Functional Group-Directed C-H Bond Selective Activation And Coordinated Regulation Mechanism With Metal Ions And Ligands

In the past ten years,the synthesis of various organic compounds catalyzed by transition metals through C-H functionalization has been proved to be an efficient synthetic method by chemists.However,how to effectively control the site selectivity of C-H functionalization is still the difficulty and focus of synthesis.The use of directing groups?DG?is a widely used effective method to control selective C-H activation.The introduction of oxidation directing groups further promotes the development of transition-metal-catalyzed redox neutral C-H activation.This dissertation explores a series of transition metals?such as Pd,Rh,Co?catalyzed C-H activation reaction processes,through theoretical and computational chemistry methods,respectively studied Rh?III?/Co?III?catalyzed C?sp²?-H functionalization and Pd?II?catalyzed C?sp³?-H functionalization.Based on transition-metal-catalyzed C-H activation mechanism by three metal complexes and six reaction systems,the selective activation of directing-group-guided C-H bond and its synergistic regulation with metal ions and ligands were discussed,and some innovative results were obtained.In addition,the effects of substituents in the process of carboncation rearrangement reaction were studied by dynamic simulation methods.The main work of this dissertation could be divided into the following seven categories:?1?We conducted a density functional theory?DFT?calculation on the mechanism of redox-neutral Rh?III?-catalyzed coupling reaction between aryl nitrone and alkyne.The free energy profiles of the entire catalytic cycle including C?sp²?-H activation,alkyne insertion,oxygen atom transfer,cyclization,and protodemetalation were explored.The results show that,in all paths,the alkyne inserted into the Rh-C rather than the Rh-O bond.The pivalate-assisted C-H activation step is a rate-determining step,while the cyclization step determines the diastereoselectivity of the reaction,which is mainly derived from the noncovalent interactions in the key transition states.We explored in detail the mechanisms of oxygen atom transfer,Rh^III-Rh^I-Rh^III vs Rh^III-Rh^V-Rh^IIIII cycle.?2?We conducted a detailed mechanism study of Rhodium-catalyzed carbamination/cyclopropanation under different reaction conditions from the same starting reactant,and elucidated the switch between carbamination and cyclopropanation reactions and the origin of chemoselectivity.The results show that the Rh^III-Rh^V-Rh^III mechanism is more favorable in two reactions than the experimentally proposed Rh^III-Rh^I-Rh^IIIII catalytic mechanism.The chemoselectivity is due to the dual effects of electronic and steric in the reduction elimination step.During the alkene migration insertion process,the interaction between the alkene and rhodacycle controls the stereoselectivity of carboamination reaction.In addition,it is important that the solvent methanol plays a dual role in controlling chemoselectivity.?3?The introduction of C=O,C=C,C=S or C=N bonds has become an effective strategy for carbocyclic synthesis.We have conducted detailed studies on the coupling reactions of alkynes with enaminones,sulfoxonium ylides,or?-carbonyl-nitrones catalyzed by Rh^III,respectively.The results reveal the mechanisms of the roles of the dual directing group in the three substrates,and confirm that the ketone group is used as the coordination group,and the C=C,C=N or C=S bond is used as the cyclization site.By comparing the coordination of the ketone group with the C=C,C=N or C=S bond and the chemoselectivity of the formation of a six-membered and a five-membered ring,the competition relationship is revealed in the dual directing group.In addition,after the alkyne insertion,it was not the direct reduction elimination mechanism previously proposed.We found that ketone enolization should occur before the reduction elimination,and subsequent C?sp²?-C?sp²?reduction elimination is more favorable than C?sp³?-C?sp²?formation.We also discussed the effect of substituents on controlling selectivity.?4?The mechanism of Cp*Co^III/Rh^III-catalyzed carboamination/olefination reaction between N-phenoxyacetamide and alkenes was studied.The chemoselectivity of the reaction was controlled by different metal catalysts.The results show that the two catalysts undergo similar reaction processes,including N-H and C-H activation and alkene insertion.The resulting seven-membered metallacycle is then divided into two different reactions.For Cp*Co^III catalysts,the generated metallacycle undergoes oxidative addition,reduction elimination,and protonation to form single carboamination product.However,the subsequent olefination reaction can be promoted under the catalysis of Cp*Rh^III,through?-H elimination,reduction reduction,oxidative addition,and protonation,which results in experimentally generated mixed products of carboamination and olefination.Our results reveal that the higher?-H elimination tendency of Cp*Rh^III than the Cp*Co^III catalyst in the olefination reaction is responsible for the difference in selectivity and reactivity of the two catalysts.?5?In the presence of the more accessible?-C?sp³?-H bonds,Pd?II?-catalyzed site-selective?-C?sp³?-H alkenylation was studied by the DFT calculation.The key step that determines the rate and selectivity of the overall reaction has been calculated to be the migration insertion process.The origin of this unusual site-selectivity was originally attributed to the difference in steric repulsion between the alkyne and palladacycle,however,our theoretical results show that it is the intrinsic electronic effect rather than steric repulsion that determines the site-selectivity.The validity of this method is further proved by the model calculation of 1,2-dimethyl acetylene and acetylene with smaller steric hindrance.In addition,we discovered a new HCO₃^--assisted N-H activation mechanism and investigated the origins of regioselectivity of unsymmetric alkynes.?6?the computational mechanism of Pd?II?-catalyzed enantioselective borylation involving acetyl-protected aminomethyl oxazolines?APAO?ligands was studied,and the selectivity and reactivity of C?sp³?-H borylation were significantly improved.Our results revealed the cycle including initial C?sp³?-H activation,formation of a five-membered palladacycle,ligand exchange,and HPO₄^2--promoted transmetalation.These obtained Pd?II?complexes further undergo reductive elimination by the coordination of APAO ligands,and then protonation to generate enantiomeric products and release the Pd?0?complex,which regenerates the catalyst through oxidation and deprotonation.We found that C?sp³?-H activation is a key step in determining rate-and enantio-selectivity,in which APAO ligands act as proton acceptors to form two enantioselective models.The results show that different APAO ligands control enantioselectivity by distinguishing between distortion and interactions between the major and minor pathways.?7?Dynamic calculations were used to explore the underlying factors that affect the velocity of hydrogen migration by different substituents.A range of aromatic and non-aromatic groups were considered and the strength of cation-?interactions has a small impact on the velocity.Our results indicate that stronger electrostatic interactions lead to slower hydrogen migration for the non-aromatic groups.