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

ABSTRACT 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(sp 2 )–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.