Hydrogen Isotope Exchange of Aromatic C(sp <sup>2</sup> )–H Bonds via Electron Donor–Acceptor Organic Photocatalysis
Riley Y. Way, Xuewen Guo, Yao Tang, Josephine Bridget Shirah, Qilei Zhu
Abstract
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(sp 3 )–H bonds adjacent to heteroatoms or conjugated systems. Herein, we report a mild, transition metal-free photocatalytic method for selective C(sp 2 )–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(sp 2 )–H bonds. This work highlights the potential of EDA catalysis to enable radical-based functionalization of strong C(sp 2 )–H bonds mediated by noncovalent photocatalyst–substrate interactions, in contrast to the more precedented cleavage and functionalization of weaker C(sp 3 )–H bonds.