Theoretical Study Of Palladium And Nickel Complexes Catalyzed Aryl-Fluorine (Ar-F) Bond Activation

Carbon–fluorine（C–F）bond is difficult to be activated by transition metal complexes under conventional conditions due to the inferior reaction activity arising from the large bond energy.One of the current challenging research fields in organic synthesis is C-F bond activation.During these years,transition metal-catalyzed C–F bond activation of fluoroarenes has been extensively reported,which has become a frontier issue in organic chemistry.Although there are a variety of advanced analysis and detection technologies,some details of the mechanism are still not clear due to the complex reaction conditions and the indeterminacy of reaction pathways,which greatly limits the subsequent experimental expansion research.It is worth noting that theoretical and computational chemistry has gradually developed,which provides a feasible method for in-depth understanding of the mechanism of reactions and solving the problem of C-F bond activation.In this paper,the potential energy surfaces of transition metal-catalyzed C-F bond borylation and silylation are studied,the reaction mechanism,and its inherent regularity are discussed by DFT calculations.Based on the understanding of the reaction mechanism,the ligand structures are further designed and these results are expected to provide theoretical support for the design and development of new catalysts and new reactions in the future.Chapter 1 introduces the history of organic fluorine chemistry and discusses the significance of C-F bond activation in fluorine-containing compounds and the latest advances in C-F bond activation.Chapter 2 briefly introduces the background of theoretical methods,including density functional theory,basis sets,solvation models,transition state theory,and reaction potential energy surfaces.Chapters 3 and 4 are focused on the mechanism of palladium-catalyzed C-F bond borylation and the mechanism of nickel-catalyzed C-F bond silylation,respectively,as shown below:1.Pd-catalyzed C-F bond activation of fluorobenzene in the presence of Li HMDS and B₂pin₂was studied by DFT calculation.The results indicated that the catalytic cycle consists of three elementary reaction steps:oxidative addition,s-bond metathesis,and reductive elimination.DFT calculations disclosed that the reaction occurs through an unprecedented 3+6-membered ring transition state,in which one Li HMDS acts as a ligand and another Li HMDS is essential to provide Li···N and Li···F interactions,overcoming the large destabilization of the strong phenyl–F bond distortion.Furthermore,we also found that the by-product FBpin generated in thes-bond metathesis step has a low energy barrier and exothermic reaction with Li HMDS,which promotes the reaction thermodynamically more favorable.Finally,the reaction barrier by using HHMDS or Na HMDS is much larger than that by using Li HMDS,which is consistent with the experimental results that HHMDS or Na HMDS is not effective for the inert Ph–F bond cleavage.To be specific,the Li···F and Li···N non-covalent interactions are stronger than Na···F and Na···N,or H···F and H···N,which makes the transition state more stable.2.The mechanism of Ni-catalyzed C-F bond silylation of fluorobenzene was investigated by DFT calculations.Computational results indicated that the C（sp²）-F bond activation occurs through oxidative addition of the C（sp²）-F bond to the Ni（0）center.The catalytic cycle consists of two elementary reaction steps,oxidative addition,and reductive elimination.It is worth noting that the F atom forms a strong non-covalent interaction with K⁺as Lewis acid,which stabilizes the transition state of C（sp²）-F activation,so that the reaction has a lower activation energy barrier.Correspondingly,in the nucleophilic aromatic substitution reaction pathway,due to the inability of K⁺and F to form an effective interaction,the transition state is not stable and the activation energy barrier is high.Therefore,K⁺is essential for the activation of the C（sp²）-F bond.We also compared the difference between the activation energy barriers of C（sp²）-F and C（sp³）-F bonds in the absence of transition metal.The results revealed that C（sp³）-F bond is more easily activated by the S_N2 nucleophilic substitution reaction than the C（sp²）-F bond by the S_NAr nucleophilic substitution reaction.