Unlocking Li/Mg-Based Photochemical Nitration Platforms for Anticancer Drug Discovery

The low toxicity and cost-effectiveness of light main-group metal photochemical systems render them highly suitable for drug development, while the redox inertness of light main-group metals significantly hinders this goal. Herein, through the in situ assembly of readily available lithium nitrate, methoxyacetic acid, and aniline substrates, an unprecedented, mild lithium-based photochemical system capable of producing valuable nitro radicals is established. This system enables selective C(sp²)-H (di-)nitration of anilines for synthesizing nitro-aromatic compounds as potential antitumor candidates. Further, replacing lithium nitrate with magnesium nitrate makes the reaction conditions milder, allowing lower-energy green-light irradiation for the (di-)nitration. The two main-group metal photochemical systems also enable direct late-stage functionalization of complex drug molecules, eliminating the risk of transition metal residue and drastically simplifying the workup procedures of pharmaceutical manufacturing processes.