ASAP (As Soon As Publishable)

The biosynthetic pathways leading to pseudoguaianolides and seco-guaianolides remain unclear. In this work, we demonstrate that highly oxidized 8,12-guaianolides serve as unprecedented precursors, enabling chemoselective, one-step access to pseudoguaianolide, seco-guaianolide, and xanthanolide-type sesquiterpenoids. Key mechanistic insights reveal the pivotal role of peroxide substituents on the guaianolide core and stereoelectronic factors in controlling reaction outcomes. These findings shed light on guaianolide selectivity and may mirror actual biosynthetic pathways, offering transformative potential for oxidative transformations in sesquiterpenoid synthesis.

Herein, an approach to a wide range of chiral 3-substituted δ-lactams from reductive coupling of Csp²-hybridized organohalides and 3-chloro-δ-lactams was described, and the products are versatile precursors for accessing enantioenriched 3-substituted piperidines. The utility of the reaction was highlighted by the economic synthesis of the chiral precursors of Preclamol and Niraparib. Notably, the modified chiral Bilm ligands were found to be the key factor for the reactivity and enantioselectivity.

The hydroarylation of methylenecyclopropanes (MCPs) is a challenging process due to the difficulty in controlling regioselectivity and the complex reaction patterns involved. Herein, we report a simple external ligand-free Ni-catalyzed ring-opening hydroarylation of MCPs with high efficiency and unprecedented regioselective arylation as well as broad functional group tolerance by using inexpensive aryl boronic acids as the arylation source. The synthetic utility has been demonstrated for the facile preparation of versatile highly valued products. Mechanistic studies suggest that Ni(II)–H, formed via the oxidative addition of Ni(0) to the proton in the system, might act as a key intermediate.

A simple and efficient method has been developed for the synthesis of 2,3-disubstituted benzo[b]thiophene-1,1-dioxides and naphtho[1,2-b]thiophene-1,1-dioxides via a ruthenium(II)-catalyzed annulation of benzenesulfonyl or naphthalene-2-sulfonyl azides with 1,4-diaryl/dialkyl-buta-1,3-diynes. The reaction proceeds through an ipso-attack, followed by an S-migration pathway. This strategy enables late-stage derivatization and offers a streamlined approach for accessing structurally diverse heterocyclic scaffolds with potential applications in therapeutics and photoluminescence materials.

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.

The use of simple raw materials to construct complex piperidine scaffolds via multicomponent reactions is highly desirable from the perspectives of atom and step-economy. In this Letter, we present a photoinduced copper-catalyzed three- or four-component [3 + 2 + 1] radical cyclization, utilizing inexpensive and readily available feedstock amines, alkynes, and aldehydes, to synthesize multisubstituted bicyclic or spirocyclic tetrahydropyridines. This method is notable for its mild conditions, atom-economic approach, excellent regio- and diastereoselectivity, and the simultaneous activation of two α-amino C(sp³)–H bonds, resulting in the formation of three C–C bonds and one C–N bond in a single step. Mechanistic studies suggest that the α-aminoalkyl radical is the key intermediate in this reaction, which undergoes sequential radical addition, 1,5-HAT, and 6-exo-trig-type radical cyclization.

Different Z/E-isomers of functional molecules display distinct chemical and biological activities. The E → Z isomerization reaction is a contra-thermodynamic direction and presents a long-standing challenge in synthetic transformation. To date, organic catalysis methods for manipulating E/Z isomerization are still under development. Here we show a new N-heterocyclic carbene (NHC)-catalyzed E/Z isomerization mode. The E-isomer enedial undergoes E/Z isomerization to give a Z-isomer Breslow intermediate via NHC catalysis, and an intramolecular hydrogen bond can greatly stabilize this conformation. Subsequently, the Brønsted acid promotes the further redox-neutral reaction. The desired ralfuranone products obtained from our method can be readily transformed to various functional molecules.

Aryl iodides are essential synthons in organic synthesis, whose conventional preparations often suffer from poor selectivity or necessitate multistep procedures. Herein, we present a light-driven denitrative iodination as a one-step approach that directly converts nitroarenes to iodoarenes under mild and transition-metal-free conditions. This streamlined method operates in the absence of strong Brønsted acids, ensuring broad functional group tolerance, including esters, cyano groups, halides, and heterocycles, while also offering operational simplicity and scalability.

Herein, we report a gold(I)-catalyzed heterocyclization/(5 + 3) cycloaddition cascade of yne-enones with imidazolidines, providing a modular, atom-economical and efficient strategy for the synthesis of cycloocta[c]furans in moderate to excellent yields. This method features readily available substrates, simple operation, mild reaction conditions, and broad substrate scope. More importantly, the asymmetric version is also achieved by employing (R)-C₂-TunePhos ligand (L7), leading to optically active cycloocta[c]furans with up to 98:2 er.

A palladium-catalyzed three-component coupling of 2-arylaziridines, α-diazo esters, and cyclic ethers, affording tertiary enamides with excellent regio- and stereoselectivity, is reported. This regioselective ring-opening of aziridines is different from the classical transition-metal/phosphine catalyzed ones. A broad spectrum of substrates is tolerated (up to 33 examples). An ortho-aryl substituent on the naphthyl ring of 1,1′-bi-2-naphthol (BINOL)-derived phosphoramidite ligand is critical for this coupling, and the additional diphosphine (DPEphos) ligand can further enhance the reactivity. Mechanistic studies suggest that 10-membered and 9-membered palladacycle intermediates may be formed and followed by twice reversible β-H eliminations.

We developed a stereoselective synthesis strategy for α-fluoroacrylate-substituted β-lactams, utilizing an innovative acid–base synergistic regulation approach. This method employs a dioxane-mediated microreaction environment to spatially separate acidic and alkaline reagents, enabling precise control over cyclization and fluorination processes. This strategy enhances catalytic efficiency and addresses challenges in Pd-catalyzed reactions, offering a new paradigm for synthesizing fluorinated drug molecules amid acid–base complexities.

A divergent copper-catalyzed defluorinative C(sp³)–C(sp²) cross-coupling of gem-diborylalkanes with polyfluoroarenes has been developed through a synergistic ligand/base-controlled strategy. Various fluorinated aromatic compounds were obtained in moderate to excellent yields. Late-stage modification of bioactive molecules, gram-scale reaction, and versatile downstream derivatization demonstrated the application value of this protocol. Preliminary mechanistic studies hinted that this transformation is a S_NAr mechanism rather than a radical pathway.

An enantioselective hydrogenation of β-azaaryl α,β-unsaturated nitriles catalyzed by a rhodium/(S_C,R_p)-N-Me-ZhaoPhos complex has been developed, offering an efficient and highly stereoselective route for the asymmetric synthesis of ruxolitinib (>99% yield, 99% ee). A wide range of α,β-unsaturated nitriles were hydrogenated to the corresponding products with excellent enantioselectivities (up to 99% ee). This methodology provides a versatile and practical approach to accessing bioactive chiral nitriles, including key intermediates for pharmaceuticals such as ruxolitinib precursors.

A novel copper-catalyzed approach for the stereoselective cyanation and phosphorylation of formamides has been developed. This protocol enables the direct conversion of a broad range of formamides and phosphorylation agents, including H-phosphonates, H-phosphinates, and H-phosphine oxides, into the target cyanation/phosphorylation products with good to excellent yields. Notably, when optically active H-phosphinates are employed, the transformation exhibits exceptional stereoselectivity. In combination with DFT calculation and systematic step-by-step control experiments, a possible reaction mechanism is proposed.

Herein we describe a modular and umpolung (4 + 1) cyclization strategy for synthesizing functionalized 2,2-disubstituted pyrrolidines decorated with versatile alkene, alkyne, and carbonyl groups under mild basic conditions. The new approach employs readily accessible N-haloalkyl hydroxylamines as distinctive carbon–nitrogen bielectrophiles, enabling a tandem C–C alkylation and umpolung C–N ring-closing reaction with diverse carbonyl nucleophiles. Furthermore, a catalytic asymmetric variant of this reaction has been also achieved with moderate enantioselectivity (72% ee) under the chiral phase-transfer catalytic conditions.

The one-pot two-step stereoselective synthesis of 1,2-trans-1-C-1,3-dithian-2-yl and 1,2-cis-1-C-nitromethyl iminosugars from sugar lactams is disclosed, exploiting Schwartz’s reagent triggered amide to imine reduction followed by Corey–Seebach or nitro-Mannich-mediated functionalizations. Processing of the dithiane moiety provided the naturally occurring β-HNJ and α-HMJ homoiminosugars, while processing of the nitromethyl group gave access to α-HNJ and pipecolic acid derivatives. Epimerization of this function was also successfully examined. Final hydrogenolysis furnished a set of known and new glycomimetics, amongst which two compounds displayed potent glycosidase inhibition.

An efficient catalytic asymmetric olefin isomerization of axially chiral methylene dihydrofuran-benzimidazoles via kinetic resolution is reported. Under mild phase-transfer catalysis, axially chiral furan-benzimidazole compounds and recovered methylene dihydrofuran-benzimidazoles were obtained in high ee. The combination of the kinetic resolution and TBD-catalyzed isomerization of recovered dihydrofuran-benzimidazoles provided access to both enantiomers of furan-benzimidazoles. Deuterium-labeling experiments reveal intramolecular [1,3]-H transfer mechanism. The utility of this method was demonstrated by scale-up synthesis and functionalization of the products.

Corymbinols A (1) and B (2a/2b), unprecedented bis-β-triketone-sesquiterpene and -chalcone hybrids, together with their biogenic precursors corymbinol C (3) and rhodomyrtosone E (4) were isolated from the untapped fruit of Corymbia citriodora. The absolute configurations of these compounds were determined by NMR spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray crystallography. Compound 1 exhibited moderate inhibitory activity against cuproptosis in HepG2 cells by 31% at a nontoxic concentration of 20 μM.

In this study, we synthesized a series of novel fused-ring azo-bridged compounds incorporating nitramine, azide, and hydrazine functional groups. The newly synthesized compounds exhibited promising energetic properties, including good densities (1.71–1.76 g cm^–3), good detonation velocities (7203–8104 m s^–1), controlled impact (2.5–40 J), and friction sensitivities (120–360 N), and the thermal stability ranged from 128 °C to 300 °C. Notably, compound 4 demonstrated exceptional thermal stability (300 °C) as an heat-resistant explosive, while compound 7 emerged as a highly promising lead-free primary explosive with an ultralow minimum primer charge of just 40 mg.

An iridium-catalyzed asymmetric allylic substitution with sequential boron incorporation is reported. The reaction accommodates a wide range of substrates, affording chiral N,O-bidentate difluoroboron complexes in excellent yields with high enantioselectivities. Furthermore, decigram-scale reaction, synthetic transformations, as well as photophysical property investigations of the N,O-bidentate difluoroboron complexes are explored.

A stereodivergent synthesis of bicyclic α-C-, β-O-, and α-O-glycosides is achieved with nonprecious Co(dpm)₃, K₂CO₃, and DBU, respectively. Cobalt-catalyzed decarboxylative allylation of 2,3-unsaturated 4-keto glycosyl carbonates with 1,3-diketones delivers α-C-glycosides in good yields with exclusive chemo- and regiocontrol and excellent diastereoselectivity (>20:1 dr). K₂CO₃ enables β-O-glycosides via a cascaded intermolecular Michael addition/S_N2-like cyclization, whereas DBU promotes further C5 epimerization to give α-O-glycosides. Mechanistic studies (deuterium labeling and intermediate capturing) validate the pathways. Gram-scale synthesis and late-stage functionalization of pharmaceuticals demonstrate practicality.

This paper describes a novel coordinating activation strategy that enables the synthesis of medium-to-large sized rings (11–17 members) via an unprecedented difluoroalkylamidation cyclization of alkynes. This method provides an efficient platform for accessing skeleton-diverse difluoroalkyl-containing cyclic enamides with complete regio- and stereoselectivity. The protocol features broad substrate compatibility, functional group tolerance, and ease of use at dilution concentrations (50 mM) that are not high. Moreover, the synthetic utility of this difunctional cyclization is underscored by its application in the late-stage modification of complex molecules. Additionally, the click reaction facilitates the derivation of alkynyl-substituted cyclization products, demonstrating the methodology’s potential in biological sciences.

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.

Biaryl frameworks are pivotal in natural products, pharmaceuticals, agrochemicals, and materials, with the 2′-amino-2′-hydroxy-1,1′-biaryl motif being especially valuable for catalysis and bioactivity. However, synthesizing these non-C₂-symmetric biaryls efficiently and regioselectively remains challenging due to limitations in current methods, such as prefunctionalization and structural constraints. Herein, we report a regioselective oxyamination of cyclometalated biaryl lanthanum reagents using nitroarenes. This lanthanum-based approach uniquely utilizes the oxophilicity and nucleophilicity of organolanthanum intermediates, enabling dual incorporation of oxygen and nitrogen into biaryl skeletons. A proposed 8-membered metallacycle intermediate avoids undesired nitrosoarene formation, delivering 2′-amino-2′-hydroxy-1,1′-biaryls with high efficiency. This one-pot, step-economical and transition-metal-free method achieves exceptional regioselectivity and a broad substrate scope, addressing longstanding challenges in biaryl functionalization and providing significant implications for catalysis, drug development, and materials science.

We present a strategy involving central-to-axial chirality conversion for the construction of axially chiral N-arylpyrroles via a cooperative copper-squaramide-catalyzed remote propargylic amination/ring closure/rearomatization cascade from yne-allylic esters. The reaction exhibits excellent chemical efficiency and enantioselectivity, involving good central-to-axial chirality conversion. The use of squaramide as cocatalyst is crucial for the success.

Triggered by the reaction of an oxime ether with a rhodium carbenoid, nitrogen-containing three-dimensional frameworks were constructed from linear motifs via the intramolecular cycloaddition of endo-cyclic azomethine ylide. In this transformation, successive stereocenters containing quaternary carbons were formed, affording the corresponding tricyclic compounds in moderate-to-good yields. The utility of these products was demonstrated through several transformations.

The example of iron-catalyzed alkenes migratory silylation and transposition has been demonstrated, affording a tunable approach to synthesize thermodynamically stable allylsilanes and internal alkenes with high efficiency and regioselectivity. These reactions showcase several advantageous features, including good functional group tolerance, excellent regioselectivity, a broad substrate scope, scalability to gram-scale synthesis, and late-stage functionalization of bio-relevant molecules. Furthermore, the relay catalytic mechanism of the migratory silylation, involving both iron-silyl and iron-hydride intermediates, provides valuable insights into iron-catalyzed coupling reactions, opening new avenues for the development of novel transformations under iron catalysis.

An efficient dehydroxythiolation between alcohols and disulfides using the widely abundant and cheapest iron as a reaction mediator was developed. The one-pot thiolation proceeded effectively via C–O bond activation with the aid of cyanuric chloride (TCT) as a hydroxyl-activating agent to give the corresponding thioethers in modest to excellent yields, displaying both a wide substrate scope (applicable to benzyl alcohol, allyl alcohol, and primary alkyl alcohol) and good functional group tolerance. In addition, diselenide was also proven to be an appropriate substrate for the protocol, and the reaction could be subjected to scale-up synthesis. Preliminary mechanistic examination revealed that transiently formed TCT-derived ether A, which is generated in situ via the reaction of TCT with alcohol, possibly serves as the pivotal intermediate of the cross-electrophile thioetherification.

The bicyclo[3.2.0]heptane scaffold is frequently found in a wide range of bioactive molecules and plays a pivotal role in constructing key modules of these compounds. In this study, we present a strategy for the synthesis of bicyclo[3.2.0]heptanes using a copper/BINAP complex to facilitate an intramolecular [2+2] cycloaddition under visible light irradiation. This methodology offers several advantages, including the use of a cost-effective copper catalyst and the ability to achieve high yields (up to 98%) and diastereoselectivity (>20:1 dr). Our approach provides an efficient strategy for constructing the bicyclo[3.2.0]heptane framework.

While saturated nitrogen heterocycles are privileged scaffolds, their streamlined catalytic synthesis with unsymmetrical substitution patterns remains a daunting challenge. Herein, we report the ruthenium(II)-catalyzed synthesis of spiro[indene-proline] derivatives via C–H activation/annulation of 5-phenyl-pyrroline-2-carboxylates with alkynes. The protocol utilized imine coordination, resulting in high reaction yields with a wide range of functional group tolerance, scalability, and scaffold diversity. This annulation was successful even with various biologically active pharmacophores. The reaction featured a reversible C–H metalation step and suggested the possibility of a base-assisted internal electrophilic substitution pathway.

An unprecedented successive radical-promoted thiolative annulation/Pd-catalyzed C–H amination of N-benzyl-N-cyanopropiolamides to access pyrrolo[2,1-b]quinazolin-1(9H)-ones in a one-pot manner is described. Moreover, altering the amination step with oxidation (reagent switch) offered maleimides from the same set of readily accessible precursors. Both transformations display versatility across a wide range of substrates, enabling the efficient access to various functionalized quinazolin-1-ones and maleimides in good yields.

We developed a novel nitration method using hypervalent iodine for site-selective C–H functionalization. This technique efficiently synthesizes nitroarenes with high regioselectivity and is scalable, enhancing the late-stage modification of bioactive pharmaceuticals.

Highly functionalized sulfone containing scaffolds are ubiquitous and are attracting increasing interest in pharmaceutical and agrochemicals owing to their enhanced activities. Herein, we present an alternative protocol to access highly substituted sulfones from readily accessible olefin feedstocks and sulfinate salts through a DABSO enabled anti-Markovnikov hydrosulfonylation process. Notably, the practical procedure features excellent compatibility with various susceptible functional groups and a broad substrate scope under mild and operationally simple conditions. Gram-scale preparation, post-functionalization of complex molecules, and applications in the synthesis of bioactive compounds underscore the potential in drug discovery.

Here, we report sulfur–azide exchange (SuAEx), which facilitates the efficient synthesis of sulfonate esters via the reaction of sulfonyl azides with phenolic substrates under mild conditions. The reaction tolerates a wide range of functional groups. Notably, SuAEx displays a distinct preference for phenolic hydroxyls over aliphatic alcohols, providing orthogonality critical for complex molecular editing. Its utility is further demonstrated through iterative ligation strategies when combined with azide–alkyne cycloaddition reactions.

A photoinduced radical arylboration of unactivated alkenes with B₂pin₂ and aryl nitriles was developed, providing a mild and efficient approach to access useful β-aryl boronates in the absence of a transition-metal catalyst. This reaction undergoes a boron radical addition to alkene and a subsequent radical–radical coupling process. This approach showcases good functional group compatibility and provides a promising and complementary strategy to boron chemistry and traditional transition-metal-catalyzed coupling.

Here, by condensing each of two bisformyl precursors with the corresponding bishydrazide partner in water, two ultrasized macrocycles could be self-assembled. One was self-assembled within the cavity of cucurbit[8]uril (CB[8]) acting as an external template, forming a ring-in-ring complex. The other requires the presence of both CB[10] and a π-electron-rich guest as an external/internal template, thus forming a ternary complex “Russian doll”. When all seven precursors were combined in water, self-sorting occurred without forming hybridized products.

The stereodivergent synthesis of δ-lactones, which are prevalent in natural product frameworks, from simple starting materials via a single transformation remains a significant challenge. Herein, we report an enantio- and diastereodivergent cascade reaction for the modular synthesis of chiral δ-lactones bearing two nonadjacent quaternary and tertiary carbon stereocenters. This approach employs bimetallic Ru/Cu relay catalysis between allylic alcohols and azaaryl acetates. This method integrates Ru-catalyzed asymmetric borrowing hydrogen reaction, Cu-catalyzed asymmetric Michael addition, and rapid lactonization into a one-pot process, with all catalysts and substrates introduced at the outset. By orthogonal permutation of two chiral metal catalysts, precise control over the relative and absolute configurations of the newly formed nonadjacent stereocenters is achieved, allowing selective access to all stereoisomers of the δ-lactone products in a predictable and efficient manner.

We synthesized three 28-membered chiral cross-chain bridging cryptands ([3.3.6], [4.4.5], and [5.5.4]) with three different linker combinations. After the separation of their enantiomers, the racemization behavior of the cryptands was evaluated by chiral high-performance liquid chromatography. As the number of ethylene glycol units in the two cross-chain linkages increased, the racemization reaction proceeded slowly.

Herein, we developed an intramolecular radical cyclization reaction between imines (or aldehydes) and olefins using Hantzsch ester as the reductant to enable the efficient and diastereoselective synthesis of 1,2,3,4-tetrahydroquinoline scaffolds with a high medicinal value. Deuteration experiments indicated that the radical intermediate abstracts a hydrogen atom directly from the 4 position of the Hantzsch ester, thereby ruling out the possibility of an anionic intermediate formation via the radical crossover pathway. A fast synthesis of BRD4 degraders and the elucidation of their cellular and enzymatic activities demonstrate the practicality of this method.

A highly oxygenated γ-pyrone with an unprecedented carbon skeleton, peunipyrone A (1), was isolated from the sponge-derived fungus Aspergillus peuniceus. Compound 1 features a unique fused 6/6/6/6/6 pentacyclic ring system. The chemical structure of compound 1 was elucidated by comprehensive spectroscopic techniques and single-crystal X-ray diffraction. The plausible biosynthetic pathway of compound 1 was proposed. Compound 1 promoted leukemic cell apoptosis by increasing p53 expression.

The Tf₂O-promoted cascade cyclization of 2-benzoylbenzoic acids with arylalkynes was achieved under solvent-free ball-milling conditions. This process renders rapid entry to the rare indene-containing spirolactones via intramolecular cyclization of 2-benzoylbenzoic acids and subsequent annulation with arylalkynes, which resulted in one C–O and two C–C bond formations. As the reactions utilize easily available starting materials and proceed in the absence of organic solvents, the present protocol constitutes an expedient and environmentally friendly access to indene-containing spirolactones.

The dithiocarbamate group is an important class of compounds whose presence in small molecules and peptides leads to antimicrobial, anticancer, and enzyme inhibition properties. This study introduces an efficient and selective method for incorporating dithioate and trithioate moieties into amino acids and peptides using CS₂ chemistry under mild conditions. Utilizing a N,N-diisopropylethylamine (DIPEA)-CS₂-benzyl chloride system, we achieved modifications at the N-terminal amines and the side chains of Lys and Cys residues through solid-phase peptide synthesis (spps). The method exhibits excellent yields and broad compatibility with diverse amino acids, their protection groups, peptide chemistry reagents, and varied peptide sequences. Notably, the successful incorporation of trithioate groups into peptides via cysteines, reported here for the first time, expands the functional repertoire of peptide chemistry, offering new possibilities for peptide-based drug design and related applications.

By combining the well-known motifs of BODIPY dyes and cycloparaphenylenes, novel nanohoop derivatives were accessible via established procedures. Absorption and emission spectra showed overall bathochromic shifts, and their photophysical behavior can be tuned by introducing steric demand to modulate the conjugation throughout the system. ¹⁹F NMR spectra underline distinct differences in the conformations, and (TD)DFT calculations provide a deeper insight into the geometry, photophysical behavior, and influence of steric demand.

We describe for the first time a photochemical branched hydrothiocarbonylation of vinyl arenes with bench-stable 1,4-dihydropyridine thioesters to furnish various thioesters in high regioselectivity. 4CzIPN assists in the activation of DHP-thioester precursors. The Pd/phosphine catalyst system plays a role in harnessing reactivity and achieving site-selectivity. In this mild and scalable method, various thioesters can be obtained with good functional group tolerance, including late-stage thioesterification to deliver drug-conjugates. A branched hydroselenocarbonylation of styrene is also achieved with DHP-selenoester to afford the selenoester.

Transition-metal-catalyzed [2 + 2 + 2] cycloaddition reactions of alkynes, nitriles, and other π partners have been recognized as economic strategies to assemble aza-six-membered rings, but access to pyrimidin-2-ones is not disclosed. Herein, we report a palladium-catalyzed [2 + 2 + 2] cycloaddition of 1,3-diyne-substituted malononitriles and isocyanates for the construction of polysubstituted pyrimidin-2-ones. This reaction features a broad substrate scope and moderate to high yields. Conjugated pyrimidin-2-one acting as a fluorophore showcased potential as a fluorescent chemosensor for Fe(III) detection.

Herein, we report a divergent synthesis of cationic azatriphenylene derivatives using orthogonal control of thermal and electro-oxidative pyridination, which transforms the single precursor into controlled products with perfect selectivity. Simultaneously, two switchable reactions afford the corresponding pyridinium salts with different optical properties such as aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) effects.

The visible-light induced cross-dehydrogenative coupling of C(sp³)–H bonds with phenols using BrCCl₃ to give aryl alkyl ethers has been achieved under transition-metal- and photocatalyst-free conditions. This operationally simple and mild protocol has a broad substrate scope, and was applied to the modification of drug molecules and on a gram-scale synthesis. The phenolate ion functions as both a substrate and photosensitizer, and BrCCl₃ serves as the oxidant and hydrogen atom transfer (HAT) agent.

A new process for the synthesis of densely functionalized N-bridged octahydrobenzofurans and hexahydrobenzofurans, by means of a two-step protocol, is reported. The mechanism involves a novel catalytic rearrangement reaction, a Diels–Alder reaction, and an intramolecular aza-addition cyclization. Preliminary bioassays showed that compound 3d more strongly inhibited Staphylococcus aureus, while compound 4d displayed excellent insecticidal activity against Spodoptera litura Fabricius.

The site-selective incorporation of sulfilimine functionalities into aromatic compounds provides a vital strategy for drug discovery in medicinal chemistry. However, green and sustainable methods for realizing the goal are still limited. Here, we report a copper-catalyzed S-arylation of sulfenamides with aryl thianthrenium salts irradiated by visible light without the photocatalyst, which exhibited fine functional-group compatibility and gave the desired products in high yields. Mechanistic investigations revealed that the key to achieving these results is the generation of an electron donor–acceptor (EDA) complex between sulfenamides and aryl thianthrenium salts under basic conditions.

Regioselectivity in C–H activation is crucial for applications in pharmaceuticals and advanced materials. Machine learning (ML) techniques enhance the speed and accuracy of regioselectivity prediction in palladium-catalyzed directing group-assisted C–H activation in aryl substrates. Among the models tested, the standard support vector machine (SVM) model demonstrated better generalizability, achieving an F1 score of 0.92 and MCC of 0.93 on the test set. This approach aids the development of efficient catalytic strategies for C–H activation.

A regioselective 1,2-carboacylation protocol of alkenes via nickel/photoredox dual catalysis has been successfully developed under mild conditions. A wide range of alkyl bromides, α-oxocarboxylic acids, and styrenes proved to be compatible under the optimized conditions, affording the corresponding 1,2-carboacylation products in up to 91% yields. Mechanistically, the key to the success of this approach is the temporal orchestration of radical generation: nickel-catalyzed halogen atom transfer (XAT) for alkyl bromides and photoredox-driven decarboxylation for α-oxocarboxylic acids.

Double [8]helicene 1, featuring a dibenzo[g,p]chrysene core, was synthesized via the Scholl reaction, and its structure was unambiguously confirmed by single-crystal X-ray diffraction analysis of its dicationic salt [1–Cl]²⁺·(SbCl₆^–)₂. The compound exhibits red fluorescence with an emission maximum at 618 nm (λ_em) and a quantum yield of 16.2%, highlighting its potential in optoelectronic applications. Furthermore, circular dichroism (CD) and circularly polarized luminescence (CPL) measurements reveal notable chiroptical activity, with absorption and emission dissymmetry factors of |g_abs| = 5.11 × 10^–3 and |g_lum| = 7.1 × 10^–4, respectively.

An asymmetric catalytic Pudovik addition/[1,2]-phospha-Brook rearrangement/allylation reaction of readily available isatins, phosphites, and vinyl ethylene carbonate enabled by a chiral iridium catalyst was developed in a one-pot fashion. A wide range of enantioenriched oxindole derivatives containing two adjacent stereocenters could be obtained in good to high yields with excellent diastereoselectivity and enantioselectivity (65–99% yield, 7:1 to >20:1 dr, and generally 99% ee). This cascade protocol owned the advantages of readily available starting materials, high regio-/diastereo-/enantioselectivity, and good substrate scope generality.

Herein, we report the concise total syntheses of (+)-leucolusine and (−)-7-epi-leucolusine achieved in 8 steps starting from commercially available piperidin-2-one. Our strategy highlights a palladium-catalyzed decarboxylative asymmetric allylic alkylation for constructing the δ-lactam bearing a C20 all-carbon quaternary stereocenter. Additionally, the cis-fused octahydrofuro[2,3-b]pyridine unit was efficiently constructed via a one-pot protocol encompassing reduction and oxa-Mannich-type cyclization processes.

Herein, we report a Pd-catalyzed β-C(sp³)–H biarylation of native amides using diaryliodonium salts. A pyridine-3-sulfonic acid ligand that might stabilize the substrate-bound palladium species was found to be essential for high catalytic activity. The reaction displayed a broad scope and showed excellent compatibility with diverse cyclic diaryliodonium salts and amide substrates. The retained iodo functionality on the product provides a versatile handle for further increasing molecular complexity.

Herein, we demonstrate chelating-group-assisted C(sp²)–O reductive elimination at gold(III) centers. Detailed stoichiometric studies highlighted the importance of a chelating group for achieving successful C–O reductive elimination, paving the way for the development of a catalytic version. The mechanistic investigations, including control experiments, ³¹P NMR, mass spectrometry, and density functional theory (DFT) studies, suggested that the synergistic effect of the ligand and chelating group creates a highly coordinated environment around the Au(III) center to facilitate the C(sp²)–O bond-forming reaction.

Arene isomerization can simultaneously edit the arene backbone and its periphery, thereby bridging the independent chemistry of two distinct arenes. Herein, a facile pyrone isomerization approach for the divergent synthesis of five- and sixfold-substituted biaryl phenols is achieved by using a relay Claisen rearrangement as a crucial step. This catalyst-free isomerization reaction features high step, atom, and redox economy by transferring the innate oxidation state of pyrone into the biaryl phenols. Additionally, an intriguing self-activation phenomenon was observed, which enabled the selective dienone–phenol rearrangement of the aryl group.

Photoredox catalysis has garnered significant attention in organic chemistry for its ability to promote chemical transformations under visible-light irradiation. To date, research on salt-based organophotoredox catalysts has mainly concentrated on the development of oxygen- and nitrogen-based catalysts such as acridinium and pyrylium salts, whereas sulfur-containing catalysts have received far less attention. Herein, we report a strongly oxidizing tert-butyl-substituted thiapyrylium organophotoredox catalyst (^tBu-TTPP) that exhibits a high excited-state reduction potential (E_1/2(C*/C^•–) = +2.23 V vs SCE) and can be activated by blue LEDs. The ^tBu-TTPP catalyst provided promising results in various photoredox reactions, such as radical-cation Diels–Alder reactions, trifluoromethylations, the [4 + 2] annulation of alkynes and thiophene, and the C–N cross-coupling of fluoroarenes, demonstrating its potential in photoredox catalysis.

The rare-earth Ce(OTf)₃-catalyzed asymmetric 6π cyclization of triaryldivinyl ketones is realized, affording methyl (R,E)-1-aryl-2-arylmethylidene-3-hydroxy-1,4-dihydronaphthalene-2-carboxylates in moderate to good yields with good to excellent enantioselectivities. The reaction provides a new strategy for the construction of optically active 3-hydroxy-1,4-dihydronaphthalene-2-carboxylic acid derivatives.

In this study, we have devised a strategy that employs oxime carbamate as a bifunctional diamination reagent in combination with SO₂ to realize imino-sulfamoylation of alkenes. This protocol is characterized by its mild conditions, operational simplicity, and metal-free nature, while demonstrating broad functional group tolerance for alkenes. Furthermore, the application of this method provides an accessible route to a diverse range of β-amino sulfonamide derivatives.

A domino inverse electron-demand Diels–Alder reaction/thermal ring expansion sequence was developed to enable the one-step synthesis of arene-annulated eight-membered nitrogen heterocycles from readily available aromatic 1,2-diazines. A boron-based, bidentate Lewis acid catalyst facilitates the initial cycloaddition of Boc-protected 2-azetine with various electron-poor and electron-rich phthalazines. The subsequent electrocyclic ring expansion furnishes azocines fused to differently substituted aromatics, a structural motif that holds vast potential for further derivatization.

A nickel-catalyzed site-selective reductive carbonylation of arenes via aryl thianthrenium salts is described. Using Mo(CO)₆ as a convenient solid CO source and reductant and employing nitroarenes and sulfonyl chlorides as readily available nitrogen and sulfur sources, a range of aryl amides and aryl thioesters were successfully synthesized in moderate to good yields. The utility of this transformation is demonstrated through the synthesis of antimicrobial agents and the late-stage functionalization of biorelevant molecules.

Aryl chlorides are more commercially available and lower cost compared with aryl bromides and iodides. However, the use of (hetero)aryl chlorides as aryl radical precursors for the di(hetero)arylation of alkenes remains an underdeveloped area. Furthermore, existing examples of theses reactions are predominantly confined to activated alkenes. In this study, we introduce a photoirradiation-promoted benzophenone-catalyzed 1,2-di(hetero)arylation process that is applicable to both activated and unactivated alkenes, utilizing (hetero)aryl chlorides and cyanoarenes as aryl sources. Importantly, this method allows for the simultaneous introduction of two heterocycles to alkenes with high regioselectivity.

A novel transition-metal-free radical coupling of 2-azaallyl anions for the synthesis of α-amino ketones has been developed. Easily accessible thioesters and 2-azaallyl anions undergo single electron transfer (SET) to generate acyl radicals, which participate in intermolecular radical coupling to generate α-amino ketones with good functional group tolerance and yields (31 examples, up to 98% yield). A telescoped gram-scale synthesis and derivatization of the product illustrate the potential synthetic utility of this method. Radical trapping and radical clock experiments support the proposed radical coupling pathway between the generated acyl radical and the 2-azaallyl radical.

Oxepino[b]indoles were obtained in good to excellent yields employing a [4 + 3]-cycloaddition initiated by a stereo- and regioselective, Rh^II-catalyzed cyclopropanation between a vinyl allene and diazooxindole to afford an intermediate cyclopropyl allene that engaged the oxindole carbonyl in a spontaneous hetero-[3,3]-rearrangement. A survey of functional group tolerance revealed a diverse array of substrates amenable to oxepino[b]indole formation. In addition to the intriguing architecture of the cycloadducts, exposure to either Brønsted acid or base enables the assembly of functionalized spirroxindoles via the unusual conversion of a 5–7 fused ring system to a 5–5 spirocycle.

Bacterial tryptophan dimers comprise a large family of natural products with promising biological activities. Herein, we report the identification of a methyltransferase, SpmM1, which acts as a gatekeeping enzyme to govern the divergent biosynthesis of tryptophan dimers spiroindimicins (SPMs) and indimicins (IDMs) in Streptomyces marincola SCSIO 03032. Bioinformatics, genetic, and biochemical studies revealed that SpmM1-catalyzed carboxyl O-methylation enabled the common precursor of SPMs and IDMs to flux into the spiro-forming pathway to generate SPMs.

Five new macrocyclic napyradiomycins with different types of scaffolds were isolated from marine-derived Streptomyces canus SJ-019. Compounds 1 and 2 are uniquely typified by a spirocyclic core, while 1, 2 and 4 also contain a unique macrolide structure not known in any other napyradiomycins. Compound 3 is composed of a dearomatized napyradiomycin core and an intramolecular double-arch bridge system. Compound 4 displays potent inhibition of Staphylococcus aureus, while C-type napyradiomycin 5 shows notable anti-inflammatory effect.

Here, we report the use of iminosulfur oxydifluorides, derived from SOF₄ and primary amines, for the generation of the unprecedented aza-analogues of fluorosulfury azide (FSO₂N₃), namely, fluorosulfonimidoyl azide (R-N═SOFN₃). Unlike FSO₂N₃, R-N═SOFN₃ acts as a sulfamoyl nitrene precursor, undergoing imidation with sulfoxides and thioethers to from products featuring unique “-N = S(VI)F–N = S(VI)-” linkages without metal catalyst. The fluoride at the S(VI) center can be sequentially exchanged to generate diverse three-deminsional structures with tunable SuFEx reactivity. Mechanistic studies reveal that R-N = SOFN₃ decomposes to the sulfamoyl nitrene intermediate, which is stabilized by the adjacent “-S(VI)=N-” nitrogen atom. This facilitates the formation of three-membered rings that react further with S(IV)/S(II). These novel transformations expand the scope of SOF₄-based SuFEx chemistry, demonstrating that R-N = SOFN₃ enables dual reactivity through both nitrene-driven and tunable SuFEx-based linkages.

Alkyl azetidines have been prepared by photochemical modifications of azetidine-2-carboxylic acids in batch and in flow. The reaction has been realized in milligram, gram, and even multigram quantities. The obtained azetidines are valuable building blocks for drug discovery.

Thiophene-based derivatives are cost-effective and promising electron-donating units in high-performance π-conjugated materials for organic electronics. Fluorination is crucial for modulating their electronic and structural properties; however, few studies have been conducted due to synthetic challenges. We developed a fluorination method that enables regioselective fluorination of thiophene-based heterocycles. Our comparative study revealed that the position and number of fluorine atoms fine-tune molecular orbital energies and interactions, providing valuable insights for organic semiconductor applications.

Two aryl substituted phenalenyl derivatives were synthesized, providing an opportunity to study the steric effects on selectivity of phenalenyl dimerization. Owing to σ-dimerization serving as the decisive step in phenalenyl–peropyrene transformation, a chiral peropyrene compound was generated by dimerization of triarylphenalenyl, while tetraarylphenalenyl did not afford any dimerized product. The structure and properties of chiral peropyrene were elaborated. Our study showcases that phenalenyl dimerization could function as a useful tool to synthesize fascinating π-conjugated hydrocarbons.