An Asymmetric Synthesis of 1,2,4-Trioxane Anticancer Agents via Desymmetrization of Peroxyquinols through a Brønsted Acid Catalysis Cascade

The desymmetrization of p-peroxyquinols
using
a Brønsted acid-catalyzed acetalization/oxa-Michael cascade was
achieved in high yields and selectivities for a variety of aliphatic
and aryl aldehydes. Mechanistic studies suggest that the reaction
proceeds through a dynamic kinetic resolution of the peroxy hemiacetal
intermediate. The resulting 1,2,4-trioxane products were derivatized
and show potent cancer cell-growth inhibition.