Immobilization of a flavin molecule onto poly(methacrylic acid)s and its application in aerobic oxidation catalysis: effect of polymer stereoregularity.

The isoalloxazine ring system, called flavin, was successfully immobilized on poly(methacrylic acid)s, PMAAs, with different tacticity via post-polymerization modification under suitable conditions. The resulting flavin-containing polymers showed catalytic activity for aerobic oxidation reactions, in which the polymer stereoregularity clearly influenced their catalytic activity.

Hydrosilane-Mediated Electrochemical Reduction of Amides.

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.

Synthesis of D-π-A type benzothiazole-pyridinium salt composite and its application as photo-degradation agent for amyloid fibrils.

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.

Unexpected formation of poly-functionalized fulvenes by the reaction of a tetraaryl[5]cumulene with iodine.

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.

Synthesis and Transformations of Nitrones for Organic Synthesis.

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.

Determination of acid dissociation constants of flavin analogues by capillary zone electrophoresis.

Acid dissociation constants (pKa ) of nine kinds of flavin analogues as molecular catalyst candidates were determined by CZE. Although some of the analogues are instable and degradable under the light exposure or in alkaline aqueous solutions, the effective electrophoretic mobility of the flavin analogue of interest has been measured with the residual substance. The pKa values of the flavin analogues were analyzed through the changes in the effective electrophoretic mobility with varying pH of the separation buffer. One or two steps pKa values were determined by the analysis. One of the degraded species from the flavin analogues, lumichrome, was also detected in the CZE analysis, and its pKa values were also determined. While coexisting impurities generated over the storage conditions were found in some analogues, the pKa values of the target analogues were successfully determined with the help of the CZE separations. A pressure-assisted CZE was utilized for the determination or the estimation of the pKa values of such analogues as possessing carboxylic acid moiety.

Two- and three-photon excitable quaternized imidazo[1,2-a]pyridines as mitochondrial imaging and potent cancer therapy agents.

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.

Selective Functionalization of Styrenes with Oxygen Using Different Electrode Materials: Olefin Cleavage and Synthesis of Tetrahydrofuran Derivatives.

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.

Enzyme-like Regiodivergent Behavior of a Flavopeptide Catalyst in Aerobic Baeyer-Villiger Oxidation.

We recently developed a flavopeptide immobilized on polystyrene resin, Fl-Pep-PS, that could realize the first N5-unmodified neutral flavin (Fl)-catalyzed aerobic oxygenation reactions under non-enzymatic conditions. Although a key active species is assumed to be the corresponding 4a-hydroperoxyflavin (Fl4aOOH) from the unprecedented activity and unique chemoselectivity, further circumstantial support would be helpful to be sure since spectroscopic evidence is difficult to obtain due to the compound's insolubility. In this article, we report that the aerobic Baeyer-Villiger oxidation of a fused cyclobutanone, (±)-cis-bicyclo[3.2.0]hept-2-en-6-one (1), can be promoted with Fl-Pep-PS in a FMO-like chemoselectivity and regiodivergent manner via Fl-related catalytic intermediates, which delivers strong evidence of the involvement of Fl4aOOH as an active species in Fl-Pep-PS-catalyzed aerobic oxygenation reactions.

Metal- and Reagent-Free Dehydrogenative Formal Benzyl-Aryl Cross-Coupling by Anodic Activation in 1,1,1,3,3,3-Hexafluoropropan-2-ol.

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.

Investigating radical cation chain processes in the electrocatalytic Diels-Alder reaction.

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.

Highly fluorescent flavins: rational molecular design for quenching protection based on repulsive and attractive control of molecular alignment.

Unprecedented intense fluorescent emission was observed for a variety of flavin compounds bearing a perpendicular cyclic imide moiety at the C7 position of an isoalloxazine platform. A series of alloxan-substituted flavins was prepared selectively by reduction of the corresponding N-aryl-2-nitro-5-alkoxyanilines with zinc dust and subsequent reaction with alloxan monohydrate in the presence of boric acid. Analogues bearing oxazolidine-2,4-dione functionality were obtained on methylation of the alloxan-substituted flavins with methyl iodide and subsequent rearrangement in the presence of an inorganic base. The flavin compounds exhibit intense white-green fluorescent emission in the solution state under UV excitation at 298 K, with emission efficiencies Φ298 K greater than 0.55 in CH3 CN, which are higher than the values for all reported flavin compounds under similar conditions. The highest Φ298 K value of 0.70 was obtained in CH3 CN for isoalloxazine bearing C7-alloxan and N10-2,6-diisopropylphenyl groups. The temperature dependence of the emission intensities indicates that the pronounced emission properties at 298 K are attributable to the highly heat resistant properties towards emission decay with increasing temperature. Mechanistic studies, including X-ray diffraction analysis, revealed that the good emission properties and high heat resistance of the alloxan-substituted flavins are due to a synergetic effect of the associative nature of the C7-alloxan unit and the repulsive nature of the perpendicular bulky substituents at the C7 and N10 positions.

Aerobic reduction of olefins by in situ generation of diimide with synthetic flavin catalysts.

A versatile reducing agent, diimide, can be generated efficiently by the aerobic oxidation of hydrazine with neutral and cationic synthetic flavin catalysts 1 and 2. This technique provides a convenient and safe method for the aerobic reduction of olefins, which proceeds with 1 equiv of hydrazine under an atmosphere of O(2) or air. The synthetic advantage over the conventional gas-based method has been illustrated through high hydrazine efficiency, easy and safe handling, and characteristic chemoselectivity. Vitamin B(2) derivative 6 acts as a highly practical, robust catalyst for this purpose because of its high availability and recyclability. Association complexes of 1b with dendritic 2,5-bis(acylamino)pyridine 15 exhibit unprecedented catalytic activities, with the reduction of aromatic and hydroxy olefins proceeding significantly faster when a higher-generation dendrimer is used as a host pair for the association catalysts. Contrasting retardation is observed upon similar treatment of non-aromatic or non-hydroxy olefins with the dendrimer catalysts. Control experiments and kinetic studies revealed that these catalytic reactions include two independent, anaerobic and aerobic, processes for the generation of diimide from hydrazine. Positive and negative dendrimer effects on the catalytic reactions have been ascribed to the specific inclusion of hydrazine and olefinic substrates into the enzyme-like reaction cavities of the association complex catalysts.

Synthesis of Optically Active Polyguanidines by Polyaddition Reaction of Biscarbodiimides with Chiral Diamines.

Herein, we present the first study on the polyaddition reaction of biscarbodiimides with chiral diamines, which focuses on a definite case using optically active trans-4a,8a-decahydroquinoxaline and 1,4-phenylenebis(arylcarbodiimide)s, which readily react with each other under ambient and catalyst-free conditions. The specific reactivity allows for facile access to not only the corresponding chiral polyguanidines under balanced stoichiometry but also their oligomeric analogues under imbalanced stoichiometry via a step-by-step procedure. Spectroscopic, chromatographic, and computational characterization of the novel molecular chains containing arrayed guanidines have revealed their structural, optical, and conformational properties as well as the mechanism of polymerization assisted by molecular association. Their potential use as asymmetric catalysts is also described.

Two-photon excitable boron complex based on tridentate imidazo[1,5-a]pyridine ligand for heavy-atom-free mitochondria-targeted photodynamic therapy.

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment.

An uncommon use of irradiated flavins: Brønsted acid catalysis.

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 upon 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 thioacetalization but also Mannich-type reactions.

Efficient Use of Photons in Photoredox/Enamine Dual Catalysis with a Peptide-Bridged Flavin-Amine Hybrid.

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).

Flavinium and Alkali-Metal Assembly on Sulfated Chitin: A Heterogeneous Supramolecular Catalyst for H2 O2 -Mediated Oxidation.

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 H2 O2 . Owing to the cooperative catalytic effect of flavinium, alkali metal, and sulfated chitin, the supramolecular flavinium assembly showed higher catalytic activity for the Baeyer-Villiger oxidation of cyclic ketones than the corresponding homogeneous flavinium catalyst. Because the ionic assembly was stable under the reaction conditions, the catalyst could be readily recovered by simple filtration and reused.

Fluorescent Imidazo[1,5-a]pyridinium Salt for a Potential Cancer Therapy Agent.

N,N'-Dimethylated imidazo[1,5-a]pyridinium salt having good water solubility and exhibiting fluorescence emission was found to work as not only a bioimaging agent but also a therapeutic agent under UVA-LED irradiation conditions. Because the continuous UVA-LED irradiation to HeLa cells stained by the synthesized salt resulted in the cell death due to the mitochondrial damage, the salt has a potential application as photodynamic therapy agent against tumor cells.

Entropic electrolytes for anodic cycloadditions of unactivated alkene nucleophiles.

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.