Modular Assembly of Polyfunctional Arenes with Three Contiguous And Different Substituents by Orchestrating Pd-Catalyzed Multi-Component Domino Reactions

Abstract

By orchestrating mechanistically sequential and compatible palladium-catalyzed domino carbopalladation of arynes and norbornene (NBE)-mediated Catellani processes, polyfunctional arenes with three contiguous and different substituents could be efficiently assembled under mild conditions in an one-pot four-component modular way. Optimization on the reaction conditions revealed that balancing the reaction parameters in general, and loading amount of NBE especially, was a linchpin for the reaction. Studies on the reaction scope indicated a wide selection of functional groups, including complex natural product derived substructures, could be tolerated, making it appealing in both early and late-stage assemblies. Post-transformations showed that not only the newly installed substituents but also the parent aromatic nucleus could be conveniently derived, enabling polyfunctional arenes with diverse substitutions in a concise manner.