Chemo selective C-H alkylation of isoquinolones with maleimides: A combined experimental and computational case study

A comparative study of C8-alkylation of isoquinolone with maleimides is reported under different catalytical systems. Among different catalytical systems, Ru and Rh catalysts were found to be excellent in providing C8alkylated products in good yields, and complete selectivity was achieved using Ru-catalyst. Density functional theory (DFT) investigations suggest a reaction mechanism involving three major steps: C-H activation at C8 position of the isoquinolone, maleimide migratory insertion into the metal-aryl bond, and protonation by the acetic acid. Non-covalent interaction (NCI) analysis was also executed to understand the reaction feasibility and selectivity pattern. Experimental mechanistic studies combined with DFT calculations and NCI analysis provide in-depth information to unravel the mystery behind the selective formation of alkylated products. The current catalytic methodology is further elaborated with a broad substrate scope and late-stage modification.