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.