Noncovalent interaction with a spirobipyridine ligand enables efficient iridium-catalyzed C-H activation.

Exploitation of noncovalent interactions for recognition of an organic substrate has received much attention for the design of metal catalysts in organic synthesis. The CH-π interaction is especially of interest for molecular recognition because both the C-H bonds and the π electrons are fundamental properties of organic molecules. However, because of their weak nature, these interactions have been less utilized for the control of organic reactions. We show here that the CH-π interaction can be used to kinetically accelerate catalytic C-H activation of arenes by directly recognizing the π-electrons of the arene substrates with a spirobipyridine ligand. Computation and a ligand kinetic isotope effect study provide evidence for the CH-π interaction between the ligand backbone and the arene substrate. The rational exploitation of weak noncovalent interactions between the ligand and the substrate will open new avenues for ligand design in catalysis.

Pd-catalyzed Aerobic Cross-Dehydrogenative Coupling of Catechols with 2-Oxindoles and Benzofuranones: Reactivity Difference Between Monomer and Dimer.

Persistent radicals, which are generated from 2-oxindole or benzofuranone dimers, are useful tools for designing the radical-based cross-coupling reaction to provide molecules containing a quaternary carbon. The persistent radical is accessible from both the dimer and monomer; however, the reactivity difference between these substrates for the oxidative cross-coupling reaction is not fully understood, most likely because of the mechanistic complexity. Here, we present details of an aerobic cross-dehydrogenative coupling (CDC) reaction using various monomers and catechols. UV-Vis analysis and mechanistic control experiments showed that the monomer is less reactive than the dimer under aerobic conditions. Our Pd(II)-BINAP-µ-hydroxo complex significantly improved the reactivity of the monomers for the aerobic CDC reaction with catechols, yielding results comparable to those of the corresponding dimer. The procedure, which enables the generation of the persistent radical in situ, is particularly useful when employing the monomer that is not readily converted to the corresponding dimer.

Remote steric control for undirected meta-selective C-H activation of arenes.

Regioselective functionalization of arenes remains a challenging problem in organic synthesis. Steric interactions are often used to block sites adjacent to a given substituent, but they do not distinguish the remaining remote sites. We report a strategy based on remote steric control, whereby a roof-like ligand protects the distant para site in addition to the ortho sites, and thereby enables selective activation of meta carbon-hydrogen (C-H) bonds in the absence of ortho or para substituents. We demonstrate this concept for iridium-catalyzed meta-selective borylation of various monosubstituted arenes, including complex drug molecules. This strategy has the potential to expand the toolbox of C-H bond functionalization to previously nondifferentiable reaction sites.