Density Functional Theory Study About A Few Organic Cyclization Reactions

Due to their electronically unfull-filled d orbitals,transition metals often show different oxidation states and strong affinity for unsaturated compounds,and can be stabilized by coordination with many compounds via formation of ?-bond or ?-bond.Transition metals can give electrons to reactants or capture electrons from them during the reaction process,and thus promote the whole reaction by changing their oxidation states and coordinates.Since this catalytic style is often used to build complex heterocyclic molecules,transition metal catalysts have been playing a very important role in organic synthesis area.In this thesis,we have carried out theoretical studies about three transition metal-catalyzed reaction systems,including nickel-,silver-and palladium-catalyzed cycloaddition reactions.Density functional theory(DFT)at IDSCRF-B3LYP/DGDZVP level is employed to explore possible reaction mechanisms by optimizing all involved reactants,products,transition states and intermediates,and corresponding frequency calculations.All energy results presented in this thesis are Gibbs free energies which have been corrected to corresponding experimental temperatures.(1)We found five possible reaction paths about the ring-opening process of vinylcyclopropane(VCP)in the nickel-catalyzed [3+2] cycloaddition reaction between VCP and imine.Based on our calculation results,the optimal reaction path(Path I)is corresponding to the coordination of nickel catalyst under the vinyl group and then induces VCP's ring-opening.In the subsequent [3+2] cycloaddition process,the reaction goes stepwisely by forming C-C bond between imine and ring-opened VCP firstly and then forming pyrrole ring through the formation of a C-N bond,wherein C-C bond forming step is the rate-determining step(RDS)of the whole reaction.Due to different orientation of benzene ring in the imine,there are two possible paths(Cis and Trans)in the process of cycloaddition.The free energy barrier corresponding to RDS transition state which leads to Trans-product is 26.9 kcal·mol-1,about 1.7 kcal·mol-1 higher than that leads to Cis-product,can basically explain Cis-product' major formation in corresponding experiments.Topological analysis of electron densities in RDS transition states show less steric hindrances in the Cis-transition state and it's thus more stable.Further calculations about the optimal path(Path Ia)of employing PMe2 Ph ligand other than dmpe ligand show worse stereoselectivity and higher free energy barrier required by forming C-N bond in the[3+2] cyclization process,which indicates poorer reactivity and stereoselectivity inthe PMe2Ph-assisted reaction then the dmpe-assisted reaction,coincides well with corresponding experimental results.Based on computational results about the optimal reaction path obtained at IDSCRF-B3LYP/DGDZVP,IDSCRF-M062X/DGDZVP and IDSCRF-B3LYP+D3/DGDZVP levels,we found computational results obtained at IDSCRF-B3LYP/DGDZVP level is the closest one with experimental data.(2)Possible reaction mechanisms about silver-catalyzed [3+2] cycloaddition of?-amino phosphate and olefins have been explored.The first step is corresponding to the proton transfer process: Ag(OTf)reacts with the ferrocene-like phosphrine ligand through ligand exchange process,helps ?-amino phosphate to realize hydrogen transfer,and releases one molecular H-HMDS meanwhile.The second step is corresponding to the [3+2] cycloaddition process.Due to different spatial orientation of the acetate groups in the olefins,two possible paths(endo-and exo-)leading to endo-and exo-products respectively were located,among which the endo-path is stepwise,while the exo-path is asynchronously concerted.Due to stabilization effect arisen from the coordination between acetate group and silver center in the endo-transition state,the free energy barrier corresponding to transition state on the endo-path is about 2.2 kcal/mol lower than that of the transition state on the exo-path,illustrates the endo-path's dominance in energy well.The third step is corresponding to the proton's transfer from H-HMDS back to reactant,accompanying by catalyst's regeneration and acts as the RDS of the whole reaction.The free energy barrier corresponding to endo-transition state in this step is calculated to be 21.5 kcal/mol,about 3.9 kcal·mol-1 lower than corresponding exo-transition state,explains why endo-product is predominant.Further explorations are carried out on the key processes of Copper(I)catalyzed [3+2] cyclization between imidazolide and acrylates.Computational results show no coordination between acetate group and copper center because of larger steric hindrance between the ligand and the acrylate,explains well why the exo-product turns to be major experimentally in this case.(3)Possible reaction mechanisms about palladium-catalyzed cross-coupling cyclization between cyclobutanone and alkyne derivatives have also been explored.Firstly,the bromine atom on 2-(2-bromobenzylidene)cyclobutanone shifts from the phenyl ring onto the palladium center,then the substituted cyclobutanone reacts with the second reactant(2-alkynylphenol)and forms new C-C bond.After this,two possible reaction paths,Path A(the six-membered ring forms firstly,then followed by the cyclobutanone derivative's ring-opening)and Path C(the cyclobutanonederivative opens ring firstly,then followed by the six-membered ring's formation)are located due to different sequences of the six-membered ring's formation and cyclobutanone derivative's ring-opening,among which Path A is dominant.The six-membered ring's formation process is proved to be the RDS on Path A,with a free energy barrier of 33.0 kcal/mol.Geometric parameters and bonding characteristics analysis about key stationary points on Paths A and C further illustrated Path A's preponderance then Path C.