The spirocyclic framework is found in many natural products, some of which are biologically active. However, It remains a challenge to develop environmentally friendly and atom-economic synthetic methods. Herein, we report an intramolecular dearomatization reaction of benzene derivatives enabled by electrochemistry-mediated two successive single-electron-transfer (SET) processes, providing an alternative method for the rapid construction of spirocyclic skeletons without using sacrificial reagents. A series of cyclohexadiene products were obtained in 25-81% yields. Furthermore, a proposed mechanism involving a sequential electron transfer event was supported by cyclic voltammetry experiments. This strategy features transition-metal-free conditions and easy handling, which will greatly enhance its practical utility. image

A palladium-catalyzed regioselective [8 + 3] cycloaddition of tropsulfimides and tropones with vinylidenecyclopropane-diesters (VDCP-diesters) has been disclosed in this paper, affording decahydro-1H-cyclohepta[b]pyridine derivatives bearing an allene moiety or decahydro-1H-cyclohepta[b]pyran derivatives having a conjugated diene unit in moderate to good yields. The reactions proceed through a zwitterionic allenyl palladium species derived from VDCP-diesters. The substrate scopes have been investigated and the plausible reaction mechanisms have also been proposed according to the previous work, the first captured zwitterionic Pd-allenyl intermediate, and control experiments.

Constructing a C-N bond by merging electrochemistry and nickel catalysis is considered a powerful strategy. Herein,we investigate highly efficient intramolecular amination at room temperature with excellent functional group tolerance. Mechanistic studies suggest that the rapid ligand exchange may lead to the Ni-I/Ni-III catalytic cycle. This method not only provides a new perspective for intramolecular amination but also offers a novel approach for constructing the benzothiazole scaffold.

Symmetrical biheteroaryl compounds, such as bypyridines and bipyrazoles, are important ligands in transition-metal catalysis. They also serve as synthetic precursors of photo catalysts/sensitizers, bioactive agents, and energetic materials. To facilitate the concise synthesis of these useful structures, an efficient Pd-catalyzed homocoupling of heteroaryl bromides has been successfully established using the electron-rich and sterically hindered monophosphorus ligand BIDIME. The coupling protocol features a tandem Miyaura borylation/Suzuki coupling sequence and exhibits unprecedented tolerance of a wide range of heteroaryl bromides, providing a series of symmetrical biheteroaryls in moderate to good yields. Notably, the use of the corresponding polymeric ligand, PolyBIDIME, enabled the recycling of a palladium catalyst, demonstrating the potential of the homocoupling in practical applications.

Liquid chromatography-mass spectrometry (LC-MS) is a powerful tool in untargeted metabolomics, enabling the high-sensitivity and high-specificity characterization of metabolites. The integration of ion mobility (IM) with LC-MS, known as LC-IM-MS, enhances the analytical depth, facilitating more comprehensive metabolite profiling. However, the complexity of data generated by these technologies presents significant challenges in data processing. Addressing these challenges, we developed Met4DX, a unified and versatile software tool for processing both 3D and 4D untargeted metabolomics data. Met4DX incorporates a new MS1-oriented peak detection approach coupled with our bottom-up assembly algorithm, enabling highly sensitive and comprehensive peak detection in untargeted metabolomics data. Additionally, Met4DX employs a uniform quantification strategy to enhance the precision of peak integration across different samples. The software provides a user-friendly interface that simplifies data processing with default parameter sets, consolidating peak detection, alignment, quantification, and other procedures into a single streamlined workflow. Together, Met4DX offers a comprehensive solution for multidimensional metabolomics data processing, transforming raw data from diverse MS instruments into a final feature table containing quantification and identification results. We postulate Met4DX facilitates metabolite discovery in biological samples by deciphering the complex untargeted metabolomics data. Met4DX is freely available on the Internet (https://met4dx.zhulab.cn/).

Reductive deoxygenation of alcohols is particularly challenging because of the high bond dissociation energy of the C-OH bond and the poor leaving ability of the hydroxyl group. Herein we describe a (Ph3PO)-O--catalyzed reductive deoxygenation of benzyl alcohols with PhSiH3 under an air atmosphere within 30 min of reaction time. The use of catalytic loading of (Ph3PO)-O- enhances the practicality of this protocol.

An efficient and E-selective monoisomerization of 1-alkenes is developed with a bis(phosphine)-based PCP-type Co complex as the catalyst. The protocol provides an atom-economical approach to trans-2-alkenes with high regio- and stereoselectivity, featuring mild conditions and wide substrate scope. Mechanistic investigation supports a cobalt-hydride pathway involving reversible alkene insertion/beta-H elimination, and the step of beta-H elimination at the allylic position is likely the rate-determining step.

Acovenoside A (1), a cardiac glycoside featuring a unique l-acovenose at C-3 and a 1 beta,3 beta,14 beta-trihydroxy aglycone (namely, acovenosigenin A), shows promising antiproliferative activities. Herein, we report the synthesis of acovenoside A (1) together with a panel of its congeners. The synthesis features the stereoselective introduction of the 1 beta,14 beta-OH and C17-butenolide moieties starting from androstenedione (7) and gold(I)-catalyzed glycosylation with superarmed glycosyl ortho-alkynylbenzoates as donors.

In comparison with the combination of p- and n-type organic semiconductors, the way to construct logic complementary circuits by ambipolar organic semiconductors has obvious advantages. However, so far, the ambipolar ones with high performance are still scarce. In this work, a series of benzo six-membered nitrogen/oxygen/sulfur heterocycles core-substituted naphthalene diimides-vinylogous tetrathiafulvalene (NDI-VTTF) derivatives 1 similar to 5 were designed by energy level regulation strategy. Subsequently, bottom-gate and top-contact organic field-effect transistors (OFETs) based on compounds 1 similar to 5 were fabricated and systematically studied. The results showed that all the OFET devices exhibit ambipolar semiconducting behaviors, among them the OFET devices based on compounds 1 , 3 similar to 5 displayed electron-dominated ambipolar charge transport characteristics, while the devices based on compound 2 showed balanced ambipolar charge transport features. Due to the improvement of thin-film crystallinity and morphology by thermal annealing treatment, the performance of OFETs based on compounds 1 similar to 5 was improved with the increase of thermal annealing temperature. When thermal annealed at 180 degrees C, OFETs based on compound 2 showed the balanced electron and hole mobilities of up to 0.037 and 0.050 cm(2)center dot V-1 center dot s(-1), respectively.

The transition metal-catalyzed direct coupling reactions involving electron-rich Fischer carbene species are largely underdeveloped and remain a big challenge. Here, a direct coupling reaction of azoles and azine N-oxides is reported with Fischer copper carbene species bearing an alpha-siloxy group i, which can be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. This coupling reaction between electron-rich alpha-siloxy Fischer Cu-carbene species with hard carbanion nucleophiles may undergo a bimetallic relay process, which is confirmed by the kinetic analysis and in situ NMR analysis. This reaction features mild conditions and remarkable heterocycle compatibility. Notably, this protocol tolerates a series of azole or azine N-oxide derivatives, including benzoxazole, benzothiazole, benzoimidazole, benzoisoxazole, oxazole, oxadiazole, triazolo[4,3-a]pyridine, purine, caffeine, pyridine N-oxide, quinoline N-oxide, pyrazine N-oxide, pyridazine N-oxide, etc. The synthetic value of this approach is demonstrated by the efficient synthesis of a histamine h4 receptor ligand and a marketed drug carbinoxamine. The coupling of azoles and azine N-oxides with the Fischer-type copper carbene species bearing a alpha-siloxyl group which can be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions, is realized. This reaction represents the first example of Cu-catalyzed coupling reaction of electron-rich Fischer carbene species with hard nucleophiles. KIE studies, kinetic analysis, and in situ NMR experiments implied a bimetallic relay process. image

Covalent organic frameworks (COFs) have been demonstrated as promising photocatalysts for hydrogen peroxide (H2O2) production. However, the construction of COFs with new active sites, high photoactivity, and wide-range light absorption for efficient H2O2 production remains challenging. Herein, we present the synthesis of a novel azobenzene-bridged 2D COF (COF-TPT-Azo) with excellent performance on photocatalytic H2O2 production under alkaline conditions. Notably, although COF-TPT-Azo differs by only one atom (-N=N- vs. -C=N-) from its corresponding imine-linked counterpart (COF-TPT-TPA), COF-TPT-Azo exhibits a significantly narrower band gap, enhanced charge transport, and prompted photoactivity. Remarkably, when employed as a metal-free photocatalyst, COF-TPT-Azo achieves a high photocatalytic H2O2 production rate up to 1498 mu mol g-1 h-1 at pH = 11, which is 7.9 times higher than that of COF-TPT-TPA. Further density functional theory (DFT) calculations reveal that the -N=N- linkages are the active sites for photocatalysis. This work provides new prospects for developing high-performance COF-based photocatalysts. A novel photoactive azobenzene-bridged 2D COF (COF-TPT-Azo) shows an excellent photocatalytic H2O2 production rate up to 1498 mu mol g-1 h-1 at pH = 11, which is 7.9 times higher than its corresponding imine-linked 2D COF (COF-TPT-TPA), although only one atom is different in the two 2D COFs (-N=N- vs. -C=N-). COF-TPT-Azo exhibits much narrower band gap, enhanced charge transport, and prompted photoactivity, which is benefited from its azo linkages. image

Fused in sarcoma (FUS), a multifunctional deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein, has been implicated in various cancer types, including sarcoma and leukemia. Despite its association with these diseases, there has been limited exploration of FUS as a cancer therapy target, primarily because its dynamic nature makes it difficult to target specifically. In this study, we explored a kind of beta-sheet peptide foldamer, named beta(4)-TAT, to influence FUS aggregation by targeting its RNA recognition motifs (RRM). This approach leverages the noncovalent interaction characteristics of peptide self-assembly processes. The beta(4) sequence, derived from the FUS RRM beta-sheet, in combination with TAT, a peptide known for its nuclear targeting capability, enables beta(4)-TAT to bind specifically to the analogous beta(4) sequence within FUS. Notably, beta(4)-TAT effectively induces FUS aggregation within cells, leading to the death of cancer cells. Our work developed a novel peptide foldamer-based strategy for inducing protein aggregation, paving the way for innovative therapeutic approaches in targeting FUS-associated cancers.