Organic Synthesis Research Articles

Access to Vinyl Gem-Difluorinated Cyclopropanes Via Photopromoted Palladium-Catalyzed Heck Reaction.

A photopromoted Pd-catalyzed Heck reaction of gem-difluorocyclopropyl bromides (DFCBs) with styrenes to deliver vinyl gem-difluorinated cyclopropanes (VDFCs) under mild conditions has been developed. The reaction demonstrates good functional group compatibility while providing high E/Z ratio of the products. Furthermore, the desired VDFCs can be easily transformed into fluorinated cyclic/acyclic architectures, which may broaden its applications in organic synthesis.

Lewis Acid‐Promoted C−H Chalcogenation of Arenes and Heteroarenes

AbstractAn efficient catalytic system employing TMS•OTf for the regioselective thiolation of electron‐rich arenes with sulfonyl hydrazides has been developed. The reaction occurs in a solvent mixture of dichloroethane and trifluoroethanol under mild conditions, with the addition of water. This method furnishes a range of para‐thio‐substituted arenes and 3‐sulfenyl‐indoles in good to excellent yields, marking a significant advancement in organic synthesis.

Multi-Omics Analysis Uncovers the Mechanism for Enhanced Organic Acid Accumulation in Peach (Prunus persica L.) Fruit from High-Altitude Areas

The early-ripening peach industry has undergone rapid development in the Panxi region of the Sichuan Basin in recent years. However, after the introduction of some new peach varieties to the high-altitude peach-producing areas in Panxi, the titratable acid content in peach fruit has significantly increased. This study compared the fruit quality indicators of early-ripening peach varieties cultivated in Xide County (a high-altitude peach-producing area) and Longquanyi District (a low-altitude peach-producing area) in Sichuan Province and analyzed the differences in organic acid metabolism by combining primary metabolomic and transcriptomic approaches. The results showed that the ‘Zhongtaohongyu’ fruit from the high-altitude peach-producing area had a much higher accumulation of malic acid and, accordingly, a significantly higher organic acid content than the other samples. The lower annual average temperature and stronger ultraviolet radiation in high-altitude peach-producing areas may lead to the increased expression of genes (PpNAD-ME1, PpNADP-ME3, and PpPEPC1) in the organic acid synthesis pathway and the decreased expression of genes (PpACO2, PpNAD-MDH2/3/4/5, and PpPEPCK2) in the organic acid degradation pathway in peach fruit, ultimately resulting in the accumulation of more organic acids. Among them, the downregulation of the key genes PpNAD-MDH3/4/5 involved in malic acid metabolism may be the main reason for the higher malic acid accumulation in peach fruit from high-altitude peach-producing areas. Overall, this study elucidates the mechanism by which environmental factors enhance the accumulation of organic acids in peach fruit from high-altitude peach-producing areas from a multi-omics perspective, as well as providing a theoretical basis for screening key genes involved in organic acid metabolism in peach fruit.

13C‐Labeling as a Method in Organic Synthesis, Catalysis and Biochemical Applications

AbstractThe incorporation of a labeled 13C atom provides a plethora of opportunities in organic synthesis and catalysis. Structure of complicated compounds can be successfully confirmed using the precise location of a labeled carbon atom; a reaction mechanism can be supported by the presence or absence of a label in reaction products; metabolic pathways of biological compounds can be found out depending on labeled products; the concentration of analyzed labeled compounds can be significantly lower for recording and successful interpretation of NMR spectra, etc. This review aims to provide a researcher with common and promising strategies for the synthesis of labeled compounds so that a researcher can select an appropriate route to save valuable labeled material. All the labeling approaches were considered based on starting labeling source. Ideological aim of the review is to demonstrate the opportunities for label incorporation so that a researcher can find the improvements in his own topic using labeled compounds. Utilization of labeled compounds in catalysis and studying reaction mechanisms were also considered to demonstrate the capabilities of labeled compounds, which may be useful in specific tasks and applications. The potential of labeled compounds in bioactive compound metabolite analysis was demonstrated on selected examples.

Visible Light-Induced Three-Component Alkoxyalkylation of Alkenes with α-Halocarbonyls and Alcohols.

A visible-light-induced three-component alkoxyalkylation of alkenes has been developed under the photocatalysis of fac-Ir(ppy)3. The alkene substrate scope included aryl and aliphatic alkenes as well as electron-rich and electron-deficient alkenes, allowing the facile coupling with a diverse array of α-halocarbonyl compounds. The redox potential-guided orchestration of radical processes with precision allows rapid access to highly functionalized products that are useful building blocks in organic synthesis.

NHC‐Catalyzed [3+3] Cycloaddition of 2‐(acetoxymethyl)buta‐2,3‐dienoates with 1 C,3O‐bisnucleophiles

AbstractDiverse transformations of allenoates catalyzed by Lewis bases have emerged as a powerful platform for generating new chemical entities in organic synthesis. Herein, an N‐heterocyclic carbene (NHC) catalyzed [3+3] cyclization of 2‐(acetoxymethyl)buta‐2,3‐dienoates with 1 C,3O‐bisnucleophiles has been developed. This approach provides a facile method to synthesize highly functionalized 4H‐pyran derivatives with a broad substrate scope (31 examples, up to 83 % yield).

Asymmetric Organocatalysed Synthesis of (R)-Mandelic Acid Esters and α-Alkoxy Derivatives from Commercial Sources.

Optically active mandelic acid esters represent a highly valuable class of building blocks in organic synthesis and recurrent motifs embedded in bioactive compounds and drugs. Herein, we provide an enantioselective one-pot synthesis based on Knoevenagel condensation/asymmetric epoxidation/domino ring-opening hydrolysis (DROH) sequence to the crude mandelic acids, which underwent a final esterification step to (R)-methyl mandelates. These products have been obtained in good to high overall yield and enantioselectivity, using commercially and widely available reagents and catalyst including aldehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, water and an epi-quinine-derived urea as the organocatalyst. Moreover, the versatility of the process has been demonstrated to prepare the corresponding α-alkoxy esters in highly enantioselective manner, when using primary alcohols in a domino ring-opening esterification (DROE) step. This system is a first example of non-enzymatic catalytic one-pot protocol which allows a straightforward asymmetric synthesis of highly valuable mandelic acid derivatives from aldehyde feedstocks.

Toward Sustainable Utilization and Production of Tartaric Acid.

Global efforts toward establishing a circular carbon economy have guided research interests towards exploring renewable technologies that can replace environmentally harmful fossil fuel-based production routes. In this context, sugar-based bio-derived substrates have been identified as renewable molecules for future implementation in chemical industries. Tartaric acid, a special C4 bio-compound with two hydroxyl and carboxylic groups in the structure, displays great potential for the food, polymer, and pharmaceutical industries due to its unique biological reactivity and performance-enhancing properties. To this point, there has yet to be a comprehensive literature review and perspective on the applications and synthesis of tartaric acid. As such, we have conducted a detailed and thorough outlook and discussion in terms of biological activity, organic synthesis, catalysis, structural characterization and synthetic routes. Lastly, we provide a critical discussion on the applications and synthesis of tartaric acid to give our insights into developing sustainable chemical technologies for the future.

A Review on Biological Activity of Quinoline-based Hybrids

Abstract: The quinoline scaffold has gained attention for its potential applications in organic synthesis and the medical field.The objective has been to identify quinoline-based hybrids with a range of biological activities, including as anti-tuberculosis, anti-cancer, antimalarial, anti-inflammatory, anti- Alzheimer's, antibacterial, and antidiabetic properties. This review provides a critical overview and highlights the latest development of quinoline-based hybrids and their potential bioactivities.

Photo-Induced Aerobic Oxidation of C–H Bonds

The photo-induced aerobic oxidation of C–H bonds has become an increasingly valuable strategy in organic synthesis, offering a green and efficient method for introducing oxygen into organic molecules. The utilization of molecular oxygen as an oxidant, coupled with visible-light photocatalysis, has gained significant attention due to its sustainability, atom economy, and environmentally benign nature. This review highlights the recent advancements in the field, focusing on the development of metal-free and transition-metal-based photocatalytic systems and novel photosensitizers capable of promoting selective C–H bond oxidation. The mechanistic pathways involved in various substrate oxidations, including benzylic, alkyl, alkene, and alkyne C–H bond transformations, are discussed. This review concludes with insights into the potential for integrating photocatalysis with renewable energy sources, positioning photo-induced aerobic oxidation as a cornerstone of sustainable chemical processes.

A photocatalytic C(sp)ꟷB bond formation employing SOMOphilic alkynyl sulfones and nucleophilic boryl radicals

Alkynylboron compounds are important scaffolds with broad applicability in Organic Synthesis. In contrast to polar or metal-catalyzed processes, here we employ a radical approach for the addition of nucleophilic boryl radicals to electrophilic SOMOphiles for the construction of the C(sp)ꟷB bond. The reaction renders the corresponding alkynylated amine boranes with broad functional group compatibility. In addition, we carried out theoretical studies by means of DFT to understand the reactivity and selectivity of the addition process.

Solvent Dictated Organic Transformations.

Solvent plays an important role in many chemical reactions. The C-H activation has been one of the most powerful tools in organic synthesis. These reactions are often assisted by solvents which not only provide a medium for the chemical reactions but also facilitate reaching to the product stage. The solvent helps the reaction profile both chemically and energetically to reach the targeted product. Organic transformations via C-H activation from the solvent assistance perspective has been discussed in this review. Various solvents such as tetrahydrofuran (THF), MeCN, dichloromethane (DCM), dimethoxyethane (DME), 1,2-dichloroethane (1,2-DCE), dimethylformamide (DMF), dimethylsulfoxide (DMSO), isopropyl nitrile (iPrCN), 1,4-dioxane, AcOH, trifluoroacetic acid (TFA), Ac2O, PhCF3, chloroform (CHCl3), H2O, N-methylpyrrolidone (NMP), acetone, methyl tert-butyl ether (MTBE), toluene, p-xylene, alcohols, MeOH, 1,1,1-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), tert-amyl alcohol and their roles are discussed. The exclusive role of the solvent in various transformations has been deliberated by highlighting the substrate scope, along with the proposed mechanisms. For easy classification, the review has been divided into three parts: (i) solvent-switched divergent C-H activation; (ii) C-H bond activation with solvent as the coupling reagent, and (iii) C-H activation with solvent caging and solvent-assisted electron donor acceptor (EDA) complex formation and autocatalysis.

Unraveling the Plasmonic Effect of Au in Promoting Photocatalytic H2 Generation and Organic Synthesis

Unraveling the Plasmonic Effect of Au in Promoting Photocatalytic H₂ Generation and Organic Synthesis

Divergent Regioselective Synthesis of Functionalized 1,2,3-1H-Triazoles from Nitriles and Arylazides Under Metal-Free and/or Solvent-Free Conditions.

Highly selective and divergent syntheses, which are crucial in both organic synthesis and medicinal chemistry, involve significant advancements in compound accessibility. By modifying α-cyano esters into α-cyano ketones, the synthesis pathway broadens to include a diverse range of 4-CN, 5-amino, and 5-arylamino derivatives of 1,2,3-triazoles, which are achieved notably through the Dimroth rearrangement. This versatility extends further with the potential for a triple cascade reaction, leading to the production of carboximidamide compounds, which are facilitated by the Cornforth rearrangement. Advancements in compound accessibility not only expand the repertoire of synthesized molecules but also open new avenues for potential pharmacological agents. Building on these findings, we have developed an innovative and efficient method for the divergent synthesis of functionalized 1,2,3-triazoles. This method strategically utilizes α-cyanocarbonyls and arylazides by harnessing their reactivity and compatibility to orchestrate a variety of molecular transformations. By optimizing these substrates, our goal is to simplify synthetic routes, improve product yields, and accelerate the discovery and development of new chemical entities with promising biological activities.

Electrochemical Synthesis of Alkenylsulfonates from Alkynes, NaHSO3 and Alcohols

Comprehensive SummaryAlkenylsulfonates are commonly encountered in medicinal chemistry, polymer chemistry, and organic synthesis. In this research, an electrochemical reaction involving alkynes, NaHSO3, and alcohols has been developed. This method yields functionalized alkenylsulfonates in good yields with broad functional group tolerance. Mechanism studies indicate that anodic oxidation of inorganic sulfite, radical insertion process, and HAT process are involved in this transformation.

Synthesis Methods of Loratadine and Its Clinical Application Comparison in Antihistamines

Loratadine is a second-generation antihistamine widely used in treating allergic diseases such as allergic rhinitis, urticaria, and conjunctivitis. Compared to first-generation antihistamines, loratadine has fewer central nervous system side effects, such as drowsiness and cognitive impairment, and exhibits prolonged efficacy. This paper comprehensively reviews the chemical structure, mechanism of action, and organic synthesis methods of loratadine. Loratadine’s tricyclic structure and selective binding to peripheral histamine H1 receptors allow it to effectively relieve allergic symptoms at low doses while minimizing side effects. The article also analyzes various classical and improved loratadine synthesis routes, comparing their advantages and disadvantages in terms of reaction conditions, yields, and environmental impact. By introducing novel catalysts and optimizing reaction conditions, the improved synthesis methods not only enhance yields and cost-effectiveness but also reduce environmental pollution. Additionally, this paper discusses the comparison of loratadine with other antihistamines in terms of efficacy and safety, highlighting its significant clinical advantages. Nonetheless, there remains a need for further optimization of its synthesis process and exploration of its potential in personalized treatment to meet the needs of different patients.

A Photochemical Strategy towards Michael Addition Reactions of Cyclopropenes.

The development of Michael addition reactions to conjugated cyclopropenes is a challenge in organic synthesis due to the fleeting and reactive nature of such strained Michael acceptor systems. Herein, the development of a photochemical approach towards such conjugated cyclopropenes is reported that serves as a strategic entry point to densely functionalized cyclopropanes in a diastereoselective fashion. The process involves the light-mediated generation of transient cyclopropenyl α,β-unsaturated esters from vinyl diazo esters, followed by an organic base catalyzed nucleophilic addition of N-heterocycles to directly access β-N-heterocyclic cyclopropanoic esters. With this synergistic approach, various trisubstituted cyclopropanes bearing N-heteroaryl and N-heterocyclic rings such as indole, pyrrole, benzimidazole, isatin, pyridinone and quinolinone were accessed efficiently in good yield and decent to good diastereoselectivities. Further, β-indolyl cyclopropanoic acids have been synthesized and were successfully evaluated as FABP-4 inhibitors. Theoretical calculations have been performed to elucidate the mechanism which was further supported by experimental findings.

Alkoxylation of Ketone Mediated by N‐Heterocyclic Carbene Borane and Sulfuric Acid in Alcohol

AbstractIn this study, a novel method for the alkoxylation of ketones has been developed, employing sulfuric acid and N‐heterocyclic carbene boranes (NHC−boranes). The ketones are reduced using NHC−borane (diMe‐Imd‐BH3) and subsequently alkoxylate with sulfuric acid in alcohol solvents. Due to the stability of NHC−borane in the presence of both moisture and air, this reaction emerges as an effective and accessible approach for organic synthesis.

The Divergent Reactivity of Acid Chlorides Under Transition Metal Catalysis.

The power and ability of catalysis to build multiple C-C bonds in a single step has had a transformative impact on organic synthesis. While the reactivity of organohalides with metal catalysts is widely appreciated, the related and more intricate reactivity of acid chlorides is less so, despite their use as common reagents in synthesis. Here, we review the transformations of acid chlorides in combination with unsaturated C-C bonds catalyzed by palladium, rhodium, or iridium and provide an outlook for future research opportunities.

One‐Pot Transition‐Metal‐Free Synthesis of Alkynyl Amides

AbstractAlkynyl amides play crucial roles in organic synthesis in the production of bioactive compounds and valuable heterocycles. Despite numerous studies on their synthesis, challenges persist due to the necessity of harsh or hazardous conditions and the use of costly or unstable reagents. Herein, we present a one‐pot method for the synthesis of all three bonds of the alkyne under transition‐metal‐free conditions. An important feature of this chemistry is the use of readily available feedstock chemicals, such as methyl esters and acetamides. This approach offers efficient access to a wide range of aryl and alkyl alkynyl amides and demonstrates excellent tolerance towards various functional groups in a sustainable and cost‐effective manner.