Enantioselective Mannich reaction of 2-fluoro-1,3-diketones to ketimines: access to fluorinated α-amino acid derivatives

Abstract

A highly enantioselective organocatalytic Mannich reaction between 2-fluoro-1,3-diketones and β,γ-alkynyl-α-imino esters has been developed, utilizing a chiral bifunctional urea catalyst. This strategy provides efficient access to a diverse range of fluorinated and non-fluorinated unnatural α-amino acid derivatives with excellent yields (up to 98 %) and enantioselectivities (up to 97 %). A wide array of substrates bearing diverse substituents is compatible with this reaction, showcasing its broad scope. The practicality of this approach was further highlighted by the successful scale-up reaction and subsequent transformations of the fluorinated amino acid derivatives.