Indoles via Arynes

The utility of benzyne and other arynes in synthesis has increased in the past decade. Accordingly, arynes have found employment in the synthesis of heterocycles, including indoles. The two main categories of arynes in indole and carbazole synthesis are Diels-Alder reactions and nucleophilic addition reactions. The first practical synthesis of indoles using aryne technology was that of Caubere and colleagues. Brown, Eastwood, and colleagues pyrolyzed qui-nolone-3,4-dicarboxylic anhydrides to give fused indoles. Guitian and colleagues employed aryne generation and intramolecular cyclization to access ergot, lycorine, and related ring systems. Oxidation of lactam indoline 3 with DDQ gave the corresponding indole (99%). In an approach similar to that of Caubere, but employing LDA, Kudzma synthesized a series of indoles and tetrahydrocarbazoles via the lithiation of 2-fluorophenyl imines, aryne formation, and cyclization.