Mechanistic insights into the nickel-catalyzed addition of amides with strained alkenes

Recent advancements have introduced a nickel-catalyzed method in which the C(aryl)–C(acyl) bond of aryl amides is activated and added to alkenes to achieve difunctionalized species. While this scenario holds significant promise for application, the underlying mechanism remains unclear, particularly with respect to the site of oxidative addition and the possible occurrence of carbonyl elimination-reinsertion. Herein, we utilize density functional theory (DFT) calculations to investigate the mechanistic pathway of nickel-catalyzed addition between aryl amides and strained alkenes. Our computational analysis demonstrates that the reaction proceeds through oxidative addition of the C(Ar)–C(acyl) bond, alkene coordination, Ni–C(acyl) insertion and reductive elimination. Alternative pathways involving oxidative addition of the C(acyl)–N bond and carbonyl elimination-reinsertion are energetically unfavorable. Although oxidative insertion into the C(acyl)–N bond faces a lower energy barrier than does the C(arcy)–C(acyl) bond, the subsequent alkene insertion step becomes kinetically unfavorable. The rate-determining step is Ni–C(acyl) insertion, which is more favorable than Ni–C(aryl) insertion. Additionally, both the choice of ligands and the indole amide substrates are critical: substituting with PCy₃ ligands or using aryl ester substrates results in challenging energy barriers. These insights provide a comprehensive understanding of the reaction mechanism and offer strategic guidance for the development and optimization of amide-involved difunctionalizations of alkenes.