ASAP (As Soon As Publishable)

Described herein is a novel base-promoted [4 + 2] annulation reaction of 3-methyl-indolin-2-ones with ortho-haloacetophenones, which enables the modular and reliable synthesis of 2,3-fused indolines bearing a quaternary carbon. Two C–C bonds can be successively constructed through a tandem sequence involving base-promoted S_NAr and aldol condensation. This protocol is highlighted by transition metal-free conditions, high efficiency, and simple operation.

The TEMPO⁺ (2,2,6,6-tetramethylpiperidine-N-oxyl cation) is a versatile chemical species commonly known as an oxidizing reagent. Nevertheless, its capability to act as a Lewis acid has been recently revealed. Here, we report a TEMPO⁺-promoted oxa-Ferrier rearrangement of glycals to chiral α,β-unsaturated δ-lactones using sodium chlorite (NaClO₂) as a cheap and environmentally friendly oxidizing reagent. Since the vinylic oxocarbenium intermediate is trapped by chlorite ion to form a carbonyl group, we name this reaction as the “Oxa-Ferrier rearrangement”. Accordingly, this reaction is suitable for various O-acetylated, O-benzoylated, and O-benzylated glycals, providing the corresponding α,β-unsaturated δ-lactones in moderate to good yield. Additionally, the synthetic utility of this methodology was applied to the synthesis and confirmation of the absolute configuration of passifetilactones B and C.

We propose a cobalt-catalyzed three-component reaction conducted under mild conditions. Following the carbonyl insertion at atmospheric pressure, the reaction proceeds via a nucleophilic attack by alcohols to form diesters. Notably, the scope of nucleophilic reagents can be extended to include a range of anilines. Furthermore, the products of this transformation serve as crucial synthetic building blocks for diverse organic synthesis processes, with subsequent derivatizations yielding promising results.

In this study, reductive breakage of the S–N bond on S-amidino sulfenamides was examined to explore prodrug or covalent drug chemistry for thiourea compounds. Upon thiol treatment, efficient release of varying thioureas could be reached, with Pd catalysis further accelerating this process. Preliminary application to antithyroid drug methylthiouracil confirmed cysteine-triggered release of the parent drug, although further development was hampered by stability issues. These findings highlight the potential of tunable sulfenamide prodrugs to balance release kinetics and stability for thiourea therapeutics.

A new combination of CuF₂/DTBP-catalyzed N-arylation of oxazolidinones, amides, amines, and azoles has been explored with arylboronic acid pinacol esters (arylBpin). This methodology has also been applied to the synthesis of oxazolidinone-based marketed drugs, including Rivaroxaban, Linezolid, Sutezolid, and Toloxatone. Mechanistic investigations using various spectroscopic techniques and DFT studies revealed the role of DTBP/MeOH in the catalytic process.

The direct alkylation of carbonyl compounds at α & β positions represents a significant challenge. Here, we report a catalyst-free visible light-induced deaminative alkylation that efficiently produces α, β-alkylated malononitrile-assisted ketones. Mechanistic studies suggested an EDA complex is formed by the Katritzky salt and the α & β carbanion of malononitrile-aided ketones, which permits the disruption of C–N bonds and the generation of alkyl radicals. Remarkably, this strategy eliminates the need for metal catalysts, additives, and ligands offering enhanced environmental sustainability and features mild, catalyst-free, and broad functional group tolerance. Our optimized catalyst-free condition under blue LED light yielded regio isomers of malononitrile-assisted ketones in good to excellent yields with diverse electronic properties and substitutions. Implementation of the flow setup to this batch protocol enhanced the efficiency of the reaction, demonstrating robustness and sustainability in organic synthesis.

CpRu-catalyzed asymmetric allylic alkylation serves as a versatile synthetic tool but remains underexplored. Herein, we report a relay system combining achiral Rh₂(OAc)₄ and a chiral pyridine-oxazoline-ligated Cp*Ru catalyst for asymmetric coupling of cinnamyl chlorides with diazo esters, generating silyl enol ethers in situ as key nucleophilic intermediates. This strategy affords chiral tetrahydrofuran derivatives with two vicinal stereocenters. Catalyst compatibility, excellent regioselectivity, and good enantioselectivity highlight its potential. Computational studies reveal the crucial role of Ru-centered chirality in reaction control.

Methods for regioselective ring-opening reactions of N-sulfonyl-protected aziridyl alcohols with azole nucleophiles have been developed. Several classes of azoles, including indazole, substituted pyrazole, benzotriazole, and tetrazole, have been employed as reaction partners, giving rise to C3-selective opening and >3:1 N-selectivity. BF₃•OEt₂ is the optimal catalyst for most substrate combinations, although examples where diphenylborinic acid (Ph₂BOH) provides higher yields, or where the reactions proceed efficiently without a catalyst, are also described. Computational modeling of the BF₃•OEt₂-catalyzed reaction is consistent with the observed regiochemical outcome. The calculated ring-opening transition state appears to be stabilized by an unconventional OH···FB hydrogen-bonding interaction.

The first total synthesis of the novel Melodinus alkaloid melohemsine K is described in five steps from known precursors. The key reaction of the synthesis is a tandem enamine formation/retro-aza-Michael reaction/Diels–Alder cycloaddition/intramolecular lactamization reaction cascade between indole-fused azepine and aldehyde precursors, forging the critical CDE tricyclic system. The synthesis provided a general approach to novel Melodinus alkaloids.

In this study, copper-catalyzed reductive hydroamination of alkenes and 1,3-dienes with nitroarenes was developed. Such umpolung hydroamination of unsaturated C═C double bonds exhibited Markovnikov selectivity, and the hydroamination of 1,3-dienes preferred 1,2-addition. Mechanistic studies suggested the system proceeds through a radical pathway with the concomitant activation of both substrates to nucleophilic alkyl radical species and electrophilic nitro-based intermediates, respectively. The attack of alkyl radical species on the N atom of nitro-based intermediates yielded the desired amines. However, this C–N cross-coupling strongly competed with the self-reduction of each species under such a system.

A photoinduced and catalyst-free radical cyclization process for the synthesis of 3,3-disubstituted oxindoles is reported. This method utilizes readily available α-bromoanilides as substrates, showcasing a broad substrate scope. The reaction mechanism is facilitated by a photoactivated charge transfer complex based on the halogen bonding of α-bromoanilide with TMG and alcohol.

Herein, an atom efficient and one-pot protocol, offering a series of sulfonylated pyrrolo[2,3-b]quinolines via C–N, C–C, and C–S bond formation, has been developed with an inexpensive copper catalyst. Notably, the reaction proceeds via a double-annulation reaction followed by a 1,3-sulfonyl migration sequence. Moreover, the method is applicable to a broad range of 2-carbonylanilines. Furthermore, synthetic applications and the scale-up reaction highlight the utility potential of this protocol. In addition, the antimalarial property of sulfonylated pyrrolo[2,3-b]quinolines showed parasite inhibition without cytotoxic effects in mammalian cells.

The mechanosynthesis of β-naphthol derivatives was accomplished through triflic anhydride-mediated cyclization reactions of arylacetic acids with arylalkynes in moderate to good yields by ball milling at room temperature. The present protocol featured solvent-free and simple conditions, a short reaction time, and easily available and inexpensive reagents.

Benzoxazine and benzoxazepine derivatives with tricyclic five-, six-, and seven-membered lactone and lactam rings were synthesized in one-pot conditions by using biochemo multienzyme cascade of lipase M and tyrosinase. The reaction involves tyrosinase-mediated ortho-hydroxylation of the phenolic moiety, followed by 1,6-Michael addition and tandem intramolecular ring closure. The method achieves high atom economy, minimizes purification steps, and provides a sustainable alternative to conventional multistep syntheses. Enzymes showed excellent reusability, further enhancing the green approach.

Herein, we developed an efficient nucleophile-controlled regiodivergent domino reaction between enetriones and γ-bromocrotonates. This method allowed for the rapid synthesis of a range of 1,3-dienic esters and tetrasubstituted pyrans under metal-free conditions. In the presence of pyridine, a S_N2 substitution/Michael addition/elimination sequence formed 1,3-dienic esters in satisfactory yields with high E-stereoselectivities. Alternatively, a S_N2 substitution/Michael addition/cyclization/cyclopropanation/cyclopropane ring-opening process forged tetrasubstituted pyrans in good yields with the help of Et₃N. It is interesting to note that the site-selective reactions of γ-bromocrotonates at the α- or γ-position were readily realized by modulating pyridine and Et₃N. Furthermore, the simple pyridine and Et₃N act as both nucleophiles in S_N2 substitution reactions and Lewis bases in deprotonation processes.

A hypervalent iodine-enabled double intramolecular electrophilic cyclization of 1,3-diynes has been employed in the synthesis of selenopheno[3,2-b]indoles and 3-selenocyanato-2-benzoselenophene indoles. A plausible mechanism involving the in situ formation of the reactive Cl-SeCN species from the reaction of PhICl₂ and KSeCN, followed by cascade cyclization involving C–N/C–Se bond formations, was postulated.

Thienoacenes are a prominent class of fused-ring conjugated organic compounds and have attracted considerable attention due to their high coplanarity, good stability, high charge-carrier mobility, etc. However, most current synthetic methods toward thienoacenes require costly starting materials and reagents, as well as a lengthy synthetic procedure with low overall yields. Herein, a nonprecious copper-catalyzed system without additional ligands was developed to facilitate C–S coupling and 5-endo-dig thienannulation reaction, leading to the synthesis of a range of thienoacenes including dithieno[3,2-b:2′,3′-d]thiophenes (DTTs) and thieno[2′,3′:4,5]thieno[3,2-b]thiophene[2,3-d]thiophene (TTAs) with yields of up to 90% (for single-sided thienannulation reactions) and 65% (for double-sided thienannulation reactions). In addition, three π-extended DTTs were studied as potential thermoelectric materials, and their composites with single-walled carbon nanotubes (SWCNTs) exhibited high thermoelectric performance with the power factor up to 399.01 ± 16.26 μW m^–1 K^–2 at room temperature, which is the highest reported for thermoelectric composites comprising small-molecule thiophene derivatives and SWCNTs, signifying a step forward in the development of high-performance thermoelectric composites based on thiophene derivatives.

3-Oxo-β-lactams are known to deliver different types of reaction products upon treatment with primary amines, predominantly governed by the nature of the C4 substituent. In this work, a C4 substituent-independent protocol for the conversion of 3-oxo-β-lactams to the corresponding 3-imino-β-lactams was developed. By using primary amine hydrochloric acid salts in combination with 2,4,6-collidine, or free primary amines in combination with acetic acid, the undesired ring opening of 4-aryl- and (S)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidine-2,3-diones toward ethanediamides and α-aminoamides, respectively, is avoided, enabling the smooth transformation of any 3-oxo-β-lactam into its imine counterpart. As demonstrated by the ensuing synthesis of 3-alkylamino-β-lactams, 3-imino-β-lactams serve as building blocks for the construction of functionalized 3-amino-β-lactams, with the latter being key motifs in drug discovery.

A new approach to 1,6-diarylhexa-1,3,5-trienes (DAHs) has been achieved. Cross-dimerization of 1-aryl-2-silylethyne (1) with benzyl((E)-buta-1,3-dien-1-yl)dimethylsilane (2c) catalyzed by [Ru(η⁶-naphthalene)(η⁴-1,5-cycloocatdiene)] produces (1E,3E)-(6-aryl-5-silylhexa-1,3,5-trien-1-yl)benzyl(dimethyl)silane (3), where the dominant stereochemistry at the 5-position in 3 is the E-form. Subsequent Hiyama cross-coupling of 3 with aryl iodide catalyzed by [Pd₂(dibenzylideneacetone)₃]·C₆H₆ in the presence of TBAF·3H₂O gives a series of (1E,3E,5E)-1,6-diarylhexa-1,3,5-trienes (DAH), showing that the C(5)═C(6) double bond rotates in the event of protodesilylation. The controlled experiments suggest that the Hiyama cross-coupling of the terminal silyl group in 3 takes place first, and then protodesilylation of the internal silyl group occurs to give (1E,3E,5E)-DAHs. An X-ray structure analysis reveals the molecular structure of (1E,3E,5E)-1-(4-acetylphenyl)-6-phenylhexa-1,3,5-triene. The photochemical study of some new DAHs has been conducted, showing bright fluorescence upon irradiation with a large Stokes shift (∼4026 cm^–1) by π–π* transition according to TD-DFT calculations.

A metal-free photocatalytic methodology for the synthesis of amides has been developed using eosin Y as a photocatalyst under ambient conditions. This approach provides a sustainable and efficient alternative for amide formation by eliminating the need for metal catalysts, and operates efficiently at room temperature. The use of eosin Y promotes high selectivity and reactivity, providing a green and cost-effective pathway for the synthesis of amides.

Polymerases are among the most powerful tools in the molecular biology toolbox; however, access to large quantities of chemically modified nucleoside triphosphates for diverse applications remains hindered by the need for purification by high-performance liquid chromatography (HPLC). Here, we describe a scalable approach to modified nucleoside triphosphates that proceeds through a P(III)–P(V) mixed anhydride intermediate obtained from the coupling of a P(III) nucleoside phosphoramidite and a P(V) pyrene pyrophosphate reagent. The synthetic strategy allows the coupling, oxidation, and deprotection steps to proceed as stepwise transformations in a single one-pot reaction. The fully protected nucleoside triphosphates are purified by silica gel chromatography and converted to their desired compounds on scales exceeding those achievable by conventional strategies. The power of this approach is demonstrated through the synthesis of several natural and modified nucleoside triphosphates using protocols that are efficient and straightforward to perform.

A supervised machine learning model has been developed that allows for the prediction of site selectivity in late-stage C–H borylations. Model development was accomplished using literature data for the site-selective (≥95%) C–H borylation of 189 unique arene, heteroarene, and aliphatic substrates that feature a total of 971 possible sp² or sp³ C–H borylation sites. The reported experimental data was supplemented with additional chemoinformatic descriptors, computed atomic charges at the C–H borylation sites, and data from parameterization of catalytically active tris-boryl complexes resulting from the combination of seven different Ir-, Ru-, and Rh-based precatalysts with eight different ligands. Of the over 1600 parameters investigated, the computed atomic charges (e.g., Hirshfeld, ChelpG, and Mulliken charges) on the hydrogen and carbon atoms at the site of borylation were identified as the most important features that allow for the successful prediction of whether a particular C–H bond will undergo a site-selective borylation. The overall accuracy of the developed model was 88.9% ± 2.5% with precision, recall, and F1 scores of 92–95% for the nonborylating sites and 65–75% for the sites of borylation. The model was demonstrated to be generalizable to molecules outside of the training/test sets with an additional validation set of 12 electronically and structurally diverse systems.

An N-heterocyclic carbene (NHC)-catalyzed [4 + 2] annulation enables the direct synthesis of 2-pyrones from α-chlorothioesters and β,γ-unsaturated α-keto esters or chalcones. The method utilizes NHC-activated α-chlorothioesters to generate key intermediates for 2-pyrone formation with high functional group tolerance. Moreover, the 2-pyrones were transformed into polysubstituted benzene and naphthalene derivatives, showcasing their synthetic value.

We disclosed an organophotoredox-catalyzed three-component oxidative radical-polar crossover strategy for constructing 1,2-alkylamination products. Cycloketone oxime derivatives were used as cyanoalkyl radical precursors and anilines were used as the nucleophiles. This facile protocol shows a good reaction yield and broad substrate scope.

Canonical thermal cycloaromatizations (Bergman, C¹–C⁶; Myers-Saito, C²–C⁷; Schmittel, C²–C⁶; Schreiner-Pascal, C¹–C⁵) are limited to the formation of five- or six-membered rings, while the formation of larger rings from enediyne (or enyne-allenes) has no precedent experimental exploration. Herein, we present a novel thermal cyclization of enediyne, leading to the formation of a stable seven-membered cyclization product. The structure of this product was elucidated by using NMR and single-crystal X-ray diffraction techniques. The presence of a maleic hydrazide moiety is postulated to facilitate the proton transfer, resulting in the rearrangement of enediyne to enyne-allene, culminating in ring closure through C^α–C⁶ cyclization. The reaction mechanism was further explored by using density functional theory (DFT), revealing a low activation barrier for the C^α–C⁶ cyclization at 19.6 kcal/mol. The newly formed seven-membered ring exhibits strong Möbius aromaticity, as confirmed by calculations of the nucleus-independent chemical shift (NICS) and anisotropy of the induced current density (ACID). In the subsequent reaction, the fusion of the oxazolidin-2-one ring and the elimination of the isobutene molecule release a significant amount of energy, further driving the formation of the final product.

A chemoselective double allylic substitution involving two different carbon nucleophiles is described. The reaction relies on a dual catalytic approach, with a Lewis acid promoting the first allylic substitution and Pd promoting the second step. Starting from simple allylic diols, a diversity of polycyclic structures can be obtained, including tetrahydroindole, tetrahydrocarbazole, and tetrahydronaphthalene.

The combination of sulfoxides with MOMCl has been found for the first time to mediate electrophilic cyclization and install a variety of sulfenyl groups onto isocoumarin skeletons via regioselective cleavage and reconfiguration of C–S bonds. Notably, MOMCl, a mild and readily available alkyl chloride, was indispensable and played a significant role as an activator under neutral conditions in this transformation, thus expanding the scope of acid-labile substrates.

Herein, we described the addition reactions of sulfur-containing reagents (sodium sulfinates, dithiosulfonates) with α-trifluoromethyl alkenes under visible light. A series of trifluoromethyl sulfonates were synthesized via the visible-light-induced radical addition reaction of sodium sulfinates and α-trifluoromethyl alkenes to obtain protons from the solvent. A series of dithiosulfonated derivatives were synthesized via visible-light-induced bifunctionalization reaction of α-trifluoromethyl alkenes with dithiosulfonates.This strategy has the advantages of mild reaction conditions, good substrate universality and high yield up to 99% yield.

A visible-light-driven intermolecular tandem α-amidotrifluoroethylation/cyclization of enaminones using a previously unreported N-trifluoroethylaminopyridinium salt was achieved in the absence of transition metal catalysts or bases. Notable features of this synthetic method include mild conditions, high selectivity, excellent functional group compatibility, and satisfactory yields. Preliminary mechanistic studies indicate that the reaction proceeds via a radical pathway, involving an in situ generated N-trifluoroethyl radical, followed by a 1,2-H shift.

Electron-withdrawing groups are traditionally considered meta-directing in aromatic substitution reactions. However, when the pre-existing substituent is a π-acceptor, both experiment and calculation indicate that substantial amounts of ortho as well as meta substitution occur, with very little para reactivity. A simple perturbative MO argument rationalizes this finding. It is therefore suggested that these substituents are best understood as ortho, meta-directors, with a preference for meta, just as electron-donating groups are considered ortho, para-directors, with a preference for para.

An unexpected electrochemical cascade reaction of 1,2,3-benzotriazinones with alkynes to assemble 3,4-dihydroisoquinolin-1(2H)-ones has been developed, which avoids the use of pressurized H₂, any metal catalysts, and stoichiometric redox agents. This route tolerates a wide range of functional groups in both reactants and can be performed under an air atmosphere. The process of continuous cathodic reduction was demonstrated by control experiments and cyclic voltammograms. Moreover, the gram-scale reaction confirmed the potential of this environmentally benign method for practical applications.

Substrate and reagent-controlled dimerization of vinyl para-quinone methides (VPQMs) is reported. When subjected to Brønsted acidic conditions, VPQM dimerization occurs via a formal 1,8-addition to provide griffipavixanthone (GPX)-type congeners. Under optimized Lewis acidic conditions, a change in regioselectivity affords limonene-containing dimers by a 1,6-addition/cyclization process. This divergent reactivity has been explored on several substrates of differing complexity, providing access to analogues of the natural product griffipavixanthone (GPX) as well as a range of novel, substituted limonene dimers.

An acid or hydrogen gas-free electrochemical protocol is established for the hydrogenation of strained rings (cyclopropane and cyclobutane) at room temperature and atmospheric pressure. The mechanistic study revealed that the reaction was initiated via the reduction of the carbonyl group. The methodology is highly specific toward strained rings such as cyclopropane and cyclobutane, which exhibit broad functional group tolerance.

We here describe a versatile, convenient, and efficient approach to synthesize cyclic nitrone compounds by diamination of alkene, which was catalyzed by simple copper salts under basic conditions with good chemoselectivity. The method utilized γ,δ-unsaturated ketoximes with O-benzoylhydroxylamines as an electrophilic nitrogen source to realize intra-/intermolecular 5-exo-trig cyclization of internal alkenes of unsaturated ketoximes without external oxidants required, and a series of substitution patterns, both donor and withdrawing substituted moieties, are well-tolerated, leading to target products in moderate to good yields.

We designed a new type of redox-active molecular triad in which two electron-donating dithiafulvene (DTF) groups are connected to a central ferrocene (Fc) hinge unit through phenylene linkers. Three structural isomers of the (DTF)₂–Fc system were synthesized through Suzuki–Miyaura cross-coupling followed by phosphite-promoted olefination reactions. The molecular structures and solid-state properties of these compounds were investigated by X-ray single-crystallographic analysis. Their electronic absorption and electrochemical properties in the solution phase were examined using UV–vis spectroscopy and cyclic voltammetry. Our studies showed that these compounds possess multistage redox activities due to the presence of electron-donating DTF and Fc groups, while detailed redox behaviors are dependent on the substitution patterns and steric crowdedness of each compound. To gain deeper insight, we performed density functional theory (DFT) and molecular dynamics (MD) simulations to examine the conformational and electronic properties of these compounds in neutral and different oxidation states. Furthermore, the para-substituted (DTF)₂–Fc was found to show intriguing supramolecular interactions with γ-cyclodextrin.

N-Heterocyclic carbene-carbodiimide (NHC-CDI) adducts are versatile compounds that can be used as ligands and (pre)catalysts, but their systematic structure–property relationships are underexplored. Herein, we investigated how structural electronic variations on both the NHC and CDI affect the inherent kinetic and thermodynamic properties of the adducts. Using in situ carbene trapping and variable-temperature NMR spectroscopy, we measured the rates of dissociation and the equilibrium constants and then used Eyring and van’t Hoff analyses to calculate ΔG^‡ and ΔG, respectively. Linear free-energy relationships indicate that changing the para position of the CDI substituents yields a similar effect to changing the NHC core. These CDI structural modifications affected the adducts’ thermodynamics (ΔG) more than the kinetics (ΔG^‡) and were found to be influenced more by inductive, rather than resonance, factors. Preliminary results suggest a steric threshold beyond which steric effects dominate electronic effects in governing the strength of the adduct bond. This systematic investigation provides valuable insight into the design of NHC-CDIs for current and future applications.

We report an optimized protocol for the solid-phase synthesis of backbone-N-aminated peptides. Electrophilic N-amination of amino acid zwitterions provides crude α-hydrazino acids that can be used directly in SPPS. In situ formation of Fmoc-protected amino acid chlorides with Ghosez’s reagent enables base-free couplings to α-hydrazino acids on an automated system. TFA-free cleavage and global deprotection affords poly-N-amino peptides in high crude purity and in a fraction of the time required by previously reported methods.

Aerobic oxidative cross-dehydrogenative couplings of 1,2,3,4-tetrahydroisoquinolines were developed using a Mn(acac)₃ and ethyl 2-(4-nitrophenyl)hydrazine-1-carboxylate cocatalytic system. Nucleophiles, including nitroalkanes, dialkyl malonates, acetophenones, indoles, phosphonates, and phosphine oxides, were successfully employed to produce α-functionalized 1,2,3,4-tetrahydroisoquinolines. Control experiments revealed that radical species are not involved in the mechanism. Additionally, ¹H NMR and HRMS analyses in the stoichiometric reaction identified an aminal structure as a crucial intermediate. Computational studies further support the plausibility of a hydride transfer process in the oxidation of 1,2,3,4-tetrahydroisoquinolines instead of the triazane pathway, which was predominantly proposed in the DEAD-mediated reaction.

A rhodium-catalyzed synthesis of isobenzofurans via donor- and donor-type metal carbenoids has been developed. Nosylhydrazones were used as carbene precursors, generating rhodium carbenoid species under basic conditions. These intermediates underwent intramolecular cyclization with ester groups to afford isobenzofurans, which subsequently participated in a highly endo-selective [4 + 2] cycloaddition with maleimides and other dienophiles. The reaction exhibited a broad substrate scope, accommodating various ester and aryl substituents while maintaining excellent regio- and stereoselectivity. Mechanistic studies, including control experiments, NMR analysis, and computational calculations, revealed that the reaction proceeds through a rhodium carbenoid intermediate, leading to the formation of isobenzofuran prior to cycloaddition. The endo-selectivity was found to originate from the difference in activation energies between the transition states, as supported by computational studies. Additionally, the isolation of the diazo intermediate and its direct conversion to isobenzofuran confirmed the stepwise nature of the transformation. This study expands the utility of donor- and donor-type carbenoids in organic synthesis, demonstrating their effectiveness in constructing highly reactive isobenzofurans under mild conditions.

A new approach for the enantioselective synthesis of various bicyclo[2.2.2]octadiene ligands has been developed, which features a chiral oxazaborolidinium-catalyzed asymmetric Diels–Alder reaction to construct the bicyclo[2.2.2]octane framework. The pivotal ketone 12 served as a common intermediate that was finally transformed into the desired C₁- and C₂-symmetric chiral dienes. This work provides an alternative method to the reported chiral diene synthesis and would be beneficial to exploration of the potentials of this type of versatile ligand in new asymmetric transformations.

A straightforward and efficient strategy for the synthesis of fully functionalized indolizines has been developed through a transition metal- and oxidant-free [3 + 2] cycloaddition reaction of zwitterionic ketenimines and pyridinium salts. This versatile method proceeds under mild conditions, affording functionalized indolizines in moderate to good yields. This efficient approach involves an intermolecular [3 + 2] cycloaddition, followed by enamine/imine tautomerization and aromatization. Notably, this method demonstrates broad functional group compatibility and allows for facile scalability, making it a valuable tool for the synthesis of indolizine-based frameworks in organic and medicinal chemistry.

A Pd-catalyzed protocol that provides efficient access to acyclic 1,2-dioxygenated dienes has been established. The installation of the bifunctional carbonate electrofuge to the diene cores enabled such dienes to undergo a regioselective decarboxylative Diels–Alder cycloaddition/aromatization reaction, affording diverse synthetic challenging multisubstituted phenols with ease.

β-Sulfido sulfonyl fluorides, incorporating a clickable sulfonyl fluoride and a thioether motif, are valuable intermediates in chemical biology, materials science, and drug discovery. Herein, we developed a rapid and additive-free synthesis of these compounds via N-methyl-2-pyrrolidinone (NMP)-promoted thia-Michael addition of thiols to ethene sulfonyl fluoride (ESF). The reaction proceeds smoothly under neutral conditions without the need for a base or catalyst, achieving high efficiency within 20 min. This method demonstrates a broad substrate scope, tolerating thiophenols, alkylthiols, thioglycosides, and cysteine-containing peptides. The resulting β-sulfido sulfonyl fluorides enable diverse transformations, such as sulfur(VI) fluoride exchange (SuFEx) reaction and thioether oxidation, facilitating applications in drug conjugates and materials, such as additives for lithium-ion battery electrolyte components.

The 1,2,3-triazole scaffolds are an important class of biologically privileged heterocyclic compounds with several key applications in chemistry, biology, medicine, agriculture, and material science. The “postclick” functionalization of 1,2,3-triazoles may emerge as a promising tactic for the construction of molecular architectures of therapeutics and is considered to be a growing area of investigation. This interest extends beyond the regioselective Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) method that involves the trapping of Cu(I)-triazole with suitable precursors. In this Perspective, we highlight the growing impact of postclick strategies in organic synthesis required for the late-stage functionalization of 1,2,3-triazoles with a hope that this emerging concept may provide ample opportunities in modern organic synthesis of notable applications in medicinal chemistry, biology, and materials science.

We present a new, straightforward, and versatile approach that utilizes regioselective brominated precursors to synthesize both asymmetric and symmetric S-zig-zag-fused BODIPYs (s-TFB and bis-TFB) in moderate yields (45% and 40%, respectively). X-ray structure analyses reveal that the planar rigidity of the BODIPY skeleton is progressively enhanced with an increasing number of thiopyran rings. The annulation of S-heteroaromatic rings at the zig-zag edge of the BODIPY core results in blue-shifted absorption and emission spectra, with bis-TFB exhibiting maxima at 530 and 539 nm and elevated LUMO energy levels. In contrast, oxidation of s-TFB and bis-TFB with m-CPBA demonstrates significant site selectivity, affording four oxidation products, namely s-s-SFB, s-bis-SFB, bis-s-SFB, and bis-bis-SFB, in yields ranging from 22% to 36%. These oxidated S-zig-zag-fused BODIPY derivatives display large red-shifted absorption and emission spectra (e.g., 648 and 735 nm for s-bis-SFB), along with more stable HOMO and LUMO energy levels and reduced HOMO–LUMO gaps. This S-zig-zag-fused cyclization/oxidation strategy enables precise tuning of the BODIPY optoelectronic properties, opening new avenues in dye design and application.

We report an efficient palladium-catalyzed ring-opening defluorinative Hiyama cross-coupling of gem-difluorocyclopropanes with structurally diverse (hetero)arylsilanes through C–C bond activation and C–F bond cleavage. This regioselective ring-opening defluorinative Hiyama cross-coupling features a broad substrate scope with excellent functional group compatibility, affording a diverse variety of linear 2-fluoroallylic scaffolds in good yields with high Z-selectivity.

The development of water-soluble multicharged macrocycles has opened promising pathways in biomedical applications, enabling selective molecular recognition for therapeutic and diagnostic uses. Yet, traditional polyanionic and polycationic receptors often face performance limitations under realistic operating conditions. A major drawback is the natural tendency of these polycharged hosts to experience increasing screening effects as concentration rises due to self-ion pairing phenomena, which can reduce binding efficiency by several orders of magnitude. These issues are further intensified when polyionic receptors are used in high-salinity environments, typically used to replicate physiological settings, where the abundance of ions introduces additional screening effects that diminish the supramolecular affinity for a wide range of guests. This study presents a new approach that leverages zwitterionic synthetic receptors with rationally engineered architectures to overcome these challenges. By incorporation of specific structural features, self-ion pairing is eliminated, effectively making host concentration no longer a controlling factor in the thermodynamics of the complexation process. Additionally, these dual-charged hosts achieve self-contained stabilization, naturally shielding recognition sites from external ion interference under high-salinity conditions. Furthermore, the ability of these supramolecular hosts to encapsulate zwitterionic guests, a challenging task due to the strong solvation of these molecules in aqueous solution, adds significant value to the functional versatility of these macrocycles. Altogether, these findings represent a significant advancement in the design of stable and adaptable receptor systems for complex environments.

Vinyl diazo carbonyl compounds have received great attention and are widely employed in the cycloadditions of in situ formed reactive intermediates. Metal carbenes are predominantly involved in cycloadditions, and transformations of vinyl diazo compounds that do not proceed via the metal carbene pathway have been seldom reported. Herein, scandium-catalyzed cycloadditions of vinyl diazo compounds and in situ formed 2-naphthoquinone-8-methides are achieved, and naphthalene-fused polycyclic products were obtained in up to 88% yield. In the transformation, the nucleophilic conjugate addition of vinyl diazo compounds to in situ formed 2-naphthoquinone-8-methides generates vinyl diazonium intermediates, which undergo an intramolecular Friedel–Crafts reaction and intramolecular transesterification to yield the final product.

Aromatic systems with bridged sulfur units in varying oxidation states have enabled photoresponsive materials for anticounterfeiting and supramolecular assembly. However, only a few sulfoxide-bridged chromophores exhibit photoinduced sulfur extrusion, leading to drastic photophysical changes that make them useful as stimuli-responsive materials. Here, we present nitrogen-substituted anthracene (aza-anthracene) with a sulfur bridge in different oxidation states. Overall, aza-anthracene produces red-shifted green-to-red chromophores with similar sulfoxide photoconversion behavior compared to the anthracene analog.

In this work, we studied the conjugated additions of bis-trimethylsilylacetalketene acetals (bis-TMSKA) to para-quinone methides (p-QMs), which are one of the most explored molecules for the study of conjugated additions and gained significant attention in organic chemistry due to their versatile reactivity, particularly in Michael addition reactions. In this study, trifluoromethanesulfonic anhydride (Tf₂O) was used as an activating agent for p-QMs, aiming to achieve 1,6-Michael addition products and the least reported 1,8-Michael addition with pyridine substituents. The reactivity of p-QMs derived from pyridine demonstrated distinct reaction pathways, leading to the formation of δ and γ lactones. The investigation also involved synthesizing a 1-indanone derived from the carboxylic acids obtained from the 1,6-addition.