Pd/LA-catalyzed decarboxylation enabled exclusive [5 + 2] annulation toward: N -aryl azepanes and DFT insights

A practical and straightforward methodology towards the synthesis of non-fused N-aryl azepane derivatives with diversity is described. These Pd/LA-catalyzed reactions proceed smoothly under extremely mild conditions with ample reaction scope and CO2 as the byproduct. The resulting products can be easily converted into a range of highly functionalized azepanes. The synthetic value of this protocol is further proved in the formal synthesis of a pharmaceutically relevant Proheptazine derivative. DFT calculations revealed the details of the reaction pathway and the origin of this unusual exclusive [5 + 2] rather than empirical [3 + 2] annulation process.