Proline-functionalized magnetic core-shell nanoparticles as efficient and recyclable organocatalysts for aldol reactions

Article abstract of DOI:10.1002/adsc.201200359

Novel magnetically tagged organocatalysts have been developed based on core-shell nanoparticles consisting of magnetite cores and polyacrylate shells containing 4-hydroxyproline moieties. These catalysts allow the performance of direct asymmetric aldol re

Full text of DOI:10.1002/adsc.201200359

FULL PAPERS
DOI: 10.1002/adsc.201200359
Proline-Functionalized Magnetic Core-Shell Nanoparticles as
Efficient and Recyclable Organocatalysts for Aldol Reactions
a
a,
a,b,
Zekarias Yacob, Alexandrina Nan, * and Jꢀrgen Liebscher *
a
National Institute of Research and Development for Isotopic and Molecular Technologies (INCDTIM), Str. 65-103
Donath, Cluj-Napoca, Cluj, RO-400293 Romania
Fax : (+40)-264-420042
b
Institute of Chemistry, Humboldt-University Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany;
e-mail: liebscher@chemie.hu-berlin.de
Received: April 25, 2012; Revised: August 3, 2012; Published online: November 12, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200359.
Abstract: Novel magnetically tagged organocatalysts and ees. Straightforward magnetic separation and re-
have been developed based on core-shell nanoparti- cycling of a catalyst for up to 9 runs is possible with-
cles consisting of magnetite cores and polyacrylate out a significant loss of efficiency.
shells containing 4-hydroxyproline moieties. These
catalysts allow the performance of direct asymmetric
aldol reactions of aromatic aldehydes with ketones Keywords: aldol reaction; asymmetric catalysis; mag-
in the presence of benzoic acid providing high yields netic properties; nanoparticles; supported catalysis
[
30]
Introduction
shell. The catalyst was applied to the direct asym-
metric aldol reaction providing high yields and stereo-
Organocatalysis has emerged to become a significant selectivities and easy recycling. In such types of cata-
field of catalysis particularly in asymmetric synthe- lysts the number of organocatalytic units is limited by
[
1–6]
sis.
Compared with metal catalysts organocatalysts the size of the surface of the nanoparticles. Organoca-
can offer several advantages such as low toxicity and talyst-containing polymer brushes can provide the ad-
robustness making them very practical for application vantage that more catalytic units can be linked to the
under non-inert and less demanding conditions, wide magnetic nanoparticles and thus may provide higher
scope and straightforward accessibility. Although or- catalyst loading, which is often crucial in organocatal-
ganocatalysts are sometimes inexpensive, e.g., simple ysis.
amino acids or alkaloids, their separation and reuse
Here we report on the development of novel orga-
are important issues in particular when it comes to nocatalytic core-shell nanoparticles (NP) consisting of
their industrial applications. Immobilization of orga- magnetite core and polymer brush-like coating with
[
7–12]
nocatalysts on solid supports or polymers
liquid-tagging
or ionic acrylates or methacrylates derived from trans-(S)-4-
[13–17]
can help to address this problem. hydroxyproline. These magnetic core-shell nanoparti-
Amongst the various known organocatalysts linked to cles show excellent catalytic performance and recycla-
polymers are also polymers derived from 4- bility in asymmetric direct aldol reactions.
methacryloyl ACHTUNGTRENNUNGo xyproline performing well in aldol reac-
[12]
tions.
Linking of catalysts to magnetic nanoparticles rep- Results and Discussion
resents a very recent, efficient and environmentally
[
18]
benign approach in recycling.
This technology Three different types of acrylate and methacrylate
allows one to perform the reaction under quasi-homo- monomers 4 differing in the mode of how the organo-
geneous conditions and to achieve separation of the catalytic moiety (4-hydroyproline) is linked to the
catalyst simply by means of an external magnet and acrylic moiety were chosen as the basic structural re-
decantation. In this attractive emerging field also peating unit of the polymer shells (Scheme 1). These
[
18–29]
some examples of organocatalysis are known.
In monomers were obtained in high yields by reaction of
one case chiral 1,2-diaminocyclohexanes were linked the corresponding alcohols with acryloyl chloride in
to magnetite nanoparticles coated with a silica acidic medium in order to prevent unwanted N-acyla-
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Zekarias Yacob et al.
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Scheme 1. Synthesis of magnetically tagged proline polyacrylates.
tion (see the Supporting Information). To enable sur- in the curve of magnetization versus applied magnetic
face-initiated radical polymerization magnetite nano- field (Figure 2 and the Supporting Information).The
particles 1 obtained by coprecipitation from FeCl3 saturation magnetization values are high thus allow-
and FeCl were covered either with the commercial ing easy magnetic separation after application to cata-
2
phosphate 2 or with acrylic acid to obtain stabilized lytic reactions. TEM investigations of the NP 3 and 5
nanoparticles 3 and 6, respectively. Magnetic particles revealed partial aggregation and average diameters of
3
were submitted to polymerization with each of the 13–15 nm and 19–23 nm, respectively (Figure 2). Mag-
three acrylates or methacrylates 4a–c, respectively, netic NPs 7 have average diameters of 15–18 nm and
using AIBN (azobisisobutyronitrile) as radical initia-
tor at 708C in dry DMF.
The resulting proline-functionalized nanoparticles
5
a–c were easily isolated from the solution containing
non-tethered polymers by means of an external
magnet and decantation. In the same way acrylate-
stabilized nanoparticles 6 were transformed into pro-
line-functionalized nanoparticles 7 using acrylate 4a
as monomer. Attachment of the proline functional-
ized polyacrylates to the magnetic core shell in nano-
particles 5 and 7 was confirmed by FT-IR spectra
where typical bands for carbonyl (1740 cm ) and
alkyl (3000 cm ) were observed together with the
iron oxide peak (570 cm ) (Figure 1, see also the
À1
À1
À1
Supporting Information). Nanoparticles 3 and 5 show
À1
characteristic bands for phosphate at 1069 cm . All
magnetic nanoparticles 5 and 7 exhibit superparamag-
netic behaviour as can be seen by missing hysteresis Figure 1. FT-IR spectra of MNPs 3 and 5a.
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Proline-Functionalized Magnetic Core-Shell Nanoparticles as Efficient and Recyclable Organocatalysts
proached their application as organocatalyst in direct
asymmetric aldol reactions (Scheme 2, Table 1). The
aldol reactions were performed with aromatic alde-
hydes 9 in excess of ketones 8 as solvent and with
about 10 mol% catalyst 5 or 7 applying sonication in
the initial phase. It turned out that the addition of
benzoic acid was crucial for excellent performance of
Figure 2. Magnetization vs. applied magnetic field at room
temperature for magnetic nanoparticles 3 and for magnetic
À1
catalyst 5a (Ms=31 emug ).
are better dispersed (see Figure 3 and the Supporting
Information). The NPs 5 and 7 formed well dispersed
colloidal suspensions in polar solvents such as water,
acetone and alcohols while aggregates were observed
in non-polar solvents such as hexane and toluene. The
loading of these NPs with organocatalytic proline
units was approximated from the nitrogen content ob-
tained by elemental analysis. The loadings ranged
À1
À1
from 1.18 mmolg (5a), through 0.57 mmolg (5b)
À1
to 0.52 mmolg (5c). These values do not fully repre-
sent the quantities of organocatalytic units because
most likely not all of the proline units are easily ac-
cessible by the reactants, i.e., the actual loading with
active catalyst is probably lower. With the proline- Scheme 2. Asymmetric direct aldol reaction of ketones 8
functionalized magnetic NPs 5 and 7 in hand, we ap- with aryl aldehydes 9.
Figure 3. TEM image of the magnetic nanoparticles 3 (a) and the magnetic catalyst 5a (b) (bar size 100 nm).
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Table 1. Application of catalysts 5 and 7 in aldol reactions.
[
a]
Entry
Product 10
Catalyst
Additive
–
Yield [%]
dr
ee [%]
1
2
3
4
5
6
7
8
9
a
a
a
a
a
a
a
a
a
a
a
a
a
b
c
d
e
a
a
f
g
h
7
7
46
75
44
73
29
77
59
82
83
85
82
84
80
77
79
94
92
66
74
84
90
76
56:44
81:19
58:42
72:28
82:18
83:7
58:42
60:40
55:45
57:43
60:40
64:36
75:25
70:30
78:22
–
48
98
57
99
88
94
96
>99
98
91
92
94
96
>99
94
>99
>99
95
PhCO H
2
5a
5a
5c
5c
5b
5b
–
PhCO H
2
–
PhCO H
2
–
PhCO H
2
st
5b 1 recycle
5b 2 recycle
5b 3 recycle
5b 4 recycle
5b 5 recycle
5b 6 recycle
5b 7 recycle
5b 8 recycle
PhCO H
2
nd
10
11
12
13
14
15
16
17
18
19
20
21
22
PhCO H
2
rd
PhCO H
2
th
PhCO H
2
th
PhCO H
2
th
PhCO H
2
th
PhCO H
2
th
PhCO H
2
th
5b 9 recycle
PhCO H
77:23
55:45
70:30
55:45
62:38
65:35
2
th
5b 10 recycle
PhCO H
2
[
b]
b]
b]
b]
5b[
PhCO H
92
88
92
88
2
5b[
5b[
5b
PhCO H
2
PhCO H
2
PhCO H
2
[
[
a]
Major diastereomer, determined by chiral HPLC, assignment according to the literature.
Second batch of catalyst.
b]
the organocatalytic nanoparticles, while other acids respectively (Table 1, entries 16 and 17). In order to
such as trifluoroacetic acid were not efficient. Eventu- check the quality of the catalyst 5b after all these re-
ally this phenomenon is caused by specific interaction cyclings it was applied to the starting combination of
of the benzoic acid with the aromatic aldehydes and/ reactants (cyclohexanone and 4-nitrobenzaldehyde) in
or the organic shell of the nanoparticles.
a tenth run (entry 18) where it still maintained the
Under these conditions all four catalytic nanoparti- very good enantioselectivity but led to lower yield
cles 5a–c and 7 gave excellent yields and enantioselec- (66%). The reason for the increase in diastereoselec-
tivities in the direct aldol reaction of 4-nitrobenzalde- tivity observed in entries 12 and 13 is unclear and is
hyde with cyclohexanone (Table 1, entries 2, 4, 6, 8). subject of future investigations. In order to check the
In these cases diastereomeric ratios ranged from reproducibility of the synthesis of our magnetically
60:40 to 83:17. The recyclability as a key property of tagged organocatalysts catalyst 5b was synthesized for
magnetically tagged organocatalysts was checked with a second time. According to its elemental analysis the
À1
catalyst 5b (Table 1, entries 8–13). which gave the catalyst loading was somewhat lower (0.53 mmolg ).
highest chemical yield and enantioselectivity Its application in the direct aldol reaction gave com-
(
entry 8). Its performance in terms of yields and ste- parable results as the first batch (Table 1, entry 19).
reoselectivity virtually did not drop during these six This catalyst was used to produce aldol products 10f–
runs. Furthermore, this repeatedly recycled catalyst h further demonstrating the scope of the method in
5
b was used in additional four runs (entries 14–17) in terms of substituents in the aryl part of starting alde-
order to check tolerance of variation of ketones 8 and hydes 9.
aryl aldehydes 9 in the aldol reaction (Scheme 2).
In order to provide more distance between the cat-
Pleasingly, also other aromatic aldehydes 9 with an alytic proline units in the polymeric shell and also to
electron-donating group or lacking substituents per- reduce the number of precious organocatalytic moiet-
[
12]
formed very well providing high yields and enantiose- ies,
lectivities as well as good diastereoselectivities amide in the presence of magnetic NPs 3 was per-
Table 1, entries 14 and 15). formed. However, the resulting core-shell nanoparti-
The same holds true if the catalyst 5b was used for cles exhibited unsatisfactory catalytic performance in
an altogether 8th and 9th time in the aldol reaction of the aldol reaction giving rise to the formation of 10a.
-nitrobenzaldehyde with acetone or cyclopentanone,
copolymerization of 4a with N-isopropylacryl-
AHCTUNGTRENNUNG
(
4
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Proline-Functionalized Magnetic Core-Shell Nanoparticles as Efficient and Recyclable Organocatalysts
Conclusions
of aldol products was deduced by comparison of the HPLC
retention times with reported values
In summary, we have developed a novel type of mag-
netically tagged organocatalysts wherein a 4-hydroxy-
proline-derived acrylate or methacrylate polymer is
layered on magnetite nanoparticles. The polymeric Acknowledgements
nature of the shell provides a high loading with the
This work was supported by the Romanian Ministry of Edu-
catalyst making it powerful and sustainable. It per-
forms very well in aldol reactions of ketones with aro-
matic aldehydes and allows easy recyclization by sep-
aration with an external magnet and multiple reappli-
cations. At present we are applying this methodology
of magnetic tagging to other organocatalytic moieties.
cation and Research under the research program POS-CCE-
METAVASINT, project no 550/2010 and project PN-II-RU-
TE-2011-3-0130. The authors wish to acknowledge Dr. Ioan
Bratu (INCDTIM) for FT-IR measurements and Dr. Cristian
Leostean (INCDTIM) for conducting magnetic measure-
ments, Dr. Lucian Barbu from Centre of Electronic Micros-
copy of Babes-Bolyai University Cluj-Napoca for TEM in-
vestigations and Dr. Ovidiu Crisan, University of Medicine
and Pharmacy, Cluj-Napoca for providing elemental analy-
ses.
Experimental Section
Preparation of starting materials 4b, characterization of
aldol products 10, FT-IR spectra, TEM images, magnetic
measurements and NMR measurements are presented in
the Supporting Information.
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