Base-mediated [3+2] annulation of trifluoroacetimidoyl chlorides and isocyanides: An improved approach for regioselective synthesis of 5-trifluoromethyl-imidazoles

Palladium‐Catalyzed Carbonylative Synthesis of 2‐(Trifluoromethyl)quinazolin‐4(3H)‐ones from Trifluoroacetimidoyl Chlorides and Nitro Compounds

“…Then, various phosphorus ligands, including TFP, P(p-CH 3 -Ph) 3 , Xantphos, dppp and dppf, were tested in the reaction, which demonstrated that the effect of dppp was superior to that of the other ligands ( Table 1, entries 6-10). The examination towards solvents implied only performing the reaction in 1,4-dioxane could lead to the targeted product in excellent yield (Table 1, entries [11][12][13][14]. The impact of various bases upon the transformation was remarkable, as verified that sluggish results were observed compared with that of Na 2 CO 3 ( Table 1, entry 15).…”

“…Since we consistently devote ourselves to explore efficient and practical methods for the construction of diverse trifluoromethyl-substituted N-heterocycles, [12] we herein report our recent discovery on palladiumcatalyzed carbonylative synthesis of 2-(trifluoromethyl)quinazolin-4(3H)-ones from readily available trifluoroacetimidoyl chlorides [13] and nitro compounds with Mo(CO) 6 as a convenient CO surrogate and reductant (Scheme 1e). It is worth noting that the incorporation of trifluoromethyl group into the heterocycles can dramatically alter the physicochemical properties of the parent molecules due to the unique properties of fluorine atoms.…”

Studies towards the Design and Synthesis of Novel 1,5-Diaryl-1H-imidazole-4-carboxylic Acids and 1,5-Diaryl-1H-imidazole-4-carbohydrazides as Host LEDGF/p75 and HIV-1 Integrase Interaction Inhibitors

“…These α-isocyanoacetates are useful multipurpose reagents for the construction of various nitrogen-containing heterocycles [34,35]. Different five-membered nitrogen-containing heterocycles like thiazole [36,37], imidazole [31][32][33][38][39][40][41][42][43], indole [44][45][46], oxazole [47], pyrrole [48,49], and triazole [50,51] have been built using these synthons. Isocyanoacetate building blocks have attracted the interest of researchers owing to their structural characteristics, reactivity, and reliability.…”

“…Additionally, Cai and co-workers [41] in 2019 reported an annulation between α-isocyanoacetates and ketenimines in the presence of a base, potassium tert-butoxide (t-BuOK), in DMF at 40 • C as an efficient and straightforward synthesis of disubstituted imidazole-4-carboxylate ester derivatives in good yields (Scheme 1e). Additionally, Hu and co-workers [42] in 2020 reported a new method for preparing 1,5-disubstituted imidazole-4-carboxylate esters by t-BuOK-mediated annulation of ester isocyanoacetates with trifluoroacetimidoyl chlorides (Scheme 1f). The methodology includes mild reaction conditions and uses readily available reagents.…”

“…Herein we describe a novel and efficient approach for the synthesis of diaryl-imidazole-4-carboxylate esters via cycloaddition of an α-isocyanoacetate with stable N-aryl-benzimidoyl chloride in-termediates (Scheme 1h). None of the previously reported synthetic methods to these compounds [33,[40][41][42][43]] make use of diarylimidoyl chlorides and isocyanoacetate esters. The carboxylate esters prepared using this new methodology were subsequently converted into the corresponding 1,5-diaryl-1H-imidazole-4-carboxylic acids and 1,5-diaryl-1H-imidazole-4-carbohydrazides, which were then evaluated for their ability to bind to the novel HIV-1 IN dimer interface pocket.…”