Theoretical Studies On The Mechanism Of Alkene Functionalization Catalyzed By Cobalt Metal Complexes

Transition-metal-catalyzed C-H functionalization has become a powerful and effective method to construct carbon-carbon and carbon-heteroatom bonds in organic synthesis.Although remarkable progress has been achieved in this field of two-component C-H activation,sequential three-component C-H bond additions across different coupling partners to access complex molecular scaffolds remain underdeveloped.Transition-metal-catalyzed direct C-H bond addition to terpenes and carbonyls provides an attractive process for the construction of homoallylic alcohols.In the terpenes,there exits two C=C bonds,which can result in four different migratory insertion intermediates.Therefore,controlling the regioselectivity is vital for the difunctionalization of terpenes.In addition,transition-metal-catalyzed cycloisomerization of 1,6-enynes and related reductive cyclizations represent powerful approaches to various chiral cyclic structural units.For enynes,the multiple coordination modes with transition metals may result in various competing reaction pathways.In this thesis,the mechanisms of Cp*Co(Ⅲ)-catalyzed three-component C-H bond addition to terpenes and formaldehydes were investigated by density functional theory(DFT)calculations.The reaction proceeds through successive C(sp2)-H activation,migration insertion,β-hydrogen elimination,hydride re-insertion,and C-C bond formation to produce the final product.The computed mechanistic scenario successfully explains the experimentally observed kinetic isotope effect.The migratory insertion is the rate-and regioselectivity-determining step of the overall reaction.We employed an energy decomposition approach to quantitatively dissect the contributions of different types of interactions to the regio selectivity.For the 2-alkyl substituted 1,3-dienes,the orbital interactions in the 3,4-insertion are intrinsically more favorable as compared to that in the 4,3-insertion,while the stronger steric effects between metallacycle and 1,3-diene override the intrinsic electronic preference.However,the steric effects failed to rationalize the unfavorable 1,2-insertion that is analogous to 4,3-insertion and even bears smaller steric effects.The donor-acceptor interactions analysis indicates that orbital interactions between σCo-C and πC=C decreased significantly in the 1,2-insertion transition state,which leads to higher activation energy barrier.We also investigated the detailed mechanism for the cobalt-catalyzed asymmetric hydroboration/cyclization of 1,6-enynes with pinacolborane by density functional theory calculations.The computations reveal that the overall catalytic cycle consists of the following elementary steps:olefin insertion,alkyne insertion andσ-complex-assisted metathesis(σ-CAM).Because the electronic configuration of the metal Co(Ⅰ)is 3d6,the corresponding metal complexes may have singlet,tripletand open-shell singlet states.In this paper,the energy barriers under the three states are investigated in details,and the optimal channel is obtained based on the comparison.The reaction pathway involving the olefin insertion,alkyne insertion and σ-CAM mechanism starting from the olefin-coordinated intermediate is the optimal reaction process.In this reaction route,the first olefin insertion is the rate-determining step and region-selectivity arising from this step can be attributed to the steric hindrance between the chiral bisphosphine ligand and the substrate.The in-depth mechanistic understandings of the cobalt-catalyzed functionalization reactions of alkenes and the obtaned insights into the dominant effects controlling the regioselectivity will enable rational design of new catalysts for selective functionalization of alkenes.