Peroxy-Carbenium Mediated Asymmetric Synthesis of 1,2-Dioxanes and 1,2-Dioxolanes

The endoperoxide scaffold is found in numerous natural products and synthetic substances with pharmaceutical interest. The principal challenge to their synthetic access remains the preparation of chiral compounds, due to the weakness of the peroxide bond, which limits the scope of available or applicable methods. Here, we demonstrate how peroxycarbenium species can be trapped by silylated nucleophiles with high enantioselectivities, and diastereoselectivities when applicable, using a chiral imidophosphorimidate (IDPi) as catalyst. The scope of the methodology is broad, encompassing a large varie-ty of enoxysilanes, and yielding 1,2-dioxanes or 1,2-dioxolanes. Peroxides can be converted into chiral alcohols or trans-epoxides, and the methodology was applied in a key step of the total synthesis of ethyl plakortide Z, enhancing the selectivi-ty compared to conventional a Lewis acid. Kinetic studies demonstrated that tert-butyldimethylsilylated nucleophiles are more potent than trimethylsilylated ones. Furthermore, it was observed that the reaction necessitates an induction period, indicating the formation of a silylium species that behaves as the true catalyst.