ASAP (As Soon As Publishable)

A novel strategy is reported for the stereoselective synthesis of C(sp²)–C(sp³) C-glycosides, which converts heteroaryl S-glycosides into heteroaryl C-glycosides with retention of configuration through a sequential process involving oxidation and Grignard reagent attack. The new method involves the generation of a S(IV) intermediate, followed by ligand coupling of the glycosyl and heteroaryl groups to yield heteroaryl C-glycosides. The diverse heteroaryl C-glycosides were achieved with good efficiency.

An electrochemical strategy for the regioselective construction of seleno-benzothiophenes/furans is reported through electrochemical selenocyclization, followed by Wagner–Meerwein rearrangement. This electro-oxidative tandem process operates under metal-free and external chemical oxidant-free conditions. Advantageously, unprotected homopropargyl alcohols were found to be compatible under the reaction conditions, releasing water and dihydrogen as the biproduct. This methodology reveals good functional group tolerance, allowing a broad spectrum of substrate scopes of up to 87% isolated yield.

Vicinal bis(tetraarylphosphonium) salts have scarcely been reported in the literature. In this study, we demonstrate that visible-light-induced difunctionalization of ortho-trifluoromethylsulfonylated diaryliodonium salts conveniently furnishes bis(phosphonium) salts without additional catalysts or photoinitiators. The methodology establishes a practical platform for the preparation of bis(phosphonium) salts using readily available tertiary phosphines. The bis(tetraarylphosphonium) salts are anticipated to garner a great deal of interest in catalytic and medicinal chemistry.

A photoacid-catalyzed method for esterification is proposed wherein eosin Y is introduced as a photoacid and photoredox catalyst that can be activated with visible light and catalyze the esterification of carboxylic acids. The strategy presented here revealed that proton-coupled electron transfer (PCET) between eosin Y and carboxylic acid might facilitate the formation of a transient ketyl radical. This ketyl radical would subsequently undergo a single electron transfer and then couple with alkyl alcohols, yielding carboxylic esters in good to excellent yields.

Two series of polycyclic aromatic hydrocarbon isomers (PT-2 and PT-3, and P2T-V and P2T-C) were designed and synthesized by isomerically fusing phenanthrene with thiophene and thieno[3,2-b]thiophene, respectively. All of the new target molecules were confirmed by single-crystal X-ray analysis, and it was found that the solid-state packing can be effectively modulated through a combination of π-extended and isomeric fused strategies. Meanwhile, compared with thiophene ring-terminated isomers PT-2 and PT-3, both having a V-shaped geometry and showing no obvious self-assembly behavior, π-extended unit thieno[3,2-b]thiophene-terminated isomer P2T-V displays a V-shaped structure with moderate self-assembly properties and isomer P2T-C exhibits a C-shaped configuration with further enhanced self-assembly properties.

Herein, we report an electricity-driven activation of aziridine via direct anodic oxidation to give N-heterocycles and 1,2-bifunctionalized products by excluding any oxidant/reductant or metal catalyst. Many structurally modified aziridines were employed in the presence of different nitriles. A large variety of nucleophiles were screened to furnish chemoselectively O-alkylated and C-alkylated products. Late-stage derivatization of aziridine with natural and medicinally active compounds has also been done. Remarkably, our strategy was found to be a greener, sustainable, and atom-economical approach (E-factor = ca. 0.8). Azetidine was also found to be compatible with our protocol and generated six-membered N-heterocycles. The detailed mechanistic study highlighted that the reaction is driven via the generation of an aziridine radical cation followed by the S_N2 nucleophilic attack.

Compared with the energetically favorable 5- or 6-membered fluoro-functionalized heterocycles, the construction of medium-sized fluoro-heterocycles is relatively under-researched because of their inherently unfavorable enthalpic and entropic nature. Based on rational design and DFT calculations, a novel photocatalytic difluoromethyl radical-initiated intramolecular 7-endo-trig cyclization was realized, thus affording a sustainable route for the synthesis of challenging fluoro-functionalized medium-sized N-heterocycles. Depending on atomic dipole moment corrected Hirshfeld population (ADCH) charge calculations, the chemoselective 6-exo-trig radical cyclizations were further replenished. Large-scale synthesis and derivatization demonstrated the wide utility of this method.

The introduction of fluorine into organic molecules is of the utmost importance in the preparation of active pharmaceutical ingredients (APIs). While a wide range of fluorine sources for organic synthesis have been used over the past decades, the associated safety risks, cost, or environmental impact are still serious limitations. Hexafluorosilicate salts are one of the most inexpensive and readily available sources of nucleophilic fluorine, but they have so far not been used in organic synthesis. Herein we report the first example of the use of a hexafluorosilicate salt as a reagent for the formation of C–F bonds. We have selected as the model reaction an electrochemical decarboxylative fluorination procedure. The synthesis of bis(5-ethyl-2-methylpyridin-1-ium) hexafluorosilicate(IV) was key to obtaining a soluble and reactive hexafluorosilicate salt. This protocol enabled the synthesis of a wide range of primary, secondary, and tertiary aliphatic fluorides (22 examples) in up to 85% yield. The electrochemical method was also successfully transferred to a flow electrolysis cell, demonstrating its robustness and scalability. Finally, we extended the scope of the fluorine source by demonstrating its applicability to electrochemical benzylic C–H fluorination.

Eleutherlene A (1), an unprecedented carbon skeleton featuring an aryl-fused 6-methyl-2,7-dioxabicyclo[3.2.1]octane unit, and eleutherlene B (2), a naphthoquinone derivative with interesting ring fusion of an α,β-unsaturated γ-lactam and a tetrahydropyran moiety, along with two novel naphthoquinone alkaloids, eleutherlenes C (3) and D (4), were isolated from Eleutherine bulbosa and identified. Their structures were elucidated by spectroscopic analyses along with computer-assisted structure elucidation, including ACD/Structure Elucidator and computational calculations and X-ray crystal diffraction. A plausible biosynthetic route for 1 and 2 was proposed. Compound 1 showed significant anti-inflammatory activity with respect to the inhibition of pro-inflammatory mediators NO, IL-1β, iNOS, and COX-2. Mechanistically, compound 1 inhibited the inflammatory response by suppressing NF-κB/MAPK and activating the Nrf2/Keap1 signaling pathway in LPS-induced RAW 264.7 cells.

1,1-Difluoroallenes underwent regioselective [2 + 2] and [3 + 2] cycloadditions with aldehydes using Au(I) catalysts. An AuCl catalyst enabled an α,β-selective [2 + 2] cycloaddition of 1,1-difluoroallenes, yielding (E)-3-alkylidene-2,2-difluorooxetanes. Conversely, an AuCl(IPr)–AgSbF₆ catalyst facilitated an α,γ-selective [3 + 2] cycloaddition, followed by dehydrofluorination to produce aromatized 2-fluorofurans. DFT calculations (B3LYP level) suggested that the former reaction proceeded through Au(III)-containing metallacycles, while the latter involved cyclic Au(I) carbenoids.

A Cu(I) photoredox-enabled reaction that selectively incorporates a difluoroalkyl group into N-aryl glycine derivatives has been established. Using a bench-stable [Ph₃PCF₂H]⁺Br^– salt, the −CF₂H group could be installed either directly on the α-carbon of the glycine backbone or in a three-component fashion using an alkene as a bridge. A series of glycine derivatives have been evaluated, providing access to diverse unnatural amino esters and dipeptides with a −CHF₂ unit. The studies of the compatibility of other perfluorinated alkyl radical precursors showed that the selectivity of direct α-coupling is closely associated with the electronic property of the radical, while the three-component reaction works well in most cases.

Reductive direct substitution of α-arylvinyl triflates on the sp² carbon atom by magnesium in the presence of chlorosilane proceeded to give the corresponding α-silylstyrenes, which could not be reduced further, and the reaction completely stopped because the reduction potential of α-silylstyrenes lies out of the reducible field of magnesium. The subsequent reduction of α-silylstyrenes by calcium brought about the second introduction of another silyl group to the vicinal carbon atom to lead a selective and simple route to a variety of 1,2-disilanes from vinyl triflates by cooperative works of magnesium and calcium with different reduction potentiality.

A palladium-catalyzed tandem reaction of 1-(2-iodophenyl)-3-arylprop-2-yn-1-ones and 1-(2-azidophenyl)propargyl ethers is developed to provide the rapid construction of a fused polycyclic indenone–indole scaffold under mild conditions. The reaction proceeds via a highly ordered process involving Sonogashira coupling, propargyl–allenyl isomerization, allene–azide cycloaddition, denitrogenation, and diradical coupling. The proposed reaction mechanism is supported by experimental and computational studies.

Natural product biosynthesis is nature’s tinkering ground for developing new enzymes that can achieve chemical transformations that are outside the purview of traditional chemical catalysis. Herein we describe a genome mining approach that leads to the discovery of a halogenase that regioselectively brominates a tryptophan side chain indole for a macrocyclic peptide substrate, enabling downstream chemical arylation by Suzuki–Miyaura coupling. The halogenase was found to prefer a macrocyclic peptide substrate over a linear peptide. The brominase presents a starting point for biocatalytic access to macrocyclic peptides bearing a chemically versatile aryl-bromide reactive handle

The translocation of an aryl group from selenium into carbon enabled by the cleavage of the C–Se bond is reported by using nitrogen atom-linked 1,7-diynes and diaryl diselenides as starting materials, leading to various selenophene derivatives in a regioselective manner. This method enables the construction of two C–Se bonds and two C–C bonds through sequential radical bicyclization and 1,2-aryl migration under metal-free conditions. Control experiments and mechanistic studies suggest that this reaction proceeds through the cleavage of the inert C(Ph)–Se bond, facilitating the aryl translocation process. This transformation enables the one-step conversion of simple diselenides into diverse selenopheno[3,4-c]quinolines via a radical-promoted process, holding significant potential for new seleniferous heterocycles.

Benzene-containing cucurbituril[2,4] and benzene-containing cucurbituril[3,6], the structures of cucurbit[n]urils with some glycoluril units replaced by benzene rings, are constructed through condensation of specific benzene-containing motifs. These novel macrocycles inherit cucurbit[n]urils’ concave cavity and provide chemical modification potentiality and chromophores. Benzene-containing cucurbituril[2,4] shows a C₂-symmetric macrocycle, while benzene-containing cucurbituril[3,6] exhibits a distinctive two-cavity structure (one big and one small) that resembles a gourd and could potentially accommodate two guests different in size simultaneously.

An unprecedented synergistic copper- and amine-catalyzed cyclization of enynone is reported. This reaction features an efficient and straightforward construction of multisubstituted tetralone through an amine-assisted regioselective oxygen atom transfer process and stereoselective intramolecular Michael addition cyclization. Under dehydrative reaction conditions, the synthesis of tetrahydronaphthylimine derivatives with ketone group tolerance is achieved, which could be challenging via traditional methods. The utility of this reaction is demonstrated by further transformations of obtained molecules toward a variety of valuable multisubstituted naphthyl skeletons.

Herein, we introduce a scandium-catalyzed synthetic strategy that provides access to a diverse and functionalized array of cyclobutene frameworks adorned with a quaternary carbon center. This approach broadens the synthetic repertoire of 2-alkynylnaphthols with alkenes, offering a versatile platform for the construction of complex molecular architectures. The asymmetric catalytic [2 + 2] cycloaddition reaction demonstrates a wide substrate scope and an impressive functional group tolerance, yielding products with high efficiency, up to 97% yield, and excellent enantiomeric excess of up to 97%. The simplicity of scaling up this process, coupled with the ease of converting these cyclobutene frameworks into a variety of substituted products, significantly enhances the synthetic utility of this method.

Here, we present a three-component successive radical addition strategy for the preparation of complex noncanonical α-amino acids from easily available glycine derivatives, alkenes, and aryl sulfonium salts via a copper-catalyzed photoredox-neutral catalytic cycle. The utility of this method is further demonstrated by its application in late-stage site-selective modifications of glycine residues in short peptides. It is worth noting that only 1 mol % copper catalyst is required in this reaction, demonstrating high catalytic efficiency.

In this work, two energetic compounds 5-(3-iminio-6-nitro-3H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-2(7H)-yl)tetrazol-1-ide (TT) and 3-nitro-7-(2H-tetrazol-5-yl)-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-6-amine (FT) were successfully synthesized from the same compound 3,6,7-triamino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazolium (TATOT). Both compounds contain three explosophores, amino, nitro, and tetrazole, on the fused ring. Through different functional group arrangements, TT possesses higher density and good thermal stability. FT exhibits a low sensitivity to mechanical stimulation. Both compounds show promising energetic performance properties.

The single-atom skeletal editing technology is an efficient method for constructing molecular skeletons, which has broad coverage in synthetic chemistry. However, its potential in the preparation of energetic heterocyclic molecules is grossly underexplored. In this work, an unexpected one-step reaction for the synthesis of novel energetic molecules was discovered which combines single-atom skeletal editing, gem-dinitromethyl functionalization, and zwitterionization in one step. The reaction demonstrates high efficiency while maintaining the characteristics of being mild and facile. The reaction mechanism was verified by experimental evidence and theoretical calculations. This reaction produces a novel energetic molecule (NPX-04) with good laser ignition performance, indicating its promise as a laser-sensitive energetic material.

An enantioselective oxypalladation/malononitrile addition cascade reaction of alkyne-tethered malononitriles was reported to synthesize enaminones bearing an all-carbon quaternary center. Using Pd(TFA)₂/Pyox as a precatalyst, an array of enaminone products were obtained in moderate overall yields, with excellent er (93.5:6.5–99.5:0.5) in solution phase and nearly racemic in solid phase. The usage of 3,5-dinitrobenzoic acid as the nucleophile was proven to be crucial to this significant chiral amplification due to a heterochiral self-assembly of the products through an intermolecular multiple π–π stacking interaction. A strong positive nonlinear effect (NLE) was observed in solution phase, which was further highlighted by the access to an enantiopure enaminone (99.5:0.5 er) even using a partially enantiopure catalyst (54:46 er).

Radical-initiated functionalization of bicyclo[1.1.0]butanes (BCBs) is a straightforward approach to accessing diverse cyclobutane derivatives. However, selective C(sp³)–H functionalization at the C2 position of BCBs remains scarce. Herein, a mild protocol for the hydrogen-evolution of C2 C(sp³)–H phosphorylation with BCBs enabled by photoinduced cobaloxime catalysis was realized in a regio- and diastereoselective manner. This oxidant- and additional photocatalyst-free method enabled C(sp³)–H phosphorylation with a wide range of BCBs and diarylphosphine oxides. The mechanism was studied via control experiments and DFT calculation. Moreover, the efficiency of this approach was highlighted in the synthesis of high-value, structurally complex molecules.

We present the serendipitous discovery of an unusual dimer formed from anthracene-derived polyarenes. Unlike the typical oxidative coupling of substituted aromatic scaffolds, the reaction yielded a dearomatized enone dimer as the sole product. This dearomatized motif, notably, does not undergo the commonly observed rearomatization, and no biaryl products were detected. The anthracene dimers were produced in excellent yields. Structural validation via single-crystal X-ray analysis revealed that the dimers feature an sp³–sp³ carbon–carbon bond connecting two α,β-unsaturated enones, existing as a pair of diastereomers. These unique dimers underscore the critical role of serendipity in advancing organic synthesis.

Energetic materials containing a pyrazolotriazine oxide skeleton have the potential for high performance. However, research on the pyrazolotriazine oxide skeleton is very limited due to the inherent ring system instability and limited synthetic approaches. In this paper, APTO and OPTO with a combination of high-nitrogen tetrazole and a promising azido-pyrazolotriazine oxide skeleton have been synthesized. Of these, OPTO and its energetic salts exhibit excellent detonation properties (D_v > 8220 m s^–1; P > 26.50 GPa). Surprisingly, APTO exhibits a detonation performance (D_v = 8913 m s^–1; P = 32.43 GPa) comparable to that of RDX.

Dehydrophenylalanine has a characteristic unsaturated double bond that makes it indispensable in the context of peptides and proteins. In this study, we report the Pd-catalyzed C(sp²)–H arylation of dehydroalanine-containing peptides with arylthianthrenium salts under mild and base free conditions, which provides efficient access to dehydrophenylalanine-containing peptides. This approach enables the efficient coupling of different drug scaffolds and bioactive molecules to the peptides. Remarkably, the method could be used for the concise synthesis of tentoxin and its analogue.

Herein, we present a metal-free, concise, and efficient protocol for the intermolecular reaction of amides (lactams) with donor–acceptor α-diazo esters to afford the functionalized α-amino-α-aroylethanoates. N-Methyl-2-pyrrolidone (NMP) and N,N-dimethylformamide (DMF) are employed as both reagents and solvents, allowing for the incorporation of all units into the products. The reaction is processed by the ester group migration and compatible with a broad range of substrates up to 50 examples.

We present a photocatalytic method for alkylamination of alkenes, enabling efficient C–C and C–N bond formation to construct aza-heterocycles valuable in drug discovery. Using a radical-polar crossover pathway, electron-deficient alkenes are reduced to electrophilic radicals, which react with electron-rich alkenes to form nucleophilic radicals. Oxidation of these intermediates yields carbocations, which are trapped by aza-heteroarenes to afford alkylaminated products. This strategy enhances molecular complexity while suppressing side reactions.

Synthesis of complex, multiring, spirocyclic, 1,3-dicarbonyl fused, and highly functionalized 5-phenyl-1-azabicyclo[3.1.0]hexanes (ABCH) has been achieved by an intermolecular reaction of 2-(2′-ketoalkyl)-1,3-indandiones or α,γ-diketo esters with (1-azidovinyl)benzenes under transition metal-free conditions. The reaction proceeds in a highly diastereoselective manner with a wide range of functional groups and provides moderate to good yields. Additionally, we have studied the preliminary biological activities of a few synthetic compounds against HeLa and triple-negative breast cancer (TNBC) cell lines.

Herein, we present an unprecedented electrochemical reductive cyclizative carboxylation of o-vinylphenyl isocyanides with carbon dioxide achieved without the use of metal catalysts. This protocol demonstrates a broad substrate scope and good functional group tolerance, facilitating the rapid assembly of 2-oxoindolin-3-acetic acids in good to high yields with excellent regioselectivity. Furthermore, these structural motifs may have potential applications in formal synthesis of bioactive natural products.

4′-Selective alkylation of nucleosides has been recognized as one of the ideal and straightforward approaches to chemically modified nucleosides, but such a transformation has been scarce and less explored. In this Letter, we combine a visible-light-mediated photoredox catalysis and hydrogen atom transfer (HAT) auxiliary to achieve β-C(sp³)–H alkylation of alcohol on tetrahydrofurfuryl alcohol scaffolds and exploit it for 4′-selective alkylation of nucleosides. The reaction involves an intramolecular 1,5-HAT process and stereocontrolled Giese addition of the resultant radicals.

α-Fluoro-α′-aryl ketones are crucial in pharmaceuticals and agrochemicals. However, synthesizing unsymmetrical α-fluoro-α′-aryl ketones poses regioselective challenges. This study presents a one-pot aryl-oxy-fluorination method for synthesizing such unsymmetrical fluoro-aryl ketones. Using ynamide, aryl boronic acid, and F-source under Pd-catalysis, this method efficiently produces a wide range of valuable α-fluoro-α′-aryl ketones with potential applications. Through a combination of control experiments and DFT studies, we proposed a reaction mechanism involving in situ acetic acid formation.

We disclose a stereodivergent strategy to prepare vicinal difluorinated tetralins from γ-substituted tetralones via a combination of catalyst-controlled transfer hydrogenation and substrate-controlled fluorinations. This process is easily scalable and amenable to highly functionalized substrates, as demonstrated here in the late-stage synthesis of casdatifan, a clinical-stage inhibitor of hypoxia-inducible factor-2α. Analysis of the physicochemical properties of casdatifan, which features a cis-vicinal difluoride, revealed a higher level of facial polarization compared to its trans-vicinal difluoride isomers.

The synthesis of radiolabeled [25-¹⁴C]-siamenoside I following a synthetic route developed using unlabeled materials is disclosed. The synthesis features an early stage labeling of the mogrol’s C25 via an oxidative cleavage–reconstruction strategy and regioselective glycosylations directed by protecting group manipulations. This route provided access to adequate amounts of [25-¹⁴C]-siamenoside I for in vivo ADME and PK studies.

Here we present a regio- and stereoselective alkylation approach for unprotected saccharides using synergistic boronic acid and photoredox catalysis. Targeting the equatorial C–H bond of the cis-1,2-diol motif, this method employs MeB(OH)₂ as a catalyst. Mechanistic investigations indicate that the formation of a tetracoordinate boron species, resulting from the interaction between the cyclic boronic diol ester and a free hydroxyl group in the saccharide, is critical to this transformation. Notably, this method enables efficient late-stage modification of complex carbohydrates, such as raffinose and the drug digoxin, expanding opportunities for carbohydrate functionalization.

An iron(III)-mediated nucleophilic cascade cyclization of N-propiolyl enamides with various diselenides was developed, which provides an efficient way to construct seleno-heterocycles. A mechanism study shows that the cascade process involves the selective addition of diselenides to the C≡C bond generating a seleniranium ion, followed by an intramolecular nucleophilic attack of enaminic carbon of tertiary enamide. Utilizing this protocol, a variety of 3-seleno-2-pyridones were successfully synthesized featuring good functional group compatibility and simple operation.

Herein, we report an approach for the synthesis of 2-sulfonyl carbazoles from the oxidative C–H sulfonylation of tetrahydrocarbazoles. The mechanistic study reveals that this special selectivity is realized by the addition of a sulfonyl radical to the 3,4-dihydrocabazole intermediate via dehydrogenative desaturation of tetrahydrocarbazoles. This approach features readily available starting materials, high regioselectivity, broad substrate scope, and attractive synthetic utility.

A novel approach for the synthesis of pyrone and indanone derivatives utilizing Fe(III)-catalyzed reductive radical ring expansion of olefins and cyclopropenone has been proposed. The preliminary mechanism study shows that the alkyl radical is formed by hydrogen atom transfer, which can open the tension ring and then generate the intermediate. There are two paths for the intermediate: when there is a hydroxyl group at the β-position of the olefin, the reaction produces pyrones, and otherwise 1-indanone is generated. This method has mild conditions and wide substrate adaptability and allows the indanone fragment to be conveniently accessed.

Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp²)–H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C–N bonds, facilitating the construction of cyclopeptides via late-stage cyclodimerization of structurally complex peptides, which poses significant challenges for organic synthesis. The synthetic utility of this protocol is demonstrated through the synthesis of 30- to 38-membered macrocyclic peptides.

Boron compounds are widely employed in organic chemistry, pharmaceuticals, and materials science. Among them, borylated heterocycles serve as versatile synthons for the construction of new C–C or C–heteroatom bonds via coupling or radical processes. Such methods for direct C–H borylation reactions are of high synthetic value to reduce the number of synthetic steps and the amount of waste and to improve efficiency. Despite significant advances, the borylation of heterocycles remains an ongoing challenge with great potential for applications in chemical synthesis. Herein, we describe a photocatalytic C–H borylation reaction of five-membered ring heterocycles by employing a stable N-heterocyclic carbene borane as the borylating reagent and a photoredox catalyst. Under green and mild conditions, C–H borylation was achieved on a series of benzo-fused five-membered heterocyclic compounds. Further studies demonstrate the utility of this approach for applications in pharmaceutical and agrochemical research.

A novel sesquiterpene lactone derivative, vernonolide A (1), featuring an unprecedented carbon skeleton, along with its plausible biosynthetic precursor, vercinolide I (2), and eight known sesquiterpene lactones (3–10) were isolated and characterized from the whole plants of Vernonia cinerea (L.). The structures of 1 and 2 were elucidated using nuclear magnetic resonance spectroscopic analysis and calculated and experimental electronic circular dichroism spectra. A plausible biosynthetic pathway for 1 was proposed. Notably, compounds 8 and 10 exhibited significant inhibitory effects on tumor necrosis factor-α-induced nuclear factor-κB activity, with IC₅₀ values of 0.95 and 5.57 μM, respectively.

General procedures for the rhodium-catalyzed annulation of aryl/heteroaryl O-pivaloyl hydroxamic acids and norbornadiene have been developed. Employing norbornadiene as an acetylene equivalent enables utilization of diverse heterocyclic substrates for this transformation which fail to react or undergo competitive Lossen rearrangement under previously reported conditions. Microwave heating significantly reduces reaction times compared to conventional protocols and allows a one-step process to be realized. The conditions described herein have been adapted for gram-scale synthesis and applied to the formal synthesis of Pfizer clinical candidates.

Herein, we report a formal C–C bond azidation and cyanation of unactivated aliphatic ketones using commercially available tosyl azide and cyanide, respectively. A visible-light-mediated organophotocatalyst enables radical azidation and cyanation of ketone-derived pro-aromatic dihydroquinazolinones (under mostly redox-neutral conditions) as supported by preliminary mechanistic studies. These metal-free and scalable protocols can be used to synthesize tertiary, secondary, and primary alkyl azides and nitriles with good functional group tolerance and postsynthetic diversification of the azide group, including bioconjugation.

A three-component cascade boronation–dearomatization reaction of alkenes, a diboron compound, and a pyridinium salt is diclosed, affording chiral boron-containing 1,4-dihyropyridines in high yields (≤98%) and diastereoselectivity (≤10:1 dr), along with excellent enantioselectivity (typically >99% ee). The catalytic system performs efficiently at low catalyst loadings (1 mol %) and was tested with >50 examples, including some biologically active molecules.

The development and enantioselective synthesis of two types of C₂-symmetric spirobi[dihydrophenalene] structures is reported. The reaction proceeds via rhodium-catalyzed 2-fold asymmetric conjugate arylation of dienones followed by BF₃·OEt₂-promoted spirocyclization to give the enantiopure spiro products. Additive-dependent chemodivergent synthesis of 3,3′-diarylated 2,2′,3,3′-tetrahydro-1,1′-spirobi[phenalene]-9,9′-diols (3,3′-Ar₂-SPHENOLs) and the corresponding spiro diary ethers from the same intermediate is achieved. The structural properties of 3,3′-Ph₂-SPHENOL are analyzed, and its application in asymmetric catalysis has been preliminarily demonstrated.

Decyanation after α-functionalization by exploiting the inherent properties of cyano groups enables the strategic assembly of a carbon scaffold. Herein, we demonstrate an amine-ligated boryl radical-mediated cyano group transfer (CGT) strategy of malononitriles under photocatalytic conditions. This strategy allows for the cleavage of C(sp³)–CN and the formation of C(sp³)–D and C(sp³) to realize decyanative deuteration and cyclization via radical-polar crossover. Computational studies successfully demonstrated the reactivity of CGT promoters can be accurately assessed.

We synthesized a series of polychlorinated trityl radical substituted phenylphosphines. Through UV–vis photoluminescence (PL) spectroscopy and cyclic voltammetry, we explored the influence of the chemical modifications (oxidation/reduction, coordination, and methylation) of the phosphorus center(s) on tuning the optical and redox properties of the tris(2,4,6-trichlorophenyl)methyl (TTM) radical framework. Those compounds hold promise for applications in coordination chemistry and luminescent materials, particularly in systems where both radical and phosphine-based functionalities can be leveraged for innovative properties.

In this work, we developed a phosphine-catalyzed cascade lactonization/[2 + 1] annulation reaction between vinyl oxiranes and sulfonium compounds for the highly diastereoselective construction of spiro-2(3H)-furanone skeletons. The cascade cycloaddition proceeds via the 2(5H)-furanone phosphonium intermediate, introducing an oxygen-containing active intermediate for phosphine catalysis. These findings highlight the significant potential of harnessing vinyl oxiranes as versatile synthons for constructing spirocyclic compounds through simultaneous multicyclic skeleton formation.

Herein, a one-pot domino catalyzed three-component process is described, which is initiated by a palladium/zinc cooperatively catalyzed cycloaddition between trimethylenemethane (TMM) and unactivated alkyl/aryl imines, followed by one-pot isomerization and Zn(OTf)₂-catalyzed DDQ oxidation, furnishing valuable substituted pyrroles. We disclose that the palladium/zinc cooperative catalysis affords a dual-Zn(OTf)₂-stabilized azapalladacycle, wherein the Pd–N bond is polarized by Zn(OTf)₂, facilitating a unique outer-sphere allylic amination. Moreover, subsequent DDQ dehydrogenation can be feasibly promoted by zinc catalysis.

Sulfone motifs play important roles in bioactive compounds and functional materials. The development of efficient methodologies for constructing sulfonyl-containing compounds has thus attracted considerable attention. Here, we introduce a protocol for the preparation of alkyl aryl sulfones under mild conditions. This protocol employs β-thioamide sulfone as a novel sulfone motif donor. It forms sulfinates in situ under basic conditions, which then undergo cross-coupling with the intermediates that were generated from ligand-free copper-catalyzed cyclopropenes (CPEs) ring opening.

A Cu-catalyzed relay process for the preparation of diazidated quinazolinone and polycyclic imidazole derivatives in which readily available alkene-tethered substrates undergo an addition/cyclization/C(sp³)–H functionalization of alkene sequences with high efficiency is described. Various functionalized N-heteropolycyclic compounds were readily prepared in good yields with a broad substrate scope. Moreover, the direct azidation of the α-C(sp³)–H bond of the corresponding N-heterocycles has been demonstrated on the basis of mechanistic studies, which provide an alternative late-stage functionalization approach for the derivatization of N-heterocyclic scaffolds.

Treatment of multisubstituted NH-enesulfinamides with tosyl isocyanate (TsNCO) at room temperature results in the formation of α-tosylcarbamoyloxy N-sulfenyl ketimines with high enantioselectivity. This process is believed to proceed via a vinylogous aza-Pummerer-type reaction pathway in which the sulfinyl oxygen atom in the enesulfinamides undergoes nucleophilic attack on tosyl isocyanate, triggering the subsequent transformations that enable the transfer of chirality from sulfur to carbon.

Thioxanthone synthesis from o-silylaryl triflates and thioureas is disclosed. Double aryne insertion into the C═S double bond of thioureas and subsequent hydrolysis realized the facile preparation of thioxanthones. A simple reaction procedure and good accessibility of o-silylaryl triflates allowed us to synthesize a wide range of highly functionalized thioxanthones.

Transition-metal-catalyzed [2 + 2 + 2] annulation of alkynes is an efficient pathway for the synthesis of aromatic compounds. However, most of the established methods require noble metal catalysts. Herein, we report a copper-catalyzed intermolecular [2 + 2 + 2] annulation of diynes with alkynes through vinyl cation intermediates, enabling the atom-economical preparation of biologically important carbazole skeletons. The reaction shows good regioselectivity in the reaction of aryl(alkyl)alkynes. Moreover, preliminary results have also been obtained for the related catalytic atroposelective transformation. This reaction represents a rare example of non-noble-metal-catalyzed intermolecular [2 + 2 + 2] annulation of ynamides through the vinyl cation pathway.

A Brønsted acid-catalyzed enantioselective synthesis of (Z)-1,3-butadienyl-2-carbinols is developed. By employing a chiral phosphoric acid as the catalyst, a variety of 1,3-butadienyl-2-carbinols were obtained in good yields with excellent Z-selectivities and enantiopurities from α-alkyl-substituted homoallenyl boronates.

We present a versatile palladium-catalyzed glycosylation platform that enables facile access to structurally diverse N–O-linked glycosides with constantly excellent regio- and stereoselectivities. Importantly, this approach offers a broad substrate scope, low catalyst loadings, and outstanding chemoselectivity, allowing for the selective reaction of oximes/hydroximic acids over hydroxyl groups that would otherwise pose challenges in conventional glycosylation methods. The synthetic utility of this method is further exemplified through a range of synthetic transformations and late-stage modification of bioactive molecules. Overall, our method provides an efficient toolkit for the synthesis of N–O-linked glycosides, which will facilitate their subsequent biological evaluations.

An anaerobic 1,2-/1,3-hydroxytrifluoromethylation of unactivated alkenes is described. This reaction proceeds in mild and environmentally friendly conditions without photocatalyst and metal catalyst, allowing access to a wide range of β- and γ-trifluoromethyl alcohols. Preliminary mechanistic investigations indicate that the accomplishment of this protocol relies on the dual functionality of the photoexcited triplet nitroarenes, which serve as the oxygen atom source and enable the single-electron transfer (SET) process with CF₃SO₂Na.

The temperature-dependent switching behavior of the saccharin radical is demonstrated, enabling the regiodivergent C₃–H and C₇–H functionalization of quinoxalin-2(1H)-ones. The saccharin radical was generated through N–Br bond cleavage in N-bromosaccharin (NBSA) and was observed to transition between radical and radicophile roles. At −10 °C, it was utilized as a radicophile, resulting in 100% C₃-amination, while at +35 °C, it acted as a radical, leading to exclusive C₇-bromination. Radical nucleophilicity was controlled by temperature modulation.

Spirochrains A–D, four undescribed spirocyclic amides, were obtained from an Antarctic fungus, Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were elucidated through spectroscopic analysis and quantum calculations. Spirochrains A–D possess a rarely reported cage-like 5/6/5 fused spirocyclic amide scaffold. Spirochrain B exerted antiviral effects by targeting the viral entry phase and inhibiting viral adsorption. Noteworthily, surface plasmon resonance (SPR) revealed strong binding affinity of 2 to RSV-G protein with a K_D value of 7.95 nM.

An entirely chromium-free synthesis of eribulin, a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin B, was achieved through iterative sulfone fragment couplings followed by an intramolecular Prins reaction involving a C.26 homoallenyl alcohol and a C.27 aldehyde acetal. A notable feature of this new macrocyclization is the employment of a β-ketosulfone at C.15/14 as an acid-stable progenitor of the notoriously acid-sensitive polycyclic ketal moiety, characteristic of the halichondrins.

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.