GreenMedChem-inspired light-air mediated C(sp³)-H bond oxidation: A new tool for isoquinolone synthesis

Isoquinolone represents a significant and promising molecular scaffold for drug development. As green chemistry advances, light-mediated C(sp³)-H bond oxidation has emerged as a pivotal tool for medicinal chemists in constructing isoquinolone framework and enabling late-stage functionalization. However, existing methods often rely on metal catalysts, hazardous peroxides, dye sensitizers, or high-temperature atmosphere, which pose environmental concerns. Inspired by "GreenMedChem", we initially developed a light-air mediated C(sp³)-H bond oxidation strategy for isoquinolone framework constructing, which offers the benefits of straightforward operation, mild reaction conditions, atomic economy, and broad substrate scope. A total of 54 isoquinolones were obtained, achieving a yield of up to 97 % under ambient conditions, using air as the sole oxygen source, and the ²H NMR analysis further verified that water was the only byproduct. Subsequently, three pharmacological agents were prepared via the late-stage C-H bond oxidation strategy.