American Chemical Society
jo2c01235_si_001.pdf (1.58 MB)

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

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journal contribution
posted on 2022-07-28, 19:05 authored by Bo Xiao, Tian-Yu Sun, Yun-Dong Wu
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.