Friedel-Crafts Alkylation Of Indoles Research Articles

Arene Diazonium Tetrafluoroborate Salts: Novel Lewis Acid Catalysts for Friedel‐Crafts Alkylation of Indoles with α,β‐Unsaturated Ketones

AbstractIn this study, the Friedel crafts alkylation of indole with α, β‐unsaturated ketones catalyzed by arene diazonium tetrafluoroborate salts is reported for the first time, and the optimal conditions of this reaction were explored. The experimental results show that the optimal conditions employed 10 mol % 2‐(2‐bromophenoxy)phenyl diazonium fluoborate (2) as a catalyst, CH3OH as a solvent, 60 °C as reaction temperature, and 24 h as reaction time. Under these optimized conditions, the reaction of indoles with various α,β‐unsaturated ketones can proceed smoothly to obtain aimed products (8). Yields of these reactions ranged from 60 % to 92 %. The reaction conditions are mild and the reaction operation is simple.

Halogen Bond-Catalyzed Friedel-Crafts Alkylation of Indole with Ketones and Aldehydes for the Synthesis of Symmetrical 3,3’-diindolylmethanes Using Simple Halogen Donor Catalyst

Abstract: The Friedel-Crafts alkylation of indole with ketones and aldehydes had been developed for the preparation of 3,3’-diindolylmethanes using iodine or NCS as catalysts. Two mild and efficient catalysis systems were provided for acti-vation of carbonyl compounds and indoles. The reaction proceeded smoothly in ethanol to produce the corresponding prod-ucts with good to excellent yields. Furtherly, the mechanism was speculated.

Quaternary ammonium functionalized polyacrylonitrile fiber supported phosphotungstic acid as efficient heterogeneous catalyst: Hydrophobic tuning of the catalytic microenvironment

Thirteen novel amine or quaternary ammonium functionalized polyacrylonitrile fiber (PANF) supported phosphotungstic acid (PTA) catalysts were designed and prepared, and their catalytic activities were screened by choosing condensation/annulation tandem synthesis of 2,3-dihydroquinazolin-4(1H)-one compound via C–N bond formation between 2-aminobenzamide and p-chlorobenzaldehyde as a model reaction. By adjusting the functionality and hydrophobic/hydrophilic property of the amine/ammonium structure as well as the density of PTA sites, the fiber catalyst CAT-12 prepared from quaternary ammonium functionalized PANF containing benzyl group with high PTA loading achieved the best catalytic activity for most reactions in water. The CAT-12 can be easily separated from the reaction system and recycled for 7 times without significant loss of catalytic activity. Moreover, the reaction proceeded smoothly in gram scale and gave nearly quantitative yield using this efficient, eco-friendly and easily recyclable catalyst with great industrial potential which was also demonstrated in Friedel-Crafts alkylation of indoles with β-nitrostyrene. Vivid PTA immobilization processes and the corresponding “catch-catalyze” catalytic modes were further schematically described to address the effect of microenvironment-tuning on immobilization and catalysis, and accordingly the possible catalytic mechanisms of the two reactions were proposed.

Friedel-Crafts alkylation of indoles with trichloroacetimidates

Substituted indole scaffolds are often utilized in medicinal chemistry as they regularly possess significant pharmacological activity. Therefore the development of simple, inexpensive and efficient methods for alkylating the indole heterocycle continues to be an active research area. Reported are reactions of trichloroacetimidate electrophiles and indoles to address the challenges of accessing alkyl decorated indole structures. These alkylations perform best when either the indole or the imidate is functionalized with electron withdrawing groups to avoid polyalkylation.

Carboxyl group functionalized hollow microporous organic nanospheres for efficient catalysis and adsorption

Abstract Carboxyl group functionalized hollow microporous organic nanospheres (HMONs-COOH) were successfully synthesized by hyper-crosslinking reaction between polylactide-b-polystyrene (PLA-b-PS) diblock copolymers and 2,4,6-tris(bromomethyl)mesitylene as well as subsequent alkaline KMnO4 oxidation. The synthesized HMONs-COOH possess the high special surface area, robust organic framework and hierarchically porous structure, which shows highly catalytic activity in the Friedel-Crafts alkylation of indole with aldehydes and outstanding adsorption efficiency toward cationic dyes.

Secondary amine-catalyzed asymmetric formal aza [3 + 3] cycloaddition to construct enantioenriched piperidines derivatives

An amine-catalyzed asymmetric formal aza [3 + 3] cycloaddition of α,β-unsaturated aldehydes with N-Ts ketimines derived from both acyclic and cyclic ketones was developed, which was followed by an oxidation to afford chiral piperidine derivatives in good yields and excellent enantioselectivities (up to 99% ee). In addition, the corresponding cycloadduct piperidin-2-ols can be easily transformed to indolyl substituted chiral piperidine derivatives in good yields and excellent diastereoselectivities (>20:1) via Friedel-Crafts alkylation of indole in the presence of BF3·Et2O.

Synthesis and Applications of (-)-(S)-3-Aminoquinuclidine- Derived Thiourea

A synthesis of enantiopure thiourea organocatalyst based on (-)-(S)-3-aminoquinuclidine dihydrochloride was developed with quantitative product yield. The catalyst was tested in different reactions: asymmetric Michael addition of ketones and malonates to nitroalkenes, nitromethane 1,4-addition to trans-chalcone, and Friedel-Crafts alkylation of indoles with trans-β-nitrostyrene. The novel thiourea proved to catalyze the aforementioned reactions and expected products were obtained in mediocre yields and low enantioselectivities.

Aza-crown ether complex cation ionic liquids: preparation and applications in organic reactions.

Aza-crown ether complex cation ionic liquids (aCECILs) were devised, fabricated, and characterized by using NMR spectroscopy, MS, thermogravimetric differential thermal analysis (TG-DTA), elemental analysis and physical properties. These new and room-temperature ILs were utilized as catalysts in various organic reactions, such as the cycloaddition reaction of CO2 to epoxides, esterification of acetic acid and alcohols, the condensation reaction of aniline and propylene carbonate, and Friedel-Crafts alkylation of indole with aldehydes were investigated carefully. In these reactions, the ionic liquid exhibited cooperative catalytic activity between the anion and cation. In addition, the aza-[18-C-6HK][HSO4]2 was the best acidic catalyst in the reactions of esterification and Friedel-Crafts alkylation under mild reaction conditions.

Highly Efficient Povidone-Phosphotungstic Acid Catalyst for the Tandem Acetalization of Aldehydes to Bis- and Tris(indolyl)methanes.

A novel, nonleachable hybrid of heteropoly acid and polyvinylpyrrolidone (or povidone) catalyzes the acetalization of aldehydes in methanol at room temperature followed by reaction with indole to give bis(indolyl)methanes (BIMs) and tris(indolyl)methanes (TIMs) in quantitative yields (90-97 %). The catalyst was shown by pyridine FTIR spectroscopy to possess Brønsted acidity, and the hybrid formation was confirmed by XRD and 31 P NMR studies. Friedel-Crafts alkylation of indole as well as the tandem synthesis of BIMs and TIMs were established with several types of carbonyl and indole substrates to give the corresponding products quantitatively. The catalyst was recycled efficiently for three successive runs without losing its original activity.

Continuous synthesis of bis(indolyl)phenylmethane over acid modified Hβ zeolite

The continuous synthesis of bis(indolyl)phenylmethane has been successfully accomplished for the first time by Friedel-Crafts alkylation of indole with benzaldehyde in a fixed-bed reactor over different zeolites. A citric acid modified Hβ (CA-Hβ) zeolite showed better catalytic performance than parent Hβ zeolite due to its larger surface area and smaller amount of weak acid sites, confirmed by the Brunauer–Emmett–Teller (BET) method, NH3 temperature-programmed desorption (NH3-TPD) and Fourier Transform Infrared Spectrometer after adsorption of pyridine (Py-IR). Furthermore, it is proposed that citric acid treatment is appropriate for dealumination of Hβ zeolite, which results in the CA-Hβ zeolite having a larger number of active centers for the desired transformation. Significantly, CA-Hβ has shown good stability during a 100h test.

Friedel-Crafts Alkylation of Indoles by tert-Enamides in Acetic Acid

Friedel-Crafts Alkylation of Indoles by tert-Enamides in Acetic Acid

Friedel‐Crafts Alkylation of Indoles with Nitroalkenes Catalyzed by Zn(II)‐Thiourea Complex

AbstractFriedel‐Crafts alkylation of indoles with nitroalkenes catalyzed by a novel Zn(II)‐thiourea complex has been developed. The remarkable advantages of this reaction are mild reaction conditions, simple workup procedure, high yield of products and the use of ethanol as acceptable solvent.

TsOH·H<sub>2</sub>O-Catalyzed Friedel-Crafts of Indoles of 3-Hydroxyisobenzofuran-1(3<i>H</i>)-One with Indoles: Highly Synthesis of 3-Indolyl-Substituted Phthalides

An efficient and facile method for the synthesis of 3-indolyl-substituted phthalides by Friedel-Crafts alkylation of indoles with 3-hydroxyisobenzofuran-1(3H)-one has been developed. Using only 2 mol-% TsOH·H2O as the catalyst, various substituted indoles can react smoothly at room temperature to give the corresponding phthalides products in good to excellent yields (up to 96%).

Asymmetric Organocatalytic Friedel-Crafts Alkylation-Cyclization Cascade Reaction of Indoles with o-Hydroxyaromatic α,β-Unsaturated Aldehydes

we recently discovered thatimidazolidinone organocatalysts are efficient for the Friedel-Crafts alkylation of indoles with o-hydroxyaromatic α,β-unsaturated aldehydes. During this reaction, the indole reactsthrough conjugate addition with o-hydroxyaromatic α,β-unsaturated aldehyde to give a chiral β-substituted aldehyde,which can be hemiacetalized to a chiral 4-substitutedchroman-2-ol (Scheme 1). Here we report our preliminaryresults from this discovery. The obtained chroman-2-ol caneasily be transform to chroman and derivatives that areubiquitously found in numerous biologically active naturalproducts. Molecules containing chroman scaffolds exhibit abroad range of biological functions, such as antiviral, anti-tumor, and antimicrobial activities.

Friedel-Crafts Alkylation of Indoles Catalyzed by a Chiral Palladium Complex

Friedel-Crafts Alkylation of Indoles Catalyzed by a Chiral Palladium Complex

Asymmetric Synthesis of β2-Tryptophan Analogues via Friedel–Crafts Alkylation of Indoles with a Chiral Nitroacrylate

The asymmetric Friedel-Crafts alkylation of various indoles with a chiral nitroacrylate provides optically active β-tryptophan analogues after reduction of the nitro group and removal of the chiral auxiliary. This reaction generally occurs in good yield and high diastereoselectivity (up to 90:10).

キラルブレンステッド酸の開発と不斉合成反応への展開

We synthesized chiral phosphoric acids bearing 3,3'-substituents starting from (R)-BINOL and demonstrated their catalytic activity as chiral Bronsted acid. Proper choice of the 3,3'-substituents of the phosphoric acid is critical to attain excellent enantioselectivity. We wish to describe in this article the background of development of the catalyst, design of the catalyst, and application of them to a range of asymmetric reactions: (1) nucleophilic addition to aldimines, (2) cycloaddition toward aldimines, (3) Friedel-Crafts alkylation of indoles with nitroalkene, α,β-unsaturated ketone, and trifluoropyruvate, (4) kinetic resolution in the intramolecular aldol reaction, and (5) desymmetrization in the intramolecular aldol reaction. We also studied the role of the phosphoric acid and elucidated that phosphoryl oxygen played a critical role as a Lewis basic site.

Efficient and Metal-Free Friedel-Crafts Alkylation of Indoles with Allyl Acetate Mediated by TFE

An efficient, metal-free and chemo-selective Friedel-Crafts allylation of indoles in 2,2,2-trifluoroethanol (TFE) is developed. A possible mechanism has also been discussed to explain the observed competitive pathways in this reaction system.

Highly Efficient Friedel-Crafts Alkylation of Indoles and Pyrrole Catalyzed by Mesoporous 3D Aluminosilicate Catalyst with Electron-Deficient Olefins

The C3-selective Friedel-Crafts alkylation of indoles with electron-deficient olefins has been achieved using a mesoporous aluminosilicate catalyst with 3D cage-type porous structure to furnish the 3-alkylindole derivatives in excellent yields due to its high surface area, large pore volume and high acidity. Pyrrole also reacted efficiently under similar reaction conditions to give the corresponding 2-alkylated pyrrole derivatives in good yields.

Highly Enantioselective Synthesis of β‐Heteroaryl‐Substituted Dihydrochalcones Through Friedel–Crafts Alkylation of Indoles and Pyrrole

A highly enantioselective Friedel-Crafts (F-C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N'-dioxide-Sc(OTf)(3) complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85-92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.