Enantioselective Synthesis of Polycyclic Spiroheterocycles by Chiral Phosphoric Acid Catalyzed Dearomative Cyclization of <i>γ‐</i> Hydroxy Ynamides

ABSTRACT Cumulene‐type reactive intermediates are pivotal in the transformation of alkynes. Compared with the generation of metal vinylidenes and allenylidenes from typical alkynes and propargyl alcohol derivatives, the activation of electron‐rich ynamides mostly relies on keteniminium intermediates. To overcome the limitations and develop new reactivities, we proposed to combine ynamides with propargylic leaving groups and design new alkylidene keteniminium intermediates, which can be applied to the catalytic enantioselective construction of biologically important chiral polycyclic spiroheterocycles. Here, we report a chiral phosphoric acid (CPA)‐catalyzed enantioselective dearomative cyclization of γ‐ hydroxy ynamides with indoles and naphthols via alkylidene keteniminium pathway, providing a straightforward access toward chiral polycyclic spiroindolines and spirodihydronaphthalenones with high enantiocontrol. Interestingly, this reaction enables the construction of three new chiral rings in one step. The product derivatizations and synthesis of the core structure of (+)‐ibophyllidine demonstrate the potential utility of this method. The reaction mechanism is rationalized by control experiments. Notably, this reaction continues the first enantioselective transformation of alkylidene keteniminium intermediates.