In‐Cell Dual Drug Synthesis by Cancer‐Targeting Palladium Catalysts

Transition metals have been successfully applied to catalyze non‐natural chemical transformations within living cells, with the highly efficient labeling of subcellular components and the activation of prodrugs. In vivo applications, however, have been scarce, with a need for the specific cellular targeting of the active transition metals. Here, we show the design and application of cancer‐targeting palladium catalysts, with their specific uptake in brain cancer (glioblastoma) cells, while maintaining their catalytic activity. In these cells, for the first time, two different anticancer agents were synthesized simultaneously intracellularly, by two totally different mechanisms (in situ synthesis and decaging), enhancing the therapeutic effect of the drugs. Tumor specificity of the catalysts together with their ability to perform simultaneous multiple bioorthogonal transformations will empower the application of in vivo transition metals for drug activation strategies.     

Recent Developments in Coinage Metal Catalyzed Transformations of Stabilized Vinyldiazo Compounds: Beyond Carbenic Pathways

Transition metal‐catalyzed transformations of vinyldiazo compounds have become a versatile tool in organic synthesis. Although several transition metals have been investigated for this purpose, this field has been mainly dominated by dirhodium catalysts. Remarkable levels of chemo‐, regio‐, diastereo‐ and enantioselectivity have been reached in some of these rhodium‐catalyzed transformations. In the last few years coinage metals have also emerged as useful catalysts in transformations involving vinyldiazo compounds. In some cases, highly efficient catalyst‐dependent protocols arising from divergent mechanistic pathways have been reported. In this Personal Account, we aim to showcase recent advances in metal coinage catalyzed transformations of vinyldiazoacetates, an exciting field of research to which our group has actively contributed in the last few years.     

Electrophilic Activation of Silicon–Hydrogen Bonds in Catalytic Hydrosilations

Hydrosilation reactions represent an important class of chemical transformations and there has been considerable recent interest in expanding the scope of these reactions by developing new catalysts. A major theme to emerge from these investigations is the development of catalysts with electrophilic character that transfer electrophilicity to silicon by Si‐H activation. This type of mechanism has been proposed for catalysts ranging from Group 4 transition metals to Group 15 main group species. Additionally, other electrophilic silicon species, such as silylene complexes and η³‐H₂SiRR′ complexes, have been identified as intermediates in hydrosilation reactions. In this Review, different types of catalysts are compared to highlight the range of hydrosilation mechanisms that feature electrophilic silicon centers. The importance of these catalysts to the development of new hydrosilation reactions is also discussed.     

Chiral N-heterocyclic carbenes as stereodirecting ligands in asymmetric catalysis

In recent years, N-heterocyclic carbenes (NHC) have proved to be a versatile class of spectator ligands in homogeneous catalysis. Being robust anchoring functions for late transition metals, their ligand donor capacity and their molecular shape is readily modified by variation of the substituents at the N-atoms and the structure of the cyclic backbone. After the first attempts to use chiral NHC ligands in asymmetric catalysis in the late 1990's, which initially met with limited success, several novel structural concepts have emerged during the past two years which have led literally to an explosion of the field. With a significant number of highly selective chiral catalysts based on chiral NHCs having been reported very recently, several general trends in the design of new NHC-containing molecular catalysts for stereoselective transformations in organic synthesis emerge.     

Earth-abundant Metal-catalyzed Reductive Amination: Recent Advances and Prospect for Future Catalysis

Nitrogen-containing compounds, as an important class of chemicals, have been used widely in pharmaceuticals, materials synthesis. Transition metal-catalyzed reductive amination of an aldehyde or a ketone with ammonia or an amine has been proved to be an efficient and practical method for the preparation of nitrogen-containing compounds in academia and industry for a century. Given the above, several effective methods using transition metals have been developed in recent years. Noble transition metals like Pd, Pt, and Au-based catalysts have been predominately used in reductive amination. Because of their high prices, strict official regulations of residues in pharmaceuticals, and deleterious effects on the biological system, their industrial applications are severely hampered. With the increasing sustainable and environmental problems, the Earth-abundant transition metals including Ti, Fe, Co, Ni, and Zr have also been investigated for the reductive amination reaction and showed great potential to the advancement of sustainable and cost-effective reductive amination processes. This critical review will mainly summarize the work using Earth-abundant metals. The effects of different transition metals used in catalytic reduction amination were discussed and compared, and some suggestions were given. The last section highlights the catalytic activities of bi- and tri-metallic catalysts. Indeed, this latter family is very promising and simultaneously benefits from increased stability, and selectivity, compared to monometallic NPs, due to synergistic substrate activation. Few comprehensive reviews focusing on Earth-abundant transition metals catalyst has been published since 1948, although several authors reported some summaries dealing with one or the other part of this aspect. It is hoped that this critical review will inspire researchers to develop new efficient and selective earth-abundant metal catalysts for highly, environmentally sustainable reductive amination methods, as well as improve the pharmaceutical industry and related chemical synthesis company traditional method with the utilization of the green method widely.     

Iron-Electrocatalyzed C−H Arylations: Mechanistic Insights into Oxidation-Induced Reductive Elimination for Ferraelectrocatalysis

Despite major advances, organometallic C−H transformations are dominated by precious 5d and 4d transition metals, such as iridium, palladium and rhodium. In contrast, the unique potential of less toxic Earth-abundant 3d metals has been underexplored. While iron is the most naturally abundant transition metal, its use in oxidative, organometallic C−H activation has faced major limitations due to the need for superstoichiometric amounts of corrosive, cost-intensive DCIB as the sacrificial oxidant. To fully address these restrictions, we describe herein the unprecedented merger of electrosynthesis with iron-catalyzed C−H activation through oxidation-induced reductive elimination. Thus, ferra- and manganaelectro-catalyzed C−H arylations were accomplished at mild reaction temperatures with ample scope by the action of sustainable iron catalysts, employing electricity as a benign oxidant.     

Ruthenium Catalysis in Biological Habitats

Recent years have witnessed a considerable progress in research aimed at merging transition metal catalysis with chemical and cell biology. Therefore, a crescent number of metal-catalyzed transformations have been shown compatible with biological media and even with living settings. Of the different transition metals used to build these biocompatible catalysts, ruthenium has demonstrated to be particularly powerful, in part because the resulting complexes exhibit a very good balance between reactivity and biological stability. Indeed, ruthenium complexes have demonstrated utility to promote a great variety of reactions in biologically relevant contexts, from deprotection and redox processes to cycloadditions or photocatalytic transformations. Many of these reactions may enable the development of new type of biological tools and pharmacological strategies.     

Bis‐Boron Compounds in Catalysis: Bidentate and Bifunctional Activation

The development of metal‐free catalysts as an alternative to the use of transition metals has gained tremendous interest in the past. In catalysis, Lewis acidity is one of the major principles used for the activation of organic compounds. Improving the reactivity and selectivity of Lewis acids by utilizing bidentate interactions was already proposed 50 years ago. Nevertheless, product inhibition due to strong binding has made applications of bidentate Lewis acids challenging for many years. Recently, bis‐boron compounds have been found to be very effective and several applications in Diels–Alder reactions, carbon dioxide reduction, and ammonia‐borane dehydrogenation were reported. All three transformations are enabled by the catalyst at different stages during the course of the reaction. These new and useful examples illustrate the great potential of the concept.     

Diesel soot combustion catalysts: review of active phases

The most relevant information about the different active phases that have been studied for the catalytic combustion of soot is reviewed and discussed in this article. Many catalysts have been reported to accelerate soot combustion, including formulations with noble metals, alkaline metals and alkaline earth metals, transition metals that can accomplish redox cycles (V, Mn, Co, Cu, Fe, etc.), and internal transition metals. Platinum catalysts are among those of most interest for practical applications, and an important feature of these catalysts is that sulphur-resistant platinum formulations have been prepared. Some metal oxide-based catalysts also appear to be promising candidates for soot combustion in practical applications, including ceria-based formulations and mixed oxides with perovskite and spinel structures. Some of these metal oxide catalysts produce highly reactive active oxygen species that promote efficient soot combustion. Thermal stability is an important requirement for a soot combustion catalyst, which precludes the practical utilisation of several potential catalysts such as most alkaline metal catalysts, molten salts, and metal chlorides. Some noble metal catalysts are also unstable due to the formation of volatile oxides (ruthenium, iridium, and osmium).     

New trends in sustainable nanocatalysis: Emerging use of earth abundant metals

Noble metals are well-known to afford highly active, selective and durable catalysts, and have thus been at the core of the development of greener processes. In recent years, however, growing concerns about their scarcity, cost and toxicity has triggered research efforts towards the development of earth-abundant catalysts. In this Current Opinion, recent examples of the use in catalysis of pure earth-abundant metals, earth-abundant metals with minute quantities of noble metals, or earth-abundant metals activated by light are presented. This highlight article showcases the current trends in sustainable organic transformations, catalyzed by nanomaterials.     

Ligand-Accelerated Catalysis

The search for new metal-catalyzed asymmetric reactions has provided some fascinating insights into the effects imposed on the metal catalysts by chiral ligands. A practical consequence is the discovery of ligand-accelerated catalysis (LAC). Thus, an existing catalyzed process is improved by the addition of a specific ligand, which leads to a faster, “ligand-accelerated” reaction. Both homogeneous and heterogeneous catalysts are known to exhibit this behavior. The concept is especially valuable in reactions catalyzed by early transition metals, where dynamic ligand exchange processes require an efficient in situ self-selection of a highly reactive catalyst from a variety of thermodynamically dictated assemblies. Results of detailed mechanistic studies will be presented, and the significance of LAC phenomena in transformations catalyzed by early and late transition metals will be discussed.     

Enantioselective C−H Activation with Earth‐Abundant 3d Transition Metals

Molecular syntheses largely rely on time‐ and labour‐intensive prefunctionalization strategies. In contrast, C?H activation represents an increasingly powerful approach that avoids lengthy syntheses of prefunctionalized substrates, with great potential for drug discovery, the pharmaceutical industry, material sciences, and crop protection, among others. The enantioselective functionalization of omnipresent C?H bonds has emerged as a transformative tool for the step‐ and atom‐economical generation of chiral molecular complexity. However, this rapidly growing research area remains dominated by noble transition metals, prominently featuring toxic palladium, iridium and rhodium catalysts. Indeed, despite significant achievements, the use of inexpensive and sustainable 3d metals in asymmetric C?H activations is still clearly in its infancy. Herein, we discuss the remarkable recent progress in enantioselective transformations via organometallic C?H activation by 3d base metals up to April 2019.     

Progress in design and architecture of metal nanoparticles for catalytic applications

Over the past few years, nanometer-sized transition metal particles have been intensively pursued as potentially advanced catalysts because their special properties lie between those of single metal atoms and bulk metal. Achieving the accurate control of particle size and overall particle size distribution is one of the most crucial challenges to provide unique chemical and physical properties. We highlight herein our recent progress in the exploitation of promising nanoparticle (NP)-based catalysts designed by precise architecture that enable efficient and selective chemical transformations and can be completely separated and are recyclable. This perspective article consists of the following two specific topics: (i) multifunctional catalysts based on magnetic NPs and (ii) new routes for the preparation of supported metal NPs catalysts. The synthetic strategies described here are simple and general for practical catalyst design, thus allowing a strong protocol for creating various nanostructured catalysts.     

Aromatic Aminocatalysis

Aromatic aminocatalysis refers to transformations that employ aromatic amines, such as anilines or aminopyridines, as catalysts. Owing to the conjugation of the amine moiety with the aromatic ring, aromatic amines demonstrate distinctive features in aminocatalysis compared with their aliphatic counterparts. For example, aromatic aminocatalysis typically proceeds with slower turnover, but is more active and conformationally rigid as a result of the stabilized aromatic imine or iminium species. In fact, the advent of aromatic aminocatalysis can be traced back to before the renaissance of organocatalysis in the early 2000s. So far, aromatic aminocatalysis has been widely applied in bioconjugation reactions through transamination; in asymmetric organocatalysis through imine/enamine tautomerization; and in cooperative catalysis with transition metals through C?H/C?C activation and functionalization. This Focus Review summarizes the advent of and major advances in the use of aromatic aminocatalysis in bioconjugation reactions and organic synthesis.     

Transition metal catalyzed synthesis of aryl sulfides

The presence of aryl sulfides in biologically active compounds has resulted in the development of new methods to form carbon-sulfur bonds. The synthesis of aryl sulfides via metal catalysis has significantly increased in recent years. Historically, thiolates and sulfides have been thought to plague catalyst activity in the presence of transition metals. Indeed, strong coordination of thiolates and thioethers to transition metals can often hinder catalytic activity; however, various catalysts are able to withstand catalyst deactivation and form aryl carbon-sulfur bonds in high-yielding transformations. This review discusses the metal-catalyzed arylation of thiols and the use of disulfides as metal-thiolate precursors for the formation of C-S bonds.     

Recent Advances Utilized in the Recycling of Homogeneous Catalysis

Homogeneous catalysts often show high activity and selectivity towards the various chemical transformations. Most of the transition metal‐based active catalysts are expensive, rare, and have strict regulations for their use in pharmaceutical products. Hence, there is a requirement to develop suitable technologies for the practical separation and recycling of metal complex catalysts along with the sustainability of the process. This review focuses on the recent techniques used for the catalyst separation, their recovery, and recyclability of the homogeneous form of catalysts based on their economic compatibility and industrial applications. Various homogeneous catalysts have been reviewed on the basis of their support or media, active centres and recyclability aspects of the catalysts. This review gives brief insights into the varied examples of different recycling techniques utilized in the past 6–7 years.     

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.     

A study of deuteron-induced delayed X-rays from some transition elements

High resolution K X-ray spectrometry preceded by activation with deuterons is an unexplored area in the field of activation analysis. This work describes the capabilities of this technique and evaluates its analytical potential for the specific determination of transition metals in small samples. Detection of the delayed X-rays coupled with their rate of decay provided a unique indication of the target component and its concentration. Analytical conditions are demonstrated for the elements of interest and the potential for application to the general routine determination of the transition metals and some of their isotopes, is discussed.     

Effect of catalyst transition metal and ancillary ligand on syndiospecific polymerization of styrene

In the coordination polymerization of styrene, selected transition metal complexes of metals other than group 4 elements and non-metallocenes have been investigated in comparison to a known half-metallocene titanium complex with regard to the catalytic activity as well as to the thermal and molecular properties of the polymers synthesized. Whereas iron catalysts lead to syndiotactic polystyrenes, catalysts with nickel as the transition metal result only in atactic polymers with an enhanced isotactic content.In addition to the influence of the transition metal, the effect of a broad variation of the ancillary ligands of a specific half-sandwich titanocene, octahydrofluorenyl titanium trimethoxide, on polymerization activity and polymer properties has been investigated and discussed in detail.     

Metal-containing ionic liquids and ionic liquid crystals based on imidazolium moiety

Ionic liquids and ionic liquid crystals of imidazolium salts composed of various transition and main group metals have been reviewed. Ionic metal complexes of imidazoles and N-heterocyclic carbenes possess the similar properties were also included. These types of ILs and ILCs have been realized as potential solvents, catalysts, catalyst precursors and reagents for many organic transformations and provide ecofriendly protocols. They have also been found to play key roles in material science. Many of these IL systems are air- and moisture stable and are considered as alternatives for air- and moisture sensitive chloroaluminate-based ILs.