Enantioselective Fluorination Reactions Catalyzed by Chiral Palladium Complexes

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

asymmetric catalysis - fluorine - palladium - medicinal chemistry - ionic liquids

References and Notes

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<A NAME="RA41006ST-39">39</A>

Hamashima, Y.; Moriya, K.; Sodeoka, M. unpublished results.