Use Of Lewis Acids Research Articles

Rapid and practical access to diverse quindolines by catalyst-free and regioselectivity-reversed Povarov reaction

Summary The Povarov reaction, a formal [4 + 2] cycloaddition between N-aryl imines and electron-rich dienophiles, has been defined as an efficient method to approach tetrahydroquinolines and has been well established in the past decades. In general, electron-rich heterosubstituted alkenes have served as the most popular dienophiles to achieve the exclusive regioselectivity. However, the use of Lewis acids and Bronsted acids as catalysts is required in these transformations, and, to our knowledge, the Povarov reaction of electron-rich heterosubstituted alkynes has not been reported. Here, we disclose a catalyst-free Povarov reaction of formyl-ynamides with anilines for the rapid and practical synthesis of a diverse range of valuable quindolines, which not only represents the first Povarov reaction of ynamides to the best of our knowledge but also constitutes a very rare example of a catalyst-free ynamide cyclization reaction. This formal [1 + 2 + 3] annulation shows a reversed regioselectivity compared with the previous protocols.

Cooperative activating effects of metal ion and Brønsted acid on a metal oxo species.

Metal oxo (M Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> O) complexes are common oxidants in chemical and biological systems. The use of Lewis acids to activate metal oxo species has attracted great interest in recent years, especially after the discovery of the CaMn4O5 cluster in the oxygen-evolving centre of photosystem II. Strong Lewis acids such as Sc3+ and BF3, as well as strong Brønsted acids such as H2SO4 and CF3SO3H, are commonly used to activate metal oxo species. In this work, we demonstrate that relatively weak Lewis acids such as Ca2+ and other group 2 metal ions, as well as weak Brønsted acids such as CH3CO2H, can readily activate the stable RuO4− complex towards the oxidation of alkanes. Notably, the use of Ca2+ and CH3CO2H together produces a remarkable cooperative effect on RuO4−, resulting in a much more efficient oxidant. DFT calculations show that Ca2+ and CH3CO2H can bind to two oxo ligands to form a chelate ring. This results in substantial lowering of the barrier for hydrogen atom abstraction from cyclohexane.

Understanding how Lewis acids dope organic semiconductors: a "complex" story.

We report on computational studies of the potential of three borane Lewis acids (LAs) (B(C6F5)3 (BCF), BF3, and BBr3) to form stable adducts and/or to generate positive polarons with three different semiconducting π-conjugated polymers (PFPT, PCPDTPT and PCPDTBT). Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations based on range-separated hybrid (RSH) functionals provide insight into changes in the electronic structure and optical properties upon adduct formation between LAs and the two polymers containing pyridine moieties, PFPT and PCPDTPT, unravelling the complex interplay between partial hybridization, charge transfer and changes in the polymer backbone conformation. We then assess the potential of BCF to induce p-doping in PCPDTBT, which does not contain pyridine groups, by computing the energetics of various reaction mechanisms proposed in the literature. We find that reaction of BCF(OH2) to form protonated PCPDTBT and [BCF(OH)]−, followed by electron transfer from a pristine to a protonated PCPDTBT chain is highly endergonic, and thus unlikely at low doping concentration. The theoretical and experimental data can, however, be reconciled if one considers the formation of [BCF(OH)BCF]− or [BCF(OH)(OH2)BCF]− counterions rather than [BCF(OH)]− and invokes subsequent reactions resulting in the elimination of H2.

Lewis Acid-Facilitated Radiofluorination of MN3PU: A LRRK2 Radiotracer.

Background: Temperature-sensitive radiopharmaceutical precursors require lower reaction temperatures (<100 °C) during nucleophilic radiofluorination in order to avoid compound thermolysis, often resulting in sub-optimal radiochemical yields (RCYs). To facilitate nucleophilic aromatic substitution (SNAr) of nucleofuges commonly used in radiofluorination (e.g., nitro group), we explored the use of Lewis acids as nucleophilic activators to accelerate [18F]fluoride incorporation at lower temperatures, and thereby increasing RCYs for thermolabile activated precursors. Lewis acid-assisted radiofluorination was exemplified on the temperature-sensitive compound 1-(4-(4-morpholino-7-neopentyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)phenyl)-3-(6-nitropyridin-3-yl)urea (MN3PU, compound 3) targeting leucine-rich repeat kinase 2 (LRRK2), an important target in the study of Parkinson’s disease and various cancers. Methods: To a vessel containing dried K[18F]F-K222 complex, a solution of precursor MN3PU ((3), 1 mg; 1.8 μmol) and Lewis acid (6 μL of 0.2 μmol: chromium II chloride (A), ferric nitrite (B) or titanocene dichloride (C)) in 500 μL of N,N-dimethylformamide (DMF) (with 10% t-BuOH for B) were added. Reactions were stirred for 25 min at 90 °C. In parallel, reactions were conducted without the addition of Lewis acids for baseline comparison. After purification via preconditioned Sep-Pak C18 plus cartridges, aliquots were analyzed by analytical radio-HPLC. Results: Non-decay corrected radiochemical yields (ndc RCYs) for [18F]FMN3PU (7) were improved from 1.7 ± 0.7% (no addition of Lewis acids) to 41 ± 1% using Cr(II) and 37 ± 0.7% using Ti(II)-based Lewis acids, with radiochemical purities of ≥96% and molar activities (Am) of up to 3.23 ± 1.7 Ci/μmol (120 ± 1.7 GBq/μmol). Conclusion: RCYs of [18F]FMN3PU (7) improved from ~5% using conventional nucleophilic radiofluorination, up to 41 ± 1% using Lewis-acid supported SNAr.

Convergent Synthesis of Immune Inhibitor IMMH002

AbstractA convergent synthesis of IMMH002 in 36% overall yield starting from bromobenzene is described with a key Suzuki–Miyaura cross-coupling reaction used to provide a crucial intermediate. The route does not require column chromatography and solves the most intractable quality problem caused by a homologue by-product in the original linear synthesis. Furthermore, reducing the use of Lewis acid mediated reactions improves the environmental impact of the synthesis and reduces overall waste. The new route described herein is more efficient, convenient, reliable, and economically more viable when compared to the previously reported linear route.

Preparation of nanocellulose by hydrolysis catalysedusing salts with different Fe valency

The production of cellulose nanocrystals (CNCs) from vegetable fibres and residues has been intensely investigated due to the properties of high crystallinity and specific surface area of these nanofillers. The most common method of obtaining CNCs is by acid hydrolysis with inorganic acids; however, this method can lead to uncontrolled depolymerisation of the cellulose. Thus, this article examines the use of Lewis acids (FeSO4, Fe2(SO4)3 and FeCl3) as co-catalysts in the acid hydrolysis process and compares their impact on the yield, reduction of particle size and crystallinity index of the CNCs. The results show that the presence of Fe2(SO4)3 and FeCl3 improved the yield (50 and 27%, respectively) and decreased the particle size (632 and 66 nm, respectively) of the CNCs obtained in the hydrolysis process. On the other hand, the crystallinity index values were similar to that of microcrystalline cellulose (MCC), which was probably due to the severe conditions of the hydrolysis process that was used. The scanning transmission microscopy (STEM) images showed a spherical morphology for the CNCs obtained by both inorganic acid and Lewis acids; once again, this was probably due to the severe hydrolysis conditions. Thus, the presence of Lewis acids in the hydrolysis process makes it more efficient because it increases the efficiency of the hydrolysis in a less corrosive environment and with less probability of depolymerisation of the cellulose.

Fundamental Mechanisms of Lewis Acid Doping of Organic Semiconductors

One key challenge in the field of organic semiconductors (OSCs) and their application in organic electronics is controlling the electronic properties of the OSC by p-/n-doping in a predictable manner. It has been established that upon dopant admixture either integer or fractional charge transfer can occur, where the parameters deciding one over the other are still under debate. In numerous studies integer charge transfer was found for conjugated polymers, while small molecular OSCs show a tendency towards fractional charge transfer forming ground state charge transfer complexes (1). The typical approach to assure integer charge transfer is using molecular dopants with a high electron affinity, exceeding the ionization energy of the OSC (for p-doping), as the dopant then exhibits an empty orbital lying lower in energy than the occupied frontier molecular orbital of the semiconductor. Recently, however, a transition between the two scenarios has been reported for polythiophene and the strong molecular p-dopant F4TCNQ, where aging of the samples appeared to promote the formation of charge-transfer complexes showing fractional charge transfer (2). Another study highlighted the key role of the microstructure for the doping process, where different polymorphs show either fractional or integer charge transfer (3).This lack of predictability of traditional doping employing strong donors/acceptors recently led to intense research efforts to find alternative approaches. There, using Lewis acids (LAs) as molecular p-dopants for OSCs has been found to be particularly promising, as these compounds react selectively with Lewis bases to form robust adducts. This makes LAs, in principle, chemically selective dopants that attack OSCs only at the sites where electron lone pairs are located. Interestingly, despite an electron affinity far below the ionization energy of polythiophene, it has been found that the LA BCF can readily ionize this material, which is incompatible with the conventional picture of integer charge transfer as detailed above (4). Very recently, it has been suggested that LA doping does not follow from the formation of an adduct, but instead, that the LA simply act as a protonating agent after forming a complex with water and, hence, becoming a Br∅nsted acid (5).In this presentation, I will briefly review these ideas and discuss how the concepts of electron affinity, ionization energy, integer, and partial charge transfer as used in the field relate to the doping using LAs. By correlating experimental data from optical and infrared spectroscopy with DFT calculations, I will provide alternative descriptors that allow to clarify the discussion and, more importantly, that have predictive power towards the use of Lewis acids as dopants for OSCs. Finally, I will show that the use of these descriptors, in the case of polythiophene doped with BCF discussed above (4), lift the apparent theoretical inconsistency, and as such, will be of high value for a comprehensive larger-scale exploration of OSCs doping using LAs. 1. Salzmann et al., Acc. Chem. Res. 2016, 49, 3702. Watts et al., Chem. Mater. 2019, 31, 6986−69943. Jacobs et al., Materials Horizons. 2018, 5, 6554. P. Pingel et al., Adv. Electron. Mater. 2016, 2:1600204.5. B. Yurash et al., Nature Materials. 2019, 18, 1327–1334

Highly efficient conversion of Kraft lignin into liquid fuels with a Co-Zn-beta zeolite catalyst

Kraft lignin depolymerization to liquid fuels with high yields is crucial to the comprehensive achievement of sustainable and economic feasibility. Herein, we prepared a bimetallic Co-Zn/Off-Al H-beta catalyst through a two-step post synthesis method composed of dealumination and metal incorporation. The bifunctional Co-Zn/Off-Al H-beta catalyst efficiently converted Kraft lignin to liquid fuels, which was attributable to the synergistic effect of Co hydrogen binding sites and Zn Lewis acid sites on H-beta support. Catalytic hydrogenation with Co:Zn = 1:3/Off-Al H-beta catalyst at 320 °C for 24 h gave the highest yield of petroleum ether soluble product (81%, mainly monomers and dimers). Under these conditions, the liquefied lignin gave a higher heating value of 33.3 MJ/kg, which is a significant increase from 26.0 MJ/kg of Kraft lignin. The catalyst stability test showed excellent recyclability. This work provides a paradigm of improving lignin depolymerization efficiency via the combined use of Lewis acid and hydrogenation catalyst.

A Phosphotungstic Acid Catalyst for Depolymerization in Bulrush Lignin

Obtaining renewable fuels and chemicals from lignin is an important challenge in the use of biomass to achieve sustainability and energy goals. At present, acid-based catalysts for lignin depolymerization are considered to be a potential but challenging way to produce low-molecular-mass aromatic chemicals. The main concerns with the use of Lewis acids and zeolite catalysts are the corrosive nature of the acids, the possible formation of unwanted byproducts, and the possible formation of harsh reaction conditions. We achieved high-yield conversion using phosphotungstic acid (PTA) polyoxometalate catalysts in ethanol/water under different reaction conditions with little formation of bio-char. The monomeric products were mainly composed of various types of aromatic compounds. Our method does not require the use of precious metals and harsh reaction conditions—it only requires relatively mild reaction conditions and homogeneous catalysis—thereby greatly reducing operating costs and increasing the yields. Therefore, this PTA catalyst, which has excellent performance in bulrush lignin catalysis, would be a good alternative to the traditional catalysts used in lignin depolymerization and have wide application in biomass use.

The Use of Lewis Acids for Repairing Chemoselectivity of the Organocatalyzed Morita‐Baylis‐Hillman Reaction

AbstractA substantial improvement in the chemoselectivity of the Morita‐Baylis‐Hillman reaction was realized by adding a diimino‐ or diaminopyridine coordination site within the backbone of bis‐imidazole organocatalysts and using Lewis acids situated at this coordination site. The optimal outcome of 90–95% selectivity was achieved by proper matching of the catalyst/additive pair, as well as their respective amount (0.4 equiv. of AgOAc per 1 equiv. of diaminopyridine‐incorporating catalyst).

Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity.

An effective technique for one-stage synthesis of new polycyclic nitrogen-containing compounds has been developed. The procedure involves refluxing mixtures of camphoric acid with aliphatic or aromatic diamine without catalysts. In cases where the starting amine has a low boiling point (less than 200 °C), phenol is used as a solvent, as it is the most optimal one for obtaining products with good yields. It has been shown that the use of Lewis acids as catalysts reduces the yield of the reaction products. A set of compounds have been synthesized, which can be attributed to synthetic analogues of alkaloids. In vitro screening for activity influenza virus A was carried out for the obtained compounds. The synthesized quinazoline-like agent 14 has inhibitory activity against different strains of influenza viruses.Graphical abstract Electronic supplementary materialThe online version of this article (10.1007/s11030-019-09932-9) contains supplementary material, which is available to authorized users.

Activation of Metal Oxo and Nitrido Complexes by Lewis Acids.

Metal oxo species (M═O) play key roles as oxidants in chemical and biological systems. Although Brønsted acids have long been known to enhance the oxidizing power of metal oxo complexes, the use of Lewis acids (LAs), such as metal ions, to activate these complexes has received much less attention until recently. The report of the presence of a Mn4CaO5 cluster active site in the oxygen-evolving center of photosystem II in 2004 has stimulated intense interest in understanding the interaction of LAs with metal oxo species. This Perspective analyzes the various modes of activation of metal oxos by LAs and the pathways for the oxidation of various substrates by LA/M═O systems. The interaction of LAs with metal nitrides will also be discussed, although it is much less studied than that with metal oxo complexes.

Radicals derived from Lewis acid/base pairs.

While conventional approaches to stabilizing main group radicals have involved the use of Lewis acids or bases, this tutorial review focuses on new avenues to main group radicals derived from combinations of donor and acceptor molecules. Reactions involving the use of both classical Lewis acid-base adducts and frustrated Lewis pair systems are discussed and the subsequent reactivity is considered.

A solid-state synthesis, mechanism, and characterization of high molecular weight poly (3-aminobenzenesulfonic acid) with FeCl3.6H2O as a binary oxidant and dopant

The homopolymerization of o,m,p-aminobenzenesulfonic acid (o,m,p-ABS) has been a challenging act because of the strong electron withdrawing nature of the sulfonic acid group (-SO3H). Therefore, polymerization was done by either sulfonating of polyaniline (PANI) or copolymerization of the corresponding monomers with aniline. In this study, we reported a novel method for the preparation of nanopolymer from m-ABS as monomer using FeCl3.6H2O as a binary oxidant and dopant agent in ratio of oxidant to the monomer equal to 5 ([Ox]/[M] = 5) in the solvent-free (solid-state) condition at 40–45 °C for 24 h and the yield of reaction was 46%. The polymer was characterized by a number of techniques such as Fourier transform infrared, ultraviolet-visible, atomic absorption, elemental analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, four probe conductimeter, and zeta potential. The morphology was determined by scanning electron microscopy, transmission electron microscopy and atomic force microscopy and particles size were found about 30–65 nm. The zeta potential by dynamic light scattering (DLS) at two concentrations of 0.20 g/l and 0.05 g/l was measured −61.7 mV and − 43.7 mV, respectively. It showed that the polymer has very good stability and it shows no coagulation and flocculation. The molecular weight was obtained by intrinsic viscosity [η], gel permeation chromatography, static light scattering (SLS) and DLS. The very high molecular weight was obtained by DLS, SLS and [η]. Mn and Mν were equal to 5200 kg/mol and 2173 kg/mol, respectively. The new mechanism based on para-head-to-tail polymerization was introduced explained poly (m-ABS) new structure containing Fe and the high molecular weight. This polymerization method was simple, effective and inexpensive, use of Lewis acid (FeCl3) for both doping and oxidation, as well as resolving the need for high pressure and a long time for dialysis and has the merits of green and solvent-free (solid-state) condition. At the best of our knowledge, this report of polymerization of m-ABS is the most efficient method that has been reported so far.

Chromophore Activation of α,β-Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions.

The first law of photochemistry, as described by Theodor von Grotthuß and John W. Draper, states that only the light absorbed by the irradiated matter can effect photochemical change. Consequently, the photochemical behavior of a molecule can be controlled by bringing its absorbance properties in line with the emission of the light source. A compound with a chromophore that only absorbs light at short wavelengths will not be excited by light of longer wavelengths. If one can reversibly modify the photophysical properties of a compound with a chemical activator, then it is possible to photoexcite only the activated species. For α,β‐unsaturated carbonyl compounds, the use of Lewis acids, Brønsted acids, or the formation of the respective iminium ions can bring about the desired chromophore activation to catalyze a photochemical reaction at a given wavelength. In this Minireview, the concept of chromophore activation will be illustrated, and examples of its implementation in enantioselective catalysis will be discussed.

A Micellar Catalysis Strategy for Suzuki–Miyaura Cross-Couplings of 2-Pyridyl MIDA Boronates: No Copper, in Water, Very Mild Conditions

Suzuki–Miyaura (SM) cross-couplings of 2-pyridyl MIDA boronates can be successfully carried out in the complete absence of copper by attenuation of the Lewis basicity associated with the pyridyl nitrogen using selected substituents (e.g., fluorine or chlorine) on the ring. This strategy imparts additional synthetic options compared with existing approaches based on the use of Lewis acids or N-oxides. Thus, access to highly valued 2-substituted pyridyl rings via an initial Suzuki–Miyaura coupling can be followed by dehalogenation, SNAr reactions, or a second SM coupling to arrive at 2,6-disubstituted pyridyl arrays, all run in a single pot, enabled by micellar catalysis in water. Accessing targets within drug-like space is demonstrated in a four-step, one-pot sequence. Computational data suggest that the major role being played by electron-withdrawing substituents in promoting these cross-couplings without the need for copper is to slow the rates of protodeboronation of intermediate 2-pyridylboronic acids.

Composition, texture and methane potential of cellulosic residues from Lewis acids organosolv pulping of wheat straw

Cellulosic pulps have been successfully isolated from wheat straw through a Lewis acids organosolv treatment. The use of Lewis acids with different hardness produced pulps with different delignification degrees. The cellulosic residue was characterised by chemical composition, X-ray diffraction, FT-IR spectroscopy, N2 physisorption, scanning electron microscopy and potential for anaerobic digestibility. Surface area and pore volume increased with the hardness of the Lewis acid, in correspondence with the decrease of the amount of lignin and hemicellulose in the pulp. The non linearity of the correlation between porosity and composition suggests that an agglomeration of cellulose fibrils occurs in the early stages of pulping. All organosolv pulps presented a significantly higher methane potential than the parent straw. A methane evolution of 295Ncm3/g OM was reached by a moderate improvement of the accessibility of the native straw.

Manganese Electrocatalysts with Bulky Bipyridine Ligands: Utilizing Lewis Acids To Promote Carbon Dioxide Reduction at Low Overpotentials.

Earth-abundant manganese bipyridine (bpy) complexes are well-established molecular electrocatalysts for proton-coupled carbon dioxide (CO2) reduction to carbon monoxide (CO). Recently, a bulky bipyridine ligand, 6,6'-dimesityl-2,2'-bipyridine (mesbpy), was utilized to significantly lower the potential necessary to access the doubly reduced states of these manganese catalysts by eliminating their ability to dimerize after one-electron reduction. Although this Mn mesbpy catalyst binds CO2 at very low potentials, reduction of a resulting Mn(I)-COOH complex at significantly more negative potentials is required to achieve fast catalytic rates. Without reduction of Mn(I)-COOH, catalysis occurs slowly via a alternate catalytic pathway-protonation of Mn(I)-COOH to form a cationic tetracarbonyl complex. We report the use of Lewis acids, specifically Mg(2+) cations, to significantly increase the rate of catalysis (by over 10-fold) at these low overpotentials (i.e., the same potential as CO2 binding). Reduction of CO2 occurs at one of the lowest overpotentials ever reported for molecular electrocatalysts (η = 0.3-0.45 V). With Mg(2+), catalysis proceeds via a reductive disproportionation reaction of 2CO2 + 2e(-) → CO and CO3(2-). Insights into the catalytic mechanism were gained by using variable concentration cyclic voltammetry, infrared spectroelectrochemistry, and bulk electrolysis studies. The catalytic Tafel behavior (log turnover frequency vs overpotential relationship) of [Mn(mesbpy)(CO)3(MeCN)](OTf) with added Mg(2+) is compared with those of other commonly studied CO2 reduction catalysts.

The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.

The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

ChemInform Abstract: Control of Hetero‐Diels—Alder Stereoselectivity Through Solvent Polarity and Broensted or Lewis Acid Catalysis; Theory and Experiment.

AbstractIt is demonstrated that the use of Lewis acids can control the selectivity of the cycloaddition of azadiene (I) and methyleneoxindole yielding either the exo‐adduct (III) with catalytic amounts of TfOH or the endo‐adduct (IV) with 1 equiv.