Mechanism Studies On Transition Metal-catalyzed Cycloaddition Reactions And Hydrofunctionalization Reactions

Computational chemistry is playing an increasingly important role in the field of various research fields in chemistry.It can not only help chemists understand the reaction mechanism,but also can predict and guide experiments to some extent.The synthesis of organic compounds mainly includes the construction of molecular framework and the conversion of functional groups.Such as transition-metal catalyzed Diels-Alder reaction and 1,3-dipolar cycloaddition,which can be used to construct six-and five-membered molecules.The hydrogenation of alkenes and hydrosilylation of alkynes are very important in the conversion of functional groups.However,the mechanisms of some challenging reactions including the oxa-Diels-Alder reaction(ODA)with unactivated substrates,1,3-dipolar cycloadditions with ?-substituted alkenyl heteroarenes,asymmetric hydrogenation of tetrasubstituted alkenes and hydrosilylation of terminal alkynes are still unclear.Thus,in this thesis,two cycloaddition reaction systems and two hydrofunctionalization reaction systems catalyzed by transition-metal complexes were systematically studied by density functional theory(DFT)and local CCSD(T)methods,which will help us to understand the reaction process,reactivity and selectivity deeply as well as could provide theoretical guidance for the design of the experiments.Firstly,systematic DFT calculations were performed to study the unclear reaction mechanism of the ODA reaction with unactivated substrates catalyzed by iron porphyrin complexes,which can be used to construct six-membered molecules.The computational results indicate that it follows a concerted synchronous mechanism,which also involves two reaction modes of six-and five-coordination modes and two spin states(quartet and sextet).Driven by the equilibrium kinetic isotope effect(1.08)owing to the change in the iron coordination mode,the five-coordinate transition states have a larger kinetic isotope effect(0.95-0.97)than the six-coordinate transition states(0.89-0.90),even though they have similar transition state structures.In addition,the regioselectivity is controlled by electrostatic matching and larger orbital overlap.The uncommon chemoselectivity of the C=O bond is related to both of the catalyst and the substituents on the ? position of the unsaturated aldehyde.This mechanism study can help design some other catalysts to catalyze such challenging ODA reactions.Secondly,systematic DFT calculations were performed to study the reaction mechanism of the 1,3-dipolar cycloadditions with bicyclic benzo[d]oxazole ring substituted alkenes,which can be used to construct five-membered molecules.The DFT results show that the reaction follows a stepwise mechanism,and the second cyclization is the rate-,stereo-determining step.In addition,both the dipole and dipolarophile were found to coordinate to the copper center.This dual activation mode can not only increase the reactivity,but also plays a vital role in the diastereoselectivity.The structural analysis of the two enantiomers indicates that the steric hindrance is an important factor for the higher enantioselectivity.Inspired by these results,we successfully predicted the enantioselective reversal for the reaction of some monocyclic heterocyclic alkene substrates and the uncommon cycloaddition on the internal C=C bond of one conjugated diene substrate,which is less reactive than the terminal C=C bond.These computational results were verified experimentally by other collaborators.This research can provide theoretical support and guidance for rational design of other reactions.In addition,DFT calculations were performed to study the reaction mechanism of the 1,3-dipolar cycloadditions with racemic alkylidene norcamphors.The DFT results show that the reaction also follows a stepwise mechanism,but the first Michael addition is the rate-,stereo-determining step.The key structural analysis indicates that the electrostatic repulsion between one bromine atom of the biphenyl ligand and the carbonyl oxygen,which can weaken the hydrogen bond between the ligand and substrate.These results ultimately lead to the change of regioselectivity of the cycloaddition.This study can provide theoretical guidance for other ligands design.In addition,DFT calculations were performed to study the reaction mechanism of asymmetric hydrogenation of tetrasubstituted alkenes catalyzed by cobalt complexes.The calculations suggest that the catalytic cycle involves migratory insertion and ?-bond metathesis,as well as the migratory insertion step is the rate-,regio-and stereo-determining step.And the stereoselectivity is mainly controlled by steric hindrance of phenyl groups between the substrate and ligand.Moreover,the DFT results of Markovnikov hydrosilylation of terminal alkynes show that the proposed active species of the system is Co(I)-H,and the catalytic cycle also involves migratory insertion and ?-bond metathesis.The migratory insertion step is the regio-determining step,and the ?-bond metathesis step is the rate-determining step.The dispersion effect was found to be very important in the control of regioselectivity of the reaction.This mechanism study should be helpful for the development of other hydrofunctionalization reactions with Markovnikov selectivity.