Solvent-Mediated Tunable Regiodivergent C6- and N1-Alkylations of 2,3-Disubstituted Indoles with p-Quinone Methides

Abstract

Indium-catalyzed, solvent-enabled regioselective C6-or N1-alkylations of 2,3-disubstituted indoles with para-quinone methides are developed under mild conditions. Notably, highly selective and switchable alkylations were selectively achieved by adjusting the reaction conditions. Moreover, scalability and further transformations of the alkylation products are demonstrated, and this operationally simple methodology is amenable to the late-stage C6-functionalization of the indomethacin drug. The reaction pathways were explained with the support of experimental and density functional theory studies.

C6–H Bond Functionalization of Indoles: A New Gate

“…38 In 2023, our group disclosed the indium(III)-catalyzed tunable N1-and C6-alkylations of 2,3-disubstituted indoles using p-QMs as the electrophile in different solvents (Scheme 26). 39 This chemistry was shown to be amenable to highly selective and switchable alkylations by adjusting the reaction conditions. The yields were generally high, the procedure was scalable, and the alkylation products underwent further transformations.…”