Scalable Synthesis of Trifluoromethylated Imidazo-Fused N‑Heterocycles Using TFAA and Trifluoroacetamide as CF₃‑Reagents

A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic <i>N</i>-trifluoroacetamides followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the preparation of benzylic <i>N</i>-trifluoroacetamides via alkylation of trifluoroacetamide with benzyl (pseudo)­halides was developed. Both methods proceed under mild conditions, and their symbiosis provides access to a wide range of novel CF₃-heterocycles