Unified Asymmetric Synthesis of Aryltetralin Lactone Cyclolignans via Conformation-Assisted Radical C–H Cyclization

Aryltetralin lactones featuring vicinal stereogenic centers at their ring junctions are important scaffolds in pharmacologically relevant cyclolignans. Currently, the direct and efficient assembly of tetracyclic core scaffolds from simple acyclic precursors is challenging. Herein, we developed a conformation-assisted radical-initiated iodocarbocyclization of C-(sp3)-H bonds in 5-alkenylmalonates. This was followed by lactonization for the direct assembly of aryltetralin lactone scaffolds. Nine aryltetralin lactone cyclolignans were successfully produced by unified asymmetric total syntheses. This methodology shows potential for advancing both medicinal chemistry and biological research.