Catalyst‐Free, Heating‐Induced Desulfurization Annulation of CF₃‐Imidoyl Sulfoxonium Ylides with Isothiocyanates for the Synthesis of 2‐Trifluoromethyl‐4‐aminoquinolines

Abstract

A heating‐induced desulfurization annulation of readily available CF3‐imidoyl sulfoxonium ylides and isothiocyanates for the construction of 2‐trifluoromethylquinolines has been achieved. The developed transformation was performed under metal‐ and additive‐free conditions, producing a variety of biologically valuable 2‐trifluoromethylquinoline derivatives with high efficiency.

Synthesis of Multifunctionalized Thiazolidine‐4‐thiones via [2+2+1] Annulation of Isothiocyanates and CF3‐Imidoyl Sulfoxonium Ylides

“…We then screened of solvents, and found that TBME improved the yield to 40%. We also noticed that 4‐aminoquinoline 7 was formed as the major byproduct in the above mentioned reactions (entries 1–5) [10b] . The addition of bases such as triethylamine, Na 2 CO 3 and K 2 CO 3 , did not give a better result (entries 6–8), while acids as additives only led to trace amounts of product formation (entries 9, 10).…”

Synthesis of 2‐Trifluoromethyl‐4‐aminoquinolines via Heating‐Promoted Multi‐component Reaction of CF3‐Imidoyl Sulfoxonium Ylides and Amines with Difluorocarbene as a C1 Synthon†

“…The intramolecular cyclization of B afforded an unstable 3‐membered ring intermediate C , followed by desulfurization process to give ketenimine intermediate D . [ 14 ] Then, an intramolecular Friedel−Crafts cyclization or electrocyclization of D occurred to lead to anion E . Finally, the protonation of E could deliver the desired 4‐aminoquinoline product 3 .…”

“…[ 12 ] Furthermore, the cascade annulation reactions employing TFISYs as multifunctional building blocks with suitable partners have successfully furnished various trifluoromethyl‐decorated heterocycles, including pyrroles, pyridones, pyrazoles, benzo[ b ][1,4]oxazines, 2,3‐dihydrothiazoles and 1,4‐dihydro‐1,2,4‐triazines. [ 13 ] Very recently, our group developed a heating‐induced desulfurization annulation of TFISYs and isothiocyanates for the preparation of 2‐trifluoromethyl quinolines, [ 14 ] whereas the isothiocyanates should be pre‐synthesized and substrate scope of the reaction was relatively limited. It is found that TFISYs could be applied as 1‐, 3‐ or 5‐atom synthons to build structurally diversified CF 3 ‐containing heterocycles.…”

Construction of trifluoromethyl-containing heterocycles from trifluoroacetimidoyl chlorides and derivatives

“…In consideration of the high reactivity of TFISYs and the precedent work about the silver-catalyzed reaction of isocyanides with sulfoxonium ylides, 64 a heating-induced desulfurization annulation of TFISYs and isothiocyanates for the construction of biologically valuable 2-trifluoromethyl-4-aminoquinolines was presented by Wu, Chen and co-workers (Scheme 51). 65 The simple transformation was performed under catalyst- and additive-free conditions, which had many advantages of easy operation, insensitivity to air and moisture, high efficiency and scalibility. The benzoyl isothiocyanate was also suitable for the reaction system, but isocyanatobenzene did not work under the standard conditions.…”