Synthesis of 2,3-Dihydrobenzofurans via a Photochemical Gold-Mediated Atom Transfer Radical Addition Reaction.

A light-mediated cyclization reaction initiated by an atom transfer radical addition (ATRA) of haloalkanes onto alkenes was exploited for the synthesis of functionalized dihydrobenzofurans. Initial investigation indicated that the dimeric gold catalyst [Au2(µ-dppm)2Cl2] can effectively be used for intermolecular ATRA reactions. Further, the reactivity was applied in a cascade-like cyclization for the preparation of dihydrobenzofuran derivatives. With the presented photochemical approach, the functionalization can be achieved directly from ortho-allylphenols in yields of up to 96% under mild conditions.

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(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.

Synthesis and structural properties of para-diselenopyrazines.

Recently, dithienopyrazines have emerged as promising building blocks in the field of materials science, showcasing their potential as hole-transport materials in organic electronic devices. Herein, we report the synthesis of its heavier analogues, the diselenopyrazines, along with an analysis of their optoelectronic and structural properties. In the acquired crystal structures, interesting molecular packing motifs suitable for potential device fabrication were observed. Additionally, short contact interactions are present in one of the investigated molecules.

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.

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 %.

[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(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 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.

Gold-Catalyzed [3,3]-Sigmatropic Rearrangement of ortho-Alkynyl-S,S-diarylsulfilimines.

Highly functionalized 5H-pyrrolo[2,3-b]pyrazine cores, carrying a diaryl sulfide moiety at the C-7 position, were obtained from a gold-catalyzed reaction using easily accessible ortho-alkynyl-substituted S,S-diarylsulfilimines as intramolecular nitrene transfer reagents for the first time. The reaction proceeds under mild conditions, providing excellent yields while tolerating a large variety of different substitution patterns. We provide experimental evidence for an intramolecular reaction mechanism, likely including an unprecedented gold-catalyzed amino sulfonium [3,3]-sigmatropic rearrangement.

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.

Three-Dimensional Metal-Insulator-Metal Decoupling Capacitors with Optimized ZrO2 ALD Properties for Improved Electrical and Reliability Parameters.

Embedded three-dimensional (3-D) metal-insulator-metal (MIM) decoupling capacitors with high-κ dielectric films of high capacitance and long-life time are increasingly needed on integrated chips. Towards achieving better electrical performance, there is a need for investigation into the influence of the variation in atomic layer deposition (ALD) parameters used for thin high-κ dielectric films (10 nm) made of Al2O3-doped ZrO2. This variation should always be related to the structural uniformity, the electrical characteristics, and the electrical reliability of the capacitors. This paper discusses the influence of different Zr precursor pulse times per ALD cycle and deposition temperatures (283 °C/556 K and 303 °C/576 K) with respect to the capacitance density (C-V), voltage linearity and leakage current density (I-V). Moreover, the dielectric breakdown and TDDB characteristics are evaluated under a wide range of temperatures (223-423 K).

Psychometric properties of the rehabilitation treatment beliefs questionnaire for psychosomatic rehabilitation.

PURPOSE: Treatment beliefs play a crucial role for patient satisfaction and the treatment outcome in psychosomatic rehabilitation. The aim of this study was the development and the psychometric evaluation of an indication-specific questionnaire of beliefs about psychosomatic rehabilitation. MATERIALS AND METHODS: The study was conducted at a psychosomatic rehabilitation clinic. The primary item list comprised k = 125 items. After a descriptive item analysis, we conducted an exploratory factor analysis. Furthermore, we tested reliability via McDonald's Omega and construct validity by analyzing correlations of the scales with related constructs. RESULTS: Of the N = 264 participants, 50% were female and the mean age was 50.4 (SD = 9.8) years. K = 85 items were suitable for factor analysis, which resulted in k = 30 items constituting six scales, explaining of 57% the overall variance. The corrected item-total correlations were between r = 0.48 and r = 0.83. Internal consistency ranged from ω = 0.81 to ω = 0.86. CONCLUSION: The newly developed questionnaire assesses specific treatment beliefs about inpatient psychosomatic rehabilitation. The psychometric properties of the six scales are acceptable. Further studies should confirm the psychometric results, such as the factorial structure of the questionnaire.IMPLICATIONS FOR REHABILITATIONTreatment beliefs are known to play an important role for the adherence, therapy outcome and satisfaction in psychosomatic rehabilitation.We developed and tested a indication-specific questionnaire assessing treatment beliefs in psychosomatic rehabilitation.The questionnaire can be used to explore patient's rehabilitation-related treatment beliefs, predict treatment outcomes, and to develop interventions attempting to modify these.

Illness Beliefs, Treatment Beliefs, and Fulfilled Treatment Expectations in Psychosomatic Rehabilitation: Associations with Patient Satisfaction.

Purpose: Patients' illness and treatment beliefs have been shown to predict health outcomes in many health care settings. However, information about their impact on patient satisfaction is scarce. The aim of this study was to investigate illness- and rehabilitation-related treatment beliefs and met rehabilitation-related treatment expectations and their relationship with patient satisfaction in psychosomatic rehabilitation. Methods: In a repeated measures study design, patients filled out questionnaires 2 to 3 weeks before the start of rehabilitation and at the end of an inpatient rehabilitation 6 to 7 weeks later. The predictive value of illness beliefs, treatment beliefs, and fulfilled treatment expectations regarding patient satisfaction was analyzed with multiple hierarchical regression analyses controlling for sociodemographic and clinical variables. Results: Two hundred sixty-four patients participated. The sample was composed of equal numbers of men and women (n = 129 each). The mean age was 50.4 years. Most patients had diagnoses from the ICD-10 diagnostic group F3 (affective disorders; n = 145) or F4 (neurotic, stress-related and somatoform disorders; n = 94). Sociodemographic and clinical variables were not associated with patient satisfaction. The explained variance of patient satisfaction increased to 10% by adding illness beliefs (namely personal control and coherence) (p = 0.006), to 5% by adding rehabilitation-related treatment beliefs (namely concerns) (p = 0.063), and to 49% by adding fulfilled expectations (namely a positive discrepancy between expectations and experiences related to outcome expectations and related to participation and treatment structure, and a negative discrepancy between expectations and experiences related to concerns) (p < 0.001) as predictor variables. Conclusion: This study highlights the relationship of fulfilled (rehabilitation-related) treatment expectations with patient satisfaction in psychosomatic rehabilitation. Given the evidence underlining the importance of patients' illness and treatment beliefs and expectations, it is vital that these constructs are addressed in corresponding interventions.

Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents.

Multisubstituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) with perfect atom-economy. The EBX reagents transfer both the carboxylate as well as the alkynyl entity. Overall, this cascade comprises the in situ generation of an alkynyl gold(III) species, a stereoselective C(sp)-C(sp2) bond formation, and a C-O coupling at the alkynyl position of the ynamides. This reaction proceeds under mild conditions and accepts a wide range of substrates. A number of tetrasubstituted amide enol 2-iodobenzoates bearing different functional groups were obtained in good to excellent yields. DFT calculations explain the observed regioselectivity. The synthetic potential of the reaction was further demonstrated by a number of selected follow-up transformations.

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.

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.

Synthesis of α-Ketoamides via Gold(I) Carbene Intermediates.

α-Ketoamides have been found to be an important functional group in a broad spectrum of inhibitors such as the Corona virus and other viruses. Here we report an unprecedented gold-catalyzed 2-fold reaction of a bromoalkyne with anthranils. Hydrolysis of the initial product then directly leads to α-ketoamides. Water addition to the intermediate α-iminoimidoyl halides delivered α-ketoamides from a broad range of bromoalkynes.

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.