Friedel-Crafts Type Reaction Research Articles

Catalytic asymmetric Friedel–Crafts alkylation of unprotected indoles with nitroalkenes using a novel chiral Yb(OTf)3–pybox complex

Chiral chloro-indeno pybox has served as a new ligand for the Yb(OTf)3-catalyzed asymmetric Friedel–Crafts alkylation reaction of indoles with nitroalkenes. The tunable nature of pybox ligands enables the rational design of catalysts for optimal performance in terms of both activity and stereoselectivity in a Friedel–Crafts-type reaction. Good to excellent yields and enantioselectivities were obtained for a relatively wide range of substrates, including sterically hindered compounds, under optimized reaction conditions.

Iridium/Zinc-Co-Catalyzed Ring-Opening Reactions of Oxabicyclic Alkenes with Indole Nucleophiles: A Combined Experimental and Theoretical Study

An experimental and theoretical investigation on the iridium/zinc-co-catalyzed ring-opening reactions of oxabicyclic alkenes with indole nucleophiles is reported. The reaction affords trans-3-indolyl-1,2-dihydronaphthalen-1-ol products in good yield with no N-alkylated products observed. The C–C bond-forming reaction does not require prior functionalization and is entirely atom-economic. The mechanism and origins of selectivity in the iridium-catalyzed ring-opening reaction have been examined at the M06-D3/Def2TZVPP level of theory. Orbital analysis and natural population analysis charges demonstrate that the Cα site of the π-allyliridium intermediate is the most electrophilic site of attack. Distortion/interaction analysis reveals that the chemoselectivity likely originates from an earlier-stage transition state between Cα and C3, which requires less distortion energy compared to Cα–N1 during the rate-determining intermolecular nucleophilic attack. Moreover, conceptual density functional theory was used to conceptualize the preferential reactive sites of the nucleophiles probed. The C–C bond-forming step is speculated to proceed through a Friedel–Crafts-type reaction.

Thermally Activated Aryl Thioureas as Brønsted Acid Catalysts for C–C Bond Forming Reactions: Synthesis of Symmetrical Trisubstituted Methanes

AbstractA study on relative catalytic efficacy of 1,3-diaryl thioureas has revealed that 1-[3,5-bis(trifluoromethyl)phenyl]-3-phenylthiourea is an efficient alternative to the Schreiner’s thiourea catalyst (STC) for acid-catalyzed activation of carbonyl compounds in the synthesis of symmetrical trisubstituted methanes (TRSMs) at an elevated temperature. Since the preparation of STC involves the use of toxic thiophosgene, the 1-[3,5-bis(trifluoromethyl)phenyl]-3-phenylthiourea represents an easily accessible and simpler alternative. Strikingly, the temperature-assisted reaction showed significantly shorter reaction time in comparison to photoirradiation in the thiourea-catalyzed Friedel–Crafts type reaction of indole with aldehydes. Simple reaction set-up and excellent yields are some of the highlights of the reported method.

Generation and Reactivity of 1-Imidocarbenium Cations in the Friedel-Crafts-type Reaction.

Herein, we discuss the formation and reactivity of 1-imidocarbenium cations in Friedel-Crafts-type reaction between 1-imidoalkylphosphonium salts and arenes. The observed weakening of Cα-P+ bond is described qualitatively and quantitatively. The determination of rate constants and activation energies of Cα-P+ bond cleavage enabled systematic reactivity investigations of a series of phosphonium salts with different structures. Finally, the application scope for the imidoalkylation of aromatic hydrocarbons was explored. The results confirm that the generated 1-imidocarbenium cations are reactive enough to alkylate strongly activated, less-activated, or even inactivated aromatic compounds.

Metal-free synthesis of 3,3′-bisindolylmethanes in water using Ph3C+[B(C6F5)4]− as the pre-catalyst

We described an efficient catalytic species generated from Ph3C+[B(C6F5)4]− by the water mediated Friedel–Crafts type reaction of indoles with carbonyl compounds to access 3,3′-bisindolylmethanes (BIMs).

Friedel-Crafts-Type Reactions with Electrochemically Generated Electrophiles from Donor-Acceptor Cyclopropanes and -Butanes.

We describe a general electrochemical method to functionalize donor-acceptor (D-A) cyclopropanes and -butanes with arenes utilizing Friedel-Crafts-type reactivity. The catalyst-free strategy relies on the direct anodic oxidation of the strained carbocycles, which leads after C(sp3)-C(sp3) cleavage to radical cations that act as electrophiles for the arylation reaction. Broad reaction scopes in regard to cyclopropanes, cyclobutanes, and aromatic reaction partners are presented. Additionally, a plausible electrolysis mechanism is proposed.

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination.

The hydrofluorocarbon 245 isomers, 1,1,1,3,3-pentafluoropropane, 1,1,1,2,2- pentafluoropropane, and 1,1,1,2,3-pentafluoropropane (HFC-245fa, HFC-245cb, and HFC-245eb) were activated through C–F bond activations using aluminium chlorofluoride (ACF) as a catalyst. The addition of the hydrogen source Et3SiH is necessary for the activation of the secondary and tertiary C–F bonds. Multiple C–F bond activations such as hydrodefluorinations and dehydrofluorinations were observed, followed by hydroarylation and Friedel–Crafts-type reactions under mild conditions.

Friedel-Crafts Type Methylation with Dimethylhalonium Salts.

The dimethylchloronium salt [Me2Cl][Al(OTeF5)4] is used to methylate electron‐deficient aromatic systems in Friedel–Crafts type reactions as shown by the synthesis of N‐methylated cations, such as [MeNC5F5]+, [MeNC5F4I]+, and [MeN3C3F3]+. To gain a better understanding of such fundamental Friedel–Crafts reactions, the role of the dimethylchloronium cation has been evaluated by quantum‐chemical calculations.

2,3,5-Trichlorocyclopent-2-enone derivatives in the Friedel–Crafts reaction with methoxybenzenes and the anticancer activity of the products

The Friedel–Crafts-type reaction of 5-allyl-2,3,5-trichlorocyclopent-2-enones with mono-, di- and trimethoxybenzenes affords the arene ketovinylation products with the cleavage of C3–Cl bond in the starting trichlorocyclopentenones. The cytotoxocity of the products toward normal HEK293 cell lines and three cancer cell lines, SH-SY5Y, A549 and MCF-7, was evaluated.

Lewis Acid Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic N-Sulfonylaziridines.

The first Lewis acid catalyzed stereoconvergent transformation of racemic 2-(hetero)aryl- N-sulfonylaziridines via C-N bond cleavage with nucleophiles is presented. This includes the [3 + 2] annulations with (hetero)aromatic aldehydes and 1,3-disubstituted indoles, asymmetric Friedel-Crafts type reaction with electron-rich (hetero)arenes, and asymmetric aminolysis with amines, providing facile access to chiral 1,3-isoxazolidines, pyrroloindolines, 2-(hetero)arylphenethylamines, and vicinal diamines. This method features a simple and cheaply available complex of Cu(I)-chiral BINAP catalyst, excellent yield and high diastereo- and enantioselectivities, and mild reaction conditions. A mechanism involving type I dynamic kinetic asymmetric transformations (DyKATs) of the racemic aziridines is proposed based on the results of control experiments.

Mechanistic investigation inspired "on water" reaction for hydrobromic acid-catalyzed Friedel-Crafts-type reaction of β-naphthol and formaldehyde.

The mechanism of the HBr-catalyzed Friedel-Crafts-type reaction between β-naphthol and HCHO was investigated by DFT to improve this reaction. The HBr-H2 O co-catalyzed the preferential pathway undergoes the concerted nucleophilic addition and hydrogen shift, stepwise followed by H2 O elimination and the CC bond formation. The origin of the high catalytic activity of HBr is ascribed to CH···Br- and OH···Br- interactions, which suggest that the active species is Br- . Moreover, water molecules efficiently assist in improving the activity of Br- . The computational results show that solvent polarity profoundly affects the activation barriers. To our delight, the activation barrier of the rate-determining step for the favored pathway in water is comparable (0.6 kcal/mol difference) with that in acetonitrile. The experimental observation further confirmed our results and demonstrated that the title reaction can be successfully achieved "on water." Therefore, we open a new efficient and green strategy for the synthesis of biphenol derivatives. © 2017 Wiley Periodicals, Inc.

Activation of Chlorinated Methanes at the Surface of Nanoscopic Lewis Acidic Aluminum Fluorides

AbstractWe report on the activation of chlorinated methanes by the heterogeneous catalysts aluminum chlorofluoride (ACF) and high‐surface aluminum fluoride (HS‐AlF3) under moderate conditions. For comparison, chlorinated toluenes and 1,2‐dichloroethane were also tested. The strong Lewis acids are able to promote the cleavage of C−Cl bonds in the presence of Et3SiH. The C−Cl bonds were converted into C−H bonds through hydrodechlorination reactions or, in the presence of benzene, into C−C bonds through Friedel–Crafts type reactions. The catalytic reactions show high conversions.

Coupling of arylboronic acids with benzyl halides or mesylates without adding transition metal catalysts

We report herein a transition-metal-free coupling reaction of arylboronic acids with benzyl halides and mesylates for the construction of C(sp2)C(sp3) bonds. A unique feature of this coupling reaction is the formation regioisomers in some cases. Mechanistic studies suggest that this reaction may proceed via an unprecedented Friedel–Crafts-type reaction pathway under base conditions with the assistance of boronic acid moiety.

Passerini/Friedel–Crafts Route towards Indole Derivatives

The Passerini adducts of various electron-rich aromatic aldehydes with pivalic acid were used as electrophiles towards indoles in a Friedel–Crafts-type reaction. The Friedel–Crafts step was performed under microwave conditions using a catalytic amount of FeCl3.

Synthesis of Spirocyclic and Fused Cyclic Compounds by Transition-Metal-Catalyzed Intramolecular Friedel–Crafts-Type Reactions of Phenol Derivatives

This account describes the development of novel dearomatization reactions of phenols using transition-metal-catalyzed ipso-Friedel–Crafts-type processes. In general, phenols function as O-nucleo­philes in transition-metal-catalyzed allylic substitution reactions, providing the corresponding aryl ethers. We found that, however, an intramolecular ipso-Friedel–Crafts allylic alkylation of phenols proceeded smoothly in the presence of a palladium catalyst, producing various spiro[4.5]cyclohexadienone derivatives. This finding led us to launch detailed investigations into this type of reaction. Pd-catalyzed intramolecular Friedel–Crafts allylic alkylation of phenols was next examined to synthesize 10-vinyl 9,10-dihydrophenanthrene derivatives. This reaction was successfully extended to a catalytic asymmetric process. We also developed a novel synthetic method for spiro[5.5]cyclohexadienones based on a Pd-catalyzed intramolecular ipso-Friedel–Crafts-type addition of phenols to η3-propargylpalladium(II) intermediates. Mechanistic studies revealed that the present reaction proceeds through a rearomatization-assisted oxidative addition. Moreover, a Au-catalyzed intramolecular ipso-Friedel–Crafts alkenylation of phenols with a terminal alkyne is discussed. 1 Introduction 2 Pd-Catalyzed Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 2.1 Synthesis of Spirocyclohexadienone Derivatives by Pd-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols 2.2 Mechanistic Considerations 2.3 Application to Cascade Reaction Processes 2.4 Asymmetric Synthesis of Dihydrophenanthrene Derivatives by Pd-Catalyzed Asymmetric Intramolecular Friedel–Crafts Allylic Alkylation of Phenols 3 Dearomatization of Phenols by Activation of Propargyl Carbonates with a Pd Catalyst 4 Au-Catalyzed Intramolecular ipso-Friedel–Crafts Alkenylation of Phenols 5 Summary and Outlook

ChemInform Abstract: Intermolecular Dearomative C2‐Arylation of N‐Ac Indoles Activated by FeCl3.

We report the FeCl3-mediated direct addition of electron-rich arenes to the C2-position of electrophilic N-Ac indoles under mild conditions (room temperature, air). No functional group is required on the arene nucleophile: one of its C–H bonds is added to the C2C3 double bond of the indole nucleus in a Friedel–Crafts-type reaction. This dearomatisation process delivered a broad range of C2-arylated indolines.

Facile synthesis of nonsymmetrical heteroaryl-substituted triarylmethanes via the FeCl3·6H2O-catalyzed two-step Friedel-Crafts-type reaction.

The FeCl3·6H2O-catalyzed three-component aza-Friedel-Crafts reaction of aromatic/heteroaromatic compounds, aromatic aldehydes and tert-butyl carbamate was reported. The subsequent Friedel-Crafts-type alkylation of the resulting tert-butyl diarylmethyl carbamate with heteroaromatic compounds under "open-flask" at room temperature was also performed. The two-step reaction was especially useful for the synthesis of functionalized nonsymmetrical heteroaryl-substituted triarylmethanes in good yields under an air atmosphere at room temperature.

Synthesis of polysubstituted 1,2-dihydroquinolines and indoles via cascade reactions of arylamines and propargylic alcohols catalyzed by FeCl3·6H2O.

An efficient, environmentally friendly and high-yielding route from inexpensive starting materials to 1,2-dihydroquinolines has been developed. This procedure proceeded via a cascade Friedel-Crafts-type reaction and 6-endo-trig hydroamination under the catalysis of FeCl3·6H2O, involving the formation of two new σ (C-C and C-N) bonds in a single operation for the construction of a 1,2-dihydroquinoline skeleton in good to excellent yields.

Friedel-Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid.

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates promoted by trifluoromethanosulfonic acid afforded diethyl 1-(pyrene-1-carbothioamido)alkylphosphonates in 83–94% yield. These compounds were transformed, in 87–94% yield, into the corresponding diethyl 1-(pyrene-1-carboxamido)alkylphosphonates by treatment with Oxone®. 1-(Pyrene-1-carboxamido)methylphosphonic acid was obtained in a 87% yield by treating the corresponding diethyl phosphonate with Me3Si-Br in methanol. All of the synthesized amidophosphonates were emissive in solution and in the solid state. The presence of a phosphonato group brought about an approximately two-fold increase in solution fluorescence quantum yield in comparison with that of a model N-alkyl pyrene-1-carboxamide. This effect was tentatively explained by stiffening of the amidophosphonate lateral chain which was caused by the interaction (intramolecular hydrogen bond) of phosphonate and amide groups. The synthesized phosphonic acid was soluble in a biological aqueous buffer (PBS, 0.01 M, pH 7.35) and was strongly emissive under these conditions (λem = 383, 400 nm, τ = 18.7 ns, ΦF > 0.98). Solid-state emission of diethyl 1-(pyrene-1-carboxamido)methylphosphonate (λmax = 485 nm; ΦF = 0.25) was assigned to π–π aggregates, the presence of which was revealed by single-crystal X-ray diffraction analysis.

An Asymmetric Organocatalytic Quadruple Domino Reaction Employing a Vinylogous Friedel-Crafts/Michael/Michael/Aldol Condensation Sequence.

An organocatalytic quadruple cascade initiated by a Friedel–Crafts-type reaction is described. The (S)-diphenylprolinol trimethylsilyl ether catalyzed reaction yields highly functionalized cyclohexenecarbaldehydes bearing a 1,1-bis[4-(dialkylamino)phenyl]ethene moiety and three contiguous stereogenic centers. The reaction tolerates various functional groups and all products are obtained with very good diastereoselectivity and with virtually complete enantiomeric excess.