Reagents In Organic Synthesis Research Articles

Diverse Catalytic Applications of Phosphine Oxide‐Based Metal Complexes

AbstractPhosphine oxides are an interesting class of compounds possessing tetracoordinate and pentavalent phosphorus atoms and have been employed in a wide range of applications including reagents in organic synthesis, metal extractants, flame retardants, pharmaceuticals, and bioactivity studies. Among all, the degree of basicity of phosphoryl oxygen driven by the nature of substituents influences the electronic properties of the central metal in a complex toward the diversified catalytic processes. Further, the presence of heteroatoms adjacent to the central phosphorus atom enhances the nucleophilicity of the phosphoryl oxygen atom. In view of this, the present review covers the past two decades of remarkable catalytic versatility of P=O‐based metal complexes and describes the governing factors influencing the structural properties and the resultant coordination behavior. Interestingly, some of the P=O bond distances of metal complexes are either longer or shorter compared to their free ligands, indicating the catalytic activity. These complexes can effectively catalyze a wide range of chemical reactions including polymerizations, C−C and Si−C bond activations, oxidation, reduction, hydroformylation, hydrophosphination, hydrogenation and cyclization reactions. Furthermore, this review emphasizes the impact of substituents, solvents, additives, light, and temperature on the catalytic efficiency.

Enhanced Synthesis of Sulfonyl Fluorides and Sulfamoyl Fluorides Using Fluorosulfonyl-Containing Radical Reagents

Sulfonyl fluorides and sulfamoyl fluorides, as the most significant species among sulfur(VI) fluorides, have garnered considerable attention in various fields, including organic synthesis, materials science, chemical biology, and drug discovery. Fluorosulfonyl-containing radical reagents have unique reactivity and exhibit notable advantages in constructing complex organic molecules, achieving selective functional group transformations. This short review provides a detailed introduction to the diverse applications of fluorosulfonyl-containing radical reagents in organic synthesis, such as C-H bond functionalizations, difunctionalization of olefins, and tandem reactions, highlighting their crucial role in synthesizing complex organic molecules.

Green Innovation: Harnessing N-Bromosuccinimide as a Versatile Reagent in Organic Synthesis

Green Innovation: Harnessing N-Bromosuccinimide as a Versatile Reagent in Organic Synthesis

Effect of Substituted Pyridine Co-Ligands and (Diacetoxyiodo)benzene Oxidants on the Fe(III)-OIPh-Mediated Triphenylmethane Hydroxylation Reaction.

Iodosilarene derivatives (PhIO, PhI(OAc)2) constitute an important class of oxygen atom transfer reagents in organic synthesis and are often used together with iron-based catalysts. Since the factors controlling the ability of iron centers to catalyze alkane hydroxylation are not yet fully understood, the aim of this report is to develop bioinspired non-heme iron catalysts in combination with PhI(OAc)2, which are suitable for performing C-H activation. Overall, this study provides insight into the iron-based ([FeII(PBI)3(CF3SO3)2] (1), where PBI = 2-(2-pyridyl)benzimidazole) catalytic and stoichiometric hydroxylation of triphenylmethane using PhI(OAc)2, highlighting the importance of reaction conditions including the effect of the co-ligands (para-substituted pyridines) and oxidants (para-substituted iodosylbenzene diacetates) on product yields and reaction kinetics. A number of mechanistic studies have been carried out on the mechanism of triphenylmethane hydroxylation, including C-H activation, supporting the reactive intermediate, and investigating the effects of equatorial co-ligands and coordinated oxidants. Strong evidence for the electrophilic nature of the reaction was observed based on competitive experiments, which included a Hammett correlation between the relative reaction rate (logkrel) and the σp (4R-Py and 4R'-PhI(OAc)2) parameters in both stoichiometric (ρ = +0.87 and +0.92) and catalytic (ρ = +0.97 and +0.77) reactions. The presence of [(PBI)2(4R-Py)FeIIIOIPh-4R']3+ intermediates, as well as the effect of co-ligands and coordinated oxidants, was supported by their spectral (UV-visible) and redox properties. It has been proven that the electrophilic nature of iron(III)-iodozilarene complexes is crucial in the oxidation reaction of triphenylmethane. The hydroxylation rates showed a linear correlation with the FeIII/FeII redox potentials (in the range of -350 mV and -524 mV), which suggests that the Lewis acidity and redox properties of the metal centers greatly influence the reactivity of the reactive intermediates.

Access to Valuable Chalcogen-Containing Biaryl Derivatives via Regioselective 2,2'-Dichalcogenation of 2-Bromobiaryls.

The regioselective installation of chalcogen atoms into biaryl scaffolds is an important synthetic task due to the great value of chalcogen-containing biaryl derivatives in many fields. Here we undertake this task by developing a regioselective 2,2'-dichalcogenation of 2-bromobiaryls with common chalcogen sources using an organolanthanum-mediated one-pot, two-step protocol. This strategy features high regioselectivity, readily available substrates, transition-metal-free conditions, and performance superior to those of previous methods, thereby demonstrating the unique advantages of organolanthanum reagents in organic synthesis.

Synthesis of N-Hydroxysuccinimide Esters, N-Acylsaccharins, and Activated Esters from Carboxylic Acids Using I2/PPh3.

A method for the syntheses of isolable, active esters is described in which carboxylic acids are treated with triphenylphosphine, iodine, and triethylamine. Active esters accessible in this way include N-hydroxysuccinimide esters, N-hydroxyphthalimide esters (N-(acyloxy)phthalimides), N-acylsaccharins, pentafluorophenol esters, pentachlorophenol esters, N-hydroxybenzotriazole esters, and hexafluoro-2-propanol esters. The approach can be similarly applied toward the formation of N-acylsaccharins and N-acylimidazoles. The method is suitable for the formation of isolable active esters of aromatic and aliphatic activated acids as well as α-amino acid derivatives. These products are widely used reagents in organic synthesis, peptide synthesis, medicinal chemistry, and chemical biology (e.g., for bioconjugations). The method has broad substrate scope, uses simple and inexpensive reagents, avoids the use of carbodiimides or other coupling agents, and occurs at room temperature. Additionally, the diastereomers of compound Boc-Ala-NHCHPh are demonstrated to be distinguishable by 1H NMR (in DMSO-d6), allowing for a straightforward NMR method to establish the degree of racemization of activated esters of Boc-Ala or amide bond formations using Boc-Ala.

Fluoroalkoxylating Reagents in Organic Synthesis: Recent Advances

AbstractThe fluoroalkoxy groups (ORf) are widely used motifs in pharmaceutical and agrochemical fields due to their unique physicochemical properties including higher lipophilicity and increased metabolic stability. Thus, the high value of ORf‐containing derivatives has stimulated the development of fluoroalkoxylation reactions. In this review, we highlight the recent progress of various trifluoroalkoxylating reagents and their applications in organic synthesis in the past five years.

Borane-Trimethylamine Complex: A Versatile Reagent in Organic Synthesis.

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.

Electrochemical Dehydration of Dicarboxylic Acids to Their Cyclic Anhydrides.

An intramolecular electrochemical dehydration reaction of dicarboxylic acids to their cyclic anhydrides is presented. This electrolysis allows dicarboxylic acids as naturally abundant, inexpensive, safe, and readily available starting materials to be transformed into carboxylic anhydrides under mild reaction conditions. No conventional dehydration reagent is required. The obtained cyclic anhydrides are highly valuable reagents in organic synthesis, and in this report, we use them in-situ for acylation reactions of amines to synthesize amides. This work is part of the recent progress in electrochemical dehydration, which - in contrast to electrochemical dehydrogenative reactions for example - is an underexplored field of research. The reaction mechanism was investigated by 18O isotope labeling, revealing the formation of sulfate by electrochemical oxidation and hydrolysis of the thiocyanate-supporting electrolyte. This transformation is not a classical Kolbe electrolysis, because it is non-decarboxylative, and all carbon atoms of the carboxylic acid starting material are contained in the carboxylic anhydride. In total, 20 examples are shown with NMR yields up to 71 %.

Recent Advances in Hypervalent Iodine Reagents and m-CPBA Mediated Oxidative Transformations

Abstract: Among the several peroxides available, meta-chloroperbenzoic acid (mCPBA) plays an efficient role of oxidizing reagent and is used for many oxidative transformations, such as oxidation of various functional groups, carbon-carbon, carbon-hetero bond formation, heterocyclic ring formation, heteroarylation, oxidative cross-coupling, lactonization, oxidative dearomatization, α-oxytosylation or α-acetoxylation, oxidative C-C bond activation and in other miscellaneous reactions. The purpose of this review is to critically discuss the significant contributions of mCPBA along with hypervalent iodine/iodine reagents in organic synthesis from mid-2015 to date.

Recent Advancements in the Utilization of s-Block Organometallic Reagents in Organic Synthesis with Sustainable Solvents.

This mini-review offers a comprehensive overview of the advancements made over the last three years in utilizing highly polar s-block organometallic reagents (specifically, RLi, RNa and RMgX compounds) in organic synthesis run under bench-type reaction conditions. These conditions involve exposure to air/moisture and are carried out at room temperature, with the use of sustainable solvents as reaction media. In the examples provided, the adoption of Deep Eutectic Solvents (DESs) or even water as non-conventional and protic reaction media has not only replicated the traditional chemistry of these organometallic reagents in conventional and toxic volatile organic compounds under Schlenk-type reaction conditions (typically involving low temperatures of -78 °C to 0 °C and a protective atmosphere of N2 or Ar), but has also resulted in higher conversions and selectivities within remarkably short reaction times (measured in s/min). Furthermore, the application of the aforementioned polar organometallics under bench-type reaction conditions (at room temperature/under air) has been extended to other environmentally responsible reaction media, such as more sustainable ethereal solvents (e.g., CPME or 2-MeTHF). Notably, this innovative approach contributes to enhancing the overall sustainability of s-block-metal-mediated organic processes, thereby aligning with several key principles of Green Chemistry.

Hypervalent Iodine Compounds in Carbohydrate Chemistry: Glycosylation, Functionalization and Oxidation.

This mini review article provides an overview on the use of hypervalent iodine compounds (HICs) in carbohydrate synthesis, focusing on their chemistry and recent applications. HICs are similar to transition metals in their reactivity but have the added benefit of being environmentally benign, and are therefore commonly used as selective oxidants and eco-friendly reagents in organic synthesis. Herein, we summarize various synthetic uses of hypervalent iodine reagents in reactions such as glycosylation, oxidations, functionalization, and C-C bond-forming reactions. The goal of this review is to illustrate the advantages and versatility of using HICs as an environmentally sustainable alternative to heavy metals in carbohydrate chemistry.

An Alternative Method for the Selective Synthesis of Ortho-nitro Anilines Using Bismuth Nitrate Pentahydrate.

Nitroaromatic compounds are important scaffolds used for the syn-thesis of a variety of compounds, such as explosives, herbicides, dyes, perfumes and phar-maceuticals. Bismuth nitrate pentahydrate is a widely used reagent in organic synthesis; how-ever, its utility as a nitrating agent for anilines is underexplored. The aim of this work is to propose and find the proper reaction conditions of an alternative nitrating agent constituted by a mixture of bismuth nitrate / acetic anhydride in DCM with a series of substituted anilines under mild reflux. Several anilines having both activating and deactivating substituents in the ortho, meta and para positions were the substrate for the nitration reaction. Experimental conditions were performed in "one-pot" conditions before product purification. Bi(NO3)3•5H2O demonstrated to be effective and somehow regioselective when it came to the nitration of anilines in the ortho position. Although other products were also identified under these conditions, in most cases, the ortho derivative was the major or even the only product obtained with moderate to high yields in the range of 50% - 96%. Bi(NO3)3•5H2O is an efficient and safe nitrating agent since the use of concen-trated and corrosive acids like sulfuric and nitric is avoided; furthermore, bismuth nitrate is low-priced and no special care nor equipment is required.

The Use of the Titanium Tetrachloride (Ticl4) Catalysts as a Reagent for Organic Synthesis

Abstract: TiCl4 is a widely utilized reagent in organic synthesis, often functioning through Lewis’s acid-promoted transformations. This review explores the potential for TiCl4 to catalyse various examples, adhering to the classic catalyst definition and allowing for the use of sub-stoichiometric quantities of the catalyst relative to the substrate. The use of metal catalysts in organic synthesis has witnessed a surge in interest due to their ability to facilitate a wide range of chemical reactions. This review article highlights the significance of titanium metal catalysts via comparison with other metal catalysts like Pd [NO3]2, IrO4, Au/Fe2O3, SnCl2, and AlCl3. Among these catalysts, titanium tetrachloride (TiCl4) has gained considerable popularity for its cost-effectiveness, eco-friendliness, enhancing reaction efficiency, and ability to accelerate reactions while reducing reaction times. This comparison helps in determining the most suitable catalyst for different chemical processes, considering efficiency, safety, and economic factors. TiCl4 operates as a non-consumable catalyst, allowing for the use of sub-stoichiometric quantities relative to the substrate. This review discusses TiCl4's applications, efficiency, and mechanisms in organic synthesis. It distinguishes itself by presenting new applications and comparative efficiencies of TiCl4, delving into detailed reaction mechanisms, and discussing its environmental, economic, and safety aspects. TiCl4's role in pivotal chemical reactions, such as Friedel-Crafts acylation and alkylation, epoxidation, cyclization, Mannich reactions, Suzuki-Miyaura reactions, Pechmann condensation, Knoevenagel condensation, anti-Markovnikov hydration, pinacol coupling, and Diels-Alder reactions. These reactions have led to the synthesis of biologically active compounds like zolmitriptan, ropinirole, risperidone, and rivastigmine. TiCl4-catalyzed reactions are characterized by their mild conditions, high efficiency, and selectivity, making them an attractive choice for modern organic cyclic, acyclic, and heterocyclic synthesis.

Iodine and DMSO as Surrogate of Hazardous Metal and Non‐Metal Reagents in Organic Synthesis

AbstractOrganic synthesis involves the production of important chemical structures using scalable and cost‐effective methods that are also environmentally friendly. In this review, a detailed analysis of the use of iodine and DMSO in various synthetic routes for the preparation of valuable targets are presented. These methods reduce the acceptance on expensive additives and reagents, and offer a more sustainable solution for the synthesis of these important chemical scaffolds.

Developments and applications of α-bromonitrostyrenes in organic syntheses.

The presence of the bromo and nitro groups in the structure of α-bromonitrostyrene makes them highly reactive and versatile reagents in organic syntheses. α-Bromonitrostyrenes act as an effective dielectrophile in the reaction with various nucleophiles. In these reactions, the bromo and nitro groups behave as good leaving groups for the assembly of a diverse range of heterocyclic compounds, such as dihydrofurans, dihydropyranes, furans, pyrroles, pyrazoles, isooxazolines, spiropyrrolidines, etc. In the current review, we have focused on the transformations of α-bromonitrostyrenes under organocatalysis, metal catalysis, and base-catalysis systems as well as catalyst-free conditions, since 2010.

Isothiocyanates: happy-go-lucky reagents in organic synthesis.

Owing to their unique structural features, isothiocyanates (ITCs) are a class of highly useful and inimitable reagents as the -NCS group serves both as electrophile and nucleophile in organic synthesis. ITCs share a rich legacy in organic, medicinal, and combinatorial chemistry. Compared to their oxygen equivalents, isocyanates, ITCs are easily available, less unpleasant, and somewhat less harmful to work with (mild conditions) which makes them happy-go-lucky reagents. Functionalized ITCs can finely tune the reactivity of the -NCS group and thus can be exploited in the late-stage functionalization processes. This review's primary aim is to outline ITC chemistry in the construction and derivatization of heterocycles through the lens of sustainability. For ease and brevity, the sections are divided based on reactive centers present in functionalized ITCs and modes of cyclisation. Scrutinizing their probable unexplored directions for future research studies is also addressed.

Multiphasic Continuous‐Flow Reactors for Handling Gaseous Reagents in Organic Synthesis: Enhancing Efficiency and Safety in Chemical Processes

AbstractThe use of reactive gaseous reagents for the production of active pharmaceutical ingredients (APIs) remains a scientific challenge due to safety and efficiency limitations. The implementation of continuous‐flow reactors has resulted in rapid development of gas‐handling technology because of several advantages such as increased interfacial area, improved mass‐ and heat transfer, and seamless scale‐up. This technology enables shorter and more atom‐economic synthesis routes for the production of pharmaceutical compounds. Herein, we provide an overview of literature from 2016 onwards in the development of gas‐handling continuous‐flow technology as well as the use of gases in functionalization of APIs.

Multiphasic Continuous-Flow Reactors for Handling Gaseous Reagents in Organic Synthesis: Enhancing Efficiency and Safety in Chemical Processes.

The use of reactive gaseous reagents for the production of active pharmaceutical ingredients (APIs) remains a scientific challenge due to safety and efficiency limitations. The implementation of continuous-flow reactors has resulted in rapid development of gas-handling technology because of several advantages such as increased interfacial area, improved mass- and heat transfer, and seamless scale-up. This technology enables shorter and more atom-economic synthesis routes for the production of pharmaceutical compounds. Herein, we provide an overview of literature from 2016 onwards in the development of gas-handling continuous-flow technology as well as the use of gases in functionalization of APIs.

Domino Reactions with Dicyanoalkenes and Fluorinated Conjugated Sulfinyl Imines. A Convenient Strategy for the Generation of Structural Diversity

AbstractDicyanoalkenes are versatile reagents in organic synthesis and they have been extensively used in a wide variety of organic transformations. However, their reactivity towards fluorinated imines remained almost unnoticed. The divergent reactivity of fluorinated conjugated sulfinyl imines with dicyanoalkenes is described herein. On the one hand, when tert‐butyl sulfinyl imines were employed, a cycloaromatization cascade process took place preferentially, rendering valuable trifluoromethyl arenes. On the other hand, the reaction with p‐tolyl sulfinyl imines mainly led to a complex tetracyclic skeleton, involving an azetidinimine rearrangement of a reaction intermediate. Finally, when 1‐indanone‐derived dicyanoalkenes were employed, the aromatization process was interrupted, rendering a new family of diene derivatives. Theoretical calculations were performed in order to shed light on the mechanistic outcome of this transformation.