Sustainable dual cobalt/photoredox catalysis for the selective synthesis of highly functionalized isoquinolones

A sustainable and versatile method for the synthesis of isoquinolones is reported. This operationally simple protocol relies on cobalt catalysis under visible-light irradiation at room temperature, avoiding stoichiometric oxidants and using readily available starting materials. Aryloxy allenes are identified as optimal coupling partners, enabling an efficient and fully regioselective formation of highly substituted isoquinolones and overcoming key limitations of related C–H functionalization strategies. The products feature a synthetically valuable diene motif, which significantly expands their potential for downstream functionalization and molecular diversification. The method shows a broad substrate scope, accommodating electronically and sterically diverse benzamides as well as heteroaromatic and complex bioactive scaffolds, with good to excellent yields and high functional group tolerance. Its applicability is further demonstrated through selective late-stage modification of pharmaceutically relevant molecules, underscoring its utility in medicinal chemistry contexts. In addition, the protocol operates under mild conditions, employs an earth-abundant cobalt catalyst, and is amenable to scale-up, collectively enhancing its synthetic and environmental appeal. Mechanistic studies support a cobaltaphotocatalytic cycle involving radical intermediates and provide insight into the key C–H activation and allene insertion steps governing regioselectivity and reactivity.