Palladium/Norbornene Cooperative Catalysis To Access Tetrahydronaphthalenes and Indanes with a Quaternary Center

A cooperative catalytic system comprising a palladium/XPhos complex and 5-norbornene-2-carboxylic acid was developed. This system promotes a two-component annulation reaction, allowing the construction of tetrahydronaphthalenes and indanes that contain quaternary centers through consecutive Catellani-type C–H activation and redox-relay Heck reaction. Inexpensive 5-norbornene-2-carboxylic acid acts as a catalytic mediator (20 mol %) in this process. This mild, scalable, and chemoselective protocol is compatible with a wide variety of readily available aryl iodides and alkylating reagents. Application of this method in a 4-step synthesis of opioid analgesic eptazocine is demonstrated. Preliminary studies underscore the future promise of rendering this Catellani/redox-relay Heck cascade enantioselective