A Theoretical Study On Ir(?)-Catalyzed Intermolecular Branch-Selective Allylic C-H Amidation

Amides are not only important intermediates in organic synthesis,but also widely applied in immunology,polymer materials science and agricultural chemicals.What is more,amidation reactions play an important role in the preparation of various bioactive molecules and in the development of new drugs.In classical ways,amides are achieved by coupling reaction between carboxylic acids and amines,in which carboxylic acids can be replaced by esters with good stability and more electrophilic properties.This method is simple,but slow condensation reaction and low atomic utilization rate are not conducive to large-scale production.In recent years,with the continuous development of transition metal-catalyzed C-H activation,the preparation of amides by transition metal complexes as catalysts is gradually replacing the traditional amide preparation methods.Rovis et al.discovered the Cp*Ir(?)-catalyzed intermolecular branch-selective allylic C-H amidation of unsaturated terminal olefins.The reaction,which uses dioxazolone as the nitrogen source,well avoids Curtius/Lossen-type rearrangement and is characterized by high activity,good regioselectivity and unique allyl branched structure of the product,so it has high research value.To further develop the transition metal-catalyzed C-H amidation,we investigated the reaction mechanism of Cp*Ir(?)-catalyzed allylic C-H amidation of terminal alkenes using density functional theory(DFT),and explored the effect of substituent effects on the kinetics and regioselectivity of the reaction,and achieved some important conclusions.(1)The catalytic cycle mainly includes the coordination of terminal alkene,C(sp3)-H activation,coordination of dioxazolone,generation and isomerization of allyl-Ir-nitrenoid intermediate,migratory insertion,and proto-demetalation.(2)Due to the solvation effect,the C-H activation undergoes the C-H oxidative addition to form a metal-hydride and the process of hydrogen capture from metal-hydride by acetate.(3)The rate of the reaction is determined by the alkene coordination,the isomerization of iridium-alkene complex,the C-H oxidative addition and the subsequent hydrogen capture of carboxylate,and the large exergonicity makes the reaction irreversible.(4)As the electron-withdrawing ability of the substituent groups on terminal alkenes increases,the activation energies required for the C-H activation and the concerted breaking of the N-O bond and the C-O bond in dioxazolone as well as the apparent activation energy of the overall reaction increase;for chain terminal alkenes,the electron energy barrier of the elementary reaction of linear and branched iridium amide complexes formed by migratory insertion of allyl groups is reduced,the regioselectivity of the reaction is enhanced;in contrast,for benzene substituted propylene,the electron energy barrier for the allyl migratory insertion reaction of the formation of branched iridium amide complex is increased,while the electron energy barrier of the elementary process of generating linear iridium amide complexes is decreased,which leads to a decrease in the regioselectivity of the reaction.(5)As the electron-withdrawing ability of substituent group on dioxazolone increases,the difference between activation energies of the elementary reactions to afford linear and branched iridium amide complexes increases,and therefore the regioselectivity of the reaction increases.Figure[31]Table[3]Reference[90]...