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DOI: 10.1055/s-2006-941578
Enantioselective Fluorination Reactions Catalyzed by Chiral Palladium Complexes
Publication History
Publication Date:
12 June 2006 (online)
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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
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References and Notes
A space-filling model depicted in Scheme [3] was generated based on MM3 calculation method using CAChe 5.0. See also ref. 18b.
21In the case of the Michael reaction, no reaction occurred with the Pd complexes 6. The addition of a strong protic acid, such as TfOH, which promotes the reaction cooperatively with the Pd enolate as an activator of the enone, was necessary.
29Recently, Kim et al. also reported the reuse of the palladium complexes in their catalytic enantioselective fluorination. See ref. 14f.
34Hamashima, Y.; Suzuki, T.; Goto, T.; Sodeoka, M. manuscript in preparation.
39Hamashima, Y.; Moriya, K.; Sodeoka, M. unpublished results.