Structure-selectivity Relationships Research Articles

Mechanistic Interrogation of Photochemical Nickel-Catalyzed Tetrahydrofuran Arylation Leveraging Enantioinduction Data.

This manuscript details the development of an asymmetric variant for the Ni-photoredox α-arylation of tetrahydrofuran (THF), which was originally reported in a racemic fashion by Doyle and Molander. Leveraging the enantioselectivity data that we obtained, a complex mechanistic scenario different from those originally proposed is uncovered. Specifically, an unexpected dependence of the product enantiomeric ratio was observed on both the halide identity (aryl chloride vs bromide substrates) and the Ni source. Stoichiometric experiments and time course analyses of the evolution of product enantioselectivity with time revealed a different initial behavior for reactions carried out with Ni(II) and Ni(0) precatalysts that later converge into a common mechanism. For studying the predominant pathway, this paper describes a rare example of the syntheses of chiral bisoxazoline Ni(II) aryl halide complexes, which proved essential for probing enantioselectivity via stochiometric experiments. These experiments identify the Ni(II) aryl halide complex as the primary species involved in the key THF radical trapping event. A multivariate linear regression model is presented that further validates the dominant mechanism and delineates structure-selectivity relationships between ligand properties and enantioselectivity. EPR analysis of Ni(0)/aryl halide mixtures highlights the fast access to a variety of Ni complexes in 0, +1, and +2 oxidation states that are proposed to be responsible for the initial divergence in mechanism observed when using Ni(0) precatalysts. More broadly, beyond advancing the mechanistic understanding of this THF arylation protocol, this work underscores the potential of leveraging enantioselectivity data to unravel intricate mechanistic manifolds within Ni-photoredox catalysis.

Structure-selectivity relationship of anion exchange resins with different quaternary amine functional groups for highly selective removal of PFAS from chromium-plating wastewater

Anion exchange resin (AER) adsorption is an effective technology for the removal of per- and polyfluoroalkyl substances (PFAS) from wastewater. However, existing AERs with tributylamine functional groups have poor adsorption selectivity for perfluorinated carboxylic acids (PFCAs) and 6:2 fluorotelomer sulfonate (6:2 FTS), and the structure-selectivity relationship is still unclear. In this study, several novel gel AERs with long-chain amine groups were prepared. It was found that their adsorption selectivity for 6:2 FTS was 3.3–5.1 times that of commercial AERs, and the adsorption amount for 6:2 FTS in chromium-plating wastewater was 2.1 times that of the commercial PFA694E. On this basis, we synthesized 16 AERs with different quaternary amine functional groups, and explored the structure-selectivity relationship through the selectivity coefficients and adsorption energies of different AERs for seven typical PFAS. The order of adsorption selectivity of AERs with different quaternary amine groups for PFAS was AER-(12–1-1) > AER-(8–1-1) > AER-(4–4-4) > AER-(4–1-1) ≈ AER-(2–2-2) > AER-(1–1-1), where the three numbers are the carbon-chain lengths of the three alkyl groups attached to the nitrogen atom of the quaternary amine group. Density functional theory (DFT) calculations confirmed the enhanced adsorption selectivity and contribution of both non-electrostatic and electrostatic interactions by the long-chain amine groups, and a quantitative relationship between theoretical calculations and experimental results was established. These results could provide guidance for the development of efficient adsorbents for PFAS removal from wastewater.

Selectivity Modulation of Multistep Reduction Reactions by Gold Nanoclusters.

The selective synthesis of valuable azo- and azoxyaromatic chemicals via transfer coupling of nitroaromatic compounds has been achieved by fine-tuning the catalyst structure. Here, a direct method to modulate nitrobenzene reduction and selectively alter the product from azobenzene to azoxybenzene by employing the size effect of Au is reported. Au nanoclusters (NCs) with smaller sizes embedded in ZIF-8 controllably converted nitrobenzene into azoxybenzene, while supported Au nanoparticles (NPs) selectively catalyzed nitrobenzene reduction to azobenzene. X-ray photoelectron spectroscopy (XPS) and Diffuse reflectance infrared Fourier transform spectroscopy on CO adsorption (CO-DRIFTS) of Au NC/ZIF-8 revealed a higher valence state and a lower electron density of Au than that of Au NP/ZIF-8, combined with the desorption of azoxybenzene from the Au NC and Au NP surface, suggesting that the Au NCs with lower electron density exhibit stronger adsorption. Density functional theory (DFT) calculations and charge density difference maps indicated that azoxybenzene bonded to Au NC/ZIF-8 with greater adsorption energy, resulting in more electron transfer between azoxybenzene and the generated Au sites, which inhibited further reduction of azoxybenzene and resulted in high azoxybenzene selectivity. The application of the size effect of Au particles to regulate nitrobenzene transfer coupling provided new insights into the structure-selectivity relationships.

Random Forest‐Based Prediction of Enantioselectivity in Thiol Addition to Imines Catalyzed by Chiral Phosphoric Acids

AbstractThis paper, for the first time, reports calculating molecular descripts from the combinations of catalysts and substrates, for enantioselectivity predictions in chiral phosphoric acid–catalyzed thiol addition to N‐acylimines. Ten molecular descriptors, together with random forest (RF) algorithm, were used to establish the quantitative structure–selectivity relationship (QSSR) model (RF Model I), yielding correlation coefficient of R=0.982, root mean square (rms) error of 0.604 kJ/mol (for 800 enantioselectivity ΔΔG from 32 catalysts in the training set), R=0.922, rms=1.075 kJ/mol (for 275 enantioselectivity ΔΔG from 11 new catalysts in the test set). The RF Model I was proved to be more accurate in enantioselectivity predictions, compared with the QSSR models reported in the literature and with the RF Model II and RF Model III in this work. Moreover, the RF Model I was based on simple Dragon descriptors and capable of extrapolative prediction for new catalysts. Therefore, it is reasonable deriving molecular descriptors from the combinations of catalysts and substrates (thiols and imines). This work provides a new method for the predictions of enantioselectivity ΔΔG.

Selective recovery of para-xylene from polyethylene terephthalate plastic

The conversion of polyethylene terephthalate (PET) plastic into low-boiling monomers like para-xylene (PX) that can be purified easier with lower energy consumption represents a promising strategy for circular economy that seamlessly integrating into current prevailing high-quality PET production chain. Herein, a selective bimetallic RuFe catalyst was successfully fabricated for hydrodeoxygenation (HDO) of dimethyl terephthalate (DMT) (a model compound of PET) and PET plastics to PX with yield as high as 88.9 % and 82.6 %, respectively, comparable to state-of-the-art examples. H2-TPR and EXAFS combined with benchmark test over model catalysts confirmed that small Ru clusters and Ru-Nx coordination are responsible for the high aromatics selectivity, on which vertical adsorption of carbonyl group (CO) is preferred. This study not only shows a promising PX-based PET recycling route, the highly selective C–O bond cleavage on Ru catalyst and corresponding structure-selectivity relationship also guide the catalyst design for other value-added biomass-based HDO reactions.

Tailoring Cu-Based Electrocatalysts for Enhanced Electrochemical CO2 Reduction to Alcohols: Structure-Selectivity Relationship.

The use of CO2 as a feedstock for the production of carbon-based fuels and value-added chemicals offers a promising route toward carbon neutrality. In this study, two Cu-based electrocatalysts, namely, Cu24/N-C and Cu2/N-C, are successfully prepared by thermal treatment of Cu24 metal-organic polyhedron-loaded zeolitic imidazolate framework-8 (ZIF-8) nanocrystals (Cu24/ZIF-8) and Cu2 dinuclear compound-loaded ZIF-8 nanocrystals (Cu2/ZIF-8), respectively. Extensive structural and compositional analyses were conducted to confirm the formation of Cu nanocluster-loaded N-doped porous carbon supports in both Cu24/N-C and Cu2/N-C and Cu nanoparticles encapsulated by graphitic carbons in Cu2/N-C as well. These two Cu-based electrocatalysts exhibited different behaviors in the electrochemical CO2 reduction reaction (CO2RR). The Cu24/N-C electrocatalyst showed high selectivity for CO production, while Cu2/N-C showed a preference for alcohol generation. The excellent stability of Cu2/N-C over a 30 h continuous electrochemical reduction further highlights its potential for practical applications. The difference in electrocatalytic performance observed in the two catalysts for CO2RR was attributed to distinct catalytic sites associated with Cu nanoclusters and nanoparticles. This research reveals the significance of their structures and compositions for the development of highly selective electrocatalysts for CO2 reduction.

Insight into Janus kinases specificity: From molecular architecture to cancer therapeutics

AbstractJanus Kinases (JAKs) play a crucial role as therapeutic targets for various cancers. However, the current JAK inhibitors (JAKi) available have limited therapeutic benefits due to their lack of selectivity. This review focuses on the structural analysis to elucidate the molecular determinants of JAKs specificity and the discovery and design of selective JAKi. It includes descriptions and comparison of different JAK structures and their binding sites, a comparative analysis of JAKi and their binding modes, detailed interaction fingerprints (IFPs), and an extensive structure‐selectivity relationship (SSRs). Moreover, the review also explores the challenges and possibilities of using computational structure‐based methods for discovering and designing selective JAKi. Other structure‐based approaches, such as targeting the pseudokinase domain, as well as covalent and allosteric designs, are also covered. Based on this analysis, key determinants corresponding to JAK specificity and rational medicinal chemistry strategies are proposed to facilitate the development of highly selective JAKi. Overall, we aim to enhance the understanding of JAK specificity and explore strategies that can lead to the discovery of effective and selective JAKi in cancer therapy, thus improving the prognosis for cancer patients.

Electrochemical Dearomatizing Methoxylation of Phenols and Naphthols: Synthetic and Computational Studies.

The electrochemical oxidative dearomatizing methoxylation of phenols and naphthols was developed. It provides an alternative route for the preparation of methoxycyclohexadienones, important and versatile synthetic intermediates, that eliminates the need for stoichiometric high-energy chemical oxidants and generates hydrogen as a sole by-product. The reaction proceeds in a simple constant current mode, in an undivided cell, and it employs standardized instrumentation. A collection of methoxycyclohexadienones derived from various 2,4,6-tri-substituted phenols and 1-substituted-2-naphthols was obtained in moderate to excellent yields. These include a complex derivative of estrone, as well as methoxylated dearomatized 1,1'-bi-2-naphthols (BINOLs). The mechanism of the reaction was subject to profound investigations using density functional theory calculations. In particular, the reactivity of two key intermediates, phenoxyl radical and phenoxenium ion, was carefully examined. The obtained results shed light on the pathway leading to the desired product and rationalize experimentally observed selectivities regarding a side benzylic methoxylation and the preference for the functionalization at the para over the ortho position. They also uncover the structure-selectivity relationship, inversely correlating the steric bulk of the substrate with its propensity to undergo the side-reaction. Moreover, the loss of stereochemical information from enantiopure BINOL substrates during the reaction is rationalized by the computations.

A step forward in unraveling the lanthanide discrimination puzzle: structure–selectivity relationship based on phenanthroline diimide ligands towards europium and terbium detection in water

Unveiling the lanthanides selectivity in aqueous media from the molecular structures bias was demonstrated which could potentially contribute to establish the structure-function relationship for intragroup lanthanides discrimination and extractions.

Gas-Phase CuPd Bimetallic Cluster-Modified Electrodes as Model Electrocatalysts for CO2 Conversion

Copper-based electrocatalysts possess the unique ability to convert CO2 to multicarbon products such as ethylene – a precursor in many industrial processes. However, their stability and product selectivity remain insufficient. A promising approach to overcome these shortcomings and design better CO2RR electrocatalysts is to tune Cu selectivity by forming bimetallic Cu-M systems [1] while establishing their detailed structure-selectivity relationship. To achieve this, we used laser ablation Cluster Beam Deposition (CBD) [2] to produce well-defined bimetallic cluster-modified electrodes [2]. More specifically, CuPd clusters with an original average size of 2.5 nm and mass loadings of 1-3 µg cm-2 were deposited onto a carbon support. To produce a model catalyst which allows the independent investigation of the electronic and geometric structural effects induced to Cu by the second element, a Cu0.9Pd0.1 composition was selected [3]. CuPd cluster-decorated electrodes were tested for CO2 electrolysis and methane (C1), and ethylene (C2) were found among the products. Observed from the electrocatalytic activity trends, the evolution of C2 products is correlated with the cluster mass loading. In addition, the cluster coverage has an effect on the onset of the competitive H2 evolution (HER); with the lowest cluster-loaded electrodes presenting more intense HER due to limited cluster coverage of the carbon substrate. High resolution (Scanning) Transmission Electron Microscopy ((S)TEM) coupled with Energy-dispersive X-ray spectroscopy (EDX), and X-ray Photoelectron Spectroscopy (XPS) analyses of the as-prepared cluster-modified electrodes, show that the clusters feature some degree of CuPd alloying in the ambient. CuPd cluster-based systems will then be investigated in-situ using X-ray absorption spectroscopy to unravel their structure-catalytic performance relationship.

Unveiled the Structure-Selectivity Relationship for Carbon Dioxide Reduction Triggered by Bi-Doped Cu-Based Nanocatalysts.

To investigate synergistic effect between geometric and electronic structures on directing CO2RR selectivity, water phase synthetic protocol and surface architecture engineering strategy are developed to construct monodispersed Bi-doped Cu-based nanocatalysts. The strongly correlated catalytic directionality and Bi3+ dopant can be rationalized by the regulation of [*COOH]/[*CO] adsorption capacities through the appropriate doping of Bi3+ electronic modulator, resulting in volcano relationship between FECO/TOFCO and surface EVBM values. Spectroscopic study reveals that the dual-site binding mode ([Cu─μ─C(═O)O─Bi3+]) enabled by Cu1Bi3+ 2 motif in single-phase Cu150Bi1 nanocatalyst drives CO2-to-CO conversion. In contrast, the study of dynamic Bi speciation and phase transformation in dual-phase Cu50Bi1 nanocatalyst unveils that the Bi0-Bi0 contribution emerges at the expense of BOC phase, suggesting metallic Bi0 phase acting as [H]˙ formation center switches CO2RR selectivity toward CO2-to-HCOO- conversion via [*OCHO] and [*OCHOK] intermediates. This work provides significant insight into how geometric architecture cooperates with electronic effect and catalytic motif/phase to guide the selectivity of electrocatalytic CO2 reduction through the distinct surface-bound intermediates and presents molecular-level understanding of catalytic mechanism for CO/HCOO- formation.

Valorization to hydrogen of bio-oil aqueous fractions from lignocellulosic biomass pyrolysis by aqueous phase reforming over Pt/C catalyst

Aqueous phase reforming was studied for the valorization to hydrogen of the aqueous fraction of bio-oil from lignocellulosic biomass pyrolysis. Aqueous phase reforming was carried out at 220 °C with a 3 % wt. Pt/carbon catalyst and an aqueous fraction of bio-oil feed containing 1 % wt. of organic matter. Binary and multicomponent mixtures representing aqueous fractions of bio-oil were studied. Strong hydrogen production dependence on aqueous fraction of bio-oil composition was evidenced. Higher processability was obtained for aqueous fractions of bio-oil rich in levoglucosan and hydroxyacetone, reaching a hydrogen production close to 40 mmol per gram of organic carbon, whereas furfural and acetic acid hampered reforming. A significant influence of minority components such as methanol and, particularly, formic acid, was observed. These components improved reforming of the whole multicomponent mixture, showing that blending with biorefinery fractions rich in them can improve the applicability of aqueous phase reforming. The catalyst exhibited stable activity and hydrogen production after 5 reaction cycles and more than 20 h. An increase in selectivity was observed during cycles 2 and 3, which was studied by characterization of fresh and used catalysts to show structure-selectivity relationships. No significant variation of Pt2+/Pt0 and metal particle mean diameter were observed, but Pt nanoparticles underwent morphological changes leading to higher prevalence of low coordination sites, in particular step-edge sites on the particle surface, resulting in higher hydrogen production. Temperature programmed desorption and oxidation analysis showed a cumulative deposition of reaction byproducts on the catalyst surface that contributed to loss of activity.

Computational workflow for steric assessment using the electric field-derived size

Molecular structure plays an important role in the selectivity and performance of catalysts. Understanding the impact of structural differences on catalyst performance via quantitative structure-selectivity relationships is key to developing high-performing catalytic systems. There are several methods that have been introduced to quantify steric contributions, including Tolman cone angles, Charton parameters, and A-values. While these have shown promise in predicting selectivity, they access similar, general steric contributions and are largely empirically derived. Alternatively, Sterimol parameters offer a specific multi-directional measure of steric bulk in the form of three vectors in units of distance. Recently, these parameters revealed strong correlations between structure and selectivity in asymmetric catalysis. Yet, despite their demonstrated performance, Sterimol parameters are commonly derived using van der Waals radii, which approximate molecular size using hard-spheres. This method may not accurately describe highly polarized systems. Recently, a new chemical system size metric based on the electric-field of a molecule was developed, which accesses the occupied space of a molecule. Here, we demonstrate that the electric field-derived Sterimol parameters reveal similar structure-selectivity relationships in asymmetric catalysis as conventional Sterimol parameters. Specifically, we present a computational workflow for calculating Sterimol parameters based on the size of a molecule’s electric field, and validate our method using several asymmetric catalysis reactions.

Surface solid frustrated Lewis pair constructed on alumina for selective hydrogenation reaction

The design of solid frustrated Lewis pairs (FLPs) in heterogeneous systems is crucial to achieve the desired catalytic behavior in vital heterogeneous processes such as hydrogenation reactions. Herein, we report a synthesis approach for FLPs via calcination of AlOOH under different atmospheres (air and N2 atmospheres), in which unsaturated Al sites near OH vacancies and surface O atoms act as Lewis acidic sites and Lewis basic sites, respectively. A study combining 1H nuclear magnetic resonance (NMR), 27Al NMR, and electron paramagnetic resonance (EPR) demonstrates the presence of different types of OH vacancies, which results in spatial hindrance in generating various FLP sites. Notably, the selectivity of the hydrogenation of unsaturated aldehydes can be switched depending on the catalyst: the Al2O3–air catalyst with AlⅣ–O FLP sites exhibits over 90% selectivity to unsaturated alcohols via CO hydrogenation, while the Al2O3–N2 catalyst with AlⅤ–O FLP sites shows a unique selectivity toward saturated alcohols via hydrogenation of CC and CO bonds with a yield above 90%. Structure–property relationship studies based on in situ Fourier transform infrared spectroscopy (FT-IR) and density functional theory (DFT) calculations reveal that the different adsorption modes, i.e., vertical adsorption configuration at the AlⅣ–O FLP sites and flat adsorption configuration at the AlⅤ–O FLP sites, are responsible for the different selectivity in the hydrogenation reactions. This in-depth study on the structure–selectivity relationship provides new insights for the development of selective hydrogenation reactions heterogeneously catalyzed by solid FLPs.

Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes.

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure-selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π-π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.

Pharmacological insights emerging from the characterization of a large collection of synthetic cannabinoid receptor agonists designer drugs

Synthetic cannabinoid receptor agonists (SCRAs) constitute the largest and most defiant group of abuse designer drugs. These new psychoactive substances (NPS), developed as unregulated alternatives to cannabis, have potent cannabimimetic effects and their use is usually associated with episodes of psychosis, seizures, dependence, organ toxicity and death. Due to their ever-changing structure, very limited or nil structural, pharmacological, and toxicological information is available to the scientific community and the law enforcement offices. Here we report the synthesis and pharmacological evaluation (binding and functional) of the largest and most diverse collection of enantiopure SCRAs published to date. Our results revealed novel SCRAs that could be (or may currently be) used as illegal psychoactive substances. We also report, for the first time, the cannabimimetic data of 32 novel SCRAs containing an (R) configuration at the stereogenic center. The systematic pharmacological profiling of the library enabled the identification of emerging Structure-Activity Relationship (SAR) and Structure-Selectivity Relationship (SSR) trends, the detection of ligands exhibiting incipient cannabinoid receptor type 2 (CB2R) subtype selectivity and highlights the significant neurotoxicity of representative SCRAs on mouse primary neuronal cells. Several of the new emerging SCRAs are currently expected to have a rather limited potential for harm, as the evaluation of their pharmacological profiles revealed lower potencies and/or efficacies. Conceived as a resource to foster collaborative investigation of the physiological effects of SCRAs, the library obtained can contribute to addressing the challenge posed by recreational designer drugs.

Structure-Selectivity Relationship Prediction of Tau Imaging Tracers Using Machine Learning-Assisted QSAR Models and Interaction Fingerprint Map.

Protein aggregates composed of tau fibrils are major pathologic findings in different tauopathies. An ideal agent for imaging tau fibrils must be highly selective. The molecular basis for the binding of current available compounds to tau aggregates is not well understood. Herein, we provide insights into previously studied positron emission tomography tracers using various computational methods, including machine learning-based quantitative structure-activity relationship (QSAR) classification, docking, and molecular dynamics (MD) simulations to investigate the structural basis of selective tau aggregate binding for potential compounds. The QSAR classification model based on the Random Forest algorithm with an accuracy of 96.6% for the selective and 97.6% for the nonselective class of compounds revealed essential selective moieties. The combination of molecular docking, MD simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) binding free-energy calculation showed superior binding energy of ligand 63 toward tau and PHF6, a key hexapeptide in tau aggregation, as the most selective compound in the data set. Dissecting the binding properties of ligand 63 and ligand 8 (the least selective compound) within tau and Aβ structures confirmed that these two compounds favor different binding sites of tau; however, the preferential binding site in Aβ was similar for both with lower binding energies calculated for ligand 8. Results revealed that the number of N-heterocycles, the position of nitrogen atoms, and the presence of tertiary amine are important components of selective binding moieties, and they should be maintained in molecules for selective binding to tau aggregates. The predicted structure-selectivity relationship will facilitate the rational design and further development of selective tau imaging agents.

Toward Understanding Base-Catalyzed Isomerization of Saccharides

This Perspective addresses recent advances in isomerization of aldoses into ketoses catalyzed by bases. In recent years, catalytic activity of a number of bases was reported, but the structure–performance correlations are typically missing or remain poorly understood. In this Perspective, the reaction mechanism and kinetics of the base-catalyzed isomerization are discussed. An overview of products obtained via base-catalyzed transformations of d-glucose (Glc), d-lactose (Lac), d-galactose (Gal), and aldopentoses d-ribose (Rib), d-arabinose (Ara), d-xylose (Xyl), and d-lyxose (Lyx) is provided. Side reactions that occur under base conditions are summarized. Catalysis by soluble metal hydroxides and general bases is considered. Moreover, structure–selectivity relationships observed for soluble bases as well as methods for stabilization of ketoses via complexation are discussed. Influences of organic (co-)solvents on reaction kinetics and acceleration of the reaction rate in aqueous phase in the presence of soluble salts–also referred to as salt effect–are addressed. Next, solid bases applied as catalysts for isomerization are considered with a focus on contributions of homogeneous and heterogeneous catalysis into the isomerization processes. The applicability of a filtration test and a contact test as tools to estimate impact of leached species onto catalysis is critically discussed.

Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols

The palladium complex [(L1)Pd(μ-OAc)]2[OTf]2 (L1 = neocuproine) is a selective catalyst for the aerobic oxidation of vicinal polyols to α-hydroxyketones, but competitive oxidation of the ligand methyl groups limits the turnover number and necessitates high Pd loadings. Replacement of the neocuproine ligand with 2,2'-biquinoline ligands was investigated as a strategy to improve catalyst performance and explore the relationship between ligand structure and reactivity. Evaluation of [(L2)Pd(μ-OAc)]2[OTf]2 (L2 = 2,2'-biquinoline) as a catalyst for aerobic alcohol oxidation revealed a threefold enhancement in turnover number relative to the neocuproine congener, but a much slower rate. Mechanistic studies indicated that the slow rates observed with L2 were a consequence of precipitation of an insoluble trinuclear palladium species─(L2Pd)3(μ-O)22+─formed during catalysis and characterized by high-resolution electrospray ionization mass spectrometry. Density functional theory was used to predict that a sterically modified biquinoline ligand, L3 = 7,7'-di-tert-butyl-2,2'-biquinoline, would disfavor the formation of the trinuclear (LPd)3(μ-O)22+ species. This design strategy was validated as catalytic aerobic oxidation with [(L3)Pd(μ-OAc)]2[OTf]2 is both robust and rapid, marrying the kinetics of the parent L1-supported system with the high aerobic turnover numbers of the L2-supported system. Changes in ligand structure were also found to modulate regioselectivity in the oxidation of complex glycoside substrates, providing new insights into structure-selectivity relationships with this class of catalysts.

Catalytic asymmetric indolization by a desymmetrizing [3 + 2] annulation strategy.

A new catalytic asymmetric indolization reaction by a desymmetrizing [3 + 2] annulation strategy is developed. The reaction proceeds via a rhodium-catalyzed enantioposition-selective addition/5-exo-trig cyclization/dehydration cascade between ortho-amino arylboronic acids and 2,2-disubstituted cyclopentene-1,3-diones to produce N-unprotected cyclopenta[b]indoles bearing an all-carbon quaternary stereocenter in high yields with good enantioselectivities. A quantitative structure-selectivity relationship (QSSR) model was established to identify the optimal chiral ligand, which effectively controlled the formation of the stereocenter away from the reaction site. Density functional theory (DFT) calculations, non-covalent interaction analysis, and Eyring analysis were performed to understand the key reaction step and the function of the ligand.