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Ligand-Controlled Synthesis of Azoles via Ir-Catalyzed Reactions of Sulfoxonium Ylides with 2-Amino Heterocycles

Research paper by Alicia M. Phelps, Vincent S. Chan, José G. Napolitano, Scott W. Krabbe, Jennifer M. Schomaker, Shashank Shekhar

Indexed on: 05 May '16Published on: 22 Apr '16Published in: Journal of Organic Chemistry



Abstract

An iridium-catalyzed method was developed for the synthesis of imidazo-fused pyrrolopyrazines. The presence or absence of a nitrogenated ligand controlled the outcome of the reaction, leading to simple β-keto amine products in the absence of added ligand and the cyclized 7- and 8-substituted-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine products in the presence of ligand. This catalyst control was conserved across a variety of ylide and amine coupling partners. The substrate was shown to act as a ligand for the iridium catalyst in the absence of other ligands via NMR spectroscopy. Kinetic studies indicated that formation of the Ir-carbene was reversible and the slow step of the reaction. These mechanistic investigations suggest that the β-keto amine products form via an intramolecular carbene N–H insertion, and the imidazopyrrolopyrazines form via an intermolecular carbene N–H insertion.

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