Asymmetric epoxidation of unfunctionalized olefins accelerated by thermoresponsive self-assemblies in aqueous systems

Article abstract of DOI:10.1039/c5cy00953g

A novel thermoresponsive surfactant-type chiral salen Mn^III catalyst was developed by axially grafting "smart" poly(N-isopropylacrylamide) (PNIPAAm) onto the metal center of a neat chiral salen Mn^III complex. Characterization data su

Full text of DOI:10.1039/c5cy00953g

Catalysis
Science &
Technology
View Article Online
View Journal
PAPER
Asymmetric epoxidation of unfunctionalized
olefins accelerated by thermoresponsive self-
assemblies in aqueous systems
Cite this: DOI: 10.1039/c5cy00953g
a
a
a
a
ab
*
*
Yaoyao Zhang, Rong Tan, Guangwu Zhao, Xuanfeng Luo and Donghong Yin
A novel thermoresponsive surfactant-type chiral salen MnIII catalyst was developed by axially grafting
“smart” polyIJN-isopropylacrylamide) (PNIPAAm) onto the metal center of a neat chiral salen MnIII complex.
Characterization data suggests thermoresponsive micellization behavior of the obtained catalyst in water.
The chiral metallomicellar catalyst acted as a nanoreactor to carry out asymmetric epoxidation of
unfunctionalized olefins in water and dramatically accelerated reaction rates. Outstanding catalytic effi-
ciency was observed in the nanoreactor system. In particular, quantitative conversion (99%) of styrene with
high enantioselectivity (39%) was achieved over 0.8 mol% of the catalyst within 3 min, giving an unprece-
dented TOF value (2.48 × 103 h−1) which is significantly higher than that obtained over previously reported
homogeneous or heterogeneous systems. Moreover, the catalyst could be easily recovered by
thermocontrolled separation and reused with high activity for five cycles.
Received 25th June 2015,
Accepted 6th August 2015
DOI: 10.1039/c5cy00953g
www.rsc.org/catalysis
reaction rate.14,17–21 The pre-organizing function of surfac-
tants in aqueous organic reactions encouraged us to envisage
Introduction
Asymmetric epoxidation of unfunctionalized alkenes catalyzed
by chiral salen MnIII complexes is of great importance in syn-
thetic organic chemistry, since the obtained enantiopure
epoxides are useful chiral intermediates for synthesizing fine
chemicals and several pharmaceuticals.1–6 Industrial practice
however is limited to the use of volatile dichloromethane as a
solvent which often results in environmental problems. Reac-
tions using water as a reaction medium are attracting much
attention, because water is inexpensive, safe and environmen-
tally benign.7–11 More importantly, water often exerts a syner-
gistic effect on chemical reactivity and selectivity.12,13 While,
to the best of our knowledge, few reports have focused on effi-
ciently performing this transformation in water because of
the insolubility of substrate and catalyst. An efficient way to
address this issue is to introduce surfactant additives or to
use surfactant-like catalysts.14–16 Generally, amphiphilic sur-
factants can self-assemble in water via the interaction
between hydrophobic blocks, spontaneously forming micelles
with hydrophilic surfaces and hydrophobic cores. Hydropho-
bic reactants are concentrated within the core through hydro-
phobic affinity, resulting in the observed acceleration in
that a surfactant-type chiral salen MnIII complex obtained by
introducing a hydrophilic block to a chiral salen MnIII com-
plex should efficiently catalyze the asymmetric epoxidation of
alkenes in water. Upon self-assembly, the hydrophobic chiral
salen MnIII complex segment confined in the core domain
can be forced into highly dense arrangements. The hydropho-
bic affinity of the core for reactants also favors the migration
of hydrophobic substrates from an aqueous medium. A high
concentration of catalyst and substrate localized within a con-
fined hydrophobic space was expected to accelerate the asym-
metric epoxidation.
However, traditional micelles are difficult to recover from
solution due to their amphiphilic nature. An ideal solution to
this problem is to develop “stimuli-responsive” micelles that
can undergo inverse solubility changes in response to local
environment changes. Temperature sensitivity is one of the
most interesting properties of “stimuli-responsive” micelles.
Polymeric N-isopropylacrylamide (PNIPAAm), with the lower
critical solution temperature (LCST, 32 °C) close to room
temperature, is an attractive thermoresponsive polymer.22–25
The thermoresponsive behavior, and that it is able to
undergo hydrophilic-to-hydrophobic transformation as tem-
perature increases, make it a promising modifier in fabricat-
ing a thermoresponsive surfactant-type chiral salen MnIII
complex for the asymmetric epoxidation of alkenes in water.
At the reaction temperature (2 °C), the catalyst incorporating
the hydrophobic chiral salen MnIII complex along with the
hydrophilic PNIPAAm moiety behaves as a surfactant to form
a Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research
(Ministry of Education), Key Laboratory of the Assembly and Application for
Organic Functional Molecules, Hunan Normal University, Changsha, Hunan,
410081, China. E-mail: yiyangtanrong@126.com (R. Tan),
yindh@hunnu.edu.cn (D. Yin); Fax: +86 731 8872531; Tel: +86 731 8872576
b Technology Center, China Tobacco Hunan Industrial Corporation, No. 426
Laodong Road, Changsha, Hunan, 410014, China
This journal is © The Royal Society of Chemistry 2015
Catal. Sci. Technol.

View Article Online
Paper
Catalysis Science & Technology
a micelle-based nanoreactor in water. After the reaction, it
can reversibly switch to a double hydrophobic block once
heated above its LCST, leading to collapse and precipitation
of the catalyst for facile recovery. This switchable behavior
allows for a typical homogeneous reaction coupled with
heterogeneous separation in the aqueous asymmetric
epoxidation.
Herein, a thermoresponsive surfactant-type chiral salen
MnIII complex (denoted as catalyst 1) was prepared by axially
grafting thermoresponsive PNIPAAm onto the metal center of
a neat chiral salen MnIII complex under basic conditions.
The axial grafting mode, which does not need to tune the
structures of chiral salen MnIII and PNIPAAm moieties, not
only represents a simple and facile process, but also mini-
mizes the formation of undesired inactive dimeric μ-oxo-
manganeseIJIV) dimers due to steric crowding at the metal cen-
ter. It has been proven that the catalyst could self-assemble
to form a nanoreactor in the asymmetric epoxidation of
unfunctionalized olefins in water, dramatically accelerating
the aqueous epoxidation. Furthermore, it could be easily
using THF as the solvent eluting at a flow of 1 mL min−1
through a Jordi GPC 10 000 A column (300 mm × 7.8 mm)
equipped with an Alltech ELSD 800 detector. The system was
calibrated with standard polystyrenes. The detection tempera-
ture is 40 °C and column temperature is 30 °C. 1H NMR spec-
tra of samples were recorded on a Varian-500 spectrometer.
FT-IR spectra were obtained as potassium bromide pellets
with a resolution of 4 cm−1 and 32 scans in the range 400–
4000 cm−1 using an AVATAR 370 Thermo Nicolet spectropho-
tometer. UV-vis spectra of the complex were recorded on a
UV-vis Agilent 8453 spectrophotometer at 300–600 nm. The
lower critical solution temperature (LCST) of the
thermoresponsive chiral salen MnIII complex in water was
measured by transmittance using a UV-visible photometer.
The concentration of the complex is 1 wt%. The rising tem-
perature ratio is 5 °C min−1. X-ray Photoelectron Spectroscopy
(XPS) data were obtained with an ESCALab220i-XL electron
spectrometer from VG Scientific using 300 W Al Kα radiation.
The base pressure was about 3 × 10−9 mbar (3 × 10−7 Pa). The
manganese content in the catalyst was determined by induc-
tively coupled plasma-atomic emission spectrometry (ICP-
AES) on a BAIRD PS-6 analyzer, after the sample was
dissolved in deionized water. The optical rotation of the cata-
lysts was measured in dichloromethane on a WZZ-2A Auto-
matic Polarimeter. The surface tension of an aqueous solu-
tion of catalyst 1 was measured as a function of catalyst
concentration (3.75 × 10−2–500.0 mmol L−1) on a Krüss K12
tensiometer using the Wilhelmy plate method at 25 °C. The
surface tension vs. catalyst concentration plot gives informa-
tion on the critical micelle concentration (CMC). Morphologi-
cal observation of the micelles was performed by TEM on a
Microscope JEM-2100F at an accelerating voltage of 200 kV.
The sample was prepared by depositing an aqueous solution
of catalyst 1 (0.5 mg mL−1) onto a carbon-coated copper grid,
followed by the removal of excess solution by blotting the
grid with filter paper. The samples were dried for 72 h at
room temperature in a desiccator containing dried silica gel.
After that, the samples were negatively stained by
phosphotungstic acid and dried for another 72 h before
examination. The average hydrodynamic diameter and size
distribution of the self-assembled aggregates were deter-
mined by dynamic light scattering (DLS) using a MS2000
Laser Particle Size Analyzer (Malvern, UK). The concentration
of the sample was 0.5 mg mL−1. Light transmittance was
fixed at 633 nm with a scattering angle of 90°.
recovered
from
the
reaction
system
through
thermocontrolled separation. Activity switching was repeat-
able even after five heating/cooling cycles. Thus, the prob-
lems associated with the mass transfer and recovery limita-
tion of the chiral salen MnIII complex in the asymmetric
epoxidation of unfunctionalized olefins in water can be
resolved.
Experimental section
Materials and reagents
N-Isopropylacrylamide (NIPAAm) was provided by Acros, and
was purified by recrystallization from n-hexane and dried at
25 °C in vacuo. N,N-AzobisIJisobutyronitrile) (AIBN), 2-amino-
ethanethiol hydrochloride and LIJ+)-tartaric acid were also pur-
chased from Acros. 2-tert-Butyl phenol was purchased from
Alfa Aesar. Pyridine-N-oxide (PyNO) was bought from Aldrich.
Indene and 1,2-dihydronaphthalene were obtained by TCI.
Other commercially available chemicals were laboratory
grade reagents from local suppliers. All solvents employed in
the reactions were distilled from appropriate drying agents
prior to use. Organic solutions were concentrated under
reduced pressure on a rotary evaporator. Styrene and indene
were passed through a pad of neutral alumina before use.
Amino-terminated PNIPAAm (PNIPAAm-NH2) was prepared
by radical polymerization using thiol compounds as a chain
transfer agent according to the procedure described in the lit-
erature.26 The neat complex of ij(R,R′)-IJN,N′-bisIJ3,5-di-tert-
butylsalicylidene)-1,2-cyclo-hexanediaminato] manganeseIJIII)–
chloride was prepared according to the described
procedure.27
Preparation of catalyst 1
The preparation of catalyst 1 is outlined in Scheme 1.
Synthesis of PNIPAAm-NH2. NIPAAm (50 mmol), 2-amino-
ethanethiol hydrochloride (1 mmol) and AIBN (0.5 mmol)
were dissolved in 20 mL of methanol in a Schlenk tube. The
reaction mixture was degassed by bubbling with nitrogen gas
at room temperature for 30 min, and polymerization was car-
ried out at 70 °C for 5 h under a N2 gas atmosphere. The mix-
ture was cooled to room temperature, and then treated with
Methods
Number-average molecular weight (Mn) of PNIPAAm was
obtained by gel permeation chromatography (GPC). Analyses
were performed on an Alltech Instrument (Alltech, America)
Catal. Sci. Technol.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Catalysis Science & Technology
Paper
washed with n-hexane (3 × 5 mL), dried in a vacuum, and
finally recharged with fresh substrate, additive, and oxidant
for the next catalytic cycle. The supernatants separated from
the reaction system were extracted with n-hexane thrice. Fur-
ther purification of the collected n-hexane phase by flash col-
umn chromatography afforded epoxides. The conversion and
enantiomeric excess (ee) were determined by a 6890 N gas
chromatograph (Agilent Co.) equipped with the chiral capil-
lary column (HP19091G-B213, 30 m × 0.32 mm × 0.25 μm)
and a FID detector. Nitrogen was used as the carrier gas with
a flow of 30 mL min−1. The injector temperature was 250 °C,
and the detector temperature was also 250 °C. The retention
Scheme 1 Schematic representation of synthesis and self-assembly of
surfactant-type catalyst 1.
times of the corresponding chiral epoxides (tabsolute
configura-
tion) are as follows: (a) styrene epoxide: the column tempera-
ture was 100 °C, major enantiomer tR = 7.1 min and minor
enantiomer tS = 7.6 min; (b) α-methylstyrene epoxide: the col-
umn temperature was 100 °C, major enantiomer tR = 8.0 min
and minor enantiomer tS = 7.7 min; (c) indene epoxide: the
column temperature was programmed from 80 to 180 °C with
5 °C min−1. Major enantiomer tRS = 11.9 min and minor
enantiomer tSR = 11.5 min; (d) 1,2-dihydronaphthalene epox-
ide: the column temperature was programmed from 80 to
180 °C with 5 °C min−1. Major enantiomer tRS = 19.4 min and
minor enantiomer tSR = 18.8 min; (e) 6-nitro-2,2′-dimethyl-
chromene epoxide: the column temperature was programmed
from 80 to 200 °C with 3 °C min−1 and retained at 200 °C for
5 min. Major enantiomer tRR = 30.8 min and minor enantio-
mer tSS = 30.3 min; (f) 6-cyano-2,2′-dimethylchromene epox-
ide: the column temperature was programmed from 80 to
200 °C with 4 °C min−1. Major enantiomer tRR = 24.3 min
and minor enantiomer tSS = 24.0 min.
KOH (1 mmol). The obtained solution was concentrated
under vacuum and then poured into diethyl ether to precipi-
tate the polymer. The crude product was further purified by
repeated precipitation from a THF solution into diethyl ether
to remove unreacted monomers, and then dried for 12 h
under a vacuum at 25 °C to give a white solid of PNIPAAm-
NH2. FT-IR (KBr): γmax/cm−1 3438, 3309, 3072, 2974, 2931,
2878, 2825, 1652, 1541, 1458, 1387, 1367, 1261, 1173, 1130,
1
1055, 987, 928, 881, 839, 633, 517 cm−1. H NMR (500 MHz,
D2O): δ 3.89 (s, 20H), 2.92 (s, 12H), 2.62 (s, 1H), 2.44 (s, 1H),
2.00 (s, 20H), 1.57 (s, 42H), 1.14 (s, 123H). The Mn of the
PNIPAAm-NH2 was ca. 2300 g mol−1, which was measured by
GPC using conventional calibration with PS standards. Thus,
the polymer was composed of ca. 20 repeating units of
NIPAAm monomer.
Synthesis of catalyst 1. A solution of neat chiral salen
MnIII complex (2.7 mmol, 1.71 g), PNIPAAm-NH2 (2.5 mmol)
and an adequate amount of sodium hydroxide in THF (50
mL) was vigorously stirred for 24 h under reflux. After remov-
ing THF, the residue was purified by precipitation from
diethyl ether (3 × 50 mL) and dried in vacuo at 25 °C to get
the thermoresponsive surfactant-type catalyst (denoted as cat-
alyst 1). FT-IR (KBr): γmax/cm−1 3309, 3072, 2974, 2931, 2878,
1652, 1541, 1458, 1387, 1365, 1254, 1173, 1130, 928, 879, 837,
644, 571, 507, 424 cm−1. UV-vis IJCH2Cl2): λmax/nm (εmax/L
mol−1 cm−1) 322 (148 162), 429 (32 119), 502 (5963). Mn ion
content: 0.33 mmol g−1 (theoretical value: 0.34 mmol g−1).
Epoxidation reaction for kinetics measurements
A cooled solution of catalyst 1 in water (1 mL) was stirred
with styrene (0.25 mmol). Buffer NaOCl (0.5 mmol, 1 mL, pH
= 11.5) was then added into the stirred solution in one por-
tion at 2 °C. To determine the rate of epoxidation, aliquots at
an interval of 1 min were drawn from the reaction mixture,
quenched with triphenylphosphine, and analyzed by GC.
Results and discussion
Preparation and characterization of catalysts
25
αD = +168 (C = 0.02 in CH2Cl2). The LCST of complex 1 in
aqueous solution was ca. 35 °C, which was determined by
transmittance
spectrophotometer.
measurements
using
the
UV-vis
Nanometer-scale reactors that mimic enzyme-based reaction
compartments have drawn much attention in recent years,
since they provide an opportunity to perform organic reac-
tions “in water”.28–31 Surfactant-type catalysts can spontane-
ously self-assemble in water to form micelle-based nano-
reactors, and hopefully accelerate the aqueous organic
reaction.15,32 Therefore, we decided to develop a surfactant-
type chiral salen MnIII complex for efficient asymmetric epox-
idation of unfunctionalized alkenes in water. PNIPAAM with
inverse temperature-dependent water solubility was intro-
duced into the structure of the chiral salen MnIII complex for
this development. Axial grafting mode, a common way to
heterogenize a chiral salen MnIII complex which does not
Catalyst testing
Unfunctionalized alkene (0.25 mmol) and PyNO (0.5 mmol,
0.048 g) were added into the solution of catalyst (0.8 mol% of
substrate, based on Mn content) in water (1 mL) at 2 °C.
Buffered NaOCl as an oxidant (0.5 mmol, 0.5 M, pH = 11.5)
was then added in one portion under stirring. The reaction
was monitored constantly by TLC. After achieving the desired
epoxidation level, the reaction mixture was heated to 40 °C.
Catalyst was precipitated out from the reaction system,
This journal is © The Royal Society of Chemistry 2015
Catal. Sci. Technol.

View Article Online
Paper
Catalysis Science & Technology
need tuning of the structure of the chiral salen MnIII com-
plex,33 was employed for this modification. It not only repre-
sents a simple and facile process, but also ensures effective
site isolation due to steric crowding at the metal center, since
catalyst density and site isolation are the key issues in giving
extremely active and selective chiral salen MnIII catalysts.33
The synthesis route for the thermoresponsive catalyst is
outlined in Scheme 1. Amino-terminated PNIPAAm, prepared
by radical polymerization using thiol compounds as a chain
transfer agent, directly reacted with the neat chiral salen
MnIII complex under basic conditions, affording catalyst 1.
and the amino-terminated PNIPAAm, as described in Fig. 2.
Obviously, the neat complex exhibited the characteristic
peaks at around 325, 438 and 509 nm (Fig. 2a), which are
due to the charge transfer transition of the salen ligand, the
metal-to-ligand charge-transfer transition and the d–d transi-
tion of the complex, respectively.35 As for catalyst 1, the corre-
sponding characteristic peaks shifted to 322, 429 and 502
nm, respectively (Fig. 2a vs. b). It was logical to relate the
blue shift with the electronegative nitrogen atom bonded on
the manganese center in catalyst 1. A similar deduction has
also been made by Huang et al.38,39 They reported axial N–
Mn bonding between chiral salen MnIII complexes and amine
(–NH2) group modified supports. These observations pro-
vided a direct proof for the presence of N–Mn bonding in cat-
alyst 1. PNIPAAm was thus axially appended on the manga-
nese center of the chiral salen MnIII complex through the
terminal amine (–NH2) group, which not only acted as a
thermoresponsive inductor to switch on and off the nano-
reactor, but also behaved as a bulk axial group to ensure the
necessary isolation of the active site.
XPS. The binding behavior can also be confirmed by char-
acterizing the neat complex and catalyst 1 using XPS, since
the electronic environment influences the binding energy of
the core electrons of the metal. XPS spectra obtained from
the neat complex and catalyst 1 are shown in Fig. 3. The neat
complex exhibits a Mn2p3/2 core level peak at a binding
energy of 642.0 eV, in accordance with an earlier literature
value.40 While, the binding energy slightly increases to 642.4
eV in the case of catalyst 1. The observed increase in the
binding energy should be attributed to the formation of the
N–Mn bond in catalyst 1, which affected the electronic envi-
ronment of the manganese center. A similar observation has
also been made for a chiral salen MnIII catalyst which was
axially grafted on an amine (–NH2) group modified support
through N–Mn bonding.41
Characterization of samples
FT-IR. The obtained catalyst 1, as well as the PNIPAAm
and neat chiral complex for comparison, were characterized
by FT-IR spectra (Fig. 1). PNIPAAm exhibits characteristic
vibration bands at around 3309 cm−1 (–NH of –CONH–), 3072
cm−1 (CH of –CH–CH–), 2974, 2931 cm−1 (–CH3 of –CH
IJCH3)2), 2878 cm−1 (CH of –CH IJCH3)2) and 1652 cm−1 (–CO
of –CONH–) (Fig. 1a) in the FT-IR spectrum.34 Upon grafting,
new characteristic bands at around 1251, 571, and 424 cm−1
appear along with the characteristic vibration bands associ-
ated with PNIPAAm (Fig. 1b), which are assigned to the char-
acteristic vibrations of Ph–O, Mn–O, and Mn–N in the salen
MnIII unit,35–37 respectively. Obviously, the structure of chiral
salen MnIII complex is maintained in catalyst 1. Notably, the
characteristic vibrations of Mn–O and Mn–N shifted from
565 and 413 cm−1 to 571 and 424 cm−1, respectively, after
grafting, compared with those of the neat chiral salen MnIII
complex (Fig. 1b vs. c). This slight shift should account for
the interaction between the metal center of the chiral salen
MnIII complex and the amino-terminated PNIPAAm. It is the
interaction that is responsible for axially bonding PNIPAAm-
NH2 to the chiral salen MnIII complex.
UV-vis. UV-vis spectra of neat complex and catalyst 1 in
dichloromethane furthermore verified the interaction
between the metal center of the chiral salen MnIII complex
CMC determination. CMC is one of the most useful
parameters for surfactant-type catalyst 1, since the catalyst
can self-assemble to form micelles above the CMC.42 Surface
Fig. 1 FT-IR spectra of PNIPAAM (a), fresh catalyst 1 (b), recovered
catalyst 1 after the 5th reuse (b′) and neat complex (c).
Fig. 2 UV-vis spectra of neat complex (a), fresh catalyst 1 (b) and
recovered catalyst 1 after the 5th reuse (b′).
Catal. Sci. Technol.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Catalysis Science & Technology
Paper
Fig. 5 TEM micrograph of self-assembled catalyst 1 stained with
phosphotungstic acid.
diameter of 78 nm. Notably, the size obtained from DLS is
much greater than that from TEM (ca. 9 nm), probably due
to the swelling of surface PNIPAAM in aqueous solution. In
fact, DLS allows determination of the hydrodynamic diameter
of the micelles in water, whereas TEM shows the dehydrated
solid state of the dried micelles. Furthermore, homogeneous
distribution and spherical morphology of the self-assemblies
led to a small polydispersity index (PDI) value of 0.282.43
Fig. 3 Mn 2p2/3 XPS spectra of neat complex (a), fresh catalyst 1 (b)
and recovered catalyst 1 after the 5th reuse (b′).
tension measurements over a wide range of concentrations
were used in the CMC determination. Fig. 4 shows the sur-
face tension versus logarithm of concentration plots for cata-
lyst 1 in water at 25 °C. Clearly, the surface tension decreased
dramatically as the concentration of catalyst 1 increased.
There was an inflection point at the characteristic concentra-
tion of 0.5 mmol L−1. And the surface tension does not
change substantially as a function of concentration of cata-
lyst 1 above 0.5 mmol L−1. Therefore, the CMC of catalyst 1 is
0.5 mmol L−1, above which, catalyst 1 could self-assemble in
water to form micelles.
LCST determination
The thermal sensitivity of these micelle structures was mea-
sured via spectrophotometry by determining the turbidity of
a solution at various temperatures (Fig. 7). A sharp decrease
in transmittance occurred at ca. 35 °C, which signified a
hydrophilic-to-hydrophobic phase transition of the PNIPAAm
block (Fig. 7a). Therefore, catalyst 1-based micelles were
formed when the local temperature was below 35 °C and
disaggregated at temperatures above 35 °C. Furthermore, the
LCST of catalyst 1 (35 °C) was 3 °C higher than that for
PNIPAAm (32 °C) (Fig. 7a vs. 7b). This trend may be attrib-
uted to the interaction between the chiral salen MnIII com-
plex moiety and the PNIPAAm component.
Morphological analyses
A TEM measurement was employed to observe the morphol-
ogy of the micelles, as shown in Fig. 5. Obviously, catalyst 1
self-assembled in water to form spherical aggregates with an
average diameter of ca. 9 nm, as confirmed by TEM. The high
dispersion of the aggregates suggests the stability of micelles
in water. In order to further determine the hydrodynamic
diameter and size distribution the self-assembled aggregates,
catalyst 1 in water (0.5 mg mL−1) was analyzed by a MS2000
Laser Particle Size Analyzer (Fig. 6). Indeed, the micelles
Catalytic performances
The catalyst 1-based micelles behave as catalytic nanoreactors
for the asymmetric epoxidation of alkenes in water. Styrene
was chosen as a model substrate to investigate the catalytic
show
a narrow diameter distribution with an average
Fig. 4 Plot of surface tension against logarithm of concentration for
catalyst 1 in water at 25 °C.
Fig. 6 Hydrodynamic diameter of self-assembled catalyst 1 (PDI =
0.282).
This journal is © The Royal Society of Chemistry 2015
Catal. Sci. Technol.

View Article Online
Paper
Catalysis Science & Technology
ee value was obtained over the neat complex under identical
conditions (Table 1, entry 3). Notably, PNIPAAm alone was
inactive (Table 1, entry 4). Therefore, the unprecedented
acceleration in reaction rate (six times faster than the neat
complex) should relate to the micellization behavior of cata-
lyst 1 in the reaction system. During the reaction, catalyst 1
containing hydrophobic and hydrophilic blocks spontane-
ously self-assembled in water to form micelles with a hydro-
phobic catalytic core and a hydrophilic surface. The hydro-
phobic core provided a hydrophobic microenvironment with
a high local concentration of catalytic sites along with the
concentrated hydrophobic substrates, while the hydrophilic
surface guaranteed water-solubility of the aggregate. The
“concentration effect” of the nanoreactor resulted in the
observed acceleration in the reaction rate. Moreover, the
remarkable enhancement of the reaction rate might also be
attributed to the phase-transfer capability of surfactant-type
catalyst 1, which transported the real oxidant HClO from the
surrounding aqueous environment to the hydrophobic core
for faster catalysis. An unprecedented TOF value (2.48 × 103
h−1) was achieved over catalyst 1 in the aqueous epoxidation
of styrene. The value was even significantly higher than that
obtained over previously reported chiral salen MnIII com-
plexes in homogeneous or heterogeneous systems.41,44–47 Fur-
thermore, in the absence of the additive PyNO, the activity
and enantioselectivity of catalyst 1 apparently decreased,
indicating that PyNO as an axial ligand had a pronounced
effect on both the activity and the enantioselectivity of the
asymmetric epoxidation reaction, which has been reported
for other chiral salen MnIJIII) catalysts (Table 1, entry 2).41
Fig. 7 Plot of the changes in solution transmittance as a function of
temperature for PNIPAAm (a) and catalyst 1 (b) solution in water. The
turbidimetry curve is drawn by measuring the transmittance (λmax
=
450 nm) of the corresponding aqueous polymer solution at a fixed
concentration (5 mg mL−1) as a function of temperature. The LCST
corresponds to the mid-point of the transition curve.
performance of catalyst 1 in pure water. All catalytic reactions
were conducted at 2 °C to ensure the formation of a nano-
reactor with a hydrophilic surface and a hydrophobic cata-
lytic core during the reaction. The results are presented in
Table 1.
As expected, catalyst 1 was extremely efficient for the
asymmetric epoxidation of styrene in water. Quantitative con-
version (99%) with high enantioselectivity (ee, 39%) was
achieved with 0.8 mol% of catalyst 1 within 3 min (Table 1,
entry 1). While only a 16% conversion of styrene with a 5%
Table 1 Results of the enantioselective epoxidation of unfunctionalized olefins over different chiral salen MnIII complexes in watera
Entry
Catalyst
Substrate
Product
t (min)
Conv.b/%
eeb/%
TOFc × 103 h−1
1
2
3
4
5
6
7
Catalyst 1
3
3
3
3
3
99
45
16
trace
48
39
27
5
2.48
1.13
0.40
/
1.20
/
Catalyst 1d
Neat complex
PNIPAAm
/
Catalyst 1
Catalyst 1
Neat complex
49
75
35
30
3
99
15
0.38
8
9
10
Catalyst 1
Catalyst 1
Neat complex
3
35
3
45
99
12
47
70
40
1.13
/
0.30
11
12
13
Catalyst 1
Catalyst 1
Neat complex
3
45
3
40
99
10
51
77
44
1.00
/
0.25
14
15
16
Catalyst 1
Catalyst 1
Neat complex
3
180
3
16
99
3
83
92
78
0.40
/
0.08
17
18
19
Catalyst 1
Catalyst 1
Neat complex
3
200
3
14
99
7
80
94
76
0.35
/
0.18
a
Catalyst (0.8 mol% of substrate, based on manganese ion content), substrate (0.25 mmol), pyridine N-oxide (0.5 mmol), NaClO (0.5 mmol, 0.5
M, pH = 11.5, added in one portion), water (1 mL), 2 °C. Determined by GC. c TOF = (moles of substrate converted)/(moles of manganese cen-
ters) per hour, calculated from 3 min conversions. Without PyNO.
b
d
Catal. Sci. Technol.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Catalysis Science & Technology
Paper
To further understand the acceleration effect of catalyst 1
in aqueous reaction systems, kinetics was used to study the
reaction rates of asymmetric epoxidation of styrene over vari-
ous amounts of catalyst 1 in water. The catalyst amount was
reduced from 0.8 to 0.1 mol%. Time-dependent plots of sty-
rene conversion with various amounts of catalyst 1 are shown
in Fig. 8A. Both reactions in water reached equilibrium
within 3 min. Notably, the conversion of styrene linearly
increased up to 1 min, after which a significant increase was
not observed. Therefore, the initial rate constant kobs values
were determined from the data within this time range.
Detailed kinetic data for the catalyst amount-dependence in
water are given in Fig. 8C-a. Obviously, reaction rates
decreased with the reduction in catalyst amount in water, in
terms of initial rate constants kobs. By reducing the amount
of catalyst 1 from 0.8 to 0.4 mol%, the kobs value decreased
smoothly (Fig. 8C-a). It was logical that lower catalyst amount
should reduce the total number of nanoreactors in solution
and hence less “catalytic pumps” to catalyze the aqueous
organic reaction. While, further lowing the catalyst amount
to 0.2 mol%, led to a sharp decrease in the kobs value
(Fig. 8C-a). In particular, a kobs value of only 17.0 M min−1
was obtained when the catalyst amount was reduced to 0.1
mol% (Fig. 8A-e). The decrease in reaction rate could be
caused by the limited amount of available catalyst 1 to form
nanoreactors in water for confined catalysis. Therefore, cata-
lyst 1 self-assembles to form micelles in aqueous reaction sys-
tems when the catalyst amount is above 0.4 mol%. Interest-
ingly, this value (0.4 mol% of substrate in 2 mL solvent)
agrees with the CMC (0.5 mmol L−1) of catalyst 1. Notably 0.8
mol% of catalyst 1-based micelles in water were sufficient for
affording a quantitative conversion (99%) of styrene with a
high ee value (39%) (Fig. 8A-a).
dependence in dichloromethane are presented in Fig. 8C-b.
Notably, catalysis in dichloromethane was far less efficient
than that in water, in terms of corresponding initial rate con-
stants kobs (Fig. 8C-b vs. a). And the kobs values in
dichloromethane decreased smoothly with the reduction in
catalyst amount from 0.8 to 0.1 mol% (Fig. 8C-b). Actually,
dichloromethane is a good solvent for the blocking of the
chiral salen MnIII complex. Hence, catalyst 1 containing a
hydrophilic PNIPAAM group and a hydrophobic complex
moiety may locate at the interface of water (aqueous NaClO)
and dichloromethane in the biphasic system. Self-assembly
into micelles didn't occur. Catalyst 1 thus behaved as a com-
mon phase-transfer catalyst, rather than a concentrator.
Lower local concentration of the reagent and catalytic species
in the common organic system was unfavorable for efficient
catalysis.
Enhanced reaction rate over catalyst 1 is also noticeable in
the case of α-methylstyrene, indene, 1,2-dihydronaphthalene,
6-cyano-2, 2-dimethylchromene, a n d 6-nitro-2, 2-
dimethylchromene, as shown by TOF in Table 1. Catalyst 1
gave significantly higher TOF values than the neat complex
in corresponding epoxidations, due to the ability of the
hydrophobic micelle cores to effectively sequester the organic
substrates from the surrounding aqueous environment (Table
1, entry 5 vs. 7, entry 8 vs. 10, entry 11 vs. 13, entry 14 vs. 16,
and entry 17 vs. 19). But unfortunately, the catalyst 1-based
nanoreactor showed substrate selectivity based on the size of
substrates. Despite still being unfunctionalized alkenes, bulk-
ier alkenes were less reactive than styrene during aqueous
asymmetric epoxidation (Table 1, entries 5, 8 and 11 vs. entry
1). In the presence of 0.8 mol% of catalyst 1,
α-methylstyrene, indene, and 1,2-dihydronaphthalene only
gave 40–48% conversions with unsatisfactory ee values. For
more sterically hindered alkenes, such as 6-nitro-2,2-dimethyl-
chromene and 6-cyano-2,2-dimethylchromene, even lower con-
versions (14–16%) were obtained during the reaction (Table
1, entries 14 and 17). While, the difference in the reactivity of
the alkenes was not obvious when the neat complex was used
as the catalyst (Table 1, entries 3, 7, 10 and 13). This type of
substrate selectivity should account for the selective shell per-
meability.48 Nanostructured shells consisting of bulky
PNIPAAm segments acted as a size-exclusion gate in the
nanoreactor, which favored the penetration of small alkenes
into the catalyst-containing micelle core for more efficient
catalysis. In particular, substituted 2,2-dimethylchromene
molecules are solid and insoluble in water, which conse-
quently have difficulty permeating into the hydrophobic core
of the nanoreactors for efficient catalysis (Table 1, entries 14
and 17). This gated permeability behavior makes the catalyst
1-based micelle a selective nanoreactor for the asymmetric
epoxidation of alkenes in water. Notably, all alkenes used in
this work get quantitatively oxidized to the corresponding
epoxides with good to excellent enantioselectivity in water, in
the case of prolonged reaction time (Table 1, entries 6, 9, 12,
15 and 18). The results suggested the flexibility of catalyst 1
in green asymmetric epoxidation. It is the first successful
For comparison, we also used kinetics to study the reac-
tion rates of asymmetric epoxidation of styrene over various
amounts of catalyst 1 in dichloromethane, as shown in
Fig. 8B. Detailed kinetics data for catalyst amount-
Fig.
8 Time-dependent plots of styrene conversion with various
amounts of catalyst 1 in water (A) and in dichloromethane (B) (catalyst
amount based on manganese ion content: 0.8 mol% (a), 0.6 mol% (b),
0.4 mol% (c), 0.2 mol% (d), and 0.1 mol% (e)), and detailed kobs values
for catalyst amount-dependence (C) in water (a) and in
dichloromethane (b).
This journal is © The Royal Society of Chemistry 2015
Catal. Sci. Technol.

View Article Online
Paper
Catalysis Science & Technology
short reaction time and low temperature, should potentially
minimize catalyst degradation.
Conclusions
We have demonstrated the first asymmetric epoxidation of
unfunctionalized olefins in pure water using a chiral salen
MnIII complex-based thermoresponsive nanoreactor. The
nanoreactor with a hydrophobic catalytic core and a hydro-
philic surface exhibited some distinct characteristics as fol-
lows: (a) the hydrophobic core created a hydrophobic micro-
environment with high local concentration of active sites and
concentrated substrates, confining the asymmetric epoxida-
tion for efficient catalysis; (b) the hydrophilic surface
guaranteed water-solubility of the nanoreactor, circumventing
the limited mass transfer associated with an aqueous organic
reaction. Furthermore, the thermoresponsivity of the nano-
reactor facilitated the recovery of the catalyst from the reac-
tion system by simply adjusting the local temperature. The
chiral salen MnIII complex-based nanoreactor thus showed
extremely high catalytic efficiency and steady reusability in
the asymmetric epoxidation of unfunctionalized olefins in
water without the need for any organic solvents. The advan-
tages allow for industrial practice of the asymmetric epoxida-
tion of unfunctionalized alkenes, and also raise the prospect
of making water a viable environmentally friendly medium
for organic synthesis.
Fig. 9 Reuse of catalyst 1 in asymmetric epoxidation of styrene with
NaClO as oxidant in water at 2 °C (a: conversion; b: ee values).
example for efficiently performing asymmetric epoxidation of
alkenes in pure water.
Recycling
Apart from its high efficiency, another salient feature of cata-
lyst 1 in water is its “smart” recovery. After each reaction, cat-
alyst 1 turned to a double hydrophobic block once heated
above its LCST, leading to precipitation of catalyst for the
next cycle. The aqueous phase was separated from the cata-
lyst by decantation. Notably, although n-hexane was used to
extract a small amount of epoxide from reaction solution in
the present work, this approach was expected in large-scale
industrial processes, in which the organic product phase can
be directly separated from water without the use of any
organic solvents. To our delight, catalyst 1 could be reused at
least five times without significant loss of activity, as shown
in Fig. 9.
Leaching tests of the reaction medium were performed by
directly determining the manganese content in the superna-
tant via chemical analysis. No manganese was detected in the
supernatant, which revealed the negligible leaching loss of
manganese species during the reaction. Moreover, chemical
analysis of the recovered catalyst gave manganese content
(0.32 mmol g−1) almost identical to that of the fresh one
(0.33 mmol g−1). FT-IR (see Fig. 1b vs. b′), UV-vis (see
Fig. 2b vs. b′) and XPS (see Fig. 3b vs. b′) spectra showed no
significant change in catalyst even after the 5th reuse. There-
fore, the efficient catalyst 1 was stable under the basic reac-
tion condition (pH 11.5, NaClO buffer), and the axial N–Mn
bonding remained intact during the epoxidation. Oxidative
decomposition of the chiral salen MnIII complex, a main rea-
son for deactivation of the complex in basic epoxida-
tion,41,49,50 was avoided by localizing the complex within a
hydrophobic core. The possibility of the formation of
undesired inactive dimeric μ-oxo-manganeseIJIV) dimers,51 the
cause for deactivation of the catalytic species, can also be
prevented because of the bulky steric encumbrance of
PNIPAAm on the manganese center. Furthermore, the mild
reaction conditions used in our studies, such as extremely
Acknowledgements
The work was supported by the National Natural Science
Foundation of China (Grant No. 21476069, 21003044), the Sci-
entific Research Fund of Hunan Provincial Education Depart-
ment (13B072), the Program for Excellent Talents in Hunan
Normal University (ET14103), the Program for Science and
Technology Innovative Research Team in Higher Educational
Institutions of Hunan Province, the Foundation for Innovative
Research Groups of the Hunan Natural Science Foundation of
China and the Construct Program of the Key Discipline in
Hunan Province.
References
1 W. Zhang, J. L. Loebach, S. R. Wilson and E. N. Jacobsen,
J. Am. Chem. Soc., 1990, 112, 2801.
2 S. Liao and B. List, Angew. Chem., Int. Ed., 2009, 48, 1.
3 S. Liao and B. List, Angew. Chem., Int. Ed., 2010, 49, 628.
4 F. Song, C. Wang and W. Lin, Chem. Commun., 2011, 47,
8256.
5 R. Luo, R. Tan, Z. Peng, W. Zheng, Y. Kong and D. Yin,
J. Catal., 2012, 87, 170.
6 S. Shabbir, Y. Lee and H. Rhee, J. Catal., 2015, 322, 104.
7 B. E. Hanson, Coord. Chem. Rev., 1999, 185–186, 795.
8 U. M. Lindstrom, Chem. Rev., 2002, 102, 2751.
9 J. Tan, H. Li and Y. Gu, Green Chem., 2010, 12, 1772.
10 P. Cotanda, A. Lu, J. P. Patterson, N. Petzetakis and R. K.
O'Reilly, Macromolecules, 2012, 45, 2377.
Catal. Sci. Technol.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Catalysis Science & Technology
Paper
11 Y. Kong, R. Tan, L. Zhao and D. Yin, Green Chem., 2013, 15,
2422.
12 Y. Jung and R. A. Marcus, J. Am. Chem. Soc., 2007, 129, 5492.
13 A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725.
14 T. Dwars, E. Paetzold and G. Oehme, Angew. Chem., Int. Ed.,
2005, 44, 7174.
15 S. Luo, X. Mi, S. Liu, H. Xu and J. Cheng, Chem. Commun.,
2006, 3687.
16 V. Rauniyar, A. D. Lackner, G. L. Hamilton and F. D. Toste,
Science, 2011, 334, 1681.
17 K. Manabe, S. Iimura, X. Sun and S. Kobayashi, J. Am. Chem.
Soc., 2002, 124, 11971.
18 Y. Wang, H. Xu, N. Ma, Z. Wang, X. Zhang, J. Liu and J.
Shen, Langmuir, 2006, 22, 5552.
19 J. Li, Y. Tang, Q. Wang, X. Li, L. Cun, X. Zhang, J. Zhu, L. Li
and J. Deng, J. Am. Chem. Soc., 2012, 134, 18522.
20 A. Lu and R. K. O'Reilly, Curr. Opin. Biotechnol., 2013, 24,
639.
31 M. J. Monteiro, Macromolecules, 2010, 43, 9598.
32 F. Tu and D. Lee, J. Am. Chem. Soc., 2014, 136, 9999.
33 C. Baleizão and H. Garcia, Chem. Rev., 2006, 106, 3987.
34 W. Chen, Y. Sung, C. Chang, Y. Chen and M. Ger, Surf. Coat.
Technol., 2010, 204, 2130.
35 L. Lou, K. Yu, F. Ding, X. Peng, M. Dong, C. Zhang and S.
Liu, J. Catal., 2007, 249, 102.
36 R. Tan, D. Yin, N. Yu, H. Zhao and D. Yin, J. Catal.,
2009, 263, 284.
37 R. Luo, R. Tan, Z. Peng, W. Zheng, Y. Kong and D. Yin,
J. Catal., 2012, 287, 170.
38 J. Huang, X. Fu and Q. Miao, Appl. Catal., A, 2011, 407, 163.
39 J. Huang, X. Fu, C. Wang, H. Zhang and Q. Miao,
Microporous Mesoporous Mater., 2012, 153, 294.
40 A. R. Silva, K. Wilson, J. H. Clark and C. Freire, Microporous
Mesoporous Mater., 2006, 91, 128.
41 B. Gong, X. Fu, J. Chen, Y. Li, X. Zou, X. Tu, P. Ding and L.
Ma, J. Catal., 2009, 262, 9.
21 Y. Liu, Y. Wang, Y. Wang, J. Lu, V. Piñón, III and M. Weck,
J. Am. Chem. Soc., 2011, 133, 14260.
42 G. Liu, W. Fan, L. Li, P. K. Chu, K. W. K. Yeung, S. Wu and
Z. Xu, J. Fluorine Chem., 2012, 141, 21.
22 T. Sun and G. Qing, Adv. Mater., 2011, 23, 57.
23 T. Sun, G. Qing, B. Sua and L. Jiang, Chem. Soc. Rev.,
2011, 40, 2909.
24 V. B. Schwartz, F. Thétiot, S. Ritz, S. Pütz, L. Choritz, A.
Lappas, R. Förch, K. Landfester and U. Jonas, Adv. Funct.
Mater., 2012, 22, 2376.
43 M. Li, S. Qi, Y. Jin, W. Yao, S. Zhang and J. Zhao, Colloids
Surf., B, 2014, 123, 852.
44 R. Tan, D. Yin, N. Yu, Y. Jin, H. Zhao and D. Yin, J. Catal.,
2008, 255, 287.
45 N. Ch. Maity, S. H. R. Abdi, R. I. Kureshy, N. H. Khan, E.
Suresh, G. P. Dangi and H. C. Bajaj, J. Catal., 2011, 277, 123.
46 R. I. Kureshy, T. Roy, N. H. Khan, S. H. R. Abdi, A.
Sadhukhan and H. C. Bajaj, J. Catal., 2012, 286, 41.
47 Y. Chen, R. Tan, Y. Zhang, G. Zhao, W. Zheng, R. Luo and
D. Yin, Appl. Catal., A, 2015, 491, 106.
48 W. Meier, Adv. Funct. Mater., 2011, 21, 1241.
49 Z. Xu, X. Ma, Y. Ma, Q. Wang and J. Zhou, Catal. Commun.,
2009, 10, 1261.
25 F. Hapiot, S. Menuel and E. Monflier, ACS Catal., 2013, 3,
1006.
26 J. E. Chung, M. Yokoyama, T. Aoyagi, Y. Sakurai and T.
Okano, J. Controlled Release, 1998, 53, 119.
27 J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. P. Hong, X. Y. Nie
and C. M. Zepp, J. Org. Chem., 1994, 59, 1939.
28 B. Roßbach, K. Leopold and R. Weberskirch, Angew. Chem.,
Int. Ed., 2006, 45, 1309.
29 B. Gall, M. Bortenschlager, O. Nuyken and R. Weberskirch,
Macromol. Chem. Phys., 2008, 209, 1152.
30 M. J. Monteiro, Macromolecules, 2010, 43, 1159.
50 W. Zheng, R. Tan, S. Yin, Y. Zhang, G. Zhao and D. Yin,
Catal. Sci. Technol., 2015, 5, 2092.
51 C. E. Song, Annu. Rep. Prog. Chem., Sect. C: Phys. Chem.,
2005, 101, 143.
This journal is © The Royal Society of Chemistry 2015
Catal. Sci. Technol.