Peroxycarbenium-Mediated Asymmetric Synthesis of 1,2-Dioxanes and 1,2-Dioxolanes

The endoperoxide scaffold is found in numerous natural products and synthetic substances of pharmaceutical interest. The main 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 a catalyst. The scope of the methodology is broad, encompassing a large variety of enoxysilanes and yielding 1,2-dioxanes or 1,2-dioxolanes. Peroxides can be converted into alcohols or trans-epoxides, and the methodology was applied in a key step of the total synthesis of ethyl plakortide Z, enhancing the selectivity compared to a conventional Lewis acid-catalyzed transformation. Kinetic studies have shown that the reaction necessitates an induction period, indicating the formation of a silylium species that behaves as a true catalyst.