Kinetic Resolutions - The Stoltz Group

Requirements
- Enantioselective reaction (some chiral influence)
- Significant difference in reaction rate
- Incomplete conversion to product
Preferable
Quick Review of KR
Kinetic Resolution - "A process in which one of the enantiomer constituents of a racemic mixture is more readily
transformed into a product than is the other." (Fiaud and Kagan, 251)
- Enantioenriched product and starting materials are easily separable
- Conversion near 50% returns high ee's for both starting material and product
(Or, even better, all is converted to a single enantiomer --> Dynamic KR)
- Inexpensive and stable reagents (Catalytic process)
R 1
R 1
R 1
R 1
OH
+
OH
OH
+
O
R 2
R 2
Oxidation to
Ketone
(McFadden)
Reduction of
Allylic Alcohol
R
R
s = k fast / k slow = ln((1-C)(1-ee)) / ln((1-C)(1+ee))
C is conversion to product
ee is enantiomeric excess of starting material
Alcohol Resolution Approaches
(±)-
R 1
Esterification
R 1
R 1
O
OH
OH
+
O
R 2
R 2
R 2
R
Epoxidation of
Allylic Alcohol
R 1
R 1
S N 2 Displacement /
Mitsunobu
R 1
R 1
OH
+
OH
O
OH
+
Nu
R 2
R 2
R
R
2