Spectroscopic Studies of the Chan-Lam Amination: A Mechanism Inspired Solution to Boronic Ester Reactivity

We report an investigation of the Chan Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) -> Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development-of a general catalytic Chan Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.