Construction of N-Heterocycles through Cyclization of Tertiary Amines

N-Heterocycles have been found in a large number of natural products, drug molecules, and bioactive compounds, and they thereby play a vital role in diverse research disciplines including drug discovery, organic synthesis, chemical biology, and material science. To this end, the development of new methods and strategies for the construction of N-heterocyclic frameworks is arguably one of the most dynamic and significant research areas in organic synthesis. One of these powerful approaches to the synthesis of N-heterocycles is to establish cyclization reactions based on the transformation of tertiary amines, which has emerged as an attractive research topic. In this Minireview, the significant achievements in the construction of N-heterocycles through cyclization of tertiary amines are highlighted and a comprehensive overview of the rational design, development, and application of these synthetic methods is presented.     

Multiple catalysis with two chiral units: an additional dimension for asymmetric synthesis

This Minireview focuses on asymmetric reactions mediated by two distinct chiral catalysts (chiral multiple catalysis). Initially, this approach appears unconventional, but indeed it allows a fast multidimensional optimization and fine-tuning of the catalytic system required to perform a given transformation. Herein, this emerging concept is presented and its potential applications are highlighted.     

From Ostwald Ripening to Single Chirality

A century ago Wilhelm Ostwald received the Nobel Prize for Chemistry. Although Ostwald was never significantly involved with the phenomenon of chirality, one of his discoveries, Ostwald ripening, is thought to be involved in a recently discovered method in which grinding‐induced attrition is used to transform racemic conglomerates virtually quantitatively into a single enantiomer. In this Minireview the basic concepts developed by Ostwald will be introduced, followed by a summary of the current status of grinding‐induced asymmetric transformations. We will see how close Ostwald himself came to discovering this technique.     

Organocatalyzed Enantioselective Desymmetrization of Diols in the Preparation of Chiral Building Blocks

Desymmetrization of diols is a powerful tool to the synthesis of chiral building blocks. Among the different approaches to perform discrimination between both enantiotopic hydroxyl groups, the organocatalytic approach has gained importance in the last years. A diverse range of organocatalysts has been used to efficiently promote this enantioselective transformation and this Minireview examines the different contributions in this field.     

The Emergence of Transition‐Metal‐Mediated Hydrothiolation of Unsaturated Carbon–Carbon Bonds: A Mechanistic Outlook

The hydrothiolation of unsaturated carbon–carbon bonds is a practical and atom‐economical approach for the incorporation of sulfur into organic frameworks. In recent years, we have witnessed the development of a range of transition‐metal‐based catalytic systems for the control of the regio‐ and stereoselectivity. In this Minireview we highlight the mechanistic background behind this transformation so as to help the design of more specific and active organometallic hydrothiolation catalysts.     

Applications of Activity‐Based Protein Profiling (ABPP) and Bioimaging in Drug Discovery

Activity‐based protein profiling (ABPP) and bioimaging have been developed in recent years as powerful technologies in drug discovery. Specifically, both approaches can be applied in critical steps of drug development, such as therapy target discovery, high‐throughput drug screening and target identification of bioactive molecules. We have been focused on the development of various strategies that enable simultaneous activity‐based protein profiling and bioimaging studies, thus facilitating an understanding of drug actions and potential toxicities. In this Minireview, we summarize these novel strategies and applications, with the aim of promoting these technologies in drug discovery.     

Metal‐Free Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen

The metal‐free activation of hydrogen by frustrated Lewis pairs (FLPs) is a valuable method for the hydrogenation of polarized unsaturated molecules ranging from imines, enamines, and silyl enol ethers to heterocycles. However, one of the most important applications of hydrogenation technology is the conversion of unsaturated hydrocarbons into alkanes or alkenes. Despite the fast development of the FLP chemistry, such reactions proved as highly challenging. This Minireview provides an overview of the basic concepts of FLP chemistry, the challenge in the hydrogenation of unsaturated hydrocarbons, and first solutions to this central transformation.     

Recent Developments in Colloidal Synthesis of CuInSe2 Nanoparticles

Ternary semiconductor nanocrystals, such as CuInSe₂, are of high interest for photovoltaic application due to their relatively low toxicity and unique properties. During the last decades great success has been achieved in the colloidal synthesis of binary nanoparticles, but for ternary compounds this research is still in an early stage of development. These materials are a challenge for synthetic chemistry, because the interaction between the three components (copper, indium, and selenium) plays a major role for the production of high quality material. The purpose of this Minireview is to provide a summary of the achievements in colloidal synthesis of CuInSe₂ nanoparticles—in particular, details of reaction mechanism and its characterization possibilities, which might be useful also for the colloidal synthesis of other multicomponent systems.     

Two-Dimensional Metal-Organic Frameworks Towards Spintronics

The intrinsic properties of predesignable topologies and tunable electronic structures, coupled with the increase of electrical conductivity, make two-dimensional metal–organic frameworks (2D MOFs) highly prospective candidates for next-generation electronic/spintronic devices. In this Minireview, we present an outline of the design principles of 2D MOF-based spintronics materials. Then, we highlight the spin-transport properties of 2D MOF-based organic spin valves (OSVs) as a notable achievement in the progress of 2D MOFs for spintronics devices. After that, we discuss the potential for spin manipulation in 2D MOFs with bipolar magnetic semiconductor (BMS) properties as a promising field for future research. Finally, we provide a brief summary and outlook to encourage the development of novel 2D MOFs for spintronics applications.     

Factors Determining the Selection of Organic Reactions by Medicinal Chemists and the Use of These Reactions in Arrays (Small Focused Libraries)

Synthetic organic reactions are a fundamental enabler of small‐molecule drug discovery, and the vast majority of medicinal chemists are initially trained—either at universities or within industry—as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead‐optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist.     

Gold for C?C Coupling Reactions: A Swiss‐Army‐Knife Catalyst?

For organic chemists, the construction of C C bonds is the most essential aspect of the assembly of molecules. Transition‐metal‐catalyzed coupling reactions have evolved as one of the key tools for this task. Lately, gold has also emerged as a catalyst for this kind of transformation. Gold, with its special properties as a mild carbophilic π Lewis acid, its ability to insert into C H bonds, and, as discovered recently, its ability to undergo redox transformations, offers the opportunity to apply all this potent proficiency for the construction of compounds in an efficient and economical way. This Minireview critically presents the C C coupling reactions enabled by gold catalysts to encourage further research activities in this promising area of oxidation/reduction gold catalysts.     

A "renaissance" in radical trifluoromethylation

This Minireview highlights recent developments in radical trifluoromethylation reactions. The trifluoromethyl group belongs to the privileged moieties in medicinal chemistry. Many drugs and drug candidates contain a trifluoromethyl substituent. Also in agrochemicals, the CF(3) moiety often appears. The present article addresses the radical trifluoromethylation of alkenes and arenes mainly focussing on recent achievements. However, important earlier work in this field is also covered.     

Transition‐Metal‐Mediated Cleavage of C−C Bonds in Aromatic Rings

Metal‐mediated cleavage of aromatic C?C bonds has a range of potential synthetic applications: from direct coal liquefaction to synthesis of natural products. However, in contrast to the activation of aromatic C?H bonds, which has already been widely studied and exploited in diverse set of functionalization reactions, cleavage of aromatic C?C bonds remains Terra incognita. This Minireview summarizes the recent progress in this field and outlines key challenges to be overcome to develop synthetic methods based on this fundamental organometallic transformation.     

Proteins in action monitored by time-resolved FTIR spectroscopy.

In the post genome era proteins coming into the focus of life sciences. X-ray structure analysis and NMR spectroscopy are established methods to determine the geometry of proteins. In order to determine the molecular reaction mechanism of proteins, time-resolved FTIR (trFTIR) difference spectroscopy emerges as a valuable tool. In this Minireview we describe the trFTIR difference spectroscopy and show its application on the light-driven proton pump bacteriorhodopsin (bR), the photosynthetic reaction center and the GTPase Ras, which is crucial in signal transduction. The main principles of the technique are presented, including a summary of triggering techniques, scan modes and analysis.     

C−F Bond Activation Mediated by Phosphorus Compounds

The activation and functionalization of C−F bonds has garnered significant attention in the scientific community as a strategy to mitigate toxicity and environmental concerns, as well as provide new pathways to agro- and pharmaceutical chemicals and materials. Although several transition-metal-based systems have been developed for this transformation, the use of main-group compounds remains less explored. In recent years, several strategies for C−F bond activation have focused on the use of phosphorus-based reagents. In this Minireview, an overview of strategies is provided that exploits P^V and P^III-based Lewis acids as well as P^III Lewis bases in frustrated Lewis pair (FLP) protocols for hydrodefluorination, C−C couplings and C−F derivatizations.     

Carbopalladation Cascades Using Carbon–Carbon Triple Bonds: Recent Advances to Access Complex Scaffolds

Alkynes are one of the most versatile functional groups as synthetic handles. They allow for a direct access to partially or fully substituted alkenes through difunctionalization reactions. A prominently utilized transformation for these sequences is the carbopalladation of alkynes, which can be followed by various termination steps such as aromatizations, dearomatizations, cross‐coupling reactions, or pericyclic processes, amongst others. This Minireview provides an overview of the recent literature published in the field of carbopalladation chemistry, both with a focus on methodology as well as its application in the syntheses of complex molecular scaffolds, natural products, and functional molecules.     

Two birds with one metallic stone: single-pot catalysis of fundamentally different transformations

Advances in metal catalysis have revolutionized organic synthesis, with the scope of metal-catalyzed reactions now covering nearly all areas of carbon-carbon, carbon-hydrogen, and carbon-heteroatom bond formation. For years, the goal was to develop catalysts that were highly selective for a single transformation. However, a promising current area of research is the use of a single catalyst to mediate more than one transformation in a selective manner. Whereas much early work was focused on using a catalyst for several similar transformations, recent investigations have shown that it is also possible to employ a single catalyst for several very different transformations in a single reaction sequence. This Minireview focuses on methods in which the mechanisms of the transformations are fundamentally very different.     

Advanced Photosensitizer Activation Strategies for Smarter Photodynamic Therapy Beacons

Photodynamic therapy (PDT) is a clinical treatment in which a light‐absorbing drug called a photosensitizer (PS) is combined with light and molecular oxygen to generate cytotoxic singlet oxygen. PDT provides additional tissue selectivity compared to conventional chemotherapy as singlet oxygen is generated only in areas in which PS accumulates and that are simultaneously illuminated by a light source with sufficient irradiance and dose. Early PDT beacons built on this concept by adding an analyte‐responsive element that simultaneously turns on PDT and fluorescence, providing both an additional layer of selectivity and real‐time feedback of the PS′s activation state. More recent PDT beacons have expanded this idea, with new methods now available for sensing analytes, generating singlet oxygen, and reporting treatment status. In this Minireview, we consider developments in advanced activation strategies implemented in therapeutic and theranostic beacons.     

Conjugated Polymers: Catalysts for Photocatalytic Hydrogen Evolution

Conjugated polymers, comprising fully π‐conjugated systems, present a new generation of heterogeneous photocatalysts for solar‐energy utilization. They have three key features, namely robustness, nontoxicity, and visible‐light activity, for photocatalytic processes, thus making them appealing candidates for scale‐up. Presented in this Minireview, is a brief summary on the recent development of various promising polymer photocatalysts for hydrogen evolution from aqueous solutions, including linear polymers, planarized polymers, triazine/heptazine polymers, and other related organic conjugated semiconductors, with a particular focus on the rational manipulation in the composition, architectures, and optical and electronic properties that are relevant to photophysical and photochemical properties. Some future trends and prospects for organic conjugated photocatalysts in artificial photosynthesis, by water splitting, are also envisaged.     

Black Phosphorus-Based Semiconductor Heterojunctions for Photocatalytic Water Splitting

Solar-to-hydrogen (H₂) conversion has been regarded as a sustainable and renewable technique to address aggravated environmental pollution and global energy crisis. The most critical aspect in this technology is to develop highly efficient and stable photocatalysts, especially metal-free photocatalysts. Recently, black phosphorus (BP), as a rising star 2D nanomaterial, has captured enormous attention in photocatalytic water splitting owing to its widespread optical absorption, adjustable direct band gap, and superior carrier migration characteristics. However, the rapid charge recombination of pristine BP has seriously limited its practical application as photocatalyst. The construction of BP-based semiconductor heterojunctions has been proven to be an effective strategy for enhancing the separation of photogenerated carriers. This Minireview attempts to summarize the recent progress in BP-based semiconductor heterojunctions for photocatalytic water splitting, including type-I and type-II heterojunctions, Z-Scheme systems, and multicomponent heterojunctions. Finally, a brief summary and perspective on the challenges and future directions in this field are also provided.