Enhancing drug efficacy often involves increasing the proportion of sp³-hybridized carbons. Three-dimensional polycyclic frameworks, such as bicyclo[1.1.1]pentanes (BCPs) and bicyclo[2.1.1]hexanes (BCHs), serve as excellent benzene bioisosteres, improving bioavailability and reducing toxicity while retaining biological activity. However, synthetic routes to 2D/3D-ring-fused BCHs via dearomatization are scarce, previously limited to cycloadditions of bicyclobutanes (BCBs) with indoles, bicyclic aza-arenes, or naphthalenes. Herein, we achieve Lewis acid-catalyzed dearomatization of BCBs with 2-naphthol. Eu(OTf)3 catalysis provides dearomatized tertiary alcohols, while AgBF4 promotes dearomatization/aromatization to directly access naphthalene-fused BCHs, showcasing remarkable reaction selectivity. Mechanistic studies definitively identify cyclobutyl carbocations as key intermediates. This strategy is anticipated to accelerate the exploration of fused BCH scaffolds in medicinal and synthetic chemistry.
