Chemistry Reference
In-Depth Information
2,5-diketopiperazine as a chiral catalyst; the presence of a chiral product enhances the
enantioselectivity of the chiral catalyst [45] .
12.3.2. Discovery of Asymmetric Autocatalysis
We have developed the addition of dialkylzincs to aldehydes using
- amino alcohols as
the chiral ligand to afford
sec
-alcohols [7b]. The coordination of nitrogen and oxygen
atoms to the zinc atom of dialkylzinc accelerates the nucleophilic attack of alkyl group
to a suitable electrophile. The formation of the complex between dialkylzinc and amino
alcohol enables the C-C bond-forming reaction [6]. Using appropriate chiral amino
alcohols as a chiral ligand, asymmetric catalysis is available, especially
N
,
N
- dibutylnor-
ephedrine (DBNE
22
) [46 - 48] and diphenyl(1 - methylpyrrolidin - 2 - yl)methanol (DPMPM
23
) [49,50] are well-established chiral catalysts to afford chiral products in high yields
and high enantiomeric excesses (Scheme 12.29 ).
β
R
R'
∗
Chiral catalyst
RCHO + R'
2
Zn
OH
Chiral catalyst
Ph
Ph
∗
Ph
Me
∗
∗
N
OH
HO
N(
n
-Bu)
2
Me
DBNE
22
DPMPM
23
Scheme 12.29.
Chiral amino alcohol-catalyzed asymmetric dialkylzinc addition to aldehydes.
During our continuing study on the enantioselective addition of dialkylzincs to
nitrogen-containing aldehydes, we found in 1990, for the fi rst time, that chiral 3-pyridyl
alkanol
25
acts as an asymmetric autocatalyst in the addition of diisopropylzinc (
i
- Pr
2
Zn)
to pyridine - 3 - carbaldehyde
24
(Scheme 12.30) [51]. In the enantioselective addition of
i
- Pr
2
Zn to 3 - pyridinecarbaldehyde
24
, (
S
) - 3 - pyridyl alkanol
25
with 86% ee acts as an
The
same
structure
The
sa
m
e
c
onfiguration
S
OH
Asymmetric
autocatalyst
(
S
)-
25
(86% ee)
S
N
CHO
OH
+
Zn
N
N
2
24
Product (
S
)-
25
(y. 67%, 35% ee)
Scheme 12.30.
Asymmetric autocatalysis of chiral pyridyl alcohol.
