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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.

NMR spectroscopy is a powerful tool for studying chemical reactions, but short-lived intermediates are hard to capture. The authors present a system combining LED and rapid-injection NMR for in situ monitoring of photochemical processes, advancing the study of reactive species and kinetics.

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.

Hydroxyl groups are among the most abundant functional groups, and thus, the development of efficient reactions for their conversion has significant importance in medicinal and process chemistry. Here, we present a redox-neutral Giese reaction via anodic oxidation to generate phosphonium ions in combination with a cathodic reduction to yield low-valent Fe-catalysts.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

Real-time single-molecule observation provides insights into transient intermediates that are normally inaccessible using ensemble measurements. This Review discusses the use of nanopores as both single-molecule nanoreactors and single-molecule sensors for elucidating reaction pathways and kinetics, while highlighting their potential to control covalent reactions under confinement.

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.

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.

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.

Thianthrene, long used in materials science, has recently emerged as a powerful reagent in organic synthesis. Its unique electronic structure enables access to diverse aryl, alkenyl and alkyl thianthrenium salts, which exhibit reactivity beyond conventional (pseudo)halides. This Review highlights the fundamental properties, distinctive reactivity and synthetic applications of these thianthrenium salts.

Branched perfluorooctanoic acid and perfluorooctanesulfonic acid have shorter half-lives, lower toxicity, and weaker serum protein binding than linear ones, offering better environmental and health safety, but methods to access such branched motifs remain underdeveloped. Here, the authors introduce a one-step dehydroxy-perfluoro-tert-butylation of alcohols, in which perfluoro-tertbutyl phenyl sulfone serves both to activate the C–O bond and to deliver the perfluoro-tert-butyl group.

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.

A new tool based on generative machine learning called FlowER uses flow matching to model reactions as the redistribution of electrons between reactants and products, enabling the enforcement of mass conservation in reaction prediction.

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.

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.

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.

The guidance of experimental studies with computational exploration of reaction mechanisms has become a key tool in chemistry. This Perspective highlights challenges and best practices for generating reliable, reproducible and reusable data for quantum chemical calculations of reaction free-energy profiles.

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.

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.

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.

Achieving catalyst-free Ullmann couplings under mild conditions is crucial to extending the scope of traditional carbon-carbon and carbon-heteroatom couplings. Here, the authors show that Ullmann couplings can be effectively achieved at room temperature without the need for metal catalysts in MeOH/H2O microdroplets.

Here, the authors report a decoupled electrochemical flow microreactor hyphenated mass spectrometry (DEC-FMR-MS) platform for high-throughput reaction screening and intermediate tracking of electrosynthesis.

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.

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.

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.

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.

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.

The Soai reaction occupies a singular role in organic chemistry and chemical kinetics due to its autocatalytic and self-amplification behavior, which has spurred intense mechanistic investigation and debate. Here, the authors use in situ high-resolution mass spectrometry and accompanying techniques to identify reaction intermediates and bring about more granular detail of the reaction.

Vibrational strong coupling (VSC) can alter energy exchange in molecules. Here, authors show that VSC delocalizes OH stretches in water, enhancing intermolecular energy transfer rates and enabling new pathways via cavity-induced resonances.

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.

The prevalence of propargylic fluorides in bioactive molecules necessitates development of synthetic methods towards this connectivity. Here, the authors present a protocol to construct propargylic fluorides from allenes via I(I)/I(III) catalysis, delivering the products in high regioselectivity.

Empirically observed regiochemistries indicate that the CF₂H radical has a nucleophilic character similar to alkyl radicals, but the CF₃ radical is electrophilic in reactions with heterocycles. Here, the authors report DFT calculations, reproducing experimental selectivities and leading to an explanation of this difference.

The synthesis of drug-like saturated cycloalkanes is more complex than their two-dimensional aromatic analogues. A formidable challenge lies in synthesizing all isomers of multi-substituted cycloalkanes. Now a cobalt-catalysed system enables diastereodivergent hydroalkylation of substituted methylenecyclohexanes with exceptional versatility. Strategic manipulation of ligands provides access to all isomers of disubstituted cyclohexanes, piperidines and multi-substituted cyclohexanes.

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

Non-covalent interactions between organocatalyst molecules can change catalytic behaviour, leading to changes in reaction rates and selectivities. This Review discusses how to identify such interactions, measure their effect on catalysis and ultimately how to avoid or exploit them in synthesis.

For the carbonylation reactions to synthesize aldehyde, ester, amide, and other carbonyl derivatives, a transition metal-free and CO- free reaction was challenging but highly demanded. Here, the authors report a transition metal-free and CO- free method for deoxygenetive/denitrogenetive conversion of phenols and anilines to aldehydes and ketones.

We present a synthetic method that transforms complex pyrimidine-containing structures into iminoenamines and then uses de novo heterocycle synthesis to obtain substituted pyrimidine and 1,2-azole analogues.

The synthesis of sequence-regulated oligosulfates has not yet been established due to the difficulties in precise reactivity control. Here, the authors report a multi-directional divergent iterative method to furnish oligosulfates based on a chain homologation approach, in which the fluorosulfate unit is regenerated.

This study introduces a sustainable light-driven method for forming C(sp³)–C(sp³) bonds using carbon nitride and nickel catalysts, offering an efficient, iridium-free alternative for pharmaceutical synthesis with broad applicability and recyclability.

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.