Silver‐Mediated N ‐Trifluoromethylation of Amides and Peptides

Summary of main observation and conclusion We report herein the direct N ‐trifluoromethylation of N ‐H amides. Promoted by AgOTf and 2‐fluoropyridine, the reaction of a variety of amides with Selectfluor, TMSCF 3 and CsF proceeds smoothly at room temperature leading to the corresponding N ‐trifluoromethylated products in satisfactory yields. The protocol is also applicable to amino acid derivatives, resulting in efficient and chemoselective N ‐trifluoromethylation of di‐ and tri‐peptides with retention of configuration. A mechanism involving reductive elimination of Ag(III) intermediates to form N—CF 3 bonds is proposed.