Transmetallation Versus β‐Hydride Elimination: The Role of 1,4‐Benzoquinone in Chelation‐Controlled Arylation Reactions with Arylboronic Acids

Abstract

The formation of an atypical, saturated, diarylated, Heck/Suzuki, domino product produced under oxidative Heck reaction conditions, employing arylboronic acids and a chelating vinyl ether, has been investigated by DFT calculations. The calculations highlight the crucial role of 1,4-benzoquinone (BQ) in the reaction. In addition to its role as an oxidant of palladium, which is necessary to complete the catalytic cycle, this electron-deficient alkene opens up a low-energy reaction pathway from the post-insertion σ-alkyl complex. The association of BQ lowers the free-energy barrier for transmetallation of the σ-alkyl complex to create a pathway that is energetically lower than the oxidative Heck reaction pathway. Furthermore, the calculations showed that the reaction is made viable by BQ-mediated reductive elimination and leads to the saturated diarylated product.

Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

“…Their results indicate that benzoquinone prevents the occurrence of β-hydride elimination after the initial migratory insertion of olefin into the Pd−Ar bond, and instead, another aryl group is transmetalated to the Pd center. 181 In the same study, a comparison between M06 and B3LYP-D3 methods showed the former to lower the relative energies of the species involved while still predicting the same reactivity trend.…”

The Transmetalation Process in Suzuki–Miyaura Reactions: Calculations Indicate Lower Barrier via Boronate Intermediate

“…[5] The mechanistic implications of the base have been analyzed by means of experimental [3,6,7] and theoretical methods. [4,[8][9][10][11] Two possible pathways for the transmetalation step have been proposed depending on the point of entry of the hydroxide anion in the reaction mechanism (Scheme 1). [7] The first route, the boronate mechanism, path A, suggests the activation of the boronic acid by nucleophilic attack of the base to form the corresponding boronate species, which replaces the halide ligand in the coordination sphere of the Pd catalyst.…”

Development of Stereocontrolled Palladium(II)‐Catalyzed Domino Heck/Suzuki β,α‐Diarylation Reactions with Chelating Vinyl Ethers and Arylboronic Acids

“…For the domino Heck/Suzuki reaction, we proposed a mechanism involving a chelation-controlled carbopalladation step,11 which was supported by recent density functional theory (DFT) calculations, highlighting the crucial role of p -BQ in the catalytic process 12. Since the diarylation reaction requires an olefin equipped with a metal coordinating group, control of the stereochemical outcome of the reaction should be possible by choosing an appropriate chiral catalyst-directing moiety, allowing the generation of diastereomerically enriched σ-intermediate II (Scheme 1).…”

“…In the same manner, different batches of solvent used in the screening processes presumably contained varying water concentrations, which could have affected the reaction outcome. Previous work by our group has also illustrated the importance of water in an achiral version of the chelation-controlled Heck/Suzuki domino reaction 12. We therefore decided to investigate the effect of water content on the outcome of this reaction.…”