HCl-catalyzed stereoselective Mannich reaction in H2O-SDS system

Article abstract of DOI:10.1055/s-2004-836062

HCl-catalyzed Mannich reaction of cyclic ketone, aromatic aldehyde, and aromatic amine proceeded smoothly in water in the presence of SDS to afford the corresponding β-amino ketone with high anti selectivity.

Full text of DOI:10.1055/s-2004-836062

3
22
LETTER
HCl-Catalyzed Stereoselective Mannich Reaction in H O–SDS System
2
H
T
Cl-Catalyzed
a
Stereoselec
k
tive
M
annich
a
R
eaction
h
inH O–SD
S
i
Syste mk o Akiyama,* Keiichiro Matsuda, Kohei Fuchibe
2
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan
Fax +81(3)59921029; E-mail: takahiko.akiyama@gakushuin.ac.jp
Received 19 October 2004
Table 1 Effect of Brønsted Acid
Abstract: HCl-catalyzed Mannich reaction of cyclic ketone, aro-
OMe
matic aldehyde, and aromatic amine proceeded smoothly in water in
the presence of SDS to afford the corresponding b-amino ketone
with high anti selectivity.
O
Acid (10 mol%)
N
H2O
+
SDS (40 mol%)
r.t., 12–24 h
Key words: Mannich reactions, Brønsted acid, water, amines, sur-
factant
Ph
ArNH
O
ArNH
O
+
Organic reactions in aqueous media have attracted much
attention of synthetic organic chemists lately not only be-
cause water is one of the most abundant, cheapest, and en-
Ph
Ph
vironmentally friendly solvent, but also because water Entry
exhibits unique reactivity and selectivity different from
those in conventional organic solvents. Development of
novel reactivity as well as selectivity that cannot be at-
tained in conventional organic solvents is, thus, one of the
challenging goals of aqueous chemistry.
Acid
HCl
Yield (%)
anti:syn
1
2
3
4
5
87
89
91
79
61
99:1
99:1
97:3
96:4
93:7
1
,2
Camphorsulfonic acid
HBF4
CF CO H
Mannich and related reactions constitute useful reactions
for the preparation of b-amino carbonyl compounds,
which are important intermediates for the synthesis of
3
2
Montmorillonite
3
biologically active nitrogen containing compounds. We
The HCl-catalyzed Mannich reaction was examined in
several kinds of solvent system (Table 2). Interestingly,
present Mannich reaction exhibited intriguing solvent
effect; excellent anti selectivity was observed in water in
the coexistence of SDS, whereas the reaction in aqueous
organic solvent or organic solvent showed low stereo-
selectivity.
have already reported that the Mannich-type reaction of
silyl enolate with aldimines proceeded smoothly under the
influence of HBF as a Brønsted acid in aqueous organic
4
solvent to give b-amino carbonyl compounds in good to
4
excellent yields. Furthermore, the HBF -catalyzed Man-
4
nich-type reaction proceeded smoothly in water in the
5
presence of SDS (sodium dodecylsulfate). It is noted that
the syn/anti selectivity of the Brønsted acid-catalyzed
Mannich-type reaction is highly dependent on the solvent
The HCl-catalyzed Mannich reaction was examined with
a number of aldimines and cyclic ketones (Table 3). Cy-
clohexanone showed good to high anti selectivities.
Cycloheptanone gave b-amino ketone with modest anti
selectivity (entry 6).
system; aqueous organic solvent and H O–SDS system
2
6
,7
exhibited different selectivity. We report herein that
excellent to good anti selectivity was observed in HCl-
8
catalyzed direct Mannich reaction of cyclic ketone and
Next we studied the three-component synthesis starting
9
–11
aldimine in water in the coexistence of SDS.
1
2
from aldehyde, amine, and ketone (Table 4). High anti
selectivity was observed in the reaction with cyclohex-
anone. Tetrahydro-4-pyrone and tetrahydro-4-thiopyrone
also furnished the Mannich adducts with high yields and
high anti selectivity. Acetophenone derivatives also gave
adducts in good yields.13
At the outset, we carried out Mannich reaction of cyclo-
hexanone with an aldimine derived from benzaldehyde
and p-anisidine and the effect of Brønsted acid was exam-
ined (Table 1). High anti selectivity was observed by
means of Brønsted acid. Because HCl exhibited excellent
anti selectivity (entry 1) and is easy to handle, we selected
HCl as a Brønsted acid for the present reaction.
In summary, we have found that good to high anti selec-
tivity was observed in the HCl-catalyzed Mannich-type
reaction of cyclic ketone and aromatic aldimines in a
water–SDS system.
SYNLETT 2005, No. 2, pp 0322–0324
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1.
0
2.
2
0
0
5
Advanced online publication: 10.12.2004
DOI: 10.1055/s-2004-836062; Art ID: U29004ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
HCl-Catalyzed Stereoselective Mannich Reaction in H O–SDS System
323
2
Table 2 Effect of Solvent System
Table 4 Three-Component Mannich Reactions
OMe
O
O
1
2
Ar CHO
+
Ar NH2
+
PhCHO
+
+
2
2
NH2
Acid (10 mol%)
Ar NH
O
Ar NH
O
Acid (10 mol%)
ArNH
O
ArNH
O
H2O
SDS (10 mol%)
r.t., 1 d
Ar1
+
Ar1
H2O
SDS (10–40 mol%)
r.t., 12 h
+
Ph
Ph
Entry Product
1
Yield (%) anti:syn
Entry
Solvent
Yield (%)
anti:syn
96:4
PhNH
O
83
94:6
1
2
3
4
H O, SDS (10 mol%)
84
42
30
36
12
2
a
MeCN–H O, (90:10)
65:35
70:30
65:35
95:5
2
Me
a
MeOH–H O, (90:10)
84a
2
2
96:4
91:9
p-MeOC6H4NH
O
MeCN
MeOH
5
a
Volume:volume.
3
PhNH
PhNH
O
O
80
88
Me
Table 3 Results of the Mannich Reaction
4
O
>98:<2
O
Ar2
Acid (10 mol%)
N
+
H O
2
SDS (10–40 mol%)
r.t.
Ar1
Cl
S
n
5
6
PhNH
O
98
86
–
–
2
Ar NH
O
2
Ar NH
O
Ph
Ph
PhNH
Ar1
+
Ar1
O
4
-MeC6H4
4-MeC6H4
n
n
a
Ar1
Ar2
40 mol% of SDS was employed.
Entry
n
Yield anti:syn
%)
(
1
2
3
4
5
6
Ph
Ph
Ph
4-MeOC H
1
1
1
1
1
2
87
90
90
90
90
89
99:1
–
6
4
X8, 50-100 mesh, Cl form) followed by sat. NaHCO . The resin
3
was removed by filtration over Celite and the filtrate was extracted
with EtOAc for 3 times. The combined organic extracts were
washed with brine, dried over anhyd Na SO , and concentrated to
dryness. The crude mixture was purified by p-TLC (SiO , hexane–
EtOAc = 4:1, R = 0.3) to afford the b-amino ketone (38.3 mg) in
7% as a 99:1 anti:syn mixture.
4-ClC H
82:18
83:17
96:4
6
4
C H
2
4
6
5
2
4-MeC H4
4-ClC H
6
6
4
4
4
f
8
4-MeOC H4
4-ClC H
98:2
6
6
Ph
4-ClC H
77:23
6
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2
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(
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T. Akiyama et al.
LETTER
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(
(
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(
(
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2
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9
,10
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(
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propiophenone did not give the Mannich adduct.
Synlett 2005, No. 2, 322–324 © Thieme Stuttgart · New York