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Aromatic nitration faces a trade-off effect between conversion and selectivity. Here, the authors develop a two-stage countercurrent microflow strategy that regulates reaction kinetics and thermodynamics, simultaneously achieving high conversion and selectivity across multiple aromatic substrates.

Predicting chemical reactions remains a challenge. Here, the authors present Loxodynamics, a machine learning method that uses statistical skewness to automatically discover reaction pathways in complex systems without prior knowledge.

Even though the application of co-solvents in glycosylation protocols is well-established, the understanding of their impact on the glycosylation mechanism as well as the reaction intermediates formed upon their addition, remains incomplete. Here, the authors report the application of relaxation and exchange NMR techniques to establish that acetonitrile and tetrahydrofuran form covalent glycosyl-nitrilium and glycosyloxonium ions, respectively.

Lactone monomers for recyclable polyesters are conventionally synthesized via endergonic, non-oxidative dehydrocyclization of fossil-derived diols in the vapor phase over precious-metal catalysts at elevated temperatures. Here, the authors demonstrate a low-temperature, solvent-free, oxidative route to lactones from bio-derivable liquid diols using earth-abundant calcium-copper mixed-metal oxide catalysts.

The activation of amines into thiocarbamoyl fluorides provides access to valuable nitrogen-based functionalities. Here, the authors report a mild, photochemical method for in-situ generation of thiocarbonyl difluoride from N-trifluoromethylthiophthalimide using visible light and organic reductants, and apply this strategy to the synthesis of azetidines from strained azabicyclo[1.1.0]butanes.

Femtosecond X-ray solution scattering reveals how solvent environments direct the outcome of ultrafast roaming reactions in bromoform, determining whether transient hot isomers undergo rapid solvolysis or rearrange into long-lived isomeric products.

The use of benzene ring contraction in chemical synthesis is challenging due to the need to disrupt aromaticity and generate highly strained intermediates. Now, a photothermal ring contraction reaction for the synthesis of multisubstituted fused pyridines is reported, from arylhydrazines and carbonyl compounds, via benzene ring contraction.

Isoxazoles, oxazoles, and other five-membered heteroaromatics are prevalent motifs in core structure of pharmaceuticals and agrochemicals. Here the authors report a photochemical platform for the selective conversion of isoxazoles into oxazoles, pyrazoles, pyrroles, and isothiazoles by exploiting excited-state reactivity.

Azobenzene photoswitches have garnered significant attention for their potential in light-responsive materials, yet challenges remain in understanding their thermal cis-trans isomerization. Here, the authors employ advanced quantum chemical methods to elucidate the rapid thermal switching mechanism in the hydrazone tautomer, revealing puckering of the tautomeric nitrogen as a key factor for accelerating isomerization kinetics.

Here the authors report a chiral hypervalent iodine(III)-catalyzed skeletal editing of pyrimidine moieties within polynitrogen heterocycles, efficiently producing optically pure multi-substituted imidazoline rings.

Glycosaminoglycans encode binding specificity through positional sulfation, but understanding these patterns is challenging due to sulfate migration during mass spectrometry (MS). Here, the authors use ion-mobility MS to investigate the isomerization reaction of heparin sulfate disaccharides in the gas phase, providing insights into the resulting isomeric products and potential rearrangement mechanisms of sulfate migration.

Pyrrole and 2-pyrrolone derivatives are often prepared using transition metal catalysis. Now, a metal-free strategy is reported whereby alkynyl O-silylimidates or alkynyl aldimines react with electrophilic alkynes to produce pyrrole-stabilized carbene intermediates via net [3 + 2] cycloaddition. These intermediates can form a range of 2-pyrrolone and pyrrole derivatives.

Radical chain initiation strategies are fundamental to the synthesis of small molecule drugs and macromolecular materials. Here a general, thermally driven and scalable method for reductive initiation is reported, in which inexpensive azo initiators are reacted with formate salts to form a carbon dioxide radical anion.

One-step, generalizable conversion of aromatic rings into heteroaromatic rings remains a challenge in organic chemistry. Here, the authors developed a heteroaromatic swapping reaction for aromatic ketones with broad substrate range and high selectivity.

Cation effects in electrocatalytic reactions have attracted considerable interest due to their role in modulating reaction kinetics and mechanisms. Here, the authors use constant-potential density functional theory and ab initio molecular dynamics simulations to study the atomic-scale synergy between Na⁺ ions and stepped Pt(311) surfaces in the alkaline hydrogen evolution reaction, reporting the formation of a Pt–H₂O–Na⁺(H₂O)ₓ adduct at the step edges that positions cations closer to the surface compared to Pt(111) terraces, resulting in a lower Volmer step activation energy.

Hidden catalysis plagues catalyst development and occurs when an impurity or species generated in situ facilitates the reaction instead of the intended catalyst. Current methods to identify hidden catalysis require time-consuming, labour-intensive mechanistic analyses, so limiting widespread use. A colorimetric indicator has been developed that enables rapid, visual detection of hidden borane catalysis.

The functionalization of carbon–carbon bonds in amines remains an important challenge in organic synthesis. Now a borane-catalysed method has been developed that enables the insertion of alkynes into the alkyl C–C bonds of amines, providing a versatile approach for the ring expansion of cyclic amines and chain elongation of acyclic amines.

A terpene-forming carbocation reaction is described for which a single transition-state structure leads to the formation of many isomeric products via pathways that feature multiple sequential bifurcations. Dynamic effects are shown to contribute to the selectivity of the reaction, with consequences for how enzymes control the biosynthesis of complex natural products.

A prototypical example of a ‘strategic atom replacement’ approach enables synthesis of N-alkyl pyrazoles from isothiazoles by swapping the sulfur atom with a nitrogen atom and its associated alkyl fragment to deliver the alkylated pyrazole.

Although Brønsted base-mediated [1,2]- phospha-Brook rearrangements have garnered considerable attention in the development of new methodologies, the strict reliance on pentavalent phosphonates imposes strong limitations on new reaction types. Here, the authors disclose a Lewis acid-mediated trivalent [1,2]- phospha-Brook rearrangement with carbonyl compounds to rapidly access tertiary phosphine oxides.

Lewis acid catalyzed tittle reaction of 1,3-dicycloalkenlidine ketones is recognized as so far the shortest and most effective 1-step method for construction of angular tricyclic scaffolds, which are extensively found in bioactive terpenoids. Here, the authors disclose the structure-reactivity relationship and a regioselectivity predicting model based on in situ IR technology, DFT calculations and machine leaning algorithms.

Ring contraction of easily available cyclic compounds to smaller cycles that are valuable but difficult to synthetically access is an important skeletal editing strategy. Here, the authors report a photo-promoted ring contraction of pyridines with silylborane to afford pyrrolidine derivatives bearing a 2- azabicyclo[3.1.0]hex-3-ene skeleton.

Transition-metal catalyzed cross-electrophile coupling (XEC) is a powerful tool for the construction of molecules but XEC between carbon electrophile and chlorosilanes to access organosilicon compounds remains underdeveloped. Here the authors disclose a highly efficient cobalt-catalyzed cross-electrophile alkynylation of a broad range of unactivated chlorosilanes with alkynyl sulfides as a stable and practical alkynyl electrophiles.

Substituted amines, especially nitrogen containing alkyl heterocyclic compounds, are widely found in nature products and drugs, but generally accessing these compounds requires multiple steps. Herein, the authors report a molecular editing strategy for the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials.

Due to the complexity of controlling factors and the diversity of reaction components, accurately delineating the bond formation mechanisms for copper-catalyzed radical transformations poses a challenge. Here, the authors reveal the linear free energy relationships for the C–C bond formation of Cu-catalyzed radical transformations.

The development of hydrogen atom transfer (HAT) in homogeneous catalytic acceptorless dehydrogenation (CAD) with selectivity for thorough aromatization under mild conditions remains challenging. Here, the authors propose a catalyst system that facilitates a double hydrogen atom transfer (HAT) processes for the CAD of inert cycloalkanes at ambient temperature under visible light irradiation.

The mechanochemical dechlorination of poly(vinyl chloride) (PVC) can catalyse reactions through the release of chlorides. Here, the authors use TiO₂ as a contact-electro-catalyst to achieve PVC dechlorination via ball-milling for the solvent-free, mechanochemical chlorination of alcohols.

Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial but the chirality orginiating from the distorted structure around heptagon-containing polyarenes is largely overlooked. Herein the authors present a highly enantioselective synthesis for fabrication of all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross–coupling of benzyl bromides and N-arylsulfonylhydrazones.

O-Sulfation is a vital post-translational modification in bioactive molecules, yet there are significant challenges for the synthesis. Here, the authors report a general and robust approach to O-sulfation by harnessing the tunable reactivity of dimethyl sulfate or diisopropyl sulfate under tetrabutylammonium bisulfate activation.

A transition-metal-free platform enables the formation of challenging C(sp³)–C(sp³) bonds in organic compounds via single-electron transfer, facilitating the coupling of functionalized fragments and expanding possibilities for efficient organic synthesis and reaction design.

Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. Herein, the authors present a simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization.

Direct and site-selective C–H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Here, the authors report a protocol for a variety of intermolecular Heck-type functionalization of C(sp2)–H bond of alkenes by thianthrenation.

When a wave packet traces a conical intersection, its phase must change a sign. The authors show direct experimental and computational evidence of this geometric phase effect for the hydrogen exchange reaction H + D₂ → HD + D.

Developing readily available and bench-stable reagents for the cyclopropanation of olefins is needed as traditional methodologies mainly rely on carbene-based strategies. Herein, the authors report a manganese-catalyzed cyclopropanation of allylic alcohols with sulfones via a borrowing hydrogen strategy under mild conditions.

Suzuki–Miyaura cross-coupling between (hetero)aryl (pseudo)halides and base-sensitive and Lewis-basic (hetero)arylboronic acids is challenging, owing to potential side reactions and catalyst poisoning. Now, the Suzuki–Miyaura cross-coupling of arylthianthrenium salts with (hetero)arylboronic acids, under acidic conditions, is reported, enabling the efficient coupling of base-sensitive and Lewis-basic (hetero)arylboronic acids.

Several methodologies have been proposed for hydroboration of cyclopropanes by activating C–C bonds, conventionally relying on noble and hazardous metal catalysts to control reaction outcomes. Here, the authors report a strategy for crafting stereochemically precise γ-borylenamides through ring-opening of cyclopropanes without metallic entities.

Using synchrotron vacuum ultraviolet photoionization mass spectrometry and quantum chemistry, this study uncovers a previously missing process by which aldehydes in engine combustion form organic acids, a finding critical for accurate emissions modelling and mitigation strategies.

Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry. But in contrast to the well-established transition-metal catalyzed methods, radical approaches are rarely explored. Here, the authors report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis

C(sp³)–H fluoroalkylation of bioactive molecules is a challenge. Now, a scalable and site-selective allylic fluoroalkylation of terpenes and olefins has been developed using a cobaloxime catalyst. Mechanistic studies reveal the process probably proceeds through halogen-atom transfer and hydrogen-atom transfer steps.

Chemoselective reactions of two or multiple functional groups with similar reactivities remain an ongoing challenge in chemistry. Here the authors disclosed a chemoselective reaction of enedial and observed that the high chemoselectivity is mainly controlled via redox (rather than steric) properties of the substrate/catalyst.

The application of catalytic dynamic kinetic asymmetric transformation (DyKAT) in axial chirality is limited to fivemembered metalacyclic intermediate-directed equilibrium of substrate enantiomers. Here, the authors report a tetracoordinate boron-directed DyKAT of racemic, configurationally stable 3-bromo- 2,1-azaborines for the construction of C-B axial chirality.

The precise and efficient construction of axially chiral scaffolds, particularly toward the aryl-alkene atropoisomers remains challenging. Here, the authors discuss an organocatalytic asymmetric nucleophilic aromatic substitution reaction of aldehyde-substituted styrenes involving a dynamic kinetic resolution process via a hemiacetal intermediate, offering a pathway to axial styrene scaffolds.

Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals but the direct single-step synthesis with broad structural diversity remains challenging. Herein, the authors report a modular assembly of tetrahydrocarboline type of indole alkaloids from simple building blocks in a single step while showing broad compatibility with medicinally relevant functionality

Regioselectivity during electrophilic aromatic substitution is typically controlled by substituents on the aryl group. Here the authors report an electrophilic aromatic substitution reaction, wherein remote chiral ester groups direct the electrophile to a precise location on the molecule.

Acceptorless dehydrogenation of simple alkanes and alcohols provides useful functionality and typically requires precious metal catalysts. Here, the authors dehydrogenate unactivated alkanes and alcohols at room temperature using earth-abundant metals with hydrogen as the sole by-product.

P-centered ring-opening of quaternary phosphirenium salts (QPrS) predominantly leads to hydrophosphorylated products, while the C-centered ring-opening results mainly in the formation of phosphorus-containing cyclization products. Here the authors synthesize β-functionalized vinylphosphine oxides by the P addition of QPrS intermediates generated in situ.

We report an S_NV reaction, a rare nucleophilic substitution that involves electronically unbiased vinyl electrophiles, which allows the synthesis of cross-conjugated polyenes and bioactive compounds with multi-substituted alkenes.

Electrochemistry offers tunable, cost effective and environmentally friendly alternatives to carry out redox reactions but the use of organoiodine compounds as electrocatalysts is largely underdeveloped. Here, the authors report an environmentally benign iodine(I/III) electrocatalytic platform for the in situ generation of dichloroiodoarenes for different reactions within a continuous flow setup.

Reforming 3d-metal-based visible light catalytic platforms for inert bulk chemical activation is highly desirable. Herein, the authors report the use of a Brønsted acid to unlock robust and practical iron ligand-to-metal charge transfer photocatalysis for the activation of multifarious inert haloalkylcarboxylates to produce halogencontaining alkyl radicals.