Enolates equilibration

The aldehyde or ketone is called the keto form and the keto enol equilibration referred to as keto-enol isomerism or keto-enol tautomerism Tautomers are constitu tional isomers that equilibrate by migration of an atom or group and their equilibration IS called tautomerism The mechanism of keto-enol isomerism involves the sequence of proton transfers shown m Figure 9 6... 

A single Kekule structure does not completely descnbe the actual bonding in the molecule Ketal (Section 17 8) An acetal denved from a ketone Keto-enol tautomerism (Section 18 4) Process by which an aldehyde or a ketone and its enol equilibrate... 

Trimethylsilyl enol ethers can also be cleaved by tetraalkylammonium fluoride (Entry 2) The driving force for this reaction is the formation of the very strong Si-F bond, which has a bond energy of 142 kcal/mol.31 These conditions, too, lead to enolate equilibration. 

The stereo- and regioselectivity of deprotonation can be kinetically or thermodynamically (equilibrium) controlled. Equilibrium between enolates occurs when a proton donor is present. The proton donor can be the solvent or an excess of the ketone in relation to the strong base present for generation of the enolate. Ketone enolate equilibration can also proceed via an aldol-rever-... 

It is possible to use a, -disubstituted cycloalkenone substrates for the construction of vicinal, quarternary carbon centers. Equation (20)96 illustrates such a successful application typically, however, enolate equilibration and steric congestion prevent straightforward application of the method. 

C-Carboxylation of enolates.1 Carboxylation of potassium enolates generated from silyl enol ethers is not regioselective because of extensive enolate equilibration. Regiospecific C-carboxylation of lithium enolates is possible with carbonyl sulfide in place of carbon dioxide. The product is isolated as the thiol methyl ester. If simple esters are desired, transesterification can be effected with Hg(OAc)2 (8, 444). Carboxylation of ketones in this way in the presence of NaH and DMSO is not satisfactory because of competing alkylation of the enolate.2 Example ... 

The even more strained alkylidene cycloproparenes gave rise to the same kind of G-complex intermediate with silver ion. In the presence of alcohol, trapping of this intermediate occurred, leading to alkoxystyrene derivatives. Water could also act in the same way, yielding arylmethylketones after keto-enol equilibration. However, if a proton was present on the alkylidene moiety, H shift occurred, leading to an arylalkyne. No dimerization was observed in this case, probably due to steric constraints in such a process (Scheme 3.17).31... 

Once again, this is very like the situation in a carboxylic acid. Thus the two enols equilibrate fast with each other in CDCI3 solution but equilibrate slowly enough with the keto form for the two spectra to be recorded at the same time. If equilibration with the keto form were fast, we should see a time-averaged spectrum of the two. In CD3OD solution the fH and 13C NMR spectra showthat only the enol form exists, presumably stabilized by hydrogen bonding. 

This principle can be extended to ketones whose enolates have less dramatic differences in stability. We said in Chapter 21 that, since enols and enolates are alkenes, the more substituents they carry the more stable they are. So, in principle, even additional alkyl groups can control enolate formation under thermodynamic control. Formation of the more stable enolate requires a mechanism for equilibration between the two enolates, and this must be proton transfer. If a proton source is available— and this can even be just excess ketone—an equilibrium mixture of the two enolates will form. The composition of this equilibium mixture depends very much on the ketone but, with 2-phenylcyclo-hexanone, conjugation ensures that only one enolate forms. The base is potassium hydride it s strong, but small, and can be used under conditions that permit enolate equilibration. 

This difference was assigned to the lesser ionicity of the OLi bond when compared to the OK one. The solvent is likely to play an important role in the equilibrium as well polar solvents seem to favor the more substituted enolate. In addition, House and Trost highlighted the fact that lithium enolates equilibrate very slowly unless a substantial excess of the free ketone is present in the solution64. Note that ab initio calculations on the naked enolates (no associated cation) of 2-butanone (Scheme 9 with R1 = H and R2 = Me) suggest that the primary and Z(O) secondary isomers are almost isoenergetic,65 while the E O) secondary analog is less stable by more than 4 kcalmol-1. Repeating these calculations for the 3-methyl-2-butanone enolates showed that the primary isomer is more stable by 4.3 kcalmol-1. 

With the 1,4-dimethoxynaphthalene ligand, cyano-stabilized anions (including cyanohydrin acetal anions) and ester enolates equilibrate even at low temperature and strongly favor addition at the a-position (C-5). The kinetic site of addition is also generally C-a. However, the 2-lithio-l,3-dithiane anion and phenyllithium do not equilibrate over the temperature range -78 to 0°C. The sulfur-stabilized anions favor addition at C-/3 (equation 119) 134,190 phenyllithium... 

The most predictable results are obtained with conformation-ally rigid systems, such as those represented in eqs 5 and 6, which possess axially oriented a-protons. This minimizes complications resulting from the presence of diastereotopic a-protons, although unexpected modes of deprotonation have been described with related chiral amides, which may involve boat conformations. To prevent enolate equilibration (with the resulting loss of stereoselectivity), Corey s internal quench method for enolate trapping with silyl chlorides is frequently used. The stereospecificity of this deprotonation is highly dependent on solvent and temperature conditions. Best results are obtained at —100 °C or lower temperatures, with THF as the solvent. 

Phenol/chloroform Ph enol equilibrated with TE should be mixed with an equal volume of chloroform. 

The electrophile must be added rapidly (an excess if possible) to trap the enolate before it can condense with the product initially formed. Unfortunately, less reactive alkylating agents often allow enolate equilibration to compete with alkylation. 

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