Field Of Synthetic Organic Chemistry Research Articles

A Decade of Advancement in Ruthenium (II)-Catalyzed Direct C-H Activa-tion and Consequent C-C/C-N Bond Formation Using Microwave Heating

Abstract: Transition-metal catalysed activation of unreactive C-H bonds and subsequent C-C bond formation has emerged as a principal and essential tool in the field of synthetic organic chemistry. On the other hand, the microwave heating technique has been intensively used to carry out organic transformation of almost all kinds and has become a promising non-conventional technique for performing synthetic reactions. Direct C-H activation for C-C bond-forming reactions using ruthe-nium as a catalyst is currently a hot topic and represents a cost-effective synthetic pathway in or-ganic chemistry which is accompanied by the advantages of MW irradiation resulting in shorter reaction time and greener 3 as well as sustainable accomplishments.

Reductive Functionalization of Pyridine-Fused N-Heteroarenes.

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair-induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C-H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H2 gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, β, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

A Brief Review on Proved Approaches for the Formation of Oxygen Containing Heterocyclic Compounds through a Tandem Prins Cyclization

: Prins reaction is a very useful and important reaction in the field of synthetic organic chemistry. Prins cyclization is one of the greatest significant synthetic approaches in the total synthesis of various natural compounds especially pyran and furan units. The addition of aldehydes to olefinic compounds utilizing acid catalyst has become important for the industry. : Aldehydes and alkenes to give different products depending on the reaction conditions, yield an acidcatalyzed reaction. Formation of Carbon-Carbon bonds is useful to produce 1,3-diol, 1,3-dioxane, β- halohydrin and allylic alcohols and tetrahydropyrans by using this methodology. Now coming to the point of tandem Prins cyclization, this method is very useful for the synthesis of fused compounds and also for the construction of spirocyclic compounds such as tetrahydropyrans or furans. The present brief review mainly deals with the development of the synthesis of oxygen-containing heterocyclic compounds by using prins/tandem prins cyclization. This current review is focused mainly on tandem prins cyclization’s reactions for the particular recent applications and what methods are used for the construction of the oxygen contained heterocyclic compounds.

Ionic Liquid-Supported Photocatalysts: A Reusable Environmentally Friendly Oxidation Reaction System That Uses Air and Light.

Ionic liquids are used in various fields due to their unique physical properties and are widely utilized as reaction solvents in the field of synthetic organic chemistry. We have previously proposed a new organic synthetic method in which the catalyst and reaction reagents are supported on ionic liquids. This method has various advantages, such as the ability to reuse the reaction solvent and catalyst and its facile post-reaction treatment. In this paper, we describe the synthesis of an ionic liquid-supported anthraquinone photocatalyst and the synthesis of benzoic acid derivatives using this system. This synthesis of benzoic acid derivatives via the cleavage of vicinal diols by an ionic liquid-supported anthraquinone photocatalyst is an environmentally friendly process, and furthermore, it has a simple post-reaction process, and the catalyst and solvent can both be reused. To the best of our knowledge, this is the first report on the synthesis of benzoic-acid derivatives via the cleavage of vicinal diols using light and an ionic-liquid-supported catalyst.

A Review on Chemistry, Synthesis and Biological Applications of Chalcone-based Schiff Bases

Heterocyclic compounds are an important class of compounds in the field of pharmaceutical and synthetic organic chemistry. The Schiff bases contain azomethine linkages which are obtained by the condensation of aldehyde/ketone with amines. Among the various types of Schiff bases, the chalcone-based Schiff bases play a vital role in the treatment of various ailments and various applications, which can be synthesized by using different types of chalcones as the starting materials. These types of compounds were synthesized by using various techniques like conventional means of synthesis, microwave-assisted reaction, heterocyclic catalyst-mediated synthesis and also by means of trituration. The chalcone or bis-chalcone-based Schiff bases and their derivatives contain -C=N linkage which exhibits various activities including antimicrobial, anticancer, antioxidant, antidiabetic and immunosuppressant activities. Beyond these activities, these types of Schiff bases are also used in various chemical industries and fluorescent sensors, which also play a major role in the field of synthetic organic chemistry and coordination chemistry as intermediates. This review discusses the numerous synthetic strategies along with their applications in the field of medicine. Thus, this review will be helpful in developing more effective drug-like scaffolds for use in future drug design.
 Keywords: Schiff bases, Chalcone-based Schiff bases, Antimicrobial, Anticancer, Antioxidant, Biological Applications

Probing Electron Transfer Events in Radical Cation Cycloadditions: Intramolecular vs. Intermolecular Single Electron Transfer

AbstractAlthough radical ion chain pathways have long been recognized in the field of synthetic organic chemistry and are expected to be operative in various reactions, it is somewhat complicated to verify their involvement, since counting the number of electrons is not straightforward. Herein, a series of bis‐styrenes is designed and synthesized to investigate electron transfer events by using radical cation [4+2] cycloadditions as probes. It is demonstrated that the intramolecular single electron transfer seems to be ineffective, while the intermolecular variants are highly effective. Therefore, a truly catalytic amount of electricity is enough for full conversions, confirming that chain pathways were definitely involved.

Gold catalysis in organic synthesis: fifteen years of research in India

Gold catalysis has emerged as an important tool in the field of synthetic organic chemistry for the selective functionalization of C–C multiple bonds. The research in India on gold catalysis focuses on diverse fields starting from the methodology developments to the synthesis of molecular scaffolds for their potential application in medicinal chemistry and material science. Herein, we present a comprehensive overview of the gold-catalyzed organic transformations that were reported in India in the last fifteen years.Graphical abstract

Tyramine Derivatives Catalyze the Aldol Dimerization of Butyraldehyde in the Presence of Escherichia coli.

Biogenic amine organocatalysts have transformed the field of synthetic organic chemistry. Yet despite their use in synthesis and to label biomolecules in vitro, amine organocatalysis in vivo has received comparatively little attention – despite the potential of such reactions to be interfaced with living cells and to modify cellular metabolites. Herein we report that biogenic amines derived from L‐tyrosine catalyze the self‐aldol condensation of butanal to 2‐ethylhexenal – a key intermediate in the production of the bulk chemical 2‐ethylhexanol – in the presence of living Escherichia coli and outperform many amine organocatalysts currently used in synthetic organic chemistry. Furthermore, we demonstrate that cell lysate from E. coli and the prolific amine overproducer Corynebacterium glutamicum ATCC 13032 catalyze this reaction in vitro, demonstrating the potential for microbial metabolism to be used as a source of organocatalysts for biocompatible reactions in cells.

(Digital Presentation) TiO2 Photoelectrochemical Radical-Cation Vinylcyclopropane Rearrangements

In the field of synthetic organic chemistry, photochemical and electrochemical methods are often considered to be competing techniques that induce single electron transfer (SET). Recently, metal complexes and organic dyes have been extensively used as molecular sensitizers that can induce homogeneous bidirectional SET. On the other hand, heterogeneous monodirectional SET can be induced by electrodes, which differs from the photochemical methods. In this context, semiconductors are unique alternatives, since they can induce heterogeneous but bidirectional SET, potentially enjoying advantages of both photochemical and electrochemical methods. Such semiconductor "photoelectrochemical" methods may trigger the reactions that are otherwise difficult to achieve.We have been developing electrochemical SET-triggered cycloadditions in lithium perchlorate (LiClO4)/nitromethane (CH3NO2) solution, which facilitates the generation of radical cations from electron-rich alkenes and styrenes. Recently, we also have been focusing on TiO2 photoelectrochemical SET-triggered cycloadditions, expanding a scope of the electrochemical versions. During the course of our study to develop new TiO2 photoelectrochemical SET-triggered cycloadditions, we unexpectedly found that vinylcyclopropane rearrangements was also possible in LiClO4/CH3NO2 solution. The reactions are initiated by oxidative SET by hole, which is followed by immediate ringopening of the cyclopropanes to generate distonic radical cations. It is expected that reductive SET by excited electron is also involved to realize effective net redox-neutral transformations. Experimental details, including preliminary mechanistic studies, will be presented in this talk.

(Digital Presentation) Scalable Synthesis of Versatile Intermediate for Azanucleoside Derivatives Via directanodic N-α Hydroxylation

Azanucleosides are found to show unique pharmacological activities even without incorporating into oligonucleotides and are used as anticancer and antivirus agents. Practical synthesis routes of azanucleosides are of exceptional importance to enhance the development of (oligo)nucleotide therapeutics. Previously, we reported the synthetic methods of azanucleosides by using electrochemical approaches, which has now been offering green and sustainable redox options in the field of synthetic organic chemistry. However, scaling-up of the reactions remains challenging since continuous production is essentially not possible. Herein, we report the direct anodic N-α hydroxylation of prolinol derivatives as useful intermediates for azanucleosides. Cyclic voltammetry study clearly reveals that the presence of water facilitates the oxidative electron transfer events. The reaction is applicable for large scale production and thus could enhance the development of (oligo)azanucleotide therapeutics.

Recent Progress in Aryltrifluoromethylation Reactions of Carbon-Carbon Multiple Bonds.

Due to the increasing relevance of fluorine-containing organic molecules in drug design, the synthesis of organofluorine compounds has gained high significance in synthetic organic chemistry. Trifluoromethylative difunctionalizations of carbon-carbon multiple bonds, with the simultaneous incorporation of a CF3 group and another functional element, have considerable potential. Because of the high importance of carbon-carbon bond-forming reactions in organic synthesis, carbotrifluoromethylations and, in particular, aryltrifluoromethylations or heteroaryltrifluoromethylations are considered to be increasing fields of synthetic organic chemistry. The aim of the current review is to summarize recent developments of aryltrifluoromethylation or heteroaryltrifluoromethylation reactions.

Decoding Key Transient Inter-Catalyst Interactions in a Reductive Metallaphotoredox-Catalyzed Allylation Reaction.

Metallaphotoredox chemistry has recently witnessed a surge in interest within the field of synthetic organic chemistry through the use of abundant first-row transition metals combined with suitable photocatalysts. The intricate details arising from the combination of two (or more) catalytic components during the reaction and especially the inter-catalyst interactions remain poorly understood. As a representative example of a catalytic process featuring such intricacies, we here present a meticulous study of the mechanism of a cobalt-organophotoredox catalyzed allylation of aldehydes. Importantly, the commonly proposed elementary steps in reductive metallaphotoredox chemistry are more complex than previously assumed. After initial reductive quenching, a transient charge-transfer complex forms that interacts with both the transition-metal catalyst and the catalytic base. Surprisingly, the former interaction leads to deactivation due to induced charge recombination, while the latter promotes deprotonation of the electron donor, which is the crucial step to initiate productive catalysis but is often neglected. Due to the low efficiency of this latter process, the overall catalytic reaction is photon-limited and the cobalt catalyst remains in a dual resting state, awaiting photoinduced reduction. These new insights are of general importance to the synthetic community, as metallaphotoredox chemistry has become a powerful tool used in the formation of elusive compounds through carbon–carbon bond formations. Understanding the underlying aspects that determine the efficiency of such reactions provides a conceptually stronger reactivity paradigm to empower future approaches to synthetic challenges that rely on dual metallaphotoredox catalysis.

Efficient methods for the synthesis of chiral 2-oxazolidinones as pharmaceutical building blocks.

Although the wide variety of heterocyclic compounds is common knowledge, chiral 2-oxazolidinones are recognized as some of the most important heterocycles in medicinal chemistry. Many important pharmaceutical molecules have been constructed based on the chiral 2-oxazolidinone backbone. Therefore, the development of even more efficient catalytic methods for the synthesis of chiral 2-oxazolidinones remains a very important pursuit in the field of synthetic organic chemistry. This review summarizes the coupling reactions of epoxides and isocyanates for the preparation of 2-oxazolidinones. Both metal catalysts and organocatalysts promote these reactions. Optically pure 2-oxazolidinones are prepared from optically pure epoxide substrates via these catalytic methods. A synthetic example of a commercially available pharmaceutical compound utilizing this method is also introduced.

Copper‐Mediated Relay Strategy Using Chlorination/Oxidation: An Effective Synthesis of Functionalized Coumarin Derivatives

AbstractChromene‐fused heterocyclic compounds have shown fascinating biological and physiochemical properties and thus, the design and development of chromene‐fused heterocyclic molecules is of significant interest in the field of synthetic organic chemistry. We report an innovative ligand‐ and additive‐free synthetic approach of 4‐(phenylethynyl)‐2H‐chromene‐3‐carbaldehyde with phenylacetylenes has been described through sequential chlorination, benzannulation, benzylic sp3 C−H bond functionalization, and ether oxidation for the formation of chloro‐substituted‐9‐phenyl‐6H‐benzo[c]chromen‐6‐ones with readily available chemicals under one‐pot, base‐free conditions using CuCl2 as sustainable catalyst. In this regioselective approach, we defined a reasonably longer cascade, which reveals the multiple role of chlorine as chlorine supplier, Lewis acid catalyst and oxidation rate promoter that tolerates a broad substrate scope and allows good product yields. The authenticated mechanism proceeds in a cascading fashion through the formation of multiple bonds.

Transition metal-catalyzed double Cvinyl-H bond activation: synthesis of conjugated dienes.

Conjugated dienes have occupied a pivotal position in the field of synthetic organic chemistry and medicinal chemistry. They act as important synthons for the synthesis of various biologically important molecules and therefore, gain tremendous attention worldwide. A wide range of synthetic routes to access these versatile molecules have been developed in the past decades. Transition metal-catalyzed cross-dehydrogenative coupling (CDC) has emerged as one of the utmost front-line research areas in current synthetic organic chemistry due to its high atom economy, efficiency, and viability. In this review, an up-to-date summary including scope, limitations, mechanistic studies, stereoselectivities, and synthetic applications of transition metal-catalyzed double Cvinyl-H bond activation for the synthesis of conjugated dienes has been reported since 2013. The literature reports mentioned in this review have been classified into three different categories, i.e. (a) Cvinyl-Cvinyl bond formation via oxidative homo-coupling of terminal alkenes; (b) Cvinyl-Cvinyl bond formation via non-directed oxidative cross-coupling of linear/cyclic alkenes and terminal/internal alkenes, and (c) Cvinyl-Cvinyl bond formation via oxidative cross-coupling of directing group bearing alkenes and terminal/internal alkenes. Overall, this review aims to provide a concise overview of the current status of the considerable development in this field and is expected to stimulate further innovation and research in the future.

Insight View on Synthetic Strategies and Biological Applications of Pyrimidobenzothiazoles

: Pyrimidobenzothiazoles and its derivatives are important structural scaffolds in the field of synthetic organic chemistry and medicinal chemistry. The review is focused on one pot multicomponent approaches for generating pyrimidobenzothiazoles and its derivatives along with their interesting biological profile over the last ten years. Several eco-benign and cost effective approaches such as nano catalyst, ionic liquid, metal, solid acid, catalyst free, solvent free, etc. for its synthesis have been discussed in this review. Different synthetic strategies of pyrimidobenzothiazole derivatives have been compiled and discussed using 2-aminobenzothiazole, 1,3 diketones, substituted aldehydes, alkynoic acid, bis-methyl thiomethylene malononitrile, Baylis Hillman acetates, etc.

Toolbox for Distal C-H Bond Functionalizations in Organic Molecules.

Transition-metal-catalyzed C-H activation has developed a contemporary approach to the omnipresent area of retrosynthetic disconnection. Scientific researchers have been tempted to take the help of this methodology to plan their synthetic discourses. This paradigm shift has helped in the development of industrial units as well, making the synthesis of natural products and pharmaceutical drugs step-economical. In the vast zone of C-H bond activation, the functionalization of proximal C-H bonds has gained utmost popularity. Unlike the activation of proximal C-H bonds, the distal C-H functionalization is more strenuous and requires distinctly specialized techniques. In this review, we have compiled various methods adopted to functionalize distal C-H bonds, mechanistic insights within each of these procedures, and the scope of the methodology. With this review, we give a complete overview of the expeditious progress the distal C-H activation has made in the field of synthetic organic chemistry while also highlighting its pitfalls, thus leaving the field open for further synthetic modifications.

An overview of iron‐catalyzed N‐alkylation reactions

AbstractN‐containing compounds are very important molecules in nature and in the field of synthetic organic chemistry. N‐alkylation reactions play crucial role in the area of pharmaceuticals and various other industrial chemical syntheses. Iron‐catalyzed N‐alkylation reactions have attained greater acceptance among the scientific community. Environmentally benign, abundant, nontoxic, biocompatible, reusable, and inexpensive iron catalysts are gaining more attention in various research fields. Green protocols, milder reaction conditions, wide substrate scope, and so forth, signify the prominent nature of iron‐catalyzed N‐alkylation reactions. Most of the protocols are eco‐friendly and atom economic since water is the only by‐product. This review gives an overview of the advances in the Fe‐catalyzed N‐alkylation reactions covering literature up to 2021.

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Chemical orthogonality, defined as 100% selectivity in chemical reactions, has proven to be a powerful concept making significant impacts in the fields of synthetic organic chemistry, chemical biology, and materials science. The review by James F. Reuther and coworkers on page 1748 details the recent advancements towards the use of chemically orthogonal reactions in synthetic polymer chemistry, allowing the synthesis of complex, structurally diverse polymer microstructures and topologies. Utilization of orthogonal “click” chemistry post-polymerization yielded complex materials that are not possible using traditional polymerization techniques. The advent of stimuli-triggered orthogonal polymerization methods that differ in mechanism has provided streamlined, one-pot routes to unique block and bottle-brush copolymer structures simplifying procedures for synthesis and purification. (DOI: 10.1002/pol.20210345)

Transition-Metal Catalyzed Stereoselective Desymmetrization of Prochiral Cyclohexadienones.

The development of transition-metal catalyzed enantioselective and diastereoselective transformations has contributed many advances in the field of synthetic organic chemistry. Particularly, stereoselective desymmetrization of prochiral cyclohexadienones represents a powerful strategy for accessing highly functionalized and stereochemically enriched scaffolds, which are often found in biologically active compounds and natural products. In recent years, several research groups including our group have made a significant progress on transition-metal catalyzed stereoselective desymmetrizations of 2,5-cyclohexadienones. In this account, we will provide an overview of the recent developments in this area employing Pd, Cu, Rh, Au, Ag, Ni, Co, and Mn-catalysts.