Biomedical Engineering Reference
In-Depth Information
Cl
Cl
O
O
Cl
Cl
1a
(10 mol%)
50% NaOH aq
Me
Ph
+
CH
3
Cl
Ph
MeO
MeO
Toluene, 20°C, 18 h
95%
(ee = 92%)
-
Cl
Br
O
OH
OH
Cl
+
Me
Ph
N
N
N
H
N
H
O
CH
2
COOH
(+)-Indacrinone
Cinchonine
1a
CF
3
SCHEME 7.1
base
2a
to produce the alkylation product (
R
)-
3a
in good yield and moderate
enantioselectivity (Scheme 7.2) [4]. Although asymmetric phase-transfer alkylation
of glycine Schiff base
2a
can be achieved by using chiral phase-transfer catalysts
derived from the relatively inexpensive and commercially available cinchona
alkaloid, research in this area had made little progress until 1997 after O'Donnell's
milestone report. However, new class of cinchona alkaloid-derived catalysts
1c
,
4a
,
and
4b
bearing an
N
-anthracenylmethyl function developed by Lygo and Corey
independently [5,6] have opened a new era of asymmetric phase-transfer catalysis.
In 1999, we designed and prepared the structurally rigid, chiral spiro
ammonium salts of type
5
derived from commercially available (
S
)- or (
R
)-1,1
0
-
bi-2-naphthol as a new
C
2
-symmetric chiral phase-transfer catalyst and successfully
applied it to the highly efficient, catalytic enantioselective alkylation of
2a
under mild
phase-transfer conditions (Scheme 7.3) [7]. A significant effect of aromatic substi-
tution (Ar) at the 3,3
0
-position of one binaphthyl subunit of the catalyst
5
was observed
for enantiofacial discrimination. (
S
,
S
)-
5e
appeared to be the catalyst of choice for the
preparation of a variety of essentially enantiopure
-amino acids using this method.
a
O
O
O
H
3
O
+
catalyst
conditions
Ph
2
C
N
H
2
N
+
PhCH
2
Br
*
*
Ph
2
C
N
O
t-
Bu
OH
O
t-
Bu
H
H
Ph
Ph
2a
3a
Phenylalanine
X
-
Cl
-
+
H
N
OH
+
N
OR
N
N
H
Ar
1b
(Ar = Ph)
1c
(Ar = 9-anthracenyl)
4a
(R = H, X = Cl)
4b
(R = allyl, X = Br)
1b
(10 mol%)
1c
(10 mol%)
4a
(10 mol%)
4b
(10 mol%)
CsOH
.
H
2
O
50% NaOH aq
50% KOH aq
50% KOH aq
CH
2
Cl
2
Toluene
CH
2
Cl
2
Toluene
25°C, 9h
rt, 18 h
rt, 18 h
-78°C, 23 h
75%
63%
68%
87%
(ee = 66%,
R
)
(ee = 89%,
R
)
(ee = 91%,
S
)
(ee = 94%,
S
)
SCHEME 7.2
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