Friedel-Crafts Type Research Articles

Self-catalytic photochemical three-component reaction for the synthesis of multifunctional 3,3-disubstituted oxindoles

A visible-light-induced, self-catalyzed multi-component reaction has been established, delivering a facile and atom-economic method to 3,3-disubstituted oxindoles with wild functional group tolerance and good to excellent yields under photocatalyst-, oxidant- and base-free conditions. The process involves photocatalytic Friedel–Crafts type coupling, halogenation, and oxidation reactions, which makes it practical and attractive. Moreover, this strategy contributes to the development of an efficient protocol for accessing electrochemically active 3,3-disubstituted oxindoles, which have potential applications in flow batteries.

HFIP-Mediated Desulfinative Friedel-Crafts Cyclobutenylation Reaction.

In 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP), gem-bis(triflyl)cyclobutenes, which can be prepared by the (2+2) cycloaddition reaction of Tf2C=CH2 with alkynes, underwent desulfination to generate the corresponding cyclobutenyl cation. This unique reactivity was successfully applied to the Friedel-Crafts type cyclobutenylation reaction of several (hetero)aromatic compounds.

A novel Fe(III) and 2-amino-perimidinium based hybrid material catalyzed friedel–Crafts type hydroarylation of alkynes: Scope and mechanism

A new inorganic-organic hybrid material with the structural formula (C51H66N9)3[FeCl4]·2Cl consisting of iron(III) center, 2-amino-perimidinium ligand and free chloride ions was synthesized. In addition, the compound was characterized by single-crystal X-ray diffraction and Fourier-transform infrared spectroscopy techniques. The structural arrangements and hydrogen bonding interactions in the compound were studied and successfully employed in the catalytic hydroarylation of alkynes and arenes to produce the corresponding 1,1-diaryl alkene derivatives. Gratifyingly, when nitromethane was employed as a solvent, the title compound displayed excellent catalytic activity with moderate to high conversions. Stoichiometric reactions and experimental data both provided key evidence in support of the reaction mechanism.

Enantioselective Synthesis of α-Quaternary Isochromanes by Oxidative Aminocatalysis and Gold Catalysis.

A novel strategy that combines oxidative aminocatalysis and gold catalysis allows the preparation of chiral α-quaternary isochromanes, a motif that is prevalent in natural products and synthetic bioactive compounds. In the first step, α-branched aldehydes and propargylic alcohols are transformed into α-quaternary ethers with excellent optical purities (>90 % ee) via oxidative umpolung with DDQ and an amino acid-derived primary amine catalyst. Subsequent gold(I)-catalyzed intramolecular hydroarylation affords the isochromane products with retention of the quaternary stereocenter. A second approach explores the use of allylic alcohols as reaction partners for the oxidative coupling to furnish α-quaternary ethers with generally lower enantiopurities. Stereoretentive cyclization to isochromane products is achieved via intramolecular Friedel-Crafts type alkylation with allylic acetates as a reactive handle. A number of synthetic elaborations and a biological study on these α-quaternary isochromanes highlight the potential applicability of the presented method.

Asymmetric Synthesis of Hydroindoles via Desymmetrizing [3+2] Annulation of p-Quinamines and Arylalkylketenes.

The asymmetric desymmetrizing [3+2] annulation reaction of p-quinamines and arylalkylketenes to synthesize hydroindoles was realized. Catalyzed by chiral bisguanidinium hemisalt via multiple hydrogen bond interactions, enantiomerically enriched products with reversal of diastereoselectivity in comparison with the racemic version were afforded in good yields under mild reaction conditions. Diaryl-substituted hydroindoles could also perform the Friedel-Crafts type of addition to give more complicated multicycles. Density functional theory calculations revealed that the enantio- and diastereoselectivity stem from varied hydrogen-bonding manners.

Synthesis of Pyrrole-Sharing Fused Porphyrinoid Hybrids by Post-fabrication of Ni(II) Porphyrins.

Pyrrole-sharing fused hybrids of NiII porphyrin with PdII N-confused(NC)-corrole and PdII NC-oxaporphyrin were synthesized by post-fabrication of NiII porphyrins. Specifically this consists of Friedel-Crafts type aromatic substitution reaction of meso-free NiII porphyrin with α,α'-dibromotripyrrin and Pd(OAc)2 assisted cyclization, and final heating to induce a Pd-C bond formation. NiII porphyrins fused with PdII NC-corrole and with PdII NC-oxaporphyrins show coplanar structures with a shared pyrrole unit. In these hybrids, the PdII NC-oxaporphyrin is aromatic and the PdII NC-corrole is moderately antiaromatic and these local electronic properties interact to influence the whole network.

Three-component Friedel–Crafts-type difunctionalization of ynamides with (hetero)arenes and iodine(iii) electrophile

A three-component Friedel–Crafts type difunctionalization of ynamides with an iodine(iii) electrophile and electron-rich (hetero)arenes has been developed, enabling regio- and stereoselective synthesis of densely functionalized enamides.

Influence of Monomer Configuration on the Performance of Poly(quaterphenyl piperidinium) Anion Exchange Membranes

Polymeric anion exchange membranes (AEM)s are crucial components in many electrochemical energy devices where the performance is strongly influenced by the ionic conductivity, mechanical robustness, and thermochemical stability of the materials.1,2 AEMs are susceptible to degradation due to the chemically aggressive nature of the hydroxide ion, which significantly restricts their long-term applicability, especially at elevated temperature.3,4 Improving the polymer backbone design by, e.g., eliminating ether linkages from the polymer backbone is an approach to improve alkaline stability.5 Moreover, by introducing multi-ring aromatic segments, the rigidity, hydrophobicity, and “blockiness” of the polymer backbone increase, leading to mechanical robustness and enhanced microphase separation (ionic clustering) of the AEM.6 Obviously, the configuration of the multi-ring aromatic segments will have an influence, which can be used to tune and improve the properties of the polymers and AEMs.7,8 In the present project, we investigated the influence of the configuration of quaterphenyl monomers in poly(quaterphenyl piperidinium)s on the corresponding AEM properties. Three different monomers (isomers) with different connectivity between the four rings were investigated: para-para, para-meta, and meta-meta. The polymers were prepared by superacid-mediated Friedel-Crafts type polycondensations (polyhydroxyalkylations) involving N-methyl piperidone and the respective quaterphenyl. Subsequently, the polymers were fully quaternized with methyl iodide to prepare a series of ether-free poly(quaterphenyl piperidinium)s with different backbone configurations and chain flexibility. In this presentation, the influence of the quaterphenyl configuration on AEM properties such as water uptake, hydroxide conductivity, ionic clustering, thermal and chemical stability will be discussed. Li, C.; Baek, J. B., Nano Energy 2021, 87, 106162.Aili, D.; Rykær Kraglund, M.; Rajappan S.C.; Serhiichuk, D.; Xia Y.; Deimede V.; Kallitsis, J.; Bae, C.; Jannasch, P.; Henkensmeier, D.; Jensen, J.O., ACS Energy Lett. 2023, 8, 1900–1910.Mohanty, A. D.; Bae, C., Mater. Chem. A 2014, 2(41), 17314-17320.Jeon, J. Y.: Park, S.; Han, J.; Maurya, S.; Mohanty, A. D.; Tian, D.; Saikia, N.; Hickner, M. A.; Ryu, C. Y.; Tuckerman, M. E.; Paddison, S. J.; Kim, Y. S.; Bae, C., Macromolecules 2019, 52(5), 2139–2147.Olsson, J. S.; Pham, T. H.; Jannasch, P., Funct. Mater. 2018, 28(2), 1702758.Liu, M.; Hu, X.; Hu, B.; Liu, L.; Li, N., Membr. Sci. 2022, 642, 119966.Pham, T. H.; Olsson, J. S.; Jannasch, P., Mater. Chem. A 2019, 7(26), 15895-15906.Lee, W-H;Park, E. J.; Junyoung, H.; Shin, D. W.; Kim, Y. S.; Bae, C., ACS Macro Lett. 2017, 6(5), 566–570.

Hydroxide Conducting Naphthalene-Containing Polymers and Membranes Via Polyhydroxyalkylations

Anion exchange membranes (AEMs) are critical components of alkaline membrane water electrolyzers and fuel cells that are under development today [1,2]. Consequently, there is a strong demand for highly conductive and alkali-stable AEMs. In this context, polyhydroxyalkylation has emerged as one of the most efficient synthetic pathways to chemically resistant polymer backbones for AEMs. In these Friedel-Crafts type polycondensations, an electron-rich aromatic compound reacts with an activated ketone or aldehyde to produce an aryl-ether-free polymer. The desired quaternary ammonium cations are then usually introduced through a Menshutkin reaction [3,4].In the current work, we have employed naphthalene-based compounds as monomers in polyhydroxyalkylations to prepare a series of high-molecular weight poly(naphthalene alkylene)s with various naphthalene contents. These polymers were then quaternized and cast into AEMs. Here, we will discuss the influence of the naphthalene monomer type and content on AEM properties such as solubility, water uptake, ion conductivity, ionic clustering, thermal and alkaline stability, and also the prospects of using these AEMs in electrochemical systems.

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.

N-heterocyclic iminium ions catalyzed Friedel–Crafts type alkenylation of arenes with alkynes: A metal free and solvent free approach

The current manuscript elucidates a pioneering approach for achieving regioselective Markovnikov-type hydroarylation of alkynes, without the use of any metal catalysts. The aforementioned process is expedited through the implementation of 2-amino-perimidinium bromide and TFA as catalyst systems and is executed in the absence of solvents, thereby expanding the range of substrates (including arenes and alkynes). The correlation between the stoichiometric reactions and experimental data substantiates the postulated reaction mechanism.

Facile Construction of Functionalized 4H‐Chromene Scaffolds via Sn(OTf)2‐Catalyzed C−H Functionalization/Cyclization Reaction and Ir‐Catalyzed Direct C−H Amidation

AbstractAn efficient strategy for the construction of 4H‐chromene scaffolds from naphthols and conjugated diketones through a sequential Sn(OTf)2‐catalyzed Friedel–Crafts type C−H functionalization/cyclization process has been described. The Ir‐catalyzed C−H amination of these products could also be performed with the assistance of the carbonyl as a weak directing group, which produced a series of amino‐modified 4H‐chromene compounds in good yields.

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.

Heptagon/Octagon-Fused Diporphyrins or Spiro-Pentagon-Bridged Dichlorin from p-Terphenylene-Bridged Diporphyrin.

Intramolecular fusion reactions of a p-terphenylene-bridged NiII porphyrin dimer gave different products, depending upon reaction conditions. Oxidation with Fe(OTf)3 provided syn- and anti-doubly heptagon-fused NiII porphyrin dimers showing enlarged π-electronic networks, probably via a radical mechanism, while treatment with methanesulfonic acid provided a spiro-pentagon-bridged NiII chlorin dimer via acid-catalyzed Friedel-Crafts type cyclization. Further, a doubly octagon-fused NiII porphyrin dimer was synthesized via a sequence of double meso-formylation, reduction to corresponding diol, and BF3 -catalyzed cyclization.

Substrate-Dependent Selectivity in Sc(OTf)3-Catalyzed Cyclization of Alkenoic Acids and N-Protected Alkenamides

Five- and six-membered ring lactones and lactams are ubiquitous frameworks in various natural and synthetic molecules and are key building blocks in organic synthesis. Catalytic addition of an O-H or N-H bond across an unactivated C–C double bond is an appealing approach to rapidly access such highly valuable N- and O-containing skeletons in a waste-free and 100% atom efficient process. Herein, we report, for the first time, the efficient and high-yield cyclization of δ/ε-alkenoic acids and N-protected δ-alkenamides catalyzedby practical and easily accessible Lewis acid scandium(III) triflate under thermal and microwave conditions. The selectivity outcome of the reaction of δ/ε-alkenoic acids was dependent on the substitution patterns of the backbone chain and alkene moiety, leading to the exclusive formation of either the corresponding γ/δ-lactones via an O-selective cyclization or the Friedel–Crafts-type product by C-selective cyclization. An uncommon and rarely disclosed O-selective cyclization occurred preferentially or exclusively when N-protected δ-alkenamides were engaged in the reaction. The atom selectivity of the cyclization was unambiguously confirmed by single crystal X-ray crystallography.

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.

Friedel-Crafts Acylation of Aminocarboxylic Acids in Strong Brønsted Acid Promoted by Lewis Base P4O10.

The amino group in aminocarboxylic acids is sufficiently basic to be protonated in strong acids, and consequently, ionization of the carboxylic acid to an acylium ion is blocked due to charge-charge repulsion. Thus, acylation of aromatic compounds is significantly retarded in Friedel-Craft type reactions. We found that Friedel-Crafts acylation with aminocarboxylic acids can proceed smoothly even in a strong Brønsted acid (triflic acid, TfOH) if the Lewis base P4O10 is added. Here we describe the Friedel-Crafts acylation reactions of anthranilic acid and α- to δ-aminocarboxylic acids with benzene derivatives in the presence of P4O10. Non-amino-containing carboxylic acids as well as N-containing heteroaromatic carboxylic acids are available, and α-amino acids can be directly utilized without any protective group. Most substrates afford acylation products in high yields, although some epimerization/racemization may occur. Density functional theory (DFT) calculations suggested that P4O10 neutralizes the protonated amine, converting the N-H covalent bond to a N-hydrogen bond and allowing the carboxylic acid OH functionality to serve as a good leaving group.

Electrochemical Dearomative Spirocyclization of N-Acyl Thiophene-2-sulfonamides.

The Friedel-Crafts type alkylation of C2-tethered thiophenes has been reported to be nonregioselective. Taking advantage of the highly regioselective 5-exo-trig spirocyclization of an electrochemically generated amidyl radical, we have unraveled an electrochemical dearomative spirocyclization of N-acyl thiophene-2-sulfonamides. Various nucleophilic agents, including carboxylates, alcohols, and fluoride, are readily incorporated to afford the remotely functionalized spirocyclic dihydrothiophenes, and their novel spirocyclic scaffolds have been shown to exhibit promising antitumor activities.

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.

Recent Progress on Trifluoromethylthiolation of (Hetero)Aryl C–H Bonds with Electrophilic Trifluoromethylthiolating Reagents

The incorporation of trifluoromethylthio group (−SCF3) into small molecules has attracted considerable attention recently, because of its unique properties, which are beneficial for drug discovery. The preparation of trifluoromethylthiolated (hetero)arenes, a leading class of trifluoromethylthiolated compounds, is one of the hot topics in organic chemistry frontiers, and much effort have been exerted to access them. In this review, special attention is given to the preparation of (hetero)aryl C–H bonds by Friedel–Crafts-type trifluoromethylthiolation and transition-metal-catalyzed aromatic C–H bond activation/trifluoromethylthiolation with electrophilic trifluoromethylthiolating reagents.