Product Control in Oxidative Aryl-Benzyl Coupling of a Phenolic 1,4-Diarylbutane

Abstract

In a recent communication we have described an unusual one step oxidative aryl-benzyl coupling reaction which provides efficient and direct access to the 1-aryltetralin ring system characteristic of podophyllin lignan lactones.¹ The key step in our synthesis of such lactones was the oxidative cyclization of the phenolic 1,4-diarylbutane I with thallium (III) trifluoroacetate (TTFA)² in 1,2-dichloroethane to give, upon reductive workup, mixtures of the cyclized catechol II and phenol III. These were convergently transformed to (±)-picropodophyllone (IV) by permethylation, C-4 oxidation and lactone construction.