Theoretical Studies On The Transition-Metal-Pd-Catalyzed C-H Functionalization

Recently,transition-metal-catalyzed C–H bond functionalizations is an important method in organic synthesis,which widely applied in drug and natural product synthesis,and palladium catalyzed C–H bond functionalizations attracted considerable intrest.Therefore,it is of great significance to explore the mechanism of palladium catalyzed C–H bond functionalizations.In this thesis,the mechanisms of Pd-catalyzed C–H functionalization reactions have been investigated by the density functional theory?DFT?.The main contents of this thesis are as follows:1.A theoretical understanding of the Pd-catalyzed C?sp³?–H activation of aliphatic amines has been examined using the B3LYP density functional theory,the basis set combining Lanl2dz for Pd and 6-31G?d,p?for other atoms.The concerted metalation–deprotonation?CMD?mechanism is identified in the rate-determining steps of all possible reaction pathways.The regio-determining step of the catalytic cycle is deprotonation of the C_methyl–H bond through a six-membered cyclopalladation transition state to generate the aziridene product.According to the relative activation barriers,the C_methyl–H activation is kinetically and thermodynamically more favorable than the C_ethyl–H activation,and the pentacoordinated Pd?IV?intermediates are favorable than the corresponding hexacoordinated intermediates.The only acetoxylation product is located,ignoring the diethyl-substituted or the dimethyl-substituted in the morpholine and not producing the lactone amines molecules,which is in good agreement with the experimental observations.2.Possible mechanisms of palladium-catalyzed C–H activation,regioselective2-alkylation of indoles have been investigated by theoretical calculations with density functional theory?DFT?.The catalytic reaction is to explore two possible mechanisms:the C3-palladation or the N-palladation mechanism.The results showed that N-palladation might be plausible.It proved that the mechanism of C–H activation is the concerted metalation deprotonation?CMD?progress,and the norbornene played crucial roles in tuning the relative barriers.We also found two possible pathways:one is n-BuBr oxidative addition to the palladacycle to give the Pd?IV?intermediate,and the other is transmetalation-type,in which the n-BuBr exchange between the different Pd?II?centers by a feasible Pd–Pd transmetalation-type process with lower activation energies.It is kinetically and thermodynamically facile.