OSMANIA UNIVERSITY COLLEGE OF TECHNOLOGY

A SEMINAR ON E1CB ELIMINATION BY SRAVAN KUMAR.D M.PHARMACY 1ST YR 1ST SEM PHARMACEUTICAL CHEMISTRY ROLL NO:1008-10-884-008

E1CB ELIMINATION

CONTENTS

INTRODUCTION

TYPES OF ELIMINATION

STEREOCHEMISTRY OF E1CB

E1,E2,E1CB DIFFERENCES

APPLICATIONS

REFERNCES

STEREOCHEMISTRY OF E1CB MECHANISMEllimination can also occur by a mechanism known as the E1cb mechansim. Theelimination first-order carbanion mechansim is used to explain the results of someelimination reactions in which a highly polar leaving group is present and the leastsubstituted alkene is the major product. But only few studies have actually proven the E1cbprocess. The kinetics of the E1cb process are shown below. The reaction is actually notfirst order but the slow step is the elimination from S-, a first order step in the process.

Syn elimination often occurs and it is associated with poor leaving groups or theabsence of an anti-beta hydrogen. The bicyclic compound shows syn elimination becauseno anti beta hydrogen is available because of the geometry of the system. In open chain

compounds, leaving groups such as +NR3 and F show strong tendencies for synelimination especially in long chain carbon systems

Reactions that produce stabilized carbanions adjacent to poor leaving groups providethe best evidence for the E1cb process. The elimination of quaternary ammoniums salts,also called Hoffmann elimination, is believed to follow a carbanion process with synelimination and the formation of the least substituted alkene

When reactions show E1cb character they generally produce the least

substitued alkene as the major product. This occurs because carbanion stability is of theorder: primary> secondary > tertiary. In the example below the major product comes fromthe carbanion formed at the secondary carbon atom.

The cis and trans 1-fluoro-2-bromocyclohexane isomers follow different eliminationpaths. The trans isomer has an anti-beta hydrogen available for elimination and the reactionproceeds with tert-butoxide. The cis isomer must use a syn hydrogen in the E1cb processthat causes loss of HF, and requires amide as a stronger base.

Evidence of a Borderline Region between E1cb and E2 Elimination Reaction Mechanisms: A Combined Experimental and Theoretical Study of Systems Activated by the Pyridine Ring

Evidence of a Borderline Region between E1cb and E2 Elimination Reaction Mechanisms: A Combined Experimental and Theoretical Study of Systems Activated by the Pyridine Ring ... The systems investigated represent borderline cases, where it is uncertain whether the reaction proceeds via a carbanion intermediate (E1cb, AxhDH + DN) or via the concerted loss of a proton and the halide (E2, ANDEDN) upon base attack. ... The comparison indicates an E1cb irreversible mechanism with F, but the deviation observed with Cl and Br does not allow a conclusive assignment

Catalysis of the β-Elimination of HF from Isomeric 2-Fluoroethylpyridines and 1-Methyl-2-fluoroethylpyridinium Salts. Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms

Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms ... The high values of MethylAF are in agreement with an irreversible E1cb mechanism (ANDE* + DN) for substrates 5 and 7

and with the high stability of the intermediate carbanion related to its enamine-type structure. ... These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (ANDEDN) mechanism. ...

Negative Ion Hyperconjugation and Its Relevance to the Mechanism of E1cB Reactions.

An ab Initio Study

Negative Ion Hyperconjugation and Its Relevance to the Mechanism of E1cB Reactions. ... Some time ago I proposed that E2 and E1cB(irrev) mechanisms could be distinguished by the observation of a leaving group isotope effect or element effect in the former but not in the latter case.1 This argument assumes that there is no weakening of the bond to the leaving group in the rate-determining proton transfer of the E1cB reaction. ... This is the kind of transition structure one would expect for a concerted E2 but not for an E1cB mechanism! ...

Large, inverse solvent isotope effects: a simple test for the E1cB mechanism

Large, inverse solvent isotope effects: a simple test for the E1cB mechanism ... Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms ... Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms

Ab Initio Molecular Dynamics Simulations of Elimination Reactions in Water Solution: Exploring the Borderline Region between the E1cb and E2 Reaction Mechanisms

We report a theoretical study, based on ab initio molecular dynamics simulations in water solution, of the mechanism of base-induced β-elimination reactions in systems activated by the pyridyl ring, with halogen leaving groups. The systems investigated represent borderline cases, where it is uncertain whether the reaction proceeds via a carbanion intermediate (E1cb, AxhDH + DN) or via the concerted loss of a proton and the halide (E2, ANDEDN) upon base attack. Recent theoretical and experimental evidence points toward the lack of a net distinction between the E1cb and E2 reaction paths, which seem to merge smoothly into each other in these borderline cases (Alunni, S.; De Angelis, F.; Ottavi, L.; Papavasileiou, M.; Tarantelli, F. J. Am. Chem. Soc. 2005, 127, 15151−15160). In this study, we explore the dynamics on the potential energy surface for the reaction of 2-(2-fluoroethyl)-1-methyl pyridinium with OH- by means of Car−Parrinello simulations in water solution. Our results indicate that the reaction mechanism effectively evolves through the potential energy region of the carbanion:

the carbon−fluoride bond breaks only after the carbon−hydrogen bond, confirming the conclusions of a recently reported study of the potential energy surface for this system.

Ketene-Forming Eliminations from Aryl Phenylacetates Promoted by R2NH/R2NH2

+ in Aqueous MeCN. Mechanistic Borderline between E2 and E1cb

Elimination reactions of 2-X-4-NO2C6H3CH2C(O)OC6H3-2-Y-4-NO2 [X = H (1), NO2 (2)]

promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) have been studied kinetically. The

base-promoted eliminations from 1 proceeded by the E2 mechanism when Y = Cl,

CF3, and NO2. The mechanism changed to the competing E2 and E1cb mechanisms

by the poorer leaving groups (Y = H, OMe) and to the E1cb extreme by the strongly

electron-withdrawing β-aryl group (2, X = NO2). The values of β = 0.14 and |βlg| =

0.10−0.21 calculated for elimination from 1 (Y = NO2) indicate a reactant-like

transition state with small extents of proton transfer and Cα−OAr bond cleavage. The

extent of proton transfer increased with a poorer leaving group, and the degree of

leaving group bond cleavage increased with a weaker base. Also, the changes in the

k1 and k-1/k2 values with the reactant structure variation are consistent with the

E1cb mechanism. From these results, a plausible pathway of the change of the

mechanism from E2 to the E1cb extreme is proposed.

Borderline between E1cB and E2 Mechanisms. Chlorine Isotope Effects in Base-Promoted Elimination Reactions

The chlorine leaving group isotope effect has been measured for the base-promoted elimination reaction of 1-(2-chloro-2-propyl)indene (1-Cl) in methanol at 30 °C: k35/k37 = 1.0086 ± 0.0007 with methoxide as the base and k35/k37 = 1.0101 ± 0.0001 with triethylamine (TEA) as the base. These very large chlorine isotope effects combined with large kinetic deuterium isotope effects of 7.1 and 8.4, respectively, are consistent not with the irreversible E1cB mechanism proposed previously (J. Am. Chem. Soc. 1977, 99, 7926) but with the E2 mechanism with transition states having large amounts of hydron transfer and very extensive cleavage of the bond to chlorineBorderline between E1cB and E2 Mechanisms. ... These very large chlorine isotope effects combined with large kinetic deuterium isotope effects of 7.1 and 8.4, respectively, are consistent not with the irreversible E1cB mechanism proposed previously (J. Am. ... Kinetic Isotope Effects for an E1cB Reaction with Internal Return

The Mechanism of Base-Promoted HF Elimination from 4-Fluoro-4-(4-nitrophenyl)butan-2-one Is E1cB. Evidence from Double Isotopic Fractionation Experiment

s

The Mechanism of Base-Promoted HF Elimination from 4-Fluoro-4-(4-nitrophenyl)butan-2-one Is E1cB. ... This new data clearly demonstrates that the elimination proceeds via an E1cB mechanism. ... These results rule out an E1 mechanism in which the rate-limiting detachment of the leaving group precedes a fast proton-transfer step but are consistent with a rate-limiting bond breakage of the proton being transferred in either a concerted E2 or a stepwise E1cB mechanism

Change in Rate-Determining Step in an E1cB Mechanism during Aminolysis of Sulfamate Esters in Acetonitrile

The kinetics of the reactions of the nitrogen−sulfur(VI) esters 4-nitrophenyl N-

methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and

of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series

of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess

amine at various temperatures. Pseudo-first-order rate constants (kobsd) have been

obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope

of a plot of kobsd vs [amine], second-order rate constants (k‘2) have been obtained for

the pyridinolysis of NPMS, and a Brønsted plot of log k‘2 vs pKa of pyridine gave a

straight line with β = 0.45. However, aminolysis with alicyclic amines of NPMS gave a

biphasic Brønsted plot (β1 = 0.6, β2 ≈ 0). Pyridinolysis and aminolysis with alicyclic

amines and quinuclidines of NPBS also gave similar biphasic Brønsted plots. This

biphasic behavior has been explained in terms of a mechanistic change within the

E1cB mechanism from an (E1cB)irrev (less basic amines) to an (E1cB)rev (more basic

amines), and the change occurs at approximately the pKa's (in ACN) of NPMS (17.94)

and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs

because the later bases are not strong enough to substantially remove the substrate

proton and initiate the mechanistic change observed in the reaction of NPMS with the

strong alicyclic amines and quinuclidines. An entropy study supports the change from a

bimolecular to a unimolecular mechanism. This is the first clear demonstration of this

E1cB mechanistic changeover involving a nitrogen acid substrate.

APPLICATIONS:

Irreversible Inhibitors of Serine, Cysteine, and Threonine ProteasesThe LC-MS and tryptic digest analysis shows elimination of the bromide ion and covalent bond formation between the enzyme active site Cys 148 and the inhibitor. ... An alternative is the isocyanate (E1cb) mechanism (Figure 81, pathway a).

Iminium CatalysisThe iminium-activated reaction will be catalytic only if the amine catalyst is released in the final hydrolysis or elimination step. ... If intermediate 449 is treated with triethylamine and a drying agent instead of K2CO3, a molecule of water is eliminated by an E1cB mechanism, yielding the condensation product 450. ...

Synthesis of Cyclopentitols by Ring-Closing ApproachesA one-pot sequential process, involving allylation, free-radical cyclization, and elimination for the preparation of multifunctional carbocycles possessing exo methylene unit, has been developed. ... The authors have suggested that the latter was caused by decomposition of the precursor dialdehyde 326 by E1cB elimination of the acetal protecting group. ...

A synthesis of the ABC framework of dumsin is described. The optically active intermediate 9b, which is expeditiously assembled from 5-oxobornyl pivalate by the sequential implementation of an oxy-Cope rearrangement and an intramolecular ene reaction, proved to be suitably functionalized for ultimate conversion to 5. The synthesis plan relies on two approaches to this targeted intermediate. In the first, the exocyclic double bond introduced during EtAlCl2-promoted closure of aldehyde 10b is cleaved to leave a carbonyl group that is amenable to hydride reduction and elimination of water. Cleavage of the resulting double bond with ruthenium tetroxide provided the seco ketoacid. The same advanced intermediate was obtained by initially positioning the double bond internal to the five-membered ring in advance of transient ring expansion via diketone formation and intramolecular aldolization. Both of these approaches bypass the complications arising from the substantial steric congestion prevailing in these structural networks. The task of covalently positioning an oxygen atom adjacent to the gem-dimethyl-substituted carbon in 5 was properly realized by oxidative decarboxylation. The stereochemical assignments to many of the intermediates were confirmed by an X-ray crystallographic analysis of

In the first, the exocyclic double bond introduced during EtAlCl2-promoted closure of aldehyde 10b is cleaved to leave a carbonyl group that is amenable to hydride reduction and elimination of water. ... The assumption was made that the syn elimination envisaged for 37 (Scheme 7) would not prove problematic in light of the possible operation of the E1cb mechanistic option. ...

Total Syntheses of Epothilones B and D

Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate.

Obviously, anion 21a had undergone an intramolecular proton shift followed by an E1cB elimination

Syntheses of gem -Dihalocyclopropanes and Their Use in Organic

SynthesisIn a now classic paper from 1954, Doering and Hoffmann showed that dichlorocarbene generated from chloroform in an α-elimination process under strictly anhydrous conditions adds to alkenes with the formation of gem-dichlorocyclopropane derivatives.1

To date, the addition of dihalocarbenes to alkenes is the most important and, in fact, the only synthetic route to gem-dihalocyclopropanes. ... The formation of cyclopropylidene dimers can occur via a direct reaction of two molecules of the halolithium carbenoid, with simultaneous extrusion of two molecules of lithium bromide,

or via a stepwise formation of the intermediate β-halobicyclopropyllithium, followed by an E1cb elimination reaction (eq 93). ...

Synthesis and Reactivity of sp 3 -Geminated Organodimetallics However, the use of an ether moiety instead of an alcoholate as a leaving group allows the quantitative formation of an olefinated product20 via an E1CB mechanism (Scheme 7). ... An alternative method has been recently developed21 for the synthesis of olefins via a double alkylation followed by a Ramberg−Bäcklund elimination

Structure-Based Design, Synthesis, and Biological Evaluation of Inhibitors of Mycobacterium tuberculosis Type II Dehydroquinase

The final step is the acid-catalyzed elimination of the C1 hydroxyl group catalyzed by His101. ... Scheme 2. Proposed E1CB Mechanism for the Enzymatic Conversion of 3-Dehydroquinic Acid (1) to 3-Dehydroshikimic Acid (2) Catalyzed by Type II Dehydroquinase Indicating the Residues Involved in the Catalysis ...

Novel 2,5-Hexanedione Analogues. Substituent-Induced Control of the Protein

Cross-Linking Potential and Oxidation Susceptibility of the Resulting Primary

Amine-Derived PyrrolesThe selective oxidation of the enolizable acetoacetamides by Mn(III) or Ce(IV), subsequent free radical addition to isopropyl acetate, and facile elimination of acetyl radical from the acetoxyalkyl adduct radical are believed to be involved (30) in this simple one-step synthesis of γ-diketones 9 and 10. ... These side products reflect an E1cb elimination reaction that competes with pyrrole formation, resulting in the generation of adducts comprised of one molecule of 3 and two molecules of amine, thereby explaining the observed protein cross-linking

1-Bromo-1-lithioethene: A Practical Reagent in Organic Synthesis

Ketone 10a is usually quite susceptible to E1cb

elimination ... 28 However, no traces of such elimination byproducts could be detected in the crude reaction mixture (by 1H NMR analysis) when 10a was allowed to react with 1. ... An efficient one-pot method for bromination−elimination ...

Identification of 3-Hydroxykynurenine Bound to Proteins in the Human Lens. A Possible Role in Age-Related Nuclear Cataract†

It is likely that each adduct undergoes elimination via an E1cb mechanism, although the reasons for the differences in stability are unclear. ...

Chiral Inversion and Hydrolysis of Thalidomide: Mechanisms and Catalysis by Bases

and Serum Albumin, and Chiral Stability of Teratogenic Metabolites

For four albumin concentrations, the observed pseudo-first-order rate constants of chiral inversion k(R-to-S) and k(S-to-R) as well as those of hydrolysis were estimated by fitting of a two-compartment kinetic model with elimination from both compartments to the measured concentrations of (R)- and (S)-thalidomide during incubation of either enantiomer. ... In theory, hydrolysis might also occur via an E1cb mechanism and a ketene intermediate stemming from the same carbanion involved in chiral inversion and deuterium exchange.

Kinetics and Mechanism of Hydrolysis of N-Acyloxymethyl Derivatives of Azetidin-2-one

The pH−rate profiles of 6a−g also differ significantly from those for simple ester hydrolysis, which occurs via an addition−elimination mechanism and usually exhibits the incursion of specific base catalyst at ph6-7The

Transformation of Arylmethylamines into α-Aminophosphonic Acids via Metalated Phosphoramidates: Rearrangement of Partly Configurationally Stable N-Phosphorylated α-Aminocarbanions

Its formation starts very likely with the generation of imine 19 by elimination (E2 or E1cB) of p-toluenesulfinate from 6b. ... LDA did not effect elimination of p-toluenesulfinate, but metalation of the p-tolyl ring ortho to the sulfonyl group

Tandem Nitroaldol−Dehydration Reactions Employing the Dianion of Phenylsulfonylnitromethane1

An E1cb pathway for the formation of the α,β-unsaturated α-nitrosulfone has been considered, but no supporting evidence has been obtained for it. ... The scope of the tandem nitroaldol−elimination sequence was next investigated by examining a series of aldehydes

A Reductive Cyclization Approach to Attenol A

. ... 24 Loss of the homoallylic silyl ethers, presumably through E1cb elimination, was evident in the 1H NMR spectrum of the crude reaction mixtures. ... The lithiated sulfone was quenched with

PhSSO2Ph,26 and Et3N was introduced into the reaction vessel to scavenge the benzenesulfinic acid generated in the elimination reaction

A Conformationally Locked Analogue of the Anti-HIV Agent Stavudine. An Important Correlation between Pseudorotation and Maximum Amplitude

This important intermediate was to be obtained from the readily accessible 5-(benzyloxymethyl)-4-(benzyloxy)bicyclo[3.1.0]hexan-2-ol (3),5 following a sequence designed to give the olefin after elimination of the C4-OH (Scheme 1). ... The optimized yield for this reaction was only 51%, possibly reflecting the less than ideal geometry (Figure 2C) that forces elimination via a two-step process (E1cB mechanism

Synthesis and Structural Analysis of the Anilides of Glucuronic Acid and Orientation of the Groups on the Carbohydrate Scaffolding

The coupling of 7 with aniline in the presence of ethyl chloroformate and triethylamine13

produced the 4,5-unsaturated amide 11 as a result of the base-promoted elimination of acetic acid in addition to the amide formation.

Kinetics of Polymerization Reaction of α,α‘-Bis(tetrahydrothiophenio)- p -xylene

Dichloride

From these results, an elimination−free radical polymerization mechanism is proposed. ... The result is consistent with the (E1cb)rev mechanism in which the departure of the leaving group is rate-limiting.

The Stereoselective Synthesis of 4‘-β-Thioribonucleosides via the Pummerer Reaction

A likely explanation for the observed difference in the reaction of R-10 and S-10 is that the reaction proceeds via an E2 type pathway, which prefers anti

elimination. ... 24 Depending on the structures of the starting sulfoxides, both E1cb and E2 type pathways are known to give the α-thiocarbocation intermediates from sulfoxides.

Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors

We envisaged that elimination of fluoride from the proposed enolate by an E1cB mechanism within the active site would generate an α,β-unsaturated thioester that may then undergo attack by an active site base or nucleophile to give the inactivated enzyme. ... The fluorination proved to be particularly low yielding (20%), a consequence of the propensity for elimination of fluoride, which could be limited at low temperature

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates ...

Carbonion (ElcB)mechanism of ester hydrolysis. I. Hydrolysis of malonate esters

Mechanistic Borderline between E2 and E1cb ... Elimination reactions of 2-X-4-NO2C6H3CH2C(O)OC6H3-2-Y-4-NO2 [X = H (1), NO2 (2)] promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) have been studied kinetically. ...

Synthesis of an Estrogen Receptor β-Selective Radioligand: 5-[18F]Fluoro-(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile and Comparison of in Vivo Distribution with 16α-[18F]Fluoro-17β-estradiol

It is of note that the fluorine analogue of DPN itself, 3-fluoro-2,3-bis(4-hydroxyphenyl)propanenitrile, was not selected because it was expected to undergo rapid defluorination under physiological conditions by a facile elimination mechanism. ... (23) Ryberg, P.; Matsson, O. The Mechanism of Base-Promoted HF Elimina

tion from 4-Fluoro-4-(4-

nitrophenyl)butan-2-one Is E1cB. ...

Synthesis of Five-, Six-, and Seven-Membered Heterocycles by Intramolecular Ring Opening Reactions of 3-Oxetanol Derivatives

Desilylation (K2CO3, MeOH) to diol 17 is facile, but it should be noted that 17 is prone to an elimination to benzofuran 19. ... Silyl ether 20 or the alkoxide 21, however, are forced to undergo an elimination with excess base by an E2 or E1cB pathway. ...

The carbanion mechanism (ElcB) of ester hydrolysis. III. Some structure-reactivity

studies and the ketene intermediate

Mechanistic Borderline between E2 and E1cb ... Elimination reactions of 2-X-4-NO2C6H3CH2C(O)OC6H3-2-Y-4-NO2 [X = H (1), NO2 (2)] promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) have been studied kinetically. ...

Synthesis of Methylene- and Alkylidenecyclopropane Derivatives

The cyclopropanation of allene itself gives poor results,40-42 but the addition of dichloro- or dibromocarbene generated in several ways (base-induced elimination from CHX3 or trihaloacetate, thermal decomposition of phenyl(trihalomethyl)mercury or trichloromethyltrifluorosilane) to 1,1-disubstituted allenes afforded MCPs 44 in high yields (Scheme 10). ... Treatment of bromoalkenes with bases (KOt-Bu) is not as effective as the previous treatments with allyl bromides,

producing always mixtures of elimination products besides ACPs and MCPs. ... The double Michael addition of malonate on trichloronitroethylene

followed by double HCl elimination produced a functionalized ACP in 34% yield.

Synthesis of Enantiomerically Pure 1,2-Diamine Derivatives of 7-Azabicyclo[2.2.1]heptane. New Leads as Glycosidase Inhibitors and Rigid Scaffolds for the Preparation of Peptide Analogues

These results can be interpreted in terms of two competitive processes: the desired SN2 displacement of endo-mesylate 14 by the azide anion and the β-elimination of methanesulfonic acid from 14 induced by the basic medium (fluoride anion-induced E1cb elimination) and producing intermediate alkene 17. ... This is consistent with the intervention of an SN2 displacement process that is retarded less at lower temperatures than the elimination process (Scheme 3). ...Glutathione-Dependent Metabolism of the Antitumor Agent Sulofenur. Evidence for the Formation of p -Chlorophenyl Isocyanate as a Reactive Intermediate

Since decomposition of carbamate thioester conjugates in aqueous media is known to take place primarily via a base-catalyzed elimination E1cb reaction (37), the GSH conjugate, SCPG, can be expected to be even more unstable in the basic environment of bile than in neutral solution. ... Most likely, depletion of substrate and product reflects elimination from each conjugate of CPIC, which undergoes hydrolysis and subsequent decarboxylation. ... However, this low molecular mass (127 Da) aniline derivative may serve as a useful indicator of metabolic flux through the isocyanate pathway, although it should be recognized that its excretion into bile would reflect the aggregate of direct hydrolysis and elimination of the parent diarylsulfonylureas. ...

Generation, Stability, and Reactivity of Small, Multiply Charged Ions in the Gas Phase

For example, the competition of substitution and elimination in the reactions of nucleophiles Y- with alkyl halides (e.g., RCH2CH2X) according to reactions 6a and 6b formed the subject of numerous studies. ... This reaction proceeds via an E1cB mechanism which involves a net cancellation of charges, i.e., an anion and a cation only yield neutral products.

Total Syntheses, Fragmentation Studies, and Antitumor/Antiproliferative Activities of FR901464 and Its Low Picomolar Analogue

FR901464 is

Facile epoxide opening by β-elimination gave two enones, one of which could undergo dehydration via its hemiketal to form a furan. ... We speculate that the low yields for these reactions are due to an intramolecular deprotonation−elimination pathway; the alkoxide generated after addition to the aldehyde can intramolecularly deprotonate a hydrogen atom at C2 and induce an E1cb reaction

Role of Y94 in Proton and Hydride Transfers Catalyzed by Thymidylate Synthase

This is followed by the release of H4folate from the ternary complex (step 5, E1CB mechanism) (13) which generates the exocyclic methylene intermediate (E). ... (ii) The abstraction of the proton from C5 of dUMP involves E2 elimination of C146 (step 4‘). ...

Effects of Altering the Electronics of 2-Methoxyestradiol on Cell Proliferation, on Cytotoxicity in Human Cancer Cell Cultures, and on Tubulin Polymerization

Application of Base Cleavable Safety Catch Linkers to Solid Phase Library Production

The sulfone resins are then cleaved by β-elimination in the gas phase or in solution by secondary amines to produce acids and primary, secondary, or tertiary amines. ... In general, cleavage rates were pseudo first order in substrate and consistent with the accepted E1cB mechanism,17 a potentially reversible deprotonation followed by an E1 elimination, and were correlated with the leaving group ability. ...

Kinetics and Mechanism of the Benzenethiolysis of 2,4-Dinitrophenyl and 2,4,6-Trinitrophenyl Methyl Carbonates and S-(2,4-Dinitrophenyl) and S-(2,4,6-Trinitrophenyl) Ethyl Thiolcarbonates

Although it is known that ArO- is a better nucleofuge compared to an isobasic Ar‘S-, as judged by elimination rate constants from the conjugate bases of the corresponding

esters (E1cB mechanism),17 presumably the rate constant k2 (DNPO- expulsion from 2) is not greater than k-1 (isobasic Ar‘S- expulsion from 2). ...

An Unexpected Highly Stereoselective Double Aza-Baylis−Hillman Reaction of Sulfonated Imines with Phenyl Vinyl Ketone

Moreover, the subsequent elimination (E2 or E1cB) from the betain intermediate (nitrogen and phosphane betain) should also have some differences (Figure 2, C and D). ...

Regioselectivity and the Nature of the Reaction Mechanism in Nucleophilic Substitution Reactions of 2,4-Dinitrophenyl X-Substituted Benzenesulfonates with Primary Amines

In fact, an upward curvature in the Hammett plots has often been reported for nucleophilic substitution reactions of the benzylic system or those of various carboxylic esters (e.g., substituted phenyl esters of 4-nitrophenylacetic acid) in which a change in reaction mechanism occurs from SN1 to SN2 for the former case and from a bimolecular reaction (either one step or a stepwise addition−elimination mechanism) to an E1cB

mechanism for the latter case. ...Elucidation of the Electron Transfer Reduction Mechanism of Anthracene Endoperoxides

elimination mechanism and formation of PPA. ... According to the mechanism in Scheme 2, protonation of the alkoxide anion portion is required for

elimination of hydroxide and formation of PPA. ... 79 Evidence for the slow protonation of the carbanion was verified with the different acids chosen, and the results illustrated in Figure 3 indicate preferential kinetic protonation of the alkoxide anion that leads to the formation of PPA via an E1CB-type elimination.

The Aminobarbituric Acid−Hydantoin Rearrangement

Fragmentation of aminobarbituric acids was not uniform but depended on the amino residue introduced at position 5.25-28 For 5-carbamoyl hydantoins, the elimination of R2NCO was the significant fragmentation29,34 accompanied by further decay that included the substituent at position 1.30-33 ... Alternatively, the formation of hydantoins 4 followed an elimination−addition mechanism, known from E1cB processes in acyl transfer reactions. ...

Carbanionic Reactivity of the Anomeric Center in Carbohydrates

Having a good leaving group in the β-position to the anionic center a glycosyl anion may undergo an E1cB elimination to give glycals VIII. ... On the other hand, elimination of an oxide or hydride, which is known with simple carbanions,43 has rarely been observed with glycosyl anions, presumably because of the slight stabilizing effect of the ring oxygen. ... On the basis of deuteration experiments, it was suggested that the reaction proceeded through an E2 rather than the expected E1cB mechanism. ...

Evolution of Enzymatic Activity in the Enolase Superfamily: Functional Studies of the Promiscuous o-Succinylbenzoate Synthase from Amycolatopsis†

Subsequent structural studies of the catalytically inactive K133R mutant (14) revealed the absolute configuration of the SHCHC substrate and lead to the conclusion that the dehydration reaction to form the OSB product necessarily proceeds via a syn elimination reaction in which Lys 133 at the end of the second β-strand is the only acid/base catalyst, first abstracting the α-proton and then, as the conjugate acid, facilitating departure of the hydroxide leaving group. ... Accordingly, in analogy with the mechanism of the OSBS from E. coli (14), we propose that this reaction proceeds via an E1cb mechanism in which α-proton abstraction of SHCHC by Lys 163 forms a Mn2+-stabilized enediolate anion intermediate that collapses to OSB with the assistance of the conjugate acid of Lys 163 (Figure 2A). Lys 263 likely forms a π-cation interaction with the SHCHC substrate, with this interaction enhanced as negative charge develops as the intermediate is formed by abstraction of the α-proton. ...

Termination and Transfer Reactions in the Group Transfer Polymerizations of Acrylates Catalyzed by Mononuclear Early d-Block and f-Block Metallocenes: A DFT Study

The proposed mechanism amounts to a Dieckmann condensation (Claisen intramolecular condensation), and it leads to elimination of a MeOH molecule and formation of an unreactive product containing a substituted cyclohexanone ring, as illustrated in Scheme 2. ... The second mechanistic possibility is that a two-step elimination occurs, following an E1cB mechanism. ...

Conformational Dynamics along an Enzymatic Reaction Pathway: Thymidylate

Synthase, “the Movie”

The trans-diequatorial arrangement would permit a concerted elimination of the cofactor and H-C5 from dUMP, and would orient the transferred methylene group in a manner consistent with the stereospecificity of hydride transfer (22, 23). ... In particular, they show that the stereospecificity of hydride transfer can be ascribed to a two-step (E1CB) elimination of first, dUMP H-C5 and then the cofactor from intermediate II, a mechanism which does not require conversion of the trans-diaxial orientation of the catalytic sulfhydryl and methylene bridge to a trans-diequatorial arrangement. ...

Biodegradable Hydrogels for Time-Controlled Release of Tethered Peptides or Proteins

To demonstrate the elimination of attached PEG chains, 100 μL of this solution were diluted with 900 μL of 50 mM borate buffer, pH 9.0, and incubated for 24 h at 50 °C. ... These carbamates hydrolyze in neutral and basic solutions by an E1cB elimination reaction involving the intermediate formation of an unstable isocyanate.

Reduction of Oxamyl and Related Pesticides by Fe II : Influence of Organic Ligands and

Natural Organic Matter

Pseudo-first-order rate constants for the reduction (kred, h-1) and E1cb elimination (kelim, h-1) of oxamyl and methomyl were determined for each batch reaction using data for both parent compound disappearance and reaction product appearance according to a procedure outlined previously (25) (details provided in the Supporting Information). ... In addition, the organic ligands have no effect on the rates of a parallel E1cb elimination reaction (discussed in detail in ref 24).

Extended ElcB mechanism for ester hydrolysis: allylic substitution via carbanion in

ester hydrolysis

Mechanistic Borderline between E2 and E1cb ... Elimination reactions of 2-X-4-NO2C6H3CH2C(O)OC6H3-2-Y-4-NO2 [X = H (1), NO2 (2)] promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) have been studied kinetically

Tight Binding Inhibitors of Scytalone Dehydratase: Effects of Site-Directed Mutations

Off and on the enzyme, scytalone undergoes E1cb-like dehydration reactions that are differentiated by the greater commitment to product formation (elimination) following enolization in the enzyme-catalyzed reaction (

Some Items of Interest to Process R&D Chemists and Engineers

Using Pd-based catalysts, the low yields observed in the coupling of certain substrates have been attributed to the slow rate of C−O reductive elimination relative to β-

hydride elimination from the LnPdII(Ar)(alkoxide) intermediate. ... The use of KOPh as an additive is significant in determining the outcome of the process since in the absence of this base, the initial product of oxidative insertion undergoes direct reaction with the ester carbonyl to yield a 2,3-dihydroquinolin-4-one. The researchers reasoned that addition of a basic species would serve to enolize the ester, but the potential for elimination of the aniline fragment via an E1cB mechanism steered them from the use of stronger bases such as KOtBu. Depending on the substrate, indolines can sometimes be isolated from this reaction, but in most cases these convert directly to indoles under the reaction conditions.

Crystal Structure of a Sulfur Carrier Protein Complex Found in the Cysteine Biosynthetic Pathway of Mycobacterium tuberculosis

This topology is consistent with other β-elimination enzymes (37). ... This suggests an E1cB mechanism rather than an E2 mechanism for this elimination reaction, which occurs with trans stereochemistry. ...

Amidates as Leaving Groups: Structure/Reactivity Correlation of the Hydroxide-Dependent E1cB-like Breakdown of Carbinolamides in Aqueous Solution

In fact, carbinolamides exhibit a form of reactivity in water wherein the amide portion of their structure acts as a leaving group in what could be formally described as an

elimination reaction (see Scheme 1). ... Previous studies investigating (E1cB)R

reactions where an amidate acted as a

leaving group were shown to undergo relatively slow rate determining departure of N-methylacetamidate in ethanol in the presence of ethoxide (kobsd

=

4.6 × 10-6 s-1 for PhSO2CH

2CH

2NHCOCH

3 in EtOH/NaOEt at 25 °C). ... These studies clearly show that amides are capable of acting as leaving groups in

elimination reaction supporting (E1cB)R

studies performed by Stirling. ...

Phosphonylpyrazoles from Bestmann−Ohira Reagent and Nitroalkenes: Synthesis and Dynamic NMR Studies

According to the proposed mechanism,(30) the nucleophilic base mediated acyl cleavage of BOR 2 followed by cycloaddition of the resulting diazomethylphosphonate anion with nitroalkene 1a provides initial cycloadduct which undergoes elimination to afford phosphonylpyrazole 3a. ... This was explained primarily in terms of the elimination of HBr by an E2 mechanism and HNO2 by an E1cB mechanism from the initial cycloadducts. ... However, in the case of 8b and 8d, a competing E1cB mechanism is also operative which leads to the formation of a mixture of 9 and 10. ...

Gas-Phase Base-Induced 1,4-Eliminations: Occurrence of Single-, Double-, and Triple-Well E1cb Mechanisms

Gas-Phase Base-Induced 1,4-Eliminations: Occurrence of Single-, Double-, and Triple-Well E1cb Mechanisms ... (1R,6R)-2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase (MenH) is an α/β fold enzyme containing a catalytically essential serine−histidine−aspartate triad typical of serine proteases but catalyzes a pyruvate elimination reaction

Mild and Safer Preparative Method for Nonsymmetrical Sulfamides via N-Sulfamoyloxazolidinone Derivatives: Electronic Effects Affect the Transsulfamoylation Reactivity

An elimination mechanism (E1cB) of reaction proceeding via the very electrophilic N-sulfonylamine RN SO2 species was established when sulfamoyl chlorides (RNHSO2Cl) were used to prepare sulfamides

9-(2-C-Cyano-2-deoxy-β-D-arabino- pentofuranosyl)guanine, a Potential Antitumor Agent against B-Lymphoma Infected with Kaposi's Sarcoma-Associated Herpesvirus

Compound 1 is chemically labile in alkaline solution, leading to epimerization and degradation via the E1cB mechanism to give cytosine. ... However, interestingly, the formation of guanine and

1,4-anhydro-2-C-cyano-2-deoxy-D-erythro-pent-l-enitol (18, glycal), which were β-elimination products of 3, was more suppressed than that of 1.

Participation of an Extended p-Oxo Ketene Intermediate in the Dissociative Alkaline Hydrolysis of Aryl 4-Hydroxycinnamates

The alkaline hydrolysis of the title esters, possessing three conjugated units between the internal nucleophile (the hydroxyl group) and the reaction center, follows an E1cB mechanism involving the participation of an extra extended p-oxo azoketene ... ... The alkaline hydrolysis of title esters possessing acidic leaving groups follows an E1cB mechanism involving the participation of an extra extended p-oxo ketene intermediate. ... Reactivity comparison, Arrhenius parameters, and trapping of the above-depicted unsaturated intermediate strongly suggest that the alkaline hydrolysis of the title ester follows a mechanism of the E1cB type.

Tandem Double Intramolecular [4+2]/[3+2] Cycloadditions of Nitroalkenes. The Fused/Bridged Mode

triethylamine12) were unsuccessful due to partial isomerization of the double bond. ... 20 Thus, it would appear most likely that the elimination takes place via either an E1cb mechanism or by an E2 mechanism in which the isomeric nitro acetates can interconvert (Scheme 17). ...

Unusual Mechanism for an Aminomutase Rearrangement: Retention of Configuration at the Migration Termini

The lyases share a characteristic active site motif, alanine−serine−glycine (ASG), that autocatalytically rearranges to form a functional 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthesis acting as a Lewis acid to promote the elimination of NH3 and H+ from the arylalanine substrate (8). ... The PAL-mediated elimination process begins with removal of the pro-3S hydrogen likely by the 137His residue of PAL from Rhodosporidium toruloides (17), followed by E1cb-type displacement of ammonia from the substrate to form trans-cinnamate (15, 17) (Figure 2B). ... Alternatively, the MIO is attacked by the amino group to facilitate Hoffmann-type elimination of the NH3/H+ (amine comple

Cycloaddition of Alkynyl Ketones with N-Tosylimines Catalyzed by Bu3P and DMAP: Synthesis of Highly Functionalized Pyrrolidines and Azetidines

Finally, the proton transfer generates intermediate 10, followed by elimination of

Bu3P to afford the desired product 3 or 4. ... Then, the trans elimination (E1cb

type) of DMAP from 14 affords product 5 with E configuration, and regenerates

DMAP. ...

Positional Ordering of Reacting Groups Contributes Significantly to the Efficiency of Proton Transfer at an Antibody Active Site

promoted E2 elimination of

substituted benzisoxazoles (Scheme 1),4,5 also known as the Kemp elimination. ... 7 Mechanistic studies suggest either an E1cb or an E2 elimination mechanism, in which GluH50, the same functional group utilized by 34E4, serves as the general base

Mechanistic Insights into the Michael Addition of Deoxyguanosine to Catechol Estrogen-3,4-quinones†

Specifically, the sequence of elimination events, glycosidic bond cleavage and rearomatization of the estrogen A ring, was explored. ... Reverse Michael addition between pyridine nucleophiles and Michael acceptors has been shown to proceed via an E1cB mechanism, where proton removal is the rate-limiting step (37). ...

Steady-State and Laser Flash Photolysis Study of the Carbon−Carbon Bond Fragmentation Reactions of 2-Arylsulfanyl Alcohol Radical Cations

Following the language used in β-elimination reactions, to which these fragmentation have been correctly assimilated,8 these transition states might be indicated as E1cb-like. ... In conclusion, stereoelectronic effects seem to play a very minor role in the fragmentation of 2-phenylsulfanyl alcohol radical cations, probably due to a process that, as said before, is shifted to the E1cb side of the mechanistic spectrum.

Rates of H/D exchange of 9-fluorenyl sulfoxides. Evidence for an irreversible E1cB mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates

Evidence for an irreversible E1cB mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates ...

Eliminations in the Reactions Catalyzed by UDP- N -Acetylglucosamine 2-Epimerase

These intermediates are formed by an anti elimination of UDP from UDP-GlcNAc and a syn elimination of UDP from UDP-ManNAc. ... The first is an E1cb mechanism in which an initial deprotonation event generates a carbanionic intermediate prior to expulsion of the leaving group.

Synthesis of Allylic Alcohols from Oxazolinyloxiranes

isomerization of the studied oxiranes. ... 3 Alternative routes planned to make the BH reaction reasonably fast use the “MAC” procedure (Michael addition−aldol reaction−Cope elimination). ...

Allylic alcohols 6a−e are likely the result of a β-elimination reaction involving the methyl group and the oxygen of the oxirane ring, the α-

elimination ...

Solvolytic Enolization of Scytalone

derivatives involving the intermediacy of ketenes is well documented. ... 17 Because the presence of electron-withdrawing groups is known to

substantially facilitate elimination reactions, some carboxylic acid derivatives possessing relatively poor leaving groups can also generate ketenes with

the elimination mechanism ranging from E2 to E1cB ... 18 Consequently, aminolysis of activated esters including acetoacetyl and malonyl coenzyme A derivatives proceed through a E1cB mechanism.

Influence of steric effects upon the rate constants for competing BAC2 and E1cB ester hydrolyses

Influence of steric effects upon the rate constants for competing BAC2 and E1cB ester hydrolyses ...

Associative and Dissociative Pathways in the Alkaline Hydrolysis of Aryl 2-

Hydroxycinnamates

The alkaline hydrolysis of title esters possessing acidic leaving groups follows an E1cB mechanism involving the participation of an extra extended p-oxo ketene intermediate. ... Reactivity comparison, Arrhenius parameters, and trapping of the above-depicted unsaturated intermediate strongly suggest that the alkaline hydrolysis of the title ester follows a mechanism of the E1cB type. ... To gain knowledge on the role played by the nature of the bridge interposed between hydroxyl and carbonyl groups in esters of the title type, in principle able to hydrolyze through dissociative pathways via the conjugate base of the substrate (E1cB ... ...

Acylation through Ketene Intermediates

derivatives involving the intermediacy of ketenes is well documented. ... 17 Because the presence of electron-withdrawing groups is known to

substantially facilitate elimination reactions, some carboxylic acid derivatives possessing relatively poor leaving groups can also generate ketenes with

the elimination mechanism ranging from E2 to E1cB ... 18 Consequently, aminolysis of activated esters including acetoacetyl and malonyl coenzyme A derivatives proceed through a E1cB mechanism

Claisen Condensation as a Facile Route to an α-Alkoxy-cinnamate: Synthesis of Ethyl (2S)-2-Ethoxy-3-(4-hydroxyphenyl)propanoate

The synthesis involves a Claisen-type condensation in which the elimination was unexpectedly promoted by an excess of the ester. ... The type of elimination (E1, E2, or E1cB) by which the reaction takes place has not been determined since such an investigation was beyond the scope of this work.

Biomimetic Transannular Oxa-Conjugate Addition Approach to the 2,6-Disubstituted Dihydropyran of Laulimalide Yields an Unprecedented Transannular Oxetane

We demonstrated that under acid-catalyzed conditions the model substrate undergoes elimination, generating a postulated activated triene, followed by oxa-conjugate addition. ... This is in direct contrast to the electronic arguments in favor of 1,4- or E1cB elimination, where the π orbital of the oxetane enol/enolate is energetically and geometrically aligned to interact with the ether σ* orbital. ... Base-mediated E1cB elimination followed by oxa-conjugate addition seemed a viable route to generating the desired dihydropyrans.

Removal of Acyl Protective Groups from Glycopeptides: Base Does Not Epimerize Peptide Stereocenters, and β-Elimination Is Slow

Removal of Acyl Protective Groups from Glycopeptides:  Base Does Not Epimerize Peptide Stereocenters, and β-Elimination Is Slow ... O-Linked glycosides of serine and threonine have been suggested to undergo E1cB elimination in aqueous sodium hydroxide with an amino acid enolate ion as an intermediate.

Large, inverse solvent isotope effects: a simple test for the E1cB mechanism

Large, inverse solvent isotope effects: a simple test for the E1cB mechanism

Large, inverse solvent isotope effects: a simple test for the E1cB mechanism ... Catalysis of the β-Elimination of HF from Isomeric 2-Fluoroethylpyridines and 1-Methyl-2-fluoroethylpyridinium Salts. ...

One-Pot Reactions of N-(Mesyloxy)phthalimides with Secondary Amines to 2-Ureidobenzamides, 2-Ureidobenzoic Acids, Ethyl 2-Ureidobenzoates, or Isatoic Anhydrides

The key step of the sequence involves addition and elimination of an enolic lactam in a single step and 70% yield, employing an organocuprate reagent. ... The elimination of the acetate group of compound 7 leading to E-Boc-pulchellalactam 8 with high E selectivity proceeded presumably via the E1cB mechanism42-46 with the help of a steric factor from the N-Boc moiety. ... We assume that allylic deprotonation of compound 4 and condensation with aldehyde led to Z-pulchellalactam 1 also through an E1cB mechanism42-46 via tert-butoxycarbonyl group (Boc) migration (Scheme 3). ...

Diastereoselective Synthesis of Diketopiperazine Bis-α,β-epoxides

13, 15) As a means to introduce desired substituents at the 3 and 6 positions of the 2,5-diketopiperazines, a majority of synthetic studies have been devoted to the elimination−nucleophilic attack of compounds A in the presence of nucleophiles, often under acidic conditions, to form B (Scheme 1a). ... (26) One plausible explanation for the cis selectivity is an E1cb pathway through the transition state 8β. ...

NaOH-Catalyzed Thiolysis of α,β-Epoxyketones in Water. A Key Step in the Synthesis of Target Molecules Starting from α,β-Unsaturated Ketones

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Benzoyloximes. ... In addition, an E1cb mechanism is negated by the substantial values of kH/kD and |β1g|.6-8 A similar mechanism has been proposed for the nitrile-forming eliminations from benzaldoxime derivatives under various conditions

3-Deoxy-3,3-difluoro-D-arabinofuranose: First Stereoselective Synthesis and Application in Preparation of gem-Difluorinated Sugar Nucleosides

benzoylcytosine failed to give our desired protected nucleosides 27‘, but the regioisomer 27 was obtained in 47% yield (two steps) along with β-

elimination product 28 in 22% yield (two steps). ... 32 Depending on the structures of the starting sulfoxides, both E1cb and E2 pathways are known to give the α-thiocarbocation intermediates. ...

Diethylzinc-Mediated One-Step Stereoselective Synthesis of α-Fluoroacrylates from Aldehydes and Ketones. Two Different Pathways Depending on the Carbonyl Partner

Aldolate A is prone to E2 elimination due to antiperiplanar arrangement of bromine atom and leaving group and as a consequence direct attack by diethylzinc affords fluoroacrylate (Z)-1. ... Moreover, two different pathways have been identified, depending on the involved carbonyl partner (E2-type mechanism for aldehydes and E1cb in the case of ketones

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Benzoyloximes. Transition State Differences for the Syn- and Anti-Eliminations Forming Nitriles

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Benzoyloximes. ... In addition, an E1cb mechanism is negated by the substantial values of kH/kD and |β1g|.6-8 A similar mechanism has been proposed for the nitrile-forming eliminations from benzaldoxime derivatives under various conditions. ...

Elimination Reactions of (Z)-Thiophene- and (Z)-Furan-2-carbaldehyde O-Benzoyloximes. Effect of β-Aryl Group upon the Nitrile-Forming Anti Transition State

Elimination Reactions of (Z)-Thiophene- and (Z)-Furan-2-carbaldehyde O-Benzoyloximes. ... In addition, an E1cb mechanism is negated by the substantial values of kH/kD and |β1g|.24,2

β-Isocupreidine-Catalyzed Asymmetric Baylis−Hillman Reaction of Imines

Among them, there would be two betaine intermediates B and C that are stabilized through hydrogen-bonding between the amidate ion and the phenolic OH. On taking the anti-periplanar arrangement13 of the ammonium portion and the α-hydrogen of the ester group in the subsequent E2 or E1cb reaction (see Newman projection D), intermediate C suffers from more severe steric interaction than intermediate B as depicted in Scheme 4. Thus, the difference in the reaction rate of the elimination step of B and C would result in (S)-enriched enantioselectivity through equilibration

Isocyanides and Arylacetic Acids: Synthesis and Reactivity of 3-Aryl-2-acyloxyacrylamides, an Example of Serendipity-Oriented Synthesis

In principle, other mechanisms could not be ruled out, for example, the direct formation of a ketene from a with a E1cb elimination and its subsequent reaction with a molecule of acid and one of isocyanide, in a way similar to that reported by Ugi, although the absence of a base catalysis makes this hypothesis less likely. ...

Multicomponent Reaction Discovery: Three-Component Synthesis of Spirooxindoles

The product of E1CB elimination of 27 (an isatylidene) cannot be ruled out as a reaction intermediate. ...

Cooperative, Highly Enantioselective Phosphinothiourea Catalysis of Imine−Allene [3 + 2] Cycloadditions

The role of Et3N is most likely to promote elimination and liberation of the phosphine catalyst via either E2 or E1cb mechanisms. ...

Structural Revision of Stemoburkilline from an E-Alkene to a Z-Alkene

e had speculated that 2 arose from 1 via a ring-opening reaction involving an elimination process. ... The stereochemical outcome of the base/TMSCl-initiated ring-opening reaction of 1 and 3 can be rationalized as occurring through an E1cB mechanism, as shown in Scheme 3.

One-Pot Organocatalytic Domino Michael-Aldol and Intramolecular SN2 Reactions. Asymmetric Synthesis of Highly Functionalized Epoxycyclohexanone Derivatives

The organocatalytic reaction is based on the full stereochemical control of first a Michael reaction, followed by an aldol reaction, and finally, depending on the product of choice, a SN2 or an E1cB reaction. ... Scheme 4. One-Pot Domino Organocatalytic Michael-Aldol and Elimination Reactiona

Improved Methodologies for the Preparation of Highly Substituted Pyridines

-9 One of the most popular versions of this reaction utilizes enamines 2 as dienophiles in an inverse-electron-demand Diels−Alder reaction, followed by in situ loss of nitrogen from 3 and subsequent elimination/aromatization (Scheme 1). ... This could allow, for instance, either an

E1cb mechanism (if the anion was sufficiently stable) or epimerization of this carbon center, leading to an anti-arrangement of proton and adjacent

leaving group and hence a facile E2 elimination. ... Thus, zwitterion 4‘ could facilitate elimination to the corresponding pyridine (by allowing an E1cb

mechanism or epimerizing adjacent to the amine leaving group).

A Carbohydrate Approach to the Enantioselective Synthesis of 1,3-Polyols

Treatment of per-O-benzoyl-D-glycero-D-gulo-heptono-1,4-lactone (2) with tertiary amines afforded selectively and with good yields the (5H)-furan-2-one derivatives 3, 4, and 5, formed by controlled elimination of one, two, or three molecules of benzoic acid, respectively. ... We have proposed15 an E1cB ... The introduction of an endocyclic double bond favors the abstraction of H-5, being the resulting carbanion stabilized by conjugation with an α,β-unsaturated carbonyl group, and also an E1cB mechanism would operate during the second elimination, which leads to 4. ...

An Unusual Michael Addition of 3,3-Dimethoxypropanenitrile to 2-Aryl Acrylates: A Convenient Route to 4-Unsubstituted 5,6-Dihydropyrido[2,3-d]pyrimidines

The E1cB mechanism in the alkaline hydrolysis of N,N-diethyl-P-(3,5-dimethyl-4-

hydroxyphenyl)phosphonamidic chloride

The E1cB mechanism in the alkaline hydrolysis of N,N-diethyl-P-(3,5-dimethyl-4-hydroxyphenyl)phosphonamidic chloride

Selective Inhibition of Type II Dehydroquinases

The elimination has been shown to proceed by an E1CB mechanism, probably via an enolate intermediate 3,12 and involves loss of the more acidic 2-pro-S hydrogen of the substrate, in an anti elimination of water (Scheme 1). ... DHQase catalyzes the elimination of a water

molecule from ...

Chichibabin Indolizine Synthesis Revisited: Synthesis of Indolizinones by Solvolysis of 4-Alkoxycarbonyl-3-

oxotetrahydroquinolizinium Ylides†

derivative with bromoacetone

followed by base treatment (eq 1).2 Later, the reaction was successfully expanded to the 1-(alkoxycarbonyl)methyl-2-methylpyridinium system leading

to 2,3-dihydro-2-indolizinones.5 A mechanism proposed for the reaction was that by the base-treatment of the pyridinium salts, the corresponding ylide

was formed as an reactive intermediate and indolizines were produced via an intramolecular nucleophilic attack of the active methylene to the carbonyl

group followed by elimination of water (or alcohol). ... For alcoholysis (R ≠ H), cyclization to indolizinone F proceeds through ketene intermediate E,

which is formed from C by the elimination of R1 presumably via the E1cB mechanism. ... 8 Furthermore, the formation of hydrolyzed betaine 19 in both reactions, though in low yield, was only explained by the ketene intermediate via the E1cB mechanism because no hydrolysis was observed with tert-butyl ester 17c in water.

Reduction of the Pesticides Oxamyl and Methomyl by Fe II : Effect of pH and Inorganic

Ligands

An FeII-independent, oxygen-independent elimination reaction (E1cb mechanism) results in the formation of an oxime product, methylamine and CO2. ... The larger value of kOH− for oxamyl (relative to methomyl) is due, in part, to greater acidity at the N-methyl carbamate amide nitrogen; the conjugate base of the amide group is the reactive species for E1cb elimination (29). ... Therefore, we ascribe methomyl degradation to an acid-catalyzed hydrolysis reaction (mech anism unclear) rather than to E1cb elimination.

Chiral Photocages Based on Phthalimide Photochemistry

A new class of photoremovable protecting groups, based on a photoinduced decarboxylation reaction coupled with the elimination of the caged molecule, is described for 2-phthalimido-3-hydroxy-propionate derivatives. ... This carbanion can be

protonated by the aqueous solvent or eliminate acetate via E1cB mechanism, yielding either the cis or the trans double bond. ...

Sulfonyl-Containing Aldophosphamide Analogues as Novel Anticancer Prodrugs Targeted against Cyclophosphamide-Resistant Tumor Cell Lines

A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via β-elimination, a nonenzymatic activation mechanism. ... Elimination of phenoxide from β-substituted ethyl phenyl ethers: Evidence for E1cB mechanism

Computer-Aided Reaction Design. Development of a New Facile Procedure to Synthesize 2-Mercapto-3-alkoxycarboxylate on the Basis of ab Initio Molecular Orbital Calculations

It was confirmed that the substrate with an ester fragment prefers the E1cB to the SN2 mechanism. ... That is, β-elimination mainly proceeds to form 5 when 1a was used as the substrate.

Novel Type Elimination Reactions of Sulfoxides Bearing Several Heteroaromatics: Trapping of Sulfines with 2,3-Dimethyl-1,3-butadiene

Novel Type Elimination Reactions of Sulfoxides Bearing Several Heteroaromatics: Trapping of Sulfines with 2,3-Dimethyl-1,3-butadiene ... Therefore, in the case of 4a, the rate-determining step is not the α-methylene hydrogen abstraction step but the elimination step of the 4-methyl-1,2,4-triazolyl group; this means that the possible mechanism for 4a will be via an E1cB or an E1cB-like transition state and, consequently, the possibility of existing as enol transition state 1a5a−4a5a will be increased, stabilized by hydrogen bonding between the hydroxy and sulfinyl groups, successively, to form (Z)-sulfine predominantly. ... In the case of 3a in the presence of an external base (entries 7−9), the trans-selectivity became very low compared with that in the absence of base, suggesting that the elimination mechanism shifts to an E1cB-like or E1cB mechanism which will raise the possibility of cis-selectivitiy. ...

Structure and Reactivity of trans-Bis[2-(2-chloroethyl)pyridine]palladium Chloride (1). A Study on the Elimination Reaction of 1 and 2-(2-Chloroethyl)pyridine Induced by Quinuclidine in Acetonitrile

A Study on the Elimination Reaction of 1 and 2-(2-Chloroethyl)pyridine Induced by Quinuclidine in Acetonitrile ... It should be considered that the mechanism of the elimination reaction from 1 can be E2 concerted or E1cb ... In previous studies,1,2,5,7 it was shown that systems where the pyridine ring is protonated or interacts with a metal ion react by the E1cb mechanism. ...

New Horner−Wadsworth−Emmons Type Coupling Reaction between Nonstabilized β-

Hydroxy Phosphonates and Aldehydes or Ketones

Treatment of nonstabilized β-hydroxy phosphonic acid mono methyl esters with diisopropyl carbodiimide at ambient temperature leads to clean stereospecific elimination. ... In the Wadsworth−Emmons reaction,6 the reversible formation of the pentavalent phosphorus species 15 is thought to precede collapse to the stabilized anion 16, and E1cb elimination leads to release of phosphate and the coupled enone product 17 (Scheme 3).

6) Cycloaddition Chemistry of 1,3-Thiazolium-4-olate Systems.† Reaction with Nitroalkenes and Interpretation of Results Using PM3 Calculations

The elimination pathway is not consistent with the E2 mechanism owing to stereoelectronic effects. ... It is known that the E1cB mechanism would most likely be found with substrates containing acidic protons and poor leaving groups

Catalytic Mechanism of SHCHC Synthase in the Menaquinone Biosynthesis of Escherichia coli: Identification and Mutational Analysis of the Active Site Residues

The 2,5-elimination of pyruvate from SEPHCHC by MenH can occur by simultaneous proton abstraction and pyruvate dissociation in a concerted E2 elimination or through a dienolate intermediate in a two-step E1cb ... The one-step elimination is not favored in view of the well-established notion that base-induced β-eliminations involving breakage of a C−H bond at an α-position to a carbonyl group proceed by an E1cb mechanism rather than a concerted mechanism (54). ... In comparison to 3-flourocyclohexene, SEPHCHC has a much more acidic proton in the elimination due to the 2-succinyl group and a poorer leaving group (pyruvyl enolate) than fluoride, both of which strongly favor an E1cb mechanism (54-56). ...

Two-Step Potentially Prebiotic Synthesis of α-D-Cytidine-5‘-phosphate from D-Glyceraldehyde-3-phosphate

6 Expectations that this E1cb irreversible elimination ... It was found that incubation of a D2O solution of 4 and 5 for a day at pD = 9.4 resulted in significant elimination of phosphate from 5 even before 4 had undergone significant enolization (as evidenced by the lack of exchange of the CH2 (and CH) protons of 4 for deuterons).

Alkyl 2,2,2-Trifluoroethanesulfonates (Tresylates): Elimination−Addition vs Bimolecular Nucleophilic Substitution in Reactions with Nucleophiles in Aqueous Media1

Alkyl 2,2,2-Trifluoroethanesulfonates (Tresylates):  Elimination−Addition vs Bimolecular Nucleophilic Substitution in Reactions with Nucleophiles in Aqueous Media1 ... Kinetic and product studies are consistent with the following:  (a) the reaction of tresylates with water is the normal sulfonic ester hydrolysis and (b) reaction with hydroxide is an (E1cB)rev process with loss of HF to yield the alkyl 2,2-difluoroethenesulfonate, ROSO2CH CF2, which rapidly yields the observed products.

Desymmetrization of a meso -Allylic Acetal by Enantioselective Conjugate Elimination

Desymmetrization of a meso-Allylic Acetal by Enantioselective Conjugate Elimination ... The sparteine, closely associated to the cation, could then either favor one of the two enantiomers through a rapid equilibration process18 of 7Li-b or accelerate the elimination step (E1cB) for one of those enantiomers (dynamic kinetic resolution).

New Telluride-Mediated Elimination for Novel Synthesis of 2′,3′-Didehydro-2′,3′-dideoxynucleosides

New Telluride-Mediated Elimination for Novel Synthesis of 2′,3′-Didehydro-2′,3′-dideoxynucleosides ... Under the NaBH4 reduction, the telluride is probably reduced first by hydride, thereby generating a carbanion at the 2′-position and followed by elimination via an E1cb mechanism

Nuclear Magnetic Resonance Studies on Covalent Modification of Amino Acids Thiol and Amino Residues by Monofunctional Aryl 13C-Isocyanates, Models of Skin and Respiratory Sensitizers: Transformation of Thiocarbamates into Urea Adducts

Kinetic evidence on the hydrolysis of N-arylcarbamate thioesters through an E1cB mechanism (unimolecular elimination via the conjugate base) and elimination of an

isocyanate was reported (39). ... This hypothesis has never been in fact definitely proved in the sense that, even if thought that the isocyanate is newly released, the

reaction with a competing nucleophile, other than water, most probably occurs through a direct addition−elimination process on the carbonyl chemical function of the thioester adduct (Bac2 mechanism) without real release of the isocyanate (E1cB

mechanism). ... The E1cB mechanism would first involve a base-catalyzed deprotonation of the nitrogen, followed by elimination of a nucleophile to release the

isocyanate, which seemed not to be likely in our experiments.

Simple Approach to β-Lactam Derivatives from N-Acylimidazoles

This would be possible if carboxylic derivatives of type 5 possess a relatively weak X-CO bond that would provide a sizable equilibrium concentration of ketene of type 2, and there is a possibility for fast elimination of HX in the absence of basic catalysts (i.e., tertiary amines) that can produce undesirable zwitter-ionic adducts. ... The only relevant, similar

examples involve generation of ethyl ketenes from N-acylbenzotriazoles by thermolysis17 or treatment with NaH.18 These harsh conditions are

understandable, since the low basicity of imidazole is not sufficient for producing ketenes from N-acylimidazoles through E1cb elimination reaction. ...

Most probably, the lack of reactivity of alkylsulfinylacetic acids is due to the lower acidity21 of the α protons that precludes E1cb elimination of

imidazole in the corresponding N-acylimidazoles and formation of ketenes of

Total Synthesis of (+)-Epilupinine via An Intramolecular Nitrile Oxide-Alkene Cycloaddition

We hypothesized that the instability of 9 and 10 may be caused by their intramolecular E1cB elimination, in which the amine group may play dual roles as shown in Scheme 5 (by using 10 as a model). ... Thus, the amide-protected(9) (as a weak base) or α,α-disubstituted(13) (without α-protons) aldehydes were successfully prepared in literature because they could not carry out an intramolecular E1cB elimination. ... aA retro-Micheal addition by an intramolecular E1cB elimination ...

An Olefination via Ruthenium-Catalyzed Decarbonylative Addition of Aldehydes to Terminal Alkyne

s

The well-known Wittig reaction provides access to C═C bonds with higher efficiency and better regio- and stereoselectivities over the classical elimination reactions (E1, E2, E1cB). ... Finally, reductive elimination affords the decarbonylative addition product and CO and regenerates the active ruthenium complex A

Probing the Catalytic Mechanism of S-Ribosylhomocysteinase (LuxS) with Catalytic Intermediates and Substrate Analogues

Since [3-F]SRH reacted much faster than [3-Br]SRH, the elimination reaction must occur through the E1cb mechanism (i.e., rate-limiting abstraction of the C2 proton to form a carbanion intermediate first, followed by the fast release of halide ion). ... [3-F]SRH and [3-Br]SRH, while disappointing as suicide inhibitors, provide alternative substrates to examine the function of active-site residues during the first catalytic step, since the E1cb elimination reaction involves initial deprotonation at the C2 position, which closely mimics the deprotonation event in the first catalytic step. ... Substrate analogues [3-F]SRH and [3-Br]SRH act as time-dependent inhibitors of LuxS, due to enzyme catalyzed elimination of the halide ions via an E1cb mechanism. ...

Use of 4-Cyanocoumarins as Dienophiles in a Facile Synthesis of Highly Substituted Dibenzopyranones

(8) In this paper, we present a simple, general, palladium-free method for the synthesis of highly substituted dibenzopyranones using a Diels−Alder reaction between 4-cyanocoumarins and 1-oxygenated dienes followed by elimination−aromatization with potassium tert-butoxide. ... Further support for the E1cb mechanism was obtained from the regioisomeric Diels−Alder

adduct 17, prepared in good yield from the reaction of 3-cyanocoumarin and the 1-silyloxybutadiene 7

Synthesis of Substituted Chromanones: An Organocatalytic Aldol/oxa-Michael Reaction

Development of this synthetic strategy revealed an unexpected kinetic anti-Saytzeff elimination; an origin for the observed selectivity is suggested on the basis of the results of quantum chemical calculations. ... Through a presumed E1cB mechanism, the 16a/16b mixture was quantitatively converted to enone phenol 26.

Room Temperature Acylketene Formation? 1,3-Dioxin-4-ones via Silver(I) Activation of Phenylthioacetoacetate in the Presence of Ketones

) Thermolysis of β-ketoesters 4 leads to the loss of ROH via concerted elimination. ... Either of the resulting cationic intermediates 17 and 18, upon proton loss, would give the zwitterion 19, which could collapse directly to acetylketene (20) [Douglas and co-workers have shown(14) that E1cb elimination from the anion of thioacetoacetates (acetoacetyl CoA) is facile

Conversion of Cyclic Vinyl Sulfones to Transposed Vinyl Phosphonates

Protection of the diol as the bismethyl ether was followed by oxidation of the sulfide to the sulfone 9b and elimination of the OMe group to yield vinyl sulfone 10 in 78% overall yield (Scheme 1). ... Anion 22b is perfectly set for an E1cb elimination of potassium phenylsulfinate to afford the desired vinyl phosphonate 21. ... This is

presumably because the initially formed alpha-sulfonyl anion suffers immediate E1cb elimination of the −OH group and gives a new vinyl sulfone. ...

Conversion of Cyclic Vinyl Sulfones to Transposed Vinyl Phosphonates

Protection of the diol as the bismethyl ether was followed by oxidation of the sulfide to the sulfone 9b and elimination of the OMe group to yield vinyl sulfone 10 in 78% overall yield (Scheme 1). ... Anion 22b is perfectly set for an E1cb elimination of potassium phenylsulfinate to afford the desired vinyl phosphonate 21. ... This is presumably because the initially formed alpha-sulfonyl anion suffers immediate E1cb elimination of the −OH group and gives a new vinyl sulfone.

New Methods for Side-Chain Protection of Cysteine

The data obtained are consistent with a mechanism for conversion of S-Fmoc to S-Fm via the expected elimination/addition reaction pathway shown in Scheme 3. ... The mechanism for β-elimination in the fulvene system has been postulated to lie on the borderline between E1cb ... When the mechanism is E1cb (presumably as it is for nitrogen), the rate of reaction becomes dependent on removal of the Fmoc β-hydrogen. ...

Stereocontrolled Synthesis of (−)-Macrolactin A

When the alcohol is protected as its methyl or silyl ether, β-elimination results, thus lowering significantly the yield of the desired adduct. ... Unfortunately, the stereoselectivity of the elimination in this case was only 2:1, E/Z. ... We postulated that the improvement in stereoselectivity may be attributed to the greater propensity of the benzoyloxy group toward elimination (Ka = 6.46 × 10-5

vs acetic acid Ka = 1.76 × 10-5). ...

Mechanisms of Decomposition of Aryl N -(Methoxycarbonyl)sulfamates in Aqueous

Media

Identity and distribution of products formed during the acidic hydrolysis of compounds 1a−h are consistent with the mechanistic pathway shown in Scheme 1 in which two competitive E1cB reactions (kCO and kSO2) are involved. ... (7) The small values of kH2O/kD2O observed for kCO in 1.0 M LCl are not incompatible with the elimination pathway c (eq 7

Nucleophilic Substitution of Methyl β-Chloro-(3-bromo-2,4,6-trimethyl)cinnamate

We are looking for probes for delineating the mechanism of bimolecular nucleophilic vinylic substitution proceeding by an initial nucleophilic attack on the double bond (the “addition−elimination” route).1 With mildly activated systems the stronger evidence for a multistep route via an intermediate carbanion (eq 1) (i.e., A being an intermediate and not a transition state) is the element effect (the relative rates k when X = F, Cl, Br, e.g., kBr/kCl),2 which is not always available.

... If elimination takes place it should then proceed via the E1cB route, which is not unlikely due to the activation of the α-CO2Me group. ... These features could be easily explained if addition of MeS-/H+ to the acetylene is sufficiently rapid, thus avoiding its accumulation, and if the elimination to 4 is an irreversible E1cB. ...

A Double Decarboxylation Reaction of an Oxazolidinone and Carboxylic Acid: Its Application to the Synthesis of a New Opioid Lead Compound

Ozonolysis of compound 4, prepared from iodide 3 by an elimination reaction, gave aldehyde 5. ... This result may suggest an E2 or E1cB elimination mechanism(13, 14) rather than a mechanism that proceeds via a β-lactone. ... (15, 16) Therefore, the double decarboxylation reaction would proceed by E1cB mechanism, in which a carbanion B, arising from the first decarboxylation of compound 6 or the deprotonation in compound 8 by potassium carbonate, might be stabilized by the phenyl ring and/or the carbonyl group in the oxazolidinone ring (Figure 1).

Formation of 9,10-Unsaturation in the Mitomycins: Facile Fragmentation of β-Alkyl-β-aryl-α-oxo-γ-butyrolactones

Olefin 7 had been prepared previously by Martin sulfurane dehydration (70%)7 where other more conventional elimination techniques proved unsuccessful. ...

Undoubtedly, this reaction can be considered of the E1cB type, owing to the presence of the cyclohexanone carbonyl.

Could Ionic γ-Elimination Be Concerted: Clocking the Internal Displacement Across a Cyclobutane Ring

Clearly, the proximity of the nucleophilic and electrophilic centers in β-elimination is the reason for the rarity of the stepwise E1cB mechanism1,2 in such reactions. ... Starting witha carbanionic intermediate, as in the E1cB mechanism, our results suggest that, under appropriate conditions, the formation of bicyclobutane could occur via a concerted γ-elimination reaction. ... In addition to being entropically favorable this must also engender enthalpic advantage to serve as a rationalization of why concerted β-elimination reactions are so frequently encountered while the E1cB mechanism is only seldom observed.

Base-Mediated Reaction of the Bestmann−Ohira Reagent with Nitroalkenes for the Regioselective Synthesis of Phosphonylpyrazoles

These pyrazoles are formed in one pot via spontaneous elimination of the nitro group. ... Protonation of 7 followed by base-assisted elimination of HNO2 (path a, E1cB) or elimination of the NO2 group followed by intramolecular proton transfer (path b) would furnish phosphonylpyrazole 5

A Theoretical Study of the Chorismate Synthase Reaction

3-5 Of the various possibilities, a concerted E2 or nonconcerted E1cb elimination involving deprotonation at C6 would likely require a strong base. ... To investigate the E1cb process, deprotonation at C6 was modeled using DHCCP, and the structure of the resulting anion was optimized (Figure 2). ... Consistent with that finding, the enzyme-catalyzed elimination of (6R)-[6-2H]-EPSP displayed a small kinetic isotope effect of 1.13, ...

Theoretical Studies of Eliminations. 6. The Regiochemistry and Stereochemistry of the Gas-Phase Reactions of 3-Halocyclohexenes with Fluoride. An ab Initio Study

The two modes of substitution (SN2 and SN2‘) have similar barriers, but are much less favorable than elimination. ... In previous computational work by Nibbering and co-workers,10 E1cb intermediates were identified in the reactions of hydroxide and fluoride with 2-butenyl methyl ether, and it was determined that these intermediates are formed via barrierless proton transfers

Diastereoselective Free Radical Halogenation, Azidation, and Rearrangement of β-Silyl Barton Esters

1,2 Recently we reported on the stereoselective formation and elimination of β-bromosilanes in Lewis acid promoted atom transfer additions to branched allylsilanes. ... This result can be rationalized by an E1cb mechanism11 for the TBAF-induced elimination from 4d and 4e, a

conclusion consistent with observations reported by Fleming.10 We conclude that the results from all of the transformations are consistent;

threo is the major product formed in every case. ... The TBAF elimination results for substrates 6d and 6e suggest an E1cb elimination

mechanism, a result that is consistent with the elimination reaction of thiopyridyls 4d and 4e

Facile Acylation of Sterically Hindered Alcohols through Ketene Intermediates

In contrast to “regular” carboxylic acids such as 1e−h that acylate alcohols through acid−DCC adducts of type 5,6 the presence of a strongly electron withdrawing group in the α-position to the carboxyl can enable an elimination pathway through an E1cB mechanism to give the corresponding ketenes of type 6 (eq 4). ... The formation of ketene intermediates through an E1cB mechanism has been well established in reactions of hydrolysis or aminolysis of activated esters including acetoacetyl and malonyl coenzyme A derivatives.7 Furthermore, it has been reported that some specific, highly stabilized ketenes can be prepared in a direct reaction from carboxylic acids and DCC in the presence of triethylamine, although under relatively harsh conditions

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Pivaloyloximes. Transition-State Differences for the Syn and Anti Eliminations Forming Nitriles

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Pivaloyloximes. ... Since the elimination reactions exhibit second-order kinetics and

substantial kH

/kD

values, all but E2 and (E1cb ... 4 The (E1cb)irr mechanism requires the formation of a carbanionic intermediate in the rate-determining step.

Metal Ion Catalysis in the β-Elimination Reactions of N-[2-(4-Pyridyl)ethyl]quinuclidinium and N-[2-(2-Pyridyl)ethyl]quinuclidinium in Aqueous Solution

Soc., Perkin Trans. 2 2000, 453), PAF = 1.5 × 106 and is in agreement with an E1cb irreversible mechanism (AxhDE* + DN) (Guthrie, R. D.; Jencks, W. P. Acc. Chem. ... This proton activation can be accounted for by an E1cb mechanism and by the high stability of the intermediate formed from the protonated substrate

NH+ (Scheme 1). ... It was previously16 shown that eq 2 reduces to = +

, owing to the operating (E1cb)I mechanism, and the values determined

are as follows: = 2.54 × 10-6 s-1 (isomer 1) and = 8.75 × 10-7 s-1 (isomer

2), = 241 M-1 s-1 (isomer 1), and = 290 M-1 s-1 (isomer 2). ...

Regio- and Stereoselective Coupling of Heteroaryl-Substituted Alkynes: New Insights into the Mechanism of Zirconium-Mediated Cyclodimerization of Alkynes and a Facile Route to 3-Methylenecyclobutenes

To account for the formation of 3-methylenecyclobutenes, an E1cb reaction pathway was suggested. ... Although we still need to wait for further investigations to explain all the above results, those reactions suggested an E1cb pathway for elimination of an amino group. ... To account for the formation of 3-methylenecyclobutenes, an E1cb reaction pathway was suggested.

Alkyl 2,2,2-Trifluoroethanesulfonates (Tresylates): Elimination−Addition vs Bimolecular Nucleophilic Substitution in Reactions with Nucleophiles in Aqueous Media1

Kinetic and product studies are consistent with the following:  (a) the reaction of tresylates with water is the normal sulfonic ester hydrolysis and (b) reaction with hydroxide is an (E1cB)rev process with loss of HF to yield the alkyl 2,2 difluoroethenesulfonate, ROSO2CH CF2, which rapidly yields the observed products. ... It would appear that the reaction of water (kw term) is exclusively the conventional solvolysis usual with sulfonic esters, whereas the reaction of hydroxide anion is clearly consistent with the reversible E1cB reaction shown below. ... A reversible E1cB process is specific base catalyzed and is therefore not expected to show any acceleration with added amines, provided they act only as bases and not as nucleophiles. ...

Novel Syn Intramolecular Pathway in Base-Catalyzed 1,2-Elimination Reactions of β-Acetoxy Esters

The more acidic thioester substrates do not produce an increased amount of syn stereoselectivity even though their elimination reactions are at the E1cb interface. ... The research began by a study of the elimination of acetic acid from S-tert-butyl (2R*,3R*)-3-acetoxy-2-2H1-butanethioate (5) using KOH in 3:1 v/v EtOH/H2O, producing S-tert-butyl (E)-2-butenethioate (6), Figure 1.5 A previous mechanistic study of the elimination reaction of S-tert-butyl 3-acetoxybutanethioate (7) had concluded that the reaction was either E2 or E1cbirrev. ... 2,3,9,10 Thus, electron-withdrawing substituents and poor leaving groups that produce transition states with more E1cb character may favor syn elimination

Nucleophilicity vs Basicity in the Reaction of Sodium tert-Butoxide with β-Stannyl Ketones

Stereochemical results suggest that the elimination reactions proceed through an (E1cB)R mechanism. ... All these observations provide strong evidence for an (E1cB)R mechanism initiated by proton abstraction by the tert-butoxide ion, as represented in Scheme 2. ...The E1cB mechanism is also supported by the effect of organotin moieties attached to C-3 and of substituents attached to C-2 on the elimination/substitution rat

The Alkaline Hydrolysis of Aryl (2E)-3-(4‘- Hydroxyphenylazo)propenoates. A Kinetic Study

The alkaline hydrolysis of the title esters, possessing three conjugated π units between the internal nucleophile (the hydroxyl group) and the reaction center, follows an E1cB mechanism involving the participation of an “extra extended” p-oxo azoketene type intermediate. ... We have been able to demonstrate that the E1cB ... In the simplest case we investigated, the hydrolysis of aryl 4-hydroxybenzoates,2 the π-system was an aromatic ring and we showed that esters having leaving groups with pKa values lower than about 6.5 hydrolyze through the E1cB mechanism with the participation of the unprecedented p-oxo ketene intermediate 1.

Mechanism of Alkaline Hydrolysis of Some HO-π-COOAr Acyl Derivatives

To gain knowledge on the role played by the nature of the bridge interposed between hydroxyl and carbonyl groups in esters of the title type, in principle able to hydrolyze through dissociative pathways via the conjugate base of the substrate (E1cB mechanism), we have studied the alkaline hydrolyses of 2,4-dinitrophenyl esters in which the π-system is a biphenyl, azobenzene, benzylideneaniline, or stilbene skeleton. ... We have been interested in the dissociative (E1cB ... We have previously found1 that the hydrolyses of aryl 4-hydroxybenzoates in moderately to strongly alkaline aqueous solution follow the usual associative route (BAc2) when the esters possess leaving groups having pKa higher than about 6.5, whereas esters having leaving groups with lower pKa hydrolyze through the E1cB mechanism with the participation of the unprecedented p-oxo ketene intermediate (1

Mechanisms of Acid−Base Catalysis of β-Elimination Reactions in Systems Activated by a Pyridine Ring

The results of a kinetic study of acid−base catalysis and H/D exchange are consistent with NH+, the protonated substrate, as the species that undergoes carbon deprotonation with an E1cb mechanism. ... In previous studies2-5 of systems activated by a nitrophenyl group, the mechanism of base-induced β-elimination reactions has been shown to be E1cb (ΑxhDH + DN)6 with the intermediate carbanion formed with different degrees of reversibility depending on the structure of the substrate. ... H/D exchange experiments showed the incorporation of deuterium at the β-carbon during the elimination reaction in D2O, in acetohydroxamate/acetohydroxamic acid buffer, at 50 °C and μ = 1 M KCl, in agreement with a stepwise reversible mechanism, (E1cb)R(AxhDH + DN*).6 Further support for the proposed mechanism has come from studies of the solvent kinetic isotope effect. ...

Synthesis of Tertiary Amides from Anionically Activated Aromatic Trifluoromethyl Groups

The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%). ... The mechanism involves initial elimination of HF (via an E1cB mechanism) to give a key electrophilic quinone methide intermediate, which can be attacked by a range of nucleophiles, such as hydroxide. ... This lower reactivity may be attributed to the lower acidity of the aniline 4b compared to the phenol 4a, thus leading to a reduced rate for the initial E1cB elimination of HF. Aliphatic amines gave good yields of the desired tertiary amides (Table 1, entries 20 and 21).

An Unprecedented Concerted Pathway in the Alkaline Hydrolysis of S-Aryl Thioesters

Kinetic data indicate that the hydrolysis of S-2,4-dinitrophenyl 4‘-hydroxythiobenzoate in mild alkaline solutions (pH 8−11) most likely follows a dissociative, E1cB pathway, through a p-oxoketene intermediate, whereas at higher pH values an associative mechanism carries the reaction flux. ... We have long been interested in the alkaline hydrolysis of active aryl esters of 4-hydroxybenzoic acid, and we have provided convincing evidence that the reaction occurs via a dissociative pathway, the E1cB mechanism, through a p-oxoketene intermediate.

Mechanism of Polymerization Reaction of 2,5-Bis(tetrahydrothiopheniomethyl)furan

Dichloride. Effect of Aromatic Resonance Energy on the Polymerization of

Bis(sulfonium) Salts

The reaction proceeds by the (E1cb)irr

mechanism to afford a 2,5-dihydrofuran intermediate M, which undergoes a free radical polymerization

reaction. ... 1,2 As the substrate was changed from SH‘ ‘ to SH‘, the mechanism of the elimination pathway changed from (E1cb)R to (E1cb)irr, the rate of the elimination reaction increased, and that of polymerization process decreased. ... This result rules out all but E2, (E1cb)irr, (E1cb)R, and (E1cb ...

New, “Elongated” Oxo Ketene Intermediate in the Dissociative Hydrolysis of 2,4-Dinitrophenyl (2E,4E)-5-(4‘-Hydroxyphenyl)pentadienoate

Reactivity comparison, Arrhenius parameters, and trapping of the above-depicted unsaturated intermediate strongly suggest that the alkaline hydrolysis of the title ester follows a mechanism of the E1cB type. ... We are interested in the factors governing the competition among different mechanisms in acyl transfer processes, in particular, dissociative (E1cB ... We have previously found1 that the

alkaline hydrolyses of aryl 4-hydroxybenzoates having leaving groups with a pKa lower than about 6.5 do not follow the usual associative pathway but proceed via an E1cB mechanism with the participation of an unprecedented p-oxo ketene intermediate (1). ...

Competitive Mechanistic Pathways for Green-to-Red Photoconversion in the Fluorescent Protein Kaede: A Computational Study

Instead, the stepwise E1 and new E1cb mechanisms are suggested to occur and may compete with each other in the electronic ground state. ... As to the proposed E2-type β-elimination mechanism for EosFP,(14) after many trials, the concerted E2-type transition state involving the simultaneous Cα−N bond cleavage and deprotonation by Glu212 could not be found for Kaede (and possible for EosFP), but the optimization all led to the E1 or E1cb (see below) pathway. ... E1cb Pathway

Occurrence of an Elongated p-Oxo Ketene Intermediate in the Dissociative Alkaline Hydrolysis of Aryl (2E,4E)-5-(4‘-Hydroxyphenyl)pentadienoates

The alkaline hydrolysis of title esters possessing acidic leaving groups follows an E1cB mechanism involving the participation of an “extra extended” p-oxo ketene intermediate. ... Break in the Brønsted plot of the apparent second-order rate constants

versus the pKa of the leaving group suggests that the reaction mechanism changes from E1cB to BAc2 for esters having pKa higher than about 6. ... In the course of our studies on acyl transfer reactions we have at first provided evidence that alkaline hydrolysis of aryl esters of 4-hydroxybenzoic acid occurs through either associative (BAc2) or dissociative (E1cB, via intermediate 1) mechanisms, depending on the basicity of the leaving group

Carboxylate-Induced Degradation of Poly(3-hydroxybutyrate)s

This communication shows that thermal degradation of poly(3-hydroxybutyrate)s (PHBs) is induced by carboxylate groups via a newly proposed E1cB mechanism. ... This phenomenon may be explained by the E1cB mechanism proposed in this work for the degradation of poly(3-hydroxybutyrate)s possessing a hydrogen atom at the C2 carbon (Scheme 2), where a crucial role is played by the carboxylate terminal groups. ... Scheme 2. E1cB Degradation Mechanism of PHBa ...

Ketene-Forming Elimination Reactions from Aryl Thienylacetates Promoted by R2NH/R2NH2

+ in 70 mol % MeCN(aq). Effect of the β-Aryl Group

As the leaving group is made poorer (X = H, OCH3, and Cl), E2 transition state becomes more skewed toward the proton transfer, as revealed by the increase in Brönsted β to 0.5−0.64, and the E1cb ... The changes in the k1 and k-1/k2 values with the reactant structure variation provide additional support for the competing E1cb mechanism. ... Extensive studies of ketene-forming elimination reactions have revealed mechanistic diversity in the E2 and E1cb

Study on the Effect of the Structure of the Leaving Group in the E1cb Mechanism of

Base-Promoted .beta.-Elimination Reactions from N-[2-(p-

Nitrophenyl)ethyl]alkylammonium Ions

Study on the Effect of the Structure of the Leaving Group in the E1cb Mechanism of

Base-Promoted .beta.-Elimination Reactions from N-[2-(p-

Nitrophenyl)ethyl]alkylammonium Ions ... Proton-Activating Factors and Methyl-

Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and

E1cb Irreversible Mechanisms ... Proton-Activating Factors and Methyl-Activating

Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb

Irreversible Mechanisms

Study of reactions leading to sulfine formation. 5. Methoxide-catalyzed decomposition of

diarylmethyl(arylsulfonyl)methyl sulfoxides: a sulfine-forming elimination on the

E1cBrev/(E1cB)irrev borderline

5. Methoxide-catalyzed decomposition of diarylmethyl(arylsulfonyl)methyl sulfoxides: a sulfine-forming elimination on the E1cBrev/(E1cB)irrev borderline

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the

Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates

Rates of H/D exchange of 9-fluorenyl sulfoxides. Evidence for an irreversible E1cB

mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates

Evidence for an irreversible E1cB mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates ...

Study of reactions leading to sulfine formation. 4. Evidence for a reversible E1cB mechanism for base-induced elimination of N,N-diisopropyl-9-fluorenesulfinamide

4. Evidence for a reversible E1cB mechanism for base-induced elimination of N,N-diisopropyl-9-

fluorenesulfinamide ... Synthesis of Carbamates from Diethoxycarbonyl Hydrazine Derivatives by E1cB

Eliminative Cleavage of the N−N′-Bond Rather than Reduction ... Synthesis of Carbamates from

Diethoxycarbonyl Hydrazine Derivatives by E1cB Eliminative Cleavage of the N−N′-Bond Rather than

Reduction ...

Equilibration of N-(2-cyanoethyl)pyridinium cations with substituted pyridines and acrylonitrile. A change in rate-determining step in an E1cb reaction

A change in rate-determining step in an E1cb reaction ...

Top of Form

Equilibration of N-(2-cyanoethyl)pyridinium cations with substituted pyridines and

acrylonitrile. A change in rate-determining step in an E1cb reaction

A change in rate-determining step in an E1cb reaction ...

Study of reactions leading to sulfine formation. 4. Evidence for a reversible E1cB mechanism for base-induced elimination of N,N-diisopropyl-9-fluorenesulfinamide

4. Evidence for a reversible E1cB mechanism for base-induced elimination of N,N-diisopropyl-9-fluorenesulfinamide ... Synthesis of Carbamates from Diethoxycarbonyl Hydrazine Derivatives by E1cB Eliminative Cleavage of the N−N′-Bond Rather than Reduction ... Synthesis of Carbamates from Diethoxycarbonyl Hydrazine Derivatives by E1cB Eliminative Cleavage of the N−N′-Bond Rather than Reduction ...

Rates of H/D exchange of 9-fluorenyl sulfoxides. Evidence for an irreversible E1cB mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates

Evidence for an irreversible E1cB mechanism for base-induced sulfine formation from methyl diarylmethanesulfinates ...

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates

A General Acid-Catalyzed Anion Breakdown Associated with an E1cB Reaction in the Hydrolysis of Aryl N-(Substituted Phenylsulfonyl)carbamates ...

Study of reactions leading to sulfine formation. 5. Methoxide-catalyzed decomposition of diarylmethyl(arylsulfonyl)methyl sulfoxides: a sulfine-forming elimination on the

E1cBrev/(E1cB)irrev borderline

5. Methoxide-catalyzed decomposition of diarylmethyl(arylsulfonyl)methyl sulfoxides: a sulfine-forming elimination on the E1cBrev/(E1cB)irrev borderline ...

Study on the Effect of the Structure of the Leaving Group in the E1cb Mechanism of Base-Promoted .beta.-Elimination Reactions from N-[2-(p-

Nitrophenyl)ethyl]alkylammonium Ions

Study on the Effect of the Structure of the Leaving Group in the E1cb Mechanism of Base-Promoted .beta.-Elimination Reactions from N-[2-(p-Nitrophenyl)ethyl]alkylammonium Ions ... Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms ... Proton-Activating Factors and Methyl-Activating Factors as a Mechanistic Test To Distinguish between Concerted E2 and E1cb Irreversible Mechanisms ...

VBSCF Calculations on the Bimolecular (E2) Elimination Reaction. The Nature of the Transition State

Valence bond state correlation diagrams (VBSCD) show that a simple proton transfer such as that in the E1cB irreversible reaction is predicted to have a lower barrier than a synchronous concerted (E2) reaction. ... They found that reactions of a number of 2-arylethyl and 2-cyanoethyl derivatives gave transition states near the upper left corner of the figure, in some cases into stepwise E1cB territory. ... (15) Figure 3 is such a diagram for an E1cB reaction with the first step rate determining. ...

Synthesis of Carbamates from Diethoxycarbonyl Hydrazine Derivatives by E1cB Eliminative Cleavage of the N−N′-Bond Rather than Reduction

Synthesis of Carbamates from Diethoxycarbonyl Hydrazine Derivatives by E1cB Eliminative Cleavage of the N−N′-Bond Rather than Reduction ... When 9a was treated with Cs2CO3 in MeCN/D2O and heated at reflux for 18 h the recovered starting material had the −NCH2CO2Me portion converted into −NCD2CO2Me, thus providing evidence for a E1cB mechanism for the reaction, the slow step being the breaking of the N−N bond

Gas-Phase Base-Induced 1,4-Eliminations: Occurrence of Single-, Double-, and Triple-

Well E1cb Mechanisms

Gas-Phase Base-Induced 1,4-Eliminations: Occurrence of Single-, Double-, and Triple-Well E1cb Mechanisms

A change in the rate-determining step in the E1cB reactions of N-[2-(4-nitrophenyl)ethyl]pyridinium cations

A change in the rate-determining step in the E1cB reactions of N-[2-(4-nitrophenyl)ethyl]pyridinium cations ...

Influence of steric effects upon the rate constants for competing BAC2 and E1cB ester hydrolysesInfluence of steric effects upon the rate constants for competing BAC2 and E1cB ester hydrolyses

Borderline between E1cB and E2 mechanisms. Elimination of hydrogen chloride from fluorene derivatives

Borderline between E1cB and E2 mechanisms. ... Ab Initio Molecular Dynamics Simulations of Elimination Reactions in Water Solution:  Exploring the Borderline Region between the E1cb and E2 Reaction Mechanisms ... Ab Initio Molecular Dynamics Simulations of Elimination Reactions in Water Solution:  Exploring the Borderline Region between the E1cb and E2 Reaction Mechanisms ...

The E1cB mechanism in the alkaline hydrolysis of N,N-diethyl-P-(3,5-dimethyl-4-hydroxyphenyl)phosphonamidic chloride

The E1cB mechanism in the alkaline hydrolysis of N,N-diethyl-P-(3,5-dimethyl-4-hydroxyphenyl)phosphonamidic chloride

Additions and Corrections - Elimination Reactions of N-(2-p-Nitrophenyl)ethyl) alkyl-ammonium Ions by an E1cB MechanismAdditions and Corrections - Elimination Reactions of N-(2-p-Nitrophenyl)ethyl) alkyl-ammonium Ions by an E1cB Mechanism ...

Reactions of Aryl Phenylacetates with Secondary Amines in MeCN. Structure−Reactivity

Relationship in the Ketene-Forming Eliminations and Concurrent E2 and E1cb

Mechanisms

Structure−Reactivity Relationship in the Ketene-Forming Eliminations and Concurrent E2 and E1cb Mechanisms ... Finally, the ketene-forming elimination reactions from p-nitrophenyl p-nitrophenylacetate promoted by R2NH/R2NH2

+ buffers in 70 mol % MeCN(aq) have been shown to proceed by concurrent E2 and E1cb mechanisms. ... The mechanistic changes from E2 to E1cb for eliminations reactions of (2-arylethyl)ammonium ions9 and 9-(2-chloro-2-propyl)fluorene12 have been concluded to be of this type

Elimination reactions of N-[2-(p-nitrophenyl)ethyl]alkylammonium ions by an E1cB

mechanism

Elimination reactions of N-[2-(p-nitrophenyl)ethyl]alkylammonium ions by an E1cB mechanism ... Ab Initio Molecular Dynamics Simulations of Elimination Reactions in Water Solution: Exploring the Borderline Region between the E1cb and E2 Reaction Mechanisms ... Ab Initio Molecular Dynamics Simulations of Elimination Reactions in Water Solution: Exploring the Borderline Region between the E1cb and E2 Reaction Mechanisms ...

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