Metal-free, C–H arylation of indole and its derivatives with aryl diazonium salts by visible-light photoredox catalysis

Zhang, Yingpeng; Feng, Xiaolong; Yang, Yun‐Shang; Cao, Bi-xia

doi:10.1016/j.tetlet.2016.04.051

Cited by 41 publications

(18 citation statements)

References 30 publications

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“…Next, 1 a was added and the reaction was allowed to proceed at room temperature for 18 h. After this time, 1‐methyl‐3‐(2‐nitrophenyl)‐1 H ‐indole ( 1 b ) was isolated in 69 % yield (Table , entry 1) over three steps (diazotization, oxidative addition, and arylation). The position of the new aryl moiety was corroborated by comparison with reported NMR data, and was in accordance with that expected for Au III . To improve the yield, we examined the effect of using Ph 3 P as a ligand (Table , entry 2), and the effect of increasing the temperature up to 50 °C (Table , entry 3), but the yields were found to be reduced.…”

Section: Resultssupporting

confidence: 76%

Ascorbic Acid as an Aryl Radical Inducer in the Gold‐Mediated Arylation of Indoles with Aryldiazonium Chlorides

Medina‐Mercado

Asomoza‐Solís

Martínez‐González

et al. 2019

Chemistry A European J

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In recent years interestint he development of protocols that facilitate the oxidativea ddition of gold to access mild cross-coupling processes mediated by this metal hasincreased. In this context, we report herein that ascorbic acid, an atural and readily accessible antioxidant, can be used to accelerate the oxidative addition of aryldiazonium chlorides onto Au I .T he aryl-Au III speciesg enerated in this way,h as been used to prepare 3-arylindoles in ao ne-pot protocol startingf rom anilines and para-, meta-, and ortho-s ubstituted aryldiazonium chlorides. The mechanism underlying the oxidative addition has been examined in detail based on EPR analyses, cyclic voltammetry,a nd DFT calculations. Interestingly, we have found that in this protocol, the chloride atom induces the Au II /Au III oxidation step.

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Section: Resultssupporting

confidence: 76%

Ascorbic Acid as an Aryl Radical Inducer in the Gold‐Mediated Arylation of Indoles with Aryldiazonium Chlorides

Medina‐Mercado

Asomoza‐Solís

Martínez‐González

et al. 2019

Chemistry A European J

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“…Supporting information for this article is given via a link at the end of the document. processes are rare, they have been accomplished through the use of hypervalent iodine reagents, [19][20][21] diazonium salts, [22] or by means of electrochemistry. [23][24][25] Our group has a longstanding interest in the reaction of indoles and related heterocycles.…”

Section: Introductionmentioning

confidence: 99%

Transition‐Metal‐Free C3 Arylation of Indoles with Aryl Halides

Chen

2017

Angewandte Chemie

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Herein, we report an unprecedented transition metal-free, coupling of indoles with aryl halides. The reaction is promoted by KOtBu and is regioselective for C3 over nitrogen. The use of degassed solvents devoid of oxygen is necessary for the success of the transformation. Preliminary studies implicate a hybrid mechanism that involves both aryne intermediates and non-propagative radical processes. Electron transfer is also a distinct possibility. These conclusions were substantiated by EPR data, isotopic labeling studies, and the use of radical scavengers and electron transfer inhibitors. Graphical AbstractMetals? What metals? Regioselective transition metal-free cross-coupling of aryl halides with indoles at C3 has been reported. The reaction proceeds through an unusual hybrid radical/aryne mechanism. Keywordsindole; transition metal-free; cross-coupling; radical; aryne Indoles with aromatic substituents at C3 are an important class of compounds, many of which possess potent biological activity. For instance, fluvastatin is an FDA-approved HMG-CoA reductase inhibitor that is used in the clinic for lowering LDL cholesterol. [1] Other C3 arylated indoles exhibit pico-to nanomolar inhibitory actions against a wide range of biological targets and processes such as the progesterone receptor, [2] COX-II enzyme, [3] carbonic anhydrase I and II, [4] and tubulin polymerization, [5] etc.The direct introduction of aromatic groups onto an extant indole nucleus at C3 is typically carried out by transition metal-catalyzed cross-coupling reactions (Figure 1). [2,[6][7][8][9][10][11][12][13][14] Methods utilizing C-H activation have also been reported. [15][16][17][18] While transition metal-free Correspondence to: Jimmy Wu. Supporting information for this article is given via a link at the end of the document. processes are rare, they have been accomplished through the use of hypervalent iodine reagents, [19][20][21] diazonium salts, [22] or by means of electrochemistry. [23][24][25] Our group has a longstanding interest in the reaction of indoles and related heterocycles. [26][27][28][29] Herein, we disclose a new approach for the intermolecular C3 arylation of unprotected indoles with simple aryl halides. The reaction is promoted by KOtBu and does not require the use of transition metal catalysts. Preliminary mechanistic investigations point towards an unusual hybrid reaction pathway that exhibits features of both radical and aryne intermediates. Although Daugulis and Tu have reported a limited number of basepromoted C2-and N-selective arylation reactions of indoles, [30][31][32] there appear to be very few precedents for C3-selective variants [32,33] and none that proceed by the proposed hybrid radical/aryne mechanism. HHS Public AccessOptimization studies were carried out on the reaction between indole (1a) and iodobenzene (Table 1). A brief solvent survey identified DMF and DMSO as the only effective solvents (entries 1-5). A reaction performed in the dark resulted in similar yield and selectivity (entry 7 vs 5). ...

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“…[2,6–14] Methods utilizing C–H activation have also been reported. [15–18] While transition metal-free processes are rare, they have been accomplished through the use of hypervalent iodine reagents, [19–21] diazonium salts, [22] or by means of electrochemistry. [23–25] …”

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confidence: 99%