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O
H
H
R
S
R
L
N
Enantioenriched
(
S
)-
33
t
-Bu
S
N
OH
N
O
H
t
-Bu
CHO
H
N
R
L
R
S
32
N
+
i
-Pr
2
Zn
Enantioenriched
(
R
)-
33
t
-Bu
R
N
OH
Steric discrimination of secondary alcohol by asymmetric autocatalysis
O
H
O
H
OH
O
H
Ph
Ph
Ph
Ph
(
R
)-
37
(
R
)-
38
(
R
)-
39
(
R
)-
40
Scheme 12.44.
The concept of steric discrimination in the enantioselective alkylation of
32
using
chiral secondary alcohols as chiral initiators.
alcohol
38
induces (
R
) -
33
. When the isopropyl group was replaced by a more bulky
tert
-
butyl group, that is,
tert
- butyl phenyl carbinol
39
was subjected to the asymmetric auto-
catalysis, the correlation was the same as the result of
38
. On the other hand, when alcohol
40
with the cyclopropyl group instead of isopropyl substitution was used, the correlation
was opposite, which means that the correlation was the same as the case of methyl phenyl
carbinol
37
, that is, the cyclopropyl group was recognized as the smaller substituent
than the phenyl group. We also investigated the unsaturated group-substituted benzyl
alcohols such as phenyl isopropenyl carbinol, phenyl vinyl carbinol, and
- branched
alkyl-substituted benzyl alcohols as chiral initiator of asymmetric autocatalysis.
β
12.5.5. Reversal Phenomena of Enantioselectivity in Asymmetric Autocatalysis
Initiated by Mixed Catalytic System of Chiral and Achiral
- Amino Alcohols
The use of achiral additives in asymmetric organometallic catalysis was shown to be a
promising approach for the optimization of the enantioselectivity of chiral catalysts
[130]. However, the achiral additives sometimes reverse the enantioselectivity of a chiral
catalyst.
We discovered an unexpected reversal of the enantiofacial selectivity of chiral β -
amino alcohol catalysts by a smaller amount of achiral β - amino alcohol catalysts in
dialkylzinc addition to aldehyde (Scheme 12.45) [131]. The addition of
i
- Pr
2
Zn to alde-
hyde
32
using a catalytic amount of chiral (1
R
,2
S
) - or (1
S
,2
R
) -
N
,
N
- dimethylnorephed-
rine (DMNE
41
,
β
99.5% ee) alone afforded (
R
) - or (
S
) - alkanol
33
with high ee,
respectively. On the other hand, when the same reaction was catalyzed by a mixture of
chiral (1
R
,2
S
) - DMNE
41
(0.5 mol %) and achiral
N
,
N
- dibutylaminoethanol (DBAE
44d
,
19.5 mol %), alkanol
33
was obtained with the opposite
S
confi guration to that of
expected from chiral catalyst. And the subsequent asymmetric autocatalysis with signifi -
cant asymmetric amplifi cation affords a highly enantiomerically enriched product. The
reversal of the sense of enantioselectivity was also observed by using the chiral catalyst
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