Cycloaddition Research Articles

Experimental and kinetic evaluation on cobalt Salen conjugated organic polymers for CO2 cycloaddition reactions and iodine vapor adsorption

The fixing reactions of carbon dioxide with epoxides will not only help to ameliorate the problem of global warming, but also facilitate the synthesis of cyclic carbonates that have a multitude of applications. Herein, a new sequence of Salen cobalt complexes adjusted with different counterions and interconnected with pyrene group were synthesized through Friedel–Crafts alkylation, which were served as conjugated organic polymers (SP-COPs) for taking advantage of catalytic CO2 fixation reactions and iodine adsorption. Further characterizations were carried out through FT-IR, UV, TGA, and SEM to comprehend the intact structure, thermal stability, morphology and other physical and chemical properties. All materials exhibited effective catalytic performance, and in particular, SP-COP-1 with co-catalyst of TBAI achieved 96.2 % conversion under ultra-mild conditions. The Ea was obtained to be 46.4 kJ·mol−1 by performing kinetic experiments at different temperatures by fitting the experimental data. The performance of iodine vapor adsorbed by these materials at ambient pressure of 75 °C reached 2.8 g·g−1, 2.2 g·g−1 and 2.6 g·g−1 respectively, and the adsorption process is describable in terms of pseudo-first-order and pseudo-second-order adsorption kinetics.

Synthesis of PEI Grafted Poly (Ionic Liquid)s: Optimization and Kinetics Modeling of Effective CO2 Fixation Reactions

AbstractFixing 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.

Zn[L-proline]2 as an Efficient Catalyst for the Synthesis of Dihydro Pyrano Thiazole Derivatives via Cycloaddition Reaction in Aqueous Medium

Abstract: In the current study, a zinc-linked amino acid complex was successfully synthesized as an efficient and recoverable catalyst for the synthesis of dihydro pyrano thiazole derivatives via the reaction of an aromatic aldehyde with malononitrile and rhodanine in one-pot, three-component reaction under green conditions. The structures of the new compounds were elucidated by elemental and spectral analyses. Environmental friendliness, low cost, operational simplicity, extensive reusability and applicability, and easy recovery of the catalyst using simple methods are the critical features of this methodology. Moreover, a series of dihydro pyrano thiazole derivatives were synthesized. This new procedure has presented remarkable advantages in terms of safety, simplicity, stability, mild conditions, short reaction time, excellent yields, and high purity without using any hazardous solvents.

Light-Induced Generation and Cycloaddition Reactions of Benzyne: Synthesis of Naphthoxindoles E and Annulated Indolizines.

By virtue of their high electrophilic nature, benzynes serve as reactive dienophiles in numerous cycloaddition reactions. However, in situ generation of benzyne involves either base-mediated thermal reactions, low-temperature conditions, or metal-catalyzed reactions of substituted arenes. This limits the applicability of benzynes as suitable dipolarophiles in cycloaddition reactions. Herein, we have reported a UVA (365 nM)-induced in situ generation of benzynes (from triazenyl benzoic acid) and subsequently their [4 + 2] Diels-Alder and [3 + 2] cycloaddition reactions with appropriate reaction partners such as N-protected alkylidene oxindole carboxylates and pyridinium ylides to afford naphthoxindoles E and pyrido[2,1-a]isoindole, respectively, in moderate to excellent yield. The reactions occurred at room temperature and under reagent-free reaction conditions. Each of these building blocks is pharmaceutically relevant; hence, this highlights an interesting strategy to access these classes of compounds.

Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity

Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges.

A High‐Yielding Active Template Click Reaction (AT−CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops

AbstractMechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments—[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles—may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal‐ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu‐catalyzed azide‐alkyne cycloaddition (AT−CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2′‐bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT−CuAAC reaction to provide [2]rotaxanes in near‐quantitative yield, which can then be converted into the fully π‐conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3‐triazole moiety replacing one phenylene ring in the [n]CPP backbone).

BUTADIENYL KETENE: AN UNEXPLORED INTERMEDIATE IN ORGANIC SYNTHESIS

Butadienyl ketene is a useful intermediate for its role as 2- components in cycloaddition reactions with a variety of substrate such as simple/conjugated imines and dienes. The current review article summarizes the different reports on the in-situ generation of butadienyl ketene and their cycloaddition reactions to afford different heterocyclic systems. The chemistry of butadienyl ketene is explored only for their [2+2] and [4+2] cycloaddition with a variety of imines and azadiene such as 1,3-diazabuta-1,3-dienes for the synthesis of four- and six-membered heterocycles respectively.

Novel amphiphilic (AB)3‐type star block polymer: Synthesis and micellization study

AbstractAn amphiphilic three‐armed star polymer was synthesized through the polar cycloaddition reaction of a polyethylene glycol‐based macro‐triazide with an Yne‐terminated polycaprolactone in a molar ratio of 1:3 (click chemistry). Thus, each arm is itself a di‐block copolymer branched from the core, which is a 1,3,5‐triazine ring. The attachment of the pre‐synthesized hydrophobic segments to the hydrophilic segments in each arm leads to the creation of a 1,2,3‐triazole ring in the structure. Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (H‐NMR) spectroscopies were used to verify the structures. The micellization process of the prepared amphiphilic polymer was investigated in aqueous medium. For this purpose, the critical micelle concentration (CMC) was specified by the fluorometric method. Using the transmission electron microscopy (TEM) technique, it was observed that spherical self‐assemblies with a mean diameter of <100 nm are formed from the aggregation of the amphiphilic macromolecules. In addition, the hydrodynamic diameter (H) of the polymeric micelles and their size distribution were examined by dynamic light scattering (DLS) technique.

Quest for a Desolvated Structure Unveils Breathing Phenomena in a MOF Leading to Greener Catalysis in a Solventless Setup: Insights from Combined Experimental and Computational Studies.

The crystal structure of the metal-organic framework (MOF), {Mn2(1,4-bdc)2(DMF)2}n (1) (1,4-bdcH2, 1,4-benzenedicarboxylic acid; DMF, N,N-dimethylformamide), is known for a long time; however, its desolvated structure, {Mn2(1,4-bdc)2}n (1'), is not yet known. The first-principles-based computational simulation was used to unveil the structure of 1' that shows the expansion in the framework, leading to pore opening after the removal of coordinated DMF molecules. We have used 1' that contains open metal sites (OMSs) in the structure in cyanosilylation and CO2 cycloaddition reactions and recorded complete conversions in a solventless setup. The pore opening in 1' allows the facile diffusion of small aldehyde molecules into the channels, leading to complete conversion. The reactions with larger aldehydes, 2-naphthaldehyde and 9-anthracenecarboxaldehyde, also show 99.9% conversions, which are the highest reported until date in solventless conditions. The in silico simulations illustrate that larger aldehydes interact with Mn(II) OMSs on the surfaces, enabling a closer interaction and facilitating complete conversions. The catalyst shows high recyclability, exhibiting 99.9% conversions in the successive reaction cycles with negligible change in the structure. Our investigations illustrate that the catalyst 1' is economical, efficient, and robust and allows reactions in a solventless greener setup, and therefore the catalysis with 1' can be regarded as "green catalysis".

Cobalt/Photoredox Cooperative Catalysis‐Enabled Cycloaddition Reactions of 1,6‐Diyne Derivatives

Cobalt catalysts have recently gained considerable attention as alternatives to catalysts based on precious transition metals such as Rh and Ir. Recently, Co/photoredox cooperative catalysis has emerged as a powerful tool that enables versatile transformations, including cycloaddition reactions of unsaturated compounds. In particular, 1,6‐diyne derivatives are fascinating substrates for these reactions because the corresponding exocyclic 1,3‐diene products can be further transformed into sp3‐rich carbocycles and heterocycles via functionalization of the diene moiety. The dual catalysis system can facilitate not only the cycloaddition based on the activation of the π‐bond only, such as alkyne cyclotrimerization, but also the cycloaddition involving σ‐bond activation. This Concept highlights the recent advances in Co/photoredox cooperative‐catalysis‐enabled cycloaddition reactions, focusing on the reactions of 1,6‐diyne substrates, which are difficult to perform when well‐defined cationic CoI catalysis is employed.

Cyclic (Alkyl)(Amino)Carbene-Iminoboryl Compounds with Three Formal Oxidation States.

BN/CC isosterism is an effective strategy to build hybrid functional molecules with unique properties. In contrast to the alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes (CAACs) that feature only one reversible reduction wave, the isoelectronic cationic CAAC-iminoboryl adducts could be singly and doubly reduced smoothly. Both the resultant neutral radical and anionic azaborataallenes bear NBC-mixed allenic structures. The former radical has a high spin-density of 0.55e at CCAAC carbon, yet exhibits formal boron-centered radical reactivity. The latter azaborataallenes feature the nucleophilic CCAAC center and polar N(δ-)═B(δ+)═C(δ-) unit, and readily undergo nucleophilic substitution, isocyanide insertion, dipolar addition and cycloaddition reactions etc. The N-substituents have been shown to have a significant influence on the solid-state structure, thermal stability, and reactivity of azaborataallenes. This work showcases the allenic BN-unsaturated species as versatile building blocks in organic synthesis.

Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-κB in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

Copper‐Catalyzed Formal [4+2] Cycloaddition of Ethynylethylene Carbonates for the Construction of 3,4‐Dihydro‐2H‐benzo[b][1,4]oxazines

A formal [4+2] cycloaddition reaction of ethynylethylene carbonates and 2‐aminophenols has been developed for the synthesis of 3,4‐dihydro‐2H‐benzo[b][1,4]oxazines bearing quaternary carbon atoms. The reaction features mild reaction conditions, good functional group compatibility and good yields. Furthermore, when using chiral PyBox ligand, this strategy could also achieve the asymmetric synthesis of 3,4‐dihydro‐2H‐benzo[b][1,4]oxazines. Application studies indicated that the hydroxymethyl group of final products was an excellent functional group that can be further modified easily.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Mechanistic Insights into the [3+1] Cycloadditions of Me3SiN3 on Bis‐silylene and the Formation of Pseudo‐Silaazatriene

The reaction mechanism for the formation of the pseudo‐silaazatriene 1 by the reaction of 1 equivalent of bis‐silylene with 3 equivalents of azide Me3SiN3 has been explored at M06/def2‐TZVPP//BP86‐D3(BJ)/def2‐TZVPP level of theory. The reaction mechanism is guided by the high Lewis basicity of the silicon lone pair and the high Lewis acidic character of Si‐N bonds, as well as by the high tendency to eliminate N2 from Me3SiN3. The first step of the reaction is the formation of [3+1] cycloaddition product (I1) by the synergetic interactions of the lone pair on the silylene silicon with the π* molecular orbital of Me3SiN3 which is majorly localized on the terminal nitrogen atom, and the donation of the σ‐type lone pair on the nitrogen atom connected to the SiMe3 group with the Si‐N σ* orbital on silylene. The elimination of N2 from I1 results in the formation of pseudo‐silaimine intermediate I2 having a dicoordinated, monovalent nitrogen atom. The Si‐Si bond cleavage of I2 results in intermediate I3, which is susceptible to [3+1] cycloaddition reaction with two molecules of Me3SiN3 in a stepwise manner results in I7 having two silaimine and one silaamine moieties. Further 1,3‐silyl migration results in pseudo‐silaazatriene 1.

Diastereoselective Synthesis of NH-Unprotected Spiropyrrolidines via the Huisgen Reaction of Acenaphthoquinone-Derived Azomethine Ylides with β-Nitrostyrenes

Abstract4′-Nitro-2H-spiro[acenaphthylene-1,2′-pyrrolidine]-2-one derivatives are prepared via [3+2] cycloaddition reactions of azomethine ylides, generated in situ from acenaphthoquinone and primary amines, with β-nitrostyrenes in the presence of ( i Pr)2NEt in methanol. Evidence for the structures of the products was obtained from single-crystal X-ray analysis. The important feature of this diastereoselective synthesis of NH-unprotected spiropyrrolidines is the formation of four contiguous stereogenic centers, one of which is quaternary, with high selectivity.

Halogen Bond-Assisted Supramolecular Dimerization of Pyridinium-Fused 1,2,4-Selenadiazoles via Four-Center Se2N2 Chalcogen Bonding.

The synthesis and structural characterization of α-haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles with various counterions is reported herein, demonstrating a strategy for directed supramolecular dimerization in the solid state. The compounds were obtained through a recently discovered 1,3-dipolar cycloaddition reaction between nitriles and bifunctional 2-pyridylselenyl reagents, and their structures were confirmed by the X-ray crystallography. α-Haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles exclusively formed supramolecular dimers via four-center Se···N chalcogen bonding, supported by additional halogen bonding involving α-haloalkyl substituents. The introduction of halogens at the α-position of the substituent R in the selenadiazole core proved effective in promoting supramolecular dimerization, which was unaffected by variation of counterions. Additionally, the impact of cocrystallization with a classical halogen bond donor C6F3I3 on the supramolecular assembly was investigated. Non-covalent interactions were studied using density functional theory calculations and topological analysis of the electron density distribution, which indicated that all ChB, XB and HB interactions are purely non-covalent and attractive in nature. This study underscores the potential of halogen and chalcogen bonding in directing the self-assembly of functional supramolecular materials employing 1,2,4-selenadiazoles derived from recently discovered cycloaddition between nitriles and bifunctional 2-pyridylselenyl reagents.

Synthesis of Fused-Ring Pyrrolizine Derivatives via a Copper-Catalyzed Radical Cascade Cyclization

AbstractHerein, an atom-economic method for the synthesis of fused-ring pyrrolizine derivatives by a cycloaddition reaction of easily accessible N-substituted pyrrole-2-carboxaldehydes with N-substituted maleimides in the presence of di-tert-butyl peroxide has been successfully developed. A total of 23 compounds were obtained by using this method, with a maximum yield of 72%, providing a practical and efficient method for the synthesis of tricyclic pyrrolizine frameworks.

Two coordination polymers based on imidazopyridine carboxylic acid ligand for efficient catalytic cycloaddition of CO2 with epoxides and cyanosilylation

Two coordination polymers (CPs){[M(L)2(H2O)2]·2H2O}n (M=Co (1) and Mn (2), HL=4-(3H-imidazo[4,5-b]pyridin-2-yl) benzoic acid) have been prepared under hydrothermal method and systematically characterized. The catalytic properties of the two CPs were investigated, the results showed that CP 1 could be used to catalyze CO2 cycloaddition reactions efficiently under eco-friendly, solvent-free conditions. The influencing factors and catalytic mechanism of cycloaddition reaction were discussed. Moreover, CP 2 exhibited catalytic performance for cyanosilylation reaction. The recycling experiments showed that the CPs 1 and 2 could be recovered and reused at least 5 reaction cycles without an obvious decrease of catalytic activity.

Isatogenols as Precursors for the Synthesis of Fully Substituted Indolines through Regio- and Stereoselective [3 + 2] Cycloaddition Using Various Olefins.

Here, we describe a unique reactivity of isatogen derivatives bearing a hydroxy group at the C3-position (isatogenol) and their synthetic application to highly regio- and stereoselective [3 + 2] cycloaddition reactions. This method provides facile access to polyfused and highly functionalized heterocycles including consecutive stereocenters. Furthermore, DFT calculations revealed that hydrogen bonding is a key to controlling the regio- and stereoselectivity in the cycloaddition using acrylates.