Spirobipyridine Ligands as a Unique Platform for Substrate Recognition and Reaction Control through Noncovalent Interactions

Transition-metal-catalyzed C-H functionalization has the potential to streamline organic synthesis, but for this purpose, catalysts that activate a C-H bond efficiently and selectively are required. To date, most strategies have relied on substrate modification, such as the introduction of directing groups, large substituents, or heteroatoms. However, these strategies are not generally applicable. This Viewpoint describes our efforts in developing catalysts that can recognize a substrate through noncovalent interactions to control reactivity and selectivity. We developed a family of spirobipyridine ligands, which possess a fluorene moiety placed perpendicular to the bipyridine plane, allowing a molecular recognition group to be placed at a remote position from the reaction center, thus minimizing repulsive interactions. Molecular recognition using three types of noncovalent interactions is discussed: remote steric interactions through a "roof" spirobipyridine ligand to recognize the shape of simple arenes and control site selectivity, CH-pi interaction between the C-H bond of the ligand and the pi electrons of the substrate to recognize arenes and accelerate the reaction, and hydrogen bonding between an OH group on a spirobipyridine ligand and a pyridine substrate to control both site selectivity and reactivity.