Enols reactions

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

Potassium Hydride. Potassium hydride [7693-26-7] KH, made from reaction of molten potassium metal with hydrogen at ca 200°C, is suppHed in an oil dispersion. Pressure Chemical Company (U.S.) is a principal suppHer. KH is much more effective than NaH or LiH for enolization reactions (63,64). Use of KH as a base and nucleophile has been reviewed (65). 

Reaction of Enolate Anions. In the presence of certain bases, eg, sodium alkoxide, an ester having a hydrogen on the a-carbon atom undergoes a wide variety of characteristic enolate reactions. Mechanistically, the base removes a proton from the a-carbon, giving an enolate that then can react with an electrophile. Depending on the final product, the base may be consumed stoichiometricaHy or may function as a catalyst. Eor example, the sodium alkoxide used in the Claisen condensation is a catalyst ... 

The stereochemical outcome of these reactions is opposite to the enolate reactions described above and has been rationalized as arising from attack on a ground-state conformation in which the sulfoxide (S = 0) and C—C double bonds are syn coplanar2-7. Nucleophilic attack occurs from the least sterically demanding 7t-face, which is anti to the phenyl substituent of the sulfur. Recent theoretical calculations also support this ground-state conformation8. 

Many enolates can exist as both E- and Z-isomers.11 The synthetic importance of LDA and HMDS deprotonation has led to studies of enolate stereochemistry under various conditions. In particular, the stereochemistry of some enolate reactions depends on whether the E- or Z-isomer is involved. Deprotonation of 2-pentanone was examined with LDA in THF, with and without HMPA. C(l) deprotonation is favored under both conditions, but the Z.E ratio for C(3) deprotonation is sensitive to the presence of HMPA.12 More Z-enolate is formed when HMPA is present. 

These examples and those in Scheme 2.6 illustrate the key variables that determine the stereochemical outcome of aldol addition reactions using chiral auxiliaries. The first element that has to be taken into account is the configuration of the ring system that is used to establish steric differentiation. Then the nature of the TS, whether it is acyclic, cyclic, or chelated must be considered. Generally for boron enolates, reaction proceeds through a cyclic but nonchelated TS. With boron enolates, excess Lewis acid can favor an acyclic TS by coordination with the carbonyl electrophile. Titanium enolates appear to be somewhat variable but can be shifted to chelated TSs by use of excess reagent and by auxiliaries such as oxazolidine-2-thiones that enhance the tendency to chelation. Ultimately, all of the factors play a role in determining which TS is favored. 

The enantioselectivity of Sn(II) enolate reactions can be controlled by chiral diamine additives. These reagents are particularly effective for silyl thioketene acetals.162 Several diamines derived from proline have been explored and l-methyl-2-(l-piperidinomethyl)pyrrolidine 21 is an example. Even higher enantioselectivity can be achieved by attachment of bicyclic amines to the pyrrolidinomethyl group.163... 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

These equations do not provide complete definition of the reactions that may be of significance in particular solvent extraction systems. For example, HTTA can exist as a keto, an enol, and a keto-hydrate species. The metal combines with the enol form, which usually is the dominant one in organic solvents (e.g., K = [HTTA]en i/[HTTA]]jet = 6 in wet benzene). The kinetics of the keto -> enol reaction are not fast although it seems to be catalyzed by the presence of a reagent such as TBP or TOPO. Such reagents react with the enol form in drier solvents but cannot compete with water in wetter ones. HTTA TBP and TBP H2O species also are present in these synergistic systems. However, if extraction into only one solvent (e.g., benzene) is considered, these effects are constant and need not be considered in a simple analysis. 

S. o-Hydroxydibenzoylmethane can be crystallized from 95% ethanol and forms crystals melting at 120°, which give a strong enol reaction with ferric chloride. Crystallization is not necessary here. 

Alkylation of Enolates Asymmetric syntheses involving enolate reactions such as alkylations, aldol additions and acylations in which the chiral auxiliary A -H is both readily obtained and easily recoverable after the desired bond construction had been achieved by Evans et al.175). 

The increasing interest in enolization reactions mediated by magnesium amides led to new investigations for structural features of these reagents . 

Examples for the alkylation of cyclobutanes by enolate reactions are given in Table 9. 

Direct evidence for dependence of the rate of photoenolization on structure has been obtained in a study of the flash spectroscopic behavior of compounds 28 and 29.513 The concentrations of quenchers required to suppress the enolization reaction are considerably greater for 29 than for 28, indicating the greater reactivity of tertiary C—H bonds as well as steric interference to energy transfer. 

Rates of Enolization Reactions. For a better understanding of the transformation and oxidation reactions of reducing sugars, methods have been developed to measure the primary rates of enolization (18). One of these methods depends on the rate at which tritium ions are released from aldoses-2- to the solvent. This is measured by separation of the water-, sublimation, and radiochemical assay of the water as the reaction proceeds. The rate constant is calculated from the first-order equation ... 

Tellurium dipropionylmethane (2 6-Dimethylcyclotelluro-pentanedione) (Formula II), obtained from the dichloride by bisulphite reduction, crystallises from methyl alcohol, benzene or aqueous ethyl alcohol as well-defined golden-yellow needles, M.pt. 151° C. with slight decomposition. Under diminished pressure it sublimes at 110° C. as slender needles, which slowly pass at this temperature into compact prisms. It readily dissolves in organic solvents, except light petroleum in water it is sparingly soluble, the solution giving no enolic reactions. 

Tellurium O-ethyldipropionylmethane trichloride (Formula III), isolated as indicated above, crystallises from a mixture of chloroform and petroleum (B.pt. 40° to 60° C.) as transparent lemon-yellow prisms, M.pt. 110° to 111° C. with blackening and decomposition. It yields pale yellow solutions in cold organic solvents, and gives no enolic reaction with feme chloride in aquo-alcoholic chloroform solution, but decomposes rapidly, giving a yellow turbidity. With aqueous alkalis it develops the earthy odour of the free O-ether of dipropionylmethane. 

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