Organocatalytic desymmetrization of triols to access O-tosylated α,β-epoxy alcohols featuring a quaternary stereocenter

Chiral epoxides are widely recognized as versatile synthetic intermediates due to their ability to undergo regioselective ring-opening reactions, enabling the formation of highly functionalized molecules with welldefined stereochemistry. Although numerous strategies for their synthesis have been developed, general methodologies for the preparation of chiral 1,1-disubstituted terminal epoxides remain scarce, despite their synthetic value in ring-opening reactions. In this work, we present a first enantioselective catalytic synthesis of O-tosylated α,β-epoxy alcohols via a desymmetrization strategy of triols. Upon transformation of the two primary alcohols into appropriate leaving groups, the remaining tertiary alcohol selectively undergoes an intramolecular SN2 reaction in the presence of a bifunctional organocatalyst, thereby affording enantioenriched chiral epoxides. These compounds can serve as valuable intermediates for the preparation of biologically active molecules via selective elaborations.