α-Diimine-mediated C-H functionalization of arenes for aryl-aryl cross-coupling reactions.

Easily accessible methods for direct C-H arylation of arenes have been explored in the presence of transition metal catalysts to facilitate C-C bond formation; however, the absence of transition-metal impurities is a significant concern in the preparation of active pharmaceutical ingredients (APIs). Herein, we examine the use of bis(imino)acenaphthene (BIAN) as a potential single-electron transfer initiator in transition metal-free C-C bond-forming reactions. Using this approach, arenes are coupled to several aryl and heteroaryl halides. Based upon preliminary mechanistic evidence and crystallographic probation of an active initiator species, we tentatively propose a potassium-stabilized 'metal-free' radical pathway is in operation.

Electrochemically Generated Carbanions Enable Isomerizing Allylation and Allenylation of Aldehydes with Alkenes and Alkynes.

The direct coupling of aldehydes with petrochemical feedstock alkenes and alkynes would represent a practical and streamlined approach for allylation and allenylation chemistry. However, conventional approaches commonly require preactivated substrates or strong bases to generate allylic or propargylic carbanions and only afford branched allylation or propargylation products. Developing a mild and selective approach to access synthetically useful linear allylation and allenylation products is highly desirable, albeit with formidable challenges. We report a strategy using hydrogen evolution reaction (HER) to generate a carbanion from weakly acidic sp3 C-H bonds (pKa ∼ 35-40) under mild reaction conditions, obviating the use of strong bases, Schlenk techniques, and multistep procedures. The cathodically generated carbanion reverses the typical reaction selectivity to afford unconventional isomerizing allylation and allenylation products (125 examples). The generation of carbanions was monitored and identified by in situ ultraviolet-visible (UV-vis) spectroelectrochemistry. Furthermore, we extended this protocol to the generation of other carbanions and their application in coupling reactions between alcohols with carbanions. The appealing features of this approach include mild reaction conditions, excellent functional group tolerance, unconventional chemo- and regioselectivity, and the diverse utility of products, which includes offering direct access to diene luminophores and bioactive scaffolds. We also performed cyclic voltammetry, control experiments, and density functional theory (DFT) calculations to rationalize the observed reaction selectivity and mechanism.

Progress in Convergent Paired Electrolysis.

Convergent paired electrolysis combines both anodic and cathodic reactions simultaneously in an electrochemical transformation. It provides a highly energy-efficient and divergent approach to conventionally challenging and useful structures. However, the physical separation of the two half-electrode reactions makes it extremely difficult to couple the intermediates arising from the two electrodes. In this concept article, four strategies used in convergent paired electrolysis will be discussed from the perspective of the reaction mechanism: a) metal-catalyzed convergent paired electrolysis, b) convergent paired electrolysis enabled by persistent radical effects, c) microfluidic chemistry applied to convergent paired electrolysis, and d) alternating current electrolysis.

Improved Syntheses of 4'-Vinylbenzo-3n-Crown-n Ethers (n = 5-7).

A convenient, high-yielding, and scalable synthetic approach to the construction of 4'-vinylbenzocrown ethers has been developed, which employs a decarboxylation and cyclization strategy. Using this method, a wide-ranging class of vinylbenzocrown ethers can be efficiently obtained. The identity of the crown ethers was further established using single-crystal X-ray diffraction studies. Two of the vinylbenzocrown ethers crystallize with water, affording infinite supramolecular assemblies containing hydrogen-bonded water molecules.

Applications of catalysis in hydroboration of imines, nitriles, and carbodiimides.

The catalytic hydroboration of imines, nitriles, and carbodiimides is a powerful method of preparing amines which are key synthetic intermediates in the synthesis of many value-added products. Imine hydroboration has perennially featured in notable reports while nitrile and carbodiimide hydroboration have gained attention recently. Initial developments in catalytic hydroboration of imines and nitriles employed precious metals and typically required harsh reaction conditions. More recent advances have shifted toward the use of base metal and main group element catalysis and milder reaction conditions. In this survey, we review metal and nonmetal catalyzed hydroboration of these unsaturated organic molecules and group them into three distinct categories: precious metals, base metals, and main group catalysts. The TON and TOF of imine hydroboration catalysts are reported and summarized with a brief overview of recent advances in the field. Mechanistic and kinetic studies of some of these protocols are also presented.

Electrochemical Arylation of Aldehydes, Ketones, and Alcohols: from Cathodic Reduction to Convergent Paired Electrolysis.

Arylation of carbonyls, one of the most common approaches toward alcohols, has received tremendous attention, as alcohols are important feedstocks and building blocks in organic synthesis. Despite great progress, there is still a great gap to develop an ideal arylation method featuring mild conditions, good functional group tolerance, and readily available starting materials. We now show that electrochemical arylation can fill the gap. By taking advantage of synthetic electrochemistry, commercially available aldehydes (ketones) and benzylic alcohols can be readily arylated to provide a general and scalable access to structurally diverse alcohols (97 examples, >10 gram-scale). More importantly, convergent paired electrolysis, the ideal but challenging electrochemical technology, was employed to transform low-value alcohols into more useful alcohols. Detailed mechanism study suggests that two plausible pathways are involved in the redox neutral α-arylation of benzylic alcohols.

Cobalt(II)-Catalyzed Stereoselective Olefin Isomerization: Facile Access to Acyclic Trisubstituted Alkenes.

Stereoselective synthesis of trisubstituted alkenes is a long-standing challenge in organic chemistry, due to the small energy differences between E and Z isomers of trisubstituted alkenes (compared with 1,2-disubstituted alkenes). Transition metal-catalyzed isomerization of 1,1-disubstituted alkenes can serve as an alternative approach to trisubstituted alkenes, but it remains underdeveloped owing to issues relating to reaction efficiency and stereoselectivity. Here we show that a novel cobalt catalyst can overcome these challenges to provide an efficient and stereoselective access to a broad range of trisubstituted alkenes. This protocol is compatible with both mono- and dienes and exhibits a good functional group tolerance and scalability. Moreover, it has proven to be a useful tool to construct organic luminophores and a deuterated trisubstituted alkene. A preliminary study of the mechanism suggests that a cobalt-hydride pathway is involved in the reaction. The high stereoselectivity of the reaction is attributed to both a π-π stacking effect and the steric hindrance between substrate and catalyst.

Iron catalysed selective reduction of esters to alcohols.

The reaction of (dppBIAN)FeCl2 with 3 equivalents of n-BuLi affords a catalytically active anionic Fe complex; the nature of the anionic complex was probed using EPR and IR experiments and is proposed to involve a dearomatized, radical, ligand scaffold. This complex is an active catalyst for the hydrosilylation of esters to afford alcohols; loadings as low as 1 mol% were employed.

Emergence and Applications of Base Metals (Fe, Co, and Ni) in Hydroboration and Hydrosilylation.

Base metal catalysis offers an alternative to reactions, which were once dominated by precious metals in hydrofunctionalization reactions. This review article details the development of some base metals (Fe, Co, and Ni) in the hydroboration and hydrosilylation reactions concomitant with a brief overview of recent advances in the field. Applications of both commercially available metal salts and well-defined metal complexes in catalysis and opportunities to further advance the field is discussed as well.

Conversion of aldimines to secondary amines using iron-catalysed hydrosilylation.

Iron-catalyzed hydrosilylation of imines to amines using a well-defined iron complex is reported. This method employs relatively mild conditions, by reaction of imine, (EtO)3SiH in a 1 : 2 ratio in the presence of 1 mol% precatalyst ([BIAN]Fe(η6-toluene), 3, BIAN = bis(2,6-diisopropylaniline)acenaphthene) at 70 °C. A broad scope of imines was readily converted into the corresponding secondary amines without the need for precatalyst activators.

Iron Catalyzed Hydroboration of Aldehydes and Ketones.

We report an operationally convenient room temperature hydroboration of aldehydes and ketones employing Fe(acac)3 as precatalyst. The hydroboration of aldehydes and ketones proceeded efficiently at room temperature to yield, after work up, 1° and 2° alcohols; chemoselective hydroboration of aldehydes over ketones is attained under these conditions. We propose a σ-bond metathesis mechanism in which an Fe-H intermediate is postulated to be a key reactive species.

Isomerization of Internal Alkynes to Iridium(III) Allene Complexes via C-H Bond Activation: Expanded Substrate Scope, and Progress towards a Catalytic Methodology.

The synthesis of a series of allene complexes (POCOP)Ir(η²-RC=(.)=CR') 1b-4b (POCOP = 2,6-bis(di-tert-butylphosphonito)benzene) via isomerization of internal alkynes is reported. We have demonstrated that the application of this methodology is viable for the isomerization of a wide variety of alkyne substrates. Deuterium labeling experiments support our proposed mechanism. The structures of the allene complexes 1b-4b were determined using spectroscopic data analysis. Additionally, the solid-state molecular structure of complex 2b was determined using single crystal X-ray diffraction studies and it confirmed the assignment of an iridium-bound allene isomerization product. The rates of isomerization were measured using NMR techniques over a range of temperatures to allow determination of thermodynamic parameters. Finally, we report a preliminary step towards developing a catalytic methodology; the allene may be liberated from the metal center by exposure of the complex to an atmosphere of carbon monoxide.

Pyrylium- and Pyridinium-Based Ionic Liquids as Friction Modifiers for Greases.

The use of ionic liquids (ILs) as lubricants or additives has been studied extensively over the past few decades. However, the ILs considered for lubricant applications have been part of a limited structural class of phosphonium- or imidazolium-type compounds. Here, new pyrylium- and pyridinium-based ILs bearing long alkyl chains were prepared and evaluated as friction- and wear-reducing additives in naphthenic greases. The physical properties of the synthetic ILs and additized naphthenic grease were measured. The tribological performance of the greases was measured by using standard benchtop tests. The addition of ILs was detrimental to wear, causing an increase in the amount of material removed by sliding relative to the base greases in most cases. In contrast, the friction performance improved under nearly all conditions tested due to the IL additives. The compatibility of the synthetic ILs with the naphthenic greases and its potential influence upon miscibility and tribological performance are tentatively proposed to be a result of the molecular structure.

Suspect screening-data independent analysis workflow for the identification of arsenolipids in marine standard reference materials.

There has been limited research into arsenolipid toxicological risks and health-related outcomes due to challenges with their separation, identification, and quantification within complex biological matrices (e.g., fish, seaweed). Analytical approaches for arsenolipid identification such as suspect screening have not been well documented and there are no certified standard reference materials, leading to issues with reproducibility and uncertainty regarding the accuracy of results. In this study, a detailed workflow for the identification of arsenolipids utilizing suspect screening coupled with data independent analysis is presented and applied to three commercially available standard reference materials (Hijiki seaweed, dogfish liver, and tuna). Hexane and dichloromethane/methanol extraction, followed by reversed-phase high-performance liquid chromatography-inductively coupled plasma mass spectrometry and liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry. Using the workflow developed, mass fragmentation matching, mass error calculations, and retention time matching were performed to identify suspect arsenolipids. Arseno-fatty acids (AsFAs), arsenohydrocarbons (AsHCs), and arsenosugar phospholipids (AsSugPLs) were identified with high confidence; AsHC332, AsHC360, and AsSugPL720 in seaweed, AsHC332 in tuna, and AsFA474 and AsFA502 in the dogfish liver. AsHC332, AsHC360, and AsFA502 were identified as promising candidates for further work on synthesis, quantification using MS/MS, and toxicity testing.

Synthesis and characterization of terpyridine-supported boron cations: evidence for pentacoordination at boron.

Hypervalent boron centers are proposed to be key intermediates in many stoichiometric and catalytic reactions. However, structurally characterized examples remain rare. We have isolated two new borocations with formal charges of 1+ and 2+. Because the dicationic complex displays evidence of pentacoordination at the boron center, we conclude that the interaction is predominantly electrostatic and is a result of the highly electrophilic dicationic boron atom.

tert-Butyl N-(thio-phen-2-yl)carbamate.

In the title compound, C9H13NO2S, the dihedral angle between the thiophene ring and the carbamate group is 15.79 (14)°. In the crystal structure, intra-molecular C-H⋯O inter-actions in tandem with the tert-butyl groups render the packing of adjacent mol-ecules in the [001] direction nearly perpendicular [the angle between adjacent thio-phene rings is 74.83 (7)°]. An inter-molecular N-H⋯O hydrogen bond gives rise to a chain extending along [001]. The crystal studied was found to be a racemic twin.

Thio-phene-2-carbonyl azide.

The title compound, C5H3N3OS, is almost planar (r.m.s. deviation for the ten non-H atoms = 0.018 Å) and forms an extended layer structure in the (100) plane, held together via hydrogen-bonding inter-actions between adjacent mol-ecules. Of particular note is the occurrence of RC-H⋯N(-)=N(+)=NR inter-actions between an aromatic C-H group and an azide moiety which, in conjunction with a complementary C-H⋯O=C inter-action, forms a nine-membered ring.

Electrochemically Driven Hydrogen Atom Transfer Catalysis: A Tool for C(sp3)/Si-H Functionalization and Hydrofunctionalization of Alkenes.

Electrochemically driven hydrogen atom transfer (HAT) catalysis provides a complementary approach for the transformation of redox-inactive substrates that would be inaccessible to conventional electron transfer (ET) catalysis. Moreover, electrochemically driven HAT catalysis could promote organic transformations with either hydrogen atom abstraction or donation as the key step. It provides a versatile and effective tool for the direct functionalization of C(sp3)-H/Si-H bonds and the hydrofunctionalization of alkenes. Despite these attractive properties, electrochemically driven HAT catalysis has been largely overlooked due to the lack of understanding of both the catalytic mechanism and how catalyst selection should occur. In this Review, we give an overview of the HAT catalysis applications in the direct C(sp3)-H/Si-H functionalization and hydrofunctionalization of alkenes. The mechanistic pathways, physical properties of the HAT mediators, and state-of-the-art examples are described and discussed.

Improved Syntheses of an Arseno-Fatty Acid (As-FA 362) and an Arseno-Hydrocarbon (As-HC 444).

Robust and reliable synthetic methods have been developed for the preparation of an arseno-fatty acid (As-FA362) and an arseno-hydrocarbon (As-HC444). An improved route to access the starting materials necessary for the new synthetic routes is also disclosed. With these improvements, an increased accessibility to arsenic-containing compounds is anticipated, which may be deployed as standards required for the development of quantitative methods in biological matrices. For the first time, stability data for these compounds are reported. With these results in hand, data on the elimination profile, bioaccumulation potential and patho-behavioral and physiological consequences of these organoarsenicals are planned.

Synthesis of p-xylene from ethylene.

As oil supplies dwindle, there is a growing need to develop new routes to chemical intermediates that utilize alternative feedstocks. We report here a synthesis of para-xylene, one of the highest volume chemicals derived from petroleum, using only ethylene as a feedstock. Ethylene is an attractive alternative feedstock, as it can be derived from renewable biomass resources or harnessed from large domestic shale gas deposits. The synthesis relies on the conversion of hexene (from trimerization of ethylene) to 2,4-hexadiene followed by a Diels-Alder reaction with ethylene to form 3,6-dimethylcyclohexene. This monoene is readily dehydrogenated to para-xylene uncontaminated by the ortho and meta isomers. We report here a selective synthesis of para-xylene, uncontaminated by the ortho or meta isomers, using ethylene as the sole feedstock.