Search

In contrast to the well‐studied 1‐vinylcyclobutanols, the reactivity of 3‐vinylazetidin‐3‐ols 1 and 3‐vinyloxetan‐3‐ols 2 under transition metal catalysis remains largely unexplored. We report herein their unique reactivity under dual palladium and acid catalysis. In the presence of a catalytic amount of Pd(OAc)2(PPh3)2, AgTFA and triflic acid, the reaction of 1 or 2 with aryl iodides affords 2,3,4‐trisubstituted dihydrofurans, which are valuable heterocycles in organic synthesis. Mechanistic studies reveal that this arylative ring‐expansion reaction proceeds via a domino process involving Heck arylation of alkene, acid‐catalyzed transposition of allylic alcohol and ring opening of the azetidine/oxetane by an internal hydroxyl group. [ABSTRACT FROM AUTHOR]

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal‐catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal‐hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well‐established HER. Using an inexpensive and bench‐stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large‐scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre‐coordination of the substrate to the nickel center. [ABSTRACT FROM AUTHOR]

Aryl diazonium intermediates have emerged as highly versatile intermediates in modern organic synthesis and chemical biology, demonstrating remarkable reactivity under mild reaction conditions. Their significance has extended to DNA‐encoded libraries (DELs), where they serve as valuable alternatives to traditional aryl halide‐based cross‐coupling reactions. Aryl diazonium intermediates as N2‐annulation synthons can efficiently transform into benzotriazinone core on DNA besides C−C coupling. This concept paper illuminates recent advances in this field, emphasizing their applications and potential across various facets of DELs, off‐DNA chemistry, DELs selection, and DNA‐based probes. It is anticipated that these developments will propel the broader utilization of DNA‐conjugated aryl diazonium salt intermediates in DELs, protein labeling, hit discovery, and other interdisciplinary fields. [ABSTRACT FROM AUTHOR]

Organoalkali compounds have undergone a far‐reaching transformation being a coupling partner to a mediator in unusual organic conversions which finds its spot in the field of sustainable synthesis. Transition‐metal catalysis has always been the priority in C(sp3)−H bond functionalization, however alternatively, in recent times this has been seriously challenged by earth‐abundant alkali metals and their complexes arriving at new sustainable organometallic reagents. In this line, the importance of MN(SiMe3)2 (M=Li, Na, K & Cs) reagent revived in C(sp3)−H bond functionalization over recent years in organic synthesis is showcased in this minireview. MN(SiMe3)2 reagent with higher reactivity, enhanced stability, and bespoke cation‐π interaction have shown eye‐opening mediated processes such as C(sp3)−C(sp3) cross‐coupling, radical‐radical cross‐coupling, aminobenzylation, annulation, aroylation, and other transformations to utilize readily available petrochemical feedstocks. This article also emphasizes the unusual reactivity of MN(SiMe3)2 reagent in unreactive and robust C−X (X=O, N, F, C) bond cleavage reactions that occurred alongside the C(sp3)−H bond functionalization. Overall, this review encourages the community to exploit the untapped potential of MN(SiMe3)2 reagent and also inspires them to take up this subject to even greater heights. [ABSTRACT FROM AUTHOR]

Organic synthesis provides an accessible route to preparative scale biological glycans, although schemes to access these complex structures are often complicated by preparation of multiple monosaccharide building blocks. Bimodal glycosyl donors capable of forming both α‐ and β‐anomers selectively, are an emerging tactic to reduce the required number of individual synthetic components in glycan construction. This review discusses examples of bimodal donors in the literature, and how they achieve their stereocontrol for both anomers. Notable examples include a bespoke O‐2 benzyl protecting group, a strained glycal for reaction using organometallic catalysis, and a simple perbenzylated donor optimised for stereoselective glycosylation through extensive reaction tuning. [ABSTRACT FROM AUTHOR]

Concerns about increasing greenhouse gas emissions and their effect on our environment highlight the urgent need for new sustainable technologies. Visible light photocatalysis allows the clean and selective generation of reactive intermediates under mild conditions. The more widespread adoption of the current generation of photocatalysts, particularly those using precious metals, is hampered by drawbacks such as their cost, toxicity, difficult separation, and limited recyclability. This is driving the search for alternatives, such as porous organic polymers (POPs). This new class of materials is made entirely from organic building blocks, can possess high surface area and stability, and has a controllable composition and functionality. This review focuses on the application of POPs as photocatalysts in organic synthesis. For each reaction type, a representative material is discussed, with special attention to the mechanism of the reaction. Additionally, an overview is given, comparing POPs with other classes of photocatalysts, and critical conclusions and future perspectives are provided on this important field. [ABSTRACT FROM AUTHOR]

A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst's superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond. Dearomative hydroboration of predominantly existing indole derivatives provides a straightforward strategy to synthesize boryl indolines, but developing eco-friendly methods for remains challenging. Here, the authors develop a method for heterogeneous photocatalytic trans-hydroboration of indole derivatives with NHC-borane. [ABSTRACT FROM AUTHOR]

The transition‐metal‐free synthesis of organic compounds especially heterocycles is in resonance with one of the twelve principles proposed by Prof. Paul Anastas in his renowned work towards the sustainable development of green chemistry. Traditional‐metal‐catalyzed reactions often involve expensive or toxic metal catalysts, and there is a growing interest in developing more sustainable and environmentally friendly methods. The arylation of heterocycles is an important area of research in organic chemistry, particularly in the synthesis of biologically active compounds and pharmaceuticals. Arylation of heterocycles at different positions enhances the potency and stability of biologically and pharmaceutically important scaffolds. In this review, an overview of the synthetic protocols developed for the arylation of a variety of heterocyclic compounds including, pyrroles, pyridines, thiophene, indole, oxindoles, purines, xanthene, etc. has been described. [ABSTRACT FROM AUTHOR]

Olefin [2+2] photocycloaddition reactions based on coordination-bond templates provide numerous advantages for the selective synthesis of cyclobutane compounds. This review outlines the recent advances in the design and construction of single crystal platforms of olefinic coordination polymers for precise organic synthesis, in situ exploration of reaction mechanisms, and possible developments as comprehensively as possible. Numerous examples are presented to illustrate how the arrangements of the olefin pairs influence the solid-state photoreactivity and examine the types of cyclobutane products. Furthermore, the photocycloaddition reaction mechanisms are investigated by combining advanced techniques such as single crystal X-ray diffraction, powder X-ray diffraction, nuclear magnetic resonance, infrared spectroscopy, fluorescence spectroscopy, laser scanning confocal microscopy and theoretical calculations. Finally, potential applications resulting from promising physicochemical properties before and after photoreactions are discussed, and existing challenges and possible solutions are also proposed. [ABSTRACT FROM AUTHOR]

The construction of two distal stereocenters through a single catalytic process is of great interest in organic synthesis. While there are some successful reports regarding stereodivergent preparation of 1,3‐ or 1,4‐stereocenters, the more challenged 1,5‐nonadjacent stereocenters have never been achieved in a stereodivergent fashion. Herein we describe a synergistic palladium/copper catalysis for 1,4‐difunctionalization reactions of 1,3‐dienes, providing access to 1,5‐nonadjacent quaternary stereocenters. Because each of the two catalysts separately controlled one of the newly formed stereocenters, stereodivergent synthesis of all four diastereomers of the products could readily be achieved simply by choosing an appropriate combination of chiral catalysts. Experimental and computational studies supported a mechanism involving a Heck/Tsuji–Trost cascade reaction, and the origins of the stereoselectivity were elucidated. [ABSTRACT FROM AUTHOR]

Selective acylation of saccharides is an important basic transformation in saccharide chemistry. Synthetic strategies and protocols for saccharides can reach broad users when reagents are simple (inexpensive and readily available), green, and easy to handle. Herein, we disclose that the simplest boric acid, B(OH)3, can work as an effective promoter for C3–OH selective acylation of unprotected monosaccharides under the catalysis of a readily available N-heterocyclic carbene catalyst. Solvents such as THF from untreated commercial sources can be directly used. Mechanistically, the boric acid plays multiple roles in benefiting reaction yields and regioselectivities, including solubilizing the saccharide substrates by forming borate esters with the saccharides, shielding the C6–OH unit of the saccharides from acylation, and enhancing the selectivity between C3–OH and C2–OH reactions. We also found that the solvent has a profounder effect on the reaction yield and selectivity than the base. Selectively acylated saccharide products can be easily obtained with good-to-excellent yields and gram scales. Our study will encourage the further development of new synthetic strategies for saccharides that can reach beyond laboratory scales and to scientists not necessarily with expertise in organic synthesis. Compared to previous methods using aryl and alkyl boronic acids as modulating reagents, the use of boric acid provides a greener solution economically and environmentally. [ABSTRACT FROM AUTHOR]

The pivotal role of electrochemistry has significantly improved the step economy of organic transformations, thereby surpassing conventional pathways. Sustainable electrochemical transformations enormously influenced the chemical synthesis and attracted significant attention towards pharmaceutical industries. More specifically, the electrochemical organic transformation streamlines the synthesis of a variety of drugs and precursors of drug-like molecules. This review summarised the electrochemical synthesis of more than 50 such drugs, therapeutic chemicals, pharmaceuticals, and precursors of drug-like molecules, which were directly or indirectly synthesised over the period of 2017–2023. [ABSTRACT FROM AUTHOR]

Cross-coupling reactions play a vital role in modern organic synthesis, enabling the construction of necessary C–C or C–(het)atom bonds for synthetic transformations. Although C(sp2)–C and C(sp2)–N cross-coupling reactions have received significant attention, recent advancements have also highlighted the significance of C(sp2)–S cross-coupling reactions. These reactions lead to the synthesis of valuable compounds, including pharmaceuticals and materials. In a recent report, we introduced Adaptive Dynamic Homogeneous Catalysis (AD-HoC) as an efficient method for C(sp2)–S cross-coupling reactions. This method operates without the need for any ligands, base, or additional additives, relying solely on essential parameters. In this report, we discuss the use of mesoporous graphitic carbon nitride (mpg-CN) as an all-organic heterogeneous photocatalyst in such transformations. The versatility and robustness of the reaction are showcased with fifty synthetic examples, achieving up to a 98% yield. The use of mpg-CN as a catalyst additionally enables the easy recovery of the photocatalyst from the reaction mixture and facilitates the sequential execution of multiple cross-coupling reactions with consistent yields of the desired products using a simple setup. This approach is a significant advancement in the field, both in terms of operational simplicity and environmental impact, traits that we all envision for sustainability. [ABSTRACT FROM AUTHOR]

Photothermal catalysis, as a green and sustainable technology, has attracted increasing attention in the fields of clean energy and green organic synthesis. Integrating photothermal catalysis with solar-driven hydrogen production and organic synthetic chemistry has become a promising strategy for sustainable energy generation with great research and practical value. In this review, we present an overview of the background of solar-driven photothermal catalytic reactions, introduce the fundamental principles of photocatalysis, thermal catalysis, and photothermal reduction of hydrogen coupled with selective oxidation of organic compounds, and summarize the recent advances in photothermal semiconductor catalysts such as carbon-based materials, titanium-based materials, noble metal composites, and metal sulfides. We also highlight the recent advances in the application of these catalysts in photothermal catalytic water splitting for hydrogen generation and selective oxidation of organic compounds. Finally, we address the challenges and opportunities faced by solar-drive photothermal catalysts in the synergism of photocatalytic hydrogen production and selective oxidation of organic compounds. The aim is to provide guiding insights for the rational design of this dual-function catalytic system, offering a green pathway for the development of clean energy and selective oxidation in organic synthesis. • Introduced the transition from photocatalysis and thermal catalysis to photothermal catalysis. • Discussed development and applications of carbon-, titanium-, noble metal-, and metal sulfide photothermal materials. • Explored prospects for dual-functional reaction systems for photothermal water splitting and organic conversion. [ABSTRACT FROM AUTHOR]

New methods and strategies for the direct oxidation of benzylic C−H bonds are highly desirable, owing to the importance of ketone motifs in significant organic transformations and the synthesis of valuable molecules, including pharmaceuticals, pesticides, and fine chemicals. Herein, we describe an electrochemical benzylic C−H oxidation strategy for the synthesis of ketones using MeOH as an oxygen source. Inexpensive and safe KBr serves as both an electrolyte and a bromide radical precursor in the reaction. This transformation also offers several advantages such as mild conditions, broad functional group tolerance, and operational simplicity. Mechanistic investigations by control experiments, radical scavenging experiments, electron paramagnetic resonance (EPR), kinetic studies, cyclic voltammetry (CV), and in‐situ Fourier transform infrared (FTIR) spectroscopy support a pathway involving the formation and transformation of benzyl methyl ether via hydrogen atom transfer (HAT) and single‐electron transfer (SET). The practical application of our strategy is highlighted by the successful synthesis of five pharmaceuticals, namely lenperone, melperone, diphenhydramine, cinnarizine, and flunarizine. [ABSTRACT FROM AUTHOR]

Stereoselective construction of g- and d-stereocenters in carbonyl compounds is a pivotal objective in asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote g-C−H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes g-tertiary and a-quaternary stereocenters simultaneously in up to >99% enantiomeric excess, providing access to a wide range of cyclic chiral synthons and bioactive molecules. The sequential enantioselective editing of two methylene C-H bonds can be achieved by using chiral ligands with opposite configuration to construct carbocycles containing three chiral centers. Enantioselective remote d-C−H (hetero)arylation is also realized to establish d-stereocenters that are particularly challenging to access using classical methodologies. [ABSTRACT FROM AUTHOR]

Frustrated Lewis Pairs (FLPs) represent a unique class of interactions in Lewis acid‐base chemistry, driven by spatial hindrance or incongruent orbital energy levels that hinder the formation of effective coordination bonds. FLPs have received significant attention for their application in activating small molecules and facilitating organic synthesis reactions. Recent developments have led to the emergence of Frustrated Radical Pairs (FRPs) as an extension of the radical family. FRPs are formed from FLPs through Single Electron Transfer (SET) and exhibit the ability to activate a variety of chemical bonds. While research on FLPs is well‐established, investigations into FRPs in organic reactions remain limited. This review highlights the current state of FRPs in organic synthesis, delves into mechanistic insights, explores their potential, and underscores the challenges in this emerging field. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A mild and practical method for synthesizing fluorinated quinoline derivatives, which have a wide range of applications in pharmaceuticals, materials, and organic synthesis, was described through C—F bond insertion into indoles using CHBr2F. The simple conditions, readily availability of CHBr2F, as well as the versatility of the transformations make this strategy very powerful in synthesizing 3‐fluoroquinoline and 3‐fluoroquinolone. The mechanistic studies reveal that bromofluorocarbene generated in‐situ under basic condition was the key intermediate. [ABSTRACT FROM AUTHOR]

This article explores the nickel-catalyzed transesterification of methyl esters, which is an important process in synthetic chemistry. The authors discuss the challenges of activating esters for cross-coupling reactions and the development of a reversible transformation using a nickel catalyst and SIPr. They also investigate the optimization of the reaction and the identification of effective ligands for different types of esters. The goal is to develop a transesterification method that is different from traditional acid- and base-mediated pathways. The article presents the development of a catalytic transesterification reaction using methyl esters and aliphatic alcohols, with optimized conditions and successful formation of diverse esters. The reaction is advantageous because it only produces methanol as waste and does not require the use of acids or bases. Mechanistic studies suggest that the cleavage of the C(acyl)-O bond is reversible, and ongoing research is being conducted on the use of methyl esters as cross-coupling electrophiles. [Extracted from the article]

This article provides an insider's perspective on the research laboratory of Keith Fagnou at the University of Ottawa. The author, a graduate student, describes the collaborative and mentoring atmosphere in the lab, which contributed to increased productivity. The lab's focus was on ligand design projects for direct arylation reactions, and they achieved early successes in developing optimized reaction conditions and expanding reactivity to more challenging substrates. The article also emphasizes Fagnou's dedication to mentorship and his students' successful careers in academia and the pharmaceutical industry. Overall, Fagnou's research group made significant contributions to chemistry, particularly in the areas of direct arylation and oxidative biaryl coupling reactions. [Extracted from the article]

Amphidinolides C, F, and U, including C2‐C4 analogs, are highly cytotoxic marine macrolides, mainly isolated from dinoflagellates of the genus Amphidinium. All these polyketides share a 75 % or more similar structure, highlighted by a macrolactone ring, at least one trans‐2,5‐substituted‐THF motif and a characteristic polyenic side chain. From their isolation and absolute configurational assignment, the total synthesis of these marine macrolides represented an intense challenge to the organic synthesis community over the last 15 years, with around 14 research groups engaged in this inspiring task. In the first part of this review, we present the different approaches to the isolation and characterization of these natural products, including the most recent analogs, which may cast doubt on the biogenetic origin of these compounds. The various synthetic approaches to the total synthesis of C, F, and U amphidinolides are presented in a second part, focusing on key reactions and/or innovative strategies. The review concludes in a third section summarizing the successful approaches leading to the total synthesis of one of the members of this amphidinolide subfamily. [ABSTRACT FROM AUTHOR]

The Wittig reaction is one of the most important processes in organic chemistry for the asymmetric synthesis of olefinic compounds. In view of the increasingly acknowledged potentiality of the electric fields in promoting reactions, here we will consider the effect of the oriented external electric field (OEEF) on the second step of Wittig reaction (i. e. the ring opening oxaphosphetane) in a model system for non‐stabilized ylides. In particular, we have determined the optimal direction and strength of the electric field that should be applied to annihilate the reaction barrier of the ring opening through the polarizable molecular electric dipole (PMED) model that we have recently developed. We conclude that the application of the optimal external electric field for the oxaphosphetane ring opening favours a Bestmann‐like mechanism. [ABSTRACT FROM AUTHOR]

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) have potential to be used in sustainable agriculture to mitigate various stresses that plants have to deal with. The natural SLs, as well as the synthetic analogs, are difficult to obtain in sufficient amounts for practical applications. At the same time, fluorescent SLs would be useful for the mechanistic understanding of their effects based on bio-imaging or spectroscopic techniques. In this study, new fluorescent SL mimics containing a substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive furan-2-one moiety were prepared. The structural, spectroscopic, and biological activity of the new SL mimics on phytopathogens were investigated and compared with previously synthetized fluorescent SL mimics. The chemical group at the C-6 position of the naphthalimide ring influences the fluorescence parameters. All SL mimics showed effects similar to GR24 on phytopathogens, indicating their suitability for practical applications. The pattern of the biological activity depended on the fungal species, SL mimic and concentration, and hyphal order. This dependence is probably related to the specificity of each fungal receptor–SL mimic interaction, which will have to be analyzed in-depth. Based on the biological properties and spectroscopic particularities, one SL mimic could be a good candidate for microscopic and spectroscopic investigations. [ABSTRACT FROM AUTHOR]

The potential of aerogels as catalysts for the synthesis of a relevant class of bis-heterocyclic compounds such as bis(indolyl)methanes was investigated. In particular, the studied catalyst was a nanocomposite aerogel based on nanocrystalline nickel ferrite (NiFe2O4) dispersed on amorphous porous silica aerogel obtained by two-step sol–gel synthesis followed by gel drying under supercritical conditions and calcination treatments. It was found that the NiFe2O4/SiO2 aerogel is an active catalyst for the selected reaction, enabling high conversions at room temperature, and it proved to be active for three repeated runs. The catalytic activity can be ascribed to both the textural and acidic features of the silica matrix and of the nanocrystalline ferrite. In addition, ferrite nanocrystals provide functionality for magnetic recovery of the catalyst from the crude mixture, enabling time-effective separation from the reaction environment. Evidence of the retention of species involved in the reaction into the catalyst is also pointed out, likely due to the porosity of the aerogel together with the affinity of some species towards the silica matrix. Our work contributes to the study of aerogels as catalysts for organic reactions by demonstrating their potential as well as limitations for the room-temperature synthesis of bis(indolyl)methanes. [ABSTRACT FROM AUTHOR]

Within the realm of organic synthesis, photocatalysis has blossomed since the beginning of the last decade. A plethora of classical reactivities, such as selective oxidation of alcohol and amines, redox radical formation of reactive species in situ, and indirect activation of an organic substrate for cycloaddition by EnT, have been revised in a milder and more sustainable fashion via photocatalysis. However, even though the spark of creativity leads scientists to explore new reactions and reactivities, the urgency of replacing the toxic and critical metals that are involved as catalysts has encouraged chemists to find alternatives in the branch of science called organocatalysis. Unfortunately, replacing metal catalysts with organic analogues can be too expensive sometimes; however, this drawback can be solved by the reutilization of the catalyst if it is heterogeneous. The aim of this review is to present the recent works in the field of heterogeneous photocatalysis, applied to organic synthesis, enabled by continuous flow. In detail, among the heterogeneous catalysts, g-CN, polymeric photoactive materials, and supported molecular catalysts have been discussed within their specific sections, rather than focusing on the types of reactions. [ABSTRACT FROM AUTHOR]

Poly (glycerol sebacate) is a widely studied elastomeric copolymer obtained from the polycondensation of two bioresorbable monomers, glycerol and sebacic acid. Due to its biocompatibility and the possibility to tailor its biodegradability rate and mechanical properties, PGS has gained lots of interest in the last two decades, especially in the soft tissue engineering field. Different synthetic approaches have been proposed, ranging from classic thermal polyesterification and curing to microwave-assisted organic synthesis, UV crosslinking and enzymatic catalysis. Each technique, characterized by its advantages and disadvantages, can be tailored by controlling the crosslinking density, which depends on specific synthetic parameters. In this work, classic and alternative synthetic methods, as well as characterisation and tailoring techniques, are critically reviewed with the aim to provide a valuable tool for the reproducible and customized production of PGS for tissue engineering applications. [ABSTRACT FROM AUTHOR]

This document provides information on the synthesis and characterization of various isoxazole compounds. The compounds were synthesized using specific reactions and their yields, physical properties, and spectroscopic data are reported. The information presented can be useful for researchers studying isoxazole compounds and their properties. The authors acknowledge the support of DST and SCXRD LAB, SAIF, IIT Madras for single-crystal X-ray analysis. Supporting information for the article is available online. [Extracted from the article]

Frustrated Lewis Pairs (FLPs) represent a unique class of interactions in Lewis acid‐base chemistry, driven by spatial hindrance or incongruent orbital energy levels that hinder the formation of effective coordination bonds. FLPs have received significant attention for their application in activating small molecules and facilitating organic synthesis reactions. Recent developments have led to the emergence of Frustrated Radical Pairs (FRPs) as an extension of the radical family. FRPs are formed from FLPs through Single Electron Transfer (SET) and exhibit the ability to activate a variety of chemical bonds. While research on FLPs is well‐established, investigations into FRPs in organic reactions remain limited. This review highlights the current state of FRPs in organic synthesis, delves into mechanistic insights, explores their potential, and underscores the challenges in this emerging field. [ABSTRACT FROM AUTHOR]

Indium triflate (In(OTf)3) has proven to be a powerful and sustainable catalyst in the synthesis of modern organic compounds, enabling a variety of transformations such as functionalization, cyclization, and multicomponent reactions. To provide insight into the most recent methods and applications, this study attempts to provide a comprehensive and up‐to‐date summary of these advances in the application of indium triflate as a catalyst in organic synthesis, focusing on the last five years of literature. The application of indium triflate as opposed to alternative indium(III) catalysts in organic transformations will be the main emphasis of this review, which will cover recent developments through research articles and reviews published between 2019 and 2023. This minireview will make a significant contribution to the existing literature by consolidating recent advancements in the use of indium triflate in modern organic synthesis. [ABSTRACT FROM AUTHOR]

The hydrogenolysis of oxygenates such as alcohols and ethers is central to the biomass valorization and also a valuable transformation in organic synthesis. However, a mild and efficient catalyst system for the hydrogenolysis of a large variety of alcohols and ethers with various functional groups is still underdeveloped. Here, we report an aluminum metaphosphate‐supported Pt nanoparticles (Pt/Al(PO3)3) for the hydrogenolysis of a wide variety of primary, secondary, and tertiary alkyl and benzylic alcohols, and dialkyl, aryl alkyl, and diaryl ethers, including biomass‐derived furanic compounds, under mild conditions (0.1–1 atm of H2, as low as 70 °C). Mechanistic studies suggested that H2 induces formation of the surface Brønsted acid sites via its cleavage by supported Pt nanoparticles. Accordingly, the high efficiency and the wide applicability of the catalyst system are attributed to the activation and cleavage of C−O bonds by the hydrogen‐induced Brønsted acid sites with the assistance of Lewis acidic Al sites on the catalyst surface. The high efficiency of the catalyst implies its potential application in energy‐efficient biomass valorization or fine chemical synthesis. [ABSTRACT FROM AUTHOR]

Birch reduction and similar dissolved metal‐type transformations hold significant importance in the organic synthesis toolbox. Historically, the field has been dominated by alkali metal reductants. In this study, we report that largely neglected, low‐reactive alkaline earth metals can become powerful and affordable reductants when used in a ball mill under essentially solvent‐free conditions, in the presence of ethylenediamine and THF as liquid additives. Calcium can reduce both electron‐deficient and electron‐rich arenes, with yields of products similar to those obtained with lithium metal. Magnesium reveals enhanced reducing power, enabling the reduction of benzoic acids while keeping electron‐rich aromatic moieties intact and allows for chemoselective transformations. The developed mechanochemical approach uses readily available and safer‐to‐handle metals, operates under air and ambient temperature conditions, and can be used for gram‐scale preparations. Finally, we demonstrate that the developed conditions can be used for other dissolved metal‐type reductive transformations, including reductive amination, deoxygenation, dehalogenation, alkene and alkyne reductions. [ABSTRACT FROM AUTHOR]

Single‐atom heterogeneous catalysts (SACs) hold promise as sustainable alternatives to metal complexes in organic transformations. However, their working structure and dynamics remain poorly understood, hindering advances in their design. Exploiting the unique features of droplet‐based microfluidics, we present the first in‐situ assessment of a palladium SAC based on exfoliated carbon nitride in Suzuki–Miyaura cross‐coupling using X‐ray absorption spectroscopy. Our results confirm a surface‐catalyzed mechanism, revealing the distinct electronic structure of active Pd centers compared to homogeneous systems, and providing insights into the stabilizing role of ligands and bases. This study establishes a valuable framework for advancing mechanistic understanding of organic syntheses catalyzed by SACs. [ABSTRACT FROM AUTHOR]

Since Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic synthesis over the past two centuries has predominantly relied on the exploration and utilization of chemical reactions rooted in two‐electron heterolytic ionic chemistry. While one‐electron homolytic radical chemistry is both rich in fundamental reactivities and attractive with practical advantages, the synthetic application of radical reactions has been long hampered by the formidable challenges associated with the control over reactivity and selectivity of high‐energy radical intermediates. To fully harness the untapped potential of radical chemistry for organic synthesis, there is a pressing need to formulate radically different concepts and broadly applicable strategies to address these outstanding issues. In pursuit of this objective, researchers have been actively developing metalloradical catalysis (MRC) as a comprehensive framework to guide the design of general approaches for controlling over reactivity and stereoselectivity of homolytic radical reactions. Essentially, MRC exploits the metal‐centered radicals present in open‐shell metal complexes as one‐electron catalysts for homolytic activation of substrates to generate metal‐entangled organic radicals as the key intermediates to govern the reaction pathway and stereochemical course of subsequent catalytic radical processes. Different from the conventional two‐electron catalysis by transition metal complexes, MRC operates through one‐electron chemistry utilizing stepwise radical mechanisms. [ABSTRACT FROM AUTHOR]

The broad applications of primary alkyl amines in various fields have spurred extensive interests in synthetic organic chemistry. Recently, the reductive amination of carboxylic acids has become an attractive and practical strategy for synthesizing primary alkyl amines, due to their wide availability and bench stability. However, the inherent stability and higher oxidation state of carboxylic acids render this new strategy with new challenges. This Concept provides a summary of the recent advancements in the reductive aminations of carboxylic acids, specifically focusing on the catalytic tactics, underlying mechanisms, and applications in the synthesis of valuable products. [ABSTRACT FROM AUTHOR]

Cyclooctane is classified as a cycloalkane, characterized by the chemical formula C8H16. It consists of a closed ring structure composed of eight carbon atoms and sixteen hydrogen atoms. A cyclooctane chain typically refers to a series of cyclooctane molecules linked together. Cyclooctane and its derivatives find various applications in chemistry, materials science, and industry. Topological indices are numerical values associated with the molecular graph of a chemical compound, predicting certain physical or chemical properties. In this study, we calculated the expected values of degree-based and neighborhood degree- based topological descriptors for random cyclooctane chains. A comparison of these topological indices' expected values is presented at the end. [ABSTRACT FROM AUTHOR]

Alcohol is ubiquitous with unparalleled structural diversity and thus has wide applications as a native functional group in organic synthesis. It is highly prevalent among biomolecules and offers promising opportunities for the development of chemical libraries. Over the last decade, alcohol has been extensively used as an environmentally friendly chemical for numerous organic transformations. In this review, we collectively discuss the utilisation of alcohol from 2015 to 2023 in various organic transformations and their application toward intermediates of drugs, drug derivatives and natural product-like molecules. Notable features discussed are as follows: (i) sustainable approaches for C–X alkylation (X = C, N, or O) including O-phosphorylation of alcohols, (ii) newer strategies using methanol as a methylating reagent, (iii) allylation of alkenes and alkynes including allylic trifluoromethylations, (iv) alkenylation of N-heterocycles, ketones, sulfones, and ylides towards the synthesis of drug-like molecules, (v) cyclisation and annulation to pharmaceutically active molecules, and (vi) coupling of alcohols with aryl halides or triflates, aryl cyanide and olefins to access drug-like molecules. We summarise the synthesis of over 100 drugs via several approaches, where alcohol was used as one of the potential coupling partners. Additionally, a library of molecules consisting over 60 fatty acids or steroid motifs is documented for late-stage functionalisation including the challenges and opportunities for harnessing alcohols as renewable resources. [ABSTRACT FROM AUTHOR]

Ligand coupling on hypervalent main group elements has emerged as a pivotal methodology for the synthesis of functionalized N‐heteroaromatic compounds in recent years due to the avoidance of transition metals and the mildness of the reaction conditions. In this direction, the reaction of N‐heteroaryl sulfur(IV) and N‐heteroaryl phosphorus(V) compounds has been well studied. However, the ligand coupling of sulfur(VI) is still underdeveloped and the reaction of alkyl N‐heteroarylsulfones is still elusive, which does not match the high status of sulfones as the chemical chameleons in organic synthesis. Here we present a ligand coupling‐enabled formal SO2 extrusion of fluoroalkyl 2‐azaheteroarylsulfones under the promotion of Grignard reagents, which not only enriches the chemistry of sulfones, but also provides a novel and practical synthetic tool towards N‐heteroaromatic fluoroalkylation. [ABSTRACT FROM AUTHOR]

DAT2 is a member of the diacyl trehalose family (DAT) of antigenic glycolipids located in the mycomembrane of Mycobacterium tuberculosis (Mtb). Recently it was shown that the molecular structure of DAT2 had been incorrectly assigned, but the correct structure remained elusive. Herein, the correct molecular structure of DAT2 and its methyl‐branched acyl substituent mycolipanolic acid is determined. For this, four different stereoisomers of mycolipanolic acid were prepared in a stereoselective and unified manner, and incorporated into DAT2. A rigorous comparison of the four isomers to the DAT isolated from Mtb H37Rv by NMR, HPLC, GC, and mass spectrometry allowed a structural revision of mycolipanolic acid and DAT2. Activation of the macrophage inducible Ca2+‐dependent lectin receptor (Mincle) with all four stereoisomers shows that the natural stereochemistry of mycolipanolic acid / DAT2 provides the strongest activation, which indicates its high antigenicity and potential application in serodiagnostics and vaccine adjuvants. [ABSTRACT FROM AUTHOR]

Klassische Schutzgruppenchemie erfordert unweigerlich einen Entschützungsschritt, um die ursprünglich blockierte Funktionalität vor weiteren Umwandlungen wiederherzustellen. Da dieser Aspekt der Schutzgruppenmanipulation zwangsläufig die Anzahl der Schritte jeder Synthesesequenz erhöht, bieten Methoden, die eine gleichzeitige Entschützung und Funktionalisierung ermöglichen („entschützende Funktionalisierung", im Gegensatz zur Entschützung mit anschließender Funktionalisierung), attraktive Vorteile, um die Effizienz zu steigern und synthetische Routen zu verkürzen. In diesem Bericht präsentieren wir eine Methode zur entschützenden Funktionalisierung der neu eingeführten Nms‐Amide, die auf einer Analyse mittels Dichtefunktionaltheorie (DFT) basiert und die inhärente Nms‐Reaktivität ausnutzt. Mechanistische Studien erklären außerdem warum andere häufig verwendete Schutzgruppen nicht die gleichen Reaktivitätsmuster aufweisen. Die Anwendbarkeit dieses Ansatzes wurde anhand zahlreicher Substrate demonstriert und schließlich verwendet, um Arzneimittelderivate effizienter und mit verkürzten Synthesewegen herzustellen. [ABSTRACT FROM AUTHOR]

The direct C(sp³)--H functionalization reactions enable the development of green and streamlined synthetic routes for structurally complex molecules by circumventing the pre-activation of the substrates. Herein, we disclose an atom- and step-economic synthetic approach for rapid access to both α-(2- indolyl) ketones and α-(3-indolyl) ketones, which are privileged structures in bioactive molecules and organic synthesis, though generally prepared by bespoke multi-step strategies. The reaction proceeded via direct acylation of indole benzylic C(sp³)--H bond under the NHC and photocatalyst catalysis. The mild conditions, broad substrate scope, and predictable regioselectivity among multiple potential reactive sites enable efficient access to α-indolyl ketones from readily available 2- or 3-alkyl-substituted indoles. Furthermore, the competitive reaction at the 2- or 3-benzylic position of the 2,3-dialkyl-substituted indoles was systematically studied. Further transformation and bioactivity studies of the obtained α-(2- or 3-indolyl) ketones highlight the potential utility of this method. [ABSTRACT FROM AUTHOR]

Rhamnolipids (RLs) are highly valuable molecules in the cosmetic, pharmaceutic, and agricultural sectors with outstanding biosurfactant properties. In agriculture, due to their potential to artificially stimulate the natural immune system of crops (also known as elicitation), they could represent a critical substitute to conventional pesticides. However, their current synthesis methods are complex and not aligned with green chemistry principles, posing a challenge for their industrial applications. In addition, their bioproduction is cumbersome with reproducibility issues and expensive downstream processing. This work offers a more straightforward and green access to RLs, crucial to decipher their mechanisms of action and design novel potent and eco-friendly elicitors. To achieve this, we propose an efficient seven-step synthetic pathway toward (R)-3- hydroxyfatty acid chains present in RLs, starting from cellulose-derived levoglucosenone, with Michael addition, Baeyer-Villiger oxidation, Bernet-Vasella reaction, and cross-metathesis homologation as key steps. This method allowed the production of (R)-3-hydroxyfatty acid chains and derivatives with an overall yield ranging from 24% to 36%. [ABSTRACT FROM AUTHOR]

The article discusses a method for synthesizing amide bonds using deoxyfluorinated carboxylic acids and pyridinesulfonyl fluoride. The authors optimized the reaction conditions and explored the substrate scope, demonstrating the versatility and utility of their method. They also showcase the application of this methodology in the synthesis of a challenging ester-linked compound and a tetrapeptide. The research was supported by various funding sources, and there are no conflicts of interest to declare. This article provides valuable information for researchers in the field of medicinal chemistry and organic synthesis. [Extracted from the article]

Cellulose derivative products, such as carboxymethyl cellulose (CMC), which are used in the food, cosmetics, and pharmaceutical industries, but still rely on cotton-derived cellulose, can be made from oil palm fruit empty bunches (OPEFB) and rice straw. This study examined how sodium monochloroacetic acid (NaMCA) concentration (3, 6, and 9 g) affected the simple synthesis and characteristics of CMC from OPEFB and rice straw cellulose. OPEFB-derived CMC produced with NaMCA (9 g) had the lowest of brightness, while rice straw CMC was brighter. NaMCA modifications altered the onset temperature (Tonset), but not maximum degradation temperature (Tmax), according to thermal analysis. The onset temperatures of OPEFB and rice straw CMC were 40--62 °C and 67--183 °C, respectively. Commercial CMC has an onset temperature of about 27 °C. The EDX analysis showed that rice straw CMC had a higher degree of substitution (DS) of 0.34-1.37 than OPEFB CMC, which had 0.30-0.70. Oil palm empty fruit bunch (OPEFB) cellulose and rice straw cellulose offer a viable carboxymethyl cellulose (CMC) alternative. This process turns agricultural waste into valuable products and enables for their usage in numerous applications. [ABSTRACT FROM AUTHOR]

Modern catalysis research, particularly in the field of organic synthesis, gives significant importance to the recovery and recycling of catalysts. Magnetic separation is now a reliable, extremely effective, simple, and quick separation method for chemicals and catalysts, compared to traditional separation. Recently, zinc ferrite (ZnFe2O4) magnetic nanoparticles have attracted the attention of the scientific community due to their unique properties in different interdisciplinary areas. Among the different applications, the use of these materials as heterogeneous catalysts in a variety of organic transformations is one of the major research areas. Based on their potential for recuperation and recyclability, zinc ferrite nanocatalysts show a renewed interest in catalysis research, with a focus on exploring their performance in a range of organic processes. The current study highlighted the synthesis, characterization, and application of zinc ferrite nanocatalysts and their nanocomposites in the formation of heterocyclic compounds, dehydrogenation, oxidation, alkylation, C–C coupling, mitigation of pollutants (dyes, nitro molecules, and antibiotics) with the available literature in the last decade. [ABSTRACT FROM AUTHOR]

Isonitriles are useful reagents that participate in many cycloaddition or multicomponent reactions of interest in organic synthesis, which are often catalyzed by transition metal complexes. Being good electron donors, RN=C bonds become activated and prone to the nuclephilic attack upon coordination to electrophilic (Lewis acidic) metal centers. Herein we explore the complexation of tBuNC to a series of iridium hydrido chlorides supported by benzene-based pincer ligands, ()IrH(Cl) ( = κ3‑C6H3–2,6-(ZPtBu2)2, where R = H (I–III), EtCO2–(IV), and Z = CH2 (I), CH2, O (II), O (III, IV)), that occurs instantaneously and quantitatively in solution yielding one of possible isomers Ia–IVa. Single crystal X-ray diffraction studies for Ia–IIIa confirmed the apical coordination of isonitrile ligand trans to hydride ligand suggested by NMR studies. Perusal of the structural data suggests stronger binding of tBuNC to PCP-supported iridium center in complex Ia in comparison to PCOP/POCOP species IIa–IIIa. Structural data also reveal a distortion in the P–Ir–P arrangement caused by tBuNC docking in apical position that is the most noticeable for asymmetric PCOP version IIa. The computational analysis of vibrational frequencies unveils an essential coupling νIr-H and νN=С modes that produce two strong bands of similar intensity in the νN=C region for Ia. Weaker isonitrile binding in IIa–IVa with shorter N=С and longer N– /Ir–CCN bonds and a plethora of intramolecular interactions result in a different degree of vibrational mixing for Ir‒H and N=C stretches as well as lead to an intense bands due to a Fermi resonance of low frequency modes involving vibrations of N–C–tBu fragment. Thus, the raw experimental IR data should be taken with care as an indicator of RN=С activation, paying attention to the vibrational coupling. An estimation of band position for the "true" (uncoupled) νNC vibration gives a small high frequency shift for Ia (+16 cm–1) but low frequency shifts for other complexes becoming less negative in the order IIa–IIa–IVa (PCOP–POCOP– EtCO2-POCOP). Overall the results obtained show the influence of the pincer ligand on the complex picture of isonitrile complexes structure and spectra, and suggest that strong binding does not always mean a strong activation. [ABSTRACT FROM AUTHOR]

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization. [ABSTRACT FROM AUTHOR]

Borane–trimethylamine complex (Me3N·BH3; BTM) is the most stable of the amine–borane complexes that are commercially available, and it is cost-effective. It is a valuable reagent in organic chemistry with applications in the reduction of carbonyl groups and carbon–nitrogen double bond reduction, with considerable examples in the reduction of oximes, hydrazones and azines. The transfer hydrogenation of aromatic N-heterocycles and the selective N-monomethylation of primary anilines are further examples of recent applications, whereas the reduction of nitrobenzenes to anilines and the reductive deprotection of N-tritylamines are useful tools in the organic synthesis. Moreover, BTM is the main reagent in the regioselective cleavage of cyclic acetals, a reaction of great importance for carbohydrate chemistry. Recent innovative applications of BTM, such as CO2 utilization as feedstock and radical chemistry by photocatalysis, have extended their usefulness in new reactions. The present review is focused on the applications of borane–trimethylamine complex as a reagent in organic synthesis and has not been covered in previous reviews regarding amine–borane complexes. [ABSTRACT FROM AUTHOR]

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-β-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis. [ABSTRACT FROM AUTHOR]

This study presents an eco‐conscious approach to enhance the efficiency of the Suzuki–Miyaura cross‐coupling reaction. We first synthesized graphene oxide nanosheets using the Hummers method and then coated them to incorporate metallic copper on their surface. Following this, we conducted various analyses, including Fourier transform infrared spectroscopy (FT‐IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) analysis, cyclic voltammetry (CV), and energy‐dispersive X‐ray spectroscopy (EDS) identification, to characterize these modified nanosheets. Subsequently, we utilized Cu‐modified graphene oxide nanosheets as cathode catalysts in an electro‐oxidation synthesis setup. To verify the effectiveness of this novel approach, we utilized bromobenzene and phenylboronic acid as model substrates to synthesize biphenyl compounds. The reaction yielded impressive product yields ranging from 87% to 93%. Operating under environmentally friendly conditions, this electro‐oxidation synthesis not only enhances selectivity but also significantly reduces the environmental impact of the reaction. Our findings highlight the potential of this green chemistry strategy, offering a promising avenue for sustainable and efficient organic synthesis, as evidenced by the successful coupling of bromobenzene and phenylboronic acid with consistently high yields. [ABSTRACT FROM AUTHOR]