Switchable annulation paths to diverse N-bridged bicyclic scaffolds via ligand-directed dicarbonylation.

N-Bridged bicyclic scaffolds bearing 3-azabicyclo[3.2.0]heptane and 3-azabicyclo[3.1.1]heptane cores have emerged as privileged bioisosteres of piperidine and meta-substituted pyridine, offering enhanced conformational rigidity and improved pharmacokinetic profiles. However, existing synthetic approaches are typically restricted to single scaffolds, limiting scaffold diversity. Here, we report a ligand-controlled, palladium-catalyzed tandem dicarbonylation of readily available cyclobutenols and amines, enabling divergent access to both 3-azabicyclo[3.2.0]heptane and 3-azabicyclo[3.1.1]heptane scaffolds from the same substrate. This strategy overcomes key challenges associated with strained-ring systems-including ring-opening side reactions and complex regio-, stereo-, and diastereoselective control-through fine-tuning of the catalyst environment. The method demonstrates excellent selectivity, broad substrate compatibility, and operational simplicity, accommodating 20 derivatives of bioactive molecules. This work provides a modular and general platform for the synthesis of structurally distinct N-bridged heterobicycles, addressing a critical gap in the development of bioisosteric nitrogen-containing scaffolds.