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Radical–radical cyclization cascades, triggered by single-electron transfer to amide-type carbonyls by SmI2–H2O, convert simple achiral barbiturates in one step to hemiaminal- or enamine-containing tricyclic scaffolds containing up to five contiguous stereocenters (including quaternary stereocenters). Furthermore, we describe the surprising beneficial effect of LiBr on the most challenging of the radical–radical cyclization cascades. An alternative fragmentation–radical cyclization sequence of related substrates allows access to bicyclic uracil derivatives. The radical–radical cyclization process constitutes the first example of a radical cascade involving ET reduction of the amide carbonyl. Products of the cascade can be readily manipulated to give highly unusual and medicinally relevant bi- and tricyclic barbiturates.

Without using any additional ligands, RuCl3 efficiently catalyses the reductive N-alkylation of aryl nitro compounds with alcohols using bio-based glycerol as the hydrogen source and without the need for any added solvents. The reaction can be easily manipulated to produce either imines or secondary amines in high yields. RuCl3-catalyzed reductive N-alkylation of nitroarenes with alcohols affords the corresponding imine products in good to excellent yields. Under the same reaction conditions, the one-pot sequential reaction of nitroarenes with alcohols and glycerol also gives amines in higher yields.

Sulfoxides are classical functional groups for directing the stoichiometric metalation and functionalization of C-H bonds. In recent times, sulfoxides have been given a new lease on life owing to the development of modern synthetic methods that have arisen because of their unique reactivity. They have recently been used in catalytic C-H activation proceeding via coordination of an internal sulfoxide to a metal or through the action of an external sulfoxide ligand. Furthermore, sulfoxides are able to capture nucleophiles and electrophiles to give sulfonium salts, which subsequently enable the formation of C-C bonds at the expense of C-H bonds. This Review summarizes a renaissance period in the application of sulfoxides arising from their versatility in directing C-H functionalization.

A novel route to medicinally-relevant dihydrobenzofurans utilises a sulfur-directed C–H ortho-coupling of arenes and unactivated terminal alkenes mediated by iron, and a palladium-catalysed deallylation/heterocyclisation sequence. The iron-mediated coupling affords linear products of alkene chloroarylation in good yield and with complete regioselectivity. The coupling likely proceeds by redox-activation of the arene partner by iron(III) and alkene addition to the resultant radical cation.

Dioxin-like compounds (DLCs) are considered persistent bioaccumulative toxicants with a number of continuing issues in the fields of ecotoxicology and bioassay. In spite of the great need to monitor these compounds, the only analytical technique with sufficient sensitivity and selectivity for determination of DLCs is a combination of high-resolution gas chromatography and high-resolution mass spectrometry. However, these methods require aseptic techniques, long incubation times, and sophisticated technical expertise for getting accurate results. Nowadays, biological techniques such as biomarkers, bioassays, enzyme immunoassays (EIAs), or other methods have been greatly developed as more sensitive, cost-effective and rapid techniques to determine the presence of DLCs in trace levels of environmental and biological samples. The main aim of this study is to review the latest analytical and bioanalytical detection methods (BDMs) for diagnosis and monitoring of DLCs. Likewise, this work characterizes the latest techniques and trends based on their application, advantages and shortcomings for the various BDMs and their differences are also noted.

Research into layered transition metal dichalcogenides (TMDCs), most notably those of molybdenum and tungsten disulfides, has become extensive, involving fields as diverse as optoelectronics, spintronics, energy storage, lubrication, and catalysis. The modification of TMDCs by transition metal doping can improve their performance in such applications and hence extend their potential for technological applications. This review concerns the synthetic strategies that have been used to incorporate transition metals into TMDCs and the applications of the resultant materials and relevant computational studies on the predicted properties of the doped materials.

The title process is mediated by a multifunctional sulfoxide directing group which captures and activates the alkyne coupling partner before delivery to the arene and C—C bond formation.

In the presence of stoichiometric or catalytic amounts of [M{N(SiMe3)2}2] (M=Fe, Co), N-heterocyclic carbenes (NHCs) react with primary phosphines to give a series of carbene phosphinidenes of the type (NHC)·PAr. The formation of (IMe4)·PMes (Mes=mesityl) is also catalysed by the phosphinidene-bridged complex [(IMe4)2Fe-(m-PMes)]2, which provides evidence for metal-catalysed phosphinidene transfer.

A metal-free approach combining sulfoxide-directed metal-free C–H cross-couplings with tuneable electrophile-mediated heterocyclizations and carbocyclative dimerizations, allows expedient access to benzothiophene-based systems that are components of important materials or are proven organic materials in their own right. As benzothiophene-based materials are typically prepared using Pd-catalyzed cross-coupling processes, our approach allows potential issues of metal cost and supply, and metal-contamination of products, to be avoided.

A general synthetic strategy to access novel tricyclic scaffolds inspired by the antibacterial pleuromutilin is developed.

A copper-catalyzed three-component coupling of allenes, bis(pinacolato)diboron, and imines allows regio-, chemo-, and diastereoselective assembly of branched α,β-substituted-γ-boryl homoallylic amines, that is, products bearing versatile amino, alkenyl, and borane functionality. Alternatively, convenient oxidative workup allows access to α-substituted-β-amino ketones. A computational study has been used to probe the stereochemical course of the cross-coupling.

For the first time, the title reaction is used to transform difluorinated silylenol ethers to difluorinated cycloalkenones under mild conditions.

The past decade has witnessed some remarkable advances in our appreciation of the structural and reaction chemistry of the heavier alkaline earth (Ae = Mg, Ca, Sr, Ba) elements. Derived from complexes of these metals in their immutable +2 oxidation state, a broad and widely applicable catalytic chemistry has also emerged, driven by considerations of cost and inherent low toxicity. The considerable adjustments incurred to ionic radius and resultant cation charge density also provide reactivity with significant mechanistic and kinetic variability as group 2 is descended. In an attempt to place these advances in the broader context of contemporary main group element chemistry, this review focusses on the developing state of the art in both multiple bond heterofunctionalisation and cross coupling catalysis. We review specific advances in alkene and alkyne hydroamination and hydrophosphination catalysis and related extensions of this reactivity that allow the synthesis of a wide variety of acyclic and heterocyclic small molecules. The use of heavier alkaline earth hydride derivatives as pre-catalysts and intermediates in multiple bond hydrogenation, hydrosilylation and hydroboration is also described along with the emergence of these and related reagents in a variety of dehydrocoupling processes that allow that facile catalytic construction of Si-C, Si-N and B-N bonds.

Stereo- and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N-heterocyclic carbenes, giving selectively either β-lactones or α-chloro esters.

The synthesis of sterically hindered anilines has been a significant challenge in organic chemistry. Here we report a Cu-catalyzed radical addition with in situ-generated nitroso compounds to prepare sterically hindered amines directly from readily available materials. The transformation is conducted at room temperature, uses abundant copper salts, and is tolerant of a range of functional groups.

Compound (I) is shown to exhibit moderate antitumoric activity and no antimicrobial activity.

This account describes the work of our group in the area of organic photovoltaics in the past six years. The emphasis is on our experiences in the development of the organic materials, their characterization, scale-up and application in devices. We share our insight into the relationship between synthetic methods, molecular properties, bulk material properties and device performance.

1,3-Enynes containing allylic hydrogens cis to the alkyne function as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration.

The regioselective synthesis of fullerene multiadducts is achieved from commercially available reagents in one pot over two steps.

Recent developments in the coordination and organometallic chemistry of beryllium are reviewed. The primary focus is on synthetic as well as theoretical reports relevant to the synthetic chemist since 2008 on molecular Be complexes bound to C, N and P ligands.

An organocatalytic enantioselective synthesis of α-(benzylamino)cyclobutanones has been achieved by employing a tandem condensation/intramolecular rearrangement/proton transfer reaction and starting from racemic α-hydroxycyclobutanone and a selection of benzylamines. This reaction sequence afforded the products in good to high yields with moderate to high enantioselectivities.

The oxidative coupling of alkylboronic acids with oxygen nucleophiles offers a strategy for replacing toxic, electrophilic alkylating reagents but, O-alkylation with boronic acids is rare.

Photoredox catalysis with the use of a stable, reusable silica-bound chromophore was applied to the intramolecular cyclization of a series of 2-benzylidenehydrazinecarbothioamides to give 5-phenyl-1,3,4-thiadiazol-2-amines. The catalyst was readily prepared by carbodiimide-mediated coupling of commercially available amine-functionalized silica beads to a carboxylic acid functionalized ruthenium complex. The immobilized catalyst was readily removed from the reaction product by filtration and was used eight times without loss of catalytic activity. This simple, safe, and practical method is an attractive alternative to conventional procedures.

A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.

A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon–carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The ‘safety-catch’ nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes.

FeCl3-Mediated coupling of alkenes to arenes in ortho-position of arylsulfanyl group give the corresponding β-chloroalkyl derivatives.

Suzuki–Miyaura coupling reactions of arylboronic acids with aryl bromides were mediated by PdCl2 and bdppmapy (N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine) that both stabilizes and solubilizes the catalyst in predominantly ethanol as a solvent. Excellent yields for a wide variety of substrates were obtained under relatively mild conditions in this ‘green’ solvent.

The solution-phase self-assembly or "polymerization" of discrete colloidal building blocks, such as "patchy" nanoparticles and multicompartment micelles, is attracting growing attention with respect to the creation of complex hierarchical materials. This approach represents a versatile method with which to transfer functionality at the molecular level to the nano- and microscale, and is often accompanied by the emergence of new material properties. In this perspective we highlight selected recent examples of the self-assembly of anisotropic nanoparticles which exploit directional interactions introduced through their shape or surface chemistry to afford a variety of hierarchical materials. We focus in particular on the solution self-assembly of block copolymers as a means to prepare multicompartment or "patchy" micelles. Due to their potential for synthetic modification, these constructs represent highly tuneable building blocks for the fabrication of a wide variety of functional assemblies.

A novel and general method for the construction of a variety of disubstituted anilines is reported.

ConspectusReductive electron transfer (ET) to organic compounds is a powerful method for the activation of substrates via the formation of radicals, radical anions, anions, and dianions that can be exploited in bond-cleaving and bond-forming processes. Since its introduction to the synthetic community in 1977 by Kagan, SmI2 has become one of the most important reducing agents available in the laboratory. Despite its widespread application in aldehyde and ketone reduction, it was widely accepted that carboxylic acid derivatives could not be reduced by SmI2; only recently has our work led to this dogma being overturned, and the reduction of carboxylic acid derivatives using SmI2 can now take its place alongside aldehyde/ketone reduction as a powerful activation mode for synthesis. In this Account, we set out our studies of the reduction of carboxylic acid derivatives using SmI2, SmI2–H2O, and SmI2–H2O–NR3 and the exploitation of the unusual radical anions that are now accessible in unprecedented carbon–carb...

The compounds LnMo16O44 (Ln: Y, La—Lu) are synthesized from stoichiometric mixtures of Ln2O3, Mo, and MoO3 (silica tubes, 700 °C, 5 d) and characterized by powder and single crystal XRD, magnetic measurements, and DFT electronic structure calculations.

This microreview details and discusses some selected examples of the accessible syntheses of useful complexes bearing N-heterocyclic carbenes (NHCs). The term "accessible", as used here, is defined as a synthetic route that does not require the isolation of the free NHC. These routes typically rely on either the generation of low equilibrium concentrations of the free NHC, which is then trapped by a metal centre, the deprotonation of the azolium salt by a suitable ligand or the activation of the C–H bond. These approaches can help to overcome a key weakness of NHCs in that they must be handled under stringently inert conditions. Studies of complexes based on metal centres from groups 8–11 are presented and discussed.

Nanoscale magnets with characteristic dimensions in the range of 1–100 nm are important in several areas of nanoscience and technology. First, this length scale spans the typical important dimensions of exchange lengths and domain-wall widths, which means that significant control of magnetic properties can be obtained by varying grain or particle dimensions. Second, the nonequilibrium synthetic processes used for clusters, particles, and films, often lead to new real-space crystal structures with completely novel spin structures and magnetic properties. Third, a basic-science challenge in this class of matter involves the spin-polarized quantum mechanics of many-electron systems containing 10–10 000 atoms. Finally, the materials under study may have important future applications in high-density data storage, ultra-small spintronic devices, or high-energy magnetic materials. In this article, we discuss our recent work on novel Fe-Au nanoclusters, MnAu-Mn coreshell structures, and complex high-anisotropy Co-rich intermetallic compound clusters. We also present new results on Fe-based alloys including the magnetic properties of semiconducting FeSi2 nanoclusters and spin correlations in FeGe nanocluster films. V C 2015 AIP Publishing LLC.

Phosphinoamide-scaffolded heterobimetallic palladium–titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts in situ and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles.

The reaction provides 3-alkyl/aryl-2-(2-nitro-1-alkyl/aryl)cyclo-1-butanones as mixture of the two diastereomers bearing a trans-ring configuration.

In this chapter we describe two SPPS approaches for producing cyclic disulfide-rich peptides in our laboratory, including cyclotides from plants, cyclic conotoxins from cone snail venoms, chlorotoxin from scorpion venom, and the sunflower trypsin inhibitor peptide, SFTI-1.

The pharmaceutical industry continues to look at the use of ‘green’ methods, including those that allow for shorter synthetic sequences. The use of biocatalysis continues to grow, including transformations that are difficult to perform by standard chemical means. Flow reactions are also growing in popularity, as the equipment becomes available at all scales. The use of flow techniques also allows for the use of high temperatures and pressures, as well as the preparation of hazardous intermediates and use of hazardous reagents, as inventories of these dangerous materials can be kept to a minimum. New reagents and reactions continue to be developed to improve important bond-forming reactions and to allow new types of reactivity, which can be exploited to provide shorter and more efficient reaction pathways. 1 Introduction 2 Green Chemistry 2.1 Biocatalytic Methods 2.2 Flow Chemistry 3 Bond-Forming Reactions 3.1 Aryl-Coupling Reactions 3.2 C–H Bond Activation 3.3 Alcohol Substitutions 3.4 Ammonolysis and Amide Bond Formation 4 Reactions In/On Water 5 Reductions 5.1 Amide Reductions 6 Summary

The stereocontrolled introduction of vicinal heteroatomic substituents into organic molecules is one of the most powerful ways of adding value and function. Although many methods exist for the introduction of oxygen- and nitrogen-containing substituents, the number of stereocontrolled methods for the introduction of sulfur-containing substituents pales by comparison. Previous reports from our laboratories have described sulfenofunctionalizations of alkenes that construct carbon-sulfur bonds vicinal to carbon-oxygen, carbon-nitrogen or carbon-carbon bonds with high levels of diastereospecificity and enantioselectivity. This process is enabled by the concept of Lewis-base activation of Lewis acids, which provides activation of Group 16 electrophiles. To provide a foundation for the expansion of substrate scope and improved selectivities, we have undertaken a comprehensive study of the catalytically active species. Insights gleaned from kinetic, crystallographic and computational methods have led to the introduction of a new family of sulfenylating agents that provide significantly enhanced selectivities.

The target compounds are synthesized using diastereoselective olefinic oxidations of enantiopure tetrahydropyridines.

The SmI2-mediated reduction of barbituric acids using ethylene glycol as coordinating co-solvent is followed by a 1,2-migration process to give 6-substituted uracils (II) and (IV).

The highly regioselective copper-catalyzed reaction of aryl allenes with silylborane (II) affords vinyl silane building blocks.

The [2 + 2]-photocycloaddition reactions of maleic anhydride (II) with either allyl alcohol (I) or propargyl alcohol (XII) is elaborated to provide access to 1,2,3-trifunctionalized cyclobutanes with three differentiated one-carbon substituents and complementary stereochemical pattern.

Single crystals of the semiconducting Ba2TeO are prepared from BaO and Te in a molten Ba flux in the molar ratio of 1:1:20 (steel crucible in evacuated quartz tube, 1000 °C, 20 h; cooling to 820 °C within 50 h).