This microreview summarizes the use of deep eutectic solvents (DESs) and related melts in organic synthesis. Solvents of this type combine the great advantages of other proposed environmentally benign alternative solvents, such as low toxicity, high availability, low inflammability, high recyclability, low volatility, and low price, avoiding many disadvantages of the more modern media. The fact that many of the components of these mixtures come directly from nature assures their biodegradability and renewability. The classification and distribution of the reactions into different sections in this microreview, as well as the emphasis paid to their scope, easily allow a general reader to understand the actual state of the art and the great opportunities opened, not only for academic purposes but also for industry. 21st Century DESs: Worries about the sustainability of our civilization on Earth are forcing changes on all aspects of industrial production. In organic synthesis, solvents (including their production and degradation) are the main waste component in reactions. Deep eutectic solvents (and related mixtures) offer an irresistible opportunity to improve the sustainability of processes in this century.
Because of its high lipophilicity, the CF3S group has always interested chemists. However, strategies to introduce it into organic molecules have been, for the most part, reserved to specialized “fluorine chemists”. Recent published work has demystified these preconceived ideas by proposing new efficient methods or easy‐to‐handle reagents to enrich the toolbox of chemists. However, all these new concepts arise from the pioneering works of the past! In this review, we will do a “back to the future” by remembering the most significant results of the past and by presenting extensions and novelties of the present and for the future. The CF3S group, owing to its high lipophilicity, has continuously received attention. In the past, trifluoromethylthiolation reactions were performed by using mainly two complementary reagents, that is, CF3SCl and CF3S–M+. Recently, the organic chemist's toolbox has gained new efficient methods based on transition‐metal catalysis and new easy‐to‐handle reagents.
Nickel catalysis for biaryl coupling reactions has received significant attention as a less expensive and less toxic alternative to “standard” palladium catalysis. Here we describe recent developments in nickel‐catalyzed biaryl coupling methodology, along with mechanistic studies and applications. In particular we focus on nickel‐catalyzed coupling reactions in which “unreactive” bonds such as C–H, C–O, and C–C bonds are converted into biaryl moieties. Biaryl coupling through nickel catalysis has been known for a few decades. The topic has recently resurfaced in synthetic chemistry, however, thanks to its use of ideal coupling partners such as simple arenes (Ar–H) and phenol derivatives (Ar–OR). In this microreview, recent achievements in nickel‐catalyzed biaryl coupling are summarized.
Base‐metal catalysis, especially with non‐noble‐metal pincer‐type catalysts, is increasingly used in organic synthesis and thus becoming more and more important for organometallic chemistry. After ruthenium‐, iridium‐ and iron‐based pincer‐type complexes became established as state‐of‐the‐art catalysts for (de)hydrogenation reactions in the past decade, manganese complexes have most recently been successfully applied in related transformations. Specifically, this microreview covers their recent progress in (de)hydrogenation and transfer (de)hydrogenation as well as in C–C and C–X bond‐forming reactions. We focus here on the development and synthesis of manganese‐based pincer‐type catalysts and on recent progress in their application. As well as for hydrogenations, we describe their utilisation for dehydrogenation, hydrosilylation, hydroboration and transfer (de)hydrogenation reactions. Additionally, the usage of manganese‐based pincer complexes for C–C, C–N and C–O bond transformations is highlighted.
Direct difunctionalization of simple alkenes, the incorporation of two functional groups onto a carbon–carbon double bond, is of particular interest to the chemical community owing to its important applications in organic synthesis. Mechanistically, two types of reactions – metal‐catalyzed nucleophilic difunctionalization and radical difunctionalization – dominate this research field. Radical difunctionalization is more appealing from a synthetic perspective than metal‐catalyzed nucleophilic difunctionalization because it allows the conversion of simple alkenes into complex molecules in a rapid and convenient manner. Furthermore, radical difunctionalization allows addition to simple alkenes by various carbon‐centered radicals and even heteroatom‐centered radicals. This review gives an overview of intermolecular and intramolecular radical difunctionalization of simple alkenes, with an emphasis on the reaction patterns and mechanisms, as well as potential applications in synthetic chemistry. Radical difunctionalization of simple alkenes, incorporating two functional groups onto a carbon–carbon double bond, is a fascinating methodology for increasing molecular complexity. This has been a rapidly developing area, especially in the last three years. This microreview collects recent advances and provides synthetic methods, catalytic systems, and reaction mechanisms.
In this review we describe the various new methodologies for synthetic postmodification of the BODIPY core designed and developed by our research groups, as well as their electronic spectroscopic properties. We discuss the different strategies created for functionalization of the BODIPY framework at the pyrrole C‐ring positions and the meso‐position. Halogenated boron dipyrrins are substrates for nucleophilic substitution or Pd‐catalyzed cross‐coupling reactions. α‐Unsubstituted BODIPYs can be functionalized with N and C nucleophiles through oxidative or vicarious nucleophilic substitution (VNS) of the α‐hydrogen atoms. Combining this methodology with reversible Michael addition onto nitrostyrenes provides a route to 3‐styrylated BODIPYs. Furthermore, the one‐step, Pd‐catalyzed C–H arylation of 3,5‐unsubstituted BODIPYs leads to 3‐ and 3,5‐arylated dyes. Finally, radical C–H arylation at the 3,5‐positions of α‐unsubstituted BODIPYs provides an additional synthesis route to arylated dyes. In this microreview, the various synthetic postmodification methodologies for functionalization of the BODIPY framework designed and developed by our research groups are comprehensively discussed, together with the electronic spectroscopic properties of the resulting dyes. With these new synthetic methodologies all the pyrrole C‐ring positions and the meso‐position can readily be substituted.
Transition-metal-catalyzed cross dehydrogenative coupling is a highly efficient tool for functionalization of C(sp(3))-H bonds. In particular, the inexpensive first-row transition metals have been demonstrated as effective catalysts in this process. This microreview summarizes recent progress in two classes of first-row-transition-metal-catalyzed dehydrogenative reactions: intramolecular cyclization for C-C bond formation, and directed site-selective C-H functionalization. These transformations provide concise and practical approaches for preparation of various organic compounds, but so far they are underdeveloped.
Direct methods of carbon‐heteroatom bond formation through functionalization of non‐reactive C–H bonds represent an attractive approach to the synthesis of interesting products. This review focuses on the development of metal‐free coupling methods for unactivated compounds under oxidative reaction conditions. The utility of these methods in syntheses of desired products and the mechanisms of their formation are discussed with numerous examples. The development of new bond formation methods through coupling of simple compounds by direct functionalization of non‐reactive C–H bonds is an important area of modern organic synthesis. The current status in the development of synthetic methodologies for carbon‐heteroatom bond‐forming reactions under metal‐free conditions is highlighted.
1,3‐Dipolar cycloaddition reactions can be considered a powerful synthetic tool in the building of heterocyclic rings, with applications in different fields. In this review we focus on the synthesis of biologically active compounds possessing the 1,2,3‐triazole core through 1,3‐dipolar cycloaddition reactions. The 1,2,3‐triazole skeleton can be present as a single disubstituted ring, as a linker between two molecules, or embedded in a polyheterocycle. The cycloaddition reactions are usually catalysed by copper or ruthenium. Domino reactions can be achieved through dipolarophile anion formation, generally followed by cyclisation. The variety of attainable heterocyclic structures gives an illustration of the importance of the 1,2,3‐triazole core in medicinal chemistry. 1,3‐Dipolar cycloaddition reactions, uncatalysed or catalysed by transition metals, constitute a powerful synthetic tool for 1,2,3‐triazole derivatives, an important class of heterocyclic compounds in medicinal chemistry.
The synthesis of amides is of huge importance in a wide variety of industrial and academic fields and is of particular significance in the synthesis of pharmaceuticals. Many of the well established methods for amide synthesis involve reagents that are difficult to handle and lead to the generation of large quantities of waste products. As a consequence, there has been a considerable amount of interest in the development of new approaches to amide synthesis. Over the past few years a wide range of new reagents and catalysts for direct amidation of carboxylic acids have been reported. In addition, the interconversion of amide derivatives through transamidation is emerging as a potential alternative strategy for accessing certain amides. This microreview covers recent developments in the direct amidation of carboxylic acids and the interconversion of amides through transamidation. The advantages and disadvantages of the various methods are discussed, as well as the possible mechanisms of the reactions. Amide formation is one of the most important processes in synthetic chemistry, particularly for pharmaceutical synthesis. Nevertheless, many existing methods are inefficient and produce large quantities of waste products. Considerable effort has thus been devoted to the development of new approaches; here we review recently reported methods for direct amidation of carboxylic acids and for transamidation.
All‐carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly applicable palladium‐catalyzed asymmetric allylic alkylation reactions of unstabilized non‐biased enolates for the synthesis of enantioenriched α‐quaternary products. This microreview outlines key considerations in the application of palladium‐catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all‐carbon quaternary stereocenters. Pd‐catalyzed asymmetric allylic alkylation reactions are powerful transformations for the direct construction of all‐carbon quaternary stereocenters. A variety of chiral building blocks can be prepared by this approach and these key intermediates have enabled the enantioselective synthesis of complex natural products. Recent advances in reaction methodology and total synthesis are discussed.
In 2008 we reported a new class of macrocyclic hosts that we named “pillararenes”. To date, pillararenes and pillararenes, containing five and six repeating units, respectively, have been synthesized. Pillararenes and pillararenes can accommodate 10 and 12 substituent groups, respectively. The position‐selective versatile functionalization of these substituents enables the preparation of various supramolecular assemblies. Here we discuss the synthesis and selective functionalization of pillararenes. We also discuss the use of the various pillararene derivatives as components of supramolecular assemblies such as sensors, a self‐inclusion complex, supramolecular dimers, polymers, an alternating polymer consisting of pillararene and pillararene units, systems in which pillararene shuttles along an axle, rotaxanes, polyrotaxanes, and pillararene‐based bulk‐materials, as well as colloidal assembly of pillararenes, biomedical applications, and hybridization with inorganic materials. We reported “pillararenes” as new macrocyclic hosts in 2008. Here we first discuss their versatile functionality, which has enabled us to prepare various supramolecular assemblies. We also discuss supramolecular assemblies based on functionalized pillararenes as building blocks.
Manganese is a non‐toxic, inexpensive and earth abundant metal, so is a perfect candidate for catalysis whether as a replacement for precious metals or in the search for novel reactivity. Despite this, manganese catalysis has not undergone the same development of other earth‐abundant metals (particularly iron and cobalt). This review details recent synthetic methodologies using manganese catalysts, including C–H activation, late stage fluorination, hydrosilylation and cross‐coupling. The manganese‐catalysed functionalisation of organic molecules is reviewed with regard to synthetic applications. Manganese‐catalysed C–H oxidations, halogenations, cross‐couplings and C–H activations are discussed with mechanisms details.
The adoption of hydrogen atom transfer (HAT) in a photocatalytic approach, in which an excited catalyst is responsible for substrate activation, offers unique opportunities in organic synthesis, enabling the straightforward activation of R–H (R = C, Si, S) bonds in desired reagents. Either a direct strategy, based on the intrinsic reactivity of a limited number of photocatalysts in the excited state, or an indirect one, in which a photocatalytic cycle is used for the generation of a thermal hydrogen or, can be exploited. This microreview summarizes the most recent advances (mainly from the last two years) in this rapidly developing area of research, collecting the selected examples according to the nature of the species promoting the HAT process. From the synthetic point of view, this area has led to the development of a plethora of strategies for C–C, C–Si, C–N, C–S, and C–halogen (particularly, fluorine) bond formation, as well as for oxidation reactions. Photocatalytic approaches involving the activation of substrates through hydrogen atom transfer (HAT) offer unique opportunities in organic synthesis. This microreview summarizes the most recent advances in this rapidly developing area, collecting the selected examples according to the nature of the species promoting the HAT process.
Cycloaddition reactions involving arynes provide privileged strategies for the convergent synthesis of polycyclic compounds containing aromatic rings. This review focuses on the application of aryne chemistry, in particular [4+2] and palladium‐catalysed [2+2+2] cycloaddition reactions, in the synthesis of large polycyclic aromatic hydrocarbons (PAHs) containing five or more fused benzene rings. Many of the polycyclic compounds included in this report display properties of interest in the field of materials science and some can be considered as nano‐sized graphene substructures or nanographenes. The cycloaddition of arynes is a powerful tool for the convergent synthesis of polycyclic aromatic compounds (PACs). The controlled synthesis of large PACs is an important challenge due to the interest in these molecules as functional materials and in graphene chemistry. This microreview covers the synthesis of a variety of large PACs, which are of interest in the field of materials science.
Dye‐sensitized solar cells (DSSCs) based on nanocrystalline semiconductors have attracted significant attention as lower‐cost alternatives to conventional silicon‐based solar cells. The photosensitizers are vital components for the development of photovoltaic devices of this kind. Over the years, the most successful sensitizers have been RuII polypyridyl complexes, achieving power conversion efficiencies up to 11.5 %. However, due to their limited light‐harvesting capacity and the high cost of Ru‐dyes, efforts have also been directed towards the use of organic dyes. Among the wide range of sensitizers of this kind, phthalocyanines (Pcs) are very attractive because of their light‐harvesting properties in the red and near‐IR spectral region, as well as their thermal and chemical stability. The performance of Pc‐based devices has improved over the years, reaching 5.9 %, thanks to rational design of the phthalocyanine structure. In this microreview we review recent advances in the use of phthalocyanines as photosensitizers for DSSC applications. Phthalocyanine‐based sensitizers have proved to be important candidates in the pursuit of efficient organic dyes for incorporation in dye‐sensitized solar cells, due to their attractive physical and optical properties. Rational design of the macrocycles has brought significant progress in the field, with the efficiencies reaching 6 %. Here we describe the latest advances in Pc‐based DSSCs.
Organic light‐emitting devices (OLEDs) are solid‐state light‐emitting devices based on organic semiconductors. Recent rapid advances in materials chemistry have enabled white OLEDs to be used for general lighting and large‐area flat panel display. White OLED panel efficacy has reached 90 lm W–1, and a tandem white OLED panel has achieved a lifetime of over 100000 h at 1000 cd m–2. LG is set to launch a 55″ OLED TV in 2013, and OLEDs will be expected to make bigger breakthroughs. Although white OLED panels show superior performance, there is still much room (nearly 160 lm W–1) for improvement, in view of the theoretical limit of 248 lm W–1. To reach this objective, OLEDs need to achieve three goals: (1) high internal quantum efficiency, (2) low operation voltage, and (3) high light‐outcoupling efficiency at the same time. For organic chemists creating new organic semiconductors, issues (1) and (2) are particularly important because these relate to materials chemistry. Here we review recent developments in phosphorescent OLED technology, especially from materials chemistry. Organic light‐emitting devices (OLEDs) are solid‐state light‐emitting devices based on organic semiconductors. Recent rapid advances in materials chemistry have enabled the use of white OLEDs for general lighting and large‐area flat panel display. Here we review recent developments in phosphorescent OLED technology.
The activation and cleavage of C–C single bonds mediated by transition metal complexes is one of the most challenging reactions, both practically and in terms of understanding, in the field of metal organic chemistry. In this review the fundamental reactions – oxidative addition, β‐carbon elimination, retro‐allylation, and radical cleavage – so far successfully applied for this transformation are discussed in terms of their mechanisms, their intrinsic problems, and their published examples, which are still fairly rare. Decarbonylation, as another fundamental reaction, is only touched briefly. This group of reactions is today poised to set aside its shadow existence as an exotic reaction class. Meanwhile the number of catalytic and even enantioselective processes involvingC–C single bond cleavage is slowly increasing, although the substrates used in these reactions are still limited to quite special connection patterns. The basic challenges for the future and the paradigms concerning this reaction are presented. Four elemental reactions have to date been applied for the cleavage of C–C single bonds by transition metal complexes: (i) oxidative addition, (ii) β‐carbon elimination, (iii) retro‐allylation, (iv) migratorycarbonyl extrusion. These reactions, their mechanisms, their limitations and their potential are presented in this review along with (still rare) examples.
We provide a brief overview of recent advances in the use of mechanochemical techniques for the synthesis of organic molecules and materials, highlighting selected examples of mechanochemical organic transformations and mechanistic studies, and especially those that illustrate chemical reactions or syntheses of molecular targets that have remained elusive to conventional solution techniques. Mechanochemistry of organic solids is advancing with explosive speed, and we now provide a brief update on the recent developments, including synthetic organic chemistry, formation of self‐assembled structures, and synthesis of organic and pharmaceutical solid materials.
Recent advances in the field of oxidative carbonylation reactions leading to carbonylated heterocyclic derivatives are presented (coverage: 2006 to the beginning of 2012). Recent developments in the application of oxidative carbonylation to the synthesis of carbonylated heterocycles are reviewed (coverage: 2006 to the beginning of 2012).