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

Abstract

A novel [4+1] spiroannulation of o-& p-bromophenols with a,b-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-2naphthols 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. Scheme 1. Electrophile-triggered dearomatization at the halogenated sites of o-& p-halophenols.

Asymmetric Catalytic Approaches Employing α,β‐Unsaturated Imines

“…in 2020, where incorporating a dearomatization/dehalogenation strategy, direct synthesis of a new family of azaspirocyclic molecules 317 were performed (Scheme 82). [92] …”

In(OTf)3-Catalyzed Reorganization/Cycloaddition of Two Imine Units and Subsequently Modular Assembly of Acridinium Photocatalysts

“…In this context, the analogous reactivity of imines with other unsaturated moieties such as C=N have been not reported yet, which likely was attributed to the instability of envisage-formed dinitrogen six-membered rings. During our research with the imine chemistry [23][24][25][26][27] , we discovered an entirely novel reactivity of imine molecules. In sharp contrast with the typical Povarov [4+2] cyclization version [28][29][30] , this observation unusually behaved formal [3+2+1] interaction via the reorganization of multiple chemical bonds.…”