Lewis Acid Catalyzed Annulation of Phenol Derivatives and Bicyclo[1.1.0]butanes to Access Arene-fused Bridged Bicycles

The development of new approaches to synthesize complex structures from readily available compounds is a topic of significant interest in synthetic chemistry. Herein, we present a straightforward strategy to access structurally intriguing arene-fused bicyclo[2.1.1]hexanes by a Lewis acid catalyzed annulation of phenol and their derivatives with bicyclo[1.1.0]butanes (BCBs). This reaction presumably proceeded through a cascade initiated by a dearomative (3+2) cycloaddition followed by rearomatization through alcohol or water elimination. The employment of hexafluoroisopropanol (HFIP) as solvent proved essential for facilitating this transformation. This methodology could accommodate a broad array of commercially available phenol derivatives including phenols and anisoles, thus allowing rapid generation of molecular complexity, which expands synthetic access to chemical space of bridged polycycles.