Reaction Of Indoles Research Articles

TfOH catalyzed synthesis of 1-substituted tetrahydrocarbazoles

Synthesis of 1-substituted tetrahydrocarbazole is accomplished by TfOH catalyzed reaction of 3-substituted indoles tethered with secondary and tertiary alcohols. The reaction was generalized for a variety of substrates and was extended to the synthesis of 2,3,3a,6-tetrahydro-1H-pyrido[3,2,1-jk]carbazole and carbazoles.

Bismuth(III) Triflate Catalyzed Three-Component Reactions of Indoles, Ketones, and α-Bromoacetaldehyde Acetals Enable Indole-to-Carbazole Transformation.

A three-component reaction of indoles, α-bromoacetaldehyde acetals, and ketones was developed by using bismuth(III) triflate as the catalyst to realize a straightforward approach for synthesizing carbazole derivatives. The reaction was established mechanistically through the autotandem catalysis of Bi(OTf)3 in the following two steps: (i) Friedel-Crafts-type alkylation of indole with α-bromoacetaldehyde acetal, which produced a tryptaldehyde-type intermediate and (ii) [4 + 2] annulation of this intermediate with the ketone component.

Metal and acid-free visible light-mediated Friedel-Crafts alkylation reactions of indole with anilines

Metal and acid-free visible light-induced Friedel-Crafts C3-alkylation reactions of indole derivatives were developed using N,N-dimethylanilines as the carbon source. A cheap and readily available organic dye, Rose Bengal, was applied as the photocatalyst. This environmentally friendly transformation afforded C3-alkylated indoles in moderate to good yields under mild conditions.

Visible‐Light‐Mediated Dearomatization/Cyanation Cascade Reaction of Indoles: Access to Highly Functionalized Spiro‐γ‐lactam Indolines with Two Contiguous Sterically Congested Quaternary Carbon Stereocenters

AbstractA protocol for visible‐light‐induced radical dearomatization/cyanation cascade reaction of indole derivatives is reported. This protocol provides straightforward access to gem‐difluorinated and cyanated 3,3’‐spirocyclic indolines with moderate to excellent diastereoselectivity and permits the construction of two contiguous sterically congested quaternary carbon stereocenters.magnified image

Green, Catalyst‐Free Reaction of Indoles with β‐Fluoro‐β‐nitrostyrenes in Water

The reaction of 2‐fluoro‐2‐nitrostyrenes with various indoles was investigated. We found that the reaction proceeds as a Michael addition in a highly regioselective manner to form 3‐(1‐aryl‐2‐fluoro‐2‐nitroethyl)‐1H‐indoles. Thus, a green and catalyst‐free synthesis of these compounds was developed using water as a reaction medium. The high effectiveness of this approach was demonstrated through the preparation of target products in up to 92 % isolated yield. Subsequent reduction of the nitro group was investigated. We found that due to the instability of the intermediate α‐fluoro amines, the reduction led to non‐fluorinated tryptamine derivatives.

Condensation reactions of indole with acetophenones affording mixtures of 3,3-(1-phenylethane-1,1-diyl)bis(1H-indoles) and 1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-diphenylcyclopent[b]indoles

Condensation of indole 1a with eight acetophenones 8a–h in ethanolic HCl afforded the corresponding mixtures of condensation products: 3,3-(1-phenylethane-1,1-diyl)bis(1H-indoles) 11a–h (2:1 condensation of indole:acetophenone, –H2O) and diastereomers of substituted 1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-diphenylcyclopent[b]indoles 12a–h and 13a–h (2:2 condensation of indole:acetophenone, –2H2O). Each mixture was analyzed by 1H NMR. The use of substituted electron-withdrawing acetophenones favored formation of 2:1 condensation products, whereas the use of substituted electron-donating acetophenones favored formation of 2:2 condensation products. Increased reaction temperature gave higher 2:2 condensation yields, but temperatures above 40 °C were unfavorable, giving complex, tarry mixtures.

An Unexpected FeCl3-Catalyzed Cascade Reaction of Indoles and o-Hydroxychalcones for the Assembly of Chromane-Bridged Polycyclic Indoles.

An unexpected FeCl3-catalyzed cascade reaction of simple indoles and o-hydroxychalcone was reported, leading to densely functionalized and strained chromane-bridged polycyclic indoles in moderate to good yields. This reaction not only establishes a new transformation of indoles and o-hydroxychalcones but also provides an efficient method for the synthesis of structurally complex and congested chromane-bridged polycyclic indoles.

Chromium-Catalyzed Asymmetric Dearomatization–Addition Reactions of Halomethyloxazoles and Indoles

The asymmetric dearomatization–addition reaction of halo­methyloxazoles and halomethylindoles with aldehydes is realized in the presence of a carbazole-based bisoxazoline CrCl2 complex to afford the corresponding enantioenriched, hydroxylated oxazoline and indoline products. The observed excellent chemo-, regio-, diastereo- and enantioselectivities are notable advantages of this protocol. The strategy established in this study is expected to find application in the synthesis of azaheterocycles with biological significance and useful functionalities.

Enantiospecific Total Syntheses of (+)-Hapalindole H and (-)-12-epi-Hapalindole U.

Enantiospecific total syntheses of (+)-hapalindole H and (-)-12-epi-hapalindole U as well as the formal syntheses of (+)-hapalindole Q and (+)-12-epi-fischerindole U isothiocyanate have been described. Key steps of our approach feature expedient, highly regio- and diastereoselective Lewis acid catalyzed Friedel-Crafts reaction of indole with cyclic allylic alcohols and intramolecular reductive Heck reaction. Efficiency of the synthetic route also relies on an alkynyl aluminate complex driven regioselective nucleophilic epoxide opening from a sterically hindered site.

Protonated Bis-1,2,3-triazole as an Anion-Binding Chiral Brønsted Acid for Catalytic Asymmetric Friedel–Crafts Reaction of Indoles with Imines

Abstract The complex of chiral C2-symmetric bis-1,2,3-triazole and an achiral Brønsted acid is introduced as a new class of chiral acid catalysts. The catalytic activity and stereocontrolling ability of this chiral Brønsted acid can be tuned simply by changing the achiral acid. The synthetic relevance of this salient feature is demonstrated in the asymmetric Friedel–Crafts reaction of indoles with N-sulfonyl imines.

CuI‐Catalyzed Selective 3‐Alkylation of Indoles with N‐Tosylhydrazones and the I2‐Mediated Further Cyclization to Chromeno[2,3‐b]Indoles

AbstractThe CuI‐catalyzed reaction of indoles with N‐tosylhydrazones derived from the ortho‐/para‐hydroxybenzaldhydes affords selectively the C‐3 alkylated products rather than the N‐alkylated products. In addition, the I2‐mediated cyclization of the generated C‐3 alkylated products allows the concise synthesis of chromeno[2,3‐b]indole derivatives.magnified image

Transition metal-catalyzed C,C- and C,N-cycloaminomethylation reactions of pyrrole and indole

Catalytic cycloaminomethylation of pyrrole with bis(methoxymethyl)alkylamines or a mixture of alkyl(phenyl)amines and paraformaldehyde in the presence of [Ni(Py)4Cl2]·0.76H2O or NiCl2·6H2O catalysts proceeded at positions 2 and 5 of pyrrole ring. Cycloaminomethylation of indole was accomplished effectively at positions 1 and 3 in the presence of ZrOCl2·8H2O catalyst. When carbazole was treated with bis(methoxymethyl)alkylamine in the presence of ZrOCl2·8H2O catalyst, it was converted to N-aminomethylated product – N-[(9H-carbazol-9-yl)methyl]-N-(methoxymethyl)alkylamine.

Selective Synthesis of 3-(9 H-Carbazol-2-yl)indolin-2-ones and Spiro[tetrahydrocarbazole-3,3'-oxindoles] via a HOTf Catalyzed Three-Component Reaction.

A HOTf catalyzed three-component reaction of indoles, acetophenones, and ( E)-3-phenacylideneoxindolinones resulted in the unexpected polysubstituted 3-(9 H-carbazol-2-yl)indolin-2-ones in good yields. A similar reaction with various cyclic ketones afforded the corresponding carbocyclic fused 3-(9 H-carbazol-2-yl)indolin-2-ones. On the other hand, ( E)-3-arylideneoxindolinones in the three-component reaction gave the expected spiro[tetrahydrocarbazole-3,3'-oxindoles] through a domino alkenylation/Diels-Alder reaction. The unusual different reactivity of ( E)-3-phenacylideneoxindolinones and ( E)-3-arylideneoxindolinones in the three-component reactions was believed to involve the different reaction paths caused by the existence of the carbonyl group.

Enantioselective Total Syntheses of Methanoquinolizidine-Containing Akuammiline Alkaloids and Related Studies.

The akuammiline alkaloids are a structurally diverse class of bioactive natural products isolated from plants found in various parts of the world. A particularly challenging subset of akuammiline alkaloids are those that contain a methanoquinolizidine core. We describe a synthetic approach to these compounds that has enabled the first total syntheses of (+)-strictamine, (-)-2( S)-cathafoline, (+)-akuammiline, and (-)-Ψ-akuammigine. Our strategy relies on the development of the reductive interrupted Fischer indolization reaction to construct a common pentacyclic intermediate bearing five contiguous stereocenters, in addition to late-stage formation of the methanoquinolizidine framework using a deprotection-cyclization cascade. The total syntheses of (-)-Ψ-akuammigine and (+)-akuammiline mark the first preparations of akuammiline alkaloids containing both a methanoquinolizidine core and vicinal quaternary centers. Lastly, we describe the bioinspired reductive rearrangements of (+)-strictamine and (+)-akuammiline to ultimately provide (-)-10-demethoxyvincorine and a new analogue thereof.

Palladium-Catalyzed Asymmetric Regioselective Addition Reaction of Indoles

Key words palladium catalysis - indoles - alkoxyallenes - addition - regioselectivity

Gold‐Catalyzed Functionalization Reactions of Indole

This review summarizes the progress achieved in the last fifteen years by application of homogeneous gold catalysis in the field of indole functionalization. Several electrophilic species obtained through gold‐catalyzed π‐activation have in fact been found to react with the nucleophilic positions of indole, thus allowing its efficient manipulation. In order to furnish a complete and clear overview on the role of the catalyst, the review is organized from the perspective of the gold‐activated substrate that is reacting with the indole. In addition, in view of the ability of gold to catalyze tandem and cascade reactions, a separate section describes tandem/cascade protocols useful for the synthesis of complex polycyclic indole derivatives. Finally, gold catalysis has also been employed for the synthesis of indole‐based natural products. For this reason, a dedicated section collects all the work in which the key step to obtain these complex indoles is represented by a gold‐catalyzed reaction.

Iodine-Catalyzed Oxidative Cross-Dehydrogenative Coupling of Quinoxalinones and Indoles: Synthesis of 3-(Indol-2-yl)quinoxalin-2-one under Mild and Ambient Conditions

A highly efficient iodine-catalyzed oxidative cross-dehydrogenative coupling reaction of quinoxalinones and indoles has been developed. Without the requirement of peroxide and acid, this reaction utilizes a catalytic amount of molecular iodine to facilitate the C–C bond formation under ambient air. This simple and easy-to-handle protocol represents an interesting synthetic alternative with a good scope and functional group compatibility.

One-pot access to indolylchromeno[2,3-b]indoles via iodine-mediated Friedel-Crafts alkylation/oxidative coupling reaction of indoles and salicylaldehydes

An I2-mediated Friedel-Crafts alkylation/oxidative coupling reaction of indoles and salicylaldehydes was developed. With the developed protocol, a series of indolylchromeno[2,3-b]indoles were obtained in good yields (up to 88%) under mild reaction conditions. Two possible reaction mechanisms were tentatively brought forward to account for the formation of the products in light of some control experiments.

Organocatalytic, Enantioselective Friedel-Crafts Reaction of Indoles in the Carbocyclic Ring and Electron-Rich Phenols.

An efficient method has been successfully developed to achieve the asymmetric C-H functionalization of indoles in the carbocyclic ring via organocatalysis, and a variety of tetrahydropyranoindoles were synthesized in good yields with excellent stereoselectivities. Further study on thermodynamic calculations indicated that the process was promoted by generating more thermodynamically stable products. This strategy, together with traditional C-3 functionalization of hydroxyindoles, could realize the switchable, regiodivergent asymmetric modification of indoles.

Synthesis of bis(indolyl)methanes Using Naturally Occurring, Biodegradable Itaconic Acid as a Green and Reusable Catalyst

Aim and Objective: To explore the use of naturally occurring biodegradable organic acids as a catalyst in organic synthesis. The development of a simple, inexpensive, highly efficient yet ecofriendly catalyst for the synthesis of bis(indolyl)methanes is explored. Materials and Method: A mixture of indole 1a (1.0 g, 8.53 mmol), benzaldehyde 2a (0.45 g. 4.26 mmol), and itaconic acid (0.12 g, 0.92 mmol, 20 mol%), in H2O (5.0 mL) was refluxed at 100°C for indicated time. After the completion of the reaction (TLC check), the reaction mixture was cooled to room temperature and extracted with ethyl acetate (3 × 5.0 mL), organic layer was dried over Na2SO4 and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel using ethyl acetate:hexane as an eluent. Results: Initially optimal reaction conditions were developed for the synthesis of bis(indolyl)methanes by selecting model reaction between indole and benzaldehyde. It was found that optimal conditions for the synthesis of bis(indolyl)methanes are use of indole (1.0 mmol), aldehyde (0.5 mmol) and catalyst 20 mol% in water as a solvent, under air atmosphere and at 100°C. Moreover, it was found that aqueous solution of the catalyst can be reused with the same catalytic efficiency for ten times without any pre-treatment. This is an important achievement with regard to the efficiency and reusability of the catalyst in synthesis. Conclusion: We have shown that itaconic acid in water can be used as an excellent green catalyst with high reusability. It efficiently catalyzes electrophillic substitution reaction of indoles (ESRI) with various aldehydes to give the corresponding BIMs in an efficient manner. Therefore, itaconic acid in water as a catalyst can be a good alternative for the use of hazardous mineral acid and Lewis acid catalyst.