Syn-elimination Reaction Research Articles

Catalytic Mechanism of Hyaluronate Lyase from Spectrococcus pneumonia: Quantum Mechanical/Molecular Mechanical and Density Functional Theory Studies

Hyaluronate lyase from Spectrococcus pneumonia can degrade hyaluronic acid, which is one of the major components in the extracellular matrix. The major functions of hyaluronan are to regulate water balance and osmotic pressure and act as an ion-exchange resin. It has been suggested in our previous molecular dynamics simulation that the binding of the substrate molecule could lead to the ionization of Y408 and protonation of H399. Followed by our recent molecular dynamics simulation of the enzyme-substrate complex, a unified proton abstraction and donation mechanism for this enzyme can be established using a combined quantum mechanical and molecular mechanical approach and density functional theory method. Y408 is shown to serve as the general base in the proton abstraction, while general acid is the next proton donation step. Overall, this reaction can be classified into syn-elimination reaction mechanism. The neutralization effects of C5 carboxylate group by several polar residues such as N349 and H399 were also examined. Finally, in combination of our previous molecular dynamics simulations, a complete catalytic cycle for the degradation of hyaluronan tetrasaccharide catalyzed by the hyaluronate lyase from Spectrococcus pneumonia is proposed.

A facile route for the synthesis of vinyl-substituted 1,3,4-oxadiazoles

An efficient synthesis of vinyl-substituted 1,3,4-oxadiazoles using o-nitrophenyl sulfoxide precursor via syn-elimination reaction using sodium acetate in THF is described. This method is cost effective as it uses cheap o-nitrothiophenol and can be used in the synthesis of vinyl intermediates during synthesis of bioactive compounds, which avoids the use of any toxic metals.

A DFT Analysis of Thermal Decomposition Reactions Important to Natural Products

The thermal decomposition reactions of several important natural flavor and fragrance chemicals have been investigated using density functional theory (DFT, B3LYP/6-31G*). Retro-aldol reactions of glucose, fructose, hernandulcin, epihernandulcin, [3]-gingerol, and [4]-isogingerol; retro-carbonyl-ene reactions of isopulegol, lavandulol, isolyratol, and indicumenone; and pyrolytic syn elimination reactions of linalyl acetate, alpha-terpinyl acetate, and bornyl acetate, have been carried out. The calculations indicate activation enthalpies of around 30 kcal/mol for the retro-aldol reactions and for retro-carbonyl-ene reactions, comparable to pericyclic reactions such as the Cope rearrangement and electrocyclic reactions, and therefore important reactions at elevated temperatures (e.g., boiling aqueous solutions, gas-chromatograph injection ports). Activation enthalpies for pyrolytic eliminations are around 40 kcal/mol and are unlikely to occur during extraction or GC analysis.

ChemInform Abstract: Synthesis and Reactivity of Enantiomerically Pure 2-Fluoromethyl-2-(1′-p-tolylsulfinyl)alkyl Oxiranes.

This paper presents an efficient procedure for preparing enantio- and diastereomerically pure 2-fluoromethyl-2-(1′-p-tolylsulfinyl)alkyl oxiranes, designed as versatile chirons to be transformed to a series of synthetically useful and biologically relevant compounds. In particular, (2S)-2-fluoromethyl-2-(1′-p-tolylsulfinyl)alkyl oxiranes, prepared by the reaction between (RS)-α-alkyl-β-keto-γ-fluoro sulfoxides and diazomethane, can be efficiently obtained in diastereomerically pure state via formation, purification and re-cyclization of the corresponding bromohydrins. Synthetic value of these oxiranes was demonstrated by their transformation to various sulfur-free synthetically and biologically interesting compounds via the reductive desulfurization, Pummerer, ring-opening and syn-elimination reactions. The presence of the methyl in α-position to the sulfoxide group in the starting compounds was found to interfere with a normal course of the Pummerer rearrangement giving rise to the corresponding vinyl sulfides in low chemical yield. By contrast the thermal syn-elimination reaction of the p-tolyl sulfoxide group provided an efficient entry to the sulfur-free vinyl derivatives.

Cyclopropenylcarbinol Derivatives as New Versatile Intermediates in Organic Synthesis: Application to the Formation of Enantiomerically Pure Alkylidenecyclopropane Derivatives

The copper-catalyzed carbomagnesiation (or hydrometalation) reaction of chiral cyclopropenylcarbinol derivatives, obtained by means of a kinetic resolution of secondary allylic alcohols, leads to an easy and straightforward preparation of enantiomerically pure alkylidenecyclopropane derivatives. The reaction mechanism is composed of a syn-carbometalation followed by a syn-elimination reaction. To gain further insight into the reaction mechanism of the carbometalation, the diastereoselective formation of cyclopropylcarbinol was also achieved and was found to be very sensitive to the nature of the organometallic species used for the addition reaction. Cyclopropylcarbinol could also be prepared through a diastereoselective reduction of cyclopropenylcarbinol derivatives. Finally, functionalization of enantiomerically enriched cyclopropenylcarbinols into the corresponding acetate or phosphinite derivatives leads, under mild conditions, to various enantiomerically pure heterosubstituted alkylidenecyclopropanes.

Enantiomerically Pure Cyclopropenylcarbinols as a Source of Chiral Alkylidenecyclopropane Derivatives

The straightforward approach: The copper-catalyzed carbomagnesiation reaction of chiral cyclopropenylcarbinol derivatives, obtained through kinetic resolution of secondary allylic alcohols, leads to the preparation of enantiomerically pure alkylidenecyclopropane derivatives. The reaction mechanism is composed of a syn carbometalation followed by a syn elimination reaction.

Ab Initio MP2 and DFT Study of the Thermal Syn Elimination Reaction in Ethyl Formate

The thermal elimination reaction that appears in some polycarbonates has been studied by density functional theory (DFT) and ab initio methods of different levels. This work has been focused in the elimination process of ethyl formate, as a good model of this kind of reaction. Different minima and the transition state have been found to characterize the thermal elimination reaction, and the activation energy has been obtained. In this study, we have used different methods to calculate the contribution of the correlation energy; different basis sets were also employed. This will allow us to perform an analysis of the influence of the applied method in the obtained results to study the thermal elimination. The lengthening of the bonds has also been analyzed to shown how concerted the thermal elimination is in the ethyl formate. Three minima have been found for the ethyl formate, two of them are very close and the third is higher in energy. In general, the DFT method with a B3LYP functional gives a less concerted reaction. A nonplanar transition state is predicted by most of the methods used.

Ab Initio Studies of Thermal Syn-Elimination Reactions in Carbonates: Effect of Structure on Reactivity

Thermal elimination reactions in carbonates are investigated from a theoretical point of view with density functional theory methods to obtain insight into the reaction mechanism and structural factors that influence the kinetics. Carbonate systems are good model systems for the kinetics of thermal degradable polycarbonates. Special attention is given to the influence of para-substituents placed either at Cα or Cβ. The results enable prediction of ρ values of the Hammett equation and confirm earlier experimental data.

Alpha-1,4-Glucan lyase performs a trans-elimination via a nucleophilic displacement followed by a syn-elimination.

alpha-Glucan lyase (EC 4.2.2.13, GLase) cleaves alpha-1,4-glucosidic bonds via an elimination reaction to produce 1,5-d-anhydrofructose. GLase was inactivated by the mechanism based alpha-glucosidase inactivator, 5-fluoro-beta-l-idosyl fluoride. The trapped glycosyl-enzyme intermediate was isolated and the nucleophilic amino acid residue (Asp 553) identified is equivalent to the residue so identified in sequence-related alpha-glucosidases. This intermediate undergoes a syn-elimination reaction to release the product. Further evidence against a direct trans-elimination mechanism was provided by the absence of a primary kinetic isotope effect on the substrate substituted with deuterium at the C2 position.

Synthesis and reactivity of enantiomerically pure 2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes

This paper presents an efficient procedure for preparing enantio- and diastereomerically pure 2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes, designed as versatile chirons to be transformed to a series of synthetically useful and biologically relevant compounds. In particular, (2 S)-2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes, prepared by the reaction between ( R S)-α-alkyl-β-keto-γ-fluoro sulfoxides and diazomethane, can be efficiently obtained in diastereomerically pure state via formation, purification and re-cyclization of the corresponding bromohydrins. Synthetic value of these oxiranes was demonstrated by their transformation to various sulfur-free synthetically and biologically interesting compounds via the reductive desulfurization, Pummerer, ring-opening and syn-elimination reactions. The presence of the methyl in α-position to the sulfoxide group in the starting compounds was found to interfere with a normal course of the Pummerer rearrangement giving rise to the corresponding vinyl sulfides in low chemical yield. By contrast the thermal syn-elimination reaction of the p-tolyl sulfoxide group provided an efficient entry to the sulfur-free vinyl derivatives.

Highly diastereoselective methylene transfer from diazomethane to the carbonyl of β-keto sulfoxides. A general approach to synthetically versatile fluorine-containing chiral building blocks

This paper describes the reactions of diazomethane with α-alkyl and α-phenyl-substituted ( R S)-β-keto sulfoxides bearing difluoro-, trifluoro- and difluorochloromethyl groups on the terminal site, to afford the corresponding diastereo- and enantiomerically pure epoxides. A plausible mechanistic rationale for the origin of the stereochemical preferences in these reactions has been provided. Synthetic versatility of the resultant epoxides has been demonstrated by a series of key transformations of the epoxide ring and the sulfinyl group including ring-opening, reductive desulfurization and syn-elimination reactions.

Theoretical studies of thermal syn elimination reaction of organic amine oxide, sulfoxide and phosphoxide by ab initio and density functional methods

The geometries of the reactants and transition structures for the Ei elimination of organic oxides (CO, PO, NO and SO) were generated with the RHF/6-31G(d), MP2/6-31G(d) ab initio, SVWN/6-31G(d) and BLYP/6-31G(d) density functional theory (DFT) models. The energies were evaluated at the same level of theory. The planarity of the transition structures was confirmed for all of the applied theory models. It was estimated that 2–7 kcal mol −1 is the necessary energy to change the reactants into a conformer which is suitable for elimination. Aldehydes and phosphoxides are not suitable starting materials for the preparation of olefins. The most reactive species are the nitroxides. The order of reactivity is in general agreement with experimental knowledge. The local and non-local DFT methods predict very similar activation energies. These activation energies are closer to the expected values than the energies predicted with the MP2/6-31G(d) theoretical model.

Theoretical Studies of Thermal Syn Elimination Reactions. The Relative Rates of Ethyl Formate, Ethyl Xanthate, and Ethyl Phosphinate Eliminations

Theoretical Studies of Thermal Syn Elimination Reactions. The Relative Rates of Ethyl Formate, Ethyl Xanthate, and Ethyl Phosphinate Eliminations

Syntheses of (2S,3R)- and (2S,3R)[3- 2h]- 3-methylaspartic acid: slow substrates for a syn-elimination reaction catalysed by methylaspartase.

Methylaspartase catalyses the slow syn-elimination of ammonia from the (2S,3R)-[L- erythro]-diastereomer of the natural substrate, (2S,3S)-3-methylaspartic acid, to give mesaconic acid. To provide material of sufficient stereochemical purity to probe the mechanism of the reaction, two synthetic routes to (2S,3R)- and (2S,3R)[3- 2H]- 3-methylaspartic acid were devised. The use of these (2S,3R)-3-methylaspartic adds revealed that the enzymic reaction does not involve C-3 epimerisation followed by normal anti-elimination, ruling-out the possibility of a carbanion intermediate. Conversely, the substrate displayed very large primary deuterium isotope effects indicating rate-limiting CH bond cleavage.

Concerning orientations of certain syn-elimination reactions

Explanation of an interesting aspect of the orientation of unsymmetrically substituted oxides.

Transition state structures in ion-pair base-promoted syn-elimination reactions

The temperature dependence of the primary deuterium kinetic isotope effect has been applied as a criterion of transition state (TS‡) structure in the syn-elimination reaction of bicyclo [2.2.1]heptan-2-exo-yl toluene-p-sulphonate, caused by two different hindered bases in a low dielectric, aprotic solvent. The isotope effect (kH/kD= 3.43 ± 0.02) was temperature independent, and identical for the two bases used (t-butoxide and cyclohexylcyclohexyl oxide). These results are interpreted to indicate a non-planar, cyclic TS‡ involving non-linear hydrogen transfer. A comparison with the analogous Hofmann and amine oxide elimination reactions affords some understanding of the factors controlling TS‡ structure in cyclic syn-elimination processes.

Carbon-14 kinetic isotope effects and kinetic studies in the syn-elimination reactions of (2-phenylethyl)dimethylamine oxides

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-14 kinetic isotope effects and kinetic studies in the syn-elimination reactions of (2-phenylethyl)dimethylamine oxidesDaniel R. Wright, Leslie B. Sims, and Arthur FryCite this: J. Am. Chem. Soc. 1983, 105, 11, 3714–3716Publication Date (Print):June 1, 1983Publication History Published online1 May 2002Published inissue 1 June 1983https://doi.org/10.1021/ja00349a063RIGHTS & PERMISSIONSArticle Views116Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (437 KB) Get e-Alerts Get e-Alerts

ChemInform Abstract: KINETIC STUDY OF THE BASE‐INDUCED ANTI AND SYN ELIMINATIONS FROM 2,3‐DIHALOGENO‐2,3‐DIHYDROBENZOFURANS IN DIFFERENT BASE‐SOLVENT SYSTEMS

dibromo-5-chloro-2,3-dihydrobenzofuran and anti eliminations from cis- 2,3-dichloro-2,3-dihydrobenzofuran have been investigated in different base-solvent systems. Anti elimination is favored over the syn by a factor of -33 000 in EtONa-EtOH, -10 000 in t-BuOK-t-BuOH, and >10 000 in t-BuOK-t-BuOH, in the presence of 18-crown-6 ether. The rate of both the anti and syn pathway increases with increasing the medium basicity, the syn path being also favored, however to much less extent, by base association. From the values of the deuterium kinetic isotope effect and substituent effect it can be concluded that the transition state structure for the syn elimination from trans2,3-dibromo-2,3-dihydrobenzofuran is significantly affected by base association, but not by medium basicity. trans-2,3-Dihalogeno-2,3-dihydrobenzofurans are very suitable substrates for the study of elimination processes owing to their tendency to be converted by bases into the aromatic benzofuran system. Recently we have investigated the reactions of trans-2,3-dibromo-2,3-dihydrobenzofuran (I) with bromide and chloride ions in dipolar aprotic so1vents.l With bromide ions I is dehalogenated to benzofuran, whereas with chloride ions it gives mainly trans- 2,3-dichloro-2,3dihydrobenzofuran (11)2 together with ca. 10% of 3-bromobenzofuran presumably formed in a syn dehydrobromination process. Syn dehydrohalogenation, however, is the only reaction observed when I or I1 reacts with an alkoxide in the corresponding alcohol. Owing to the increasing importance of syn elimination reactions, it seemed interesting to carry out a detailed kinetic investigation, including the determination of deuterium kinetic isotope effect and substituent effect of the reactions of I and I1 in different alkali alkoxide-alcohol systems. For comparison purposes some anti eliminations from cis -2,3dichloro-2,3-dihydrobenzofuran (111) have also been studied.3 Results and Discussion The eliminations from 1-111, trans-2,3-dibromo-3-deuterio-2,3-dihydrobenzofuran (IV), and trans-2,3-dibromo5-chloro-2,3-dihydrobenzofuran (V) have been studied in EtOK-EtOH, n-BuOK-n-BuOH, t-BuOK-t-BuOH, nRuOK-18C6-n-BuOH (18C6 is 18-crown-6 ether), and t BuOK-18C6-t-BuOH. Some experiments for the reactions of 1-111 in EtONa-EtOH have been also carried out. In each

A novel syn-elimination reaction of two cis-hydroxy-tosylates

The cis-hydroxy-tosylates (1b) and (4) on treatment with potassium t-butoxide in t-butyl alcohol give the corresponding epoxides (3) and (6) by a novel syn-elimination–ring closure reaction.