Hydrogen Isotope Exchange of Aromatic C(sp²)-H Bonds via Electron Donor-Acceptor Organic Photocatalysis

Despite the recent emergence of photocatalytic strategies for incorporating heavier hydrogen isotopes─deuterium and tritium─in therapeutic molecules, most established methods focus on the cleavage and labeling of relatively weak C(sp³)-H bonds adjacent to heteroatoms or conjugated systems. Herein, we report a mild, transition metal-free photocatalytic method for selective C(sp²)-H/D exchange via D-atom transfer to an in situ generated arene radical cation intermediate. This protocol enables efficient hydrogen isotope exchange (HIE) across a diverse range of aniline, pyrrole, and indole substrates. Mechanistic studies reveal that the electron donor-acceptor (EDA) complex formed between the electron-deficient photocatalyst and the arene substrate plays a critical role in promoting photoinduced electron transfer (PET) and the selective deuteration of C(sp²)-H bonds. This work highlights the potential of EDA catalysis to enable radical-based functionalization of strong C(sp²)-H bonds mediated by noncovalent photocatalyst-substrate interactions, in contrast to the more precedented cleavage and functionalization of weaker C(sp³)-H bonds.