Ligand Accelerated Hydrogen Isotope Exchange: Switching C-H Activation from Functionalization Towards C-D Bond Formation

Hydrogen isotope exchange (HIE) has emerged as a unique strategy for labelling, affording plenty of deuterated chemicals with varieties in patterns. Although the HIE based on electrophilic C-H activation could utilize the economic heavy water as deuterium source, the poor kinetic feature and side reactions still hampered its further application. In this work, an acceleration strategy for HIE had been proposed based on ligand-modified C-H insertion intermediate. As a proof of concept, experimental evidence was found by different ligand preference of HIE an functionalizations based on a non-directed Pd-catalyzed dual-ligand system. The competing experiment suggested the functionalization could be partial suppressed by using steric MPAA ligands, which facilitate the progression of C-D bond formation.