Esters as enolates

A second example of the use of esters as enolates is the formation of Meerwein s ester, an intermediate in the synthesis of substituted adamantanes (6). Dimethyl... 

CLAISEN IRELAND Rearrangment Rearrangement ol allyl phenyl ethers to o (or p-)allylphenols or of allyl vinyl ethers to 7,5-unsaturated aldehydes or ketones (Claisen) Rearrangement of allyl esters as enolate anions to Y. unsaturated acids (Ireland)... 

Mono and Di-iubstitution Derivatives. The enolic sodium derivative of ethyl acetoacetate (E) is prepared by mixing ethanolic solutions of the ester and of sodium ethoxide. It should not be prepared by the direct action of metallic sodium on the ester, as the reaction is slow and the nascent hydrogen evolved reduces some of the ester to ethyl p4iydroxy- butyrate, CH3CH(OH)CHjCOOEt. 

Most of the reactions of ester enolates described so far have centered on stabilized eno lates derived from 1 3 dicarbonyl compounds such as diethyl malonate and ethyl ace toacetate Although the synthetic value of these and related stabilized enolates is clear chemists have long been interested m extending the usefulness of nonstabilized enolates derived from simple esters Consider the deprotonation of an ester as represented by the acid—base reaction... 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

Flavone formation is believed to proceed through a similar mechanism as the synthesis of chromones, albeit aromatic acid anhydrides and their corresponding salts are used. The first step is benzoylation of 12 to give the ester 14. Enolization and o-alkylation then affords the enolbenzoate 15. Enolbenzoate 15 then undergoes an acyl transfer to yield... 

As enolate precursors can be used CH-acidic carbonyl compounds such as malonic esters, cyanoacetic esters, acetoacetic esters and other /3-ketoesters, as well as aldehydes and ketones. Even CH-acidic hydrocarbons such as indene and fluorene can be converted into suitable carbon nucleophiles. 

Due to the nonaromatic character of the oxepin system the oxepinones do not usually form stable enol structures. By O-acylation or O-alkylation, however, the enol forms can be stabilized as enol esters and ethers, respectively. A large number of substituted 1-benzoxepins have been synthesized by this route. Acetylation of l-benzoxepin-3(2//)-ones 1 and l-benzoxepin-5(2/T)-ones 3 was readily achieved with acetic anhydride in the presence of an appropriate base such as pyridine, triethylamine or sodium acetate.t5,t6 t72 176... 

Thus the product in such cases can exist as two pairs of enantiomers. In a di-astereoselective process, one of the two pairs is formed exclusively or predominantly as a racemic mixture. Many such examples have been reported. In many of these cases, both the enolate and substrate can exist as (Z) or (E) isomers. With enolates derived from ketones or carboxylic esters, (E) enolates gave the syn pair of enantiomers (p. 146), while (Z) enolates gave the anti pair. Addition of chiral additives to the reaction, such as proline derivatives, or (—)-sparteine lead to product formation with good-to-excellent asynunetric induction. Ultrasound has also been used to promote asymmetric Michael reactions. Intramolecular versions of Michael addition are well known. ... 

In lipase-catalyzed transesterifications, frequent use of enol esters as acyl agents has been seen [1, 5], since the leaving unsaturated alcohol irreversibly tautomerizes to an aldehyde or a ketone, leading to the desired product in high yields. The polymerization of divinyl adipate and 1,4-butanediol proceeded in the presence of lipase PF at 45 °C [39]. Under similar reaction conditions, adipic acid and diethyl adipate did not afford the polymeric materials, indicating the high polymerizability of bis(enol ester) toward lipase catalyst. 

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 very important type of reaction known as enolization is catalyzed by both acids and bases. Also, the hydrolysis of an ester,... 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

J. P. Patel, A. J. Repta, Enol Esters as Potential Prodrugs. I. Stability and Enzyme-Mediated Hydrolysis of a-Acetoxystyrene , lnt. J. Pharm. 1980, J, 329-333. 

Nucleophilic addition of ester-derived enolate to the bicyclo[3.3.0]octan-2-one system of diacetone glucos-3-ulose usually occurs at the convex jS-face of the carbonyl (as for other nucleophiles), except for senecioate-derived enolate (from 3-methyl cro-tonate) for which a-attack in diethylether solvent is in contrast to the jS-face attack in THF the reason for this anomalous behaviour is not clear. 

In this case, we formulate the Claisen reaction between two ester molecules as enolate anion formation, nucleophilic attack, then loss of the leaving group. Now reverse it. Use hydroxide as the nucleophile to attack the ketone carbonyl, then expel the enolate anion as the leaving group. All that remains is protonation of the enolate anion, and base hydrolysis of its ester function. 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

With diketene, intermediates of type (III) were isolated and subsequently cyclized under basic conditions following step (b). In the case of 3-oxo-carboxylic acid esters or 3-acyl Meldrum s acids, cyclization step (b) immediately follows reaction step (a), if a slight excess of amine is employed (85TH1 87TH1). Note that conversion of (III) to (V) involves the (IH)-enol (Table I cf. 75BSF2731). The relatively low yield in the case of malonic acid ester, as well as the failure of the reaction with the non-enolizable diphenyl phosphinylacetic ester and cyanoacetate, points to the participation of an enol structure of (III). 

Molecules in which the enolic double bond is in conjugation with another double bond. Some of these are shown in Table 2.1. As the table shows, carboxylic esters have a much smaller enolic content than ketones. In molecules like acetoacetic ester, the enol is also stabilized by internal hydrogen bonding, which is unavailable to the keto form ... 

The adduct then decomposes with the loss of the enolate anion of the ester as a leaving group. Draw this. 

Weber et al. have reported that the condensation product (26) of the reaction between methyl cyanoacetate and 6-chloro-2,4-dimethoxy-l,3,5-triazine exists as two tautomeric forms in rapid equilibrium. The ester is enolized readily (A). The second exchange involves the breaking of an intramolecular hydrogen bond (B) (Scheme 5) (78RTC107). 

Co2(CO)8-catalyzed reactions of benzylic acetates with trimethylsilane and CO proceed under mild reaction conditions to give trimethylsilylethers of /3-phenethylalcohol in 43-76% yield. The highest yields are observed for benzyl acetates with electron-donating substituents.111 Secondary alkyl acetates are also good substrates in the reaction system, yielding enol silyl ethers.112 In addition, the cobalt complex is an effective catalyst for siloxymethylation of five-membered cyclic ortho esters, as shown in Eq. (41).113... 

Enol esters.1 In the presence of (CgHn Ru and P(Bu)3 in the molar ratio 1 2, a,p-unsaturated acids add to terminal alkynes to form enol esters as the major product. 

This protecting group can direct enolate formation of an ester as well as the site of alkylation. Thus the enolate of 2 is alkylated at the benzylic position rather... 

This reaction is quite special in that it is an aldol-type addition in which a thioester is the donor (nucleophile) and a keto acid is the acceptor (electrophile). From the discussion in Section 18-8E, you will see that reactions of this kind involving an ester as the donor and an aldehyde or ketone as the acceptor can be achieved in the laboratory only under rather special conditions. For the thioester to function as a nucleophile at the a carbon under the restraints imposed by having the reaction occur at the physiological pH, the catalyzing enzyme almost certainly must promote formation of the enol form of the thioester. The enol then could add to the ketone carbonyl with the assistance of a basic group on the enzyme. This kind of catalysis by enzymes is discussed in Section 25-9C. 

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