Design of Ligands for Selective and Efficient C-H Functionalization

Direct functionalization of organic molecules through transition-metal-catalyzed C-H activation enables the straightforward creation of molecular complexity. For these reactions to be useful, the catalyst must efficiently and chemoselectively cleave the inert C-H bond, and also differentiate between the various C-H bonds in an organic molecule. To achieve these requirements, modification of the substrate has been the most popular strategy: the introduction of directing groups, large substituents, or heteroatoms to induce an electronic or steric bias and control reactivity, and more importantly, selectivity. However, these strategies are dependent on the substrate, and therefore not generally applicable. We have started a program aimed at the development of catalysts that can recognize a substrate through noncovalent interactions to control reactivity and selectivity. Thus, we developed a terpyridine ligand that undergoes rollover cyclometallation to create an N,N,C-iridium complex that can selectively borylate the C-H bond adjacent to a fluorine atom in fluoroarene. We also developed spirobipyridine ligands, which possess a fluorene moiety placed perpendicular to the bipyridine plane, allowing molecular recognition groups to be placed at a remote position from the reaction center, thus minimizing repulsive interactions. A spirobipyridine ligand bearing a “steric roof” moiety recognizes a substrate molecule through remote steric interactions to enable meta-selective iridium-catalyzed borylation of monosubstituted arenes. We also found that a spirobipyridine ligand accelerates iridium-catalyzed borylation of arenes through an attractive CH-π interaction between the C-H bond of the ligand and the π electrons of the substrate.