Enolate compounds ester derivatives

A Michael reaction involves the conjugate addition of a stable enolate ion donor to an o,/3-unsaturated carbonyl acceptor, yielding a 1,5-dicarbonyl product. Usually, the stable enolate ion is derived from a /3-diketone, jS-keto ester, malonic ester, or similar compound. The C—C bond made in the conjugate addition step is the one between the a carbon of the acidic donor and the (3 carbon of the unsaturated acceptor. 

The enolates of other carbonyl compounds can be used in mixed aldol reactions. Extensive use has been made of the enolates of esters, thiol esters, amides, and imides, including several that serve as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, titanium, and tin derivatives have all been widely used. The silyl ethers of ester enolates, which are called silyl ketene acetals, show reactivity that is analogous to silyl enol ethers and are covalent equivalents of ester enolates. The silyl thioketene acetal derivatives of thiol esters are also useful. The reactions of these enolate equivalents are discussed in Section 2.1.4. 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

The preferential -configuration of the enol esters, derived from p-dicarbonyl compounds under phase-transfer conditions, contrasts with the formation of the Z-enol esters when the reaction is carried out by classical procedures using alkali metal alkoxides. In the latter case, the U form of the intermediate enolate anion is stabilized by chelation with the alkali metal cation, thereby promoting the exclusive formation of the Z-enol ester (9) (Scheme 3.5), whereas the formation of the ion-pair with the quaternary ammonium cation allows the carbanion to adopt the thermodynamically more stable sickle or W forms, (7) and (8), which lead to the E-enol esters (10) [54],... 

Other simple alkenois (enols) also rearrange to carbonyl compounds. However, ether and ester derivatives of enols are known and can be prepared by... 

Besides the glycinate ester derivatives described above, other types of enolate-forming compounds have proved to be useful substrates for enantioselective alkylation reactions in the presence of cinchona alkaloids as chiral PTC catalysts. The Corey group reported the alkylation of enolizable carboxylic acid esters of type 57 in the presence of 25 as organocatalyst [69]. The alkylations furnished the desired a-substituted carboxylate 58 in yields of up to 83% and enantioselectivity up to 98% ee (Scheme 3.23). It should be added that high enantioselectivity in the range 94-98% ee was obtained with a broad variety of alkyl halides as alkylation agents. The product 58c is a versatile intermediate in the synthesis of an optically active tetra-hydropyran. 

Bisenolates such as compound A derived from the acetoacetic ester in Figure 13.32 react with one equivalent of alkylating reagent in a regioselective fashion to give the enolate C. This could be the result of product development control, since the isomeric alkylation product... 

The addition of an alkaline earth metal enolate A to a carbonyl compound is always an exer-gonic process irrespective of whether the enolate is derived from a ketone, an ester, or an amide and whether the carbonyl compound is an aldehyde or a ketone (Figure 13.44, top). One of the reasons for this exergonicity hes in the fact that the alkaline earth metal ion is part of a chelate in the alkoxide B of the aldol addition product. The driving forces for the additions of alkaline earth metal enolates of esters and amides to carbonyl compounds are further increased because the aldol adducts B are resonance-stabilized, whereas the enolates are not. 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophihc selenium species. " They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nifro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding a ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

E1V- and ll NMR-spectroscopic studies of tris-malonic ester derivative of 1,3,5-triazine in various solvents indicated that the enamine structure 182 (R = COOMe) predominates in CHC13, dioxane, MeOH, and H20. A small amount of the enolate is present in acetonitrile and a larger amount in DMSO, DMF, and cyclohexylamine. It is concluded that in a basic solvent this compound exists as a tautomeric mixture of the enamine form and resonance-stabilized enolate ion (75JHC295). 

Alkylation of enolate anions usually gives C-alkylation and is therefore not suitable for the preparation of enol ethers. The exception is when triethyloxonium tetrafluoroborate is used as the alkylating agent in a dipolar aprotic solvent. 0-Alkylation can be regioselectiveiy achieved if the enolate anion is derived from acetoacetate or a similar compound. On the other hand, 0-acylation of enols or enolate anions is quite common. Enol esters can therefore be prepared readily from the parent carbonyl compounds. For... 

The next objective of the synthesis was the lactone 122, a compound that is also readily available from annotinine (1). Borohydride reduction of the enol acetate 123 derived from 121 yielded a mixture of the hydroxy esters 124 and 125. This mixture was hydrolysed to the corresponding acids, 126 and 127, and the acids treated with p-toluene-sulfonic acid in boiling benzene. The product was a mixture of the desired lactone 122 and the hydroxy acid 127 in approximately equal amounts. Another less attractive method of preparation of 124 was described in the course of the structural study of annotinine (1). 

Esters - Compounds formally derived from an oxoacid RC(=0)(0H) and an alcohol, phenol, heteroarenol, or enol by linking, with formal loss of water from an acidic hydroxy group of the former and a hydroxy group of the latter. [5]... 

Many other reactions in nature use enamines, mostly those formed from lysine. However, a more common enol equivalent is based on thiol esters derived from coenzyme A. Coenzyme A is an adenine nucleotide at one end, linked by a S -pyrophosphate to pantothenic acid, a compound that looks rather like a tripeptide, and then to an amino thiol. Here is the structure broken down into its parts. 

Esters, Nitriles, Amides, Mines, and Enamines. Pd-Catalyzed a-arylation of extrastabilized enolates and related derivatives containing esters and nitrile groups developed by Uno, Takahashi, and co-workersf (Sect. B.i.b,) has been applied to the synthesis of cyclic compounds with moderate success, as indicated by the results shown in Scheme... 

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