Ketone-Directed Cobalt(III)-Catalyzed Regioselective C2 Amidation of Indoles

Abstract

An efficient cobalt­(III)-catalyzed method for the direct C–H amidation of unprotected indoles for 2-amino indole scaffold construction has been developed. With dioxazolone as the amidating reagent, a variety of 2-amino indole derivatives were achieved in moderate to excellent yields using an organic acid as the additive and a ketone as the directing group.

Ruthenium(ii)-catalyzed regioselective direct C4- and C5-diamidation of indoles and mechanistic studies

“…The use of other catalysts did not improve the yield of 5a. For example, 5a was isolated in 51% yield when [Cp*IrCl 2 ] 2 was used as catalyst, but no 5a was obtained from [Cp*Co(CO)I 2 ] (entries [15][16]. The 1 H NMR of 5a showed a singlet peak corresponding to the aldehyde proton at δ 9.64 ppm, the vinyl proton on the pyrrole ring at δ 8.42 ppm as a singlet, and two amide proton peaks at δ 11.67 and 9.89 ppm as two singlets.…”

“…C4-amination of 3-carbonylindoles using sulfonyl azides was described by the Prabhu 14 and You groups 15 (Scheme 1A). Recently, Wang et al developed a Co(III)-catalyzed regioselective C2-amidation of 3-acetylindoles using phenyl dioxazolone 16 (Scheme 1B).…”

RuV‐Acylimido Intermediate in [RuIV(Por)Cl2]‐Catalyzed C–N Bond Formation: Spectroscopic Characterization, Reactivity, and Catalytic Reactions

“…For N ‐tolyl indole, its amination by [Ru IV (TDCPP)Cl 2 ](0.5 mol %)/ 1 d under similar conditions led to <20 % conversion (major product: 6 fd ). In literature, reports on installing N ‐acyl amine groups by metal‐catalyzed functionalization of indole C(sp 2 )−H bonds are usually focused on indoles bearing DGs for C2‐ [28a,c–f] and C7 [28b] ‐amination, except for the C2‐amination of N ‐methylindole catalyzed by CuBr(20 mol %)/“H(R)NCOMe+ t BuOO t Bu” [29a] leading to tertiary N ‐acyl amines (yields: 36–70 %) [29a] . The [Ru IV (TTP)Cl 2 ]/N 3 COR method resulted in C3‐amination of indoles without DGs (Figure 5) to give secondary N ‐acyl amines [29b] in 70–88 % yields.…”

Revisiting the mechanism of the Fujiwara–Moritani reaction

“…Brønsted acid additives are commonly employed in many transition metal-catalysed C-H functionalisation reactions (for e.g. Cu, 33 Ru, 34 Co, 35 Rh, 36 Ir, 37 as well as Pd (ref. 38 and 39)) for a variety of reasons, although their roles in the Reaction Chemistry & Engineering Paper catalytic cycles are rarely studied.…”