Biomedical Engineering Reference
In-Depth Information
O
N
Ph
2
C
O
O
t
-Bu
(
S
)-
17a
(2 mol%)
Ph
2
C
N
2a
O
t
-Bu
+
CsOH
Toluene
-40°C, 5 h
87%
Br
OBn
O
(ee = 97%)
O
BnO
O
O
1.
TFA, H
2
O
EtOH, rt, 1 h
2.
Pd/C, H
2
Ar
40°C, 24 h
Br
-
63%
+
Bu
Bu
PO(OH)
2
OH
N
Ar
N
H
CO
2
H
N
H
CO
2
t
-Bu
(
S
)-
17a
(Ar = 3,4,5-F
3
-C
6
H
2
)
(dr = 10:1)
Selfotel
SCHEME 7.10
Since the aldimine Schiff base
23
can be readily prepared from glycine, direct
stereoselective introduction of two different side chains to
23
by appropriate chiral
phase-transfer catalysis would provide an attractive yet powerful strategy for the
asymmetric synthesis of structurally diverse
-amino acids. This possi-
bility of the one-pot asymmetric double alkylation has been realized by using
N
-spiro
chiral quaternary ammonium bromide
5e
. Hence, initial treatment of the toluene
solution of
23
and (
S
,
S
)-
5e
(1 mol%) with allyl bromide (1 equiv) and CsOH
H
2
O
at -10
C and the subsequent reaction with benzyl bromide (1.2 equiv) at 0
C resulted
in the formation of the double alkylation product (
R
)-
24
in 80%yield and 98%ee after
hydrolysis. Notably, in the double alkylation of
23
by the addition of the halides in a
reverse order, the absolute configuration of the product (
S
)-
24
was confirmed to be
opposite (Scheme 7.11) [33].
a
,
a
-dialkyl
a
O
1. CH
2
=CHCH
2
Br
H
2
N
O
t
-Bu
2. PhCH
2
Br
3. 10% citric acid
80%
Ph
(
S
,
S
)-
5e
(1 mol%)
(
R
)-
24
O
(ee = 98%)
Ar
N
CsOH
.
H
2
O
Toluene
-10~0 °C
O
t
-Bu
23
(Ar = 4-Cl-C
6
H
4
)
1. PhCH
2
Br
2. CH
2
=CHCH
2
B
r
O
H
2
N
O
t
-Bu
3. 10% citric acid
74%
Ph
(
S
)-
24
Ar
(ee = 92%)
-
Br
+
N
Ar
(
S
,
S
)-
5e
(Ar = 3,4,5-F
3
-C
6
H
2
)
SCHEME 7.11
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