Interface-Suppressed Nematicity and Enhanced Superconducting Pairing Strength of FeSe/NdFeO3 in the Low-Doping Regime.

The discovery of interfacial superconductivity in monolayer FeSe/oxides has spurred intensive research interest. Here we not only extend the FeSe/FeOx superconducting interface to FeSe/NdFeO3 but also establish robust interface-enhanced superconductivity at a very low doping level. Specifically, well-annealed FeSe/NdFeO3 exhibits a low doping level of 0.038-0.046 e-/Fe with a larger superconducting pairing gap without a nematic gap, indicating an enhancement of the enhanced superconducting pairing strength and suppression of nematicity by the FeSe/FeOx interface compared with those of thick FeSe films. These results improve our understanding of the roles of the oxide interface in the low-electron-doped regime.

Inferior Interfacial Superconductivity in 1 UC FeSe/SrVO3/SrTiO3 with Screened Interfacial Electron-Phonon Coupling.

Single-unit cell (1 UC) FeSe interfaced with TiOx or FeOx exhibits significantly enhanced superconductivity compared to that of bulk FeSe, with interfacial electron-phonon coupling (EPC) playing a crucial role. However, the reduced dimensionality in 1 UC FeSe, which may drive superconducting fluctuations, complicates our understanding of the enhancement mechanisms. We construct a new superconducting interface, 1 UC FeSe/SrVO3/SrTiO3. Here, the itinerant electrons of highly metallic SrVO3 films can screen all high-energy Fuchs-Kliewer phonons, including those of SrTiO3, making it the first FeSe/oxide system with screened interfacial EPC while maintaining the 1 UC FeSe thickness. Despite comparable doping levels, the heavily electron-doped 1 UC FeSe/SrVO3 exhibits a pairing temperature (Tg ∼ 48 K) lower than those of FeSe/SrTiO3 and FeSe/LaFeO3. Our findings disentangle the contributions of interfacial EPC from dimensionality in terms of enhancing Tg in FeSe/oxide interfaces, underscoring the critical importance of interfacial EPC. This FeSe/VOx interface also provides a platform for studying interfacial superconductivity.

Unlocking the Potential of Oxidative Asymmetric Catalysis with Continuous Flow Electrochemistry.

In the field of catalytic asymmetric synthesis, the less-treated path lies in oxidative catalytic asymmetric transformations. The hurdles of pinpointing the appropriate chemical oxidants and addressing their compatibility issues with catalysts and functionalities present significant challenges. Organic electrochemistry, employing traceless electrons for redox reactions, is underscored as a promising solution. However, the commonly used electrolysis in batch cells introduces its own set of challenges, hindering the advancement of electrochemical asymmetric catalysis. Here we introduce a microfluidic electrochemistry platform with single-pass continuous flow reactors that exhibits a wide-ranging applicability to various oxidative asymmetric catalytic transformations. This is exemplified through the sulfenylation of 1,3-dicarbonyls, dehydrogenative C-C coupling, and dehydrogenative alkene annulation processes. The unique properties of microfluidic electrochemical reactors not only eliminate the need for chemical oxidants but also enhance reaction efficiency and reduce the use of additives and electrolytes. These salient features of microfluidic electrochemistry expedite the discovery and development of oxidative asymmetric transformations. In addition, the continuous production facilitated by parallel single-pass reactors ensures straightforward reaction upscaling, removing the necessity for reoptimization across various scales, as evidenced by direct translation from milligram screening to hectogram asymmetric synthesis.

Electrochemical Azidocyanation of Alkenes.

The difunctionalization of alkenes-a process that installs two functional groups in a single operation and transforms chemical feedstocks into value-added products-is one of the most appealing synthetic methods in contemporary chemistry. However, the introduction of two distinct functional groups via two readily accessible nucleophiles remains a formidable challenge. Existing intermolecular alkene azidocyanation methods, which primarily focus on aryl alkenes and rely on stoichiometric chemical oxidants. We report herein an unprecedented electrochemical strategy for alkene azidocyanation that is compatible with both alkyl and aryl alkenes. This is achieved by harnessing the finely-tuned anodic electron transfer and the strategic selection of copper/ligand complexes. The reactions of aryl alkenes were rendered enantioselective by employing a chiral ligand. Crucially, the mild conditions and well-regulated electrochemical process assure exceptional tolerance for various functional groups and substrate compatibility with both terminal and internal alkyl alkenes.

Photoelectrochemical Asymmetric Catalysis Enables Enantioselective Heteroarylcyanation of Alkenes via C-H Functionalization.

The asymmetric difunctionalization of alkenes, a method transforming readily accessible alkenes into enantioenriched chiral structures of high value, has long been a focal point of organic synthesis. Despite tremendous efforts in this domain, it remains a considerable challenge to devise enantioselective oxidative dicarbofunctionalization of alkenes, even though these transformations can utilize stable and unfunctionalized functional group donors. In this context, we report herein a photoelectrocatalytic method for the enantioselective heteroarylcyanation of aryl alkenes, which employs unfunctionalized heteroarenes through C-H functionalization. The photoelectrochemical asymmetric catalysis (PEAC) method combines photoredox catalysis and asymmetric electrocatalysis to facilitate the formation of two C-C bonds operating via hydrogen (H2) evolution and obviating the need for external chemical oxidants.

Continuous Flow Electrochemistry Enables Practical and Site-Selective C-H Oxidation.

The selective oxygenation of ubiquitous C(sp3 )-H bonds remains a highly sought-after method in both academia and the chemical industry for constructing functionalized organic molecules. However, it is extremely challenging to selectively oxidize a certain C(sp3 )-H bond to afford alcohols due to the presence of multiple C(sp3 )-H bonds with similar strength and steric environment in organic molecules, and the alcohol products being prone to further oxidation. Herein, we present a practical and cost-efficient electrochemical method for the highly selective monooxygenation of benzylic C(sp3 )-H bonds using continuous flow reactors. The electrochemical reactions produce trifluoroacetate esters that are resistant to further oxidation but undergo facile hydrolysis during aqueous workup to form benzylic alcohols. The method exhibits a broad scope and exceptional site selectivity and requires no catalysts or chemical oxidants. Furthermore, the electrochemical method demonstrates excellent scalability by producing 115 g of one of the alcohol products. The high site selectivity of the electrochemical method originates from its unique mechanism to cleave benzylic C(sp3 )-H bonds through sequential electron/proton transfer, rather than the commonly employed hydrogen atom transfer (HAT).

Organoelectrocatalysis Enables Direct Cyclopropanation of Methylene Compounds.

Cyclopropane is a prevalent structural unit in natural products and bioactive compounds. While the transition metal-catalyzed alkene cyclopropanation of functionalized compounds such as α-diazocarbonyl derivatives has been well established and provides straightforward access to cyclopropanes, cyclopropanation directly from the more stable and simpler methylene compounds has remained an unsolved challenge despite the highly desirable benefits of minimal prefunctionalization and increased operational safety. Herein we report an electrocatalytic strategy for the cyclopropanation of active methylene compounds, employing an organic catalyst. The method shows a broad substrate scope and excellent scalability, requires no metal catalyst or external chemical oxidant, and provides convenient access to several types of cyclopropane-fused heterocyclic and carbocyclic compounds. Mechanistic investigations suggest that the reactions proceed through a radical-polar crossover process to form the two new carbon-carbon bonds in the nascent cyclopropane ring.

Cu-Electrocatalytic Diazidation of Alkenes at ppm Catalyst Loading.

The 1,2-diamine motif is prevalent in natural products, small-molecule pharmaceuticals, and catalysts for asymmetric synthesis. Transition metal catalyzed alkene diazidation has evolved to be an attractive strategy to access vicinal primary diamines but remains challenging, especially for practical applications, due to the restriction to a certain type of olefins, the frequent use of chemical oxidants, and the requirement for high loadings of metal catalysts (1 mol % or above). Herein we report a scalable Cu-electrocatalytic alkene diazidation reaction with 0.02 mol % (200 ppm) of copper(II) acetylacetonate as the precatalyst without exogenous ligands. In addition to its use of low catalyst loading, the electrocatalytic method is scalable, compatible with a broad range of functional groups, and applicable to the diazidation of α,ß-unsaturated carbonyl compounds and mono-, di-, tri-, and tetrasubstituted unactivated alkenes.

Photoelectrochemical Asymmetric Catalysis Enables Direct and Enantioselective Decarboxylative Cyanation.

The development of efficient and sustainable methods for decarboxylative transformations is of great importance due to the ease of availability and nontoxicity of carboxylic acids. Despite tremendous efforts in this area, it remains challenging to develop enantioselective transformations direct from carboxylic acids. Herein we disclose a photoelectrocatalytic method for the direct and enantioselective decarboxylative cyanation. The photoelectrochemical reactions convert carboxylic acids to enantioenriched nitriles by employing cerium/copper relay catalysis with a cerium salt for catalytic decarboxylation and a chiral copper complex for stereoselective C-CN formation.

Role of FUS-CHOP in Myxoid Liposarcoma via miR-486/CDK4 Axis.

This study aimed to explore the roles and relationship between FUsed in Sarcoma (FUS)-C/EBP HOmologous Protein (CHOP), microRNA (miR)-486 and cyclin dependent kinase 4 (CDK4) in myxoid liposarcoma, and determined whether FUS-CHOP can regulate proliferation and apoptosis of myxoid liposarcoma cells by regulating miR-486/CDK4 axis. The levels of miR-486, CDK4 and FUS-CHOP in myxoid liposarcoma samples/adjacent normal muscle tissues and myxoid liposarcoma/human adipose-derived stem cell line were evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation and apoptosis were performed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and flow cytometry, respectively. Furthermore, the apoptosis-related proteins were determined using Western blot assay. We found that miR-486 was down-regulated, FUS-CHOP and CDK4 were up-regulated in myxoid liposarcoma tissues and myxoid liposarcoma cell lines. Moreover, FUS-CHOP-siRNA distinctly suppressed FUS-CHOP level and increased miR-486 levels in 1955/91 cells. Our results demonstrated that knockdown of FUS-CHOP by siRNA inhibited 1955/91 growth, promoted cell apoptosis and enhanced cleaved Caspase3 protein expression. However, all these data were reversed by miR-486 inhibitor. Similarly, compared to mimic control, miR-486 mimic markedly reduced 1955/91 cells growth, induced cell apoptosis and fortified cleaved Caspase3 level, while these results were abolished by CDK4-plasmid. Collectively, our observations clearly suggested that FUS-CHOP regulated myxoid liposarcoma cell proliferation and apoptosis by the regulation of miR-486/CDK4 axis, indicating the potential use of FUS-CHOP-siRNA as a promising therapy for myxoid liposarcoma.

Electrocatalytic Allylic C-H Alkylation Enabled by a Dual-Function Cobalt Catalyst.

The direct functionalization of allylic C-H bonds with nucleophiles minimizes pre-functionalization and converts inexpensive, abundantly available materials to value-added alkenyl-substituted products but remains challenging. Here we report an electrocatalytic allylic C-H alkylation reaction with carbon nucleophiles employing an easily available cobalt-salen complex as the molecular catalyst. These C(sp3 )-H/C(sp3 )-H cross-coupling reactions proceed through H2 evolution and require no external chemical oxidants. Importantly, the mild conditions and unique electrocatalytic radical process ensure excellent functional group tolerance and substrate compatibility with both linear and branched terminal alkenes. The synthetic utility of the electrochemical method is highlighted by its scalability (up to 200 mmol scale) under low loading of electrolyte (down to 0.05 equiv) and its successful application in the late-stage functionalization of complex structures.

Electrochemically Driven Radical Reactions: From Direct Electrolysis to Molecular Catalysis.

Organic radicals are versatile synthetic intermediates that provide reactivities and selectivities complementary to ionic species. Despite its long history, electrochemically driven radical reactions remain limited in scope. In the past few years, there have been dramatic increase in research activity in organic electrochemistry. We have been developing electrochemical and electrophotocatalytic methods for the generation and synthetic utilization of organic radicals. In our studies, various radical species such as alkene and arene radical cations and carbon- and heteroatom-centered radicals are generated from readily available precursors through direct electrolysis, molecular electrocatalysis or molecular electrophotocatalysis. These radical species undergo various inter- and intramolecular oxidative transformations to rapidly increase molecular complexity. The simultaneous occurrence of anodic oxidation and cathodic proton reduction allows the oxidative reactions to proceed through H2 evolution without external chemical oxidants.

Electrocatalytic Dehydrogenative Cyclization of 2-Vinylanilides for the Synthesis of Indoles.

Indole is prevalent in bioactive compounds and natural products. The development of efficient and sustainable methods to access this privileged structural scaffold has been a long-standing interest of synthetic chemists. Herein, we report an electrocatalytic method for the synthesis of indoles through dehydrogenative cyclization of 2-vinylanilides. The reactions employ an organic redox catalyst and do not require any external chemical oxidant, providing speedy and efficient access to 3-substituted and 2,3-disubstituted indoles.

Discovery of a tetraarylhydrazine catalyst for electrocatalytic synthesis of imidazo-fused N-heteroaromatic compounds.

The development of electrocatalytic synthetic methods hinges on efficient molecular catalysts. Triarylamines are well-known redox catalysts because of the good stability of their corresponding amine radical cations. Herein we show that tris(4-(tert-butyl)phenyl)amine decomposes unexpectedly during electrolysis in MeOH/THF to afford a tetraarylhydrazine, 1,1,2,2-tetrakis(4-(tert-butyl)phenyl)hydrazine. In addition, we have applied this tetraarylhydrazine, which is either preprepared or formed in situ from tris(4-(tert-butyl)phenyl)amine, as an electrocatalyst for the synthesis of imidazopyridines and related N-heteroaromatic compounds through intramolecular [3 + 2] annulation. This metal-free electrocatalytic method provides straightforward access to the N-heteroaromatic compounds from readily available materials without the need for external chemical oxidants.

Catalyst- and Reagent-Free Formal Aza-Wacker Cyclizations Enabled by Continuous-Flow Electrochemistry.

The development of efficient and sustainable methods to access saturated N-heterocycles is of great importance because of the prevalence of these structures in natural products and bioactive compounds. Pd-catalyzed aza-Wacker type cyclization is a powerful method and provides access to N-heterocycles bearing an alkene moiety available for further synthetic manipulations from readily available materials. Herein we disclose a catalyst- and reagent-free formal aza-Wacker type cyclization reaction for the synthesis of functionalized saturated N-heterocycles. Key to the success is to conduct the reactions in a continuous-flow electrochemical reactor without adding supporting electrolyte or additives. The reactions are characterized by broad tolerance of di-, tri- and tetrasubstituted alkenes.

Site-Selective Electrochemical Benzylic C-H Amination.

C-H/N-H cross-coupling is an ideal strategy to synthesize various amines but remains challenging owing to the requirement for sacrificial chemical oxidants and the difficulty in controlling the regio- and chemo-selectivity. Herein we report a site-selective electrochemical amination reaction that can convert benzylic C-H bonds into C-N linkages via H2 evolution without need for external oxidants or metal catalysts. The synthetic strategy involves anodic cleavage of benzylic C-H to form a carbocation intermediate, which is then trapped with an amine nucleophile leading to C-N bond formation. Key to the success is to include HFIP as a co-solvent to modulate the oxidation potentials of the alkylbenzene substrate and the aminated product to avoid overoxidation of the latter.

Electrocatalytic C(sp3)-H/C(sp)-H cross-coupling in continuous flow through TEMPO/copper relay catalysis.

Electrocatalytic dehydrogenative C(sp3)-H/C(sp)-H cross-coupling of tetrahydroisoquinolines with terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward and sustainable access to 2-functionalized tetrahydroisoquinolines.

Chemistry with Electrochemically Generated N-Centered Radicals.

N-centered radicals are versatile reaction intermediates that can react with various π systems to construct C-N bonds. Current methods for generating N-centered radicals usually involve the cleavage of an N-heteroatom bond; however, similar strategies that are applicable to N-H bonds prove to be more challenging to develop and therefore are attracting increasing attention. In this Account, we summarize our recent efforts in the development of electrochemical methods for the generation and synthetic utilization of N-centered radicals. In our studies, N-aryl amidyl radical, amidinyl radical and iminyl radical cation intermediates are generated from N-H precursors through direct electrolysis or indirect electrolysis assisted by a redox catalyst. In addition, an electrocatalytic method that converts oximes to iminoxyl radicals has also been developed. The electrophilic amidyl radical intermediates can participate in 5-exo or 6-exo cyclization with alkenes and alkynes to afford C-centered radicals, which can then undergo various transformations such as H atom abstraction, single-electron transfer oxidation to a carbocation, cyclization, or aromatic substitution, leading to a diverse range of N-heterocyclic products. Furthermore, amidinyl radicals, iminyl radical cations, and iminoxyl radicals can undergo intramolecular aromatic substitution to afford various N-heteroaromatic compounds. Importantly, the electrochemical reaction can be channeled toward a specific product despite the presence of other competing pathways. For a successful electrosynthesis, it is important to take into consideration of both the electron transfer steps associated with the electrode and the nonelectrode related processes. A unique feature of electrochemistry is the simultaneous occurrence of anodic oxidation and cathodic reduction, which, as this Account demonstrates, allows the dehydrogenative transformations to proceed through H2 evolution without the need for chemical oxidants. In addition, cathodic solvent reduction can continuously generate a low concentration of base, which facilitates anodic substrate oxidation. Such a mechanistic paradigm obviates the need for stoichiometric strong bases and avoids base-promoted decomposition of sensitive substrates or products. Furthermore, electrode materials can also be adjusted to control the reaction outcome, as demonstrated by the synthesis of N-heteroaromatics and the corresponding N-oxides from biaryl ketoximes.

Electrophotocatalytic Decarboxylative C-H Functionalization of Heteroarenes.

Decarboxylative C-H functionalization reactions are highly attractive methods for forging carbon-carbon bonds considering their inherent step- and atom-economical features and the pervasiveness of carboxylic acids and C-H bonds. An ideal approach to achieve these dehydrogenative transformations is through hydrogen evolution without using any chemical oxidants. However, effective couplings by decarboxylative carbon-carbon bond formation with proton reduction remain an unsolved challenge. Herein, we report an electrophotocatalytic approach that merges organic electrochemistry with photocatalysis to achieve the efficient direct decarboxylative C-H alkylation and carbamoylation of heteroaromatic compounds through hydrogen evolution. This electrophotocatalytic method, which combines the high efficiency and selectivity of photocatalysis in promoting decarboxylation with the superiority of electrochemistry in effecting proton reduction, enables the efficient coupling of a wide range of heteroaromatic bases with a variety of carboxylic acids and oxamic acids. Advantageously, this method is scalable to decagram amounts, and applicable to the late-stage functionalization of drug molecules.

Scalable Photoelectrochemical Dehydrogenative Cross-Coupling of Heteroarenes with Aliphatic C-H Bonds.

Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross-coupling of heteroarenes with aliphatic C-H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross-coupling of heteroarenes and C(sp3 )-H donors through H2 evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp3 )-H donor is converted to a nucleophilic carbon radical through H-atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl2 from Cl- . The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.