Base-catalyzed Research Articles

Lewis Base Catalyzed, Sulfenium Ion Initiated Enantioselective, Spiroketalization Cascade.

A Lewis base catalyzed, enantioselective sulfenocyclization of alkenes to afford [6,6]spiroketals has been developed. The method uses a chiral Lewis base catalyst with an electrophilic sulfur source to generate enantioenriched thiiranium ion with alkenes. Upon formation, the thiiranium ion is subsequently captured in a cascade-type reaction, wherein a ketone oxygen serves as the nucleophile to open the thiiranium ion and an alcohol provides the secondary cyclization to form biorelevant spiroketals. A variety of electron-rich and electron-neutral E-substituted styrenes form the desired spiroketals in good yields with excellent enantio- and diastereoselectivities. Alkyl-substituted and terminal alkenes participate in the cascade reaction, but with a limited scope compared to the styrenyl substrates. This method allows for rapid formation of highly substituted spiroketals in good yield and excellent enantioselectivity.

Spatiotemporal coordination of the RSF1-PLK1-Aurora B cascade establishes mitotic signaling platforms

The chromatin remodeler RSF1 enriched at mitotic centromeres is essential for proper chromosome alignment and segregation and underlying mechanisms remain to be disclosed. We here show that PLK1 recruitment by RSF1 at centromeres creates an activating phosphorylation on Thr236 in the activation loop of Aurora B and this is indispensable for the Aurora B activation. In structural modeling the phosphorylated Thr236 enhances the base catalysis by Asp200 nearby, facilitating the Thr232 autophosphorylation. Accordingly, RSF1-PLK1 is central for Aurora B-mediated microtubule destabilization in error correction. However, under full microtubule-kinetochore attachment RSF1-PLK1 positions at kinetochores, halts activating Aurora B and phosphorylates BubR1, regardless of tension. Spatial movement of RSF1-PLK1 to kinetochores is triggered by Aurora B-mediated phosphorylation of centromeric histone H3 on Ser28. We propose a regulatory RSF1-PLK1 axis that spatiotemporally controls on/off switch on Aurora B. This feedback circuit among RSF1-PLK1-Aurora B may coordinate dynamic microtubule-kinetochore attachment in early mitosis when full tension yet to be generated.

Lewis Base Catalyzed Dioxygenation of Olefins with Hypervalent Iodine Reagents.

1,2-Diols are extremely useful building blocks in organic synthesis. Hypervalent iodine reagents are useful for the vicinal dihydroxylation of olefins to give 1,2-diols under metal-free conditions, but strongly acidic promoters are often required. Herein, we report a catalytic vicinal dioxygenation of olefins with hypervalent iodine reagents using Lewis bases as catalysts. The conditions are mild and compatible with various functional groups.

Synergistic Copper and Chiral Lewis Base Catalysis for the Asymmetric Synthesis of Pyrrolo[1,2‐a]indoles

Main observation and conclusionThe first asymmetric decarboxylative [3+2]‐cycloaddition of ethynyl indoloxazolidones with carboxylic acids has been developed under synergistic catalysis of copper and chiral Lewis base. This protocol provides a direct and modular approach to biologically important pyrrolo[1,2‐a]indoles bearing two vicinal stereogenic centers with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr and >99% ee). In addition, the utility of this methodology was demonstrated by scaled‐up reaction and several synthetic transformations of the cycloadduct.

Effects of the feeding procedure on the thermal behaviors of autocatalytic esterifications in semibatch processes

Esterification reactions between anhydrides and alcohols catalyzed by sulfuric acid have broad applications in the food, cosmetic, and pharmaceutical industries. However, the exothermic behavior cannot be well explained, especially in semibatch reactors with different feeding procedures. In this study, a series of esterification processes in semibatch systems were conducted with a wide range of feeding rates with two different substrates. The structures of initial catalytic substrates were characterized using in situ Fourier Transform Infrared (FTIR) spectroscopy. A total of 11 reaction pathways, including those for the initial activation of substrates and the subsequent reactions of the feeding process, were calculated by the density functional theory (DFT) method. Three possible catalytic cycles of the esterification with specific acid catalysis, protonated intermediate, and protonated intermediate and H2O, were established for the semibatch esterification reaction based on calculated results and experimental evidence. Thermal safety parameters such as reaction enthalpy (ΔHr), adiabatic temperature rise (ΔTr,ad), and maximum temperature of the synthetic reaction (MTSR) were determined based on Wilson equation used to calibrate mixing heat. The results reveal that mixing heat was 2.5 kJ/mol with same mole ratio of n-butanol (nB) and propionic anhydride (PA). The reactions started by PA are dominant, no matter whether the substrate is nB or PA. The initial reaction rate is restricted by the low concentration of catalyst and active reactant when nB is used as substrate, which lead to significant reactant accumulation with high MTSR of approximately 160 °C. Furthermore, feeding nB into PA allows a controllable increase in the ΔTr,ad realized by changing the feeding rate and limiting the accumulation of reactant.

Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines.

A ring expansion of 2-benzoylpyrrolidines, which involves the formal fluorinative ring opening utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis and a subsequent intramolecular reductive amination, was developed. The operationally simple three-step protocol provides an efficient access to 2-aryl-3-fluoropiperidines. The methodology was further applied to the syntheses of azepanes and tetrahydroquinolines.

NaOH-Catalyzed Methanolysis Optimization of Biodiesel Synthesis from Desert Date Seed Kernel Oil.

Biodiesel synthesis from non-edible vegetable oil via catalytic transesterification is one of the effective ways to replace petroleum-based fuels in the area of renewable energy development and is beneficial to environmental security. Therefore, this research investigates the optimization of process parameters (temperature, methanol to oil ratio, and NaOH catalyst dose) for the conversion of biodiesel from non-edible desert date (Balanites Aegyptiaca) seed kernel oil using the Box–Behnken experimental design of response surface methodology statistical analysis. Accordingly, the optimum values of reaction conditions, namely, a temperature of 60.5 °C, methanol to oil ratio of 6.7:1, and catalyst dose of 0.79 %wt, yielded 93.16% biodiesel. Fourier transform infrared spectroscopy analysis confirmed the cracking of a single glycerol backbone from the triglycerides and the substitution by methoxyl in the presence of a NaOH catalyst. The physicochemical properties of the biodiesel were investigated and compared with standards in terms of its density, viscosity, higher heating value, acid value, saponification value, cetane number, cloud point, pour point, and flash point, and the values are within the recommended standard limits of American Standard for Testing Material (ASTM D6751) and European Committee for Standardization (EN14214). Thus, the results revealed that homogeneous base catalysis of non-edible oil under optimum reaction conditions provides high yield of biodiesel.

Biodiesel Production Using Modified Direct Transesterification by Sequential Use of Acid-Base Catalysis and Performance Evaluation of Diesel Engine Using Various Blends

Biodiesel is a seemingly suitable alternative substitute for conventional fossil fuels to run a diesel engine. In the first part of the study, the production of biodiesel by modified direct transesterification (MDT) is reported. An enhancement in the biodiesel yield with a considerable reduction in reaction time with the MDT method was observed. The required duration for diesel and biodiesel blending was minimized including glycerol separation time from biodiesel in the MDT method. The development in the automotive sector mainly focuses on the design of an efficient, economical, and low emission greenhouse gas diesel engine. In the current experimental work Ceiba pentandra/Nigella sativa and diesel blends (CPB10 and NSB10) were used to run the diesel engine. A variety of approaches were implemented to improve the engine performance for these combinations of fuels. The fuel injector opening pressure (IOP) was set at 240 bar, the torriodal re-entrant combustion chamber (TRCC) having a six-hole injector with a 0.2 mm orifice diameter each, provided better brake thermal efficiency (BTE) with lower emissions compared with the hemispherical combustion chamber (HCC) and trapezoidal combustion chamber (TCC) for both CPB10 and NSB10. CPB10 showed better performance compared with NSB10. A maximum BTE of 29.1% and 28.6% were achieved with CPB10 and NSB10, respectively, at all optimized conditions. Diesel engine operation with CPB10 and NSB10 at 23° bTDC fuel injection timing, and 240 bar IOP with TRCC can yield better results, close to a diesel run engine at 23° bTDC fuel injection timing, and 205 bar IOP with HCC.

Nanoalkalinecellulose immobilized on magnetic nanoparticles as a green catalyst for the synthesis of tetrahydrodipyrazolopyridines and mechanistic insights under base catalysis

AbstractThe cotton‐derived nanoalkalinecellulose (NAC) flocculated on the Fe3O4‐nanoparticles was analytically characterized as Fe3O4@NAC. With the 1:5.7 weight ratio for organic:inorganic and the base‐capacity equal to 7.5 mmol HO−/g, the Fe3O4@NAC represented a catalytic advantage in the room‐temperature one‐pot pseudo‐multicomponent synthesis of tetra‐hydrodipyrazolopyridines (THDPPs) in water. Mechanistic monitoring supported no requisite to acid/base catalyst in the first phase for rapid formation of intermediate 3‐methylpyrazolone (A) by Knorr reaction of the ethylacetoacetate with hydrazine hydrate in water at room temperature. Alternatively, Fe3O4@NAC showed catalytic roles in the further reaction phases in synthesis of THDPPs from the A. Excellent base capacity, hydrogen‐bonding performance, and stability due to no significant activity loss and leaching after five reaction cycles are advantages of this organometallic catalyst.

The role of methoxy species on the transesterification reaction of castor oil on Ni-Mg-Al calcined hydrotalcites

In this work hydrotalcites with Ni/(Ni + Mg) ratios = 0.0, 0.33, 0.66 and ratio (Ni+Mg)/Al= 3, were synthesized. The hydrotalcite precursors were calcined and used as catalysts to study the effect of Ni content on the activity for transesterification of castor oil. The catalysts were characterized by physisorption of N2, X-Ray Diffraction (XRD), temperature programmed desorption (TPD) of CO2 and Fourier transform-infrared (FT-IR) spectroscopy of methanol adsorption. The reaction activity was measured by the production of each fatty acid methyl esters (FAMEs) using gas chromatography (GC). The highest activity and quantity of adsorbed methanol corresponds to the Ni2Mg1-C sample. It was found that the addition of nickel increases the number of sites of medium basic force. Methanol adsorption on the catalysts was studied by FT-IR and a relationship was established between the methoxy ions on the surface and the activity towards transesterification. Attenuated total reflectance infrared spectroscopy (ATR-IR) showed the existence of methoxy ions in solution when methanol was added to a calcined hydrotalcite and heated; with this data an alternative mechanism for basic heterogeneous catalysis was proposed. The reaction main steps are formation of a methoxy ion on the catalyst surface, followed by the reaction of the methoxy ion with triglycerides or fatty acid in the liquid phase.

Doubly Decarboxylative Synthesis of 4-(Pyridylmethyl)chroman-2-ones and 2-(Pyridylmethyl)chroman-4-ones under Mild Reaction Conditions.

The doubly decarboxylative Michael–type addition of pyridylacetic acid to chromone-3-carboxylic acids or coumarin-3-carboxylic acids has been developed. This protocol has been realized under Brønsted base catalysis, providing biologically interesting 4-(pyridylmethyl)chroman-2-ones and 2-(pyridylmethyl)chroman-4-ones in good or very good yields. The decarboxylative reaction pathway has been confirmed by mechanistic studies. Moreover, attempts to develop an enantioselective variant of the cascade are also described.

Ein zur Basenkatalyse befähigtes Ligationsauxiliar ermöglicht die cysteinfreie native chemische Ligation an anspruchsvollen Verknüpfungsstellen

AbstractLigationsauxiliare werden in der chemischen Proteinsynthese eingesetzt, um den Anwendungsbereich der nativen chemischen Ligation (NCL) über Cystein hinaus zu erweitern. An sterisch anspruchsvollen Ligationsstellen erweisen sich Auxiliar‐vermittelte Ligationen allerdings als schwierig. Oft akkumuliert das im Thiolaustauschschritt der NCL gebildete Thioester‐Intermediat, da der anschließende S→N‐Acyltransfer nur sehr langsam abläuft. In dieser Arbeit stellen wir die 2‐Mercapto‐2‐(pyridin‐2‐yl)ethyl (MPyE)‐Gruppe als das erste Auxiliar vor, welches in der Lage ist, die Ligationsreaktion durch interne Katalyse zu unterstützen. Bemerkenswerterweise liefert das MPyE‐Auxiliar auch dann nützliche Reaktionsraten, wenn Prolin oder eine β‐verzweigte Aminosäure an der Verknüpfung beteiligt sind. Quantenchemische Rechnungen deuten darauf hin, dass der Pyridin‐Stickstoff im geschwindigkeitsbestimmenden Protonentransferschritt als eine intramolekulare Base agiert. Das Auxiliar wird in nur zwei Schritten hergestellt und durch reduktive Alkylierung in das Peptid eingeführt. Die Abspaltung des Auxiliars erfolgt durch Behandlung mit TCEP/Morpholin in Gegenwart eines MnII‐Komplexes als Radikalstarter. Die Synthese eines de novo designten 99mer‐Peptids und eines 80 Aminosäuren langen MUC1‐Peptids demonstrieren die Nützlichkeit des MPyE‐Auxiliars.

Enabling Cysteine-Free Native Chemical Ligation at Challenging Junctions with a Ligation Auxiliary Capable of Base Catalysis.

Ligation auxiliaries are used in chemical protein synthesis to extend the scope of native chemical ligation (NCL) beyond cysteine. However, auxiliary‐mediated ligations at sterically demanding junctions have been difficult. Often the thioester intermediate formed in the thiol exchange step of NCL accumulates because the subsequent S→N acyl transfer is extremely slow. Here we introduce the 2‐mercapto‐2‐(pyridin‐2‐yl)ethyl (MPyE) group as the first auxiliary designed to aid the ligation reaction by catalysis. Notably, the MPyE auxiliary provides useful rates even for junctions containing proline or a β‐branched amino acid. Quantum chemical calculations suggest that the pyridine nitrogen acts as an intramolecular base in a rate‐determining proton transfer step. The auxiliary is prepared in two steps and conveniently introduced by reductive alkylation. Auxiliary cleavage is induced upon treatment with TCEP/morpholine in presence of a MnII complex as radical starter. The synthesis of a de novo designed 99mer peptide and an 80 aa long MUC1 peptide demonstrates the usefulness of the MPyE auxiliary.

Enhancement of kinetic rates of CO2 in aqueous solutions of piperazine and methyldiethanolamine with addition of sulfolane

AbstractMeasurements of kinetics rates of CO2 in aqueous solutions of methyldiethanolamine (MDEA), piperazine (PZ), and mixtures of (MDEA + PZ), (PZ + sulfolane) and (MDEA + sulfolane) were carried out using the stopped flow technique, and reported in terms of pseudo‐first‐order rate constants (k0). When possible, the second‐order reaction rate constants (k2) were regressed from the data. Experiments were performed over new concentration ranges of (10–60), (200–800), (200–800, 10–40), (10–40, 10–200), and (200–800, 10–200) mol/m3 for the above‐mentioned five systems, respectively, and at temperatures varying from (298.15–313.15 K). When sulfolane was added to the amine solution, pseudo‐first‐order rate constants in the mixed solvents were higher than in aqueous MDEA and PZ solutions at all temperatures. The kinetic rates were highest at 298.15 K and decreased at higher temperatures for aqueous (MDEA + sulfolane) solutions but increased with temperature for aqueous (PZ + sulfolane) systems. Reaction orders for both PZ and MDEA were practically one at all sulfolane concentrations and temperatures. The base catalysis mechanism was used to regress very well data for aqueous MDEA and (MDEA + sulfolane + water) and the termolecular mechanism was used for (PZ + sulfolane + water) system. Both the zwitterion and termolecular models were able to fit the experimental data for the aqueous PZ system well. Finally, the termolecular and a hybrid model based on the combination of the Zwitterion and base catalysis mechanisms were able to successfully correlate the experimental data for the mixed aqueous (MDEA + PZ) systems.

α-Heteroarylation of Thioethers via Photoredox and Weak Brønsted Base Catalysis

We report the C-H activation of thioethers to α-thio alkyl radicals and their addition to N-methoxyheteroarenium salts for the redox-neutral synthesis of α-heteroaromatic thioethers. Studies are consistent with a two-step activation mechanism, where oxidation of thioethers to sulfide radical cations by a photoredox catalyst is followed by α-C-H deprotonation by a weak Brønsted base catalyst to afford α-thio alkyl radicals. Further, N-methoxyheteroarenium salts play additional roles as a source of methoxyl radical that contributes to α-thio alkyl radical generation and a sacrificial oxidant that regenerates the photoredox catalytic cycle.

Effects of Heme Electronic Structure and Local Heme Environment on Catalytic Activity of a Peroxidase-Mimicking Heme-DNAzyme.

The catalytic cycle of a peroxidase-mimicking heme-DNAzyme involves an iron(IV)oxo porphyrin π-cation radical intermediate known as compound I formed through heterolytic O-O bond cleavage of an Fe3+-bound hydroperoxo ligand (Fe-OOH) in compound 0, like that of a heme enzyme such as horseradish peroxidase (HRP). Peroxidase assaying of complexes composed of chemically modified hemes possessing various electron densities of the heme iron atom (ρFe) and parallel-stranded tetrameric G-quadruplex DNAs of oligonucleotides d(TTAGGG), d(TTAGGGT), and d(TTAGGGA) was performed to elucidate the effects of the heme electronic structure and local heme environment on the catalytic activity of the heme-DNAzyme. The study revealed that the DNAzyme activity is enhanced through an increase in the ρFe and general base catalysis of the adenine base adjacent to the heme, which are reminiscent of the "push" and "pull" mechanisms in the catalytic cycle of HRP, respectively, and that the activity of the heme-DNAzyme can be independently controlled through the heme electronic structure and local heme environment. These findings allow a deeper understanding of the structure-function relationship of the peroxidase-mimicking heme-DNAzyme.

Base Catalysis of Sodium Salts of [Ta6−xNbxO19]8− Mixed-Oxide Clusters

The solid base catalysis of sodium salts of Lindqvist-type metal oxide clusters was investigated using a Knoevenagel condensation reaction. We successfully synthesized the sodium salts of Ta and Nb mixed-oxide clusters Na8−nHn[(Ta6−xNbx)O19]·15H2O (Na-Ta6−xNbx, n = 0, 1, x = 0–6) and found them to exhibit activity for proton abstraction from nitrile substrates with a pKa value of 23.8, which is comparable to that of the conventional solid base MgO. The Ta-rich Na-Ta6 and Na-Ta4Nb2 exhibited high activity among Ta and Nb mixed-oxide clusters. Synchrotron X-ray diffraction (SXRD) measurements, Fourier-transform infrared (FT-IR) spectroscopy, and X-ray absorption spectroscopy (XAS) revealed the structure of Na-Ta6−xNbx: (1) The crystal structure changed from Na7H[M6O19]·15H2O to Na8[M6O19]·15H2O (M = Ta or Nb) by the anisotropic expansion of the unit cell with an increase in Ta content; (2) Highly symmetrical Lindqvist [Ta6−xNbxO19]8− was generated in Na-Ta4Nb2 and Na-Ta6 because of the symmetrical association of Na+ ions with [Ta6−xNbxO19]8− in the structure. DFT calculation revealed that the Lindqvist structures with high symmetry have large NBO charges on surface oxygen species, which are strongly related to base catalytic activity, whereas the composition hardly affects the NBO charges. The above results showed that the Brønsted base catalysis was sensitive to the symmetry of the Lindqvist [Ta6−xNbxO19]8− structure. These findings contribute to the design of solid base catalysts composed of anionic metal oxide clusters with alkaline-metal cations.

Oxoammonium salts are catalysing efficient and selective halogenation of olefins, alkynes and aromatics

Electrophilic halogenation reactions have been a reliable approach to accessing organohalides. During the past decades, various catalytic systems have been developed for the activation of haleniums. However, there is still a short of effective catalysts, which could cover various halogenation reactions and broad scope of unsaturated compounds. Herein, TEMPO (2,2,6,6-tetramethylpiperidine nitroxide) and its derivatives are disclosed as active catalysts for electrophilic halogenation of olefins, alkynes, and aromatics. These catalysts are stable, readily available, and reactive enough to activate haleniums including Br+, I+ and even Cl+ reagents. This catalytic system is applicable to various halogenations including haloarylation of olefins or dibromination of alkynes, which were rarely realized in previous Lewis base catalysis or Lewis acid catalysis. The high catalytic ability is attributed to a synergistic activation model of electrophilic halogenating reagents, where the carbonyl group and the halogen atom are both activated by present TEMPO catalysis.

Kemp-type elimination of 1-arylsulfonyl-3-iodo-1H-indazoles

An intriguing ring-opening reaction of 1-arylsulfonyl-3-iodo-1H-indazoles, which can afford the corresponding ortho-(arylsulfonylamino)benzonitriles under base catalysis, was obtained unexpectedly. Herein, the optimal reaction conditions were explored and the results showed that high temperature and aprotic polar solvent are favorable to the ring-opening reaction. Most of the substrates studied can provide the corresponding ring-opening products in moderate to good yields after stirring in DMSO with K2CO3 at 120 °C for 18 h, suggesting the excellent compatibility of functional groups and the broad substrate scope of this reaction. Furthermore, the control experiments implied that 1-arylsulfonyl-3-iodoindazoles go through an E2 elimination mechanism similar to Kemp elimination.

A Tailored Heptazine-Based Porous Polymeric Network as a Versatile Heterogeneous (Photo)catalyst.

A heptazine-based microporous polymeric network, HMP-TAPA was synthesised by direct coupling of trichloroheptazine and tris(4-aminophenyl)amine (TAPA). A high surface area of 424 m2 /g was achieved, which is the highest surface area among heptazine-based polymeric networks (HMPs). The tailored electron-donor and -acceptor units in HMP-TAPA give broad visible-light absorption. HMP-TAPA was employed as metal-free photocatalyst for oxidative coupling of amines to imines under visible light irradiation with 98 % selectivity. Furthermore, the surface basicity of HMP-TAPA was used to achieve metal-free heterogeneous base catalysis for Knoevenagel condensation under base-free conditions with >99 % conversion. In addition, HMP-TAPA showed extreme robustness over a wide pH range (1-14). The versatility and flexibility of the current material design is beneficial for understanding its photoactivity and surface basicity so as to design dual active (photo)catalyst materials for specific applications.