Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction.

8-hydroxyquinoline (oxine) is a widely known and frequently used chelating agent, and the pharmacological effects of the core molecule and its derivatives have been studied since the 19th century. There are several synthetic methods to modify this core. The Mannich reaction is one of the most easily implementable examples, which requires mild reaction conditions and simple chemical reagents. The three components of the Mannich reaction are a primary or secondary amine, an aldehyde and a compound having a hydrogen with pronounced activity. In the modified Mannich reaction, naphthol or a nitrogen-containing naphthol analogue (e.g., 8-hydroxyquinoline) is utilised as the active hydrogen provider compound, thus affording the formation of aminoalkylated products. The amine component can be ammonia and primary or secondary amines. The aldehyde component is highly variable, including aliphatic and aromatic aldehydes. Based on the pharmacological relevance of aminomethylated 8-hydroxyquinolines, this review summarises their syntheses via the modified Mannich reaction starting from 8-hydroxyquinoline, formaldehyde and various amines.

Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees.

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee's alarm pheromone component isoamyl acetate (IAA) is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and disappears at higher concentrations. We investigated the underlying mechanisms at the level of the olfactory receptor neurons by means of electroantennography, finding the responses to mixtures of geosmin and IAA to be lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. Calcium imaging of the antennal lobe (AL) revealed that neuronal responses to geosmin decreased with increasing concentration, correlating well with the observed behaviour. Computational modelling of odour transduction and coding in the AL suggests that a broader activation of olfactory receptor types by geosmin in combination with lateral inhibition could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.

Long pepper (Piper longum) derived carbon dots as fluorescent sensing probe for sensitive detection of Sudan I.

In this piece of work, microwave-assisted conversion of a natural precursor in to high-valued nano-scale material was carried out by a completely greener method. The fluorescent carbon dots prepared, designated as long pepper derived carbon dots (LPCDs), have been thoroughly characterized to explore the physical and chemical properties. The system exhibits excitation dependent emission behavior and from the optimal studies the excitation and emission wavelength of the system was found to be 330 nm and 455 nm respectively. On account of the superior fluorescent behavior of the LPCDs, it was successfully employed as a fluorescent sensing probe to detect Sudan I with good level of selectivity and sensitivity. This carcinogenic dye extensively used as food adulterant can impart several health issues. Food product safety is of high concern, therefore a simple facile and economical analytical method was proposed based on the fluorescence of LPCDs for this dye detection with satisfactory statistical parameters. A linear relationship was maintained in the range of 0 to 27.27 µM Sudan I with limit of detection of 0.92 µM. The quenching mechanism was studied and finally attributed to Förster resonance energy transfer (FRET) mechanism. In addition, the probe was effectively implemented for Sudan I detection in commercial chili powder samples with good level of recovery parameters.

The importance of nutrient ratios in determining elevations in geosmin synthase (geoA) and 2-MIB cyclase (mic) resulting in taste and odour events.

Geosmin synthase (geoA) and 2-MIB cyclase (mic) are key biosynthetic genes responsible for the production of taste and odour (T&O) compounds, geosmin and 2-MIB. These T&O compounds are becoming an increasing global problem for drinking water supplies. It is thought that geosmin and 2-MIB may be linked to, or exacerbated by, a variety of different environmental and nutrient triggers. However, to the best of our knowledge, no studies to date have evaluated the combined effects of seasonality, temperature, and nutrient concentrations on geoA and mic copy numbers in conjunction with T&O concentrations. In this study, environmental triggers behind geosmin and 2-MIB production were investigated in nine reservoirs across Wales, U.K. between July 2019 - August 2020. The abundance of geoA and mic were quantified through quantitative Polymerase Chain Reaction (qPCR). Temporal changes in geoA and geosmin concentrations revealed geoA to be an indicator of monthly geosmin concentrations, although only when geosmin concentrations exceeded 100 ng L-1. Model analysis of a reservoir with elevated geosmin concentrations revealed geoA to be significantly associated with mean temperature (p < 0.001) and the nutrients dissolved reactive silicate (p < 0.001), dissolved iron (p < 0.001), total inorganic nitrogen to phosphorous ratio (TIN:TP) (p < 0.001) and ammonium to nitrate ratio (NH4+:NO3-) (p < 0.001). Sulphate also demonstrated a significant positive linear relationship with geoA (p < 0.001). For mic analysis, NH4+:NO3- was significantly associated with mic (p < 0.05) and an association with dissolved reactive silicate was also observed (p = 0.084). Within this study we also report extreme variance in gene copy numbers between the study seasons. No consistent relationship could be determined for mic copy numbers mL-1 and 2-MIB (ng L-1). The findings from this study indicate that TIN:TP and NH4+:NO3- serve as good predictors for elevated geoA and mic, along with negative linear relationships observed for mean temperature and dissolved reactive silicate. Overall, our findings demonstrate the importance of nutrient concentrations, nutrient ratios and temperature for evidence based predictive capacity of taste and odour events in drinking water reservoirs.

Theoretical Study on the Copper-Catalyzed ortho-Selective C-H Functionalization of Naphthols with α-Phenyl-α-Diazoesters.

The aromatic C(sp2)-H functionalization of unprotected naphthols with α-phenyl-α-diazoesters under mild conditions catalyzed by CuCl and CuCl2 exhibits high efficiency and unique ortho-selectivity. In this study, the combination of density functional theory (DFT) calculations and experiments is employed to investigate the mechanism of C-H functionalization, which reveals the fundamental origin of the site-selectivity. It explains that CuCl-catalyzed ortho-selective C-H functionlization is due to the bimetallic carbene, which differs from the reaction catalyzed by CuCl2 via monometallic carbene. The results demonstrate the function of favourable H-bond interactions on the site- and chemo-selectivity of reaction through stabilizing the rate-determining transition states in proton (1,3)-migration.

SAR study of piperidine derivatives as inhibitors of 1,4-dihydroxy-2-naphthoate isoprenyltransferase (MenA) from Mycobacterium tuberculosis.

The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13-22 µM, GIC50 = 8-10 µM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.

New magnetic nanocomposite Fe3O4@Saponin/Cu(II) as an effective recyclable catalyst for the synthesis of aminoalkylnaphthols via Betti reaction.

In this research, a new magnetic nanocomposite Fe3O4@Saponin/Cu(II) based on quillaja saponin was prepared and the catalyst structure was characterized thoroughly using FT-IR, EDS, TGA, XRD, VSM, HR-TEM, SEM, ICP, BET analyzes. The catalyst prepared in the three-component synthesis of several Betti bases, 1-(α-aminoalkyl)naphthols, under environmentally friendly conditions was used. The advantage of this reaction is the high efficiency of the products and the short reaction time. Furthermore, Fe3O4@Saponin/Cu(II) nano-catalyst is recoverable magnetically and is reusable for other processes with no reduction in its activity.

Supramolecular Room-Temperature Phosphorescent Hydrogel Based on Hexamethyl Cucurbit[5]uril for Cell Imaging.

The host-guest interaction between hexamethyl cucurbit[5]uril (HmeQ[5]) and 1,4-diaminobenzene (DB) was investigated, and a new low-molecular-weight supramolecular gel was prepared by a simple heating/mixing cooling method. The structure and properties of the supramolecular gel were characterized. Results revealed that DB molecules did not enter the cavity of HmeQ[5] and that hydrogen bonding between the carbonyl group at the HmeQ[5] port and the DB amino groups, together with dipole-dipole interactions and outer wall interactions, were the main driving forces for the formation of the supramolecular gel. The HmeQ[5]/DB gel system exhibits temperature sensitivity. The phosphor 6-bromo-2-naphthol (BrNp) was embedded in the gel to give the gel fluorescent phosphorescence double emission. The double emission ability at room temperature can be attributed to the ordered microstructure of the supramolecular gel, which effectively avoids the nonradiative transition of BrNp. Meanwhile, HmeQ[5]/DB-BrNp has good biocompatibility and low biotoxicity, which is compatible with HeLa cells to achieve cytoplasmic staining of HeLa in the red channel. The supramolecular gels constructed by this supramolecular assembly strategy not only have good temperature sensitivity but also extend the application of Q[n]s in biomedical fields.

Selecting Counterions to Improve Ionized Hydrophilic Drug Encapsulation in Polymeric Nanoparticles.

Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid-state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion-drug-polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature (Tg; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and pKa with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π-π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811-free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation.

Construction of Diverse N-Heterocycles by Formal (3 + 3) Cycloaddition of Naphthol/Thionaphthol/Naphthylamine and 1,3,5-Triazinanes.

Here, we report a facile and metal-free method for the construction of dihydrooxazine derivatives via a formal (3 + 3) annulation reaction of naphthols and 1,3,5-triazinanes. The 1,3,5-triazinanes were utilized as a formal three-atom synthon (C-N-C) for cycloaddition. In addition, dihydrothiazine and tetrahydrobenzoquinazoline derivatives could also be produced in good yields by this strategy under catalyst-free and additive-free conditions.

Substituted naphthoxy-phthalonitrile derivatives: Synthesis, substituent effects, DFT, TD-DFT Calculations, antimicrobial properties and DNA interaction studies.

Herein, substituted-naphthol derivatives 4a-e were synthesized in two steps, namely the Diels Alder cycloaddition and Cu-catalyzed aromatization reactions, respectively. Then, pththalonitrile derivatives 7-12 have been prepared by a nucleophilic displacement reaction of 3-nitrophthalonitrile with the naphthol derivatives 4a-e, 5 and, obtained in excellent yields. Structural characterization of the compounds was identified by different spectroscopic techniques. Antimicrobial properties of the synthesized compounds were determined by the microdilution procedure against Gram-positive, Gram-negative bacteria, and yeast. Furthermore, the DNA interaction of the compounds were determined by gel electrophoresis. One of the most prominent findings is that compounds 9 and 10 have more inhibitory effects on Gram-positive bacteria than Gram-negative bacteria. These compounds especially exhibited the highest antibacterial potency against S. aureus (625 µg/mL) among Gram-positive bacteria. According to the plasmid DNA interaction results, the synthesized compounds caused changes in the structure and mobility of the plasmid DNA. Then, geometry optimizations and frequency calculations were conducted at B3LYP/6-311 G(d,p) level of DFT, and optimized structures were used for further analyses. The NBO results revealed that the π→π * and n→π * interactions were greatly contributed to lowering the stabilization energy of all compounds (7-12). FMO energy analyses showed that compound 9 has the biggest electrodonating power.

A novel and simple naphthol azo dye chemosensor as a naked eye detection tool for highly selective, sensitive and accurate determination of thiourea in tap water, juices and fruit skins.

In the present study, a highly accurate and sensitive azo-dye-based colorimetric sensor based on Eriochrome Black T (EBT) was proposed to detect and determine thiourea (TU). TU is truly an important toxic and carcinogenic hazardous pollutant as approved by EPA and IARC. This chemosensor shows a distinct color change from blue to pink during interaction with TU in aqueous medium. So EBT is capable as an applied tool for naked eye detection of TU as its color change is easily observed without any means. The sensing mechanism was also investigated using UV-vis absorption and FT-IR spectra. The linear range and the detection limit of TU sensing were respectively 0.15-18.5 µmol/L and 0.02 µmol/L. In addition, the relative standard deviation (RSD) based on ten repetitions calculated for two different TU concentrations 4.4 and 9.0 µmol/L were 2.3 % and 1.8 %, respectively. Besides its useful application as a naked eye detection tool, the advantages of the developed method include simplicity, elimination of tedious separation and pre-concentration steps, executable in neutral aqueous media, low costs, high accuracy, linear response for wide range of concentrations, low detection limit, high sensitivity, compatibility, and excellent selectivity. The concentration of TU in tap water, fruit juices or fruit skin samples can be visually detected and determined easily using this method. The results showed that EBT is an ideal colorimetric chemosensor for TU, which has been reported for the first time.

A naphthol hydrazone Schiff base bearing benzothiadiazole unit for fluorescent detection of Fe3+ in PC3 cells.

Naphthol hydrazone derivatives are recognized as efficient chelating agents for both qualitative and quantitative detection of metal ions. Here we design a naphthol hydrazine-based chemosensor with covalently linking a strong electron-withdrawing benzothiadiazole group to modulate the molecular electronic structure, nominated as NtHzBtd. The fluorescent probe performs excellent selectivity and sensitivity towards Fe3+ with 1:1 binding stoichiometry, while exhibiting a quick response at 55 s with a relatively low limit of detection of 0.036 µM. A series of spectroscopic measurements in tandem with theoretical calculations suggest that the probe undergoes both intramolecular charge transfer (ICT) and chelation enhanced quenching (CHEQ) processes. Successful color rendering of paper strips and bioimaging in PC3 cells demonstrate the promising applicability of NtHzBtd for portable Fe3+ detection in real samples and biosystems.

A chiral BINOL-based supramolecular gel enabling sensitive enantioselective and chemoselective collapse toward histidine.

A chiral small molecule gelator (R)-H3L based on 1,1'-bi-2,2'-naphthol (BINOL)-phosphoric acid was designed and prepared, which spontaneously forms a stable water-induced gel. The gelation mechanism was revealed by single crystal X-ray diffraction analysis and a number of spectroscopic methods. Addition of Cu2+ improved the gelation ability, and the resultant metal organic gel realized visual enantioselective and chemoselective recognition toward L-histidine from enantiomers of 19 amino acids via gel collapse. The gel showed a highly sensitive response to L-histidine, and as low as 0.01 equiv. of L-histidine relative to the critical gelation concentration of (R)-H3L-Cu caused the gel to collapse. This strategy of regulating the assembly behavior through the interaction of amino acids and metal ions not only provides a simple and direct way to distinguish enantiomers, but also provides insight into how metal ions regulate the organization of biological supramolecular systems.

Chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of naphthols and electron-rich phenols with 2-aryl-3H-indol-3-ones.

The enantioselective aza-Friedel-Crafts reaction is one of the most straightforward and efficient strategies for constructing a new carbon-carbon bond bearing quaternary stereocenter in organic synthesis, but the catalytic asymmetric aza-Friedel-Crafts reaction of naphthols/phenols with cyclic-ketimines attached to a neutral functional group remains still relatively unexplored. Herein, a highly enantioselective aza-Friedel-Crafts reaction of cyclic-ketimines and naphthols/phenols has been realized using a chiral phosphoric acid catalyst. A variety of chiral aminonaphthols (chiral indolin-3-ones) containing a quaternary stereocenter at the C2 position were obtained with excellent outcomes (up to 97% yield, 98% ee). Moreover, the synthetic utility of the enantiomerically enriched chiral aminonaphthols was demonstrated in some efficient transformations. According to the experimental results, a possible transition state model has been proposed to rationalize the origin of asymmetric induction.

Synthesis, crystal structure and biological properties of a fluorophore-labelled mixed-ligand copper(II) complex incorporating N-hydroxynaphthalene-1,8-dicarboximide.

The mixed-ligand fluorophore-labelled copper(II) complex aqua[2,4-dioxo-3-azatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaen-3-olato-κ2O2,O3](1,10-phenanthroline-κ2N,N')copper(II) nitrate, [Cu(C12H6NO3)(C12H8N2)(H2O)]NO3·CH3OH or [Cu(L)(phen)(H2O)]NO3·CH3OH (where phen is 1,10-phenanthroline and HL is N-hydroxynaphthalene-1,8-dicarboximide), (1), was synthesized and structurally characterized. The structure of (1) was confirmed by single-crystal X-ray structure determination. The complex crystallized in the triclinic space group P-1. The geometry around the copper centre is distorted square pyramidal, with the apical position occupied by a water molecule. The complex is highly fluorescent in organic and aqueous solutions. It has good anticancer activity, with an IC50 value of 17 µM, which is almost five times greater than cisplatin (IC50 = 82 µM) under identical experimental conditions.

Multivalent SnO2 quantum dot-decorated Ti3C2 MXene for highly sensitive electrochemical detection of Sudan I in food.

Quantum dots functionalization has been proven to be a simple modification strategy for improving the electroanalytical performance of two-dimensional electrode materials by increasing the specific surface area and active reaction sites. Herein, a new electrochemical sensing platform was fabricated by SnO2 quantum dot-functionalized Ti3C2 MXene (Ti3C2-SnO2QDs) for the highly sensitive detection of Sudan I in food. Ti3C2-SnO2QDs were prepared via in situ synthesis, which can control the nucleation and growth of SnO2QDs, resulting in the well-dispersed SnO2QDs with 2-3 nm size on the intersheet surface of MXene. Moreover, the formation of Ti3C2-SnO2QDs can effectively restrict the aggregation of Ti3C2 and improve the stability of SnO2QDs in aquatic environment. The prepared nanocomposite can be used as an improved modified material to further increase the electrocatalytic performance and electrochemical signal of Sudan I on the surface of a glassy carbon electrode. Under optimized conditions, the proposed analytical method displayed a linear dependence for Sudan I concentration ranging from 0.008 to 10 µM with a detection limit of 0.27 nM (S/N = 3) by electrochemical cyclic voltammetry. This sensor with excellent selectivity, reproducibility and accuracy was quantitatively validated in commercial ketchup and chili powder. This Ti3C2-SnO2QDs-based Sudan I sensor is expected to expand the application of MXene nanocomposites in electrochemical analysis and is envisioned as a promising candidate for monitoring illegal food additives in real food samples.

Molecular Z-Scheme for Solar Fuel Production via Dual Photocatalytic Cycles.

Natural photosynthesis uses an array of molecular structures in a multiphoton Z-scheme for the conversion of light energy into chemical bonds (i.e., solar fuels). Here, we show that upon excitation of both a molecular photocatalyst (PC) and a substituted naphthol (ROH) in the presence of a sacrificial electron donor and proton source, we achieve photocatalytic synthesis of H2. Data support a multiphoton mechanism that is catalytic with respect to both PC and ROH. The use of a naphthol molecule as both a light absorber and H2 producing catalyst is a unique motif for Z-scheme systems. This molecular Z-scheme can drive a reaction that is uphill by 511 kJ mol-1 and circumvents the high-energy constraints associated with the reduction of weak acids in their ground state, thus offering a new paradigm for the production of solar fuels.

Chiral Phosphoric Acid-Catalyzed Enantioselective Aza-Friedel-Crafts Addition of Naphthols with Isatin-Derived Ketimines.

The enantioselective Friedel-Crafts addition of naphthols with isatin-derived ketimines was developed with H8-BINOL-derived chiral biaryl phosphoric acid. A wide range of isatin-derived ketimines and naphthols were successfully applied and gave a series of chiral 3-amino-2-oxindoles in excellent yields with high optical purities.

Atroposelective Synthesis of C-C Axially Chiral Compounds via Mono- and Dinuclear Vanadium Catalysis.

ConspectusAxially chiral compounds with rotationally constrained σ-bonds that exhibit atropisomerism are lucrative synthetic targets because of their ubiquity in functional materials and natural products. The metal complex-catalyzed enantioselective fabrication of axially chiral scaffolds has been widely investigated, and thus far, considerable progress has been made. Over the past two decades, we have developed a highly efficient strategy for constructing axially chiral biarenol derivatives using chiral mono- and dinuclear vanadium complexes. These complexes are readily prepared from vanadium(IV) salts and Schiff base ligands (generated from the condensation of (S)-tert-leucine and di- or monoformyl-(R)-1,1'-bi-2-naphthol (BINOL) derivatives) under O2 and act as highly active catalysts for highly stereoselective C-C bond formation. In particular, the vanadium complex-catalyzed enantioselective oxidative coupling of 2-naphthols 1 under oxygen or in air, which is a green oxidant, affords the desired axially chiral molecules in high yields and high stereoselectivity (up to quantitative yield and 97% ee), along with water as the sole coproduct. This coupling reaction tolerated various functional groups (such as halogens, alkoxys, and boryls) and avoided overoxidation of coupling products.The key feature of dinuclear vanadium(V) catalysts such as (Ra,S,S)-5a is an outstanding mode of the homocoupling reaction, in which a single molecule of the catalyst activates two molecules of the starting material (e.g., 2-naphthols) simultaneously. With this "dual activation" mechanism, the oxidative coupling promoted by the dinuclear catalyst proceeds in an intramolecular manner. The homocoupling rate using 5 mol % of the dinuclear vanadium(V) complex (Ra,S,S)-5a was measured to be 111 times faster than that of the mononuclear vanadium(IV) complex (S)-4a bearing a half motif of the dinuclear vanadium complex.In the case of the heterocoupling reaction utilizing two different kinds of arenol derivatives, only a starting arenol having lower oxidation potential seems to be activated by the mononuclear vanadium complex. The reaction rate of the heterocoupling using either mono- or dinuclear vanadium complexes showed no difference to give the coupling product in high yields but with a different enantioselective manner; chiral mononuclear vanadium(V) complexes showed better enantioselectivites than that of the dinuclear vanadium(V) complexes. A competing heterocoupling study and a linear correlation between the ee of the mononucaler vanadium catalyst and ee of the heterocoupling suggested that the heterocoupling involves an intermolecular radical-anion coupling pathway.In this Account, we summarize the recent advances in vanadium-catalyzed coupling reactions that produced important chiral molecules, such as biresorcinols, polycyclic biphenols, oxa[9]helicenes, bihydroxycarbazoles, and C1-symmetrical biarenols, and their coupling reaction mechanisms. By pursuing vanadium catalysis, we believe numerous additional transformations as well as a renewed interest in catalytic and chemo-, regio-, and enantioselective aryl-aryl bond constructions will be manifested.