Construction of N ‐ CF ₂ H , N ‐ CF ₃ , and N ‐ CH ₂ CF ₃ Motifs

Traceless N‐Polyfluoroalkylation of Weakly Nucleophilic Nitrogen Containing Compounds

“…One strategy, among others, to access N ‐polyfluoroalkyl building‐blocks or ingredients, [8] is the electrophilic N ‐polyfluoroalkylation of precursors containing a nitrogen atom substituted by an electron‐withdrawing group (EWG), such as sulfonamides, N ‐sulfonyl carbamates and phthalimide, followed by cleavage of the appropriately selected EWG. However, they are generally weaker nucleophiles than their parent amine.…”

“…For example, the highly potent butanolide insecticide flupyradifurone (Sivanto®), approved in Europe in 2015, required 2,2-difluoroethylamine for its preparation; [6] quazepam (Doral®) is a N-trifluoroethylated benzodiazepine derivative used as a treatment for insomnia (Scheme 1a). [7] One strategy, among others, to access N-polyfluoroalkyl building-blocks or ingredients, [8] is the electrophilic N-polyfluoroalkylation of precursors containing a nitrogen atom substituted by an electron-withdrawing group (EWG), such as sulfonamides, N-sulfonyl carbamates and phthalimide, followed by cleavage of the appropriately selected EWG. However, they are generally weaker nucleophiles than their parent amine.…”