Selective Ru(0)-Catalyzed Deuteration of Electron-Rich and Electron-Poor Nitrogen-Containing Heterocycles

Abstract

A highly selective Ru(3)(CO)(12)-catalyzed deuteration method using t-BuOD as deuterium source is reported. Electron-rich and electron-poor N-heteroarenes such as indoles, azaindoles, deazapurines, benzimidazole, quinolines, isoquinolines, and pyridines were efficiently deuterated at specific positions with high selectivity; in most cases, deuterium incorporation was close to the theoretically possible values. To further increase deuteration degrees, several cycles of the reaction protocol can be carried out which gave superior deuteration degrees employing a much lower excess of deuterating agent compared to established protocols. It was proved that the same protocol can in principle be applied to tritiation reactions important for radioactive labeling of bioactive molecules.

Molecular tools for GABAA receptors: High affinity ligands for β1-containing subtypes

“…Compounds 1 and 4 – 7 contain a methoxy group, which can be used to introduce [ 11 CH 3 ] in the last stage of the synthesis, starting from the corresponding phenols. Furthermore, Schnürch and coworkers have published a proof of principle study for the tritiation of nitrogen containing heterocycles 36 , and this method can be applied to all described compounds. Radioligands will accelerate the testing of candidate compounds for α+/β− binding sites considerably, as the screening for new hits using functional assays is very slow.…”

Highlights of C (sp2)–H hydrogen isotope exchange reactions

“…Ru 3 (CO) 12 was also recently reported as an effective catalyst for the deuteration of heteroarenes, with a number of indoles and isoquinolines included as examples (Figure ).…”

Base metal‐catalyzed hydrogen isotope exchange

“…Previous examples on synthesis of deuterium‐labeled compounds containing N ‐heteroarenes were reported with the precious metals Pd,[12a] Pt,, Rh, and Ru in combination with D 2 O or other deuterated reagents as the isotope sources. Heterogeneous Rh black and Raney nickel are also known to be effective catalysts for tritiation of N ‐heteroarenes, exclusively at the α‐position in N ‐heteroarenes, using T 2 gas or tritiated water as the isotope sources.…”