Mono-Metallation of Carbonyl and Thiocarbonyl Compounds

The very acidic (in the region of pK 10) 1,3-dicarbonyl compounds (—CO—CH— CO—), diketones, and ketoesters are readily converted into the enolates by reaction with alkali hydrides in polar as well as in apolar solvents [1]. Also some acidic mono-ketones, e.g., PhCH2COCH3, react smoothly with sodium hydride [4], Potassium hydride has been used to convert aldehydes into the enolates [2, compare 3]. A serious drawback of this method is the handling of the commercially available potassium hydride, which inter alia involves removal of the protecting mineral oil. Reaction of kinetically less acidic ketones and carboxylic esters with alkali hydrides, in general, gives rise to extensive formation of self-condensation products [3,6], 

The deprotonations with LDA are generally extremely fast, even at temperatures far below 0 °C and side- or subsequent reactions such as displacement of the OR group in carboxylic esters, or self-condensations, respectively, remain limited to a minimum. Enolates derived from lactones, e.g., y-butyrolactone, are extremely unstable and must be generated and functionalized below — 70 °C [7]. 

Alkali amides, MNH2, in situ prepared in liquid ammonia, are efficient deprotonating agents in reactions with ketones, carboxylic t-butyl esters, N,N-dialkylcarboxamides, and the analogous sulfur compounds. Primary-alkyl carboxylic esters RR CHCOOR and the sulfur analogues RR CHCOSR and RR CHCSOR (R is prim.-alkyl), however, undergo serious competitive substitution of OR or SR by NH2 [6]. 

Alkali amides seem unsuitable for the generation of kinetic enolates from non-symmetrical ketones, since in the presence of ammonia a ready transformation (via proton donation and abstraction) into the thermodynamic enolate can occur. 

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