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.     

Bifurcating reactions: distribution of products from energy distribution in a shared reactive mode

Bifurcating reactions yield two different products emerging from one single transition state and are therefore archetypal examples of reactions that cannot be described within the framework of the traditional Eyring''s transition state theory (TST). With the growing number and importance of these reactions in organic and biosynthetic chemistry, there is also an increasing demand for a theoretical tool that would allow for the accurate quantification of reaction outcome at low cost. Here, we introduce such an approach that fulfils these criteria, by evaluating bifurcation selectivity through the energy distribution within the reactive mode of the key transition state. The presented method yields an excellent agreement with experimentally reported product ratios and predicts the correct selectivity for 89% of nearly 50 various cases, covering pericyclic reactions, rearrangements, fragmentations and metal-catalyzed processes as well as a series of trifurcating reactions. With 71% of product ratios determined within the error of less than 20%, we also found that the methodology outperforms three other tested protocols introduced recently in the literature. Given its predictive power, the procedure makes reaction design feasible even in the presence of complex non-TST chemical steps.

Reactive Mode Composition Factor (RMCF) analysis is a powerful tool to forecast the product distribution of bifurcating reactions through analysis of the kinetic energy distribution within the first transition state traversed by the reacting system.     

Highly effective and chemoselective hydrodeoxygenation of aromatic alcohols

Effective hydrodeoxygenation (HDO) of aromatic alcohols is very attractive in both conventional organic synthesis and upgrading of biomass-derived molecules, but the selectivity of this reaction is usually low because of the competitive hydrogenation of the unsaturated aromatic ring and the hydroxyl group. The high activity of noble metal-based catalysts often leads to undesired side reactions (e.g., saturation of the aromatic ring) and excessive hydrogen consumption. Non-noble metal-based catalysts suffer from unsatisfied activity and selectivity and often require harsh reaction conditions. Herein, for the first time, we report chemoselective HDO of various aromatic alcohols with excellent selectivity, using porous carbon–nitrogen hybrid material-supported Co catalysts. The C–OH bonds were selectively cleaved while leaving the aromatic moiety intact, and in most cases the yields of targeted compounds reached above 99% and the catalyst could be readily recycled. Nitrogen doping on the carbon skeleton of the catalyst support (C–N matrix) significantly improved the yield of the targeted product. The presence of large pores and a high surface area also improved the catalyst efficiency. This work opens the way for efficient and selective HDO reactions of aromatic alcohols using non-noble metal catalysts.

Porous carbon–nitrogen hybrid material-supported Co catalysts can effectively promote the chemoselective hydrodeoxygenation reaction of a various of aromatic alcohols in ethanol and hydrogen atmosphere, under relatively mild conditions.     

超临界二氧化碳中过渡金属催化有机反应研究进展

主要综述了近年来超临界二氧化碳作为反应介质过渡金属催化有机反应的最新进展.通过与常规有机溶剂中有机反应的对比,着重介绍了超临界二氧化碳作为反应介质在有机反应中所显示出的优越性,例如调控反应的选择性,提高反应速度和增加催化剂催化效率等.     

Reductive aminations by imine reductases: from milligrams to tons

The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry. Asymmetric reductive amination for the formation of chiral amines, which are required for the synthesis of pharmaceuticals and other bioactive molecules, is often achieved through transition metal catalysis, but biocatalytic methods of chiral amine production have also been a focus of interest owing to their selectivity and sustainability. The discovery of asymmetric reductive amination by imine reductase (IRED) and reductive aminase (RedAm) enzymes has served as the starting point for a new industrial approach to the production of chiral amines, leading from laboratory-scale milligram transformations to ton-scale reactions that are now described in the public domain. In this perspective we trace the development of the IRED-catalyzed reductive amination reaction from its discovery to its industrial application on kg to ton scale. In addition to surveying examples of the synthetic chemistry that has been achieved with the enzymes, the contribution of structure and protein engineering to the understanding of IRED-catalyzed reductive amination is described, and the consequent benefits for activity, selectivity and stability in the design of process suitable catalysts.

IRED-catalyzed reductive aminations have progressed from mg to ton scale, through advances in enzyme discovery, protein engineering and process biocatalysis.     

Mechanistic considerations on catalytic H/D exchange mediated by organometallic transition metal complexes

The purpose of this review is to analyze the different reaction mechanisms of the H/D exchange on organic substrates catalyzed by transition metal complexes in homogeneous phase. The metal-catalyzed H/D exchange is a multifaceted reaction whose mechanism depends strongly on the reaction conditions and on the metal complex used as a catalyst. It is possible to group the different mechanisms into three main families depending on the “role” and behavior of the catalyst: (i) Lewis acid–base catalysis; (ii) CH activation (iii) insertion/β-elimination. For each macro-group, several representative examples are discussed and critically evaluated in order to provide the reader with keys to the understanding of how the different catalytic systems act and how their modification may affect their performance in terms of activity and selectivity. This knowledge is fundamental for designing improved organometallic H/D catalysts for labeling organic products in greener conditions with more cost-effective processes.     

Paired Electrochemical Reactions and the On‐Site Generation of a Chemical Reagent

While the majority of reported paired electrochemical reactions involve carefully matched cathodic and anodic reactions, the precise matching of half reactions in an electrolysis cell is not generally necessary. During a constant current electrolysis almost any oxidation and reduction reaction can be paired, and in the presented work we capitalize on this observation by examining the coupling of anodic oxidation reactions with the production of hydrogen gas for use as a reagent in remote, Pd‐catalyzed hydrogenation and hydrogenolysis reactions. To this end, an alcohol oxidation, an oxidative condensation, intramolecular anodic olefin coupling reactions, an amide oxidation, and a mediated oxidation were all shown to be compatible with the generation and use of hydrogen gas at the cathode. This pairing of an electrolysis reaction with the production of a chemical reagent or substrate has the potential to greatly expand the use of more energy efficient paired electrochemical reactions.     

Phenanthroline-imine ligands for iron-catalyzed alkene hydrosilylation

Iron-catalyzed organic reactions have been attracting increasing research interest but still have serious limitations on activity, selectivity, functional group tolerance, and stability relative to those of precious metal catalysts. Progress in this area will require two key developments: new ligands that can impart new reactivity to iron catalysts and elucidation of the mechanisms of iron catalysis. Herein, we report the development of novel 2-imino-9-aryl-1,10-phenanthrolinyl iron complexes that catalyze both anti-Markovnikov hydrosilylation of terminal alkenes and 1,2-anti-Markovnikov hydrosilylation of various conjugated dienes. Specifically, we achieved the first examples of highly 1,2-anti-Markovnikov hydrosilylation reactions of aryl-substituted 1,3-dienes and 1,1-dialkyl 1,3-dienes with these newly developed iron catalysts. Mechanistic studies suggest that the reactions may involve an Fe(0)–Fe(ii) catalytic cycle and that the extremely crowded environment around the iron center hinders chelating coordination between the diene and the iron atom, thus driving migration of the hydride from the silane to the less-hindered, terminal end of the conjugated diene and ultimately leading to the observed 1,2-anti-Markovnikov selectivity. Our findings, which have expanded the types of iron catalysts available for hydrosilylation reactions and deepened our understanding of the mechanism of iron catalysis, may inspire the development of new iron catalysts and iron-catalyzed reactions.

Newly developed iron complexes bearing 2-imino-9-aryl-1,10-phenanthroline ligands were successfully used to catalyze hydrosilylation of terminal alkenes and conjugated dienes in high yields with excellent anti-Markovnikov selectivity.     

Iron-catalysed hydroalumination of internal alkynes

Although research on iron-catalysed reactions has recently achieved significant progress, the activity and selectivity of iron catalysts are generally inferior to those of noble-metal catalysts. The development of new iron-catalysed reactions, especially those in which iron catalysts exhibit superior activity or selectivity to other catalysts, is the key to promote iron catalysis. Herein, we report the first protocol for iron-catalysed hydroalumination of internal alkynes. Specifically, in the presence of iron catalysts bearing 2,9-diaryl-1,10-phenanthroline ligands, internal alkynes were stereo- and regioselectively hydroaluminated with the commercially available reagent diisobutylaluminum hydride. Compared with other metal-catalysed alkyne hydroalumination reactions reported in the literature, the iron-catalysed protocol has the following advantages: unusual amino-group-directed regioselectivity, a wide substrate scope, good functional group tolerance, high selectivity, and mild reaction conditions. The alkenylaluminum products prepared in this way could undergo a diverse array of transformations, and were used for the synthesis of bioactive compounds. The current study expands the scope of iron catalysis, provides a new efficient access to alkenylaluminum, discloses the origin of the superiority of iron catalysts, and thus may inspire further studies in related fields.

An iron-catalysed hydroalumination of internal alkynes featuring with unusual amino-group-directed regioselectivity, a wide substrate scope, good functional group tolerance, high selectivity, and mild reaction conditions was realized.     

Paired electrolysis enabled annulation for the quinolyl-modification of bioactive molecules

A paired electrolysis enabled cascade annulation that enables the efficient synthesis of highly functionalized quinoline-substituted bioactive molecules from readily available starting materials is reported. Using this methodology, two goals, namely, the direct synthesis of quinolines and the introduction of quinoline moieties to bioactive molecules, can be simultaneously achieved in one simple operation. The use of electroreduction for the activation of isatin, together with the further anodic oxidation of KI to catalytically result in a cascade annulation, highlight the unique possibilities associated with electrochemical activation methods. This transformation can tolerate a wide range of functional groups and can also be used as a functionalization tactic in pharmaceutical research as well as other areas.

A paired electrolysis enabled cascade annulation that enables the efficient synthesis of highly functionalized quinoline-substituted bioactive molecules from readily available starting materials is reported.     

Paired Electrolysis of Aldoses in a Divided Flow Cell

Simultaneous anodic oxidation and cathodic reduction of aldoses in a divided flow cell were studied. The stream of the anolyte was an aqueous solution containing D-glucose, sodium bromide, and sodium bicarbonate. The stream of the catholyte was also an aqueous solution containing xylose and sodium sulfite. The factors which affected both the anodic and cathodic reactions were studied. The results indicate that the flow rates and temperatures of the anolyte and the catholyte, concentrations of the aldoses, pH values and the material of electrodes significantly affect both anodic and cathodic yields. The selectivities of gluconic acid in the anode and xylitol in the cathode were very high. The power consumption of paired electrolysis in the flow system was less than paired electrolysis in a batch system.     

Advancing homogeneous catalysis for parahydrogen-derived hyperpolarisation and its NMR applications

Parahydrogen-induced polarisation (PHIP) is a nuclear spin hyperpolarisation technique employed to enhance NMR signals for a wide range of molecules. This is achieved by exploiting the chemical reactions of parahydrogen (para-H₂), the spin-0 isomer of H₂. These reactions break the molecular symmetry of para-H₂ in a way that can produce dramatically enhanced NMR signals for reaction products, and are usually catalysed by a transition metal complex. In this review, we discuss recent advances in novel homogeneous catalysts that can produce hyperpolarised products upon reaction with para-H₂. We also discuss hyperpolarisation attained in reversible reactions (termed signal amplification by reversible exchange, SABRE) and focus on catalyst developments in recent years that have allowed hyperpolarisation of a wider range of target molecules. In particular, recent examples of novel ruthenium catalysts for trans and geminal hydrogenation, metal-free catalysts, iridium sulfoxide-containing SABRE systems, and cobalt complexes for PHIP and SABRE are reviewed. Advances in this catalysis have expanded the types of molecules amenable to hyperpolarisation using PHIP and SABRE, and their applications in NMR reaction monitoring, mechanistic elucidation, biomedical imaging, and many other areas, are increasing.

We detail recent advances in homogeneous catalysts for deriving enhanced NMR signals using parahydrogen. Growing applications of this catalysis in mechanistic elucidations, mixture analysis, and biomedical imaging are also discussed.     

铜催化碳杂偶联反应的新进展

某些过渡金属可催化亲电性不饱和碳与含活泼氢的氮、氧、硫、碳原子直接成键,这种交叉偶联反应是现代有机合成中重要的手段之一.与钯、镍等过渡金属相比,铜是一种廉价且毒性低的金属,用铜来催化这些交叉偶联反应不仅可以节省贵金属的消耗,降低成本,而且可以减少对环境的污染,促进绿色化学的发展.对铜催化碳杂键偶联反应的最新研究进展做了综述。     

Direct Arylation of α‐Amino C(sp3)‐H Bonds by Convergent Paired Electrolysis

A metal‐free convergent paired electrolysis strategy to synthesize benzylic amines through direct arylation of tertiary amines and benzonitrile derivatives at room temperature has been developed. This TEMPO‐mediated electrocatalytic reaction makes full use of both anodic oxidation and cathodic reduction without metals or stoichiometric oxidants, thus showing great potential and advantages for practical synthesis. This convergent paired electrolysis method provides a straightforward and powerful means to activate C?H bonds and realize cross‐coupling with cathodically generated species.     

The (not so) simple prediction of enantioselectivity – a pipeline for high-fidelity computations

The computation of reaction selectivity represents an appealing complementary route to experimental studies and a powerful means to refine catalyst design strategies. Accurately establishing the selectivity of reactions facilitated by molecular catalysts, however, remains a challenging task for computational chemistry. The small free energy differences that lead to large variations in the enantiomeric ratio (er) represent particularly tricky quantities to predict with sufficient accuracy to be helpful for prioritizing experiments. Further complicating this problem is the fact that standard approaches typically consider only one or a handful of conformers identified through human intuition as pars pro toto of the conformational space. Obviously, this assumption can potentially lead to dramatic failures should key energetic low-lying structures be missed. Here, we introduce a multi-level computational pipeline leveraging the graph-based Molassembler library to construct an ensemble of molecular catalysts. The manipulation and interpretation of molecules as graphs provides a powerful and direct route to tailored functionalization and conformer generation that facilitates high-throughput mechanistic investigations of chemical reactions. The capabilities of this approach are validated by examining a Rh(iii) catalyzed asymmetric C–H activation reaction and assessing the limitations associated with the underlying ligand design model. Specifically, the presence of remarkably flexible chiral Cp ligands, which induce the experimentally observed high level of selectivity, present a rich configurational landscape where multiple unexpected conformations contribute to the reported enantiomeric ratios (er). Using Molassembler, we show that considering about 20 transition state conformations per catalysts, which are generated with little human intervention and are not tied to “back-of-the-envelope” models, accurately reproduces experimental er values with limited computational expense.

The computation of reaction selectivity represents an appealing complementary route to experimental studies and a powerful mean to refine catalyst design strategies.     

Self-supported ultrathin Co3O4 nanoarray enabling efficient paired electrolysis of 5-hydroxymethylfurfural for simultaneous dihydroxymethylfuran (DHMF) and furandicarboxylic acid (FDCA) production

Production of value-added chemicals and fuels from biomass via electrochemical methods has been of emerging interest in light of the increasing environmental, economic, and political challenges. Paired electrolysis, with anodic oxidation and cathodic reduction reactions pairing in a single electrochemical cell, offers an effective way to produce desired products in both electrodes, thus achieving complete electron economy. In this work, an efficient 5-hydroxymethylfurfural (HMF) paired electrolysis system is developed over a self-supported ultrathin Co₃O₄ nanoarray electrocatalyst for simultaneous production of value-added 2,5-dihydroxymethylfuran (DHMF) and 2,5-furandicarboxylic acid (FDCA). The as-designed paired electrolysis cell achieves a high HMF conversion and DHMF/FDCA selectivity at both anode and cathode without external hydrogen and oxygen input. A near-quantitative yield (95.7%) of FDCA and 78.8% yield of DHMF can be achieved in the paired electrolysis system, with a total Faradaic efficiency of 127%. This work will open up new opportunities in designing efficient electrochemical devices to simultaneously produce building-block chemicals from biomass-derived molecules in both anode and cathode.     

Electrochemical impedance spectroscopy in interfacial studies

A fundamental aim in the field of electrochemistry is to investigate electron transfer events caused by electrode processes, which are more commonly described as redox reactions. In this short review, an overview of the use of electrochemical redox reactions in the realm of organic synthesis is given. These reactions can be divided into three subcategories: cathodic reduction, anodic oxidation, and a paired approach. This short review illustrates the basic schemes of these reactions and introduces representative examples that have been reported in the past 2 years, with a particular emphasis on the development of novel reactions.     

Selective catalytic monoreduction of dichlorooligosilanes with Grignard reagents

Transition metal-catalyzed monoreduction of dichlorooligosilanes with Grignard reagents is reported. Among the examined catalysts, group 4 metal chlorides such as TiCl₄ and Cp₂TiCl₂ gave the highest reactivity and good selectivity. The reducing power is effectively controlled by changing the catalysts and Grignard reagents to achieve sufficient selectivity depending on the oligosilane substrates.     

Electrolysis of water in the diffusion layer: first-principles molecular dynamics simulation

With Car-Parrinello molecular dynamics simulations the elementary reaction steps of the electrolysis of bulk water are investigated. To simulate the reactions occurring near the anode and near the cathode, electrons are removed or added, respectively. The study focuses on the reactions in pure water. Effects depending on a particular electrode surface or a particular electrolyte are ignored. Under anodic conditions, the reaction continues till molecular oxygen is formed, under cathodic conditions the formation of molecular hydrogen is observed. In addition the formation of hydrogen peroxide is observed as an intermediate of the anodic reaction. The simulations demonstrate that the electrochemistry of oxygen formation without direct electrode contact can be explained by radical reactions in a solvent. These reactions may involve the intermediate formation of ions. The hydrogen formation is governed by rapid proton transfers between water molecules.     

Dual electrochemical and chemical control in atom transfer radical polymerization with copper electrodes

In Atom Transfer Radical Polymerization (ATRP), Cu⁰ acts as a supplemental activator and reducing agent (SARA ATRP) by activating alkyl halides and (re)generating the Cu^I activator through a comproportionation reaction, respectively. Cu⁰ is also an unexplored, exciting metal that can act as a cathode in electrochemically mediated ATRP (eATRP). Contrary to conventional inert electrodes, a Cu cathode can trigger a dual catalyst regeneration, simultaneously driven by electrochemistry and comproportionation, if a free ligand is present in solution. The dual regeneration explored herein allowed for introducing the concept of pulsed galvanostatic electrolysis (PGE) in eATRP. During a PGE, the process alternates between a period of constant current electrolysis and a period with no applied current in which polymerization continues via SARA ATRP. The introduction of no electrolysis periods without compromising the overall polymerization rate and control is very attractive, if large current densities are needed. Moreover, it permits a drastic charge saving, which is of unique value for a future scale-up, as electrochemistry coupled to SARA ATRP saves energy, and shortens the equipment usage.

The use of a Cu cathode in eATRP allows exploiting the synergistic effect between electrochemical and chemical stimuli to halt or accelerate polymerizations, reduce energy consumption and achieve control in challenging systems.