Deuteration of arenes in pharmaceuticals via photoinduced solvated electrons

By:Yi Tao；Cuihua Jin；Chuanwang Liu；Jiawei Bu； Ling Yue； Xipan Li；Kangjiang Liang；Chengfeng Xia

Chem

DOI：https://doi.org/10.1016/.chempr.2024.06.029

Published：2024-07-18

Abstract

      Deuterium incorporation into pharmaceutical molecules has been recognized as having a positive impact on drug efficacy and safety，allowing improvements in pharmacokinetic and/or toxicity profiles.Due to the high chemical inertness of arenes toward the hydrogen atom and the electron transfer processes, the visible light-induced direct deuteration of aromatic C(sp2)–H bonds via hydrogen is otope exchange remains unexplored. Herein, we report a photochemical deuteration protocol for efficient incorporation of deuterium into arenes in a single step, tolerating manifold functionalities in pharmaceutical compounds. Mechanistic studies provided evidence that solvated electrons were generated by light illumination with a phenolate-type photocatalyst and were involved in deuterium incorporation. This protocol was successfully applied to the late-stage deuteration of pharmaceuticals by photochemical aromatic H/D exchange on arenes.