One-pot relay reduction-isomerization of β-trifluoromethylated-α,β-unsaturated ketones to chiral β-trifluoromethylated saturated ketones over combined catalysts in aqueous medium

Article abstract of DOI:10.1039/c5gc00479a

Despite great achievements obtained in tandem reactions, a solution for the incompatible nature of bimetal complexes participating in a multi-step catalytic process is still an unmet challenge. Herein, we utilize a functionalized periodic mesoporous organ

Full text of DOI:10.1039/c5gc00479a

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One-pot Relay Reduction-Isomerization of β-Trifluoromethylated-α,β-
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DOI: 10.1039/C5GC00479A
Unsaturated Ketones to chiral β-Trifluoromethylated Saturated Ketones
Over Combined Catalysts in Aqueous Medium
Xuelin Xia, Meng Wu, Ronghua Jin, Tanyu Cheng, Guohua Liu*
5
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
Despite great achievements obtained in tandem reactions, solution of the incompatible nature of
bimetal complexes participated in a multi-step catalytic process is still an unmet challenge. Herein,
10 we utilize an functionalized periodic mesoporous organosilica with well-defined single-site chiral
organoruthenium active centers in its ordered dimensional-hexagonal mesopores as
a
heterogeneous catalyst, and combine it and [RuCl2(PPh3)3] to enable an efficiently one-pot relay
reduction-isomerization from achiral β-trifluoromethylated-α,β-unsaturated ketones to chiral β-
trifluoromethylated saturated ketones in water with up to 97% ee and 100% enantiospecificity,
15 supplying a gap of their incompatibility. Furthermore, the heterogeneous catalyst can be recovered
conveniently and reused repeatedly for at least eight times without loss of reactivity in the
enantioselective reduction of 4,4,4-trifluoro-1,3-diphenylbut-2-enone, showing particularly
attractive in the practice of organic synthesis in an environmentally friendly manner.
process, the incompatible nature of dual organoruthenium
complexes compels to employ a two-pot catalytic reactions.
Moreover, some inherent drawbacks, such as environmentally
55 unfriendly solvent (toluene and Et3N-HCOOH as solvents),
sensitive reaction system (strict isomerization condition),
especially, inevitable transition-metal contamination and
complicated product isolation, are still difficulty to meet the
demand of green chemistry. Thus, based on environmental
60 consideration, exploration of an immobilization strategy to
realize expensive transition-metal recycling and development
of one-pot reaction concomitant with microwave-assisted
catalysis to overcome the limit of solvent and reaction system,
are highly desirable both in fundamental research, as well as
65 practical application.
1. Introduction
20 Tandem reactions as an important branch of green chemistry
can reduce greatly pollution due to atom economy and
minimum workup,[1] whilst microwave-assisted catalysis as a
nontraditional methodology can accelerate significantly
organic transformation from days or hours to minutes to
25 enhance catalytic efficiency.[2] Together both, construction of
optically pure molecules with CF3-bearing chiral tertiary
carbon center is particularly attractive because it acts as an
motif of chiral trifluoromethyl family and can be converted
into many types of biologically active compounds in fluorine
30 chemistry.[3] So far, one-step enantioselective construction of
these molecules from β-CF3-substituted α,β-unsaturated
carbonyl compounds have involved in different types of
asymmetric reactions.[4] However, among these methods, high
pressure of hydrogen in asymmetric hydrogenation,[4a]
35 sensitive chiral diphosphine ligands in asymmetric conjugate
reduction or addition,[4b,4c] and high catalytic amount in
Friedel-Crafts alkylation[4d,4e] still limit their practical
applications. Recently, an interesting two-step construction of
Periodic mesoporous organosilica (PMO) as a support for
immobilization of various organometallic complexes
possesses attractive feature in asymmetric catalysis.[6] Besides
general advantages, such large specific surface area/pore
70 volume to enhance the loadings, the significant benefit of
PMO materials has highly hydrophobic inner-surface derived
from its intrinsic organosilicate inner wall[6a,6i] that are
superior markedly to common Si-O-Si-linked mesoporous
chiral
β-CF3-substituted
saturated
ketones
through
materials.[7] Such
a feature can facilitate efficiently an
40 enantioselective reduction of β-CF3-substituted α,β-
unsaturated carbonyls followed by isomerization of a C=C
bond of O-allylic substrates have been explored by Cahard
groups.[5] Such an alternative strategy nicely complements the
synthetic challenge in construction of these chiral β-CF3-
45 substituted saturated ketones. However, in this catalytic
75 aqueous asymmetric reaction, where fastly concentrating
organic substrates from aqueous medium into active center
can result in
a highly catalytic efficiency for organic
transformations.[6i]
In this contribution, we utilize the benefit of PMO materials in
80 aqueous asymmetric reaction to construct an ethylene-bridged
chiral organoruthenium-functionalized PMO as a heterogeneous
catalyst,[8] and combine the advantage of one-pot reaction
concomitant with microwave-assisted catalysis to explore one-pot
relay reduction-isomerization in water. As presented in this study,
85 combination of heterogeneous catalyst and [RuCl2(PPh3)3]
Key Laboratory of Resource Chemistry of Ministry of Education,
Shanghai Normal University, Shanghai,
200234, China. E-mail: ghliu@shnu.edu.cn
50 Fax: 86-21-64321819;Tel: 86-21-64321819
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 1

Green Chemistry
Page 2 of 8
realizes successfully an efficiently heterogeneous Ru-catalyzed
enantioselective reduction from β-CF3-substituted α,β-unsaturated
carbonyls to β-CF3-substituted allylic alcohols followed by a
homogeneous Ru-catalyzed isomerization under microwave
irradiation from β-CF3-substituted allylic alcohols to
enantioenriched β-CF3-substituted saturated ketones in one-pot
relay manner, overcoming their incompatible drawbacks.
Furthermore, the heterogeneous catalyst can be conveniently
recovered and reused repeatedly for at least eight times without
cymene)]2 and 2 followed by further Soxhlet extraction for
clearness of its nanochannels as a light-yelloDwOpI:o1w0.d10e3r.9/C5GC00479A
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5
10 loss of reactivity in the enantioselective reduction of 4,4,4-
trifluoro-1,3-diphenylbut-2-enone. As expected, this one-pot
enantioselective reduction concomitant with microwave-assisted
catalysis solves the limitation of Cahard’s method, and realizes
the recycling of chiral organoruthenium complex in first-step
15 asymmetric transfer hydrogenation. This strategy offers an
attractive method in the practical synthesis of valuable chiral β-
CF3-substituted saturated ketones.
Scheme 1. Immobilization of CymeneRuArDPEN-functionality within
60 the PMO silicate network.
2. Experimental
2.1. Preparation of CymeneRuArDPEN-PMO (3)
2.3. Characterization
20 In a typical synthesis, [RuCl2(p-cymene)]2 (0.22 g, 0.40 mmol)
were added to a suspension of 2 (1.00 g) in 20.0 mL of dry
CH2Cl2 at 20 °C, and the resulting mixture was stirred at
20 °C for 24 h. The mixture was filtered through filter paper
and then rinsed with excess CH2Cl2. After Soxhlet extraction
25 for 12 h in CH2Cl2 to remove homogeneous and unreacted
starting materials, the solid was dried at ambient temperature
under vacuum overnight to afford catalyst 3 (1.09 g) as a
light−yellow powder. ICP analysis showed that the Ru
loading-amount was 10.42 mg (0.103 mmol) per gram catalyst.
30 IR (KBr) cm−1: 3443.6 (s), 3066.2 (w), 2975.8 (w), 2912.9 (w),
1627.3 (m), 1501.5 (w), 1456.3 (w), 1413.1 (w), 1330.5 (w),
1267.6 (m), 1161.4 (s), 1098.5 (s), 1025.8 (s), 907.8 (m),
764.4 (m), 701.4 (m), 575.6 (m), 448.7 (m). 13C CP/MAS
NMR (161.9 MHz): 150.0, 137.5, 128.7 (C of Ph and Ar),
Ru loading amounts in catalysts were analyzed using an
inductively coupled plasma optical emission spectrometer (ICP,
Varian VISTA-MPX). Fourier transform infrared (FT-IR) spectra
65 were collected on a Nicolet Magna 550 spectrometer using KBr
method. Transmission electron microscopy (TEM) images were
performed on a JEOL JEM2010 electron microscope at an
acceleration voltage of 220 kV. X-ray photoelectron spectroscopy
(XPS) measurements were performed on a Perkin-Elmer PHI
70 5000C ESCA system. A 200 μm diameter spot size was scanned
using a monochromatized Aluminum Kα X-ray source (1486.6.6
eV) at 40 W and 15 kV with 58.7 eV pass energies. All the
binding energies were calibrated by using the contaminant carbon
(C1s = 284.6 eV) as a reference. Nitrogen adsorption isotherms
75 were measured at 77 K with a Quantachrome Nova 4000 analyzer.
The samples were measured after being outgassed at 423 K
overnight. Pore size distributions were calculated by using the
BJH model. The specific surface areas (SBET) of samples were
determined from the linear parts of BET plots (p/p0 = 0.05-1.00).
80 Solid state NMR experiments were explored on a Bruker
AVANCE spectrometer at a magnetic field strength of 9.4 T with
1H frequency of 400.1 MHz, 13C frequency of 100.5 MHz and
29Si frequency of 79.4 MHz with 4 mm rotor at two spinning
frequency of 5.5 kHz and 8.0 kHz, TPPM decoupling is applied
i
35 99.8, 87.7, 81.9 (C6 of MeC6H3 Pr in p-cymene group),
76.3−69.6 (C of −NCHPh−), 58.8 (O-CH2CH3), 31.5 (C of
−CH2Ar), 24.4 (C of CH3C6H3CH(CH3)2 in p-cymene group),
23.4-13.2 (C of CH3C6H3CH(CH3)2 in p-cymene group, and
O-CH2CH3), 5.4 (C of −CH2Si) ppm. 29Si MAS/NMR (79.4
40 MHz): T1 (δ = −48.9 ppm), T2 (δ = −57.4 ppm), T3 (δ = −64.9
ppm).
2.2. Synthesis of the heterogeneous catalyst 3
1
85 in the during acquisition period. H cross polarization in all solid
state NMR experiments was employed using a contact time of 2
ms and the pulse lengths of 4μs.
Chiral CymeneRuArDPEN-functionality embedded within the
PMO network, abbreviated as CymeneRuArDPEN-PMO (3),
45 (CymeneRuArDPEN:[9] ((η6-cymene)RuC1[N-((1R,2R)-2-amino-
1,2-diphenylethyl)-4-ethylbenzenesulfonamide], where ArDPEN
2.4. General procedure for the one-pot enantioselective
reduction-isomerization
of
β-trifluoromethylated-α,β-
=
N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-
90 unsaturated ketones
ethylbenzenesulfonamide) was prepared as outlined in Scheme 1.
Firstly, key chiral ArDPEN-derived siloxane (1), (R,R)-4-
50 (trimethoxysilyl)ethyl)phenylsulfonyl-1,2-diphenylethylene-
diamine, was synthesized according to the reported method.[8a]
Co-condensation of 1 and 1,2-bis(triethoxysilyl)ethylane did then
afford chiral ligand-functionalized material ArDPEN-PMO (2) as
a white powder. Finally, the heterogeneous catalyst 3 was
55 obtained successfully by the direct complexation of [RuCl2(p-
A typical procedure was as follows: The catalyst 3 (29.1 mg, 3.0
μmol of Ru, based on ICP analysis), β-trifluoromethylated-α,β-
unsaturated ketones (0.15 mmol), HCO2Na (204.0 mg, 3.0 mmol),
and 2.0 mL of water were added sequentially to a 5.0 of mL thick
95 walled Pyrex tube. The mixture was then stirred at room
temperature (20 °C) for 17h. During this period, the reaction was
monitored constantly by TLC. When the reaction was completed,
2
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Page 3 of 8
Green Chemistry
the tube was added [RuCl2(PPh3)3] (2.77 mg, 3.0 μmol) and 40 atoms.[8a] As compared with those typical isomer shift values in
View Article Online
positioned in a circular single-mode cavity CEM Microwave
reactor with optional cooling using nitrogen gas from CEM
Corporation (USA), adjusting the reaction temperature at 70 ºC
and producing continuous irradiation at 2.45 GHz, and the
the literature[12] (-48.5/-58.5/-67.5 DpOpI:m10.10f3o9r/C5GTC10/T042/7T93A
{[R(HO)2SiOSi]/[R(HO)Si(OSi)2]/[RSi(OSi)3]}), two strong T
signals at -57.4 and -64.9 ppm were corresponding to T2 [R-
Si(OSi)2(OH)] and T3 [R-Si(OSi)3] (R = CymeneRuArDPEN-
5
mixture was irradiated with 170 W for 15 minutes. After 45 functionalized alkyl-linked group or ethylene-bridged group),
completion of the reaction, catalyst was separated by
centrifugation (10,000 rpm) for the recycling experiment. The
aqueous solution was extracted with ethyl ether (3 × 3.0 mL). The
which were strongly similar to those reported literatures.[13] Both
typical T signals demonstrated that 2 and catalyst 3 possessed the
organosilicate networks with R-Si(OSi)2(OH) and [R-Si(OSi)3]
species as their main orgnaosilicate walls. Furthermore, the
10 combined ethyl ether extracts were washed with NaHCO3 and
brine, and then dehydrated with Na2SO4. After evaporation of 50 absence of signals for Q-series from - 90 to -120 ppm indicated
ethyl ether, the residue was purified by silica gel flash column
chromatography to afford the desired product. The yields were
determined by H-NMR, and the ee values were determined by a
that no cleavage of carbon–silicon bond occurred during co-
condensation process.
1
15 HPLC analysis using a UV-Vis detector and a Daicel chiralcel
column (Φ 0.46 × 25 cm).
g
c
c
b
i
a
b
e
Ru
f
Cl
h
OCH2CH3
O
O
d
a
a
3. Results and discussion
N
S
H2N
Si
O
Si CH2CH2 Si
a
Ph
Ph
h
3.1. Characterization of the heterogeneous catalyst 3
b
h
FT-IR spectra of 2 and catalyst 3 (see SI in Figure S1). Showed
20 that both 2 and 3 exhibited the characteristic bands of the
organosilicate materials around 3443, 1627 and 1098 cm−1 for
υ(O−H), δ(O−H) and υ(Si−O), respectively.[10] The relatively
weak bands between 3100−2800 cm−1 were assigned to the
asymmetric and symmetric stretching vibrations of the C−H
25 bonds. The peaks indicative of υ(Si−C) should appear at 1100
cm−1, however, they were difficult to be distinguished due to the
overlapping absorbance peaks from υ(Si−O).[11] The bands
between 1510−1450 cm−1 were attributed to the breathing
vibrations of the C=C bonds in the aromatic ring.[10] The intensity
30 of these peaks in catalyst 3 increased consistently relative to those
in 2, implying the coordination of [RuCl2(p-cymene)]2 occurs.
These observations suggested the incorporation of the chiral
CymeneRuArDPEN moiety within its organosilicate network.
2
d
g
c
Catalyst 3
i
f
g
e
200
150
100
50
0 ppm
Figure 2. Solid-state 13C CP/MAS NMR spectra of 2 and 3.
Ru 3d
CymeneRuTsDPEN
Catalyst 3
10000
8000
6000
4000
2000
0
5/2
C 1s
281.52
T2
T3
281.59
2
Catalyst 3
278
280
282
284
286
288
290
Electron Binding Energy (eV)
T1
55
Figure 3. XPS spectra of the homogeneous CymeneRuArDPEN and 3.
-90ppm
-20
-30
-40
-50
-60
-70
-80
Incorporation
of
well-defined
single-site
active
CymeneRuArDPEN center within its organosilicate network of 3
could be proven by solid-state 13C cross-polarization (CP)/magic
35 Figure 1. Solid-state 29Si CP/MAS NMR spectra of 2 and 3.
60 angle spinning (MAS) NMR spectroscopy. As shown in Figure 2,
both 2 and catalyst 3 produced strongly characteristic carbon
signals of -SiCH2 groups at ~5 ppm that were ascribed their
ethylene-bridged silica embedded within their organosilicate
networks. The carbon signals at ~70 ppm and ~129 ppm were
65 corresponded to carbon atoms of the –NCHPh groups and of the
As shown in Figure 1, the 29Si magic angle spinning (MAS)
NMR spectra disclosed that both 2 and catalyst 3 presented one
group of exclusive T signals that were derived from organosilica,
suggesting that all Si species were covalently attached to carbon
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Green Chemistry
Page 4 of 8
–C6H5 groups in ArDPEN moiety, respectively. Peaks between
dimensional-hexagonal pore structure (p6mm) observed in
ArDPEN-PMO (2) could be retained.[8a] DSOiIm: 1i0la.1r0ly3V,9i/eCwb5oAGtrhtCic0let0hO4en7l9inAe
nitrogen adsorption-desorption isotherms (Figure 5) also
exhibited the typical IV type isotherms with H1 hysteresis loop
35 and a visible step at P/P0 = 0.50-0.90, corresponding to capillary
condensation of nitrogen in mesopores. Their structural
parameters were listed in Table that were inserted in Figure 4.
The TEM morphology (see SI in Figure S3) further confirmed
that catalyst 3 possessed the ordered mesostructure with the
40 dimensional-hexagonal arrangements.
100 and 75 ppm in the spectrum of 3 were assigned to the carbon
atoms of the aromatic ring in p-cymene moiety, and peaks at ~24
and ~20 ppm in the spectrum of 3 are attributed to the carbon
atom of the CH3 and CH groups attached to the aromatic ring in
p-cymene moiety. These peaks were absent in the spectrum of 2,
suggesting the formation of the CymeneRuArDPEN functionality
as single-site center in catalyst 3. These chemical shifts of
catalyst 3 were similar to those of its homogeneous counterpart
5
10 CymeneRuTsDPEN,[9a] confirming that they had the same well-
defined single-site active species. The XPS investigation (Figure
3) further testified both had similar electronic environments,
where catalyst 3 and its counterpart showed the similar Ru 3d5/2
electron binding energy (281.52 eV for its homogeneous
15 counterpart versus 281.59 eV for catalyst 3) that were obviously
different from that of their parent [RuCl2(p-cymene)]2 (see SI in
Figure S2). In addition, the peaks around 16 and 58 ppm should
be attributed to the nonhydrolyzed ethoxy groups (CH3CH2O-)
that often appeared in the CP MAS spectra.[14]
3.2. Catalytic performance of the heterogeneous catalyst
3.2.1. Catalytic properties
Based on the idea of one-pot relay enantioselective reduction-
isomerization of β-trifluoromethylated-α,β-unsaturated ketones,
45 two single-step model reactions, the enantioselective reduction of
4,4,4-trifluoro-1,3-diphenylbut-2-enone to (R)-4,4,4-trifluoro-1,3-
diphenylbut-2-enol catalyzed by 3 and the isomerization of (R)-
4,4,4-trifluoro-1,3-diphenylbut-2-enol to (R)-4,4,4-trifluoro-1,3-
diphenylbutan-1-one catalyzed by [RuCl2(PPh3)3], were
50 investigated separately. In the case of first-step enantioselective
reduction, the asymmetric reaction catalyzed by 3 was screened
through the use of HCOONa as a hydrogen resource and H2O as a
solvent that was inspired by the works of Xiao and Deng on
asymmetric transfer hydrogenation.[15] The result showed that the
55 enantioselective reduction of 4,4,4-trifluoro-1,3-diphenylbut-2-
enone gave (R)-4,4,4-trifluoro-1,3-diphenylbut-2-enol with 96%
yield and 97% ee. Such an ee value was comparable to that of its
homogeneous counterpart, even that obtained with HCO2H-NEt3
azeotropic mixture as a hydrogen source and solvent.[5, 8f] Notably,
60 water as a solvent is greener than that obtained in HCO2H-NEt3
reaction system. In the case of second-step isomerization using
6000
Table: Structural parameters
Material SBET (m2/g) Dp (nm) Vp (cm3/g)
5000
2
3
562
419
5.2
4.8
0.60
0.57
4000
3000
2000
1000
0
Catalyst 3
2
1
2
3
4
5
2 Theta/degree
20
Figure 4. Small-angle powder XRD patterns of 2 and 3.
H2O as
catalyzed by [RuCl2(PPh3)3] did not occur from (R)-4,4,4-
trifluoro-1,3-diphenylbut-2-enol to (R)-4,4,4-trifluoro-1,3-
65 diphenylbutan-1-one although various traditional reaction
conditions had been screened. To our delight, under
nontraditional microwave irradiation, this single-step
a solvent, however, the single-step isomerization
400
2
350
a
Catalyst 3
300
isomerization could be completed rapidly within 15 minute, in
which the quantitative yield and the retaining ee value of (R)-
70 4,4,4-trifluoro-1,3-diphenylbutan-1-one could be obtained. Such
a high catalytic efficiency indicated the benefit of microwave-
assisted catalysis, which could boost greatly the reaction rate
from 2 hours to 15 minutes.[5] More importantly, by combining
both into one-pot relay process, the 3-catalyzed enantioselective
75 reduction followed by the [RuCl2(PPh3)3]-catalyzed isomerization,
still retained the same results as two single-step process (Entry 1
versus Entry 1 in brackets, Table 1).[5] It was worth mentioning
that this one-pot relay enantioselective reduction-isomerization of
4,4,4-trifluoro-1,3-diphenylbut-2-enone to (R)-4,4,4-trifluoro-1,3-
80 diphenylbutan-1-one was significantly better than that obtained
with the mixed homogeneous CymeneRuTsDPEN plus
[RuCl2(PPh3)3] because the mixed dual catalysts afforded a
mixture of the intermediate of (R)-4,4,4-trifluoro-1,3-
diphenylbut-2-enol (90% ee) and the target product of (R)-4,4,4-
85 trifluoro-1,3-diphenylbutan-1-one (75% ee) (the mole ratio of 59
to 41) (Entry 2, Table 1). This comparison demonstrated that the
250
200
150
100
0.0
0.2
0.4
0.6
0.8
1.0
Relative Pressure (P/P0)
Figure 5. Nitrogen adsorption-desorption isotherms of 2 and 3.
Their orderly mesostructures and well-defined pore
25 arrangements were also investigated using X-ray diffraction
(XRD), transmission electron microscopy (TEM), and nitrogen
adsorption–desorption technique. As shown in Figure 4, the
small-angle XRD patterns revealed that both 2 and catalyst 3
presented one similar intense d100 diffraction peak along with two
30 similar weak diffraction peaks (d110, d200), suggesting that the
4
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Page 5 of 8
Green Chemistry
d
two single-step reactions.
Data were obtained using the mixed
designed dual catalyst in relay reaction could overcome
efficiently the incompatible nature of dual organoruthenium
complexes.
e
View Article Online
DOI: 10.1039/C5GC00479A
homogeneous CymeneRuTsDPEN plus [RuCl2(PPh3)3] as catalysts. Data
a parallel CymeneRuArDPEN-SBA-15 (3')
plus[RuCl2(PPh3)3] as catalysts within 40 h plus 15 minute reaction time.
were obtained using
Table 1. One-pot enantioselective reduction-isomerization of β-
5 trifluoromethylated-α,β-unsaturated ketones.a
20
Having established an efficiently one-pot relay enantioselective
reduction-isomerization, we further investigated the general
applicability with a series of substituted substrates. As shown in
Table 1, in general, high yields and enantioselectivities of chiral
β-CF3-substituted saturated ketones could be obtained steadily. In
25 particular, relative to the single-step enantioselective reduction of
4,4,4-trifluoro-1,3-diphenylbut-2-enone to chiral intermediate
(R)-4,4,4-trifluoro-1,3-diphenylbut-2-enol catalyzed by catalyst 3
that were also performed and listed in the column 3 of Table 1,
these chiral β-CF3-substituted saturated ketones had very high
Alcohol
(5a-5r)
Ketone
(6a-6r)
Compound
(R1, R2)
Ent
ry
%es
%ee b
%Yield
%ee b
b
30 enantiospecificities (%es) [%es
= 100 (product ee)/(chiral
1
4a (Ph, Ph)
97(97)c 96 (92)
97(97)c 100
intermediate ee)], ranging from 95 to 100%,[5,16] confirming the
advantage of microwave-assisted catalysis. Furthermore, it was
found that the structures and electronic properties of substituents
on the aromatic rings at R1 or R2 did not affect the
35 enantiospecificity. Taking the reactions with substrates bearing
phenyl groups at R2 as examples, we found that the asymmetric
reactions with various electron-withdrawing and -donating
substituents on the aryl moiety at R1 were equally efficient
(Entries 4–10). Moreover, the reactions with both substrates
40 bearing aromatic rings at R1 and R2 were enantioselective toward
the target products, in which two representative examples with
high enantiospecificities could be obtained (Entries 19-20, Table
1).
2 d
3 e
4
4a (Ph, Ph)
90
93
94
95
96
95
95
94
95
90
91
94
95
90
94
93
92
91
93
41 (29)
88 (76)
96 (89)
97 (91)
95 (90)
94 (88)
97 (91)
96 (91)
92 (85)
97 (92)
96 (91)
95 (89)
95 (87)
92 (89)
95 (91)
96 (92)
95 (90)
95 (91)
94 (89)
75
92
92
95
94
95
93
93
93
88
88
94
90
90
93
93
92
91
90
83
4a (Ph, Ph)
99
4b (p-FPh, Ph)
4c (p-ClPh, Ph)
4d (p-BrPh, Ph)
4e (m-BrPh, Ph)
4f (p-CF3Ph, Ph)
4g (p-MePh, Ph)
4h (p-MeOPh, Ph)
4i (Me, Ph)
98
5
100
98
6
7
100
98
8
3.2.2. Investigation of factors affecting catalytic performance
9
99
45
Besides the markedly enhanced reaction rate in the second
microwave-assisted [RuCl2(PPh3)3]-catalyzed isomerization-step
of the relay reaction, it was found that the first enantioselective
reduction-step catalyzed by 3 had also a relatively high catalytic
efficiency. In order to demonstrate the role of catalyst 3 in the
10
11
12
13
14
15
16
17
18
19
20
98
98
4j (Ph, p-ClPh)
4k (Ph, p-BrPh)
4l (Ph, p-MePh)
4m (Ph, p-MeOPh)
4n (Ph, m-ClPh)
4o (Ph, m-BrPh)
4p (Ph, o-MeOPh)
4q (p-FPh, p-BrPh)
4r (p-BrPh, p-BrPh)
97
50 first-step enantioselective reduction of the relay reaction, the
single-step reaction from 4,4,4-trifluoro-1,3-diphenylbut-2-enone
to (R)-4,4,4-trifluoro-1,3-diphenylbut-2-enol catalyzed by 3 was
further investigated. It was found that the asymmetric reaction
could be completed within 17 h, which was slightly longer than
55 that obtained with homogeneous counterpart (15 h). This
phenomenon is rare in a generally heterogeneous catalytic system
since a heterogeneous catalysis often needs an obviously longer
reaction time than its corresponding homogeneous counterpart
due to slow diffusion of reactants and products. Thus, such a near
60 reaction time indicated that a positive hydrophobic effect
dominated its catalytic performance that was possibly attributed
to the hydrophobic nature of the PMO-type organosilicate
network in catalyst 3. In order to confirm this judgment, two
comparable analogs with the similar ordered mesostructures and
100
95
100
99
100
100
100
97
65 dimensional-hexagonal
ArDPEN-functionalized material (ArDPEN-SBA-15 (2')) and
CymeneRuArDPEN-functionalized material
(CymeneRuArDPEN-SBA-15 (3')), were prepared through the
use of the similar synthetic process.[8g] Differed from ethylene-
70 bridged units as their main networks of 2-3, the parallel analogs
2'-3' had Si-O-Si-linked units as their main networks. In this case,
we performed a parallel adsorption experiment to investigate their
arrangements,
SBA-15-supported
a Reaction conditions: catalyst 3 (29.1 mg, 3.0 μmol of Ru, based on ICP
analysis) or CymeneRuTsDPEN (1.91 mg, 3.0 μmol), β-
trifluoromethylated-α,β-unsaturated ketones (0.15 mmol), 2.0 mL of
10 water were added sequentially to a 5.0 mL of thick walled Pyrex tube.
The mixture was then stirred at room temperature (20 °C) for 17h. After
that, [RuCl2(PPh3)3] (2.77 mg, 3.0 μmol) was added and the mixture was
irradiated with 170 W for 15 minutes. bYields were determined by 1H-
NMR (data in bracket is isolated yield) and ee values were determined
15 chiral HPLC analysis (see SI in Figures S4-5, S7). c Data were obtained in
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Green Chemistry
Page 6 of 8
hydrophobic differences through the analyses of changes of
substrate’s concentrations, where the tested substrate of 4,4,4-
trifluoro-1,3-diphenylbut-2-enone, and equivalent 2 or 2' were
suspended 2.0 mL of water respectively. After stirring for 5.0
hours and filtrating, it was found that the mole ratio of 4,4,4-
trifluoro-1,3-diphenylbut-2-enone for 2'-to-2 in solution was 1.6 :
1, suggesting that 2 had a high hydrophobicity due to the high
concentration of 4,4,4-trifluoro-1,3-diphenylbut-2-enone in solid-
state relative to 2'. This observation demonstrated that the
10 organosilicate network of 2 had a stronger ability than the Si-O-
Si-linked silicate network of 2' to draw 4,4,4-trifluoro-1,3-
diphenylbut-2-enone into the catalytically activity center from
aqueous system, thereby accelerating reaction rates.[8a-c]
homogeneous CymeneRuTsDPEN. Reactions were carried out at
View Article Online
substrate-to-catalyst mole ratio of 100.
DOI: 10.1039/C5GC00479A
A further direct evidence to support this judgment came from a
20 kinetic investigation in the enantioselective reduction of 4,4,4-
trifluoro-1,3-diphenylbut-2-enone catalyzed by catalyst 3, its
silicate analog 3', and its homogeneous counterpart as shown in
Figure 6. It was found that the enantioselective reduction of
4,4,4-trifluoro-1,3-diphenylbut-2-enone catalyzed by catalyst 3
25 resulted in an initial activity obviously higher than that achieved
with its silicate analog 3' (the initial TOFs were 9.1 versus 4.7
molmol-1h-1), and slightly lower than that obtained with its
homogeneous counterpart (the initial TOFs were 9.1 versus 10.5
molmol-1h-1). Notably, the highly hydrophobic nature of PMO-
30 type catalyst 3 relative to that of SBA-15-type silicate analog 3'
was responsible for its fast reaction rate in the 3-catalyzed
enantioselective reduction.
5
100
80
3.2.3. Catalyst’s stability and recyclability
60
CymeneRuArTsDPEN
In addition to the realization of one-pot relay enantioselective
35 reduction-isomerization, another aim in the design of the
heterogeneous catalyst 3 is the ease of separation and ability of
the catalyst to retain its reactivity and enantioselectivity after
multiple recycling. As observed, the heterogeneous catalyst 3 is
easy to recover from the reaction system by simple centrifugation.
40 As shown in Table 2, in eight consecutive reactions, the the
heterogeneous catalyst 3 still produced (R)-4,4,4-trifluoro-1,3-
diphenylbut-2-enol with 91% yield and 90% ee in the
enantioselective reduction of 4,4,4-trifluoro-1,3-diphenylbut-2-
enone to (R)-4,4,4-trifluoro-1,3-diphenylbut-2-enol.
Catalyst 3
40
Inorganosilicate analog 3'
Ph
OH
Ph
O
20
0
HCOONa
H2O, 20 o
C
F3C
30
Ph
F3C
6
Ph
18
0
12
24
36
Raction time (h)
15 Figure 6. Comparison of the enantioselective reduction of 4,4,4-trifluoro-
1,3-diphenylbut-2-enone catalyzed by 3, its silicate analog 3', and the
45 Table 2. Reusability of catalyst 3 for enantioselective reduction of 4,4,4-trifluoro-1,3-diphenylbut-2-enone to (R)-4,4,4-trifluoro-1,3-diphenylbut-2-enol.a,b
Run time
Yield [%]
ee [%]
1
2
3
4
5
6
7
8
96
97
96
96
96
97
96
97
96
96
95
94
93
92
91
90
a Reaction conditions: catalyst 3 (291.0 mg, 0.030 mmol of Ru based on ICP analysis), 4,4,4-trifluoro-1,3-diphenylbut-2-enone (1.50 mmol), HCO2Na
(2.04 g, 30.0 mmol), 20.0 mL of water, reaction time (17 h). b Determined by chiral HPLC analysis (see SI in Figure S6).
overcoming incompatible nature of bimetal complexes
participated in one-pot process, which are an attractive in the
Conclusions
65 practical preparation of valuable chiral β-CF3-substituted
In conclusions, we develop an ethylene-bridged PMO-supported
saturated ketones in an environmentally friendly manner.
50 chiral ruthenium-functionalized heterogeneous catalyst 3. By
combining it and [RuCl2(PPh3)3] as dual catalysts, we realize
successfully an efficiently one-pot relay reduction-isomerization
Acknowledgements
We are grateful to China National Natural Science Foundation
(21402120), the Shanghai Sciences and Technologies
70 Development Fund (13ZR1458700), the Shanghai Municipal
Education Commission (14YZ074, 13CG48, Young Teacher
Training Project), Specialized Research Fund for the Doctoral
Program of Higher Education (20133127120006) for financial
supports.
of β-trifluoromethylated-α,β-unsaturated ketones to chiral β-CF3-
substituted saturated ketones in water. As presented in this study,
55 the hydrophobic nature of the heterogeneous catalyst 3 and the
benefit of microwave-assisted catalysis further promote the
catalytic performance. Furthermore, the heterogeneous catalyst 3
could be recovered easily and reused repeatedly eight times
without obvious effect on its reactivity in the enantioselective
60 reduction of 4,4,4-trifluoro-1,3-diphenylbut-2-enone to (R)-4,4,4-
trifluoro-1,3-diphenylbut-2-enol. The outcomes from the study
afford a practical approach for realization of one-pot reaction by
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View Article Online
DOI: 10.1039/C5GC00479A
A table of contents entry.
Combined rutheniumꢀfunctionalized organosilica and tris(triphenylphosphine)ruthenium as dual
catalysts enable oneꢀpot relay reductionꢀisomerizations of βꢀCF3ꢀsubstitutedꢀα,βꢀunsaturated
ketones to chiral βꢀCF3ꢀsubstituted saturated ketones.