Photocatalytic Nitrile Insertion of Cyanoarenes into the C(O)–N Bond of Trifluoroacetamides: Reaction Discovery and Mechanistic Study

Insertion of unsaturated functionalities into the amide C(O)-N bond has emerged as an important approach for constructing nitrogen-containing scaffolds with high atom economy. While insertions of alkynes, arynes, alkenes, and imines are established, the insertion of nitriles remained unexplored. Herein, we present the discovery and mechanistic study of a Lewis base-boryl radical-mediated nitrile insertion of cyanoarenes into the C(O)-N bond of trifluoroacetamides. Under photoredox catalysis, trifluoroacetamides, cyanoarenes, and 4-dimethylaminopyridine-borane (DMAP-BH₃) are converted into <i>N</i>-trifluoroacetyl-substituted aminals. The reaction mechanism was elucidated through a series of experiments and theoretical calculations. The results revealed that the key step involves the combination of a carbon radical-generated from 4-dimethylaminopyridine (DMAP)-boryl radical attack on the amide oxygen of trifluoroacetamide-with a keteniminyl radical anion formed by single-electron reduction of the cyanoarene, affording a 1,3-diazetidin-1-ide intermediate. Subsequent ring-opening of the intermediate, followed by radical boron migration and protonation, leads to the <i>N</i>-trifluoroacetyl-substituted aminal product.