Catalytic generation of α-CF₃ enolate: Direct catalytic asymmetric Mannich-type reaction of α-CF₃ amide

The introduction of the CF₃ unit is a common strategy for modifying pharmacokinetic properties and slowing metabolic degradation in medicinal chemistry. A catalytic and enantioselective addition of α-CF₃ enolates allows for expeditious access to functionalized chiral building blocks with CF₃-containing stereogenicity. To date, α-CF₃ enolates have been a less explored class of nucleophiles because of rapid defluorination. The present study reveals that a designed α-CF₃ amide enables a direct asymmetric Mannich-type reaction in a cooperative catalytic system.