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

Abstract

The Rh­(III)-catalyzed regioselective C–H amidation of N-methoxy-1H-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 KHSO4 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-1H-indole-1-carboxamide.

A Cascade Rh(III)‐catalyzed C−H Activation/Chemodivergent Annulation of N‐carbamoylindoles with Sulfoxonium Ylides for the Synthesis of Dihydropyrimidoindolone and Tricyclic [1,3]Oxazino[3,4‐a]indol‐1‐ones Derivatives

“…To gain more insight into the mechanism of these protocols, several mechanism experiments were conducted. It was found that the stable complex 6 , which can be synthesized smoothly by the previous literature procedure, [6k] could act as an active catalyst intermediate to catalyze the reaction between 1 a and 2 a , affording the expected 3 aa (63%) and 4 aa (79%), respectively. Subsequently, a kinetic isotope effect value of 1.1 was observed, which suggests that the C−H activation events is not involved in the rate‐determining step.…”

Selective Synthesis of Fused Tricyclic [1,3]oxazino[3,4‐a]indolone and Dihydropyrimido [1,6‐a]indolone via Rh(III)‐catalyzed [3+3] or [4+2] C−H Annulation

“…In 2017, the same group reported a Rh(III)‐catalyzed C−H cyclization of N ‐carboxamide indoles and diazonaphthalen‐2(1 H )‐ones to synthesize lactones (Scheme 1b) [14] . More recently, a Rh(III)‐catalyzed regioselective C−H amidation of N ‐carbamoylindoles with 1,4,2‐dioxazol‐5‐ones was reported by Zou and co‐workers (Scheme 1c) [15] …”

Indole‐N‐Carboxylic Acids and Indole‐N‐Carboxamides in Organic Synthesis

“…Recently, the Zou group reported a series of Rh‐catalyzed C−H amination of indole‐ N ‐carboxamides 113 with dioxazol‐5‐ones 114 . This process could selectively obtain four types of products by changing reaction conditions (Scheme ).…”

“…The obtained products could Recently, the Zou group reported a series of Rh-catalyzed CÀ H amination of indole-N-carboxamides 113 with dioxazol-5ones 114. [38] This process could selectively obtain four types of products by changing reaction conditions (Scheme 28). When N-methoxy Indole-N-carboxamides 113 were treated with 5 mol % [Cp*RhCl 2 ] 2, 30 mol % Zn(OTf) 2 and 1 equivalent of NaOAc at ambient temperature in THF, DG-retained products 2acylamino indoles 115 could be formed up to 92% yields.…”