Gold-Catalyzed Synthesis of sp³-Rich Nortricyclanes from Norbornenes

Rigid, three-dimensional (3D) all-carbon sp³-rich skeletons have gained increasing attention as effective isosteric replacements for benzene rings in drug discovery, offering enhanced metabolic stability and lipophilicity. However, reliable and concise synthetic methods for constructing these extraordinary highly strained 3D-shaped structures remain a significant challenge. In this study, we report a novel external oxidant-free Au^I/Au^III-catalyzed strategy for the direct synthesis of nortricyclanes from readily available norbornenes (NBE) via a tandem alkene difunctionalization and subsequent C(sp³)-H activation. A broad range of alkynyl, alkenyl, and aryl iodides are suitable coupling partners. The key to this transformation is the formation of a nonclassical carbocation intermediate facilitated by gold catalytic process, with which the well-known paradigm of Catellani reaction rule in Pd/Ni catalysis system has been expanded. This protocol demonstrates a high functional group tolerance and scalability, achieving gram-scale synthesis with excellent modularity. Mechanistic studies offer insight into the formation of C(sp³)-C(sp³) cross-bridge bond, enabling efficient construction of complex 3D structures without prefunctionalization.