Magnetic nanoparticle-supported Morita-Baylis-Hillman catalysts

Article abstract of DOI:10.1002/adsc.200700318

A magnetic nanoparticle-supported quinuclidine was prepared and evaluated as a recoverable Morita-Baylis-Hillman catalyst. The supported catalyst 2 demonstrated comparable activity with that of DABCO and could be simply recycled with the assistance of an

Full text of DOI:10.1002/adsc.200700318

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DOI: 10.1002/adsc.200700318
Magnetic Nanoparticle-Supported Morita–Baylis–Hillman
Catalysts
Sanzhong Luo,a,* Xiaoxi Zheng,a Hui Xu,a Xueling Mi,b Long Zhang,b
and Jin-Pei Chengb,*
a
Beijing National Laboratory for Molecular Sciences (BNLMS), Centre for Chemical Biology, Institute of Chemistry and
Graduate School, Chinese Academy ofSciences, Beijing, 100080, Peopleꢀs Republic ofChina
Fax : (+86)-10-6255-4446; e-mail: luosz@iccas.ac.cn
Department ofChemistry and State Key Laboratory ofElemento-organic Chemistry, Nankai University, Tianjin, 300071,
b
Peopleꢀs Republic ofChina; e-mail: chengjp@mail.most.gov.cn
Received: June 28, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A magnetic nanoparticle-supported qui-
nuclidine was prepared and evaluated as a recover-
able Morita–Baylis–Hillman catalyst. The supported
catalyst 2 demonstrated comparable activity with
that ofDABCO and could be simply recycled with
the assistance ofan external magnet. The thus recy-
cled catalyst could be reused for 7 times without
significant loss of activity.
tions.[4] Fan and co-workers reported dendritic
DMAP, which exhibited promising biphasic character
in Baylis–Hillman catalysis.[5] These supported cata-
lysts normally demonstrated reduced activities com-
pared to their non-supported counterparts and in
some cases an additional activating step was required
in order for the immobilized catalyst to be reused.[4]
As a result, their applications have been mainly limit-
ed to active Baylis–Hillman substrates such as methyl
vinyl ketone (MVK) and acrylonitrile. Thus, despite
these advances, a supported MBH catalyst that fully
addresses the critical issues on activity and catalyst re-
cyclability has yet to be reported. In a more recent
study, Shi and Toy developed bifunctional polymeric
MBH catalysts by anchoring a hydrogen bonding
Keywords: magnetic nanoparticles; Morita–Baylis–
Hillman reaction; organocatalysts; support
The Morita–Baylis–Hillman (MBH) reaction is one of donor (e.g., phenol group) onto the backbone ofpoly-
the most popular C C bond-forming strategies in meric Lewis bases.[6] The obtained bifunctional cata-
À
modern organic synthesis due to its advantages in lysts showed superior activity to their non-hydroxylat-
regard to atom economy, non-metal catalysis, mild ed derivatives. Although the catalytic activity still fell
conditions, and the promising utility ofits multiufnc-
below that oftheir homogeneous non-supported
tional products.[1] As a classical organocatalytic pro- counterparts in most cases, the bifunctional strategy
cess, the MBH reaction is typically known for its high provides a potential solution to the design ofrecover-
loading ofcatalysts and sluggish reaction rates.
Hence, significant efforts have been made in order to
able MBH catalysts.
We have long been interested in developing effi-
overcome these limitations. Remarkable advances cient MBH catalytic systems.[7] Previously, we report-
along this line in the past decade have led to the dis- ed that ionic liquid-supported quinuclidine was a
covery ofnew catalysts with superior activity, the de-
velopment ofnovel chemical and physical strategies
highly efficient and reusable MBH catalyst.[7f] It was
further demonstrated that the use of hydroxylated
for rate accelerations as well as the development of ionic liquids as supports led to further improvements
reusable Baylis–Hillman catalysts.[2] Recently, several in activity due to the synergistic effect of the hydroxy
research groups have reported supported Lewis bases group.[7g] In these cases, the ionic liquid-type catalysts
as reusable Baylis–Hillman catalysts. Shi and Corma were recycled via ether precipitation. To further ad-
independently investigated the use ofcommercially
dress the issue ofrecyclability and reusability, we
available poly-DMAP as the recyclable Baylis–Hill- present herein the use ofmagnetic nanoparticles as
man catalyst.[3] Furthermore, Shi and co-workers ex- MBH catalyst supports. Owing to their good stability,
amined the activity and reusability ofPEG and poly-
high surface area and easy synthesis, magnetic nano-
styrene-bound phosphines in Baylis–Hillman reac- particles (MNP) have recently been applied as hetero-
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Sanzhong Luo et al.
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Scheme 1. Synthesis ofthe magnetic nanoparticle-supported quinuclidine 2.
Figure 1. TEM images ofcatalyst 2: (left) before reaction and (right) after reusing it 7 times.
geneous catalytic supports.[8] An attractive feature of scopy (TEM) confirmed the nanometer dimensions of
MNP-supported catalysts is that they can be easily catalyst 2 (Figure 1, a). However, powder X-ray dif-
separated with the aid ofan external magnet, thus af -
fraction (XRD) indicated that the final MNP catalyst
cilitating easy catalyst recycling without using extra was partially oxidized from magnetite to maghemite
organic solvents and additional filtration steps. Fur- (g-Fe2O3). The final MNP-supported quinuclidine 2 is
thermore, high activity is usually achieved in the well dispersed in polar solvents such as methanol, eth-
nanometer-sized supported catalyst due to the high anol, THF and dichloromethane and can be easily
accessible surface area. We therefore envisaged that separated by a small magnet. This property meets
the use ofMNPs as a support would properly address
well with the criteria for the use of MNPs as catalyst
the efficiency issues in organocatalysis by providing supports and the magnetic catalyst 2 was therefore
readily recyclable and reusable catalysts with reasona- used as is. Using a similar strategy, silica surface-
bly high activity. Indeed, parallel to this work, two bound quinuclidine 3 was also prepared for the pur-
other groups reported MNP-supported phase-transfer pose ofcomparison.
catalysts and DMAP catalysts, respectively, showing
The MNP-supported quinuclidine 2 was next tested
good activity and reusability.[9] These publications in the model reaction ofmethyl acrylate and p-nitro-
prompted us to report our exploration ofMNP-sup-
ported MBH catalysts.
benzaldehyde. As shown in Table 1, the reaction oc-
curred smoothly in the presence of10 mol% of 2, af -
MNP-supported quinuclidine 2 was synthesized ac- fording the desired product with high yields. The use
cording to the procedure shown in Scheme 1. Polyvi- ofprotic solvent such as methanol was shown to sig-
nylpyrrolidone (PVP, average MW: 40,000)-protected nificantly accelerate the reaction and the reaction
magnetic nanoparticles of8–12 nm were prepared fol-
time could be shortened from 12 h to 2 h in the pres-
lowing the published co-precipitation procedure.[10] ence ofmethanol compared with that in aprotic sol-
The obtained MNPs were sonicated for one hour vents (Table 1, entry 6 vs. entries 1–4). This observa-
before being treated with excess triethoxysilane 1 in tion is in line with the well-proved accelerating effect
[11]
anhydrous toluene under refluxing. This one-step pro- ofhydroxy group-containing additives
and is also
cedure gave MNP-supported quinuclidine 2 with a consistent with our previous observation.[7g] Interest-
À1
loading of0.88 mmolg
which was consistent in sev- ingly, conducting the reaction under neat conditions
eral different batches. Transmission electron micro- (with 2.0 equivs. ofmethyl acrylate) led to an equally
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Adv. Synth. Catal. 2007, 349, 2431 – 2434

Magnetic Nanoparticle-Supported Morita–Baylis–Hillman Catalysts
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Table 1. MBH reactions ofmethyl acrylate catalyzed by
Table 2. Substrate scope ofMNP-supported quinuclidine 2.[a]
MNP-quinuclidine.[a]
Entry E
R
Conditions Time
[h]
Yield
[%][b]
Entry
R
Cat.
Solvent Time [h] Yield [%][b]
1
2
3
4
CO2Me 4-
NO2C6H4
CO2Me 2-
NO2C6H4
CO2Me 3-
NO2C6H4
CO2Me 2-Pyridin-
yl
CO2Me 2-Furyl
CO2Me i-C4H9
CO2Me 4-ClC6H4
CO2Me Ph
A
A
A
A
2
6
5
2
88
92
95
94
1
2
3
4
5
6
7
8
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
2
2
2
2
2
2
2
2
CH3CN 12
CH2Cl2 12
CHCl3 12
87
92
92
THF
12
90
EtOH 12
95
MeOH
H2O
neat
2
12
2
88
<5
87
5
6
7
8
9
10
11
A
B
B
B
B
B
B
3
90
80
9
NO2 MNP
MeOH 24
No reaction
36
24
24
24
24
5
86 (84)[c]
83 (86)[c]
62 (56)[c]
88 (81)[c]
88
10
11
12
Cl
Cl
Cl
2 (20 mol%) MeOH 24
3 (20 mol%) MeOH 48
DABCO
86
71
88
MeOH 24
CO2Me 4-MeC6H4
CO2Et 4-ClC6H4
(20 mol%)
CN
4-
[a]
Carried out on a 0.5-mmol scale in the presence of
0.1 equiv. ofthe catalyst (except those speciifed) at room
temperature. Molar ratio ofaldehyde:methyl acrylate =
1:2. Solvent: 4.0 equivs.
NO2C6H4
2-Pyridin-
yl
12
CN
B
5
99
13
14
15
CN
CN
CN
4-ClC6H4
Ph
4-MeC6H4
B
B
B
16
24
24
92
95
80
[b]
Isolated yields ofpure product.
[a]
Carried out on a 0.5-mmol scale in the presence of
0.1 equiv. ofthe catalyst (except those speciifed) at room
temperature. Molar ratio ofaldehyde:methyl acrylate =
1:2. Entries 9–15: 0.2 equivs. ofcatalyst were used.
Isolated yields ofpure product.
Numbers in the parentheses refer to the data obtained
under neat conditions with 2.0 equivs. ofacrylate. Condi-
tions A: in the presence of4.0 equivs. ofmethanol; Con-
ditions B: neat.
fast reaction (Table 1, entry 8 vs. 7). The concentra-
tion effect and the free hydroxy groups on the MNP
surface may both contribute to the rate enhancement
in this case. MNP-supported quinuclidine 2 was then
compared with the classical MBH catalyst DABCO
using a less active aldehyde, showing comparable cat-
alytic activity with DABCO (Table 1, entry 10 vs. 12).
Furthermore, catalyst 2 also demonstrated significant-
[b]
[c]
ly higher activity than the silica-bound quinuclidine 3, magnet is placed nearby. The separated catalyst was
suggesting the importance ofa nanosized support then washed with ether and dried under vacuum to
(Table 1, entry 10 vs. 11). In a control reaction, the remove residual solvent. The catalyst could be reused
magnetic nanoparticle itselfwas shown to be inert for
catalysis (Table 1, entry 9).
and recycled for 7 times with essentially no loss of ac-
tivity (Table 3). TEM shows that the MNP catalyst
The substrate scope ofcatalyst 2 was then exam-
ined. The catalyst could be well-applied to a range of
Michael donors and a wide array ofaldehydes
(Table 2). It should be noted that the reactions work
equally well with or without the addition ofmethanol
(Conditions A and B, respectively), providing one of
the most effective heterogeneous MBH catalysts.
Product separation and recycling ofthe MNP-sup-
ported quinuclidine 2 were indeed quite easy and
simple (for pictures, see Supporting Information).
After the reaction, diethyl ether was added to dilute
the reaction mixture and the organic layer was simply
decanted, assisted by a nearby magnet, to afford the
desired products. The MNP catalyst was quickly con-
centrated to the side wall ofthe reaction vial once a
Table 3. Recycle ofcatalyst 2.[a]
Cycle
1
2
3
4
5
6
7
Time [h]
5
88
5
87
5
88
5
88
5
85
5
79
7
80
Yield [%][b]
[a]
The reaction was carried out on a 0.5 mmol scale.
Isolated yields.
[b]
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Sanzhong Luo et al.
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reuse, proving its robustness (Figure 1, b).
In summary, we have prepared the first MNP-sup-
ported quinuclidine as a robust and efficient hetero-
geneous Baylis–Hillman catalyst. The catalyst is easily
synthesized and can catalyze the MBH reactions with
comparable activity as the traditional catalyst,
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General Procedure
To the solution ofcatalyst 2 (29 mg, 0.025 mmol) in CH3OH
(41 mL, 4.0 equivs.) were added aldehyde (0.25 mmol) and
activated alkene (0.5 mmol). The resulting solution was
stirred at ambient temperature and monitored by TLC.
After the indicated reaction time, diethyl ether (2 mL”3)
was added, and a small magnet was then applied to separate
the organic layer and to recycle the catalyst. The extracts
were concentrated to afford the essentially pure products.
The crude product could also be purified by flash chroma-
tography on silica gel to afford the desired product. The re-
cycled catalyst was dried under vacuum, and reused directly
for the next run. The reactions using the recycled catalyst
were conducted in a similar manner. All the Baylis–Hillman
products are known compounds (see Supporting Informa-
tion for further details).[7]
Acknowledgements
This work was supported by Natural Science Foundation of
China (NSFC 20421202, 20632060, 20542007), the Ministry
of Science and Technology (MoST) of China and the Chinese
Academy of Sciences.
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Adv. Synth. Catal. 2007, 349, 2431 – 2434