Biomedical Engineering Reference
In-Depth Information
(
R
,
R
)-
21
(3 mol%)
O
O
Ph
2
C
N
+
PhCH
2
Br
Ph
2
C
N
O
t
-Bu
O
t
-Bu
50% KOH aq
Toluene, 0°C, 96 h
H
Ph
2a
3a
Si
Si
82% (ee = 90%)
Si
Si
reuse of
21
-
Br
79% (ee = 92%)
+
reuse of
21
N
81% (ee = 92%)
Si
Si
Si
Si
(
R
,
R
)-
21
(
Si
= SiMe
2
(CH
2
CH
2
C
8
F
17
))
SCHEME 7.8
O
(
S
,
S
)-
5e
(1 mol%)
O
1N HCl
Br
Br
O
t
-Bu
Ph
2
C
N
+
O
t
-Bu
NH
2
50% KOH aq
Toluene
0°C, 6 h
THF
2a
Br
NaHCO
3
(excess)
82%
Ar
-
Br
O
+
N
O
t
-Bu
NH
Ar
22
(ee = 98%)
(
S
,
S
)-
5e
(Ar = 3,4,5-F
3
-C
6
H
2
)
SCHEME 7.9
with an excess amount of NaHCO
3
facilitated the intramolecular ring closure to afford
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
tert
-butyl ester
22
in 82% yield and
98% ee (Scheme 7.9) [29].
The synthetic utility of the asymmetric alkylation of
2a
was also demonstrated
in the asymmetric synthesis of Selfotel (CGS-19755) [30], which is a potent NMDA
receptor antagonist, as shown in Scheme 7.10 [31].
7.2.2. Asymmetric Synthesis of
a
,
a
-Dialkyl
a
-Amino Acids
Nonproteinogenic, chiral
-amino acids possessing stereochemically
stable quaternary carbon centers have been significant synthetic targets not only
because they were shown to be effective enzyme inhibitors but also because they are
indispensable for the elucidation of enzymatic mechanisms. Accordingly, numerous
studies have been conducted to develop truly efficient methods
a
,
a
-dialkyl-
a
for
their
preparation [32], and phase-transfer catalysis has made unique contributions.
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