Synthesis of difluoromethylated formimidamides from primary aryl amines using TMSCF2Br as a dual C1 synthon

Photoredox Catalysis for the Synthesis of N‐CF2H Compounds Using 1‐((N‐(difluoromethyl)‐4‐methylphenyl)‐sulfonamido)pyridin‐1‐ium Trifluoromethanesulfonate

“…Herein, we report a new pyridinium reagent 1 a , enabling ⋅N(Ts)CF 2 H generation to forge C( sp 2 )−N(Ts)CF 2 H and C( sp 3 )−N(Ts)CF 2 H bonds (Scheme 1d). The electron withdrawing tosyl moiety (Ts) is utilized as a bifunctional handle for potential derivatization and to prevent fluoride elimination as seen with unprotected fluoroalkylamines [26, 27] . Pyridinium 1 a is synthesized in two steps from commercially available 1‐aminopyridinium iodide and non‐ODS difluoromethyl trifluoromethanesulfonate (CF 2 HOTf) to yield a free‐flowing shelf‐stable solid.…”

“…The electron withdrawing tosyl moiety (Ts) is utilized as a bifunctional handle for potential derivatization and to prevent fluoride elimination as seen with unprotected fluoroalkylamines. [26,27] Pyridinium 1 a is synthesized in two steps from commercially available 1-aminopyridinium iodide and non-ODS difluoromethyl trifluoromethanesulfonate (CF 2 HOTf) to yield a free-flowing shelf-stable solid. From a retrosynthetic standpoint, this would provide direct access to the NCF 2 H moiety, diversifying N-(difluoromethyl)aminated compounds, which would be highly valued for medicinal chemistry and discovery of future drug candidates.…”

Copper-Catalyzed Synthesis of Difluoromethyl Alkynes from Terminal and Silyl Acetylenes

“…Among the various strategies to introduce fluorine atoms into molecules, the development of difluoromethylation protocols is on the rise and has been of interest for several recent investigations. − The difluoromethyl group has been described as a lipophilic bioisostere of thiol (−SH) and amino (−NHR) groups due to their similar hydrogen bond acidity and as a less lipophilic bioisostere to the −CH 3 group. , Reportedly, the hydrogen bond donor capabilities of the −CF 2 H moiety are heavily influenced by the chemical environment of a given compound. These properties make the difluoromethyl group an attractive moiety to tune the physicochemical properties of bioactive compounds.…”