Metadynamics simulations of R–NHC reductive elimination in intermediate palladium complexes of cross-coupling and Mizoroki–Heck reactions

• Published in: Mendeleev communications 2023-03, Vol.33 (2), p.153-156
• Main Authors: Kostyukovich, Alexander Yu, Gordeev, Evgeniy G., Ananikov, Valentine P.
• Format: Article
• Language: English
• Subjects: catalyst evolution; metadynamics; molecular dynamics; palladium catalysis; reaction mechanism; R–NHC coupling
• ISSN: 0959-9436
• DOI: 10.1016/j.mencom.2023.02.002

[Display omitted] Exploring the free energy surface of the R–NHC coupling reaction in the key intermediates of the Mizoroki–Heck and cross-coupling catalytic cycles has been conducted by the methods of biased and unbiased molecular dynamics. Molecular dynamics simulations were carried out both in vacuum and in a polar solvent, with the following main observations on the influence of the media: (1) the solvent prevents the dissociation of the solvate ligand, so the R–NHC coupling proceeds in a four-coordination complex (rather than in a three-coordination one, as in the case of a gas-phase reaction); (2) in the condensed phase, the potential barrier of the reaction is significantly higher compared to the same process in vacuum (17.7 vs. 21.8 kcal mol-1); (3) polar solvent stabilizes the R–NHC coupling product. The reaction in a polar medium is exergonic (ΔG = −3.9 kcal mol-1), in contrast to the in vacuum modeling, where the process is endergonic (ΔG = 0.4 kcal mol-1).