Diverse Bicyclic Heterocyclic Scaffolds via Palladium-Catalyzed C(sp3)–H Activation of Amides and Amines

Abstract A carboxamide- or amine-directed Pd(II)-catalyzed tandem intramolecular β-C(sp3)–H olefination/N-cyclization has been developed for the rapid construction of [3.2.1] N-heterobicyclic frameworks, which are ubiquitous in bioactive natural products and pharmaceuticals. The transformation accommodates a range of [3.2.1] N-heterobicyclic amide and amine substrates, exhibits good functional-group tolerance, and provides access to seven-membered bicyclo[4.2.1] lactams. Moreover, this strategy provides access to complex [3.3.1] and [4.3.1] bicyclic lactams via β-C(sp3)–H activation followed by an intramolecular [4 + 2] annulation with dienes. This concise and general approach offers a valuable disconnection for the streamlined construction of diverse sp3-rich bicyclic heterocyclic scaffolds.