DFT-Based Insights into Pd–Zn Cooperative Effects in Oxidative Addition and Reductive Elimination Processes Relevant to Negishi Cross-Couplings

Abstract

The individual steps of a model Pd-catalyzed Negishi coupling between vinyl bromide and MeZnClS 2 (S = THF), using Pd(PMe 3 ) 2 as catalyst, have been examined with the aid of DFT computations in THF solution with the B97D functional to gain further insight into the role of Pd−Zn interactions on the oxidative addition and reductive elimination steps. Comparisons between such processes taking place on monometallic Pd complexes and on bimetallic Pd−Zn complexes reveal a detrimental effect of Pd−Zn interactions in oxidative addition, whereas reductive elimination is favored by Pd−Zn cooperativity. Additionally, a cis transmetalation pathway has been characterized that complements previous studies involving trans complexes.

Catalyst Activation, Deactivation, and Degradation in Palladium‐Mediated Negishi Cross‐Coupling Reactions

“…The above-mentioned quantum-chemical calculations by Gonzµlez-PØrez et al predict that the association of Pd(PMe 3 ) 2 with MeZnCl(THF) slows down the oxidative addition. [24] An analogous effect could also lead to the bimodal behavior observed in the kinetic measurements, when the solution of the catalyst was added to a mixture of ArI and RZnBr·LiBr in THF. The extremely fast reaction progress in the initial phase presumably reflects the exclusive presence of free and more reactive [LPd] complexes just after the addition of the catalyst solution.…”

“…[24] In contrast, structure B seems less likely because such bridging binding modes are uncommon for tertiary phosphines. [36] We also exclude structure C; if it formed, one would expect other ethers, such as the abundantly present THF, to coordinate to the ZnBu + moiety as well.…”

“…[23] Gonzµlez-PØrez et al recently even postulated that Pd-Zn interactions may control the oxidative addition. [24] However, this conclusion drawn from quantum-chemical calculations so far lacks experimental verification.…”

Understanding palladium complexes structures and reactivities: beyond classical point of view

“…Interestingly, cooperative effects between metal centers could also lower reductive elimination barriers . These effects are important for the design of effective catalysts for alkyl–alkyl coupling, for which reductive elimination could be rate determining, and to tune the steric demands of ligands to minimize formation of side products …”

“…22 Interestingly, cooperative effects between metal centers could also lower reductive elimination barriers. 23 These effects are important for the design of effective catalysts for alkylalkyl coupling, 24 for which reductive elimination could be rate determining, and to tune the steric demands of ligands to minimize formation of side products. 25 Both homo-and heterogeneous cascades involving boronic acids as coupling partners were studied with computational tools, as a result of the impact of Suzuki coupling on organic synthesis.…”