Theoretical Study On C-N Bond Coupling Catalyzed By Transition Metal Copper Organic Complex

Nitrogen-containing compounds are an important class of organic compounds with significant biological activity,widely present in natural products and drug molecules.The construction of C-N bonds has received extensive attention from many researchers.The construction of C(sp2)-N bonds involves synthetic methods such as Buchwald-Hartwig,Ullmann coupling,Chan-Lam amination,etc.The construction of C(sp3)-N bonds is usually achieved through nucleophilic substitution(SN1/SN2),Mitsunobu alkylation,carbonyl reduction amination,and olefin hydrogenation amination reactions.While achieving the construction of C(sp3)-N bonds,chemists continuously explore and develop new synthetic methods to overcome the limitations and deficiencies in reaction activity,chemical selectivity,and enantioselectivity of the above methods.Among them,the use of transition metal-catalyzed radical reactions to construct C(sp3)-N bonds by generating highly active carbon radicals in coupling reactions can significantly improve reaction activity.This paper uses density functional theory to conduct theoretical calculations on the series of reactions that construct C-N bonds through single-electron transfer and halogen atom transfer pathways under the catalysis of transition metal copper complexes.The main research contents are as follows:1.Theoretical study on the enantioselective construction of chiral secondary amines via photoinduced copper-catalyzed redox reactions.Density functional theory(DFT)calculations were performed to investigate the reaction pathways of copper-catalyzed C-N coupling reactions under vacuum and solvent conditions.The effects of ligands on the catalytic activity of the metal center and their own redox properties,as well as the reasons for the regioselectivity of chiral secondary amines,were explored.The rate-determining step and dominant pathway of the reaction were determined.The computational results showed that the photo-induced redox catalytic cycle proceeds through an oxidation-quenching mechanism CuⅠ-CuⅠ*-CuⅡ-CuⅢ,which involves C-Br bond activation,ligand exchange,acylamide ion/Br ion exchange,and C-N coupling processes.The process of single-electron transfer to generate alkyl radicals is the rate-determining step of the reaction,with a barrier of 13.9 kcal/mol.The chelating bidentate phosphine ligand enhances the reductivity of the catalyst through charge transfer(CT)under visible light irradiation,thereby enhancing the ability to activate C-Br bonds.The exchange between bidentate phosphine ligands and diamine ligands achieves the self-redox of copper.The chiral plane constructed by the CuⅡ-O1-N1-N2-N3 coordination of the catalyst provides the necessary prerequisite for the generation of enantioselective products.2.Theoretical study on the α-aminoalkyl radical-mediated C-N coupling reaction.Density functional theory calculations were performed to determine the rate-controlling step and dominant reaction pathway of the reaction system under vacuum and solvent conditions,and the solvent effect on the XAT process was investigated.The reaction mainly includes six processes:substrate coordination with the catalyst,single-electron transfer,hydrogen atom transfer,halogen atom transfer,carbon radical capture,and reductive elimination,among which single-electron transfer is the rate-determining step of the reaction,with a barrier of 5.3 kcal/mol.In the presence of polar mixed solvents(acetonitrile and tert-butanol in a volume ratio of 1:1),the C-I bond in α-iodoamine is polarized to eliminate iodide ions and generate imines,and this polarization process releases a large amount of heat,providing thermodynamic driving force for the reaction.3.Theoretical study on the Ullmann coupling reaction catalyzed by Ir/Cu cooperative catalysis.The mechanism of Ir/Cu bimetallic cooperative catalysis in the Ullmann reaction was investigated based on density functional theory.The main research contents include the dominant reaction pathway,ratecontrolling step of the reaction,the pathway for the formation of key divalent copper-nucleophilic intermediates,and the attacking preference of carbon radicals.The computational results showed that in the cooperative photo-induced redox catalytic cycle of super-silyl alcohol-oxygen-transition metal iridium complex,C-Br bond activation and efficient generation of carbon radicals are achieved with very low barriers.In the catalytic cycle of copper transition metal complexes,carbon radical capture and reductive elimination are realized to construct C-N bonds.