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The Minisci reaction constitutes a straightforward and convenient strategy to achieve the direct C–H functionalization of heterocyclic molecules. This radical-based reaction platform has received increasing attention due to the predictability of its outcome according to the nature of the radicals and heterocycles involved. Considering the importance of these heterocyclic scaffolds in the development and production of drug molecules, it is inevitable that scaling up this reaction manifold is of utmost importance. This review will present recent strategies to achieve the goal, which mostly involve implementing the reaction conditions under continuous flow. [ABSTRACT FROM AUTHOR]

Intramolecular C−H bond activation via 1,4‐palladium migration has become a synthetic tool to enable remote functionalization of C−H bonds. In this work, we report a Pd‐catalyzed remote alkenylation with unactivated alkenyl alcohols involving a 1,4‐palladium migration step. This method provides a regioselective access to synthesize substituted unsaturated alcohols in a single operational step. [ABSTRACT FROM AUTHOR]

Oxazolidinone represents a class of most important five‐membered cyclic carbamates. They are of great significance for modern organic synthesis and are widespread as pharmacologically active compounds. This review summarizes recent advances in the chemistry of 2‐oxazolidinones, with an emphasis on their synthesis, employing different catalytic systems or catalyst‐free conditions, as well as on their ring‐opening transformations through decarboxylative coupling, covering the period from 2010 to early 2021. Detailed mechanistic aspects are highlighted, hoping to help researchers to explore the hidden opportunities for reaction discoveries. [ABSTRACT FROM AUTHOR]

Polycycles are abundantly present in numerous advanced chemicals, functional materials, bioactive molecules and natural products. However, the strategies for the synthesis of polycycles are limited to classical reactions and transition metal‐catalyzed cross‐coupling reactions, requiring pre‐functionalized starting materials and lengthy synthetic operations. The emergence of novel approaches shows great promise for the fields of organic/medicinal/materials chemistry. Among them, transition metal‐catalyzed C−H activation followed by intermolecular annulation reactions prevail, due to their straightforward manner with high atom‐ and step‐economy, providing rapid, concise and efficient methods for the construction of diverse polycycles. Several strategies have been developed for the synthesis of polycycles, relying on sequential multiple C−H activation/annulation, or combination of C−H activation/annulation and further interaction with a proximal group, or merger of C−H activation with a cycloaddition reaction, or in situ formation of the directing group. These are attractive, efficient, step‐ and atom‐economic methods starting from commercially available materials. This Minireview will provide an introduction to transition metal‐catalyzed C−H activation for the synthesis of polycycles, helping researchers to discover indirect connections and reveal hidden opportunities. It will also promote the discovery of novel synthetic strategies relying on C−H activation. [ABSTRACT FROM AUTHOR]

Metal‐free decarboxylative coupling reactions represent an alternative paradigm for carbon–carbon or carbon–heteroatom bond formation that complement more traditional metal catalysis approaches. In this review, recent advances in metal‐free decarboxylation reactions of α,β‐unsaturated carboxylic acids are highlighted. Two major reaction classes are covered: 1) generation of C–C, C–N, C–S, C–X bonds using propiolic acids; 2) transformations of alkenyl acids for C–C, C–P, C–N, C–S, C–X bond‐forming. Some cases involving electrochemistry and photochemistry represent a frontier area for carbon–carbon and carbon–heteroatom coupling processes. Additionally, the proposed mechanisms for both types of reactions are discussed. [ABSTRACT FROM AUTHOR]

Peptidomimetics have been extensively explored in many area due to their ability to improve pharmacological qualities and interesting biological activities. Cycles could be incorporated in peptides to reduce their flexibility, often enhancing the affinity for a certain receptor. Many efforts have been made to synthesize various peptidomimetics. Among them, the Ugi reaction is a popular way for the synthesis of peptidomimetics because it provides peptide‐like products. The Ugi reaction consists of the condensation of an aldehyde or ketone, a carboxylic acid, an amine, and an isocyanide usually giving a linear peptidomimetic. In order to obtain other linear, cyclic or polycyclic peptidomimetics, the acyclic products have to undergo additional transformations or cyclizations. This review covers the years from 2018–2023, regarding the synthesis of linear, cyclic and polycyclic peptidomimetics, employing Ugi reactions eventually followed by post‐Ugi transformations. Organo‐catalyzed reactions, base‐promoted reactions, and metal‐free reactions toward peptidomimetics are highlighted. [ABSTRACT FROM AUTHOR]

In the realm of flow chemistry, Do-It-Yourself (DIY) flow setups represent a versatile and cost-effective alternative to expensive commercially available reactors. Not only they are budget friendly, but also unlock a world of possibilities for researchers to explore and create customized setups tailored to their specific needs. This minireview serves as a short compendium of DIY flow systems to assist flow researchers in the challenging task of finding a suitable setup for their experiments and facilitate the transition from batch to flow chemistry. Our goal is to demonstrate that flow chemistry can be affordable, easy-to-build, and reproducible at the same time. Therefore, herein we review and describe selected illustrative examples of easily assembled/constructed DIY flow setups, with a particular emphasis on how to select the most suitable one based on the specific chemistry of interest, ranging from simple homogeneous monophasic reactions to more complex systems for photo-, electrochemistry, and so on. In addition, we briefly comment on the significance of DIY approach on education, particularly its integration into the standard undergraduate curriculum as a key educational tool for young chemists. Ultimately, we hope this mini review will help and encourage the reader to go with the flow and get started with the fine art of flow chemistry. [ABSTRACT FROM AUTHOR]

A high-yielding, temperature switchable divergent approach towards the synthesis of either spiro-indolenines or quinolines is described, starting from easily available indolyl ynones. The application of TFA at rt promotes the dearomatization of the indole, resulting in the formation of the spiro-indolenine, while at higher temperature, rearrangement results in the formation of the quinoline. [ABSTRACT FROM AUTHOR]

The Ugi reaction has become one of the highly explored reactions for the formation of multifunctional adducts, due to the mild reaction conditions, wide scope and high variability. By carefully selecting the starting four components, Ugi‐adducts could undergo different kinds of post‐transformations for the synthesis of bioactive heterocycles, natural products and macrocycles. Considering the significance of polycycles, diverse post‐Ugi transformations have been developed over the years for constructing structurally novel polycycles. In this account, we summarize important efforts for the synthesis of polycyclic N‐heterocycles via post‐Ugi cyclizations from the Van der Eycken laboratory onwards 2016. With the aid of transition metal catalysis from gold, rhodium, silver and palladium, as well as metal‐free strategies, versatile polyheterocycles are prepared with high efficiency and step‐economy. [ABSTRACT FROM AUTHOR]

A novel method of transition metal‐free N−S bond cleavage and subsequent C−N bond activation of Ugi‐adducts was developed. Diverse primary amides and α‐ketoamides were prepared in a rapid, step‐economical and highly efficient manner in two steps. This strategy features excellent chemoselectivity, high yield and functional‐group tolerance. Primary amides derived from the pharmaceuticals probenecid and febuxostat were prepared. This method opens a new pathway for the simultaneous synthesis of primary amides and α‐ketoamides in an environmentally friendly manner. [ABSTRACT FROM AUTHOR]

Nitrogen containing compounds are of great importance because of their interesting and diverse biological activities. The construction of the C–N bond is of significant importance as it opens avenues for the introduction of nitrogen in organic molecules. Despite significant advancements in this field, the construction of the C–N bond is still a major challenge for organic chemists, due to the involvement of harsh reaction conditions or the use of expensive catalysts in many cases. Thus, it is a challenge to develop alternative, milder and cheaper methodologies for the construction of C–N bonds. Herein, we have selected some prime literature reports that may serve this purpose. [ABSTRACT FROM AUTHOR]

Among the fundamental transformations in the field of synthetic organic chemistry, transition-metal-catalyzed reactions provide some of the most attractive methodologies for the formation of C–C and C-heteroatom bonds. As a result, the application of these reactions has increased tremendously during the past decades and cross-coupling reactions became a standard tool for synthetic organic chemists. Furthermore, a tremendous upsurge in the development of new catalysts and ligands, as well as an increased understanding of the mechanisms, has contributed substantially to recent advances in the field. Traditionally, organic reactions are carried out by conductive heating with an external heat source (for example, an oil bath). However, the application of microwave irradiation is a steadily gaining field as an alternative heating mode since its dawn at the end of the last century. This tutorial review focuses on some of the recent developments in the field of cross-coupling reactions assisted by microwave irradiation. [ABSTRACT FROM AUTHOR]

Abstract: Microwave irradiation was applied in the racemization and dynamic kinetic resolution of primary benzylic amines. Racemization reactions catalyzed by 5% Pd/BaSO4 and 5% Pd/CaCO3 were faster and more selective when performed under microwave conditions. The use of microwave irradiation stopped the formation of side products, such as secondary amines and ethylbenzene. This was correlated with the selective heating of the metal sites under microwave heating. The influence of the microwave irradiation also was checked in the kinetic resolution; no influence on the activity and enantioselectivity of the immobilized Candida Antarctica Lipase B (Novozym 435) was observed when both conventional and microwave heating were compared. The racemization catalysts were combined in one pot with the biocatalyst Novozym 435 to perform the dynamic kinetic resolution of benzylic amines under microwave irradiation. High yields (up to 88%) of enantiopure amides were obtained in less than 1 h when microwave irradiation was applied. [Copyright &y& Elsevier]

Inter- and intramolecular hetero-Diels-Alder reactions in a series of functionalized 2(1H)-pyrazinones were investigated under controlled microwave irradiation. The cycloaddition reactions were efficiently performed in sealed tubes, utilizing either a combination of 1,2-dichloroethane and a thermally stable ionic liquid, or 1,2-dichlorobenzene as reaction medium. In all cases, a significant rate-enhancement using microwave flash heating as compared to thermal heating was observed. [ABSTRACT FROM AUTHOR]

Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification and holds great potential for the treatment of mental disorders. However, several important factors are needed to transform current practice into a precision psychiatry framework. Most important are 1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, 2) the development and validation of advanced analytical tools for stratification and prediction, and 3) the development of clinically useful management platforms for patient monitoring that can be integrated into health care systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements—well-powered samples from large biobanks integrated with electronic health records and health registry data using novel artificial intelligence algorithms—to predict outcomes in severe mental disorders and translate these models into clinical management and treatment approaches. Key elements are massive mental health data and novel artificial intelligence algorithms. For the clinical translation of these strategies, we discuss a precision medicine platform for improved management of mental disorders. We use cases to illustrate how precision medicine interventions could be brought into psychiatry to improve the clinical outcomes of mental disorders. [ABSTRACT FROM AUTHOR]

The chemistry of boron compounds has been profoundly investigated in the last decades, leading to ubiquity in many synthetic applications as well as biologically active molecules. Since the advent of photoredox catalysis, an upsurge in the discovery of suitable radical precursors has been witnessed, and boron is becoming a protagonist in this field. Despite many studies focused on trifluoroborates, the use of boronic acids and esters have received much less attention in this regard. Because of their high oxidation potential, the development of methods to enable their involvement in photocatalyzed reactions is only recent. Nonetheless, this review summarizes novel strategies developed to unlock their role as radical precursors in photochemical reactions and discloses the potential that boronic acids and esters own, when their intrinsic chemical properties are exploited. [ABSTRACT FROM AUTHOR]

Microwave irradiation and post-Ugi reactions own their respective advantages in comparison with other strategies. The combination of microwave irradiation and post-Ugi reactions shows paramount importance in the construction of polycycles. This minireview outlines the recent developments of microwave-assisted post-Ugi reactions for the synthesis of polycycles. Through transition metal-catalyzed or transition metal-free transformations, diverse polycycles are prepared in an efficient, rapid, and step-economical manner. [ABSTRACT FROM AUTHOR]

Heterocycles are important compounds existed in diverse advanced chemicals, functional materials, bioactive molecules and natural products. Different strategies through transition metal‐catalyzed alkyne cyclization have been developed to synthesize various heterocycles. The merger of alkyne cyclization and metal nanoparticle catalysis has emerged as an important approach to diverse heterocycles. By using different kinds of metal nanoparticle catalysts, such as gold, silver, copper and palladium nanoparticles, a number of heterocycles are prepared with high yield and selectivity in a green, sustainable and highly efficient manner. This review summarizes and discusses recent achievements in metal nanoparticle‐catalyzed alkyne cyclization for the synthesis of heterocycles. [ABSTRACT FROM AUTHOR]

Visible-light photoredox catalysis has been regarded as an extremely powerful tool in organic chemistry, bringing the spotlight back to radical processes. The versatility of photocatalyzed reactions has already been demonstrated to be effective in providing alternative routes for cross-coupling as well as multicomponent reactions. The photocatalyst allows the generation of high-energy intermediates through light irradiation rather than using highly reactive reagents or harsh reaction conditions. In a similar vein, organic electrochemistry has experienced a fruitful renaissance as a tool for generating reactive intermediates without the need for any catalyst. Such milder approaches pose the basis toward higher selectivity and broader applicability. In photocatalyzed and electrochemical multicomponent reactions, the generation of the radical species acts as a starter of the cascade of events. This allows for diverse reactivity and the use of reagents is usually not covered by classical methods. Owing to the availability of cheaper and more standardized photo- and electrochemical reactors, as well as easily scalable flow-setups, it is not surprising that these two fields have become areas of increased research interest. Keeping these in view, this review is aimed at providing an overview of the synthetic approaches in the design of MCRs involving photoredox catalysis and/or electrochemical activation as a crucial step with particular focus on the choice of the difunctionalized reagent. [ABSTRACT FROM AUTHOR]

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor activity has obtained more and more attention from organic and pharmaceutical chemists. As a member of the aromathecin alkaloids, rosettacin has been synthesized via different methods. This review summarizes recent advances in the synthesis of rosettacin. [ABSTRACT FROM AUTHOR]

Transition metal‐catalysed processes have been widely used for the functionalization of inert C−H bonds. Strategies for the functionalization of the benzylic C−H position having a relatively weak C−H bond (bond dissociation energy∼ 80–90 kcal/mol) differ from the inert aliphatic and aromatic C−H positions with stronger C−H bonds. The recent advances in the direct activation of the benzylic position through the generation of C(sp3) radicals have demonstrated the potential of electrochemistry and photochemistry as a means for constructing new chemical bonds. This review will cover the recent progress of benzylic C−H functionalization through organic radical strategies employing photochemistry and electrochemistry as sustainable tools. In addition, the mechanistic details of the typical reactions have been included which, in turn, will help the researchers to look at this promising area from a different perspective towards new discoveries and often hidden opportunities. [ABSTRACT FROM AUTHOR]

Dearomatization strategies in a multicomponent fashion often result in complex heterocyclic frameworks, which have attracted the attention of chemists due to their natural product-like structures. The combination of these two processes can easily achieve extended molecular complexity and diversity from simple starting materials with high atom economy. Thus, this field has attracted extensive interest owing to its potential significance in both asymmetric catalysis and convenient build-up of libraries of molecules with novel three-dimensional scaffolds, which may find application in medicinal chemistry. Accordingly, a systematic review on this topic will provide the synthetic organic community with a conceptual overview and comprehensive understanding of the different multicomponent reaction (MCR) cascades involving dearomatization as the characteristic step. In addition, this review will help researchers to look at this promising area from a different perspective with respect to drug discovery, new MCR-based disconnections and often hidden opportunities. [ABSTRACT FROM AUTHOR]

The development of methods for deuterium incorporation has gained increased attention owing to the importance of deuterated molecules in chemical, medicinal and biological sciences. Despite the number of procedures reported so far, including acid/base promoted protocols and direct C–H bond functionalization, photochemical deuteration of organic molecules accounts for a limited number of reports only. Over the passage of time, these methods have been developed in line with the goal of broad applicability, sustainability and milder reaction conditions. In addition, visible-light induced deuteration of drug molecules and natural products has been achieved, often allowing for the late-stage deuteration of complex structures. Despite these appealing features, this vibrant and challenging field is still in its infancy. This review, therefore, provides an overview of the recent achievements in photochemical deuteration strategies and a starting point for understanding the potential of this field. [ABSTRACT FROM AUTHOR]

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines. [ABSTRACT FROM AUTHOR]

Under microwave (MW) irradiation at 150 °C in toluene and in the presence of nucleophiles (DMAP, triphenylphosphine and tetrahydrothiophene) 1‐substituted 1‐ethynyl‐2‐vinyldi‐ and tetrahydroisoquinolines undergo [3,3]‐sigmatropic rearrangement providing pyrrolo[2,1‐b][3]benzazepines in good yields. The replacement of toluene with acetonitrile directs the rearrangement towards the formation of 7,11b‐dihydro‐6H‐pyrido[2,1‐a]isoquinolines. [ABSTRACT FROM AUTHOR]

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing the high value of distinctly different ways of bond creation. Indoles and related heterocycles are widely-present in natural products, biologically active compounds, drugs, and agrochemicals. This review summarises the impact of visible light-promoted chemistry on the functionalization of indoles and on the synthesis and modification of indolines, indolin-2-ones, indolin-3-ones, and isatins. Almost 100 references starting from 2012 are cited. [ABSTRACT FROM AUTHOR]

A catalyst‐controlled intramolecular carbocyclization of 2‐alkynyl aryl ketones is presented. Under rhodium(III) catalysis, 1‐indanones are formed through 5‐exo‐dig carbocyclizations with exclusive chemo‐, regio‐ and stereoselectivity. When catalyzed by copper(I), 1‐naphthols are obtained through 6‐endo‐dig carbocyclizations with exclusive chemo‐ and regioselectivity. [ABSTRACT FROM AUTHOR]

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing high value for distinctly different ways of bond creation. Halogenated compounds are the cornerstone of contemporary organic synthesis: it is almost impossible to develop a route towards a pharmaceutical reagent, agrochemical, natural product, etc. without the involvement of halogen-containing intermediates. Moreover, the halogenated derivatives as final products became indispensable for drug discovery and materials science. The idea of this review is to understand and summarise the impact of visible light-promoted chemistry on halogenation and halofunctionalisation reactions. [ABSTRACT FROM AUTHOR]

The highly efficient construction of complicated heterocyclic frameworks in an atom‐ and step‐economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal‐free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017–2023) in metal‐free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo‐catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid‐ or base‐promoted dearomatization reactions, photoredox‐catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions. [ABSTRACT FROM AUTHOR]

Oxygen‐containing heterocycles are common in biologically active compounds. In particular, phthalan and coumaran cores are found in pharmaceuticals, organic electronics, and other useful medical and technological applications. Recent research has expanded the methods available for their synthesis. This Minireview presents recent advances in the chemistry of phthalans and coumarans, with the goal of overcoming synthetic challenges and facilitating the applications of phthalans and coumarans. O me, O my! Oxygen‐containing heterocycles are common in biologically active compounds. In particular, phthalan and coumaran cores are found in pharmaceuticals, organic electronics, and other useful medical and technological applications. This Minireview presents recent advances in the chemistry of phthalans and coumarans, with the goal of overcoming synthetic challenges and facilitating their application. [ABSTRACT FROM AUTHOR]

[Display omitted] • Evaluating the performance of diaryl-substituted alkynes employed in annulation. • Providing an efficient method to isolate positional isomers. • Accomplishing the synthesis of diverse heterocyclic products. • Furnishing an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor. An intermolecular annulation of 2-acetylenic aldehydes or ketones with O -substituted N -hydroxybenzamides or N -hydroxyacrylamides through rhodium(III)-catalyzed C–H activation for the synthesis of isoquinolones and indolizinones is developed. This reaction features excellent functional-group tolerance and broad substrate scope, including annulation of various heterocyclic substrates. This approach evaluates the chemoselectivity of the reaction when sterically hindered diaryl-substituted alkynes are incorporated. This method also furnishes an efficient approach for the total synthesis of rosettacin and a topoisomerase I inhibitor. [ABSTRACT FROM AUTHOR]

Spiroindolines and spiroindoles are an important class of spirocyclic compounds present in a wide range of pharmaceuticals and biologically important natural alkaloids. Various spiroindolines and spiroindoles possess versatile reactivity which enables them to act as precursors for other privileged heterocycles. In view of the importance of this scaffold, many researchers focused their efforts to develop facile and mild synthetic methods for spirocyclization of indoles. However, the synthesis of spiroindolines and spiroindoles is known to be difficult due to rapid 1,2-migration to restore aromaticity. This review aims to briefly discuss the latest developments to access highly functionalized spiroindolines and spiroindoles to stimulate further research in the field to find new and efficient methodologies for accessing new spiroindolines and spiroindoles. [ABSTRACT FROM AUTHOR]

Review: 50 refs. [ABSTRACT FROM AUTHOR]

Review: 88 refs. [ABSTRACT FROM AUTHOR]

An oxidative cascade cyclization of propargylguanidines promoted by phenyliodonium diacetate (PIDA) was developed. The protocol provides an efficient route for the synthesis of the alkaloids kealiinines B and C as well as homologues. The difference in the electronic nature of the acetylene substituent resulted in two ways of the cyclization. A plausible mechanism is proposed based on the experimental results. [ABSTRACT FROM AUTHOR]

Copper-catalyzed enantioselective coupling has been widely investigated, which allows rapid construction of various chiral molecules. Despite important advances via polar and radical mechanisms, exploring general and practical strategies for the regio-, enantio- and diastereoselective assembly of stereogenic centers is of significant value but remains highly problematic. The integration of photocatalysis with asymmetric copper catalysis could provide appealing access to the development of new reaction pathways and structurally diverse chiral compounds, and extend the boundaries of radical chemistry. This review summarizes recent advances in photoinduced copper-catalyzed enantioselective coupling reactions, and discusses the mechanistic aspects. [ABSTRACT FROM AUTHOR]

The isoindolo[2,1‐b]isoquinolin‐5(7H)‐one scaffold is widely present in lots of bioactive natural products. Diverse types of strategies have been developed to construct this scaffold. Recently, transition metal‐catalyzed C−H activation/annulation is emerging as a powerful and straightforward method to construct diverse polyheterocycles with high atom‐ and step‐economy. It also has been employed for the synthesis of the isoindolo[2,1‐b]isoquinolin‐5(7H)‐one scaffold. This review provides an introduction to recent advances for the preparation of isoindolo[2,1‐b]isoquinolin‐5(7H)‐ones by using transition metal‐catalyzed C−H activation/annulation. It will help researchers to find hidden opportunities and accelerate the discovery of novel transformations based on C−H activation/annulation. [ABSTRACT FROM AUTHOR]

1,3‐Dipolar cycloadditions are the preferred method to generate five‐membered heterocyclic rings. Surprisingly, cycloadditions based on acyl‐isocyanide ylides have remained underexplored by the chemical community. Acyl‐isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1‐pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron‐poor and electron‐rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl‐isocyanide ylides motif. [ABSTRACT FROM AUTHOR]

A novel strategy for the synthesis of various N-alkenylisoquinolinones is reported, which features broad functional group tolerance, and good chemoselectivity. This reaction proceeds through sequential palladium-catalyzed cyclization and C4–O bond cleavage of oxazolidines to form carbon–carbon and carbon–oxygen double bonds. In addition, the practical value of this method has been explored by conducting a millimole reaction, as well as via the palladium-catalyzed C–H arylation and visible-light-assisted photocatalyzed conversion of the cyclic enamide to valuable compounds. [ABSTRACT FROM AUTHOR]

We report herein an efficient Pd-catalyzed direct CH bond functionalization of heteroarenes via an isocyanide insertion strategy for the synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines. The methodology involves a three component reaction between an azole, a haloarene and an isocyanide resulting in the formation of an imine, which in turn is either hydrolyzed or reduced to get the desired product. [ABSTRACT FROM AUTHOR]

Background: Internet-based Cognitive Behaviour Therapy (iCBT) for depression have been implemented in routine care across Europe in varying ways, at various scales and with varying success. This study aimed to advance our understanding of organisational implementation climate from the perspectives of implementers and mental health service deliverers.Methods: Qualitative and quantitative methods were combined to study the concept of organisational implementation climate in mental health care settings. Based on concept mapping, a qualitative workshop with implementers was used to conceptualise organisational implementation climate for optimizing iCBT use in routine practice. Service deliverers involved in the provision of iCBT were invited to participate in an explorative cross-sectional survey assessing levels of satisfaction and usability of iCBT, and organisational implementation climate in implementing iCBT. The two methods were applied independently to study viewpoints of implementers as well as service deliverers. Corresponding to the explorative nature of the study, inductive reasoning was applied to identify patterns and develop a reasonable explanation of the observations made. Correlative associations between satisfaction, usability and implementation climate were explored.Results: Sixteen implementers representing fourteen service delivery organisations across Europe participated in the workshop. The top-three characteristics of a supportive organisational implementation climate included: (1) clear roles and skills of implementers, (2) feasible implementation targets, and (3) a dedicated implementation team. The top-three tools for creating a supportive implementation climate included: (1) feedback on job performance, (2) progress monitoring in achieving implementation targets, and (3) guidelines for assessing the impact of iCBT. The survey (n=111) indicated that service providers generally regarded their organisational implementation climate as supportive in implementing iCBT services. Organisational implementation climate was weakly associated with perceived usability and moderately with satisfaction with iCBT services.Conclusions: Organisational implementation climate is a relevant factor to implementers and service deliverers in implementing iCBT in routine care. It is not only an inherent characteristic of the context in which implementation takes place, it can also be shaped to improve implementation of iCBT services. Future research should further theorise organisational implementation climate and empirically validate the measurement instruments such as used in this study. [ABSTRACT FROM AUTHOR]

A transition metal-free C–S bond cleavage and subsequent Mannich reaction of Ugi-adducts with alcohols as well as thiols is developed. Diverse novel peptidomimetics containing N,O- or N,S-aminals are synthesized in a rapid, highly efficient and step-economical fashion. This method features exclusive selectivity, broad substrate scope, excellent yield and functional group tolerance, and was applied on substrates derived from the pharmaceuticals febuxostat, probenecid and memantine. [ABSTRACT FROM AUTHOR]

A new route for the construction of 2-aminoimidazolidines including analogues of the α2 adrenergic agonist drug clonidine is elaborated. The key step is an intramolecular microwave-assisted Staudinger/aza-Wittig cyclization of an in situ generated urea intermediate (formed by the reaction of β-amino azide and isocyanate) upon treatment with Bu3P or polymer-supported phosphine reagent, allowing the introduction of various substituents at the N1 and the 2-amino function. Furthermore, a useful one-pot Staudinger/aza-Wittig/Buchwald-Hartwig protocol leading to bicyclic guanidines has been elaborated. [ABSTRACT FROM AUTHOR]

Dreierbande: Eine kupferkatalysierte Heteroaren ‐ Amin ‐ Aldehyd/Keton ‐ Dreikomponentenkupplung bietet einen neuen Ansatz für die bislang schwierige direkte Alkylierung sekundärer/tertiärer C ‐ H ‐ Einheiten von Azolen. Diese einfache Methode ermöglicht die Einführung von unterschiedlich substituierten, verzweigten und Stickstoff ‐ haltigen Alkyl ‐ oder Alkaloid ‐ Seitenketten am Azol ‐ Kern ausgehend von leicht verfügbaren Ausgangsverbindungen. [ABSTRACT FROM AUTHOR]

Coupling the strangers: A copper‐catalyzed three‐component heteroarene–amine–aldehyde/ketone coupling affords a novel approach to the hitherto difficult direct secondary/tertiary CH alkylation of azoles. This simple method allows the facile installation of diversely substituted, branched and nitrogen‐containing alkyl or alkaloid side chains on the azole moiety by using readily available starting materials (see scheme). [ABSTRACT FROM AUTHOR]

This minireview describes the progress made in the development of direct CH arylation approaches through the application of focused microwave irradiation. The synergistic combination of microwave-assisted techniques with the rapidly evolving domain of CH arylation has opened new vistas in the efficient synthesis of a diverse array of biologically important (hetero)arenes. [ABSTRACT FROM AUTHOR]

The direct C-H arylation of 1,3,4-thiadiazoles with a wide range of (hetero)aryl iodides, bromides, and triflates is described using a Pd/Cu-catalyzed protocol. The methodology is compatible with substrates possessing electron-donating or electron-withdrawing substituents and also tolerates sterically hindered aryl halides. The utility of the developed protocol is demonstrated by a one-pot C-H arylation-Suzuki coupling sequence. [ABSTRACT FROM AUTHOR]

The direct cross-coupling of tautomerizable heterocycles with various unfunctionalized heteroarenes has been achieved through PyBroP-mediated and Pd/Cu-catalyzed sequential C–OH/C–H activation. The methodology allows a facile entry into novel diazine-azole biheterocyclic frameworks. Moreover, an unprecedented Pd-catalyzed phosphonium homocoupling of tautomerizable heterocycles was also developed to afford a direct synthetic route to symmetrical 1,2-, 1,3-, and 1,4-bidiazine units. [ABSTRACT FROM AUTHOR]

An expedient route for the synthesis of differently substituted 2(1H)-pyrazinones applying a microwave-assisted palladium-catalyzed phosphonium coupling procedure is reported. The method has also been successfully extended to tome other tautomerizable heterocycles for efficient C—C cross-coupling. [ABSTRACT FROM AUTHOR]