Surface premelting of ice far below the triple point.

Premelting of ice, a quasi-liquid layer (QLL) at the surface below the melting temperature, was first postulated by Michael Faraday 160 y ago. Since then, it has been extensively studied theoretically and experimentally through many techniques. Existing work has been performed predominantly on hexagonal ice, at conditions close to the triple point. Whether the same phenomenon can persist at much lower pressure and temperature, where stacking disordered ice sublimates directly into water vapor, remains unclear. Herein, we report direct observations of surface premelting on ice nanocrystals below the sublimation temperature using transmission electron microscopy (TEM). Similar to what has been reported on hexagonal ice, a QLL is found at the solid-vapor interface. It preferentially decorates certain facets, and its thickness increases as the phase transition temperature is approached. In situ TEM reveals strong diffusion of the QLL, while electron energy loss spectroscopy confirms its amorphous nature. More significantly, the premelting observed in this work is thought to be related to the metastable low-density ultraviscous water, instead of ambient liquid water as in the case of hexagonal ice. This opens a route to understand premelting and grassy liquid state, far away from the normal water triple point.

Multiscale Anion-Hybrid in Atomic Ni Sites for High-Rate Water Electrolysis: Insights into the Charge Accumulation Mechanism.

Single-atom catalysts, characterized by transition metal-(N/O)4 units on nanocarbon (M-(N/O)4-C), have emerged as efficient performers in water electrolysis. However, there are few guiding principles for accurately controlling the ligand fields of single atoms to further stimulate the catalyst activities. Herein, using the Ni-(N/O)4-C unit as a model, we develop a further modification of the P anion on the outer shells to modulate the morphology of the ligand. The catalyst thus prepared possesses high activity and excellent long-term durability, surpassing commercial Pt/C, RuO2, and currently reported single-atom catalysts. Notably, mechanistic studies demonstrated that the pseudocapacitive feature of multiscale anion-hybrid nanocarbon is considerable at accumulating enough positive charge [Q], contributing to the high oxygen evolution reaction (OER) order (ß) through the rate formula. DFT calculations also indicate that the catalytic activity is decided by the suitable barrier energy of the intermediates due to charge accumulation. This work reveals the activity origin of single atoms on multihybrid nanocarbon, providing a clear experiential formula for designing the electronic configuration of single-atom catalysts to boost electrocatalytic performance.

Unraveling the Structure and Reactivity Patterns of the Indole Radical Cation in Regioselective Electrochemical Oxidative Annulations.

Oxidation-induced strategy for inert chemical bond activation through highly active radical cation intermediate has exhibited unique reactivity. Understanding the structure and reactivity patterns of radical cation intermediates is crucial in the mechanistic study and will be beneficial for developing new reactions. In this work, the structure and properties of indole radical cations have been revealed using time-resolved transient absorption spectroscopy, in situ electrochemical UV-vis, and in situ electrochemical electron paramagnetic resonance (EPR) technique. Density functional theory (DFT) calculations were used to explain and predict the regioselectivity of several electrochemical oxidative indole annulations. Based on the understanding of the inherent properties of several indole radical cations, two different regioselective annulations of indoles have been successfully developed under electrochemical oxidation conditions. Varieties of furo[2,3-b]indolines and furo[3,2-b]indolines were synthesized in good yields with high regioselectivities. Our mechanistic insights into indole radical cations will promote the further development of oxidation-induced indole functionalizations.

Comprehensive Comparisons between Directing and Alternating Current Electrolysis in Organic Synthesis.

Organic electrosynthesis has consistently aroused significant interest within both academic and industrial spheres. Despite the considerable progress achieved in this field, the majority of electrochemical transformations have been conducted through the utilization of direct-current (DC) electricity. In contrast, the application of alternating current (AC), characterized by its polarity-alternating nature, remains in its infancy within the sphere of organic synthesis, primarily due to the absence of a comprehensive theoretical framework. This minireview offers an overview of recent advancements in AC-driven organic transformations and seeks to elucidate the differences between DC and AC electrolytic methodologies by probing into their underlying physical principles. These differences encompass the ability of AC to preclude the deposition of metal catalysts, the precision in modulating oxidation and reduction intensities, and the mitigation of mass transfer processes.

Electroreduction Enables Regioselective 1,2-Diarylation of Alkenes with Two Electrophiles.

Precisely introducing two similar functional groups into bulk chemical alkenes represents a formidable route to complex molecules. Especially, the selective activation of two electrophiles is in crucial demand, yet challenging for cross-electrophile-coupling. Herein, we demonstrate a redox-mediated electrolysis, in which aryl nitriles are both aryl radical precursors and redox-mediators, enables an intermolecular alkene 1,2-diarylation with a remarkable regioselectivity, thereby avoiding the involvement of transition-metal catalysts. This transformation utilizes cyanoarene radical anions for activating various aryl halides (including iodides, bromides, and even chlorides) and affords 1,2-diarylation adducts in up to 83 % yield and >20 : 1 regioselectivity with more than 80 examples, providing a feasible approach to complex bibenzyl derivatives.

Electrophotochemical Ce-Catalyzed Ring-Opening Functionalization of Cycloalkanols under Redox-Neutral Conditions: Scope and Mechanism.

Selective cleavage and functionalization of C-C bonds in alcohols is gaining increasing interest in organic synthesis and biomass conversion. In particular, the development of redox-neutral catalytic methods with cheap catalysts and clean energy is of utmost interest. In this work, we report a versatile redox-neutral method for the ring-opening functionalization of cycloalkanols by electrophotochemical (EPC) cerium (Ce) catalysis. The EPC-Ce-enabled catalysis allows for cycloalkanols with different ring sizes to be cleaved while tolerating a broad range of functional groups. Notably, in the presence of chloride as a counteranion and electrolyte, this protocol selectively leads to the formation of C-CN, C-C, C-S, or C-oxime bonds instead of a C-halide bond after ß-scission. A preliminary mechanistic investigation indicates that the redox-active Ce catalyst can be tuned by electro-oxidation and photo-reduction, thus avoiding the use of an external oxidant. Spectroscopic characterizations (cyclic voltammetry, UV-vis, electron paramagnetic resonance, and X-ray absorption fine structure) suggest a Ce(III)/Ce(IV) catalytic pathway for this transformation, in which a Ce(IV)-alkoxide is involved.

In Situ Synthesis of CuN4 /Mesoporous N-Doped Carbon for Selective Oxidative Crosscoupling of Terminal Alkynes under Mild Conditions.

The 1,3-conjugated diynes are an important class of chemical intermediates, and the selective crosscoupling of terminal alkynes is an efficient chemical process for manufacturing asymmetrical 1,3-conjugated diynes. However, it often occurs in homogenous conditions and costs a lot for reaction treatment. Herein, a copper catalyzed strategy is used to synthesize highly ordered mesoporous nitrogen-doped carbon material (OMNC), and the copper species is in situ transformed into the copper single-atom site with four nitrogen coordination (CuN4 ). These features make the CuN4 /OMNC catalyst efficient for selective oxidative crosscoupling of terminal alkynes, and a wide range of asymmetrical and symmetrical 1,3-diynes (26 examples) under mild conditions (40 °C) and low substrates ratio (1.3). Density functional theory (DFT) calculations reveal that the aryl-alkyl crosscoupling has the lowest energy barrier on the CuN4 site, which can explain the high selectivity. In addition, the catalyst can be separated and reused by simply centrifugation or filtration. This work can open a facile avenue for constructing single-atom loaded mesoporous materials to bridge homogeneous and heterogeneous catalysis.

Recent advances in electrochemical oxidative cross-coupling with hydrogen evolution involving radicals.

Oxidative cross-coupling has developed into a robust method for carbon-carbon (C-C), carbon-heteroatom (C-X), and heteroatom-heteroatom (X-Y) bond formation. Despite considerable advances in this field, the traditional oxidative cross-coupling reactions usually employ stoichiometric amounts of chemical oxidants to clean up surplus electrons from substrates to form new chemical bonds. Organic electrosynthesis is recognized as an environmentally benign and particularly powerful synthetic platform. Recent advancements have revealed that radical-involved electrochemical oxidative cross-coupling reactions can be achieved under exogenous-oxidant-free conditions. This tutorial review provides an overview of the most recent developments in electrochemical oxidative cross-coupling with hydrogen evolution involving radicals. Emphasis is mainly placed on synthetic and mechanistic aspects. We hope that this tutorial review can promote the development of radical chemistry, electrochemistry, and oxidative cross-coupling reactions.

Synthesis of Cyclopentene Derivatives via Electrochemically Induced Intermolecular Selective (3+2) Annulation.

Cyclopentenes are common cores in many natural products, and in bioactive and functional molecules. However, their synthesis remains challenging in terms of harsh conditions, poor selectivity, prefunctionalization of the substrates, over-reliance on volatile activating reagents and the use of noble metals. Herein, we develop an electrochemical mediator-induced intermolecular selective (3+2) annulation of readily available alkenes and alkynes/alkenes, which provides a simple and efficient method for the synthesis of a library of decorated cyclopentenes and cyclopentanes. This protocol features high efficiency, mild reaction conditions, broad substrate scope, good functional group tolerance, and high regioselectivity. Potential applications are demonstrated by gram-scale synthesis as well as the construction of structural diversity and complexity. A preliminary mechanistic investigation was performed, which indicated that an iodine radical and carbon radicals are involved in this transformation.

Alternating Current Electrolysis Enabled Formal C-O/O-H Cross-Metathesis of 4-Alkoxy Anilines with Alcohols.

While multiple bond metathesis reactions, for example olefin metathesis, have seen considerable recent progress, direct metathesis of traditionally inert C-O single bonds is extremely rare and particularly challenging. Undoubtedly, metathesis reaction of C-O bonds is one of the most ideal routes for the value-added upgrading of molecules involving C-O bonds. Reported here is a new protocol to achieve the formal C-O/O-H cross-metathesis via alternating current electrolysis. Featuring mild reaction conditions, the protocol allows readily available 4-alkoxy anilines and alcohols to be converted into a wide range of valuable products in highly regioselective and chemoselective manner. Moreover, the present strategy can be used in the late-stage modification of pharmaceuticals as well as biologically active compounds, which demonstrated the potential application.

Time-Resolved EPR Revealed the Formation, Structure, and Reactivity of N-Centered Radicals in an Electrochemical C(sp3)-H Arylation Reaction.

Electrochemical synthesis has been rapidly developed over the past few years, while a vast majority of the reactions proceed through a radical pathway. Understanding the properties of radical intermediates is crucial in the mechanistic study of electrochemical transformations and will be beneficial for developing new reactions. Nevertheless, it is rather difficult to determine the "live" radical intermediates due to their high reactivity. In this work, the formation and structure of sulfonamide N-centered radicals have been researched directly by using the time-resolved electron paramagnetic resonance (EPR) technique under electrochemical conditions. Supported by the EPR results, the reactivity of N-centered radicals as a mediator in the hydrogen atom transfer (HAT) approach has been discussed. Subsequently, these mechanistic study results have been successfully utilized in the discovery of an unactivated C(sp3)-H arylation reaction. The kinetic experiments have revealed the rate-determined step is the anodic oxidation of sulfonamides.

Electrochemical Palladium-Catalyzed Oxidative Sonogashira Carbonylation of Arylhydrazines and Alkynes to Ynones.

Oxidative carbonylation using carbon monoxide has evolved as an attractive tool to valuable carbonyl-containing compounds, while mixing CO with a stoichiometric amount of a chemical oxidant especially oxygen is hazardous and limits its application in scale-up synthesis. By employing anodic oxidation, we developed an electrochemical palladium-catalyzed oxidative carbonylation of arylhydrazines with alkynes, which is regarded as an alternative supplement of the carbonylative Sonogashira reaction. Combining an undivided cell with constant current mode, oxygen-free conditions avoids the explosion hazard of CO. A diversity of ynones are efficiently obtained using accessible arylhydrazines and alkynes under copper-free conditions. A possible mechanism of the electrochemical Pd(0)/Pd(II) cycle is rationalized based upon cyclic voltammetry, kinetic studies, and intermediates experiments.

Electrochemical Oxidation Enables Regioselective and Scalable α-C(sp3)-H Acyloxylation of Sulfides.

A highly selective, environmentally friendly, and scalable electrochemical protocol for the construction of α-acyloxy sulfides, through the synergistic effect of self-assembly-induced C(sp3)-H/O-H cross-coupling, is reported. It features exceptionally broad substrate scope, high regioselectivity, gram-scale synthesis, construction of complex molecules, and applicability to a variety of nucleophiles. Moreover, the soft X-ray absorption technique and a series of control experiments have been utilized to demonstrate the pivotal role of the self-assembly of the substrates, which indeed is responsible for the excellent compatibility and precise control of high regioselectivity in our electrochemical protocol.

Recent Advances in Oxidative R1-H/R2-H Cross-Coupling with Hydrogen Evolution via Photo-/Electrochemistry.

Photo-/electrochemical catalyzed oxidative R1-H/R2-H cross-coupling with hydrogen evolution has become an increasingly important issue for molecular synthesis. The dream of construction of C-C/C-X bonds from readily available C-H/X-H with release of H2 can be facilely achieved without external chemical oxidants, providing a greener model for chemical bond formation. Given the great influence of these reactions in organic chemistry, we give a summary of the state of the art in oxidative R1-H/R2-H cross-coupling with hydrogen evolution via photo/electrochemistry, and we hope this review will stimulate the development of a greener synthetic strategy in the near future.

Electrochemical Oxidative Carbon-Atom Difunctionalization: Towards Multisubstituted Imino Sulfide Ethers.

Ethers (C-O/S) are ubiquitously found in a wide array of functional molecules and natural products. Nonetheless, the synthesis of imino sulfide ethers, containing an N(sp2 )=C(sp2 )-O/S fragment, still remains a challenge because of its sensitivity to acid. Developed here in is an unprecedented electrochemical oxidative carbon-atom difunctionalization of isocyanides, providing a series of novel multisubstituted imino sulfide ethers. Under metal-free and external oxidant-free conditions, isocyanides react smoothly with simple and readily available mercaptans and alcohols. Importantly, the procedure exhibited high stereoselectivities, excellent functional-group tolerance, and good efficiency on large-scale synthesis, as well as further derivatization of the products.

Manganese-Catalyzed Oxidative Azidation of C(sp3)-H Bonds under Electrophotocatalytic Conditions.

The selective installation of azide groups into C(sp3)-H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C(sp3)-H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine(III) reagent or NFSI. A series of tertiary and secondary benzylic C(sp3)-H, aliphatic C(sp3)-H, and drug-molecule-based C(sp3)-H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C(sp3)-H bond and selectivity of the tertiary aliphatic C(sp3)-H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.

Electrochemical Oxidative Cross-Coupling with Hydrogen Evolution Reactions.

Oxidative cross-coupling has proved to be one of the most straightforward strategies for forming carbon-carbon and carbon-heteroatom bonds from easily available precursors. Over the past two decades, tremendous efforts have been devoted in this field and significant advances have been achieved. However, in order to remove the surplus electrons from substrates for chemical bonds formation, stoichiometric oxidants are usually needed. Along with the development of modern sustainable chemistry, considerable efforts have been devoted to perform the oxidative cross-coupling reactions under external-oxidant-free conditions. Electrochemical synthesis is a powerful and environmentally benign approach, which can not only achieve the oxidative cross-couplings under external-oxidant-free conditions, but also release valuable hydrogen gas during the chemical bond formation. Recently, the electrochemical oxidative cross-coupling with hydrogen evolution reactions has been significantly explored. This Account presents our recent efforts toward the development of electrochemical oxidative cross-coupling with hydrogen evolution reactions. (1) We explored the oxidative cross-coupling of thiols/thiophenols with arenes, heteroarenes, and alkenes for C-S bond formation. (2) Using the strategy of electrochemical oxidative C-H/N-H cross-coupling with hydrogen evolution, we successfully realized the C-H amination of phenols, anilines, imidazopyridines, and even ethers. (3) Employing halide salts as the green halogenating reagents, we developed a clean C-H halogenation protocol under electrochemical oxidation conditions. To address the limitation that this reaction had to carry out in aqueous solvent, we also developed an alternative method that uses CBr4, CHBr3, CH2Br2, CCl3Br, and CCl4 as halogenating reagents and the mixture of acetonitrile and methanol as cosolvent. (4) We also developed an approach for constructing C-O bonds in a well-developed electrochemical oxidative cross-coupling with hydrogen evolution manner. (5) Under mild external-oxidant-free electrochemical conditions, we realized the C(sp2)-H and C(sp3)-H phosphonylation with modest to high yields. (6) We successfully achieved the S-H/S-H cross-coupling with hydrogen evolution under electrochemical oxidation conditions. By anodic oxidation instead of chemical oxidants, the overoxidation of thiols and thiophenols was well avoided. (7) The methods for constructing structurally diverse heterocyclic compounds were also developed via the electrochemical oxidative annulations. (8) We have also applied the electrochemical oxidative cross-coupling with hydrogen evolution strategy to the alkenes difunctionalization for constructing multiple bonds in one step, such as C-S/C-O bonds, C-S/C-N bonds, C-Se/C-O bonds, and C-Se/C-N bonds. We hope our studies will stimulate the research interest of chemists and pave the way for the discovery of more electrochemical oxidative cross-coupling with hydrogen evolution reactions.

Cobalt-Catalyzed α-Arylation of Substituted α-Bromo α-Fluoro ß-Lactams with Diaryl Zinc Reagents: Generalization to Functionalized Bromo Derivatives.

A cobalt-catalyzed cross-coupling of α-bromo α-fluoro ß-lactams with diarylzinc or diallylzinc reagents is herein disclosed. The protocol proved to be general, chemoselective and operationally simple allowing the C4 functionalization of ß-lactams. The substrate scope was expanded to α-bromo lactams and amides, α-bromo lactones and esters as well as N- and O-containing heterocycles.

Electrochemical Oxidative [4+2] Annulation for the π-Extension of Unfunctionalized Heterobiaryl Compounds.

Considering their unique electronic properties and diverse biological activities, regioselective access to fused aromatic compounds is significantly important in the field of organic materials and pharmaceutical science. Herein, we developed electrochemical oxidative [4+2] annulation reactions of heterobiaryl compounds with alkynes or alkenes, leading to the formation of several polycyclic heteroaromatic compounds. This electrosynthetic methodology serves for the straightforward π-extension of unfunctionalized heterobiaryl compounds. The requirements of additional oxidants and prefunctionalization of starting materials are obviated. Through the in situ generation of heterobiaryl radical cation intermediates, various fused aromatic compounds were obtained with good yields and excellent regioselectivity.

Electrooxidation Enables Selective Dehydrogenative [4+2] Annulation between Indole Derivatives.

Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.