Abstract
On the basis of our chiral palladium enolate chemistry, efficient catalytic enantioselective
fluorination reactions have been developed. These reactions can be carried out in
environmentally friendly alcoholic solvents without any precaution to exclude water
and moisture. The reaction was found applicable to a wide range of active methine
compounds including β-ketoesters, β-ketophosphonates, and other related compounds
(up to 99% ee). Furthermore, we succeeded in developing efficient fluorination reactions
of 3-substituted oxindoles, which are found among many natural products. Interestingly,
sequential fluorination-solvolysis reaction of a 3-nonsubstituted oxindol allowed
monofluorination of an active methylene compound, and an optically active α-fluoroarylacetate
was obtained (93% ee). To confirm the utility of these reactions, stereoselective
synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic
asymmetric synthesis of BMS204352, which is a promising agent for the treatment of
stroke, were demonstrated.
1 Introduction
2 Chiral Palladium Enolates for Fluorination Reactions
3 Catalytic Enantioselective Fluorination Reactions of β-Ketoesters
4 Reuse of the Pd Catalysts in the Fluorination Reactions Using Ionic Liquids as
a Reaction Medium
5 Catalytic Enantioselective Fluorination of β-Ketophosphonates and Related Compounds
5.1 Fluorination of β-Ketophosphonates
5.2 Fluorination of Other Active Methine Compounds
6 Catalytic Enantioselective Fluorination Reactions of Oxindole Derivatives
7 Summary
Key words
asymmetric catalysis - fluorine - palladium - medicinal chemistry - ionic liquids
References and Notes
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[3 ]
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