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A relay catalytic system is developed for the asymmetric hydrogenative coupling of indoles with α,β-unsaturated ketones, affording enantioenriched chiral γ-indole alcohols with broad substrate scope and excellent enantioselectivities (32 examples, up to >99% ee). Mechanistic studies suggest that the relay catalytic system consists of copper-catalyzed alkylation and ruthenium-catalyzed asymmetric hydrogenation. [ABSTRACT FROM AUTHOR]

The Friedel-Crafts alkylation reaction represents a pivotal organic transformation for the formation of carbon-carbon bonds, holding extensive applications within the realms of both organic synthesis and pharmaceutical chemistry. This article presents a comprehensive review of the mechanism underlying the Friedel-Crafts alkylation reaction, alongside recent advancements in various catalytic approaches, such as metal catalysis, organocatalysis, visible light photocatalysis, enzymatic and electrochemical catalysis. By merging cutting-edge scientific developments with undergraduate teaching content, this review endeavors to inspire students' learning interests while fostering their capacity for innovative thinking. [ABSTRACT FROM AUTHOR]

This article provides an overview of recent advancements in C–H functionalization using NHC-Ni/Al bimetallic catalysis. The combination of N-heterocyclic carbene (NHC) ligands with nickel and aluminum catalysts allows for the activation of C–H bonds, enabling the direct functionalization of aromatic compounds. The use of bulkier and electron-donating NHC ligands has improved reactivity, and chiral NHC ligands have enabled enantioselective C–H alkylation reactions. However, challenges remain, and further research is needed to expand the range of substrates and reactions and develop new ligands and catalysis modes for wider synthetic applications. [Extracted from the article]

The dual‐site synergistic effect in heterogeneous catalysis is quite interesting, and also complex because at least two substrate molecules are adsorbed or activated on the catalyst surface, which apparently needs two spatially separated and functionally independent active sites. It would become more difficult when the substrate molecules are large ones. The replacement of Al3+ in Al4B6O15 lattice with Co2+ leads to the formation of unsaturated Co2+ (4‐fold coordination) along with oxygen vacancies (Ov). The former one behaves as a medium‐strength Lewis acid site, and can adsorb and activate molecules with a nitro group (e. g., β‐nitrostyrene). The latter one can adsorb and activate oxygen species, which further activates the indole derivatives. Next, the spatially separated dual sites on the catalyst surface can synergistically and efficiently catalyze their Friedel‐Crafts alkylation reactions under mild conditions. The high durability can be proved by the as‐maintained high yields, that is, 98, 93, 96, 92 and 90 % for 5 runs, respectively. The reaction kinetics obey the second‐order characteristic. Annealing under hydrogen condition can further generate more surficial Ov, leading to an improvement to the catalytic activity. A simple and probably routine aliovalent doping endows such a complex synergistic catalysis involving two large substrate molecules, providing an inspired perspective of developing dual‐site catalysts. [ABSTRACT FROM AUTHOR]

A novel enantiopure π‐allylruthenium(IV) precatalyst allowed the enantioselective and stereospecific allylations of indoles and gave access to indolin‐3‐ones, containing vicinal stereogenic centers. Facile separation of diastereoisomers exhibiting opposite circularly polarized luminescence (CPL) activities in diverse solvents, including water, demonstrated the potential of these sustainable transformations and of the newly prepared molecules. [ABSTRACT FROM AUTHOR]

The incorporation of organocatalysts into protein scaffolds holds the promise of overcoming some of the limitations of this powerful catalytic approach. Previously, we showed that incorporation of the non‐canonical amino acid para‐aminophenylalanine into the non‐enzymatic protein scaffold LmrR forms a proficient and enantioselective artificial enzyme (LmrR_pAF) for the Friedel‐Crafts alkylation of indoles with enals. The unnatural aniline side‐chain is directly involved in catalysis, operating via a well‐known organocatalytic iminium‐based mechanism. In this study, we show that LmrR_pAF can enantioselectively form tertiary carbon centres not only during C−C bond formation, but also by enantioselective protonation, delivering a proton to one face of a prochiral enamine intermediate. The importance of various side‐chains in the pocket of LmrR is distinct from the Friedel‐Crafts reaction without enantioselective protonation, and two particularly important residues were probed by exhaustive mutagenesis. [ABSTRACT FROM AUTHOR]

The exploitation of high efficiency non-precious metal electrocatalysts towards oxygen reduction reaction (ORR) is great significant for large-scale commercialization of next-generation fuel cells. In this work, we designed and fabricated a series of porous carbazole-based N and M (Co, Fe) doped carbon framework catalysts which were obtained by the pyrolysis of a N-rich hypercrosslinked polymers derived from Friedel–Crafts reaction (abbreviated as TSP-HCP-900) followed by the incorporation of metal into the as-resulted N rich carbon (abbreviated as M-TSP-HCP-900, M = Co, Fe). Based on the high specific surface, excellent porosity, large pyridine nitrogen content and synergistic catalytic effects between the N dopants and metal nanoparticles, the M-TSP-HCP-900 exhibited superior ORR catalytic activity. Among them, the Co-TSP-HCP-900 possesses better electrocatalysis, i.e., a high diffusion limiting current density of 4.74 mA cm−2, half-wave potential of 0.8 V (vs. RHE, the same below) and onset potential of 0.9 V were found, respectively. In addition, this catalyst also discloses an excellent methanol tolerance, better durability and a biased 4e− reaction pathway, which are comparable to state-of-the-art Pt/C catalysts. Taking advantage of mentioning above, the M-TSP-HCP-900 may hold great potentials as promising alternative of precious metal catalysts for electrochemical energy conversion and storage. • Transition metal and nitrogen co-doped carbon (M-N/C) were prepared as non-precious ORR electrocatalysts. • It yields a half-wave potential of 0.80 V and onset potential of 0.90 V (vs. RHE) in alkaline medium. • It exhibits a high diffusion limiting current density of 4.74 mA cm−2. • It shows better stability and methanol resistance than that of commercial 20 wt% Pt/C. [ABSTRACT FROM AUTHOR]

Hydroarylation reactions via C−H activation, which compensate for shortcomings of classical methods based on the Friedel‐Crafts reaction, is one of the most attractive methods to synthesize substituted arenes. This Personal Account reviews our recent studies on iridium‐catalyzed intermolecular hydroarylation of vinyl ethers, alkynes, bicycloalkenes, and 1,3‐dienes, and intramolecular hydroarylation of m‐allyloxyphenyl ketones, where asymmetric addition reactions are included. A cationic iridium catalyst, which is generated from chloroiridium [IrCl] and NaBArF4 [ArF=3,5‐(CF3)2C6H3], or a hydroxoiridium [Ir(OH)] complex is effective in catalyzing the hydroarylation depending on the substrates. 1,5‐Cyclooctadiene (cod), chiral dienes, and conventional bisphosphines function as ligands controlling the high reactivity and selectivity of the catalysts in the hydroarylation. H/D exchange reaction of alkenes by use of a key intermediate of the hydroarylation reaction is also described. [ABSTRACT FROM AUTHOR]

Chalcogen bonding results from non‐covalent interactions occurring between electrodeficient chalcogen atoms and Lewis bases. Among the chalcogens, tellurium is the strongest Lewis acid, but Te‐based compounds are scarcely used as organocatalysts. For the first time, telluronium cations demonstrated impressive catalytic properties at low loadings in three benchmark reactions: the Friedel–Crafts bromination of anisole, the bromolactonization of ω‐unsaturated carboxylic acids and the aza‐Diels–Alder between Danishefsky's diene and imines. The ability of telluronium cations to interact with a Lewis base through chalcogen bonding was demonstrated on the basis of multi‐nuclear (17O, 31P, and 125Te) NMR analysis and DFT calculations. [ABSTRACT FROM AUTHOR]

Phosphazene‐containing porous materials are of a great interest due to their unique properties, caused by the synergetic presence of nitrogen and phosphorus atoms, and have found applications as adsorbents, basic catalysts, etc. On the other hand, cage‐like silsesquioxanes are ideal building blocks for the preparation of covalently‐linked porous materials. Here two new phosphazene‐functionalized organosilsesquioxane cage‐based porous polymers were synthesized successively by a Friedel‐Crafts reaction of hexapyrrolylcyclotriphosphazene with octavinylsilsesquioxane in the presence of AlCl3 and CF3SO3H as catalysts. The nature of acid catalysts barely influenced the character of pores due to the interaction of catalysts with basic nitrogen atoms of phosphazene units. The obtained polymers exhibited high efficiency as metal‐free catalysts for the Knoevenagel reaction. This work opens new perspectives in the use of porous polymers based on cage‐like organosiloxane compounds as basic catalysts for various reactions. [ABSTRACT FROM AUTHOR]

Quaternary phosphonium salts have been extensively used in organic synthesis as Lewis acid organocatalysts. This review covers recent applications of phosphonium salts as Lewis acidic catalysts for Mannich, Strecker, and Friedel‐Crafts reactions for the formation of C−C bonds, annulation reactions, etc., allowing the construction of structurally diverse and synthetically useful architectures. [ABSTRACT FROM AUTHOR]

The tight binding enabled by tailor‐made macrocycles can be manipulated for tuning the catalysis process. In parallel to well‐developed crown ether‐based cation‐binding catalysis, a macrocycle‐enabled counteranion trapping strategy is presented for boosting highly efficient and enantioselective catalysis. A set of bis‐diarylthiourea macrocycles containing two BINOL moieties were designed and synthesized. They possess a well‐confined chiral cavity and strong binding affinities towards disulfonate anions. Caused by the tight binding, just 1 mol % macrocycle in combination with 1 mol % ethanedisulfonic acid can promote excellent conversion and up to 99 % ee in the Friedel–Crafts reaction of indoles with imines. The acid or the macrocycle alone do not afford any reactivity. The high catalytic efficiency and excellent stereocontrol was ascribed to large, complexation‐induced acidity enhancement and tight ion‐pairing facilitated by cave‐like macrocyclic cavity. [ABSTRACT FROM AUTHOR]

We examine the cyclization of chiral bis-benzylidenesuccinate 6 (precursor to podophyllotoxin-related cyclolignans) in different conditions. Under acid catalysis, a new type of cyclolignan was obtained via cyclization/intramolecular Friedel-Crafts tandem reaction. The structure of the product was confirmed by spectroscopic data and X-ray diffraction. Also, a plausible mechanism of this transformation was proposed. [ABSTRACT FROM AUTHOR]

Friedel–Crafts alkylation reactions constitute a very important class of reactions which are usually catalysed in the liquid phase using Lewis acids at the industrial scale. Diphenyl methane synthesised by Friedel–Crafts alkylation from benzene with benzyl chloride has been interesting in organic synthesis, perfumes and dyes. The new environmental legislation recommends a green and reusable catalyst system that is environmentally benign which leads to minimal pollution and waste generation. Chloroaluminate ionic liquids (ILs) have been used immensely as homogeneous catalyst in the organic synthetic processes. Though these ILs have multiple advantages, their synthesis process involves certain disadvantages like multiple step synthesis, viz. use of solvents and its removal after reaction, removal of precursors, solvent washing for removal of trace impurities and drying of salt/adduct. We have established a novel single-step synthesis method of chloroaluminates from tributylamine and aluminium chloride via amine–aluminium chloride adduction using suitable solvent or one of the reactants as reaction medium. The process improved the atom economy, reduced the use of volatile organic chemicals and drastically minimised the generation of wastes. Formation of chloroaluminate ILs was confirmed by FTIR, 27Al NMR and mass spectroscopy (ESI–MS), and other physicochemical properties were also determined. The chloroaluminate IL was used as catalyst for Friedel–Crafts benzylation of benzene. The performance of the ILs as catalyst showed higher catalytic activity and could be recycled twice for benzylation reaction. Reaction parameters were also optimised to achieve higher yields of diphenyl methane. Tributylamine can be easily recovered by hydrolysis of spent IL which would moderate the chemical oxygen demand in generated effluent. [ABSTRACT FROM AUTHOR]

Since the first report by Evans in asymmetric Friedel‐Crafts reactions, the use of acyl‐imidazoles has blossomed as powerful ester/amide surrogates. The imidazole scaffold indeed displays stability and special activation features allowing both better reactivity and selectivity in traditional ester/amide functionalizations: α‐(enolate chemistry), β‐(conjugate additions), α,β‐(cycloadditions) or γ/δ‐(vinylogous). An overview of the contemporary and growing interest in acyl‐imidazoles in metal‐ and organo‐catalyzed transformations (bio‐hybrid catalytic systems will be fully described in a back‐to‐back Minireview) will be highlighted. Moreover, post‐functionalization expediencies are also going to be discussed in this Minireview. [ABSTRACT FROM AUTHOR]

A stereoselective synthesis of functionalized β‐amino α‐substituted tryptamines has been achieved by a sequential asymmetric organocatalytic three‐component electrophilic amination and photocatalyzed Friedel‐Crafts reaction of indoles with moderate to high diastereoselectivities (up to >99 : 1 dr) and excellent enantioselectivities (up to >99 % ee). We also demonstrated that the β‐amino α‐substituted tryptamines can be successfully engaged in a further catalytic step, furnishing various α,β‐substituted tryptamines without erosion of enantioselectivity and with complete diastereoselectivity. [ABSTRACT FROM AUTHOR]

Crystalline solid materials are platforms for the development of effective catalysts and have shown vast benefits at the frontiers between homogeneous and heterogeneous catalysts. Typically, these crystalline solid catalysts outperformed their homogeneous analogs due to their high stability, selectivity, better catalytic activity, reusability and recyclability in catalysis applications. This point of view, comprising significant features of a new class of porous crystalline materials termed as metal‐organic frameworks (MOFs) engendered the attractive pathway to synthesize functionalized heterogeneous MOF catalysts. The present review includes the recent research progress in developing both hydrogen‐bond donating (HBD) MOF catalysts and MOF‐supported single‐site catalysts (MSSCs). The first part deals with the novel designs of urea‐, thiourea‐ and squaramide‐containing MOF catalysts and study of their crucial role in HBD catalysis. In the second part, we discuss the important classification of MSSCs with existing examples and their use in desired catalytic reactions. In addition, we describe the relative catalytic efficiency of these MSSCs with their homogeneous and similarly reported analogs. The precise knowledge of discussed heterogeneous MOF catalysts in this review may open the door for new research advances in the field of MOF catalysis. [ABSTRACT FROM AUTHOR]

The catalytic activity, kinetics, and quantification of H‐bonding ability of incompletely condensed polyhedral oligomeric silsesquioxane (POSS) silanols are reported. POSS‐triols, a homogeneous model for vicinal silica surface sites, exhibit enhanced H‐bonding compared with other silanols and alcohols as quantified using a 31P NMR probe. Evaluation of a Friedel–Crafts addition reaction shows that phenyl‐POSS‐triol is active as an H‐bond donor catalyst whereas other POSS silanols studied are not. An in‐depth kinetic study (using RPKA and VTNA) highlights the concentration‐dependent H‐bonding behavior of POSS‐triols, which is attributed to intermolecular association forming an off‐cycle dimeric species. Binding constants provide additional support for reduced H‐bond ability at higher concentrations, which is attributed to competitive association. POSS‐triol self‐association disrupts H‐bond donor abilities relevant for catalysis by reducing the concentration of active monomeric catalyst. [ABSTRACT FROM AUTHOR]

Alkylation of arenes is one of the most fundamental transformations in chemical synthesis and leads to privileged scaffolds in many areas of science. Classical methods for the introduction of alkyl groups to arenes are mostly based on the Friedel–Crafts reaction, radical additions, metalation, or prefunctionalization of the arene: these methods, however, suffer from limitations in scope, efficiency, and selectivity. Moreover, they are based on the innate reactivity of the starting arene, favoring the alkylation at a certain position and rendering the introduction of alkyl chains at other positions much more challenging. This can be addressed by the use of a directing group that facilitates, in the presence of a metal catalyst, the regioselective alkylation of a C−H bond. These directed alkylations of C−H bonds in arenes will be comprehensively summarized in this Review. [ABSTRACT FROM AUTHOR]

The Friedel–Crafts alkylation is commonly used in organic synthesis to form aryl–alkyl C−C linkages. However, this reaction lacks the stereospecificity and regiocontrol of enzymatic catalysis. Here, we describe a stereospecific, biocatalytic Friedel–Crafts alkylation of the 2‐position of resorcinol rings using the cylindrocyclophane biosynthetic enzyme CylK. This regioselectivity is distinct from that of the classical Friedel–Crafts reaction. Numerous secondary alkyl halides are accepted by this enzyme, as are resorcinol rings with a variety of substitution patterns. Finally, we have been able to use this transformation to access novel analogues of the clinical drug candidate benvitimod that are challenging to construct with existing synthetic methods. These findings highlight the promise of enzymatic catalysis for enabling mild and selective C−C bond‐forming synthetic methodology. [ABSTRACT FROM AUTHOR]

A bis-acylation strategy to access functionalized anthraquinones via one-pot relay process, is presented. The first acylation was feasible under [Pd]-catalyzed intermolecular direct acylation reaction, while, the second acylation was accomplished by using intramolecular Friedel–Crafts acylation. Notably, benchtop aldehydes have been utilized as non-toxic acylation agents in the key [Pd]-catalyzed acylation. [ABSTRACT FROM AUTHOR]

Abstract Studies on the mechanism and intermediate products in the Friedel–Crafts reaction between oxetanols and phenols are presented. The formation of O -alkylated intermediates is identified using 1H NMR spectroscopy, in a reversible formation of the kinetic oxetane ether products. An interesting relationship between the electronic nature of the nucleophile and the degree of O -alkylation is uncovered. For phenols substituted with an electron withdrawing group such as CN, oxetane ethers are the only products isolated regardless of reaction time. Increasing the electron rich nature of the phenol leads to an increased proportion of the thermodynamic C -alkylated Friedel–Crafts products after just 1 h and as the sole product/s after extended reaction times. These studies have enabled a more complete catalytic cycle to be proposed. Using the same lithium catalyst and carefully selected reaction times, several examples of oxetane ethers are successfully isolated as novel bioisosteres for ester groups. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A methodology for the synthesis of indolo[1,2-b]isoquinoline derivatives by Lewis acid-catalyzed intramolecular Friedel–Crafts alkylation reaction has been developed. The reaction proceeds well with both secondary and primary 2-indolylmethanols. The method efficiently affords pharmaceutically important polycyclic fused indole derivatives in moderate to high yields with good functional group tolerance. In addition, the reaction proceeded in large scale indicating that this method could be scaled up for the synthesis of indolo[1,2-b] isoquinoline derivatives. [ABSTRACT FROM AUTHOR]

The InCl3-catalyzed reaction of ferrocene with orthohydroxybenzyl alcohols is reported and represents a convenient route for the synthesis of ferrocenyl phenols. This carbon–carbon bond forming process is believed to proceed through an ortho-quinone methide intermediate that can be interceptedby ferrocene through a Friedel–Crafts-type process. Preliminary cytotoxic screening carried out on several cancer cell lines revealed that some of the compounds exhibit moderate cytotoxicity [ABSTRACT FROM AUTHOR]

Abstract: A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self‐assembled cage was exploited to promote the Friedel–Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen‐bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C−Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N‐methylpyrrole is preferentially benzylated in the unusual β‐position while mesitylene reacts faster than 1,3‐dimethoxybenzene despite the greater π‐nucleophilicity of the latter compound. [ABSTRACT FROM AUTHOR]