Heterogeneous Cu/OMS-2 as an efficient catalyst for the synthesis of tetrasubstituted 1,4-enediones and 4H-pyrido[1,2-a]-pyrimidin-4-ones

Article abstract of DOI:10.1039/c5ra17351e

An efficient Cu/OMS-2-catalyzed oxidative heterogeneous protocol has been developed for the synthesis of tetrasubstituted unsymmetrical 1,4-enediones and 4H-pyrido[1,2-a]-pyrimidin-4-ones from 1,4-enediones and amines or 2-aminopyridines. The present catalytic system employs air as the terminal oxidant and tolerates a broad range of substrates using low loading copper (1.3 wt%). The Cu/OMS-2 was characterized by various methods, including XRD, XPS, BET as well as TEM/SEM, and the results of H₂-TPR shows that the redox ability of the catalyst was improved by the combination of Cu and OMS-2. Moreover, the catalyst is recyclable.

Full text of DOI:10.1039/c5ra17351e

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Heterogeneous Cu/OMS-2 as an Efficient Catalyst for the
Synthesis of Tetrasubstituted 1,4-Enediones and 4H-pyrido[1,2-a]-
pyrimidin-4-ones
Received 00th January 20xx,
Accepted 00th January 20xx
Jinqi Zhang,a,c Xu Meng,a,b Chaoying Yu,a Gexin Chena and Peiqing Zhao*a,b
DOI: 10.1039/x0xx00000x
An efficient Cu/OMS-2-catalyzed oxidative heterogeneous protocol has been developed for the synthesis of
tetrasubstituted unsymmetrical 1,4-enediones and 4H-pyrido[1,2-a]-pyrimidin-4-ones from 1,4-enediones and amines or
2-aminopyridines. The present catalytic system employs air as the termial oxidant and tolerates a broad range of
substrates using low loading copper (1.3 wt%). The Cu/OMS-2 was characterized by various methods, including XRD, XPS,
BET as well as TEM/SEM, and the results of H2-TPR shows that the redox ability of the catlayst was improved by the
www.rsc.org/
combination
of
Cu
and
OMS-2.
Moreover,
the
catalyst
is
recyclable.
In recent years, the 1,4-enedione skeleton has received great
attention since it widely presents in bioactive natural products and
pharmaceutical compounds (Figure 1).8 More importantly, 1,4-
Introduction
From economic and industrial points of views, heterogeneous
catalysis is more attractive because of catalyst recyclability,
handling and easy separation of catalyst from the products.1,2 In
recent decades, manganese oxide octahedral molecular sieves
(OMS-2) have gained attention mainly due to its unique nature in
heterogeneous catalysis. OMS-2 is microporous material with a
composition of KMn8O16·nH2O. The structure of it contains 4.6×
4.6 Å tunnels that arise from the 2×2 arrangement of octahedron
and the average oxidation state of Mn is 3.8 with the presence of
Mn4+, Mn3+, and Mn2+ ions in the framework.3 Consequently, the
mixed valent, crystalline and semi-conductive properties make
OMS-2 have a wide range of applications.4
OH
O
O
H
HO
H
O
OH
O
Cholest-4-ene-3,6-dione
Rhabdastrellin D
HO
O
O
O
O
O
NH
O
Our group has been committed to studying OMS-2-based
heterogeneous catalysis and found that solid supported catalyst
Cu/OMS-2 with the low-loading copper has the interaction of
electron transfer between metal catalytic species and support.5
Based on the previous reports, it is believed that the catalytic ability
of Cu/OMS-2 can be significantly improved by the electronic
interaction, which might facilitate organic transformations and
make them proceed under a low-energy pathway.6,7 Therefore, the
development of efficient heterogeneous protocol for organic
transformation using Cu/OMS-2 is appreciated.
O
HO
O
O
Olean-13(18)-ene-3,12,19-trione
Hygrocins A
O
O
O
O
O
OH
CO
O
HO
O
O
(E)-Non-3-ene-2,5-dione
Antioxidant lignans
Strongylophorine-7
Figure 1. Natural products and pharmaceutical compounds
containing 1,4-enedione motifs.
a State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of
Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000 (China).
Fax:+96 931 827700; E-mail: zhaopq@licp.cas.cn
enediones are significant synthetic drug precursors for further
elaboration.9 Thus, numerous synthetic methods have been
established to produce this unit.10 Nevertheless, to the best of our
knowledge, only Wu’s group reported a homogeneous method
promoted by Cu(OAc)2 for the synthesis of tetrasubstituted
unsymmetrical 1,4-enediones in 2013.11 Based on the above works
and our previous studies,12 we herein describe a heterogeneous
b State Key Laboratory for Oxo Synthesis and Selective Oxidatio, Suzhou Research
Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of
Sciences, Lanzhou 730000 (China).
c University of Chinese Academy of Sciences, Beijing 100049 (China).
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oxidative method for the synthesis of tetrasubstituted The Cu/OMS-2 catalyst was isolated by centrifugation after each
unsymmetrical 1,4-enediones using Cu/OMS-2 as catalyst under air. run of reactions, then washed by ethanol and water. After drying at
110 oC for 5 hours, the catalyst was reused with fresh charge of
solvent and reactant for subsequent reaction under the same
Experimental section
conditions.
Preparation of OMS-24a
Characterization
5.89 g of KMnO4 in 100 mL of deionized water was added to a
The specific surface areas (SBET) of the catalysts were measured
solution of 8.8 g of MnSO4·H2O in 30 mL of deionized water and 3
from a multipoint Braunauer-Emmett-Teller (BET) analysis of the
mL concentrated HNO3. The solution was refluxed at 100 oC for 24
nitrogen adsorption isotherms at 77K recorded on a Quantachrome
hours, and the product was filtered, washed, and dried at 120 oC for
Autosorn-1 apparatus. The morphologies of the samples were
8 hours. Finally, the dry OMS-2 was calcined in a muffle furnace at
characterized by a TF20 transmission electron microscope (TEM)
350 oC for 2 hours. Then, the black powder OMS-2 was obtained.
and SM-5600LV scanning electron microscope (SEM). The crystal
phase and composition of catalysts were determined by power X-
Preparation of Cu/OMS-25
ray diffraction (XRD) using a X-Pert PRO X-ray diffractometer with
Cu Ka radiation in the 2θ ranges of 10–90o. The surface properties
Support OMS-2 (2 g) was added to a 50 mL round-bottom flask. A
of the catalyst were analyzed by a Thermo Scientific ESCALAB 250Xi
solution of Cu(NO3)2·3H2O (0.15 g) in deionized water (10 mL) was
X-ray photoelectron spectrometer (XPS). The reducibility of the
added to OMS-2, and additional deionized water (10 mL) was added
catalysts was measured by the hydrogen temperature-programmed
to wash down the sides of the flask. Then the flask was submerged
reduction (H2-TPR) technique. 50 mg of catalyst was placed in a
into an ultrasound bath for 3 hours at room temperature and
quartz reactor that was connected to a TPR apparatus and the
stirred for further 20 hours at room temperature. After that, the
reactor was heated from r.t. to 550 oC with a heating rate of 10
water was distilled under reduced pressure on a rotary evaporator
oC/min. The reducing atmosphere was the mixture of H2 and N2 with
a total flow rate of 30 mL/min and the amount of H2 uptake during
the reduction was measured by a thermal conductivity detector
(TCD).
at 80 oC for more than 2 hours. Finally, the black powder was dried
o
o
into an oven at 110 C for 4 hours followed by calcination at 350 C
for hours. The Inductive Coupled Plasma Optical Emission
2
Spectrum (ICP-OES) showed Cu content is 1.3 wt%.
General procedure for Cu/OMS-2-catalyzed synthesis of
tetrasubstituted 1,4-enediones 3
Results and discussion
The catalyst was synthesized by wet impregnation method. The BET
surface areas and porosities of Cu/OMS-2 were determined by N2
adsorption-desorption at 77 K and the results showed that the BET
surface area is 127 m2/g, pore volume is 0.48 cm3/g and pore size is
137.2 Å (Table S1, see ESI).
Cu/OMS-2 (30 mg, 2 mol%), 1,4-enediones 1 (0.3 mmol), N-
substituted nucleophiles 2 (0.6 mmol), DMSO (1.8 mL) were added
to a flask with a stirring bar. The flask was stirred at 80 oC for 12
hours under air. After cooling to room temperature, the mixture
was diluted with ethyl acetate and filtered. The filtrate was
removed under reduced pressure to get the crude product, which
was further purified by silica gel chromatography (petroleum/ethyl
acetate = 4/1 as eluent) to yield corresponding product. The
identity and purity of the products was confirmed by 1H and 13C
NMR spectroscopic analysis.
The morphology of Cu/OMS-2 was inspected by TEM and SEM
(Figure 2), the images show that the synthetic material is uniform
nanorod with diameters of about 8 nm and lengths of 70-120 nm.13
General procedure for Cu/OMS-2-catalyzed synthesis of 4H-
pyrido[1,2-a]-pyrimidin-4-ones 5
Cu/OMS-2 (30 mg, 2 mol%), 1,4-enediones 1 (0.3 mmol), 2-
aminopyridines 4 (0.6 mmol), DMSO (1.8 mL) were added to a flask
o
with a stirring bar. The flask was stirred at 80 C for 12 hours under
air. After cooling to room temperature, the mixture was diluted
with ethyl acetate and filtered. The filtrate was removed under
reduced pressure to get the crude product, which was further
purified by silica gel chromatography (petroleum/ethyl acetate =
2/1 as eluent) to yield corresponding product. The identity and
purity of the products was confirmed by 1H and 13C NMR
spectroscopic analysis.
Figure 2. TEM (a) and SEM (b) image of Cu/OMS-2.
Figure 3 plots the XPD patterns of OMS-2 and Cu/OMS-2, the
results show that no signals caused by copper oxide or copper
metal (cluster) were observed and the XRD pattern of Cu/OMS-2
was identical to that of support OMS-2,14 which further illustrated
copper oxide is highly dispersed on support OMS-2. Besides, the
structure of resued catalyst was not altered (see below for the test
of catalyst recyclability).
Catalyst durability
2 | J. Name., 2012, 00, 1-3
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the support OMS-2. Moreover, the extra peaks γ and δ appeared in
the TPR profile of the Cu/OMS-2 are related to the reduction of CuO
o
to Cu. The γ peak observed at 210 C corresponds to the reduction
of the finely dispersed CuO particles and the higher-temperature
peak δ represents the reduction of the bulk CuO particles.19
Next, we employed 1,4-enedione 1a and pyrazole 2a as the
model substrates to optimize the reaction conditions (Table 1). In
the first attempt, the reaction was run using OMS-2 as the catalyst
under air at room temperature, but no desired product was
observed (Table 1, entry 1). To our delight, 58% yield of the target
product was obtained when Cu/OMS-2 was used as the catalyst
Table 1. Optimization of the reaction conditionsa
O O
H
N
O O
Cat.
Ph
N
Ph
Ph
Solvent
Ph
Ph
Ph
Figure 3. XRD patterns of (a) OMS-2, (b) Cu/OMS-2 and (c) Cu/OMS-
N
+
Oxidant
Temp. 12 h
2 after one cycle.
N
O
O
To explore the surface properties of the catalyst, Cu/OMS-2 was
characterized by XPS (Figure S2, see ESI). The Mn 2p spectrum
shows that Mn 2p1/2 peak and Mn 2p3/2 peak are centred at 654.0
eV and 642.4 eV respectively, indicating this sample contains both
1a
2a
3aa
Entry
Cat.
Solvent
Temp. Oxida
Yieldb
(%)
(oC)
nt
1
OMS-2
Cu/OMS-2
DMSO
DMSO
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
120
r.t.
r.t.
r.t.
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
O2
0
58
0
0
0
Mn3+ and Mn4+ 15
The Cu 2p spectrum shows that the binding
.
2c
energies of Cu 2p1/2 and Cu 2p3/2 are about 954.0 eV and 934.3 eV,
and the shake-up satellite peaks of Cu 2p1/2 and Cu 2p3/2 are at
962.1 eV and at 944.7 eV, respectively, which demonstrates that
Cu2+ species are existed on the surface of the catalyst.15, 19a
3
4
5
6
Cu(OH)x/OMS-2 DMSO
Cu/ATP
Cu/C
Cu/Al2O3
DMSO
DMSO
DMSO
DMSO
DMF
0
The redox ability of the catalyst was studied by H2-temperature
programmed reduction (H2-TPR) and the profiles are presented in
Figure 4. For the support OMS-2, the overloping peaks (marked as
7
Cu/Al2O3
7
0
8c
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
Cu/OMS-2
CuO+OMS-2
CuO (1 equiv.)
9c
DCB
CH3NO2
Toluene r.t.
CH2Cl2
THF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
0
10c
11c
12c
13c
14c
15c
16c
17c
18c
19d
20
21
36
43
34
27
60
72
54
75
＜5
15
56
41
r.t.
r.t.
40
80
100
80
80
80
80
80
N2
Air
N2
CuO (0.1 equiv.) DMSO
Air
a
Unless otherwise specified, all reactions were carried out using 1a
(0.3 mmol), 2a (0.6 mmol) and catalysts (30 mg) in 1.8 mL solvent
b
c
d
under air for 12 h. Isolated yields. Cu content: 1.3 wt%. CuO (2
mol%), OMS-2 (30 mg).
Figure 4. H2-TPR profiles of OMS-2 and Cu/OMS-2.
(Table 1, entry 2). Then, Cu(OH)X/OMS-2 was examined in the
reaction and it did not better the reaction (Table 1, entry 3).
Besides, various supports were tested, such as ATP (attapulgite), C
(charcoal) and Al2O3, and it was found that OMS-2 is optimal for this
reaction (Table 1, entries 4-6). Importantly, a very low yield of 3aa
was observed when the reaction temperature was increased from
o
α, β) from 369 C to 390 oC are ascribed to the reduction of MnO2
to MnO.16,18 Compared with OMS-2, the reduction peaks of
Cu/OMS-2 shift to low temperature, suggesting that the existence
of copper species improves the reducibility of manganese oxide by
a hydrogen spillover effect.17,19a More importantly, the reduction
peaks αˊ and βˊ of Cu/OMS-2 became obvious, which probably is
caused by the enhanced mobility of oxygen.15,18 These results all
confirm the interaction between the catalystic metal copper and
o
r.t. to 120 C with the Cu/Al2O3 as the catalyst. These observations
perhaps indicate that Cu/Al2O3 is not able to lower the redox energy
barriers while high temperature made the reaction work to some
extent by overcoming the redox energy barriers (Table 1, entry 7).
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Next, we tried different solvents, which shows the reaction did not Additionally, the life span of the catalyst is another aspect of the
proceed in DMF (dimethyl formamide) and DCB (dichlorobenzene) heterogeneous catalysis. The reactions between 1,4-enedione 1g
(Table 1, entries 8 and 9). DMSO (dimethylsulfoxide) led to the best and pyrazole 2a was used as the model reactants to test the
result and other solvents, like nitromethane, toluene, recyclability of Cu/OMS-2. The catalyst was recovered by filtration
dichloromethane and THF (tetrahydrofuran), could give the desired and centrifugation, and results showed that the catalyst can recycle
product to some extent (Table 1, entries 10-13). Subsequently, the at least 3 times with slightly decrease of catalytic activity (Figure 5).
reaction temperature was optimized, and we found that 80 oC is the Furthermore, the result of TEM indicated that the used Cu/OMS-2
best choice (Table 1, entries 14-16). More experiments was intact in morphology, implying the stability of Cu/OMS-2
demonstrated that using O2 as the oxidant did not better the (Figure S1, see ESI). From the results of the hot filtration experiment
reaction obviously and only trace amount of 3aa was observed (specific details see ESI), we can speculate that the loss of the
under N2 (Table 1, entries 17 and 18). Finally, the catalytic activity of catalytic activity most likely results from the leaching of copper
physical mixture of bulk CuO and OMS-2 was much lower than this from the support.
of Cu/OMS-2, which indicates highly dispersed Cu species played a
crucial role in the reaction (Table 1, entry 19). Furthermore, without
the external oxidant, equivalent unsupported CuO could also give Table 2. Scope of the reactions between 1,4-enediones 1 and
moderate yield (Table 1, entry 20), while catalytic amount of CuO pyrazole 2a a
gave the poor yield of 3aa with oxygen as the external oxidant
(Table 1, entry 21). These observations indicate that the reduced
copper species cannot be reoxidized by O2 due to the high-energy
barrier of direct reoxidation without the help of OMS-2.
Entry
1
R1
R2
R3
3
Yieldb (%)
O O
O O
H
N
Ph
Ph
Ph
N
Ph
Cu/OMS-2
DMSO, 80 o
air, 12 h
N
+
1
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
3aa
3ba
3ca
3da
3ea
3fa
72
C
OEt
N
OEt
2
4-Me-Ph
4-OMe-Ph
4-Cl-Ph
4-Br-Ph
4-F-Ph
Ph
Ph
Ph
57
O
O
3
Ph
Ph
68
1g
4
Ph
Ph
56
3ga
2a
5
Ph
Ph
59
6
7c
8c
9c
Ph
Ph
75
1g
1h
1i
Ph
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OMe
OMe
3ga
3ha
3ia
80 (E:Z=66:34)
78 (E:Z=77:23)
87 (E:Z=67:33)
67 (E:Z=87:13)
88 (E:Z=90:10)
90 (E:Z=81:19)
84 (E:Z=88:12)
87 (E:Z=89:11)
81 (E:Z=88:12)
78 (E:Z=63:37)
86 (E:Z=86:14)
91 (E:Z=74:26)
83 (E:Z=92:8)
4-Me-Ph
4-OMe-Ph
4-NO2-Ph
4-CF3-Ph
2-naphthyl
4-Cl-Ph
4-Br-Ph
4-F-Ph
Ph
Ph
Ph
10c
11c
12c
13c
14c
15c
16c
17c
18c
19c
1j
Ph
3ja
1k
1l
Ph
3ka
3la
Ph
1m
1n
1o
1p
1q
1r
Ph
3ma
3na
3oa
3pa
3qa
3ra
Ph
Ph
4-OMe-Ph
4-F-Ph
4-OMe-Ph
4-Cl-Ph
Ph
Ph
1s
Ph
3sa
a
Unless otherwise specified, all reactions were carried out using 1
(0.3 mmol), 2a (0.6 mmol) and Cu/OMS-2 (30 mg, 2 mol%) in 1.8 mL
Figure 5. The recyclability of Cu/OMS-2. Reaction conditions: 1g (0.3
mmol), 2a (0.6 mmol) and Cu/OMS-2 (30 mg, 2 mol%) in 1.8 mL
DMSO under air for 12 h .
b
c
solvent under air for 12 h. Isolated yields. A mixture of E/Z-
isomers was obtained, E:Z ratio determined by 1H NMR.
To examine whether the observed catalytic activity is generated
from the solid catalyst Cu/OMS-2 or the leached copper species, the
hot filtration experiment was carried out with 1,4-enedione 1g and
pyrazole 2a as substrates (specific details see ESI). The catalyst was
removed after the reaction was run for 3 hours, then the reaction
was kept on, but the yield did not increase. At the same time, the
filtrate was analyzed by inductively coupled plasma-atomic
emission spectrometry (ICP-AES), and the result displayed that the
concentration of copper species in the solution is 0.45 ppm. Hence,
it is concluded that the copper species leached from the catalyst is
catalytically inactive and the catalysis is truly heterogeneous.
With the optimized conditions in hand, we investigated the scope
of this amination catalyzed by Cu/OMS-2 (Table 2). Generally, this
catalytic system could tolerate a large range of substrates and lead
to moderate to good yields of corresponding products. In terms of
R1 substituents, good yields were gained with various substituted
groups, such as –Me, -OMe and halogenated substituents (Table 2,
entries 1-6). Delightedly, when R3 was alkyloxy groups (-OMe, -OEt),
the reaction proceeded smoothly with good to excellent yields of
tetrasubstituted unsymmetrical 1,4-enediones (Table 2, entries 7-
19).
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Next, the scope of N-substituted nucleophiles was tested under and they extensively exist in natural products and pharmaceutical
the standard conditions with 1,4-enedione 1g as the model drugs.20 So far, a number of synthetic protocols for construction of
substrate (Table 3). Anilines proceeded very well in this system and this skeleton have been reported.21 However, as far as we know,
moderate to good yields of corresponding products were observed this is the first example to synthesize 4H-pyrido[1,2-a]-pyrimidin-4-
with electron-neutral (3gb), electron-donating (3gc, 3gd), electron- ones under the heterogeneous conditions. Therefore, the scope of
withdrawing (3ge, 3gf, 3gg) substituents. Besides, N-methylaniline cyclizations was examined with a series of different 1,4-enediones 1
(3gh) and 6-chloropyridin-2-amine (3gi) could also be used as suited and various substituted 2-aminopyridines 4 under the present
substrates. To our delight, aliphatic N-nucleophiles were also reaction conditions (Table 4). Many 1,4-enediones with different
tolerated in this reaction and gave moderate yields of desired substituted groups were employed as the substrates and good to
products (3gj, 3gk) with excellent E/Z ratio.
excellent yields of desired products were obtained. We also
examined the scope of 2-aminopyridines in this reaction.
Specifically, 3-methylpyridin-2-amine afforded the corresponding
Table 3. Scope of the reactions between 1,4-enedione 1g and N- product in good yield (5gb). However, 6-chloropyridin-2-amine
substituted nucleophiles 2a
provided the product 3gi via C-N bond-forming instead of cyclied
product 5gc because of the steric hindrance.
Table 4. Scope of the synthesis of 4H-pyrido[1,2-a]-pyrimidin-4-
ones 5a
a Unless otherwise specified, all reactions were carried out using 1g
(0.3 mmol), 2 (0.6 mmol) and Cu/OMS-2 (30 mg, 2 mol%) in 1.8 mL
DMSO under air for 12 h, isolated yields. E/Z ratio determined by 1H
NMR.
a
Unless otherwise specified, all reactions were carried out using 1
(0.3 mmol), 4 (0.6 mmol) and Cu/OMS-2 (30 mg, 2 mol%) in 1.8 mL
DMSO under air for 12 h, isolated yields.
Based on the reported literatures and our results, we proposed a
possible mechanism for these two kinds of reactions respectively.
The first amination reaction consists of aza-Michael addition
reaction between amine 2a and 1,4-enedione 1a with assistance of
Cu and a following supported copper species catalyzed aerobic
oxidative dehydrogenation of intermediate A under air (Figure
6).14,22 For the cyclization, the first two steps are same as these of
the amination. After that, the E-isomer amination intermediate (E)-
C produces its Z-isomer amination intermediate (Z)-C through
isomerization, finally the cyclized product 5ga is formed by
Surprisingly, a cyclized product 4H-pyrido[1,2-a]-pyrimidin-4-one
was obtained in 91% yield when 1,4-enedione 1g reacted with 2-
aminopyridine under our standard reaction conditions. It is believed
after 2-aminopyridine and 1,4-enedione undergo the aza-Michael
addition and aerobic dehydrogenation, the nitrogen in pyridine ring
further undergoes intramolecular amidation under the present
conditions to generate the heterocycles 5. It is an encouraging
result because 4H-pyrido[1,2-a]-pyrimidin-4-ones are a class of
nitrogen-containing heterocycles with pharmacological activities,
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supported copper species catalyzed intramolecular amidation allow it to apply to other oxidative processes and reactions.
(Figure 7).21f In the two kinds of reaction mechanisms, the reduced Further applications of this strategy are underway in our
copper species is reoxidized by OMS-2, and the reduced OMS-2 is laboratory.
reoxidized by O2 of air to finish the whole redox cycle.
Acknowledgements
O
O
O
O
Ph
We gratefully acknowledge the National Natural Science
Foundation of China (Grant Nos. 21403256, 21573261) and the
Suzhou Industrial Technology and Innovation Project (Grant No.
SYG201531).
Ph
N
Ph
Ph
Ph
O
O
[Cull]
+
[Cull]
N
N
H
N
Ph
1a
A
2a
[Cull]
[Cul]
OMS-2red
1/2O2
Notes and references
1
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4
OMS-2ox
H2O
2
O
O
O
Ph
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3aa
Figure 6．The proposed mechanism of the amination.
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]
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[Cull
]
N
NH2
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B
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3
4
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1g
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OMS-2red
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,
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(Z)-C
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E
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,
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5ga
5
,
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D
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Figure 7．The proposed mechanism of the cyclization.
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Conclusions
In summary, we have developed an efficient heterogeneous
strategy for the synthesis of tetrasubstituted 1,4-enediones
and 4H-pyrido[1,2-a]-pyrimidin-4-ones catalyzed by Cu/OMS-
2. The excellent catalytic ability of Cu/OMS-2 is attributed to
OMS-2 which accelerates the reoxidation of reduced copper
species through rapid electron transfer. This superiority might
Terasaki and J. E. Bäckvall, Adv. Synth. Catal., 2008, 350
,
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5RA17351E
Journal Name
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J. Name., 2013, 00, 1-3 | 7
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RSC Advances
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DOI: 10.1039/C5RA17351E
Heterogeneous Catalytic Oxidative Synthesis of Tetrasubstituted 1,4-Enediones
and 4H-pyrido[1,2-a]-pyrimidin-4-ones by Cu/OMS-2
J. Zhang, X. Meng, C. Yu, G. Chen and P. Zhao*
O
O
R4
NH
R5
O
O
O
R1
R4
R2
R3
amination
R1
R2
R3
+
+
up to 91% yield
N
R5
O
O
29 examples
Cu/OMS-2
In Air
O
O
O
R9
R6
R7
O
R6
R7
amination/cyclization
up to 93% yield
9 examples
N
OR8
N
NH2
N
O
R9
Broad substrate generality
Economy and green with mild condition
N-nucleophile-dependent divergent outcomes
Copper supported on OMS-2: Heterogeneous catalyst Cu/OMS-2 was prepared for
the synthesis of tetrasubstituted 1,4-enediones and 4H-pyrido[1,2-a]-pyrimidin-4-ones
under the same conditions with air as the oxidant. The present catalytic system that
proceeds under mild conditions can tolerate a broad range of substrates.