Asymmetric Friedel-Crafts Alkylation Research Articles

Asymmetric Friedel–Crafts alkylation of indoles with 2-nitro-3-arylacrylates catalyzed by a metal-templated hydrogen bonding catalyst

An asymmetric Friedel–Crafts alkylation of indoles with 2-nitro-3-arylacrylates catalyzed by a metal-templated hydrogen bonding catalyst has been established. The asymmetric induction relies on chirality transfer solely from the octahedral metal stereocenter via three weak hydrogen bonds. All the products are provided with good to excellent enantioselectivities while modest diastereoselectivities, which can be converted into a variety of valuable indole-containing chiral building blocks including tryptophan derivatives.

ChemInform Abstract: Chiral Broensted Acid‐Catalyzed Friedel—Crafts Alkylation of Electron‐Rich Arenes with in situ‐Generated ortho‐Quinone Methides: Highly Enantioselective Synthesis of Diarylindolylmethanes and Triarylmethanes.

AbstractAn efficient asymmetric Friedel—Crafts alkylation of indoles and naphthols with in‐situ‐generated ortho‐quinone methides using an (R)‐BINOL derived phosphoric acid (BIN) as catalyst.

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations.

The first immobilization of a MacMillan’s first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a–c was tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles.

Asymmetric Friedel–Crafts alkylation of pyrrole with nitroalkenes catalyzed by a copper complex of a bisphenol A-derived Schiff base

The asymmetric Friedel–Crafts (FC) alkylation of pyrrole with nitroalkenes was mediated by CuBr2 and a novel bisphenol A-derived chiral catalyst at room temperature. The catalyst was found to be applicable for the asymmetric FC alkylation of pyrrole with a wide range of nitroalkenes, affording optically active alkylated pyrroles with enantioselectivities up to 94%. Furthermore, enantiomerically pure 3-nitro-2-arylpropanamides were prepared by the oxidative cleavage of the pyrrole rings in the FC products with NaIO4/RuCl3 to demonstrate the synthetic application of the products.

Enantioselective Friedel–Crafts reaction of 4,7-dihydroindoles with β-CF3-β-disubstituted nitroalkenes

Indoles bearing C2-trifluoromethylated quaternary stereocenters were obtained with high enantioselectivities by Ni-catalyzed asymmetric Friedel–Crafts alkylation of 4,7-dihydroindoles and subsequent oxidation.

A highly diastereoselective Friedel-Crafts reaction of indoles with isatin-derived N-sulfinyl ketimines towards the efficient synthesis of chiral tetrasubstituted 3-indolyl-3-aminooxindoles.

A Lewis acid promoted highly diastereoselective asymmetric Friedel-Crafts alkylation of indoles with isatin-derived N-tert-butanesulfinyl ketimines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Bi(OTf)3, providing a series of 3-indolyl-3-aminooxindoles in excellent diastereoselectivities (up to 98% de) and yields (up to 99%).

Synthesis of a chiral fluorescence active probe and its application as an efficient catalyst in the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes

A green protocol for the asymmetric Friedel–Crafts alkylation of indole derivatives with nitrostyrene using chiral Zn(ii) catalyst has been developed.

Asymmetric Friedel–Crafts Alkylation Catalyzed by Copper

Asymmetric Friedel–Crafts Alkylation Catalyzed by Copper

ChemInform Abstract: Asymmetric Friedel—Crafts Alkylation Reaction in the Construction of Trifluoromethylated All‐Carbon Quaternary Stereocenters.

Construction of all-carbon quaternary stereocenter by asymmetric Friedel–Crafts alkylation reaction remains a significant challenge. By the introduction of CF3 group at the β-position of nitroalkene, a highly enantioselective Friedel–Crafts reaction of indoles with β-CF3-β-substituted nitroalkenes was achieved using Ni(ClO4)2-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereogenic centers in good yields and excellent enantio­selectivities.

ChemInform Abstract: Highly Enantioselective Friedel—Crafts Alkylation of Indole with Electron Deficient trans‐β‐Nitroalkenes Using Zn(II)—Oxazoline—Imidazoline Catalysts.

The catalytic asymmetric Friedel–Crafts alkylation of indole with trans-β-nitroolefins has been developed via the catalysis of Zn(II)–oxazoline–imidazoline complexes. The reaction furnished nitroalkylated indoles in excellent yields (up to 95%) and with high enantioselectivities (up to 99% ee). The effects of solvent, temperature, the metal-triflate, and the ligand structure on the reaction are discussed. The substrates of the reaction can be substituted aromatic nitroolifins. The higher reactivity and enantioselectivity of the reaction could be due to the activation and asymmetric induction of chiral Lewis acids coordinated by the nitroolefin through a 1,3-metal bonded intermediate.

Synthesis of chiral benzene-based tetraoxazolines and their application in asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes

A series of new chiral benzene-based tetraoxazoline ligands were prepared in good yields through the reaction of 1,2,4,5-benzenetetracarboxylic acid and chiral β-amino alcohols by continuous removal of water, and the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes was tested using the chiral catalysts, which were generated in situ by refluxing the above ligands and anhydrous zinc chloride in solvent. In most case, good yields (up to 99%) and excellent enantioselectivities (up to 98% ee) were obtained.

Remote Enantioselective Friedel–Crafts Alkylations of Furans through HOMO Activation

AbstractCatalytic asymmetric Friedel–Crafts alkylation is a powerful protocol for constructing a chiral C(sp2)C(sp3) bond. Most previous examples rely on LUMO activation of the electrophiles using chiral catalysts with subsequent attack by electron‐rich arenes. Presented herein is an alternative strategy in which the HOMO of the aromatic π system of 2‐furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine. Exclusive regioselective alkylation at the 5‐position occurred with alkylidenemalononitriles, and high reactivity and excellent enantioselectivity (up to 95 % ee) was obtained by this remote activation.

Remote enantioselective Friedel-Crafts alkylations of furans through HOMO activation.

Catalytic asymmetric Friedel-Crafts alkylation is a powerful protocol for constructing a chiral C(sp(2))-C(sp(3)) bond. Most previous examples rely on LUMO activation of the electrophiles using chiral catalysts with subsequent attack by electron-rich arenes. Presented herein is an alternative strategy in which the HOMO of the aromatic π system of 2-furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine. Exclusive regioselective alkylation at the 5-position occurred with alkylidenemalononitriles, and high reactivity and excellent enantioselectivity (up to 95% ee) was obtained by this remote activation.

Synthesis of β2,2-Amino Acids via Asymmetric Friedel–Crafts Alkylation

Synthesis of β2,2-Amino Acids via Asymmetric Friedel–Crafts Alkylation

Copper-Catalyzed Asymmetric Friedel–Crafts Alkylation of Indoles

Copper-Catalyzed Asymmetric Friedel–Crafts Alkylation of Indoles

Chiral Bis(Oxazolinyl)thiophenes for Enantioselective Cu(II)-Catalyzed Friedel–Crafts Alkylation of Indole Derivatives with Nitroalkenes

A series of chiral bis(oxazoline)thiophenes were used as chiral ligands in the Cu(II)-catalyzed asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes, and the effects of reaction conditions on the yield and enantioselectivity were investigated. The ligand 1c was identified as the best ligand of this family in the same reaction.

Asymmetric Friedel–Crafts Alkylation of α-Substituted β-Nitroacrylates: Access to β2,2-Amino Acids Bearing Indolic All-Carbon Quaternary Stereocenters

A highly enantioselective Friedel-Crafts alkylation reaction of indoles with acyclic α-substituted β-nitroacrylates is developed under the catalysis of Ni(ClO4)2-bisoxazoline complex at 1 mol % catalyst loading, affording chiral indolic β-nitroesters bearing all-carbon quaternary stereocenters in excellent yields and ees of up to 97%. Transformation of one of the products to β(2,2)-amino ester and tetrahydro-β-carboline through nitro reduction and sequential Pictet-Spengler cyclization was exemplified.

Highly enantioselective Friedel–Crafts alkylation of indole with electron deficient trans-β-nitroalkenes using Zn(II)–oxazoline–imidazoline catalysts

The catalytic asymmetric Friedel–Crafts alkylation of indole with trans-β-nitroolefins has been developed via the catalysis of Zn(II)–oxazoline–imidazoline complexes. The reaction furnished nitroalkylated indoles in excellent yields (up to 95%) and with high enantioselectivities (up to 99% ee). The effects of solvent, temperature, the metal-triflate, and the ligand structure on the reaction are discussed. The substrates of the reaction can be substituted aromatic nitroolifins. The higher reactivity and enantioselectivity of the reaction could be due to the activation and asymmetric induction of chiral Lewis acids coordinated by the nitroolefin through a 1,3-metal bonded intermediate.

Asymmetric Friedel–Crafts Alkylation Reaction in the Construction of Trifluoromethylated All-Carbon Quaternary Stereocenters

Construction of all-carbon quaternary stereocenter by asymmetric Friedel–Crafts alkylation reaction remains a significant challenge. By the introduction of CF₃ group at the β-position of nitroalkene, a highly enantioselective Friedel–Crafts reaction of indoles with β-CF₃-β-substituted nitroalkenes was achieved using Ni(ClO₄)₂-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereogenic centers in good yields and excellent enantio­selectivities.

A trinuclear Cu2Eu complex catalyzed asymmetric Friedel–Crafts alkylations of indoles with nitroalkenes

Catalytic enantioselective Friedel–Crafts alkylations of indoles and nitroalkenes were carried out by using a new heterotrimetallic Cu/Eu/Cu complex catalyst based on the simple chiral ligand, reduced Schiff base 1, to give the Friedel–Crafts adducts with up to 88% yield and 80% ee. The trimetallic catalyst is air-stable and can be formed in-situ by a facile solution self-assembly during the catalytic reaction.