Enantioselective Friedel Crafts Alkylation Reaction Research Articles

Enantioselective Synthesis of an All-Carbon Quaternary Stereocenter by Chiral Brønsted Acid-Catalyzed Friedel-Crafts-Type Reaction between Pyrroles and 3-Indolylmethanols.

We have developed a chiral phosphoric acid-catalyzed enantioselective Friedel-Crafts alkylation reaction between pyrroles and indolylmethanols. Wide substrate scope was observed, and a chiral all-carbon quaternary center was constructed at the 3 position of indoles in high yields with high to excellent enantioselectivities (up to 99% ee).

Enantioselective Friedel-Crafts Alkylation Reaction of Pyrroles with N-Unprotected Alkynyl Trifluoromethyl Ketimines.

Developed herein is an enantioselective Friedel-Crafts alkylation reaction of N-unprotected alkynyl trifluoromethyl ketimines with pyrroles catalyzed by chiral phosphoric acid to furnish chiral primary α-trifluoromethyl-α-(2-pyrrolyl)propargylamines with high enantioselectivity. Transformation of the alkynyl group of the adducts afforded optically active α-trifluoromethylated amines bearing various substituents such as alkyl, alkenyl, enyne, and triazole without loss of optical purity.

Chiral Calcium Phosphate Catalyzed Enantioselective Synthesis of All-Carbon Quaternary Center by Friedel–Crafts Alkylation Reaction of Pyrroles and Trifluoromethylated Nitrostyrenes

AbstractA chiral calcium phosphate-catalyzed enantioselective Friedel–Crafts alkylation reaction of pyrroles and α-trifluoromethyl-β-nitrostyrenes has been developed. Pyrroles bearing an all-carbon quaternary center at 2-position were obtained with high to excellent enantioselectivity. Use of 4,7-dihydroindole as a nucleophile and subsequent oxidation resulted in the formation a 2-substituted indole derivative with excellent enantioselectivity. A 3,4-dihydropyrrolo[1,2-c]pyrimidine derivative was successfully synthesized by reduction followed by benzoylation of the product without loss of enantioselectivity. Application to a 1 mmol scale reaction was successfully achieved.

Enantioselective Friedel–Crafts Alkylation Reaction of Indoles with α-Trifluoromethylated β-Nitrostyrenes Catalyzed by Chiral BINOL Metal Phosphate

An efficient enantioselective Friedel–Crafts alkylation reaction of indoles with α-CF3-substituted β-nitrostyrenes is disclosed. The key to success is the use of a chiral calcium BINOL bis(phosphat...

Enantioselective Friedel-Crafts Alkylation Reaction of Heteroarenes with N-Unprotected Trifluoromethyl Ketimines by Means of Chiral Phosphoric Acid.

An enantioselective Friedel-Crafts alkylation reaction of pyrroles and indoles with N-unprotected trifluoromethyl ketimines by use of chiral phosphoric acid provided α-trifluoromethylated primary amines bearing chiral tetrasubstituted carbon centers in high yields and with high to excellent enantioselectivities. The present reaction is unique to N-unprotected trifluoromethyl ketimines. No reaction took place with N-p-methoxyphenyl (PMP)-substituted ketimine. Corresponding α-trifluoromethylated amines were transformed without loss of enantioselectivity.

Enantioselective Friedel-Crafts Alkylation Reactions of β-Naphthols with Donor-Acceptor Aminocyclopropanes.

The enantioselective Friedel-Crafts alkylation reaction of β-naphthols with donor-acceptor aminocyclopropane was developed. In the presence of a copper complex derived from Cu(OTf)2 and bisoxazoline, a series of γ-substituted γ-aminobutyric acid derivatives were obtained with good yields (up to 98 %) and excellent enantioselectivities (up to 98 %). Using this catalytic system, the 2-amino cyclopropane-1,1-dicarboxylate was obtained with high enantiomeric excess (up to 98 %) by an efficient kinetic resolution (s values of up to 90). The Friedel-Crafts alkylation product could be transformed into a tetracyclic 1,3-oxazine derivative.

Bifunctional Amine‐Squaramide Catalyzed Friedel–Crafts Alkylation Based on ortho‐Quinone Methides in Oil‐Water Phases: Enantioselective Synthesis of Triarylmethanes

AbstractAn efficient enantioselective Friedel–Crafts alkylation reaction of electron‐rich β‐naphthol with in situ generated ortho‐quinone methides catalyzed by chiral bifunctional amine‐squaramide catalysts has been developed. The chiral triarylmethane derivatives were obtained in good to high yields (up to 97% yield) with high enantioselectivities (up to 97% ee) for most substrates under mild conditions. This study also revealed that the oil‐water biphase could significantly improve the efficiency of this catalytic system.magnified image

ChemInform Abstract: Chiral Phosphoric Acid Catalyzed Highly Enantioselective Friedel—Crafts Alkylation Reaction of C3‐Substituted Indoles to β,γ‐Unsaturated α‐Ketimino Esters.

AbstractThe scalable reaction allows the preparation of C2‐substituted indole derivatives bearing an α‐ketimino ester motif in moderate to high yields.

Enantioselective Construction of Cyclic Indolyl α‐Amino Esters via a Friedel–Crafts Alkylation Reaction

AbstractAn enantioselective Friedel–Crafts alkylation reaction of indoles with cyclic N‐sulfonyl ketimino esters was developed. Under the optimized conditions using a chiral copper(II) triflate‐bisoxazoline complex as the catalyst, a range of N‐sulfonyl ketimino ester derivatives and indoles reacted smoothly to afford indole‐containing chiral cyclic α‐amino esters bearing tetrasubstituted α‐stereogenic centers [3‐ethoxycarbonyl‐3‐(3‐indolyl)‐2,3‐dihydrobenzo[d]isothiazole 1,1‐dioxides] in excellent yields and with high enantioselectivities (up to 99% ee). Pyrrole and N,N‐dimethylaniline were also investigated as aromatic substrates to afford the corresponding products with good results. An asymmetric induction model was then proposed on the basis of the observed absolute configuration of the product 3‐ethoxycarbonyl‐3‐(5‐bromo‐3‐indolyl)‐2,3‐dihydrobenzo[d]isothiazole 1,1‐dioxide. Synthetic transformations to convert the products into cyclic chiral N‐sulfonamido alcohols and the deprotection of the sulfonamides were performed. This study provides an efficient approach to chiral α‐tetrasubstituted indolic α‐amino acids as potential building blocks for peptides and biologically active molecules.magnified image

Chiral phosphoric acid catalyzed highly enantioselective Friedel-Crafts alkylation reaction of C3-substituted indoles to β,γ-unsaturated α-ketimino esters.

A highly enantioselective C2 Friedel-Crafts alkylation reaction of 3-substituted indoles to β,γ-unsaturated α-ketimino esters has been developed. This reaction was efficiently catalyzed by a chiral phosphoric acid catalyst. The corresponding C2-substituted indole derivatives, bearing an α-ketimino ester motif, were obtained in moderate to high yields (up to 93%) and with high enantioselectivities (up to >99% ee).

ChemInform Abstract: Enantioselective Friedel—Crafts Alkylation of Indoles with β,γ‐Unsaturated α‐Ketoesters Catalyzed by New Squaramide‐Linked Bisoxazoline—Zn(OTf)2 Complexes.

Abstract Enantioselective Friedel–Crafts alkylation reactions of indoles with β,γ-unsaturated α-ketoesters catalyzed by novel chiral C 2 -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.

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.

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.

ChemInform Abstract: Highly Enantioselective Construction of Trifluoromethylated All‐Carbon Quaternary Stereocenters via Nickel‐Catalyzed Friedel—Crafts Alkylation Reaction.

A highly enantioselective Friedel–Crafts alkylation reaction of indoles with β-CF3-β-disubstituted nitroalkenes was achieved using a Ni(ClO4)2–bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereocenters in good yields with excellent enantioselectivities (up to 97% ee). The transformation of one of the products into first a trifluoromethylated tryptamine and then a trifluoromethylated tetrahydro-β-carboline by sequential nitro reduction and Pictet–Spengler cyclization were realized with complete preservation of enantiopurity.

Highly Enantioselective Construction of Trifluoromethylated All-Carbon Quaternary Stereocenters via Nickel-Catalyzed Friedel–Crafts Alkylation Reaction

A highly enantioselective Friedel-Crafts alkylation reaction of indoles with β-CF(3)-β-disubstituted nitroalkenes was achieved using a Ni(ClO(4))(2)-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereocenters in good yields with excellent enantioselectivities (up to 97% ee). The transformation of one of the products into first a trifluoromethylated tryptamine and then a trifluoromethylated tetrahydro-β-carboline by sequential nitro reduction and Pictet-Spengler cyclization were realized with complete preservation of enantiopurity.

ChemInform Abstract: Catalytic Enantioselective Friedel—Crafts Alkylation of Indoles with Fumarate Derivatives in the Presence of Chiral Palladium Complexes.

The catalytic enantioselective Friedel–Crafts alkylation reaction promoted by chiral palladium complexes is described. The treatment of indoles with fumarate derivatives under the mild reaction conditions afforded the corresponding Friedel–Crafts alkylation adducts with high enantioselectivities (up to 91% ee).

Catalytic Enantioselective Friedel-Crafts Alkylation of Indoles with Fumarate Derivatives in the Presence of Chiral Palladium Complexes

The catalytic enantioselective Friedel–Crafts alkylation reaction promoted by chiral palladium complexes is described. The treatment of indoles with fumarate derivatives under the mild reaction conditions afforded the corresponding Friedel–Crafts alkylation adducts with high enantioselectivities (up to 91% ee).

ChemInform Abstract: Highly Enantioselective Friedel—Crafts Alkylation Reaction Catalyzed by Rosin‐Derived Tertiary Amine—Thiourea: Synthesis of Modified Chromans with Anticancer Potency.

AbstractSeveral of the chromans of type (IV) show in vitro cytotoxic activity against 6 different tumor cell lines.

Highly enantioselective Friedel–Crafts alkylation reaction catalyzed by rosin-derived tertiary amine–thiourea: synthesis of modified chromanes with anticancer potency

We present herein for the first time the synthesis and preliminary biological evaluation of various modified chromanes via a rosin-derived tertiary amine-thiourea-catalyzed highly enantioselective Friedel-Crafts alkylation reaction.