A Modular Approach To Dibenzo-Fused Epsilon-Lactams: Palladium-Catalyzed Bridging-C-H Activation

Tricyclic ring systems possessing a dibenzo structure joined to a seven-membered heterocyclic ring frequently show important biological activities. However, a modular approach to these molecules based on efficient intermolecular reaction of readily available chemicals is lacking. Herein, an unprecedented palladium-catalyzed formal [4+3] annulation for modular construction of these tricyclic systems is described. This reaction features easily accessible reactants (o-haloarylaldehydes andN-tosylhydrazones), broad substrate scope, and excellent functional group compatibility. The synthetic potential is demonstrated by the easy scale-up reactions, late-stage modification of complex molecules, and collective synthesis of bioactive molecules and approved drugs.