Nanosheet-enhanced efficiency in amine-catalyzed asymmetric epoxidation of Α, Β-unsaturated aldehydes via host-guest synergy

Article abstract of DOI:10.1016/j.mcat.2017.09.035

Amine-catalyzed asymmetric epoxidation of α, β-unsaturated aldehydes has been promoted by attaching the nanosheets of layered double hydroxides (LDHs), a natural and/or synthetic anionic layered compound. 76% of epoxide yield and 93% ee of major diastereomer have been afforded in the asymmetric epoxidation of cinnamaldehyde. The amine sites employed here are the amino group in α-amino acid anion intercalated in the interlayer space of LDHs. The nanosheets of LDHs have been revealed to play key role in the enhancement of catalytic activity by affording the desired basicity and the boost of enantioselectivity by serving as the rigid substituent of amino acids. The hydrophobic interlayer microenvironment and ordered arrangement of intercalated amino acid anions additionally contribute to the catalytic efficacy. Stronger interlayer hydrophobicity favors the conversion and epoxide yield and better arrangement of interlayer anions favors the ee.

Full text of DOI:10.1016/j.mcat.2017.09.035

Molecular Catalysis 443 (2017) 69–77
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
Nanosheet-enhanced efficiency in amine-catalyzed asymmetric
epoxidation of ␣, ˇ-unsaturated aldehydes via host-guest synergy
Hui Liu, Zhe An, Jing He∗
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Amine-catalyzed asymmetric epoxidation of ␣, ˇ-unsaturated aldehydes has been promoted by attaching
the nanosheets of layered double hydroxides (LDHs), a natural and/or synthetic anionic layered com-
pound. 76% of epoxide yield and 93% ee of major diastereomer have been afforded in the asymmetric
epoxidation of cinnamaldehyde. The amine sites employed here are the amino group in ␣-amino acid
anion intercalated in the interlayer space of LDHs. The nanosheets of LDHs have been revealed to play key
role in the enhancement of catalytic activity by affording the desired basicity and the boost of enantiose-
lectivity by serving as the rigid substituent of amino acids. The hydrophobic interlayer microenvironment
and ordered arrangement of intercalated amino acid anions additionally contribute to the catalytic effi-
cacy. Stronger interlayer hydrophobicity favors the conversion and epoxide yield and better arrangement
of interlayer anions favors the ee.
Received 19 April 2017
Received in revised form
14 September 2017
Accepted 30 September 2017
Keywords:
LDH nanosheet
Asymmetric epoxidation
Organocatalysis
Solid bases
Rigid substituent
© 2017 Published by Elsevier B.V.
1. Introduction
and amides. Recently, small organic molecules have been used
as the asymmetric epoxidation catalysts because of their notable
Catalytic enantioselective epoxidation of olefins holds a promi-
nent place in organic chemistry [1–3] since the optically active
epoxy products are both valuable organic intermediate [4,5] and
important building blocks in pharmaceuticals [6–8]. For exam-
ple, epoxy products ethyl (2R, 3R)-3-phenylglycidate can be used
for the synthesis of side chain of Taxol, a frontline anticancer
drug for the treatment of ovarian, breast, and lung cancer [9–11].
For enantiopure epoxide preparation, the kinetic resolution of
racemic epoxides was initially employed [12–16]. Lately, in terms
of overall cost, reaction speed, raw material availability, and robust-
ness, asymmetric catalytic epoxidation was developed. The pioneer
work of enantioselective epoxidation of olefins was achieved on
organometallic catalysts [17–19]. Katsuki and Sharpless demon-
strated that the titanium-tartrate complexes were highly efficient
asymmetric epoxidation catalysts of allylic alcohols [20]. Chiral
manganese-salen complexes were reported as excellent catalysts
for the asymmetric epoxidation of conjugated cis-disubstituted
olefins [21]. The complexes of Li [22], Mg [23,24], Sc [25], Zn
[26–31], Fe [32–41], and lanthanides [42–48] have been employed
for the asymmetric epoxidation of ␣, ˇ-unsaturated ketones, esters,
advantages over metal complexes, such as lower cost, better resis-
tance to moisture and oxygen, and absence of metal residues and
toxicity in products [49–52]. The organocatalysts employed for the
enantioselective epoxidation of olefins include phase-transfer cata-
lysts [53–56], peptide-type catalysts [57,58], chiral ketone catalysts
[52,59], and chiral amine catalysts [60–63].
Enantiomerically enriched ␣, ˇ-epoxy carbonyl compounds
(such as ␣, ˇ-epoxy aldehyde [4,5,64], ␣, ˇ-epoxy ketone [7], and
␣, ˇ-epoxy ester [65]) are especially useful in total synthesis. Chi-
ral amine catalysts were found to be very efficient organocatalysts
in the asymmetric epoxidation of ␣, ˇ-unsaturated carbonyl com-
pounds via iminium-activation mechanism and steric-shielding
approach. Following the iminium-activation of carbonyl by amine
sites, the carbon–carbon double bonds in the resulting iminium
intermediate are inclined to be nucleophilic attacked by activated
oxidant. In order to facilitate the activation of oxidant, exogenous
additives, such as NaOH, KOH, Urea, Na2CO3, NaHCO3 [66–69] tri-
fluoroacetic acid, achiral or chiral phosphoric acids [61–63], were
generally used. The use of solid bases, which are much more
environment-friendly and green, to assist the activation of oxidant
has not been reported so far in the enantioselective epoxidation
of olefins. The attack of activated oxidant to the iminium inter-
mediate is the enantioselectivity determining step. Computational
[70] and experimental results both revealed that the catalysts with
more hindered structures, such as the pyrrolidine-derivatives with
∗
corresponding author at: Postal address: Box 98, 15 Beisanhuan Dong Lu, Beijing
100029, China.
E-mail address: jinghe@263.net.cn (J. He).
http://dx.doi.org/10.1016/j.mcat.2017.09.035
2468-8231/© 2017 Published by Elsevier B.V.

70
H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
Avance 400 MHz NMR spectrometer (Bruker, Bremen, Germany) at
ambient temperature. 1H NMR data are reported as the following:
chemical shift in parts per million (␦, ppm) from chloroform (CHCl3)
taken as 7.26 ppm, intergration, multiplicity (s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, dd = doublet of doublets) and
coupling constant (Hz). The reaction progress was monitored by
TLC (hexane/ethyl acetate (v/v = 4/1)). All the molecular dynam-
ics simulations were performed using the Discover module in the
Materials Studio software package.
2.2. Preparation of ˛-amine acid anions intercalated LDH
nanosheets
The preparation of ␣-amine acid anions intercalated MII/Al-
LDHs (MII = Mg, Ni, Zn, or Ca, ␣-amine acid (AA) = l-serine,
l-alanine, l-leucine, l-phenylalanine, l-tyrosine, or 4-methy-l-
phenylalanine) were accomplished through the coprecipitation
approach [78,79] by addition of a mixed solution of 1 M M(NO3)2
(M = Mg, Ni, Zn, or Ca) and Al(NO3)3 dropwise to a stirred 50 mM
␣-amine acid solution, with a molar ratio of M2+/Al3+/␣-amine acid
anions molar ratio = 2/1/1. The solution pH was maintained at 10
for ␣-amine acid anions intercalated Mg/Al-LDHs, 8 for ␣-amine
acid anions intercalated Ni/Al-LDHs, 9 for ␣-amine acid anions
intercalated Zn/Al-LDHs, and 11.5 for ␣-amine acid anions interca-
lated Ca/Al-LDHs. by dropwise addition of 1 M NaOH solution under
stirring. The suspension was stirred at 313 K in N2 atmosphere
for 6 h. The resulting suspension was filtrated, washed thoroughly
with decarbonated deionized water and anhydrous alcohol, and
dried in a vacuum oven at room temperature. The preparation
of Mg/Al-Pro-LDHs and Mg/Al-Me-Pro-LDHs was accomplished
through the reconstruction method [80]. The Mg/Al-CO32−-LDHs
precursor was first synthesized by addition of a mixed solution of
0.16 M Mg(NO3)2 and Al(NO3)3 (Mg/Al molar ratio = 2/1) in 225 mL
of deionized water to a stirred solution of NaOH and Na2CO3 in
225 mL of deionized water with pH maintained at 9.5. The concen-
tration of the base was related to the concentration of metal ions:
[NaOH] = 1.6 [Mg2+ + Al3+] and [CO32−] = 2.0 [Al3+]. The suspension
was aged at 373 K for 18 h. The final precipitate was filtered, washed
thoroughly with deionized water and anhydrous alcohol, and dried
at 333 K for 24 h. The Mg/Al-CO32−-LDHs was then calcined at 773 K
for 5 h with a temperature-programmed rate of 5 K/min from room
temperature to 773 K, and then naturally cooled, producing lay-
ered double oxides (LDO). 0.5 g of LDO was added to a freshly
prepared solution of 0.006 mol (or 0.009 mol) of l-proline or ␣-
methyl-l-proline and 0.006 mol (or 0.009 mol) of NaOH in 100 mL
of decarbonated deionized water. The suspension was stirred at
298 K in N2 atmosphere for 24 h. The resulting precipitate was fil-
tered, washed thoroughly with decarbonated deionized water and
anhydrous ethanol, and dried in a vacuum oven at 313 K.
Scheme 1. Schematic illustration of LDH nanosheets as both solid base and rigid
planar substituent for ␣-amino acids.
sterically encumbered aryl [70–72], the peptides with a minimum
of one helical turn [58,59,73] afforded better asymmetric induc-
tion via steric-shielding approach. Those effective catalysts with
bulky and complicated entities usually require complicated multi-
step synthesis and are often very expensive. Elaborately designed
strategies, which are facile but could effectively afford remarkable
enantioselectivity, are highly desired.
Here, we propose an efficient strategy to promote amine-
catalyzed asymmetric epoxidation of ␣, ˇ-unsaturated aldehyde,
which simply utilizes inorganic nanosheets to supply the desired
basicity and steric hindrance around the amine sites (Scheme 1).
The inorganic nanosheets employed here are the positively-
charged brucite-like layers of layered double hydroxides (LDHs), a
natural and/or synthetic anionic compound and also a well-known
basic catalyst [74–77]. The strategy proposed here demonstrates
efficacy, in that 76% of yield, 82:18 of dr (trans:cis), and 93% of ee for
major diastereomer (trans) have been afforded in the asymmetric
epoxidation of cinnamaldehyde.
2. Experimental
2.1. General
l-Serine, l-alanine, l-leucine, l-phenylalanine, l-tyrosine,
4-methy-l-phenylalanine,
cinnamaldehyde, 4-methyl-cinnamaldehyde,
l-proline,
␣-methyl-l-proline,
4-chloro-
cinnamaldehyde, 4-trifluoromethyl- cinnamaldehyde, 30%
aqueous H2O2, dimethyl maleate, pyrene, and (2S)-2-[Bis[3,5-
bis(trifluoromethyl)phenyl](trimethylsiloxy)methyl]pyrrolidine
(the Jørgensen-Hayashi catalyst) were purchased from Sigma-
Aldrich and Alfa-Aesar. All the reagents and commercial chemicals
were of analytical purity and used as received without further
purification.
2.3. General procedure for the asymmetric epoxidation reactions
and catalyst recycling
The powder X-ray diffraction (XRD) patterns were taken on a
Shimadzu XRD-6000 diffractometer with Cu Ka radiation (40 kV
and 30 mA) at a scanning rate of 5◦/min and step size of 0.02◦.
The content of Mg, Ni, Zn, Ca, and Al was determined on induc-
tively coupled plasma (ICP) atomic emission spectrophotometry
(Shimadzu ICPs-7500) by dissolving the samples in dilute HNO3.
The C, H and N element analysis was performed on an Elementar
Co. Vario elemental analyzer. The Fourier transform infrared (FT-
IR) spectra were recorded on a Bruker Vector 22 FT-IR spectrometer
with a resolution of 4 cm−1 using the standard KBr pellet method.
The fluorescence spectra were recorded at room temperature on
a Shimadzu RF-5301PC spectrophotometer operating in the spec-
trum mode. 1H spectra were recorded in CDCl3 solutions on Bruker
Without any particular precautions to extrude oxygen or mois-
ture, 0.25 mmol ␣, ˇ-unsaturated aldehyde and 1.06 equiv. of H2O2
(30% aqueous solution) in 1 mL acetone were weighted in a flask
and allowed to stir for 10 min MII/Al-AA-LDHs (AA: 10 mol%) was
then added and the reaction was sealed and allowed to stir at 25 ◦C.
In 3 or 4 h, the solid catalyst was recovered by filtration, and the
reaction mixture was quenched by H2O, extracted with Et2O. The
water phase was washed for two times with Et2O. The organic phase
was then dried over anhydrous Na2SO4 and evaporated to give the
epoxy aldehydes.
For easy identification, the epoxy aldehydes were reduced to
the corresponding epoxy alcohols by NaBH4. The epoxy aldehydes
were redissolved in 1 mL MeOH and cooled to 0 ◦C, then followed by

H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
71
addition of NaBH4 (25 mg). After 30 min, the reaction was quenched
by saturated NH4Cl, extracted with Et2O, dried over anhydrous
Na2SO4 and concentrated in vacuo. Dimethyl maleate (1 equiv.)
was added into the crude product as internal standard. The con-
version, yield, and dr were determined by 1H NMR. The ee were
determined by HPLC analysis on chiral OD-H or OJ-H column for
aromatic compounds or by Mosher’s MTPA method for aliphatic
compounds.
formed using the Andersen method [85] and the Berendsen method
[86], respectively. Long-range Coulombic interactions and van der
Waals interactions were computed by the Ewald summation tech-
nique. The simulation time-step was set to be 1 fs and the total
simulation time was 200 ps. All the simulations were performed
using the Discover module in the Material Studio software package
[87].
After the reaction terminated, the solid catalyst was recovered
by filtration and washed with 5 mL Et2O for three times. Then the
solid was dried in a vacuum oven at 313 K and used directly for the
next catalytic reaction.
3. Results and discussion
3.1. Structural properties of ˛-amine acid anions intercalated
LDH nanosheets
2.4. Detection of interlayer hydrophobicity
The nanosheets employed here are the brucite-like layers of
magnesium and aluminum hydroxides (Mg/Al-LDHs), calcium
and aluminum hydroxides (Ca/Al-LDHs), nickel and aluminum
hydroxides (Ni/Al-LDHs), and zinc and aluminum hydroxides
(Zn/Al-LDHs). The amine sites employed here are the amino group
in alpha-amino acid anion intercalated in the interlayer space of
LDHs. The intercalation of l-serine (Ser), l-alanine (Ala), l-leucine
(Leu), l-phenylalanine (Phe), l-tyrosine (Tyr), and 4-methy-l-
phenylalanine (Me-Phe) was performed by the co-precipitation
method and of l-proline (Pro) and ␣-methyl-l-proline (Me-Pro)
by the reconstruction method. The basal spacing is calculated
from the 003 reflection of the XRD patterns (Fig. 1, A) as 0.90,
0.88, 0.88, 1.80, 1.50, 1.82, 0.78, 0.78, 1.75, 1.65, and 1.82 nm for
Mg/Al-Ser-LDHs, Mg/Al-Ala-LDHs, Mg/Al-Leu-LDHs, Mg/Al-Phe-
LDHs, Mg/Al-Tyr-LDHs, Mg/Al-Me-Phe-LDHs, Mg/Al-Pro-LDHs,
Mg/Al-Me-Pro-LDHs, Ca/Al-Phe-LDHs, Ni/Al-Phe-LDHs, and Zn/Al-
Phe-LDHs. Subtracting the brucite-like layer thickness (0.48 nm)
from the calculated basal spacing, the interlayer spacing is esti-
mated to be 0.42, 0.40, 0.40, 1.32, 1.02, 1.34, 0.30, 0.30, 1.27,
1.17, and 1.34 nm, indicating a monolayer tilted arrangement of
interlayer amino acid anions for Mg/Al-Ser-LDHs, Mg/Al-Ala-LDHs,
or Mg/Al-Leu-LDHs, monolayer horizontal arrangement for Mg/Al-
Pro-LDHs or Mg/Al-Me-Pro-LDHs, bilayer vertical arrangement for
Mg/Al-Phe-LDHs, Mg/Al-Tyr-LDHs, Mg/Al-Me-Phe-LDHs, Ca/Al-
Phe-LDHs, Ni/Al-Phe-LDHs, or Zn/Al-Phe-LDHs (Fig. 1, B) in light
of the dimension of ␣-amino acid anions measured by Materials
Studio Program (Fig. S1). It is interesting that the aliphatic ␣-amino
acid anions are all arranged in monolayer and the aromatic ␣-
amino acid anions in bilayer in the interlayer regions. The M2+/Al3+
molar ratio was determined according to the ICP results as in a
narrow range of 1.78–2.22 for the LDHs intercalated with primary
␣-amino acid anions, and 2.70 for the LDHs intercalated with
l-proline or ␣-methyl-l-proline anions (Table S1). The interlayer
␣-amino acid anions were determined according to the CHN results
in the percentage of 21% to 33% for the case of monolayer arrange-
ment, and 64% to 97% for the case of bilayer arrangement (Table
S1). The rest of interlayer anions are co-existing carbonate and/or
To determine the interlayer hydrophobic microenvironment,
pyrene was used as a fluorescent probe [81]. Batch sorption experi-
ments were performed in 50-mL centrifuge tubes with Teflon-lined
screw caps. For each experiment, the Mg/Al-AA-LDHs with the
same amount of ␣-amine acid anions were dried under a flow of
dry N2 to remove any surface-bound solvent. Then 30 mL of the cor-
responding liquid phases (vwater/vmethanol = 1/1) was added to the
tubes. Pyrene was added to the tubes by direct injection of an aque-
ous solution of pyrene and kept constant at 1 ␮M. The centrifuge
tubes were sealed and wrapped with aluminum foil to protect
them from light and placed on a wrist shaker for 24 h. The tubes
were removed from the shaker, placed horizontally on a bench,
and shaken for the following 2 days. Then the pyrene-loaded Mg/Al-
amine acid anions-LDHs were obtained by centrifugation. The solid
was dried under a flow of dry N2 and analyzed with a Shimadzu
RF-5301PC spectrometer. Samples were excited at ␭ = 335 nm and
pyrene emission spectra were recorded from 350 to 490 nm. Both
excitation and emission slit widths were set at 2.5 nm.
2.5. Structural model and molecular dynamics (MD) simulation
method
MD simulations were used to understand the arrangement of
␣-amine acid anions in the Mg/Al-LDHs interlayer space. The lat-
tice containing 18 Mg atoms and 9 Al atoms was built on the basis
of each [AlO6] octahedron surrounded by six [MgO6] and each
[MgO6] octahedron, in turn, surrounded by three [AlO6] octahe-
dron, because the ratio of Mg to Al is 2:1, which ensures that Al
atoms will not occupy adjacent octahedron. According to the liter-
ature [82,83], the lattice parameters of the 2-dimensional layer are
a = b = 3.142 Å. On the basis of the model of the host layer, a supercell
was constructed, with lattice parameter a = 28.278 Å, b = 9.426 Å,
and the initial interlayer spacing 17.960 Å for Mg2.03/Al-Phe0.79
-
LDHs and 18.170 Å for Mg2.03/Al-Me-Phe0.97-LDHs, ␣ = ˇ = 90◦,
ꢀ = 120◦ (equivalent to 9 × 3 × 1 in the a, b, and c directions). The
supercell was treated as P1 symmetry and all of lattice parameters
were considered as independent variables during the simulation.
A 3-dimensional periodic boundary condition was applied to the
system, so the simulated supercell can be repeated infinitely in
three directions. Then, for maintaining the whole system elec-
trically neutral and matching the chemical compositions, seven
l-phenylalanine anions, one carbonate ion, and twenty eight water
molecules were introduced into the simulated supercell randomly
for Mg2.03/Al-Phe0.79-LDHs and eight 4-methy-l-phenylalanine
anions, one nitrate ion, and thirty six water molecules were intro-
duced for Mg2.03/Al-Me-Phe0.97-LDHs. All MD simulations were
performed by adopting the LDHFF force field developed by Zhang
et al. [84]. After energy minimization was applied on the initial
models, MD simulations were performed in an isothermal–isobaric
(NPT) ensemble with the temperature of 298 K and the pressure of
0.1 MPa (about 1 atm). Temperature and pressure control were per-
nitrate. The asymmetric (ꢁCOOas) and symmetric vibrations (ꢁCOOs
)
of carboxylate group in the LDH nanosheets-attached ␣-amine acid
anions are resolved at 1607 and 1348 cm−1 for Mg2.03/Al-Ser0.21
-
LDHs, 1617 and 1357 cm−1 for Mg2.03/Al-Ala0.21-LDHs, 1580 and
1362 cm−1 for Mg1.78/Al-Leu0.22-LDHs, 1591 and 1354 cm−1 for
Mg2.03/Al-Phe0.79-LDHs, 1597 and 1362 cm−1 for Mg2.22/Al-Tyr0.71
-
LDHs, 1593 and 1363 cm−1 for Mg2.03/Al-Me-Phe0.97-LDHs, 1577
and 1369 cm−1 for Mg2.70/Al-Pro0.26-LDHs, 1581 and 1389 cm−1
for Mg2.70/Al-Pro0.33-LDHs, 1574 and 1361 cm−1 for Mg2.70/Al-
Pro0.33-LDHs, 1573 and 1354 cm−1 for Ca2.03/Al-Phe0.64-LDHs,
1579 and 1362 cm−1 for Ni1.78/Al-Phe0.97-LDHs, and 1577 and
1360 cm−1 for Zn1.86/Al-Phe0.66-LDHs in the FT-IR spectra (Fig. 1,
C). The ꢂꢁCOO (ꢁCOOas –ꢁCOOs) is 259, 260, 218, 237, 235, 230,
208, 192, 213, 219, 217, and 217 cm−1, respectively. The ꢂꢁCOO
of the corresponding ␣-amine acid sodium salt [88–95] is 207,

72
H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
Me-Pro0.26-LDHs, Ca2.03/Al-Phe0.64-LDHs, Ni1.78/Al-Phe0.97-LDHs,
and Zn1.86/Al-Phe0.66-LDHs. Increasing the intercalated amounts
of l-proline anions from 26% (Mg2.70/Al-Pro0.26-LDHs) to 33%
(Mg2.70/Al-Pro0.33-LDHs) altered the electrostatic interactions
between l-proline anions and brucite-like layer from monoden-
tate to bidentate mode, though the interlayer l-proline anions
remained in a monolayer horizontal arrangement.
3.2. Effects of LDH nanosheets on amine-catalyzed asymmetric
epoxidation of ˛, ˇ-unsaturated aldehyde
The l-proline anions intercalated in LDHs was first applied in the
asymmetric epoxidation of cinnamaldehyde. As shown in Table 1,
94% conversion of cinnamaldehyde and 70% yield of glycidaldehyde
(isolated yield of 67%) were obtained in 3 h on Mg2.70/Al-Pro0.33
-
LDHs (entry 1). Partly hydrolysis of cinnamaldehyde was observed
as a side reaction, producing benzaldehyde as byproduct, which has
been reported previously [98–102], accounting for the yield infe-
rior to the conversion (a selectivity of 74%). In 2 h (entry 2), 82%
cinnamaldehyde conversion and 54% epoxide yield were afforded.
Prolonging the reaction time to 4 h (entry 3), 98% cinnamaldehyde
conversion and 72% epoxide yield were afforded. The similar cin-
namaldehyde conversion, epoxide yield, and ee value were reached
in 3 h and 4 h. Decreasing the amount of Mg2.70/Al-Pro0.33-LDHs
in half (5 mol% amino acid anions), 78% cinnamaldehyde conver-
sion and 40% epoxide yield were afforded (entry 4). So it is obvious
that l-proline anions intercalated in LDHs are efficient catalysts for
epoxidation of cinnamaldehyde. No epoxidation reaction occurred
in the absence of l-proline anion (entry 5), indicating that the
−NH- in the l-proline anion was the catalytic center. With l-proline
sodium salt as the catalyst (entry 6), 67% conversion was afforded,
but with only an epoxide yield of 7%. No epoxide was produced
with l-proline ethylester (entry 7) or l-proline (entry 8) as catalyst,
although a 20% or 10% cinnamaldehyde conversion was afforded.
By adding 10 mol% NaOH together with l-proline sodium salt as the
catalyst (entry 9), the epoxide yield increased from 7% to 22% with a
cinnamaldehyde conversion of 60%, revealing that the epoxide yield
was improved with increasing basicity. But a lower epoxide yield
was achieved with l-proline sodium salt together with 10 mol%
NaOH than with intercalated l-proline anions. The better conver-
sion of cinnamaldehyde to its epoxide with Mg2.70/Al-Pro0.33-LDHs
than with l-proline sodium salt revealed that the LDH nanosheets
afforded the desired basicity more effectively to activate the oxi-
dant, facilitating the attack of HOO− to the carbon–carbon double
bonds in the iminium intermediate, and the epoxidation domi-
nated. But the LDH nanosheets with the l-proline anion just simply
adsorbed on the exterior surface (entry 10) were invalid to pro-
mote the epoxidation, affording only an epoxide yield of <5% under
58% conversion, similar to the case with l-proline sodium salt. It
is the nanosheets with amine sites encapsulated in the interlayer
regions that function synergically as solid base to facilitate the acti-
vation of oxidant and the subsequent nucleophilic attack. With
Mg2.70/Al-Pro0.26-LDHs as catalyst (entry 11), in which the electro-
static interactions between l-proline anions and brucite-like layer
are monodentate mode, 96% conversion of cinnamaldehyde and
76% yield of glycidaldehyde were obtained. Mg2.70/Al-Pro0.33-LDHs
(entry 1) and Mg2.70/Al-Pro0.26-LDHs (entry 11) afforded similar
cinnamaldehyde conversion and epoxide yield, indicating that the
bidentate or monodentate interactions impose no visible effects on
the synergy of LDH nanosheets with intercalated amine sites.
Simple small primary amines are generally inferior to secondary
amines in the catalytic activity due to unfavorable imine-enamine
equilibria [103–105]. But promotion of cinnamaldehyde conver-
sion and epoxide yield was observed in this work by intercalating
primary amines in LDHs. As shown in Table 1, the conversion of
cinnamaldehyde increased from 30% for Me-Phe-Na to 88% for
Fig. 1. The XRD patterns (A), schematic structures (B), and FT-IR spectra (C) of
a) Mg2.03/Al-Ser0.21-LDHs, b) Mg2.03/Al-Ala0.21-LDHs, c) Mg1.78/Al-Leu0.22-LDHs, d)
Mg2.03/Al-Phe0.79-LDHs, e) Mg2.22/Al-Tyr0.71-LDHs, f) Mg2.03/Al-Me-Phe0.97-LDHs, g)
Mg2.70/Al-Pro0.26-LDHs, h) Mg2.70/Al-Pro0.33-LDHs, i) Mg2.70/Al-Me-Pro0.26-LDHs, j)
Ca2.03/Al-Phe0.64-LDHs, k) Ni1.78/Al-Phe0.97-LDHs, and l) Zn1.86/Al-Phe0.66-LDHs.
213, 175, 216, 193, 212, 196, 196, 181, 216, and 216 cm−1. Fol-
lowing the method reported in literature [96,97] by comparing
the ꢂꢁCOO between the value of the interlayer ␣-amino acid
anions with the value of the corresponding ␣-amino acid sodium
salts, the electrostatic interactions between the brucite-like layer
and ␣-amino acid anions were identified as monodentate mode
for Mg2.03/Al-Ser0.21-LDHs, Mg2.03/Al-Ala0.21-LDHs, Mg1.78/Al-
Leu0.22-LDHs, Mg2.03/Al-Phe0.79-LDHs, Mg2.22/Al-Tyr0.71-LDHs,
Mg2.03/Al-Me-Phe0.97-LDHs, Mg2.70/Al-Pro0.26-LDHs, Mg2.70/Al-

H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
73
Table 1
Catalytic asymmetric epoxidation of ␣, ˇ-unsaturated aldehydesa.
Entry
Catalyst
Time
(h)
Conversion of
aldehyde (%)b
1H NMR yield
(%)b
Selectivity to
epoxide (%)
drb
(trans/cis)
ee of trans (%)c
ee of cis
(%)c
1
2
3
4
Mg2.70/Al-Pro0.33-LDHs
Mg2.70/Al-Pro0.33-LDHs
Mg2.70/Al-Pro0.33-LDHs
3
2
4
3
94
82
98
78
70/67d
54
72
74
65
73
51
83:17
78:22
81:19
75:25
93
90
95
92
70
73
62
71
Mg2.70/Al-Pro0.33
-
40
LDHse
5
6
7
8
Mg/Al-CO32−-LDHs
Pro-Na
3
3
3
3
3
3
3
4
0
67
20
10
60
58
96 (94)
88 (90)
0
7
0
0
0
10
0
0
37
<9
79 (77)
68 (64)
NDf
70:30
ND
ND
82:18
70:30
82:18 (83:17)
73:27 (76:24)
ND
0
ND
ND
0
39
93 (91)
28 (27)
ND
0
ND
ND
0
58
78 (73)
11 (10)
Pro ethylester
Pro
9
Pro-Na + NaOHg
Pro/Mg/Al-CO32−-LDHs
Mg2.70/Al-Pro0.26-LDHs
22
<5
76 (72)
60 (58)
10
11
12
Mg2.03/Al-Me-Phe0.97
LDHs
-
13
14
15
16
17
18
19
20
21
Mg2.03/Al-Phe0.79-LDHs
Mg1.78/Al-Leu0.22-LDHs
Mg2.22/Al-Tyr0.71-LDHs
Mg2.03/Al-Ala0.21-LDHs
Mg2.03/Al-Ser0.21-LDHs
Ca2.03/Al-Phe0.64-LDHs
Ni1.78/Al-Phe0.97-LDHs
Zn1.86/Al-Phe0.66-LDHs
4
4
4
4
4
4
4
4
3
82 (80)
80 (78)
62 (64)
60 (60)
52 (54)
92
48
30
92
48 (46)
42 (40)
32 (32)
26 (26)
20 (18)
58
14
5
74
59 (58)
52 (51)
52 (50)
43 (43)
38 (33)
63
29
17
80
81:19 (79:21)
75:25 (76:24)
76:24 (75:25)
77:23 (77:23)
75:25 (78:22)
72:28
86:14
80:20
83:17
44 (42)
42 (40)
38 (38)
36 (35)
27 (27)
42
31
36
63
17 (17)
17 (17)
18 (17)
19 (20)
24 (24)
32
18
28
79
Mg2.70/Al-Me-Pro0.26
LDHs
-
Mg2.03/Al-Me-Phe0.97-LDHs (entry 12), from 34% for Phe-Na to 82%
for Mg2.03/Al-Phe0.79-LDHs (entry 13), from 38% for Leu-Na to 78%
for Mg1.78/Al-Leu0.22-LDHs (entry 14), from 22% for Tyr-Na to 62%
for Mg2.22/Al-Tyr0.71-LDHs (entry 15), from 26% for Ala-Na to 60%
for Mg2.03/Al-Ala0.21-LDHs (entry 16), and from 32% for Ser-Na to
52% for Mg2.03/Al-Ser0.21-LDHs (entry 17). But the yields of gly-
cidaldehyde were only observed with LDH nanosheets-attached
amines (entries 12, 13, 14, 15, 16, and 17). Only trace or no epox-
ide was observed with Me-Phe-Na, Phe-Na, Leu-Na, Tyr-Na, Ala-Na,
and Ser-Na. Similar to the case with intercalated secondary amine,
the basicity provided by the LDH nanosheets could facilitate the
epoxidation on the primary amine sites, affording the selectivity to
epoxide. The dependence of epoxide selectivity on the basicity of
brucite-like layers further proves the assistance of LDH nanosheets
as a solid base. For Ca2.03/Al-Phe0.64-LDHs, with a higher basic-
ity than Mg2.03/Al-Phe0.79-LDHs, 63% selectivity (92% conversion
and 58% yield) was observed (entry 18). For Ni1.78/Al-Phe0.97-LDHs,
with a lower basicity than Mg2.03/Al-Phe0.79-LDHs, 29% selec-
tivity (48% conversion and 14% yield) was observed (entry 19).
For Zn1.86/Al-Phe0.66-LDHs, with a lower basicity than Ni1.78/Al-
Phe0.97-LDHs, 17% selectivity (30% conversion and 5% yield) was
observed (entry 20). The observations in this work are sustained by
our previous work [106], where the improvement of catalytic activ-
ity has been achieved by using ligand-attached LDH nanosheets
to afford the desired basicity in Rh(III)-catalyzed C H activation
reaction.
Even for primary amines, with acyclic structure and thus diffi-
cult to produce enantioselectivity, the ee was also evoked by the
attachment of LDH nanosheets. 28% ee for major diastereomer
was afforded with Mg2.03/Al-Me-Phe0.97-LDHs (entry 12), 44% ee
with Mg2.03/Al-Phe0.79-LDHs (entry 13), 42% ee with Mg1.78/Al-
Leu0.22-LDHs (entry 14), 38% ee with Mg2.22/Al-Tyr0.71-LDHs (entry
15), 36% ee with Mg2.03/Al-Ala0.21-LDHs (entry 16), and 27%
ee with Mg2.03/Al-Ser0.21-LDHs (entry 17). The LDH nanosheets
are supposed to supply the desired steric hindrance around
the amine sites as attached rigid planer substituent, and direct
the access trajectory of activated oxidant to the carbon–carbon
double bond in the iminium intermediate. The observations
in this work are sustained by our previous work [107,108],
where the boosting of enantioselectivity has been achieved by
using LDH nanosheets as the rigid planer substituent in both
organometallic-catalyzed epoxidation and organo-catalyzed aldol
addition reaction. The Jørgensen-Hayashi catalyst, ((2S)-2-[Bis[3,5-
bis(trifluoromethyl)phenyl](trimethyl- siloxy)methyl]pyrrolidine)
[60], which was known as the most successful organocatalyst and
very related to the amino acid system in our work, has been
evaluated under our reaction condition, affording 80% cinnamalde-
hyde conversion, 62% glycidaldehyde yield, and 93% ee for major
diastereomer (trans). The heterogeneous catalyst in our work,
Mg2.70/Al-Pro0.33-LDHs, is comparable to the homogeneous system
in both yield and ee. Using organic peroxides m-chloro perben-
zoic (m-CPBA) as oxidant, <5% cinnamaldehyde conversion with
no epoxide yield was produced with Pro-Na, Pro ethylester, or
Mg2.70/Al-Pro0.33-LDHs as catalysts. m-CPBA was unlikely an effi-
cient oxidant in amino acid systems, consistent with the results
reported by the literature with Jørgensen-Hayashi catalyst [60].
The substrate scope for Mg2.70/Al-Pro0.26-LDHs-catalyzed asym-
metric epoxidation of ␣, ˇ-unsaturated aldehydes was then
explored (Table 2). For aromatic aldehydes, both electron-
withdrawing and electron-donating substituents were well
tolerated. In 3 h, > 99% conversion, 32% epoxide yield, and 89% ee
for trans isomer were obtained for the asymmetric epoxidation
The LDH nanosheets play a more critical role in improv-
ing the ee of glycidaldehyde, as can be clearly seen from entry
1 and entry 8. With Mg2.70/Al-Pro0.33-LDHs, 93% ee for major
diastereomer (trans) was achieved, while no ee was observed with
l-proline sodium salt. 39% ee for major diastereomer (trans) was
produced (entry 10) even with the l-proline anion just simply
adsorbed on the exterior surface of Mg/Al-CO32−-LDHs, demon-
strating that the enantioselective enhancement originated from
LDHs nanosheets, and the enhancement was especially obvious
with the amine sites located at the interlayer regions of LDHs.

74
H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
Table 2
Substrate scope for Mg2.70/Al-Pro0.26-LDHs-catalyzed asymmetric epoxidation of ␣, ˇ-unsaturated aldehydesa.
Entry
Substrate
Conversion of
aldehyde (%)b
1H NMR Yield (%)b
Isolated yield of
Selectivity (%)
ee of trans isomerd (%)
epoxide aldehyde (%)c
1
2
>99 (>99)
86 (88)
32 (34)
44 (42)
30
40
32 (34)
51 (48)
89 (89)
96 (96)
3
90 (86)
72 (70)
48 (46)
44 (40)
45
40
53 (53)
61 (57)
94 (95)
88 (88)
4
5e
96
60
57
62
89
6e
96 (94)
62 (62)
ND (ND)f
64 (66)
77g
a
Reaction conditions: 0.25 mmol of ␣, ˇ-unsaturated aldehydes, 1.06 equiv. of H2O2 in 30% aqueous solution, 10 mol% of ␣-amino acid anions, 1 mL of acetone, 25 ◦C, 3 h
of reaction time.
b
Determined by 1H NMR using dimethyl maleate as internal standard after reduced by NaBH4.
c
All the isolated yields were consistent with the 1H NMR yield.
d
Determined by HPLC analysis on chiral OD-H or OJ-H column after reduced by NaBH4.
5 h of reaction time.
Not Determined due to the volatility of the product, the 3-isopropyl-oxirane-2-carbaldehyde cannot be isolated.
Determined by Mosher’s MTPA method. The figures in the parenthesis are reproduced results.
e
f
g
of 4-trifluoromethyl-cinnamaldehyde (entry 1); 86% conversion,
44% epoxide yield, and 96% ee were obtained for 4-bromo-
cinnamaldehyde (entry 2); 90% conversion, 48% epoxide yield,
and 94% ee were obtained for 4-chloro-cinnamaldehyde (entry
3); 72% conversion, 44% epoxide yield, and 88% ee were
obtained for 4-methyl-cinnamaldehyde (entry 4). With increas-
ing electron-donating effects, the aromatic aldehydes were more
difficult to be activated. It is very likely that the electron-
withdrawing substituents decrease the electron density of the
carbon–carbon double bond, making the carbon–carbon double
bond susceptible to being nucleophilically attacked. While the
electron-donating substituents increase the electron density of
the carbon–carbon double bond, making the nucleophilic attack
of carbon–carbon double bond more difficult. But by prolong-
ing the reaction time to 5 h, 96% conversion, 60% epoxide yield,
and 89% ee were obtained for 4-methyl-cinnamaldehyde (entry
5). Then the aldehydes were extended from aromatic aldehy-
des to aliphatic aldehyde. 96% conversion, 62% epoxide yield,
and 77% ee were observed in 5 h for the ˇ-disubstituted ␣,
ˇ-unsaturated aldehyde (4-methyl butenal) (entry 6). With an
attempt to further extend the substrate generality, the asymmetric
epoxidation of 2H-chromene-3-carbaldehyde, trans-4-phenyl-3-
buten-2-one, trans-methyl-cinnamate, trans-cinnamonitrile, and
trans-3-(2-furyl)acrolein was also examined. Unfortunately, no
reaction occurred. The development of more effective catalysts for
more extensive substrates merits further efforts.
Table 1, those with LDH nanosheet attached afforded a con-
version changing from 52% to 88%. The epoxide yields on LDH
nanosheets-attached primary amines also differ greatly from each
other (from 20%–60%). That means the catalytic activities of
primary amines might be affected by the interlayer microenvi-
ronment. The interlayer hydrophobicity was then explored by the
fluorescence spectra of pyrene molecules, which were encapsu-
lated in the interlayer of amine-intercalated LDHs. The vibronic
structure of pyrene is known to be sensitive to the polarity of
the environment [109–114]. The ratio of the fluorescence inten-
sity of the first to the third vibronic peaks (I373/I384) increased
from ∼0.6 to ∼2.0 with the increasing polarity of the environ-
ment [115,116]. The I373/I384 was 1.43 for Mg2.03/Al-Ser0.21-LDHs,
1.34 for Mg2.03/Al-Ala0.21-LDHs, 1.30 for Mg1.78/Al-Leu0.22-LDHs,
and 1.20 for Mg2.03/Al-Phe0.79-LDHs (Fig. 2A), revealing that the
interlayer hydrophobicity gradually increased. With increasing
interlayer hydrophobicity, the cinnamaldehyde conversion and
epoxide yield were improved (Fig. 2A). The hydrophobicity was
further tailored by changing the substituent on the aromatic ring
(Fig. 2B). With a 4-hydroxyl substituent on the aromatic ring,
the I373/I384 was 1.32 (Mg2.22/Al-Tyr0.71-LDHs). With a 4-methyl
substituent on the aromatic ring, the I373/I384 was 1.07 (Mg2.03/Al-
Me-Phe0.97-LDHs). The cinnamaldehyde conversion and epoxide
yield were also observed to increase with increasing interlayer
hydrophobicity (Fig. 2B). For LDH nanosheets-attached proline
based amine, the hydrophobicity was also tailored by substi-
tuting the H atom in 2-C of l-proline with methyl group. The
I373/I384 was 1.40 for Mg2.70/Al-Pro0.26-LDHs and 1.37 for Mg2.70/Al-
Me-Pro0.26-LDHs. Mg2.70/Al-Me-Pro0.26-LDHs (Table 1, Entry 21)
afforded 92% cinnamaldehyde conversion and 74% epoxide yield,
similar to Mg2.70/Al-Pro0.26-LDHs (96% cinnamaldehyde conversion
and 76% epoxide yield (Table 1, Entry 11)). The slight differ-
ence of hydrophobicity between the Mg2.70/Al-Pro0.26-LDHs and
3.3. Influence of hydrophobicity and ordered arrangement of
interlayer amines on catalytic efficacy
It is interesting that, the primary amines without attachment
to LDH nanosheets provided similar cinnamaldehyde conver-
sion (in the range of 22% to 38%), but as can be seen from

H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
75
Fig. 2. The interlayer hydrophobic microenvironment and its influence on the conversion and epoxide yield. In the schematic illustration of intercalated LDHs, the H atoms
have been omitted.
Fig. 3. (A) Side view of the simulated arrangement of interlayer ␣-amino acid anions, carbonate ion (or nitrate ion), and water molecules, (B) Atomic density profiles along
the c-stacking axis (the black line represents Mg atoms in the LDHs layer, the red line represents O atoms in the LDHs layer, the green line represents H atoms in the LDHs
layer, the blue line represents O atoms in the water molecules, the orange line represents O atoms in the ␣-amino acid anions, and the magenta line represents C atoms of
the phenyl rings in the ␣-amino acid anions), and (C) the distribution of distance between two adjacent centroids of the phenyl rings for a) Mg2.03/Al-Phe0.79-LDHs and b)
Mg2.03/Al-Me-Phe0.97-LDHs. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
the Mg2.70/Al-Me-Pro0.26-LDHs make no visible effects on the cin-
namaldehyde conversion and epoxide yield.
afforded 63% ee, lower than the ee (93% as shown in Table 1,
Entry 11) afforded by less hydrophobic Mg2.70/Al-Pro0.26-LDHs.
So the interlayer arrangement of intercalated amines was stud-
ied, and then related to the ee of epoxide. The arrangement of
interlayer anions in Mg2.03/Al-Phe0.79-LDHs and Mg2.03/Al-Me-
Phe0.97-LDHs was simulated by molecular dynamics (MD) (Fig. 3).
According to the side view of the simulated arrangement of inter-
layer anions and water molecules (Fig. 3A), Mg, O, and H atoms
in the brucite-like layer along the c-stacking axis were profiled
The observed enantioselectivites were then related to the inter-
layer hydrophobicity. For intercalated primary amines, the ee was
improved with increasing interlayer hydrophobicity. But an excep-
tion arose for Mg2.03/Al-Me-Phe0.97-LDHs, which afforded a lower
ee with a stronger interlayer hydrophobicity than other inves-
tigated catalysts. Similarly, for intercalated proline based amine,
more hydrophobic Mg2.70/Al-Me-Pro0.26-LDHs (Table 1, Entry 21)

76
H. Liu et al. / Molecular Catalysis 443 (2017) 69–77
Fig. 5. Reusability of Mg2.70/Al-Pro0.33-LDHs catalyst in asymmetric epoxidation of
cinnamaldehyde.
Fig. 4. Reusability of Mg2.70/Al-Pro0.26-LDHs catalyst in asymmetric epoxidation of
cinnamaldehyde.
4. Conclusions
In conclusion, the amine-catalyzed asymmetric epoxidation of
␣, ˇ-unsaturated aldehydes was promoted by attaching to LDH
nanosheets. 76% of epoxide yield and 93% ee for major diastereomer
have been achieved in the asymmetric epoxidation of cinnamalde-
hyde. The strategy of attaching amines to LDH nanosheets proves
versatile and viable to facilitate the asymmetric epoxidation of
␣, ˇ-unsaturated aldehydes. The catalytic activity was enhanced
by the basicity of LDH nanosheets and further improved by
increasing hydrophobicity of interlayer amines. The enantiose-
lectivity was boosted by the steric synergies of LDH nanosheets
and further improved by better ordered arrangement of inter-
layer amines. Nevertheless, there remain great challenges that are
worth of further in-depth investigation. One is how to inhibit the
leaching of interlayer anions. The non-covalent interactions (elec-
trostatic interaction, H-bonding interaction, and etc) between LDH
nanosheets and interlayer amines are superior in the preservation
of original asymmetric environment, yet are not strong enough
to resist the exchange by ambient anions. The other is how to
ameliorate the efficacy of heterogeneous asymmetric catalysis.
The amine-intercalated LDHs in our work are inefficient for more
challenging substrates, such as ␣, ˇ-unsaturated ketones, ␣, ˇ-
unsaturated esters, and ␣, ˇ-unsaturated nitriles.
(Fig. 3B) at 0.2 and 18.1 Å, 1.2 and 17.1 Å, and 2.2 and 16.2 Å
for Mg2.03/Al-Phe0.79-LDHs, and at 0 and 18.7 Å, 1.0 and 17.7 Å,
and 1.9 and 16.8 Å for Mg2.03/Al-Me-Phe0.97-LDHs. The O atoms
in interlayer water molecules and ␣-amino acid anions were pro-
filed at 4.0 Å and 14.4 Å for Mg2.03/Al-Phe0.79-LDHs, and 3.7 Å
and 15.0 Å for Mg2.03/Al-Me-Phe0.97-LDHs. The profile distance
between the O atoms in interlayer water/anions and the H atoms
in the OH groups of brucite-like layers is estimated as 1.8 Å for both
Mg2.03/Al-Phe0.79-LDHs and Mg2.03/Al-Me-Phe0.97-LDHs, which is
consistent with the binding length of hydrogen bonds. The C atoms
in the phenyl rings of interlayer ␣-amino acid anions are pro-
filed at 7.1-11.6 Å for Mg2.03/Al-Phe0.79-LDHs and 6.5-12.1 Å for
Mg2.03/Al-Me-Phe0.97-LDHs. The distribution range of the phenyl
rings along the c-stacking axis was 4.5 Å for Mg2.03/Al-Phe0.79-LDHs
and 5.6 Å for Mg2.03/Al-Me-Phe0.97-LDHs. The narrower distribu-
tion range of phenyl rings in Mg2.03/Al-Phe0.79-LDHs than that
in Mg2.03/Al-Me-Phe0.97-LDHs revealed that the arrangement of
interlayer l-phenylalanine anions was less stagger than interlayer
4-methy-l-phenylalanine anions. The distance between two adja-
cent centroids of phenyl ring along ab-plane (Fig. 3C) is estimated
from Fig. 3A with the maximum at 5.5 Å for Mg2.03/Al-Phe0.79-LDHs,
and at 3.8 Å to 5.0 Å for Mg2.03/Al-Me-Phe0.97-LDHs. Both of the pro-
file distance along c-stacking axis and ab-plane indicate that the
arrangement of interlayer l-phenylalanine anions is better ordered
than that of interlayer 4-methy-l-phenylalanine anions, account-
ing for the enhancement of ee in the asymmetric epoxidation.
Acknowledgements
Financial supports by NSFC (No. 21673016) and 973 Project
(2014CB932101) are gratefully acknowledged.
Appendix A. Supplementary data
3.4. Catalyst reusability
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.mcat.2017.09.
035.
The secondary amine intercalated Mg/Al-LDHs catalyst has been
recycled and reused without any treatment. On Mg2.70/Al-Pro0.26
-
LDHs (Fig. 4), the cinnamaldehyde conversion and epoxide yield
declined in the recycles. As discussed above, the electrostatic inter-
actions between interlayer l-proline anions and brucite-like layer
are monodentate mode for Mg2.70/Al-Pro0.26-LDHs, which was not
strong enough to prevent the amine leaching. But the ee was well
preserved in the recycle runs. On Mg2.70/Al-Pro0.33-LDHs (Fig. 5),
93% ee was also well preserved in ten cycles. The cinnamaldehyde
conversion and epoxide yield were well maintained in eight cycles.
Visible decline of cinnamaldehyde conversion and epoxide yield
was only observed in the last two cycles due to the slight leaching
of interlayer amines (Table S2). That means the bidentate electro-
static interactions could effectively hold the interlayer l-proline
anions attached to the brucite-like layer.
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