Ortho-C-H methoxylation of aryl halides enabled by a polarity-reversed N-O reagent

Oxygen-substituted arenes widely exist in biologically important molecules and can serve as versatile handles to install other functional groups. However, direct and site-selective installation of oxygen groups to common aromatic compounds remains challenging, especially when additional arene functionalization is simultaneously required. Current arene C-H oxidation strategies generally require directing groups or precisely prefunctionalized substrates to control site-selectivity. While palladium/norbornene cooperative catalysis is promising for site-specific arene vicinal difunctionalization through simultaneous reactions with an electrophile and a nucleophile, the electrophile scope has been limited to species based on relatively 'soft' elements, such as carbon, nitrogen and sulfur. Here we report the development of an ortho oxygenation reaction with common aryl halides to rapidly deliver diverse aryl ethers. The coupling of the 'hard' oxygen electrophile is enabled by a stable, polarity-reversed, conformationally predistorted N-O reagent and facilitated by a C7-bromo-substituted norbornene mediator. Mechanistic studies reveal a unique S_N2-type pathway between the N-O reagent as the oxygen electrophile and an electron-rich Pd(II) nucleophile.