Showing papers by "Burkhard König published in 2020"
01 Jan 2020
TL;DR: In this article, the authors demonstrate that the organization of the reacting species in microstructured, aqueous solutions allows generation of carbon-centred radicals from non-activated alkyl chlorides in the presence of double bonds via assembly-promoted single electron transfer.
Abstract: Photoredox catalysis has developed into a powerful tool for the synthesis of organic compounds with diverse structures. However, stable carbon–chloride bonds remain beyond the energetic limits of the outer-sphere photoreductive activation. Here, we demonstrate that the organization of the reacting species in microstructured, aqueous solutions allows generation of carbon-centred radicals from non-activated alkyl chlorides in the presence of double bonds via assembly-promoted single electron transfer. Photocatalytic systems consisting of a surfactant, organic substrates and additives have been designed, characterized and applied for radical dechlorination, addition and cyclization reactions. Cheap and commercially available blue light-emitting diodes are used as the irradiation source for the transformations. Mechanistic studies indicate the accumulation of the energy of two visible light photons in one catalytic cycle. Photocatalytic activation of alkyl carbon–chlorine bonds has constantly proven difficult due to the high energies needed to cleave this stable bond. Here a surfactant-based photocatalytic system is used, allowing for the radical dehalogenation and subsequent reactivity of unactivated alkyl chlorides.
128 citations
TL;DR: A series of investigations including radical inhibition, deuterium labeling, fluorescence quenching, cyclic voltammetry, and control experiments support the proposed radical-carbanion relay mechanism.
Abstract: The combination of photoredox catalysis with the Wolff-Kishner (WK) reaction allows the difunctionalization of carbonyl groups by a radical-carbanion relay sequence (photo-Wolff-Kishner reaction). Photoredox initiated radical addition to N-sulfonylhydrazones yields α-functionalized carbanions following the WK-type mechanism. With sulfur-centered radicals, the carbanions are further functionalized by reaction with electrophiles including CO2 and aldehydes, whereas CF3 radical addition furnishes a wide range of gem-difluoroalkenes through β-fluoride elimination of the generated α-CF3 carbanions. More than 80 substrate examples demonstrate the broad applicability of this reaction sequence. A series of investigations including radical inhibition, deuterium labeling, fluorescence quenching, cyclic voltammetry, and control experiments support the proposed radical-carbanion relay mechanism.
80 citations
TL;DR: In this article, a redox-neutral C─H carboxylation of arenes and styrenes using a photocatalytic approach is presented, where the anthrolate anion photocatalyst is able to reduce many aromatic compounds to their corresponding radical anions, which react with CO2 to afford carboxylic acids.
61 citations
TL;DR: The preparation of activated carbon materials is discussed along selected examples of precursor materials, of available production and modification methods and possible characterization techniques and important parameters for metal loading are identified.
Abstract: The preparation of activated carbon materials is discussed along selected examples of precursor materials, of available production and modification methods and possible characterization techniques. We evaluate the preparation methods for activated carbon materials with respect to its use as catalyst support and identify important parameters for metal loading. The considered carbon sources include coal, wood, agricultural wastes or biomass as well as ionic liquids, deep eutectic solvents or precursor solutions. The preparation of the activated carbon usually involves pre-treatment steps followed by physical or chemical activation and application dependent modification. In addition, highly porous materials can also be produced by salt templating or ultrasonic spray pyrolysis as well as by microwave irradiation. The resulting activated carbon materials are characterized by a variety of techniques such as SEM, FTIR, nitrogen adsorption, Boehm titrations, adsorption of phenol, methylene blue and iodine, TPD, CHNS/O elemental analysis, EDX, XPS, XRD and TGA.
60 citations
TL;DR: The synergistic combination of a heterogeneous organic semiconductor mesoporous graphitic carbon nitride (mpg-CN) and a homogeneous nickel catalyst with visible-light irradiation at room temperatur... is described in this paper.
Abstract: The synergistic combination of a heterogeneous organic semiconductor mesoporous graphitic carbon nitride (mpg-CN) and a homogeneous nickel catalyst with visible-light irradiation at room temperatur...
50 citations
TL;DR: Visible light-mediated chemical reactions have become very popular within the last 15 years as discussed by the authors, and are not anymore a merely academic field of research, finding its way increasingly into applications in the chemical and pharmaceutical industry.
45 citations
TL;DR: In this article, a photoinduced copper(II) peroxide catalytic system was proposed for the alkylation of N-H bonds with alkanes using photoinduced peroxide.
Abstract: We report a practical method for the alkylation of N–H bonds with alkanes using a photoinduced copper(II) peroxide catalytic system. Upon light irradiation, the peroxide serves as a hydrogen atom t...
44 citations
TL;DR: In this article, a C(sp(3))-C(sp (3)) cross-coupling of alkyl bromides with ethers by dual photoredox-nickel catalysis was reported.
Abstract: We report a C(sp(3))-C(sp(3)) cross-coupling of alkyl bromides and alkyl chlorides with ethers by dual photoredox-nickel catalysis. The catalytic system comprises of the organic photocatalyst 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4-CzIPN) and bench stable nickel (II) acetylacetonate in the presence of visible-light, providing the coupling products in up to 92% yield. Preliminary mechanistic studies suggest two catalytic cycles, as well as the photogeneration of bromine or chlorine radicals from halide atoms that are present in the structures of the coupling partners. The halide radical mediates the hydrogen atom transfer event, avoiding the need of an additional HAT catalyst.
33 citations
TL;DR: This work reports practically important transition-metal-free regioselective thiol–yne addition and formation of the demanding Markovnikov-type product by a radical photoredox process.
Abstract: An associative electron upconversion is proposed as a key step determining the selectivity of thiol–yne coupling. The developed synthetic approach provided an efficient tool to access a comprehensive range of products – four types of vinyl sulfides were prepared in high yields and selectivity. We report practically important transition-metal-free regioselective thiol–yne addition and formation of the demanding Markovnikov-type product by a radical photoredox process. The photochemical process was directly monitored by mass-spectrometry in a specially designed ESI-MS device with green laser excitation in the spray chamber. The proposed reaction mechanism is supported by experiments and DFT calculations.
33 citations
TL;DR: This study provides first evidence that the reductive power of excited deazaflavin semiquinones can be used in photocatalytic reductive chemistry and their application in catalytic photodehalogenations.
Abstract: Flavin-mediated photocatalytic oxidations are established in synthetic chemistry. In contrast, their use in reductive chemistry is rare. Deazaflavins with a much lower reduction potential are even better suited for reductive chemistry rendering also deazaflavin semiquinones as strong reductants. However, no direct evidence exists for the involvement of these radical species in reductive processes. Here, we synthesise deazaflavins with different substituents at C5 and demonstrate their photocatalytic activity in the dehalogenation of p-halogenanisoles with best performance under basic conditions. Mechanistic investigations reveal a consecutive photo-induced electron transfer via the semiquinone form of the deazaflavin as part of a triplet-correlated radical pair after electron transfer from a sacrificial electron donor to the triplet state. A second electron transfer from the excited semiquinone to p-halogenanisoles triggers the final product formation. This study provides first evidence that the reductive power of excited deazaflavin semiquinones can be used in photocatalytic reductive chemistry. Flavins and deazaflavins are well suited for photoredox processes but their application in photoreductions is challenging. Here, the authors provide direct evidence of the high reductive power of excited deazaflavin semiquinones and their application in catalytic photodehalogenations.
22 citations
TL;DR: It was demonstrated that alkyl radicals could also be engaged into cascades consisting of an intermolecular Giese‐type addition followed by an intramolecular homolytic aromatic substitution to rapidly assemble valuable azepinoindolones.
Abstract: In this work, a photocatalytic strategy for a rapid and modular access to polycyclic indolones starting from readily available indoles is reported. This strategy relies on the use of redox-active esters in combination with an iridium-based photocatalyst under visible-light irradiation. The generation of alkyl radicals through decarboxylative single electron reductions enables intramolecular homolytic aromatic substitutions with a pending indole moiety to afford pyrrolo- and pyridoindolone derivatives under mild conditions. Furthermore, it was demonstrated that these radicals could also be engaged into cascades consisting of an intermolecular Giese-type addition followed by an intramolecular homolytic aromatic substitution to rapidly assemble valuable azepinoindolones.
TL;DR: The synthesis and characterization of novel tariquidar-related inhibitors are included, obtained by bioisosteric replacement of the labile moieties in the authors' previous tarLiquidar analog UR-ME22-1, helping to further elucidate the (patho)physiological role of ABCG2.
TL;DR: A photocatalytic approach to the Corey–Seebach reaction is reported, which operates under mild redox‐neutral and base‐free conditions giving the desired product with high functional group tolerance.
Abstract: A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey-Seebach reaction. The presented method operates under mild redox-neutral and base-free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo- and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C-H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α-hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical-radical homocoupling and deuterium labeling studies as well as by calculated redox-potentials and bond strengths.
TL;DR: The results of an experimental and computational investigation of arylazo-3(5)-arylazo-1H-pyrazoles are presented and solvent and substitution effects on their light absorption, thermal half-lives, photostationary states (PSS), fatigue and quantum yields were determined.
Abstract: The desire to photocontrol molecular properties ranging from materials to pharmacology using light as an external trigger with high spatiotemporal resolution led to the development of a broad range of photochromic scaffolds. Among them, azobenzenes are synthetically well accessible and show excellent fatigue resistance. Their photochromic properties vary with the substitution pattern and for different heteroarenes. However, the photochromism of 3(5)-substituted-1H-pryazoles has not yet been investigated, although this compound class offers interesting possibilities of metal ion coordination and hydrogen bond formation via its NH moiety. Herein, we present the results of an experimental and computational investigation of arylazo-3(5)-arylazo-1H-pyrazoles. To elucidate their properties, solvent and substitution effects on their light absorption, thermal half-lives, photostationary states, fatigue, and quantum yields were determined.
TL;DR: This work describes a photocatalytic Minisci-type C-H functionalization of heteroarenes with non-activated alkyl bromides with critical importance of microstructuring and organization of the components in the reaction mixture.
Abstract: Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci-type C-H functionalization of heteroarenes with non-activated alkyl bromides. The reaction avoids stoichiometric radical-promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon-centered alkyl radicals are generated by merging the photoredox approach with bromide anion co-catalysis and spatial pre-aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.
TL;DR: A visible‐light photochemical approach for practical helicene functionalization at very mild reaction conditions is described, and six different functional groups are introduced to the helicene scaffold through C−C and four different C‐heteroatom bond‐forming reactions.
Abstract: Herein, a visible-light photochemical approach for practical helicene functionalization at very mild reaction conditions is described. The photochemical reactions allow for the regiospecific and innate late-stage functionalization of helicenes and are easily executed either through the activation of C(sp2 )-Br bonds in helicenes using K2 CO3 as inorganic base or direct C(sp2 )-H helicene bond functionalization under oxidative photoredox reaction conditions. Overall, using these transformations six different functional groups are introduced to the helicene scaffold through C-C and four different C-heteroatom bond-forming reactions.
TL;DR: Glyght, a GlyR ligand controlled with light is developed, which is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action.
TL;DR: In this article, electron-rich arenes are oxidatively photochlorinated in the presence of catalytic amounts of bromide ions, visible light, and 4CzIPN as organic photoredox catalyst.
TL;DR: Findings confirm that signal transduction from HisF to HisH in ImGPS involves the closing of the cyclase:glutaminase subunit interface and that incorporation of AzoF at a hinge position reinforces this catalytically relevant conformational change.
Abstract: Imidazole glycerol phosphate synthase (ImGPS) from Thermotoga maritima is a model enzyme for studying allostery. The ImGPS complex consists of the cyclase subunit HisF and the glutaminase subunit HisH whose activity is stimulated by substrate binding to HisF in a V-type manner. To investigate the significance of a putative closing hinge motion at the cyclase:glutaminase interface for HisH activity, we replaced residue W123 in HisH with the light-switchable unnatural amino acid phenylalanine-4'-azobenzene (AzoF). Crystal structure analysis employing angle, buried surface area, and distance measurements showed that incorporation of AzoF at this position causes a closing of the interface by ∼18 ± 3%. This slightly different interface configuration results in a much higher catalytic efficiency in unstimulated HisH due to an elevated turnover number. Moreover, the catalytic efficiency of HisH when stimulated by binding of a substrate to HisF was also significantly increased by AzoF incorporation. This was caused by a K-type stimulation that led to a decrease in the apparent dissociation constant for its substrate, glutamine. In addition, AzoF improved the apparent binding of a substrate analogue at the HisF active site. Remarkably, light-induced isomerization of AzoF considerably enhanced these effects. In conclusion, our findings confirm that signal transduction from HisF to HisH in ImGPS involves the closing of the cyclase:glutaminase subunit interface and that incorporation of AzoF at a hinge position reinforces this catalytically relevant conformational change.
TL;DR: The host-guest system containing [Ru(bpy)3]2+ can bind suitable substrates, and essential criteria for its use as a supramolecular photocatalyst are investigated.
Abstract: This work outlines a strategy to combine the use of visible light and confined spaces to form a supramolecular photocatalyst system Polypyridyl ruthenium(II) complexes [Ru(bpy)3]2+ (bpy = 2,2′-bip
TL;DR: In this paper, the authors used deep eutectic solvents (DESs) for luminescence measurements in quantitative analysis of trivalent lanthanide ions.
01 Apr 2020
TL;DR: A mild, efficient and straightforward visible-light-driven method has been developed to construct 1,2-diarylvinyl sulfides under catalyst-and additive-free conditions as discussed by the authors.
Abstract: A mild, efficient and straightforward visible-light-driven method has been developed to construct 1,2-diarylvinyl sulfides under catalyst- and additive-free conditions. The formation of small amounts of thiyl radicals under visible light irradiation allows the synthesis of 1,2-diarylvinyl sulfides in good yield with an excellent functional group tolerance.
TL;DR: Fulgazepam is reported, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ‐aminobutyric acid receptors (GABAARs) and displays full and reversible photoswitching in vitro and in vivo.
Abstract: Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABAA Rs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition.
TL;DR: Based on the crystal structure of the D3 receptor in complex with eticlopride, caged D2/D3 receptor ligands by rational design are developed and the 2-nitrobenzyl derivative 4 showed excellent photochemical stability, pharmacological behavior and decaging properties when interacting with dopamine receptor-expressing cells.
Abstract: Dopamine is a neurotransmitter of great physiological relevance. Disorders in dopaminergic signal transduction are associated with psychiatric and neurological pathologies such as Parkinson's disease, schizophrenia and substance abuse. Therefore, a detailed understanding of dopaminergic neurotransmission may provide access to novel therapeutic strategies for the treatment of these diseases. Caged compounds with photoremovable groups represent molecular tools to investigate a biological target with high spatiotemporal resolution. Based on the crystal structure of the D3 receptor in complex with eticlopride, we have developed caged D2/D3 receptor ligands by rational design. We initially found that eticlopride, a widely used D2/D3 receptor antagonist, was photolabile and therefore is not suitable for caging. Subtle structural modification of the pharmacophore led us to the photostable antagonist dechloroeticlopride, which was chemically transformed into caged ligands. Among those, the 2-nitrobenzyl derivative 4 (MG307) showed excellent photochemical stability, pharmacological behavior and decaging properties when interacting with dopamine receptor-expressing cells.
TL;DR: In this paper, a simple three-step synthesis of naphtho[2,1]-b:7,8-b′]bis[1]benzothiophene was described, which is scalable to multi-hundred-grams.
15 Oct 2020
TL;DR: In this paper, a method for catalyst preparation using deep eutectic solvents (DES) was developed, where the pyrolysis of a metal-containing DES leads to a material consisting of metal embedded in a carbon support rich in oxygen and nitrogen functional groups (CNO).
Abstract: Electrochemical CO(2)reduction on Cu-based catalysts can form a variety of products including hydrocarbons, alcohols and formate, besides carbon monoxide and hydrogen. Compared to other electroactive metals, copper has a rather low cost and low toxicity. We have developed a novel method for catalyst preparation using deep eutectic solvents (DES), where the pyrolysis of a metal-containing DES leads to a material consisting of a metal embedded in a carbon support rich in oxygen and nitrogen functional groups (CNO). We focus on the preparation of copper-based materials as catalysts for the electrochemical CO(2)reduction. Depending on the nature of DES, the properties of the carbon support can be changed. The electrochemical activity of the materials was correlated with the preparation parameters such as variation of DESs, copper precursor and/or pyrolysis temperature. These Cu/CNO copper catalysts showed formate formation rates up to 85.5 mu mol h(-1) cm(-2)at 1.5 Vvs. Ag/AgCl.