Dhillon Prakriti, Kathiravan Subban, Wiklander Jesper G, Nicholls Ian A
Bioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, Kalmar SE-391 82, Sweden.
J Org Chem. 2025 Jul 10. doi: 10.1021/acs.joc.5c00702.
A novel iridium/silver-based method for catalyzing C-H deuterium labeling of indoles and carbazoles using DO 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] as catalyst, DO 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.
本文介绍了一种新型的铱/银基方法，该方法使用DO催化吲哚和咔唑的C-H氘代反应。该方法利用基于羰基的导向基团实现同位素掺入。此方法具有广泛的底物范围和出色的官能团耐受性，能够对具有生物学重要性的杂环进行多样且精确的标记。值得注意的是，所开发的方案成功应用于卡维地洛的后期官能化，展示了其修饰复杂分子的潜力。操作简便、条件温和、使用市售的[Cp*IrCl]作为催化剂、DO作为易于获得的廉价氘源以及高同位素富集度，使得该方法成为药物和机理研究中合成氘标记化合物的有价值工具。
