Quantitative Analysis Of Selectivity In Alkene And Alkyne Functionalization

Functionalization of olefins and alkynes is one of the most effective methods to construct C-C bonds and C-X bonds and is widely used in organic synthesis,materials chemistry,pharmaceutical science,and many other fields.Although considerable experimental progress has been made in this area,the mechanisms involved and the selectivity of the reactions remain unclear.With the continuous development of computer technology and quantitative methods,theoretical calculations have become an important tool for investigating reaction mechanisms and selectivity.Therefore,the mechanism of transition metal-catalyzed alkene and alkyne functionalization reactions as well as regioselectivity and stereoselectivity are systematically investigated using Density Function Theory(DFT),and the dominant factors controlling the selectivity of the reactions are quantitatively revealed using Energy Decomposition Analysis(EDA).The first part of this thesis explores the mechanism of the silver-catalyzed hydroalkylation of terminal alkynes with alkylboron for the synthesis of cis-olefins and the factors controlling the stereoselectivity of the reaction.The results show that the terminal alkyne undergoes C(sp)-H activation to form an alkynyl silver intermediate,which subsequently reacts with alkyl boron to form a tetra-coordinated alkynyl boron intermediate.This intermediate undergoes subsequent steps such as 1,2-alkyl migration,transmetallation,and protonation to produce the cis-alkene.The irreversible 1,2-alkyl migration is the key step,which determines both the reactivity and stereoselectivity.By the use of energy decomposition analysis,we found that theσ)(π Pauli repulsion is the dominant factor for destabilizing the syn-1,2-migration,thus favoring the anti-1,2-migration pathway.We anticipate that modulating the unstable Pauli repulsion can improve the selectivity of reactions with various boronate complexes.The second part of this thesis explores the mechanism of the reaction mechanism and the dominant factors controlling the stereoselectivity of copper-catalyzed selective carboxylation of terminal alkynes with CO2 and alkylboron.The results show that the terminal alkyne undergoes C(sp)-H activation to form an alkynyl copper intermediate,which subsequently reacts with alkyl boron to form a tetra-coordinated alkynyl boron intermediate.This intermediate undergoes subsequent steps such as 1,2-alkyl migration,transmetallation,and CO2 insertion leading to the α-alkyl acrylic acids.The favored geminal addition proceeds through the cationic Cu-mediated stereoselective 1,2-migration pathway.The energy decomposition analysis indicates that the σ)(π Pauli repulsion is the dominant factor for controlling the stereoselectivity.We hope that this research will provide a more theoretical basis for subsequent studies on the conversion of CO2.The third part of this thesis explores the mechanism and origin of ligand effects on stereoinversion of Pd-catalyzed synthesis of tetrasubstituted olefins using DFT calculations and the approach of energy decomposition analysis(EDA).With the bulkier Xantphos ligand,the reaction proceeds oxidative addition,1,2-migration,and reductive elimination to produce the trans-tetrasubstituted alkene.In the overall energy profile,the 1,2-migration is an irreversible process,thus determining the stereoselectivity of the reaction.The energy decomposition analysis indicates that the σ)(π Pauli repulsion is the dominant factor for controlling the stereoselectivity.For the monodentate phosphine ligand((o-Tol)3P),the reaction proceeds oxidative addition,migrator insertion,1,3-migration,and reductive elimination to produce the cis-tetrasubstituted alkene.In the overall energy profile,the 1,3-migration is an irreversible process,thus determining the stereoselectivity of the reaction.The energy decomposition analysis indicates that polarization of the Pd-alkenyl fragment is the dominant factor for controlling the stereoselectivity.We hope that this study will provide a more theoretical basis for the design of ligands for subsequent transition metal-catalyzed alkyne functionalization reactions.In the fourth part of this thesis,with the assistance of EDA,we computationally analyze a series of hydrocupration transition states to identify the dominant factors controlling the regioselectivity for hydrofunctionalizations of both activated and unactivated olefins.The results demonstrate that the Markovnikov-selective hydrocupration with electronically activated mono-substituted olefins is mostly affected by the destabilizing Pauli repulsion,which is due to the electron delocalization effect.The anti-Markovnikov-selective hydrocupration with 1,1-dialkyl-substituted terminal olefins is dominated by the repulsive electrostatic interactions,which is because of the unequal π electron distribution caused by the induction effect of alkyl substituents.We expect that this study will provide a more theoretical basis for subsequent finely tune the regioselectivity in olefin and alkyne hydrofunctionalizations.