Atom Economy Research Articles

Iodine-Catalyzed Diversity-Oriented Synthesis of 3,4-Heterocycle-Fused Coumarins from 4-Aminocoumarins and Aurones in Different Solvent.

An unprecedented protocol has been developed for the synthesis of 3,4-heterocycle-fused coumarins from 4-aminocoumarins and aurones through iodine-catalyzed cascade reactions. Dihydropyridine-fused coumarin, pyridine-fused coumarin, and pyrrole-fused coumarin derivatives were achieved in good yields with high selectivity when CH3CN, AcOH, and DMSO were used as the solvent, respectively. This protocol provides several advantages, such as easily available starting materials, high atom economy, friendly environment, and simple procedure.

Atom-Level Tandem Catalysis in Lithium Metal Batteries.

High-energy-density lithium metal batteries (LMBs) are limited by reaction or diffusion barriers with dissatisfactory electrochemical kinetics. Typical conversion-type lithium sulfur battery systems exemplify the kinetic challenges. Namely, before diffusing or reacting in the electrode surface/interior, the Li(solvent)x + dissociation at the interface to produce isolated Li+, is usually a prerequisite fundamental step either for successive Li+ "reduction" or for Li+ to participate in the sulfur conversions, contributing to the related electrochemical barriers. Thanks to the ideal atomic efficiency (100 at%), single atom catalysts (SACs) have gained attention for use in LMBs toward resolving the issues caused by the five types of barrier-restricted processes, including polysulfide/Li2S conversions, Li(solvent)x + desolvation, and Li0 nucleation/diffusion. In this perspective, the tandem reactions including desolvation and reaction or plating and corresponding catalysis behaviors are introduced and analyzed from interface to electrode interior. Meanwhile, the principal mechanisms of highly efficient SACs in overcoming specific energy barriers to reinforce the catalytic electrochemistry are discussed. Lastly, the future development of high-efficiency atomic-level catalysts in batteries is presented.

Catalytic Eoconvergent C(sp3)−N Coupling to Access Chiral Amines: A Concept Review

AbstractNitrogen containing compounds like chiral amines have been widely used in synthetic medicines, biomass, and fine chemical products because of their particularly valuable motifs and exceedingly broad range of functionality. Enantioconvergent synthesis of chiral amines has high atomic economy and enantioselectivity with theoretically 100 % yield of enantioenriched products. In this concept article, we hope to provide a further understanding of chiral amines enantioconvergent synthesis methodology with an introduction of recent progresses in enantioconvergent amination reactions catalyzed by early transition metals and facilitate the development of enantioconvergent C(sp3)−N coupling for benign and efficient preparation of highly valuable chiral nitrogen‐containing units.

Photogeneration of Hydrogen: Insights from a Pt(II)‐Complex Incorporated into a Covalent Organic Framework

Pt(II)‐based molecular catalysts stand as a prototypical system in hydrogen evolution reactions (HER) owing to their consistently elevated activity levels. Their integration into heterogeneous systems thus provides an ideal platform to develop catalytic materials with optimal atom economy. In this work, by rational molecular design, we have synthesized a novel two‐dimensional photoactive Covalent Organic Framework (COF), wherein the pore walls host a quinoline‐based α‐diimine ligand serving as a coordination site for anchoring a Pt(II) molecular catalyst. Thorough structural analyses, employing X‐ray photoelectron spectroscopy (XPS), infrared spectroscopy (FT‐IR), diffuse reflectance spectroscopy (DR), coupled with DFT calculations, distinctly confirm the Pt(II) complexation through the coordination site of the α‐diimine ligand. The Pt(II)‐metalated COF exhibits photocatalytic activity with a hydrogen evolution rate reaching up to 1300 umol g‐1 h‐1. Nevertheless, the occurrence of platinum nanoparticles in postcatalytic samples, along with reduced photocatalytic activity in the presence of chloride ions, suggests that Pt(II) anchored into the COF backbone might not be the primary catalytic site.

Electrochemical E-Selective Semireductive Dicarboxylation of Aryl Alkynes with CO2.

Herein, we report an electrochemical protocol for the dicarboxylation of aryl alkynes using CO2. With a graphite rod as the cathode and Al as the sacrificial anode, a series of valuable butenedioic acids are obtained in moderate to excellent yields with an E/Z ratio up to 50:1. This method features high E-selectivity, high step and atom economy, easy scalability, and a nice substrate scope, which renders it appealing for promising applications in organic synthesis and materials chemistry.

Valorization of humins into furanyl functionalized biochar for selective hydrogenation of five-member rings of furan compounds

Humins, an unavoidable by-product of the acid-catalyzed conversion of carbohydrates, significantly limits the yield of platform molecules and accounts for the majority of carbon loss in the biomass utilization processes. Therefore, the utilization and recovery of humins is highly importance to enhance the atom efficiency of biomass valorization. In this work, using potassium ferrate (K2FeO4) to realize synchronous carbonization and graphitization, humins obtained from the dehydration of fructose is transformed into a novel porous biochar material and further applied to prepare noble metal based hydrogenation catalysts. By tuning the carbonization temperature, we demonstrate biochar calcined at 600 °C has large mass specific surface area while retaining abundant furan groups in the framework. With the high density of furan groups in structure, the Pd/biochar catalysts enhances the preferential adsorption capability of furanyl functional groups, thereby promoting the hydrogenation rate of furan compounds and improving the hydrogenation selectivity of furan rings. The demonstration of this novel application of humins will not only enhance the carbon efficiency of biomass conversion processes but also provide functionalized materials for catalytic applications.

A directed enolization strategy enables by-product-free construction of contiguous stereocentres en route to complex amino acids.

Homochiral α-amino acids are widely used in pharmaceutical design as key subunits in chiral catalyst synthesis or as building blocks in synthetic biology. Many synthetic methods have been developed to access rare or unnatural variants by controlling the installation of the α-stereocentre. By contrast, and despite their importance, α-amino acids possessing β-stereocentres are much harder to synthesize. Here we demonstrate an iridium-catalysed protocol that allows the direct upconversion of simple alkenes and glycine derivatives to give β-substituted α-amino acids with exceptional levels of regio- and stereocontrol. Our method exploits the native directing ability of a glycine-derived N-H unit to facilitate Ir-catalysed enolization of the adjacent carbonyl. The resulting stereodefined enolate cross-couples with a styrene or α-olefin to install two contiguous stereocentres. The process offers very high levels of regio- and stereocontrol and occurs with complete atom economy. In broader terms, our reaction design offers a unique directing-group-controlled strategy for the direct stereocontrolled α-alkylation of carbonyl compounds, and provides a powerful approach for the synthesis of challenging contiguous stereocentres.

Microwave accelerated green access to functionalized pyrazolo[5,1-b]quinazoline-3-carboxylate scaffold and their pharmacological screening

Herein, we explored an environmentally benign synthesis of pyrazolo[5,1-b]quinazoline-3-carboxylate derivatives 4(a-u) as potential antimicrobial, antitubercular as well as antimalarial agents. Our approach employed microwave-assisted PEG-400 as a biodegradable reaction medium to expedite the one-pot fusion of 1,3-dicarbonyl compounds 1(a-c), substituted aldehydes 2(a-g), and ethyl-3-aminopyrazole-4-carboxylate (3a). The current protocol offers the advantages of a low E-factor, high atom economy, mild reaction condition, reusability of PEG-400 and produce water as a byproduct with a favorable yield (up to 96% yield) in a short reaction time. Compared to the MIC values of standard antibiotics against their respective strains, compounds 4g exhibited superior activity against Bacillus subtilis while compound 4r demonstrated a more favorable MIC against Pseudomonas aeruginosa. Against Candida albicans, compounds 4c, 4f, 4i, 4o, 4r, and 4u showed excellent antifungal activity as compared standard medications griseofulvin and fluconazole. Compounds 4d and 4p showed significant antitubercular activity against Mycobacterium tuberculosis H37Rv whereas compounds 4d, 4e, 4p and 4q showed good antimalarial activity against Plasmodium falciparum in contrast to standard drug ciprofloxacin and quinine respectively. In vitro cytotoxicity assay against S. pombe cells indicated that the majority of tested compounds exhibit more than 80% cell viability, suggesting their non-toxic nature. A molecular docking study was conducted to elucidate the potential interactions between compound 4u and the active site of DNA gyrase. Based on the noteworthy findings from the investigation of drug-like properties and ADMET predictions, these derivatives depict an efficient multifunctional action and offer prospective access for future discoveries of antimicrobial, antitubercular, as well as antimalarial studies.

Copper-catalyzed aerobic oxidative dehydrogenative cyclization to construct polycyclic aromatic hydrocarbons

The copper-catalyzed aerobic oxidative dehydrogenative cyclization of benzo[b]thiophene represents an efficient approach for the rapid construction of polycyclic aromatic hydrocarbons (PAHs) containing benzo[b]thiophene groups. However, this remains an underexplored field. Here, we establish a new type of copper-catalyzed aerobic oxidative dehydrogenative cyclization of benzo[b]thiophene that enables the utilization of benzo[b]thiophene functionality to access polycyclic aromatic hydrocarbons. This methodology features mild reaction conditions, high atom economy, and remarkable chemo-selectivity, delivering a diversity of PAHs containing benzo[b]thiophene groups. Mechanistic experiments and DFT calculations demonstrate that the in situ generation of benzothiophenyl radical cation intermediate undergoes the intermolecular cyclization and the capture of H2O to furnish the oxidative cycloaromatization reaction. Labeling experiment disclosed that the carbonyl oxygen atom of the product originates from H2O generated during the reaction.

Selective Oxidation by TS-1 coupled with in-situ Synthesised H2O2

Feedstock valorisation with preformed H2O2 in conjunction with titanosilicate zeotypes is particularly attractive due to the increased selectivity, lower operating temperatures and improved process efficiency (particularly lower energy usage and enhanced atom economy) compared to aerobic pathways or alternative stoichiometric oxidants. However, numerous environmental and financial concerns associated with the application of commercial H2O2 remain. These concerns have led to a growing interest in the application of the in-situ synthesized oxidant for a range of chemical transformations. Herein, we provide an overview of the key contributions to this emerging field of oxidative catalysis, with a particular focus on propene epoxidation and ketone ammoximation, which are currently two crucial industrial-scale processes that utilise preformed H2O2 with the titanosilicate catalyst TS-1 for chemical synthesis. This contribution will highlight the potential for in-situ H2O2-mediated feedstock upgrading to replace existing technologies and contribute to the declared sustainability goals of the chemical synthesis sector.

Regio- and Diastereoselective Annulation of α,β-Unsaturated Aldimines with Alkenes via Allylic C(sp3)-H Activation by Rare-Earth Catalysts.

The [3 + 2] or [4 + 2] annulation of α,β-unsaturated aldimines with alkenes via β'- or γ-allylic C(sp3)-H activation is, in principle, an atom-efficient route for the synthesis of five- or six-membered-ring cycloalkylamines, which are important structural motifs in numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due to the lack of suitable catalysts. We report herein for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of α,β-unsaturated imines with alkenes via allylic C(sp3)-H activation by half-sandwich rare-earth catalysts having different metal ion sizes. The reaction of α-methyl-substituted α,β-unsaturated aldimines with alkenes by a C5Me4SiMe3-ligated scandium catalyst took place in a trans-diastereoselective [3 + 2] annulation fashion via C(sp3)-H activation at the α-methyl group (β'-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans-diastereoselectivity. In contrast, the reaction of β-methyl-substituted α,β-unsaturated aldimines with alkenes by a C5Me5-ligated cerium catalyst proceeded in a cis-diastereoselective [4 + 2] annulation fashion via γ-allylic C(sp3)-H activation, selectively yielding multisubstituted 2-cyclohexenylamines with excellent cis-diastereoselectivity. The mechanistic details of these transformations have been elucidated by deuterium-labeling experiments, kinetic isotope effect studies, and the isolation and transformations of key reaction intermediates. This work offers an efficient and selective protocol for the synthesis of a new family of cycloalkylamine derivatives, featuring 100% atom efficiency, high regio- and diastereoselectivity, broad substrate scope, and an unprecedented reaction mechanism.

TfOH-Catalyzed Facile Access for One-Pot Synthesis of β-Acylamino Ketones by Avoiding the Usage of Acetyl Chloride

AbstractWe have developed a TfOH-catalyzed, highly efficient protocol for the synthesis of biologically active β-acylamino ketones from aldehyde, ketone, and nitrile by avoiding the use of acetyl chloride. The reaction proceeds through a sequential aldol reaction followed by a nucleophilic attack of nitrile and hydrolysis of nitrile in one pot. The attractive features of this tandem process are mild reaction conditions, high atom economy, broad substrate scope with 51–87% yield, gram-scale reaction, and ease of operation.

Cascade Cyclization/Amination of para‐Quinone Methides with β‐Ketodinitriles: Synthesis of Polysubstituted Furans

AbstractA protocol for the synthesis of trisubstituted furans via phosphoric acid‐catalyzed regioselective cascade cyclization/amination of para‐quinone methides (p‐QMs) with β‐ketodinitriles has been disclosed for the first time. Various kinds of p‐QMs and β‐ketodinitriles can effectively produce the desired polysubstituted furan derivatives in 64–95% yields, demonstrating high atomic economy and their application in the construction of polysubstituted furan heterocycles. Preliminary biological activity assay suggests that these furans have potential anticancer activities.

Synthesis of 3‐Arylazoindoles through Iron(III)‐Catalyzed C−H Azolation of Indoles and Arylhydrazines

AbstractA variety of functionalized 3‐arylazoindoles were prepared in good to excellent yields through an iron(III)‐catalyzed C−H azolation of 2‐substituted indoles with arylhydrazines under mild reaction conditions. The reaction underwent an initial TBN‐mediated nitrosation, 1,5‐hydrogen migration, intramolecular condensation, and 1,5‐hydrogen migration over four steps in one pot. A paracyclophane‐derived 3‐phenylazoindole could be prepared in 25% yield over three steps and some prepared 3‐arylazoindoles showed a different fluorescence emission wavelength and existed obvious pH conditions response. The present method highlights broad substrate scope of easily available starting materials, wide range of functional group compatibility, gram scalable preparations, high atom economy, avoidance of unstable and explosive azolation reagents, and simple purification operations by extraction, washing, and recrystallization without flash column chromatography.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Sulfur in Waste‐Free Sustainable Synthesis: Advancing Carbon–Carbon Coupling Techniques

AbstractThis review explores the pivotal role of sulfur in advancing sustainable carbon‐carbon (C−C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C−H‐activation, and facilitating cycloaddition and C−S bond dissociation reactions. These attributes are crucial for developing waste‐free methodologies in green chemistry. Our mini‐review is focused on existing sulfur‐directed C−C coupling techniques, emphasizing their sustainability and comparing state‐of‐the‐art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal‐catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Bifunctional Chiral Agent Enables One-pot Spontaneous Deracemization of Racemic Compounds.

A novel one-pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α-diphenyl-2-pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)-enantiomer and (2S,3S)-enantiomer in solution, achieving a one-pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)-carprofen, (R,S)-indoprofen, and (R,S)-indobufen.The one-pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization-induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.

Photoredox-Catalyzed Acylchlorination of α-CF3 Alkenes with Acyl Chloride and Application as Masked Access to β-CF3-enones.

We disclose a photocatalytic strategy that simultaneously addresses the construction of trifluoromethylated quaternary carbon centers and the preparation of β-CF3-enones through radical difunctionalization of α-CF3 alkenes with acyl chlorides. This method is characterized by its broad functional group compatibility, high efficiency, and atom economy. The versatility of this transformation is poised to broaden the applications of α-CF3 alkenes, providing new pathways for the rapid assembly of structurally diverse fluorinated compounds.

Bifunctional Chiral Agent Enables One‐pot Spontaneous Deracemization of Racemic Compounds

A novel one‐pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α‐diphenyl‐2‐pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)‐enantiomer and (2S,3S)‐enantiomer in solution, achieving a one‐pot spontaneous deracemization.  This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)‐carprofen, (R,S)‐indoprofen, and (R,S)‐indobufen.The one‐pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization‐induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.

Photoinduced Generation of Active Intermediates from Unmodified 1,3‐Dicarbonyl Compounds for Organic Transformations

AbstractPhotocatalysis utilizes light as the initial driving force for chemical reactions, enabling reactions with high energy barriers in traditionally thermal chemistry to proceed under mild conditions. 1,3‐Dicarbonyl compounds occur as important active molecules in nature and are intermediates in pharmaceutical syntheses. In recent years, there have been numerous studies of these compounds, and it is common practice to pre‐modify them before the reaction, which is, however, unfavorable for the atom economy of the process. This paper provides a comprehensive review of the latest advancements in the site‐specific activation of unmodified 1,3‐dicarbonyl compounds by photoinduction. The focus is on elucidating the mechanisms of these reactions to provide insights and directions for future research in designing novel reactions.