Magnetic Nanoparticles-Supported Chiral Catalyst with an Imidazolium Ionic Moiety: An Efficient and Recyclable Catalyst for Asymmetric Michael and Aldol Reactions

Article abstract of DOI:10.1002/adsc.201600145

A magnetic nanoparticles-supported chiral aminocyclohexane in combination with sulfamide, which was modified by an imidazolium ionic moiety, was prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transm

Full text of DOI:10.1002/adsc.201600145

FULL PAPERS
DOI: 10.1002/adsc.201600145
Magnetic Nanoparticles-Supported Chiral Catalyst with an
Imidazolium Ionic Moiety: An Efficient and Recyclable Catalyst
for Asymmetric Michael and Aldol Reactions
Anguo Ying,a,* Shuo Liu,c Zhifeng Li,b Gang Chen,a Jianguo Yang,a Hua Yan,a
and Songlin Xub,*
a
School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou 318000, Peopleꢀs Republic of China
Fax : (+86)-576-8866-0359; e-mail: agying@tzc.edu.cn or yinganguo@163.com
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, Peopleꢀs Republic of China
b
Fax : (+86)-22-8740-2107; e-mail: slxu@tju.edu.cn
College of Chemistry, Nankai University, Tianjin 300071, Peopleꢀs Republic of China
c
Received: February 2, 2016; Revised: March 19, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600145.
Abstract: A magnetic nanoparticles-supported chiral tivity (ee: 92–100%, dr: 91:9–99:1).The role of the
aminocyclohexane in combination with sulfamide, ionic moiety was verified by comparison of the cata-
which was modified by an imidazolium ionic moiety, lyst with an ionic moiety-free counterpart. The heter-
was prepared and characterized by Fourier transform ogeneous catalyst was easily separated and recovered
infrared spectroscopy (FT-IR), X-ray diffraction using external magnetic force and can be used for up
(XRD), transmission electron microscopy (TEM), vi- to five times without obvious loss in its catalytic ac-
brating sample magnetometry (VSM), thermal gravi- tivity.
metric (TG) analysis and elementary analysis. The
catalyst was successfully applied not only in the
enantioselective Michael addition but also in the Keywords: asymmetric aldol reactions; asymmetric
asymmetric aldol condensation to afford good to ex- Michael addition; ionic moiety; magnetic nanoparti-
cellent yields (70–94%) and satisfactory stereoselec- cles; recyclability
Introduction
as Heck reactions.[3] Magnetic nanoparticles-support-
ed guanidine was developed and was successfully
Due to their unique properties such as ready synthesis used to catalyze the cyanosilylation of carbonyl com-
and functionalization, high surface area, low toxicity pounds.[4] In addition, some pioneering contributions
and cost, good stability, facile separation by superpar- regarding asymmetric reactions promoted by organo-
amagnetic forces, magnetic nanoparticles (MNPs) catalysts grafted on MNPs have been emerging in the
have been widely exploited as a new kind of catalyst field of organic synthesis.[5]
support.[1] A large number of hydroxy groups on the
Ionic liquids (ILs), especially task-specific ionic liq-
surface of MNPs, especially Fe3O4 coated with silica uids (TSILs), have emerged as viable alternatives to
(SiO2@Fe3O4), renders the immobilization of various existing traditional organic solvents or catalysts in the
homogeneous catalysts on the surface of MNPs much fields of organic transformations, as they have low
easier. Thus, versatile catalytic organic transforma- melting points, negligible vapor pressure, tunable
tions promoted by MNPs-supported catalysts have functionalities, excellent solvating ability, and ease of
been extensively reported. For example, Xu and his recyclability.[6] Recently, a new concept using support-
co-workers described the preparation of magnetic ed ionic liquid catalysis or ionic liquid modification
nano-Fe3O4-supported 1-benzyl-1,4-dihydronicotina- catalysis has been presented.[7] The novel catalysts
mide (BNAH) which showed efficient activity in the combine advantages of both heterogeneous catalysts
catalytic reduction of a,b-epoxy ketones.[2] Palladium- and ionic liquids, which include highly catalytic activi-
based catalysts supported on MNPs were prepared ty on catalytic sites, ready recovery, recyclability, and
and were found as magnetically separable and highly so on. Especially, those catalysts with an ionic moiety
active catalysts for Suzuki coupling reactions as well demonstrate much better catalytic activity than the
Adv. Synth. Catal. 0000, 000, 0 – 0
1
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
ionic liquid (IL)-free counterpart in organic transfor- Results and Discussion
mations. At the same time, the unique properties of
magnetic nanoparticles (MNPs), such as high surface The schematic procedure for preparing MNPs-sup-
area, good stability, ready preparation and functional- ported catalyst C1 is depicted in Scheme 1. The first
ization, easy recovery because of superparamagnetic step was to prepare the Fe3O4 nanoparticles by
behaviour, have attracted increased interest in the a chemical co-precipitating method in accordance
field of organic synthesis as a support for various cat- with the literature.[8b,12] In order to prevent aggrega-
alysts.[8,1c] As a quasi-homogeneous catalyst, the tion of the ferromagnetic nanoparticles and to pro-
À
MNPs-supported catalyst is a bridge between homo- vide numerous Si OH groups for further functional-
geneous and heterogeneous catalysts.[1b] Thus, the ized modification, a silica shell surrounding the out-
design and synthesis of new catalysts grafted on the side of the Fe3O4 nanoparticles was formed by the
MNPs with an ionic tag as well as their application in well-known Sstçber method.[13] The silica-coated mag-
organic reactions is still highly needed.
netic nanoparticles were subsequently reacted with
Asymmetric Michael additions and aldol condensa- triethoxy-3-(chloropropyl)-silane to obtain the liner 1,
tions through catalysis have advanced rapidly in followed by reaction with the chiral organic molecule
recent years as a versatile and powerful tool for the 2. The formed intermediate 3 was deprotected in the
synthesis of structurally diverse chiral organic mole- presence of TFA to give the desired grey catalyst C1
cules.[9] Very recently, organocatalytic asymmetric cat- with an ionic moiety. For comparison, the ionic-free
alysis has been identified as one of most efficient and counterpart C2 was obtained from the reaction of the
economical entries to enantioenriched Michael ad- solid supported linker 4 with an amine functionality
ducts[10] and aldol condensation products.[11] General- with organic molecule 5, which was synthesized in ac-
ly, asymmetric Michael addition as well as aldol con- cordance with the literature.[14] Removal of the pro-
densation is promoted as the mode of bifunctional tecting group Boc in 6 using TFA gave the catalyst C2
catalysis. As shown in Figure 1, the nitrogen motif of as grey powder (Scheme 2).
the left side of the catalyst can enhance the nucleo-
Figure 3 shows the FT-IR spectrum of the unsup-
philic activity of the aldehyde or ketone through the ported magnetic nanopaticles (MNPs), catalyst C1,
formation of an enamine while the right nitrogen catalyst C2 and corresponding chiral molecule 2. It
motif provides the acidic hydrogen as H-bond donor shows that the bands at 586 cmÀ1 and 1090 cmÀ1 of
to activate the electrophilic reagent. Influenced by samples MNPs, C1 and C2 were, respectively, assigned
À
À
the process of designing bifunctional chiral catalyst, to the adsorption vibration of Fe O bonds and Si O
herein, we disclose a novel bifunctional catalyst with bonds, which indicate the existence of Fe3O4 and its
ionic moiety supported on superparamagnetic nano- silica layer. The IR curve of intermediate 2 shows
particles (Figure 2) and its application as catalyst for bands at 914 cmÀ1 (C N stretching vibration),
À
asymmetric Michael addition and Aldol condensation. 1174 cmÀ1 (C N vibration), 1280 cm (S=O stretch-
À1
À
ing vibration), 1457 cmÀ1, 2859 cmÀ1, 2933 cmÀ1 (vibra-
À1
À
À
tion mode of C H), 3356 cm (N H), which can be
detected in both C1 and C2, indicating the successful
grafting of the chiral aminocyclohexane with the func-
tionality of sulfamide. The appearance of a character-
istic band at 1521 cmÀ1, corresponding to the stretch-
ing vibration of the C=N and C=C confirms the exis-
tence of the imidazolium moiety[15] in the catalyst C1.
The disappearance of the absorption of the carbonyl
group at 1685 cmÀ1 and the production of new bands
at 3332 cmÀ1 (NH2) indirectly prove the efficient re-
moval of the Boc group. Thus, the above results pro-
vide evidence that the chiral aminocyclohexane-based
molecule with an ionic moiety and its counterpart (no
ionic modifier) were successfully grafted onto the car-
rier (MNPs) to form the catalysts C1 and C2.
Figure 1. Mechanistic hypothesis for a bifunctional catalytic
Michael addition as well as aldol condensation
The high angle X-ray diffraction (XRD) patterns of
the MNPs, immobilized catalyst C1 and C2 were dem-
onstrated in Figure 4. Diffraction peaks at around
29.628, 35.538, 43.788, 53.768, 57.058 and 62.888 corre-
sponding to the diffraction of (200), (311), (400),
(422), (511) and (440) are readily assigned to the stan-
dard structure of nano-Fe3O4 (JCPDS, file No. 19-
Figure 2. The structure of supported catalyst C1.
Adv. Synth. Catal. 0000, 000, 0 – 0
2
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Scheme 1. Preparation of catalyst C1.
Scheme 2. Preparation of catalyst C2.
Figure 3. FT-IR spectra of MNPs, C1, 2 and C2.
0629). It could also be seen that all three samples
have a broad peak from 2q=208 to 308, which is the
characteristic of an amorphous silica phase in the
shell of the silica-coated Fe3O4 nanoparticles (MNPs). C1 and C2. As judged from Figure 5a, b and c, the un-
The results indicate that the modification reaction on supported MNPs or the supported catalysts C1 and
the surface of MNPs did not significantly affect the C2 all had a mean diameter range of 20–30 nm, with
phase composition of the silica shell as well as the a mostly spherical shape. The three samples are simi-
core of Fe3O4.
lar in the morphology of the nano-Fe3O4 core sur-
A transmission electron microscope (TEM) was ex- rended by a thin silica layer of 3–5 nm, which proves
ploied to obtain direct information regarding the mor- that the magnetic ferrite and the outside silica layer
phology and structure of blank MNPs, and catalysts remained intact during the immoblization process of
Adv. Synth. Catal. 0000, 000, 0 – 0
3
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Figure 4. XRD patterns of MNPs (left), C1 (middle) and C2 (right).
Figure 5. Transmission electron microscope (TEM) images of MNPs (a), C1 (b), C2 (c) and reused C1 (d).
grafting the imidazolium ionic liquid and chiral sulfa- ration and recovery as catalysts. The magnetic proper-
mide-functionalized aminocyclohexane on the MNPs.
ties of SiO2@Fe3O4 (MNPs), immobilized catalysts C1
The magnetic property is crucial to superparamag- and C2 were investigated by vibrating sample magne-
netic nanoparticles for their applications in fast sepa- tometer (VSM). Hysteresis loops of MNPs, C1 and
Adv. Synth. Catal. 0000, 000, 0 – 0
4
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Figure 8. TG-DTG analysis for C2.
Figure 6. Magnetic curves of MNPs, C1 and C2.
1958Cand 2708C is attributed to the thermal decom-
C2 in an applied magnetic field of 20000 qe at room position of the ionic modified chiral aminocyclohex-
temperature are shown in Figure 6. The bare MNPs ane with the functionality of a sulfamide. Subsequent-
exhibited the higher saturation magnetization of ly, a weight loss of about 7.0% above 2708C can be
15.0 emugÀ1 while C1 and C2 had a relatively lower associated with the decomposition of the silica layer
magnetic property of 7.9 emugÀ1, 7.2 emugÀ1, respec- of the MNPs. As far as the TG of C2 is concerned
tively. The reason is mainly attributed to the outside (Figure 8), the significant decrease in weight is found
layer of the grafted catalyst. It is worthwhile to note in the temperature range of 2038C to 2688C. The
that no magnetic hysteresis was observed in three loading amounts of chiral molecules on MNPs were
samples. As a result, the superparamagnetic behav- determined to be 0.16 mmolgÀ1 (C1) and
iour of C1 and C2 can make them disperse well in the 0.18 mmolgÀ1 (C2) by elemental analysis, which was
reaction solution and be readily separated from the in good agreement with the results indicated by TG
mixture in the presence of an external magnetic field. analysis.
The thermogravimetric (TG) analysis can not only
The Michael addition reaction, especially the asym-
investigate the stability of the supported catalysts, but metric conjugated reaction, has become one of the
also indicate the amount of chiral molecule grafted most versatile and powerful approaches for the for-
[10b,16]
À
on the surface of the MNPs. As shown in Figure 7, mation of C C bonds in organic synthesis.
Ini-
the mass loss of the organic functional group in cata- tially, the enantioselective reaction of isobutyralde-
lyst C1 was observed when the decomposition temper- hyde and trans-b-nitrostyrene was chosen as the
ature was increased from 208C to 6008C. The initial model reaction to optimize the reaction conditions.
weight loss of 2.9% below 1958C was due to the loss As shown in Table 1, ionic tagged catalyst C1 plays an
of the absorbed water and surface hydroxy groups in important role on the reaction efficiency and enantio-
the sample. The main weight loss of 8.6% between selectivity. The satisfying results in terms of reaction
yield and enantioselectivity were achieved with the
reaction time of 120 h (Table 1, entry 3). On the con-
trary, a yield of only 18% was obtained in the pres-
ence of the ionic-free catalyst C2 while a significant
improvement was observed when the reaction solvent
water was replaced by CHCl3 (Table 1, entry 4 vs.
entry 5). The reason may be attributed to the poor
solubility of organic chiral amine (C2) in water, which
leads to the decrease in its catalytic efficiency. When
the reaction was run in the presence of 1,2-diaminocy-
clohexane and blank carrier MNPs (Fe3O4@SiO2) or
in the absence of catalyst, almost no product was de-
tected (Table 1, entries 1, 2 and 6).
As shown in Table 1, without any catalyst, the use
of C1 could give the Michael adduct at the cost of
a long reaction time (120 h), which prompted us to
Figure 7. TG-DTG analysis for C1.
seek suitable additives to shorten the reaction time.
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Table 1. Screening of the catalysts.[a]
amount of 20 mol% was the best loading for the reac-
tion (Table 2, entries 6, 9 and 10). Lower catalyst
loadings resulted in inferior yields as well as ee values
in elongated times (Table 2, entries 6 and 11–14).
Thus, the best result was obtained in water at room
temperature in the presence of 20 mol% of catalyst
C1 with the assistance of 20mol% of DMAP as coca-
talyst (Table 2, entry 6).
Having established the optimal conditions, we ex-
plored the reaction scope by varying the nitroolefins.
As demonstrated in Table 3, a number of nitroal-
kenes, whether substituted by electron-donating
groups or electron-withdrawing groups on the aromat-
ic ring, afforded high levels of chemical yield (>80%)
and enantioselectivity (>95%) at room temperature
within 5 h (Table 3, entries 1–9). When the aromatic
ring of the nitroolefin carrying two substituents was
used as electrophile, the reaction gave the corre-
sponding adduct in excellent yield with high enantio-
purity, indicating that the steric hindrance at the aro-
matic ring of the Michael acceptor has little effect on
the reactivity (Table 3, entries 8 and 9). In addition,
Entry Catalyst
t
Yield[b] Enantiomeric
[h] [%]
excess[c] (ee [%])
1
2
blank
Fe3O4@SiO2
120 trace
120 trace
nd
nd
(40 mg)
3
C1
120 76
120 18
120 78
120 12
91
59
85
nd
4
C2
C2
5[d]
6
1,2-diaminocyclo-
hexane
[a]
All reactions were performed using trans-b-nitrostyrene
(0.2 mmol), isobutyraldehyde (1.0 mmol), catalyst
(20 mmol%) in water (1 mL) at room temperature.
Isolated yield.
Determined by chiral HPLC analysis.
The reaction was carried out in CHCl3 instead of water.
[b]
[c]
[d]
Various traditional cocatalysts, including PhCOOH, a polyaromatic-based olefin as well as a 2-thienyl-de-
acetic acid, DIPEA, Et3N, DMAP, DABCO, and pyr- rived olefin were also suitable Michael acceptors for
rolidine were investigated in the model reaction be- the asymmetric reaction (Table 3, entries 10 and 11).
tween trans-b-nitrostyrene and isobutyraldehyde
We proposed the following transition state to ex-
(Table 2, entries 1–8). DMAP can significantly accel- plain the stereoselectivity of the catalyst C1 in the Mi-
erate the reaction rate and the reaction was complet- chael reaction between isobutyraldehyde and trans-b-
ed within 4 h to afford an 87% yield of desired prod- nitrostyrene. As shown in Figure 9, the secondary
uct with 97% ee (Table 2, entry 6). Further examina-
tion of the amount of DMAP revealed that the
Table 3. Conjugated addition of isobutyraldehyde to b-aryl-
nitroolefins catalyzed by C1.[a]
Table 2. Effect of additives and catalytic amount on the re-
action of trans-b-nitrostyrene (0.2 mmol), isobutyraldehyde
(1.0 mmol), C1 (0.04 mmol) in water at room temperature.
En- Additive (mol%) t [h] Yield[a] [%] Enantiomeric
try
excess[b] (ee[%])
Entry Ar
t
Yield[b] Enantiomeric excess[c]
[h] [%]
(ee [%])
1
2
3
4
5
6
7
8
9
PhCOOH (20)
CH3COOH (20) 48
DIPEA (20)
Et3N (20)
imidazole (20)
DMAP (20)
DABCO (20)
pyrrolidine (20)
DMAP (10)
DMAP (30)
48
15
trace
67
54
79
87
82
72
84
81
64
76
79
87
35
nd
92
91
93
97
89
91
95
96
91
93
96
96
1
2
3
4
5
6
7
8
C6H5
4
4
3
5
4
4
3
5
87
91
92
89
94
81
85
83
97
99
100
97
97
97
95
96
8
6
5
4
5
6
4
4
8
6
4
4
4-NO2C6H4
3-NO2C6H4
2-ClC6H4
4-ClC6H4
4-OMeC6H4
4-OHC6H4
3,4-
(OMe)2C6H3-
3-OMe,4-
OHC6H3
10
11[c] DMAP (20)
12[d] DMAP(20)
13[e] DMAP (20)
14[f] DMAP(20)
9
4
86
99
10
11
1-naphthyl
2-thienyl
6
5
84
86
96
99
[a]
[a]
Isolated yield.
The reactions were carried out with C1 (0.04 mmol), iso-
butyraldehyde (1.0 mmol), nitrostyrene (0.2 mmol) and
DMAP(0.04 mmol) in water (1 mL) at room tempera-
ture.
Isolated yield.
Determined by chiral HPLC analysis.
[b]
Determined by chiral HPLC analysis.
The catalyst amount was 5 mmol%.
The catalyst amount was 10 mmol%.
The catalyst amount was 15 mmol%.
The catalyst amount was 30 mmol%).
[c]
[d]
[e]
[f]
[b]
[c]
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Figure 9. Proposed transition state for the asymmetric Mi-
chael reaction of isobutyraldehyde and trans-b-nitrostyrene
catalyzed by C1.
Figure 10. Calculated 3D structures of TS1 and TS2.
amine of the pyrrolidine activates the isobutyralde-
hyde through the formation of an enamine intermedi-
ate. Then the activated nucleophile reacts with the ni-
troolefin, stabilized by hydrogen bonding interactions
between the nitro group and the amide group, to
form the Michael product with high stereoselectivity.
As demonstrated in Table 1 (entries 3–5) and
Figure 9, it is worthy of note that the ionic moiety
plays an important role in the acceleration of the re-
action rate. The reason may be attributed to the
bridging role of the ionic moiety between catalytic
sites and substrates in water. Moreover, the ionic
moiety presents electrosteric activation to stablize the
transition state of the reaction.[17] The bifunctional
chairal induction as well as the hydrophic property of
ionic moiety facilitate this type of reaction efficiently.
To further clarify the chiral induction of the support-
ed catalyst C1, transtion station models between iso-
butyraldehyde and trans-b-nitrostyrene were also in-
vestigated by DFT calculations. All calculations were
conducted using the functional B3LYP the 6-311+
G(d,p) basis set as implemented in Gaussian 09.[18]
The energy of TS1 state is lower than that of TS2 due
to the formation of H-bond between O atoms at the
nitro group of the nitroolefin and the NH of amide,
which preferentially lead to the (R)-enantiomer, in ac-
cordance with experimental results (Figure 10).
Figure 11. (a) C1 dispersion in water; (b) C1 separation with
a small magnet.
Table 4. Recyclability of C1 in the asymmetric Michael reac-
tion of nitrostyrene with isobutyraldehyde in water.[a]
Entry
Run
Yield [%]
ee [%]
1
2
3
4
5
fresh
second
third
fourth
fifth
87
85
85
83
83
97
96
95
96
95
[a]
The reactions were carried out with C1 (0.04 mmol), iso-
butyraldehyde (1.0 mmol), nitrostyrene (0.2 mmol) and
DMAP(0.04 mmol) in water (1.0 mL) at room tempera-
ture.
The outstanding feature of the protocol is the ver-
satility as the catalyst C1 can be readily separated and
Considering the bifunctional catalytic mode of C1,
recovered in the presence of an external magnet we attempted to use it as catalyst for the asymmetric
force, which can avoid the tedious work-up, including aldol condensation of cyclohexanone and aromatic al-
filtration and extraction (Figure 11). Table 4 presents dehydes. To our delight, all aldehydes listed in Table 5
the results of recovery and recyclability of C1 in the reacted smoothly with cyclohexanone to give the de-
asymmetric Michael addition of nitrostyrene and iso- sired products in good yields and high levels of selec-
butyraldehyde in water. The fresh catalyst C1 can be tivity. Because of the activation of the electrophile
reused for up to five times with no obvious decrease produced by the decrease in the electron density, al-
in catalytic efficiency in terms of stereoselectivity and dehydes bearing electron-withdrawing groups reacted
product yield. From the other side, the TEM and FT- slightly faster than those bearing electron-donating
IR have also verified that the catalyst remains intact substituents (Table 5, entries 2–4 vs. 5 and 6). Pleas-
after five times of reuse (Figure 5d, Figure 12).[19]
ingly, the heterogeneous catalyst C1 can also be readi-
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
chael addition and stereoselective aldol condensation.
The ionic moiety plays a role as a bridge between re-
actants and catalytic sites in water, which makes the
protocol very attractive from the viewpoints of green
chemistry. Finally, the supported catalyst C1 can be
readily recovered using a permanent magnet and can
be reused for five times without obvious loss of cata-
lytic efficiency. And the TEM and FT-IR show that
C1 remains intact after five runs.
Experimental Section
General Remarks
All the commercially available chemicals were purchased
from Aladdin or J&K Chemicals and used without any fur-
ther purification, unless otherwise noted. 1H NMR and
13C NMR spectra were recorded using a Bruker Advance
400 MHz spectrometer. FT-IR spectra were registered with
a Nicolet 5700 Fourier infrared spectrophotometer. X-ray
diffraction (XRD) was detected using a Bruker D8 X-ray
diffractometer. Transmission electron microscopy (TEM)
was performed with a Tecnai G2 F20 transmission electron
microscope. Magnetization curves were determined by using
Figure 12. FT-IR spectra of C1 and reused C1.
Table 5. Asymmetric aldol reaction between cyclohexanone
and various aldehydes in presence of C1.[a]
a
SQUID magnetometer. Thermogravimetric analysis
(TGA) was carried out on an SDT Q600 simultaneous ther-
mal analyzer.
Entry Ar
t [h] Yield[b] [%] anti/syn[c] ee[d] [%]
1
2
3
4
5
6
C6H5
6
4
4
4
7
8
8
8
85
91
89
93
83
81
80
78
70
96:4
95:5
99:1
96:4
96:4
94:6
95:5
94:6
91:9
94
95
100
96
94
92
95
93
94
4-NO2C6H4
4-CF3C6H4
4-FC6H4
4-CH3C6H4
4-OCH3C6H4
thienyl
Preparation of Catalysts C1 and C2
Synthesis
of
silica-coated
Fe3O4
nanoparticles
(SiO2@Fe3O4):[8b,12,13] FeCl3·6H2O (11.0 g) and FeCl2·4H2O
(4.0 g) were dissolved in 200 mL deionized water under ni-
trogen with mechanical stirring at 858C. A solution of con-
centrated aqueous ammonia (20 mL, 25 wt%) was added to
the solution in a drop-wise manner using a dropping funnel.
After continuous stirring for 4 h, the magnetite precipitates
were washed using deionized water. The black precipitate
(Fe3O4) was collected by a permanent magnet. Sonication of
a dispersion of the above black precipitate (1.0 g) with etha-
nol (50 mL) was done for 30 min at room temperature, then
concentrated NH3·H2O (6 mL) and TEOS (2.0 mL) were
added successively. After mechanical stirring for 24 h, the
black precipitate (SiO2@Fe3O4) was collected using a perma-
nent magnet, followed by washing with ethanol several
times and drying in a vacuum.
7
8[e]
9[f]
thienyl
thienyl
[a]
The reactions were carried out with C1 (0.04 mmol), al-
dehyde (0.2 mmol), cyclohexanone (0.6 mmol) and
DMAP(0.04 mmol) in water (1 mL) at room tempera-
ture.
[b]
[c]
[d]
[e]
[f]
Isolated yield.
Determined by chiral HPLC analysis.
Determined by chiral HPLC analysis of the anti product.
Third usage of C1.
Fifth usage of C1.
ly recovered by magnetic force and repeatedly used
Synthesis of 2: The Boc-protected 1,2-diaminocyclohex-
to promote the aldol reaction without significant loss ane was synthesized according to the procedures reported in
the literature.[20]
of yield and selectivity (Table 5, entries 8 and 9).
To a solution of Boc-protected 1,2-diaminocyclohexane
(1.18 g, 5.5 mmol) and Et3N (0.85 g, 3.6 mmol) in CH2Cl2
(8.5 mL) was added 1-methyl-2-sufonylchlorideimidazole
1 (1.0 g, 5.5 mmol) in CH2Cl2 (3.5 mL) at 08C. After addi-
Conclusions
tion, the reaction mixture was warmed up to room tempera-
A chiral aminocyclohexane combined with a sulfamide
ture and stirring continued for 1 h. Then water was added
was successfully grafted on the magnetic nanoparti-
cles (C1), which was linked by an imidazolium ionic
liquid. The nano-sized catalyst was applied as a highly
and the reaction mixture was extracted with CH2Cl2, the or-
ganic phase was dried over Na2SO4. Filtration, removal of
the solvent, and purification by flash column chromatogra-
efficient and reusable catalyst in the asymmetric Mi- phy (eluent: ethyl acetate) afforded the product 2.
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Synthesis of C1: 1.0 g of SiO2@Fe3O4 was dispersed in
50 mL ethanol by sonication for 1 h. 4 mL of 3-chloropropyl-
triethoxysilane were then added, and the reaction mixture
was refluxed for 24 h under nitrogen. After cooling to room
temperature, 1 was collected by a permanent magnet and
rinsed with ethanol, then dried under vacuum.
phases were concentrated and purified by column chroma-
tography (petroleum-ethyl acetate). All of the products gen-
erated in this way were characterized by comparison of their
spectral with those of the authentic samples.
0.3 g of 1 and 0.358 g of 2 were dispersed in 20 mL anhy-
drous toluene by sonication for 1 h. Then the reaction mix-
ture was refluxed for 48 h under nitrogen. After cooling to
room temperature, 3 was collected by a permanent magnet
and rinsed with ethanol, then dried under vacuum.
To a solution of 3 in dichloromethane (10 mL) was added
trifluoroacetic acid (1 mL). The reaction mixture was stirred
at room temperature for 10 h and the solvent removed, the
solid residue was washed with saturated NaHCO3, water
and methanol successively, then dried under vacuum at
608C to give C1.
Synthesis of C2: 1.0 g of SiO2@Fe3O4 was dispersed in
50 mL ethanol by sonication for 1 h. 3.9 mL of 3-aminopro-
pyltriethoxysilane were then added, and the reaction mix-
ture was refluxed for 24 h under nitrogen. After cooling to
room temperature, 4 was collected by a permanent magnet
and rinsed with ethanol, then dried under vacuum.
0.3 g of 4 and 0.386 g of 5 were dispersed in 20 mL anhy-
drous toluene by sonication for 1 h. Then the reaction mix-
ture was refluxed for 48 h under nitrogen. After cooling to
room temperature, 6 was collected by a permanent magnet
and rinsed with ethanol, then dried under vacuum.
Acknowledgements
We are grateful for the financial support for this research by
the Zhejiang ProvincialNatural Science Foundation of China
(No. LY15B060002), and National Natural Science Founda-
tion of China (Grants 21576176, 21106090, 21176170, and
21272169).
References
[1] a) V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M.
Bouhrara, J. M. Basset, Chem. Rev. 2011, 111, 3036–
3075; b) R. Baig, R. Varma, Chem. Commun. 2013, 49,
752–770; c) M. Gawande, P. S. Branco, R. S. Varma,
Chem. Soc. Rev. 2013, 42, 3371–3393; d) R. B. N. Baig,
R. S. Varma, Green Chem. 2013, 15, 398–417.
[2] H. J. Xu, X. Wan, Y. Y. Shen, S. Xu, Y. S. Feng, Org.
Lett. 2012, 14, 1210–1213.
[3] a) Q. Du, W. Zhang, H. Ma, J. Zheng, B. Zhou, Y. Li,
Tetrahedron 2012, 68, 3577–3584; b) R. B. N. Baig, R. S.
Varma, Ind. Eng. Chem. Res. 2014, 53, 18625–18629.
[4] B. Atashkar, A. Rostami, B. Tahmasbi, Catal. Sci. Tech-
nol. 2013, 3, 2140–2146.
[5] a) A. G. Hu, S. Liu, W. B. Lin, RSC Adv. 2012, 2, 2576–
2580; b) P. Riente, C. Mendoza, M. A. Pericꢃs, J. Mater.
Chem. 2011, 21, 7350–7355; c) R. B. N. Baig, M. N. Na-
dagouda, R. S. Varma, Coord. Chem. Rev. 2015, 287,
137–156.
[6] a) Q. H. Zhang, S. G. Zhang, Y. Q. Deng, Green Chem.
2011, 13, 2619–2637; b) N. Isambert, M. M. S. Duque,
J. C. Plaquevent, Y. Gꢄnisson, J. Rodriguez, T. Constan-
tieux, Chem. Soc. Rev. 2011, 40, 1347–1357; c) S. Tang,
G. A. Baker, H. Zhao, Chem. Soc. Rev. 2012, 41, 4030–
4066; d) A. Ying, S. Xu, S. Liu, Y. Ni, J. Yang, C. Wu,
Ind. Eng. Chem. Res. 2014, 53, 547–552; e) A. Ying, Y.
Ni, S. Xu, S. Liu, J. Yang, R. Li, Ind. Eng. Chem. Res.
2014, 53, 5678–5682; f) A. Ying, Z. Li, J. Yang, S. Liu,
S. Xu, H. Yan, C. Wu, J. Org. Chem. 2014, 79, 6510–
6516; g) A. Ying, S. Liu, J. Yang, H. Hu, Ind. Eng.
Chem. Res. 2014, 53, 16143–16147; h) L. Pan, Z. Li, Y.
Ni, Z. Yao, Z. Yu, W. Wu, A. Ying, Chem. J. Chinese
Universities 2015, 36, 81–86.
To a solution of 6 in dichloromethane (10 mL) was added
trifluoroacetic acid (1 mL). The reaction mixture was stirred
at room temperature for 10 h and the solvent removed, the
solid residue was washed withg saturated NaHCO3, water
and methanol successively, then dried under vacuum at
608C to give C2.
General Procedure for the Michael Addition of
Isobutyraldehyde to Nitroolefins
trans-b-Nitrostyrene (0.2 mmol), C1 (250.0 mg, 0.04 mmol),
4-dimethylaminopyridine (4.9 mg, 0.04 mmol), isobutyralde-
hyde (0.91 mL, 1.0 mmol) and H2O (1 mL) in a 5-mL flask
were stirred at room temperature. The reaction progress
was monitored by TLC. After completion of the reaction,
the catalyst was collected by a permanent magnet and
washed with ethyl acetate (10 mLꢂ3). The reaction mixture
was extracted three times with ethyl acetate. The combined
organic phases were concentrated and purified by column
chromatography (petroleum-ethyl acetate). All of the prod-
ucts generated in this way were characterized by comparison
of their spectral with those of the authentic samples.
[7] a) J. L. Bideau, L. Viau, A. Vioux, Chem. Soc. Rev.
2011, 40, 907–925; b) Q. Zhang, J. Luo, Y. Wei, Green
Chem. 2010, 12, 2246–2254; c) Y. Gu, G. Li, Adv. Synth.
Catal. 2009, 351, 817–847.
[8] a) S. Liu, Y. Ni, J. Yang, H. Hu, A. Ying, S. Xu, Chinese
J. Chem. 2014, 32, 343–348; b) Y. Jiang, C. Guo, H.
Gao, H. Xia, I. Mahmood, C. Liu, H. Liu, AIChE J.
2012, 58, 1203–1211.
[9] a) D. Almasi, D. A. Alonso, C. Najera, Tetrahedron:
Asymmetry 2007, 18, 299–365; b) S. B. Tsogoeva, Eur. J.
Org. Chem. 2007, 1701–1716; c) B. M. Trost, C. S. Brin-
dle, Chem. Soc. Rev. 2010, 39, 1600–1632.
General Procedure for the Aldol Reaction of
Cyclohexanone with Aldehydes
Cyclohexanone (0.06 mL, 0.6 mmol), C1 (250.0 mg,
0.04 mmol), 4-dimethylaminopyridine (4.9 mg, 0.04 mmol),
aldehyde (0.2 mmol) and H2O (1 mL) in a 5-mL flask were
stirred at room temperature. The reaction progress was
monitored by TLC. After completion of the reaction, the
catalyst was collected by a permanent magnet and washed
with ethyl acetate (10 mLꢂ3). The reaction mixture was ex-
tracted three times with ethyl acetate. The combined organic
Adv. Synth. Catal. 0000, 000, 0 – 0
9
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
[10] a) A. Alcaine, E. Marquꢄs-Lꢅpez, R. P. Herrera, RSC
Adv. 2014, 4, 9856–9865; b) E. Rodrigo, J. L. G. Ruano,
M. B. Cid, J. Org. Chem. 2013, 78, 10737–10746; c) Y. F.
Ting, C. Chang, R. J. Reddy, D. R. Magar, K. Chen,
Chem. Eur. J. 2010, 16, 7030–7038; d) G. Sahoo, H. Ra-
haman, A. Madarꢃsz, I. Pꢃpai, M. Melarto, A. Valko-
nen, P. M. Pihko, Angew. Chem. Int. Ed. 2012, 51,
13144–13148.
[11] a) C. Shen, P. Zhang, Cur. Org. Chem. 2013, 17, 1507–
1524; b) H. Y. Bae, J. H. Sim, J. W. Lee, B. List, C. E.
Song, Angew. Chem. Int. Ed. 2013, 52, 12143–12147;
c) K. Armacost, O. Acevedo, J. Am. Chem. Soc. 2014,
136, 147–156; d) M. Angeloni, O. Piermatti, F. Pizzo, L.
Vaccaro, Eur. J. Org. Chem. 2014, 1716–1726.
[13] W. Stçber, A. Fink, E. Bohn, J. Colloid. Interface Sci.
1968, 26, 62–69.
[14] X. Zhang, S. Liu, X. Li, M. Yan, A. S. C. Chan, Chem.
Commun. 2009, 45, 833–835.
[15] A. Bordoloi, S. Sahoo, F. Lefebvre, S. B. Halligudi, J.
Catal. 2008, 259, 232–239.
[16] J. He, Q. Chen, B. Ni, Tetrahedron Lett. 2014, 55, 3030–
3032.
[17] a) M. Lombardo, C. Trombini, ChemCatChem 2010, 2,
135–145; b) H. K. Stassen, R. Ludwig, A. Wulf, J.
Dupont, Chem. Eur. J. 2015, 21, 8324–8335.
[18] a) A. Avila, R. Chinchilla, B. Fiser, E. Gꢅmez-Bengoa,
C. Nꢃjera, Tetrahedron: Asymmetry 2014, 25, 462–467;
b) A. Avila, R. Chinchilla, E. Gꢅmez-Bengoa, C.
Nꢃjera, Tetrahedron: Asymmetry 2013, 24, 1531–1535.
[19] S. Hubner, J. G. de Vries, V. Farina, Adv. Synth. Catal.
2016, 358, 3–25.
[12] a) K. Nishioa, M. Ikedaa, N. Gokonb, S. Tsubouchi, H.
Narimatsua, Y. Mochizuki, Sakamotoa, A. Sandhuc, M.
Abe, H. Handa, J. Magn. Magn. Mater. 2007, 310,
2408–2410.
[20] Y. K. Kim, S. J. Lee, K. H. Ahn, J. Org. Chem. 2000, 65,
7807–7813.
Adv. Synth. Catal. 0000, 000, 0 – 0
10
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
Magnetic Nanoparticles-Supported Chiral Catalyst with an
Imidazolium Ionic Moiety: An Efficient and Recyclable
Catalyst for Asymmetric Michael and Aldol Reactions
11
Adv. Synth. Catal. 2016, 358, 1 – 11
Anguo Ying,* Shuo Liu, Zhifeng Li, Gang Chen,
Jianguo Yang, Hua Yan, Songlin Xu*
Adv. Synth. Catal. 0000, 000, 0 – 0
11
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!