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Longer cumulenes have come to draw considerable attention due to their unique properties and reactivities, leading to various hydrocarbons. In this manuscript, we describe the reaction of tetrakis(p-methoxyphenyl)[5]cumulene with iodine to afford poly-functionalized fulvenes via unexpected migration of a terminal aryl ring under ambient conditions. The obtained iodinated fulvenes were utilized in Suzuki-Miyaura cross-coupling reactions affording penta- and fully-arylated fulvenes successfully.

We have synthesized and characterized an acceptor-π-donor-π-acceptor type pyridinium salt. The salt exhibited yellow emission with large Stokes shift in solution and was successfully excited by NIR...

We present that thioacetalization of aldehydes can be induced by blue light irradiation in the presence of a catalytic amount of riboflavin tetraacetate (RFTA) under aerobic conditions. Several control experiments have suggested that the reaction is more likely to be catalyzed by acidic species generated in situ during the light irradiation. We have proposed that single electron transfer from a thiol (RSH) to the excited state of RFTA can take place to give a one-electron oxidized thiol (RSH+•) and the one-electron reduced RFTA (RFTA–•), which can be trapped by molecular oxygen to be stabilized as Brønsted acids including the protonated RFTA–• (RFTAH•). Finally, we have demonstrated that such acidic species can be prepared in advance as a solution and used as Brønsted acid catalysts for not only the thioacetalization but also Mannich-type reactions.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.

An isoalloxazine (flavin) ring system and a secondary amine have been integrated through a short peptide linker with the aim of using photons as efficiently as possible in photoredox/enamine dual catalysis. We herein report a peptide-bridged flavin-amine hybrid that can catalyze α-oxyamination of aldehydes with TEMPO under weak blue light irradiation to achieve an extremely high quantum yield of reaction (Φ = 0.80).

Nitrones are important compounds and are highly useful in many aspects. The first part describes the methods for synthesis of nitrones, which are useful and environmentally friendly. Catalytic oxidations, condensations, and other useful reactions are described. The nitrones thus obtained are key intermediates for the synthesis of biologically important nitrogen compounds. The second part describes the fundamental transformations of nitrones, which will provide the strategies and means for the construction of nitrogen compounds. The reactions with nucleophiles or radicals, C-H functionalization, and various addition reactions are described. The last reactions are particularly important for highly selective carbon-carbon bond formations. 1,3-Dipolar cycloaddition reactions are excluded because the size of the review is limited and excellent reviews have been published in Chemical Reviews.

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5

Electrochemical reduction of amides was achieved by using a hydrosilane without any toxic or expensive metals. The key reactive ketyl radical intermediate was generated by cathodic reduction. Continuous reaction with anodically generated silyl radicals or zinc bromide resulted in chemoselective deoxygenation to give the corresponding amines.

N5-Modified alloxazinium salts including 5-ethyl-1,3-dimethylalloxazinium and 5-ethyl-1,3-dimethyl-8-(trifluoromethyl)alloxazinium salts were readily prepared as alloxazinium-resins from the corresponding N5-unmodified ingredients via the aerobic oxidation—ion exchange protocol, previously introduced by us for the preparation of isoalloxazine analogues, and their catalysis and reusability in H2O2 oxidations were evaluated.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.

Isoalloxazine ring systems are found in flavin cofactors in nature, and the simulation of their redox catalyses is an important task for developing sustainable catalytic oxidation reactions. Although 5- ethyl-4a-hydroxyisoalloxazines are among the most promising candidates as catalyst for such purposes, the use of them for laboratorial as well as industrial synthetic chemistry has so far been quite limited presumably due to the lack of their preparation methods readily, safely, and inexpensively available. In this communication, we introduce an environmentally benign and practical preparation of 5-ethyl-4a-hydroxy-3,7,8,10-tetramethylisoalloxazine (1EtOH) from 3,7,8,10-tetramethylisoalloxazine (1), in which conventional synthetic requirements, including (i) operations under inert conditions, (ii) risky or expensive chemicals, and (iii) isolation of labile intermediates, have all been dissolved. In addition, we have presented that 1EtOH could be an effective catalyst for Baeyer-Villiger oxidation as well as sulfoxidation with molecular oxygen (O2) as a terminal oxidant under suitable conditions, which is the first report on aerobic oxygenations catalyzed by 5-alkyl-4a-hydroxyisoalloxazines.

Electrode materials can have a significant impact on the course of an electrolysis reaction. Of particular interest is that different electrodes can generate different products from the same substrate. The electrode-material-selective transformations of styrene derivatives with molecular oxygen are reported. Platinum electrodes afford carbonyl products via cleavage of olefins, whereas tetrahydrofuran formation is achieved with carbon electrodes. A variety of different styrenes are available for both reactions. Electrolysis allows straightforward and mild chemical conversions that are metal- and oxidant-free. Electrochemical measurements illuminate the different effects of platinum and carbon electrodes on styrenes. The key to the differing reactions is probably that the oxidation potentials of the substrates are lower (higher HOMO energy) on carbon electrodes than on platinum electrodes. The adsorption of the substrates on carbon electrodes can also promote tetrahydrofuran formation.

A variety of biological redox reactions are mediated by flavoenzymes due to the unique redox activity of isoalloxazine ring systems, which are found in flavin cofactors. In the field of synthetic organic chemistry, the term “flavin” is generally used for not only isoalloxazines but also related molecules including their isomers and some analogues, and those having catalytic activity are called flavin catalyst. Flavin catalysts are typically metal-free, and their catalytic activity can be readily accessed using mild terminal oxidants such as H2O2 and O2; therefore, redox reactions with these compounds have great promise as alternatives to reactions with conventional metal catalysts for the sustainable production of important chemicals. We recently became interested in using polymers for the development of flavin catalysts, especially to improve their practicality and advance the field of catalysis. Here, we summarize our recent research on such flavin-polymer collaborations including the development of facile preparation methods for flavin catalysts using polymers, readily reusable polymer-supported flavin catalysts, and flavin-peptide-polymer hybrids that can catalyze the first flavoenzyme-mimetic aerobic oxygenation reactions.

A selective dehydrogenative electrochemical functionalization of benzylic positions that employs 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) has been developed. The electrogenerated products are versatile intermediates for subsequent functionalizations as they act as masked benzylic cations that can be easily activated. Herein, we report a sustainable, scalable, and reagent- and metal-free dehydrogenative formal benzyl-aryl cross-coupling. Liberation of the benzylic cation was accomplished through the use of acid. Valuable diarylmethanes are accessible in the presence of aromatic nucleophiles. The direct application of electricity enables a safe and environmentally benign chemical transformation as oxidizers are replaced by electrons. A broad variety of different substrates and nucleophiles can be employed.

Single electron transfer (SET)-triggered radical ion-based reactions have proven to be powerful options in synthetic organic chemistry. Although unique chain processes have been proposed in various photo- and electrochemical radical ion-based transformations, the turnover number, also referred to as catalytic efficiency, remains unclear in most cases. Herein, we disclose our investigations of radical cation chain processes in the electrocatalytic Diels–Alder reaction, leading to a scalable synthesis. A gram-scale synthesis was achieved with high current efficiency of up to 8000%. The reaction monitoring profiles showed sigmoidal curves with induction periods, suggesting the involvement of intermediate(s) in the rate determining step.

We have synthesized a cyan fluorescent benzothiazole-pyridinium salt composite based on D-π-A architecture. This salt was found to work as not only a two- and three-photon excitable fluorophore but also a degradation agent against amyloid fibrils under LED irradiation conditions.

2’,4’-p-Vinylbenzylideneriboflavin (2’,4’-PVBRFl) was prepared as a flavin-containing monomer and copolymerized with divinylbenzene and styrene or its p-substituted derivatives such as 4-acetoxystyrene, 4-vinylbenzyl alcohol, and 4-vinylbenzoic acid to give the corresponding non-functionalized and functionalized PS-DVB-supported flavins PS(H)-DVB-Fl, PS(OAc)-DVB-Fl, PS(CH2OH)-DVB-Fl, and PS(COOH)-DVB-Fl, respectively. PS(OH)-DVB-Fl was also prepared by hydrolysis of PS(OAc)-DVB-Fl under basic conditions. These novel flavin-containing insoluble polymers exhibited characteristic fluorescence in solid state, except PS(OH)-DVB-Fl, and different catalytic activities in aerobic reduction of olefins by in-situ generated diimide from hydrazine depending on their pendant functional group. For example, PS(H)-DVB-Fl was found to be particularly effective for neutral hydrophobic substrates, which could be readily recovered by a simple filtration and reused more than 10 times without loss in catalytic activity. On the other hand, PS(OH)-DVB-Fl and PS(COOH)-DVB-Fl proved to be highly active for phenolic substrates known to be less reactive in the reaction with conventional non-supported flavin catalysts.

Unactivated alkenes were previously found to be effective carbon nucleophiles for anodic cycloadditions in lithium perchlorate/nitromethane electrolyte solution. Herein, 7Li NMR analysis and calorimetric studies clearly illustrate that the entropic effect is essential for these anodic cycloadditions, which has led to the successful screening of novel effective electrolytes.

Chemical reactions via radical cation intermediates are of great interest in photoredox catalysis and electrosynthesis, while their reactivities are not clearly understood. For example, how the counter anions correlate with the reactivity of radical cations is still ambiguous. Here we report the effect of anions and fluorinated alcohols on the reactivity of organic radical cations in hole catalysis. The addition of salts in a radical cation Diels–Alder reaction under photoredox catalysis demonstrates that common anions significantly decease the efficiency of hole catalysis. The use of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) restores the reaction efficiency in the presence of salts, presumably due to solvation of the anions by HFIP to reduce their nucleophilicity. These findings enable hole catalysis under electrolytic conditions with greatly improved efficiency. The effect of anions and fluorinated alcohol described in this paper gives important insights on the fundamental understanding for the reactivity of arene radical cations. Fluorinated solvents such as hexafluoroisopropanol (HFIP) are often useful in reactions involving radical cations. Here the role of HFIP in photoredox and electrochemical Diels-Alder reactions is explored experimentally and theoretically, and attributed to solvation of anions to reduce their nucleophilicity.

Heterogeneous multiple-catalyst assemblies were developed in which the flavinium cation and Na or Li cations were easily immobilized on a chitin-derived anionic polymeric scaffold through noncovalent ionic interactions. The supramolecular flavinium catalysts were successfully employed in the environmentally friendly heterogeneous Baeyer-Villiger oxidation and sulfoxidation by H

We have designed and synthesized an iridium(III) complex of pincer type imidazo[1,5-a]pyridine ligand. The complex has a broad absorption band and shows the yellow emission in solution. When the complex was used as a photocatalyst in the visible-light-induced oxidative coupling reaction of benzylic amines, the corresponding imines were obtained in quantitative yields.

Riboflavin tetramethacrylate (RFlTMA) was prepared as a flavin monomer and copolymerized with ethylene glycol dimethacrylate (EGDMA) under polymerization-induced phase separation conditions. The resulting flavin-containing mesoporous network polymer, poly(RFlTMA-co-EGDMA), was found to be a more effective catalyst than riboflavin tetraacetate (RFlTA), a soluble analogue, for aerobic hydrogenation of olefins despite its heterogeneity, which allowed for its multiple recovery and reuse through simple filtrations and washings without loss in catalytic activity. In addition, the polymeric flavin was demonstrated to be utilized also as an effective photocatalyst in the oxidation of benzyl alcohols.

The thermoresponsive properties of aqueous poly (2-propionamidoacrylic acid) (PPA) solutions were studied in the presence of calcium chloride (CaCl2). The turbidity and viscosity of a PPA solution depended on temperature and concentration of the polymer and salt added. For example, a transparent PPA solution changed to a turbid gel at a temperature higher than the cloud point in the presence of a relatively high concentration of CaCl2. The mechanism of physical gelation was considered by comparing the thermoresponsive properties between PAA and a more hydrophilic polymer, poly (acetamidoacrylic acid) (P4A), which has similar structure to that of PPA. In the case of P4A, physical gelation was not observed under similar conditions to those at PPA gelation. This result indicates that hydrophobic interaction among the alkyl groups at one of the polymer side-chains is necessary for the gelation. Dynamic viscoelasticity measurements of these aqueous polymer solutions by use of a rotation rheometer gave quantitative data such as the complex viscosity and the storage and loss moduli, which strongly depended on the solution composition. It is concluded that both hydrophobic interaction among alkyl groups and ionic crosslinking by calcium ion play an important role for the gelation. The drastic change in the rheological property indicates that the sol-gel transition of PPA solution can be successfully controlled by adjusting the temperature and concentration of each component. The controllable rheological property is expected to be useful for various applications, especially in the biomedical field.

The front cover artwork for Issue 1/2015 is provided by the research group of Synthetic Organic Chemistry, Graduate School of Engineering Science, Osaka University (Japan). The image shows the catalytic activities of puffball-shaped nanoparticles for environmentally benign aerobic oxidation and reduction. See the Full Paper itself at http://dx.doi.org/10.1002/cctc.20140916.

Although there has been marked progress in the chemistry of five- and six-membered cyclic nitrones, medium- and large-sized cyclic nitrones have remained untouched despite their potential as functional materials. Herein, we report that medium-sized cyclic nitrones undergo ring-expanding dimerization/oligomerization in the presence of organic or inorganic acids, and we have successfully characterized a series of novel macrocyclic polynitrones up to a 50-membered ring size. An unprecedented ring-size-dependent specificity was observed for this reaction, in which cyclic nitrones with odd-number-membered rings are converted into dimers with high selectivity, whereas even-number-membered rings undergo consecutive ring-expansion reactions to afford macrocyclic polynitrones.

The catalytic activities of the cationic synthetic flavin adduct 1 with various dendritic and non-dendritic 2,6-bis(acylamino)pyridines 2 were examined for the oxidation of organic sulfides with H2O2. The adduct of 5-ethyllumiflavinium perchlorate 1a with 2b–d bearing poly(benzyl ether) dendron units acts as an efficient organocatalyst for the oxidative transformation of sulfides to the corresponding sulfoxides under mild conditions.

A variety of association complexes of synthetic flavin with diaminopyridine and melamine receptors are described in terms of synthesis, association properties, and catalytic activities for aerobic hydrogenation of olefins. The 1:1 association complex of lumiflavin 1 with 2,6-bis(acylamino)pyridine receptor bearing 3,4,5-trialkoxybenzyl ether dendron unit 2 acts as an efficient supramolecular organocatalyst for the aerobic reduction of styrene at ambient temperature under atmospheric air pressure.

5-Ethyl-3-methyl-2′,4′:3′,5′-di-O-methylenedioxyriboflavinium perchlorate (1, DMRFlEt+ClO4 –), derived readily from commercially available vitamin B2 (riboflavin), exhibits high catalytic activity for the oxidation of organic sulfides with hydrogen peroxide. The reaction provides an efficient and selective method for the oxidative transformation of organic sulfides to the corresponding sulfoxides under mild conditions. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]

5-Ethyl-3-methyl-2′,4′:3′,5′-di-O-methylenedioxy-riboflavinium perchlorate (DMRFlEt+ClO4 –) is readily derived from commercially available vitamin B2 (riboflavin) and exhibits high catalytic activity for the oxidation of organic sulfides under an oxygen atmosphere (1 atm) with the assistance of hydrazine hydrate as a reductant. This is an inexpensive, convenient, and environmentally benign method for the selective oxidative transformation of sulfides into sulfoxides.

The Diels-Alder (DA) reaction is one the most used reaction for the construction of organic compounds. However, the DA reactions between electronically mismatched partners are difficult to achieve thermally. A few methods can perform this transformation using a radical cation strategy. These approaches either give low yields of DA products or require the use of expensive materials or specialized setups. We have found that a paperclip can catalyze/initiate a Diels-Alder (DA) reaction at room temperature between electron-rich dienes and electron-rich dienophiles. The reaction gives excellent yields of DA products in a highly regio- and diastereoselective manner. The reaction mechanism is speculated to involve an electron transfer from one of the metals present in the paperclip to the dienophile. The talk will discuss our efforts in testing the hypothesis that certain metal(s) in a paperclip are responsible for the DA reaction and showcase our systematic search for this metal catalyst/initiator in light of suspected reaction mechanisms. Preliminary screening of substrate scope of the reaction will also be presented. The reaction has the potential to become the most economical, sustainable and practical method for the formation of DA products between electron-rich partners, thus expanding the scope of the DA reaction.