2-Lithiomethylindoles: Untapped Anions for the Synthesis of 2-Functionalized Indoles

Optimal conditions for the metalation via α-lithiation of 1,2-dimethylindoles were established with <i>n</i>BuLi at room temperature, providing the most effective protocol. The resulting organolithium reagents bearing the structure of 2-lithiomethylindole were efficiently trapped with diverse electrophiles, including Weinreb amides, ketones, alkyl bromides, and epoxides, affording a broad range of C2-functionalized indoles in good yields. The methodology proved general and was successfully applied to 2-methylindoles bearing different substituents at the benzenoid ring, C3, and on the nitrogen atom, as well as to 2-benzylindoles, giving access to new functionalized indole derivatives. Importantly, deep eutectic solvents enabled these transformations under air- and moisture-tolerant conditions, highlighting their greener and operationally simple character. The synthetic utility of the method was further demonstrated through subsequent derivatizations, exemplified by the two-step preparation of 2,4-disubstituted carbazoles.