Palladium-catalyzed tandem addition/cyclization in aqueous medium: synthesis of 2-arylindoles

Abstract

An efficient protocol to construct 2-arylindoles was developed through palladium-catalyzed tandem addition/cyclization of potassium aryltrifluoroborates with aliphatic nitriles in aqueous medium. The use of water as the reaction medium makes the synthesis process environmentally benign. A plausible mechanism for the formation of 2-arylindoles involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed. Moreover, the utility of this catalytic tandem transformation was also demonstrated in an efficient gram-scale synthesis. This method provides an alternative synthetic tool for accessing a more diverse array of 2-arylindoles.

Palladium-Catalyzed Three-Component Cascade Reaction of Nitriles: Synthesis of 2-Arylquinoline-4-carboxylates

“…On the basis of these experimental observations and our previous studies, − a plausible reaction mechanism is proposed for the cascade sequences in Scheme . Initially, the arylpalladium species A is generated from transmetalation of arylboronic acid to Pd­(II) catalyst.…”

“…In the past few years, our group has been running ongoing researches targeted on N -heterocycles development from easily available nitriles by transition-metal catalyzed. A series of N -heterocycles have been constructed by our strategies. − However, the synthesis of 2-arylquinoline-4-carboxylate still remains unsolved. Herein, we report the Pd­(II)-catalyzed three-component addition/ring expansion/esterification reaction of 2-(2-oxoindolin-3-yl)­acetonitrile, arylboronic acids, and alcohols, which can serve as a new strategy for one-pot assembly of 2-arylquinoline-4-carboxylates (Scheme e).…”

Recent Progress in the Transition Metal Catalyzed Synthesis of Indoles

“…The lowest yields were found in the reaction of relatively strong electron-withdrawing trifluoromethyl and acetyl groups. The same research group repeated the reaction with potassium aryltrifluoroborates (Scheme 32, Equation (2)) [59]. A reaction with 2-[2-(methylamino)phenyl]acetonitrile led to N-methyl indole in 37% yield.…”

The Role of Green Solvents and Catalysts at the Future of Drug Design and of Synthesis

“…Green Chemistry reaction is one of the promising reactions those run in water. The reaction's yield was calculated as 92% and derivatization of indole was also studied (Scheme 18) [37].…”