Evolution of microwave irradiation and its application in green chemistry and biosciences

Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwave-assisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.     

Ketenes in polymer-assisted synthesis

Since its inception, ketene chemistry has developed into a unique and well-established source of useful transformations for conventional synthetic organic chemistry. It is, therefore, not surprising that soon after their movement from the realm of peptide and peptoid libraries to that of small molecules, combinatorial chemists have sought the benefits of ketene chemistry to satisfy their own synthetic needs. The ability of these versatile molecules to undergo reactions with nucleophiles, and to participate in cycloadditions and cyclocondensations, has been utilized for the preparation of diverse heterocyclic compounds, and has added to the advantages of polymer-assisted synthesis for rapid purification. Different types of ketenes and different methods for their generation have been involved, which illustrates the potential diversity of the chemistry. There is now a better grasp of the effect of the fragility of these sometimes transient molecules on the reactions involving solid supports, and this augurs well for the application of some of the more recent developments in ketene chemistry to the generation of small-molecule libraries.     

Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy towards heterocycle synthesis

Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C-O, C-S and C-C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C-N, C-O, C-S as well as C-C coupling processes are summarized.     

Electric-Field-Induced Organic Transformations

Experiments showed that the existence of electric fields in non-redox processes may alter the catalytic activity, rate enhancement, and selection of organic reactions. It is expected that the interaction between electric fields and chemical reactions will create new avenues for producing materials with desired properties in several chemical disciplines, including synthetic organic chemistry, catalysis, nanotechnology, membrane technology, and enzyme catalysis. Specifically, in this review, we discuss the elegant experimental investigations carried out using the scanning tunneling microscope, the interfacial electric field, and designed local electric fields. The results of these studies are remarkable, leading to new information on the function of electric fields in controlling chemical reactivity and selectivity in different reactions and offering a glimpse of the great potential of electrostatic fields. This article not only presents the core concepts of field-induced chemical transformations but also illustrates the potential use of electric field catalysis in chemistry and other fields.     

Microwave-assisted C-C bond forming cross-coupling reactions: an overview

Among the fundamental transformations in the field of synthetic organic chemistry, transition-metal-catalyzed reactions provide some of the most attractive methodologies for the formation of C-C and C-heteroatom bonds. As a result, the application of these reactions has increased tremendously during the past decades and cross-coupling reactions became a standard tool for synthetic organic chemists. Furthermore, a tremendous upsurge in the development of new catalysts and ligands, as well as an increased understanding of the mechanisms, has contributed substantially to recent advances in the field. Traditionally, organic reactions are carried out by conductive heating with an external heat source (for example, an oil bath). However, the application of microwave irradiation is a steadily gaining field as an alternative heating mode since its dawn at the end of the last century. This tutorial review focuses on some of the recent developments in the field of cross-coupling reactions assisted by microwave irradiation.     

High‐Oxidation‐State Palladium Catalysis: New Reactivity for Organic Synthesis

Recent years have seen the rapid development of a new field of palladium catalysis in organic synthesis. This chemistry takes place outside the usually encountered Pd⁰/Pd^II cycles. It is characterized by the presence of strong oxidants, which prevent further palladium(II)‐promoted reactions at a given point of the catalytic cycle by selective metal oxidation. The resulting higher‐oxidation‐state palladium complexes have been used to develop a series of new synthetic transformations that cannnot be realized within conventional palladium catalysis. This type of catalysis by palladium in a higher oxidation state is of significant synthetic potential.     

可见光促进的光氧化还原催化的三氟甲基化反应

全氟烷基化反应,特别是三氟甲基化反应一直是有机化学领域的研究热点。近几年来,可见光促进的光氧化还原催化的有机化学反应,因其本身所固有的条件温和、绿色和环保等优点而倍受合成化学家的青睐。该方法学也被成功地应用于一系列三氟甲基化反应。本文主要按照三氟甲基源分类,总结了近年来可见光促进的光氧化还原催化的三氟甲基化反应的研究进展,并对其发展趋势进行了展望。     

Flow Photochemistry as a Tool in Organic Synthesis

Photochemical transformations of molecular building blocks have become an important and widely recognized research field in the past decade. Detailed and deep understanding of novel photochemical catalysts and reaction concepts with visible light as the energy source has enabled a broad application portfolio for synthetic organic chemistry. In parallel, continuous-flow chemistry and microreaction technology have become the basis for thinking and doing chemistry in a novel fashion with clear focus on improved process control for higher conversion and selectivity. As can be seen by the large number of scientific publications on flow photochemistry in the recent past, both research topics have found each other as exceptionally well-suited counterparts with high synergy by combining chemistry and technology. This review will give an overview on selected reaction classes, which represent important photochemical transformations in synthetic organic chemistry, and which benefit from mild and defined process conditions by the transfer from batch to continuous-flow mode.     

Visible‐Light‐Induced Organic Photochemical Reactions through Energy‐Transfer Pathways

Visible‐light photocatalysis is a rapidly developing and powerful strategy to initiate organic transformations, as it closely adheres to the tenants of green and sustainable chemistry. Generally, most visible‐light‐induced photochemical reactions occur through single‐electron transfer (SET) pathways. Recently, visible‐light‐induced energy‐transfer (EnT) reactions have received considerable attentions from the synthetic community as this strategy provides a distinct reaction pathway, and remarkable achievements have been made in this field. In this Review, we highlight the most recent advances in visible‐light‐induced EnT reactions.     

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.     

Revisiting the Chemistry of Vinylpyrazoles: Properties,Synthesis, and Reactivity

Vinylpyrazoles, also known as pyrazolyl olefins, are interesting motifs in organic chemistry but have been overlooked. This review describes the properties and synthetic routes of vinylpyrazoles and highlights their versatility as building blocks for the construction of more complex organic molecules. Concerning the reactivity of vinylpyrazoles, the topics surveyed herein include their use in cycloaddition reactions, free-radical polymerizations, halogenation and hydrohalogenation reactions, and more recently in transition-metal-catalyzed reactions, among other transformations. The current state of the art about vinylpyrazoles is presented with an eye to future developments regarding the chemistry of these interesting compounds. Styrylpyrazoles were not considered in this review, as they were the subject of a previous review article published in 2020.     

Arynes and cyclohexyne in natural product synthesis

This Minireview highlights recent advances in the field of aryne and cyclohexyne chemistry that have allowed the extraordinary reactivity of these entities to be harnessed during the course of natural product syntheses. The syntheses presented rely on the use of these reactive species in chemoselective transformations and follow unprecedented synthetic strategies that are inspiring for the practitioners of synthetic organic chemistry.     

Chemistry in microstructured reactors

The application of microstructured reactors in the chemical process industry has gained significant importance in recent years. Companies that offer not only microstructured reactors, but also entire chemical process plants and services relating to them, are already in existence. In addition, many institutes and universities are active within this field, and process-engineering-oriented reviews and a specialized book are available. Microstructured systems can be applied with particular success in the investigation of highly exothermic and fast reactions. Often the presence of temperature-induced side reactions can be significantly reduced through isothermal operations. Although microstructured reaction techniques have been shown to optimize many synthetic procedures, they have not yet received the attention they deserve in organic chemistry. For this reason, this Review aims to address this by providing an overview of the chemistry in microstructured reactors, grouped into liquid-phase, gas-phase, and gas-liquid reactions.     

Alkyl Enol Ethers: Development in Intermolecular Organic Transformation

Alkyl enol ethers (AEE) are versatile synthetic intermediates with a unique reactivity pattern. This review article summarizes the synthesis of AEE as well as its reactivity and how enol ether undergoes intermolecular reactions for various bond formation, leading to the construction of several useful organic molecules. The synthetic applications of alkyl enol ethers towards intermolecular bond-forming reactions include metal-catalyzed reactions, cycloaddition and heterocycle formation as well as rwactions in the field of natural products synthesis. The achievement of these impressive transformations prove the countless synthetic potential of AEE. The main objective of this review is to bring attentiveness among synthetic chemists to show how AEE extensively can be used to react with both electrophiles as well as nucleophiles, thereby behaving as an ambiphilic reactant. We trust that the unique reactivity pattern of alkyl enol ethers and the fundamental mechanistic idea can attract chemists in AEE chemistry. Exclusively, intermolecular reactions of AEE with other functionalized moieties have not been reviewed to the best of our knowledge.     

Gold catalysis in organic transformations: A review

This review updates the explosive development of gold catalysis for organic transformation focusing on the current literature over last 3 years. Recent investigations have shown that gold catalysis provides catalytically active systems, whereas selectivity and reusability are advantages over noncatalyzed organic transformations. The collected literature is focusing for new organic reactions and synthetic methodologies. Gold can also be suggested for green processes dedicated to fine chemicals, pharmaceuticals, and the food industry due to its recognized biocompatibility. The current review is focused on new methods in the organic synthesis that could be of interest in the wide area of organic chemistry for developing new catalytic pathways.     

Tosylhydrazones: new uses for classic reagents in palladium-catalyzed cross-coupling and metal-free reactions

Tosylhydrazones are useful synthetic intermediates that have been used in organic chemistry for almost 60 years. The recent discovery of a palladium-catalyzed cross-coupling reaction involving a tosylhydrazone coupling partner has triggered renewed interest in these reagents. This reaction shows nearly universal generality with regard to the hydrazone and can be employed for the preparation of polysubstituted alkenes. In the course of this research, novel metal-free C-C and C-O bond-forming reactions have been discovered. Since tosylhydrazones are readily prepared from carbonyl compounds, these transformations offer new synthetic opportunities for the unconventional modification of carbonyl compounds. This Minireview discusses all of these new reactions of a classic reagent.     

Multi-Step Continuous-Flow Organic Synthesis: Opportunities and Challenges

Continuous-flow multi-step synthesis takes the advantages of microchannel flow chemistry and may transform the conventional multi-step organic synthesis by using integrated synthetic systems. To realize the goal, however, innovative chemical methods and techniques are urgently required to meet the significant remaining challenges. In the past few years, by using green reactions, telescoped chemical design, and/or novel in-line separation techniques, major and rapid advancement has been made in this direction. This minireview summarizes the most recent reports (2017–2020) on continuous-flow synthesis of functional molecules. Notably, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous-flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplified the feasibility of using modern continuous-flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.     

Rare‐Earth‐Metal Methylidene Complexes

Transition‐metal carbene complexes have been known for about 50 years and widely applied as reagents and catalysts in organic transformations. In contrast, the carbene chemistry of the rare‐earth metals is much less developed, but has attracted the research interest in the recent years. In this field rare‐earth‐metal alkylidene, especially methylidene, compounds are an emerging class of compounds with a high synthetic potential for organometallic chemistry and maybe in the future also for organic chemistry.     

Reactions of hypervalent iodine reagents with palladium: mechanisms and applications in organic synthesis

The unique reactivity of hypervalent iodine reagents with Pd0 and PdII complexes has been exploited for a variety of synthetically useful organic transformations. For example, IIII reagents have been used in place of aryl halides for diverse Pd-catalyzed C-C and C-heteroatom bond-forming cross-coupling reactions. In addition, these reagents have found application in Pd-catalyzed oxidation reactions, including the oxidative functionalization of C-H bonds and the 1,2-aminooxygenation of olefinic substrates. This review discusses both the synthetic utility and the interesting mechanistic features of these transformations.     

Indole‐N‐Carboxylic Acids and Indole‐N‐Carboxamides in Organic Synthesis

Indoles are ubiquitous structures that are found in natural products and biologically active molecules. The synthesis of indoles and indole‐involved synthetic methodologies in organic chemistry have been receiving considerable attention. Indole‐N‐carboxylic acids and derived indole‐N‐carboxamides are intriguing compounds, which have been widely used in organic synthesis, especially in multicomponent reactions and C?H functionalization of indoles. This Minireview summarizes the advances of reactions involving indole‐N‐carboxylic acids and indole‐N‐carboxamides in organic chemistry, and discusses the synthetic potential and perspective of this field.