MPAThio Ligand-Accelerated Palladium-Catalyzed Nondirected Hydrogen Isotope Exchange of Arenes with D2O

Hydrogen isotope exchange is an atom-economical strategy for accessing deuterium-labeled molecules, but its synthetic utility is often limited by slow exchange kinetics and poor reactivity of π-extended arenes. Herein, we report a palladium-catalyzed nondirected hydrogen isotope exchange (HIE) enabled by a dual-ligand combination of a monoprotected aminoethyl thioether (MPAThio) and an N-heteroarene ligand. This system exhibits faster HIE kinetics, reaching isotopic equilibrium within 30 min at 105 °C (and within 60 min at 90 °C), and enables efficient deuterium incorporation under mild conditions using D2O as the deuterium source. The protocol enables efficient deuteration of a broad range of mono- and multisubstituted arenes. For poorly soluble substrates relevant to organic light-emitting diode materials, a cosolvent strategy addresses solubility limitations, affording high deuterium incorporation. Mechanistic studies indicate that the MPAThio ligand lowers the barrier of accessing the reactive C-H activation manifold, thereby favoring efficient reversible HIE.