Organic Nucleophiles Research Articles

Boosting urea electrooxidation on oxyanion-engineered nickel sites via inhibited water oxidation

Renewable energy-based electrocatalytic oxidation of organic nucleophiles (e.g.methanol, urea, and amine) are more thermodynamically favourable and, economically attractive to replace conventional pure water electrooxidation in electrolyser to produce hydrogen. However, it is challenging due to the competitive oxygen evolution reaction under a high current density (e.g., >300 mA cm−2), which reduces the anode electrocatalyst’s activity and stability. Herein, taking lower energy cost urea electrooxidation reaction as the model reaction, we developed oxyanion-engineered Nickel catalysts to inhibit competing oxygen evolution reaction during urea oxidation reaction, achieving an ultrahigh 323.4 mA cm−2 current density at 1.65 V with 99.3 ± 0.4% selectivity of N-products. In situ spectra studies reveal that such in situ generated oxyanions not only inhibit OH− adsorption and guarantee high coverage of urea reactant on active sites to avoid oxygen evolution reaction, but also accelerate urea’s C − N bond cleavage to form CNO − intermediates for facilitating urea oxidation reaction. Accordingly, a comprehensive mechanism for competitive adsorption behaviour between OH− and urea to boost urea electrooxidation and dynamic change of Ni active sites during urea oxidation reaction was proposed. This work presents a feasible route for high-efficiency urea electrooxidation reaction and even various electrooxidation reactions in practical applications.

(Invited) Molecular Design for Reactive Redox Separations

This talk presents the rational molecular design of next-generation redox-active sorbents for the capture of carbon dioxide from dilute sources such as air. We discuss the electrochemical generation of organic nucleophiles (C and O-nucleophiles), with a focus on chemical species known to rapidly capture CO2 under cathodic conditions, and that release the bound CO2 under anodic conditions. We first introduce the thermodynamics of redox-reactive CO2-binder chemical space for electrochemical reactive capture and release of CO2 by electrochemically-generated nucleophiles. We then use this thermodynamic understanding to guide the synthetic development of new robust redox-reactive media for the capture of CO2 from dilute sources that take advantage of the beneficial bulk properties of ionic liquids and the well-established redox chemistries of reduced quinones.

Directed, Remote Dirhodium C(sp3)-H Functionalization, Desaturative Annulation, and Desaturation.

Iminodirhodium reactive intermediates generated in situ from O-tosyloximes using Rh2(esp)2 in CH2Cl2 at rt were exploited for an agile trichotomy of challenging transformations: (1) remote C-H functionalizations using an exceptionally broad diversity of inorganic and organic nucleophiles including several unconventional examples, for example, ethers and acyl silanes; (2) desaturative annulation, a biomimetic 1,3-methylene C-C ring-closure with an overall loss of two hydrogens; and (3) directed desaturation for the acceptor-less, regioselective creation of γ,δ- or γ,δ,ε,ζ-olefins. Compared with typical iminyl transition-metal-mediated and 1,5-hydrogen atom-transfer (1,5-HAT) processes, iminodirhodium intermediates are largely underexplored, especially with respect to C(sp3)-H centers and, yet, have the potential to be transformative by virtue of their substrate breadth, regiocontrol, and elusive reaction modality. A substrate scope includes benzylic, allylic, propargylic, tertiary, and α-alkyloxy centers.

Calcareous organic matter coatings sequester siderophores in alkaline soils

Although most studies of organic matter (OM) stabilization in soils have focused on adsorption to aluminosilicate and iron-oxide minerals due to their strong interactions with organic nucleophiles, stabilization within alkaline soils has been empirically correlated with exchangeable Ca. Yet the extent of competing processes within natural soils remains unclear because of inadequate characterization of soil mineralogy and OM distribution within the soil in relation to minerals, particularly in C poor alkaline soils. In this study, we employed bulk and surface-sensitive spectroscopic methods including X-ray diffraction, 57Fe-Mössbauer, and X-ray photoemission spectroscopy (XPS), and transmission electron microscopy (TEM) methods to investigate the minerology and soil organic C and N distribution on individual fine particles within an alkaline soil. Microscopy and XPS analyses demonstrated preferential sorption of Ca-containing OM onto surfaces of Fe-oxides and calcite. This result was unexpected given that the bulk combined amounts of quartz and Fe-containing feldspars of the soil constitute ~90% of total minerals and the surface atomic composition was largely Fe and Al (>10% combined) compared to Ca (4.2%). Soil sorption experiments were conducted with two siderophores, pyoverdine and enterobactin, to evaluate the adsorption of organic molecules with functional groups that strongly and preferentially bind Fe. A greater fraction of pyoverdine was adsorbed compared to enterobactin, which is smaller, less polar, and has a lower aqueous solubility. Using NanoSIMS to map the distribution of isotopically-labeled siderophores, we observed correlations with Ca and Fe, along with strong isotopic dilution with native C, indicating associations with OM coatings rather than with bare mineral surfaces. We propose a mechanism of adsorption by which organics aggregate within alkaline soils via cation bridging, favoring the stabilization of larger molecules with a greater number of nucleophilic functional groups.

Syntheses of biodynamic heterocycles: baker’s yeast-assisted cyclocondensations of organic nucleophiles and phenacyl chlorides

Substituted phenacyl chlorides (1a–f) were cyclocondensed with nucleophiles thiourea (2a) and thiobenzamide (2b) in presence of baker’s yeast (Saccharomyces cerevisiae) as whole-cell enzyme source in acetonitrile at room temperature to obtain 4-(4-substituted phenyl)thiazol-2-amines (3a–f) and 4-(substituted phenyl)-2-phenylthiazoles (4a–f), respectively. Moreover, substituted phenacyl chlorides also reacted with nucleophiles 2-amino-1,3,4-thiadiazole (2c), o-phenylenediamine (2d), 1-amino-2-mercapto-5-phenyl triazole (2e), and pyridin-2-amine (2f) at room temperature in presence of baker’s yeast to give fused heterocycles 6-(4-substituted phenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazoles (5a–f), 2-(4-substituted phenyl)quinoxalines (6a–f), 6-(4-substituted phenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (7a–f), and 2-(4-substituted phenyl)H-imidazo[1,2-a]pyridines (8a–f), respectively. The experimental conditions for these cyclocondensations were optimized to obtain the biodynamic heterocycles in high yield. The unique features of this work are use of baker’s yeast as a cheap and readily available natural source of biocatalyst, noticeable rate acceleration, convenient route to products, cost effectiveness, and scalability.

ChemInform Abstract: Cross‐Couplings Using Aryl Ethers via C‐O Bond Activation Enabled by Nickel Catalysts

AbstractReview: 61 refs.

Cross-Couplings Using Aryl Ethers via C-O Bond Activation Enabled by Nickel Catalysts.

Arene synthesis has been revolutionized by the invention of catalytic cross-coupling reactions, wherein aryl halides can be coupled with organometallic and organic nucleophiles. Although the replacement of aryl halides with phenol derivatives would lead to more economical and ecological methods, success has been primarily limited to activated phenol derivatives such as triflates. Aryl ethers arguably represent one of the most ideal substrates in terms of availability, cost, safety, and atom efficiency. However, the robust nature of the C(aryl)-O bonds of aryl ethers renders it extremely difficult to use them in catalytic reactions among the phenol derivatives. In 1979, Wenkert reported a seminal work on the nickel-catalyzed cross-coupling of aryl ethers with Grignard reagents. However, it was not until 2004 that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)-O bonds was appreciated with Dankwardt's identification of the Ni(0)/PCy3 system, which significantly expanded the efficiency of the Wenkert reaction. Application of the nickel catalyst to cross-couplings with other nucleophiles was first accomplished in 2008 by our group using organoboron reagents. Later on, several other nucleophiles, including organozinc reagents, amines, hydrosilane, and hydrogen were shown to be coupled with aryl ethers under nickel catalysis. Despite these advances, progress in this field is relatively slow because of the low reactivity of benzene derivatives (e.g., anisole) compared with polyaromatic substrates (e.g., methoxynaphthalene), particularly when less reactive and synthetically useful nucleophiles are used. The "naphthalene problem" has been overcome by the use of N-heterocyclic carbene (NHC) ligands bearing bulky N-alkyl substituents, which enables a wide range of aryl ethers to be coupled with organoboron nucleophiles. Moreover, the use of N-alkyl-substituted NHC ligands allows the use of alkynylmagnesium reagents, thereby realizing the first Sonogashira-type reaction of anisoles. From a mechanistic perspective, nickel-catalyzed cross-couplings of aryl ethers are at a nascent stage, in particular regarding the mode of activation of C(aryl)-O bonds. Oxidative addition is one plausible pathway, although such a process has not been fully verified experimentally. Nickel-catalyzed reductive cleavage of aryl ethers in the absence of an external reducing agent provides strong support for this oxidative addition process. Several other mechanisms have also been proposed. For example, Martin demonstrated a new possibility of the involvement of a Ni(I) species, which could mediate the cleavage of the C(aryl)-O bond via a redox-neutral pathway. The tolerance of aryl ethers under commonly used synthetic conditions enables alkoxy groups to serve as a platform for late-stage elaboration of complex molecules without any tedious protecting group manipulations. Aryl ethers are therefore not mere economical alternatives to aryl halides but also enable nonclassical synthetic strategies.

Dynamics of the NbCl5-catalyzed cycloaddition of propylene oxide and CO2 : assessing the dual role of the nucleophilic Co-catalysts.

A mechanistic study on the synthesis of propylene carbonate (PC) from CO2 and propylene oxide (PO) catalyzed by NbCl5 and organic nucleophiles such as 4-dimethylaminopyridine (DMAP) or tetra-n-butylammonium bromide (NBu4 Br) is reported. A combination of in situ spectroscopic techniques and kinetic studies has been used to provide detailed insight into the reaction mechanism, the formation of intermediates, and interactions between the reaction partners. The results of DFT calculations support the experimental observations and allow us to propose a mechanism for this reaction.

Amino acids as novel nucleophiles for silver nanoparticle-luminol chemiluminescence.

The use of noble metal nanoparticles (NPs) as reductants in chemiluminescence (CL) has been reported only rarely owing to their high oxidation potentials. Interestingly, nucleophiles could dramatically lower the oxidation potential of Ag NPs, such that in the presence of nucleophiles Ag NPS could be used as reductants to induce the CL emission of luminol, an important CL reagent widely used in forensic analysis for the detection of trace amounts of blood. Although nucleophiles are indispensible in Ag NP-luminol CL, only inorganic nucleophiles such as Cl(-), Br(-), I(-) and S2O3 (2-) have been shown to be efficient. The effects of organic nucleophiles on CL remain unexplored. In this study, 20 standard amino acids were evaluated as novel organic nucleophiles in Ag NP-luminol CL. Histidine, lysine and arginine could initiate CL emission; the others could not. It is proposed that the different behaviors of 20 standard amino acids in the CL reactions derive from the interface chemistry between Ag NPs and these amino acids. UV/vis absorption spectra were studied to validate the interface chemistry. In addition, imidazole and histidine were chosen as a model pair to compare the behavior of the monodentate nucleophile with that of the corresponding multidentate nucleophile in Ag NP-luminol CL.

Cyclodimerization versus Polymerization of Methyl Methacrylate Induced byN‐Heterocyclic Carbenes: A Combined Experimental and Theoretical Study

The activation behavior of two N-heterocyclic carbenes (NHCs), namely, 1,3-bis(isopropyl)imidazol-2-ylidene(NHCiPr) and 1,3-bis(tert-butyl) imidazol-2-ylidene (NHCtBu), as organic nucleophiles in the reaction with methyl methacrylate (MMA) is described. NHCtBu allows the polymerization of MMA in DMF at room temperature and in toluene at 50 °C, whereas NHCiPr reacts with two molecules of MMA, forming an unprecedented imidazolium-enolate cyclodimer (NHCiPr/MMA=1:2). It is proposed that the reaction mechanism occurs by initial 1,4-nucleophilic addition of NHCiPr to MMA, generating a zwitterionic enolate 2, followed by addition of 2 to a second MMA molecule, forming a linear imidazolium-enolate 3 (NHCiPr/MMA=1:2). Proton transfer, generating intermediate 5, followed by cyclization and release of methanol yielded the aforementioned zwitterionic cyclodimer 1:2 adduct 7, the molecular structure of which has been established by NMR spectroscopy, X-ray diffraction, and mass spectrometry. This unexpected difference between NHCtBu and NHCiPr in the reaction with MMA (polymerization and cyclodimerization, respectively) can be rationalized by using DFT calculations. In particular, the nature of the NHC strongly influences the cyclodimerization pathway, the cyclization of 5 and the release of methanol are the discriminating step and limiting step, respectively. In the case of NHCtBu, both steps are strongly disfavoured compared with that of NHCiPr (energetic difference of around 14 and 9 kcal mol(-1), respectively), preventing the cyclization mechanism from a kinetic viewpoint. Moreover, addition of a third molecule of MMA in the polymerization pathway results in a lower activation barrier than that of the limiting step in the cyclodimerization pathway (difference of around 14 kcal mol(-1)), in agreement with the formation of polymethyl methacrylate (PMMA) by using NHCtBu as nucleophile.

Zwitterionic Ring-Opening Polymerization for the Synthesis of High Molecular Weight Cyclic Polymers

Cyclic polymers are an intriguing class of macromolecules. Because of the constraints of the cyclic topology and the absence of chain ends, the properties of these molecules differ from those of linear polymers in ways that remain poorly understood. Cyclic polymers present formidable synthetic challenges because the entropic penalty of coupling the chain ends grows exponentially with increasing molecular weight. In this Account, we describe recent progress in the application of zwitterionic ring-opening polymerization (ZROP) as a strategy for the synthesis of high molecular weight, cyclic polymers. Zwitterionic ring-opening polymerization involves the addition of neutral organic nucleophiles to strained heterocyclic monomers; under appropriate conditions, cyclization of the resultant macrozwitterions generates cyclic macromolecules. We discuss the mechanistic and kinetic features of these zwitterionic ring-opening reactions and the conditions that influence the efficiency of the initiation, propagation, and cyclization to generate high molecular weight cyclic polymers. N-Heterocyclic carbenes (NHC) are potent nucleophiles and relatively poor leaving groups, two features that are important for the generation of high molecular weight polymers. Investigations of the nature of the monomer and nucleophile have helped researchers understand the factors that govern the reactivity of these systems and their impact on the molecular weight and molecular weight distributions of the resulting cyclic polymers. We focus primarily on ZROP mediated by N-heterocyclic carbene nucleophiles but also discuss zwitterionic polymerizations with amidine, pyridine, and imidazole nucleophiles. The ZROP of N-carboxyanhydrides with N-hetereocyclic carbenes generates a family of functionalized cyclic polypeptoids. We can synthesize gradient lactone copolymers by exploiting differences in relative reactivity present in ZROP that differ from those of traditional metal-mediated polymerizations. These new synthetic methods have allowed us to investigate the influence of topology on the crystallization behavior, stereocomplexation, and solution properties of cyclic macromolecules.

Breaking C–F Bonds via Nucleophilic Attack of Coordinated Ligands: Transformations from C–F to C–X Bonds (X= H, N, O, S)

In this review, transformations of C–F to C–X bonds mediated by transition-metal complexes are considered from the ligand’s perspective. In C–F bond activation reactions, the ligands (L) bonded to transition-metal complexes can act as spectators but can also assist the reaction. The latter case is important in the heterolytic cleavage of C–F bonds by nucleophilic addition reactions. When L is an electrophile (E), the assistance of the ligand facilitates the fluoride departure when the metal attacks at C. In contrast, when L is a nucleophile (X), the ligand is responsible for the nucleophilic addition and the reaction leads to a new C–X bond, allowing the direct functionalization of C–F bonds. This article presents an overview of the reactions that are initiated by the nucleophilic attack of a coordinated ligand (a hydride or an N-, O-, or S-nucleophile) to a CF carbon resulting in formation of a new C–H, C–N, C–O, or C–S bond. The possible mechanisms are discussed. The attack of a nucleophilic ligand at the electrophilic carbon of a C–F bond is comparable to fluoride elimination by organic nucleophiles. However, the presence of the metal center introduces new features in this process, both in the selectivity and in the thermodynamics. Herein these effects are analyzed. Thus, the aim of this review is to show how these kinds of processes put together the best of both organic and inorganic worlds in order to achieve a wide range of reactions with fluorinated compounds.

Insights into the Reaction Behaviour of Stannylated Allylic Substrates

AbstractStannylated allylic substrates are versatile building blocks for organic synthesis. Pd0‐catalysed coupling reactions of 2‐stannylated allylic carbonates, acetates and phenoxides with amines, malonates, phenoxides, imides and distannanes provide the corresponding substituted allylic compounds, which are suitable for subsequent modifications including Stille coupling reactions. The reaction mechanisms are dependent on the temperature and the nucleophiles used. Tsuji–Trost allylic substitution takes place with organic nucleophiles at low temperature. When distannane is employed at higher temperature, on the other hand, Pd0‐catalysed bismetallation of allenes formed in situ by elimination of tributyltin methoxide predominates.

Polarization of the Pyridine Ring: Highly Functionalized Piperidines from Tungsten−Pyridine Complex

The N-acetylpyridinium complex of {TpW(NO)(PMe3)} undergoes regio- and stereoselective reactions with a broad range of common organic nucleophiles, providing a family of 1,2-dihydropyridine (DHP) complexes of the form TpW(NO)(PMe3)(3,4-η(2)-DHP). The present study explores the elaboration of these systems into novel piperidines. The addition of an acid to the DHP complexes generates highly asymmetric π-allyl complexes that in turn react with a second nucleophile at either C3 or C5. The subsequent oxidative decomplexation of these materials yields several piperidinamides with unconventional substitution patterns.

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II: Synthesis of Novel Thiazolyl Acetonitriles and Thiazolyl Acrylonitriles and Their Derivatives Containing Dimethylsulfonamide Moiety

Thiazolyl acetonitrile (2) was prepared and converted to pyrazolo[5,1-c][1,2,4]triazine (5), thiazoline-4-one derivatives (10,12), thiazolo[3,2-a]pyridine (13), coumarin (14), and benzo[f]coumarin (16) derivatives through reactions with a variety of organic electrophiles and nucleophiles. Thiazolyl acrylonitrile derivatives (17, 18, 21, 26–28, 31–33) were also prepared, and their activity with a variety of reagents was investigated. The structure of these compounds was elucidated on the basis of elemental analysis, IR, 1H-NMR, and mass spectra. The antimicrobial and antifungal activities of the prepared compounds are also reported.

Engaging Zwitterions in Carbon−Carbon and Carbon−Nitrogen Bond-Forming Reactions: A Promising Synthetic Strategy

An Account of carbon-carbon and carbon-nitrogen bond-forming reactions mediated by zwitterions generated by the addition of organic nucleophiles to activated unsaturated systems highlighting their synthetic potential is presented.

Novel 10‐I‐3 Hypervalent Iodine‐Based Compounds for Electrophilic Trifluoromethylation

The synthesis of a new family of 10-I-3 hypervalent iodine compounds is described in which the CF3 functionality participates directly in the hypervalent bond. These materials are accessible by nucleophilic ligand substitution at iodine using Me3SiCF3 in the presence of a substoichiometric amount of fluoride. The expected T-shaped geometry at iodine was verified by X-ray crystallographic analyses of three of the products (1-trifluoromethyl-1,2-benziodoxol-3-(1 H)-one and two substituted 1-trifluoromethyl-1,3-dihydro-1,2-benziodoxoles). Preliminary results for the direct electrophilic transfer of the trifluoromethyl moiety onto organic nucleophiles show modest reactivity in polar aprotic solvents under relatively mild conditions. The overall process can be understood as a formal umpolung of the CF3 group.

Heterogeneous Kinetics of the Dissolution of an Inorganic Salt, Potassium Carbonate, in an Organic Solvent, Dimethylformamide

Understanding the mechanisms of solid-liquid systems is fundamental to the development and operation of processes for the production of agrochemicals and pharmaceuticals. The use of a strong inorganic base in an organic solvent, typically, potassium carbonate in dimethylformamide, is often used to facilitate the formation of a required anionic organic nucleophile. In this paper, the dissolution kinetics of potassium carbonate in dimethylformamide at elevated temperatures is studied in the presence of ultrasound, as revealed via monitoring of the deprotonation of 2-cyanophenol by dissolved K2CO3. Two independent experimental methods were employed; the loss of 2-cyanophenol was detected electrochemically at a platinum microdisk working electrode, and the formation of the 2-cyanophenolate anion was monitored via UV/visible spectroscopic analysis. The results were modeled by fitting the experimental data to a theoretical model for the surface-controlled dissolution of solid particles. The dissolution rate constant, k, for the dissolution of K2CO3 in DMF was found to have a value of (1.3 +/- 0.2) x 10(-7) mol cm(-2) s(-1) at 100 degrees C, and the activation energy for the dissolution was 44.2 +/- 0.4 kJ mol(-1) over the temperature range of 70-100 degrees C studied.

A LIMITATION OF REUSING THE CATALYST IN TRI-LIQUID-PHASE CATALYTIC SYSTEMS

This work demonstrates important factor influencing the reusability of the phase transfer catalyst in the third liquid phase in addition to the role of the possible loss of catalyst due to the dissolution of the catalyst into the aqueous and organic phases. When the catalyst might react with the byproducts, in addition to reacting with the organic substrate and aqueous nucleophile, it would lose its catalytic activity. The substitution reaction between the organic substrate and an aqueous nucleophile (sodium phenolate) with tetra-n-butylammonium bromide as a phase-transfer catalyst was employed as a model reaction and was performed in a batch reactor. Three organic substrates, including allyl bromide, n-butyl bromide, and ethyl 2-bromoisobutyrate, were tested. Each of the third liquid phases formed in these tri-liquid-phase catalytic systems was utilized three times to observe the change in the activity of the catalyst. The catalyst in the third liquid phase can be reused without any loss of its catalytic activity when allyl bromide or n-butyl bromide is utilized as the organic substrate; however, the catalytic activity declines when ethyl 2-bromoisobutyrate is the organic reactant. Therefore, the organic reactant plays a crucial role in determining whether the catalyst can be reused or not.

Side Group Exchange in Poly(organophosphazenes) with Fluoroalkoxy Substituents

Several poly(alkoxyphosphazenes) and poly(fluoroalkoxyphosphazenes) were synthesized and allowed to react with various organic nucleophiles. Reactions were carried out at room temperature (25 °C) and at 67 °C in tetrahydrofuran (THF) and were monitored by 31P NMR spectroscopy. The possible use of single-substituent polymers as hydrolytically stable macromolecular intermediates for mixed-substituent polyphosphazene synthesis is discussed, and factors that influence side group replacement in poly(organophosphazenes) are examined. In addition, evidence for a random, irreversible SN2-like mechanism of side group replacement is presented.