Lithium Diisopropylamide Mediated Synthesis of 3-Amino-1,2-Disubstituted Indoles via Intramolecular Cyclization of Amides

A novel transition-metal-free protocol has been established for the intramolecular cyclization of N-(2-(aminomethyl)phenyl)-N-substituted amides to afford 1,2-disubstituted-3-aminoindoles and their 3-(azol-1-yl) counterparts. This method offers high yields and good functional-group tolerance, making it particularly advantageous for the synthesis of 3-aminoindole scaffolds with a wide range of possible substituents at different positions. Mechanistic studies have shown that the main pathway of indole formation is nonclassical. This protocol has also been successfully applied on a gram scale.