Origin of Enantioselectivity: A Model Study of Sharpless …
445
tartrate (DET) (Takano et al. 1991). The higher space-filling feature of isopropyl
moiety may play a crucial role in etching a reaction route yielding product with
high enantiomeric excess feature and thereby paves a fine way for resolution. In
kinetic resolution, emphasis was given on three facts, viz, the extent of conversion, relative rate and enantiomeric enrichment achieved during resolution. Alkene
having E-geometry is resolved as erythro epoxide in a better manner. In case of Zstereoisomer, however, inclination of epoxide towards erythro form is abruptly less.
The (E.R) form is reported to exhibit higher relative rate difference. Higher
K fast
K slow
illustrates (E,R) stereoisomer is resolved at a faster rate.
3.4 Model Study Based on Structural Formula
The rate of epoxidation as well as ratio of purified enantiomers can be perceived by
a model study. In this discussion, model structure is drawn on the basis of probable
geometry of participating molecules. In dimeric form of homogeneous catalyst, titanium tetra isopropoxide, (+) DIPT is used as chiral auxiliary, the ligand isopropoxide
directs Re-facial approach of epoxidating oxygen, exclusively produces (S,R) form.
A model TS of allyl alcohol having (E,R) orientation is likely to be the structure as
shown in Fig. 1.
In the TS, incipient epoxide ring and hydrogen of chiral alcoholic carbon are in
same face. Space-filling moieties are so oriented that do not encourage repulsive
interaction. When chiral carbon having alcoholic –OH group is in R-orientation, Refacial approach of epoxidating oxygen seems very likely as hydrogen not cyclohexyl
group is projected along this face. Moreover, electron-releasing effect of isopropyl
group of tartrate can set an attractive interaction. All these decrease energies of
TS specifically produce (S,R) epoxide at a faster rate. This TS produces epoxide
with extremely high optical purity (96%). Rate enhancement and product selectivity
together assist kinetic resolution. The approach from Si-face has a very low probability. The stepwise addition allows rotation about C–C bond prior to epoxide ring
formation giving rise to (RR) product. This possibility is extremely low owing to
highly energized TS. Now, the same reaction route is analysed with enantiomeric
allyl alcohol in (E,S) form as shown in Fig. 2.
In TS, incipient epoxide ring and cyclohexyl group of chiral alcoholic carbon are
in same face. The tartrate ligand-guided reaction route makes product spread of (E,S)
isomer into 62% SS isomer and 38% RS isomer. First one, i.e. SS form is formed by
Re-facial approach of epoxidating oxygen while second one, i.e. RS form is resulted
from Si-facial attack. Interaction between more space-filling cyclohexyl group and
epoxidating ring is mandatory in the Re-facial approach of epoxidating oxygen. Van
der Walls repulsive interaction greatly hinders epoxidation resulting only 62% SS
isomeric epoxide. This enhances the magnitude of
K T(S,S)
K E(R,S)
.
The alkyl group of tartrate ester group does offer an influence on the reaction
course. Among several chiral auxiliary (+), DIPT is found to be best for kinetic
445
tartrate (DET) (Takano et al. 1991). The higher space-filling feature of isopropyl
moiety may play a crucial role in etching a reaction route yielding product with
high enantiomeric excess feature and thereby paves a fine way for resolution. In
kinetic resolution, emphasis was given on three facts, viz, the extent of conversion, relative rate and enantiomeric enrichment achieved during resolution. Alkene
having E-geometry is resolved as erythro epoxide in a better manner. In case of Zstereoisomer, however, inclination of epoxide towards erythro form is abruptly less.
The (E.R) form is reported to exhibit higher relative rate difference. Higher
K fast
K slow
illustrates (E,R) stereoisomer is resolved at a faster rate.
3.4 Model Study Based on Structural Formula
The rate of epoxidation as well as ratio of purified enantiomers can be perceived by
a model study. In this discussion, model structure is drawn on the basis of probable
geometry of participating molecules. In dimeric form of homogeneous catalyst, titanium tetra isopropoxide, (+) DIPT is used as chiral auxiliary, the ligand isopropoxide
directs Re-facial approach of epoxidating oxygen, exclusively produces (S,R) form.
A model TS of allyl alcohol having (E,R) orientation is likely to be the structure as
shown in Fig. 1.
In the TS, incipient epoxide ring and hydrogen of chiral alcoholic carbon are in
same face. Space-filling moieties are so oriented that do not encourage repulsive
interaction. When chiral carbon having alcoholic –OH group is in R-orientation, Refacial approach of epoxidating oxygen seems very likely as hydrogen not cyclohexyl
group is projected along this face. Moreover, electron-releasing effect of isopropyl
group of tartrate can set an attractive interaction. All these decrease energies of
TS specifically produce (S,R) epoxide at a faster rate. This TS produces epoxide
with extremely high optical purity (96%). Rate enhancement and product selectivity
together assist kinetic resolution. The approach from Si-face has a very low probability. The stepwise addition allows rotation about C–C bond prior to epoxide ring
formation giving rise to (RR) product. This possibility is extremely low owing to
highly energized TS. Now, the same reaction route is analysed with enantiomeric
allyl alcohol in (E,S) form as shown in Fig. 2.
In TS, incipient epoxide ring and cyclohexyl group of chiral alcoholic carbon are
in same face. The tartrate ligand-guided reaction route makes product spread of (E,S)
isomer into 62% SS isomer and 38% RS isomer. First one, i.e. SS form is formed by
Re-facial approach of epoxidating oxygen while second one, i.e. RS form is resulted
from Si-facial attack. Interaction between more space-filling cyclohexyl group and
epoxidating ring is mandatory in the Re-facial approach of epoxidating oxygen. Van
der Walls repulsive interaction greatly hinders epoxidation resulting only 62% SS
isomeric epoxide. This enhances the magnitude of
K T(S,S)
K E(R,S)
.
The alkyl group of tartrate ester group does offer an influence on the reaction
course. Among several chiral auxiliary (+), DIPT is found to be best for kinetic