Catalytic Enantioselective α-Fluorination of Ketones with CsF

Abstract

Disclosed here is a catalytic enantioselective nucleophilic α-fluorination of simple ketones. A new hydrogen bonding donor catalyst was designed to not only overcome the competing catalyst deactivation but also enable efficient enantiocontrol in C–F bond formation between racemic α-keto sulfoniums and CsF. Careful condition optimization resulted in a general and mild protocol applicable for the configurational flexible acyclic α-fluoro ketones bearing a tertiary stereogenic center, thus complementary to the previous electrophilic fluorination methods that were only effective to cyclic ketones and/or tetrasubstituted stereogenic centers. Preliminary mechanistic studies support a phase transfer and dynamic kinetic resolution pathway operated by HBD-enabled anion-binding.