Nucleophiles as Reaction Switches: Dearomative Multifunctionalization of Isoquinoliniums to Rigid Bridged-Ring Architectures

-rich bridged bis-tetrahydroisoquinolines. Nucleophiles serve dual roles as reaction switches and stereodefined bridging linkers, enabling precise regio-, chemo-, and stereocontrol. This streamlined approach unlocks the full reactive potential of isoquinolines for constructing architecturally complex polycyclic frameworks with broad applicability to carbon-, nitrogen-, and sulfur-centered nucleophiles. PMI analysis and physicochemical evaluation confirm their pronounced three-dimensionality and drug-like profiles.