Copper-Catalyzed Synthesis of Medium-Sized Cyclic Aminals via Annulation of Ketenimines and <i>N</i> -Acyliminium Ions

A CuBr-catalyzed intermolecular cascade strategy was developed to access medium-sized polycyclic aminals. While conventional cyclization encounters severe limitations due to inherent enthalpic and entropic constraints, this approach overcomes such challenges through in situ generation of ketenimines via a Cu-catalyzed click reaction, followed by their cyclization with N -acyliminium ions. The protocol features broad substrate compatibility, scalability, and versatility. Notably, a wide range of polycyclic aminals, from 6- to 10-membered frameworks, can be achieved using this strategy.