Alkynyl Indoles Research Articles

Gold(I)-Catalyzed Cascade Cyclization of Alkynyl Indoles for the Stereoselective Construction of the Quaternary Carbon Center of Akuammiline Alkaloids.

A gold-catalyzed cyclization reaction of alkynyl-indoles has been developed for the stereoselective construction of the quaternary carbon center of fused indolines. This reaction efficiently produces fused indolines via diastereoselective 6-endo-dig cyclization controlled by a bulky TIPS group, followed by nucleophilic attack of the carboxy group on the resulting imine. The lactone moiety of the fused indoline can be reductively cleaved to produce a tricyclic indoline, which could be useful for the synthesis of akuammiline alkaloids.

Access to Polycyclic Thienoindolines via Formal [2+2+1] Cyclization of Alkynyl Indoles with S8 and K2S.

The syntheses of polycyclic thienoindolines bearing a dihydrothiophene or tetrahydrothiophene subunit have not been reported, despite the fact that such compounds may have interesting medicinal properties. Herein, we report a protocol for accessing polycyclic dihydrothiophenes by means of formal [2+2+1] intramolecular dearomatizing cyclization of alkynyl indoles with K2S and S8 as the sources of sulfide. In addition, tetrahydrothienoindolines were stereoselectively synthesized via a one-pot, two-step protocol involving AgNO3-catalyzed alkenyl dearomatization followed by two nucleophilic addition reactions involving K2S.

Access to Polycyclic Indol(en)ines viaBase‐Catalyzed Intramolecular Dearomatizing 3‐Alkenylation of Alkynyl Indoles

Main observation and conclusionPolycyclic indolines and indolenines were synthesized via base‐catalyzed intramolecular dearomatizing 3‐alkenylation reactions of alkynyl indoles 1 at room temperature. The base enhanced the nucleophilicity of the carbon at the 3‐position of the indole moiety, facilitating an exclusive 5‐exo‐dig cyclization reaction with the alkyne to form spiroindolenines 2. The imine functionality of 2 could undergo in situ nucleophilic addition to form spiroindolines 3 when R was a carbamoyl group or reduction to form spiroindolines 4 when R was H.

Efficient synthesis of pyrano[4,3-b]indol-1(5H)-ones from CO2 and alkynyl indoles promoted by a protic ionic liquid

An efficient method was developed for the synthesis of pyrano[4,3-b]indol-1(5H)-ones, which uses a protic ionic liquid [HTBD+][TFE–] as both the solvent and reaction promoter. The reactions could be efficiently carried out at atmospheric pressures of CO2, and various pyrano[4,3-b]indol-1(5H)-ones bearing versatile functionalities were obtained in moderate to high yields (71–99%).

Palladium-catalyzed regioselective C–H alkynylation of indoles with bromoalkynes in water

A palladium-catalyzed regioselective C(sp2)–H alkynylation between indoles and bromoalkynes in water has been developed, affording diverse functionalized 2-alkynylindoles in good yields.

Coupling Reactions of Alkynyl Indoles and CO2 by Bicyclic Guanidine: Origin of Catalytic Activity?

Density functional theory calculations were used to investigate the three possible modes of activation for the coupling of CO2 with alkynyl indoles in the presence of a guanidine base. The first of these mechanisms, involving electrophilic activation, was originally proposed by Skrydstrup et al. (Angew. Chem. Int. Ed. 2015, 54, 6682). The second mechanism involves the nucleophilic activation of CO2 . Both of these electrophilic and nucleophilic activation processes involve the formation of a guanidine-CO2 zwitterion adduct. We have proposed a third mechanism involving the bifunctional activation of the bicyclic guanidine catalyst, allowing for the simultaneous activation of the indole and CO2 by the catalyst. We demonstrated that a second molecule of catalyst is required to facilitate the final cyclization step. Based on the calculated turnover frequencies, our newly proposed bifunctional activation mechanism is the most plausible pathway for this reaction under these experimental conditions. Furthermore, we have shown that this bifunctional mode of activation is consistent with the experimental results. Thus, this guanidine-catalyzed reaction favors a specific-base catalyzed mechanism rather than the CO2 activation mechanism. We therefore believe that this bifunctional mechanism for the activation of bicyclic guanidine is typical of most CO2 coupling reactions.

Cationic AuIII versus AuI : Catalyst-Controlled Divergent Reactivity of Alkyne-Tethered Lactams.

Switchable reactivity through cationic gold-based catalyst control built on the oxidation state, namely cationic AuIII versus AuI , has been achieved in the direct functionalization of 2-azetidinone-tethered alkynyl indoles.

ChemInform Abstract: Piperazine as Leaving Group in A3 Adducts: Fast Access to Alkynyl Indoles.

ChemInformVolume 47, Issue 44 Preparative Organic Chemistry ChemInform Abstract: Piperazine as Leaving Group in A3 Adducts: Fast Access to Alkynyl Indoles. Mansour Dole Kerim, Mansour Dole Kerim Lab. Synth. Org., CNRS, Ec. Natl. Super. Tech. Av., F-91128 Palaiseau, Fr.Search for more papers by this authorLaurent El Kaim, Laurent El Kaim Lab. Synth. Org., CNRS, Ec. Natl. Super. Tech. Av., F-91128 Palaiseau, Fr.Search for more papers by this author Mansour Dole Kerim, Mansour Dole Kerim Lab. Synth. Org., CNRS, Ec. Natl. Super. Tech. Av., F-91128 Palaiseau, Fr.Search for more papers by this authorLaurent El Kaim, Laurent El Kaim Lab. Synth. Org., CNRS, Ec. Natl. Super. Tech. Av., F-91128 Palaiseau, Fr.Search for more papers by this author First published: 13 October 2016 https://doi.org/10.1002/chin.201644035Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue44October, 2016 RelatedInformation

Rhodium‐Catalyzed/Copper‐Mediated Selective C2 Alkynylation of Indoles and C1 Alkynylation of Carbazoles with γ‐Substituted tert‐Propargyl Alcohols

AbstractA novel rhodium‐catalyzed/copper‐mediated C2‐selective C−H alkynylation of indoles using γ‐substituted tert‐propargyl alcohols as the alkynylating reagent and a removable 6‐methylpyridin‐2‐yl as the directing group has been developed, which provides a viable pathway for direct C2‐selective alkynylation of indoles. Moreover, this strategy could be extended to the C−H alkynylation of carbazoles at the C1 position.

Piperazine as Leaving Group in A3 Adducts: Fast Access to Alkynyl Indoles

The A3 coupling between N-ethylpiperazine and electron-rich aromatic aldehydes forms adducts that may be easily used as electrophiles towards electron-rich heterocycles such as indoles. The removal of the piperazine moiety is triggered by the addition of 1,2-dibromoethane. Overall, the reaction provides efficient access to alkynyl indoles and pyrroles.

ChemInform Abstract: Organocatalyzed CO2 Trapping Using Alkynyl Indoles.

AbstractThis first organocatalyzed trapping of CO2 gives access to new heterocyclic structures.

Cobalt(III)-Catalyzed C2-Selective C-H Alkynylation of Indoles.

A cobalt(III)-catalyzed C-2 selective C-H alkynylation of indoles using hypervalent iodine-alkyne reagents is described. A broad range of synthetically useful functional groups (-F, -Cl, -Br, -CO2Me, -CN) were tolerated, providing an efficient and robust protocol for the synthesis of C-2 alkynylated indoles. The pyrimidyl and silyl protecting groups could be easily removed to give the corresponding 2-ethynyl-1H-indole.

Organocatalyzed CO2 Trapping Using Alkynyl Indoles.

The first organocatalyzed trapping of CO2 through C-C and C-O bond formation is reported. Alkynyl indoles together with catalytic amounts of an organic base and five equivalents of CO2 resulted in the formation new heterocyclic structures. These tricyclic indole-containing products were successfully prepared under mild reaction conditions from aromatic, heteroaromatic, and aliphatic alkynyl indoles with complete regioselectivity. Further investigations suggest that C-C bond formation is the initial intermolecular step, followed by lactone-forming C-O bond formation.

Organocatalyzed CO2 Trapping Using Alkynyl Indoles

AbstractThe first organocatalyzed trapping of CO2 through CC and CO bond formation is reported. Alkynyl indoles together with catalytic amounts of an organic base and five equivalents of CO2 resulted in the formation new heterocyclic structures. These tricyclic indole‐containing products were successfully prepared under mild reaction conditions from aromatic, heteroaromatic, and aliphatic alkynyl indoles with complete regioselectivity. Further investigations suggest that CC bond formation is the initial intermolecular step, followed by lactone‐forming CO bond formation.

Mechanism of the N-protecting group dependent annulations of 3-aryloxy alkynyl indoles under gold catalysis: a computational study

The mechanism of the gold-catalyzed annulations of 3-aryloxy alkynyl indoles developed by Tu et al. was studied by DFT calculations. It was found that both indole derivatives of electron-donating and electron-withdrawing protective groups would first undergo the 5-exo-dig cyclization simultaneously upon activation by cationic [PR(3)Au(+)] species. However, divergent reactivity of the resulting spirocyclic intermediate in competitive 1,2-alkenyl migration and nucleophilic water addition reactions towards C3 was predicted. When protected by electron-donating group, the 1,2-alkenyl migration occurs to generate a tricyclic intermediate, from which an aromatic Claisen rearrangement/nucleophilic addition sequence results in the observed 1,2-phenoxy migration. In case of electron-withdrawing group, the 1,2-alkenyl migration would be unfavorable. Instead, the nucleophilic addition of water oxygen to C3 is more facile, and leads to the hemiketal intermediate. The possible roles of water-cluster and OTf anion as proton shuttles in both reactions were also evaluated.

ChemInform Abstract: Regiodivergent Annulation of Alkynyl Indoles to Construct Spiro‐pseudoindoxyl and Tetrahydro‐β‐carbolines.

AbstractThe N‐protecting group in the starting alkynyl indoles determines the reaction path.

ChemInform Abstract: Palladium‐Catalyzed, One‐Pot , Three‐Component Approach to α‐Alkynyl Indoles from o‐Bromo‐(2,2‐dibromovinyl)benzenes, Terminal Alkynes and Arylamines.

AbstractA variety of alkynyl indoles is obtained from polyhalo compounds (I) and (VIII), arylamines (II) and (V), and alkynes (III) and (VI).

Regiodivergent Annulation of Alkynyl Indoles To Construct Spiro-pseudoindoxyl and Tetrahydro-β-carbolines

Regiodivergent annulations of 3-phenoxy alkynyl indoles have been developed and tuned by protective groups through gold catalysis. With electron-donating protective groups, the substrate followed a C3-selective annulation and gave structurally interesting tetrahydro-β-carboline derivatives possessing potential bioactivity. Using electron-withdrawing protective groups, the substrate underwent a C2-selective annulation and afforded the structurally useful spiro-pseudoindoxyl found in natural indole alkaloids. Notably, an interesting and unusual 1, 2-migration of the phenoxy group was found in the C3-selective process.

Tandem indole C–H alkenylation/arylation for tetra-substituted alkene synthesis

Alkynyl indoles undergo a novel sequence of Pd-catalysed indole C-H activation/alkyne carbopalladation/arylation, with diaryliodonium salts providing the aryl components. An array of functionalised indole alkenes have been prepared in good to excellent yield, with the reaction being selective for the Z-alkene.

Direct palladium-catalyzed C-3 alkynylation of indoles

The direct palladium-catalyzed coupling reaction of indoles with alkynyl bromides was described in this paper. In the presence of catalytic amount of PdCl 2(PPh 3) 2 and 2.0 equiv. NaOAc, the coupling reaction of indoles with alkynyl bromides proceeded smoothly at 50 °C to give the corresponding 3-alkynylindoles with high regioselectivity in good to excellent yields.