The Role of AQ in the Regioselectivity of Strong Alkyl C–O Bond Activation Catalyzed by Pd(OAc)₂: A Density Functional Theory Mechanistic Study

Abstract

A density functional theory method was employed to investigate the mechanism of C–O bond activation of butanoic acid substrates bearing the 8-aminoquinoline (AQ) group catalyzed by Pd­(OAc)2. The whole reaction consists of five fundamental steps: the chelation of substrate A1, the C–H activation step, the C–N coupling step, the protodepalladation step, and the release of the final product. The calculated results indicated that the protodepalladation step is the rate-determining step with a free energy barrier of 24.3 kcal/mol. This theoretical study pointed out that the energy barriers of C–H activation in the presence and absence of AQ are 11.3 and 26.6 kcal/mol, respectively. This is to say that the installation of the AQ directing group is critical to the regioselectivity of C–H activation and the β-O elimination steps, and this reason enables selective activation of the γ C–O bond. Furthermore, this chelating functionality facilitated the protodepalladation step because the energy barrier of the protodepalladation step was decreased with the coordination of the AQ directing group with a Pd center, and that was 39.3 kcal/mol in the absence of AQ. This also explains why no product formation was observed in the experiment upon changing the directing AQ group to a phenylamino group. Finally, other substrates bearing the phenol leaving group at the β- and δ-positions of carbonyl were investigated in order to expand the applicability of the AQ directing strategy. This work could provide new theoretical insights into the activation of strong alkyl C­(sp3) covalent bonds via the AQ directing strategy.

Hydroboration of CO2 to Methyl Boronate Catalyzed by a Manganese Pincer Complex: Insights into the Reaction Mechanism and Ligand Effect

“…On the basis of our previous computational studies catalyzed by TM complexes, − all geometry optimizations in this paper were carried out at B3LYP-D3/BS-I level using Gaussian 09 program. , Other DFT functionals were tested, but no qualitatively different results were obtained (see Table S1 in the Supporting Information). BS-I denotes that the Mn center adopted the LANL2DZ basis set based on the effective nuclear potential energy approximation (ECP), and for other nonmetal atoms, we applied the Pople’s 2-zeta 6-31G­(d) all-electron basis sets .…”

Catalytic σ-Bond Annulation with Ambiphilic Organohalides Enabled by β-X Elimination

“…To probe the potential intermediacy of a a Pd II (π-alkene) species, independently prepared alkene 1m' was subjected to the standard conditions, and excellent yield and diastereoselectivity of product 3ma were obtained (Figure 2B), establishing the competency of (Pd II •1m') as an intermediate in the catalytic cycle. Based on these data and literature precedents [3,12,18], a plausible mechanism is depicted in Figure 2C, which involves a sequence of C(sp 3 )-H activation, β-heteroatom elimination, nucleopalladation, oxidative addition and reductive elimination. This cascade process exemplifies successful integration of diverse organometallic elementary steps into a productive catalytic system.…”

Improved Elastic Image Pair Method for Finding Transition States

“…Transition metal catalysts are widely used in organic synthesis. − To evaluate the efficacy of the i-EIP method for transition metal-catalyzed reactions, five reactions were selected from a variety of published libraries − for use as a test set. The selected reactions contain different transition metal atoms, and the size of these reaction systems is relatively large.…”

“…Reactants, TSs, and products of (a) Ru-PNP pincer-catalyzed imine hydrogenation, (b) Co­(III)-catalyzed C–C coupling, (c) Mn pincer-catalyzed HCOOBpin hydroboration, (d) Pd­(OAc)-catalyzed nucleopalladation, and (e) Rh­(III)-catalyzed alkyne insertion . Part of hydrogen atoms is omitted for clarity.…”