A Dearomatization/Debromination Strategy for the [4+1] Spiroannulation of Bromophenols with α,β-Unsaturated Imines

A novel [4+1] spiroannulation of o- & p-bromophenols with α,β-unsaturated imines has been developed for the direct synthesis of a new family of azaspirocyclic molecules. Notably, several other halophenols (X=Cl, I) were also applicable for this transformation. Moreover, a catalytic asymmetric version of the reaction was realized with 1-bromo-2-naphthols by using a chiral Sc^III /Py-Box catalyst. Mechanistic studies revealed that this domino reaction proceeded through electrophile-triggered dearomatization of phenol derivatives at their halogenated positions and followed by halogen-displacement with N-nucleophiles via a radical-based S_RN 1 mechanism.