Ground state oxygen in synthesis of cyclic peroxides. Part 1: Benzo fused ketals

A thiol-olefin-cooxygenation (TOCO) radical chain reaction involving ground state molecular oxygen converts 2′-isopropenyl acetophenones directly into cyclic peroxy hemiketal products with three new bonds. Starting with 4-t-butylbenzenethiol, this TOCO process proceeds reproducibly on gram scale in 86% yield. Hemiketal→ketal and sulfide→sulfone transformations finally provide a series of sulfonyl cyclic peroxy ketals. The in vitro antimalarial activities of some of these structurally simple benzo-fused cyclic peroxides are reported.

Graphical Abstract