Mediated Cycloaddition Reactions Research Articles

Novel flurbiprofen clubbed oxadiazole derivatives as potential urease inhibitors and their molecular docking study.

In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), (S)-flurbiprofen (1), were synthesized via I2 mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, 1H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease (in vitro) inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC50 values of 12 ± 0.9 to 20 ± 0.5 μM, better than the standard thiourea (IC50 = 22 ± 2.2 μM), whereas the remaining fourteen derivatives displayed good to moderate activity. The in silico study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme.

Cover Picture: Construction of Enantioenriched 4,5,6,7‐Tetrahydrofuro[2,3‐b]pyridines through a Multicatalytic Sequence Merging Gold and Amine Catalysis (Adv. Synth. Catal. 19/2021)

The inside cover picture, designed by Fabrice Goursaud, holder of a PhD in organic chemistry and recently graduated from art school, illustrates the stereoselective synthesis of tetrahydro[2,3-b]pyridine frameworks via one-pot metal-organo relay catalysis. The strategy, which involves a gold-catalyzed cycloisomerization and a chiral amine mediated cycloaddition reaction, provides the targeted molecules in yields ranging from 27 to 90% and high levels of stereoselectivity (de>95%, 93–99% ee). Details can be found in the Communication by Manon Genet, Abdelilah Takfaoui, Jérôme Marrot, Christine Greck and Xavier Moreau. (M. Genet, A. Takfaoui, J. Marrot, C. Greck, X. Moreau, Adv. Synth. Catal. 2021, 363, 4516–4520; DOI: 10.1002/adsc.202100756).

Water-Tolerant DUT-Series Metal-Organic Frameworks: A Theoretical-Experimental Study for the Chemical Fixation of CO2 and Catalytic Transfer Hydrogenation of Ethyl Levulinate to γ-Valerolactone.

A series of highly thermally and hydrolytically stable porous solids with intriguing properties of zirconium- and hafnium-based metal-organic frameworks (MOFs) [Dresden University of Technology (DUT) series] was synthesized. The DUT MOFs were found to be effective catalysts for both epoxide-CO2 cycloaddition reactions and the catalytic transfer hydrogenation (CTH) of ethyl levulinate (EL). In particular, 12-connected DUT-52(Zr) showed higher catalytic activity than eight- and six-connected catalysts in the synthesis of cyclic carbonates as well as in the production of γ-valerolactone (GVL). The secondary building unit connectivity, coexistence of a moderate number of acidic and basic sites, Brunauer-Emmett-Teller surface area, and combined effects of the pores of the MOFs seem to influence the catalytic activity. The reaction mechanism for the DUT-52(Zr)-mediated cycloaddition reaction of CO2 and the CTH reactions were investigated in detail by using periodic density functional theory calculations. To the best of our knowledge, this is the first detailed computational study for the formation of GVL from EL by using MOF as the catalyst. In addition, grand canonical Monte Carlo simulations predicted the strong interaction of CO2 molecules with the DUT-52(Zr) framework. Remarkably, the DUT-series catalysts possess extraordinary tolerance toward water. Further, DUT-52(Zr) is recyclable and is an efficient catalyst for cycloaddition and CTH reactions for at least five uses without obvious reductions in the activity or structural integrity.

ChemInform Abstract: Synthesis of Dispirocyclopentyl‐3,3′‐bisoxindoles via Domino Cycloaddition Reactions of 4‐Dimethylaminopyridinium Bromides with 3‐Phenacylideneoxindoles.

The base mediated cycloaddition reactions of 4-dimethylamino-1-phenacylpyridinium bromides with two molecular 3-phenacylideneoxindoles in methylene dichloride afforded functionalized dispirocyclopentyl-3,3′-bisoxindoles in good yields and with high diastereoselectivity. The similar cycloaddition reactions of 1-(N,N-dialkylcarbamoylmethyl) and 1-cyanomethyl 4-dimethylamino-pyridinium bromide in refluxing ethanol in the presence of triethylamine also resulted in dispirocyclopentyl-3,3′-bisoxindoles with high diastereoselectivity. The stereochemistry of dispirocyclopentyl-3,3′-bisoxindoles was elucidated on the basis of 1H NMR data and single crystal structures.

Synthesis of Dispirocyclopentyl‐3,3′‐bisoxindoles via Domino Cycloaddition Reactions of 4‐Dimethylaminopyridinium Bromides with 3‐Phenacylideneoxindoles

AbstractThe base mediated cycloaddition reactions of 4‐dimethylamino‐1‐phenacylpyridinium bromides with two molecular 3‐phenacylideneoxindoles in methylene dichloride afforded functionalized dispirocyclopentyl‐3,3′‐bisoxindoles in good yields and with high diastereoselectivity. The similar cycloaddition reactions of 1‐(N,N‐dialkylcarbamoylmethyl) and 1‐cyanomethyl 4‐dimethylamino‐pyridinium bromide in refluxing ethanol in the presence of triethylamine also resulted in dispirocyclopentyl‐3,3′‐bisoxindoles with high diastereoselectivity. The stereochemistry of dispirocyclopentyl‐3,3′‐bisoxindoles was elucidated on the basis of 1H NMR data and single crystal structures.

Cycloaddition Reactions of Deoxyribosylpropynoates

Pure anomers of either α or β 3-(2-deoxyribofuranosyl)propynoates reacted with the tetramethylcyclobutadiene–aluminum trichloride complex to yield the corresponding diastereoisomeric Dewar benzenes. Thermal- or ultraviolet light–initiated rearrangement gave rise to highly substituted C-aryldeoxyribosides as single anomers. The same compounds as well as other substituted deoxyribosides were obtained also by transition metal–mediated cycloaddition reactions.

PEGylation of bovine serum albumin using click chemistry for the application as drug carriers

Monomethyl poly(ethylene glycol) (mPEG)-modified bovine serum albumin (BSA) conjugates (BSA-mPEG) were obtained by the mild Cu(I)-mediated cycloaddition reaction of azided BSA (BSA-N(3) ) and alkyne-terminated mPEG. The structure and characteristics of BSA-mPEG conjugates were thoroughly investigated. There were about two PEG chains conjugated onto each BSA molecule as determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) analysis. The intrinsic nonspecific binding ability of BSA was used for adsorption and sustained release of both rifampicn and 5-fluorouracil (5-FU). The helical structures of BSA were preserved to a large extent after modification and drug adsorption on BSA was confirmed via circular dichroism spectroscopy. Drugs adsorbed onto the conjugated formulation to a lesser extent than on BSA due to mPEG modification. The in vitro release of both rifampicin and 5-FU, however, indicated that BSA-mPEG can function as a drug carrier. Overall, the click reaction provided a convenient tool for the pegylation of BSA. The biological activity of the BSA-mPEG conjugates, including the drug transportation capacity and biocompatibility, were largely retained.

Design, synthesis and biological activity evaluation of regioisomeric spiro-(indoline-isoxazolidines) in the inhibition of TNF-α-induced ICAM-1 expression on human endothelial cells

Different regioisomeric spiro-(indoline-isoxazolidines) have been synthesized by the microwave mediated cycloaddition reaction between ethyl(5-fluoro-3-indolylidene)-acetate/ethyl(3-indolylidene)-acetate and the substituted α,N-diphenylnitrones. These compounds were screened for their anti-inflammatory activities through inhibition of TNF-α-induced ICAM-1 expression on human endothelial cells. Spiro-(indoline-isoxazolidine) 9p was found to be the most potent compound in inhibiting the ICAM-1 expression. Furthermore, compound 9p significantly inhibited the adhesion of neutrophils to the endothelium in a concentration-dependent manner and also blocked the translocation of NF-κBp65 subunit from the cytoplasm to the nucleus. We believe that compound 9p could be useful in developing better anti-inflammatory molecules for various inflammatory diseases where NF-κB plays a key role.

Stereoselectivity in Trimethylenemethane (TMM) Diyl Mediated Cycloaddition Reaction to Angularly Fused Triquinanes

A thorough study on the diastereoselectivity in the TMM diyl mediated [2+3] cycloaddition reaction of monosubstituted linear substrates to form angularly fused triquinanes was carried out. Substitution at position 3 provided complete diastereoselectivity, while positions 1 and 4 induced marginal stereoselectivity. Position 2 did not show any influence on the diastereoselectivity. Position 4 turned out to be incompatible with the cycloaddition reaction as the carbene intermediate underwent O-Si bond insertion to form a dihydrofuran ring.

ChemInform Abstract: Cu(I)‐Mediated Cycloaddition Reaction of Zirconacyclopentadienes with Fumaronitrile and Application for Synthesis of Monocyano‐Substituted Pentacenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Cu(I)-mediated cycloaddition reaction of zirconacyclopentadienes with fumaronitrile and application for synthesis of monocyano-substituted pentacenes

Cu(I)-mediated reactions of zirconacyclopentadienes with fumaronitrile afforded the corresponding dicyanocyclohexadiene and benzonitrile derivatives in good yields. These products were selectively prepared by controlling the reaction temperature. Furthermore, the reaction was applicable for monocyano-substituted pentacene derivatives.

Reactivity of [Cp ∗Rh(η 6-C 6H 3NH 2-2,6- i-Pr 2)](OTf) 2 toward phosphines and alkynes

The cationic aniline complex [Cp ∗Rh(η 6-2,6-(Me 2CH) 2C 6H 3NH 2)](OTf) 2 ( 1) was prepared from either [Cp ∗Rh(η 2-NO 3)(η 1-OTf)] or [Cp ∗Rh(OH 2) 3](OTf) 2 and 2,6-diisopropylaniline. Complex 1 underwent substitution with phosphines or phosphites, indicating the labile character of the η 6-aniline ligand. Complex 1 mediated cycloaddition reactions of several alkynes in refluxing ethanol: the [2 + 2] dimerization for Ph C C Ph and the [2 + 2 + 1] trimerization for Ph C C H and CH 3C 6H 4 C C H. The unexpected cyclobutadiene complex [Cp ∗Rh(η 4-C 4(C(O)CH 3) 2H(SiMe 3))] was obtained from complex 1 and Me 3Si C C C C SiMe 3 and structurally characterized by X-ray diffraction.

Precursor Mediated Cycloaddition Reaction of Ethylene on Si(100)c(4*2)

The adsorption states of ethylene on Si(100)c(4×2) were studied by means of high-resolution electron energy loss spectroscopy at low temperatures. We found that some of ethylene molecules are weakly bonded to the surface as a π-complex type at low temperatures (∼50 K). This species is converted to di-σ bonded ethylene by heating. Thus, we conclude that the π-complex species is a stable intrinsic precursor for the cycloaddition reaction (the di-σ bond formation) of ethylene on Si(100)c(4×2). The activation energy from the π-complex precursor to the di-σ chemisorption state is experimentally estimated to be 0.20 eV.

Precursor mediated cycloaddition reaction of ethylene to the Si(100)c(4 x 2) surface.

We report the direct observation of a precursor state for the cycloaddition reaction (the di-sigma bond formation) of ethylene on Si(100)c(4 x 2) using high-resolution electron energy loss spectroscopy at low temperature, and the meta-stable precursor state is identified as a weakly bonded pi-complex type. The activation energy from the pi-complex precursor to the di-sigma bonded species is experimentally estimated to be 0.2 eV. First-principles calculations support the pi-complex precursor mediated cycloaddition reaction of ethylene on Si(100)c(4 x 2).

ChemInform Abstract: Molybdenum‐Catalyzed and ‐Mediated Cycloaddition Reactions: Efficient Synthesis of Complex Products from 1‐Oxa‐1,3‐dienes and Cyclotrienes or ‐tetraenes

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Molybdenum‐Catalysed and ‐Mediated Cycloaddition Reactions: Efficient Synthesis of Complex Products from 1‐Oxa‐1,3‐dienes and Cyclotrienes or ‐tetraenes

AbstractMolybdenum‐mediated [6 + 2]‐cycloaddition reactions of unsaturated ketones to cyclotri‐ or ‐tetraenes, e.g. cyclohepta‐1,3,5‐triene or cyclooctatetraene, proceed under very mild conditions, in high yields and with excellent stereoselectivity starting from the appropriate dicarbonylbis[π4‐(1‐oxa‐1,3‐diene)]molybdenum complexes. The stereochemistry of the product arising from the reaction of dicarbonylbis[π4‐(5‐methylhex‐3‐en‐2‐one)]molybdenum with cyclohepta‐1,3,5‐triene allows one to deduce a stepwise mechanism for this addition. The reactants are fused, as would be expected from an exo‐type approach, thus indicating an intermolecular attack of the cycloheptatriene. Tungsten oxadiene complexes are effective in analogous reactions at somewhat reduced reaction rates. Catalytic cycloadditions are observed in several cases when 1–5 mol% of the highly reactive dicarbonylbis[π4‐(R‐(+)‐pinocarvone)]molybdenum is employed as the catalyst. Cycloadducts are formed diastereospecifically in most cases. When cyclooctatrienes are employed as reactants, a sequence of electrocyclization of the triene and subsequent [4 + 2]‐cycloadditon occurs with high selectivity and efficiency, leading to a pentacyclic ketone. The product structure reveals an endo‐type approach of the polyene in this case.

ChemInform Abstract: Reactivity of Radical Cations. Effect of Radical Cation and Alkene Structure on the Absolute Rate Constants of Radical Cation Mediated Cycloaddition Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reactivity of Radical Cations. Effect of Radical Cation and Alkene Structure on the Absolute Rate Constants of Radical Cation Mediated Cycloaddition Reactions1

Absolute rate constants for the reactions of styrene, 4-methylstyrene, 4-methoxystyrene, and β-methyl-4-methoxystyrene radical cations with a series of alkenes, dienes, and enol ethers have been measured by laser flash photolysis. The measured rate constants correspond to either addition or electron transfer reactions, with the latter predominating when the oxidation potential of the alkene is lower than that of the styrene. The measured rate constants for the diene additions provide some of the first absolute kinetic data for the initial step in the synthetically-useful radical cation mediated Diels−Alder reaction. The addition reactions are sensitive to steric and electronic effects on both the radical cation and the alkene or diene. For example, the reactivity of the radical cations follows the general trend of 4-H > 4-CH3 > 4-CH3O > 4-CH3O-β-CH3. The effects of alkyl substitution on the relative reactivity of alkenes toward styrene radical cations may be summarized as 1,2-dialkyl < 2-alkyl < trialkyl ...

Organotin mediated cycloaddition reactions: a re-investigation of the reaction between organotin azides and isothiocyanates

Organotin derivatives of 1-organo-5-thiotetrazole (RN 4CS) have been synthesised by two methods: (i) a cycloaddition reaction between Bu 3SnN 3 and RNCS, and (ii) reaction between the sodium salt of the preformed tetrazole and an organotin halide. The structure of Bu 2Sn(SCN 4Ph) 2 has been determined, and the ligand shown to be in the thio form, attached to tin through sulphur, rather than through nitrogen as previously reported. An analysis of the azide-isothiocyanide cycloaddition reaction based upon molecular orbital calculations is presented.

ChemInform Abstract: Enhanced Reactivity of Iminium Ions as Heterodienophiles in Lewis Acid Mediated (4+2)Cycloaddition Reactions.

AbstractThe trimeric imine (I) is converted to the iminium salts (II) and (III).