Palladium‐Catalyzed Direct Denitrogenative C‐3‐Arylation of 1<i>H</i>‐Indoles with Arylhydrazines using Air as the Oxidant

Chen, Yongxin; Guo, Shuaibo; Li, Kangning; Qu, Jinpeng; Yuan, Hua; Hua, Qiuru; Chen, Baohua

doi:10.1002/adsc.201200997

Cited by 92 publications

(38 citation statements)

References 55 publications

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“…Chen, 223 Yao, 224 Liu, 225 and Gao and Yin 226 have applied arylhydrazines in aerobic Pd-catalyzed cross-coupling reactions in the past two years (Scheme 83). The corresponding 3-substituted indole derivatives 289, diaryls 290, α-C-glycosides 291, and arylphosphonates 292 could be prepared by these simple and environmentally friendly approaches.…”

Section: Amidesmentioning

confidence: 99%

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

et al. 2015

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Section: Amidesmentioning

confidence: 99%

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

et al. 2015

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“…[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.…”

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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“…[108] Moderate to good yields were obtained in most cases,b ut extremely electron-deficient indoles( elaborated with CN or NO 2 groups at C-5 position) were sluggish substrates (Scheme 49).…”

Section: Scheme45mentioning

confidence: 98%

“…Reaction Couplingpartner/reagentC atalyst References 1a rylation aryl halides Pd [101,102,104,105] 2b enzoic acids Pd [107] 3a rylhydrazines Pd [108] 4c yclohexanones Pd [109] 5d iaryliodonium salts Cu [110] 6N -heterocyclic compounds Pd [111][112][113][114] 7a lkynylation alkynes Au [115] 8b enzylation benzylic alcohols Au [116] 9o lefination alkenes Pd [117,118] 10 acylation benzaldehydes Pd [119] 11 TMEDA Cu [120] 12 nitrilesP d [121] 13 CO and alcohols Rh [122] 14 a-amino carbonyl compounds Cu [123] 15 Pd [124] 16 synthesis of bisindoles alcohols Pd [141,142] 17 aldehydes Ag [143] 18 amines Pd [144] 19 annulation alkenes Pd 21 cyanation CuCN Pd [150] 22 K 4 [Fe(CN) 6 ]P d [151] 23 t-BuNC Pd [152] 24 NH 4 HCO 3 and DMSOP d [153] 25 amidation isocyanides Pd [154] Scheme 44. Pd-catalyzedarylation.…”

Section: Entrymentioning

confidence: 99%

Transition Metal‐Catalyzed CH Activation of Indoles

2015

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Thel ast decades have seen at remendous expanse in the applicationo fC À Ha ctivation of many different substrate classes,including the invaluable indole scaffold. Following the exciting emergence of C À Ha ctivation as am ulti-faceted platform for functionalization, av ersatile toolb ox has been developed for the preparation of structurally diverse indoles. This review article discussesr ecent advances and strategies for transitionm etal-catalyzed C À Ha ctivationofi ndoles.

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Palladium‐Catalyzed Direct Denitrogenative C‐3‐Arylation of 1H‐Indoles with Arylhydrazines using Air as the Oxidant

Cited by 92 publications

References 55 publications

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

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

Transition Metal‐Catalyzed CH Activation of Indoles

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