DFT Mechanistic Study on Palladium‐Catalyzed Redox‐Neutral Hydroarylation of Unactivated Alkenes with Arylboronic Acids

Abstract

Density functional calculations were carried out on the mechanism of a palladium‐catalyzed hydroarylation reaction of β,γ‐unsaturated carbonyl compounds with arylboronic acids reported by Engle's group. The proposed reaction pathway consists of several key mechanistic steps, including the chelation of substrate 1 a, transmetalation of organoboron 2 a, migratory insertion, protodepalladation, and dechelation of product 3 a, among which the transmetalation step is rate‐determining with a free‐energy barrier of 27.0 kcal/mol. Experimental researchers proposed that the chelation of Daugulis's 8‐aminoquinoline (AQ) directing group facilitated the desired hydroarylation in a γ‐selective manner. However, the present study revealed that the chelation of AQ indeed retarded the delivery of the aryl group to the double bond and the regioselectivity was not necessarily the result of this group. Indeed, it could effectively prevent the homocoupling of 2 a, because the homocoupling was predicted to be easier than the desired hydroarylation in the absence of AQ. Additionally, some reductive coupling pathways between 1 a and 2 a were designed, and the competition of them was discussed in great detail. Lastly, the extension of this synthetic strategy to other types of alkenes was predicted.

A Computational Study on Cycloaddition Reactions between Isatin Azomethine Imine and in situ Generated Azaoxyallyl Cation

“…DFT calculation is a powerful tool for designing some unreal reaction pathways for comparative purposes [31,32] . We theoretically design the possible [3+3] cycloaddition pathways between two 1,3‐dipoles, azomethine imine and 2 b .…”

Nickel(0)-catalysed linear-selective hydroarylation of 2-aminostyrenes with arylboronic acids by a bifunctional temporary directing group strategy

“…1,2 Among them, the nickel(0)-catalyzed hydroarylation of styrenes with organoboron compounds has received considerable attention owing to its redox-neutral nature as well as the ready abundance of both nickel catalysts and substrates. 3–5 As pioneered by Zhou and coworkers, 4 a such transformation proceeds through the activation of the alkene moiety by a nickel-hydride species generated from nickel(0) and protic solvents such as methanol via oxidative addition. The resulting benzylic nickel intermediate could be stabilized by the adoption of an η-3-coordination mode by the adjacent aryl group, thus controlling the hydroarylation process to proceed in a highly branched-selective manner to afford 1,1-diarylalkanes (Scheme 1A).…”

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

“…Recently, Zhang and co-workers performed a DFT study for the palladium-catalyzed hydroarylation of β,γ-unsaturated carbonyl compounds with arylboronic acids. The calculated results indicated that installation of an AQ directing group into the substrates retarded the transmetalation process and prevented the homocoupling reaction of the substrate …”