Crafts Alkylation Of Indoles Research Articles

Asymmetric Friedel−Crafts Alkylation of Indoles with α,β‐unsaturated Trifluoromethyl Ketones Using a Squaramide Organocatalyst

AbstractThis study explores the asymmetric Friedel−Crafts alkylation of indoles with α,β‐unsaturated trifluoromethyl ketones using a squaramide organocatalyst. The squaramide organocatalyst efficiently promoted the asymmetric Friedel−Crafts alkylation of indoles with α,β‐unsaturated trifluoromethyl ketones, affording the corresponding products bearing both indole motif and trifluoromethyl group in high yields with excellent enantioselectivities (up to 99% ee). The transformation of the obtained adduct to chiral spiro indoline 3‐one was also demonstrated.

Calcium-Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles

Calcium-Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles

Oxidative Asymmetric Aza-Friedel-Crafts Alkylation of Indoles with 3-Indolinone-2-carboxylates Catalyzed by a BINOL Phosphoric Acid and Promoted by DDQ.

An asymmetric aza-Friedel-Crafts alkylation reaction between indoles and indolenines that were derived in situ from 3-indolinone-2-carboxylates has been developed by using 3,3'-bis(triphenylsilyl)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate as a catalyst. The reaction proceeded under mild conditions and provided chiral indol-3-yl-3-indolinone-2-carboxylate derivatives in good yields with excellent ee values (up to 98.6 %). Similarly, the Mannich-type addition of indoline-3-ones to indolenines provided heterodimers with vicinal chiral quaternary centers. This method was successfully applied to the construction of the core structure of trigonoliimine C.

TiCl2(OTf)-SiO2: A solid stable lewis acid catalyst for Michael addition of α-Aminophosphonates, Amines, Indoles and Pyrrole

ABSTRACTTiCl2(OTf)-SiO2 is simply prepared by immobilization of TiCl3(OTf) on silica gel surface and introduced as a non-hygroscopic Lewis acid catalyst for C-N and C-C bond formation via Michael addition reaction. A variety of structurally diverse nitrogen nucleophiles including α-aminophosphonates, aliphatic and aromatic amines and imidazole were evaluated as Michael donors. Friedel–Crafts alkylation of indoles and pyrrole was also investigated through Michael addition reaction in the presence of TiCl2(OTf)-SiO2 as a catalyst. The reactions were conducted at room temperature or 60 °C under solvent-free conditions and the desired Michael adducts were obtained in high to excellent yields.

New thiourea organocatalysts and their application for the synthesis of 5-(1H-indol-3-yl)methyl-2,2-dimethyl-1,3-dioxane-4,6-diones a source of chiral 3-indoylmethyl ketenes

ABSTRACTThe stereoselective properties of modified thiourea organocatalysts were tested in the Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones, which produces chiral 5-((1H-indol-3-yl)(aryl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-diones. Based on a tentative reaction mechanism for ((S)-N-benzyl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethylbutanamide organocatalysts, modifications were applied in four selected regions. Systematic structure-stereoselectivity relationship study allowed designing the best efficient organocatalyst for the investigated Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones.

Friedel–Crafts Alkylation of Indoles with 3-Indolylmethanols

Friedel–Crafts Alkylation of Indoles with 3-Indolylmethanols

Friedel–Crafts Alkylation of Indoles by Using Supported Imidazolidinones

Friedel–Crafts Alkylation of Indoles by Using Supported Imidazolidinones

Copper-Catalyzed Asymmetric Friedel–Crafts Alkylation of Indoles

Copper-Catalyzed Asymmetric Friedel–Crafts Alkylation of Indoles

Chiral Bis(oxazolidine)pyridine–Copper-Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with Nitroalkenes

Catalytic asymmetric Friedel–Crafts reaction of indoles with nitroalkenes was catalyzed by the stereochemically tunable bis(oxazolidine)pyridine (PyBodine)–Cu(OTf)2 complex. Using the PyBodine(Val)–Cu(OTf)2 catalyst gave the Friedel–Crafts ­adducts with highly enantioselective manner. For the 1,4-bis[(E)-2-nitrovinyl]benzene, the reaction proceeded in a meso-trick manner to give the chiral double Friedel–Crafts adduct with 97% enantiomeric excess.

ChemInform Abstract: Gallium(III)‐Catalyzed Tandem Cycloisomerization/Friedel—Crafts Alkylation: A Facile Synthesis of 2,5‐Disubstituted Furans.

Abstract A tandem cycloisomerization/Friedel–Crafts alkylation of indoles has been achieved in a one-pot process to produce 2,5-disubstituted furans using gallium-catalyzed sequential nucleophilic addition onto metal-activated 1-alkynyl-2,3-epoxy acetates. The reaction proceeds efficiently under mild conditions with complete regioselectivity to afford the substituted furan derivatives in good yields with high diversity.

Gallium(III)-catalyzed tandem cycloisomerization/Friedel–Crafts alkylation: a facile synthesis of 2,5-disubstituted furans

A tandem cycloisomerization/Friedel–Crafts alkylation of indoles has been achieved in a one-pot process to produce 2,5-disubstituted furans using gallium-catalyzed sequential nucleophilic addition onto metal-activated 1-alkynyl-2,3-epoxy acetates. The reaction proceeds efficiently under mild conditions with complete regioselectivity to afford the substituted furan derivatives in good yields with high diversity.

ChemInform Abstract: Organocatalytic Synthesis of α‐Quaternary Amino Acid Derivatives via Aza‐Friedel—Crafts Alkylation of Indoles with Simple α‐Amidoacrylates.

Abstract The first (organo)catalytic method for regio- and chemoselective aza-Friedel–Crafts (FC) alkylation of indoles and pyrroles with commercially available methyl α-acetamidoacrylates has been discovered. It minimizes/eliminates common competing reactions that occur due to the high and multiatom-nucleophilic character of indole and pyrrole. Diverse quaternary α-amino acids were successfully prepared in good yield and high selectivity using low catalyst loading. The enantioselective variant using BINOL-derived phosphoric acids was also explored with indole providing the desired F–C alkylation product with moderate enantioselectivities.

Friedel–Crafts alkylation of indoles with nitroalkenes catalyzed by Cu(II)–imine complex

Abstract A series of new ligands L 1 –L 7 were readily prepared in one step. Friedel–Crafts alkylation of indoles with nitroalkenes catalyzed by a novel Cu(II)–L complex has been developed. The remarkable advantages of this reaction are mild reaction conditions, simple workup procedure, high yields of products and the use of ethanol as a green solvent.

Enantioselective Friedel−Crafts Alkylation of Indoles with Trifluoroethylidene Malonates by Copper−Bis(oxazoline) Complexes: Construction of Trifluoromethyl-Substituted Stereogenic Tertiary Carbon Center

An enantioselective alkylation of indoles with trifluoroethylidene malonates catalyzed by copper(II)-bis (oxazoline) complexes has been developed. The expected adducts with a stereogenic tertiary carbon center bearing a trifluoromethyl group were obtained in excellent yields (up to 99%) and ee values (up to 96% ee). The synthetic utility of this asymmetric catalytic reaction was demonstrated by the preparation of β-CF(3)-tryptophan and 4-CF(3)-β-carboline in high ee.

Boric Acid–Mediated Mild and Efficient Friedel–Crafts Alkylation of Indoles with Nitro Styrenes

An efficient method has been developed for the synthesis of indole 3-derivatives by the Friedel–Crafts alkylation of indole with nitro olefins in presence of boric acid in aqueous medium.

AgAsF6/Sm(OTf)3 Promoted Reversal of Enantioselectivity for the Asymmetric Friedel−Crafts Alkylations of Indoles with β,γ-Unsaturated α-Ketoesters

The first example of central metal controlled reversal of enantioselectivity in asymmetric Friedel-Crafts alkylation of indoles and beta,gamma-unsaturated alpha-ketoesters has been developed. Using the same chiral starting material derived N,N'-dioxides 1a and 1b as ligands, various indole esters 4 were obtained in good to excellent yields and enantioselectivities. The reaction also featured mild reaction conditions and remarkably low catalyst loading (down to 0.01 mol %).

Switchable Reactivity of Acylated α, β-Dehydroamino Ester in the Friedel−Crafts Alkylation of Indoles by Changing the Lewis Acid

Highly regioselective electrophilic substitution of indoles with N-acetylated alpha,beta-dehydroalanine methyl ester, promoted by different transition metal salts was achieved. The orthogonal regioselectivity provides an efficient protocol toward highly functionalized 3-indolyl-alpha-amino acids. The mechanism of the reactions was explored by NMR studies.

Silica Sulfuric Acid–Catalyzed Friedel–Crafts Alkylation of Indoles with Nitro Olefins

The 1,4‐conjugate addition of indoles to nitro olefins was efficiently carried out using an environmentally benign catalyst, silica sulfuric acid, at ambient temperature. IICT Communication No. 070512

Highly Enantioselective Friedel−Crafts Alkylations of Indoles with Simple Enones Catalyzed by Zirconium(IV)−BINOL Complexes

Complexes of BINOL-based ligands with Zr(OtBu)4 catalyze the Friedel-Crafts alkylation reaction of indoles and pyrrole with nonchelating beta-substituted alpha,beta-enones at room temperature affording the expected products with good yields and ee above 95% in most of the studied examples.

Catalytic Enantioselective Friedel−Crafts Alkylations of Indoles with α‘-Phosphoric Enones

The C2-symmetric bis(oxazoline) copper(II) complex proves to be an excellent catalyst in the Friedel-Crafts alkylation of indoles with alpha'-phosphoric enones. The enantioselectivities of this reaction are obtained in up to 98% ee.