramide molecules are anchored within a silicate channel as an outer shell while amine-functionalities are entrapped onto a silicate yolk as an inner core. Structural analyses and characterizations of the heterogeneous catalyst reveal its well-defined single-site chiral active species within its silicate network. Electron microscopy confirms the yolk-shell-structured mesoporous material. As presented in this study, as a bifunctional heterogeneous catalyst, it enables an efficiently nitroaldol-Michael cascade reaction to conduct the three-component coupling of nitromethane, aldehyde and acetylacetone into various chiral diones with high yields and up to 99% enantioselectivities in a one-pot process. As expected, this active site-isolated catalyst not only enhances the catalytic selectivity of the first-step nitroaldol condensation, but also keeps the enantioselectivity of the second-step Michael addition. Moreover, the heterogeneous catalyst can be also recovered easily and recycled repeatedly, making it an interesting feature in a three-component organic transformation.

Full text of DOI:10.1039/c6cy00716c

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Yolk–Shell–Structured Mesoporous Silica: A Bifunctional Catalyst for
Nitroaldol–Michael One-Pot Cascade Reaction
Juzeng An, Tanyu Cheng, Xi Xiong, Liang Wu, Bing Han and Guohua Liu*
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
5
An important interest in heterogeneous asymmetric catalysis expects to obtain an enantioselective
cascade reaction through a controllable active siteꢀisolated heterogeneous catalyst. Herein, we
utilize a yolkꢀshellꢀstructured mesoporous silica and assemble an active siteꢀisolated bifunctional
heterogeneous catalyst, where chiral cinchonineꢀbased squaramide molecules are anchored within
silicate channel as an outer shell while amineꢀfunctionalities are entrapped onto silicate yolk as
inner core. Structural analyses and characterizations of the heterogenesous catalyst reveal its wellꢀ
defined singleꢀsite chiral active species within its silicate network. Electron microscopies confirm
its yolkꢀshellꢀstructured mesoporous material. As presented in this study, as a bifunctional
heterogeneous catalyst, it enables an efficiently nitroaldol–Michael cascade reaction to convert
threeꢀcomponent coupling of nitromethane, aldehyde and acetylacetone into various chiral diones
with high yields and up to 99% enantioselectivities in oneꢀpot process. As expected, this active
siteꢀisolated catalyst not only enhances the catalytic selectivity of firstꢀstep nitroaldol condensation
but also keeps the enantioselectivity of secondꢀstep Michael addition. Moreover, heterogeneous
catalyst can be also recovered easily and recycled repeatedly, making it an interesting feature in a
threeꢀcomponent organic transformation.
1
1
2
0
5
0
heterogeneous asymmetric catalysis.
1
. Introduction
Nitroaldol condensation and Michael addition, as two classical
carbonꢀcarbon bond formation reactions, have been studied both
theoretically and practically. In particular, nitroaldol condensation
of nitromethane and aromatic aldehyde, and enantioselective
Michael addition of βꢀdicarbonyl compounds to nitrostyrene are
Development of mesoporous silicas as supports for construction
of silicaꢀsupported catalysts and their application in
enantioselective reactions have obtained great achievements in
heterogeneous asymmetric catalysis, where benefits from
confinement effect and synergistic effect of mesoporous silicas
have led to lots of highly efficient heterogeneous catalysts.
Especially, siteꢀisolated strategy used in mesoporous silicate
materials have opened new opportunity for construction of
bifunctional heterogeneous catalysts. This strategy not only
complements nicely the drawbacks of homogeneous catalysis
through overcoming intrinsic incompatibility of two types of
active species in oneꢀpot reaction, but also finds a new tandem
reaction that is unfeasible in a homogeneous condition. Recently,
some significiant cascade reactions catalyzed by active siteꢀ
5
6
6
7
7
5
0
5
0
5
2
3
3
4
4
5
0
5
0
5
[4]
wellꢀdocumented in the literature, respectively. Despite of great
interest in nitroaldol–Michael oneꢀpot reaction for construction of
complicated organic molecules because of atom economy and
minimum workup, direct oneꢀpot nitroaldol–Michael reactions
[
1]
[5]
are still rare, especially for nitroaldol–Michael oneꢀpot cascade
[
2]
reaction for construction of optically pure products. Recently,
chiral cinchonineꢀbased squaramides have exhibit excellent
enantioselectivity in asymmetric Michael addition of 1,3ꢀ
[6]
dicarbonyl compounds to nitroalkenes. These findings offer a
practical approach to explore their application in oneꢀpot
nitroaldol–Michael cascade reaction. Therefore, utilizing the
advantage of yolkꢀshellꢀstructured mesoporous silica, facile
construction of an active siteꢀisolated heterogenous catalyst and
realization of a nitroaldol–Michael oneꢀpot cascade reaction are
highly desirable.
[
2fꢀ
isolated heterogeneous catalysts had appeared in the literatures.
2h]
Yolkꢀshellꢀstructured silicas, as a kind of special mesoporous
[
3]
materials, possess inherent superiority in design of active siteꢀ
isolated heterogenous catalysts because their yolk and shell can
anchor separately different active species. This feature make
these yolkꢀshellꢀstructured mesoporous silicas attracting in
construction of various novel active siteꢀisolated bifunctional
As an effort to develop silicaꢀsupported heterogeneous
[7]
catalysts,
recently, we found that chiral cinchonineꢀbased
squaramides supported on ionic liquid could retain the
enantioselectivity performance of homogeneous catalytic system
in asymmetric Michael addition of acetylacetone to nitrostyrene
[
3a]
heterogenous catalysts,
unexplored tandem reactions is still unmit challenge in
however, application them in some
while
nickelꢀamineꢀfunctionalized
periodic
mesoporous
organosilica promoted the catalytic performance of asymmetric
Key Laboratory of Resource Chemistry of Ministry of Education,
Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai
Normal University, Shanghai,
200234, China. E-mail: ghliu@shnu.edu.cn
Fax: 86-21-64322511;Tel: 86-21-64322280
[
7aꢀ7c]
80 Michael addition.
Based on these findings, together with the
benefit of yolkꢀshellꢀstructured mesoporous silicas, we herein
assemble conveniently amineꢀfunctionality onto silicate yolk as
inner core and chiral cinchonineꢀbased squaramide within silicate
5
0
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channel as an outer shell, constructing a yolkꢀshellꢀstructured
active siteꢀisolated bifunctional heterogeneous catalyst through a
simple thiolꢀene click reaction. As expected, this bifunctional
heterogeneous catalyst enables an efficiently nitroaldol–Michael
h. Then, 0.25 g of 1,2ꢀbis(triethoxysilyl)ethane (0.70 mmol) in 2
mL of ethanol and 0.15 (0.60 mmol) of 3ꢀ
mercaptopropyltrimethoxylsilane (2 min later) were added
subsequently under vigorous stirring for 1.5 h. Finally, the
g
5
cascade reaction to convert threeꢀcomponent coupling of 60 temperature was raised to 80 °C and the mixture was stirred at
nitromethane, aldehyde and acetylacetone into various chiral
diones with high yields and up to 99% enantioselectivity in oneꢀ
pot process. Moreover, heterogeneous catalyst can be also
recovered easily and recycled repeatedly four times without
obvious loss of its catalytic activity.
80 °C for another 5 h. After cooling the above mixture down to
room temperature, the solid was collected by filtration. (The third
step for the selective etching) To remove the surfactant and form
yolkꢀshell structured mesoporous nanoparticles, the collected
65 solids (1.0 g) were dispersed in 120 mL of solution (80 mg (1.0
mmol) of ammonium nitrate in 120 mL (95%) of ethanol), and
the mixture was stirred at 60 °C for 12 h. After cooling the above
mixture down to room temperature, the solid was filtered and
washed with excess water and ethanol, and dried at ambient
10
2
. Experimental
2
.1. Characterization
Fourier transform infrared (FTꢀIR) spectra were collected on a 70 temperature under vacuum overnight to afford SH@NH2@NMPs
−
1
Nicolet Magna 550 spectrometer using KBr method. Scanning
electron microscopy (SEM) images were obtained using a JEOL
JSMꢀ6380LV microscope operating at 20 kV. Transmission
electron microscopy (TEM) images were performed on a JEOL
(1) as a white powder (0.65 g) [IR (KBr) cm : 3442.7 (s), 2928.2
13
15
20
25
30
(w), 1633.0 (m), 1391.6 (w), 1064.6 (s), 784.6 (m), 457.4 (m). C
CP MAS NMR (161.9 MHz): 57.9 (CH of −OCH CH ), 42.8 (C
of −SiCH CH N), 31.3−17.2 (C of −SCH , −SiCH CH CH N and
2
2
3
2
2
2
2
2
2
2
9
JEM2010 electron microscope at an acceleration voltage of 220 75 −OCH CH ), 5.7 (C of −SiCH group) ppm. Si MAS NMR
2
3
2
2
3
2
kV. Nitrogen adsorption isotherms were measured at 77 K with a
Quantachrome Nova 4000 analyzer. The samples were measured
after being outgassed at 423 K overnight. Pore size distributions
were calculated by using the BJH model. The specific surface
(79.4 MHz): T (δ = −57.9 ppm), T (δ = −65.9 ppm), Q (δ =
3
4
−91.9 ppm), Q (δ = −101.8 ppm), Q (δ = −110.8 ppm)]. (The
fourth step for the thiol-ene click reaction). a dry 50 mL roundꢀ
bottom flask was charged with SH@NH2@NMPs (1) (0.50 g),
areas (SBET) of samples were determined from the linear parts of 80 squaramide (2) (75.0 mg, 0.12 mmol), and 2.0 mol% of 2,2ꢀ
BET plots (p/p = 0.05ꢀ1.00). Thermal gravimetric analysis (TGA)
was performed with a PerkinꢀElmer Pyris Diamond TG analyzer
under air atmosphere with a heating ramp of 5 K/min. Solid state
dimethoxyꢀ1,2ꢀdiphenylethanone photoinitiator, backfilled with
argon, and irradiated for 24 h with a 15 W blacklight (λmax = 365
nm). The mixture was filtered through filter paper and then rinsed
with excess CH Cl . After Soxhlet extraction for 24 h in CH Cl
2
85 to remove homogeneous and unreacted starting materials, the
solid was dried at ambient temperature under vacuum overnight
0
NMR experiments were explored on a Bruker AVANCE
2
2
2
1
spectrometer at a magnetic field strength of 9.4 T with
H
1
3
29
frequency of 400.1 MHz, C frequency of 100.5 MHz and Si
frequency of 79.4 MHz with 4 mm rotor at two spinning
frequency of 5.5 kHz and 8.0 kHz, TPPM decoupling is applied
to afford Squaramide@NH @MNPs (3) (0.53 g) as a lightꢀyellow
2
−1
powder. IR (KBr) cm : 3433.6 (s), 2939.4 (w), 1623.9 (m),
1531.5 (w), 1475.1 (w), 1391.6 (w), 1287.8 (w), 1064.4 (s), 784.6
1
in the during acquisition period. H cross polarization in all solid
13
state NMR experiments was employed using a contact time of 2 90 (m), 701.1 (m), 457.4 (m). C CP MAS NMR (161.9 MHz):
ms and the pulse lengths of 4ꢁs.
184.7−181.1 (C of C=O groups), 161.9ꢀ168.9 (C of
COCH=CHCO group), 152.3ꢀ115.9 (C of Ar, Ph and CF ), 58.6
−
3
35
2.2. Preparation of the heterogeneous Catalyst 3.
(
CH of −OCH CH ), 49.8−34.9 (C of carbon connected to N
2 2 3
In a typical synthesis, (The first step for the synthesis of silinate
atom in alkyl part), 31.3−16.9 (C of −SCH , −SiCH CH CH N, C
2
2
2
2
yolk) 0.10 g (0.27 mmol) of cetyltrimethylammonium bromide 95 of cyclic alkyl groups in cycling group without connected to N
2
9
(
CTAB) was completely dissolved in 45.0 mL of aqueous sodium
atom and −OCH CH ), 5.8 (C of −SiCH group) ppm. Si MAS
2
3
2
2
3
2
hydroxide (0.35 mL, 2.0 N). The mixture was stirred at room
temperature for 0.5 h. Subsequently, 0.20 g (0.90 mmol) of 3ꢀ
NMR (79.4 MHz): T (δ = −57.1 ppm), T (δ = −66.3 ppm), Q (δ
= −91.8 ppm), Q (δ = −102.2 ppm), Q (δ = −110.3 ppm).
3
4
40
45
50
55
(
triethoxysilyl)propanꢀ1ꢀamine, and 0.43 g of (2.07 mmol) of
2
.3. General procedure for the one-pot enantioselective
tetraethoxysilane (TEOS) was added at room temperature under
vigorous stirring. Finally, 0.40 mL of ethyl acetate was added and
the mixture was stirred at 80 °C for 2 h. (The second step for the
coating above yolk) After cooling the above mixture down to
3
0
was added and the mixture was stirred 38 °C for 0.5 h.
Subsequently, 0.5 mL, 0.47 g (2.26 mmol) of TEOS was added
and the mixture was stirred at 38 °C for another 2 h. After that, an
aqueous solution (3 mL of water containing 0.040 g (0.044 mmol)
1
00 nitroaldol–Michael coupling of aldehydes, nitromethane and
acetylacetone.
A typical procedure was as follows: catalyst 3 (25.0 mg, 5.0 ꢁmol
of squaramide based on the TG analysis) and aldehydes (0.50
mmol) in 1.0 mL of nitromethane were added in a 10 mL
05 round−bottom flask. The mixture was allowed to react at 90 °C
for 3ꢀ6 h. During that time, the reaction was monitored constantly
by TLC to determine the completion of reaction, After cooling
down to room temperature, acetylacetone (2.0 mmol) in 1.0 mL
of CH Cl was added and the mixture was allowed to further
110 react at room temperature for 12–24 h. Then the heterogeneous
catalyst was separated by centrifugation (10,000 rpm) for the
recycling experiment. The aqueous solution was extracted by
Et O (3 × 3.0 mL). The combined Et O was washed with brine
8 °C, an aqueous solution (80 mL of water, 50 mL of ethanol,
.30 g (0.82 mmol) of CTAB and 1.0 mL (25 wt%) of NH ·H O)
3
2
1
of
FCꢀ4
2
2
+
ꢀ
([C F O(CF(CF )CF O) CF(CF )CONH(CH ) N (C H ) CH ]I ),
3 7 3 2 2 3 2 3 2 5 2 3
0
.080 g (0.22 mmol) of CTAB and 0.20 mL (25 wt%) of
NH ·H O) was added and the mixture was stirred at 38 °C for 0.5
3
2
2
2
2
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twice and dehydrated with Na SO . After the evaporation of Et O, 40 of of propyl groups in propylamine or propanethiol moieties,
2
4
2
the residue was purified by silica gel flash column
chromatography to afford the desired product. The conversion
was calculated by the internal standard method and the ee value
could be determined by chiral HPLC analysis with a UVꢀVis
which were similar to those of its parent material 1 that were
[
3a]
marked in the spectrum of 3.
catalyst produced the characteristic carbon signals of
squaramide groups between ~161 and ~185 ppm for the carbon
It was worth mentioning that
3
5
detector using a Daicel ODꢀH, ASꢀH, or ADꢀH chiralcel column 45 atoms of –COCH=CHCO– moieties in fourꢀring squaramide
(
Φ 0.46 × 25 cm).
molecule. In addition, the strong signals for those carbon atoms
of aromatic ring could be observed clearly in the spectrum of 3.
All these peaks are absent in the spectrum of 1, suggesting that
chiral cinchonineꢀbased squaramide molecules were anchored
successfully onto 1 through the thiolꢀene click reaction. Chemical
3
. Results and discussion
50
3
.1. Synthesis and structural characterization of the
shifts of
3 were similar to those of its homogeneous
1
0
heterogeneous catalyst
[
8a]
counterpart, demonstrating that they had the same wellꢀdefined
singleꢀsite active species.
Shell
a c
b
O
m
O
d
b
H
2
N
j
CF
3
Si
S
b
g
Si
Yolk
Si
k NH
a
NH
N
j
2 2
OCH CH
d b
e
f
l OMe
CF
3
j
h
N
a
c
e,f,g
b
Catalyst 3
1
h,i,j,k
d
l,m
300
250
200
150
100
50
0
ꢀ50ppm
Scheme 1. Preparation of the heterogeneous catalysts 3.
13
55
Figure 1. The solidꢀstate C CP MAS NMR spectra of of 1 and catalyst
3.
Yolkꢀshellꢀstructured chiral cinchonineꢀbased squaramideꢀ
functionalized
mesoporous
silica,
abbreviated
as
1
2
2
3
3
5
0
5
0
5
Squaramide@NH @MNPs (3), was synthesized through a dual
silicaꢀcoated strategy. As shown in Scheme 1, a silicate yolk was
formed by coꢀcondensation of tetraethoxysilane (TEOS) and 2ꢀ
2
(
triethoxysilyl)propylamine, and the continuous grown of TEOS
followed by further coꢀcondensation of 1,2ꢀ
bis(triethoxysilyl)ethane and 3ꢀ(triethoxysilyl)propanethiol led to
coreꢀshellꢀstructured mesoporous silica. This coreꢀshellꢀ
3
T
Catalyst 3
1
a
3
structured mesoporous silica was then etched selectively,
Q
4
Q
affording a yolkꢀshellꢀstructured SH@NH @MNPs (1) as a white
2
2
T
2
[
3a]
[8]
powder. Finally, a direction thiolꢀene click reaction of 1 and
Q
[
6a]
chiral squaramide (2) afforded the rude catalyst 3, which was
subjected to Soxhlet extraction to give its pure form as a lightꢀ
yellow powder (see SI in Experimental Section, and in Figures
S1ꢀS2). The thermal gravimetric (TG) analysis revealed that the
loadings of chiral squaramide in catalyst 3 was 128.90 mg (0.20
mmol) per gram catalyst (see SI in Figure S2).
0
ꢀ25
ꢀ50
ꢀ75
ꢀ100
ꢀ125 ppm
2
9
Figure 2. The solidꢀstate Si MAS NMR spectra of of 1 and catalyst 3.
Incorporation of chiral cinchonineꢀbased squaramideꢀ
functionality within the yolkꢀshellꢀstructured mesoporous silicate
13
In addition, its organosilicate network and composition of
network of 3 could be confirmed by solidꢀstate C crossꢀ
polarization (CP)/magic angle spinning (MAS) NMR
spectroscopy. As shown in Figure 1, catalyst 3 produced the
strong carbon signals of –SiCH CH Si– groups around 6 ppm for
29
6
0
catalyst 3 could be confirmed by the solidꢀstate Si MAS NMR
spectroscopy. As shown in Figure 2, both 1 and 3 produced two
groups of typical signals (Qꢀ and Tꢀseries) distributed broadly
from ꢀ40 to ꢀ150 ppm as marked in its spectrum, where Q signals
are attributed to inorganosilica while T signals are corresponded
to organosilica. As compared with those typical isomer shift
2
2
the ethyleneꢀbridged moiety, suggesting its ethyleneꢀbridged
network of organosilicate shell. Peaks around ~5, ~16 and ~31 or
65
~
49 ppm in the spectrum of 3 were corresponded to carbon atoms
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3
values in the literature, the strong T signal of Tꢀseries at −66.3
ppm in the spectrum of 3 suggested the organosilicate R–Si(OSi)3
species (R = alkylꢀlinked chiral squaramide and amine groups) as
3.2. Catalytic performance of the heterogeneous catalyst
Based on the obtained siteꢀisolated bifunctional heterogeneous
catalyst, two singleꢀstep reactions, nitroaldol condensation of
nitromethane and benzaldehyde to nitrostyrene, and
enantioselective Michael addition of acetylacetone to nitrostyrene,
was investigated separately. In the firstꢀstep nitroaldol
condensation, in order to gain better insight into the catalytic
nature of amineꢀfunctionality, several affecting factors coming
from squaramideꢀfunctionality and surface silanols of materials in
3
its main part of organosilica while the strongest Q signal of Qꢀ
series at −102.2 ppm demonstrated its main inorganosilicate
networks of [(OH)Si(OSi)3].
5
30
4
3
2
1
00
00
00
00
1
35 catalyst 3 were evaluated, determining the optimal nitroaldol
condensation of nitromethane and benzaldehyde to nitrostyrene.
Catalyst 3
a
Table 1. Nitroaldol condensation of nitromethane and benzaldehyde.
O
NO2
NO
Catalyst
NO
2
H
+
CH NO2
3
2
o
9
0 C
4a
5a
5b
Amount of
catalyst
(mol%)
Conv.
of 4a
(%)
Yield of
5a (Sel.
) (%)
0.0
0.2
0.4
0.6
0.8
1.0
Entry
Catalyst
Time
[
b]
[c]
Relative Pressure (P/P0)
2
3
3
3
1.0
1.0
3.0
5.0
5.0
5.0
12
3
18
17 (99)
76 (97)
85 (99)
99 (99)
45 (94)
79 (80)
1
2
Figure 3. The nitrogen adsorptionꢀdesorption isotherms of
1
and catalyst
3
.
78
3
4
5
3
86
3
>99
48
Capped
3
3
6
Propylamine
3
98
a
Reaction conditions: catalyst and benzaldehyde (1.0 mmol) in 1.0 mL of
b
40
nitromethane was reacted at 90°C for 3ꢀ12 h.
determined by HꢀNMR. (Yield/Conversion) ×100.
Conversions were
1
c
As shown in Table 1, firstly, we investigated the basic role of
squaramideꢀfunctionality in the firstꢀstep nitroaldol condensation
through the use of homogeneous chiral squaramide (2) as a
parallel base. It was found that the singleꢀstep nitroaldol
condensation catalyzed by 2 only gave very poor conversion of
4
5
5
6
5
0
5
0
1
0
4
a in an obviously prolonged reaction time, suggesting
Figure 4. (a) The SEM images of catalyst
catalyst
3, (b) The TEM images of
squaramideꢀfunctionality within 3 did only slightly affect the
nitroaldol condensation (Table 1, entry 1). This result eliminated
the interference coming from squaramideꢀfunctionality within 3.
Then, we investigated the affecting factor of the loading
amount of amineꢀfunctionality in order to elucidate the role of
amineꢀfunctionality onto the silicate yolk. In this case, three
different loading amount of amineꢀfunctionality the silicate yolk
was tested in singleꢀstep nitroaldol condensation (Table 1, entries
3
.
The ordered mesostructure and morphology of 3 were further
investigated by nitrogen adsorption–desorption measurements,
scanning electron microscopy (SEM), and transmission electron
microscopy (TEM). As shown in Figure 3, the nitrogen
adsorption–desorption isotherm of 3 demonstrated its mesoporous
15
20
25
structure due to its typical type IV isotherm with an H hysteresis
1
2
ꢀ4). The results showed that the nitroaldol condensation
loop and a visible step at P/P = 0.40–0.90, where its pore size
0
depended heavily on the loading amount of amineꢀfunctionality
in catalyst 3, where 5% loading amount of amineꢀfunctionality
could reach the reaction completion within 3.0 h. As expected,
the singleꢀstep nitroaldol condensation catalyzed by 3 should be
of first order because the initial reaction rate was proportional to
distribution reveals that catalyst 3 has uniform mesopores of
about 2.2 nm (see SI in Figure S3). Figure 4 presented the yolkꢀ
shellꢀstructured morphology of catalyst 3, where SEM image
disclosed its monodisperse nanospheres (Figure 4a) while TEM
image confirmed its yolkꢀshell nanostructure (Figure 4b, also see
enlarge TEM images in Figure S4 of SI).
the loading amount of amineꢀfunctionality (Table 1, entry 2ꢀ4),
[10]
indicating the nitro Mannich pathway
rather than nitroaldol
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XXX
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[
11]
pathway
(nitro Mannich and nitroaldol pathways are two
the designed silicaꢀsupported heterogeneous catalyst 3, we also
proved the cooperative role of surface silanols in the promotion
of the singleꢀstep nitroaldol condensation reported by Katz, Asefa
typically chemical mechanisms for nitroaldol condensation of
nitromethane and aromatic aldehyde). An evidence to support the
nitro Mannich pathway came from
[
13]
a
FTꢀIR spectrum 25 and Davis groups.
In this case, we utilized a parallel
5
investigation (see SI in Figure S1). It was found that the
comparison of nitroaldol condensation catalyzed by 3 and 3
capped with ꢀSi(CH3)3 groups (The 3 capped withꢀSi(CH3)3
−1
characteristic vibrations of C=N bond at 1643 cm for reactive
imine intermediate could be observed clearly when the supported
propylamine in 1 was treated with benzaldehyde. This finding
groups was obtained by silanization of
3
and
hexamethyldisilazane), demonstrating their differences in the
confirm its nitro Mannich pathway in the nitroaldol condensation 30 catalytic performance. It was found that the former had obviously
[
2d, 12]
1
0
of nitromethane and benzaldehyde.
higher yield and selectivity than that attained with the latter
Table 1, entry 4 versus entry 5), elucidating that surface silanols
in catalyst could promote synergistically nitroaldol
condensation. This observation is strongly similar to that reported
(
Table 2. Oneꢀpot cascade nitroaldol–Michael coupling of nitromethane,
3
a
aldehydes and acetylacetone.
[
5a, 2d]
35
in literature,
disclosing the superiority of the designed
catalyst 3.
It was worth mentioning that the singleꢀstep nitroaldol
condensation of nitromethane and benzaldehyde catalyzed by 3
had obviously higher selectivity than that attained with its parent
propylamine (Table 1, entry 6 versus entry 4). Notably, relatively
high yield in the 3ꢀcatalyzed nitroaldol condensation benefited
from its higher selectivity, which should be ascribed as its nitro
Mannich pathway and suitable cavum to restrain the formation of
byproducts. Furthermore, when catalyst 3 was applied to the
4
0
Conv. of
Yield of
6 (%)
Ee
(%)[
Entry
R
6
[b]
b]
4
(%)
1
2
3
4
5
6
7
8
9
H
6a
6a
6b
6c
6d
6e
6f
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
99
93
77
95
96
96
94
95
95
96
97
95
93
94
93
95
91
99
[
c]
H
97
99
99
99
99
99
95
99
97
99
97
99
99
98
97
45 singleꢀstep enantioselective Michael addition, we find that
enantioselective Michael addition of acetylacetone to nitrostyrene
could afford the same ee value as its homogeneous counterpart 2
although the reaction time was prolonged to 12 hour due to slow
4ꢀF
4ꢀCl
3ꢀCl
2ꢀCl
4ꢀBr
3ꢀBr
[8c]
diffusible nature of substrates in heterogeneous catalysis. More
5
5
6
6
7
7
0
5
0
5
0
5
importantly, when two singleꢀstep reactions was combinated into
oneꢀpot nitroaldol–Michael cascade reaction, it was found that
this cascade reaction catalyzed by 3 could still afford target chiral
products of (S)ꢀ3ꢀ(2ꢀnitroꢀ1ꢀphenylethyl)pentaneꢀ2,4ꢀdione with
9
3% yield and 99% ee value, where ee value was comparable to
its singleꢀstep enantioselective Michael addition catalyzed by its
[
8c]
6g
6h
6i
homogeneous counterpart (2). It was notable that nitroaldol–
Michael oneꢀpot cascade reaction catalyzed 3 was better than that
catalyzed by its homogeneous counterparts (the mixed
propylamine plus 2 as dual catalysts) (Table 2, entry 2), further
confirming the superiority of the designed catalyst 3.
4ꢀCF
3
1
0
3ꢀCF
3ꢀNO
4ꢀMe
3ꢀMe
3
Table 2 summarized the general applicability of catalyst 3 in
nitroaldol–Michael oneꢀpot cascade reactions with a series of
substituted aromatic aldehydes as substrates. As expected, oneꢀ
pot cascade reactions catalyzed 3 could convert smoothly various
threeꢀcomponent substrates to the responding chiral diones with
high yields and high enatioselectivities. It was found that the
structures and electronic properties of the substituents on the
aromatic ring at R group did not affect significantly their
enantioselectivities, that were, various electronꢀwithdrawing and ꢀ
donating R groups regardless of at 2ꢀ or 3ꢀ or 4ꢀposition on the
aromatic ring were equally efficient (Entries 3–16).
11
2
6j
1
1
1
1
2
3
4
5
6
6k
6l
4ꢀOMe
3ꢀOMe
2ꢀOMe
6m
6n
6o
1
a
Beyond the aim for construction of a siteꢀisolated bifunctional
heterogeneous catalyst 3 for the enantioselective cascade
Reaction conditions: catalyst
3 (25.0 mg, 5.0 ꢁmol of squaramide based
on the TG analysis) aldehydes (0.50 mmol) in 1.0 mL of nitromethane
was reacted at 90°C for 3ꢀ6 h. After that, acetylacetone (2.0 mmol) in 1.0
1
5
0
nitroaldol–Michael oneꢀpot reaction, another important
consideration in the design of heterogeneous catalyst is the ease
of separation by simple centrifugation and the ability to retain its
catalytic activity and enantioselectivity after multiple recycles. It
was found that the heterogeneous catalyst 3 could be easily
recovered by simple centrifugation. It was found that, in four
mL CH Cl was added and the mixture was stirred in room temperature
2 2
b
1
for 12ꢀ24 h. Conversions were determined by HꢀNMR and ee values
c
were determined chiral HPLC analysis (see SI in Figure S5, S7). Data
were obtained using the mixed propylamine plus 2 as dual catalysts.
2
Thirdly, in order to elucidate the benefit of surface silanols for
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X
X
consecutive reactions, the recycled catalyst 3 could still give 86%
yield and 96% ee in the nitroaldol–Michael oneꢀpot cascade
reaction of nitromethane, aldehyde and acetylacetone (see SI
Figure S6).
60
Chem. Soc., 2007, 129, 9216; (e) L. Soldi, W. Ferstl, S. Loebbecke, R.
Maggi, C. Malmassari, G. Sartori, S. Yada, J. Catal., 2008, 258, 289.
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1
30, 14416; (b) H. Jiang, M. W. Paixão, D. Monge, K. A. Jørgensen, J.
Am. Chem. Soc., 2010, 132, 2775; (c) H. Y. Bae, S. Some, J. S. Oh, Y.
S. Lee, C. E. Song, Chem. Commun., 2011, 47, 9621; (d) W. Yang, D.
M. Du, Org. Lett., 2010, 12, 5450; (e) D. Enders, R. Hahn, I.
Atodiresei, Adv. Synth. Catal., 2013, 355, 1126; (f) T. S. Pham, K.
Gönczi, G. Kardos, K. Süle, L. Hegedüs, M. Kállay, M. Kubinyi, P.
Szabó, I. Petneházy, L. Tőke, Z. Jászay, Tetrahedron: Asymmetry,
2013, 24, 1605; (g) Z. Dong, G. Qiu, H. Zhou, C. Dong, Tetrahedron:
Asymmetry, 2012, 23, 1550; (h) L. Dai, S. Wang, F. Chen, Adv. Synth.
Catal., 2010, 352, 2137; (i) D. Mailhol, M. del Mar Sanchez Duque,
W. Raimondi, D. Bonne, T. Constantieux, Y. Coquerel, J. Rodriguez,
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Turkmen, V. H. Rawal, J. Am. Chem. Soc., 2013, 135, 16050; (k) K.
Bera, I. N. N. Namboothiri, Chem. Commun., 2013, 49, 10632l; (l)Y.
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Green Chem., 2012, 14, 893; (m)X. C. Ren, C. Y. He, Y. L. Feng, Y. H.
6
7
7
8
8
9
9
5
0
5
0
5
0
5
5
Conclusions
In conclusions, by utilizing yolkꢀshellꢀstructured mesoporous
silica, we assemble conveniently a yolkꢀshellꢀstructured, active
siteꢀisolated bifunctional heterogeneous catalyst. As presented in
this study, this catalyst undergoes a nitroꢀMannich pathway in
nitroaldol condensation of nitromethane and aromatic aldehyde,
realizing an efficient nitroaldol–Michael cascade reaction through
threeꢀcomponent coupling of aldehydes, nitromethane and
acetylacetone to afford various chiral diones with high yield and
up to 99% enantioselectivity in oneꢀpot manner. Furthermore,
catalyst can be also recovered, and the recycled catalyst could
still afford a highly catalytic performance in four consecutive
reactions in nitroaldol–Michael coupling of nitromethane,
benzaldehyde and acetylacetone.
10
15
Chai, W. Yao, W. P. Chen, S. Y. Zhang, Org. Biomol. Chem., 2015, 13,
5054.
7
.
(a) X. M. Xu, T. Y. Cheng, X. C. Liu, J. Y. Xu, R. H. Jin, G. H. Liu,
ACS Catal., 2014, , 2137; (b) Jin, R. H.; Liu, K. T.; Xia, D. Q.; Qian,
4
Q. Q.; Liu, G. H.; Li, H. X. Adv. Synth. Catal., 2012, 354, 3265; (c)
Liu, K. T.; Jin, R. H.; Cheng, T. Y.; Xu, X. M.; Gao, F.; Liu, G. H.; Li,
H. X. Chem. Eur. J., 2012, 18, 15546; (d) D. C. Zhang, X. S. Gao, T. Y.
Acknowledgements
Cheng, G. H. Liu, Sci. Rep., 2014,
Zhang, M. Wu, T. Y. Cheng, G. H. Liu, Chem. Eur. J., 2014, 20, 1515;
f) R. Liu, R. H. Jin, J. Z. An, Q. K. Zhao, T. Y. Cheng, G. H. Liu,
Chem. Asian J., 2014, , 1388; (g) H. S. Zhang, R. H. Jin, H. Yao, S.
Tang, J. L. Zhuang, G. H. Liu H. X. Li. Chem. Commun., 2012, 48
874
8. A. K. TuckerꢀSchwartz, R. A. Farrell, R. L. Garrell, J. Am. Chem. Soc.,
011, 133, 11026.
4, 5091; (e) X. S. Gao, R. Liu, D. C.
20
We are grateful to China National Natural Science Foundation
(
(21402120), Shanghai Sciences and Technologies Development
9
Fund (13ZR1458700), the Shanghai Municipal Education
Commission (14YZ074, 13CG48, Young Teacher Training
Project) for financial support.
,
,
7
.
2
9
. O. Krőcher, O. A. Kőppel, M. Frőba, A. Baiker, J. Catal., 1998, 178,
284.
25
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DOI: 10.1039/C6CY00716C
Graphical Abstract：
Yolk–Shell–Structured Mesoporous Silica: A Bifunctional Catalyst for Nitroaldol–Michael
One-Pot Cascade Reaction
Juzeng An, Tanyu Cheng, Xi Xiong, Liang Wu, Bing Han and Guohua Liu*
A site-isolated yolk-shell-structured mesoporous silica for nitroaldol–Michael one-pot enantio–
relay reaction of aldehydes, nitromethane and acetylacetone to convert chiral diones are
developed.