Annulation of Hydroxyarenes and Derivatives with Bicyclo[1.1.0]butanes by Synergistic Combination of Metal Lewis Acid and Organic Acid

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 Lewis acid-catalyzed annulation of hydroxyarenes and their ether 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 acidic hexafluoroisopropanol (HFIP) as a solvent proved essential for facilitating this transformation by a synergistic combination with Lewis acid. This methodology could accommodate a broad array of commercially available arene materials including phenols, anisoles, and naphthyl methyl ethers, thus allowing rapid generation of molecular complexity, which expands synthetic access to the chemical space of bridged polycycles.