Heterogeneous Rh and Rh/Ag bimetallic nanoparticle catalysts immobilized on chiral polymers

Article abstract of DOI:10.1039/c9sc02670c

The development of heterogeneous chiral catalysts has lagged far behind that of homogeneous chiral catalysts in spite of their advantages, such as environmental friendliness for a sustainable society. We describe herein novel heterogeneous chiral Rh and Rh/Ag bimetallic nanoparticle catalysts consisting of polystyrene-based polymers with chiral diene moieties. The catalysts enable high-to-excellent yields and enantioselectivities to be obtained in asymmetric 1,4-addition reactions of arylboronic acids with α,β-unsaturated carbonyl compounds such as ketones, esters, and amides, and in other asymmetric reactions. The catalysts could be readily recovered by simple filtration and reused; they could also be applied to continuous-flow synthesis. We also discuss the nature of possible reaction species based on XPS analysis.

Full text of DOI:10.1039/c9sc02670c

View Article Online
View Journal
Chemical
Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: H. Min, H.
Miyamura, T. Yasukawa and S. Kobayashi, Chem. Sci., 2019, DOI: 10.1039/C9SC02670C.
Volume
Number
9
1
This is an Accepted Manuscript, which has been through the
7
January 2018
Pages 1-268
Royal Society of Chemistry peer review process and has been
accepted for publication.
Chemical
Science
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
rsc.li/chemical-science
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 2041-6539
EDGE ARTICLE
Xinjing Tang et al.
Caged circular siRNAs for photomodulation of gene
expression in cells and mice
rsc.li/chemical-science

Please do not adjust margins
Page 1 of 8
Chemical Science
View Article Online
DOI: 10.1039/C9SC02670C
ARTICLE
Heterogeneous Rh and Rh/Ag Bimetallic Nanoparticle Catalysts
Immobilized on Chiral Polymer
Hyemin Min, Hiroyuki Miyamura, Tomohiro Yasukawa and Shū Kobayashi*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The Development of heterogeneous chiral catalysts has lagged far behind that of homogeneous chiral catalysts in spite of
their advantages, such as environmental friendliness toward
a sustainable society. We describe herein novel
heterogeneous chiral Rh and Rh/Ag bimetallic nanoparticle catalysts consisting of polystyrene-based polymers with chiral
diene moieties. The catalysts enable high-to-excellent yields and enantioselectivities to be obtained in asymmetric 1,4-
addition reactions of arylboronic acids with ,-unsaturated carbonyl compounds such as ketones, esters, and amides,
and in other asymmetric reactions. The catalysts could be readily recovered by simple filtration and reused; they could also
be applied to continuous-flow synthesis. We also discuss the nature of possible reaction species based on XPS analysis.
intermolecular cyclopropane synthesis.13 In both cases,
however, only moderate enantioselectivities were observed,
and the development of heterogeneous chiral NP catalysts
with chiral supports for asymmetric C–C bond-forming
reactions that show high enantioselectivity is still desired.14
Since our initial study in 2012, we have reported on
Introduction
Catalytic asymmetric C–C bond-forming reactions provide
among the most efficient protocols for preparing optically
active compounds. While much progress has been made with
homogeneous chiral complexes as catalysts, the development
of heterogeneous chiral catalysts has lagged far behind in spite
of their advantages, such as environmental friendliness toward
a sustainable society.1 A general method for the preparation of
heterogeneous chiral catalysts involves formation of metal–
ligand complexes from supported/immobilized chiral ligands
and metal sources.2-5 However, these metal–ligand complexes
are often unstable, and metal leaching and decomposition of
ligands sometimes occur.5,6 The use of chiral metal
nanoparticles (NPs) can address these issues because of their
high activity/selectivity as well as their robustness.7-9 Indeed,
some metal NP catalysts immobilized on achiral supports, such
as metal oxides and activated carbon, with externally added
chiral modifiers have been reported for some asymmetric
reactions.10,11 In these cases, unfortunately, collapse of the
chiral reaction environments can easily occur and recovery of
chiral ligands is difficult. To overcome these problems, a few
catalysts in which metal NPs were immobilized on chiral
supports were reported. Glorius and coworkers synthesized Pd
NPs supported on Fe3O4 that contained chiral N-heterocyclic
carbene moieties, and this catalyst was applied to asymmetric
allylation of 4-nitrobenzaldehyde with allyltributyltin.12 Toste,
Somorjai, and coworkers reported Au NPs in a chiral self-
assembled monolayer as an efficient catalyst for
asymmetric 1,4-addition reactions of arylboronic acids to ,-
unsaturated carbonyl compounds, which constitute one of the
most useful methods for the preparation of chiral aryl-
substituted compounds15-17 using Rh/Ag bimetallic NP catalysts
with externally added binap or chiral diene ligands. Excellent
yields and outstanding enantioselectivities were observed,
especially with amide-substituted chiral diene ligands, without
metal leaching.18-23 Recovery and reuse of these catalysts was
possible because of their robustness; however, in every
reaction for the recovery and reuse, the chiral ligand had to be
externally added. Moreover, in a continuous-flow reaction, the
chiral ligand must flow together with substrates.
a.Department of Chemistry, School of Science, The Uiversity of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
† Footnotes relating to the title and/or authors should appear here.
Electronic
Supplementary
Information
(ESI)
available:
See
Scheme 1 Concept scheme for this work
DOI: 10.1039/x0xx00000x
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 2 of 8
ARTICLE
Journal Name
Table 1 Effect of the amount of ligand incorporation
Herein, we describe novel heterogeneous chiral Rh and Rh/Ag
bimetallic NP catalysts consisting of polystyrene-based
polymers with chiral diene moieties (Scheme 1). The catalysts
successfully promoted asymmetric 1,4-addition reactions of
View Article Online
DOI: 10.1039/C9SC02670C
arylboronic acid with
,-unsaturated carbonyl compounds
and other asymmetric reactions. The catalysts could be readily
recovered by simple filtration and reused, and further applied
to continuous-flow synthesis.
Results and discussion
Preparation of polymers and catalysts
Entry
Cat.
2a
2b
2c
X/S/L (Target)
7:2:1
Yield (%)
Eea (%)
97
98
Chiral polymer
1 was prepared by copolymerization of styrene,
1
2
3
79
98
98
trimethoxysilylstyrene (a cross-linking moiety),24,25 and a chiral
diene monomer, according to Scheme 2(a). By using
6:2:2
5:2:3
98
copolymer 1
and carbon black (CB) as a second support,26,27 Rh
a Determined by HPLC analysis.
and Rh/Ag bimetallic NP catalysts were prepared as shown in
Scheme 2(b). Rh or Rh/Ag bimetallic NPs were formed from
reduction with NaBH4, and then cross-linking was conducted
by heating under basic conditions in a sol-gel process. A
second reduction with NaBH4 was conducted to increase the
activity of the catalyst in some cases.18 STEM and EDX mapping
experiments showed that NPs of 4 nm average size were
formed and, in the case of Rh/Ag, an alloyed conformation was
confirmed, while the ratios of Rh and Ag were random,
depending on NPs (see the Electronic Supplementary
Information [ESI], Figures S1-S5). In this chiral ligand-
immobilized organic–inorganic hybrid CB Rh NP catalyst
First, we prepared catalysts 2a, 2b, and 2c containing different
amounts of the chiral diene ligand moiety while maintaining
the amount of the cross-linking moiety (trimethoxysilyl group).
1
The ratios of the monomer moieties were determined by H
NMR analysis, and almost the same amount of the ligand
moiety as the target amount was immobilized. Actual Rh
loadings were also close to the target loadings of Rh (0.2
mmol/g). The activity of the LIHBCB-Rh catalysts (2a
2c) was estimated in the 1,4-addition of phenylboronic acid
4a) to 2-cyclohexenone (3a) (Table 1). When around 10%
, 2b, and
(
(mole fraction) of the ligand monomer moiety (L) was
immobilized (2a), an excellent enantioselectivity was obtained,
but with a yield of 79% (Table 1, entry 1). When the ratio of L
in the polymer was increased to 20% (2b), the yield was
improved and high ee was maintained (entry 2); the same
(LIHBCB-Rh (
interactions from abundant
2
)), metal NPs were stabilized by multiple weak
-electrons of the benzene rings,

and these interactions meant that active but stable metal NP
catalysts could be realized.28 Actual loadings of Rh, determined
by Inductively coupled plasma atomic emission spectroscopy
(ICP-AES) analyses, were close to the target loadings.
result was observed with a further increased ratio of L (2c
)
(entry 3). Thus, an excess amount of L against Rh was required
to achieve a high yield. On the other hand, excellent
enantioselectivities were observed in all cases. Based on these
results, the polymer that was used in catalyst 2b was used for
further optimizations.
Scheme 2 Preparation of chiral polymer and catalyst
Optimization of catalyst and reaction conditions with α,β-
unsaturated acyclic ketone substrate
LIHBCB-Rh (2b) showed good activity in the reaction with α,β-
unsaturated cyclic ketone substrate 3a. We then applied this
catalyst to the
,-unsaturated acyclic ketone substrate
benzalacetone (3b) (Table 2).
In the reaction between benzalacetone
(3b) and 4-
methoxyphenylboronic acid (4b) under the same conditions,
the desired product was obtained in 52% yield with excellent
enantioselectivity (Table 2, entry 1). Although no improvement
of the yield was observed using 2 mol% catalyst (entry 2), a
slight increase of the yield was obtained using 2 equivalents of
4b (entry 3). In our previous report, Rh/Ag bimetallic NP
catalysts showed higher activity than Rh NP catalysts because
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 8
Chemical Science
Please do not adjust margins
Journal Name
ARTICLE
Table 2 Optimization of the reaction with α,β-unsaturated acyclic ketone
Table 3 Substrate scope of the reaction with α,β-unsaturated carbonyl compounds
View Article Online
DOI: 10.1039/C9SC02670C
Entry
1
2
3
4
5
6
7
8
3
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
4
Conditionsa
Yield (%)
98
95
94
96
95
89
91
89
92
88
93
94
90
87
quant.
91
63
73
90
90
64
70
71
87
85
Eeb (%)
98
98
97
97
97
98
98
98
98
96
91
97
96
97
97
98
94
94
98
98
87
93
93
94
93
99
4a
4a
4b
4c
4d
4e
4f
4g
4h
4b
4a
4a
4a
4a
4a
4c
4c
4c
4a
4a
4b
4g
4a
4i
A
B
A
A
A
A
C
Entry
1
Catalyst (2)
Yield (%)
52
Eea (%)
96
2b
3c
4
5
6
7c
LIHBCB-Rh (2b)
53
64
55
42
68
88
96
96
95
95
96
96
LIHBCB-Rh/Ag (1:1) (2d)
LIHBCB-Rh/Ag (2:1) (2e)
LIHBCB-Rh/Ag (1:2) (2f)
LIHBCB-Rh/Ag (1:2) (2f)
C
C
9
10
11
12
13
14
15c
16c
17c
18c,d
19e
20e
21
22
23
24
25
26
B
B
B
B
B
B
B
B
B
B
B
D
D
D
B
B
B
b
c
a Determined by HPLC analysis. 2 mol% of 2b was used. 2 equivalents of 4-
methoxyphenylboronic acid (4b) were used.
of better dispersion of Rh NPs.18 Considering this result, we
prepared chiral diene-immobilized hybrid Rh-Ag bimetallic NP
catalysts with different ratios of Rh and Ag; LIHBCB-Rh/Ag (1:1)
3g
3g
3h
3h
3i
(2d), LIHBCB-Rh/Ag (2:1) (2e), and LIHBCB-Rh/Ag (1:2) (2f).
Among them, 2f showed the highest reactivity while
maintaining excellent enantioselectivity (entries 4, 5, and 6);
when 2 equivalents of 4b were used, high yield and excellent
enantioselectivity were obtained (entry 7).
3j
3k
3k
3l
3m
3n
3o
Substrate Scope for 1,4-addition of boronic acids to α,β-
unsaturated carbonyl compounds
4a
4g
We then surveyed the substrate scope of this asymmetric 1,4-
addition reaction (Table 3). First, the reaction of 3a with a
range of arylboronic acids including various substituents was
examined. With phenylboronic acid (4a), excellent yield and
enantioselectivity were obtained using Rh 2b (entry 1). Rh/Ag
bimetallic catalyst 2f also worked as well as catalyst 2b (entry
2). When para-, meta-, and ortho- methoxyphenylboronic
74
acids 4b–d were used, excellent results were obtained in all
cases (entries 3–5). With a phenyl group at the para-position
of phenylboronic acid (4e), satisfactory results were obtained
(entry 6). Next, the reactions with arylboronic acids having
electron-withdrawing groups such as trifluoromethyl (4f),
fluoro (4g), and acetoxy groups (4h) were examined. It was
found that these substrates were less active than arylboronic
acids having electron-donating groups; however, high yields
with excellent enantioselectivities were obtained by using a
slight excess of the arylboronic acids (entries 7–9). For further
less-active substrates such as 2-cyclopentenone (3d) and
acyclic ,-unsaturated ketones (3b, 3c, 3e and 3f), high yields
with excellent enantioselectivities were observed by using
Rh/Ag 2f (entries 10–14) instead of Rh 2b. We then optimized
less reactive unsaturated carbonyl compounds.29 Rh/Ag 2f also
showed good activity toward
3h, although 1 equivalent of K2CO3 was needed as an additive
(entries 15–18). Interestingly, high yield and excellent
enantioselectivity were obtained with ,-unsaturated amides
3i and 3j without any additive (entries 19 and 20). We also
tried cinnamaldehyde (3k) and 4-methyl substituted
,-unsaturated esters 3g and
a Conditions A: LIHBCB-Rh (2b, 1 mol% Rh), ArB(OH)2 (1.5 equiv); B: LIHBCB-Rh/Ag
(2f, 1 mol% Rh), ArB(OH)2 (2 equiv); C: LIHBCB-Rh (2b, 1 mol% Rh), ArB(OH)2 (2
equiv); D: LIHBCB-Rh/Ag (2d, 1 mol% Rh), ArB(OH)2 (2 equiv). Determined by
HPLC analysis. c 1 equiv of K2CO3 was used. d 3 mol% of 2f was used. e 2 mol% of
2f was used. f 3 equiv of 4a were used.
b
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 4 of 8
ARTICLE
Journal Name
Table 6 Hydrogen adsorption analysis
View Article Online
DOI: 10.1039/C9SC02670C
Table 4 Recovery and reuse of the catalyst a
Amount of adsorbed hydrogen gas
Catalyst
(cm3/g)
0.2413
0.0783
0.0206
0
HBCB Cat. (6)
Fresh 2f
Deactivated 2f (after 5th run)
Immobilized ligand + CB
In the 4th or 5th run, the yields decreased, but the
enantioselectivities remained high. We carefully analyzed the
reused catalysts; however, no significant aggregation or
damage was observed by STEM analysis (see ESI, Figures S6-
S7). We consider that the decreased yields might arise from
adsorbed contaminants generated during the reactions
(byproducts or co-products). We check the reaction profile in
the recovery/reuse experiments until 3rd run, and gradually
decreased reaction rates in the successive runs were observed,
while yields were reached >90% after 24 h reaction time in
each run (see ESI, Figure S18). It was probably derived from
decrease in available reaction sites due to remained
contaminants. Washing the catalyst in basic media (0.5 M-1 M
NaOH(aq.)) or acidic media (0.5 M HCl (aq.)) was conducted for
removal; however, no further improvement was obtained.
Another possibility for the reduced yield is decomposition of
the diene ligand during the reaction. To test this, we
conducted a number of control experiments (Table 5).
Result
3rd
86
98
90
1st
2nd
93
98
90
98
4th
76
98
87
98
5th
-
-
32
98
Yielda (%)
Eeb (%)
Yielda (%)
Eeb (%)
90
98
84
98
5aa
5ia
98
a Isolated yield. b Determined by HPLC analysis.
cinnamaldeyde (3l) as substrate, and it showed good yields
and enantioselectivities with various arylboronic acid (entries
21-23). To confirm further utility of this catalyst, the
preparation of natural product and drug precursors was
examined. Ester 5mi can be used as a precursor of various
anticancer and antimicrobial materials,30,31 and it was
successfully prepared by asymmetric 1,4-addition of 4-
methoxyphenylboronic acid (4i) to
,-unsaturated ester 3m
in 87% yield with 94% enantio selectivity (entry 24). Ester 5na
Catalyst 2f was stirred at 100 C in the presence of the solvent
,
for 96 h, which was the same as the total reaction time until
the 4th run in recovery/reuse experiments, and then both
substrates 3i and 4a were added. In this case, excellent yield
and ee of the desired product (5ia) were obtained, and the
possibility of ligand degradation through thermal
decomposition could be excluded (Table 5, entry 1). To
examine the effect of substrates in the reaction medium,
a precursor of (–)-indatraline, was also obtained in good yield
with high enantioselectivity (entry 25).32 Amide substrate 3o
reacted with 4-fluorophenylboronic acid (4g) to afford 5og, a
precursor of (–)-paroxetine, in good yield with excellent
enantioselectivity (entry 26).21,33
Recovery and reuse of the catalyst
catalyst 2f was heated at 100
96 h, followed by the addition of other substrates. In the case
of heating at 100 C with amide 3i, an excellent result was still
obtained (entry 2). We also conducted the heating treatment
with phenylboronic acid 4a; in this case, the desired product
C in the presence of 3i or 4a for
We next conducted catalyst recovery and reuse experiments.
The heterogeneous catalyst could be recovered by simple
filtration, and the recovered catalyst was used for the next run
after washing with toluene/H2O and drying in vacuo. Both
monometallic Rh catalyst (2b, for 5aa) and Rh/Ag bimetallic
catalyst (2f, for 5ia) were tested, and could be recovered and
reused 3-4 times without significant decrease in activity.

(5ia) was not obtained, probably because of the hydrolysis of
4a to benzene during the first 96 h (entry 3). On the other
hand, when a new portion of 4a was added after the same
heating treatment with 3i, a slight decrease in yield was
obtained; however, the desired product 5ia was obtained with
high enantioselectivity. It may be possible that decomposed
(or co-products of) arylboronic acid generated in the
asymmetric 1,4-addition reaction somehow deactivated the
catalysts in the recovery and reuse experiments.
Table 5. Control experiment
We also analyzed the amount of adsorbed hydrogen gas (H2) in
Addition after
Entry
Set-up
Yielda (%)
Eeb (%)
HBCB-Rh/Ag (1:2) (
the polymer, fresh 2f, and recovered 2f after the 5th run
(Table 6). Whereas catalyst
adsorbed 0.2413 cm3/g H2, fresh
2f adsorbed only 0.0783 cm3/g H2, even though the size of NPs
is smaller than (13 nm ( ) vs. 4 nm (2f)). This may be
6), prepared without a ligand component in
96 h
3i, 4a
4a
3h
3i, 4a
1
2
3
4
2f
Quant (92)
Quant (83)
No desired product
72 (74)
98
98
6
2f, 3i
2f, 4a
2f, 4a
97
6
6
explained by considering that certain amounts of ligand
coordinate to the surface of metal NPs competing with H2 in
a
b
Determined by GC analysis. The number in parenthesis is isolated yield.
Determined by HPLC analysis.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 8
Chemical Science
Please do not adjust margins
Journal Name
ARTICLE
Scheme 3 Possible mechanisms of heterogeneous metal nanoparticle catalysts
Scheme 4 Reaction with the mixture of Rh NPs and chiral ligand on different
supports
View Article Online
DOI: 10.1039/C9SC02670C
complexes or
a
small metal clusters coordinated with
immobilized ligands catalyzes the reaction as an active species,
which returns back to NPs after the reaction, and NPs act as a
reservoir for these small clusters; and (c)
a leached
homogeneous metal complex from nanoparticles works as an
active species. Hot filtration tests were conducted to
determine whether the reaction proceeded through
mechanism (c) by leached homogeneous complex (Figure 1).
The reaction profile was monitored by using a filtrate obtained
in the middle of a reaction. We conducted this test for both
cyclic (3a) and acyclic (3e) ketone substrates, and no increase
in yield was observed after removal of the catalyst in either of
the experiments; therefore, it was confirmed that this reaction
was catalyzed in a heterogeneous manner. ICP analysis of the
reaction medium revealed that trace amounts of Rh and Ag
were detected after the reaction of 3e (0.111% Rh, 0.035% Ag
(Rh detection limit: 0.045%, Ag detection limit: 0.007%)).
Based on the results of the hot filtration tests, we conclude
that leached Rh or Ag did not catalyze the reactions, and that
metal species in the catalysts that were not fully
immobilized/fixed were washed out during the reactions.
To confirm the importance of physical proximity between
metal NPs and chiral diene ligands, we prepared an
immobilized ligand on carbon black (see ESI, Scheme S3), and
the reaction was conducted together with a Rh/Cellulose
catalyst, which was an easily prepared and highly active
catalyst (Scheme 4).20 As a result, only a trace amount of the
product (5gc) was obtained. It confirms that this reaction
proceeds by ligand acceleration and the reaction hardly occurs
on the non-coordinated metal NPs. Also, physical proximity is
an important factor required to make highly active species. To
gather further information on the reaction mechanism and the
active species, we conducted XPS analysis of several states of
catalyst 2f: (A) fresh, (B) recovered during the reaction (1 h),
(C) after 1st run, and (D) after 5th run. HBCB-Rh/Ag (1:2)
2f. Interestingly, in the case of recovered 2f after the 5th run,
the amount of adsorbed H2 decreased further. As a control, we
also examined the H2 adsorption of an immobilized ligand
(containing carbon black, without metal NPs); no adsorption of
H2 was observed, so H2 would be adsorbed on metal NPs.
Although these results are indirect, they suggested that
contaminants not removed by washing gradually coordinated
to the surface of the metal NPs and accumulated during the
recovery and reuse of the catalyst.
Mechanistic Insight
There are broadly three categories of possible catalytically
active species in NP catalyst systems, as shown in Scheme
334,35: (a) a reaction occurs on the surface of metal NPs
coordinated with immobilized ligands; (b) a detached metal
Figure 1 Hot filtration test
catalyst (6) was also analyzed: (E) fresh and (F) after the
reaction using 2.5 mol% of externally added amide-substituted
chiral diene (Table 7).
In all data, Rh binding energy (BE) showed more distinct
differences compared with that of Ag (see ESI, Table S1), and
based on these results, we concluded the following. First,
lower Rh BE was obtained in fresh 2f (A) compared with that of
6
(E), and we supposed that this difference in Rh BE came from
coordination of the ligand to Rh NPs. Second, in the case of 2f
,
almost the same Rh BE was observed in the fresh catalyst (A)
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 6 of 8
ARTICLE
Journal Name
Table 7 Binding energy of Rha
Table 8 Asymmetric arylation of nitroolefin and imine compoundsa
DOI: 10.1039/C9SC02670C
View Article Online
2f
state
(A)
(B)
(C)
(D)
496.9
Rh (eV)
(3p 3/2)
497.0
497.4
496.9
6
Rh(OH)-diene
state
(7)
(E)
497.2
(F)
Entry
1
2
3
4
5
6
7
8
8
4
4g
4j
Yield (%)
84
Quant
69
93
98
63
50
53
61
Eeb (%)
88
92
98
88
86
82
98
99
98
97
98
97
Rh (eV)
(3p 3/2)
498.2
497.3
8a
8a
8a
8b
8c
8d
9a
9a
9b
9c
9d
9e
a
For 2f: (A) fresh, (B) recovered during the reaction (1 h), (C) after 1st run, (D)
4k
4c
4c
4c
4a
4g
4a
4a
4a
4a
after 5th run; for 6: (E) fresh, (F) after the reaction using 2.5 mol% of externally
added amide-substituted chiral diene.
and the recovered catalysts after the reactions (C and D), while
Rh BE of
added chiral diene (E and F). Moreover, a significant amount of
metal leaching was observed in the reaction with and the
externally added chiral diene ligand (see ESI, Scheme S5).
Although it is unclear whether this change in Rh BE of is due
6 was changed after the reaction using an externally
9
6
10
11
12
51
59
70
6
to metal leaching or changed states of Rh NPs, it was assumed
that more stable Rh species was generated and maintained in
the presence of the immobilized chiral diene ligand. Lastly, a
change in Rh BE was observed when the catalyst was
recovered during the reaction (B). For comparison, we
prepared Rh(OH)-diene complex (
ESI, Scheme S4), and confirmed that the Rh BE of
7
) adsorbed on carbon (see
was similar
7
to that in (B). We consider that the active species of this
reaction might be a species which has a similar electronic state
to hydroxyl-rhodium species; however, it is not defined
whether monometallic complex or oligomeric nanoclusters
formed at this stage. Based on the experiments described
above, it is feasible that detached Rh species from NPs
coordinate to the chiral diene ligand immobilized on the
polymer support, may be active for this asymmetric 1,4-
addition reaction. Since the XPS analysis indicted the same Rh
BE after use, the active species presumably returns to the NPs
after the reaction. From these results, catch-and-release
mechanism (b) may be more likely than reaction-on-surface
mechanism (a), but we cannot exclude the possibility of
mechanism (a).36
a
Solvent ratio: Tol/H2O (5:1) for nitroolefin (entries 1-6), Tol/H2O (8:1) for imine
b
c
(entries 7-12). Determined by HPLC analysis. 2 mol% 2d, 3 equivalents of
boronic acid (4) were used.
contain an electron-donating group or a heteroaromatic ring
were also reacted, and the desired products were obtained in
excellent yields with high enantioselectivities (entries 4 and 5).
Notably, even the aliphatic nitroolefin 8d could form the
desired 1,4-addition product in good yield with high
enantioselectivity (entry 6). On the other hand, in the
reactions of imine substrates, it was found that yields were a
little lower because of the relatively rapid hydrolysis of imines;
however, excellent enantioselectivities were obtained. 4-
Asymmetric arylation of nitroolefin and imine compounds
We next examined the ability of the current heterogeneous
chiral Rh/Ag bimetallic NP catalyst (2d) to mediate other
asymmetric reactions; to this end, we examined the
asymmetric arylation of nitroolefins and the asymmetric
arylation of imines (Table 8).
In the reaction of nitrostyrene (8a) with phenylboronic acid
bearing electron-withdrawing groups (4g and 4j), the desired
1,4-addition products were obtained in high-to-excellent yields
with high enantioselectivities (Table 8, entries 1 and 2). With 2-
methylphenylboronic acid, which has a sterically-hindered
structure, a good yield and excellent enantioselectivity were
obtained, although increased amounts of both catalyst and
boronic acid were needed (entry 3). Other nitroolefins that
Methyl-substituted tosyl imine
(
9a
)
reacted with
phenylboronic acid (4a) and 4-fluorophenylboronic acid (4g) to
afford the desired 1,2-addition products in 50% yield with 98%
ee (entry 7) and in 53% yield with 99% ee (entry 8),
respectively. In the reaction of 4-methoxy-substituted tosyl
imine (9b), the yield was slightly increased and the excellent
enantioselectivity was maintained (entry 9). The desired amine
products were also obtained with good yields and excellent
enantioselectivities from 2- or 1-naphthyl (9c or 9d) and 2-
thienyl substituted imine (9e) substrates (entries 10–12). It is
noted that chiral Rh/Ag bimetallic NP catalyst 2d worked well
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 8
Chemical Science
Please do not adjust margins
Journal Name
ARTICLE
Scheme 5 Application to flow system
There are no conflicts to declare.
View Article Online
DOI: 10.1039/C9SC02670C
Acknowledgements
The authors are grateful to Mr. Kohei Nishino for his
contribution to the initial stage of this work. This work was
supported in part by a Grant-in-Aid for Scientific Research
from JSPS, The University of Tokyo, and MEXT (Japan), JST. We
also thank Mr. Noriaki Kuramitsu (The University of Tokyo) and
Mr. Tei Maki (JEOL, The University of Tokyo) for STEM and EDX
analysis.
for both asymmetric arylation of nitroolefins and asymmetric
arylation of imines. Given that nitro groups can be readily
reduced to the corresponding amines, two types of optically
active amine derivatives can be prepared using these methods.
Notes and references
Application to flow system
1
K. Ding and Y. Uozumi, Handbook of Asymmetric
Heterogeneous Catalysis; Wiley-VCH, Weinheim, 2008.
M. Heitbaum, F. Glorius and I. Escher, Angew. Chem. Int. Ed.
2006, 45, 4732-4762.
B. Pugin and H. U. Blaser, Top. Catal. 2010, 53, 953-962.
T. Sawano, P. F. Ji, A. R. McIsaac, Z. K. Lin, C. W. Abney and
Finally, this catalyst system was applied to a continuous-flow
system (Scheme 5). Flow reactions have advantages over batch
reactions in terms of environmental friendliness, efficiency,
and safety.37 Among several flow reactions, those using
heterogeneous catalysts are very efficient because a product
can be obtained simply by passing starting materials through a
column filled with the catalyst and, at the same time, the pro
duct and the catalyst can be separated.38 In spite of the
potential utility of this system, applicable heterogeneous
catalysts, particularly heterogeneous chiral catalysts, are
limited.
2
3
4
W. B. Lin, Chem. Sci. 2015,
S. H bner, J. G. de Vries and V. Farina, Adv. Synth. Catal.
2016, 358, 3-25.
6, 7163-7168.
5
6
ü
N. E. Leadbeater and M. Marco, Chem. Rev. 2002, 102, 3217-
3274.
7
8
G. Schmid, Chem. Rev. 1992, 92, 1709-1727.
D. Astruc, Nanoparticles and Catalysis; Wiley-VCH Verlag
GmbH & Co.: KGaA, 2008.
Rh/Ag 2f was mixed with celite and the mixture was packed in
9
H. Cong and J. A. Porco, ACS Catal. 2012, 2, 65-70.
a column.
,-Unsaturated ketone 3a in toluene and an
10 Y. Orito, S. Imai, S. Niwa and G. H. Nguyen, J. Syn. Org. Chem.
Jpn. 1979, 37, 173-174.
aqueous solution of phenylboronic acid 4a were flowed into
the column using separate pumps. To prevent evaporation of 11 T. Yasukawa, H. Miyamura and S. Kobayashi, Chem. Soc. Rev.
2014, 43, 1450-1461.
the solvents in the column, back-pressure was maintained. As
a result, the desired product 5aa was obtained in >90% yield
with 98% ee for 17 h (productivity (STY): 348 g/d.L).
12 K. V. S. Ranganath, A. H. Schafer and F. Glorius,
ChemCatChem 2011, 3, 1889-1891.
13 E. Gross, J. H. Liu, S. Alayoglu, M. A. Marcus, S. C. Fakra, F. D.
Toste and G. A. Somorjai, J. Am. Chem. Soc. 2013, 135, 3881-
3886.
Conclusions
14 In 2016, Hua et al. reported asymmetric oxidation reactions
using bimetallic nanoclusters supported on chiral-substituted
poly-N-vinylpyrrolidinones with good to excellent
enantioselectivities. B. Hao, M. J. Gunaratna, M. Zhang, S.
Weerasekara, S. N. Seiwald, V. T. Nguyen, A. Meier and D. H.
Hua, J. Am. Chem. Soc. 2016, 138, 16839-1848.
15 T. Hayashi and K. Yamasaki, Chem. Rev. 2003, 103, 2829-
2844.
We have developed heterogeneous chiral Rh and Rh/Ag
bimetallic NP catalysts immobilized on
a chiral diene-
containing polymer. The catalysts showed high-to-excellent
yields and enantioselectivities in asymmetric 1,4-addition
reactions of arylboronic acids with
,-unsaturated carbonyl
compounds such as ketones, esters, and amides. The catalysts
could be recovered and reused without external addition of
other portions of the chiral diene ligand while maintaining
their activities. We also presented a reaction mechanism and
discussed the nature of the active species involved in the
heterogeneous asymmetric catalysis. Furthermore, the catalyst
could be applied to other asymmetric reactions, asymmetric
arylation of nitroolefins and imines, and a continuous-flow
system. To our knowledge, this is the first example of a
catalyst in which a chiral ligand is immobilized together with
metal NPs on the same support that shows both high yields
and enantioselectivities in asymmetric C–C bond-formation
reactions.
16 P. Tian, H. Q. Dong and G. Q. Lin, ACS Catal. 2012, 2, 95-119.
17 K. Okamoto, T. Hayashi and V. H. Rawal, Org. Lett. 2008, 10
,
4387-4389.
18 T. Yasukawa, H. Miyamura and S. Kobayashi, S. J. Am. Chem.
Soc. 2012, 134, 16963-16966.
19 T. Yasukawa, A. Suzuki, H. Miyamura, K. Nishino and S.
Kobayashi, J. Am. Chem. Soc. 2015, 137, 6616-6623.
20 T. Yasukawa, H. Miyamura and S. Kobayashi, Chem. Sci. 2015,
6
, 6224-6229.
21 T. Yasukawa, Y. Saito, H. Miyamura and S. Kobayashi, Angew.
Chem. Int. Ed. 2016, 55, 8058-8061.
22 T. Yasukawa, T. Kuremoto, H. Miyamura and S. Kobayashi,
Org. Lett. 2016, 18, 2716-2718.
23 H. Miyamura, K. Nishino, T. Yasukawa and S. Kobayashi,
Chem. Sci. 2017, 8, 8362-8372.
24 T. Matsumoto, M. Ueno, N. Wang and S. Kobayashi, Chem. -
Asian J. 2008, , 239-243.
3
25 H. Miyamura, K. Maehata and S. Kobayashi, Chem. Commun.
2010, 46, 8052-8054.
Conflicts of interest
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 8 of 8
ARTICLE
Journal Name
26 W. -J. Yoo, H. Miyamura and S. Kobayashi, J. Am. Chem. Soc.
2011, 133, 3095-3101.
View Article Online
DOI: 10.1039/C9SC02670C
27 H. Miyamura, A. Sonoyama, D. Hyrapetyan and S. Kobayashi.
Angew. Chem. Int. Ed. 2015, 54, 10559-10563.
28 S. Kobayashi and H. Miyamura, Aldrichim. Acta 2013, 46, 3-
19.
29 We monitored profiles of the reactions with α,β-unsaturated
ketone, ester, amide and aldehyde substrates under the
same conditions. As a result, slower reaction rate (ester,
aldehyde) or lower final yield (amide) was observed, and we
optimized reaction conditions for each substrates (see ESI,
Table S2 and Figure S17).
30 S. Afewerki, P. Breistein, K. Pirttila, L. Deiana, P. Dziedzic, I.
Ibrahem and A. Cordova, Chem. -Eur. J. 2011, 17, 8784-8788.
31 J. Q. Li, X. Quan and P. G. Andersson, Chem. -Eur. J. 2012, 18
,
10609-10616.
32 W. T. Wei, J. Y. Yeh, T. S. Kuo and H. L. Wu, Chem. -Eur. J.
2011, 17, 11405-11409.
33 M. S. Yu, I. Lantos, Z. Q. Peng, J. Yu and T. Cacchio,
Tetrahedron Lett. 2000, 41, 5647-5651.
34 T. Yasukawa, H. Miyamura and S. Kobayashi, ACS Catal. 2016,
6
, 7979-7988.
35 V. P. Ananikov and I. P. Beletskaya, Organometallics 2012,
31, 1595-1604.
36 Preparation of small nanoclusters on same polymer support
was tried by lowering the target loading, but still colonies of
nanoparticles were formed (see ESI, Figure S11).
37 S. Kobayashi, Chem. -Asian J. 2016, 11, 425-436.
38 T. Tsubogo, H. Oyamada and S. Kobayashi, Nature 2015, 520
,
329-332.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins