Imino-Diels-Alder and imino-aldol reactions catalyzed by samarium diiodide

Article abstract of DOI:10.1016/S0040-4039(01)01581-7

In the presence of a catalytic amount of samarium diiodide in methylene chloride, aromatic imines react with Danishefsky diene to form tetrahydropyridine-4-ones in high yields. Under the same conditions, various imino-aldol reactions afford β-amino esters or β-amino ketones.

Full text of DOI:10.1016/S0040-4039(01)01581-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7405–7407
Imino-Diels–Alder and imino-aldol reactions catalyzed by
samarium diiodide
Jacqueline Collin,* Nada Jaber and Marie Isabelle Lannou
Laboratoire de Catalyse Mole´culaire ESA 8075, ICMO, Baˆtiment 420 Universite´ Paris-Sud, F-91405 Orsay, France
Received 2 August 2001; revised 24 August 2001; accepted 28 August 2001
Abstract—In the presence of a catalytic amount of samarium diiodide in methylene chloride, aromatic imines react with
Danishefsky diene to form tetrahydropyridine-4-ones in high yields. Under the same conditions, various imino-aldol reactions
afford b-amino esters or b-amino ketones. © 2001 Elsevier Science Ltd. All rights reserved.
In our previous work, we have shown that samarium
diiodide is an efficient Lewis acid-type catalyst for a
variety of carbonꢀcarbon bond-forming reactions.1 We
have performed aldol and Michael reactions,2 Diels–
Alder and hetero Diels–Alder reactions3 and, more
recently, tandem Michael-aldol reactions4,5 by the use
of catalytic amounts of samarium diiodide. Moreover,
we have found that iodo samarium binaphthoxides are
enantioselective catalysts for Diels–Alder reactions.6 In
all these reactions, an aldehyde or a ketone was used as
the electrophile. For the lanthanide triflate-catalyzed
reactions, the preferential activity of aldimines over
aldehydes has been established7 and subsequently used
for the development of lanthanide triflate-catalyzed
three-component reactions with in situ formation of
imines.8 This prompted us to investigate the catalytic
activity of samarium diiodide for reactions involving
imines, aza-Diels reactions and imino-aldol reactions,
in order to evaluate the possibility of further develop-
ments for lanthanide iodides in the synthesis of hetero-
cycles or in enantioselective catalysis.
diiodide (10 mol%), in methylene chloride at room
temperature (Eq. (1), Table 1) to form tetra-
hydropyridine-4-ones 3 which were isolated in high
yields. As for reactions involving aldehydes,2 when the
imine is added to the reaction mixture, the color turns
from blue to yellow or orange and remains unchanged
until the end of the reaction, which is indicative of a
trivalent active species. We checked that samarium
triiodide can be used alternatively as a catalyst and
shows the same activity as samarium diiodide (Table 1,
entries 2 and 3). The presence of a chelating group on
the imine increases the rate of the reaction. The activity
of samarium diiodide is similar to that of ytterbium and
scandium triflates in reactions involving preformed
imines or in three-component reactions (in all cases
reactions are carried out in acetonitrile with 10 mol%
catalyst at room temperature or 0°C)9,10 while with
indium triflate11 and bismuth chloride or triflate12
smaller amounts of catalyst were needed.
Typical procedure: In a Schlenk tube, a samarium diio-
dide solution 0.1 M in THF (1 mL, 0.1 mmol) is
evaporated until obtention of a blue powder of
SmI2(thf)2 and after addition of CH2Cl2 (5 mL) under
argon, a suspension 0.02 M is obtained. Then are
The cycloaddition reactions of imines with various
dienes or alkenes were first examined. Imines 1 react
with Danishefsky diene 2 in the presence of samarium
OMe
R1
R1
10% SmI2(THF)2
CH2Cl2, rt
N
N
(1)
+
R2
R2
O
OTMS
1
2
3
Keywords: samarium diiodide; catalysis; cycloadditions; imines; aldol reaction.
* Corresponding author. Fax 33 (0) 1 69154680; e-mail: jacollin@icmo.u-psud.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01581-7

7406
J. Collin et al. / Tetrahedron Letters 42 (2001) 7405–7407
Table 1. Imino Diels–Alder reactions catalyzed by samar-
ium diiodide
(pentane/ethyl acetate: 40/60) to yield 86% of pure
product.
Entry
R1
R2
t (h)
Yield (%)a
Samarium diiodide (10 mol%) also catalyzes the addi-
tion of imines to cyclopentadiene at room temperature
in methylene chloride. In this reaction the imine
behaves as an azadiene, and the adduct is obtained as a
mixture of cis and trans isomers (Eq. (2)). Samarium
diiodide shows higher activity than other catalysts such
as ytterbium triflate10 or indium chloride.13
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
24
5
5
61
72
71b
82
86
86
87
63
79
o-CH3OC6H4
o-CH3OC6H4
p-CH3OC6H4 18
o-CH3OC6H4 Ph
p-CH3OC6H4 Ph
p-CH3OC6H4 p-CH3OC6H4 36
p-CH3C6H4
CH2C6H5
16
36
Ph
36
6
The catalytic activity of samarium diiodide for the
cycloaddition of imines onto ethyl vinyl ether 6 has also
been studied (Eq. (3)). In this reaction, as for cyclopen-
tadiene, the imine again works as an azadiene. With
several imines crude products were mixtures of the
cycloadduct 7 and of the corresponding quinoline 8,
that could be separated by column chromatography on
deactivated silica (eluent pentane/ether: 80/20). In ytter-
bium triflate-catalyzed reactions, Fujiwara14 and
Kobayashi9 described different conditions for the treat-
ment of crude products which allowed them to isolate
o-CH3OC6H4
a Isolated yield %, all products were fully characterized by spectro-
scopic data.
b 10% SmI3(THF)3.
successively added, a solution of N-phenyl-2-methoxy-
benzaldimine (211 mg, 1 mmol) in CH2Cl2 (2 mL), and
Danishefsky’s diene (293.2 mL, 1.5 mmol). After stirring
overnight, hydrolysis by HCl 0.1 M and extraction with
CH2Cl2, the crude product is purified on silica gel
HN
HN
10% SmI2(THF)2
(2)
N
H
H
+
+
CH2Cl2, MS 4A, rt, 2h
66%
H
H
13
87
1
4
5
R3
R3
HN
N
N
10 % SmI2(THF)2
CH2Cl2, rt
R3
+
+
O
O
R4
R4
R4
(3)
6
8
7
1
R3 = R4 = H
20
35
14
25
3
R3 = OCH3 R4 = H
R3 = H R4 = OCH3
28
Table 2. Imino-aldol reactions catalyzed by samarium diiodide
Entry
R1
R2
Silyl derivative
Product
Yielda
1
2
3
p-CH3OC6H4
o-CH3OC6H4
Ph
CO2Et
Ph
Ph
9
9
9
10
10
10
90b
85b
88b
4
5
6
7
8
9
10
p-CH3OC6H4
o-CH3OC6H4
o-CH3OC6H4
p-CH3OC6H4
o-CH3OC6H4
o-CH3OC6H4
p-CH3OC6H4
CO2Et
Ph
p-CF3
CO2Et
Ph
11
11
11
13a
13a
13a
13b
12
12
12
14a
14a
14a
14b
63b,c
53b,c
82b,c
95d
95d
p-CF3
CO2Et
93d
81d
a All products were fully characterized by spectroscopic data.
b Isolated yield %, reaction time 18 h.
c Reaction performed with 1.3 equiv. enoxysilane.
d Yield % in crude product (decomposed by chromatography on silica).

J. Collin et al. / Tetrahedron Letters 42 (2001) 7405–7407
7407
R1
R1
10% SmI2(THF)2
CH2Cl2, rt
HN
N
OCH3
OTMS
+
CO2Me
R2
R2
1
9
10
R1
R1
O
10% SmI2(THF)2
CH2Cl2, rt
HN
N
Ph
+
(4)
Ph
R2
R2
OTMS
1
11
12
R1
R1
OTMS
O
HN
10% SmI2(THF)2
CH2Cl2, rt
N
R2
+
R2
(n)
(n)
14a n = 1
14b n = 2
13a n = 1
13b n = 2
1
either pure quinoline 8 or tetrahydroquinoline 7. Both
methods have been tested, always leading to mixtures of
these two products.
for fruitful discussions. We thank the CNRS for financial
support.
The reaction of glyoxylic and aromatic imines with ketene
silyl acetal 9 in equimolar amounts, in the presence of 10%
SmI2(THF)2 in methylene chloride (Eq. (4), Table 2) gave
the b-amino ester adducts in high yields at room temper-
ature. While activity of samarium diiodide is similar to
that described with samarium triiodide,15 our procedure
is much simpler, as with other catalysts such as B(C6F5),16
or TiI4,17 reactions need to be carried out at low
temperature and with excess of ketene silyl acetal.
Imino-aldol reactions were also observed by reaction of
a glyoxylic imine as well as aromatic imines with enoxysi-
lane 11 (Table 2, entries 4–6). In lanthanide triflate-cat-
alyzed reactions, cycloaddition of enoxysilane 11 onto
imines have been first reported,9,14 and later on, in
competitive reactions with aldehydes, the iminoaldol
products were isolated.7 Catalysis by bismuth derivatives
with the same substrates yields to aza-Diels reactions,12
while with BF3·OEt2 Mannich reactions are observed.18
Recently indium chloride was reported to promote
Mannich reactionswithenoxysilanes bythree-component
reactions in water, but with high amounts of catalyst (20%
at least).19 Samarium diiodide catalyzes also imino-aldol
reactions with cyclic enoxysilanes 13a and 13b (Table 2,
entries 7–10), leading to b-amino ketones.
References
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We are indebted to Professor Kagan and Professor Namy