Mechanism and Stereoselectivity of Directed C(sp(3))-H Activation and Arylation Catalyzed by Pd(II) with Pyridine Ligand and Trifluoroacetate: A Computational Study

摘要

Density functional theory (DFT) calculations were conducted to elucidate the mechanism of a novel Pd(II) catalyzed C(sp(3))-H activation and the subsequent arylation reactions of amides in the presence of pyridine derivatives as ligands. All plausible pathways were carefully studied, and the minimum energy pathway was located successfully. Being different from most of the C-H activation reactions, 2-picoline used in this reaction reacts with Pd(TFA)(2) (trifluoroacetate) to form a very stable precatalyst. Measures should thus be taken to activate the precatalyst, including the modification of the amide substrate and a proper choice of solvent. Our calculations helped to reveal the relevant details. An unconventional deprotonation mechanism for the C-H activation step, which is different from the traditional CMD (or AMLA) mechanism, was found through our theoretical studies. The methyl group is deprotonated by an out-of-plane (external) TFA, rather than a TFA ligand directly bound to the Pd(II) atom. As part of the uncommon Pd(II)-Pd(IV)-Pd(II) catalytic cycle, the succeeding arylation reaction, which takes place on the product of the C-H activation reaction, was also studied by us. The arylation reaction was found to have a lower barrier compared to that of the C-H activation reaction, which confirms that the C-H activation is the rate-determining step. On the basis of our newly found minimum energy pathway (MEP), the secondary C(sp(3))-H activation reaction was also investigated and the results helped us to unveil the origins of the diastereoselectivity. Some other aspects that affect the C-H activation, such as the agostic interaction and the Nand effect, were also discussed in this article.