Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides.

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

Hydroboration and hydrosilylation of alkenes catalyzed by an unsymmetrical magnesium methyl complex.

The hydroboration and hydrosilylation of alkenes catalyzed by the unsymmetrical ß-diketiminate magnesium methyl complex [(DippXylNacnac)MgMe (THF)] (1) have been reported. When complex 1 was employed as a highly efficient catalyst in the hydroboration of various alkenes with HBpin, only the anti-Markovnikov hydroboration products were obtained in high yields and with high regioselectivities under mild reaction conditions (60 °C). To our surprise, it showed different regioselectivities in the hydrosilylation of a range of alkenes with PhSiH3. Aromatic alkene substrates afforded the corresponding branched Markovnikov hydrosilylation products in high yields and with high regioselectivities; conversely, aliphatic alkenes produced the linear anti-Markovnikov products in moderate yields. This is completely consistent with the corresponding density functional theory (DFT) calculations. In addition, the practical utility was demonstrated via scale-up reactions of boronate esters and a preliminary plausible mechanism of hydroboration and hydrosilylation have been investigated as well.

Combining Hydrodefluorination and Defluorophosphorylation for Chemo- and Stereoselective Synthesis of gem-Fluorophosphine Alkenes.

A chemo-, regio-, and stereoselective reaction of trifluoromethyl enones, phenylsilane, and phosphine oxides through a sequential hydrodefluorination and defluorophosphorylation relay is developed for the synthesis of distinctive gem-fluorophosphine alkenes. This multicomponent reaction occurred under transition-metal-free conditions with good functional group tolerance. Moreover, the preinstalled carbonyl auxiliary is important for tuning the reactivity of ß-trifluoromethyl enones, thereby enabling controllable and selective functionalization of two fluorine atoms in trifluoromethylated enones.

Defluorinative Thiolation of gem-Difluoroalkenes by Convergent Paired Electrolysis.

Herein, we have successfully developed a convergent paired electrolysis strategy for the defluorinative thiolation process utilizing thiols and gem-difluoroalkenes as precursors. This protocol exhibits remarkable tolerance toward a wide range of functional groups, as exemplified by the successful late-stage defluorothiolation of complex molecules. Additionally, this strategy is amenable to gram-scale synthesis, making use of both anodic oxidation and cathodic reduction processes in an efficient manner. Several control studies were conducted and suggested a convergent paired electrolysis mechanism.

Cooperative effects of SIRT1 and SIRT2 on APP acetylation.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by amyloid-ß (Aß) deposition and neurofibrillary tangles. Although the NAD+ -dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age-related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aß challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aß-induced neurotoxicity. We find that SIRT1 impedes SIRT2-mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD.

Regioselective Deuteration of Arenes Enabled by Simple Heterogeneous Palladium Catalysis.

A heterogeneous redox-neutral palladium-catalytic platform was reported for the preparation of deuterated (hetero) arenes from (hetero) arenes mediated by regioselective C(sp2)-H thianthrenation utilizing commercially available and recyclable Pd/C catalyst. A wide range of deuterated compounds could be obtained in high yields with excellent levels of deuterium incorporation under these simple heterogeneous catalytic conditions with the requirement of stable and easily handled DCOONa as a deuterium source. The late-stage deuteration of pharmaceuticals and bioactive molecules was also achieved by this approach.

Nickel-Catalyzed Direct Cross-Coupling of Unactivated Aryl Fluorides with Aryl Bromides.

A nickel-catalyzed direct cross-coupling of unactivated aryl fluorides with aryl bromides is realized. The one-pot reaction, which avoids the use of preformed and sensitive organometallic reagents, proceeds effectively via C-F bond cleavage at room temperature in THF in the presence of the phosphine ligand and magnesium powder (with or without TMSCl) to produce the desired biaryls in modest to good yields.

Preparation of new chiral diene ligands and their use in the rhodium catalyzed asymmetric annulation of 2-formylarylboronic acid with dialkylalkynes.

Herein, we report the rhodium-catalyzed domino arylation/cyclization reaction of unactivated internal alkynes to afford the optically active indenols in excellent yields (up to 92%) and extremely high enantioselectivities (up to 99% ee) in the presence of new amide substituted chiral diene ligands. Notably, a total of 21 new chiral diene ligands are synthesized, which are potential choices for other asymmetric reactions.

Na2S·9H2O Enabled Defluorodisulfuration and Hydrodefluorination of Perfluorobutyl Tetralones: Synthesis of Trifluoromethyl 1,2-Dithioles.

An unprecedented defluorocyclization of perfluorobutyl tetralones with Na2S·9H2O was developed for the synthesis of trifluoromethyl 1,2-dithioles, which provided chemists novel access to biologically and pharmaceutically relevant organofluorides. Successive C(sp3)-F bond functionalization at the perfluoroalkyl chain is vital for the formation of four C-H/C-S/S-S bonds and a five-membered S-heterocycle assembly. Cheap, weakly toxic, and odorless inorganic sulfide Na2S·9H2O acts as both a disulfurating precursor and a hydrodefluorinating reagent in this tandem multi-bond-interconverting reaction.

Selective and Controllable Defluorophosphination and Defluorophosphorylation of Trifluoromethylated Enones: An Auxiliary Function of the Carbonyl Group.

The auxiliary function of a carbonyl group in the tunable defluorophosphination and defluorophosphorylation of trifluoromethylated enones with P(O)-containing compounds was demonstrated. Controlled replacement of one or two fluorine atoms in trifluoromethylated enones while maintaining high chemo- and stereoselectivity was achieved under mild conditions, thus enabling diversity-oriented synthesis of skeletally diverse organophosphorus libraries─(Z)-difluoro-1,3-dien-1-yl phosphinates, (1Z,3E)-4-phosphoryl-4-fluoro-buta-1,3-dien-1-yl phosphinates, and (E)-4-phosphoryl-4-fluoro-1,3-but-3-en-1-ones─in good yields with excellent functional group tolerance.

Magnesium halide-catalyzed hydroboration of isocyanates and ketones.

Alkaline-earth metals have attracted increasing attention because they are cheap, Earth abundant and environmentally friendly, and have gradually become inexpensive and sustainable alternatives to traditional precious transition metal catalysts in many organic reactions. Recently, the hydroboration of unsaturated organic substrates has been extensively investigated. However, reports on alkaline-earth metal catalyzed hydroboration of isocyanates and ketones are rare. Herein, we report that simple, commercially available, and air-stable magnesium halides have been successfully employed as highly efficient catalysts in the hydroboration of isocyanates and ketones. Various boronate products were obtained in high yields with low catalyst loading under mild conditions.

Rhodium-Catalyzed Asymmetric Annulation of Unactivated Alkynes with 3-(ortho-Boronated Aryl) Conjugated Enones: Enantioselective Synthesis of 2,3-Disubstituted Indenes.

A rhodium-catalyzed tandem arylation/cyclization reaction of 3-(ortho-boronated aryl) conjugated enones with unactivated alkynes is reported. By using a rhodium(I)/chiral-diene complex as the catalyst, the protocol was processed smoothly to provide various 2,3-disubstituted indene compounds in high yields with excellent regioselectivities and enantioselectivities. The approach outlined herein is appealing, as simple diarylalkynes, diakylalkynes, and alkyl(aryl)alkynes are the starting materials.

De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity.

Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Metallic and Dimensional Optimization of Metal-Organic Frameworks for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) have been considered as one of the most promising energy storage systems owing to their high theoretical energy density and abundant sulfuric resources. However, their commercial application is limited by rapid capacity decline and low Coulombic efficiency. Metal-organic frameworks (MOFs) made of metallic nodes and organic ligands can suppress polysulfide shuttling and promote redox kinetics. In this paper, the effects of crystallographic dimensions and metallic categories on chemical performance of LSBs have been meticulously explored electrochemical performance. As a result, exposed Ni active sites in a lamellar Ni-MOF was found to deliver a superior electrochemical performance. The as-assembled LSBs with 2D-Ni-MOF/CNTs cathode deliver a much superior initial discharge capacity, (820 mAh g-1 at 0.5 C), and exhibit excellent cycling stability over 550 cycles than those analogues of 3D stereoscopic Ni-MOF and 2D lamellar Co-MOF. This work proposed a perspective in elevating LSBs performance through synergistic optimization of the MOFs dimensions and the metallic nuclei in the cathodes.

Nickel-Catalyzed Direct Cross-Coupling of Aryl Thioether with Aryl Bromide.

A straightforward cross-coupling of aryl thioether with aryl bromide with the aid of nickel salt, magnesium, and lithium chloride in tetrahydrofuran at ambient temperature was accomplished. The one-pot reactions proceeded efficiently via C-S bond cleavage to produce the desired biaryls in modest to good yields, avoiding the use of pregenerated or commercial organometallic reagents.

Nickel-Catalyzed Direct Cross-Coupling of Aryl Fluorosulfates with Aryl Bromides.

A one-pot, direct cross-coupling of aryl fluorosulfate with aryl bromide, which is step-economical and avoids the use of a preprepared/commercial organometallic reagent, could be accomplished by performing the reaction in THF at room temperature in the presence of nickel catalyst, magnesium turnings, and lithium chloride, giving rise to the corresponding biaryls in moderate to good yields with reasonable functional group compatibility.

Catalyst-Free Electrochemical Sulfonylation of Organoboronic Acids.

A simple and efficient electrochemical sulfonylation of organoboronic acids with sodium arylsulfinate salts has been reported for the first time. A variety of aryl, heteroaryl, and alkenylsulfones were obtained in good to excellent yields via a simple electrochemical sulfonylation of various arylboronic acids, heterocyclic boronic acids, or alkenylboronic acids with sodium arylsulfinate at room temperature in 5 h under the catalyst-free and additive-free conditions. A plausible mechanism has been proposed based on various radical-trapping and CV control experiments.

Highly Specific Antibiotic Detection on Water-Stable Black Phosphorus Field-Effect Transistors.

Two-dimensional (2D) black phosphorus (BP) has been reported to have appealing semiconducting properties as the sensing channel in field-effect transistor (FET) sensors. However, the intrinsic instability of BP in water greatly hinders its application, and little is known about its sensing performance and mechanism in aqueous medium. Herein, a water-stable BP FET sensor for antibiotic detection is reported. A novel surface engineering strategy with Ag+ coordination and melamine cyanurate (MC) supramolecular passivation is utilized to enhance the stability and transistor performance of BP. With molecularly imprinted polymers (MIPs) as the detection probe for tetracycline, the BPAg(+)/MC/MIPs sensor shows high sensitivity to tetracycline with a detection limit of 7.94 nM and a quick response within 6 s as well as high selectivity against other antibiotics with similar molecular structures. A new sensing mechanism relying on the conjugation effect of the probe structure is proposed, and new knowledge about alkalinity-enhanced and ionic strength-related response from the electrostatic gating effect is given based on the solution chemistry impact study. This work offers an efficient surface engineering strategy to enable the application of 2D BP for antibiotic detection in aqueous medium and presents a new sensing mechanism in chemical analysis by FET sensors.

Manipulating K-Storage Mechanism of Soft Carbon via Molecular Design-Driven Structure Transformation.

The emerging potassium-ion batteries (PIBs) have been placing stratospheric expectations for realizing grid-scale electrochemical storage of renewable energy. However, the unsatisfactory K-storage of PIB anode materials, especially promising carbonaceous materials, significantly limited the development of PIBs. Here, a molecular design strategy was proposed to realize controllable structure transformation of soft carbon (SC) materials for enhanced K-storage performance. The optimized SC-PCN material delivered a high reversible K-storage capacity of 838 mAh/g at 50 mA/g, outstanding rate capability (213 mAh/g at 1000 mA/g), and excellent long-term cycling performance (301 mAh/g maintained after 300 cycles at 500 mA/g), superior to most previously reported carbon-based PIB anodes materials. Reaction kinetic analysis revealed that the proposed molecular design strategy can achieve the transformation from a surface capacitive-dominated mechanism to a capacitive-diffusion hybrid mechanism for SC-PCN, benefiting from its unique microstructures with highly defective surface generated via the synergistic effect from template removal, N doping, and surface reconstruction. The optimal hybrid K-storage mechanism should be responsible for the excellent K-storage properties of the prepared SC-PCN.