Aza-Michael reactions catalyzed by samarium diiodide

Article abstract of DOI:10.1016/j.tetlet.2005.09.039

Samarium diiodide catalyzes the Michael addition of aromatic amines onto α,β-unsaturated N-acyloxazolidinones to form β-aminoacid derivatives. Aza-Michael reactions can be followed by an amidation reaction with the aromatic amine, leading to β-aminoamides

Full text of DOI:10.1016/j.tetlet.2005.09.039

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7761–7764
Aza-Michael reactions catalyzed by samarium diiodide
*
*
´
Irena Reboule, Richard Gil and Jacqueline Collin
ˆ
´
Laboratoire de Catalyse Mole´culaire UMR 8075, ICMMO, Batiment 420, Universite Paris-Sud, 91405 Orsay, France
Received 18 July 2005; revised 5 September 2005; accepted 7 September 2005
Available online 22 September 2005
Abstract—Samarium diiodide catalyzes the Michael addition of aromatic amines onto a,b-unsaturated N-acyloxazolidinones to
form b-aminoacid derivatives. Aza-Michael reactions can be followed by an amidation reaction with the aromatic amine, leading
to b-aminoamides. b-Amino-N-acyloxazolidinones are selectively obtained with o-anisidine, while amidation reaction is observed
with p-anisidine.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
an efficient precatalyst for carbon–carbon bond forming
reactions, such as aldol, Michael, Diels–Alder, or tan-
dem Michael-aldol reactions.12 Samarium diiodide is
also an active catalyst for carbon–nitrogen bond form-
ing reactions, such as the ring opening of epoxides by
amines, to give b-aminoalcohols.13 In this letter, we
present our results concerning samarium diiodide-cata-
lyzed aza-Michael additions of amines to a,b-unsatu-
rated N-acyloxazolidinones.
The development of catalysts for the formation of car-
bon–nitrogen bonds by simple addition of amines to
double bonds is a focus of increasing interest.1 The
few examples of catalyzed reactions involving aliphatic
olefins are realized using high pressures and high tem-
peratures.2 Palladium-catalyzed addition of amines to
2,3-dihydrofuran or 3,4-dihydro-2H-pyran forms a-
aminotetrahydrofurans and a-aminopyrans,3 while cat-
ionic Pd diphosphine complexes catalyze the addition
of amines on styrene as well as on a,b-unsaturated
esters.4 The aza-Michael reaction, that is, addition of
nitrogen nucleophiles on activated double bonds, is of
synthetic interest since it provides an easy route to b-
aminoacid derivatives.5 This latter reaction is catalyzed
by Lewis acids such as silica,6 transition metal and lan-
thanide chlorides,7 or triflates.8 Recently, several types
of transition metals have been found by high-through-
put method to catalyze the addition of amines to acrylic
acid derivatives.9 Diastereoselective or enantioselective
catalytic aza-Michael reactions have been reported,10
although reactions involving amines have been scarcely
investigated.11
2. Results
a,b-Unsaturated N-acyloxazolidinones have found
numerous applications as chelating substrates in Lewis
acid catalyzed reactions, especially for enantioselective
catalysis.14 By the use of these substrates in Diels–Alder
reactions catalyzed by lanthanide iodo binaphthoxides,
we have carried out cycloadditions with moderate
enantioselectivity.15 We then wished to investigate the
reactivity of a,b-unsaturated N-acyloxazolidinones as
Michael acceptors in samarium diiodide-catalyzed addi-
tions of aromatic amines, as a new method of carbon–
nitrogen bond forming reactions (Scheme 1). The results
are gathered in Table 1. Addition of various aromatic
amines to oxazolidinone derived from fumaric ethyl
ester 1a was readily performed in the presence of 10%
samarium diiodide in methylene chloride at room tem-
perature to give the expected products 3 (entries 1–5).
A total conversion of the unsaturated product was ob-
served in all cases. Whereas reaction of substrate 1b with
aniline led to total conversion, a slower reaction was ob-
served with o- and p-anisidine (entries 7 and 8). The
reaction of a,b-unsaturated acyloxazolidinone 1b with
We have previously studied the scope of the reactivity of
samarium diiodide as a Lewis acid type catalyst. We
have reported SmI2(THF)2 in methylene chloride to be
Keywords: Samarium diiodide; Catalysis; Amines; Aza-Michael reac-
tion; Carbon–nitrogen bond formation.
Corresponding authors. Tel.: +33 (0) 1 69154740; fax: +33 (0) 1
69154680; e-mail: jacollin@icmo.u-psud.fr
*
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.039

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I. Reboule et al. / Tetrahedron Letters 46 (2005) 7761–7764
O
O
O
O
O
ArHN
R
ArHN
R
10% SmI (THF)
2
2
Ar
ArNH
+
+
2
O
N
R
N
N
O
CH Cl , rt, 48 h
2
2
H
1a R = CO Et
2
3
4
2
1b R = CH
3
1c R = C H
3
7
1d R = H
Scheme 1.
Table 1. Aza-Michael reactions catalyzed by samarium diiodide
Entry
R
Amine
Ratio 2/1
Product
Conversiona,b
1
2
3
4
5
6
7
8
9
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CH3
CH3
CH3
C3H7
PhNH2
1.2
1
1
1.2
1.2
1.2
1.2
1.2
1.2
3a
3b
3c
3d
3e
3f
100 (49)
100 (77)
100 (60)
100 (68)
100 (64)
98c
o-MeOC6H4NH2
p-MeOC6H4NH2
p-BrC6H4NH2
p-ClC6H4NH2
PhNH2
o-MeOC6H4NH2
p-MeOC6H4NH2
p-MeOC6H4NH2
3g
3h
3i
90d
60e
100f
a For a typical procedure see Ref. 17.
b Isolated yield in 3. All products were fully characterized by physical and spectroscopic data.
c Mixture of 3 and 4 in crude product 3f/4f: 39/61.
d Mixture of 3 and 4 in crude product 3g/4g: 78/22.
e Mixture of 3 and 4 in crude product 3h/4h: 10/90.
f Mixture of 3 and 4 in crude product 3i/4i: 12/88.
aniline afforded a mixture of two products with 3f as the
minor one, the major 4f arising from an amidation reac-
tion of product 3f with aniline (entry 6). The reaction of
1b with o-anisidine afforded the Michael adduct 3g as
the major product (entry 7), while with p-anisidine only
small amounts of b-aminoacyloxazolidinone 3h were
observed and b-aminoamide 4h was the major product
(entry 8). a,b-Unsaturated propyl substituted N-acyl-
oxazolidinone 1c reacted with p-anisidine, to give the
same ratio of products as 1b (entry 9). A similar amida-
tion reaction following the aza-Michael addition of
O-benzylhydroxylamine on a pyrazole-derived croton-
amide promoted by MgBr2 has been mentioned in the
literature.10c
substrate 1b did not permit to form selectively the b-
aminoacyloxazolidinone 3f, which was obtained as a
mixture with the amidation product 4f (entry 1). The
4f/3f ratio increased on using 2 equiv of aniline, and 4f
was the sole product formed in high yield using a large
excess of aniline (entries 2 and 3). Reactions of the same
substrate with o-anisidine afforded the aza-Michael
adduct 3g as the major product whatever quantity of
amine was employed (entries 4–6). Reaction with p-
anisidine showed the opposite trend, with formation of
the b-aminoamide 4h resulting from amidation reaction
even with substoichiometric amount of p-anisidine (en-
tries 7–9). Michael addition onto substrate 1c furnished
a mixture of products 3i and 4i with substoichiometric
amount of amine but led selectively to the amidation
product 4i with an excess of amine (entries 10 and 11).
Reaction of acryloyloxazolidinone 1d with 2 equiv of
o-anisidine allowed to isolate selectively b-amino-
acyloxazolidinone 3k (entry 13), while reactions with
aniline or p-anisidine (entries 12 and 14) afforded mix-
tures of 3 and 4, with 3j and 3l as major products.
We then tested scandium triflate, which is known to be a
very efficient Lewis acid catalyst in aza-Michael reac-
tions.16 Addition of p-anisidine on 1b in the presence
of 10% Sc(OTf)3 afforded after 2 days reaction the same
3h/4h ratio as the one obtained with SmI2(THF)2
although with a lower conversion (35%). Samarium di-
iodide seems thus to be a more active catalyst for aza-
Michael reactions.
We also examined if amidation reaction could occur
from compound 1a by performing the aza-Michael in
the presence of a large excess of amine. The b-amino-
amide products 4a and 4c could be isolated, respectively,
from reactions with aniline and p-anisidine (entries 15
and 17), whereas only the Michael adduct 3b was ob-
served with o-anisidine (entry 16). The comparison of
reactions involving o-anisidine and p-anisidine shows
that higher amounts of products 3 are obtained with
o-anisidine (see entries 5 and 8, 13 and 14, 16 and 17).
This difference of reactivity of o-anisidine and p-anisi-
dine in the aza-Michael reactions with substrates 1 can
Aza-Michael reactions involving 1a and a slight excess
of aromatic amine afforded selectively the aza-Michael
adduct 3. Similar reactions with alkyl substituted a,b-
unsaturated N-acyloxazolidinones 1b and 1c led to a
subsequent amidation reaction. We examined the influ-
ence of the nature and the quantity of aromatic amine
on the chemoselectivity of the samarium diiodide-cata-
lyzed reactions for the preparation of Michael adducts
3 or 4. The results are collected in Table 2. The use of
a substoichiometric amount of aniline relative to the

I. Reboule et al. / Tetrahedron Letters 46 (2005) 7761–7764
7763
Table 2. Influence of the ratio amine/Michael acceptor on the structure of addition product
Entry
R
Amine
Ratio 2/1
Ratio 3/4
Major product
Yielda,b
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
C3H7
C3H7
H
H
H
CO2Et
CO2Et
CO2Et
PhNH2
PhNH2
PhNH2
0.8/1
2/1
5/1
0.8/1
2/1
5/1
0.8/1
2/1
5/1
0.8/1
5/1
2/1
67/33
53/47
0/100
90/10
78/22
65/35
0/100
0/100
0/100
54/46
0/100
71/29
100/0
62/38
35/65
100/0
0/100
3f
3f
4f
3g
3g
3g
4h
4h
4h
3i
—
32
95
64
—
51
—
—
93
49c
83
43
60
57d
40
—
70
o-MeOC6H4NH2
o-MeOC6H4NH2
o-MeOC6H4NH2
p-MeOC6H4NH2
p-MeOC6H4NH2
p-MeOC6H4NH2
p-MeOC6H4NH2
p-MeOC6H4NH2
PhNH2
o-MeOC6H4NH2
p-MeOC6H4NH2
PhNH2
o-MeOC6H4NH2
p-MeOC6H4NH2
9
10
11
12
13
14
15
16
17
4i
3j
2/1
2/1
5/1
5/1
3k
3l
4a
3b
4c
5/1
a For a typical procedure see Ref. 19.
b Isolated yield in major product, calculated from 1 or 2 according to the stoichiometry.
c Isolated yield for the mixture 3i+4i, which could not be separated by chromatography.
d Isolated yield for mixture 3l+4l, which could not be separated by chromatography.
be explained by a steric effect. The amidation is slower in
Acknowledgements
the case of the bulkier o-anisidine. Similarly, compari-
son of reactions involving aniline and p-anisidine indi-
cates that a higher yield of product resulting from
amidation reaction is observed with p-anisidine (see
entries 2, 8, 12, 14, 15 and 17). An electron-donating
group on the aromatic amine increases the rate of the
amidation.
We thank CNRS for financial support and MENRT for
´
´ `
Irena Reboule Ph.D. grant. We are indebted to Helene
Guerrand for technical assistance and to Professor
Fiaud for fruitful discussions and preparation of this
manuscript.
Recent reports on aza-Michael additions of oxazolidi-
none on a,b-enones or a,b-unsaturated esters catalyzed
by ammonium fluoride18 prompted us to check that
samarium diiodide does not catalyze the reaction of
a,b-unsaturated N-acyloxazolidinones with oxazolidi-
none. Furthermore, in our reactions, we did not detect
formation of any aza-Michael products resulting from
the reaction of oxazolidinone with substrate 1.
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Samarium diiodide catalyzes the Michael addition of
aromatic amines onto a,b-unsaturated N-acyloxazolidi-
nones yielding b-aminoacid derivatives either as b-
amino-N-acyloxazolidinones, or as b-amino amides, or
as mixtures, depending on the nature of amine and on
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matic amine. Amidation reactions occurred with high
rates in experiments involving aniline and p-anisidine.
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obtained as the major product. On the contrary, the use
of o-anisidine led selectively to b-amino-N-acyloxazolid-
inones 3. Recently, we reported that samarium iodo
binaphtholates are enantioselective catalysts for Diels–
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for Mannich reactions and aminolysis of epoxides.20,21
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a
solution of a,b-unsaturated acyloxazolidinone 1a
(212 mg, 1 mmol) in 4 mL CH2Cl2 at room temperature.
The reaction mixture was stirred for 2 days and quenched
by addition of 10 mL of HCl, 0.1 N aqueous solution
and extracted by CH2Cl2. The crude product was purified
by crystallization (CH2Cl2/heptane 1:1) to give 201 mg of
3c (60%). Mp 109 °C. 1H NMR (250 MHz, CDCl3): d
6.74 (d, 2H, J = 8.8 Hz), 6.64 (d, 2H, J = 8.8 Hz), 4.45–
4.30 (m, 3H), 4.15 (q, 2H, J = 7.3 Hz), 3.97 (t, 2H,
J = 7.8 Hz), 3.72 (s, 3H), 3.55 (dd, 1H, J = 5.8 and
16.6 Hz), 3.38 (dd, 1H, J = 5.4 and 16.6 Hz), 1.15 (t, 3H,
J = 7.3 Hz). 13C NMR (62.9 MHz, CDCl3): d 172.62,
170.47, 153.99, 152.99, 140.46, 115.69, 114.76, 62.17,
61.49, 55.62, 54.54, 42.32, 38.03, 14.05. IR (CaF2,
CHCl3) (cmÀ1): m 3394, 1784, 1735, 1602, 1389, 1336.
HRMS: calcd for C16H20N2O6Na 359.1214, found
359.1231.
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´
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19. Typical procedure for preparation of 4c: Same experimen-
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anisidine (615 mg, 5 mmol). Two hundred and sixty
1
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´
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J = 9.50 Hz), 6.69–6.82 (m, 6H), 4.30–4.40 (m, 1H),
4.14–4.18 (m, 2H), 3.74 (s, 3H), 3.72 (s, 3H), 2.75–2.85
(m, 2H), 1.20 (t, 3H, J = 7.58 Hz). 13C NMR (62.9 MHz,
CDCl3): d 172.76, 167.78, 156.37, 153.73, 139.93, 130.74,
121.78, 116.80, 114.86, 114.03, 56.02, 55.59, 55.39, 53.39,
39.54, 14.07. IR (CaF2, CHCl3) (cmÀ1): m 3429, 1780,
1717, 1698, 1602, 1335. HRMS: calcd for C20H24N2O5Na
395.1577, found 395.1580.
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tube, a solution of SmI2 in THF (0.1 M, 1 mL, 0.1 mmol)
was carefully evaporated in vacuo to give SmI2(THF)2
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