Chemistry Reference
In-Depth Information
environment in our bodies. Given that nature so gracefully exploits water, why should
mankind not perform synthesis in water too?
1.2.1. Chiral Lewis Acid Catalysis in Water
In general, the formation of chiral Lewis acid complex is much more diffi cult in water
than in organic media, since a chiral ligand competes with water in coordination with
Lewis acid. Although there are successful reports to realize chiral Lewis acid catalyzed
asymmetric reactions in
aqueous media
, it is still very challenging to use
water as sole
solvent
[1,2] .
1.2.1.1. Mannich-Type Reaction in Water
Asymmetric Mannich reactions provide
useful routes for the synthesis of optically active β-amino ketones and esters, which are
versatile chiral building blocks for the preparation of many nitrogen-containing biologi-
cally important compounds [3] . Diastereo - and enantioselective Mannich - type reactions
of α - hydrazono ester
1
with silicon enolates in aqueous media can be successfully
achieved with a ZnF
2
- chiral diamine
L - 1
complex (Scheme 1.1) [4]. This complex enables
reactions in water without any organic cosolvents or additives to proceed smoothly,
affording the corresponding products in high yields and high stereoselectivities (Condi-
tions A) [5]. In the reaction of α - monosubstituted ketone - derived silyl enol ether with
1
, cetyltrimethyl ammonium bromide (CTAB) is necessary to accelerate the reaction. It
is also noted that, in contrast to most asymmetric Mannich-type reactions, either syn- or
anti - adducts are stereospecifi cally obtained from (E)- or (Z)-silicon enolates in the
present reaction (Conditions B). Moreover, the amount of ZnF
2
and
L - 1
can be success-
fully reduced to 10 and 5 mol %, respectively, maintaining the same level of result
(Conditions C).
Ph
Ph
MeO
NH
HN
OMe
L-1
(
x
mol %)
ZnF
2
(
y
mol %)
CTAB (
z
mol %)
0°C, H
2
O
NHBz
BzHN
N
N
H
O
OSiMe
3
+
EtO
EtO
R
1
R
3
H
R
3
O
O
R
1
R
2
R
2
1
(3.0 equiv)
Conditions A:
x
= 10,
y
= 100,
z
= 0,
R
1
=
R
2
= H, 20 h
Conditions B:
x
= 10,
y
= 100,
z
= 2, 20 h
Conditions C:
x
= 5,
y
= 10,
z
= 2, 40 h
Scheme 1.1.
1.2.1.2. Michael Reaction in Water
AgOTf - PPh
3
complex - catalyzed Michael addi-
tions of
-ketoesters to nitroalkenes proceed effi ciently only in water but not in organic
solvents (Scheme 1.2 ).
β
