Catalytic Asymmetric [3+2] Cycloadditions of Ketenes with Epoxides and Aziridines
Final Report Abstract
In this project a novel and efficient methodology for the synthesis of enantiomerically enriched α,α-disubstituted γ-lactams and γ-lactones by means of a catalytic asymmetric [3+2] cycloaddition of ketenes with either N-protected aziridines or epoxides should be developed. Whereas the ring expansion of epoxides could not be realized, it was proved that such [3+2] cycloadditions with aziridines are in principle amenable to catalysis. In a comprehensive survey including various parameters as well as different amine and phosphine catalysts, Taniaphos was found to promote the reaction between phenyl ethyl ketene and 2-(trifluoromethylbenzene)sulfonyl aziridine to afford the desired γ-lactam in 36% yield, albeit as racemate. In the second part of this project a novel catalytic asymmetric methodology for the synthesis of tertiary α-fluoroesters has been developed, which complements recent achievements in enantioselective carbon-fluorine bond forming processes. The enantiomerically enriched products are formed by reaction of disubstituted ketenes with the commercially available fluorinating agent NFSi in the presence of sodium pentafluorophenoxide and the planar-chiral 4-pyrrolidinopyridine PPY*. Alkyl aryl ketenes possessing miscellaneous substituents could be fluorinated in moderate to excellent yields and enantiomeric excesses up to 96%.
