Cerium(IV) ammonium nitrate (CAN) catalyzed aza-Michael addition of amines to α,β-unsaturated electrophiles

Article abstract of DOI:10.1016/j.tetlet.2006.05.182

Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic amines with α,β-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.

Full text of DOI:10.1016/j.tetlet.2006.05.182

Tetrahedron Letters 47 (2006) 5433–5436
Cerium(IV) ammonium nitrate (CAN) catalyzed
aza-Michael addition of amines to a,b-unsaturated electrophiles
Zheng Duan,* Xuejie Xuan, Ting Li, Chenfei Yang and Yangjie Wu*
Chemistry Department, The Key Lab of Chemical Biology and Organic Chemistry of Henan Province,
The Key and Open Lab of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, PR China
Received 12 April 2006; revised 30 May 2006; accepted 31 May 2006
Abstract—Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic
amines with a,b-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.
Ó 2006 Elsevier Ltd. All rights reserved.
The development of catalysts for the formation of
carbon–nitrogen bonds by simple addition of amines to
double bonds is a focus of increasing interest.1 The aza-
Michael reaction provides an easy and direct route to
b-amino esters.2 In general, this type of conjugated addi-
tion reaction of nucleophiles to unsaturated carbonyl
compounds requires basic conditions or acidic catalysts.3
In order to overcome some of these limitations, a number
of alternative procedures have been reported over the
past few years using a variety of reagents such as Pd
compounds,4 InCl3,5 CeCl3Æ7H2O–NaI,6 Yb(OTf)3,7
Bi(NO3)3,8 Bi(OTf)3,9 Cu salts,10 LiClO4,11 clay,12 silica
gel,13 boric acid,14 KF/alumina15 and SmI2.16 FeCl3Æ
7H2O, CrCl3Æ6H2O and SnCl4Æ4H2O had been used to
catalyze aza-Michael reactions under mild conditions in
aqueous solution, both aliphatic and aromatic amines
could be used as the nucleophiles.17 Due to the inertness
of aromatic amines relative to aliphatic ones, most of
these procedures are not successful with arylamines. Very
recently, Rao and co-workers reported b-cyclodextrin
promoted aza-Michael addition of arylamines.18 In these
reactions, an equivalent amount of the recyclable catalyst
was added. The development of less expensive, simpler,
‘greener’ metal catalysts for the aza-Michael addition
with arylamines is still highly desirable.
organic solvents, have made CAN attractive in organic
synthesis.19 Very recently, CAN catalyzed Michael addi-
tion of indole to a,b-unsaturated ketones was re-
ported.20 Substitution took place at the 3-position, and
N-alkylation products were not observed. To the best
of our knowledge, CAN catalyzed aza-Michael addition
of amines to a,b-unsaturated compounds are unknown.
Herein we would like to report CAN as an efficient cat-
alyst in the aza-Michael addition. The advantages of this
protocol include high yield reactions that can be con-
ducted under ambient temperature without solvent.
CAN is suitable to activate aliphatic amines and even
aromatic amines for the aza-Michael addition reactions.
At first, aniline and ethyl acrylate were chosen as model
system. We found that this CAN catalyzed aza-Michael
Table 1. CAN catalyzed Michael addition of aniline to ethyl acrylate
in various solvents
O
O
CAN (10mmol%)
+
NH2
NH
OEt
OEt
60°C, 24h,solvent
1a
2a
3a
Entry
Solventa
Yieldb(%)
1
2
3
4
5
6
H2O
39
38
75
78
8
C2H5OH/H2Oc
C2H5OH
THF
The readily available, cheap, low toxicity, easy handling
and profound reactivity combined with its solubility in
Dioxane
CH3CN
66
Keywords: CAN; Amines; Michael addition; Catalysis; Ultrasound.
a 2 ml was added.
b Isolated yield.
c v/v = 1/1.
*
Corresponding authors. Tel.: +86 371 67767993; fax: +86 371
67979408; e-mail addresses: duanzheng@zzu.edu.cn; duanzheng@
yahoo.com; wyj@zzu.edu.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.182

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Z. Duan et al. / Tetrahedron Letters 47 (2006) 5433–5436
addition was strongly dependent on the solvent. Among
the solvents tested, THF and EtOH gave fair yields
(75–78%), as well as CH3CN (66%). Low yields were
obtained with the other solvents (Table 1).
graphy (TLC). The results are summarized in Table 2.
1
All the products were characterized by H, 13C NMR
and mass spectrometry.
As can be seen from Table 2, primary aromatic
amines with electron-donating group gave better re-
sults. When p-chloroaniline was used, Michael adduct
product formed only in moderate yield (entry 7). No
reaction was observed when m-nitroaniline (entry 8)
was used.
In a typical procedure, to a THF solution of aniline
(1.5 mmol) and ethyl acrylate (1 mmol) was added
CAN (0.1 mmol). The reaction mixture was stirred at
60 °C for 24 h under air atmosphere. Then the crude
reaction mixture was purified by thin layer chromato-
Table 2. CAN catalyzed aza-Michael addition of amines
H
N
R
N
CAN
R2
R1
R2
R1
+
R
1
2
3
Entry
1
Amine
Reaction time (h)a
24 (6)
Product
Yieldb (%)
78 (80)c
H
N
PhNH2
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
Ph
CO2Et
H
78 (78)c
77 (71)c
(56)c
N
2
3
4
5
6
7
p-MePhNH2
m-MePhNH2
o-MePhNH2
p-MeOPhNH2
m-MeOPhNH2
p-ClPhNH2
24 (4)
24 (4)
(6)
p
-MePh
CO2Et
H
N
m-MePh
CO2Et
Me
H
N
CO2Et
H
82 (80)c
74 (82)c
64 (72)c
N
24 (4)
24 (6)
24 (6)
p-MeOPh
CO2Et
CO2Et
CO2Et
H
N
m
-MeOPh
H
N
1g
3g
Cl
8
9
m-NO2PhNH2
1k
1l
N/A
N/A
(60)c
N
N
(4)
3l
NH
CO2Et
N
10
11
12
13
14
1m
1m
1n
(20 min)
(20 min)
(20 min)
(40 min)
(1)
CO2Et
CN
3m
3n
3o
3p
3q
(Quant.)c
(96)c
NH
NH
N
N
H
C4H9NH2
C4H9NH2
Ph2CH2NH2
(93)c
N
C4H9
CN
C4H9
N
1n
(98)d
EtO2C
EtO2C
CO2Et
CO2Et
CH2Ph
N
1o
(90)d
a Reaction times with ultrasonic irradiation are given in parentheses.
b Isolated yields. Yields for reactions with ultrasonic irradiation are given in parentheses.
c 1.5 equiv amine was added.
d 2.5 equiv ethyl acrylate was added.

Z. Duan et al. / Tetrahedron Letters 47 (2006) 5433–5436
5435
Under the same condition, the reaction of a secondary
aromatic amine, N-methylaniline, with ethyl acrylate
did not work very well. To our surprise, when a mixture
of N-methylaniline, ethyl acrylate and a catalytic
amount of CAN was sonicated21 at room temperature
in an ultrasonic cleaner, a faster reaction occurred to
give the desired product in 83% isolated yield (Eq. 1).
Fund for Outstanding Scholar of Henan Province (No.
0621001100) for financial support.
References and notes
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1h
1.0 mmol
2a
1.5mmol
3h
iso.83%
ð1Þ
This result promoted us to investigate the ultrasound-
assisted aza-Michael addition. To our gratified, all the
reactions proceeded with reduced reaction time (Table
2) and no solvent was needed. The electron poor aryl-
amines showed no reactivity (entry 8). Due to the stereo-
hindrance effect, o-toluidine showed lower reactivity
(entry 4) than p-toluidine and m-toluidine (entries 2
and 3). Imidazole also could be used as the nucleophile
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OEt
ð2Þ
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2.5mmol
OEt
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O
3i R=Me, iso.72%
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Acknowledgements
The author thanks the National Natural Science Foun-
dation of China (No. 20472074) and The Innovation

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