Umpolung Strategy for Ynamide Difunctionalization

ABSTRACT Tetrasubstituted enamides, a subclass of tetrasubstituted olefins, are valuable structural motifs found in conjugated materials and biologically active molecules. Among various synthetic approaches, the difunctionalization of electron‐rich ynamides offers a concise and atom‐economical route to access these frameworks. Due to their intrinsic electronic polarization, ynamides undergo highly regioselective additions with nucleophiles preferentially attacking the α −carbon, while electrophiles target the β −carbon. Although this conventional paradigm is effective, it is restricted to predictable reactivity patterns. Umpolung reactivity, which reverses the native polarity of reactive centers, offers a powerful solution by enabling new bond‐forming patterns and expanding access to otherwise challenging molecular architectures. This review highlights recent advances in ynamide difunctionalization using umpolung strategies.