Esters enol equivalents

The stability of the phosphonium-stabilized enolates also means that, although they react well with aldehydes, their reactions with ketones are often poor, and it is better in these cases to use phos-phonate-stabilized enolates. Being anionic, rather than neutral, these are more reactive. If an ester enolate equivalent is being used, the best base is the alkoxide ion belonging to the ester with a ketone enolate equivalent, use sodium hydride or an alkoxide. 

Silyl alkyl ketene acetals, as ester enolate equivalents, are capable of regioselective acylation by acid chlorides. Rathke and Sullivan showed that a variety of acid chlorides reacted with the acetal (3) to give protected -keto esters (Scheme 11). Acid hydrolysis of the silylated products gave the free -keto ester. The reaction was successful with a variety of acyl chlorides, including acetic, butanoic, (2 )-buten-... 

An alternative to the bis-lactim ether approach is based on condensations of saturated five-membered heterocycles such as imidazolidinone (532) which can now be obtained in an optically pure state by a straightforward classical resolution/ The related oxazolidinone (533) has been obtained from methionine and used to prepare (R)-amino-acids [cf. (528) ] as well as the vinyl substituted derivatives(534) by oxidation and elimination of the sulphur group." Yet more general routes to chiral amino—acids have been reported using a variety of asymmetrically substituted ester enolate equivalents (535) in combination with the electrophilic nitrogen source di-t-butyl... 

For aldol reactions with an ester enolate equivalent, use ... 

Before going further, there are two points we must clarify. The first is a problem of nomenclature, and concerns the enolates of esters. Here are two closely related ester enolate equivalents, drawn with the same double bond geometry. Is it f or Z ... 

The Bode group have documented an NHC-catalyzed enantioselective synthesis of ester enolate equivalents with a,p-unsaturated aldehydes as starting materials and their application in inverse electron demand Diels-Alder reactions with enones. Remarkably, the use of weak amine bases was crucial DMAP (conjugate acid = 9.2) andN-methyl morpholine (NMM, conjugate acid pAa = 7.4) gave the best results. A change in the co-catalytic amine base employed in these reactions could completely shift the reaction pathway to the hetero-Diels-Alder reaction, which proceeded via a catalytically generated enolate. An alternative pathway that occurred via a formal homoenolate equivalent was therefore excluded. It is demonstrated that electron-rich imidazolium-derived catalysts favor the homoenolate pathways, whereas tri-azolium-derived structures enhance protonation and lead to the enolate and activated carboxylates (Scheme 7.71). 

In the same year, Chi and coworkers reported a direct a-functionalisation of simple aldehydes to produce ester enolate equivalents under oxidative NHC catalysis. The ester enolate equivalents reacted with enones to give dihydropyrones 152 in good yields with an excellent diastereomeric ratios and enantiomeric excesses (Scheme 20.63). ... 

Next, the application of ketene silyl acetals was tried in the above aqueous reactions of silyl enolates with aldehydes. Ketene silyl acetals are useful ester enolate equivalents that can be isolated [27, 28], and the aldol-type reaction of ketene silyl acetals with aldehydes is among the most important and mildest methods of carbon-carbon bond formation [29]. Disappointingly, no aldol adduct was obtained when the ketene silyl acetal derived from methyl 2-methylpropionate (3) was employed as a representative ketene silyl acetal (structure 3 is shown later in Table 8.10). In aqueous media, hydrolysis of the ketene silyl acetal preceded the desired aldol reaction. 

The power of NHC catalysts lies in the ability of these heterocycles to promote the transient generation of reactive species, such as acyl anion equivalents or activated carboxylates. Using the mechanistic postulates for these processes, it is possible to predict that the combination of an NHC catalyst and an a,p-unsaturated aldehyde could lead to the generation of a wide variety of cata-lytically generated reactive intermediates (Scheme 14.12). Over the past 5 years, the rapid developments of new catalysts and reaction conditions have made possible the selective generation of eaeh of these classes of reactive species, including the synthetically powerful homoenolate and ester enolate equivalents. 

Enantioselective Annulations with NHC-bound Ester Enolate Equivalents... 

In order to separate structural effects from the electronic differences of these two catalyst classes. Bode synthesized chiral imidazolium salt 57 (Scheme 14.28). This allowed direct comparison of imidazolium versus triazolium precatalysts across a number of different reaction manifolds including those involving the catalytic generation of homoenolate equivalents, ester enolate equivalents, and acyl anions. These studies conclusively demonstrated that imidazolium-derived catalysts are superior for homoenolate reactions with less reactive electrophiles, while the triazolium-derived pre-catalysts are preferred for all other reactions. Interestingly, from the currently published body of the work, it does not appear to be any effects from the counterion of the azolium pre-catalysts in the presence of bases. 

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