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, as well as the side reactions still hampered its further application. In this work, an acceleration strategy for HIE development had been proposed based on ligand-modified C-H activation intermediate. According to the strategy, high efficiency HIE condition could be stemmed from the moderate-potency conditions in the corresponding functionalizations, which may fail in balancing the C-H activation and the subsequent coupling. Thus, as a proof of concept, experimental evidence was provided by different ligand preferences of HIE and functionalizations based on a non-directed Pd-catalyzed dual-ligand system. The competing experiment suggested the functionalization could be partially suppressed by using steric MPAA ligands, which facilitated the progression of C-D bond formation.