Enolates ketone enolate reaction with esters

Cleavage of enol estersEnol esters arc converted to oximes of the corresponding ketone by reaction with excess hydroxylamine in THF or pyridine. 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

The most useful method is reaction of ketone (and ester) hthium enolates, usually prepared by deprotonation of ketones with LDA, with either Ce H5 SeBr or Ce Hs SeCl. Enol acetates can be converted into a-phenylseleno ketones by reaction with phenylselenenyl trifluoroacetate, prepared in situ by treatment of CeHsSeCl or CeHsSeBr with silver trifluoroacetate or by conversion to the lithium enolate and reaction with CeHsSeBr. It is sometimes possible to obtain isomeric a-phenylseleno ketones by use of these two methods (equations 1 and II). 

The key step in a basealdol reaction is nucleophilic addition of the enolate anion from one carbonyl-containing molecule to the carbonyl group of another carbonyl-containing molecule to form a tetrahedral carbonyl addition intermediate. This mechanism is illustrated by the aldol reaction between two molecules of acetaldehyde. Notice that OH is a true catalyst An OH is used in Step 1, but another OH is generated in Step 3. Notice also the parallel between Step 2 of the aldol reaction and the reaction of Grignard reagents with aldehydes and ketones (Section 12.5) and the first step of their reaction with esters (Section 14.7). Each type of reaction involves the addition of a carbon nucleophile to the carbonyl carbon of another molecule. 

Enol esters may be prepared from ketones by reaction with an anhydride or by exchange with isopropenyl acetate under acidic catalysis (Eq. 6.11) [16]. 

Ester enolates, much more sensitive and capricious than ketone and amide enolates, seemed to be unsuitable for palladium-catalyzed allylic alkylations. Thus, Hegedus and coworkers [24] reported on low yields and predominant side reactions in the allylation of the lithium enolate of methyl cyclohexanecarboxylate. It seems that so far the only reliable and efficient version of a Tsuji-Trost reaction with ester enolates is based on the chelated zinc enolates 41 derived from N-protected glycinates 40 - a procedure that was developed by Kazmaier s group. 

There are numerous noteworthy structural aspects of N-acyl oxazolidinones that give them a central role as auxiliaries for a large array of asymmetric transformations. Although the enolization reaction of esters and ketones can lead to mixtures of cis- and trans-enolates, the oxazolidinone imi-des exclusively form the corresponding cis-enolates. This observation has been attributed to the pronounced destabilization of the trans-enolate and the transition state structure leading to its formation as a consequence of A, 3 steric interactions (cf 124, Scheme 3.19) [15]. A second important feature of the oxazolidinone enolates relates to the ability of the auxiliary carbonyl functionality to form a chelate with coordinatively unsaturated metal centers (cf 118,121, or 125). This organizing feature provides rigidity to the en-... 

In a reaction related to the mixed Claisen condensation nonenolizable esters are used as acylatmg agents for ketone enolates Ketones (via their enolates) are converted to p keto esters by reaction with diethyl carbonate... 

Esters of nonenolizable monocarboxylic acids such as ethyl benzoate give p diketones on reaction with ketone enolates... 

Even though ketones have the potential to react with themselves by aldol addition recall that the position of equilibrium for such reactions lies to the side of the starting materials (Section 18 9) On the other hand acylation of ketone enolates gives products (p keto esters or p diketones) that are converted to stabilized anions under the reaction conditions Consequently ketone acylation is observed to the exclusion of aldol addition when ketones are treated with base m the presence of esters... 

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. Table 22.1 lists the approximate pKa values of different types of carbonyl compounds and shows how these values compare to other acidic substances we ve seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions. 

An alkylation reaction is used to introduce a methyl or primary alkyl group onto the a position of a ketone, ester, or nitrile by S 2 reaction of an enolate ion with an alkyl halide. Thus, we need to look at the target molecule and identify any methyl or primary alkyl groups attached to an a carbon. In the present instance, the target has an a methyl group, which might be introduced by alkylation of an ester enolate ion with iodomethane. 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

---