Transition metal-catalyzed electrochemical C-H annulation with alkynes has emerged as a promising method for constructing heterocycles via formal cycloadditions. However, catalytic electrochemical C-H annulation with alkenes has been less explored. In this study, we report a cathodic oxygen reduction-enabled rhodium catalyzed (5 + 1) annulation reaction between readily available alkenylphenols and alkenes, yielding valuable 2-substituted 2H-chromenes. Unlike existing methods that involve direct oxidation of catalysts at the anode, our protocol uses a sacrificial anode to protect the substrate from overoxidation, while the cathode reduces oxygen, coupling with the RhI. to regenerate the rhodium catalyst. This efficient, atom-economical heterocyclization reaction demonstrates a broad scope and functional-group tolerance for diverse biologically relevant molecules, with a Faradaic efficiency greater than 100%.

A Pd-catalyzed enantioselective alpha-arylation of alpha,alpha-disubstituted esters with aryl bromides is established for the first time by employing P-chiral monophosphorus ligand 3-Pent-BIDIME as a chiral ligand, leading to a series of enantioenriched alpha,alpha-diaryl esters possessing quaternary carbon stereocenters in moderate to good yields and high enantioselectivities. The method features a broad substrate scope, mild conditions, excellent functional group compatibility, and low Pd loadings (as low as 1 mol%). The synthetic power of this protocol is exemplified by the efficient preparation of a chiral alpha,alpha-diaryl substituted gamma-lactone and asymmetric synthesis of (R)-amolanone. DFT calculation revealed an NaBr-bridged downstream transmetallation and the importance of noncovalent interaction in controlling the enantioselectivity.

Difluoromethyl 2-pyridyl sulfone (2-PySO2CF2H) is a readily accessible, cost-effective, and versatile reagent with broad applications in fluoroalkylation and fluoroolefination. Here, we unveil a novel application of 2-PySO2CF2H in electrophilic difluoromethylthiolation. Key to this advance is the strategic N-activation of 2-PySO2CF2H to generate stable N-methylpyridinium salt and pyridine N-oxide derivatives. When synergistically combined with (EtO)2P(O)H/TMSCl, these activated sulfones facilitate efficient difluoromethylthiolation of electron-rich heteroarenes, such as indoles and pyrroles. This research not only introduces a new strategy for electrophilic difluoromethylthiolation but also provides new insights into the mechanism of (EtO)2P(O)H/TMSCl-mediated difluoromethylthiolation reactions.

Organic room-temperature phosphorescence (RTP) and afterglow materials show great potential for applications in anti-counterfeiting, data encryption, and bioimaging. Among these, the organic long persistent luminescence (OLPL) materials have attracted considerable attention over the past decades. Herein, we present a three-component system with intriguing photophysical mechanism to achieve bright OLPL materials. Difluoroboron beta-diketonate (BF2bdk) molecules with intramolecular charge-transfer (ICT) character were employed as luminescent dopants. An electron donor, N,N,N',N'-tetramethylbenzidine (TMB), is introduced as a hole-trapping agent, facilitating charge separation and enabling hour-long OLPL emission. Through systematic screening of organic matrices, phenyl 4-methoxybenzoate (MeOPhB) was identified as the optimal matrix to prepare OLPL materials. The resulting BF2bdk-MeOPhB-TMB systems achieve bright and long-lasting afterglow emission lasting up to 2.5 h under ambient conditions, comparable to the performance of inorganic Sr2Al14O25/Eu2+, Dy3+ materials. This offers a versatile framework for extending the design principles of OLPL systems, greatly enriching the repertoire of OLPL materials. Moreover, the aqueous dispersion of this three-component system retains its long-lived afterglow properties, further demonstrating its potential for applications in bioimaging.

The defluorination of trifluoromethyl groups typically involves breaking one or all three C-F bonds, while selectively cleaving exactly two C-F bonds presents a considerable challenge. In this work, we present a method for the sequential defluorination of trifluoromethyl hydrazones under photocatalytic conditions, which involves the specific breakage of two C-F bonds followed by thiolation to yield monofluorinated alkenes containing a thiol group. Transforming trifluoromethyl-containing polyfluoroalkyl substances into fluorinated non-PFAS compounds holds potential practical implications.

Herein, we report a new dehydrative glycosylation protocol mediated by Cp2ZrCl2-AgN(SO2F)22MeCN combination, which efficiently afforded a diverse array of O- and S-glycosides in good to excellent yields (up to 91% yield). A series of armed pyranosyl and furanosyl donors are shown to be suitable donors, and primary, secondary and tertiary alcohols and aliphatic and aromatic thiols are suitable acceptors. In the absence of external acceptors, self-condensation could occur to provide a convenient approach to symmetrical 1,1'-disaccharides. An intriguing rearrangement of 3,4,6-tri-O-benzyl-2-deoxy-D-glucosose under the Zr promoter system was discovered to provide a C2-branched pyranose derivatives.

The abnormal accumulation of misfolded proteins is a common hallmark of many neurodegenerative disorders. Among these proteins, alpha-synuclein (alpha syn) is a well-characterized pathogenic protein in Parkinson's disease (PD) and other synucleinopathies. alpha syn can be hyperphosphorylated and form pathological aggregates, leading to neurodegeneration. Thus, chemical modulators of pathological alpha syn may suppress its downstream toxicity and provide entry points to therapeutic intervention. Here, we identified mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitors as negative modulators of basal alpha syn in wild-type cells and that pathological alpha syn in alpha syn preformed fibrils (alpha syn-PFF) induced the neuroblastoma cell line SHSY-5Y, PC12 cells, and primary cultured neurons. We further demonstrated that these inhibitors suppressed Ser129 phosphorylated alpha syn (p-alpha syn) through the kinase PLK2 downstream of MEK1/2-ERK2 in PD cell models. We established a humanized PD mouse model by injecting human alpha syn-PFF into mice with homozygous knock-in of human SNCA. Oral administration of blood-brain barrier-penetrable MEK1/2 inhibitors lowered pathological alpha syn and rescued PD-relevant phenotypes with an acceptable safety profile in these mice. Collectively, these data highlight MEK1/2 inhibitors as a potential therapeutic strategy for PD.

An efficient method for the synthesis of 2H-1,2-oxazin-3(6H)-one via the nitroso-Diels-Alder reaction of nitrosobenzene with gem-difluoro-1,3-dienes is developed under mild conditions. This strategy features good functional group tolerance, good to high yields, and free of catalyst. The de-aromatization of heterocyclic gem-difluoroalkenes is successfully achieved by this method. The product can be converted into beta-lactams through base-promoted rearrangement.

Fluorine-containing siloxanes are useful synthetic intermediates in a variety of organic transformations and material chemistry due to their high reactivity. Fluorine-containing siloxanes can also be used as coupling agents and wetting agents. However, the catalytic synthesis of fluorine-containing siloxanes remains elusive. Here, we reported a simple and mild method for hydrofluoroalkylation of alkenylsiloxanes with trifluoromethyl arenes under visible light induced arenethiolate as a dual functional catalyst, affording a range of valuable 1,2-disubstituted fluorine-containing siloxanes in up to 57% yield. This research was distinguished by broad functional group tolerance, moderate-to-good yields, and gram-scale synthesis.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.