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

Chemistry. 2024 May 1:e202401034. doi: 10.1002/chem.202401034. Online ahead of print.ABSTRACTSyntheses 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 SNAr-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 hexa-methyl-di-silazide (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.PMID:38693605 | DOI:10.1002/chem.202401034

Source: Chemistry - May 1, 2024 Category: Chemistry Authors: Christian Weindl Lukas Hintermann Source Type: research