A Simple Copper‐Catalyzed Cascade Synthesis of 2‐Amino‐1H‐indole‐3‐carboxylate Derivatives

Abstract

Abstract:We have developed a simple and efficient copper-catalyzed method for the synthesis of 2-amino-1H-indole-3-carboxylate derivatives via cascade reactions of substituted N-(2-halophenyl)-2,2,2-trifluoroacetamide with alkyl 2-cyanoacetate or malononitrile under mild conditions, and the method is of wide practical application.

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

“…Based on the previous work [22], four copper catalysts were screened at 80 °C using L-proline as ligand, and K 2 CO 3 as base in a mixed solvent of DMSO and H 2 O (volume ratio 1:1) (Table 1, entries 1–4). To our delight, the desired product 4a was obtained in 36% yield using CuI as catalyst and 50% yield with Cu 2 O (Table 1, entries 1 and 4).…”

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

“…Tandem formation of benzofurans 28. [62] What is more, 2-(o-bromophenyl)benzimidazoles 60 were also demonstrated by Fu and co-workers to be good reaction partners of 2-cyanoacetate for the synthesis of heterocycles with interesting fused structures through domino reactions that were initiated by C À C coupling reactions. [57] Further exploration from the same group in the cascade reactions of CÀC coupling and amino condensation led to the development of a useful synthetic method of isoquinolines.…”

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.…”

“…The 2-amino-3-cyanoindoles were obtained in 72% to 93% yield with malononitrile [86]. The copper(I)-catalyzed reaction between 2-haloanilines and β-dicarbonyls (or equivalent compounds), irrespective of the actual pathway, is an extremely versatile and efficient indole synthesis, and many applications are known.…”