Esters, enolates, reaction with

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... 

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. 

Asymmetric hydraxylation of lithium enolates of esters and amides.2 Hydroxylation of typical enolates of esters with ( + )- and (-)-l is effected in 75-90% yield and with 55-85% ee. The reaction with amide enolates with ( + )- and ( — )-l results in the opposite configuration to that obtained with ester enolates and with less enantioselectivity. Steric factors appear to predominate over metal chelation. 

Fujisawa et al. [89] have reported the stereodivergent synthesis of spiro-[S-1 act a ms 64, 65 (Scheme 17) by reaction of lithium or titanium ester enolates 62 with single chiral imines 63 by taking advantage of different coordination states of the enolate metals. Almost complete reversal of the diastereofacial-discrimination with respect to the C-4 of the (3-lactam skeleton has been attained in this reaction coupled with flexibility in the selection of the enolates and ready removal of the chiral auxiliary. 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1R2C02R3) with (Rs)-2-(p-tolylsulftnyI (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The 0-metallated /Miydroxyalkanoates formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /i-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

The Claisen rearrangement, Cope rearrangement, and associated variants are powerful tools that can be used to create a number of new chiral centers in an expeditious manner, but the use of heavy metals, such as mercury, should be avoided. Of these reactions, the Ireland-Claisen ester enolate reaction provides the most versatile synthetic pathway with minimal scale up problems. 

Reductive acylation of enones.1 The lithium enolate generated by reduction of enones with Li/NH, is converted to a (1-keto ester by reaction with this reagent in ether (THF promotes O-acylation). 

Not surprisingly, thiol ester enolates combine with ketones (and many aldehydes) to form predominantly the less sterically crowded p-lactone diastereomers, in some cases with excellent stereoselectivity. However, the stereochemical course of reactions involving aldehydes has proved to be rather complicated, and further studies are required to clarify the factors that control the stereochemical outcome of these reactions. 

The best results are obtained with trisyl azide, which again leads to high yields of the azide transfer product 2, especially if the enolate 1 is added to trisyl azide (see entries 1 and 2). Interestingly, the best chemoselectivity and, in addition, identical yields of azide (73%) result from the reaction of the lithium enolate with trisyl azide (entry 3). The reaction of the ester enolate 1 with trisyl azide is less sensitive to the nature of the enolate metal than is the corresponding imide enolate reaction (see Section 7.1.1.). Acetic acid quench, on the other hand, again proved to be useful. Unfortunately, bis-azidation to 3 and diazo transfer to 4 are also observed. 

The reaction of a lithium ester enolate (146) with a nitrone (147) to yield a fi-hydroxylamino acid ester (149) has been recently investigated by Domingo, Merino and coworkers, using DFT (B3LYP/6-31G ) methods, to gain insight on the molecular mechanism. The proposed transition structure (148) shown in equation 42 derives from attack of the most nucleophilic center of enolate 146 on the most electrophilic center of... 

Preparation of enolphosphates. The reagent is used in ether solution to convert A4-cholestene-3-one (I) into the enol form for reaction with diethyl phosphoro-chloridatc and tricthylamine to give the phosphate ester (3). Reaction with lithium and ethylamine, and treatment with t-butyl alcohol then affords 5-methyl-A -coprostene (4). 

Aldehydes may be prepared from the lower homolog or a ketone or ester by reaction with the anion of formaldehyde mono- or dithioacetal. The j6-hydroxythioacetal may be reduced with elimination of a hydroxyl group and phenylthiolate. The resulting enol ether or thioenol ether can be transformed into an aldehyde on acid hydrolysis or reaction with mercuric chloride [82],... 

Along these lines, cyclic enol esters, after reaction with dichlorocarbene, were found to undergo smooth expansion to the 2-chlorocycloheptenones on room temperature treatment with ethanolic potassium carbonate (Scheme 41). ... 

Notably, this latter reaction proceeded with 92% ds and tolerates the ketone functionality at C5 of the aldehyde. An alternative approach to C2-C3 bond formation hoped for substrate control in uniting chiral ester enolate 207 with chiral aldehydes 208 and 209. However, this led to a non-selective reaction in each case... 

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