Field Of Synthetic Organic Chemistry Research Articles

Gold-Catalyzed Cope Rearrangements

AbstractOver decades, Cope rearrangements have attracted significant research interest in the field of synthetic organic chemistry relying on their ability to undergo stereoselective structural reorganization. Despite substantial progress, the development of this field remained confined to the use of parent 1,5-hexadienes. Against the backdrop of classical Cope reaction, we report the utilization of unconventional 1,6-heptadienes to develop the arylative Cope rearrangement by harnessing the interplay between the π-activation and cross-coupling reactivity mode of gold complexes. Several mechanistic investigations such as 31P NMR study, HRMS analysis, cross-over experiment, control experiments were performed to support the proposed cyclization-induced [3,3]-rearrangement mechanism in arylative Cope reaction.1 Gold-Catalyzed Cope Rearrangements2 Gold-Catalyzed Arylative Cope Rearrangement3 Conclusion

Gold‐Catalyzed Heck and Suzuki‐Type Reactions: Challenges and Recent Advances

AbstractTransition metal‐catalyzed Suzuki and Heck reactions are two of the most common carbon‐carbon bond formation reactions. Gold, unlike other transition metals (Pd, Ni, and Cu), offers unique reactivity profiles, and has emerged as an efficient tool in the field of synthetic organic chemistry. This mini‐review focused on the recent work in gold‐catalyzed Heck and Suzuki‐type reactions, especially by photocatalysts or ligand design, which show reactivities and features distinct from other transition metals. These discoveries will further facilitate the development of gold redox catalysis as well as applications in organic synthesis, biochemistry, and medicinal chemistry.

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

: 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.

Structural Chemistry of C-N Axially Chiral Compounds.

In the last several years, atropisomers owing to the rotational restriction around a C-N single bond (C-N axially chiral compounds) have attracted significant attention in the field of synthetic organic chemistry. In particular, the highly enantioselective synthesis of various C-N axially chiral compounds and their application to asymmetric reactions have been reported by many groups. On the other hand, studies on the structural chemistry of C-N axially chiral compounds have attracted scant attention in comparison with synthetic studies. For over 25 years, our group has explored asymmetric synthesis of C-N axially chiral compounds and their synthetic application. In the course of these synthetic studies, we found several notable structural properties in relation to the C-N bond rotation and an association of enantiomers (the relationship between the rotational stability and the structure or electronic effect, the chirality-dependent halogen bond, and the self-disproportionation of enantiomers). Furthermore, on the basis of these structural properties, the development of acid-mediated molecular rotors and the synthesis of isotopic atropisomers possessing high stereochemical purity and rotational stability were achieved. Through this Perspective, I wish to make the chemistry community aware that C-N axially chiral compounds are attractive molecules from the viewpoints of both synthetic organic chemistry and structural chemistry.

Voltammetric Investigations of Low-Coordinate Manganese As an Electrocatalyst for Organic Coupling and Functionalization

Earth-abundant, first row, low coordinate transition metal complexes are considered promising candidates for the electrocatalysis of many organic reactions. The use of transition metal catalysts is no stranger to the field of synthetic organic chemistry; however, many of the existing catalysts require the use of rare and expensive metals such as platinum, palladium, ruthenium, and iridium. In this study, we seek to identify and understand the mechanism by which an Mn(I) complex may act as an electrocatalyst for simple organic coupling and C-H functionalization reactions, beginning with the radicalization of benzyl bromide and benzyl chloride as representative organic halide substrates. The careful design and evaluation of this manganese complex has the potential to offer an effective non-toxic 3d metal electrocatalyst, provided that common transition metal behaviors, such as disproportionation or carbon-metal bond formation, are avoided. Initial characterization of the complex by cyclic voltammetry (CV) demonstrates general reversibility of the catalyst, while additions of benzyl halide exhibit the execution of the electron transfer and catalytic step. Electrochemical simulations run in parallel with CV experiments provide supplementary guidance into the relationship between the substrate and catalyst. Additional studies conducted using bulk electrolysis, mass spectrometry, nuclear magnetic resonance, and density functional theory (DFT) calculation will help to further characterize the mechanism and supporting details. Elucidation of the catalytic mechanism will allow us to use this electrocatalyst in a series of synthetic organic conditions and aid in our advancement toward sustainable organometallic catalysis.

Franziska Schoenebeck is the Thieme-IUPAC Prize Winner 2024

Abstract We are delighted to announce that the 2024 Thieme–IUPAC Prize has been awarded to Franziska Schoenebeck of RWTH Aachen University. Professor Schoenebeck becomes the 16th recipient of the prize and joins a distinguished group of scientists whose research has had a major impact on the field of synthetic organic chemistry. The prize, which is awarded every two years and includes an award of € 5000, will be presented to Schoenebeck at the ICOS-24 conference before her Thieme–IUPAC lecture.

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.