Palladium-catalyzed selective assembly of carbamoylated indoles and aminophenanthridinones via β-carbon elimination switch

Palladium-catalyzed switchable β-carbon elimination to extrude norbornene for selective synthesis of different heterocyclic skeletons is a long-standing challenge. Herein, we describe the switchable chemoselective synthesis of biologically active C4-carbamoylated indoles and C10-aminophenanthridinones by controlling β-carbon elimination, using chlorocarbamates as C–H carbamoylation reagents. Among them, C4-carbamoylated indoles are used for the synthesis of M2 receptor antagonists and p38α inhibitors. Mechanistic studies show that when β-carbon elimination is inhibited, the catalytic cycle goes through C–N bond coupling and retro-Diels-Alder reaction to generate C4-carbamoylated indoles. Alternatively, when β-carbon elimination to extrude norbornene occurs, an intramolecular C–H arylation cyclization reaction generates C10-aminophenanthridinones. Palladium-catalyzed β-carbon elimination for selective synthesis of diverse heterocyclic skeletons has been a persistent challenge. Here, the authors achieve switchable chemoselective synthesis of C4-carbamoylated indoles and C10-aminophenanthridinones by controlling β-carbon elimination using chlorocarbamates.