CH Bond Arylation in the Synthesis of Aryltetralin Lignans: A Short Total Synthesis of Podophyllotoxin

A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported. Key to the success of this synthetic pathway is a Pd‐catalyzed C(sp³)–H arylation reaction enabled by a conformational biasing element to promote C–C reductive elimination over an alternative C? N bond‐forming pathway. This strategy allows for access to the natural product in five steps from commercially available bromopiperonal, and sheds light on subtle conformational effects governing reductive elimination pathways from high‐valent palladium centers.