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Herein, we report concise total syntheses of diterpene natural products (-)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. Our synthesis features a convergent Kozikowski β-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2 + 2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5-6-4-5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5-6-4-5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed us to complete total syntheses of (-)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR3-catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.

[Display omitted] • Confinement of cross-linked ionic polymer within the pores of porous carbon. • Ionic liquid@porous carbon composites with accessible active sites. • Exceptional catalytic conversion across various epoxides. • Confinement effect enhancing stability and activity. • Novel insights for functionalized porous carbon catalyst design. It is crucial to employ an integrated catalyst to avoid the complications of the recovery process. This work reports the fabrication of porous carbon@ionic liquid (PC@IL) composites with readily accessible active ion sites, achieved by confining cross-linked ionic liquid (IL) within the channels of porous carbon (PC). The incorporation of porous carbon not only confines the IL within its framework, creating microsites for CO 2 adsorption and conversion, but also simplifies catalyst recovery. The results indicate that PC@IL composites exhibit excellent cycloaddition activity towards CO 2 in a co-catalyst- and solvent-free environment. Notably, PC@IL(C)-24 demonstrates remarkable catalytic performance across various epoxides under 1 bar of CO 2 , with yields above 90 % at 90 °C for 12 h, and achieving a remarkable styrene carbonate yield of up to 92.8 % under a CO 2 pressure of 1 bar (at 100 °C for 12 h). Control experiments confirm that the confinement effect exerted by N,S co-doped carbon on cross-linked IL plays a pivotal role in enhancing both stability and activity of PC@IL composites, thereby providing novel insights for designing functionalized porous carbon catalysts for CO 2 cycloaddition conversion. [ABSTRACT FROM AUTHOR]

Schiff‐base materials are known ligands for the coordination of metal ions and the synthesis of various stable and useful complexes. Therefore, herein, a novel Schiff‐base compound {2,2′‐((1E,11E)‐2,5,8,11‐tetra azadodeca‐1,11‐diene‐1,12‐diyl) bis (4‐bromophenol)} was introduced that formed from condensation of triethylenetetramine (TETA) and 5‐bromo‐2‐hydroxybenzaldehyde (5B2HB). This Schiff‐base ligand was labeled as TADDbBP. Besides, mesoporous MCM‐41 was synthesized using tetraethyl orthosilicate (TEOS), hydrolyzing cetyltrimethylammonium bromide (CTAB) and NaOH solution (2 M), followed by calcination at 550 °C, and further, the silanol sites on the MCM‐41's surface were modified by 3‐chloropropyltriethoxysilane (3Cl‐PTES), which modified MCM‐41 was labeled as 3‐Cl‐Pr@MCM‐41. In the next step, the synthesized TADDbBP (as Schiff‐base ligand) was grafted on 3‐Cl‐Pr@MCM‐41, which was labeled as TADDbBP@MCM‐41, and further, it was coordinated with samarium ions (which was labeled as Sm‐TADDbBP@MCM‐41 nanocatalyst) using Sm (CH3COO)3. This is the first report on the production of Sm‐TADDbBP@MCM‐41 nanocatalyst, this nanocatalyst was characterized by TEM, SEM, EDX, elemental mapping, BET method, ICP, XRD, and TGA techniques. In the final step, the catalytic performance of Sm‐TADDbBP@MCM‐41 nanocatalyst has been checked in the homo‐selective producing of tetrazoles through [2 + 3] cycloaddition of benzonitriles and sodium azide (NaN3) in PEG‐400 as available, nontoxic, green, and safe solvent. This nanocatalyst provides excellent selectivity in the synthesis of tetrazoles. In addition, Sm‐TADDbBP@MCM‐41 nanocatalyst can be separated and recycled for several cycles without significant reactivation or metal leaching. [ABSTRACT FROM AUTHOR]

Context: The analysis of the changes in the electronic structure along intrinsic reaction coordinate (IRC) paths for model reactions: (i) ethylene + butadiene cycloaddition, (ii) prototype SN2 reaction Cl− + CH3Cl, (iii) HCN/CNH isomerization assisted by water, (iv) CO + HF → C(O)HF was performed, in terms of changes in the deformation density (Δr) and the deformation of MEP (ΔMEP). The main goal was to further examine the utility of the ΔMEP as a descriptor of chemical bonding, and to compare the pictures resulting from Δr and ΔMEP. Both approaches clearly show that the main changes in the electronic structure occur in the TS region. The ΔMEP picture is fully consistent with that based on Δρ for the reactions of the neutral species leading to the neutral products without large charge transfer between the fragments. In the case of reactions with large electron density displacements, the ΔMEP picture is dominated by charge transfer leading to more clear indication of charge shifts than the analysis of Δr. Methods: All the calculations were performed using the ADF package. The Becke–Perdew exchange–correlation functional was used with the Grimme's dispersion correction (D3 version) with Becke-Johnson damping. The Slater TZP basis sets defined within the ADF program were applied. For the analysed reactions, the stationary points were determined and verified by frequency calculations, and the IRC was determined. Further analysis was performed for the structures of reactants, TS, products, and the points corresponding to the minimum and maximum of the reaction force. For each point, two fragments, A and B, corresponding to the reactants were considered. The deformation density was calculated as the difference between the electron density of the system AB and the sum of densities of A and B, Δ ρ r = ρ AB r - ρ A r - ρ B r , with the same fragment definition as in the ETS-NOCV method. Correspondingly, deformation in MEP was determined as Δ V r = V AB r - V A r - V B r . [ABSTRACT FROM AUTHOR]

Herein, Sonogashira coupling at the vinyl bromide position of triazole-bearing benzosuberene has been introduced for the synthesis of potentially bioactive 1,2,3-triazole and conjugated enynes containing benzosuberene analogues. The instalment of triazole moiety on the allylic position dictates the Sonogashira coupling at the vinylic position, the absence of which failed to execute the desired reaction. The Cu-catalyzed cycloaddition initially led to the incorporation of 1,2,3-triazole, which subsequently directed the Pd/Cu-catalyzed Sonogashira coupling to deliver new class of benzosuberene analogues in appreciable yields. The regioselective synthesis of 1,2,3-triazole and conjugated enynes containing benzosuberene analogues has been reported under operationally simple and milder reaction conditions. [ABSTRACT FROM AUTHOR]

A highly convenient and straightforward strategy for the synthesis of difluoromethyl substituted tricyclic fused chromono[3,2- c ]pyrazolines/pyrazoles is developed via [3+2]-cycloaddition of difluoroacetohydrazonoyl bromides to chromene derivatives bearing an electron-withdrawing group at the 3-position. The reaction has the advantages of mild conditions, good tolerance of functional groups, and simple operation. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reaction holds promise for synthesizing of biologically active heterocyclic compounds. However, to fully exploit its synthetic potential and utilize the reactivity of 1,2-cyclooctadiene as convenient building blocks in the one-step formation of complex cycloadducts, it is crucial to understand the regio- and stereochemical considerations associated with this reaction. Herein, density functional theory (DFT) study has been carried out to explore the chemo-, regio- and stereoselectivities of the 32CA reaction of 1-pyrrolidine-1-oxide (cyclic nitrone) and a C, N-diphenyl nitrones (acyclic nitrone) with a 1,2-cyclooctadiene carboxylate at the M062X/6-311G (d, p) level of theory. The preferred pathway involves the addition of the acyclic nitrone to the substituted olefinic bond of the allene to form 4-methylene isoxazolidine. The free activation energy of 1.8 kcal/mol and the associated rate constant of 7.50 × 1011 s−1 are calculated for the process. This is 113.5 times higher than the formation of 5-methylene isoxazolidine, its regioisomeric product. For the formation of 5-methylene isoxazolidine, the calculated free activation energy is 5.4 kcal/mol. Strong electron-releasing and electron-withdrawing groups lower the activation energies to speed up the reaction. Substituents on B2 (R = CH3 and CH2CH3) have slightly high activation energies compared to the parent reaction. The decrease in activation energies relative to the parent is CH3 < CH2CH3 < OCH3 < NH2. The acyclic and cyclic nitrone derivatives add across the atomic centers with the largest atomic spin densities as evidenced by the local electrophilic (PK+) and nucleophilic (PK−) Parr functions of the various reaction centers. Results from the global electron density transfer (GEDT) reveal the low polar nature of the reactions. [ABSTRACT FROM AUTHOR]

Ambient condition-determined chemical CO2 fixation affords great promise for remitting the pressure of CO2 release. The construction of a microporous environment easily captures CO2 molecules around the reactive sites of the catalyst to reinforce the reaction process. Herein, multi-hydroxyl-containing hyper-crosslinked organic polymers (HCPs-OH-n) are synthesized by the polymerization of 1,4-dichlorobenzyl (DCX) and m-trihydroxybenzene in the monosaccharide form in a Friedel–Crafts alkylation hypercrosslinking process (FCAHP). By tuning the DCX ratio in the FCAHP, the structural properties can be regulated to create a more microporous surface in the HCPs-OH-n; meanwhile, the formed multi-hydroxyl species in the microporous environment could induce the easy interaction between hydroxyls and epoxides by forming a hydrogen bond, which improves the activation of epoxides during the cycloaddition reaction to synthesize the cyclic carbonates at ambient conditions. The structural properties suggest that HCPs-OH-n possess a large surface area with appreciable microporous and mesoporous distribution. As expected, the HCPs-OH-3 bearing the most abundant mesoporosity affords the highest reactivity in the chemical CO2 fixation to cyclic carbonates and is endowed with rational recoverability. [ABSTRACT FROM AUTHOR]

Tetradentate ONNO donor ligands H2hz(fp)2 (I), H2hz(butp)2 (II) and H2hz(bp)2 (III) synthesized by the reaction of hydrazine hydrate with 4‐formyl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (fp), 4‐butyryl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (butp) and 4‐benzoyl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (bp), respectively, react with [MoVIO2(acac)2] in 1 : 2 molar ratio in refluxing methanol to give binuclear complexes [(μ‐O){MoVIO2(H2O)}2hz(fp)2] (1) and [(μ‐O){MoVIO2(H2O)}2hz(butp)2] (2) and [(μ‐O){MoVIO2(H2O)}2hz(bp)2] (3). All ligands and complexes are characterized by several techniques that include, FT‐IR, UV/Vis, 1H NMR, 13C NMR spectroscopy, elemental and thermal analysis, and single crystal X‐ray analysis of 2 and 3. Ligands coordinate through a set of ON functionalities of the same ligand to two MoVIO2 groups attached through an oxido‐bridge. Additional coordination of water to each vanadium makes each of them to maintain an octahedral geometry. Azine moiety coordinates to two molybdenum through the symmetrical μ‐{η2‐(N−N)} fashion. Catalytic activity of these complexes was studied for the cycloaddition of CO2 with epoxides. A pressure of 4 bar CO2, 3.0 mg catalyst, 1 mmol of tetrabutylammonium bromide (TBAB) at 120 °C for 6 h were found to be most suited reaction condition for 10 mmol epoxide. Under the optimized reaction conditions, the product yield and selectivity of alkene carbonate for all complexes were investigated. As high as 96 % yield with almost 99 % selectivity for styrene carbonate under these optimized reaction conditions was achieved. [ABSTRACT FROM AUTHOR]

The Diels-Alder cycloaddition is one of the most powerful approaches in organic synthesis and is often used in the synthesis of important pharmaceuticals. Yet, strictly controlling the stereoselectivity of the Diels-Alder reactions is challenging, and great efforts are needed to construct complex molecules with desired chirality via organocatalysis or transition-metal strategies. Nature has evolved different types of enzymes to exquisitely control cyclization stereochemistry; however, most of the reported Diels-Alderases have been shown to only facilitate the energetically favourable diastereoselective cycloadditions. Here we report the discovery and characterization of CtdP, a member of a new class of bifunctional oxidoreductase/Diels-Alderase, which was previously annotated as an NmrA-like transcriptional regulator. We demonstrate that CtdP catalyses the inherently disfavoured cycloaddition to form the bicyclo[2.2.2]diazaoctane scaffold with a strict α-anti-selectivity. Guided by computational studies, we reveal a NADP+/NADPH-dependent redox mechanism for the CtdP-catalysed inverse electron demand Diels-Alder cycloaddition, which serves as the first example of a bifunctional Diels-Alderase that utilizes this mechanism.

We report the detection of 5-vinyluridine (5-VUrd) in RNA at single nucleotide resolution via mutational profiling. Maleimide cycloadducts with 5-VUrd in RNA cause a stop in primer extension during reverse transcription, and the full-length cDNA product from reverse transcription contains misincorporation across the cycloadduct site.

A silver‐catalyzed regioselective one‐pot cyclization reaction of diazo reagents with fluoronitroalkenes was developed. This transformation presents a method for accessing a series of 4‐aryl‐3‐fluoropyrazoles that are substituted with various groups such as trifluoromethyl, carboxylic ester, nitrile, and phosphonate ester. Further synthetic transformations offered the corresponding fluorinated and trifluoromethylated analogues of two fungicide compounds. [ABSTRACT FROM AUTHOR]

Ionic liquid immobilization is an effective means for preparing metal-free heterogeneous catalysts for the CO2 conversion. Herein, a series of quaternary ammonium ionic liquids functionalized MCM-41 heterogeneous catalysts, integrating hydrogen bond donors and nucleophilic ion sites, were prepared by a post-synthetic modification method for the CO2 cycloaddition reaction. The physicochemical properties of the catalysts were analyzed by XRD, EA, SEM, TEM, BET, FT-IR, TGA, NMR and XPS. The results show that the quaternary ammonium ionic liquids are successfully immobilized onto the MCM-41 molecular sieves. The obtained catalysts maintain an excellent pore structure and have the good thermal stability. The effects of catalytic conditions on the catalytic performance, the recyclability of the catalysts and their generalizability to epoxide substrates were systematically investigated. In addition, the catalytic performance was evaluated for low concentrations of CO2 (20% CO2, 80% N2). The synergy of multifunctional active sites makes the obtained materials exhibit the high catalytic activity without metals, co-catalysts and solvents. Furthermore, a possible mechanism for the conversion of CO2 to cyclic carbonate catalyzed by the MCM-41-N/CH3(1:3) was proposed. [ABSTRACT FROM AUTHOR]

Detailed herein are our synthetic studies toward the preparation of the C18- and C19-benzenoid cephalotane-type norditerpenoids. Guided by chemical network analysis, the core structure of this natural product family was constructed in a concise manner using an iterative cross-coupling, followed by a formal inverse-electron-demand [4 + 2] cycloaddition. Initial efforts to functionalize an alkene group in the [4 + 2] cycloadduct using a Mukaiyama hydration and a subsequent olefination led to the complete C18-carbon framework. While effective, this approach proved lengthy and prompted the development of a direct alkene difunctionalization that relies on borocupration to advance the cycloadduct to the natural products. Late-stage peripheral C-H functionalization facilitated access to all of the known cephanolides in 6-10 steps as well as five recently isolated ceforalides in 8-13 steps.

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.

Bioorthogonal cycloaddition reactions between tetrazines and strained dienophiles are widely used for protein, lipid and glycan labelling because of their extremely rapid kinetics. However, controlling this chemistry in the presence of living mammalian cells with a high degree of spatial and temporal precision remains a challenge. Here we demonstrate a versatile approach to light-activated formation of tetrazines from photocaged dihydrotetrazines. Photouncaging, followed by spontaneous transformation to reactive tetrazine, enables live-cell spatiotemporal control of rapid bioorthogonal cycloaddition with dienophiles such as trans-cyclooctenes. Photocaged dihydrotetrazines are stable in conditions that normally degrade tetrazines, enabling efficient early-stage incorporation of bioorthogonal handles into biomolecules such as peptides. Photocaged dihydrotetrazines allow the use of non-toxic light to trigger tetrazine ligations on living mammalian cells. By tagging reactive phospholipids with fluorophores, we demonstrate modification of HeLa cell membranes with single-cell spatial resolution. Finally, we show that photo-triggered therapy is possible by coupling tetrazine photoactivation with strategies that release prodrugs in response to tetrazine ligation.

The cycloaddition of CO2 to epoxides to afford versatile and useful cyclic carbonate compounds is a highly investigated method for the nonreductive upcycling of CO2. One of the main focuses of the current research in this area is the discovery of readily available, sustainable, and inexpensive catalysts, and of catalytic methodologies that allow their seamless solvent-free recycling. Water, often regarded as an undesirable pollutant in the cycloaddition process, is progressively emerging as a helpful reaction component. On the one hand, it serves as an inexpensive hydrogen bond donor (HBD) to enhance the performance of ionic compounds; on the other hand, aqueous media allow the development of diverse catalytic protocols that can boost catalytic performance or ease the recycling of molecular catalysts. An overview of the advances in the use of aqueous and biphasic aqueous systems for the cycloaddition of CO2 to epoxides is provided in this work along with recommendations for possible future developments. [ABSTRACT FROM AUTHOR]

The research progress of metal-organic framework (MOFs) materials in photocatalytic carbon dioxide (CO2) cycloaddition reaction in recent years was reviewed ・ The mechanism of cycloaddition reaction of CO2 under photocatalysis was analyzed, and four modification strategies of MOFs were introduced, including structural defects of MOFs, MOFs with active catalytic metal s让es, heterojunctions with semiconductor materials, and co-catalyst functionalization of MOFs. Based on the current research status of CO2 cycloaddition reaction, the prospects and challenges of MOFs and its composites in the field of photocatalysis are presented. [ABSTRACT FROM AUTHOR]

By treating KSiiPr3 with Sn[N(SiMe3)2]2 the distannene Sn2(TIPS)4 (TIPS=SiiPr3) is formed in a metathesis reaction. The crystal structure analysis of Sn2(TIPS)4 reveals a planar arrangement of the substituents in the solid‐state and hence the second planar alkene like distannene of its kind. Due to the TIPS substituents, Sn2(TIPS)4 is well soluble in all commonly used organic solvents, opening the door for various analytics and reactivity studies. Due to its stability in solution, various reactions can be performed such as cycloaddition reactions with 2,3‐dimethyl‐1,3‐butadiene (DMBD) and TMS‐azide. [ABSTRACT FROM AUTHOR]

Fixing the greenhouse gas CO2 through epoxide helps to mitigate worldwide ecological troubles. The applications of metal‐free and solvent‐free catalysts remain a challenge for CO2 catalytic conversion. In this work, an array of quaternary ammonium salts derived from polyethyleneimine with hydroxyl groups ([PEI‐GDMAB‐Cn]Br) were constructed by the reaction of branched PEI with a molecular weight of 10000 and glycidyl alkyl dimethylammonium bromide. A range of experiments were designed to demonstrate that [PEI‐GDMAB‐Cn]Br can be considered as a valid metal‐free and solvent‐free homogeneous catalyst for the CO2‐epoxide cycloaddition reaction. Among of [PEI‐GDMAB‐Cn]Br, [PEI‐GDMAB‐C18]Br catalyzed the model reaction of CO2 and epichlorohydrin under optimized reaction conditions (T=80 °C, 1.0 atm CO2, catalyst 1 mol%, ECH 15 mmol, 16 h) and the conversion achieved at 97.5 %. Moreover, the catalyst exhibited stable reusability and broad substrate applicability, which was used in the following cycle succinctly, because of self‐separated properties by temperature control. The [PEI‐GDMAB‐C18]Br catalyzed reaction process was detected as a pseudo‐first‐order reaction after kinetic studies and an Ea was calculated to be 50.65 kJ/mol. A combinatorial catalytic mechanism of hydrogen bonding and bromide ions is suggested to explain the remarkable catalytic performance of this bifunctional catalyst. [ABSTRACT FROM AUTHOR]

Over the last few years, benzimidazole-heterocycle hybrid compounds have received considerable attention due to the wide spectrum of their biological property and many important chemical and pharmacological applications. These compounds have revealed antibacterial, antimicrobial, anticoagulant, antidiabetic and other activities, and they have been used as drugs in the market to treat several diseases. Furthermore, hybrid heterocyclic compounds possessing a benzimidazole skeleton exhibit significant complexing and anticorrosive properties. All of these applications have favored the development of a large number of synthetic strategies to prepare these heterocyclic systems in different reaction conditions. Many research articles on the synthesis of benzimidazole-heterocycle hybrid compounds have been reported in the literature. In this review, we present and discuss the synthetic routes of several benzimidazole-heterocycle hybrid compounds. [ABSTRACT FROM AUTHOR]

Rising carbon dioxide (CO2) levels in the atmosphere are recognized as a threat to atmospheric stability and life. Although this greenhouse gas is being produced on a large scale, there are solutions to reduction and indeed utilization of the gas. Many of these solutions involve costly or unstable technologies, such as air‐sensitive metal–organic frameworks (MOFs) for CO2 capture or "non‐green" systems such as amine scrubbing. Conjugated microporous polymers (CMPs) represent a simpler, cheaper, and greener solution to CO2 capture and utilization. They are often easy to synthesize at scale (a one pot reaction in many cases), chemically and thermally stable (especially in comparison with their MOF and covalent organic framework (COF) counterparts, owing to their amorphous nature), and, as a result, cheap to manufacture. Furthermore, their large surface areas, tunable porous frameworks and chemical structures mean they are reported as highly efficient CO2 capture motifs. In addition, they provide a dual pathway to utilize captured CO2 via chemical conversion or electrochemical reduction into industrially valuable products. Recent studies show that all these attractive properties can be realized in metal‐free CMPs, presenting a truly green option. The promising results in these two fields of CMP applications are reviewed and explored here. [ABSTRACT FROM AUTHOR]

The reaction of 1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)ethan-1-one 1 with dimethylformamide dimethyl acetal (DMF-DMA) afforded 3-(dimethylamino)-1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)prop-2-en-1-one 2. Then the treatment of enaminone 2 with the appropriate hydrazonoyl halides 3a–f in chloroform in the presence of triethylamine at reflux gave novel bipyrazolyl methanone derivatives 4a–f. The novel bipyrazole derivatives 4a–c and 4d–f reacted with hydrazine hydrate in ethanol at reflux to give the corresponding pyrazolopyridazinones 9a–c and pyrazolopyridazines 10d–f, respectively. Stirring of hydroximoyl chlorides 11a,b with enaminone 2 in chloroform in the presence of triethylamine at room temperature afforded isoxazole derivatives 12a,b. The reaction of isoxazoles 12a,b with hydrazine hydrate in refluxing ethanol gave the corresponding isoxazolopyridazines 14a,b. [ABSTRACT FROM AUTHOR]

Developing a highly efficient and environmentally friendly catalytic system for CO2 cycloaddition reactions is an attractive way to achieve carbon neutrality. In this work, tetrabutylammonium iodide (TBAI) and polyethylene glycol (PEG) were used to produce novel deep eutectic solvents (DESs), which could serve as both solvents and catalysts, displaying excellent activity to synthesis styrene carbonates from CO2 and styrene oxide under metal‐free, cocatalyst‐free, solvent‐free and mild conditions. A detailed study was undertaken on the effects of reaction parameters, recyclability, and substrate scope. Additionally, the H‐bond interaction between the substrate and TBAI/PEG200 was thoroughly investigated using FT‐IR and 1H NMR techniques. The synergistic interaction between the two components of the DES, TBAI, and PEG200, may be the key to the high catalytic activity of this system. The tetrabutylammonium iodide‐based system is an innovative strategy for the CO2 cycloaddition with epoxides, achieved by elaborately devising the H‐bonds of DESs to enhance reactivity. This provides a novel green strategy for potential industrial applications. [ABSTRACT FROM AUTHOR]

1,2,3-Triazines and 1,2,3,5-tetrazines react rapidly, efficiently, and selectively with amidines to form pyrimidines/1,3,5-triazines, exhibiting an orthogonal reactivity with 1,2,4,5-tetrazine-based conjugation chemistry. Whereas the mechanism of the reaction of the isomeric 1,2,4-triazines and 1,2,4,5-tetrazines with alkenes is well understood, the mechanism of the 1,2,3-triazine/1,2,3,5-tetrazine-amidine reaction as well as its intrinsic reactivity remains underexplored. By using 15N-labeling, kinetic investigations, and kinetic isotope effect studies, complemented by extensive computational investigations, we show that this reaction proceeds through an addition/N2 elimination/cyclization pathway, rather than the generally expected concerted or stepwise Diels-Alder/retro Diels-Alder sequence. The rate-limiting step in this transformation is the initial nucleophilic attack of an amidine on azine C4, with a subsequent energetically favored N2 elimination step compared with a disfavored stepwise formation of a Diels-Alder cycloadduct. The proposed reaction mechanism is in agreement with experimental and computational results, which explains the observed reactivity of 1,2,3-triazines and 1,2,3,5-tetrazines with amidines.

The tetrazine/trans-cyclooctene ligation stands out from the bioorthogonal toolbox due to its exceptional reaction kinetics, enabling multiple molecular technologies in vitro and in living systems. Highly reactive 2-pyridyl-substituted tetrazines have become state of the art for time-critical processes and selective reactions at very low concentrations. It is widely accepted that the enhanced reactivity of these chemical tools is attributed to the electron-withdrawing effect of the heteroaryl substituent. In contrast, we show that the observed reaction rates are way too high to be explained on this basis. Computational investigation of this phenomenon revealed that distortion of the tetrazine caused by intramolecular repulsive N-N interaction plays a key role in accelerating the cycloaddition step. We show that the limited stability of tetrazines in biological media strongly correlates with the electron-withdrawing effect of the substituent, while intramolecular repulsion increases the reactivity without reducing the stability. These fundamental insights reveal thus far overlooked mechanistic aspects that govern the reactivity/stability trade-off for tetrazines in physiologically relevant environments, thereby providing a new strategy that may facilitate the rational design of these bioorthogonal tools.

The biosynthesis of pyrroindomycins A and B features a complexity-building [4 + 2] cycloaddition cascade, which generates the spirotetramate core under the catalytic effects of monofunctional Diels-Alderases PyrE3 and PyrI4. We recently showed that the main functions of PyrI4 include acid catalysis and induced-fit/conformational selection. We now present quantum mechanical and molecular dynamics studies implicating a different mode of action by PyrE3, which prearranges an anionic polyene substrate into a high-energy reactive conformation at which an inverse-electron-demand Diels-Alder reaction can occur with a low barrier. Stereoselection is realized by strong binding interactions at the endo stereochemical relationship and a local steric constraint on the endo-1,3-diene unit. These findings, illustrating distinct mechanisms for PyrE3 and PyrI4, highlight how nature has evolved multiple ways to catalyze Diels-Alder reactions.

Mass spectrometry-based chemoproteomics has enabled functional analysis and small molecule screening at thousands of cysteine residues in parallel. Widely adopted chemoproteomic sample preparation workflows rely on the use of pan cysteine-reactive probes such as iodoacetamide alkyne combined with biotinylation via copper-catalyzed azide-alkyne cycloaddition (CuAAC) or "click chemistry" for cysteine capture. Despite considerable advances in both sample preparation and analytical platforms, current techniques only sample a small fraction of all cysteines encoded in the human proteome. Extending the recently introduced labile mode of the MSFragger search engine, here we report an in-depth analysis of cysteine biotinylation via click chemistry (CBCC) reagent gas-phase fragmentation during MS/MS analysis. We find that CBCC conjugates produce both known and novel diagnostic fragments and peptide remainder ions. Among these species, we identified a candidate signature ion for CBCC peptides, the cyclic oxonium-biotin fragment ion that is generated upon fragmentation of the N(triazole)-C(alkyl) bond. Guided by our empirical comparison of fragmentation patterns of six CBCC reagent combinations, we achieved enhanced coverage of cysteine-labeled peptides. Implementation of labile searches afforded unique PSMs and provides a roadmap for the utility of such searches in enhancing chemoproteomic peptide coverage.

Pericyclases, enzymes that catalyze pericyclic reactions, form an expanding family of enzymes that have biocatalytic utility. Despite the increasing number of pericyclases discovered, the Diels-Alder cyclization between a cyclopentadiene and an olefinic dienophile to form norbornene, which is among the best-studied cycloadditions in synthetic chemistry, has surprisingly no enzymatic counterpart to date. Here we report the discovery of a pathway featuring a norbornene synthase SdnG for the biosynthesis of sordaricin-the terpene precursor of antifungal natural product sordarin. Full reconstitution of sordaricin biosynthesis reveals a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder cycloaddition. SdnG generates the norbornene core of sordaricin and accelerates this reaction to suppress host-mediated redox modifications of the activated dienophile. Findings from this work expand the scopes of pericyclase-catalyzed reactions and P450-mediated terpene maturation.

{Co 3 }-based nanoporous material of {[Co 3 (TNBTB) 2 (PTP)]·7DMF·6H 2 O} n (NUC-82) displays the ultra-high C 2 H 2 separation performance over the mixture of C 2 H 2 /CH 4 and CO 2 /CH 4 and high catalytic performance on cycloaddition reaction of epoxides with CO 2 and Knoevenagel condensation. [Display omitted] Enhancing the catalysis of metal–organic frameworks (MOFs) by regulating inherent Lewis acid-base sites to realize the efficient seperation and chemical fixation of inert carbon dioxide (CO 2) is crucial but challenging. Herein, the solvothermal self-assembly of Co2+, 5′-(4-carboxy-2-nitrophenyl)-2,2′,2′',4′,6′-pentanitro-[1,1′:3′,1′'-terphenyl]-4,4′'-dicarboxylic acid (H 3 TNBTB) and 4′-phenyl-4,2′:6′,4′'-terpyridine (PTP) generated a highly robust cobalt-organic framework of {[Co 3 (TNBTB) 2 (PTP)]·7DMF·6H 2 O} n (NUC-82). In NUC-82 , the tri-core clusters of {Co 3 } with linear shape are bridged by TNBTB3– to form two-dimensional structure in ac plane, which is further linked by PTP to generate a three-dimensional framework with two kinds of solvent-accessible channels: rhombic-like (ca. 11.57 × 10.76 Å) along a axis and rectangular-like (ca. 7.32 × 11.56 Å) along b axis. Furthermore, it is worth emphasizing that the confined pore environments are characterized by plentiful Lewis acid-base sites of tricobalt clusters, grafted nitro groups and free pyridinyl, high specific surface area and solvent-free nano-caged windows. Activated NUC-82a owns the ultra-high ethylene (C 2 H 2) separation performance over the mixture of C 2 H 2 /CH 4 and CO 2 /CH 4 with the selectivity of 223.1 and 44.7. Thanks to the great Lewis-acid sites as well as the large pore volume, activated NUC-82a displays the high catalytic performace on the cycloaddition of CO 2 with epoxides under wield condtions such as amibient pressure. Furthermore, because of the rich Lewis base sites, NUC-82a can efficiently catalyze Knoevenagel condensation of aldehydes and malononitrile. In the above organic reactions, NUC-82a not only shows the high catalytic activity, but also exhibits the high selectivity, satifactory recyclability and easy-to-separate heterogeneity, confirming that NUC-82a is a promising catalyst. Hence, this work provides in-depth insight into the construction of multifunctional MOFs by modifying the traditional ligands with as many Lewis acid-base active sites as possible. [ABSTRACT FROM AUTHOR]

We present a theoretical study of the [3+2] cycloaddition (32CA) reactions of N‐benzyl fluoro nitrone with a series of maleimides producing isoxazolidines. We use the Molecular Electron Density Theory at the MPWB1K/6‐311G(d) level. We focus on the reaction mechanism, selectivity, solvent, and temperature effects. In addition, we perform topological analyses at the minimal and transition states to identify the intermolecular interactions. Electron Localization Function approach classifies the N‐benzyl fluoro nitrone as zwitterionic (zw‐) three‐atom components (TACs), associated with a high energy barrier. The low polar character of the reaction is evaluated using the Conceptual Density Functional Theory analysis of the reactants, confirmed by the low global electron density transfer computed at the transition states. Computations show that these 32CA reactions follow a one‐step mechanism under kinetic control, with highly asynchronous bond formation and no new covalent bond is formed at the TS. Besides, the potential energy surfaces along the reaction pathways in gas phase and in solvent are mapped. The corresponding Gibbs free energy profiles reveal that the exo‐cycloadducts are kinetically and thermodynamically more favored than endo‐cycloadducts, in agreement with the exo‐selectivity observed experimentally. In particular, we found that solvent and temperature did not affect this selectivity and mainly influence the activation energies and the exothermic character of these 32CA reactions. [ABSTRACT FROM AUTHOR]

Utilization of anthropogenic CO2 for the synthesis of valuable heterocyclic compounds is a very significant strategy to alleviate environmental issues. Herein, a hollow CeO2 nanosphere (HNS–CeO2) material made using solvothermal-method-assisted synthesis was employed as an efficient catalyst for the selective benzimidazole synthesis under neat and temperate reaction conditions. We examined the controlled reaction conditions for the design of the HNS–CeO2 material through the study of various reaction parameters. Very interestingly, the HNS–CeO2 material exhibited different surface morphological disparities due to the effect of various reaction parameters that were examined comprehensively using field emission scanning electron microscopy analysis. The HNS–CeO2 material was systematically well characterized using various analytical and spectroscopic techniques. The competent catalyst of HNS–CeO2 showed superior catalytic activity (100% conversion, 96% selectivity, and yield) under mild reaction conditions, and these conditions are successfully identified by studying the effect of various reaction parameters. Remarkably, the inherent properties of the HNS–CeO2 catalyst boosted the synergistic effect with the model reagents of o-phenylenediamine, carbon dioxide, dimethylamine borane (DMAB), and base. Moreover, different functional groups substituted benzimidazole compounds are successfully synthesized in good to excellent yields under optimized reaction conditions. The effective contributions of DMAB, base, Lewis acidic, and Lewis basic sites were successfully revealed by proposing a tentative benzimidazole reaction mechanism. Notably, the examined 15 successive recycles with stable catalytic activity performance demonstrated the stable catalytic activity and structural and physicochemical properties of the HNS–CeO2 catalyst. [ABSTRACT FROM AUTHOR]

The study investigates the reactivity of a cyclic five‐membered intramolecular P/B frustrated Lewis pair towards acrolein through a cycloaddition reaction. Intrinsic reaction coordinate (IRC) calculations suggest the single‐step mechanism. It has been observed that the cycloaddition reaction occurs through a concerted mechanism in both the presence and absence of the catalyst. Analysis of reaction force and reaction electronic flux provides valuable information about the total work required and electronic activity along the IRC. Additionally, natural bonding orbital (NBO) analyses enrich the understanding of the mechanism in terms of the electron transfer process during the chemical reaction. [ABSTRACT FROM AUTHOR]

Available online A mild and efficient photocatalytic-induced radical method has been developed for [4 þ 1] cycloaddition reaction of 1,4-disubstituted 1,2,3-triazoles with N-tosylhydrazides and primary amines. The reaction is catalyzed by 20 mol% of I2 under metal, azide and oxidant-free conditions. The method is based upon the photocatalytic generation of allyl-type radicals, followed by the iodine-catalyzed production of azoalkenes, which react rapidly with various anilines. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs) as new efficient catalysts have been developed for the Knoevenagel condensation reaction and the synthesis of cyclic carbonates under solvent‐free conditions. Six kinds of carbon dots with different numbers of amino groups were synthesized. The amine‐terminated carbon dot (NCDs‐1) was synthesized using arginine and ethylenediamine by a microwave technique, and its catalytic action was studied. NCDs‐1 with the highest numbers of amino groups was used as new metal‐free and effective heterogeneous catalysts to perform essential Knoevenagel condensation and cycloaddition reactions in solvent‐free conditions. 1H NMR was used to demonstrate the Knoevenagel condensation mechanism, in situ Fourier infrared spectroscopy was used to investigate CO2 cycloaddition and a catalytic mechanism was postulated. NCDs‐1 showed a yield of 96.3±1.5 % for Knoevenagel condensation of benzaldehyde and malononitrile. In addition, NCDs‐1/TBAB showed a yield of (97.0±1.0 %) of 4‐phenyl‐1,3‐dioxolan‐2‐one for styrene oxide at 100 °C and 0.1 MPa in 1.5 h. A simple and convenient method for catalytic reactions with amine‐terminated carbon dots was developed. [ABSTRACT FROM AUTHOR]

Reaction of substituted acetylpyrazole with methyl hydrazinecarbodithioate using hydrochloric acid as a catalyst in absolute ethanol afforded methyl 2-(1-(1H-pyrazol-4-yl)ethylidene)hydrazinecarbodithioate derivative. Refluxing of the latter product with hydrazonoyl halides in absolute ethanol in the presence of triethylamine afforded the corresponding 1,3,4-thiadiazoles. Heating the same acetylpyrazole with hydrazinecarbothioamide in refluxing ethanol using hydrochloric acid as a catalyst afforded 2-(1-(1H-pyrazol-4-yl)ethylidene)hydrazinecarbothioamide derivative. The reaction of the latter compound with 1-bromoacetophenone derivatives in absolute ethanol at reflux afforded the corresponding thiazole derivatives. [ABSTRACT FROM AUTHOR]

BACKGROUND: Carbon dioxide is not only a major greenhouse gas but also an important carbon resource, which is abundant, renewable, low cost and non‐toxic. The coupling reaction of CO2 with epoxides has shown great potential in the field of chemical carbon fixation due to its 100% atomic utilization efficiency. Deep eutectic solvents (DESs) based on tetrabutylammonium bromide (TBAB) were evaluated for cycloaddition reaction of CO2 with propylene oxide (PO) to propylene carbonate (PC). Density functional theory (DFT) was used to calculate the catalytic performance of DES in CO2 cycloaddition reaction. RESULTS: The utilization of DES containing triethanolamine (TEA) as hydrogen bond donor significantly shortened the reaction time. Under optimal reaction conditions (30 mmol PO, 5 mol% TBAB/TEA (1:1) DES, 1.0 MPa CO2, 90 °C, 2 h), high PC yield (98%) was obtained. DFT calculations revealed that TBAB/TEA (1:1) DES was used as the catalyst for the coupling reaction between PO and CO2, with the ring‐opening process serving as the rate‐determining step and energy barrier of 17.9 kcal mol−1. TBAB/TEA (1:1) DES exhibited excellent recyclability and could be reused more than five times. CONCLUSION: TBAB/TEA (1:1) DES is a highly efficient homogeneous catalyst for the synthesis of cyclic carbonates through the cycloaddition reaction of CO2 and epoxides. The synergistic catalytic effect of the double hydrogen bonds between DES and Br anions is the reason for its high efficiency. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Pyridyl tetrazines coordinated to metals like rhenium have been shown to be more reactive in [4 + 2] cycloadditions than their uncomplexed counterparts. Using density functional theory calculations, we found a more favorable interaction energy caused by stronger orbital interactions as the origin of this increased reactivity. Additionally, the high regioselectivity is due to a greater degree of charge stabilization in the transition state, leading to the major product.

The mechanism and dynamics for the formation of the delitschiapyrone family of natural products are studied by density functional theory (DFT) calculations and quasiclassical molecular dynamics simulations with DFT and xTB. In the uncatalyzed reaction, delitschiapyrones A and B are formed by Diels-Alder reactions through a single transition state and a post-transition state bifurcation that favors formation of delitschiapyrone B. In water and most likely in the enzyme, the acidic hydroxyquinone ionizes, and the resulting conjugate base undergoes cycloaddition preferentially to delitschiapyrone A. We demonstrate a new type of biosynthetic transformation and variable selectivity from a (4 + 2)/(4 + 3) ambimodal transition state.

Strained cyclic allenes, first discovered in 1966 by Wittig and co-workers, have recently emerged as valuable synthetic building blocks. Previous experimental investigations, and computations reported here, demonstrate that the Diels-Alder reactions of furans and pyrroles with 1,2-cyclohexadiene and oxa- and azaheterocyclic analogs proceed with endo selectivity. This endo selectivity gives the adduct with the allylic saturated carbon of the cyclic allene endo to the diene carbons. The selectivity is very general and useful in synthetic applications. Our computational study establishes the origins of this endo selectivity. We analyze the helical frontier molecular orbitals of strained cyclic allenes and show how secondary orbital and electrostatic effects influence stereoselectivity. The LUMO of carbon-3 of the allene (C-3 is not involved in primary orbital interactions) interacts in a stabilizing fashion with the HOMO of the diene in such a way that the carbon of the cyclic allene attached to C-1 favors the endo position in the transition state. The furan LUMO, allene HOMO interaction reinforces this preference. These mechanistic studies are expected to prompt the further use of long-avoided strained cyclic allenes in chemical synthesis.

Bioorthogonal phosphines were introduced in the context of the Staudinger ligation over 20 years ago. Since that time, phosphine probes have been used in myriad applications to tag azide-functionalized biomolecules. The Staudinger ligation also paved the way for the development of other phosphorus-based chemistries, many of which are widely employed in biological experiments. Several reviews have highlighted early achievements in the design and application of bioorthogonal phosphines. This review summarizes more recent advances in the field. We discuss innovations in classic Staudinger-like transformations that have enabled new biological pursuits. We also highlight relative newcomers to the bioorthogonal stage, including the cyclopropenone-phosphine ligation and the phospha-Michael reaction. The review concludes with chemoselective reactions involving phosphite and phosphonite ligations. For each transformation, we describe the overall mechanism and scope. We also showcase efforts to fine-tune the reagents for specific functions. We further describe recent applications of the chemistries in biological settings. Collectively, these examples underscore the versatility and breadth of bioorthogonal phosphine reagents.

旨在为植物油基环状碳酸酯产品的制备提供新的研究思路，以环氧大豆油脂肪酸甲酯和二氧化碳为原料，在催化剂季铵盐和氢键供体的作用下，合成植物油基环状碳酸酯。通过单因素实验对植物油基环状碳酸酯的合成条件进行优化，对反应动力学进行了分析，同时对产物植物油基环状碳酸酯进行了红外表征。结果表明：植物油基环状碳酸酯最佳合成条件为以芝麻酚为氢键供体、四丁基溴化铵与芝麻酚物质的量比2∶ 1、四丁基溴化铵用量10%（以原料环氧键物质的量计）、反应温度120 ℃、反应压力1.0 MPa、反应时间10 h，在此条件下植物油基环状碳酸酯的产率达914%；反应动力学分析表明，芝麻酚的加入降低了反应的活化能，有利于植物油基环状碳酸酯的合成；红外光谱表征结果证明成功合成了产物。综上，实现了无溶剂条件下高效合成植物油基环状碳酸酯。 To provide new research ideas for the preparation of vegetable oil-based cyclic carbonate products, epoxidized soybean oil fatty acid methyl ester and carbon dioxide were used as raw materials, and the vegetable oil-based cyclic carbonate was synthesized by catalyzing with quaternary ammonium salt catalyst and hydrogen bond donor. The synthesis conditions of vegetable oil-based cyclic carbonate were optimized by single factor experiment, the reaction kinetic was analyzed, and the product of vegetable oil-based cyclic carbonate was characterized by infrared spectroscopy. The results showed that the optimum conditions for the synthesis of vegetable oil-based cyclic carbonate were as follows: with sesamol as the hydrogen bond donor, molar ratio of tetrabutylammonium bromide to sesamol 2∶ 1, dosage of tetrabutylammonium bromide 10%(on the basis of molar amount of raw material epoxy bond), reaction temperature 120 ℃, reaction pressure 1.0 MPa and reaction time 10 h. Under the the optimum conditions, the yield of vegetable oil-based cyclic carbonate could reach 91.4%. The kinetic analysis of the reaction showed that the addition of sesamol reduced the activation energy of the reaction and facilitated the synthesis of vegetable oil-based cyclic carbonate. The infrared spectroscopy test showed that the target product was successfully synthesized. In summary, the vegetable oil-based cyclic carbonate under solvent-free conditions can be efficiently synthesized.

Interest in covalent organic frameworks as high-value materials has grown steadily since their development in the 2000s. However, the great advantage that allows us to obtain these crystalline materials—the reversibility of the bonds that form the network—supposes a drawback in terms of thermal and chemical stability. Among the different strategies employed for the stabilization of imine-based Covalent Organic Frameworks (COFs), cycloaddition and other related cyclization reactions are especially significant to obtain highly stable networks with extended π-delocalization and new functionalities, expanding even further the potential application of these materials. Therefore, this entry gathered the most recent research strategies for obtaining stable COFs by means of cyclization reactions, including the Povarov reaction and intramolecular oxidative cyclization reactions as well as some other recent innovative approaches.

Chemoproteomics has enabled the rapid and proteome-wide discovery of functional, redox-sensitive, and ligandable cysteine residues. Despite widespread adoption and considerable advances in both sample-preparation workflows and MS instrumentation, chemoproteomics experiments still typically only identify a small fraction of all cysteines encoded by the human genome. Here, we develop an optimized sample-preparation workflow that combines enhanced peptide labeling with single-pot, solid-phase-enhanced sample-preparation (SP3) to improve the recovery of biotinylated peptides, even from small sample sizes. By combining this improved workflow with on-line high-field asymmetric waveform ion mobility spectrometry (FAIMS) separation of labeled peptides, we achieve unprecedented coverage of >14000 unique cysteines in a single-shot 70 min experiment. Showcasing the wide utility of the SP3-FAIMS chemoproteomic method, we find that it is also compatible with competitive small-molecule screening by isotopic tandem orthogonal proteolysis-activity-based protein profiling (isoTOP-ABPP). In aggregate, our analysis of 18 samples from seven cell lines identified 34225 unique cysteines using only ∼28 h of instrument time. The comprehensive spectral library and improved coverage provided by the SP3-FAIMS chemoproteomics method will provide the technical foundation for future studies aimed at deciphering the functions and druggability of the human cysteineome.

Oxanorbornadienes (ONDs) undergo facile Michael addition with thiols and then fragment by a retro-Diels-Alder (rDA) reaction, a unique two-step sequence among electrophilic cleavable linkages. The rDA reaction rate was explored as a function of the furan structure, with substituents at the 2- and 5-positions found to be the most influential and the fragmentation rate to be inversely correlated with electron-withdrawing ability. Density functional theory calculations provided an excellent correlation with the experimentally measured OND rDA rates.

Computational studies with ωB97X-D density functional theory of the mechanisms of the steps in Trauners biomimetic synthesis of preuisolactone A have elaborated and refined mechanisms of several unique processes. An ambimodal transition state has been identified for the cycloaddition between an o-quinone and a hydroxy-o-quinone; this leads to both (5 + 2) (with H shift) and (4 + 2) cycloaddition products, which can in principle interconvert via α-ketol rearrangements. The origins of periselectivity of this ambimodal cycloaddition have been investigated computationally with molecular dynamics simulations and tested further by an experimental study. In the presence of bicarbonate ions, the deprotonated hydroxy-o-quinone leads to only the (5 + 2) cycloaddition adduct. A new mechanism for a benzilic acid rearrangement resulting in ring contraction is proposed.