Aza-Berson–Willcott Rearrangement

Abstract The Berson–Willcott rearrangement (BWR) has long been restricted to all-carbon systems, hampered by harsh conditions, reversible equilibria, and underexplored stereochemistry. Herein, we disclose the first aza-Berson–Willcott rearrangement transformation. By circumventing the all-carbon constraint, this strategy enables the efficient construction of cyclopropane-fused quinolines with complete regio- and diastereocontrol under operationally simple conditions. Density functional theory calculations unravel a distinctive noncanonical mechanistic pathway, wherein ring expansion toward a benzazepine intermediate, conformational inversion, and successive ring closure collectively govern the high-fidelity stereospecificity of this transformation. This method directly converts planar quinolines and analogues into rigid three-dimensional bicyclic scaffolds and enables late-stage cyclopropanation of pharmaceutically relevant agents. This work establishes a robust paradigm for precise stereochemical elaboration of heteroaromatic scaffolds and expands the chemical space accessible through sigmatropic rearrangements.