Ligand controlled regiodivergent C₁ insertion on arynes for construction of phenanthridinone and acridone alkaloids

A palladium-catalyzed regiodivergent C₁ insertion multicomponent reaction involving aryne, CO, and 2-iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand-free condition. In comparison, application of the electron-abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method. Divergent alkaloid synthesis: A multicomponent, regioselective approach for palladium-catalyzed C₁ insertion is described. This reaction was applied in the divergent synthesis of phenanthridinone and acridone natural product core scaffolds.