9-Membered carbocycle formation: development of distinct Friedel-Crafts cyclizations and application to a scalable total synthesis of (±)-caraphenol A

Explorations into a series of different approaches for 9-membered carbocycle formation have afforded the first reported example of a 9-exo-dig ring closure via a Au(III)-promoted reaction between an alkyne and an aryl ring as well as several additional, unique Friedel-Crafts-type cyclizations. Analyses of the factors leading to the success of these transformations are provided, with the application of one of the developed 9-membered ring closures affording an efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol A. That synthesis proceeded with an average yield of 89% per step (7.8% overall yield) and has provided access to more than 600 mg of the target molecule.