Redox-Tag Processes: Intramolecular Electron Transfer and Its Broad Relationship to Redox Reactions in General.

Recently, electron has been recognized as the simplest catalyst in the field of synthetic organic chemistry. Addition or removal of electron can activate small molecules for further chemical transformations, which is referred to as redox catalysis. Reductive and/or oxidative single electron transfer (SET) can be induced by means of electro- and photochemistry, where an electron can play a role of catalysts. Radical ions are primarily generated via SET, offering unique reactive intermediates.Distonic radical ions are transient species with formally separated radical and charge cites. They potentially exhibit radical and ion reactivities independently, which may differ from usual radical ions. However, distonic radical ions are not commonly used as reactive intermediates in the field of synthetic organic chemistry, probably because of lack of their simple generation methods.We have been developing oxidative SET-triggered cycloadditions in a lithium perchlorate/nitromethane solution. Radical cations are involved in the reactions as distinctive reactive intermediates, facilitating intermolecular carbon-carbon bond formations. We questioned whether the distonic radical cation can also be generated by oxidative SET, leading to novel chemical transformations. In this presentation, oxidative SET-catalyzed vinylcyclopopane rearrangements will be described. Figure 1

Although 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.

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

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.

In the field of synthetic organic chemistry, photochemical and electrochemical approaches are often considered to be competing technologies that induce single electron transfer (SET). Recently, their fusion, i. e., the "photoelectrochemical" approach, has become the focus of attention. In this approach, both solar and electrical energy are used in creative combinations. Historically, the term "photoelectrochemistry" has been used in more inorganic fields, where a photovoltaic effect exhibited by semiconducting materials is employed. Semiconductors have also been studied intensively as photocatalysts; however, they recently have taken a back seat to molecular photocatalysts. In this account, we would like to revisit semiconductor photocatalysts in the field of synthetic organic chemistry to demonstrate that semiconductor "photoelectrochemical" approaches are more than mere alternatives to molecular photochemical and/or electrochemical approaches.

Single-electron oxidation enables the conversion of electron-rich alkenes such as styrene derivatives to radical cation species. We have been developing various cycloaddition reactions of radical cations produced by single-electron oxidation using electrochemical and TiO2 photochemical methods. Introducing an electron-rich aryl group which we call a redox tag is a critical part of the process to control the reactivity of the radical cations. During carbon-carbon bonds formation the motif functions as both electron donor and electron acceptor. In addition to styrene derivatives, enol ethers can also be readily oxidized by single electron transfer (SET) electrochemically or photochemically to generate the radical cations. For instance, enol ethers tethered redox tag serves efficient radical cation precursors for [2+2] cycloadditions.[1] The cycloadditions are net redox-neutral reactions and are initiated by the formation of a radical cation by single-electron oxidation and completed by reduction after ring formation.Herein, we present [4+2] cycloadditions using enol ethers as dienophiles by electrochemical oxidation in lithium perchlorate (LiClO4)/nitromethane (MeNO2) system. In the case of disubstituted enol ethers prepared from aldehydes, the approach involving redox tag was successful in obtaining the corresponding cycloadducts, while the desired products were not obtained when the substrates without redox tag were subjected.[2] This result suggests that intramolecular electron transfer from the redox tag is crucial for the formation of the cyclohexene ring systems. In contrast, the trisubstituted enol ethers prepared from ketones allowed the cycloaddition reaction to proceed without the involvement of redox tag. It is expected that the methyl group significantly stabilizes the cyclohexene radical cations to have enough lifetime to be reduced by intermolecular SET. Furthermore, since the cycloaddition reaction of enol ether was completed with a catalytic amount of electricity (0.4 F/mol), a radical cation chain mechanism is proposed in which electron acts as a catalyst.

The advent of photoredox catalysis has created a massive buzz in the field of synthetic organic chemistry. As the photoredox process is invariably mediated by the transfer of single electrons, species such as radical cations are inevitable. These species have orcastracized various synthetic transformations that otherwise would have been difficult to achieve. One such class of transformations is the cycloaddition reaction. For driving such reactions, it is often necessary that the radical and cation sites are present on different atoms, in other words, are distal or “ distonic” in nature. In the present review, the development of distonic radical cations has been brought forth and their tactical exploitation over the years for the purpose of cycloaddition reactions in the visible‐light realm. The entirety of the manuscript has been divided into categories discussing [2 + 2], [3 + 2], and [4 + 2] cycloadditions. In each case, the distonic radical cation that drives the cycloaddition has been highlighted along with necessary discussions, providing readers with an opportunity to appreciate the power of these wonderful intermediates.

In addition to electrochemical and photochemical approaches, the photoelectrochemical method using semiconductors as photoelectrodes is a third type of approach in the field of synthetic organic chemistry that enables precise control of single electron transfer (SET) reactions. Herein, we report mechanistic studies on TiO2 photoelectrochemical redox neutral reactions, where both reductive and oxidative SET are involved, using radical cation [2 + 2] cycloadditions as models. In the presence of platinum nanoparticles or molecular oxygen as electron sink or electron acceptor, respectively, the mechanistic details for the photoelectrochemical reactions can be investigated because the excited electron at the conduction band of TiO2 is removed.

In the periodic table of elements, indium is located within group 13, and has the atomic number 49. Indium is classified as one of the chemical elements of post-transition metals. Indium is silvery-white in color, soft, and possesses a high level of malleability. Although indium is a relatively rare element, it is indispensable in industry applications worldwide. German metallurgists discovered indium in 1863. It was not until the early 1990s, however, that scientists in the field of synthetic organic chemistry attempted genuine studies to explore the roles of indium or indium-related reagents. Focusing on indium or indium-related reagents, many recent investigations have led to significant advances in synthetic organic chemistry. Various applications have been examined and a growing number of useful chemical transformations using indium or indium-related reagents are being revealed and reported. Chemical transformations of the reactive functional groups are an essential point, particularly for the successful implementation of a sequence of multiple-step chemical schemes. For this purpose, a variety of strategic reaction methodologies have been developed, including those utilizing indium or indium-related reagents. Indium metal was discovered to be useful for the protection and deprotection of functional groups, while trivalent indium Lewis acids have been effective in a wide variety of chemical transformations. This chapter describes an efficient oxone-mediated esterification of aldehydes using indium(III) triflate, which is also one of the trivalent indium Lewis acids. Esterification is performed primarily on aromatic and heterocyclic aldehydes. The results show the effectiveness of this esterification methodology and suggest the potential in the further development of these reagents, which could enhance the field of synthetic organic chemistry.

17 - Applications of the Olefin Metathesis Reaction

Trifluoromethyl (CF3) and difluoromethyl (CF2H) groups are versatile structural motifs, especially in the fields of pharmaceuticals and agrochemicals. Thus, the development of new protocols for tri- and difluoromethylation of various skeletons has become a vital subject to be studied in the field of synthetic organic chemistry. For the past decades, a variety of fluoromethylating reagents have been developed. In particular, bench-stable and easy-to-use electrophilic fluoromethylating reagents such as the Umemoto, Yagupolskii-Umemoto, Togni, and Hu reagents serve as excellent fluoromethyl sources for ionic and carbenoid reactions. Importantly, the action of catalysis has become a promising strategy for developing new fluoromethylations. For the past several years, photoredox catalysis has emerged as a useful tool for radical reactions through visible-light-induced single-electron-transfer (SET) processes. Commonly used photocatalysts such as [Ru(bpy)3](2+) and fac-[Ir(ppy)3] (bpy = 2,2'-bipyridine; ppy = 2-pyridylphenyl) have potential as one-electron reductants strong enough to reduce those fluoromethylating reagents, resulting in facile generation of the corresponding fluoromethyl radicals. Therefore, if we can design proper reaction systems, efficient and selective radical fluoromethylation would proceed without any sacrificial redox agents, i.e., via a redox-neutral process under mild reaction conditions: irradiation with visible light, including sunlight, below room temperature. It should be noted that examples of catalytic fluoromethylation of compounds with carbon-carbon multiple bonds have been limited until recent years. In this Account, we will focus on our recent research on photoredox-catalyzed fluoromethylation of carbon-carbon multiple bonds. First, choices of the photocatalyst and the fluoromethylating reagent and the basic concept involving a redox-neutral oxidative quenching cycle are explained. Then photocatalytic trifluoromethylation of olefins is discussed mainly. Trifluoromethylative difunctionalization reactions, i.e., simultaneous introduction of the CF3 group and a different functional group across carbon-carbon double bonds, are in the middle of the discussion. Oxy-, amino-, and ketotrifluoromethylation allow us to synthesize various organofluorine compounds bearing C(sp(3))-CF3 bonds. In addition, the synthesis of valuable trifluoromethylated alkenes is also viable when the olefins have an appropriate leaving group or undergo deprotonation. The present reaction system features high functional group compatibility and high regioselectivity. Furthermore, future prospects, especially trifluoromethylative difunctionalization of alkynes and difluoromethylation of alkenes, are also discussed.

In recent years, the most significant development in the field of synthetic organic chemistry has been the application of biological systems to chemical reactions. Reactions catalyzed by enzymes and enzyme systems display far greater specificities than more conventional organic reactions. Biological and/or enzymatic syntheses and transformations, that is, “microbial transformations,” have great potential. Some of these reactions have already been shown to have useful applications in the fields of synthetic organic chemistry and biotechnology. This article reviews the current status of the rapidly developing field of microbial transformation, the methodology, available technological procedures, and fields of application being described especially in relation to conventional organic synthesis methods.

The sulphur centered radicals, produced from various organic compounds, in high efficiency by single-electron-transfer (SET) oxidation. These radicals are highly reactive intermediates having various applications in the construction of organosulphur compounds in the field of synthetic organic chemistry. These S-centred radical-mediated organic transformations have been achieved using photoredox catalysts, including organic dyes and transition metal catalysts, as well as in the absence of any catalyst. Compared with previous methods, photoredox catalysis is inexpensive and features the advantages of being environmentally benign, highly efficient and easy to use. This review focuses on recent developments in the photocatalyzed carbon–sulphur bond formation.

Transition metal-catalyzed carbonylative cross-coupling reactions are some of the most widely used methods in organic synthesis. However, despite the obvious advantages of iron as an abundant and low toxicity transition metal catalyst, its practical application in carbonylation reaction remains largely unexplored. Here we report our recent study on Fe-catalyzed alkoxycarbonylation of alkyl halides. Mechanistic studies indicate that the reaction is catalyzed by an in situ generated Fe2- complex. This low-valent iron species activates alkyl bromides via a distinctive two-electron transfer (TET) process, whereas it proceeds via a single electron transfer (SET) process for alkyl iodides which is consistent with literature.

Trinuclear Nickel Catalyst for Water Oxidation: Intramolecular Proton-Coupled Electron Transfer Triggered Trimetallic Cooperative O–O Bond Formation