Yolk-Shell-Mesostructured Silica-Supported Dual Molecular Catalyst for Enantioselective Tandem Reactions

Article abstract of DOI:10.1002/cplu.201800377

Yolk-shell-mesostructured silica was used as a support in the development of an active-site-isolated bifunctional catalyst that can mediate a sequential organic transformation. Herein, through immobilization, the location of two catalytic species is controlled: a base functionality is anchored in the channels of the outer silica shell and a chiral ruthenium/diamine functionality is anchored on the inner silica yolk. The result is a yolk-shell-mesostructured silica-supported active-site-isolated dual molecule catalyst. Structural analysis through solid-state carbon ¹³C NMR spectroscopy reveals its well-defined single-site dual active centers. Electron microscopy investigations disclose its uniformly distributed mesoporous nanoparticles. As envisaged, this bifunctional catalyst enables a controllable aza-Michael addition/asymmetric transfer hydrogenation catalytic sequence, where the base-catalyzed aza-Michael addition of enones and amines to aryl-substituted β-secondary amino ketones is followed by a Ru-catalyzed asymmetric transfer hydrogenation. Various aryl-substituted γ-secondary amino alcohols are obtained in high yields and enantioselectivities via this one-pot enantioselective organic transformation. Furthermore, the heterogeneous catalyst can be applied in a continuous-flow process, which was shown to be particularly attractive for the practical preparation of aryl-substituted γ-secondary amino alcohols in an environmentally friendly medium.

Full text of DOI:10.1002/cplu.201800377

Accepted Article
Title: Yolk-Shell-Mesostructured Silica-Supported Dual Molecular
Catalyst for Enantioslective Tandem Reactions
Authors: Guohua Liu, Jingrong Lin, Ronghua Jin, Liang Wu, Jingjing
Meng, and Yilong Li
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Yolk–Shell–Mesostructured Silica–Supported Dual Molecular
Catalyst for Enantioselective Tandem Reactions
Liang Wu, Yilong Li, Jingjing Meng, Ronghua Jin, Jingrong Lin and Guohua Liu*
Dedication ((optional))
Abstract: Utilization of yolk–shell–mesostructured silica as a support
to develop an active site–isolated bifunctional catalyst benefits a
sequential organic transformation. Herein, through the control of
immobilized position of two catalytic species, we anchor base–
functionality into the channels of outer silica shell and chiral
ruthenium/diamine–functionality onto inner silica yolk, constructing a
yolk–shell–mesostructured silica–supported active site–isolated dual
molecule catalyst. Structural analysis via solid–state carbon spectrum
reveals its well–defined single–site dual active centers, and
morphology via electron microscopy investigations discloses its
uniformly distributive mesoporous nanoparticles. As we envisaged,
minimum workup.[3] Recently, some explorations in construction
of active site–isolated bifunctional catalyst have led to various
highly efficient catalytic reactions,[1a, 4] which cover nicely the
shortages of homogeneous catalysis in one–pot multi–step
sequential organic transformations. Although some scattered
reports in fabrication of yolk–shell–structured silica-supported
active site–isolated bifunctional catalysts have appeared in
literatures,[
4, 5]
their applications limit mainly in the preparation of
nonchiral organic molecules[ whereas that used in synthesis of
optically pure organic molecules is still rare.[5] Accordingly,
development of yolk–shell–mesostructured silica–supported dual
molecule catalysts and exploration of their applications in
preparation of optically pure organic molecules via an atom–
economic tandem reactions are highly desirable.
4]
this bifunctional catalyst enables
a controllable aza–Michael
addition/asymmetric transfer hydrogenation catalytic sequence,
where the base–catalyzed aza–Michael addition of enones and
amines to aryl–substituted β–secondary amino ketones followed by
the Ru–catalyzed asymmetric transfer hydrogenation provides
various aryl–substituted γ–secondary amino alcohols with high yields
and enantioselectivities via this one–pot enantioselective organic
transformation. Furthermore, the heterogeneous catalyst can be
appliced in a continuous–flow process, showing particularly attractive
in a practical preparation of aryl–substituted γ–secondary amino
alcohols in an environmentally friendly medium.
Optically pure γ–secondary amino alcohols, as a kind of
valuable chiral pharmaceutical intermediates, are well–known to
be used in preparation of antidepressants.[ So far, main methods
to synthesize these chiral γ–secondary amino alcohols depend
heavily on the enantioselective reductions of prochiral β–amino
ketones in homogeneous conditions.[7] Earlier works employed
chiral Rh–MCPPM complex (MCPPM: 4–dicyclohexylphosphino–
2–diphenylphosphinomethyl–1–(N–methylcarbamoyl)pyrrolidine)
and chiral Rh–Duanphos complex as catalysts converted β–
amino ketones into chiral γ–secondary amino alcohols.[
Recent reports utilized chiral Rh–benzbisphosphine complex as a
6]
7a-7d]
Introduction
catalyst and ZnCl
2
as an activator via asymmetric
hydrogenation[7e-7g] and chiral Ru–diamine complexes via
Yolk–shell–structured silicas,[1] one kind of typical member of
mesoporous silica family,[2] have attracted much interest in
catalysis.[1a] Unique feature originates from their specically
structural morphology, where silica shell and silica yolk are able
to immobilize seperately different catalytic species and to form an
active site–isolated bifucntional catalyst. This kind of superiority
makes some unfeasible homogeneous catalysis in sequential
reactions into possibility through the adjustment of inherent
incompatibility of two distinct different homogeneous species in
one-pot process, realizing some unexplored multi–step sequential
organic transformation. Especially, catalyst applied to a tandem
reaction can reduce greatly pollution due to atom economy and
asymmetric transfer hydrogenation (ATH) [7h] to perform the highly
efficient preparations of γ–secondary amino alcohols. Despite of
these well–established asymmetric catalysis, the inherent
drawbacks of homogeneous catalysis, such as expensive
transition–metal cost, environmentally unfriendly solvent and
inevitable product contamination, still greatly hinder their
applications. Therefore, development of a practical immobilization
approach to overcome these drawbacks and exploration of an
atom–economic tandem reaction for highly efficient preparation of
γ–secondary amino alcohols are a significant challenge in
heterogeneous asymmetric catalysis.
As our ongoing research programs for development of
recoverable heterogeneous catalysts used in asymmetric transfer
hydrogenation,[ herein we take advantage of yolk–shell–
mesostructured silica to assemble base–functionality into the
channels of the outer silica shell and chiral ruthenium/diamine–
functionality onto the inner silica yolk, forming yolk–shell–
mesostructured silica–supported active site–isolated dual
molecule catalyst. As we envisaged, this recoverable bifunctional
catalyst performs an efficient aza–Michael addition/asymmetric
transfer hydrogenation one–pot reaction of aryl–substituted
8]
[
a]
L. Wu, Y. Li, J. Meng, R. Jin, J. Lin, Prof. G. Liu.
Department Key Laboratory of Resource Chemistry of Ministry of
Education, Shanghai Key Laboratory of Rare Earth Functional
Materials
Institution Shanghai Normal University
Address 1 No.100 Guilin Rd
E-mail: ghliu@shnu.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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enones and amines to prepare various γ–secondary amino
alcohols via a tandem process.
as
a
separated unit, it ensures that the chiral
MesityleneRuArDPEN–functionality was on the silica yolk
whereas the achiral DABCO–functionality was located in the
nanochannels of the silica shell, forming the silica–supported
active site–isolated bifunctional catalyst.
Results and Discussion
Scheme 1. Preparation of catalysts 3.
Figure 1. Solid-state 13C CP/MAS NMR spectra of 1 and catalyst 3.
Assembly of the active site–isolated dual functionalities, basic
DABCO–functionality (DABCO:[9] 1–(3–(triethoxysilyl)propyl)–
1
,4–diazabicyclo[2.2.2]octanium
chloride)
and
MesityleneRuArDPEN–functionality (MesityleneRuArDPEN:[
10]
Mesitylene = 1,3,5–trimethylbenzene and ArDPEN = (S,S)–4–
(
(trimethoxysilyl)ethyl)phenylsulfonyl–1,2–diphenylethylene–
diamine), within the yolk–shell–structured mesoporous silicate
nanoparticles (MSNs) provided the bifunctional heterogeneous
catalyst
3,
abbreviated
as
DABCO@MesityleneRuArDPEN@MSNs, as outlined in Scheme
1
. Firstly, according to the reported method with the slight
modification,[ the co–condensation of tetraethoxysilane (TEOS)
1a]
and
(S,S)–ArDPEN–siloxane
through
the
use
of
cetyltrimethylammonium bromide (CTAB) as a structure–directing
template afforded a silicate nanoparticle (yolk), which were
followed by the further grown of TEOS to produce the SiO
coated yolk. Continuous condensation of 1,2–
bis(triethoxysilyl)ethylane and DABCO–siloxane onto this SiO
2
–
Figure 2. Solid–state 29Si CP/MAS NMR spectra of 1 and catalyst 3.
2
–
coated
O(CF(CF
yolk
)CF
using
CF(CF )CONH(CH
FC–4
(FC–4:
+
–
[
C
3
F
7
3
2
O)
2
3
2
)
3
N (C
2
H
5
)
2
CH
3
]I )
Determination of the well–defined, active site–isolated dual
functionalities within the yolk–shell–mesostructured silicate
network of 3 could be provided via an analysis of its solid–state
13C cross–polarization (CP)/magic angle spinning (MAS) NMR
spectroscopy as shown in Figure 1. In the case of shell for the
part of DABCO–functionality, besides general carbon signals of –
and CTAB as dual structure–directing templates then led to an
ethylene–bridged DABCO–functionalized silica shell, where the
2
SiO –coated layer in this core–shell–structured silicate
nanoparticles could be etched selectively to form the yolk–shell–
structured MSNs, Yolk@Shell@MSNs (1). Finally, the direct
complexation of 1 with (MesityleneRuCl ) (2) followed by a strict
2 2
Soxhlet extraction process to clean the nanochannels afforded
the expected catalyst, DABCO@MesityleneRuArDPEN@MSNs
SiCH
organic silica, the characteristic peaks at 46.9 and 54.7 ppm were
attributed to the carbon atoms of –CH N– groups in DACBO
moiety. These observed carbon signals were similar to those of
2 2
CH Si– moiety around 7 ppm for the ethylene–bridged
2
(
3), in the form of a yellow powder. (see SI in Figures S1–S2).
During this precedure, due to the sandwiched SiO –coated layer
2
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10.1002/cplu.201800377
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its homogeneous counterpart, demonstrating the successful
immobilization of basic DABCO–functionality.[9a] In the case of
yolk for the part of chiral ruthenium/diamine–functionality, catalyst
and [Si(OSi)
4
], respectively), demonstrating the types and
compositions of catalyst 3. It was noteworthy that the intensities
of T–series signals were stronger than those of Q–series signals,
3
produced the characteristic carbon signals at 107.7, 104.2 ppm,
2
indicating that most inorganic silica (SiO –coated layer) had been
and 22.5 ppm, where the first two peaks were responded to the
carbon atoms of the aromatic ring in the mesitylene moiety, and
the third peak ascribed the carbon atoms of methyl groups
attached to the aromatic ring. Above three characteristic carbon
signals demonstrated the formation of the coordinative complexes
since they were absent in its parent material 1. Moreover, these
characteristic carbon signals of 3, along with the carbon signals
between 68 and 74 ppm observed for carbon atoms of the –NCH
groups in the TsDPEN moiety, disclosed that catalyst 3 had the
same well–defined single–site active species as homogeneous
counterpart MestyleneRuTsDPEN[10a] since both had similar
chemical shifts. In addition, the other peaks denoted by asterisks
are the rotational sidebands, and/or the carbon signals of the
CTAB moiety remaining in the material, which often appeared in
the MAS high speed rotation process.
etched successfully during the prepared process. Notably, the T–
series signals in the spectrum of 3 was attributed to the R–
Si(OSi)
2
(OH)
and
R–Si(OSi)
3
species
(R
=
MesityleneRuTsDPEN–linked and DACBO–linked alkyl groups,
or ethylene–bridged group), whereas the Q–series signals
ascribed [(HO)
These observations suggested that catalyst 3 possessed the R–
Si(OSi) species as its main organic silica shell and the
(OH)Si(OSi) ] species as its main inorganic silica yolk.
2 2 3 4
Si(OSi) ], [(HO)Si(OSi) ], and [Si(OSi) ] species.
3
[
3
Figure 3. Nitrogen adsorption–desorption isotherms of 1 and catalyst 3.
Verification of the types and components of silicate network in
3
could be obtained via an investigation of its 29Si magic angle
spinning (MAS) NMR spectroscopy. As shown in Figure 2, both 1
and catalyst 3 had two groups of typical signals (Q– and T–series
signals) with the broad distribution from −10 to −150 ppm. Three
Q signals were the inorganic silica type and suggested its
inorganic silicate network as its silica core, whereas two T signals
were the organic silica type and indicated its organic silicate
network as its silica shell. Through analysis of these isomer
chemical shift values in catalyst 3, it was found that all observed
values are similar to those typically reported values in the
literatures[11] (T–series: −58.5, and −67.5 ppm for T2 and T of
Figure 4. (a) SEM images of 3, (b) TEM images of 3.
Control over the monodispersed morphologies and orderly pore
arrangentments of the as–made catalyst 3 could truely reflect its
catalytic nature in tandem reactions, where 3 were further
characterized using nitrogen adsorption–desorption technique,
scanning electron microscopy (SEM), transmission electron
microscopy (TEM). As shown in Figure 3, the nitrogen
adsorption–desorption isotherms of 1 and catalyst 3 presented a
typical IV character with an H1 hysteresis loop, disclosing their
3
[
R(HO)Si(OSi)
2 3
] and [RSi(OSi) ]. Q–series: −91.5, −101.5, and
2
3
4
−110.0 ppm for Q , Q , and Q of [(HO) Si(OSi) ], [(HO)Si(OSi) ],
2 2 3
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mesoporous nanostructures with the orderly pore arrangentments
since they were same as that of yolk–shell–mesostructured silica
material reported in literature.[1a] Figure 4 showed the SEM and
TEM images and revealed the monodispersed morphologies of
catalyst 3, where the SEM images confirmed the uniformly
distributed nanospheres with an average diameter size of 250 nm
was comparable to that obtained with its homogeneous
DABCO.[ This finding suggested that the DABCO–functionality
anchored in the silica shell of 3 acted the same basic role as its
counterpart to retain its homogeneous catalytic efficiency.
9a]
In second stage, we optimized the second–step generally used
ATH[13] of 1–phenyl–3–(phenylamino)propanone to convert into
(S)–1–phenyl–3–(phenylamino)propanol for the investiation of
enantioselectivity. Because of water as reaction solvent in first–
step aza–Michael addition, we chose sodium formate system as
a hydrogen resource. In this case, the reaction was carried out in
aqueous system (water plus sodium formate) by using 1.0 mol%
of ruthenium–loading in 3 as a catalyst. However, this single–step
ATH transformation in water only afforded chiral product of (S)–
1–phenyl–3–(phenylamino)propanol in 58% yield with 76% ee. As
(
Figure 4a) whereas the TEM images proved its yolk–shell–
mesostructured silica nanospheres with the silica yolk
encapsulated by an average 20 nm silica shell in thickness
(
Figure 4b). It is clear that the each silica yolk with chiral
ruthenium/diamine species was succussfully separated by the
Lewis basic silica shell, leaving enough room for mass transfer to
allow for reactants, intermediates and products in and out of the
materials freely. Also, it was worth mentioning that more than 95%
of the as–made catalyst 3 had the well–defined yolk–shell–
mesostructured monodispersed morphology, ensuring a credible
catalytic performance.
All these characterizations, together with the obtained
investigations and analyses, illuminate that catalyst 3 with the
well–defined active site–isolated dual functionalities, the chiral
MesityleneRuArDPEN–functionality on the silica yolk and the
achiral DABCO–functionality in the silica shell, could be fabricated
readily, forming the uniformly distributed silica–supported
bifunctional catalyst via this successive assembled process
we
predicted,
the
poor
solubility
of
1–phenyl–3–
(phenylamino)propanone in water was responsible for its low yield
since the addtion of alcohols could enhance greatly its yield.
Subsequently, we optimized a few alcohols as co–solvents to
improve the solubility of substrate in this two–phase reaction
system and to compare their catalytic performances (see SI in
i
Table S2). It was found that, in the case of PrOH/H
2
O (1:1, v/v)
as
a
co–solvent,
the
ATH
of
1–phenyl–3–
(phenylamino)propanone catalyzed by 3 could afford (S)–1–
phenyl–3–(phenylamino)propanol in 95% yield with 96% ee. Such
an ee value was comparable to that attained with its
homogeneous counterpart MesityleneRuArDPEN, indicating the
well-defined single–site ruthenium/diamine centres in catalyst 3
verified by its 13C CP/MAS NMR spectra keeps its original
homogeneous catalytic environment. Furthermore,
a XPS
investigation of catalyst 3 and its coresponding homogeneous
MesityleneRuTsDPEN also confirmed this judgement (Figure 5)
becase catalyst 3 had the similar Ru 3d5/2 electron binding energy
to its homogeneous counterpart (281.52 eV versus 281.53 eV).
Table 1. Synthesis of Chiral γ–Secondary Amino Alcohols via Michael
[
a]
addition/ATH One–pot Enantioselective Tandem Reactions.
Figure 5. XPS spectra of homogeneous MesityleneRuTsDPEN and catalyst 3.
Entry
1
Ar
1
, Ar
2
(5)
Time (h)
Yield (%)[b]
Ee (%)[c]
Ph, Ph (5a)
12
24
12
92
58
79
90
84
88
87
90
86
82
96
2
3
4
5
6
7
8
9
Ph, Ph (5a)
76 [d]
With the well–defined active site–isolated bifunctional catalyst
3
in hand, we assessed the aza–Michael addition/ATH one–pot
95 [e]
Ph, Ph (5a)
enantioselective tandem process following below three stages. In
the first stage, we investigated the single–step aza–Michael
addition of 1–phenylprop–2–enone and aniline in water based on
the consideraton of green catalysis for the verification of catalytic
efficiency.[12] To determine the nature of DABCO–bifunctionality in
catalyst 3, we compared its catalytic performance with a few
homogeneous bases (see SI in Table S1). It was found that the
single–step aza–Michael addition catalyzed by 3 with 10 mol% of
DABCO–loading could give the Michael addition product of 1–
phenyl–3–(phenylamino)propanone in 98% yield, which was
markedly better than those obtained with the other bases, and
Ph, 4–ClPh (5b)
Ph, 3–ClPh (5c)
Ph, 2–ClPh (5d)
Ph, 4–BrPh (5e)
15
15
15
15
15
15
12
92
94
97
92
99
96
96
Ph, 4–NO
2
Ph (5f)
Ph (5g)
Ph, 3–NO
2
10
Ph, 4–MePh (5h)
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11
12
13
14
15
16
17
18
19
Ph, 3,4–Me
2
Ph (5i)
12
12
12
12
12
12
12
15
15
74
68
73
72
89
90
88
82
77
94
96
93
96
89
92
93
95
96
aromatic rings of Ar1 group had lower ee values than those
attained with electron–donating substituents on the aromatic rings
Ph, 3,5–Me
2
Ph (5j)
1
of Ar group (entries 15–17 versus entries 18–19).
Ph, 3-Cl-4-MePh (5k)
Ph, 3–MeOPh (5l)
4–FPh, Ph (5m)
4–ClPh, Ph (5n)
4–BrPh, Ph (5o)
4–MePh, Ph (5p)
4–MeOPh, Ph (5q)
[
a] Reaction conditions: catalyst 3 (12.35 mg, 1.0 μmol of Ru based on ICP
analysis), enones (0.10 mmol), amines (0.11 mmol), HCOONa (1.0 mmol),
i
2
.0 mL of PrOH/H
2
O (v/v = 1 : 1), and reaction time (12–24 h). [b] Isolated
yields. [c] The ee was determined by chiral HPLC analysis (see SI in Figures
S3, S5). [d] Data were obtained using water as solvent. [e] Data were
obtained using the mixed DABCO–siloxane and its homogeneous
MesityleneRuTsDPEN as dual catalysts.
In third stage, we combined two single–step reactions, aza–
Michael addition and ATH reduction, into Michael addition/ATH
one–pot process, where the tandem reaction was performed
through the use of the 1.0 mol% Ru–loading of 3 as a catalyst and
i
Figure 6. Time course of the aza–Michael addition/ATH of 1–phenylprop–2–
enone and aniline to (S)–1–phenyl–3–(phenylamino)propanol (reaction was
performed with 1 equivalent of 1–phenylprop–2–enone, 1.1 equivalent of aniline,
1.0 mol % of catalyst 3, 10.0 equivalent of HCOONa at 40 °C ).
the HCOONa as a hydrogen resource in PrOH/H
2
O (1:1, v/v) at
4
0 °C in the organic transformation of 1–phenylprop–2–enone
and aniline. Result showed that this one–pot transformation still
gave the target product of (S)–1–phenyl–3–
phenylamino)propanol in 92% yield and 96% ee with the tiny Ru-
(
Due to the feature of the catalytically active site–isolation of
catalyst 3, it is expected that catalyst 3 with the achiral Lewis basic
species in the nanochannels of the silica shell and the chiral
ruthenium/diamine species on the silica yolk can undergo an aza–
Michael addition/ATH catalytic sequence, where the reaction
initially goes through an aza–Michael addition between the
enones and amines followed by an asymmetric transfer
hydrogenation process during the synthesis of chiral γ–secondary
amino alcohols. In order to prove the controllable catalytic
sequence and explore the nature of this tandem reaction, a kinetic
investigation in the one–pot transformation of 1–phenylprop–2–
enone and aniline catalysed by 3 was performed through an
examination of its reaction time course. As shown in Figure 6, it is
found that the aza–Michael addition of 1–phenylprop–2–enone
leaching during the catalytic process, which was markedly higher
than that attained with the use of water as single solvent (Table 1,
entry 1 versus entry 2). It is worth mentioning that such a result
was also better than that obtained using the mixed homogeneous
DABCO–siloxane plus homogeneous MesityleneRuTsDPEN as
dual catalysts because the latter only gave the targeting chiral
product in 79% yield and 95% ee (Table 1, entry 3), in which 16%
of the 1–phenyl–3–(phenylamino)propanone intermediate was
1
not converted into the product, as proven by H–NMR analysis.
Table 1 further confirmed the general feasibility of this tandem
process, where the 3–catalyszed aza–Michael addition/ATH one–
pot enantioselective transformations with a series of aryl–
substituted enones and amines could be used to synthesize a
variety of chiral γ–secondary amino alcohols. It was found that all
the tested reactions afforded steadily the corresponding aryl–
substituted chiral γ–secondary amino alcohols in high yields and
enantioselectivities. It was noteworthy that the structures and
electronic properties of the substituents on the aromatic rings of
Ar2 group did not significantly affect their enantioselectivities,
where various electron–withdrawing and –donating substituents
(
4a) and aniline occurs quickly at first, where the aza–Michael
addition reaction produces the 1–phenyl–3–
phenylamino)propanone intermediate (A) with maximum
(
a
conversion of 84% within 1 h. Subsequently, the ATH of A
proceeds smoothly, providing the target product of (S)–1–phenyl–
3–(phenylamino)propanol (5a) in 92% yield after 12 h. As we
expected, the obtained kinetic investigation supports the
controlled catalytic sequence comprised of an aza–Michael
addition reaction followed by an asymmetric transfer
hydrogenation process
2
on the aromatic rings of Ar group were equally efficient (Entries
4–14). On the contrary, the slight enantioselectivity was affected
by the electronic property of the substituents on the aromatic rings
Another concern for the design of the yolk–shell–
1
of Ar group, where the electron–withdrawing substituents on the
mesostructured silica–supported dual malecule catalyst
3
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expected to explore its potential possibility in a continuous–flow
process.[14] In this case, we investigated the 3-catalysed aza–
Michael addition/ATH enantioselective tandem reaction of 1–
phenylprop–2–enone and aniline to prepare (S)–1–phenyl–3–
are attributed to the combined contributions of uniformly
distributed morphology, active site–isolated–feature, and single–
site dual species catalytic nature. Furthermore, the catalyst can
be applied in a continuous flow process, presenting a significant
benefit in its practical application. The study described here
highlights a site–isolated bifunctional catalyst realizes an efficient
one–pot enantioselective tandem reaction for preparation of
valuable chiral aryl–substituted γ–secondary amino alcohols.
(
phenylamino)propanol as a model process, as showed in Figure
7
a
. During this continuous–flow process, the packed bed reactor of
X–Cube (ThalesNano) instrument was filled with the
heterogeneous catalyst 3 (300 mg of catalyst, 0.6 mL volume, 70
mm mm), whereas a diluted solution containing 1–
phenylprop–2–enone (1.00 mmol), aniline (1.20 mmol) and
sodium formate (10.0 mmol) in a mixed aqueous co–solvent Experimental Section
comprised of 20 mL of i–PrOH and 20 mL of H O was prepared.
At the beginning, when the reaction parameters were stabilizing
reaction temperature = 40 °C, and flow rate = 0.1 mL/min), the
processing was started with a blank diluted solution comprised of
sodium formate in i–PrOH and H O without 1–phenylprop–2–
×
4
2
Preparation of catalyst 3
(
In a typical synthesis, (First step for the formation of mesoporous yolk
functionalized with chiral ArDPEN–siloxane) 0.10 g (0.27 mmol) of
cetyltrimethylammonium bromide (CTAB) was completely dissolved
in 45.0 mL of aqueous sodium hydroxide (0.35 mL, 2.0 N). The
mixture was stirred at room temperature for 0.5 h. Subsequently,
2
enone and aniline. After the desired reaction parameters and
stabilized process were achieved, the prepared diluted reaction
solution was pumped. It is found that, in a continuous run for 4.5
hours, the product of (S)–1–phenyl–3–(phenylamino)propanol in
0.125 g (0.25 mmol) of ArDPEN–siloxane and 0.47 g of (2.26 mmol)
of tetraethoxysilane (TEOS) was added at room temperature under
vigorous stirring. Finally, 0.40 mL of ethyl acetate was added and the
mixture was stirred at 80 °C for 2 h. After cooling the above mixture
down to 38 °C, an aqueous solution (80 mL of water, 50 mL of ethanol,
9
1% yield and 95% ee from the washings was obtained after 4.5
hours (see SI in Table S3 and Figure S4), suggesting a potential
industrial application. Obviously decreased reactivity after 5.5 h
runs in this continuous flow process was attributed to a large
amount of Ru-leaching, where an inductively coupled plasma
optical emission spectrometer (ICP-OES) analysis showed that
about 10% Ru in catalyst 3 lost
3 2
0.30 g (0.82 mmol) of CTAB and 1.0 mL (25 wt%) of NH ·H O) was
added and the mixture was stirred 38 °C for 0.5 h. Subsequently, 0.5
mL, 0.47 g (2.26 mmol) of TEOS was added and the mixture was
stirred at 38 °C for another 2 h. (Second step for the coating above
SiO
siloxane, and the selective etching) An aqueous solution (3 mL of
water containing 0.04 (0.044 mmol) of FC–4
O(CF(CF )CF CF(CF )CONH(CH ]I ), 0.08 g
0.22 mmol) of CTAB and 0.20 mL (25 wt%) of NH O) was added
2
–coated yolk with 1,2–bis(triethoxysilyl)ethane and DABCO–
g
+
–
3
([C F
7
3
2
O)
2
3
2 3 2 5 2 3
) N (C H ) CH
(
3 2
·H
and the mixture was stirred at 38 °C for 0.5 h. Then, 0.25 g of 1,2–
bis(triethoxysilyl)ethane (0.70 mmol) in 2 mL of ethanol and 0.050 g
(0.135 mmol) of DABCO–siloxane in 2 mL of ethanol were added at
room temperature, followed by stirring overnight. Then, the mixture
was transferred to a Teflon–lined autoclave at 100 °C for 20 h to form
yolk–shell structured mesoporous nanoparticles. After cooling the
above mixture down to room temperature, the solid was collected by
filtration. To remove the surfactant, the collected solids (0.96 g) were
dispersed in 120 mL of solution (80 mg (1.0 mmol) of ammonium
nitrate in 120 mL (95%) of ethanol), and the mixture was stirred at
Figure 7. Schematic representation of continuous flow process for the aza–
Michael addition/ATH of 1–phenylprop–2–enone and aniline to (S)–1–phenyl–
60 °C for 10 h. After cooling the above mixture down to room
3–(phenylamino)propanol.
temperature, the solid was filtered and washed with excess water and
ethanol, and dried at ambient temperature under vacuum overnight to
afford the pure Shell@Yolk@MSNs (1) as a white powder (0.80 g).
Conclusions
(
(
(
Third step for the complexation) 50.0 mg of (MesityleneRuCl
0.086 mmol) was added to a suspension of Shell@Yolk@MSNs (1)
0.50 g) in 20.0 mL of dry CH Cl at room temperature, and the
2 2
) (2)
In conclusions, by utilizing a site–isolated immobilization strategy,
we develop a yolk–shell–mesostructured silica–supported active
site–isolated dual molecule catalyst, where the well–defined
single–site chiral ruthenium/diamine–functionality and basic
DABCO–functionality are immobilized in its silicate yolk and shell,
respectively. As demonstrated in the presented study, this
bifunctional catalyst produces the chiral products with high
catalytic activity and enantioselectivity in the Michael
addition/ATH one–pot enantioselective tandem reaction, which
2
2
resulting mixture was stirred at 25 °C for 12 h. The mixture was filtered
through filter paper and then rinsed with excess CH Cl . After Soxhlet
extraction for 24 h in CH Cl to remove homogeneous and unreacted
2
2
2
2
starting materials, the solid was dried at ambient temperature under
vacuum overnight to afford DABCO@MesityleneRuArDPEN@MSNs
(
3) (0.52 g) as a yellow powder. ICP analysis showed that the Ru
13
loadings was 8.26 mg (0.0809 mmol of Ru) per gram of catalyst.
C
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10.1002/cplu.201800377
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CP/MAS NMR (161.9 MHz): 157.8−121.9 (C of Ar and Ph groups),
Commun. 2015, 51, 8496-8499.
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07.7, 104.2 (C of Arene group), 88.1−75.9 (C of –N CH
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– in DACBO moiety), 36.6−26.6 (C
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=
−95.0 ppm), Q (δ = −104.4 ppm), Q (δ = −114.2 ppm).
General procedure for tandem reaction
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ICP analysis), enones (0.10 mmol), amines (0.11 mmol), HCOONa
i
(
1.0 mmol), and 2.0 mL of PrOH/H
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sequentially to a 10.0 mL round−bottom flask. The mixture was then
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Entry for the Table of Contents (Please choose one layout)
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Liang Wu, Yilong Li, Jingjing Meng,
Ronghua Jin, Jingrong Lin and Guohua
Liu*
Page No. – Page No.
Yolk–Shell–Mesostructured
Silica–
Supported Dual Molecular Catalyst for
Enantioslective Tandem Reactions
A yolk–shell–structured active site–isolated bifunctionalized heterogeneous catalyst
is developed, which enables an efficient aza–Michael addition/asymmetric transfer
hydrogenation tandem reaction to synthesize chiral aryl–substituted γ–secondary
amino alcohols.
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[
a]
L. Wu, Y. Li, J. Meng, R. Jin, J. Lin, Prof. G. Liu.