Stereoselective reactions. XXI. Asymmetric alkylation of α-alkyl β-keto esters to α,α-dialkyl β-keto esters having either ( R)- or ( S)-chiral quaternary center depending on the solvent system

Abstract

Asymmetric alkylation reaction of chiral enamines prepared from α-alkyl β-keto esters and ( S)-valine tert-butyl ester leading to either enantiomer is described. Lithiated chiral enamines can be alkylated with alkyl halides in a toluene solvent in the presence of HMPA to give, after hydrolysis, α,α-dialkyl β-keto esters in 70–99%ee. The reactions in the presence of THF, dioxolane, or trimethylamine, instead of HMPA, afford the corresponding antipodes with enantiomeric purities of 44–92%ee. The present method provides a procedure for the synthesis of both enantiomers of α,α-dialkyl β-keto esters in high enantiomeric purities starting from the same chiral enamines.