Cu(I)-catalyzed coupling reactions of fluorinated imidoyl halides with terminal alkynes: Convenient synthesis of fluorinated alkynyl imines

Trifluoroacetimidoyl halides: a potent synthetic origin

“…In 2011, Wu and co-workers demonstrated a Cu(I)-catalyzed coupling reaction of fluorinated imidoyl halides with terminal alkynes to construct fluorinated alkynyl imines (Scheme 21). 37 Compared with a similar work of synthesizing fluorinated alkynyl imines via a Pd/Cu-catalyzed coupling reaction of bromodifluoroacetimidoyl iodide with terminal alkynes previously reported by the same group, 38 the reaction could be realized by a Cu(I) catalyst only. The transformation proceeds smoothly with respect to bromodifluoromethylated imidoyl halides and trifluoromethylated imidoyl halides, whereas the latter required stoichiometric amounts of Cu(I).…”

Trapped in Misbelief for Almost 40 Years: Selective Synthesis of the Four Stereoisomers of Mefloquine

“…The synthesis of the literature‐known19 imidoyl iodide building block 3 is inspired by the work of Sadighi et al 20. The preparation starts with the trifluoroacetylation of commercially available 2‐trifluoromethylaniline 5 with trifluoroacetic acid anhydride and a catalytic amount of 4‐dimethylaminopyridine (DMAP) in CH 2 Cl 2 using pyridine as base to yield the trifluoroacetamide 6 in quantitative yield.…”

“…With this overview in mind, the retrosynthetic analysis of 1 a is based on an Li-mediated alkyne addition to construct the stereogenic centre on C-11 and a domino Sonogashira-6p-electrocyclisation reaction as key step for the establishment of the quinoline moiety ( Figure 2). [18] The synthesis of the literature-known [19] imidoyl iodide building block 3 is inspired by the work of Sadighi et al [20] The preparation starts with the trifluoroacetylation of commercially available 2-trifluoromethylaniline 5 with trifluoro-acetic acid anhydride and a catalytic amount of 4-dimethylaminopyridine (DMAP) in CH 2 Cl 2 using pyridine as base to yield the trifluoroacetamide 6 in quantitative yield. Trifluoroacetamide 6 is subsequently converted into the trifluoroacetimidoyl iodide 3 using PPh 3 and I 2 in toluene and iPr 2 NEt as base ( Figure 3).…”

Vinyldiazo Compounds as 3-Carbon Radical Acceptors: Synthesis of 4-Fluoroacridines via Visible-Light-Promoted Cascade Radical Cyclization

“…We have previously reported a highly functionalized difluoromethyl radical precursor, 11 namely N-aryl chlorodifluoromethyl alkynyl ketoimine (Scheme 2, compound 1), which is readily prepared from ClF 2 CO 2 H, CCl 4 , and aniline followed by a Sonogashira coupling with terminal alkyne. 12 Its reaction with alkenes provides a facile method for the synthesis of gem-difluorinated fused quinolines by visible light photo- However enticing this proposal might appear, it was conceived to have two major challenges: (1) How will initial radical A be generated if less reactive C−Cl was used? (2) If photocatalyst was employed to generate radical A, how will the background pyrazole formation mediated by light or base be suppressed?…”

“…We have previously reported a highly functionalized difluoromethyl radical precursor, namely N-aryl chlorodifluoromethyl alkynyl ketoimine (Scheme , compound 1 ), which is readily prepared from ClF 2 CO 2 H, CCl 4 , and aniline followed by a Sonogashira coupling with terminal alkyne . Its reaction with alkenes provides a facile method for the synthesis of gem -difluorinated fused quinolines by visible light photoredox catalysis.…”