Divergent Synthesis of Polycyclic Derivatives via Gold Catalysis

Gold(I)‐catalyzed cycloisomerization reactions provide powerful access to structurally complex and 3D molecular frameworks from simple enyne precursors. Herein, we report a divergent gold‐catalyzed strategy for the synthesis of densely functionalized bicyclic and tricyclic polycyclic scaffolds from a common alkynyl ketone platform. Depending on the reaction conditions, solvent, and catalyst, the transformation proceeded through either a 6‐ endo ‐dig or a 5‐ exo ‐dig cyclization pathway, leading to distinct molecular architectures. Under selected conditions, bicyclo[3.3.1]nonane derivatives were obtained with high selectivity, while alternative conditions promote skeletal rearrangements delivering bridged tricyclic frameworks, including tricyclo[3.2.1.0 2,7 ]octanes and tricyclo[3.3.1.0 2,8 ]nonanes. According to literature mechanistic investigations, the involvement and evolution of key vinyl–gold and gold carbene intermediates may govern regioselectivity and product distribution. The role of solvent effects and substituent electronics in controlling pathway divergence was highlighted. This gold‐catalyzed divergent approach enabled rapid molecular complexity generation and provided efficient access to rigid, 3D polycyclic scaffolds of potential interest for medicinal chemistry and drug discovery applications.