Divergent synthesis of CF₃-substituted polycyclic skeletons based on control of activation site of acid catalysts

We report a divergent synthesis of CF₃-substituted fused skeletons based on precise control of the activation site through the selection of acid catalysts. When trifluoromethyl ketones with an ortho-phenethyl ether group were treated with a catalytic amount of Sc(OTf)₃, a hydride shift triggered C(sp³)–H bond functionalization proceeded to give CF₃-substituted isochromene derivatives by selective activation of the carbonyl group. In sharp contrast, CF₃-substituted bicyclo[3.3.1]nonanes were obtained exclusively via the activation of ether oxygen initiated sequential reactions (nucleophilic attack of carbonyl oxygen, and intramolecular Friedel–Crafts reaction) under strong Brønsted acid catalysis (Tf₂NH).