Application of Isocyanides as Amide Surrogates in the Synthesis of Diverse Isoindolin‐1‐one Derivatives by a Palladium‐Catalyzed Tandem Carboxamidation/Hydroamidation Reaction

Abstract

The rapid synthesis of the isoindolinone skeleton has been accomplished by a palladium‐catalyzed one‐pot tandem process, which consists of an isocyanide insertion/hydration (carboxamidation) and 5‐ exo ‐ dig cycloisomerization (hydroamidation) reaction sequence that afforded the products in good to excellent yields. Preliminary mechanistic studies of this sequential C–C/C–O/C–N bond formation process suggests that the carboxamidation step is palladium‐dependent, whereas the hydroamidation step is solely mediated by the base and is driven by the electrophilicity of the alkyne.