Remote Hydrogen Bonding between Ligand and Substrate Accelerates C–H Bond Activation and Enables Switchable Site Selectivity

Abstract

Transition-metal-catalyzed selective and efficient activation of an inert C−H bond in an organic substrate is of importance for the development of streamlined synthetic methodologies. An attractive approach is the design of a metal catalyst capable of recognizing an organic substrate through noncovalent interactions to control reactivity and selectivity. We report here a spirobipyridine ligand that bears a hydroxy group which recognizes pyridine and quinoline substrates through hydrogen bonding, and in combination with an iridium catalyst enables site-selective C−H borylation. The site selectivity can be switched by simply changing the position of the hydroxy group on the ligand. The catalyst also accelerates the reactions, overrides steric bias, and selectively recognizes a pyridine substrate in the presence of other hydrogen bond acceptors. These features are reminiscent of enzymatic catalysis and suggest that judicious design of the recognition group on the ligand can become a general strategy to selectively and efficiently functionalize organic substrates.