Carboxylic esters, magnesium enolate

Reactions presented below show that this method is used frequently to prepare magnesium enolates derived from functionalized carboxylic esters or lactones (equations 18-24, Tables 2 and 3). 

The magnesium amides of choice for the preparation of magnesium enolates via met-allation are the Hauser bases, such as 39 and 40, or (bis)amidomagnesium reagents, such as 46 and 47. The reaction has been successfully applied to the preparation of enolates derived from cyclic, acyclic and a-siloxyketones, benzyUc ketones, aldehydes, carboxylic esters and amides, even with the less hindered Hauser bases. 

Magnesium or lithium enolates of thiol carboxylic esters can be acylated with suitable reagents (c/ Volume 2, Part 1). Highly functionalized new derivatives are obtained. The example shown in equation (35)33,102 J5 closely related to the C-acylation of malonyl-CoA with acetyl-CoA, which plays an important role in the biosynthesis of polypeptides and fatty acids. (S)-4-Hydroxy-5-methyl-3-oxo-hexanoyl-L-leucine esters (41), 2-demethyl analogs of the Hip-Leu moiety of didemnin antibiotics, can be prepared via the 3-keto thiol carboxylic esters (40 equation 36). ° ... 

The bisacylation of methylene-active compounds mentioned above can be avoided by using acylimidazoles in place of acyl halides (acylimidazoles are obtained from the carboxylic acid and sulfinyldiimidazole) for example, reaction of the magnesium enolate of ethyl hydrogen malonate and an acylimid-azole, with concomitant decarboxylation, gives the corresponding / -oxo ester 430... 

With the aid of Rieke magnesium, fused carbocyclic enols can be effordessly synthesized from 1,3-diene-magnesium complexes by reacting with carboxylic esters [116]. By controlling the reaction temperature, p,y-unsaturated ketones can also be produced. 

This new methodology is quite general and can be applied to the magnesium complexes of 1,2-dimethylenecyclopentane, 1,2-dimethylenecyclohep-tane, and 2-methyl-3-phenyl-l,3-butadiene. Likewise, other carboxylic esters, such as butyl and ethyl benzoates, can also be used to make various fused carbocyclic enols or p,y-unsaturated ketone products. Significantly, the overall synthetic process to form fused carbocyclic enols from the corresponding l,2-bis(methylene)cycloalkanes represents a formal [4+1] annulation. 

If we copy Nature rather more exactly, the Claisen ester condensation can be carried out under neutral conditions. This requires rather different reagents. The enol component is the magnesium salt of a malonate mono-thiol-ester, while the electrophilic component is an imidazolide—an amide derived from the heterocycle imidazole. Imidazole has a pK of about 7, Imidazolides are therefore very reactive amides, of about the same electrophilic reactivity as thiol esters. They are prepared from carboxylic acids with carbonyl diimidazole (CDI). 

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