Study of Pd-catalyzed Selective Mono- and Di-C(sp³)-H Bond Activation: A Bi-ligand Model

Controlling the number of C-H bond activation is a long-standing challenge in organic synthesis. Recently, Yu's group demonstrated that in Pd-catalyzed alanine's arylation, pyridine-type ligands favor a mono-C-H bond activation, while quinoline-type ligands favor a di-C-H bond activation. To disclose the underlying principles, a theoretical study (density functional theory (DFT)) has been carried out. Our study indicates that a mono-ligand model, which is generally adopted in the community, does not reproduce the experimentally observed mono-/di-selectivity, while a bi-ligand model can rationalize the experimental observations well, including the observed diastereoselectivity in diarylation. The electron-rich pyridine-type ligands with less steric congestion can promote the C-H bond activation reaction of alanine derivatives. The quinoline-type ligands have a better π back-donation interaction with the metal, which makes a more active C-H bond activation than the pyridine-type ligands for this reaction. This bi-ligand model, which is a necessity, allows the understanding and future design of a dual ligand effect in C-H bond activation.