Applications In Organic Synthesis Research Articles

Deoxygenation of benzylphenyl sulfones using 1,2-bis(diphenylphosphino)ethane (dppe)/NBS under metal-free conditions

An efficient route for the chemoselective deoxygenation of benzylphenyl sulfones to the corresponding sulfides has been developed using a mixture of 1,2-bis(diphenylphosphino)ethane(dppe) and NBS as an effective promoter. This is the first development on the deoxygenation of diverse benzylphenyl sulfones under metal-free conditions. The mild reaction conditions, formation of the water soluble by-product and tolerance of a wide range of functional groups promote its broad applications in organic synthesis.

Photoinduced Electron Donor Acceptor Complex-Enabled α-C(sp3)-H Alkenylation of Amines.

Allylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide-ranging applications in organic synthesis. However, direct α-C(sp3)-H alkenylation of feedstock amines, particularly for the preparation of α-alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition-metal-free α-alkenylation of various readily available amines with alkenylborate esters in excellent E/Z - and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late-stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor-acceptor complex between 2-iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5-hydrogen atom transfer to generate the crucial α-amino radicals, is the key to success of this chemistry.

Photoinduced Electron Donor Acceptor Complex‐Enabled α‐C(sp3)−H Alkenylation of Amines

AbstractAllylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide‐ranging applications in organic synthesis. However, direct α‐C(sp3)−H alkenylation of feedstock amines, particularly for the preparation of α‐alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition‐metal‐free α‐alkenylation of various readily available amines with alkenylborate esters in excellent E/Z ‐ and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late‐stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor‐acceptor complex between 2‐iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5‐hydrogen atom transfer to generate the crucial α‐amino radicals, is the key to success of this chemistry.

Post‐Functionalization of Organoboranes by Cu‐Catalyzed Azide Alkyne [3+2]‐Cycloaddition Reaction

AbstractThe copper‐catalyzed azide alkyne [3+2]‐cycloaddition (CuAAC) reaction of organoboranes represents an attractive area of research within the field of click chemistry, with diverse applications in organic synthesis, medicinal chemistry, or materials science. Despite the potential issues caused by the copper insertion into the carbon‐boron bond, significant progress has been made to harness the reactivity of organoboron compounds in CuAAC. This review provides an overview of the catalytic methods reported for CuAAC with various organoboranes, discussing the stability of the boron group and highlighting recent advancements in this area.

C–H/C–H Aromative carbonylation of diarylalkynes enabled palladium-catalyzed by 6-endo-dig carbocyclization

Transition metal-catalyzed cycloaromatization reactions of diarylalkynes offer a swift and versatile approach to synthesizing a wide array of polycyclic aromatic compounds. However, the specific mechanism of Pd-catalyzed C–H/C–H aromative carbonylation of diarylalkynes, particularly those bearing adjacent functional groups, remains a relatively unexplored area. Herein, we present a palladium-catalyzed C–H/C–H aromative carbonylation of diarylalkynes, which proceeds through an exclusive 6-endo-dig carbocyclization pathway, followed by the incorporation of CO to yield carbonyl compounds. This methodology provides a novel and efficient route for generating complex aromatic structures, thus expanding the potential applications in organic synthesis.

An Overview of Hydrogen Production from Renewable Sources and Its Main Applications

AbstractThere is a misconception that sustainability is only related to greenhouse gas emissions into the atmosphere, and that this is the only risk to which the planet is exposed. Sustainability is a multidimensional concept and must advance simoutaneously on several fronts, such as the urgent need to increase energy, clean water, clean air, food, mobility, health, and poverty reduction. All the problems of these multi‐dimensions are aggravated by the continuous growth of the world population, mainly in economic and socio‐environmental issues. However, the biggest challenge is to increase the supply of clean energy from renewable sources, as all other dimensions of sustainability depend on energy supply and policy decisions. The consumption of fossil fuels has supplied the current energy demand by approximately 87 %. Still, there are predictions of depletion, and the effects caused on the environment by the production of greenhouse gases bring significant economic losses. In this review, we will address the most common methods for hydrogen production, as well as its main technological applications in organic synthesis and for energy generation.

"Cation Pool" generated from DMSO and 1,2-dihaloethanes and their application in organic synthesis.

Conventionally, carbenium and onium ions are prepared in the presence of nucleophiles due to their instability and transient nature. The nucleophiles that are unstable or inert to the reaction media cannot be used for reaction with the cationic species to access the desired compounds. To overcome these limitations, developing methods for generating organic cations irreversibly in the absence of nucleophiles is essential. The "cation pool" method developed by Yoshida and co-workers stands out as a reliable strategy to generate and accumulate the reactive cations in solution in the absence of nucleophiles. The cation pool method involves the electrolysis of the substrate in the absence of nucleophiles, usually at low temperature. Moreover, the generation of halogen and chalcogen cations through electrolysis needs extra care because of their low stability. This review covers our effort in generating and accumulating halogen cations as "cation pools", most importantly by simply heating a mixture of dimethyl sulfoxide (DMSO) and 1,2-dihaloethane (DXE, X = Cl, Br, I), and their use in the halogenation reactions. Furthermore, condition-dependent Pummerer-type fragmentations of DMSO-stabilized halogen cations to methyl(methylene)sulfonium ions and chlorodimethylsulfonium ions for synthetic applications are described.

C–X (X = C, O, S, N, B, P) Bond Deuteration and Late‐Stage Applications

Precise deuterium labeling has gained significant attentions owing to the wide applications in organic synthesis, medicinal chemistry, and organic materials. C−C and C−heteroatom bonds constitute the skeleton of organic molecules. This review summarizes the advancements on C−C and C−heteroatom bond deuterations as well as their applications in late‐stage deuterations of natural products and pharmaceutically relevant molecules.

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

Gellan gum-cellulose hydrogel incorporating with graphene oxide and magnetic nanoparticles as a novel nanocatalyst for the synthesis of dihydropyrano derivatives

In this project, a highly efficient catalyst with a remarkable yield of over 97 % was developed for the synthesis of dihydropyrano[2,3-c] pyrazole derivatives. A Gellan Gum-Cellulose hydrogel was prepared using Glutaraldehyde as the cross-linker, which served as the matrix for further modifications. Synthesized graphene oxide was then incorporated into the hydrogel structure using a modified Hummers method, enhancing the catalytic properties of the material. To facilitate the separation and recovery of the catalyst, the resulting structure was magnetized, leading to the formation of a magnetic nanocomposite. Even after undergoing four cycles of catalyst recovery, the GG-Cell hydrogel/GO/Fe3O4 nanocomposite retained 90 % of its initial catalytic activity, highlighting its robustness and stability. Detailed physical and chemical analyses were conducted to gain a comprehensive understanding of the synthesized magnetic catalyst, contributing to the advancement of the field of catalysis and holding great potential for various applications in organic synthesis and related fields.

Cu(II)-Organic Framework for Carboxylative Cyclization of Propargylic Amines with CO2.

Effective CO2 transformations hold essential significance for carbon neutrality and sustainable energy development. Carboxylative cyclization of propargylic amines with CO2 serves as an atom-economic reaction to afford oxazolidinones, showing broad applications in organic synthesis and pharmaceutical fields. However, most catalysts involved noble metals, exhibited low efficiency, or required large amounts of base. Hence, it is imperative to explore alternative noble-metal-free catalysts in order to achieve efficient conversion while minimizing the use of additives. Herein, a novel nanopore-based Cu(II)-organic framework (1) based on a new imidazole carboxylic ligand was successfully constructed and exhibited excellent stability. Catalytic investigations revealed that the combination of 1 with 1,4-diaza[2.2.2]bicyclooctane (DABCO) efficiently catalyzed the carboxylative cyclization of propargylic amines with CO2, achieving turnover numbers of 142 based on the catalyst and 7.1 based on DABCO. 1 as a heterogeneous catalyst maintained high catalytic performance even after being reused at least 5 cycles, with its structure remaining stable. The strong activation of Cu(II) cluster nodes of catalyst 1 toward -NH- groups within organic substrates, as demonstrated by mechanism experiments, along with excellent CO2 adsorption performance and the presence of regular 1D channels, synergistically facilitates the reaction rate. This research presents the first instance of a Cu(II)-organic framework achieving this cyclization reaction, offering wide prospects for novel catalyst design and CO2 utilization.

High Rotational Barrier Atropisomers.

Atropisomers have attracted a great deal of attention lately due to their numerous applications in organic synthesis and to their employment in drug discovery. However, the synthetic arsenal at our disposal with which to access them remains limited. The research described herein is two-pronged; we both demonstrate the use of MCR chemistry as a synthetic strategy for the de novo synthesis of a class of atropisomers having high barriers to rotation with the simultaneous insertion of multiple chiral elements and we study these unprecedented molecular systems by employing a combination of crystallography, NMR and DFT calculations. By fully exploiting the synthetic capabilities of our chemistry, we have been able to monitor a range of different types of interaction, i. e. π-π, CH-π, heteroatom-π and CD-π, in order to conduct structure-property studies. The results could be applied both to atroposelective synthesis and in drug discovery.

ULTRASOUND IN CATALYSIS

The results of studied on the use of ultrasound in catalyst synthesis and processing are summarised. It is demonstrated that exposure to ultrasound can regulate the textural and structural characteristics of catalysts by varying exposure time and the amplitude of ultrasonic radiation. Optimisation of the conditions of ultrasonic treatment of the catalysts is determined to provide improvement of their physicochemical properties. This allows achieving higher reagents conversion and selectivity of the formation of target products in various chemical reactions. Examples of ultrasound application from the viewpoint of following the green chemistry principles are considered. It is shown that ultrasound application in organic synthesis promotes improvement of chemical process characteristics and reduces reaction time.

A concise review on recent development of indole derivatives for anticancer activities

Indole heterocycles have been considered as noteworthy associated hybrids because of their diverse applications in organic synthesis, and coordination chemistry, as well as in the field of medicinal chemistry. Hence, numerous researchers around the globe have produced indole and its derivatives as objective motifs and exploited their biological activities. This review article intended to represent information about the synthesis, potential of the anticancer property, cytotoxicity, and level of clinical treatments, which could lay out the investigation to extend more effective indole-derived anticancer medicines. This insight also presents advanced synthetic analogs of indole derivatives and their anti-cancer activity. The literature report represented for the anticancer agents herein covers largely for the year 2014–2023.

CO2-switchable emulsion with controllable stability and viscosity based on chitosans and cetyltrimethylammonium bromide

Emulsions have extensive applications in food, cosmetics, and agriculture, while the requirements for emulsions differ in various fields. It is a challenge for one emulsion to satisfy multiple requirements in different applications. Herein, CO2-switchable emulsions with controllable stability and viscosity were prepared by a mixture of chitosans (CS) and CTAB. After adding low concentrations of CTAB (e.g. 0.5 mM), the viscous Pickering emulsions stabilized by CS alone were converted into moderate-viscous Pickering emulsions due to the competition adsorption between CS aggregates and CTAB at the oil-water interface. The transformation of emulsion types (such as Pickering and conventional emulsions) and the emulsion's stability and viscosity were controlled by CO2/N2 trigger. Furthermore, at high CTAB concentrations (≥ 0.8 mM), a novel long-term stable conventional emulsion was obtained after the CS aggregates at the oil-water interface were entirely replaced by CTAB. Compared with other stimuli, CO2 is recognized as a green trigger that doesn't cause contaminations in the system, which has potential applications in organic synthesis and polymerization. Our strategy provides a simple and effective method to smartly control the properties of the emulsions (such as the emulsion type, stability, and viscosity), obtaining an intelligent emulsion to meet different requirements in many applications.

Recent Advances in Halogen-Metal Exchange Reactions.

ConspectusThe halogen-metal exchange reaction is a very powerful method for preparing functionalized organometallic reagents in the fields of organic and organometallic chemistry. Since its inception, significant interest has been directed toward the on-demand development of new halogen-metal exchange reactions, primarily through the upgrading of exchange reagents. The enduring quest for optimal reactivity, superior functional group compatibility, and innovative synthetic applications of exchange reagents remains a fundamental objective. In the past several years, the emergence of some significant discoveries in halogen-metal exchange reactions has proclaimed a renaissance to this field. This Account outlines the latest advances within the domain contributed by the Knochel group, including the main points as follows.The stereoretentive I/Li exchange on stereodefined secondary alkyl iodides was developed for the synthesis of nonstabilized chiral secondary alkyllithium reagents. This provided a straightforward method to access chiral organolithium reagents, which can be trapped by various electrophiles or transmetalated with other metals such as copper, zinc, and magnesium, thus enabling the stereoselective synthesis of a series of functionalized compounds and natural products.Faster halogen-magnesium and halogen-zinc exchanges in toluene were realized using a novel kind of exchange reagent complexed with lithium alkoxide. These highly efficient exchange reactions are much faster than traditional ones and performed in an industrially friendly solvent. These advantages are of great value in practical synthesis, paving the way for new developments in this evolving area.Halogen-lanthanide exchanges and their novel applications in organic synthesis were established. These new exchanges introduced the lanthanide metals into halogen-metal exchange reactions for the first time, thereby opening new avenues in synthetic chemistry. Building on these achievements, a comparative analysis of the exchange reaction rates by kinetic study has quantified the relationship between the electronegativity of metals and the rates of halogen-metal exchanges.Br/Na exchange in continuous flow was achieved using a hexane-soluble exchange reagent, 2-ethylhexylsodium. This approach effectively circumvented the poor solubility of the organosodium reagent, which has proven to be of significant practical value and greatly enhanced the synthetic utility of the organosodium reagent in organic synthesis.These remarkable breakthroughs as mentioned above are fueled mainly by upgrading the exchange reagents, resulting in the development of new halogen-metal exchange reactions and innovative applications in organic synthesis. Given the importance of halogen-metal exchanges in synthetic chemistry, the pursuit of other types of exchange reactions, particularly those involving new metals, will be in continuous demand. This Account provides a timely summary of recent progress and will undoubtedly inspire further advances to drive this research field forward.

Carbon-doped carbon nitride with improved photocatalytic performance for visible-light-driven Giese reaction

In recent research, there has been significant focus on developing highly efficient photocatalysts for forming C(sp3)-C(sp3) bonds. In this study, a series of carbon-doped carbon nitride (C-CN-x) materials were synthesized through molecular self-assembly and thermal polymerization. The introduction of carbon atoms was found to modulate the band gap, specific surface area, and photoelectric properties of the C-CN-x catalysts. These catalysts were applied in the conjugate addition reaction of 1,3-dioxolane with electron-deficient olefins under blue light irradiation. Among them, C-CN-2 exhibited the highest photocatalytic activity with a yield of 91 %. Remarkably, a comparable yield was achieved under sunlight exposure. Furthermore, a detailed investigation into the reaction mechanism was conducted. This study provided valuable insights into the design and development of highly efficient photocatalysts for C(sp3)-C(sp3) bond formation, with potential applications in organic synthesis and green chemistry.

Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer.

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion of low energy starting materials such as H2O and CO2 into higher energy products in the form of carbohydrates and O2. While this model for utilizing light-driven charge transfer to drive catalytic reactions thermodynamically "uphill" has been extensively adapted for small molecule activation, molecular machines, photoswitches, and solar fuel chemistry, its application in organic synthesis has been less systematically developed. However, the potential benefits of these approaches are significant, both in enabling transformations that cannot be readily achieved using conventional thermal chemistry and in accessing distinct selectivity regimes that are uniquely enabled by excited-state mechanisms. In this Account, we present work from our group that highlights the ability of visible light photoredox catalysis to drive useful organic transformations away from their equilibrium positions, addressing a number of long-standing synthetic challenges.We first discuss how excited-state ET enabled the first general methods for the catalytic anti-Markovnikov hydroamination of unactivated alkenes with alkyl amines. In these reactions, an excited-state iridium(III) photocatalyst reversibly oxidizes secondary amine substrates to their corresponding aminium radical cations (ARCs). These electrophilic N-centered radicals can then react with olefins to furnish valuable tertiary amine products with complete anti-Markovnikov regioselectivity. Notably, some of these products are less thermodynamically stable than their corresponding amine and alkene starting materials. We next present a strategy for light-driven C-C bond cleavage within various aliphatic alcohols mediated by homolytic activation of alcohol O-H bonds by excited-state proton-coupled electron transfer (PCET). The resulting alkoxy radical intermediates then undergo C-C β-scission to ultimately provide isomeric linear carbonyl products that are often higher in energy than their cyclic alcohol precursors. Applications of this chemistry for the light-driven depolymerization of lignin biomass, commercial phenoxy resin, hydroxylated polyolefin derivatives, and thermoset polymers are presented as well. We then describe a method for the contrathermodynamic positional isomerization of highly substituted olefins by means of cooperative photoredox and chromium(II) catalysis. In this work, generation of an allylchromium(III) species that can undergo highly regioselective in situ protodemetalation enables access to a less substituted and thermodynamically less stable positional isomer. Product selectivity in this reaction is determined by the large differential in oxidation potentials between differently substituted olefin isomers. Lastly, we discuss a light-driven deracemization reaction developed in collaboration with the Miller group, wherein a racemic urea substrate undergoes spontaneous optical enrichment upon visible light irradiation in the presence of an iridium(III) chromophore, a chiral Brønsted base, and a chiral peptide thiol. Excellent levels of enantioselectivity are achieved via sequential and synergistic proton transfer (PT) and H atom transfer (HAT) steps. Taken together, these examples highlight the ability of excited-state ET events to enable access to nonequilibrium product distributions across a wide range of catalytic, redox-neutral transformations in which photons are the only stoichiometric reagents.

Linkage Conversion in Covalent Organic Frameworks: An Efficient Strategy to Promote Photocatalytic Organic Transformations

Covalent organic frameworks (COFs) are emerging as promising heterogeneous photocatalysts for organic transformations, owning to their fascinating optical properties, excellent recyclability, and customizable chemical structures. To maximize the photocatalytic activity of COFs, various strategies have been explored, including metal complexation, construction of donor‐acceptor structures, modification of functional groups, hybridization with inorganic semiconductors, and linkage conversion. Among these, linkage conversion has proved to be particularly effective, driving the production of numerous value‐added organic chemicals. In this concept article, we present a comprehensive overview of the latest advancements in linkage conversion and highlight the most enlightening examples that have adopted such a strategy to boost the photocatalytic capabilities of COFs for organic transformations. It is anticipated that this concept will assist researchers in designing novel COFs with multifunctional linkages, paving the way for their broader application in organic synthesis.

Blue LED assisted indazolone preparation using reusable CuWO4/g-C3N5 nanocomposite

In this study, CuWO4, g-C3N5, and CuWO4/g-C3N5 nanocomposites were successfully synthesized. The synthesized materials were examined using several characterization methods including XRD, FT-IR, XPS, UV–Vis DRS, PL, EIS, FE-SEM, and HR-TEM. The CuWO4/g-C3N5 nanocomposites were utilized for the synthesis of tetrahydroindazolone derivatives under blue light. The nanocomposite exhibited the maximum yield (86 %) within 1 h compared with the other pristine materials. The photocatalyst could be utilized six times with no major reduction in its photocatalytic effect. To the best of our knowledge, there is no existing research on the use of CuWO4/g-C3N5 nanocomposites for the synthesis of tetrahydroindazolones under blue light conditions. This paper presents a new framework for advancing the development of photocatalysts based on graphitic carbon nitride (g-C3N5) for applications in organic synthesis.