Ligand-Controlled Synthesis of Azoles via Ir-Catalyzed Reactions of Sulfoxonium Ylides with 2-Amino Heterocycles.
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.
Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
Alicia M
AM
Phelps
Vincent S
VS
Chan
José G
JG
Napolitano
Scott W
SW
Krabbe
Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
Jennifer M
JM
Schomaker
Shashank
S
Shekhar
D001393:Azoles / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D003622:Dapsone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007495:Iridium / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
D001393:Azoles; D006571:Heterocyclic Compounds; D008024:Ligands; C036115:sulfoxone; D007495:Iridium; D003622:Dapsone