Synthesis of α-Secondary Carbon Fluorine Amides via Successive Acylation and Fluorination of Schiff Bases: A Modification Strategy for Oxalyl Amides

A practical, efficient synthesis of α-fluorinated alkyl amides is achieved via successive acylation/fluorination of disubstituted Schiff bases under mild conditions. The reaction shows good scope, tolerates various functional groups including aryl- and alkyl-groups and imines and acyl chlorides, with moderate-to-good yields. Based on mechanistic insights, the reaction could be accelerated via α-phenyl groups via stabilizing benzylic carbocations. This method could provide a complementary strategy for modifying bioactive molecules and for drug development.