نبذة مختصرة : The observation of post-transition-state dynamic effects in the context of metal-based transformation is rare. To date, there has been no reported case of a dynamic effect for the widely employed class of palladium-mediated coupling reactions. We performed an experimental and computational study of the trifluoromethylation of Pd (II) F, which is a key step in the Pd (0) /Pd (II) -catalyzed trifluoromethylation of aryl halides or acid fluorides. Our experiments show that the cis / trans speciation of the formed Pd (II) CF 3 is highly solvent- and transmetalation reagent-dependent. We employed GFN2-xTB- and B3LYP-D3-based molecular dynamics trajectory calculations (with and without explicit solvation) along with high-level QM calculations and found that depending on the medium, different transmetalation mechanisms appear to be operative. A statistically representative number of Born–Oppenheimer molecular dynamics (MD) simulations suggest that in benzene, a difluorocarbene is generated in the transmetalation with R 3 SiCF 3 , which subsequently recombines with the Pd via two distinct pathways, leading to either the cis - or trans- Pd (II) CF 3 . Conversely, GFN2-xTB simulations in MeCN suggest that in polar/coordinating solvents an ion-pair mechanism is dominant. A CF 3 anion is initially liberated and then rebinds with the Pd (II) cation to give a cis - or trans- Pd (II) . In both scenarios, a single transmetalation transition state gives rise to both cis - and trans -species directly, owing to bifurcation after the transition state. The potential subsequent cis - to trans isomerization of the Pd (II) CF 3 was also studied and found to be strongly inhibited by free phosphine, which in turn was experimentally identified to be liberated through displacement by a polar/coordinating solvent from the cis -Pd (II) CF 3 complex. The simulations also revealed how the variation of the Pd-coordination sphere results in divergent product selectivities.
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