Chemistry Reference
In-Depth Information
Since the stereochemistry of the newly created quaternary carbon center was deter-
mined in the second alkylation process, this method should be applicable to the asym-
metric alkylation of the aldimine Schiff base
22
derived from the corresponding
- amino
acids. Several groups pursued this approach, and the results are summarized in Scheme
2C.12 .
α
O
O
H
3
O
+
Catalyst
Conditions
Ar
N
H
2
N
+
*
PhCH
2
Br
O
t
-Bu
O
t
-Bu
Me
Me
Ph
23
22
-
1b
(10 mol %)
Ar = 4-Cl-C
6
H
4
K
2
CO
3
/KOH
aq
CH
2
Cl
2
rt
80%, 44% ee (
R
)
O'Donnell and Wu [29]
6c
(10 mol %)
Ar = 4-Cl-C
6
H
4
K
2
CO
3
/KOH
aq
Toluene
rt
95%, 87% ee (
S
)
Lygo and others [30]
-
Cl
Cl
O
H
+
H
N
+
N
OH
N
H
N
1b
6c
Br
-
-
8a
(10 mol %)
Ar = 4-Cl-C
6
H
4
CsOH·H
2
O
Toluene-CH
2
Cl
2
-70°C
83%, 89% ee (
R
)
Shibasaki and others [12b]
6a
(10 mol %)
Ar = 2-Np
RbOH
Toluene
-35°C
91%, 95% ee (
S
)
2BF
4
Me
4-MeO-C
6
H
4
+
H
N
+
N
F
O
Me
4-MeO-C
6
H
4
F
4-MeO-C
6
H
4
O
t
-Bu
O
N
+
N
F
Me
4-MeO-C
6
H
4
Park, Jew, and others [31]
6a
8b
Ar
Ar
5e
(1 mol %)
Ar = 4-Cl-C
6
H
4
CsOH·H
2
O
Toluene
0°C
85%, 98% ee (
R
)
Br
-
16
(0.05 mol %)
Ar = 4-Cl-C
6
H
4
CsOH·H
2
O
Toluene
0°C
63%, 98% ee (
R
)
Maruoka and others [22]
-
Br
+
+
Bu
Bu
N
N
Ar
Ar
Maruoka and others [28]
(
S
,
S
)-
5e
(Ar = 3,4,5-F
3
-C
6
H
2
)
(
S
)-
16 (
Ar = 3,4,5-F
3
-C
6
H
2
)
Scheme 2C.12.
2C.3.3. Asymmetric Alkylation of β - Keto Esters
Asymmetric alkylation of
-keto ester under phase-transfer condition can be a unique
tool to construct an all-carbon chiral quaternary carbon center easily. Manabe designed
chiral phosphonium salts of type
26
that have multiple hydrogen-bonding sites [32]. The
utility of
26
was demonstrated in the asymmetric alkylation of
β
- keto ester
24
(Scheme
2C.13). Although the reactivity and selectivity need to be improved, this study advances
in the development of a new chiral onium salt.
N
- benzyl cinchoninium bromide
1d
is
applied to the reaction and gives the benzylated compound
25
in an excellent chemical
yield with 46% ee [33] . Effi cient, highly enantioselective construction of quaternary
stereocenter on
β
-keto esters under phase-transfer conditions has been achieved using
N
-spiro chiral quaternary ammoniumu bromide
5f
as catalyst [34]. This system has a
broad generality in terms of the structure of
β
β
- keto esters and alkyl halides.
