Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction.

Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.

Gold Meets Selenium: Dual Activation of Selenium-Containing Propargyl Alcohols Towards the Synthesis of 2H-Chromenes and Mechanistic Insights.

Herein, we report the synthesis of seleno-substituted chromenes from selenoalkynes and phenols. In this cascade reaction, the applied gold catalyst not only functions as a π-acid, but also as a Lewis acid, enabling the propargylic substitution in the first step to connect the oxygen carbon bond. Under the optimal reaction condition a total of 26 chromenes were accessible by this modular access. During scale up experiments, the hydrolysis of the vinylselenium substructure to the corresponding chromenones was observed. By revisiting the electron-rich starting materials, four chromenones were produced following a one-pot reaction using a single gold catalyst. To better understand the interaction of gold and selenium, a series of nuclear magnetic resonance studies and high-resolution mass spectrometry studies were performed, which led to the proposal of a mechanism for this transformation.

A systematic review of deep learning-based spinal bone lesion detection in medical images.

Spinal bone lesions encompass a wide array of pathologies, spanning from benign abnormalities to aggressive malignancies, such as diffusely localized metastases. Early detection and accurate differentiation of the underlying diseases is crucial for every patient's clinical treatment and outcome, with radiological imaging being a core element in the diagnostic pathway. Across numerous pathologies and imaging techniques, deep learning (DL) models are progressively considered a valuable resource in the clinical setting. This review describes not only the diagnostic performance of these models and the differing approaches in the field of spinal bone malignancy recognition, but also the lack of standardized methodology and reporting that we believe is currently hampering this newly founded area of research. In line with their established and reliable role in lesion detection, this publication focuses on both computed tomography and magnetic resonance imaging, as well as various derivative modalities (i.e. SPECT). After conducting a systematic literature search and subsequent analysis for applicability and quality using a modified QUADAS-2 scoring system, we confirmed that most of the 14 identified studies were plagued by major limitations, such as insufficient reporting of model statistics and data acquisition, a lacking external validation dataset, and potentially biased annotation. Although we experienced these limitations, we nonetheless conclude that the potential of these methods shines through in the presented results. These findings underline the need for more stringent quality controls in DL studies, as well as model development to afford increased insight and progress in this promising novel field.

The association of early response with the outcome of psychosomatic rehabilitation in patients with mental disorders and its link to treatment and illness beliefs-A prospective longitudinal cohort study.

Early response is considered to be an important predictor for therapy outcomes; yet little is known about its relevance in psychosomatic rehabilitation. This paper aims to describe the association of early response in psychosomatic rehabilitation, as well as the associations of early response with pre-rehabilitative factors such as illness and treatment beliefs.A longitudinal study with three measurement points was applied. Early response was defined using the percent improvement method after two weeks of treatment. Its association with therapy outcome and with illness and treatment beliefs was analyzed using multiple regression analyses.A total of 264 participants took part. Early response was a significant predictor of psychosomatic rehabilitation outcome, explaining an incremental variance of 1-30% after controlling for initial symptom burden. Illness and treatment beliefs predicted 6-20% variance in early response. Important illness beliefs referred to perceived symptoms, consequences and comprehensibility of the illness. Important treatment beliefs referred to expectations about rehabilitation structure, processes and concerns.Early response is associated with the therapy outcome of psychosomatic rehabilitation, with illness and treatment beliefs found to be associated with early response. Further research on the predictors of early response in psychosomatic rehabilitation is needed.

Title Selective Coupling of ß-(Borylvinyl)silanes by a Gold-catalyzed Hiyama Reaction - An Easy Way to Diaryl-Substituted Vinyl Boronates.

Diaryl-substituted vinyl boronates as potent building modules are challenging to synthesize. Herein, we present a convenient strategy based on a gold-catalyzed Hiyama arylation of (Z)-ß-(borylvinyl)silanes which are easily accessible by hydroboration of silylalkynes. By exploiting the highly electronegative nature of the Au(III) intermediate (which is accessed by the light-assisted oxidation with aryl diazonium salts), a selective activation of the silyl group in the presence of the boron moiety is achieved. This opens a route to selectively synthesize diaryl-substituted vinyl boronates. The reaction shows a broad substrate range, excellent functional group tolerance and perfect chemo-selectivity. Experimental studies and DFT calculations allowed us to elucidate the mechanism of the reaction, the synthetic potential was demonstrated by downstream transformations providing a facile route to bifunctional phenanthrenes and triaryl-substituted olefins.

Cascade Reactions of Aryl-Substituted Terminal Alkynes Involving in Situ-Generated α-Imino Gold Carbenes.

An efficient, highly selective and divergent synthetic method to construct 2-substituted indoles and aryl-annulated carbazoles via the intermolecular generation of α-imino gold carbenes from terminal alkynes or diynes in combination with sulfilimines is disclosed. Importantly, the tandem reaction is proposed to proceed through an intermolecular gold carbene generation/C-H annulation followed by the activation of a second alkyne leading to 6-endo-dig cyclization, which is significantly different from previous dual activation or 1,6-carbene shift approaches for diyne systems. In the case of ortho-alkynylaniline as starting material, an unexpected regioselective formation of the indole moiety via the intermolecular path, instead of intramolecular hydroamination was discovered. This reactivity paved the way for a one-pot synthesis of the 11H-indolo [3,2-c] quinoline scaffold by exploiting the formed amino indole for a subsequent Pictet-Spengler reaction with aldehydes. The photophysical properties of the carbazoles indicated good violet-blue emission with quantum yields up to 40 %.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Gold(I)-Mediated Cyclizations of Triene-Yne Systems: An Easy Access to Cyclopenta-Fused Anthracenes.

The direct synthesis of cyclopenta-fused anthracenes (CP-anthracenes) through a gold(I)-catalyzed cyclization reaction of easily available triene-yne systems bearing a benzofulvene substructure, is reported. The targets are of great interest due to the potential use as organic materials and the preparation of these compounds is gaining huge importance. The applied starting materials are readily available through a three-step synthesis, which further contributes to the advantages of this route. In addition, UV-Vis and fluorescent spectra of the obtained CP-anthracenes were recorded.

Gold-Catalyzed Regio- and Stereoselective α-Acyloxy-ß-Alkynylation of Ynol Ethers.

Enol esters and conjugated enynes are valuable structural motifs for synthetic chemistry and material sciences. Herein, the synthesis of tetra-substituted enol ester 2-iodobenzoate derivatives was achieved in good yields at room temperature through a gold-catalyzed acyloxyalkynylation of sensitive ynol ethers with ethynylbenziodoxolones (EBXs), the latter acting as bifunctional reactants. The conversion is highly regioselective with a broad substrate scope. Mechanistically, an Au(III) species is the key intermediate of an Au(I)/Au(III) redox cycle. The reaction is synthetically useful and can easily be scaled up to gram scale.

[Stress and suffering from tinnitus-a psychosomatic approach]. / Stress und Leiden am Tinnitus aus psychosomatischer Sicht.

The development and processing of tinnitus is often associated with stress. There are many publications on this subject that have investigated possible connections between stress perception and tinnitus symptoms using different concepts and different test inventories. In this review, we present the development of Selye's concept of stress using the transactional stress model of Lazarus and its transfer to patients suffering from tinnitus. The literature evaluating the influence of stress on tinnitus symptoms with partly very different concepts is critically reviewed. For example, it is suggested that psychosocial stress has the same likelihood of contributing to tinnitus as noise in the workplace. However, what is striking in previous studies is that "stress" as an influencing variable could not be clearly verified with suitable psychometric test procedures or that no significant differences-to very different comparison groups-could be shown. Finally, a possible therapeutic approach to stress management is outlined.

Light-Induced Metal-Free Generation of Cyanocarbenes from Alkynyl Triazenes for the Synthesis of Nitrile Derivatives.

The chemistry of alkynyl triazenes is an emerging field for organic chemists and especially acid-induced nucleophilic functionalizations, either directly, or after a prior reaction towards aromatic triazenes under extrusion of nitrogen, paved the way for fruitful strategies. In contrast, the chemical behavior of alkynyl triazenes upon irradiation with light is still unknown. Herein we present the first photoactivation of alkynyl triazenes that triggers an uncommon reactivity pattern involving the cleavage of the N1-N2 bond of the triazene moiety resulting in a unique approach to cyanocarbenes from a readily available, stable, and insensitive precursor. This allows to access various nitrile compounds without the use of a toxic cyanating agent by exploiting the reactivity pattern of carbenes. By variation of the reaction conditions and light sources, different substitution patterns can be obtained selectively in good yields under mild and metal-free conditions, thus introducing the alkynyl triazene unit as a photo accessible methylene nitrile synthon. Using this synthon, subclasses like α-alkoxynitriles, α-aminonitriles and α-cyanohydrazones become easily available. These exhibit synthetically valuable substitution patterns for the synthesis of pharmaceuticals, intermediates for total synthesis and amino acid synthesis.

Gold-Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor-Active Spirocyclic Oxindoles from Alkynes and Isatin-Derived Ketimines.

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones.

Efficient Synthesis of Dipyrrolobenzenes and Dipyrrolopyrazines via Bidirectional Gold Catalysis: a Combined Synthetic and Photophysical Study.

New N-heterocyclic fluorophores are sought-after compounds for organic electronic devices. Here, we report on a straightforward synthesis to access meta/para-dipyrrolobenzenes and para-dipyrrolopyrazines in high yields using a bidirectional gold-catalyzed cyclization strategy. The versatility of our reaction protocol was showcased by preparing dipyrroloarenes with different substituents, various functional groups, and in a multitude of substitution patterns. Furthermore, we showed that the dipyrroloarenes can be post-modified by N-alkylation to improve the solubility or bromination to yield precursors for further derivatization via cross-coupling. Investigation of the photophysical properties of the─mostly unprecedented─dipyrroloarenes identified strong blue emitters such as the diphenyl meta-dipyrrolobenzene with a quantum yield of 98%. Moreover, we showed that changes in the solvent polarity or interactions with Lewis acids such as borane can be used to fine-tune the photophysical properties of the fluorophores.

Entropy-Induced Selectivity Switch in Gold Catalysis: Fast Access to Indolo[1,2-a]quinolines.

New N-heterocyclic compounds for organic functional materials and their efficient syntheses are highly demanded. A surprising entropy-induced selectivity switch in the gold-catalyzed intramolecular hydroarylation of 2-ethynyl N-aryl indoles was found and its exploitation led to straightforward syntheses of indolo[1,2-a]quinolines. Experimental and computational mechanistic investigations gave insight into this uncommon selectivity phenomenon and into the special reactivity of the indolo[1,2-a]quinolines. The high functional group tolerance of this methodology enabled access to a diverse scope with high yields. In addition, bidirectional approaches, post-functionalization reactions, and π-extension of the core structure were feasible. An in-depth study of the photophysical properties explored the structure-effect relationship for different derivatives and revealed a high potential of these compounds for future applications as functional materials.

Cyclopentannulated Dihydrotetraazapentacenes.

The transition-metal-catalyzed cyclization of bissilylethynylated N,N'-dihydrotetraazapentacene (TIPS-TAP-H2 ) into bissilylated cyclopenta[fg,qr]pentacenes is reported. Depending on the catalyst either none, one or two silyl groups migrate and change their positions in the formed five-membered rings. The optoelectronic properties are quite similar, whereas the packing motifs differ dramatically. Control experiments and quantum chemical calculations were performed to investigate the mechanism of the reaction and the selectivity of the silyl shift.

Gem-Diaurated Gold(III) Complexes: Synthesis, Structure, Aurophilic Interaction, and Catalytic Activity.

We present a protocol to synthesize air stable gem-diaurated gold(III) compounds from 1,3-diketones in a single cycloauration step with tetrachloroauric acid. So far related species were only accessible from phosphonium bis(ylide) ligands which hold the two gold atoms in close proximity. Lacking such a constraint, our compounds show the longest Au-Au distances of all gem-diaurated carbons, ranging from 3.26 to 3.32 Å. Modeling based on results of CCSD(T) calculations shows no stabilization by aurophilic interactions for our gold(III) systems, compared to 9.1 kcal/mol for gold(I) gem-diauration. This demonstrates no aurophilic interactions are needed for the isolation of air stable gem-diaurated gold(III) complexes. We show the new gem-diaurated gold(III) compounds are active in the gold-catalyzed phenol synthesis and highly active in the cycloisomerization of an N-propargylcarboxamide; here, we obtained the so far highest known TON of over 2500 per gold atom with respect to the oxazole formation.

Kontextfaktoren der patient*innenseitigen Selbstregulation in der psychosomatischen Rehabilitation ­ eine Querschnittsanalyse vor Rehabilitationsbeginn.

BACKGROUND: Contextual factors are a central element of the ICF and important factors for therapy planning in psychosomatic rehabilitation. At the same time, little is known about the relationship between contextual factors and patient self-regulation, an important goal of rehabilitation.The aim of this study is therefore to investigate the relationship between contextual factors and illness belies. Illness beliefs are a core element of self-regulation in psychosomatic rehabilitation and part of the common sense model of self-regulation. METHODS: Between April 2019 and January 2020, a cross-sectional questionnaire study was conducted in a psychosomatic rehabilitation clinic, in which registered rehabilitation patients were questioned about their illness beliefs using the Illness Perception Questionnaire (IPQ-R). Contextual factors were divided into clinically modifiable and non-clinically modifiable and included gender, age, duration of illness, subjective social status, main diagnosis (dichotomised: F3/F4), occupational stress, depressive stress as well as activity and participation (operationalised by the Health-49). Multiple regressions were used for the analysis, in which the scales of the IPQ-R served as dependent variables. RESULTS: N=264 rehabilitants took part in the survey, 50% of them were female. The average age was 50 years. With regard to the non-clinically modifiable contextual factors, it was shown that a younger age was associated with higher control assumptions, but that younger rehabilitation patients simultaneously perceived more symptoms due to their illness (identity). A longer duration of illness showed a connection with the chronic timeline assumptions. A lower social status showed correlations with lower control assumptions and more assumptions about the cyclical timeline. Regarding clinically modifiable contextual factors, an F3 diagnosis was associated with more expected consequence, but also with a higher perceived personal control than an F4 diagnosis. A higher occupational burden was associated with the assumption of a more chronic course of the disease. Reduced activity and participation were associated with more expected consequences and more perceived symptoms (identity). Depressive stress showed associations with six out of eight domains of illness beliefs. CONCLUSION: The study supports the relevance of contextual factors, which in majority can be discussed as person-related factors, for patient self-regulation in psychosomatic rehabilitation. Interventions to increase self-regulation, e. g. by taking illness beliefs into account, have already achieved promising results, also in the context of rehabilitation. The patient-oriented approach of these interventions could be further strengthened by a stronger inclusion of contextual factors.

Modular Two-Step Access to π-Extended Naphthyridine Systems-Potent Building Blocks for Organic Electronics.

Efficient synthetic approaches for the incorporation of nitrogen into polyaromatic compounds (PACs) in different patterns as stabilising moiety for π-extended systems and modification tool for optoelectronic properties remain a challenge until today. Herein, we developed a new versatile pathway to napthyridine-based PACs as non-symmetric and regioisomeric pendant to pyrazine-based PACs. A combination of a gold-catalysed synthesis of 2-aminoquinolines and the development of an in situ desulfonation and condensation of these precursors are the key steps of the protocol. The shape and type of attached functional groups of the PACs can be designed in a late stage of the overall synthetic procedure by the chosen anthranile and backbone of the ynamide introduced in the gold-catalysed step. Single-crystal X-ray diffraction and the investigation of electronic properties of the compounds show the influence of the attached substituents. All naphthyridine-based PACs show halochromic behaviour implying their use as highly sensitive proton sensor in non-protic solvents.

Environmentally Friendly, Photochemical Access to [ N ∧ C ∧ N ]AuIII Pincer Complexes By Oxidative Addition.

Starting from commercially available DMSAuCl and diazonium salts, cationic [ N ∧ C ∧ N ]AuIII complexes were synthesized in a selective, photosensitizer-free, photochemical reaction by irradiation with blue LED light. This new protocol represents the first easy synthesis of these types of pincer complexes in moderate to excellent yield starting from a readily available gold(I) precursor with nitrogen as the only by-product. Owing to the disadvantages of known protocols, especially the toxicity in the case of a transmetalation with mercury or the necessity for a mostly twofold excess of a gold precursor, this method offers an attractive alternative towards this kind of gold(III) complexes. In addition, the first arylated [ N ∧ C ∧ N ]Au(III) pincer complex was synthesized by using this technology.

Gold-Catalyzed Annulation of 1,8-Dialkynylnaphthalenes: Synthesis and Photoelectric Properties of Indenophenalene-Based Derivatives.

A simple gold-catalyzed annulation of 1,8-dialkynylnaphthalenes utilizing a cationic gold catalyst was developed. Such a peri-position of two alkynyl substituents has not been studied in gold catalysis before. Dependent on the substrate, the reactions either follow a mechanism involving vinyl cation intermediates or involve a dual gold catalysis mechanism which in an initial 6-endo-dig-cyclization generates gold(I) vinylidene intermediates that are able to insert into C-H bonds. Indenophenalene derivatives were obtained in moderate to high yields. In addition, the bidirectional gold-catalyzed annulation of tetraynes provided even larger conjugated π-systems. The optoelectronic properties of the products were also investigated.