Copper-Catalyzed Synthesis of Medium-Sized Cyclic Aminals via Annulation of Ketenimines and N‑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.