Chemistry Reference
In-Depth Information
Sharpless's Chirally Catalyzed Oxidations
Parallel to the progress in catalytic asymmetric hydrogenations Barry Sharpless has developed chiral catalysts for
very important oxidation reactions. The epoxidation reaction discovered in 1980 by Sharpless and Kazuki is an
example of a strategy of using a reagent to achieve stereochemical control. Using titanium(IV) tetraisopropoxide,
tert
-butyl hydroperoxide, and an enantiomerically pure dialkyl tartrate, the Sharpless reaction accomplished the
epoxidation of allylic alcohols with excellent etereoselectivity. This powerful reaction is very predictable. If the D-(-
)-tartrate ligand [D-(-)-DET] is used in epoxidation, the oxygen atom is delivered to the top face of the olefin where
the allylic alcohol is depicted as in Fig.
12
(i.e. the OH group in the lower right hand corner).
HO
CO
2
Et
D-(-)-DET
HO
CO
2
Et
(2
S
,3
S
)
"O"
O
R
3
R
2
R
1
D-(-)-DET
R
2
Ti(O
i
-Pr)
4
t
-BuOOH, CH
2
Cl
2
4 A mol. sieves, - 20ºC
OH
R
3
R
1
(70-90% yield,
> 90% ee)
º
O
H
OH
O
R
1
R
2
L-(+)-DET
"O"
R
3
HO
CO
2
Et
L-(+)-DET
HO
CO
2
Et
(2R,3R)
Figure 12:
The predictive stereoselectivity of the Sharpless epoxidation.
The L-(+)-tartrate ligand [L-(+)-DET] allows the bottom face of the olefin to be epoxidised. When achiral allylic
alcohols are employed, the Sharpless reaction exhibits exceptional enantiofacial selectivity (
ca.
100:1) and provides
convenient access to synthetically versatile epoxy alcohols.
Ti(OPr
i
)
4
(+)-Diisopropyl tartrate
Cumene hydroperoxide
ArONa
Ti(OPr
i
)
4
H
OH
O
OH
OH
O
OH
Allyl alcohol
HBr/AcOH
OH
-
NH
2
OH
H
N
O
OAc
O
O
O
OH
(
S
)-Propranolol
48% overall yield
Figure 13:
Routine synthesis of (
S
)-propranolol.
The emergence of the powerful Sharpless asymmetric epoxidation in the 1980s has stimulated major advances in
both academic and industrial organic synthesis. Through the action of an eantiomerically pure titanium-tartrate
complex, a myriad of achiral and chiral allylic alcohols can be epoxidised with exceptional stereoselectivity. Interest
