Enantioselective Friedel Crafts Reaction Research Articles

Enantioselective Friedel–Crafts reactions between phenols and N-tosylaldimines catalyzed by a leucine-derived bifunctional catalyst

Enantioselective Friedel-Crafts reactions between phenols and N-tosylaldimines were developed using a bifunctional catalyst readily prepared from L-leucine. The chiral benzylic amine products were obtained in high yields (up to 96% yield) and good to high enantiomeric excesses (up to 95% ee).

Highly enantioselective Friedel–Crafts reaction of indoles with N-sulfonyl aldimines catalyzed by heteroarylidene malonate-type bis(oxazoline) copper(II) complexes

The enantioselective Friedel–Crafts addition of indoles to N-sulfonyl aldimines was studied using a heteroarylidene malonate-type bis(oxazoline) as a chiral ligand. High to excellent enantioselectivities (up to >99% ee) were achieved using the complex of copper(II)– L1b with a benzyl group. The effects of ligand structure, solvent, temperature and substrate on the reaction were also investigated.

Enantioselective Friedel–Crafts Reaction of Acylpyrroles with Glyoxylates Catalyzed by BINOL–Ti(IV) Complexes

We report the first efficient enantioselective Friedel-Crafts hydroxyalkylation of pyrroles having one electron-withdrawing group at the α, β or N-positions with alkyl glyoxylates catalyzed by readily available chiral BINOL-Ti(IV) complexes (1-5 mol %). The reaction regioselectively led to the desired pyrrole-hydroxyacetic acid derivatives with good yields (70-96%) and enantiomeric excesses up to 96%, and is applicable in multigram scale with low loading of the catalyst (1 mol %).

ChemInform Abstract: Chiral Pd‐Catalyzed Enantioselective Friedel—Crafts Reaction of Indoles with γ,δ‐Unsaturated β‐Keto Phosphonates.

Abstract The catalytic enantioselective Friedel–Crafts alkylation reaction promoted by chiral palladium complexes is described. The treatment of indoles with γ,δ-unsaturated β-keto phosphonates under the mild reaction conditions afforded the corresponding Friedel–Crafts alkylation adducts with excellent enantioselectivities (up to 99% ee).

Linking Conformational Flexibility and Kinetics: Catalytic 1,4‐Type Friedel–Crafts Reactions of Phenols Utilizing 1,3‐Diamine‐Tethered Guanidine/Bisthiourea Organocatalysts

Herein, we present details of our conformationally flexible, 1,3-diamine-tethered guanidine/bisthiourea organocatalysts for chemo-, regio-, and enantioselective 1,4-type Friedel-Crafts reactions of phenols. These organocatalysts show a unique stereo-discrimination governed by the differential activation entropy (ΔΔS(≠)), rather than by the differential activation enthalpy (ΔΔH(≠)). Extensive kinetic analyses using Eyring plots for a series of guanidine/bisthiourea organocatalysts revealed the key structural motif in the catalysts associated with a large magnitude of differential activation entropy (ΔΔS(≠)). A plausible guanidine-thiourea cooperative mechanism for the enantioselective Friedel-Crafts reaction is proposed.

Enantioselective Friedel–Crafts reaction of indoles with trifluoroacetaldehyde catalyzed by Cinchona alkaloids

The first direct asymmetric synthetic preparation of trifluoro-1-(indol-3-yl)ethanols (TFIEs) is described by an enantioselective organocatalytic method from indoles and inexpensive trifluoroacetaldehyde methyl hemiacetal. The reaction is catalyzed by hydroquinine to produce TFIEs in an almost quantitative yield and with enantioselectivities up to 75% at room temperature. The enantioselectivity is strongly dependent on the concentration of substrates and catalyst due to the competitive noncatalyzed reaction.

Chiral Pd-catalyzed enantioselective Friedel–Crafts reaction of indoles with γ,δ-unsaturated β-keto phosphonates

The catalytic enantioselective Friedel–Crafts alkylation reaction promoted by chiral palladium complexes is described. The treatment of indoles with γ,δ-unsaturated β-keto phosphonates under the mild reaction conditions afforded the corresponding Friedel–Crafts alkylation adducts with excellent enantioselectivities (up to 99% ee).

ChemInform Abstract: Organocatalytic Enantioselective Friedel—Crafts Reactions of 1‐Naphthols with Aldimines.

AbstractThe reaction is catalyzed best by the alkaloid‐derived bifunctional catalyst.

ChemInform Abstract: SPINOL‐Derived Phosphoric Acids: Synthesis and Application in Enantioselective Friedel—Crafts Reaction of Indoles with Imines.

AbstractA number of SPINOL‐derived phosphorus acids are prepared and tested in the title reaction.

ChemInform Abstract: Chiral Broensted Acid Catalyzed Enantioselective Friedel—Crafts Reaction of 4,7‐Dihydroindoles with Trifluoromethyl Ketones.

AbstractIn the presence of a chiral phosphoric acid, reaction of substrates (I) with aromatic trifluoromethyl ketones (II) and ethyl 4,4,4‐trifluoroacetoacetate (V) gives 2‐substituted 4,7‐dihydroindoles with a trifluoromethylated tertiary alcohol moiety.

Enantioselective Organocatalytic Synthesis of Quaternary α-Amino Acids Bearing a CF3 Moiety

A highly enantioselective Friedel-Crafts reaction catalyzed by a chiral phosphoric acid was developed. N-Boc-protected ethyl trifluoropyruvate imine was activated by 6 mol % of catalyst and reacted with a wide variety of indole derivatives to afford quaternary α-amino acids in excellent yields (up to 99%) and high enantioselectivities (up to 98:2 er).

Organocatalytic Enantioselective Friedel−Crafts Reactions of 1-Naphthols with Aldimines

An organocatalytic enantioselective Friedel-Crafts reaction of 1-naphthols with aldimines has been developed. The method affords a direct access to chiral aminoarylnaphthols in good yields and with good to high enantioselectivities.

Asymmetric synthesis of chiral trifluoromethylated heliotridane via highly catalytic asymmetric Friedel–Crafts alkylation with β-trifluoromethylated acrylates and pyrroles

Chiral Ph-dbfox (Ph-dbfox = (R,R)-4,6-dibenzofurandiyl-2,2′-bis(4-phenyloxazoline))/Zn(NTf2)2 catalyzed enantioselective Friedel–Crafts reactions of β-CF3 acrylates with pyrroles and indoles have been investigated, which afforded the corresponding chiral trifluoromethyl pyrrole and indole derivatives in high yields (90–99%) with a range of 66–99% ee values. With the aid of the chiral adduct of the asymmetric Friedel–Crafts reaction, the chiral trifluoromethylated heliotridane has been successfully constructed in good total yield.

DFT Study of Chiral‐Phosphoric‐Acid‐Catalyzed Enantioselective Friedel–Crafts Reaction of Indole with Nitroalkene: Bifunctionality and Substituent Effect of Phosphoric Acid

The enantioselective Friedel-Crafts reaction of indoles with nitroalkenes proceeds catalytically by means of a chiral-phosphoric-acid catalyst to afford products with high enantioselectivities (up to 91% ee). The use of a 3,3'-SiPh(3)-substituted (R)-binol-derived (binol=1,1'-binaphthyl-2,2'-diol) catalyst and a free indole that bears an N-H moiety is essential to achieving high enantioselectivity as well as high yield. To elucidate the reaction mechanism and the origin of the high enantioselectivity, DFT calculations were carried out. The reaction proceeded through a cyclic transition state formed by the two-point binding of both substrates to the conjugated O-P-O moiety of the catalyst, in which indoles and nitroalkenes could be simultaneously activated by Brønsted acidic (proton) and basic (phosphoryl oxygen) sites, respectively. The enantioselectivity was entirely controlled by the steric effect between the 3,3'-substituent group on the (R)-binol-derived phosphoric acid catalyst and the indole ring. When the sterically demanding SiPh(3) group was used as the 3,3'-substituent group, the energy difference between the most-stable diastereomeric transition states that afforded the S and R products was increased to lead to the high enantioselectivity in agreement with the experimental results.

Chiral Brønsted Acid‐Catalyzed Enantioselective Friedel–Crafts Reaction of 4,7‐Dihydroindoles with Trifluoromethyl Ketones

AbstractIn the presence of chiral phosphoric acid, an enantioselective Friedel–Crafts reaction of 4,7‐dihydroindoles with aromatic trifluoromethyl ketones and ethyl 4,4,4‐trifluoroacetoacetate has been realized. A series of 2‐substituted 4,7‐dihydroindoles with a trifluoromethylated tertiary alcohol moiety were obtained in 45–95% yields with 60–93% ee. Furthermore, 2‐functionalized indole derivatives could be produced through a one‐pot process.

ChemInform Abstract: Squaramide‐Catalyzed Enantioselective Friedel—Crafts Reaction of Indoles with Imines.

AbstractChiral squaramides bearing hydrogen bond donor functions are found to be highly active catalysts for the enantioselective Friedel—Crafts reaction of indole (I) with tosyl imines (II) affording 3‐indolylmethanamines (III) in high yields and enantioselectivities.

ChemInform Abstract: Facile Creation of 3‐Indolyl‐3‐hydroxy‐2‐oxindoles by an Organocatalytic Enantioselective Friedel—Crafts Reaction of Indoles with Isatins.

The first direct enantioselective Friedel-Crafts reaction of indoles with isatins has been developed. The process is catalyzed by simple cupreine under mild reaction conditions and affords synthetically and biologically interesting, chiral 3-indolyl-3-hydroxy-2-oxindoles in good yields (68-97%) and with high enantioselectivities (76-91%).

ChemInform Abstract: Enantioselective Friedel—Crafts Reaction of β‐Trifluoromethylated Acrylates with Pyrroles and Its Application to the Synthesis of Trifluorinated Heliotridane.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Binary‐Acid Catalysis with Chiral Phosphoric Acid and MgF2: Catalytic Enantioselective Friedel—Crafts Reactions of β,γ‐Unsaturated α‐Ketoesters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective aza-Friedel–Crafts reaction catalyzed by a water inclusion complex of O, O′-diacyl tartaric acid

The efficiency of an O, O′-diacyl tartaric acid derivative as a chiral Brønsted acid catalyst was investigated in the enantioselective Friedel–Crafts reaction of indoles with an α-imino ester. The inclusion of water in the O, O′-di- p-toluoyl- d-tartaric acid catalyst is crucial for obtaining the enantioselectivity, and under optimal conditions the corresponding Friedel–Crafts product was obtained with an enantioselectivity of up to 88% ee.