Acid-catalyzed Epoxide Research Articles

Post-synthetic modification of NH2-MIL88B(Fe) with sulfonic acid groups for acid-catalyzed epoxide ring-opening reaction

A new metal–organic framework-based solid acid catalyst was successfully prepared and exploited in the catalytic ring-opening of epoxides.

Substituted 9-Anthraldehydes from Dibenzocycloheptanol Epoxides via Acid-Catalyzed Epoxide Opening/Semipinacol Rearrangement.

Starting from benzaldehyde derivatives, the corresponding dibenzocycloheptenol could be prepared in five steps. Under both substrate (secondary vs tertiary alcohol and the substituents on the aromatic ring(s)) and condition control, the subsequent epoxidation and acid-catalyzed epoxide opening/semipinacol rearrangement/aromatization afforded the corresponding 9-anthraldehydes in good yields, up to 88% over two steps. The presence of the electron-withdrawing group(s) on the aromatic ring(s) suppressed the rate of the epoxidation while the subsequent semipinacol rearrangement step required heating; the presence of the electron-donating group(s), on the other hand, frequently led to the decomposition during the epoxidation. From the mechanistic studies, the semipinacol rearrangement of the epoxide could precede the ionization at the bisbenzylic position, yielding the aldehyde intermediate. The ensuing dehydrative aromatization led to the formation of 9-anthraldehyde. Conversely, nucleophilic addition to the aldehyde and dehydrative aromatization with concomitant loss of formic acid led to anthracene.

Semisynthesis of Dolabellane Diterpenes: Oxygenated Analogues with Increased Activity against Zika and Chikungunya Viruses.

Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone (1) and (1R,7R,8R,11S)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (2), isolated from Eunicea genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC50) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound 9 showed an EC50 = 0.92 ± 0.08 μM and SI = 820 against ZIKV.

How Lewis Acids Catalyze Ring-Openings of Cyclohexene Oxide.

We have quantum chemically studied the Lewis acid-catalyzed epoxide ring-opening reaction of cyclohexene epoxide by MeZH (Z = O, S, and NH) using relativistic dispersion-corrected density functional theory. We found that the reaction barrier of the Lewis acid-catalyzed epoxide ring-opening reactions decreases upon ascending in group 1 along the series Cs+ > Rb+ > K+ > Na+ > Li+ > H+. Our activation strain and Kohn–Sham molecular orbital analyses reveal that the enhanced reactivity of the Lewis acid-catalyzed ring-opening reaction is caused by the reduced steric (Pauli) repulsion between the filled orbitals of the epoxide and the nucleophile, as the Lewis acid polarizes the filled orbitals of the epoxide more efficiently away from the incoming nucleophile. Furthermore, we established that the regioselectivity of these ring-opening reactions is, aside from the “classical” strain control, also dictated by a hitherto unknown mechanism, namely, the steric (Pauli) repulsion between the nucleophile and the substrate, which could be traced back to the asymmetric orbital density on the epoxide. In all, this work again demonstrates that the concept of Pauli-lowering catalysis is a general phenomenon.

Synthesis of Bradyrhizose from d-Glucose.

We describe the synthesis of the unusual bicyclic sugar bradyrhizose in 14 steps and a 6% overall yield from d-glucose. The synthesis involves the elaboration of a trans-fused carbocyclic ring onto the preexisting glucopyranose framework followed by adjustment of the oxidation levels. Key steps include radical extension of the glucopyranose side chain, ring closing metathesis, allylic oxidation, Luche reduction, hydroxy-directed epoxidation, and acid-catalyzed epoxide opening at the more substituted position.

An Acid-Catalyzed Epoxide Ring-Opening/Transesterification Cascade Cyclization to Diastereoselective Syntheses of (±)-β-Noscapine and (±)-β-Hydrastine.

An acid-catalyzed stereoselective epoxide ring-opening/intramolecular transesterification cascade cyclization reaction and N-Boc deprotection was found to be a successful strategy to construct the phthalide tetrahydroisoquinoline skeleton in one pot. Based on this strategy, the unified and highly diastereoselective routes for the total syntheses of (±)-β-Noscapine and (±)-β-Hydrastine were exploited.

Efficient Isomerization of α-Pinene Oxide to Campholenic Aldehyde Promoted by a Mixed-Ring Analogue of Molybdenocene

The MoIV complex [(η5-indenyl)(η5-cyclopentadienyl)Mo(MeCN)2](BF4)2 (1) has been used to promote two acid-catalyzed epoxide ring-opening reactions under ambient conditions. The alcoholysis of styre...

Microwave-Assisted, Asymmetric Synthesis of 3-Amino-2,3-Dihydrobenzofuran Flavonoid Derivatives from Chalcones.

A route to access 3-amino-2,3-dihydrobenzofurans that utilizes microwave-assisted organic synthesis to rapidly generate analogues has been developed. The route begins with an acid-catalyzed, microwave-assisted aldol condensation to generate chalcone intermediates, followed by a Corey-Bakshi-Shibata reduction and subsequent Sharpless asymmetric epoxidation to access stereoisomeric epoxyalcohols. The final step is a one-pot, microwave-assisted, regioselective, acid-catalyzed epoxide opening with various amines followed by an intramolecular nucleophilic aromatic substitution reaction to generate the 3-amino-2,3-dihydrobenzofurans. This route provides ready access to stereochemically and structurally diverse analogues of these flavonoid scaffolds. Additionally, a pilot library was synthesized, and the biological activity diversity of the chalcones and dihydrobenzofurans was explored in human carcinoma cell lines.

Acid-catalyzed epoxide alcoholysis in the presence of indenyl molybdenum carbonyl complexes

The indenyl molybdenum carbonyl complexes [IndMo(CO)2(L)n]BF4 (L = NCMe with n = 3 (1), 2,2′-bipyridine (2) or 1,4,7-trimethyltriazacyclononane (3) with n = 1) promote epoxide alcoholysis under moderate reaction conditions. Complexes 1 and 2 showed the best performance for the alcoholysis of styrene oxide with different alcohol nucleophiles (acting as both reactant and solvent), leading to the corresponding 2-alkoxy-2-phenylethanol with 100% yield at 10 min and 35 °C. These catalytic results are far superior to those found for previously studied molybdenum carbonyl complexes. An efficient procedure for catalyst recovery and reuse without decrease in reaction rate is described.

Biomimetic Total Synthesis of Hyperjapones A-E and Hyperjaponols A and C.

Hyperjapones A-E and hyperjaponols A-C are complex natural products of mixed aromatic polyketide and terpene biosynthetic origin that have recently been isolated from Hypericum japonicum. We have synthesized hyperjapones A-E using a biomimetic, oxidative hetero-Diels-Alder reaction to couple together dearomatized acylphloroglucinol and cyclic terpene natural products. Hyperjapone A is proposed to be the biosynthetic precursor of hyperjaponol C through a sequence of: 1) epoxidation; 2) acid-catalyzed epoxide ring-opening; and 3) a concerted, asynchronous alkene cyclization and 1,2-alkyl shift of a tertiary carbocation. Chemical mimicry of this proposed biosynthetic sequence allowed a concise total synthesis of hyperjaponol C to be completed in which six carbon-carbon bonds, six stereocenters, and three rings were constructed in just four steps.

Identification of phenylmethylene as an active intermediate of the acid-catalyzed styrene epoxide oxidation in polar solvents

After the acid-catalyzed conversion of styrene epoxide under the action of p-toluenesulfonic acid (acetonitrile, ButOH (90%) + chlorobenzene (10%) (v/v), 343 K) in the presence of pyridine, a spectrum of iminium ylide was obtained (λmax = 450 nm), coinciding with the spectrum of the ylide product formed upon the reaction of pyridine with phenylmethylene (published data) during generation of carbenes from diazo compounds by flash photolysis. In an oxygen atmosphere, no ylide absorption band is recorded. This result confirms the previous assumption according to which in epoxide–acid systems, carbene species are formed, react with O2 in an oxygen atmosphere, and destroy the added hydroperoxides in the absence of O2.

The use of sodium chlorite in the non-racemic synthesis of a potent inhibitor of glycolipid biosynthesis

A facile and environmentally friendly synthesis of both enantiomers of a biologically important 1-N-iminosugar (azasugar) is presented. To this end, the use of a very cheap and non-toxic reagent, such as sodium chlorite, is featured in two key reactions. Additionally, a highly stereoselective epoxidation with dimethyloxirane (DMDO), and regioselective acid-catalyzed epoxide ring opening are also two environmentally friendly reactions that are employed in this synthesis. For all the above-mentioned, and also taking into account that protecting groups were not employed, we would like to present this synthetic route as an efficient approach for the development of environmental and sustainable syntheses of highly oxygenated biologically important compounds.

ChemInform Abstract: The First Total Synthesis of Synparvolide C.

The first stereoselective total synthesis of synparvolide C has been accomplished. An acid-catalyzed epoxide ring-opening reaction and ring-closing metathesis (RCM) were used for the cyclic ether and δ-lactone formation, respectively, to furnish the core structure of the target molecule. These reactions along with a succession of functional group manipulations led to the preparation of the natural product. The spectral and analytical data were used to establish the absolute configuration.

Fatty ketones from the rearrangement of epoxidized vegetable oils

The rearrangement of epoxidized vegetable oils to produce fatty ketones, catalyzed by acidic resins, is disclosed. The non-microbial production of fatty ketones from epoxidized vegetable oils has not been previously reported. Some of the variables affecting the ketone formation such as acidic strength of the catalyst, temperature and solvent are studied in order to determine the conditions that favor the rearrangement. Epoxidized vegetable oils can be easily transformed to the respective ketones via a rearrangement reaction catalyzed by acidic resins. Other kind of acidic catalysts are active for this reaction if their Brönsted acid sites are accessible to protonate the epoxide. Formation of ketones, from the rearrangement of epoxidized methyl oleate, is favored in the presence of strongly acidic catalysts and enhanced by increasing temperature. Polar-protic solvents increase the ketone yield but decrease the ketone selectivity because they are added to the epoxide ring. The mechanism for the epoxide rearrangement is very likely to take place through a hydride migration to the carbocation generated in the acid-catalyzed epoxide ring opening.

Epoxidation of allylic alcohols on self-assembled polyoxometalates hosted in layered double hydroxides with aqueous H 2O 2 as oxidant

A series of self-assembled polyoxometalate (POM) catalysts were directly immobilized into layered double hydroxides (LDH) by a selective ion-exchange method. Sandwich-type POM species are found to be more favorable than Keggin-type POM for the direct immobilization in LDH, because strict pH controlling is not needed and the LDH hosts can be kept intact. The resulting LDH–POM catalysts were evaluated in the epoxidation of allylic alcohols with aqueous H 2O 2 as the oxidant without using organic solvent. The heterogeneous LDH–POM catalysts show much higher epoxide selectivity than the corresponding homogeneous Na–POM catalysts, which can be attributed to the beneficial effect of basic LDH host on the suppression of the acid-catalyzed epoxide hydrolysis. The cooperation between the POM guest and the LDH host can achieve up to 99% selectivity of epoxide, 95% H 2O 2 efficiency and 37200 h −1 TOF without the need of base additives and pH controlling, and the host-guest catalysts can be readily recycled with no apparent loss of catalytic performance.

Ring-Opening and Ring-Closing Reactions of a Shikimic Acid-Derived Substrate Leading to Diverse Small Molecules

An epoxide derived from (-)-shikimic acid was attached to a solid support and used to synthesize over 5000 diverse small molecules. Key transformations include a Lewis acid-catalyzed epoxide opening with amines and an intramolecular Heck reaction with aryl iodides. Compounds derived from this pathway were printed onto small-molecule microarrays and screened for binding to proteins. Compounds that bound to Aurora A kinase were characterized using surface plasmon resonance.

Construction of a C(30-38) dioxabicyclo[3.2.1]octane subtarget for (+)-sorangicin A, exploiting a regio- and stereocontrolled acid-catalyzed epoxide ring opening.

[reaction: see text] In this paper, we report assembly of the novel dioxabicyclo[3.2.1]octane subtarget (-)-2, comprising the signature structural element of the potent antibiotic (+)-sorangicin A (1). The synthesis was achieved in 15 steps (1.5% overall yield) via a series of acid-catalyzed epoxide ring openings. The first, facilitated by the complex of alkyne (+)-3 with Co(2)(CO)(8), proceeded in a highly regio- and stereoselective fashion.

Change of Rate Limiting Step in General Acid-Catalyzed Benzo[a]pyrene Diol Epoxide Hydrolysis

The rates of reaction of (±)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (1) in 1:9 dioxane−water buffer solutions containing primary amines whose pKa values span the range of 5.4−10.7 have been determined. For those amines with pKa values < ca. 8, only the acid form (RNH3+) gives rise to a kinetic term for reaction with 1. The rate-limiting step of this reaction is general acid-catalyzed epoxide ring opening to yield a discrete α-hydroxycarbocation, followed by a fast reaction of this intermediate with solvent. The intermediate α-hydroxycarbocation is sufficiently stable so that its reactions with external nucleophiles and bases compete with its reaction with solvent. For those amines with pKa > ca. 8, both acid and base forms of the buffer react with 1. The magnitude of the kinetic term in the base form of the amine (RNH2) increases with amine pKa and is attributed to nucleophilic addition of the amine to the epoxide group. Curvatures in plots of the kinetic term due to buffer (kbuff) as a function of the mole fraction of buffer acid for substituted ammonium ions with pKa > 8 are interpreted in terms of a change in rate-limiting step of the general acid-catalyzed pathway from epoxide ring opening at low amine base concentrations to reaction of amine base acting as either a general base or nucleophile with an α-hydroxycarbocation at higher amine base concentrations. Thus, epoxide ring opening of 1 in buffer solutions of the more basic amines is a reversible reaction. Rate and product studies of the reaction of 1 in acid solutions (pH 5.5) and in Tris buffer solutions containing sodium azide show that azide ion is effective in trapping the α-hydroxycarbocation intermediate, subsequent to its rate-limiting formation by reaction of 1 with either H+ or Tris-H+. These results demonstrate that the intermediate formed from epoxide ring opening of 1 with acids has a sufficient lifetime so that its reaction with azide ion competes with its reaction with solvent.

The chemistry of khat. An approach to the synthesis of euonyminol

Abstract

Curing reactions in elastomers. II. Carboxy‐terminated polybutadiene

AbstractAttempts have been made to understand the curing reactions in carboxy‐terminated polybutadiene (CTPB), which happens to be the most practical binder in advanced solid composite propellants. The curing of CTPB has been studied for different ratios of curing agents (MAPO and Epoxide) by gel content, molecular weight, crosslink density, and penetration temperature measurements, and the optimum composition of curators for effective curing of CTPB has been determined. Activation energy calculations on the curing of CTPB with 9.5% epoxide and 0.5% MAPO in the temperature range 75–100°C gave 14.1 kcal/mol for which a diffusion‐controlled or acid‐catalyzed epoxide ring opening mechanism has been suggested for the curing process in CTPB.