FORMATION OF ENOLATES

The idea of kinetic versus thermodynamic control can be illustrated by discussing briefly the case of formation of enolate anions from unsymmetrical ketones. This is a very important matter for synthesis and will be discussed more fully in Chapter 1 of Part B. Most ketones, highly symmetric ones being the exception, can give rise to more than one enolate. Many studies have shown tiiat the ratio among the possible enolates that are formed depends on the reaction conditions. This can be illustrated for the case of 3-methyl-2-butanone. If the base chosen is a strong, sterically hindered one and the solvent is aptotic, the major enolate formed is 3. If a protic solvent is used or if a weaker base (one comparable in basicity to the ketone enolate) is used, the dominant enolate is 2. Enolate 3 is the kinetic enolate whereas 2 is the thermodynamically favored enolate. 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Another example of enzyme- and acid-catalyzed DKR has been reported by Bornscheuer [45]. Acyloins were racemized by using an acidic resin through the formation of enol intermediates. The enzymatic resolution was catalyzed by CALB. Since deactivation of this enzyme occurred in the presence of the acidic resin, they designed a simple reactor setup with two glass vials cormected via a pump to achieve a spatial separation between the acidic resin and the enzyme (Figure 4.20). 

However, the observations of Ward and Sherman need not rule out triple-bond participation and vinyl cations in the systems studied by Hanack and co-workers (75-79). Presumably, the enol formate 61 itself arises via a transition state involving a rate-determining protonation and vinyl cation 62 (see previous section). A vinyl cation such as 62 with an adjacent phenyl group is considerably more stable and hence more accessible than a vinyl cation such as 63, stabilized only by a neighboring alkyl group. Hence, formation of enol formate 61 and its... 

See Section 362 (Ester-Alkene) for the formation of enol esters and Section 367 (Ether-Alkenes) for the formation of enol ethers. Many of the methods in Section 60A (Protection of Aldehydes) are also applicable to ketones. 

C in CH2CI2, in the formation of enol ethers 404 in high yields [26] (Scheme 5.4). Likewise, silylated alcohols 13 and free 1,2- and 1,3-glycols react with ketones in the presence of TMSOTf 20 to cyclic ketals [27]. 

The aldol reaction is one of the best known means of C-C-bond formation in organic chemistry. The reaction needs the formation of enolates, which themselves are one of the most extensive species permitting C-C-bond formation [15]. 

BSTFA or BSA Reagents of choice for the formation of N-TMS derivatives. May promote the formation of enol-TMS ethers unless ketone groups are protected. 

The initial addition products to alkynes are not always stable. Addition of acetic acid, for example, results in the formation of enol acetates, which are converted to the corresponding ketone under the reaction conditions.151... 

Table 1 EDA complex formation of enol silyl ethers with various electron acceptors in dichloromethane.

From the reactions shown in Scheme 5, it is obvious that only those uronic acid derivatives whose elimination proceeds with the formation of enolic or aldehydic groups, or both, afford products capable of reducing the Cu(II) ion. Although such structures can be expected from hexo- and hepto-furanuronic, as well as from hep-topyranuronic, acid derivatives, glycosides of pentofuranuronic and of hexopyranuronic acid derivatives do not exhibit reducing properties. However, in view of this generalization, the zero reducing power observed for compound 26 requires a different explanation. 

With ethoxypropadiene, the vinylic copper intermediate formed via the allylzinc-cation reacts with another molecule of ethoxyallene leading to the formation of enol ether 112 as an E-Z mixture [55],... 

We start the scheme after the oxidative addition of diphenylsilane and coordination of acetophenone has taken place, after the classic mechanism by Ojima [28], The formation of enol ethers proves, that at least for this part of the products formed (up to 22%, Brunner [27], 40% [29]), the reaction proceeds... 

Formation of enol ethers from aldehydes or ketones... 

Treatment of aldehydes or ketones with acceptor-substituted carbene complexes leads to formation of enol ethers [1271-1274], oxiranes [1048], or 1,3-dioxolanes [989,1275] by O-alkylation of the carbonyl compound. Carboxylic acid derivatives... 

Probably the most significant examples of carbon nucleophiles are enolate anions. These can participate in a wide variety of important reactions, and simple nucleophilic substitution reactions are included amongst these. However, we shall consider these reactions at a later stage, when the nature and formation of enolate anions is discussed (see Chapter 10). 

Aldehydes and ketones nndergo acid- and base-catalysed halogenation in the a position. This is also dependent on enolization or the formation of enolate anions. 

Any process that produces an enol, including the formation of enolate anions. Enols (i.e., entities containing the moiety HO—C(Ri)=C(R2Rs)) appear as intermediates in a wide variety of enzyme-catalyzed reactions, and Rose has presented the following diagram to describe... 

Scheme 10.1 Selective formation of enol carbamates from secondary amines, CO2, and terminal alkynes.

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