<i>ortho</i> ‐C─H Alkylation of Aryl Chlorides by a Catellani Strategy

Herein we report a general and practical palladium/norbornene catalysis system that effectively promotes difunctionalization of less reactive aryl chlorides. The key to success lies in the use of a particular norbornene (NBE) derivative as a powerful mediator that synergistically cooperates with the palladium catalyst and an electron-rich phosphine ligand. A broad spectrum of electronically diverse aryl chlorides (57 examples) delivered the corresponding ortho-C─H alkylation/ipso-olefination products in moderate to good yields. Notably, this protocol features excellent functional-group tolerance, high concentration, scalability, and late-stage functionalization of complex aryl chlorides. Furthermore, by integrating this chemistry with its counterparts involving aryl iodides and bromides, an intriguing triple-Catellani reaction sequence was developed, rapidly increasing molecular complexity and diversity. Finally, DFT calculations were performed, revealing that noncovalent C─H⋯O interactions between the XPhos ligand and the NBE mediator promote the pivotal NBE insertion step.