Ring Opening Of Epoxides Research Articles

Efforts toward the Total Synthesis of Thuggacin A.

Thuggacin A (1) is a 17-membered-ring-polyketide antibiotic compound with excellent antituberculosis activity. The total synthesis of thuggacin A has not yet been reported so far. Herein, we disclose our efforts toward the convergent total synthesis of thuggacin A. The key synthetic features include our own one-pot cascade thiazole formation, Evans syn-aldol, Mukaiyama asymmetric aldol reaction, organosilicon-promoted selective alkyne reduction, Shiina macrolactonization, and a nucleophilic ring-opening of epoxide with alkyne to assemble the main framework of thuggacin A. The enantioselective synthesis of trimethylsilyl ethoxymethyl (SEM) derived thuggacin A analogue 2 was achieved in 18 longest linear steps with 2.0% overall yield, and the bioassay of 2 exhibited moderate antituberculosis activity with minimum inhibitory concentration (MIC) of 320 μg/mL.

One-step condensation synthesis of di-tertiary ammonium salt protic ionic liquid for efficiently catalytic CO2 cycloaddition reaction under cocatalyst- and solvent-free conditions

A novel protic ionic liquid di-tertiary ammonium bromide ionic liquid (DTAB-IL) was synthesized by one-step condensation at 0 ℃ with 85 % yield. DTAB-IL also exhibited effective catalytic activity for CO2 cycloaddition without cocatalyst and solvent. The catalytic reaction conditions were optimized to 90 ℃, 4 h, 1 MPa, and the yield of propylene carbonate was obtained 96 % with high selectivity 99 %. Under the optimal conditions, DTAB-IL catalyst exhibited good recyclability and universality to various epoxides. Furthermore, temperature influence and kinetic investigation for propylene carbonate synthesis were studied. The activation energy for DTAB-IL catalyzing CO2 cycloaddition reaction was 43.93 kJ/mol, and the reaction was found to follow first-order for propylene oxide. Efficient cycloaddition reaction of CO2 and epoxide was attributed to the activation of epoxide and CO2 by di-tertiary ammonium and epoxide ring-opening by bromide anion in DTAB-IL.

Synthesis of 1,3-thiazolidine-2-thiones using CS2 and epoxy amines

An efficient method for the synthesis of 5-(hydoxymethyl)-1,3-thiazolidine-2-thiones is developed via the reaction of carbon disulfide with N-alkyl(aryl) epoxy amines. The reaction proceeds via intramolecular epoxide ring opening with in situ prepared dithiocarbamic acid. The products were obtained in good to high yields.

Physicochemical and biological evaluation of ‘click’ synthesized vinyl epoxide-chitosan film for active food packaging

Chitosan (Cs) being a natural biopolymer serves as an excellent template to construct active packaging materials for achieving sustainable development. In this study, Cs was chemically modified via epoxide ring opening click reaction using vinyl epoxide to obtain a novel chitosan vinyl epoxide (Cs-VE) derivative with hydroxyl and olefinic functional groups. The Cs-VE transparent film was fabricated through the eco-friendly solution casting technique. A meticulous investigation into the chemical structure and physicochemical properties of the synthesized films was conducted using FT-IR, 1H NMR and XRD analyses. The thermal stability and homogeneity of the film were verified by thermogram and FE-SEM images respectively. Improved mechanical properties (tensile strength of 24.64 MPa and 12.08 % elongation at break) and excellent UV-light blocking ability (9.3 % transmittance at 350 nm and 22.15 % transparency at 600 nm) were observed. Also, important parameters such as water vapor permeability (WVP), swelling degree, water solubility and UV-barrier properties were found to be adequate for food packaging application. Similarly, enhanced antioxidant activity with 27.2 % and 73.6 % radical scavenging against DPPH and ABTS radicals respectively was observed for the synthesized Cs-VE film. The film showed antimicrobial activity against both bacteria and fungi. These results along with food packaging studies on Grewia asiatica fruit established the developed Cs-VE film as a suitable candidate for active food packaging application.

A Dynamic Loop in Halohydrin Dehalogenase HheG Regulates Activity and Enantioselectivity in Epoxide Ring Opening.

Halohydrin dehalogenase HheG and its homologues are remarkable enzymes for the efficient ring opening of sterically demanding internal epoxides using a variety of nucleophiles. The enantioselectivity of the respective wild-type enzymes, however, is usually insufficient for application and frequently requires improvement by protein engineering. We herein demonstrate that the highly flexible N-terminal loop of HheG, comprising residues 39 to 47, has a tremendous impact on the activity as well as enantioselectivity of this enzyme in the ring opening of structurally diverse epoxide substrates. Thus, highly active and enantioselective HheG variants could be accessed through targeted engineering of this loop. In this regard, variant M45F displayed almost 10-fold higher specific activity than wild type in the azidolysis of cyclohexene oxide, yielding the corresponding product (1S,2S)-2-azidocyclohexan-1-ol in 96%eeP (in comparison to 49%eeP for HheG wild type). Moreover, this variant was also improved regarding activity and enantioselectivity in the ring opening of cyclohexene oxide with other nucleophiles, demonstrating even inverted enantioselectivity with cyanide and cyanate. In contrast, a complete loop deletion yielded an inactive enzyme. Concomitant computational analyses of HheG M45F in comparison to wild type enzyme revealed that mutation M45F promotes the productive binding of cyclohexene oxide and azide in the active site by establishing noncovalent C-H ··π interactions between epoxide and F45. These interactions further position one of the two carbon atoms of the epoxide ring closer to the azide, resulting in higher enantioselectivity. Additionally, stable and enantioselective cross-linked enzyme crystals of HheG M45F were successfully generated after combination with mutation D114C. Overall, our study highlights that a highly flexible loop in HheG governs the enzyme's activity and selectivity in epoxide ring opening and should thus be considered in future protein engineering campaigns of HheG.

Complementary Tandem Reaction Manifolds and "Switch Mechanisms" in the Reaction of Epoxides with Selectfluor.

Tandem reactions are highly sought after transformations in organic synthesis as they accomplish multiple steps at once and can serve as golden keys unlocking mechanistic complexities. Reactions that operate through different mechanisms depending on the conditions ("switch mechanisms") are of intense interest to organic chemists as fonts of new reactivity. We report that Selectfluor can catalyze the rearrangement of 1,1-disubstituted epoxides, providing a new approach to benzylic fluorination. These results complement earlier work involving radical-cation-based ring opening of epoxides.

Allylic Epoxides Increase the Strain Energy of Cyclic Olefin Monomers for Ring-Opening Metathesis Polymerization.

Ring-opening metathesis polymerization (ROMP) is an effective method for synthesizing functional polymers, but since the technique typically relies on high ring strain cyclic olefins, the most common monomers are norbornene derivatives. The reliance on one class of monomer limits the obtainable properties of ROMP polymers. In this work, we investigate new bicyclic monomers synthesized via epoxidation of commercial dienes. DFT estimates of these monomers' ring strains suggests a significant increase in strain for cyclic olefins containing allylic epoxides. We found that the eight-membered (3,4-COO) and five-membered (CPO) cyclic olefins were particularly effective for ROMP. CPO was of especially intriguing due to its excellent polymerizability when compared to the limited reactivity of other five-membered rings. Unlike polynorbornenes, the resulting polymers of both monomers displayed glass transition temperatures well below room temperature. Interestingly, poly(3,4-COO) showed both high stereo- and regioregularity while poly(CPO) showed little regularity. Both polymers could be readily modified via post-polymerization ring-opening of the reactive allylic epoxides. With a high epoxide density in poly(CPO), CPO is an exciting new ROMP monomer that is easily synthesized, can be polymerized to high conversion at room temperature, and may be facilely modified to yield a wide range of functional materials.

Frustrated Al/M Heterobimetallic Complexes (M = Cr, Mo, W) That Exhibit Both Lewis and Radical Pair Behavior.

Exploration of new heterobinuclear Al/M combinations is relevant to contemporary strategies for cooperative bond activation. Here, we report the synthesis and characterization of six new Al/M heterobimetallic complexes (M = Cr, Mo, W) that exhibit end-on "isocarbonyl"-type Al─O═C═M bridges with metalloketene character rather than featuring Al─M─C≡O motifs with metal-metal bonding. The new compounds were characterized experimentally by nuclear magnetic resonance and infrared spectroscopies and theoretically using density functional theory, natural bond orbital, and quantum theory of atoms in molecules calculations. Factors influencing Al─O═C═M vs Al─M─C≡O isomerism were probed both experimentally and computationally. Crossover experiments between different group VI Al/M derivatives and regioselective epoxide ring opening indicate that the Al/M complexes act as masked frustrated Lewis pairs in solution under certain conditions. However, crossover experiments between group VI Al/M complexes and a previously studied Al-Fe complex, as well as computational modeling, imply that the same complexes can also reasonably act as masked frustrated radical pairs (FRPs). FRP reactivity with the group VI Al/M complexes was achieved under photochemical conditions, producing unsaturated metal-carbonyl dimers [(CpCr)2(CO)3]2- and [Mn2(CO)8]2-, which would otherwise be unstable under standard conditions but that are isolable here due to Al(III) coordination. The metal-metal bonding in these unsaturated metal-carbonyl dimers was also analyzed theoretically.

Exploring Cu(triNHC) as a Bifunctional Catalyst for Carbonate Synthesis From CO2 and Epoxy Amines/Sulfides/Ethers

ABSTRACTThis study highlights the synergistic interplay between a Lewis acidic copper ion and a dissociated ligand from Cu(triNHC) complexes in the synthesis of cyclic carbonates from CO2 and epoxy compounds. The reactions were found to proceed efficiently under Cu(triNHC)‐catalyzed conditions, yielding significant quantities of cyclic carbonates across various epoxy substrates encompassing amine, sulfide, and ether functionalities. Stereochemical analyses underscore a pronounced propensity for retaining the stereochemistry of epoxy compounds in the resultant carbonates. This suggests a mechanism involving double inversion of stereochemistry during the reaction, which comprises catalyst‐mediated epoxide ring opening, subsequent CO2 addition, and carbonate ring closing. These findings align with established mechanisms for CO2 fixation reactions, shedding light on the intricate pathways underlying this catalytic process.

The effects of 1D multi‐wall carbon nanotubes and 2D graphene nanoplatelets on curing behavior of epoxy/vinyl ester interpenetrating polymer network nanocomposites

AbstractThis study meticulously investigated the effect of two carbon allotrope nanofillers, two‐dimensional graphene nanoplatelets (GnPs) and one‐dimensional multi‐wall carbon nanotubes (MWCNTs) individually, at various loadings on the kinetics of curing of the epoxy (EP)/vinyl ester (VE) based interpenetrating polymer network (IPN) system, with a mass ratio of 1:1. The IPN system is including a liquid epoxy resin based on bisphenol A which has been cured by methyltetrahydrophthalic anhydride (MTHPA) in the presence of 1‐methyl imidazole (Mi) as an accelerator and a vinyl ester resin based on bisphenol A which has been cured by methyl ethyl ketone peroxide (MEKP). The curing behavior of all prepared nanocomposites under non‐isothermal conditions was studied using DSC at four heating rates. Two different isoconversional approaches were applied to evaluate the reaction kinetics, that is, the Friedman and the advanced Vyazovkin methods. The obtained activation energy curves for all samples revealed a complex curing behavior involving three stages: early IPN stage, IPN growth stage, and late IPN stage. Then, the activation energy values for each reaction step were determined based on the Friedman method. The presence of GnPs showed no catalytic effect on the reaction of VE with MEKP. In contrast, incorporating MWCNT nanoparticles considerably decreases the activation energy values of the reaction of ring opening of epoxides with MTHPA‐Mi and the reaction of esterification of the hydroxyl groups of VE with MTHPA.Highlights MWCNTs reduce activation energy in curing reactions for EP/MTHPA‐Mi and VE/MTHPA. GnPs do not catalyze VE/MEKP reaction unlike MWCNTs. Combining MWCNTs and GnPs enhances properties of IPN nanocomposites. Curing process includes early, growth, and late IPN stages impacting activation energy. SEM analysis reveals better dispersion of GnPs in IPN nanocomposites with MWCNTs.

Remediation of water containing lead(II) using (3-iminodiacetic acid) propyltriethoxysilane graphene oxide

A novel chelating adsorbent based on (3-iminodiacetic acid) propyltriethoxysilane graphene oxide (IAT-GO) has been developed, showing exceptional promise for capturing lead. IAT-GO is made by combining a high-surface-area graphene oxide with a specially designed chelating ligand, which can selectively and efficiently remove lead. The synthesis of IAT-GO involves a two-step progression. In the first step, covalent bonds form between graphene oxide and (3-aminopropyl)-triethoxysilane (AT) through hydrolysis, condensation, and epoxide ring opening reactions. In the second step, nucleophilic substitution reactions occur between the primary amines and chloroacetic acid (CAA). A comprehensive suite of characterization techniques, including XPS, UV–Vis, XRD, Raman, FTIR, TEM, and SEM, provides detailed insights into the IAT-GO adsorbent's chemical composition and physical form, elucidating its intricate structure and morphology. Optimizing the experimental conditions for using the adsorbent material to remove Pb(II) ions from contaminated water revealed a maximum adsorption capacity of 124.0 mg/g at pH 5 and 30 min. The IAT-GO displays high selectivity for Pb(II) in a mixture of six metal ions containing 100 ppm of each one. Moreover, the IAT-GO shows 100% removal of Pb(II) for concentrations lower than 50 ppm. The excellent fit of the experimental data with the Langmuir adsorption isotherm and pseudo-second-order kinetic models (R2 > 99%) indicates that Pb(II) ion uptake onto the IAT-GO surface occurs via the monolayer formation of mercury ions. IAT-GO demonstrates exceptional potential as an innovative adsorbent for lead-contaminated water. Nitric acid (0.4 M) effectively regenerates the material, while its reusability remains impressive even after five cycles (> 97% removal efficiency). Therefore, this study highlights the development of a groundbreaking material, IAT-GO, with exceptional potential for remediating lead-contaminated water. Its high efficiency, selectivity, reusability, and cost-effectiveness make it a promising candidate for real-world applications.

Superior and efficient performance of cost-effective MIP-202 catalyst over UiO-66-(CO2H)2 in epoxide ring opening reactions

This study explored the catalytic performance of two robust zirconium-based metal–organic frameworks (MOFs), MIP-202(Zr) and UiO-66-(CO2H)2 in the ring-opening of epoxides using alcohols and amines as nucleophilic reagents. The MOFs were characterized by techniques such as FT-IR, PXRD, FE-SEM, and EDX. Through systematic optimization of key parameters (catalyst amount, time, temperature, solvent), MIP-202(Zr) achieved 99% styrene oxide conversion in 25 min with methanol at room temperature using 5 mg catalyst. In contrast, UiO-66-(CO2H)2 required drastically harsher conditions of 120 min, 60 °C, and four times the catalyst loading to reach 98% conversion. A similar trend was observed for ring-opening with aniline –MIP-202(Zr) gave 93% conversion in one hour at room temperature, while UiO-66-(CO2H)2 needed two hours at 60 °C for 95% conversion. The superior performance of MIP-202(Zr) likely stems from cooperative Brønsted/Lewis acid sites and higher proton conductivity enabling more efficient epoxide activation. Remarkably, MIP-202(Zr) maintained consistent activity over five recycles in the ring-opening of styrene oxide by methanol and over three recycles in the ring-opening of styrene oxide by aniline. Testing various epoxide substrates and nucleophiles revealed trends in reactivity governed by electronic and steric effects. The results provide useful insights into tuning Zr-MOF-based catalysts and highlight the promise of the cost-effective and sustainable MIP-202(Zr) for diverse epoxide ring-opening reactions on an industrial scale.

Novel Radical Cyclization Cascade for the Unified Synthesis of the Cedrane and Clovane Sesquiterpene Skeletons

AbstractRadical cyclization cascade reactions of epoxycyclohexanes possessing alkene and alkyne side chains have been achieved. Sequential 5‐ or 6‐exo‐trig/5‐exo‐dig reactions triggered by epoxide ring opening with Cp2TiCl were found to provide a useful unified synthetic method for generating the carbon skeletons of clovane and cedrane, two tricyclic sesquiterpenes. The factors responsible for the development of stereoselectivity during cyclization are also discussed.

Rapidly Diverse Synthesis of N‐Aryl‐5‐Substituted‐2‐Oxazolidinones via Nucleophilic Epoxide Ring Opening and Intramolecular Acyl Substitution of Epoxy Carbamates

AbstractThe method for converting epoxy carbamates to oxazolidinones is outlined in this study. This innovative approach combines intermolecular nucleophilic epoxide ring opening with intramolecular acyl substitution in a single step, thereby facilitating rapid conversion. Significantly, this method effectively addresses challenges associated with the use of expensive reagents, harsh reaction conditions, and prolonged reaction times, presenting a more efficient alternative. Demonstrating favorable reactivity across a diverse range of aryl groups, as well as benzyl or tert‐butyl carbamates, the method consistently yields satisfactory results, with oxazolidinone formation ranging from 55 % to 99 % in over 24 examples. The synthesized oxazolidinones, including 5 v–5 x, hold substantial promise as intermediates for the synthesis of crucial synthetic molecules. Furthermore, the versatility of this method is underscored by its successful application in the formation of the 6‐membered ring 1,3‐oxazinan‐2‐one. These findings not only contribute to the advancement of synthetic methodologies but also pave the way for a streamlined synthesis of important pharmaceutical compounds.

Stereoselective Synthesis of Polyketide Segments of Nemamide A and Euglenatides D–E

AbstractA convergent strategy for the stereoselective synthesis of polyketide segments of hybrid natural products nemamide A and euglenatides D–E has been developed for the first time. The salient features of this gram-scale synthesis include Trost–Rychnovsky alkyne rearrangement, HWE olefination, regioselective epoxide ring opening, Prins–Ritter cyclization, and subsequent reductive cleavage of the substituted THP ring. The optimized route is modular and could be tunable to access the other polyketide counterparts of these families of metabolites.

Consequences of Pore Polarity and Solvent Structure on Epoxide Ring-Opening in Lewis and Brønsted Acid Zeolites.

The structure of solvent molecules within zeolite pores influences the rates and selectivities of catalytic reactions by altering the free energies of reactive species. Here, we examine the consequences of these effects on the kinetics and thermodynamics of 1,2-epoxybutane (C4H8O) ring-opening with methanol (CH3OH) in acetonitrile (CH3CN) cosolvent over Lewis acidic (Zr-BEA) and Brønsted acidic (Al-BEA) zeolites of varying (SiOH) x density. Despite ostensibly identical reaction mechanisms across materials, turnover rates depend differently on (SiOH) x density between acid types. (SiOH) x -rich Zr-BEA (Zr-BEA-OH) provides ∼10 times greater rates than a (SiOH) x -poor material (Zr-BEA-F), while Al-BEA-OH and Al-BEA-F give turnover rates within a factor of 2. Zr-BEA-OH shows more positive activation enthalpies and entropies than Zr-BEA-F across the range of [CH3OH], which reflect the displacement of solvent molecules and lead to greater rates in Zr-BEA-OH due to the dominant role of entropic gains. Measurements of the density and composition of solvent within the pores show that the (SiOH) x nests within Zr-BEA-OH promote hydrogen-bonded solvent structures distinct from Zr-BEA-F, while the Brønsted acid sites confer interactions similar to (SiOH) x nests and give solvent structures within Al-BEA-F that resemble those within Al-BEA-OH. Correlations between apparent activation enthalpies and C4H8O adsorption enthalpies show that interactions with solvent molecules give proportional changes to both C4H8O adsorption and ring-opening transition state formation. The differences in intrapore environment carry consequences for both rates and regioselectivities of epoxide ring-opening, as demonstrated by product regioselectivities that increase by a factor of 3 in response to changes in solvent composition and the type of acid site in the *BEA structure (i.e., Lewis or Brønsted). These results demonstrate the ability to control rates, regioselectivities, and adsorption thermodynamics relevant for industrially relevant liquid-phase reactions through the design of noncovalent interactions among solvating molecules, reactive species, and (SiOH) x functions.

Ultrasound-assisted ring opening of epoxides in HFIP: THF: Synthesis, characterization, computational studies and molecular docking of novel 2‑hydroxy dithiocarbamates

Under the influence of ultrasonic irradiation, pyridazinone, triazinone, or phthalimide containing 2‑hydroxy dithiocarbamates, a biologically relevant novel organo-sulfur compound, was synthesized. Detailed characterization, computational, and molecular docking studies are being investigated. Molecular interactions were studied using 3D Hirshfeld surfaces and corresponding 2D fingerprint plots. Theoretical (DFT) studies on the molecular structure, HOMO, LUMO, and quantum chemical descriptors were performed at the B3LYP/6–311++G(d,p) level of theory. At the same time, the interaction energy was computed using the B3LYP/6–31G(d,p) level of theory. The FMO study revealed that molecules 4a and 4p in the gas phase have 3.545 eV and 3.263 eV HOMO-LUMO energy gaps, respectively, and they are hence kinetically stable. Quantum chemical calculations confirm the electrophilic character of compounds 4a and 4p, as the molecule is stable and highly electrophilic. The interactions of 2‑hydroxy dithiocarbamate derivatives (4a-4t) with the ligand-binding site of the target COX-2 (cyclooxygenase-2) enzyme were investigated using in-silico molecular docking experiments. Compared to the standard medicine celecoxib, the results showed that most synthesized derivatives had better glide scores and interaction. The docking study of all the synthesized compounds revealed that compounds 4a, 4e, and 4o interact well with the COX-2 enzyme as anti-inflammatory drugs. Molecular dynamic simulation was utilized to validate the docking study and explore the stable binding site and interaction of compound 4o, which is the most potent. The findings indicated that compound 4o exhibited better stability and interaction when compared to the reference drug.

Comparison of the Effect of a Nucleophile on Epoxide Ring Opening Catalyzed by Potassium tert-Butoxide or Tris(pentafluorophenyl)borane

Comparison of the Effect of a Nucleophile on Epoxide Ring Opening Catalyzed by Potassium <i>tert</i>-Butoxide or Tris(pentafluorophenyl)borane

Highly Enantiomerically Enriched Secondary Alcohols via Epoxide Hydrogenolysis.

In this article, we report the development of ruthenium-catalyzed hydrogenolysis of epoxides to selectively give the branched (Markovnikov) alcohol products. In contrast to previously reported catalysts, the use of Milstein's PNN-pincer-ruthenium complex at room temperature allows the conversion of enantiomerically enriched epoxides to secondary alcohols without racemization of the product. The catalyst is effective for a range of aryl epoxides, alkyl epoxides, and glycidyl ethers and is the first homogeneous system to selectively promote hydrogenolysis of glycidol to 1,2-propanediol, without loss of enantiomeric purity. A detailed mechanistic study was conducted, including experimental observations of catalyst speciation under catalytically relevant conditions, comprehensive kinetic characterization of the catalytic reaction, and computational analysis via density functional theory. Heterolytic hydrogen cleavage is mediated by the ruthenium center and exogenous alkoxide base. Epoxide ring opening occurs through an opposite-side attack of the ruthenium hydride on the less-hindered epoxide carbon, giving the branched alcohol product selectively.

A Three-Step Catalytic Asymmetric Sequence from Alkynes to α-Silyloxyaldehydes and Its Application to a C22-C41 Fragment of Bastimolide A.

1,5-Polyol structures present challenges in stereocontrol, configurational assignment, and diastereomer separation; these are all compromised by remote stereochemical relationships. A configuration-encoded approach with alcohol configurations previously established within enantiopure building blocks offers a versatile solution to these issues. The iterative construction begins with α-silyloxyaldehydes; here, we introduce an enantioselective and step-economical route from alkynes to α-silyloxyaldehydes via silyl cation-induced ring opening of enol ester epoxides. This development enables an efficient configuration-encoded synthesis of the C22-C41 fragment of the bastimolides.