Montmorillonite K10 catalyzed nucleophilic addition reaction to aldimines in water

Article abstract of DOI:10.1055/s-2005-872162

Montmorillonite K10 catalyzed Mannich-type reaction and hydrophosphonylation proceeded smoothly in water at room temperature to give β-amino esters and α-amino phosphonates, respectively, in good to high yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872162

2606
SPECIAL TOPIC
Montmorillonite K10 Catalyzed Nucleophilic Addition Reaction to Aldimines
in Water
Nucleophilic
A
d
a
dition Rea
k
ction to
A
ldi
a
mine
s
in
W
h
ater iko Akiyama,* Keiichiro Matsuda, Kohei Fuchibe
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan
E-mail: takahiko.akiyama@gakushuin.ac.jp
Received 14 June 2005
OMe
OMe
Abstract: Montmorillonite K10 catalyzed Mannich-type reaction
and hydrophosphonylation proceeded smoothly in water at room
temperature to give b-amino esters and a-amino phosphonates, re-
spectively, in good to high yields.
PMP
K10
N
+
N
H2O
Ar
O
OTMS
Ar
Key words: water, Montmorillonite K10, Mannich-type reaction,
hydrophosphonylation, imine
Scheme 1 Montmorillonite K10 catalyzed aza-Diels–Alder reac-
tion (PMP = paramethoxyphenyl)
The results of the Mannich-type reaction of a ketene silyl
acetal with a range of aldimines derived from aromatic al-
dehydes catalyzed by Montmorillonite K10 in water at
ambient temperature are shown in Table 1. Aldimines de-
rived from heteroaromatic aldehyde as well as aromatic
aldehyde gave corresponding b-amino esters in high
yields.
The development of carbon–carbon bond forming reac-
tions with simple experimental procedures has been a rap-
idly growing area in synthetic organic chemistry over the
past few years. Along the line, interest has been focused
on developing organic reactions in environmentally
friendly media, the so-called ‘green’ solvent.1 Organic re-
actions in aqueous media have attracted much attention of
synthetic organic chemists lately2 not only because water
is one of the most abundant, the cheapest, and environ-
mentally friendly solvent, but also because water exhibits
unique reactivity and selectivity different from that in
conventional organic solvents.3 In order to carry out or-
ganic reactions in aqueous media, water tolerant activator
has to be employed. Lewis acid catalysts, which are fre-
quently used in carbon–carbon bond forming reactions,
however, are generally sensitive to moisture4 though wa-
ter-tolerant Lewis acid catalyst have recently been devel-
oped.5 Brønsted acid is an acid catalyst of choice in
aqueous media. Along the line, we have already reported
Brønsted acid catalyzed Mannich-type reaction6 and aza-
Diels–Alder reaction in aqueous media.7
Table 1 Effect of the Aryl Group in Mannich-Type Reactiona
OMe
PMP
Ar
OTMS
OMe
NH
O
K10
+
N
H2O
OMe
1.5–3.5 h
Ar
Entry
Ar
Ph
Yield (%)
100
100
93
1
2
3
4
5
6
4-MeC6H4
4-ClC6H4
2-MeOC6H4
2-furyl
92
98
Solid acid catalyst such as clays, Nafion-H, and ion ex-
change resin have enjoyed popularity among synthetic or-
ganic chemists.8 Ease of recovery of the catalyst is one of
the advantage of the solid acid catalyst. We have already
reported that Montmorillonite K10 is an effective acid cat-
alyst for the aza-Diels–Alder reaction of Danishefsky’s
diene with imines in aqueous media (Scheme 1).9 We
wish to report herein that the Mannich-type reaction10 of
silyl enolate with aldimine is effected by Montmorillonite
K10 in water to afford b-amino carbonyl compounds in
high yields.11 Furthermore, hydrophosphonylation12 of
imine with dialkyl phosphite took place smoothly by
means of Montmorillonite K10 to afford a-amino phos-
phonates in high yields.
2-thienyl
97
a 3.0 Equiv of ketene silyl acetal was employed.
The results of the Mannich-type reaction of a range of
ketene silyl acetals with an aldimine are shown in Table 2.
Ketene silyl acetals 2a–e were found to be viable nucleo-
philes (entries 1–5). The ketene silyl thioacetal 2f also
afforded corresponding b-amino acid thioester in quanti-
tative yield (entry 6). The silyl enol ether 2g reacted slug-
gishly (entry 7).
Because aldimines, in particular, derived from aliphatic
aldehydes are generally labile and difficult to purify, it
would be synthetically quite useful if aldimines were gen-
erated in situ and were allowed to react with silyl enolate
under one-pot conditions.6,13 Thus, the three-component
SYNTHESIS 2005, No. 15, pp 2606–2608
x
x.
x
x
.
2
0
0
5
Advanced online publication: 12.08.2005
DOI: 10.1055/s-2005-872162; Art ID: C04205SS
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Nucleophilic Addition Reaction to Aldimines in Water
2607
domimetics and in enzyme inhibitory activity.14 Lewis
acid catalyzed addition of dialkyl phosphites to imines is
a useful method for the preparation of a-amino phospho-
nates.15 On treatment of aldimines with diethyl phosphite
in H2O in the presence of Montmorillonite K10 at room
temperature for one day, a-amino phosphonates were ob-
tained in good yields (Table 4). It is noted that the present
hydrophosphonylation did not proceed by means of HBF4
in the presence of sodium dodecyl sulfate in water.
Table 2 Results of the Mannich-Type Reactiona
OMe
PMP
OTMS
R3
NH
O
K10
R1
+
N
Ph
R3
H2O
R2
R1 R2
1.5–4 h
Ph
OTMS
OMe
OTMS
OCH3
OTMS
OEt
Ph3SiO
Table 4 Results of the Hydrophosphonylationa
2b (E:Z = 68:32)
2c (E:Z = 94:3)
2a
OTMS
OMe
OTMS
OMe
OTMS
OTMS
Ph
PMP
O
P
NH
K10
OCH3
+
OEt
OEt
OEt
OEt
SEt
N
t-BuMe2SiO
2d (E:Z = 95:5)
H2O
Ph
H
R
P
2g
2f
r.t., 1 d
O
R
2e (E:Z = 72:28)
Entry
R
Yield (%)
Entry
Nucleophile
Yield (%)
100
1
2
3
4
Ph
88
99
89
73
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
2-MeC6H4
2-furyl
92 (40:60)b
100 (81:19)b
96 (50:50)b
69 (50:50)b
100
PhCH=CH
a 3.0 equiv of diethyl phosphite was employed.
In summary, Montmorillonite K10 catalyzed Mannich-
type reaction and hydrophosphonylation in H2O were re-
ported. It is noted that both reactions were performed at
ambient temperature with simple operations and the solid
acid could be readily recovered.
2g
28
a 3.0 Equiv of silyl enolate was employed.
b Syn:anti ratio.
Mannich-type reaction of aliphatic aldehydes were exam-
ined next (Table 3). Although simple aldehyde such as cy-
clohexanecarbaldehyde gave b-amino ester in moderate
yield (entry 1), highly reactive aldehyde such as a-oxyace-
taldehydes gave adducts in high yields (entries 2 and 3).
Mannich-Type Reactions Catalyzed by Montmorillonite; Meth-
yl 3-(4-Methoxyanilino)-2,2-dimethyl-3-phenylpropanoate;
Typical Procedure (Entry 1 of Table 2)
To a suspension of Montmorillonite K10 (32.3 mg) in H2O (0.7 mL)
were added N-benzylidene p-anisidine (19.8 mL, 0.0937 mmol) and
2-methyl-1-methoxy-1-trimethylsiloxypropene (2a; 58 mL, 0.284
mmol) at r.t. After stirring at r.t. for another 1.5 h, the reaction was
quenched by addition of aq NaHCO3 solution and a mixture of
CH2Cl2–MeOH (4:1, 10 mL). The catalyst was removed by filtra-
tion. The montmorillonite K10 was washed with a mixture of
CH2Cl2-MeOH (4:1). The filtrate was dried (Na2SO4), and concen-
trated to dryness. Purification of the crude mixture by preparative
TLC (SiO2, hexane–EtOAc, 5:1) gave b-amino ester (30.8 mg) in
quantitative yield.
Next, we paid attention to hydrophosphonylation of
imines leading to a-amino phosphonates. a-Amino phos-
phonates are biologically important compounds as pepti-
Table 3 Three Component Mannich-Type Reactiona
NH2
PMP
R
OTMS
OMe
NH
O
K10
+
+
RCHO
H2O
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OMe
2.5–4 h
OMe
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Synthesis 2005, No. 15, 2606–2608 © Thieme Stuttgart · New York

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T. Akiyama et al.
SPECIAL TOPIC
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Synthesis 2005, No. 15, 2606–2608 © Thieme Stuttgart · New York