Modular Synthesis of C5 Sulfur‐Functionalized Oxazolidinones via Thiol‐Induced Cascade Reactions of Epoxy Carbamates

Abstract

ABSTRACT A modular cascade strategy has been developed for the synthesis of C5 sulfide‐functionalized oxazolidinones from epoxy carbamates and structurally diverse thiols. The transformation is initiated by intermolecular nucleophilic epoxide ring opening and followed by intramolecular acyl substitution, enabling simultaneous construction of the oxazolidinone core and installation of a sulfur‐containing side chain. Reaction optimization identified DBU (1.5 equiv) and thiol (1.5 equiv) in tert ‐butanol at 50°C as suitable conditions. The method accommodates benzylic, aromatic, linear and branched aliphatic, and cycloalkyl thiols, as well as electronically diverse epoxy carbamates, providing 20 sulfide‐functionalized oxazolidinones in 68%–98% isolated yields. The synthetic practicality of the protocol was demonstrated by a gram‐scale reaction, which afforded the desired product in 87% yield. Furthermore, selective oxidation of the resulting sulfides with m ‐CPBA provided the corresponding sulfones, enabling subsequent oxidation‐state diversification of the installed sulfur functionality. This strategy provides a practical and modular platform for accessing structurally diverse C5 sulfur‐functionalized oxazolidinones.