Chemistry Reference
In-Depth Information
(
R
,
R
)-
19
(3 mol %)
O
O
Ph
2
CN
Ph
2
CN
+
PhCH
2
Br
O
t
-Bu
O
t
-Bu
50% KOH
aq
Toluene
0°C, 96 h
2a
H
Ph
3a
82%
90% ee
79%
92% ee
81%
92% ee
Si
Si
Si
Si
-
Reuse of
19
Br
+
N
Reuse of
19
Si
Si
Si
Si
(
R
,
R
)-
19
[
Si
= SiMe
2
(CH
2
CH
2
C
8
F
17
)]
Scheme 2C.10.
O
1) CH
2
=CHCH
2
Br
H
2
N
O
t
-Bu
O
2) PhCH
2
Br
3) 10% citric acid
Ph
(
S
,
S
)-
5e
(1 mol %)
21
Ar
N
O
t
-Bu
80%, 98% ee (
R
)
20
(Ar =4-Cl-C
6
H
4
)
CsOH·H
2
O
Toluene
-10~0°C
O
1) PhCH
2
Br
2) CH
2
=CHCH
2
Br
H
2
N
O
t
-Bu
3) 10% citric acid
Ph
Ar
21
-
Br
74%, 92% ee (
S
)
+
N
Ar
(
S
,
S
)-
5e
(Ar = 3,4,5-F
3
-C
6
H
2
)
Scheme 2C.11.
Since the aldimine Schiff base
20
can be readily prepared from glycine, direct stere-
oselective introduction of two different side chains to
20
by appropriate chiral phase-
transfer catalysis would provide an attractive yet powerful strategy for the asymmetric
synthesis of structurally diverse α , α - dialkyl - α-amino acids. This possibility of the one-
pot asymmetric double alkylation has been realized by using
N
- spiro chiral quaternary
ammonium bromide
5e
. Initial treatment of the toluene solution of
20
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
21
in 80% yield with 98% ee after hydrolysis. Notably, in the double
alkylation of
20
by the addition of the halides in a reverse order, the absolute confi gura-
tion of the product
21
was confi rmed to be opposite (Scheme 2C.11) [28].
