A heterogeneous layered bifunctional catalyst for the integration of aerobic oxidation and asymmetric C-C bond formation

Article abstract of DOI:10.1039/c3cc46204h

The design and synthesis of a heterogeneous bifunctional chiral catalyst for the sequential aerobic oxidation-asymmetric Michael reactions between primary allylic alcohols and dibenzyl malonate are described. Interestingly, we found that layering bimetallic nanoparticles over the organocatalyst, within the chiral composite material, is crucial for catalytic activity.

Full text of DOI:10.1039/c3cc46204h

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A heterogeneous layered bifunctional catalyst for the
integration of aerobic oxidation and asymmetric
C–C bond formation†
Cite this: Chem. Commun., 2013,
49, 9917
Received 13th August 2013,
Accepted 3rd September 2013
Hiroyuki Miyamura, Gerald C. Y. Choo, Tomohiro Yasukawa, Woo-Jin Yoo and
Shu Kobayashi*
DOI: 10.1039/c3cc46204h
www.rsc.org/chemcomm
The design and synthesis of a heterogeneous bifunctional chiral catalyst We were interested in whether metal NPs could be immobilized
for the sequential aerobic oxidation–asymmetric Michael reactions together with a chiral moiety to form a heterogeneous bifunctional
between primary allylic alcohols and dibenzyl malonate are described. chiral catalyst that could be used in an asymmetric TOP with oxygen
Interestingly, we found that layering bimetallic nanoparticles over as the terminal oxidant. The concept of bifunctional catalysis is best
the organocatalyst, within the chiral composite material, is crucial exemplified in nature with multienzyme complexes, where the spatial
for catalytic activity.
arrangement of enzymes within such complexes is optimized such
that a neighboring enzyme within the same complex preferentially
The in situ generation and elaboration of highly reactive/unstable transforms the intermediate produced by another enzyme.16–18 We
compounds in reactions is a crucial concept in organic synthesis. This envisioned a heterogeneous bifunctional chiral catalyst that would
concept allows chemists to take advantage of the high chemical mimic enzymes by providing a confined environment19 for catalysis to
reactivity of the compounds when isolation of the desired intermediates take place, thereby offering the advantage of rate enhancement for the
is impossible.1 Thus, methods to carry out two or more transformations asymmetric TOP. In addition, the facile separation of catalysts from
in one reaction pot are highly desirable. A well-established method is the product and the prevention of probable undesired interactions
the tandem oxidation process (TOP)2 and recently, one-pot organo- between the two catalysts in a completely homogeneous system are
catalytic reactions that introduce chirality into the final product are possible via immobilization (Fig. 1).20–22
gaining much attention.3–5 On the other hand, heterogeneous catalysts
have attracted much attention in the field of catalysis due to the
advantages that they offer, such as ease of handling, and their industrial
applications.6 To the best of our knowledge, there are no reported
examples of a heterogeneous bifunctional chiral catalyst for an asym-
metric TOP with molecular oxygen as the terminal oxidant.
Our group has established a method for immobilizing metal
nanoparticles (NPs) onto a polymer support and we have already
demonstrated that these polymer-incarcerated (PI) metal catalysts
Fig. 1 Preventing undesired interactions between catalysts.
effectively facilitate aerobic oxidations, reductions, coupling reac-
tions and other C–C bond formations with little to no leaching of
Herein, we report a novel layered heterogeneous bifunctional
metal from the polymer support.7–9 Furthermore, the activity of the chiral catalyst consisting of metal NPs and a chiral Jørgensen–
PI metal catalysts was shown to be very high and comparable or, in Hayashi-type organocatalyst (OC) supported on different polymers.
some cases, superior to that of the original homogeneous metal This catalyst could be applied to the integration of aerobic oxidation
catalysts when small metal NPs were formed and immobilized.10,11 of primary allylic alcohols to the corresponding a,b-unsaturated
Recently, we succeeded in catalyzing several TOPs with oxygen as the aldehydes and asymmetric 1,4-Michael addition of a malonate to
terminal oxidant.12–15 In these TOPs, the reaction intermediate was these newly generated aldehydes.
either a ketone or an aldehyde generated in situ, via the aerobic
We began the investigation by screening several Jørgensen–
oxidation of the corresponding secondary or primary alcohol. Hayashi-type OCs and co-monomers23 and immobilizing the most
suitable one (1) with acrylamides via suspension copolymerization
Department of Chemistry, School of Science, The University of Tokyo, Hongo,
with optimized amounts of N-tert-butylacrylamide (3), N,N0-methyl-
Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
enebismethacrylamide (4) and dimethyl 2,20-azobis(2-methyl-
† Electronic supplementary information (ESI) available: General procedures, materials,
propionate) (V-601 initiator) to form polymer beads 5 containing
and instrumentation; synthesis, characterization and relevant spectra/charts. See DOI:
10.1039/c3cc46204h
the OCs (Fig. 2a).23 The beads exhibited activity for the
c
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Chem. Commun., 2013, 49, 9917--9919 9917

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Table 1 Optimization of conditions for the asymmetric TOP
Entry Catalyst (mol%)
Conv.a (%) Yieldb (%) eec (%)
1
2
3
4
6 (Au = 1, Pd = 1, OC = 5)
7 (Au = 1, Pd = 1, OC = 5)
PI/CB–Au/Pd (Au, Pd = 1) & 1 (5) 39
6 (Au = 2, Pd = 2, OC = 10) 97
76
nr
nd
—
nd
75
91
—
85
90
a
b
Conversion of 9 based on 1H NMR analysis (nr = no reaction).
Isolated yield (nd = not determined). Determined by chiral HPLC
c
analysis after oxidation to the corresponding methyl ester.
Fig. 2 Fabrication procedure for (a) polymer-supported OC (5); (b) PI(Au/Pd)–
CO catalyst (6); (c) IOC/PI/CB–Au/Pd catalyst (7). Blue represents the layer
containing OC 1 while red represents the layer containing Au–Pd alloy NPs.
would then undergo an asymmetric 1,4-Michael addition, facilitated
by OC-containing polymer beads 5, to afford the desired asymmetric
adduct. Our initial screening revealed that only PI(Au/Pd)–CO 6
asymmetric Michael reaction between trans-cinnamaldehyde demonstrated catalytic activity and satisfactory conversion of dibenzyl
and dibenzyl malonate, affording the desired product in quan- malonate was observed (entry 1). It was a challenge to determine the
titative yield with >90% ee under our optimized reaction con- best reaction conditions for the asymmetric TOP, as some reaction
ditions.23 We chose acrylamides as co-monomers after taking conditions that are suitable for the first step may not be so for the
into account commercial availability, hydrophilicity and ease of second step. Fortunately, having water as a co-solvent did not pose
handling of the resulting beads.23
any problem for the aerobic oxidation and in fact, might have
We then proceeded to incorporate Au–Pd bimetallic alloy NPs promoted the aerobic oxidation.15,24,25 Interestingly, we observed that
with polymer beads 5 to form a heterogeneous bifunctional chiral the aerobic oxidation of the allylic alcohols proceeded smoothly
catalyst. In one of our previous TOP reports, PI Au–Pd alloy NPs with even in the presence of acetic acid that is required to accelerate
carbon black as a secondary support (PI/CB–Au/Pd) demonstrated the OC-catalyzed 1,4-Michael addition;26 aerobic oxidation is
high activity for the aerobic oxidation of secondary allylic alcohols to usually difficult under acidic conditions.27
the corresponding a,b-unsaturated ketones,14 and we expected
On the other hand, the reaction did not proceed with catalyst 7
similar activity for primary allylic alcohols. We examined the effect (entry 2), suggesting that the layering order of catalysts within the
of the ratio of Au : Pd on the aerobic oxidation of cinnamyl alcohol to composite structure affects its ability to facilitate this tandem
trans-cinnamaldehyde and determined that a 1 : 1 ratio was the best, reaction. As a control, we also performed the reaction using the
and that Au or Pd alone was not efficient.23 The styrene-based PI/CB–Au/Pd heterogeneous catalyst and the homogeneous OC 1
copolymer with cross-linking moieties 2 that is used during the (entry 3), and we found that the conversion was poor and the
fabrication of PI heterogeneous catalysts10,12–14 was employed for the enantioselectivity decreased slightly.
incorporation of Au–Pd alloy NPs and beads 5. Polymer beads 5 were
After further optimization using catalyst 6, we adopted
added to polymer 2, followed by the addition of Au and Pd salts for the conditions shown in entry 4 of Table 1 as the optimized
the formation of bimetallic alloy NPs (Fig. 2b). After coacervation and conditions.23 It should be noted that no leaching of Au or Pd
cross-linking of polymer 2,10 we obtained the PI(Au/Pd)-coated OC was detected under these reaction conditions.28
(PI(Au/Pd)–CO) 6. We expected polymer 2 to form a coating around
To demonstrate the generality of this novel layered heterogeneous
polymer beads 5, assisted by the interactions between the polar bifunctional chiral catalyst, we attempted the reaction using the
moieties found on each polymer, such that the alloy NPs would be in optimized conditions with cinnamyl alcohol analogues as substrates
the outer layer of this two-layered heterogeneous catalyst, while the (Table 2). The catalyst could be applied to a variety of substrates
OC would exist in the inner layer. Simultaneously, we also prepared including aliphatic allylic alcohols and heteroatom-containing allylic
another two-layered heterogeneous bifunctional chiral catalyst, alcohols. The yields ranged from moderate to excellent with high
where the placement of NPs and the OC was reversed. This was enantioselectivity observed for many substrates.
accomplished by first preparing the PI/CB–Au/Pd catalyst based on a
We have demonstrated that the order of the layers of catalysts for
method established by us in our previous work14 and then coating it this heterogeneous bifunctional chiral catalyst is crucial for its
with the polyacrylamide that contains OC 1 via pseudo suspension catalytic activity (Table 1). IOC/PI/CB–Au/Pd catalyst 7, in which the
copolymerization to form an immobilized-organocatalyst-coated bimetallic alloy NPs are in the inner layer and the OC is in the outer
(IOC) PI/CB–Au/Pd catalyst (IOC/PI/CB–Au/Pd) 7 (Fig. 2c). The target layer, gave no reaction (Table 1, entry 2). A possible reason would be
mole ratio of Au to OC was 1:5 in both cases.
that the OC, which contains an amine moiety, deactivated the
Next, we investigated the activity of these catalysts when bimetallic alloy NPs during the fabrication of the catalyst. From our
applied to our model reaction for the desired asymmetric TOP, control experiment, we confirmed that the unsupported OC has a
with cinnamyl alcohol and dibenzyl malonate as the model deactivating effect on the bimetallic alloy NPs (entry 3). However,
substrates (Table 1). The aerobic oxidation of cinnamyl alcohol some activity was still observed in the case of the latter as compared to
to the corresponding trans-cinnamaldehyde would be catalyzed the zero activity of the former (entry 2), which suggests poisoning
by Au–Pd alloy NPs and the trans-cinnamaldehyde intermediate of the bimetallic alloy NPs via some kind of coordination by
c
9918 Chem. Commun., 2013, 49, 9917--9919
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Table 2 Substrate scope
avoided using this strategy. The order of the two layers containing
the respective catalysts was crucial and it determined the
catalytic activity of the composite catalyst for the asymmetric
TOP. Good yield and excellent enantioselectivity were observed
for many substrates, demonstrating the effectiveness of this
catalyst, and offering proof of concept for this novel method for
preparing a heterogeneous bifunctional chiral catalyst. This
preparation method may be applied to other catalytic systems
where undesired interactions between two types of catalysts
must be avoided.
Entry
8
R
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
9
8a
8b
8c
8d
8e
8f
8g
8h
8ic
8j
Ph
75
79
66
80
83
35
56
61
34
42
90
91
87
91
91
86
91
74
83
87
p-Me-C6H4
p-MeO-C6H4
p-F-C6H4
p-Cl-C6H4
p-O2N-C6H4
p-Ph-C6H4
2-Naphthyl
Me
This work was partially supported by
a Grant-in-Aid
for Scientific Research from JSPS, MEXT (Japan) and JST.
T. Yasukawa thanks JSPS for the Research Fellowship for Young
Scientists. We thank Mr Noriaki Kuramitsu (The University of
Tokyo) for STEM and EDS analyses.
This communication is dedicated to Professor Irina
Petrovna Beletskaya for her great contributions to metal-
catalyzed reactions.
10
2-Thienyl
a
b
Isolated yield. Determined by chiral HPLC analysis after oxidation to
the corresponding methyl ester for 10a–10h and 10j, and direct analysis
c
for 10i. 4 equivalents of 8i was used.
acrylamides29 during fabrication of the composite catalyst, and
highlights the importance of microscopic structural differences
between catalysts resulting from layering order. We were able to
remove all these undesired interactions between the NPs and the
OC by arranging the catalysts in the manner described in Fig. 2b
to form PI(Au/Pd)–CO catalyst 6.
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Fig. 3 (a) PI(Au/Pd)–CO 6 (above). (b) IOC/PI/CB–Au/Pd 7 (below). From left to
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Au, green = Pd and orange = Si.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 9917--9919 9919