Elimination enolate intermediate

A range of a-functionalised aldehydes have been used to generate acylazolium species via the corresponding enol intermediate. For example, addition of an NHC to an a-halo aldehyde 84 presumably generates the Breslow species 86, with elimination of HX to afford the enol 87. Subsequent in situ tautomerisation generates... 

The isomerization of allylic alcohols provides an enol (or enolate) intermediate, which tautomerizes to afford the saturated carbonyl compound (Equation (8)). The isomerization of allylic alcohols to saturated carbonyl compounds is a useful synthetic process with high atom economy, which eliminates conventional two-step sequential oxidation and reduction.25,26 A catalytic one-step transformation, which is equivalent to an internal reduction/oxidation process, is a conceptually attractive strategy due to easy access to allylic alcohols.27-29 A variety of transition metal complexes have been employed for the isomerization of allylic alcohols, as shown below. 

A number of methods can assist in identifying and characterizing enol intermediates (as well as eneamine and carbanion intermediates) in enzyme-catalyzed reactions. These include (1) proton isotope exchange (2) oxidation of the intermediate (3) coupled elimination (4) spectrophotometric methods (5) use of transition-state inhibitors (6) use of suicide inhibitors (7) isolation of the enol and (8) destructive analysis. 

By means of in situ NMR spectroscopy combined with deuterium incorporation experiments, van Leeuwen has elucidated the mechanism of termination by protonolysis, showing that the fl-chelates are in equilibrium with their enolate form by a p-H elimination/hydride migration process (Scheme 7.19). The enolate intermediates are regioselectively protonated at the C2 carbon atom by either MeOH or H2O to give Pd-OMe or Pd-OH and keto terminated copolymer. The enolate formation has been reported to be rate determining in the chain transfer [19]. 

For example, in one pathway H-atom elimination reactions generate the enol intermediate, which eventually rearranges to 2-butanone. In a second competing reaction pathway, H-atom addition results in direct hydrogenation to the saturated alcohol 2-butanol. 

As with the strongly basic NH, [Problem 20.25(a), nucleophilic attack by OH at C , followed by H -elimination, yields an enolic intermediate that tautomerizes to 2-pyridone. 

The mechanisms proposed for these reactions are all quite analogous, and only the intramolecular cases will be considered in detail (Scheme 5). Oxidative addition by Pd° into the allylic C—O bond of the allyl 0-ketocaiboxylate produces an allylpalladium caxboxylate. This species then undergoes decarboxylation to yield an allylpalladium enolate (oxa-ir-allyl), which subsequently eliminates a 0-H to form the enone and provide an allyl-Pd-H. Reductive elimination from the allyl-Pd-H yields propene and returns Pd to its zero oxidation state. A similar mechanism can be imagined for the alkenyl allylcarbonate. Oxidative addition by the Pd° forms an allylpalladium carbonate, which decarboxylates again to give an allylpalladium enolate (oxa-ir-allyl). 0-Hydride elimination and reductive elimination complete the process. The intermolecular cases derive the same allylpalladium enolate intermediates, only now as the result of bimolecular processes. 

The reaction of 3-ketoacids with allyl carboxylates is also believed to proceed via a palladium enolate intermediate.126 Less than complete stereospecificity is also observed in these reactions (equation 163). Interestingly, the bicyclic lactone substrate employed to ascertain the stereointegrity of this reaction, in addition to being incapable of any syn-anti isomerization, cannot epimerize the starting material by car-boxylate attack at the metal. The observed stereochemical leakage could be due to epimerization of the intermediate allyl complex (equation 164) or reductive elimination of an allylpalladium enolate (retention) (equation 165). 

It has been postulated (37) that lactulose is formed from lactose by the Lobry de Bruyn and Alberda van Ekenstein transformation, whereby glucose is isomerized to fructose via an enol intermediate. In turn, two mechanisms have been proposed for the degradation of this intermediate (38)- One involves the addition of a proton to the enediol resulting in epimeric aldoses and the original ketose, while the other involves 8-elimination to yield galactose and saccharinic acids. The authors experimental data would tend to better support the second pathway. 

The suggested mechanistic pathway for this transformation implicates carbenoid 98 as a key intermediate, generated by a-elimination of the metallated oxirane. The highly reactive carbenoid undergoes intramolecular insertion rearrangement via either route A or B to yield dilithiated alkoxy enolate intermediates which, after usual workup, furnish the a,/3-unsaturated ketones, via H2O elimination <1995JA12700>. 

In this initial step, an aldol condensation takes place. The solvent of this reaction is an ionic liquid. It is a very polar solvent that is able to stabilize polar molecules and can act as an acceptor for hydrogen bonds. Thus, it is able to shift the equilibrium towards the enol tautomers. After the aldol addition, the intermediate can eliminate water via a second enol intermediate. Although the substrates are both aldehydes, only one product is formed because 19 lacks an acidic position, so it cannot become a nucleophile. Owing to its tendency to form homodimers, a two-fold excess of propionaldehyde 20 is needed. 

The reaction is believed to proceed via allyl complex 11, alkene insertion to form 12, isomerization of this enolate intermediate 12 to a new enolate complex 13 and ring closure via reductive elimination to afford 5. Electron-poor alkenes fail to react, therefore carbenes are thought not to be intermediates. Carbene intermediates would lead to different stereochemistry in the products instead of the exo-exo configuration. 

The double bond can be restored after a conjugate addition to an electrophilic alkene if the enolate intermediate 110 is trapped as a silyl enol ether 111 and then combined with a sulfur or selenium electrophile which is later eliminated. Organocuprates are ideal nucleophiles for this process as the intermediate enolate can be trapped as a silyl enol ether and reacted directly with PhSCl or PhSeCl. 

Like PEP carboxylase, PEP carboxykinase forms an enolate by phosphate transfer from PEP, thus eliminating the thermodynamically unfavorable proton removal step. Like PEP carboxylase, the enolate then reacts with CO2. The enzymes differ in the means that are used for delivering CO2 to the active site PEP carboxylase has an active mechanism for delivery, whereas PEP carboxykinase uses the second substrate to trap CO2 on the enzyme. Both enzymes may use similar metal ion complexation for stabilizing the enolate intermediate. 

Petasis and Teets reported the study shown in Scheme 7-30 [158]. The silylallene ester 130 was metalated with LDA to give an alkynyllithium enolate intermediate which was reacted with the propaigyl aldehyde 129, and the resulting alkoxysilane eliminated under acidic condi-... 

Now for the first nucleophilic aromatic substitution.The amino group attacks in the position ortho to the carbonyl group so that an enolate intermediate can be formed. The first fluoride is expelled in the elimination step. 

D Ordine, R.L., Bahnson, B.J., Tonge, P.J. Anderson, V.E. (1994) Biochemistry 33, 14733-14742. Enoyl-coenzyme A hydratase-catalyzed exchange of the a -proton of coenzyme A thiol esters a model for an enolized intermediate in the enzyme-catalyzed elimination ... 

Before the structure of the enzyme was determined, chemical modification experiments (using proteolysis and mass spectrometry to identify the modified residue) and site-directed mutagenesis were used to identify Arg 21, Tyr 28, and a His as catalytically important side chains.Substrate and solvent H isotope effects, proton inventory studies, and the pH-dependence of the kinetic parameters and were used to identify the enzyme mechanismas an E]CB elimination reaction proceeding via an enolate intermediate, with the initial proton abstraction as the rate-limiting step. The unusual sharp increase in and above pH 9 was interpreted as the effect of an active-site Arg side chain on the basicity of a His. " ... 

For the synthetic application of this method to Erythrina alkaloids, Anh Tuan and Kim [56] reinvestigated the palladium catalyzed cyclization of the requisite precursor which could be formed from the condensation of ketoester 43 and bromo-arylamine 44. In the reaction, two main products were formed. When the intermediate 45 was treated with Pd(OAc)2 in DBU, an enol intermediate (46) was formed in 30% yield through y-lactam enolate formation followed by cyclization. Some amoimt of the eorresponding ketal compound, the precursor of the enol intermediate, could be obtained if the reaction process was quenched earlier. Treatment of 46 with TsOH in acetone afforded compound 47 in 71% yield. Reduction of the carbonyl compound 47 under Luche condition, affording a mixture of diasteromers in a 2.6 1 ratio, was followed by elimination to afford the known intermediate (48) for erysotramidine (49) in 64% yield. 

A number of intramolecular Mizoroki-Heck reactions yield the product consistent with a formal a r/-elimination of the HPdX [11], These experimental findings are in opposition to the generally accepted mechanism of a 5y -elimination however, a reasonable explanation is at hand in most cases. There are two main types of alkenyl derivatives which, if added to an CT-aryl- or cr-alkenylpalladium(II) complex, deliver the formal a ft-elimination product. The first case is intramolecular Mizoroki-Heck reactions with o ,jS-unsaturated carbonyl systems which result in the product of a formal 1,4-addition. The initially formed <7-(y3-aryl)- or <7-(/3-alkenyl)alkylpalladium complex should be long-lived enough to epimerize through a palladium(II) enolate intermediate and, thus, deliver the formal anr/-elimination product through conventional 5yn-elimination (Scheme 6.2). 

Scheme 6.2 Mizoroki-Heck reaction proceeding via syn-elimination through a palladium(ll) enolate intermediate.

The mechanism of Rh-catalysed decarboxylative conjugate addition (Scheme 2) has been investigated by DFT calculations, which indicate that the selectivity towards hydrolysis or jS-hydride elimination, affording (68) and (69), respectively, is a compromise between diffusion control and kinetic control. Ligand control can be adjusted by modifying the intermolecular interaction between the Rh(I) enolate intermediate and water. ... 

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