Synthesis of Indolines via Base-Mediated C−H Activation and Defluorinative C−N Coupling, with no Need for Transition-Metals

Syntheses of (partially) aromatic nitrogen heterocycles increasingly rely on transition-metal catalyzed C−C- and C−N-cross-coupling reactions. Here we describe a different approach to the synthesis of indolines by a domino C(sp³)−H activation, 1,2-addition, and defluorinative S_NAr-cyclization sequence to provide the target 1,2-diarylindolines (1,2-diaryl-2,3-dihydroindoles) from ortho-fluorinated methyl-arenes and N-aryl imines (benzylidene anilines) in a cyclocondensation that is mediated by potassium hexamethyldisilazide (KHMDS) as base exclusively. This transition-metal-free process via C−H and C−F bond activation provides a one-step entry into a wide array of indoline scaffolds (43 examples, up to 96 % yield). This privileged substructure is common in natural products and pharmaceuticals alike, and cannot be accessed by traditional condensation reactions.