Zorzatto Renan, Mulrainey Paul T, Reid Marc, Tuttle Tell, Lindsay David M, Kerr William J
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, G1, Scotland, 1XL, U.K.
Chemistry. 2024 Dec 10;30(69):e202403090. doi: 10.1002/chem.202403090. Epub 2024 Oct 30.
Hydrogen isotope exchange (HIE) via C-H activation constitutes an efficient method for the synthesis of isotopically-enriched compounds, which are crucial components of the drug discovery process and are extensively employed in mechanistic studies. A series of iridium(I) complexes, bearing a chelating phosphine-N-heterocyclic carbene ligand, was designed and synthesized for application in the catalytic HIE of challenging N- and O-aryl carbamates. A broad range of substrates were labeled efficiently, and applicability to biologically-relevant systems was demonstrated by labeling an ʟ-tyrosine-derived carbamate with excellent levels of deuterium incorporation. Combined theoretical and experimental studies unveiled intriguing mechanistic features within this process, in comparison to C-H activation and hydrogen isotope exchange catalyzed by monodentate Ir(I) NHC/phosphine complexes.
通过C-H活化进行的氢同位素交换（HIE）是合成同位素富集化合物的有效方法，这些化合物是药物发现过程的关键组成部分，并广泛用于机理研究。设计并合成了一系列带有螯合膦-N-杂环卡宾配体的铱（I）配合物，用于具有挑战性的N-和O-芳基氨基甲酸酯的催化HIE。有效地标记了广泛的底物，并通过用优异的氘掺入水平标记一种L-酪氨酸衍生的氨基甲酸酯，证明了其在生物相关系统中的适用性。与单齿Ir（I）NHC/膦配合物催化的C-H活化和氢同位素交换相比，理论和实验相结合的研究揭示了该过程中有趣的机理特征。
