20.500.12556/RUL-173870 Transition metal-free ortho-deuteration of electron-deficient N-heteroarenes Selectively deuterated electron-deficient N-containing heteroaromatic systems can enable modulation of metabolism with enhanced therapeutic efficacy in pharmaceuticals and improved properties and stability of functional materials, e.g., imaging dyes, light emitters, and catalysts. Current synthetic approaches to selectively deuterate N-heteroaromatic rings largely rely on transition metal (TM) catalysts, prone to inducing over-deuteration while posing several environmental and sustainability concerns and requiring onerous purification to remove metal traces. In this work, an alternative TM-free approach is reported based on directed ortho metalation, which employs lithium 2,2,6,6-tetramethylpiperidide (LiTMP) such as the base and D$_2$O as a green and accessible electrophilic source of deuterium (D). Since the O-carbamate and carboxamide directing groups (DGs) can be transformed into other functional groups or cross-coupled with aromatic or aliphatic moieties, this enables a modular approach to synthesize a series of drug analogs, as exemplified by the synthesis of a precursor to momelotinib-d$_1$ and the key building block pyrimidine-4-carboxylic-5-d$_1$ acid. deuteration directed ortho-matalation ortho-deuteration N-heterocycles O-carbamates carboxamides N-heteroarene pyrazine pyridazine pyrimidine devteriranje usmerjeno ortometaliranje ortodevteriranje N-heterocikli O-karbamati karboksamidi true false true Angleški jezik Slovenski jezik Članek v reviji 2025-09-24 13:11:56 2025-09-24 13:11:57 2025-12-17 04:40:04 0000-00-00 00:00:00 2025 0 0 10 str. iss. 42, art. e202500667 Vol. 28 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.8 1434-193X 10.1002/ejoc.202500667 247384835 Eur_J_Org_Chem_-_2025_-_Orazem_-_Transition_Metal‐Free_Ortho‐Deuteration_of_Electron‐Deficient_N‐Heteroarenes.pdf Eur_J_Org_Chem_-_2025_-_Orazem_-_Transition_Metal‐Free_Ortho‐Deuteration_of_Electron‐Deficient_N‐Heteroarenes.pdf 1 FBF9EF4BD1787D6FEC4DB058BB09BA08 a965917c82c5970605e178ff44194adb8b76dc9f789ae55c74d711c23943e0f9 b72c492b-da7d-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=223975 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202500667 1 1989f3f0-9937-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=218550 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0