Rhodium(I)‐Catalyzed C2‐Selective Decarbonylative C−H Alkylation of Indoles with Alkyl Carboxylic Acids and Anhydrides

Abstract

A Rh(I)-catalyzed chelation-assisted C2-selective CÀ H decarbonylative alkylation of indoles with readily available, cheap, safe and structurally diverse alkyl carboxylic acids or anhydrides has been developed. A wide variety of primary and secondary alkyl carboxylic acids and differently substituted indoles are compatible with this transformation, allowing facile synthesis of various C2-alkylated indoles with high efficiency and broad tolerance of diverse functional groups. The reaction proceeds in the absence of any external oxidant, and the presence of readily installable and removable N-pyrimidyl directing group is critical for catalysis. The process is convenient and scalable, and avoids the use of a dried solvent and an inert atmosphere. Moreover, selective C7-alkylation and C2, C7-dialkylation have also been achieved by slightly modifying the reaction conditions.

Rhodium and Iridium Mediated C-H and O-H Bond Activation of Two Schiff Base Ligands: Synthesis, Characterization and Catalytic Properties of the Organometallic Complexes

“…In the next step C-H activation at the 3-position of the heterocyclic ring takes place, whereby oxidative insertion of rhodium into the C-H bond takes place generating a hydrido-rhodium(III) species. Such rhodium(I) assisted C-H bond activation is well documented in the literature (Wiedemann et al, 2006;Gardiner et al, 2015;Chen et al, 2021;Lou et al, 2021;Wang et al, 2021;Yu et al, 2021). The rhodium-bound hydride then interacts with the nearby phenolic O-H fragment, which leads to abstraction of the O-H proton and furnish the final product via elimination of molecular hydrogen.…”

Rhodium-Catalyzed C(sp2)–H Alkoxycarbonylation/Acylation of Indolines with Anhydrides as a Carbonyl Source

“…Based on the experimental results and previous reports in the literature, , the reaction mechanism for the additive-free alkoxycarbonylation is proposed (Figure ). The C–O bond of dicarbonate 2 undergoes oxidative addition to rhodium­(I) A to form a rhodium­(III) intermediate B along with the extrusion of CO 2 .…”

“… 5 This is due to the decarbonylation process that occurs at high temperatures (>130 °C). 19 It was assumed that the C7-acylation of indolines using a carboxylic acid anhydride might proceed without decarbonylation if the optimized reaction conditions were applied. The reaction of indoline 1a with acetic anhydride was initially examined under the optimal conditions for the alkoxycarbonylation.…”

“…Although carboxylic acid anhydrides are known to be good acyl sources in the C3-selective Friedel–Crafts acylation of indoles, the corresponding C7-acylation has scarcely been reported . This is due to the decarbonylation process that occurs at high temperatures (>130 °C) . It was assumed that the C7-acylation of indolines using a carboxylic acid anhydride might proceed without decarbonylation if the optimized reaction conditions were applied.…”

Rhodium(III)-Catalyzed C–H Activation in Indole: A Comprehensive Report (2017–2022)

“…Wang, Shi, Xu, and co-workers reported a noteworthy discovery involving a Rh(I)-catalyzed, chelation-assisted C2-selective C–H decarbonylative alkylation of indoles utilizing primary and secondary alkyl carboxylic acids or alkyl carboxylic anhydrides (Scheme 36 ). 76 The optimized reaction conditions using 1-(pyrimidin-2-yl)-1 H -indole and 3-phenylpropanoic acid with 1 mol% [Rh(CO) 2 Cl] 2 , Boc 2 O (1.2 equiv) and PivOH (1.2 equiv) as acid activators for the in situ conversion of 3-phenylpropanoic acid into its corresponding anhydride in 1,4-dioxane at 130 °C for 8 hours gave 2-phenethyl-1-(pyrimidin-2-yl)-1 H -indole in 92% yield. The optimized conditions were then applied to a wide range of substituted 1-(pyrimidin-2-yl)-1 H -indole and carboxylic acids.…”