Visible-light-driven metal-free C-H functionalization: access to new bioactive tetrahydroisoquinoline-butenolide hybrids via domino amine oxidation/vinylogous mannich reaction

An efficient metal-free visible-light-driven two-step domino reaction towards new bioactive tetrahydroisoquinoline-butenolide hybrid compounds was developed for the first time. The combination of fluorescein as photosensitizer and thiourea as an additive was found to be the most effective way to promote an aerobic amine oxidation/vinylogous Mannich domino reaction sequence with yields up to 97% for a broad substrate scope. Both experimental and computational evidence supported the crucial role of singlet oxygen in the developed C H functionalization reaction. Furthermore, the data suggest that thiourea is essential due to its ability to act as an electron-transfer mediator and/or scavenger of reactive oxygen species. In addition, in vitro studies of tetrahydroisoquinoline-butenolide hybrid compounds demonstrated their high antischistosomal and anti-cancer activities.