Biomedical Engineering Reference
In-Depth Information
Since the stereochemistry of the newly created quaternary carbon center was
determined in the second alkylation process, this method should be applicable to the
asymmetric alkylation of the aldimine Schiff base
25
derived from the corresponding
a
-amino acid. Several groups pursued this approach and the results are summarized
in Table 7.2.
Ooi and coworkers have successfully demonstrated that
P
-spiro chiral tetra-
aminophosphonium salt
27
can function as an effective catalyst for the highly
enantioselective alkylation of azlactones derived from
-amino acids. The resulting
alkylated azlactones can be readily converted into the corresponding
a
,
-dialkyl
a
a
-amino acids through acidic hydrolysis (Scheme 7.12) [37].
The efficient phase-transfer-catalyzed alkylation strategy with
5e
and
17b
was
successfully applied to the asymmetric synthesis of
a
-alkyl serines using phenyl
oxazoline derivative
28
as a requisite substrate [38,39]. The reaction is general and
provides a practical access to a variety of optically active
a
-alkyl serines through
a
acidic hydrolysis of
29
as exemplified in Scheme 7.13.
The catalytic and chiral efficiency of
17a
was appreciated in the asymmetric
synthesis of cyclic
-alkyl amino acid derivatives. Treatment of
25
with dihaloalkane
under phase-transfer conditions in the presence of (
S
)-
17a
gave the corresponding
a
O
O
O
H
2
N
27
(1 mol%)
TFA
OH
Ph
O
+
O
Br
Ph
K
3
PO
4
t
-BuOMe
-30°C, 18 h
91%
N
N
Ph
Ph
Ph
(ee = 91%)
-
SiMe
2
t
-Bu
Cl
Ar
Ar
Ph
Ph
N
N
+
Ar =
P
N
N
SiMe
2
t
-Bu
Ph
Ph
Ar
Ar
27
SCHEME 7.12
(
S
,
S
)-
5e
(2.5 mol%)
or
(
S
)-
17b
(1 mol%)
CO
2
t
-Bu
R
H
3
O
+
CO
2
t
-Bu
N
N
H
2
N
COOH
+
Ph
RX
Ph
KOH or CsOH
.
H
2
O
Toluene
O
O
HO
R
28
29
α
-Alkyl serines
(ee = 90-99%)
Ar
Ar
Br
-
-
Br
+
+
Bu
Bu
N
N
Ar
Ar
(
S
,
S
)-
5e
(Ar = 3,4,5-F
3
-C
6
H
2
)
(
S
)-
17b
(Ar = 3,5-(CF
3
)
2
-C
6
H
3
)
SCHEME 7.13
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