Synthesis of 2-Aminoindole-3-carboxylic Acid Derivatives by the Copper(I) Iodide Catalyzed Reaction of N-(2-Iodophenyl)formamides with Malononitrile or Cyanoacetates

Abstract

An efficient method for the synthesis of 2-aminoindole-3-carbonitriles and 2-aminoindole-3-carboxylates by the reaction of N-(2-iodophenyl)formamides with malononitrile and cyanoacetates, respectively, in the presence of a catalytic amount of copper(I) iodide using potassium carbonate as a base is reported.

A Facile Copper-Catalyzed One-Pot Domino Synthesis of 5,12-Dihydroindolo[2,1-b]quinazolines

“…Over the past years, copper-catalyzed coupling reactions in C–C, C–heteroatom bond formation have achieved remarkable progress. , Many types of heterocycles have been constructed via copper-catalyzed domino processes; attractively, some tricyclic and tetracyclic systems, e.g. imidazoindolone, pyrrolo[1,2- a ]quinoxaline, pyrrolo[2,1- a ]isoquinoline, pyrido[1,2- a ]benzimidazole, and 4-oxo-indeno[1,2- b ]pyrroles, have also been constructed. , We are interested in a copper-catalyzed domino process for efficient synthesis of indole fused heterocycles.…”

Copper‐Catalyzed Indole Synthesis

“…Miura's synthesis of 3-acetyl-2-methylindole implicates copper-catalyzed carbon-carbon coupling of enolates with 2-iodoaniline, followed by indolization (Scheme 9, equation 1) [83]. Fu, Oiao, and coworkers [86] and Kobayashi [87] independently arrived at the same 2-aminoindole synthesis involving the copper-catalyzed reaction between 2-haloanilines and cyanoacetates or malononitriles (equations 3 and 4). Ma and colleagues reported similar indole syntheses (equation 2) [84,85], where the formation of 2-trifluoromethylindoles entails deacylation of COR 3 and retention of the trifluoromethyl group.…”

Advances in Copper‐Catalyzed CC Coupling Reactions and Related Domino Reactions Based on Active Methylene Compounds

“…A domino reaction process of C À C coupling/condensation of benzamides 44 with a-ketoesters furnishing isoquinolin-1(2H)-ones 45 in moderate to good yields in the presence of CuI and Cs 2 CO 3 has been devised (Scheme 27). [66] As shown in Scheme 28, the N-(o-halophenyl)-2-halobenzamides (46) were successfully coupled with 2-cyanoacetates or malononitrile to provide multicyclic products (49) in the presence of CuCl and K 2 CO 3 under mild reaction conditions.…”

“…These reactions took place rapidly and the loss of the formyl group during the reaction demonstrated that formamides might serve as potential N-protecting groups in similar transformations. [66]…”