Enantioselective Friedel-Crafts Research Articles

ChemInform Abstract: Asymmetric Friedel—Crafts Alkylation of α‐Substituted β‐Nitroacrylates: Access to β2,2‐Amino Acids Bearing Indolic All‐Carbon Quaternary Stereocenters.

AbstractA highly enantioselective Friedel—Crafts alkylation reaction of indoles with acyclic α‐substituted β‐nitroacrylates is developed under the catalysis of a Ni(ClO4)2—bisoxazoline complex, affording chiral indolic β‐nitroesters bearing an all‐carbon quaternary stereocenter.

Enantioselective Friedel–Crafts alkylation of indoles with β,γ-unsaturated α-ketoesters catalyzed by new squaramide-linked bisoxazoline–Zn(OTf)2 complexes

Enantioselective Friedel–Crafts alkylation reactions of indoles with β,γ-unsaturated α-ketoesters catalyzed by novel chiral C2-symmetric squaramide-linked bisoxazoline–Zn(OTf)2 complexes were investigated. The corresponding indole ketoesters were obtained in good to excellent yields (up to 98%) and with high enantioselectivities (up to 94% ee). This is the first report on the use of chiral squaramide-linked bisoxazoline SQBOX in a catalytic enanitioselective Friedel–Crafts alkylation reaction.

Copper-catalyzed enantioselective Friedel-Crafts alkylation of pyrrole with isatins.

The highly enantioselective Friedel-Crafts alkylation of pyrrole with isatins catalyzed by the tridentate Schiff base/Cu catalyst was developed. Hexafluoroisopropanol (HFIP) was used as a crucial additive to improve the enantioselectivity. In the case of N-unprotected isatins, an innovative substrate slow-releasing strategy was applied by virtue of a Henry/retro-Henry reaction.

ChemInform Abstract: Facile Synthesis of Chiral 2‐Amino‐4‐(indol‐3‐yl)‐4H‐chromene Derivatives Using Thiourea as the Catalyst.

Abstract The enantioselective Friedel–Crafts alkylation of indoles with iminochromenes catalyzed by a bifunctional thiourea organocatalyst was investigated. This reaction afforded chiral functionalized 2-amino-4-(indol-3-yl)-4 H -chromenes in good yields (up to 87% yield) and with moderate to good enantioselectivities (up to 86% ee).

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.

ChemInform Abstract: Organocatalytic Enantioselective Friedel—Crafts Reaction of Naphthol with β,γ‐Unsaturated α‐Keto Esters

Abstractusing a binaphthyl‐modified squaramide as organocatalyst

ChemInform Abstract: Enantioselective Friedel—Crafts Alkylation for Synthesis of 2‐Substituted Indole Derivatives.

AbstractThe catalytic asymmetric intermolecular C2 Friedel—Crafts alkylation of N‐methyl skatole (I) with β,γ‐unsaturated α‐ketoesters (II) is realized by a chiral Ni(II)‐complex.

Organocatalytic asymmetric Friedel–Crafts reaction of 1-naphthols with isatins: an enantioselective synthesis of 3-aryl-3-hydroxy-2-oxindoles

An organocatalytic enantioselective Friedel–Crafts reaction of 1-naphthols with isatins has been developed employing bifunctional thiourea–tertiary amine organocatalysts. A variety of isatin derivatives react well with 1-naphthols in the presence of Cinchona derived thiourea 1a to provide biologically important chiral 3-aryl-3-hydroxy-2-oxindoles (3a–zg) in good yield (70–84%) and moderate to good enantioselectivity (37–83%).

Asymmetric catalysis with substitutionally labile yet stereochemically stable chiral-at-metal iridium(III) complex.

A metal-coordination-based high performance asymmetric catalyst utilizing metal centrochirality as the sole element of chirality is reported. The introduced substitutionally labile chiral-at-metal octahedral iridium(III) complex exclusively bears achiral ligands and effectively catalyzes the enantioselective Friedel-Crafts addition of indoles to α,β-unsaturated 2-acyl imidazoles (19 examples) with high yields (75%-99%) and high enantioselectivities (90-98% ee) at low catalyst loadings (0.25-2 mol %). Counterintuitively, despite its substitutional lability, which is mechanistically required for coordination to the 2-acyl imidazole substrate, the metal-centered chirality is maintained throughout the catalysis. This novel class of reactive chiral-at-metal complexes will likely be of high value for a large variety of asymmetric transformations.

Enantioselective Continuous‐Flow Production of 3‐Indolylmethanamines Mediated by an Immobilized Phosphoric Acid Catalyst

A polystyrene-supported 1,1'-bi-2-naphthol derived phosphoric acid has been synthesized and applied in the enantioselective Friedel-Crafts reaction of indoles and sulfonylimines. The immobilized catalyst was highly active and selective, and gave rise to a broad range of 3-indolylmethanamines (19 examples) in high yields and excellent enantioselectivities (up to 98 % enantiomeric excess) after short reaction times under very convenient reaction conditions (RT in dichloromethane). Moreover, repeated recycling (14 cycles) was possible with no substantial loss in catalytic performance and the system could be adapted to a continuous-flow operation (6 h). Finally, the applicability of the system was further confirmed by rapid access to a library of compounds with three points of diversity in a single continuous-flow experiment that involved sequential pumping of different substrate combinations.

Metal–Nitroalkene and aci-Nitro Intermediates in Catalytic Enantioselective Friedel–Crafts Reactions of Indoles with trans-β-Nitrostyrenes

The half-sandwich aqua complex (SRh,RC)-[(η5-C5Me5)Rh{(R)-Prophos}(H2O)][SbF6]2 (Prophos = propane-1,2-diylbis(diphenylphosphane)) efficiently catalyzes the asymmetric reaction between N-methyl-2-m...

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.

Stereoselective construction of all-carbon quaternary center by means of chiral phosphoric acid: highly enantioselective Friedel–Crafts reaction of indoles with β,β-disubstituted nitroalkenes

Chiral phosphoric acid catalyzed Friedel–Crafts reaction of indoles with β-alkoxycarbonyl-β-disubstituted nitroalkenes was achieved.

Cinchonidine thiourea catalyzed asymmetric addition of phenols to oxindole derivatives

A highly enantioselective Friedel–Crafts reaction of phenols with isatin derivatives catalyzed by Cinchona-derived thiourea provides biologically important 3-aryl-3-hydroxy-2-oxindoles in good to excellent yield with enantioselectivity up to 92% ee.

C3-Symmetric chiral trisimidazoline-catalyzed Friedel-Crafts (FC)-type reaction.

Imidazoline-catalyzed enantioselective Friedel-Crafts (FC)-type reactions were established using C3-symmetric chiral trisimidazolines. The imidazoline catalysts promoted the FC-type reaction of aldimines with 2-naphthols to produce the corresponding adducts in high yields with up to 99% ee.

Organocatalytic Enantioselective Friedel-Crafts Reaction of Naphthol with β,γ-Unsaturated α-Keto Esters

E-mail: dyoung@sch.ac.kr Received August 16, 2013, Accepted September 3, 2013Key Words : Asymmetric catalysis, β,γ-Unsaturated α-keto esters, Friedel-Crafts reaction, Organocatalysis,ChromanesThe chromane and benzopyrane structures are present as acharacteristic structural motif in a large number of naturalproducts that possess a broad array of biological activitiessuch as antimicrobial, antiviral, antitumor, and central nervesystem activity.

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.

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.

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.