Temperature-responsive hairy particle-supported proline for direct asymmetric aldol reaction in water

Article abstract of DOI:10.1039/c5ra16393e

In this paper, three kinds of hairy particles with different brush structures were prepared and evaluated as chiral catalysts in the direct asymmetric aldol reaction. Compared to other hairy particles, hairy particle (1) grafted with amphiphilic copolymer

Full text of DOI:10.1039/c5ra16393e

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Temperature-responsive hairy particle-supported
proline for direct asymmetric aldol reaction in
water†
Cite this: RSC Adv., 2015, 5, 89149
Xinjuan Li,* Beilei Yang, Xianbin Jia, Maoqin Chen and Zhiguo Hu*
In this paper, three kinds of hairy particles with different brush structures were prepared and evaluated as
chiral catalysts in the direct asymmetric aldol reaction. Compared to other hairy particles, hairy particle
(1) grafted with amphiphilic copolymer chains showed a good conversion rate and an outstanding
enantioselectivity in pure water. The copolymer brush on the surface of hairy particle (1) contained
temperature responsive poly(N-isopropylacrylamide) which underwent a coil-to-globule transition at
a lower critical solution temperature (LCST). The brush formed a hydrophobic nanocavity for the organic
substrates, and it provided a suitable reaction microenvironment below and above the LCST of PNIPAM.
Received 14th August 2015
Accepted 13th October 2015
ꢀ
The aldol reaction was promoted by the catalytic system and it showed stable reactivity from 25 C to
ꢀ
5
0
C. The significant advantages of the hairy particle supported catalytic system were that it was more
DOI: 10.1039/c5ra16393e
efficient than the corresponding homogeneous polymer supported proline, and it can be recycled five
www.rsc.org/advances
times while maintaining activity and selectivity.
block copolymers have also been extensively studied for their
uses in catalytic systems, and they can also provide a protected
Introduction
1
3–20
One of the most important carbon–carbon bond-forming hydrophobic environment in water.
Amphiphilic copoly-
reactions in synthetic organic chemistry, the asymmetric mers supported catalysts can catalyze asymmetric reaction in
aldol reaction, has been intensively studied. Since list reported water effectively and can be reused. But the catalyst was recy-
the direct aldol reaction catalyzed by L-proline under mild cled by precipitating in the organic solvent, the environment
1
reaction conditions, L-proline has been widely used in asym- would be polluted. During the application of the phase
metric organic reactions. Its catalytic efficiency in organic switchable behavior of amphiphilic copolymer, the copolymer
2
1–23
solvents such as dimethylformamide, dimethyl sulfoxide and will collapse and precipitate for facile recovery.
However,
chloroform has been documented. On adding a small amount the recovery rate was not very ideal. Although, numerous
of water to the polar solvent, the reaction rate can be acceler- strategies have been used to immobilize chiral catalysts onto
ated. However, when the reaction is carried out with a large solid-supported materials such as polystyrene (beads), den-
amount of water (or in pure water), it always resulted in low drimers, ionic liquids and inorganic particles or crosslinked
2
4–27
yield with low or no enantioselectivity because of the limited insoluble polymers,
they usually show relatively poor
affinity between the hydrophobic reactant and hydrophilic catalytic efficiency in water-medium. The intrinsic problem in
2
–4
catalyst.
the heterogeneous catalytic systems is the lower degree of
Asymmetric reactions in aqueous solutions have become an exposure to the reactants. It is still a challenging work to
area of fast growing interest recently because water is a safe, synthesize excellent catalytic systems to combine the advan-
cheap, and environmentally friendly medium. Numbers of tages of both homogeneous catalyst and heterogeneous cata-
water-soluble chiral catalysts have been developed and thus lysts in water.
5
–10
contributed to the growth of green chemistry.
In cases, the
Herein, we synthesized three kinds of hairy particles sup-
catalyst was modied so as to be more hydrophobic, such as ported proline by RAFT precipitation polymerization combining
formed a concentrated organic phase, which resulted in an with surface-initiated RAFT copolymerization. Hairy particle (1)
1
1,12
observed acceleration in the rate of reaction.
Amphiphilic contained with hydrophobic styrene, N-isopropylacrylamide
NIPAM) and chiral polymer chain; while hairy particle (2)
(
contained with chiral polymer chain and NIPAM, without
styrene; and hairy particle (3) contained with chiral polymer
chain and styrene, without NIPAM (Fig. 1). Furthermore, the
obtained catalysts were used in asymmetric aldol reaction in
water, and the catalytic activity, asymmetric selectivity
School of Chemistry and Chemical Engineering, The Key Laboratory of Green Chemical
Media and Reactions, State Education Ministry of China, Henan Normal University,
Xinxiang 453007, P. R. China. E-mail: xinjuanli2009@163.com; zghu@htu.cn
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c5ra16393e
1
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Fig. 1 The synthesized method of hairy particles and the structure diagram of hairy particles.
and recyclability were also further studied. Poly(N-iso- Fourier transform infrared spectrometer using KBr pellets.
propylacrylamide) (PNIPAM) is a temperature-responsive poly- Elemental analysis was performed on a Thermo FLASH 1112
mer that exhibits a sharp phase transition at a lower critical elementar. The morphologies and sizes of the samples were
solution temperature (LCST). Use thermo-responsive polymers characterized by scanning electron microscopy (SEM, JSM-
to load L-proline to prepare “smart” catalysts, so that the cata- 6390LV) and eld-emitting scanning electron microscope
n
lytic activities can be switched by adjusting the temperature (FESEM, JEOL-JSM-6700F). The number-average diameter (D )
2
2,23
below or above the LCST.
was determined by the SEM image. Molecular weights of the
polymers were measured with GPC by using PEO as a standard
and DMF as a mobile phase, and RI detector was also used.
Experimental section
ꢀ
Two shodex LF-404 columns were conditioned at 35 C and
ꢁ1
Materials and reagents
ow rate ¼ 0.3 mL min . HPLC analysis was carried out on
Agilent TM 1100 HPLC equipment. The static water contact
angles of the lms that prepared with microspheres were
determined as follows: the lms of the hairy particles were
prepared by casting their suspension solutions in DMF (10 mg
Styrene, methacrylic acid (MAA, Aldin, 98%), ethylene glycol
dimethacrylate (EGDMA, Alfa Aesar, 98%), and 1,4-dioxane
Jiangtian Chemicals, China) were puried by distillation under
vacuum. NIPAM and azobisisobutyronitrile (Chemical Plant of
Nankai University, AR) was recrystallized from ethanol. Cumyl
dithiobenzoate (CDB) and boc-protected O-acrylic hydroxy-
(
ꢁ
1
mL , aer ultrasonic dispersion) on clean glass surfaces.
Aer the solvent was allowed to evaporate at ambient
28
ꢀ
20
temperature and the resulting lms were dried at 25 C under
proline were prepared following the literature procedure, and
all the other chemicals were used as received.
vacuum overnight, a Kr u¨ ss FM40 Easy Drop contact angle
equipment (Germany) was utilized to determine hairy parti-
cles' static water contact angles. The dynamic light scattering
was conducted on an ALVCGS-3 in order to investigate the
particle size of the micelle.
Measurements
1
H NMR spectra were recorded on a Bruker AV-400 NMR
spectrometer. FT-IR spectra were recorded on a Nicolet NEXUS
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Preparation of the hairy particles supported catalyst
and boc-protected O-acrylic hydroxyproline was 7/3. Hairy
particle (3) was prepared and puried under the identical
conditions except without NIPAM, and the mole ratio of styrene
and boc-protected O-acrylic hydroxyproline was 7/3. The
method of deprotection was the same as the hairy particle (1).
Elem. anal. of the hairy particle (2): C, 61.69; H, 7.45; N, 1.36;
Preparation of poly(MAA-co-EGDMA) microspheres by RAFT.
MAA (0.12 g, 1.50 mmol), CDB (18.2 mg, 0.66 mmol), EGDMA
(1.41 mL, 7.50 mmol), a mixture of methanol and water (4/1, v/v,
120 mL) were added into a one-neck round bottom ask (250
mL) successively. Aer stirring for 30 min at room temperature,
AIBN (54.1 mg, 0.33 mmol) were added. The reaction mixture
was purged with nitrogen for 30 min and then sealed. The ask
was then attached to the rotor-arm of an evaporator, and
ꢁ
1
S, 2.32% (the proline loading was 0.43 mmol g ).
Elem. anal. of the hairy particle (3): C, 60.73; H, 7.42; N, 0.46;
ꢁ
1
S, 2.68% (the proline loading was 0.33 mmol g ).
ꢀ
The three free copolymers were also deprotected according
to the above ways. Aer reaction, the free polymer solution was
submerged in a 60 C oil bath and rotated slowly (ca. 20 rpm) for
24 h. The resulting polymer particles were collected by ltration
ꢀ
concentrated and puried by precipitation in diethyl ether,
and puried with methanol. Aer the solid was dried at 40 C
under vacuum for 48 h, a light pink solid was obtained in a yield
of 69%. Elem. anal.: C, 58.74; H, 7.03; S, 2.48% (the CTA loading
ꢀ

ltered and dried at 30 C under vacuum for 48 h, providing the
homogeneous polymer supported proline.
ꢁ
1
was 0.39 mmol g ).
General procedure for the asymmetric aldol reaction
Preparation of hairy particle (1). The microspheres with
graed polymer brushes were prepared via surface-initiated
RAFT polymerization according to the following procedure:
poly(MAA-co-EGDMA) microspheres (the CTA loading 0.26
mmol), NIPAM (3.39 g, 30.0 mmol), styrene(0.39 g, 3.70 mmol),
boc-protected O-acrylic hydroxyproline (1.13 g, 10.89 mmol),
CDB (30.4 mg, 0.11 mmol), AIBN (3.3 mg, 0.02 mmol), and 1,4-
Different substituted benzaldehyde (0.25 mmol) and cyclohex-
anone (104 mL, 1.0 mmol) were dissolved in solvent (1 mL), and
then the catalyst was added. Aer the reaction, the reaction
mixture was isolated by centrifugation, and the hairy particles
were washed with ethyl acetate and dried in a vacuum to use
again. The aqueous layer was extracted into ethyl acetate, and
dioxane (5 mL) were added into a two-neck round-bottom ask the organic layers were combined and dried over MgSO . The
4
(
25 mL) successively. Aer being degassed with ve freeze–
solvent was removed under vacuum, and the crude residue was
puried by ash column chromatography on silica gel and
yielded the pure aldol product. The diastereomeric ratio (dr)
was determined by H NMR spectroscopy, and the enantiomeric
excess (ee) was determined by chiral HPLC.
pump–thaw cycles, the ask was sealed and immersed in
a thermostated oil bath at 75 C and stirred for 24 h. Aer
centrifugation, the resulting solid products were thoroughly
washed with DMF and methanol, and then dried at 30 C under
ꢀ
1
ꢀ
vacuum to give a pale powder. The supernatant solutions were
ꢀ
precipitated in ether, ltered and dried at 30 C under vacuum
Results and discussion
Preparation of the hairy particles supported catalyst
for 48 h, and then the free N-boc protected polymer was
obtained.
The above hairy particles (1.00 g) were dispersed in dry
The poly(MAA-co-EGDMA) microspheres with surface-
immobilized dithioester groups were prepared via RAFT
precipitation polymerization (RAFTPP) following the ref. 28 and
CH Cl (5 mL), and the solution of TFA (5 mL) in CH Cl (5 mL)
2
2
2
2
was dropwise added for 0.5 h at ice bath, then the mixture was
stirred for 0.5 h at ambient temperature. Aer centrifugation,
the solid products were thoroughly washed with water and
29. Furthermore, three kinds of hairy particles were synthesized
by the modication of the preformed polymer microspheres via
surface-initiated reversible addition-fragmentation chain
transfer (RAFT) copolymerization. Hairy particle (1) was
synthesized by copolymerization with N-boc protected chiral
monomer, NIPAM and styrene; hairy particle (2) with chiral
monomer, NIPAM but no styrene; hairy particle (3) with chiral
monomer, styrene but no NIPAM (Fig. 1). The synthesized
method was the same as follows: poly(MAA-co-EGDMA)
ꢀ
methanol, and then dried at 40 C under vacuum to obtain nal
particles.
Elem. anal. of the hairy particle (1): C, 59.74; H, 7.29; N, 1.45;
ꢁ
1
S, 3.08% (the proline loading was 0.38 mmol g ).
Preparation of hairy particle (2) and hairy particle (3). Hairy
particle (2) was prepared and puried under the identical
conditions except without styrene, and the mole ratio of NIPAM
Table 1 Characterization data for copolymer brush-grafted particle samples and the corresponding free copolymers
M
n
,
PDI, GPC
(free polymer)
Graing density
(chain per nm )
d
2
Free copolymer ratio
GPC (free polymer)
Graing copolymer ratio
a
a
Hairy particle 1
Hairy particle 2
Hairy particle 3
0.64 : 0.21 : 0.15
43 100
50 100
31 200
1.43
1.31
1.52
0.56 : 0.27 : 0.17
0.96
0.83
0.82
b
b
0.67 : 0.33c
0.72 : 0.28c
0.53 : 0.47
0.59 : 0.41
a
1
b
Molar mass value of [NIPAM] : [St] : [N-boc protecting chiral polymer] determined by H NMR. Molar mass value of [NIPAM] : [N-boc protecting
1
c
1
d
chiral polymer] determined by H NMR. [St] : [N-boc protecting chiral polymer] determined by H NMR. Molar mass value of graing copolymer
calculated from the relation [NIPAM]graed ¼ [NIPAM]
0
ꢁ [NIPAM]free polymer, [St]graed and [N-boc protecting chiral polymer]graed were determined
RSC Adv., 2015, 5, 89149–89156 | 89151
by the same way.
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Fig. 2 SEM images of no grafted poly(MAA-co-EGDMA) microspheres (a) and hairy particle (1) (b), hairy particle (2) (c), hairy particle (3) (d) in dry
state, FESEM images of hairy particle (1) (e) and hairy particle (2) (f) and hairy particle (3) (g) after swelling in water.
microspheres as chain transfer agents (CTA), AIBN as the agent), and the results were listed in Table 1. The free
initiator, and 1,4-dioxane as the solvent. A certain amount of copolymer ratio for hairy particle (1) was 0.64 : 0.21 : 0.15,
CDB was added into the reaction system as the sacricial chain and the graed polymer ratio was 0.56 : 0.27 : 0.17. The
transfer agent in order to increase the control over the poly- polymer mole ratio on the particle was different from the free
30
merization. The weight increases of 16.7 wt%, 14.6 wt% 14.3 polymer. However, the difference was not very obvious. The
wt% were observed for microspheres. other hairy particles also got the same results. So the free
The synthesis of statistical copolymers will lead to different polymer can be utilized to represent those of the graed
3
1,32
products depending on whether the reaction takes place in polymer brushes.
solution or from the surface of a polymeric particle, due to the
different kinetics of copolymerization. So, we investigated the
The free N-boc protected polymers were characterized with
H-NMR (Fig. 3a, c and e), and the percentage content of the
1
structure of the polymer graed on the particles and the free copolymer 1 was determined by comparing distinct polymer
polymer generated in the surface-initiated RAFT polymeriza- signals (d 1.2–1.5 ppm for boc-protected O-acrylic hydroxypro-
tion system (due to the addition of sacricial chain transfer line H , d 6.2–7.3 ppm for styrene H , and d 3.86 ppm for NIPAM
d
b
1
Fig. 3 H-NMR spectra of the free copolymer (1) before deprotection in DMSO-d
copolymer (2) before deprotection in DMSO-d
DMSO-d (e) and the free copolymer (3) in DMSO-d
6
6
(a) and the free copolymer (1) in DMSO-d (b); the free
6
(c) and the free copolymer (2) in DMSO-d
6
(d); the free copolymer (3) before deprotection in
6
6
(f).
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H
a
). The ratio of different composition (NIPAM, styrene and N- corresponding catalyst loadings were 0.38 mmol, 0.43 mmol
boc-L-proline) was 0.64 : 0.21 : 0.15, with an average molecular and 0.33 mmol catalyst per g particles.
weight of 43 100, PDI ¼ 1.43 (GPC analysis). The free copolymer The average surface graing density can be calculated
without styrene contained 33% of N-boc chiral monomer according to the ref. 27, an average surface graing density of
2
2
under a good polymerization control (M
1.19). The free copolymer 3 without NIPAM, contained 47% of graed polymer microspheres (in Table 1). The results indi-
N-boc chiral monomer with an average molecular weight of cated the graed chiral copolymer is in a densely brushy state,
n
(GPC) ¼ 50 100, M
w
/M
n
about 0.96, 0.83 and 0.82 chains per nm can be derived for the
¼
3
1 200, PDI ¼ 1.52.
and the difference of the graing density was small.
The N-boc protecting groups for the amine can be readily
The hydrophobic and hydrophilic performances of hairy
33
deprotected under acidic conditions. Thus, the graed chiral particles were investigated from static water contact angles. It
polymer brushes were deprotected in dry CH Cl in the pres- was anticipated that the hairy particle (2) graed with hydro-
2
2
ence of triuoroacetic acid (TFA) to afford the nal hairy philic polymer brushes should show much reduced static water
particle. Successful deprotection was conrmed by comparing contact angles, while hairy particle (3) graed with hydrophobic
1
the H NMR signals of the free polymer given in Fig. 3. The tBu polymer brushes should show much higher static water contact
signals (at 1.2–1.5 ppm) disappeared following deprotection, angles. The experimental results indeed supported this
and it turned out that the deprotection of hairy particle was hypothesis (Fig. 5). Hairy particle (1) with amphiphilic copol-
ꢀ
successful. The morphology and particle size of the nal hairy ymer chain has the contact angles at 126.1 , which contains
particles were characterized with SEM (Fig. 2), and the number- some hydrophobic performance. The result provided strong
average diameters (D ) of the hairy particles were determined to evidence for the presence of different polymer shells on the
n
be 2.78, 2.83 and 2.76 mm, an increases of 320 nm, 370 nm and modied polymer microspheres.
3
18 nm in D
microspheres, from which the layer's thickness of 160 nm, 185
nm and 158 nm (i.e., DD /2) could be derived from the graed
n
values were obtained for the graed polymer
The hairy particles supported organocatalyst for the
asymmetric aldol reaction
n
polymer brushes. The FESEM image (Fig. 2e, f and g) showed
particles coated with a thin polymer shell, which further prove
that the polymer chains successfully graed on the surface of
particles. FT-IR was also employed to characterize the graed
polymer microspheres (Fig. 4). It can be seen clearly that in
addition to the peaks corresponding to the ungraed one, some
The catalytic activity of the synthesized hairy particles sup-
ported L-proline was tested by using a representative aldol
reaction between cyclohexanone and 4-nitrobenzaldehyde. The
reactions were rst carried out with 10 mol% catalyst loading at
different temperatures in pure water for 72 h. PNIPAM has been
widely studied mainly because of the sharpness of its phase
ꢁ1
characteristic peaks such as the amide I band (1529 cm , C]O
ꢀ
26,27
transition and the closeness of its LCST about 32 C.
chose this reaction temperature range to study the different
We
ꢁ
1
stretching), amide II band (1627 cm , C–N stretching) were
also observed, to further verify the successful graing of chiral
polymer brushes. The N contents of hairy particles for
elemental analysis were 1.45 wt%, 1.36 wt% and 0.46 wt%, and
according to the content of proline in copolymer, the
possible states of the catalyst system (Table 2): (i) the occurrence
ꢀ
of micelles at 0 and 25 C (i.e., below the LCST), (ii) a little above
ꢀ
ꢀ
the LCST at 35 C, and (iii) far above the LCST at 50 C. The hairy
particle (1) as catalyst has good catalytic activity and stereo-
selectivity with 84% conversion, 91/9 dr (anti/syn) and >99% ee
ꢀ
ꢀ
at 0 C. Increasing the reaction temperature from 0 to 35 C, the
conversions increased obviously, but the diastereoselectivity
and ee values changed little. When further increasing temper-
ꢀ
ꢀ
ature from 35 C to 50 C, the conversion almost had no change,
but the selectivity decreased obviously. The conversion was the
ꢀ
highest (97%) at 35 C, and with a good selectivity (anti/syn 89/
11, ee 97%). Hairy particle (3) with hydrophobic part showed
Fig. 4 Fourier transform infrared (FT-IR) spectra of no grafted poly-
(
MAA-co-EGDMA) microspheres (a), hairy particle (1) (b), and hairy Fig. 5 Profiles of a water drop on the films of the grafted polymer
particle (1) after five cycles as catalysts (c), hairy particle (2) (d), hairy microspheres (1) hairy particle (1), (2) hairy particle (2), (3) hairy particle
particle (3) (e).
(3).
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Table 2 Comparison of the different catalyst system catalyzing the
aldol reaction between cyclohexanone and 4-nitrobenzaldehyde for
72 h
Temperature
( C)
ꢀ
a
a
b
Catalysts
% Conversion syn/anti % ee (anti)
Hairy particles (1)
0
84
90
97
97
5
32
16
17
10
67
9/91
>99
95
97
93
87
53
77
42
88
95
Hairy particles (1) 25
Hairy particles (1) 35
Hairy particles (1) 50
10/90
11/89
22/78
20/80
27/73
20/80
28/72
21/79
12/88
Hairy particles (2)
0
Hairy particles (2) 25
Hairy particles (2) 35
Hairy particles (2) 50
Hairy particles (3)
Hairy particles (3) 25
Fig. 6 Kinetics for aldol reaction catalyzed by hairy particle (1) and the
corresponding free polymer at 10 mol% catalyst loading at different
temperatures.
0
a
b
1
Determined by H NMR spectroscopic analysis of the crude product.
Determined by HPLC using a chiral column.
effective than free polymer supported system at 10 mol%
loading at different temperature from 25 to 50 C. These results
ꢀ
have shown the advantage of the hairy particles supported
system. From the reaction kinetics, we also nd the reaction
rate increased with increasing reaction temperature. It is well
known that PNIPAM is a typical thermoresponsive polymer,
which undergoes a coil-to-globule transition at the lower critical
weak catalytic activity at lower temperature. Increasing reaction
temperature from 0 to 50 C, the conversions increased sharply
ꢀ
(from 10% to 80%), and the reason can be attributed to the
ꢀ
solution temperature (LCST) at about 32 C. The smart polymer
increasing solubility at higher temperature. According to the
ref. 34, L-Pro attached to a folded PEG based amphiphilic
polymer did show good activity in water, but not very ideal
selectivity (eeanti ¼ 72%). This ee value was attributed to a too
hydrophilic environment in the vicinity of the catalyst. In the
absence of a hydrophobic pocket by using hairy particle (2) at 10
mol% catalyst loading, the aldol reaction in water reached <32%
yield at different temperatures, the regioselectivity was also
moderate (ee <87%), supporting the effect of the hydrophobic
of PNIPAM is always chosen as the copolymer chains for two
reasons. First, the PNIPAM chains become hydrophobic and
collapse as core, which can provide a nano environment for
hydrophobic guest molecules in water just by increasing the
36
temperature above its phase transition temperature. Second,
PNIPAM can be recycled due to the reversible phase transition.
In this paper, the copolymer chains graing on hairy particle (1)
contain hydrophobic styrene and hydrophilic NIPAM, which
form micelles below the phase transition temperature and
provide a nanoreactor on the surface of particles. When the
temperature increases above the phase transition temperature,
the PNIPAM chains collapse and provide a hydrophobic nano
cavity for the organic substrates. So the aldol reaction can be
aroused above and below the transition temperature of
PNIPAM.
35
pocket for efficient catalysis.
By contrast, hairy particle (1) has the excellent catalytic
activity and stereoselectivity, and our design is successful in
loading L-proline at a well dened interface between the
hydrophobic and hydrophilic portions of the graed polymers.
Comparison of above catalysis results with recent literature
examples, although L-Pro-based block copolymers or nanogels
reported by O'Reilly and coworkers show good catalytic results
at low catalyst loading (1 mol%), our catalytic system needs
more catalyst loading (10 mol%). However, our catalytic system
could be easily separated aer reaction, to be reused for the
subsequent catalysis cycle.
In order to further investigate the activity and selectivity of
the hairy particle (1), we compared the catalytic performance of
the hairy particle (1) supported system with the corresponding
free polymer supported proline system. Fig. 6 shows the kinetics
of the reaction catalyzed by the hairy particle (1) and the cor-
responding free copolymer. Although the differences in ster-
eoselectivity and nal conversion aer 72 hours are not
signicant, it can be observed that hairy particle (1) is more
In order to ascertain the contribution of the graed copol-
ymer on the catalytic property of hairy particle (1), the thermo-
responsive conformation changes of free polymer (1) were
monitored by TEM (Fig. S1†) and DLS (Fig. 7). The TEM
ꢀ
observation showed that, at low temperature (25 C), micelles
containing a hydrophobic backbone core and a PNIPAM corona
were formed in the solution of brush copolymers. Micelles in
random brush copolymer solution showed irregular shape, and
the diameter was approximate 35–45 nm. DLS was carried out
ꢁ
1
ꢀ
with a 3 mg mL free copolymer (1) solution from 25 to 50 C.
As shown in Fig. 7, the insets concerned the DLS spectra of the
intensity distribution, and the copolymer showed a hydrody-
ꢀ
namic diameter (dH) (116.98 nm) in water at 25 C. PNIPAM was
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ꢁ1
ꢀ
ꢀ
Fig. 7 DLS of 3 mg mL free copolymer (1) solution at 25 C (a), 35 C
ꢀ
(
b) and 50 C (c).
Fig. 8 Recycle data for the aldol reaction using the hairy particles (1)
ꢀ
soluble in water at low temperature, thus, the peak is mostly at supported catalyst at 35 C for 72 h.
ꢀ
2
5 C, which probably indicates the formation of the micelles.
However, above the transition temperature, with the tempera-
ture increasing persistently, the dH went through a decrease value > 91% in each cycle, and only slightly decreases in
ꢀ
with a lower dH (63.7 nm) at 35 C, which may result from the conversion and enantioselectivity were observed. The recovery
collapse of the aggregates by removing more water molecules rate of the hairy particles was very high (>97%). FTIR also
and forming more compact and regular structures. When the proved that the structure of the chiral polymer chain was not
ꢀ
temperature increased to 50 C, the size of micelles increased changed aer 5 cycles (Fig. 4c).
(
dH ¼ 79.98 nm) and the peak changed broadly. There is almost
no obvious shrinkage in the corona of micelles when the
temperature is far above LCST. It is certain that the strong
repulsive interaction among the denser PNIPAM side chains
Conclusions
This paper proves that RAFT precipitation polymerization
combining with surface-initiated RAFT polymerization is an
efficient approach to obtain hairy particles supported proline
system. The catalysts were well-dened copolymers of styrene,
NIPAM and L-proline functionalized chiral monomer, which can
catalyst the direct aldol reaction in water efficiently. PNIPAM is
a temperature-responsive polymer, which undergoes a coil-to-
globule transition at a lower critical solution temperature
37
within micelle leads to the above phenomenon.
We also investigated the reaction between cyclohexanone
and several substituted benzaldehydes with hairy particle (1) as
catalyst. In contrast, o-NO C H CHO showed a lower conversion
2
6
4
and ee value (entry 2 in Table 3), the reaction gave the best
conversion when p-NO C H CHO was used as the reaction
2
6
4
substrate,
and
m-NO
2
C
6
H
4
CHO
showed
the
best
stereoselectivity.
(LCST) and provides a different reaction interface. The experi-
Recovery and recycling of the catalytic system were next
investigated. The potential recycling of the hairy particle (1)
supported catalytic system was studied by using the same aldol
reaction between 4-nitrobenzaldehyde and cyclohexanone. This
adjustment was done to keep the aldol reaction at 10 mol%
mental results also proved that the aldol reaction can be
accelerated both above and below LCST (32 C) of poly(N-iso-
ꢀ
propylacrylamide) and showed a good catalytic activity as well as
ꢀ
ꢀ
an asymmetric selectivity from 25 C to 50 C. The reaction
catalyzed by the hairy particles (1) supported system was more
efficient than the homogeneous polymer supported proline.
The hairy particles graing with amphiphilic copolymer chains
and temperature responsive polymer chains can provide a new
and practical way for chiral catalyst load in pure water.
ꢀ
catalyst loading throughout different cycles at 25 C (Table S1†)
ꢀ
and 35 C (Fig. 8). The catalyst was successfully used in multiple
cycles without losing signicant activity or selectivity, and ee
Table 3 Aldol reaction between different substitution benzaldehyde
ꢀ
and cyclohexanone in water at 35 C
Acknowledgements
Entry Aldehyde
Conversion (%) syn/anti ee (%)
This work was supported by the National Natural Science
Foundation of China (No. 21204019), the Post-doctoral Foun-
dation of China (No. 2012M521398), the Post-doctoral Foun-
dation of Henan Province and the International Cooperation
Project of Henan Province (No. 134300510055).
1
2
3
p-NO
o-NO
m-NO
2
C
6
H
H
4
CHO 97
CHO 57
11/89
50/50
1/99
97
2
C
6
4
75(anti), 58(syn)
2
C
6
H
4
CHO 68
98%
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