Chemistry Reference
In-Depth Information
O
O
Catalyst
Conditions
Ph
2
CN
Ph
2
CN
+
*
PhCH
2
Br
O
t-
Bu
O
t-
Bu
2a
H
Ph
3a
Cinchona alkaloid derivatives
Br
-
Br
-
6a
(10 mol %)
50% KOH
aq
Toluene-CHCl
3
(7:3)
0°C
90%, 96% ee (
S
)
6b
(5 mol %)
50% KOH
aq
Toluene-CHCl
3
(7:3)
0°C
94%, 96%
ee (
S
)
+
+
H
H
N
F
N
F
O
O
+
N
N
N
F
O
-
Park, Jew, and others [8]
Park, Jew, and others [9]
6b
6a
7
(3-5 mol %)
50% KOH
aq
Toluene-CHCl
3
(7:3)
0°C
7a
: 91%, 90%
ee (
S
)
7b
: 93%, 94%
ee (
S
)
-20°C
7c
: 94%, 94%
ee (
S
)
Park, Jew, and others [10,11]
Q
Q
X
Q
+
H
N
-
3Br
-
2Br
=
Q
Q
O
Q
N
7a
(X = H)
7b
(X = F)
7c
Tartrate derivatives
MeO
H
OMe
H
Me
4-MeO-C
6
H
4
8a
(10 mol %)
CsOH·H
2
O
Toluene-CH
2
Cl
2
(7:3)
-70°C
87%, 93% ee (
R
)
9
(30 mol %)
1M KOH
aq
CH
2
Cl
2
0°C
55%, 90% ee
(
R
)
Nagasawa and others [13]
+
N
+
N
O
Me
t
-Bu
-
4-MeO-C
6
H
4
2I
4-MeO-C
6
H
4
H
H
O
O
N
+
O
-
Me
4-MeO-C
6
H
4
Cl
Shibasaki and others [12]
Me
Me
8a
9
Scheme 2C.4.
only 4% yield (92% ee), while similar benzylation of
2a
in the presence of 18-crown-6
(0.05 mol %) proceeded smoothly to furnish
3a
in 90% yield with 98% ee. The origin of
this dramatic rate enhancement would be the ability of the crown ether to extract KOH
into toluene phase, accelerating otherwise slow deprotonation process (Scheme 2C.6)
[21] .
We discovered the very powerful chiral quaternary ammonium bromide
16
possess-
ing fl exible straight-chain alkyl groups instead of a rigid binaphthyl moiety functions as
an unusually active chiral phase-transfer catalyst. Most notably, the reaction of
2a
with
various alkyl halides proceeded smoothly under mild phase-transfer conditions in the
presence of only 0.01 - 0.05 mol % of (
S
) -
16
to afford the corresponding alkylation prod-
ucts with excellent enantioselectivities (Scheme 2C.7 ) [22] .
The enantioselective synthesis of α-amino acids employing easily available and reus-
able chiral catalysts or reagents presents clear advantages for large-scale application.
Nájera and others prepared resin-supported ammonium salt
17a
by reaction of cross-
linked chloromethylated polystyrene (Merrifi eld resin) and employed it as a chiral
phase-transfer catalyst for the alkylation of glycine isopropyl ester-derived Schiff base
2b
[23]. Optimization of the reaction parameters for the benzylation led to the formation
of
3b
in 90% yield with 90% ee (Scheme 2C.8). Cahard, Plaquevent, and others suc-
