Enolate Stabilized

Scheme 1.3. Alkylation of Enolates Stabilized by Two Functional Groups...

Detailed binding with substrate and transition state analogs has also been reported on KSI [83, 84] using a wide range of techniques, highlighting the subtle interplay of the electrostatic and geometric properties of the enolate stabilizing active site. 

Figure 2.19 Difluorovinyl lithium enolates stabilized by heteroatom. ...

It is also appropriate to recognize the role of enolates stabilized by an exocyclic carbonyl function in C-glycoside synthesis. The use of LN to achieve reductive cleavage of anomeric sulfones to provide access to an ester-stabilized enolate and, ultimately, 2-deoxy- -C-glycosides has already been illustrated in Scheme 11 (Sect. 2.1.1). 

A striking example of enolate stability is that of 2, a ft-lactone enolate. Deprotonation of 1 with LDA at — 78 °C yields 2, which is stable at this temperature and can be alkylated to give 3a in excellent yields (see the following table). The diastereoselectivity is >98 249 51. When the enolate 2 is warmed to room temperature the expected -elimination occurs and pure (E)-4 is formed in quantitative yield. 

FIGURE 85. Schematic structures of zinc enolates stabilized by intramolecular nitrogen coordination... 

Simple enols stabilized by bulky aryl groups have been reviewed.131 Amide enols, tip2C=C(OH)NR1R2 (tip = 2,4,6-triisopropylphenyl), can be generated by reaction of amines with ditipyl ketene, are observable by NMR, and slowly tautomerize. Vinyl alcohols with two or three bulky aryls have propeller conformations and are chiral, but are not easily resolved. 

Obviously, these results cannot be explained by a very enol-like transition state. This does not mean that enol stability does not affect reactivity, but that it probably does so to a lesser extent than at first expected. Such a conclusion runs counter to the first assertions and to what is usually assumed (see e.g. Lamaty, 1976), but is in agreement with the data cited above concerning Bronsted a-exponents. Indeed, the a-value of 0.74 observed for acid-catalysed enolisation of cyclohexanone (Lienhard and Wang, 1969) corresponds to a relatively early transition state since the Bronsted / for base-promoted proton abstraction from the hydroxycarbenium ion intermediate [see eqn (3)] equals 1 — 0.74, or 0.26. As pointed out above, some data on the stereochemistry of ketonisation were accounted for by assuming an enol-like transition state. Clearly, these interpretations need to be re-examined. 

In contrast to kinetic data, thermodynamic data on enol and enolate formation are far more scarce. This results from the usually very low enol and enolate stabilities which, at equilibrium, make it difficult to measure their proportions relative to the carbonyl compound. This section deals with available data on keto-enol equilibria as well as on acidity constants of the two tautomers. 

For example, bromination of pentan-3-one gives mostly 2,2-dibromopentan-3-one. After one hydrogen is replaced by bromine, the enolate ion is stabilized by both the carbonyl group and the bromine atom. A second bromination takes place faster than the first. Notice that the second substitution takes place at the same carbon atom as the first, because that carbon atom bears the enolate-stabilizing halogen. 

Other 1,3-dicarbonyl compounds also exist largely in the enol form. In some examples there is an additional stabilizing factor, intramolecular hydrogen bonding. Diethyl malonate (diethyl propane-dioate) has a symmetrical enol stabilized by conjugation. The enol form is also stabilized by a very diethyl maionate favourable intramolecular hydrogen bond in a six-membered ring. 

The new keto-ester is very like the acetoacetates we used in Chapter 27 to make stable enolates and the CoA thiol ester will exist mainly as its enol, stabilized by conjugation,... 

Tantalum enolate chemistry shows the dichotomy for the carbonylation reaction " of Cp Ta(CH2R)Cl3 with CO which results in the mono-THF adduct of rj -acyl complex Cp Ta(0=CCH2R)Cl3(THF) for R = t-Bu (the acyl group is anionic) but the isomeric enolate Cp Ta((Z)-7j -OCH=CHR)Cl3 for R = p-Tol. This invites the question of the relative thermodynamic stabilities of metal complexes of RCH2CO and RCHCHO and additionally the question of Z vs. E enolate stabilities. Only for organometalhc compounds (X = [M]) do we find examples where RCH2COX is less stable than RCH=CHOX. 

Enols (pATa ca = 11-12) are usually more acidic than alcohols [e.g. EtOH pATa (H2O) = 15.9 ] but are less acidic than phenols [e.g. PhOH pATa(H20) = 9.95 ]. The acidity of enols (and the basicity of the corresponding enolate) is surprisingly uniform when considering the relative acidity of the carbonyl derivative. The majority of enols derived from saturated aldehydes and ketones have pATa ca 11-12. For simple aldehydes and ketones, such as acetaldehyde (45) and acetone (45 ), their enol acidity (pATa ) in water is similar even when their keto acidity (pATa ) is moderately different. It is interesting to note that relative enol stability (pATs) plays little or no role in the relative acidity of enols for example, as is the case of 45 and 45. ... 

---