Chemistry Reference
In-Depth Information
O
∗
OH
∗
OH
i
-Pr
N
i
-Pr
N
N
26
27
Figure 12.2.
Asymmetric autocatalysts containing quinoline and carbamoylpyridine ring for the
reaction of
i
- Pr
2
Zn and the corresponding aldehydes.
asymmetric autocatalyst to afford the same compound
25
with 35% ee. In this reaction,
the resulting product
25
forms the amino alcohol moiety, and it acts as the chiral catalyst
for the next
i
- Pr
2
Zn addition, that is, catalyzes its own production. This is the fi rst experi-
mental observation that realizes asymmetric autocatalysis.
After searching various nitrogen-containing compounds, we found that the zinc alk-
oxide of 2 - methyl - 1 - (3 - quinolyl)propan - 1 - ol
26
catalyzes the enantioselective formation
of itself with the same confi guration in the reaction between quinoline-3-carbaldehyde
and
i
- Pr
2
Zn to afford the product
26
in high ee (up to 94% ee) [52]. In addition, 5-
carbamoyl - 3 - pyridyl alkanol
27
can act as the effi cient autocatalyst to catalyze its own
production in highly enantioselective manner (up to 86% ee) (Fig. 12.2) [53].
Then, we discovered that chiral 2 - methyl - 1 - (5 - pyrimidyl)propan - 1 - ol
29
serves as a
highly enantioselective asymmetric autocatalyst for the addition of
i
- Pr
2
Zn to pyrimi-
dine - 5 - carbaldehyde
28
(Scheme 12.31) [54]. In this compound, the formyl group is
connected to the symmetric pyrimidine ring instead of the pyridine ring. When highly
enantioenriched (
S
) - pyrimidyl alkanol
29
with 99% ee was employed as an asymmetric
autocatalyst, (
S
) -
29
with 95% ee composed of both the newly formed and the initially
used
8
was obtained. The yield of the newly formed
29
was calculated to be 67%, and
the enantiomeric excess was 93% ee.
The
same
structure
The
sa
me
configuration
S
N
OH
(
S
)-
29
(99% ee)
S
CHO
N
OH
N
N
Asymmetric autocatalyst
+
Zn
N
N
2
Product
Toluene, 0
°
C
28
(
S
)-
29
(y. 67%, 95% ee)
Scheme 12.31.
Highly enantioselective asymmetric autocatalysis of pyrimidyl alkanol in the enan-
tioselective
i
- Pr
2
Zn addition.
The result of such a high enantioselectivity in asymmetric autocatalytic reaction
encouraged us to investigate the enantioselective alkylation utilizing the asymmetric
autocatalyst with low ee of 2%. In this pyrimidine system, we found for the fi rst
time asymmetric autocatalysis with amplifi cation of enantiomeric excess, that is,
the initial small enantioenrichment (2% ee) was signifi cantly enhanced to the high
