Metal‐Free Oxidative <i>para</i> Cross‐Coupling of Phenols

Sakamoto, Kazuma; Ohnishi, Yusuke; Miyamoto, Takeshi; Ito, Minoru; Dohi, Toshifumi; Kita, Yasuyuki

doi:10.1002/chem.201301028

Cited by 104 publications

(52 citation statements)

References 79 publications

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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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Section: Introductionmentioning

confidence: 99%

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

Chen

2017

Angewandte Chemie

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

Chen

2017

Angew Chem Int Ed

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“…[2b] Am ajor reason for this side reaction is the difficulty associated with the tunable reactivity of phenols by controlling their oxidation potential using aprotecting group for the phenol hydroxy group.T herefore,t he development of an efficient catalytic cross-coupling of unprotected phenols for the construction of biaryl compounds is still highly desirable.R ecently,W aldvogel and co-workers reported an electrochemical phenolarene cross-coupling reaction using boron-doped diamond electrodes. [10][11][12][13][14][15] Inspired by these studies,wenow report abroadly applicable organoiodine(III)-catalyzed oxidative cross-coupling reaction of phenols using Oxone as aterminal oxidant (Scheme 1). [9] While recent metal-catalyzed cross-couplings of phenols have been studied, the organocatalytic cross-coupling reaction still remains particularly challenging.R ecently,w e developed the oxidative cross-coupling reaction of aromatic compounds using hypervalent iodine reagents.…”

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Organo‐Iodine(III)‐Catalyzed Oxidative Phenol–Arene and Phenol–Phenol Cross‐Coupling Reaction

et al. 2016

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The direct oxidative coupling reaction has been an attractive tool for environmentally benign chemistry.Reported herein is that the hypervalent iodine catalyzed oxidative metalfree cross-coupling reaction of phenols can be achieved using Oxone as at erminal oxidant in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This method features ah igh efficiency and regioselectivity,a sw ell as functional-group tolerance under very mild reaction conditions without using metal catalysts.

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Metal‐Free Oxidative para Cross‐Coupling of Phenols

Cited by 104 publications

References 79 publications

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

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

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

Organo‐Iodine(III)‐Catalyzed Oxidative Phenol–Arene and Phenol–Phenol Cross‐Coupling Reaction

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