Donor Reagents Research Articles

Advances in Light Promoted Transformation of N-Heterocyclic Carbene-Ligated Boryl Radical

Organoboron compounds are integral to modern life, with extensive applications in synthesis, materials science, medicine, and various other domains closely linked to human endeavors. NHC-BH3, noted for its stability, ease of synthesis, and high reactivity as a boryl radical precursor, has emerged as a key focus in boryl radical chemistry. Recently, the visible-light-induced single electron transfer (SET) and hydrogen atom transfer (HAT) processes have garnered considerable interest, presenting innovative strategies for generating boryl radicals from NHC-BH3. In the context of this review, our focus is on the synthesis of C-B and X-B bonds under visible light irradiation, facilitated by NHC-BH3. Furthermore, we explored the role of NHC-BH3 as a hydrogen donor or halogen atom transfer reagent in the construction of C-C bond.

Manganese-Mediated Electrochemical Oxidation of Thioethers to Sulfoxides Using Water as the Source of Oxygen Atoms.

Oxygen-atom transfer reactions are a prominent class of synthetic redox reactions that often use high-energy oxygen-atom donor reagents. Electrochemical methods can bypass these reagents by using water as the source of oxygen atoms through pathways involving direct or indirect (mediated) electrolysis. Here, manganese porphyrins and related mediators are shown to be effective molecular electrocatalysts for selective oxidation of thioethers to sulfoxides, without overoxidation to the sulfone. The reactions proceed by proton-coupled oxidation of a MnIII-OH2 species to generate a MnIV-OH and MnV═O species. This methodology is compared to direct electrolysis methods initiated by single-electron oxidation of the thioether, and chloride-mediated electrochemical oxidation of thioethers. The Mn-mediated reactions operate at lower applied potential and exhibit improved substrate scope and functional group compatibility relative to direct electrolysis, and the tunability of the Mn-based mediators allows for improved performance relative to chloride-mediated electrolysis. An electrochemical parallel screening platform is developed and applied to a library of pharmaceutically relevant thioethers.

Vinyl 3-(Dimethylamino)propanoate as an Irreversible Acyl Donor Reagent in a Chromatography-free Lipase-Catalyzed Kinetic Resolution of sec-Alcohols.

The reported chemoenzymatic strategy involves the employment of vinyl 3-(dimethylamino)propanoate as an irreversible acyl donor in a chromatography-free lipase-catalyzed kinetic resolution (KR) of racemic sec-alcohols. This biotransformation is achieved in a sequential manner using CAL-B to affect the kinetic resolution, followed by a simple acidic extractive work-up furnishing both KR products with excellent enantioselectivity (E>200; up to 98 % ee). The elaborated method eliminates a single-use silica gel chromatographic separation and significantly reduces organic solvent consumption to foster a more environmentally friendly chemical industry.

Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor-Acceptor Photoactivation.

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.

Microwave-Assisted One Pot Cascade Conversion of Furfural to γ-Valerolactone over Sc(OTf)3.

γ-Valerolactone (GVL) is considered as a star biochemical which can be used as a green solvent, fuel additive and versatile organic intermediate. In this study, metal triflate (M(OTf)n ) was utilized as the catalyst for one-pot transformation of furfural (FF) to GVL in alcohol media under microwave irradiation. Alcohol plays multiple functions including solvent, hydrogen donor and alcoholysis reagent in this cascade reaction process. And process efficiency of GVL production from FF upgrading is strongly related to the effective charge density of selected catalyst and the reduction potential of selected alcohol. Complex (OTf)n -M-O(H)R, presenting both Brønsted acid and Lewis acid, is the real catalytic active species in this cascade reaction process. Among various catalysts, Sc(OTf)3 exhibited the best catalytic activity for GVL production. Various reaction parameters including the Sc(OTf)3 amount, reaction temperature and time were optimized by the response surface methodology with the central composite design (RSM-CCD). Up to 81.2 % GVL yield and 100 % FF conversion were achieved at 143.9 °C after 8.1 h in the presence of 0.16 mmol catalyst. This catalyst exhibits high reusability and can be regenerated by oxidative degradation of humins. In addition, a plausible cascade reaction network was proposed based on the distribution of product.

Mechanistic Investigation of the Nickel-Catalyzed Transfer Hydrocyanation of Alkynes.

The implementation of HCN-free transfer hydrocyanation reactions on laboratory scales has recently been achieved by using HCN donor reagents under nickel- and Lewis acid co-catalysis. More recently, malononitrile-based HCN donor reagents were shown to undergo the C(sp3)-CN bond activation by the nickel catalyst in the absence of Lewis acids. However, there is a lack of detailed mechanistic understanding of the challenging C(sp3)-CN bond cleavage step. In this work, in-depth kinetic and computational studies using alkynes as substrates were used to elucidate the overall reaction mechanism of this transfer hydrocyanation, with a particular focus on the activation of the C(sp3)-CN bond to generate the active H-Ni-CN transfer hydrocyanation catalyst. Comparisons of experimentally and computationally derived 13C kinetic isotope effect data support a direct oxidative addition mechanism of the nickel catalyst into the C(sp3)-CN bond facilitated by the coordination of the second nitrile group to the nickel catalyst.

Electron and hydrogen atom donor photocatalysts in situ generated from benzimidazolium salts and hydride reagents

Photocatalytic systems consisting of 2-substituted benzimidazoliums (BI+–R, R = polycyclic aryl, triarylamine or phenyl-sulfate) and stoichiometric hydride donor reagents were developed. Light emitting diode irradiation of these photocatalysts in the presence of NaBH4 or picoline borane promotes desulfonylation reactions of an N-sulfonyl indole, N-sulfonyl amide and α-sulfonyl ketone. Absorption spectroscopic and redox potential measurements as well as density functional theory calculations were carried out to gain mechanistic information. Benzimidazolines (BIH–R), generated in situ by hydride reduction of BI+–R, serve as both an electron and hydrogen atom donor photocatalysts in these reductive desulfonylation reactions, which contrasts to ordinary reducing photocatalysts that simply donate electrons.

Iron-Catalyzed Deoxynitrogenation of Carboxylic Acids with Cyanamides to Access Nitriles.

Efficient strategies to access nitriles from common organic functionalities are highly important, given their significance in synthetic and medicinal chemistry. Although the direct transformation of carboxylic acids to nitriles have been explored for decades, there is few general and practical protocol to access nitriles from carboxylic acid precursors. Herein, an iron-catalyzed deoxynitrogenaton strategy to convert carboxylic acids into nitriles is described. This method utilizes a cyanamide as the recyclable nitrogen donor and deoxygenating reagent, operates broadly across aryl, alkenyl, and alkyl carboxylic acids, and features an easy setup without inert gas protection. The synthetic value of this method is demonstrated by application in late-stage modification of drug molecules, synthesis of a pharmaceutical structure, and scaleup reactions and downstream derivatizations.

Recent advances in base metal-catalyzed cooperative transfer hydrogenation and hydrodeuteration of alkenes

Catalytic alkene hydrogenation is a powerful method that has been widely used in the syntheses of valuable products ranging from commodity chemicals to pharmaceuticals. Hydrogenation has also been a key strategy for selectively introducing heavy hydrogen isotopes to small molecules, a key strategy for metabolism studies and even the synthesis of “heavy drugs,” where the hydrogen isotope is a key element of the active pharmaceutical ingredient. Traditional hydrogenations with pressurized H2 gas are atom economic but often require complex reaction setups or expensive metal catalysts. Further, use of diatomic hydrogen necessarily limits the ability to incorporate different hydrogen isotopes at each alkene position, with H2, D2, and T2 each resulting in compete labeling of the alkene. In response to these challenges, a recent and growing movement has sought to develop transfer hydrogenation methods using non-H2 hydrogen sources and earth abundant element catalysts to simplify reaction operation. Excitingly, recent developments have delivered transfer hydrogenations that proceed using cooperative hydrogen donor reagents, permitting the controllable incorporation of different hydrogen isotopes at each position of the alkene via reagent control. In this Digest, we disclose recent advances in Earth-abundant metal-catalyzed cooperative transfer hydrogenation of alkenes with various combinations of two distinct transfer hydrogen reagents as non-H2 hydrogen sources.

Transition metal-free electrochemical fluorotrifluoromethylation of Styrenes

An environmentally friendly electrochemical fluorotrifluoromethylation of styrenes is developed using CF3SO2Na and Et3N·3HF as the F-containing donor reagents. This synthetic strategy features step economy and sustainability.

Engineered Myoglobin Catalysts for Asymmetric Intermolecular Cyclopropanation Reactions.

Biocatalysis has covered an increasingly important role in the synthesis and manufacturing of pharmaceuticals and other high value compounds. In the interest of expanding the range of synthetically useful reactions accessible via biocatalysts, our group has explored the potential and application of engineered myoglobins for 'abiological' carbene transfer catalysis. These transformations provide a direct route for the construction of new carbon-carbon and carbon-heteroatom bonds, including the synthesis of cyclopropane rings, which are key motifs and pharmacophores in many drugs and bioactive natural products. In this award article, we survey the progress made by our group toward the development of myoglobin-based catalysts for asymmetric intermolecular cyclopropanation reactions. The high stereoselectivity exhibited by these biocatalysts in these reactions, combined with their broad substrate scope, scalability, and robustness to high substrate loading and organic co-solvents, contribute to make these systems particularly useful for chemical synthesis and biocatalysis at the preparative scale. Extension of the scope of biocatalytic carbene transfer reactions to include different classes of carbene donor reagents has created new opportunities for the asymmetric synthesis of functionalized cyclopropanes. Furthermore, the integration of myoglobin-catalyzed stereoselective cyclopropanations with chemical diversification of the enzymatic products has furnished attractive chemoenzymatic strategies to access a diverse range of optically active cyclopropane scaffolds of high value for drug discovery, medicinal chemistry, and the synthesis of natural products.

Synthesis of 2-Deoxyglycosides Bearing Free Hydroxyl Substituents on the Glycosyl Donor.

Recent efforts in the field of carbohydrate chemistry have focused on the site- and stereocontrolled synthesis of O-glycosides derived from acceptors bearing multiple hydroxyl substituents. By comparison, there are few examples of the site-selective synthesis of O-glycosides bearing free hydroxyl substituents on the donor reagent. Here, we report the application of an umpolung glycosylation strategy to the synthesis of O-glycosides derived from donors bearing free hydroxyl substituents. The reaction proceeds via prior deprotonation of one or more free hydroxyl groups on a thiophenylglycoside donor, reductive lithiation to generate an anomeric anion intermediate, and addition of this anion to an alkyl 2-(2-methyltetrahydropyranyl) peroxide. By this approach, α-linked glycosides were obtained in 39-84% yields and with >50:1 α/β selectivities. In many instances, β-linked products could be obtained by thermal equilibration of the anomeric anion intermediate (selectivities = 3.8-8:1 β/α; yields = 33-68%). The strategy is applicable to polyhydroxyl donors bearing up to three free hydroxyl groups, N-acylated carbohydrates, and the single-flask syntheses of oligosaccharides.

Investigation of the effect of antibiotics on 5-formylcytosine content in mazie seedling tissues based on photoelectrochemical biosensor

Given the improved photoactivity of Bi2S3 by MXene, an article photoelectrochemical biosensor was designed for 5-formyl-2′-deoxycytidine (5fdCTP) detection, where Bi2S3: MXene was selected as photoactive material, polydopamine was used as solid electron donor and 5fdCTP capture reagent, calcined ZIF-8(C-ZIF-8) was chosen as the artificial enzyme. With the catalyzed by C-ZIF-8, 4-chloro-1-naphthol was allegro oxidized by H2O2 to form the insoluble benzo-4-chlorohexadienone, and then deposited on the surface of the electrode, Resulting in a decrease of the PEC response. Under the optimum conditions, the sensor has a linear range of 0.001–200 nM and a detection limit of 0.51 pM (3σ). The suitability of the developed method was appraised by investigating the effect of antibiotics on 5fdCTP content in the genomic DNA of the roots of maize seedlings. As a new detection platform, the application of this approach can be expanded to investigative the impact of other pollutants on the content of 5fdCTP in plant or animal tissues, explore the feasibility of 5fdCTP as a new indicator for the ecotoxicological effect of pollutants, and the photoelectrochemical method as a new assessment technique for the ecotoxicological effects of pollutants.

Catalytic reduction of nitroarenes and Suzuki-Miyaura reactions using Pd complex stabilized on the functionalized polymeric support

The significance of aromatic amines as crude substances in diverse applications has attracted extensive consideration in the field of economic procedures for the reduction of nitroarenes. Also, the formation of CarbonCarbon bond as a dominant step in the structure of complex molecules is an important phenomenon in chemical reactions. Improvements of eco-friendly methodologies for reduction process and CarbonCarbon bond formation have been noticeable. The present work represents through a capable heterogeneous Pd catalyst, the reduction of nitroarenes to the corresponding amines in the presence of N2H4 as a weak hydrogen donor reagent in the room temperature and solvent-free condition was progressed. In addition, several CC bond formations through Suzuki-Miyaura reaction using one-pot mixture containing aryl halide, arylboronic acid in the presence of Pd catalyst at refluxed condition proceeded. Furthermore, the reusability of Pd catalyst for both reduction and Suzuki reactions showed five successive runs without any significant loss in its activity.

Photocatalytically reductive defluorination of perfluorooctanoic acid (PFOA) using Pt/La2Ti2O7 nanoplates: Experimental and DFT assessment

To enable efficient degradation of perfluorooctanoic acid (PFOA), we prepared and investigated a nanosheet photocatalyst (Pt/La2Ti2O7). Doping platinum nanoparticles on La2Ti2O7 varied the band structure and improved the photocatalytic activity due to the enhanced charge separation. Methanol as the electron donor and sacrificial reagent significantly promoted the photocatalytically reductive degradation of PFOA that reduced by 40% within 180 min under UV254 irradiation (1 mW∙cm2). The density functional theory calculations were used to analyze the effects of Pt doping and band structures on interfacial electron transfer and degradation pathways. As opposed to photocatalytic oxidation, this UV/Pt/La2Ti2O7/CH3OH photocatalysis could abstract electrons from methanol and convert to free reactive radicals and photo-generated electrons to reductively defluorinate PFOA and potentially other polyhalogenated or perhalogenated organic compounds.

Pd‐Catalyzed Domino Cross‐Coupling: Synthesis of Functionalized 4‐(Arylethynyl)Coumarins

AbstractA Pd‐catalyzed domino cross‐coupling methodology was developed to synthesize various 4‐(arylethynyl)coumarin derivatives involving 4‐(gem‐dibromovinyl)coumarins and triarylbismuths as threefold aryl donor reagents. In these reactions, 4‐(gem‐dibromovinyl)coumarin derivatives have been cross‐coupled with sub‐stoichiometric amounts of triarylbismuth reagents. This study involving mono‐, chemoselective and bis‐couplings have been demonstrated with versatile reactivity under the established Pd‐catalyzed domino coupling conditions affording good to high product yields.

A Diverse Library of Chiral Cyclopropane Scaffolds via Chemoenzymatic Assembly and Diversification of Cyclopropyl Ketones.

Chiral cyclopropane rings are key pharmacophores in pharmaceuticals and bioactive natural products, making libraries of these building blocks a valuable resource for drug discovery and development campaigns. Here, we report the development of a chemoenzymatic strategy for the stereoselective assembly and structural diversification of cyclopropyl ketones, a highly versatile yet underexploited class of functionalized cyclopropanes. An engineered variant of sperm whale myoglobin is shown to enable the highly diastereo- and enantioselective construction of these molecules via olefin cyclopropanation in the presence of a diazoketone carbene donor reagent. This biocatalyst offers a remarkably broad substrate scope, catalyzing this reaction with high stereoselectivity across a variety of vinylarene substrates as well as a range of different α-aryl and α-alkyl diazoketone derivatives. Chemical transformation of these enzymatic products enables further diversification of these molecules to yield a collection of structurally diverse cyclopropane-containing scaffolds in enantiopure form, including core motifs found in drugs and natural products as well as novel structures. This work illustrates the power of combining abiological biocatalysis with chemoenzymatic synthesis for generating collections of optically active scaffolds of high value for medicinal chemistry and drug discovery.

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity.

Amino imidazole carbonitrile derivatives decorated with α-amino acid side-chains have been synthesized by a multicomponent microwave assisted reaction inspired by the prebiotic chemistry of aminomalononitrile as a tool for generating high chemical diversity. These compounds were used as annulation synthons for the preparation of 8,9-disubstituted-6,9-dihydro-1H-purin-6-ones by reaction with formic acid as a simple C-1 donor reagent. The novel heterocycles were characterized by significant activity against influenza A virus, amino imidazole carbonitrile derivatives showing the highest activity. Thus, the chemical complexity generated by prebiotic chemistry furnished a general tool for the identification of novel antiviral agents.

Synthesis of Oxazoline and Oxazole Derivatives by Hypervalent-Iodine-Mediated Oxidative Cycloaddition Reactions

Organohypervalent iodine reagents are widely used for the preparation of various oxazolines, oxazoles, isoxazolines, and isoxazoles. In the formation of these heterocyclic compounds, hypervalent iodine species can serve as the activating reagents for various substrates, as well as the heteroatom donor reagents. In recent research, both chemical and electrochemical approaches toward generation of hypervalent iodine species have been utilized. The in situ generated active species can react with appropriate substrates to give the corresponding heterocyclic products. In this short review, we summarize the hypervalent-iodine­-mediated preparation of oxazolines, oxazoles, isoxazolines, and isoxazoles starting from various substrates.1 Introduction2 Synthesis of Oxazolines3 Synthesis of Oxazoles4 Synthesis of Isoxazolines5 Synthesis of Isoxazoles6 Conclusion

Alcohol-mediated Reduction of Biomass-derived Furanic Aldehydes via Catalytic Hydrogen Transfer

With the depletion of fossil energy, liquid biofuels are becoming one of the effective alternatives to replace fossil fuels. The catalytic transfer and hydrogenation of biomass-based furanic compounds into fuels and value-added chemicals has become a spotlight in this field. Gas hydrogen is often used as the H-donor for the hydrogenation reactions. It is a very straightforward and simple method to implement, but sometimes it comes with the danger of operation and the difficulty of regulation. In recent years, diverse liquid hydrogen donor reagents have been employed in the catalytic transfer hydrogenation (CTH) of biomass. Amongst those H-donors, alcohol is a kind of green and benign reagent that has been used in different biomass conversion reactions. This type of reagent is very convenient to use, and the involved operation process is safe, as compared to that of H2. In this review, the application of alcohols as liquid H-donors in the catalytic transfer hydrogenation of biomass-derived furanic compounds is depicted, and the representative reaction mechanisms are discussed. Emphasis is also laid on the selective control of product distribution in the described catalytic systems.