PAA-supported Hantzsch 1,4-dihydropyridine ester: An efficient catalyst for the hydrogenation of α,β-epoxy ketones

Article abstract of DOI:10.1016/j.tetlet.2013.07.112

A new type of water-soluble polymer-supported NADH co-enzyme model-PAA (polyacrylic acid)-supported Hantzsch 1,4-dihydropyridine ester (PAA-HEH) was designed and synthesized. Catalytic amount of the supported reagent was used in the hydrogenation of α,β-epoxy ketones to the corresponding β-hydroxy ketones and showed great catalytic efficiency in the reduction reaction. This PAA-HEH was an optimal potential for recycling use.

Full text of DOI:10.1016/j.tetlet.2013.07.112

Tetrahedron Letters 54 (2013) 5374–5377
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
PAA-supported Hantzsch 1,4-dihydropyridine ester: an efficient
catalyst for the hydrogenation of a,b-epoxy ketones
Xin-Feng Zhou a, Peng-Fei Wang a, Ye Geng a, Hua-Jian Xu a,b,
⇑
a School of Chemical Engineering, School of Medical Engineering, Hefei University of Technology, Hefei 230009, PR China
b Key Laboratory of Advanced Functional Materials and Devices, Anhui Province, Hefei 230009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new type of water-soluble polymer-supported NADH co-enzyme model-PAA (polyacrylic acid)-sup-
ported Hantzsch 1,4-dihydropyridine ester (PAA–HEH) was designed and synthesized. Catalytic amount
Received 20 May 2013
Revised 15 July 2013
Accepted 22 July 2013
Available online 27 July 2013
of the supported reagent was used in the hydrogenation of
a,b-epoxy ketones to the corresponding b-
hydroxy ketones and showed great catalytic efficiency in the reduction reaction. This PAA–HEH was an
optimal potential for recycling use.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
NADH co-enzyme model
Water-soluble polymer
Hantzsch ester
a,b-Epoxy ketones
b-Hydroxy ketones
NAD(P)H co-enzyme is a kind of oxidoreductase co-enzyme
with great importance.1 It participates in more than 400 kinds of
important biological redox reactions in vivo. NAD(P)H coenzyme
is also a kind of natural organic hydride compound.2 Based on
the active core, 1,4-dihydropyridine ring, of NAD(P)H, a series of
model compounds have been synthesized to mimic the reductive
performance of NADH coenzyme in vitro, such as BNAH, HEH,
and AcrH2.3 Some of these models synthesized, like Hantzsch ester,
accompanied with some small-molecule organocatalysts, were ap-
plied in the reductive reactions of aldehydes, ketones, activated
the support and they were connected to form a novel water-solu-
14
ble polymer-supported reagent.
The synthesis of the PAA-sup-
ported Hantzsch ester is presented herein as well as the
application of the reagent in the hydrogenation of the
ketones in homogeneous reaction system.
a,b-epoxy
Polyacrylic acid-supported Hantzsch ester was synthesized
according to the following protocol (Scheme 1). PAA was directly
purchased and the Hantzsch 1,4-dihydropyridine ester was pre-
pared according to the literature.15 HEH was co-valently connected
with the carboxyl group of PAA through amide bond. Firstly, the
mixture of formaldehyde, ethyl acetoacetate, and ammonium ace-
tate was dissolved in ethanol and refluxed then to get Hantzsch
1,4-dihydropyridine ester. At the same time, the polyacrylic acid
3000 was treated with thionyl dichloride in DMF to obtain the cor-
responding partly chloride-PAA, which was then refluxed with the
Hantzsch ester synthesized in DMF to get the PAA-partly-sup-
ported Hantzsch ester which was a light milky solid at room tem-
perature and could be dissolved in water easily. The supported-
reagent was characterized by elemental analysis and the loadings
of PAA–HEH were 0.34 mmol/g.
olefins, and the hydrogenation of b-unsaturated aldehydes,
a,b-
epoxy ketones, imines, and showed great reductive activities and
selectivities.4 However, the separating operation of these reactions
is complicated. To simplify the separation process and promote the
extensive use of the models, they have been immobilized on the
surface of some supports, which combines the advantages of both
the models and the supports.5 In the past few decades, the sup-
ports of the NADH coenzyme model compounds have experienced
the Merrifield resin,6 SiO2,7 polysiloxane,8 water-soluble polymer
like PEG,9 ferrocene,10 carbon nanotubes,11 magnetic nano like
Fe3O4,12 graphene,13 etc.
To examine the reducibility and application of the PAA–HEH,
we herein present the use of the supported-reagent in the reduc-
Considering our group’s experience in the synthesis, applica-
tion, and characterization of NADH coenzyme model compounds,
herein we chose Hantzsch 1,4-dihydropyridine ester as the co-en-
zyme model and water-soluble polymer polyacrylic acid (PAA) as
tion of a series of
a,b-epoxy ketones. According to our previous
work,16 all of the reactants including the phenyl(3-phenyloxi-
ran-2-yl)methanone, the supported-reagent, Na2S2O4 (3 equiv),
Na2CO3 (5 equiv) were mixed together and dissolved in mixed
AcOEt/H2O (v:v = 1:1) solvent in one tube. The solution was irra-
diated with a 450 W high-pressure mercury lamp at room tem-
⇑
Corresponding author. Tel.: +86 551 62904353; fax: +86 551 62904405.
E-mail address: hjxu@hfut.edu.cn (H.-J. Xu).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.112

X.-F. Zhou et al. / Tetrahedron Letters 54 (2013) 5374–5377
5375
H
H
O
O
C2H5OOC
EtOH
COOC2H5
CH3
HCHO
H3C CCH2CCH2CH3
+
CH3COONH4
+
reflux
H3C
N
H
H
H
C2H5OOC
H3C
COOC2H5
CH3
COOH
O
N
H
EtOOC
N
SOCl2
n
DMF, 70 oC, 24 h
OH
O
DMF, Et3N, 75 oC, 24 h
COOH
H
O
Cl
H
COOEt
PAA-HEH
Scheme 1. The synthetic protocol of the PAA–HEH.
Table 1
The hydrogenation of
a
,b-epoxy ketones to b-hydroxy ketonesa
O
PAA-HEH (5 mol%)
O
OH
R2
AcOEt/H2O (1:1)
R2
R1
R1
Na2CO3, Na2S2O4
Ar, hv, rt, 12 h
O
2a-2s
1a-1s
Substrates
Products
Yieldsa (%)
Substrates
Products
Yieldsb (%)
O
OH
Ph
O
O
OH
O
O
O
Ph
Ph
Ph
Br
Ph
Ph
Ph
96
96
95
90
87
95
89
97
O
1j
O
2a
1a
2j
O
O
OH
O
O
OH
Ph
Ph
O
Ph
O
Br
Br
2b
2k
1b
1k
Br
O
O
O
O
OH Br
O
O
OH
Ph
Br
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O
O
2c
2l
1c
1l
O
O
OH
O
O
OH
Ph
Ph
O
O
Cl
F
Cl
F
2m
2d
1m
1d
OH
O
O
OH
Ph
Ph
91
95
91
97
O
O
1n
2n
1e
2e
OH
O
O
O
O
OH
Ph
Ph
Ph
Ph
O
O
Cl
Cl
O
O
2f
Cl
Cl
1f
1o
2o
OH
O
O
O
O
OH Cl
O
O
O
Cl
Ph
Ph
Ph
Ph
Ph
93
90
89
94
Ph
Ph
O
S
O
S
O
O
1g
2p
1p
2g
OH
O
OH
Ph
O
O
2q
1q
2h
1h
(continued on next page)

5376
X.-F. Zhou et al. / Tetrahedron Letters 54 (2013) 5374–5377
Table 1 (continued)
Substrates
Products
Yieldsa (%)
Substrates
Products
Yieldsb (%)
O
O
OH
O
O
OH
Ph
Ph
O
Ph
89
88
Ph
O
O
2r
1r
O
1i
2i
O
O
OH
Ph
2s
43
Ph
O
1s
a
Compound 1 (0.2 mmol), Na2S2O4 (0.6 mmol), Na2CO3 (1.0 mmol), and PAA–HEH (0.01 mmol) were dissolved in 2 mL of AcOEt/H2O (1:1). The solution was irradiated
with a 450 W mercury lamp (k >320 nm) under an argon atmosphere at room temperature for 12 h.
b
Isolated yields.
Table 2
supported reagent was used in the hydrogenation of a,b-epoxy ke-
Reducibility of the PAA–HEH after recycling
tones to obtain the corresponding b-hydroxy ketones and showed
great reducibility after being reused for at least 5 times. We are
now working on the application of the supported reagent in other
reactions.
O
OH
O
PAA-HEH (5 mol%)
AcOEt/H2O (1:1)
Na2CO3, Na2S2O4
Ar, hv, rt, 12 h
O
Cl
Cl
Acknowledgments
Recycle time
Isolated yields (%)
1a
97
2b
3b
92
4b
5b
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (Nos. 21272050, 21072040,
21071040) and the Program for New Century Excellent Talents in
University of the Chinese Ministry of Education (NCET-11-0627).
94
90
90
a
Compound 1 (0.2 mmol), Na2S2O4 (0.6 mmol), Na2CO3 (1.0 mmol), and PAA–
HEH (0.01 mmol) were dissolved in 2 mL of AcOEt/H2O (1:1). The solution was
irradiated with a 450 W mercury lamp (k >320 nm) under an argon atmosphere at
room temperature for 12 h.
See references and notes.17
b
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
07.112. These data include MOL files and InChiKeys of the most
important compounds described in this article.
perature. And the reaction must be conducted under an argon
atmosphere. After being stirred for 12 h, the reaction was com-
pleted and phenyl(3-phenyloxiran-2-yl)methanone was reduced
to the corresponding 3-hydroxy-1,3-diphenyl-propan-1-one in
satisfactory yield.
References and notes
We then explored the use of this new PAA-supported NADH
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data). The amount of reactants was recalculated by the amount of recycling
catalyst. And the other reaction conditions are constant.