Chemistry Reference
In-Depth Information
Cl
Cl
O
O
Cl
Cl
1a
(10 mol %)
Me
Ph
+
CH
3
Cl
Ph
50% NaOH
aq
MeO
MeO
Toluene
20°C, 18 h
95%, 92% ee
-
Br
OH
OH
+
N
N
N
H
N
H
Cinchonine
1a
CF
3
Scheme 2C.1.
2C.3. ALKYLATION
- Amino Acids
After 5 years of the groundbreaking work by the Merck group, similar
N
- benzyl cincho-
ninium halide
1b
has been successfully utilized by O'Donnell and others as a chiral
phase-transfer catalyst for the asymmetric alkylation of glycine Schiff base
2a
. This
produced the alkylation product (
R
) -
3a
in good yield and moderate enantioselectivity
(Scheme 2C.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, commercially available cinchona alkaloid, research in this area had made
little progress until recently after O'Donnell's milestone reports. However, the new class
of cinchona alkaloid-derived catalysts
1c
and
4a
,
b
bearing an
N
- anthracenylmethyl func-
tion developed by Lygo, Corey, and others independently [5,6] has 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 ′ - bi - 2 - naphthol as a new
C
2
-symmetric chiral phase-transfer catalyst and successfully applied it to the highly
effi cient, catalytic enantioselective alkylation of
2a
under mild phase-transfer conditions
(Scheme 2C.3 ) [7] . A signifi cant effect of aromatic substitution (Ar) at the 3,3
2C.3.1. Asymmetric Synthesis of
α
- Alkyl -
α
- position
of one binaphthyl subunit of the catalyst
5
was observed for enantiofacial discrimination.
(
S
,
S
) -
5e
was revealed to be the catalyst of choice for the preparation of a variety of
essentially enantiopure
′
-amino acids by this transformation. Compared with cinchona
alkaloid - derived phase - transfer catalysts, 1 mol % of
5e
is suffi cient for smooth alkyla-
tion. Since both enantiomers of the catalyst of type
5
can be readily assembled starting
from either (
S
) - or (
R
) - 1,1 ′-bi-2-naphthol, a wide variety of natural and unnatural α -
amino acids can be synthesized in enantiomerically pure form by the phase-transfer
catalytic alkylation of
2a
.
These reports have accelerated research into improvements of the asymmetric alkyla-
tion of
2a
, and have resulted in the emergence of a series of cinchona alkaloid-derived
catalysts, as well as the elaboration of purely synthetic chiral quaternary ammonium
α
