Iridium/Silver-Catalyzed H/D Exchange for Perdeuteration of Indoles and Site-Selective Deuteration of Carbazoles: Application in Late-Stage Functionalization
Prakriti Dhillon, Subban Kathiravan, Jesper G. Wiklander, Ian A. Nicholls
Abstract
High Resolution Image Download MS PowerPoint Slide A novel iridium/silver-based method for catalyzing C–H deuterium labeling of indoles and carbazoles using D 2 O is presented. The method leverages a carbonyl-based directing group to achieve isotopic incorporation. This method demonstrates broad substrate scope and excellent functional group tolerance, enabling diverse and precise labeling of biologically important heterocycles. Notably, the developed protocol is successfully applied to the late-stage functionalization of carvedilol, showcasing its potential for modifying complex molecules. The operational simplicity, mild conditions, commercially available [Cp*IrCl 2 ] 2 as catalyst, D 2 O as the easily available cheap deuterium source, and high isotopic enrichment make this approach a valuable tool for the synthesis of deuterium-labeled compounds in pharmaceutical and mechanistic studies.