Endo-exo Selectivity Research Articles

η6 -Metalated Aryl Iodides in Diels-Alder Cycloaddition Reactions: Mode of Activation and Catalysis.

The potential application of η6 -metalated aryl iodides as organocatalyst has been explored by means of computational methods. It is found that the enhanced halogen bonding donor ability of these species, in comparison with their demetalated counterparts, translates into a significant acceleration of the Diels-Alder cycloaddition reaction involving cyclohexadiene and methyl vinyl ketone. The factors behind this acceleration, the endo-exo selectivity of the process and the influence of the nature of the transition metal fragment in the activity of these species are quantitatively explored in detail by means of the combination of the Activation Strain Model of reaction and the Energy Decomposition Analysis methods.

Study and optimization of Diels-Alder reaction of piperine in aqueous ionic solutions using Gn.HCl as a catalyst

Study and optimization of Diels-Alder reaction of piperine in aqueous ionic solutions using Gn.HCl as a catalyst

Isolation, characterization and semi-synthesis of natural products dimeric amide alkaloids

Isolation, characterization and semi-synthesis of natural products dimeric amide alkaloids

3-Methyleneisoindolin-1-one Assembly via Base- and CuI/l-Proline-Catalyzed Domino Reaction: Mechanism of Regioselective Anionic Cyclization.

Anionic cyclization of o-alkynylbenzamides is proposed as a crucial step in many heterocycle syntheses. The cyclization can produce three products: Z-3-methylenisoindolin-1-one (Z-5-exo), E-3-methylenisoindolin-1-one (E-5-exo), and isoquinolinone (6-endo). Under base catalysis, the selectivity is generally poor. However, a copper-involved domino reaction of coupling and cyclization gives surprising selectivity for the thermodynamically disfavored Z-5-exo product (Org. Lett. 2009, 11, 1309-1312). We study the selectivity of anionic cyclization in the presence of K2CO3 and copper-l-proline, using surveys of the experimental literature and density functional theory (DFT) calculations. The o-alkynylbenzamide is predicted to be readily deprotonated by many bases, with subsequent cyclization via nucleophilic attack of the amide N- to alkynyl. In the absence of copper, endo-exo selectivity is predicted to arise from substituent effects, while Z/E selectivity is a sensitive function of the tautomerization rate of an alkenyl anion intermediate. Most importantly, we predict that the remarkable selectivity of the copper-involved reaction occurs because copper-l-proline "locks" the alkene anion intermediates into the initially formed Z-5-exo configuration. Calculations on other metals suggest that soft Lewis acid additives provide a potential route to improved regiocontrol of other anionic cyclizations.

Substituent effects in the Diels–Alder reactions of butadienes, cyclopentadienes, furans and pyroles with maleic anhydride

In this study, activation energies in the Diels–Alder reactions of a series of substituted butadienes, cyclopentadienes, furans and pyroles with maleic anhydride were calculated by the M06‐2X/6‐31G(d) method. The substituent effects on the reactivity and the endo–exo selectivity have been examined. The strength of reactivity effect has an order of pyroles > furans > cyclopentadienes > butadienes, which is highly correlated with the lowest unoccupied molecular orbital energy, the electronic chemical potential and the electrophilicity of parent diene but relatively less correlated with the highest occupied molecular orbital energy and chemical hardness. The trend that an increase of necleophilicity caused by an electron‐donating group on the diene favors the endo TS is effective with C2 substitution. With C1 substitution, the trend is ambiguous or even opposite. Copyright © 2015 John Wiley & Sons, Ltd.

ChemInform Abstract: X=Y-ZH Systems as Potential 1,3-Dipoles. Part 40. Chiral Azomethine Ylides from Homochiral Cyclic α-Amino Esters. Unusual Regiospecific Deprotonation of Iminium Ions.

Abstract A1,3-Strain and charge accelerated 1,5-H shifts are important factors in the stereospecific formation of iminium ions from cyclic secondary α-amino esters and bifunctional carbonyl compounds and their regiospecific or regioselective conversion to homochiral azomethine ylides. The endo-exo selectivity in the cycloadditions of these azomethine ylides is sensitive to the bifunctional carbonyl compound employed.

A Theoretical Analysis of a Diels−Alder Reaction in Ionic Liquids

The Diels-Alder reaction of cyclopentadinene (CP) with methyl acrylate (MA) in room-temperature ionic liquids (RTILs) is theoretically examined. In the present study, quantum molecular orbital theory is combined with a multicomponent reference interaction site model (RISM). Because RISM is free from statistical error, it is possible to overcome the serious difficulty in the description of the strong Coulombic interaction in RTILs. We focused on the origin of the relatively moderate solvation effects of RTILs and the mechanism of endo-exo selectivity.

Integration of Computational and Preparative Techniques To Demonstrate Physical Organic Concepts in Synthetic Organic Chemistry: An Example Using Diels-Alder Reactions

Preparative experiments in organic chemistry rarely invoke physical organic principles explicitly, even at the intermediate level where these principles are taught. Computational exercises often address such topics as molecular orbital theory and reaction energetics, but may not allow students to make the conceptual leap from computer to flask. The experiment described, based on endo–exo selectivity of Diels–Alder reactions, bridges this gap by integrating computational and preparative experiments.

Exo selectivity and the effect of disubstitution in the Diels–Alder reactions of butadiene with 3,3-disubstituted cyclopropenes

A density functional computational study was performed to accomplish two tasks: to examine the endo–exo selectivity in the Diels–Alder reactions of 3,3-disubstituted cyclopropenes with s-cis-butadiene, and to study the effect of disubstitution on the reactivity of the cyclopropene dienophile. Cyclopropene is substituted at C-3 with CH3, SiH3, NH2, PH2, OH, SH, F, and Cl; both 3-substituted and 3,3-disubstituted ground states are examined to determine relative reactivities. The exo transition-state structures are consistently lower in energy than the endo transition-state structures for the 3,3-disubstituted cyclopropene – butadiene system, and surprisingly, both modes of addition have lower activation barriers than the syn 3-substituted cyclopropene – butadiene system. Through a series of isodesmic reactions, we have concluded that there is an additional stabilization in the transition-state structures of the 3,3-disubstituted system that can account for the lowering of the activation barriers below that of the 3-substituted cases. This stabilization is a combination of the anomeric effect and the ring relaxation that occurs in the transition-state structure.Key words: Diels–Alder reaction, cyclopropene, exo selectivity, anomeric effect.

Endo-exo and facial stereoselectivity in the Diels-Alder reactions of 3-substituted cyclopropenes with butadiene.

A computational examination of the four modes of addition in the Diels-Alder reactions of 3-substituted cyclopropene derivatives (substituents: BH(2), CH(3), SiH(3), NH(2), PH(2), OH, SH, F, and Cl) with butadiene have been carried out at the B3LYP/6-31++G(d)//HF/6-31++G(d) level. The degree of stabilization of these derivatives at the ground state correlates with the electronegativity of the substituent. This attenuation of reactivity and differences in steric interactions are the only factors needed to explain both the high facial selectivity and the differences in the endo-exo selectivity seen in these reactions. Furthermore, evidence is presented that indicates that stabilization by an interaction involving the syn C-3 hydrogen of cyclopropene and butadiene is small or irrelevant in controlling the endo-exo selectivity of the Diels-Alder reaction.

ChemInform Abstract: Transition Metal Catalyzed [5 + 2] Cycloadditions of Allenes and Vinylcyclopropanes: First Studies of endo—exo Selectivity, Chemoselectivity, Relative Stereochemistry, and Chirality Transfer.

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.

Lewis Acid Catalysis of a Diels−Alder Reaction in Water

Here we report the first detailed study of a Diels-Alder (DA) reaction that is catalyzed by Lewis acids in water. The effect of Co2+, Ni2+, Cu2+ and Zn2+ ions as Lewis acid catalysts on the rate and endo-exo selectivity of the DA reaction between the bidentate dienophiles 3-phenyl-1-(2-pyridyl)-2-propen-1-ones (1a-e) and cyclo-pentadiene (2) in water has been studied. Relative to the uncatalyzed reaction in acetonitrile, catalysis by 0.010 M CU(NO3)(2) in water accelerates the reaction by a factor of 79 300. The kinetics of the catalyzed reaction were analyzed in terms of equilibrium constants for complexation of the Lewis acid with 1a-e and rate constants for the reaction of the resulting complexes with 2. The rate enhancement imposed upon the uncatalyzed DA reaction of substrates 1 with 2 by water is much more pronounced than that for the catalyzed reaction. The increase of the endo-exo selectivity induced by water in the uncatalyzed process is completely absent for the Lewis acid catalyzed reaction. The modest solvent and substituent effects observed for the catalyzed reaction indicate that the change in charge separation during the activation process is not larger than the corresponding change For the uncatalyzed reaction.

A sulfinyl trialkoxycarbonyl ethene as a new enantiopure dienophile in asymmetric diels-alder reactions

The synthesis and the asymmetric Diels-Alder reactions of the enantiomerically pure ( S)- p-tolylsulfinyl trialkoxycarbonyl ethene 3 with cyclic and acyclic dienes are reported. π-Facial selectivity and regioselectivity are very high in all studied cases. Reactions with cyclopentadiene exhibit moderated or high exo-selectivity, which disappears with acyclic dienes. The use of high pressure improves the π-facial selectivity but does not substantially modify the endo-exo selectivity.

Acid catalyzed intramolecular Diels-Alder reactions in lithium perchlorate-diethyl ether: Enhanced reaction rates and diastereoselectivity

The addition of 1.0–10 mol% of camphorsulfonic acid to 5.0 M lithium perchlorate in diethyl ether dramatically accelerates intramolecular Diels-Alder reactions and enhances the endo-exo selectivity.

X = Y - ZH systems as potential 1,3-dipoles. Part 40. Chiral azomethine ylides from homochiral cyclic α-amino esters. Unusual regiospecific deprotonation of iminium ions.

A 1,3-Strain and charge accelerated 1,5-H shifts are important factors in the stereospecific formation of iminium ions from cyclic secondary α-amino esters and bifunctional carbonyl compounds and their regiospecific or regioselective conversion to homochiral azomethine ylides. The endo-exo selectivity in the cycloadditions of these azomethine ylides is sensitive to the bifunctional carbonyl compound employed.

An intramolecular Diels-Alder reaction of vinylsilanes

Dialkylvinylsilyl ethers of dienols undergo a smooth intramolecular Diels-Alder reaction to yied a versatile bicyclic product with and endo-exo selectivity influenced by the substituents on silicon

ChemInform Abstract: Cytochalasan Synthesis: Total Synthesis of the Naturally Occurring (13)Cytochalasan Proxiphomin.

Proxiphomin (1), a naturally occurring [13]cytochalasan, has been synthesized by a route which uses an intramolecular Diels–Alder reaction of the long chain 3-(1-oxotrienyl)pyrrol-2(5H)-one (18) to form the 13-membered ring. This cyclization gave a mixture of endo and exo isomers (19) and (21), the endo isomer (19) being carried through to proxiphomin. Although the endo–exo selectivity was small, (19) : (21)= 52 : 48, the Diels–Alder cyclization was useful in that no epimerization had occurred at C-5. Cyclization of a mixture of Diels–Alder precursors (18) and (33) prepared from racemic pyrrolidinone (32) gave all four cyclized products (19), (21), (34), and (36) which were 1-debenzoylated, separated, and characterized.

Cytochalasan synthesis: total synthesis of the naturally occurring [13]cytochalasan proxiphomin

Proxiphomin (1), a naturally occurring [13]cytochalasan, has been synthesized by a route which uses an intramolecular Diels–Alder reaction of the long chain 3-(1-oxotrienyl)pyrrol-2(5H)-one (18) to form the 13-membered ring. This cyclization gave a mixture of endo and exo isomers (19) and (21), the endo isomer (19) being carried through to proxiphomin. Although the endo–exo selectivity was small, (19) : (21)= 52 : 48, the Diels–Alder cyclization was useful in that no epimerization had occurred at C-5. Cyclization of a mixture of Diels–Alder precursors (18) and (33) prepared from racemic pyrrolidinone (32) gave all four cyclized products (19), (21), (34), and (36) which were 1-debenzoylated, separated, and characterized.

Highly diastereoselective diels-alder reaction of optically active 2- p-tolylsulphinyl-2-cycloalkenones with cyclopentadiene

The Diels-Alder reaction of (S)-2- p-tolylsulphinyl-2-cyclopentenone (and 2-cyclohexenone) with cyclopentadiene, catalized by AlCl 3 and AlEtCl 2, occurs at room temperature with complete facial diastereoselectivity, but with moderate endo-exo selectivity.

Enhanced endo-exo selectivity in the stereochemistry of ketonization of enols. Part 201

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnhanced endo-exo selectivity in the stereochemistry of ketonization of enols. Part 201Howard E. Zimmerman and Linus W. LinderCite this: J. Org. Chem. 1985, 50, 10, 1637–1646Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://doi.org/10.1021/jo00210a016RIGHTS & PERMISSIONSArticle Views471Altmetric-Citations24LEARN 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 (2 MB) Get e-Alerts Get e-Alerts