L -Proline-functionalized Fe3O4 nanoparticles as a novel magnetic chiral catalyst for the direct asymmetric Mannich reaction

Article abstract of DOI:10.1002/aoc.3333

l-Proline has been successfully anchored on the surface of magnetic nanoparticles and characterized using various techniques. These nanoparticles as a chiral catalyst have been employed to promote the direct asymmetric Mannich reaction. The corresponding

Full text of DOI:10.1002/aoc.3333

Full paper
Received: 27 February 2015
Revised: 23 April 2015
Accepted: 26 April 2015
Published online in Wiley Online Library: 11 June 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3333
L-Proline-functionalized Fe O nanoparticles as
3
4
a novel magnetic chiral catalyst for the direct
asymmetric Mannich reaction
Javad Safaei-Ghomi* and Safura Zahedi
L-Proline has been successfully anchored on the surface of magnetic nanoparticles and characterized using powder X-ray diffrac-
tion, scanning electron microscopy, vibrating sample magnetometry and Fourier transform infrared spectroscopy. These nanopar-
ticles as a chiral catalyst have been employed to promote the direct asymmetric Mannich reaction. The corresponding products
are obtained in high yields with high level of diastereoselectivity (up to 99:1 dr) in the presence of Fe O –L-proline. Also this
3
4
heterogeneous catalyst can be recovered easily and reused many times without significant loss of its catalytic activity.
Copyright © 2015 John Wiley & Sons, Ltd.
3 4
Keywords: magnetic materials; asymmetric catalysis; Mannich reaction; L-proline; Fe O nanoparticles
[
33]
has gained popularity. A variety of catalysts such as Zn(OTf) ,
Introduction
2
[
34]
[35]
[36]
H PW O ,
ZrOCl ꢀ8H O,
(S)-serine,
1,1,3,3-tetramethylguanidine,
dodecylbenzene-
3
12 40
2
2
[37]
[38]
Recently, magnetic nanoparticles (MNPs) have been widely
employed as alternative catalyst supports. Most importantly, these
MNP-supported catalysts show not only high catalyst recycling
but also high surface area resulting in high catalyst loading capac-
ity, high dispersion and good stability.
offers a very expedient approach for removing and recycling
sulfonic
acid,
proline–
have been
[
39]
[40]
[41]
thiourea,
HClO –SiO2
and silica sulfuric acid
4
utilized for three-component synthesis of β-amino carbonyl
compounds. A powerful way of catalysing the direct asymmetric
Mannich reaction is the use of proline and proline derivatives
[
1–3]
Magnetic separation
[
42]
as catalysts.
On the basis of these observations, herein we
[
4–6]
particles/composites by applying external magnetic fields.
Fe nanoparticles have plentiful hydroxyl groups on their sur-
report the Mannich reaction between aldehydes, amines and cyclo-
hexanone using magnetic chiral organocatalytic nanoparticles
(Fe O –L-proline) under mild conditions (Scheme 1).
3 4
O
faces, and hence they are naturally hydrophilic. The surface coating
or modification of iron oxide nanoparticles is very important in
many applications, because of their aggregation and difficulty in
3
4
dispersion in organic media. Conventionally, heterogeneous cataly- Experimental
sis is favoured over homogeneous catalysis due to ease of handling
[7–12]
Materials and physical measurements
and regenerability.
Proline as an important chiral small-
molecule organocatalyst has attracted much attention since it is
easily accessible, environmentally safe and available in both enan-
All the chemicals reagents used in our experiments were of analyt-
ical grade and were used as received without further purification.
Powder X-ray diffraction (XRD) was carried out using a Philips X’pert
diffractometer with monochromatized Cu Kα radiation (k = 1.5406
[13–15]
tiomeric forms.
L-Proline is not very expensive, and studies
of supported proline and its derivatives still have important signifi-
cance. Immobilization and recycling of L-proline have received
considerable attention in recent years. Supported proline catalysts
can be easily recovered from a reaction mixture and retain stable
catalytic activity and selectivity after being reused many times,
which is meaningful for environmental protection and energy con-
1
13
Å). H NMR and C NMR spectra were measured, respectively, at
400 and 100 MHz. The solvent used for NMR spectroscopy was
CDCl , using tetramethylsilane as the internal reference. FT-IR spec-
3
tra of all compounds were recorded with an FT-IR Magna 550 appa-
ratus using KBr plates. Elemental analyses (C, H, N) were conducted
using a Carlo Erba model EA1108 analyser. Melting points were
determined with an Electro Thermal 9200, and are not corrected.
Microscopic morphology of products was visualized using SEM
[
16–19]
servation. Several types of supports, such as polymers,
[20–24]
[25,26]
[27]
[28]
silica,
ionic liquids,
β-cyclodextrin, Merrifield resin
and magnetite, are usually considered for the immobilizations
[
29]
of proline and its derivatives.
(LEO 1455VP).
The catalytic asymmetric Mannich reaction has proven to be a
powerful tool to access optically active nitrogen-containing com-
pounds such as β-amino carbonyl compounds, which are important
synthetic intermediates for various pharmaceuticals and natural
* Correspondence to: Javad Safaei-Ghomi, Department of Organic
Chemistry, Faculty of Chemistry, University of Kashan, Kashan 87317,
IR Iran. E-mail: safaei@kashanu.ac.ir
[30–32]
products.
Hence, the synthesis of these compounds is an
important and useful task in organic chemistry. Recently, the
three-component condensation of aldehydes, amines and ketones
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan,
Kashan 87317, IR Iran
Appl. Organometal. Chem. 2015, 29, 566–571
Copyright © 2015 John Wiley & Sons, Ltd.

L-Proline-functionalized Fe O NP-catalysed Mannich reaction
3
4
Scheme 1. One-pot, three-component Mannich reaction catalysed by
Fe –L-proline nanoparticles (NPs).
3 4
O
Figure 1. Structures of products 4d and 4i.
(
4
C-17), 117.23 (C-12), 113.11 (C-10,14), 57.59 (C-6), 54.99 (C-7),
2.80 (C-2), 32.74 (C-3), 27.85 (C-4), 24.80 (C-5). Anal. Calcd for
C H ClNO (%): C, 72.72; H, 6.42; N, 4.46. Found (%): C, 72.69; H,
19 20
6.35; N, 4.41.
2
-((4-Methoxyphenyl)(phenylamino)methyl)cyclohexanone (4i).
1
H NMR (400 MHz, CDCl , δ, ppm): 7.25 (d, J = 8.4 Hz, 2H,
3
HC-16,20), 7.14 (d, J = 7.6 Hz, 2H, HC-10,14), 7.10–7.07 (m, 2H,
HC-11,13), 6.63 (t, J = 7.2 Hz, 1H, HC-12), 6.66 (d, J = 8.4 Hz, 2H,
HC-17,19), 4.71 (br s, 1H, NH), 4.62 (d, J = 7.2 Hz, 1H, HC-7),
3 4
Scheme 2. Schematic procedure for the preparation of Fe O –L-proline
nanoparticles.
2
.72–2.76 (m, 1H, HC-6), 2.34–2.38 (m, 2H, HC-2), 1.83–1.93 (m, 4H,
ꢁ
1
HC-4,5), 1.68–1.75 (m, 3H, HC-3). FT-IR (KBr, ν, cm ): 3332.42,
13
Preparation of Fe O –L-Proline nanoparticles
1707.26, 1600.92, 1532.21, 800.33. C NMR (100 MHz, CDCl , δ,
3
4
3
ppm): 212.73 (C-1), 147.01 (C-18), 138.38 (C-9), 136.47 (C-15),
The overall procedure used to synthesize the magnetic catalyst is
illustrated in Scheme 2. The detailed procedure was as follows.
FeCl ꢀ6H O (0.54 g) and FeCl ꢀ4H O (0.2 g) salts (with molar ratio
1
1
2
29.21 (C-11,13), 128.77 (C-16,20), 126.96 (C-12), 117.16 (C-17,19),
13.34 (C-10,14), 57.39 (C-21), 57.30 (C-6), 41.43 (C-7), 30.92 (C-2),
7.92 (C-3), 23.28 (C-4), 20.81 (C-5). Anal. Calcd for C20H23NO (%):
2
3
2
2
2
of 2:1) were dissolved in 100 ml of deionized water and kept at a
constant temperature of 40°C for 15 min with vigorous stirring.
C, 77.64; H, 7.49; N, 4.53. Found (%): C, 77.43; H, 7.56; N, 4.54.
Then, 0.3 g of L-proline and NH OH solution (25 wt%) were added
4
to the mixture until the pH was raised to 11 at which point a black
suspension was formed. This suspension was then refluxed at 100°C
Results and discussion
3 4
for 6 h, with vigorous stirring. Fe O –L-proline nanoparticles were
The asymmetric Mannich reaction is a well-known and widely used
synthetic pathway for carbon–carbon bond formation in organic
synthesis. The catalytic performance of the Fe O –L-proline
nanoparticles was evaluated in the synthesis of β-amino ketones
in the Mannich reaction.
separated from the aqueous solution by magnetic decantation,
washed with distilled water several times and then dried in an oven
overnight. The whole synthesis was done under nitrogen atmo-
3
4
sphere. The L-proline content in the Fe
3
O
4
–L-proline nanoparticles
was 4.68 mmol g , which was determined according to the
content of nitrogen element in Fe –L-proline nanoparticles from
elemental analyses.
ꢁ
1
3 4
O
Characterization of catalyst
Initially, in order to investigate the structure of the catalyst, we
characterized the Fe O –L-proline nanoparticles using XRD, FT-IR
spectroscopy, vibrating sample megnetometry (VSM) and SEM.
3
4
General procedure for Mannich reaction catalysed by Fe O –L-
proline nanoparticles
3
4
Phase investigation of the crystalline Fe O and Fe O –L-proline
3
4
3 4
In a typical Mannich reaction, the novel Fe O –L-proline nanoparti-
nanoparticles was performed using XRD and the diffraction pattern
is presented in Fig. 2. The same peaks are observed in both the
Fe O and Fe O -L-proline patterns, indicating retention of the
3
4
cles catalyst (0.03 g), aromatic aldehyde (2.5 mmol), aromatic amine
2.5 mmol), cyclohexanone (3 mmol) and ethanol were added into a
(
3
4
3 4
round-bottomed flask and stirred at 100°C. After completion of the
reaction, the mixture was cooled to room temperature, the catalyst
was recovered using an external magnet and the reaction mixture
was purified by flash column chromatography to give pure β-amino
ketone derivatives. Products 4d and 4i (Fig. 1) were completely
characterized from spectroscopic data as follows.
crystalline spinel ferrite core structure during the immobilization
of L-proline. The XRD pattern indicates diffraction peaks at 2θ of
30.4°, 35.8°, 43.5°, 53.7°, 57.2° and 62.9° corresponding to the spinel
structure of Fe O , which can be assigned to the diffractions of the
3
4
(220), (311), (400), (422), (511) and (440) faces of the crystals, respec-
tively. All of the observed diffraction peaks are indexed to the cubic
structure of Fe O (JCPDS no. 79-0417) revealing a high phase
2
-((2-Chlorophenyl)(phenylamino)methyl)cyclohexanone (4d).
3
4
1
H NMR (400 MHz, CDCl , δ, ppm): 7.61 (d, J = 8.0 Hz, 1H, HC-19),
purity of magnetite.
3
7
.53 (m, 1H, HC-17), 7.24 (m, 1H, HC-18), 7.05–7.13 (m, 3H,
The FT-IR spectra of L-proline and Fe
3
O
4
–L-proline nanoparticles
–L-proline the intense
peak at 1632 cm is derived from C¼O stretching. The absorption
HC-11,12,13), 6.66 (d, J = 7.2 Hz, 1H, HC-16), 6.54 (d, J = 8.0 Hz, 2H,
HC-10,14) 4.91 (br s, 1H, NH), 4.81 (d, J = 6.4 Hz, 1H, HC-7),
3 4
are shown in Fig. 3. In the spectrum of Fe O
ꢁ
1
ꢁ
1
2.95–2.99 (m, 1H, HC-6), 2.30–2.41 (m, 2H, CH-2), 1.95–2.14 (m, 4H,
peak at 589 cm is characteristic of Fe–O bond which confirms the
ꢁ
1
HC-4,5), 1.59–1.85 (m, 2H, HC-3). FT-IR (KBr, ν, cm ): 3396.45,
presence of Fe
3
O
4
nanoparticles. It is worth noting that the C¼O
13
ꢁ1
1
697.69, 1601.76, 1502.64, 809.08. C NMR (100 MHz, CDCl
ppm): 212.89 (C-1), 146.69 (C-9), 140.43 (C-15), 132.31 (C20),
29.01 (C-11,13), 128.90 (C-16), 128.28 (C-19), 127.34 (C-18), 123.61
3
, δ,
stretch band of the carboxyl group is present at 1621 cm in the
spectrum of L-proline, but is absent in the spectrum of Fe
line. Two new bands appear at 1632 and 1400 cm , which are
3 4
O –L-pro-
ꢁ
1
1
Appl. Organometal. Chem. 2015, 29, 566–571
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

J. Safaei-Ghomi and S. Zahedi
ꢁ
1
and the metal atom. The largest D (200–320 cm ) corresponds
ꢁ
1
to monodentate interaction and the smallest D (<110 cm
corresponds to chelating bidentate interaction. Intermediate
)
ꢁ
1
[43]
D (140–190 cm ) corresponds to bridging bidentate.
In the
ꢁ
1
present study, D (1632 ꢁ 1400 = 232 cm ) corresponds to
monodentate interaction.
SEM imaging provides more accurate information on the particle
size and morphology of the functionalized MNPs (Fig. 4). These im-
ages show that the nanoparticles have a uniform size and a spher-
ical shape. It can be seen from Fig. 4(a) that magnetite Fe O4
3
particles have a mean diameter of about 40–50 nm and a nearly
spherical shape. The SEM image shown in Fig. 4(b) demonstrates
that most of the Fe O –L-proline nanoparticles are spherical with
3
4
the same particle size.
The magnetic properties of Fe O and Fe O –L-proline nanopar-
3
4
3 4
ticles were measured via VSM at room temperature (Fig. 5). It can be
seen that the saturation magnetization values of the samples are
ꢁ
1
3
4.5 and 26.3 emu g for Fe O and Fe O –L-proline nanoparticles,
3 4 3 4
respectively. Thus, our catalyst can be recovered using an external
magnetic field.
3 4 3 4
Figure 2. XRD patterns of (a) naked Fe O and (b) Fe O –L-proline
nanoparticles.
3 4
Catalytic behaviour of Fe O –L-Proline nanoparticles
3 4
The catalytic activity of the Fe O –L-proline nanoparticles in the
asymmetric Mannich reaction was investigated by performing a
model reaction of benzaldehyde, aniline and cyclohexanone. In
order to determine the optimal catalyst loading, the three-
component model Mannich reaction was carried out using
3 4
0.01–0.04 g of Fe O –L-proline nanoparticles. The best result in
terms of yield (90%) for the formation of β-amino ketone is
achieved within 1.5 h with a catalyst loading of 0.03 g (Table 1).
Interestingly, the Mannich reaction shows an intriguing solvent
effect; therefore, Table 1 also summarizes the results obtained
using various solvents. High yield and good anti selectivity of the
reaction are observed for EtOH compared with MeOH, CH
and H O.
3 4
Further, we investigated the general applicability of Fe O –L-pro-
2 2
Cl
2
line in the coupling of various aldehyde and aniline derivatives with
cyclohexanone under the optimized conditions. As evident from
Table 2, the reactions of various aromatic aldehydes, anilines and
cyclohexanone give the β-amino ketone adduct in good to high
yield with good to excellent anti selectivity at 100°C.
Mechanistic aspects
In order to explain the observed stereoselectivities, it is proposed
that the reaction occurs via the transition state shown in Scheme 3.
The proposed mechanism of the Mannich reaction catalysed by
the Fe O –L-proline nanoparticles is depicted in this scheme: the
3
4
nucleophilic attack of the proline moiety on cyclohexanone (a),
the dehydration of the carbinol amine to give an enamine (b),
carbon–carbon bond forming between imine and enamine in the
transition state (c) and, after hydrolysis, reaction to give the
diastereoselective Mannich product (d and e). Typically, Mannich
products are formed via si-face attack on an imine. Accordingly, in
the Mannich transition state we assume that the configurations of
Figure 3. FT-IR spectra of Fe
3 4
O –L-proline nanoparticles (top) and L-proline
(bottom).
ꢁ
ꢁ
[44]
ascribed to asymmetric νas(COO ) and symmetric ν
stretching of carboxyl group. These results reveal that L-proline is
chemisorbed onto the Fe nanoparticles in a monodentate
manner. According to Zhang et al. the wavenumber separation, D,
s
(COO )
both the proline enamine and the imine are in E form. The si-face
of the imine is selectively attacked by the re-face of enamine to
allow for protonation of the lone pair and compensation of
vnegative charge formation. Attack of the imine re-face would
result in unfavourable steric interactions between the pyrrolidine
and the aromatic ring.
3 4
O
ꢁ
ꢁ
s
between the νas(COO ) and ν (COO ) FT-IR bands can be used to
distinguish the type of interaction between the carboxylate head
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 566–571

L-Proline-functionalized Fe O NP-catalysed Mannich reaction
3
4
Table 1. Solvent screening and effect of catalyst loading on three-com-
ponent Mannich reaction
a
Entry
Catalyst (g)
Solvent
Temperature (°C)
Yield (%)
1
2
3
4
5
6
7
8
0.03
0.03
0.03
0.01
0.01
0.02
0.03
0.04
H
2
O
50
50
Trace
45
MeOH
CH Cl
2
2
50
35
EtOH
EtOH
EtOH
EtOH
EtOH
50
57
70
66
90
75
100
100
90
90
a
Isolated yield.
Table 2. Direct asymmetric Mannich reaction catalysed by Fe
proline nanoparticles
3 4
O –L-
a
c
Entry
R
R′
Product Time Yield Anti/syn
b
(
h)
(%)
Figure 4. SEM images of (a) naked Fe
nanoparticles.
3 4 3 4
O and (b) Fe O –L-proline
1
2
3
4
5
6
7
8
9
H
H
4a
4b
4c
4d
4e
4f
1.5
2
90
86
85
90
85
89
90
85
85
85
89
85
90
85
85
99:1
98:2
97:3
97:3
99:1
99:1
99:1
98:2
98:2
99:1
98:2
99:1
99:1
98:2
98:2
H
4-Cl
3-Me
H
H
2
2-Cl
4-Me
4-Cl
4-Br
4-Cl
1.5
2
H
H
1.5
1.5
2
H
4g
4h
4i
4-Me
H
4-OMe
H
2
10
11
12
13
14
15
4-Me
4-Cl
H
4j
2
H
4k
4l
2
2-OMe
2-Br
2
H
4m
4n
4o
1.5
2
2,3-OMe
H
2,5-OMeC
H
6 3
Ph
2
a
Reaction conditions: aromatic aldehyde (2.5 mmol), aromatic amine
(
3 4
2.5 mmol), cyclohexanone (3 mmol), Fe O –L-proline nanoparticle
(
0.03 g).
b
c
Isolated yield.
1
Anti/syn ratio determined using H NMR analysis.
[
45]
isomers (ca 4.5 Hz) in these types of systems.
were determined from the relative areas under the absorption
peaks for H
The isomers
3 4
Figure 5. Magnetization curves for the prepared Fe O MNPs (red curve)
and Fe –L-proline (green curve) at room temperature.
3 4
O
β
.
1
The anti/syn ratio was identified using H NMR analysis, ac-
cording to the values of the coupling constants between the
vicinal protons α and β to C¼O. It has been reported that the J
values of anti isomers (ca 7.5 Hz) are higher than those of syn
Recycling of catalyst
The recycling and recovery of catalysts are key from both practical
and environmental points of view. Therefore, we explored the
Appl. Organometal. Chem. 2015, 29, 566–571
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

J. Safaei-Ghomi and S. Zahedi
stability, high catalytic activity and easy recovery for this reaction.
Furthermore, it can be used repeatedly five times with minor
variation of catalytic activity.
Acknowledgment
The authors are grateful to the University of Kashan for supporting
this work under grant no. 159148/XII.
References
[
1] V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara, J. M. Basset,
Chem. Rev. 2011, 111, 3036–3075.
2] S. Shylesh, V. Schünemann, W. R. Thiel, Angew. Chem. Int. Ed. 2010, 49,
428–3459.
3] Y. Chi, Q. Yuan, Y. Li, J. Tu, L. Zhao, N. Li, X. Li, J. Colloid Interface Sci. 2012,
83.
4] Y. Deng, Y. Cai, Z. Sun, D. Zhao, Chem. Phys. Lett. 2011, 510, 1–13.
5] A. M. Balu, B. Baruwati, E. Serrano, J. Cot, J. Garcia-Martinez, R. S. Varma,
R. Luque, Green Chem. 2011, 13, 2750–2758.
6] M. Cano, K. Sbargoud, E. Allard, C. Larpent, Green Chem. 2012, 14,
786–1795.
7] M. Mingliang, Q. Zhang, D. Yin, J. Dou, H. Zhang, H. Xu, Catal. Commun.
012, 17, 168–172.
8] Y. He, C. Cai, Catal. Commun. 2010, 12, 678–683.
9] X. Zhang, A. Liu, W. Chen, Org. Lett. 2008, 10, 3849–3852.
[
3
[
3
[
[
[
1
[
3 4
Scheme 3. Proposed mechanism of Mannich reaction catalysed by Fe O –
L-proline.
2
[
[
[
10] Y. Gao, C. Chen, H. Gau, J. Bailey, E. Akhadov, D. Williams, H. Wang,
Chem. Mater. 2008, 20, 2839–2844.
[
[
[
11] T. Mishra, Catal. Commun. 2008, 9, 21–26.
12] W. Li, J. Liu, C. Yan, Carbon 2011, 49, 3463–3470.
13] B. List, R. A. Lerner, C. F. Barbas, J. Am. Chem. Soc. 2000, 122,
2
395–2396.
14] K. Sakthivel, W. Notz, T. Bui, C. F. Barbas, J. Am. Chem. Soc. 2001, 123,
260–5267.
[
5
[
[
15] P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 43, 5138–5175.
16] M. Gruttadauria, F. Giacalone, A. M. Marculescu, R. Notoa, Adv. Synth.
Catal. 2008, 350, 1397–1405.
[
[
17] M. Gruttadauria, A. M. P. Salvo, F. Giacalone, P. Agrigento, R. Noto, Eur. J.
Org. Chem. 2009, 2009, 5437–5444.
18] S. Calogero, D. Lanari, M. Orrù, O. Piermatti, F. Pizzo, L. Vaccaro, J. Catal.
2011, 282, 112–119.
Figure 6. Easy separation of Fe
magnet.
3 4
O –L-proline nanoparticles using an external
[19] J. Zou, W. Zhao, R. Li, H. Zhang, Y. Cui, J. Appl. Polym. Sci. 2010, 118,
020–1026.
1
[
20] A. Lu, T. P. Smart, T. H. Epps, D. A. Longbottom, R. K. O’Reilly,
reusability of the catalyst in the model reaction between benzalde-
hyde, aniline and cyclohexanone in the presence of 0.03 g of cata-
lyst at 100°C. The MNP-supported chiral catalyst is easily and
completely separated from the mixture reaction using an external
magnetic field. As shown in Fig. 6, the Fe O –L-proline nanoparti-
cles have a good dispersion in the ethanol solvent, and an excellent
magnetic separation capability appears when a magnet is applied
to the vessel. After the separation from the reaction mixture using
a magnet, the catalyst was reused in the model reaction for five
reaction cycles. It is found that product yields decrease to a
small extent on each reuse (run 1, 90%; run 2, 90%; run 3, 89%;
run 4, 89%; run 5, 88%).
Macromolecules 2011, 44, 7233–7241.
[
[
21] S. J. Bae, S. W. Kim, T. Hyeon, B. M. Kim, Chem. Commun. 2000, 31–32.
22] A. Zamboulis, N. J. Rahier, M. Gehringer, X. Cattoën, G. Niel,
C. Bied, J. J. E. Moreau, M. W. C. Man, Tetrahedron Asymm. 2009, 20,
2880–2885.
3
4
[23] F. Calderón, R. Fernndez, F. Snchez, A. Fernndez-Mayoralas, Adv. Synth.
Catal. 2005, 347, 1395–1403.
24] E. G. Doyagüez, F. Calderon, F. Sanchez, A. Fernndez-Mayoralas, J. Org.
[
Chem. 2007, 72, 9353–9356.
[
[
25] W. Miao, T. H. Chan, Adv. Synth. Catal. 2006, 348, 1711–1718.
26] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J. Cheng, Angew. Chem. Int. Ed. 2006,
45, 3093–3097.
[
[
[
27] J. Huang, X. Zhang, D. W. Armstrong, Angew. Chem. Int. Ed. 2007, 46,
9
073–9077.
28] J. Li, G. Yang, Y. Qin, X. Yang, Y. Cui, Tetrahedron Asymmetry 2011, 22,
13–618.
29] H. Yang, S. Li, X. Wang, F. Zhang, X. Zhong, Z. Dong, J. Ma, J. Mol. Catal. A
012, 404.
6
2
Conclusions
[
[
30] C. Mannich, W. Krosche, Arch. Pharm. 1912, 250, 647–667.
31] M. Arend, B. Westerman, N. Risch, Angew. Chem. Int. Ed. 1998, 37,
In summary, we demonstrated the preparation of novel MNPs by
anchoring L-proline on the surface of iron oxide nanoparticles as a
chiral magnetically separable catalyst for the asymmetric Mannich
reaction. This protocol is compatible with various aldehydes and
anilines, thus affording β-amino ketones with high yields and
excellent diastereoselectivities (up to 99:1 dr). Also, the resultant
catalyst combines many advantages such as low cost, long-term
1
044–1070.
[32] D. Enders, S. Oberborsch, J. Adam, D. Ward, Synthesis 2002, 18,
2737–2748.
[
33] Y. G. Wang, Y. Y. Yang, W. G. Shou, Tetrahedron Lett. 2006, 47,
845–1847.
1
[
[
34] N. Azizi, L. Torkiyan, M. R. Saidi, Org. Lett. 2006, 8, 2079–2082.
35] B. Eftekhari-Sis, A. Abdollahifa, M. M. Hashemi, M. Zirak, Eur. J. Org.
Chem. 2006, 2006, 5152–5157.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 566–571

L-Proline-functionalized Fe O NP-catalysed Mannich reaction
3
4
[
36] I. Ibrahem, W. B. Zou, M. Enggvist, Y. M. Xu, A. Cordova, Chem. Eur. J.
[41] H. Wu, Y. Shen, L. Fan, Y. Wan, P. Zhang, C. Chen, W. Wang, Tetrahedron
2007, 63, 2404–2408.
2
005, 11, 7024–7029.
[
[
[
[
37] K. Manabe, S. Kobayashi, Org. Lett. 1999, 1, 1965–1975.
[42] P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 43, 5138–5175.
[43] L. Zhang, R. He, H. C. Gu, Appl. Surf. Sci. 2006, 253, 2611–2617.
[44] B. List, P. Pojarliev, W. T. Biller, H. J. Martin, J. Am. Chem. Soc. 2002, 124,
827–833.
38] Q. Guo, J. C. Zhao, H. Arman, Tetrahedron Lett. 2012, 53, 4866–4869.
39] A. S. Demir, S. Basceken, Tetrahedron Asymmetry 2013, 24, 515–525.
40] M. A. Bigdeli, F. Nemati, G. H. Mahdavinia, Tetrahedron Lett. 2007, 48,
6801–6804.
[45] T. Ollevier, E. Nadeau, J. Org. Chem. 2004, 69, 9292–9295.
Appl. Organometal. Chem. 2015, 29, 566–571
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc