Chameleon-like Behavior of the Directing Group in the Rh(III)-Catalyzed Regioselective C–H Amidation of Indole: An Experimental and Computational Study

The Rh(III)-catalyzed regioselective C–H amidation of N -methoxy-1 H -indole-1-carboxamides by 1,4,2-dioxazol-5-ones was studied. N -Methoxy amide, the directing group (DG) of interest, undergoes four different transformations through DG-retained, -coupled, -eliminated, or -migrated processes under moderately varied reaction conditions. Solvents, additives, and temperature play important roles in these selective transformations; a trace addition of water favors the functional group (FG)-assisted DG elimination; extra addition of KHSO 4 greatly enhances the formation of the DG-coupled product; high-temperature and proper FG together can shift the position of DG through intermolecular Friedel–Crafts-like acylation. The catalytic mechanisms underlying these reactions were further investigated through density functional theory calculations and experimental studies including the characterization of amido-inserted rhodacycle. An overall catalytic pathway was proposed to illustrate the reactions involved in the regioselective amidation of N -methoxy-1 H -indole-1-carboxamide.